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The evaluation of multiple sclerosis through static chromatic perimetry Kozak, John François 1987

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THE EVALUATION OF MULTIPLE SCLEROSIS THROUGH STATIC CHROMATIC PERIMETRY  by JEAN FRANCOIS KOZAK B.A., THE UNIVERSITY OF BRITISH COLUMBIA, 1975 M.A., THE UNIVERSITY OF BRITISH COLUMBIA, 1980  A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF  PHILOSOPHY  in THE FACULTY OF GRADUATE STUDIES Department of Psychology We a c c e p t t h i s t h e s i s as c o n f o r m i n g t o the r e q u i r e d s t a n d a r d  THE UNIVERSITY OF BRITISH COLUMBIA F e b r u a r y , 1987 ©  Jean F r a n c o i s Kozak, 1987  In p r e s e n t i n g  this  thesis  in  partial  fulfilment  requirements f o r an advanced degree at the The B r i t i s h Columbia, I agree that the freely  available  for  reference  Library and  this  scholarly  by  the  Department  or  understood  that  f i n a n c i a l gain  by  may his  copying  shall  not  be or  granted her  be  1987  representatives.  allowed  Department of Psychology  Date: February,  thesis Head  Columbia  without  my  of it  agree  of It  or p u b l i c a t i o n of t h i s t h e s i s  permission.  The U n i v e r s i t y of B r i t i s h 1956 Main M a l l Vancouver, Canada V6T 1Y3  make  study. I f u r t h e r of  the  University  shall  that permission f o r e x t e n s i v e copying purposes  of  for my is for  written  ii  Abstract  The  purpose of the present  whether  or  not  luminance  chromatic perimetry threshold  losses  functioning.  losses  would  be  thresholds  to  examine static,  c o u l d be used to d i s t i n g u i s h  visual  multiple It  was  greater  f o v e a l e c c e n t r i c i t i e s due  sclerosis proposed  at to  both the  cone system, u n l i k e the rods, by  was  through  in  normal  study  from that of  that  the  threshold  fovea  assumption  and  near  that  the  would be the most e f f e c t e d  MS. Twenty-two  MS  patients  and  thirty  normals were t e s t e d on an e x t e n s i v e l y of were  the Fieldmaster established  stimulus  along  done using  a  matched  modified  version  F225 Automatic Perimeter. Thresholds for  an  a 195 45  age  achromatic,  red,  and  blue  - 15 degree m e r i d i a n . T e s t i n g  apostilb  background,  to  which  was the  s u b j e c t s were preadapted p r i o r to t e s t i n g . Results involvement subjects.  indicated  that  there  was  ( l o s s in chromatic t h r e s h o l d s ) Significant  extensive for  the  d i f f e r e n c e s e x i s t e d at the  between normal and c l i n i c a l l y d e f i n i t e s u b j e c t s but between indicated  normal great  and  probable. functional  Correlational changes  in  cone MS  fovea not  analyses retinal  sensitivity obtained  for  the  between MS  MS p a t i e n t s . S i m i l a r r e s u l t s were  patients  with  and  without  optic  neuritis. Discriminant  analyses  i n d i c a t e d that the red f i l t e r  correctly  classify  86.27% of the normals and MS  could  p a t i e n t s with few threshold  difference  degree nasal threshold from MS The clinical  positives  values  eccentricity  value  which  between  were  could  or  negatives.  Log  the fovea and 30  used  to  determine  a  separate normal p r o f i l e s  profiles. typical  "swiss cheese" d e f e c t s  literature  and  blue  the  red f i l t e r . A  false  filters.  possible  was d i s c u s s e d .  were found only  reported  i n the  f o r the achromatic  No i r r e g u l a r p r o f i l e s were  found  for  t h e o r e t i c a l model based on the r e s u l t s  Limitations  p o s s i b l e future r e s e a r c h  of  the  were a l s o  study  as  discussed.  well  as  iv  TABLE OF CONTENTS  Abstract  i i  Table of Contents  iv  List  of Tables  vii  List  of F i g u r e s  xi  Acknowledgement  xiv  I. I n t r o d u c t i o n  1  A. Symptomatology  3  B. Disease Onset  11  C. Mode of Onset  16  D. Motor/Brain Stem Involvement  19  1 . Nystagmus  20  2. Smooth Eye Movement  21  E. Sensory Involvement  22  1 . General  22  2. S p e c i f i c  25  3. P s y c h o p h y s i c a l Assessment  of MS  F. V i s u a l Evoked P o t e n t i a l s  29 30  1 . Technique  30  2. A p p l i c a t i o n  32  3. M o d i f i c a t i o n s  36  G. S p a t i a l Contrast S e n s i t i v i t y 1 . Technique 2. A p p l i c a t i o n  43 43  .  46  H. Temporal Contrast S e n s i t i v i t y  47  1 . Technique  47  2. A p p l i c a t i o n  48  I. Colour V i s i o n  55  1. Systems of C l a s s i f i c a t i o n  56  2. Assessment of Colour V i s i o n  68  3. A p p l i c a t i o n  75  J . Perimetry 1. Chromatic  83 Perimetry  88  2. T h r e s h o l d E s t i m a t i o n  89  3. Adaptation  94  4. S p a t i a l Summation  101  5. A p p l i c a t i o n  105  6. Hypothesis  114  I I . Instrumentation  •  118  1 . Apparatus  118  2. P h y s i c a l S p e c i f i c a t i o n s  118  3. C o n t r o l F u n c t i o n s  119  4. Stimulus C h a r a c t e r i s t i c s and P r e s e n t a t i o n  126  5. Background Luminance  133  6. T h r e s h o l d E s t i m a t i o n  137  7. Instrumental M o d i f i c a t i o n s III. Pilot  ..144  Study  150  1 . Purpose  150  2. S u b j e c t s  150  3. Method  151  4. R e s u l t s and D i s c u s s i o n  153  vi  5. M o d i f i c a t i o n t o A d a p t a t i o n IV. Study  159 164  1 . Subjects  1 64  2. Procedure  165  3. R e s u l t s  173  V. D i s c u s s i o n  224  V I . Summary  250  Bibliography  253  V I I . Appendix A  284  1. Power Supply 2. Instrument S h e l l  .....285 287  V I I I . Appendix B  300  IX. Appendix C  303  1 . Contents X. Appendix D 1 . Contents XI . Appendix E 1 . Contents XII . Appendix F 1. Computer I n t e r f a c e XIII . Appendix G  304 305 306 307 308 309 310 311  vii  List Table  of Tables  1. Major Symptoms Found During The Course Of MS 12  Table 2. E a r l y Symptoms Found In MS 17 Table 3. Neuro-Ophthalmological Non-MS P a t i e n t s Table 4. Percentage  F i n d i n g s In MS And 27  Of MS P a t i e n t s With Abnormal VEP's 34  Table 5. D i s t i n g u i s h i n g Features Of The Major Colour Defects Table 6. N e u t r a l Colour Area Of P a t i e n t Groups As Determined By The Gunkel Chromograph Table 7. F a c t o r s E f f e c t i n g  63  82  Perimetry 92  Table 8. C o l o r i m e t r i c S p e c i f i c a t i o n Of F225 Table 9. S c a l a r Values For O b t a i n i n g  Filters  Thresholds  127 1 54  Table 10. Threshold Values ( A p o s t i l b ) For MS P a t i e n t s By E c c e n t r i c i t y And F i l t e r For A 5 A p o s t i l b Background 1 56 Table  Table  11. Foveal Threshold Values ( A p o s t i l b ) For MS P a t i e n t s During Adaptation 12. Mean and Standard D e v i a t i o n For S u b j e c t s C a t e g o r i e s By Age (Years)  Table  13. D i a g n o s t i c Demographics Of Subjects  Table  14. Duration  (Years) From D i a g n o s i s  161  166 167 168  viii  Table  15. Mean And Standard D e v i a t i o n s For T h r e s h o l d Values ( A p o s t i l b s ) By E c c e n t r i c i t y And Group For The Achromatic F i l t e r 174  Table  16. Mean And Standard D e v i a t i o n s For T h r e s h o l d Values ( A p o s t i l b s ) By E c c e n t r i c i t y And Group For The Red F i l t e r  175  Table  17. Mean And Standard D e v i a t i o n s For T h r e s h o l d Values ( A p o s t i l b s ) By E c c e n t r i c i t y And Group For The Blue F i l t e r 176  Table  18. Mean And Standard D e v i a t i o n s For T h r e s h o l d Values ( A p o s t i l b s ) By E c c e n t r i c i t y And Group For The Achromatic F i l t e r 1 77  Table  19. Mean And Standard D e v i a t i o n s For T h r e s h o l d Values ( A p o s t i l b s ) By E c c e n t r i c i t y And Group For The Red F i l t e r 1 78  Table 20. Mean And Standard D e v i a t i o n s For T h r e s h o l d Values ( A p o s t i l b s ) By E c c e n t r i c i t y And Group For The Blue F i l t e r 179 Table 21. M u l t i v a r i a t e A n a l y s i s Of V a r i a n c e Between Normals (n=30), C l i n i c a l l D e f i n i t e (n=14), And Probable (n=8) MS P a t i e n t s 190 Table  22. Mean Thresholds ( A p o s t i l b s ) For Normals (n=30), C l i n i c a l l y Definite (n=14), And Probable (n=8) MS P a t i e n t s Across F i l t e r s and Eccentricities 1 92  Table 23. Absolute Mean Threshold D i f f e r e n c e ( A p o s t i l b s ) For Normals (n=30), Clinically Definite (n=14), And Probable (n=8) MS P a t i e n t s Across F i l t e r s and E c c e n t r i c i t i e s 1 93 Table 24. Absolute Mean T h r e s h o l d D i f f e r e n c e ( A p o s t i l b s ) For Normals (n=30), Clinically Definite (n=14), And Probable (n=8) MS P a t i e n t s Across Filters 195  ix  Table 25. Mean Thresholds ( A p o s t i l b s ) For A l l Groups And F i l t e r s By E c c e n t r i c i t y 196 Table 26. Absolute Mean Threshold D i f f e r e n c e ( A p o s t i l b s ) By E c c e n t r i c i t y Across Groups And F i l t e r s 197 Table 27. Absolute Mean Threshold D i f f e r e n c e Between F i l t e r s By E c c e n t r i c i t y  (Apostilbs)  Table 28. Absolute Mean Threshold D i f f e r e n c e Between Groups By E c c e n t r i c i t y  (Apostilbs)  199  201  Table 29. Absolute Mean Threshold D i f f e r e n c e ( A p o s t i l b s ) Between Groups By Eccentricity For The Achromatic F i l t e r 203 Table 30. Absolute Mean Threshold D i f f e r e n c e ( A p o s t i l b s ) Between Groups By E c c e n t r i c i t y For The Red Filter 204 Table 31. Absolute Mean Threshold D i f f e r e n c e ( A p o s t i l b s ) Between Groups By E c c e n t r i c i t y For The Blue Filter 205 Table 32. C o r r e l a t i o n s Between The Fovea And E c c e n t r i c i t i e s By Group For The Achromatic Filter Table 33. C o r r e l a t i o n s Between The Fovea And E c c e n t r i c i t i e s By Group For The Red F i l t e r Table 34. C o r r e l a t i o n s Between The Fovea And E c c e n t r i c i t i e s By Group For Filter  The  208  209  Blue 210  Table 35. M u l t i v a r i a t e A n a l y s i s Of V a r i a n c e Between Optic Neuritis (n=14) And Non O p t i c N e u r i t i s (n=8) MS P a t i e n t s 213  X  T a b l e 36. A b s o l u t e Mean T h r e s h o l d D i f f e r e n c e ( A p o s t i l b s ) F o r O p t i c N e u r i t i s And Non O p t i c Neuritis MS P a t i e n t s By F i l t e r 214 T a b l e 3 7 . Mean T h r e s h o l d s ( A p o s t i l b s ) F o r O p t i c N e u r i t i s And Non O p t i c Neuritis MS Patients Across F i l t e r s By E c c e n t r i c i t y 216 T a b l e 3 8 . A b s o l u t e Mean T h r e s h o l d D i f f e r e n c e ( A p o s t i l b s ) By E c c e n t r i c i t y A c r o s s O p t i c N e u r i t i s P a t i e n t s and Non O p t i c N e u r i t i s P a t i e n t s And F i l t e r s 217 T a b l e 3 9 . Mean T h r e s h o l d s ( A p o s t i l b s ) F o r O p t i c N e u r i t i s And Non O p t i c N e u r i t i s MS P a t i e n t s By Filters And E c c e n t r i c i t y 218 T a b l e 40. A b s o l u t e Mean T h r e s h o l d ( A p o s t i l b s ) D i f f e r e n c e By B e t w e e n F i l t e r s By E c c e n t r i c i t y 219 T a b l e 4 1 . P e r c e n t C l a s s i f i c a t i o n Of S u b j e c t s By D i a g n o s i s ( N o r m a l VS. MS) And F i l t e r s  221  L i s t of F i g u r e s Figure  1. Charcot's  T r i a d OF MS 5  F i g u r e 2. Formation Of Myelin  Sheath 7  F i g u r e 3. VEP From Foveal S t i m u l a t i o n With A Red And Achromatic Source F i g u r e 4. Contrast  S e n s i t i v i t y For Sine Wave  F i g u r e 5. Delay Campimetry F i e l d s On A MS P a t i e n t F i g u r e 6. Impaired Temporal S e n s i t i v i t y In A Normal And MS P a t i e n t  F i g u r e 9. D i s c r i m i n a t i o n Losses On The FM 100-Hue Of The Major Colour V i s i o n Defects F i g u r e 10. E f f e c t Of Fatigue On FM 100-Hue E r r o r Scores For An MS P a t i e n t ( A f f e c t e d Versus Unaffected Eye).  F i g u r e 13. S t a t i c Thresholds Photopic, Mesopic, Conditions  51  53  F i g u r e 8. C o l o r i m e t r i c Information On Anomaloscope Equations Based Upon The P-N Anomaloscope  F i g u r e 12. Achromatic Thresholds For 4 Monochromatic L i g h t s  44  Fields  F i g u r e 7. Confusion L o c i , Centre Of Confusion, And N e u t r a l Axes For Dichromats  F i g u r e 11. Isopter And P r o f i l e Perimetry In R e l a t i o n To The Retina  42  65  71  76  79  Plots 86  At 0 Asb Background 96  For F u l l y And Fully-Scotopic 98  xii  F i g u r e 14. Standard R e l a t i v e S p e c t r a l Luminous E f f i c i e n c y Functions For Photopic Scotopic V i s i o n  And 99  F i g u r e 15. S t a t i c Thresholds (45 - 225) Of The Eye (asymptomatic) Of An MS P a t i e n t  Right  F i g u r e 16. Mesopic And MS P a t i e n t  An  Photopic  Thresholds  For  107  111  F i g u r e 17. Thresholds Of Colours Generated On A T e l e v i s i o n Screen For Normals And MS P a t i e n t s ( A f f e c t e d And U n a f f e c t e d Eyes) Figure  18. F225 C o n t r o l  112  Panel 120  Figure  19. Alignment Of  Subject 123  F i g u r e 20. C.I.E. C h r o m a t i c i t y F225 Chromatic F i l t e r s F i g u r e 21. Transmittance F i g u r e 22.  Coordinates  The 129  Values Of F225 F i l t e r s  Bowl P o s i t i o n And  Testing  130  Background Luminance  F i g u r e 23. Bowl P o s i t i o n s Measured By P r i t c h a r d Photometer F i g u r e 24. Threshold  For  135  The 136  Algorithm 141  F i g u r e 25. S t a t i c Threshol d Provided By F i e l d m a s t e r F225 Sales Brochure  The  F i g u r e 26. R e p l i c a t e d Fiedmaster F225 Threshold F i g u r e 27.  195  - 15 Test Threshold  Profile  1 45 Profile 146 152  xiii  F i g u r e 28. S e n s i t i v i t y G r a d i e n t s For MS At 5 A p o s t i l b Background  Subjects 157  F i g u r e 29. S e n s i t i v i t y G r a d i e n t s For A Normal Subject At 5 A p o s t i l b Background 158 F i g u r e 30. S e n s i t i v i t y G r a d i e n t s For Normal, Clinically Definite, And Probable MS Subjects For An Achromatic F i l t e r At 45 A p o s t i l b Background 180 F i g u r e 31. S e n s i t i v i t y G r a d i e n t s For Normal, Definite, And Probable S u b j e c t s For F i l t e r At 45 A p o s t i l b Background  Clinically A Red 181  F i g u r e 32. S e n s i t i v i t y G r a d i e n t s For Normal, Clinically Definite, And Probable S u b j e c t s For A Blue F i l t e r At 45 A p o s t i l b Background 182 F i g u r e 33. S e n s i t i v i t y G r a d i e n t s For Optic N e u r i t i s Non-Optic N e u r i t i s S u b j e c t s For An Achromatic F i l t e r At 45 A p o s t i l b Background F i g u r e 34. S e n s i t i v i t y G r a d i e n t s For Optic N e u r i t i s Non-Optic N e u r i t i s S u b j e c t s For A Red F i l t e r At 45 A p o s t i l b Background F i g u r e 35. S e n s i t i v i t y G r a d i e n t s For Optic N e u r i t i s Non-Optic N e u r i t i s S u b j e c t s For A Blue F i l t e r At 45 A p o s t i l b Background F i g u r e 36. S e n s i t i v i t y G r a d i e n t s For A MS P a t i e n t  And 183 And 184 And 185 186  F i g u r e 37. S e n s i t i v i t y G r a d i e n t s For A Normal Subject 187  xiv  Acknowledgement T h i s study i s d e d i c a t e d  to my  mother Ida Kozak.  I would l i k e to express my gratitude to Drs. R. Lakowski, D.J. Crockett, S. Coren and S.M. Drance f o r t h e i r a s s i s t a n c e and guidance. I would e s p e c i a l l y like to single out Dr. R. Lakowski f o r h i s a s s i s t a n c e and guidance throughout my academic s t u d i e s and the time and i n s i g h t s he gave to my r e s e a r c h . I would a l s o like to thank Dr. Crockett, f o r without h i s h e l p t h i s study would have taken longer, i f ever, to complete. I wish to acknowledge the following external reviewers for their comments and suggestions: Dr. A. E i s e n ( P r o f e s s o r and A s s o c i a t e Dean of Research, F a c u l t y of Medicine, U . B . C ) ; Dr. D.J. MacFadyen ( P r o f e s s o r and Head, Department of Clinical Neurological Sciences, U n i v e r s i t y of Saskatchewan); Dr. D.N. Paty (Professor and D i r e c t o r , Department of Neurological Sciences, U . B . C ) ; and Dr. R. Wong ( P r o f e s s o r , Department of Psychology, U . B . C ) . I would a l s o l i k e to thank Ms. K. E i s e n of the MS C l i n i c , Acute Care H o s p i t a l , and Ms. Mo Gupta, Mr. D.R. Drysserinck and Mr. K. Wijsman of the Eye Care C l i n i c , Acute Care H o s p i t a l f o r t h e i r h e l p i n the s c h e d u l i n g of the p a t i e n t s . F i n a l l y , I would l i k e to express my a p p r e c i a t i o n of the p a t i e n t s who gave t h e i r time and e f f o r t throughout the v a r i o u s phases of t h i s study.  1  I.  Multiple  sclerosis  clinicians  with  as  in  well  as  Treatment  at  has presented  enormous  present  is  which  sclerosis  100 y e a r s  to  develop  features;  and, therefore, a s on  Symptomatically, impairment  as well  as  patient in  modalities.  Both  motor  alone  some  combination.  or  in  progression actually  of  have  d i f f i c u l t  to  the  several  is  -  protean  of  one or  In  c l i n i c a l  differentiate  i t s  in  of  i t s  conducting  sensory may  the  so v a r i a b l e  are  seen  appear  severity  that  that  an argument  it  motor  impairment  addition,  in  disease.  more  diseases  manner  description  the  onset  disease.  h a s made  may e x h i b i t  and sensory  'disease'  Despite  d i f f i c u l t y  epidemiology  losses  the  itself  and  early  of  c l i n i c a l  created  the  detecting  ago, the  an accurate  the  researchers  course(s)  may p r e s e n t  d i f f i c u l t  such  the  in  symptomatic.  over  multiple  both  problems  understanding  identification  research  INTRODUCTION  and  o n e may too  in  schizophrenia. One that  of  prominent the  sensory  Non-invasive the  area  system,  procedures  detection  of  of  for  involvement  in  MS a p p e a r s  especially  the  v i s u a l .  diagnosing  the  disease  abnormalities  in  the  sensory  to  rely  system  be  upon  of  interest. A major examination  assessment or  c l i n i c a l  procedure,  apart  procedures  such  from as  postmortem  electrophoresis,  2 is  the  visual  s y s t e m due reduction  to in  they  literature  in  other  is  the  optic  examining  retina  the  1.  of  nerve  retinal  system  assessing  MULTIPLE  Multiple  being  to  is  the  the  that  of  the or  belief  the  losses. in  affected  Because  as a  visual  of  MS, w i t h  the the  the  it  through  is  effects  of  (retina)  as w e l l  as p o s s i b l y  both  presence and  macula  cone and  more  sensitivity  proposed that  chromatic  the  retina  the  earliest apparent  that  function  confuse  Both  for  following  macula and p e r i p h e r a l  demyelination,  the  visual  studied  writer's  ignore  affected  functioning  being  The p u r p o s e  to  the  evoked p o t e n t i a l  currently  it  in  latency.  functional  are  rods.  the  demonstrate  employed tend  o n e may u n d e r s t a n d visual  are  results.  to  possibly  than  greater  methods  r e v e a l i n g MS r e l a t e d  severely  for  or  contributions  functioning  appear  involvement,  review  and p e r i p h e r a l  of  to  ambiguous  currently  specific in  MS t e n d  visual  provide  tests  Abnormalities  amplitude  Although assessing  evoked p o t e n t i a l .  demyelination  perimetry on  the  provide  severity  of  by  a  method  MS.  SCLEROSIS  sclerosis is  characterized  by  nervous  system.  affect,  or  between  the  at  the It  least  ages of  a remissively p r e s e n c e of  is  plaques  multi-focal  in  be s y m p t o m a t i c 10 a n d 5 0 ,  progressive  with  in  nature  in  the  disease central  and appears  males and  to  females  females being  affected  3 1.7:1 times more than males. Prevalence r a t e s f o r m u l t i p l e s c l e r o s i s are higher i n the northern l a t i t u d e s and comparably rare contracting greater  in Asiatic countries.  multiple  s c l e r o s i s i s s a i d t o be four  f o r those l i v i n g  workers, h i g h e r  or managerial groups than  f o r C a u c a s i a n s than  f i f t e e n t o twenty times greater of m u l t i p l e  times  i n m e t r o p o l i t a n c e n t r e s than s m a l l  towns, higher f o r p r o f e s s i o n a l unskilled  The r i s k f o r  for f i r s t  sclerosis victims. Multiple  negroids,  degree  relatives  sclerosis i s also  more l i k e l y t o be manifested i n i n d i v i d u a l s with a h i s t o r y of  infectious diseases.  myriad of f a c t o r s f e l t multiple  Apart  from i n f e c t i o n s , some of the  t o e i t h e r p r e c i p i t a t e or aggravate  s c l e r o s i s have been trauma, pregnancy, emotional  stress, vaccination  and/or i n n o c u l a t i o n ,  menstruation,  temperature changes, and f a t i g u e . A e t i o l o g y has,  at one time or another, been a s c r i b e d  of the d i s e a s e to a latent  virus  which may or may not l e a d t o an anti-immunal myelin response, t o the presence of h i s t o c o m p a t i b i l i t y (HLA)  antigens  [ r e l a t e d t o four l o c i on chromosome number s i x ] as  w e l l as d i e t  (saturated  f a t s ) and c l i m a t e .  A. SYMPTOMATOLOGY  The  first  account of m u l t i p l e  s c l e r o s i s (MS) appears t o be  that of Augustus d'Este' (1830) who prepared a d i s s e r t a t i o n on the p r o g r e s s i o n  of the d i s e a s e i n h i m s e l f ,  preceding the  4 p e r s o n a l i n s i g h t s p r o v i d e d by Lumsden (1970) some one hundred y e a r s . Although C a r s w e l l i n 1838  and  Cruveilhier  (1835-1842) are a t t r i b u t e d with demonstrating of l e s i o n s i n the c e n t r a l nervous (1868) who  system,  (Field,  Charcot  felt  or disseminated  that MS d i d not occur p r i o r to the age of - a belief  still  h e l d today d e s p i t e  evidence to the c o n t r a r y (eg. Friedman & Davison, 1977;  Ziegler,  clinical  1977).  fourteen and a f t e r f i f t y  Elian,  presence  i t i s Charcot  i s g e n e r a l l y a c c r e d i t e d with the f i r s t  d e s c r i p t i o n of the syndrome known as MS sclerosis  the  F i e l d , S i n c l a i r & Swank, 1980;  1945;  Bejar, Dewey &  1984). His d e s c r i p t i o n of the c y c l i c a l  ( r e m i s s i o n - p r o g r e s s i o n ) nature of the symptoms, the of plaques  in r e l a t i o n  to e i t h e r  sensory and/or motor  d i s t u r b a n c e s as well as the problematic presence of cases  (asymptomatic) i s so complete  l i t t l e has been added s i n c e . Of p a r t i c u l a r  importance  presence  (Field,  silent  that many f e e l that very 1977).  are those d i a g n o s t i c s i g n s  typically  r e f e r r e d to as Charcot's T r i a d of M u l t i p l e  Sclerosis  (Figure 1) (Newell, 1978). According to Charcot,  MS  i s c h a r a c t e r i z e d by the presence  atrophy  of nystagmus, o p t i c  ( o p t i c n e u r i t i s ) and scanning speech  p r e s s u r e d speech). The  importance  (slow,  of t h i s t r i a d l i e s  i n the  f a c t that the m a j o r i t y of i t s symptoms i n v o l v e the v i s u a l system,  i n d i c a t i n g , as indeed i s the case, that the v i s u a l  system appears e f f e c t s of  MS.  to be h i g h l y s e n s i t i v e to the d e m y e l i n a t i v e  OPTIC ATROPHY  NYSTAGMUS (JERK & VESTIBULAR)  , SCANNING SPEECH  FIGURE  1  CHARCOT'S TRIAD OF MULTIPLE SCLEROSIS  6 M u l t i p l e s c l e r o s i s i s b e l i e v e d to be the r e s u l t of c e n t r a l nerve  f i b e r demyelination  Lumsden & Acheson, 1972)  (Lumsden, 1970;  McAlpine,  as w e l l as p o s s i b l e v a s c u l a r  changes i n regions such as the r e t i n a  (Lumsden,  1970;  Bervoets & De L a c t , 1984), l o s s of o l i g o d e n d r o g l i o c y t e s and i n c r e a s e i n f i b r o u s a s t r o c y t e s (McDonald, 1974). Through unknown mechanisms, p o s s i b l y by responses to v i r u s e s wherein  lymphocytes  1  immunal  and macrophages  invade the b r a i n and a t t a c k the myelin, the myelin surrounding the axon of a c e n t r a l nerve fragments  (Lumsden, 1970;  sheath  f i b r e s w e l l s and  McDonald, 1974). The d e s t r o y e d  sheath i s r e p l a c e d by a s c l e r o t i c plaque, a scar r e s u l t i n g from the p r o l i f e r a t i o n of g l i a l (Lumsden, 1970). I t i s thought of  MS  c e l l s around  the axon  that symptoms c h a r a c t e r i s t i c  are the r e s u l t of an i n a b i l i t y of such plaques to  conduct  impulses along the axon.  M y e l i n , f i r s t d i s c o v e r e d by Leeuwenhoek i n 1717, c o n s i s t s of a plasma membrane d e p o s i t e d by Schwann c e l l s ( F i g u r e 2). The myelin sheath i s the r e s u l t of a membrane of the Schwann c e l l f i r s t forming a " f l a t t e n e d sheet" that envelops the axon. The Schwann c e l l then r o t a t e s around the axon u n t i l s e v e r a l l a y e r s of a conductive l i p i d known as sphingomyelin i s d e p o s i t e d . I t i s t h i s l i p i d that i n c r e a s e s the r e s i s t a n c e to ion flow almost 5,000 f o l d and decreases c a p a c i t a n c e by 1,000 f o l d (Guyton, 1981). An unmyelinated area between the j u n c t i o n of two adjacent Schwann c e l l s where ions may flow e a s i l y between the e x t r a c e l l u l a r f l u i d and the axon i s known as the node of Ranvier. The f u n c t i o n of such nodes i s to a l l o w s a l t a t o r y conduction wherein a neuronal s i g n a l jumps along a f i b e r . Although the nodes of Ranvier are unmyelinated, they are covered with a conductive membrane that surrounds the axon underneath the myelin. The f u n c t i o n of t h i s nodal (high potassium channels) and i n t e r n o d a l (high sodium channels) axon membrane i s p r e s e n t l y u n c l e a r , but i s f e l t to p l a y a major r o l e i n s p e c i f y i n g which areas of the axon w i l l become myelinated (Waxman & F o s t e r , 1980). 1  Schwann celt nucleus Layers of Schwann cell membranes ( Myelin sheath)  FIGURE 2 FORMATION OF MYELIN SHEATH IN THE PERIPHERAL NERVOUS SYSTEM. MODIFIED FROM GUYTON ( 1 9 8 1 , p . 1 1 6 )  8 A f t e r a p e r i o d of time, slow conduction demyelinated neurons r e t u r n s  and  within  the neurons begin to  f u n c t i o n on a p r i n c i p l e s i m i l a r to the conduction method reported  i n unmyelinated axons (Smith, Blakemore & McDonald,  1981). T h i s resumption of s i g n a l p r o c e s s i n g responsible  f o r the  is felt  r e m i t t i n g nature of the d i s e a s e .  a d d i t i o n , s i g n a l conduction i n damaged neurons may result  from p a r t i a l r e m y e l i n a t i o n  - the  by undamaged o l i g o d e n d r o g l i a l c e l l s 1  T h i s process i s a l i m i t e d one  synthesis  be  In  also of myelin  ( M o r e l l & Norton, 1972).  i n that  c e l l s are not capable of i n c r e a s i n g therefore  to  oligodendroglial  i n s i z e and  unable to remyelinate plaques of any  are significant  size. The  process d e s c r i b e d  based on n e u r o p a t h o l o g i c a l  above regarding  demyelination i s  models i n v o l v i n g the  peripheral  nervous system. Moreover, the normal formation of myelin discussed  e a r l i e r and  which i s b e l i e v e d The  shown i n F i g u r e  2 represents  only  that  to occur i n the p e r i p h e r a l nervous system.  involvement of the c e n t r a l nervous system with  to myelin damage and  neural  respect  f u n c t i o n i n g as seen i n MS  is  I t has r e c e n t l y been p o s t u l a t e d that the r e m i t t i n g c y c l e of the d i s e a s e may be due to an i n t e r m i t t e n t d i s r u p t i o n i n the opening of the b l o o d / b r a i n b a r r i e r , a l l o w i n g some m y e l i n o l y t i c f a c t o r to enter the b r a i n ( B a r r e t t , Drayer and Shin, 1985). Increased p e r m e a b i l i t y of the e n d o t h e l i a l c e l l s comprising the b a r r i e r has been shown to e x i s t f o r v a r i o u s i n f e c t i o u s diseases such as herpes simplex e n c e p h a l i t i s as w e l l as p s y c h o p h y s i o l o g i c s t a t e s such as hypertension (Fishman, 1980). Although the f i n d i n g s regarding p e r m e a b i l i t y changes i n the b a r r i e r are c o n t r o v e r s i a l and have been conducted on lower animals such as r a t s , the t r a n s i e n t t r a n s p o r t a t i o n of macromolecules across the e n d o t h e l i a l c e l l s have been observed i n MS p a t i e n t s (Fishman, 1980). 1  9 still  not completely  understood*  According to Hashimoto and Paty changes found  (1986) the p a t h o l o g i c a l  i n MS, both i n the p e r i p h e r a l and c e n t r a l  nervous systems, f o l l o w a r e l a t i v e l y c o n s i s t e n t p a t t e r n : inflammation,  oedema and s w e l l i n g , demyelination, and  g l i o s i s . However, the s i t e and degree of n e u r a l  involvement  as w e l l as symptomatic e x p r e s s i o n may vary c o n s i d e r a b l y from p a t i e n t to p a t i e n t . The authors s t a t e that the e a r l i e s t found  " i n MS i s probably  inflammatory."  p.539). Whether or not v i r a l  symptomatic  lesion  (Hashimoto & Paty,  i n a e t i o l o g y , the inflammation  leads to oedema and s w e l l i n g a t the n e u r a l s i t e i n v o l v e d . At t h i s p o i n t , i f the symptoms of oedema and s w e l l i n g c o n t i n u e , d e m y e l i n a t i o n may occur. As noted by Hashimoto and Paty, i t is s t i l l  u n c l e a r whether demyelination r e s u l t s from the l o s s  of e i t h e r myelin or o l i g o d e n d r o c y t e s . If the p a t h o l o g i c a l process i s h a l t e d , p a r t i a l and/or complete r e m y e l i n a t i o n may occur - as has been demonstrated in the p e r i p h e r a l nervous system. I f the process c o n t i n u e s , however, the f i n a l stage, inflammation  stage of g l i o s i s  and oedema tend t o decrease as plaques  form and age (Hashimoto & Paty, astrocytes  i s reached. At t h i s  1986). The i n c r e a s e of  ( g l i o s i s ) at the s i t e s i n v o l v e d r e s u l t e v e n t u a l l y  in the formation of f i b r a l p a t t e r n s ( s c a r s ) along the axons. No r e m y e l i n a t i o n i s b e l i e v e d to be p o s s i b l e once g l i o s i s occurs and the plaques  mature.  10 It has  r e c e n t l y been argued t h a t demyelination does not  i n v o l v e d e s t r u c t i o n of Schwann c e l l s as was p r e v i o u s l y assumed ( Sumner, 1985). Instead, work with a l i p i d c a l l e d g a l a c t o c e r e b r o s i d e , which causes conduction s i m i l a r to MS,  has  l e d to the s p e c u l a t i o n that  r e q u i r e s an i n t a c t Schwann c e l l . An due  to some pathogen causes the c e l l  demyelination  sheath.  The  that causes the  demyelination.  demyelination: except  over-encompassing use of the term  there appear to be two  distinct  types of  (1) i n v o l v i n g damage to a l l p a r t s of the axon  the d i s t a l p a r t of the nerve  f i b r e and  W a l l e r i a n type i n v o l v i n g a l l of the f i b r e Presumably, some a b i l i t y to conduct first  any  from o c c u r r i n g .  D e s p i t e Charcot's demyelination  (2) the  (McDonald, 1974).  an impulse  exists  block experienced  Donny-Brown & Brenner, 1944:  Morgan-Hughes, 1968;  Fowler & G i l l i a t t , r e s u l t s not  1972;  from the i n a b i l i t y  normal and demyelinated Waxman, 1978).  i n MS  areas  (eg.  Ochoa,  Smith, Blakemore & McDonald,  i n s t e a d , as a r e s u l t of an  1978;  i n the  type of degeneration. T h i s i n turn r a i s e s the q u e s t i o n  as to whether the conduction  but  conduction  of an i n t a c t Schwann c e l l  D e s t r u c t i o n of the Schwann c e l l would preclude demyelination  cell  to r e l e a s e endogenous  protease causes l y s i s of the membrane, l e a d i n g to  ( c r e a t i o n of protease)  blocks  i n s u l t of a Schwann  p r o t e a s e s w i t h i n the f o l d s of the myelin  b l o c k . I t i s the response  antigen  to e x c i t e demyelinated  1981) areas,  "impedance mismatch" between (Sears, Bostock & S h e r r a t t ,  11 B. DISEASE ONSET M u l t i p l e s c l e r o s i s i s c l a s s i c a l l y c h a r a c t e r i z e d by two phases, which are (1) a t t a c k  and (2) r e m i s s i o n .  or r e l a p s e phase i s u s u a l l y e p i s o d i c e i t h e r acute or slowly p r o g r e s s i v e being  The a t t a c k  i n nature and may be  ( c h r o n i c ) with the l a t t e r  c h a r a c t e r i s t i c of about 10% of cases (Fog, 1977).  Onset tends t o be r a p i d , u s u a l l y w i t h i n minutes or hours (McAlpine et a l . , 1955, 1972) as w e l l as v a r i e d a c c o r d i n g t o symptomology. Table 1 p r o v i d e s  a summary of the types and  frequency of l o s s g e n e r a l l y a s s o c i a t e d with MS. As i s evident  from the t a b l e , the frequency v a r i e s g r e a t l y with  the most common type being  v i s u a l and motor  disturbances.  During the acute phase, the symptoms expressed by the p a t i e n t become severe.  The p a t i e n t tends t o remain at t h i s  l e v e l f o r a p e r i o d of days or weeks u n t i l  s/he enters the  second stage - that of r e m i s s i o n . In r e m i s s i o n ,  the p a t i e n t experiences a l e s s e n i n g of  the symptoms with a p o s s i b l e r e t u r n to some previous  level  of f u n c t i o n i n g . Although symptoms may f l u c t u a t e during p e r i o d , the p a t i e n t ' s l e v e l of f u n c t i o n i n g relatively  s t a b l e u n t i l a r e l a p s e occurs.  r e l a p s e s per year may vary  remains The number of  g r e a t l y (Thygesen, 1953) with no  apparent decrease i n the r e l a p s e (Lhermitte,  this  r a t e as the i n d i v i d u a l ages  Marteau, Gazengel, Dorda & Deloche, 1973).  Furthermore, there does not appear to be a s i g n i f i c a n t c o r r e l a t i o n between the number of r e l a p s e s and s e v e r i t y of the a t t a c k  (Fog & Linnemann, 1970).  12  TABLE 1 Major Symptoms Found During the Course Symptoms  Kuroiwa et a l . (1982) (n=488)  1  Kuroiwa e t a l . (1982) (n=177)  2  of  MS  Poser et a l . (1978) (n=127l)  Field (1977) (n=527)  Visual  68.7%  63.8%  66.0%  2 3 . 1%  Diplopia  26.0  44.6  34.0  -  Optic Atrophy  58.2  57.1  -  -  Nystagmus  37.5  74.6  -  -  Balance or A t a x i a  40.8  79.7  -  76.7  Paraesthesia  60.5  77.4  87.0  -  Bowel or Bladder  59.9  69.5  63.0  19.4  Paresis  ' Asian s e r i e s Hungarian s e r i e s C l a s s i f i e d under t h e g e n e r a l  -  82.0 88.0  3  2 3  heading  of c e r e b e l l a r  dysfunction  13 Regarding the acute phase, Kurtzke p a t i e n t s who  experienced  which the d i a g n o s i s was  an a t t a c k p r i o r to the one made were l e s s a f f e c t e d by  d i s e a s e than those p a t i e n t s whose onset d i a g n o s t i c bout. The l a t t e r group was  (1970) r e p o r t e d that  one  bout was  upon the  the  d i s t i n g u i s h i n g f e a t u r e of  the  the preponderance of motor symptoms. In  a d d i t i o n , prognosis appears to be more favourable  i f the  onset bout i s a l s o c h a r a c t e r i z e d by the presence of  optic  neuritis  be  (Newell,  discussed  1978)  - a r e l a t i o n s h i p which w i l l  later. From the combination  of acute and  remission  phases, there appear to be four general types of d i s e a s e course Chitnis, found  ( K r a f t , C o r y e l l , F r e a l , Hanan &  1979). The  first,  i n about 20% of MS  exacerbation recovery  little  is  (acute) - r e m i s s i o n p a t t e r n , where  are m i l d and  relatively  subsequent  relatively  such p a t i e n t s are not  experience  course,  p a t i e n t s . I t i s of an  i s almost complete and  exacerbations Although  the benign  infrequent.  symptom f r e e , they  do  long s t a b l e p e r i o d s , with  or no r e s t r i c t i o n s p l a c e d on t h e i r p h y s i c a l  and/or mental f u n c t i o n i n g . The course,  second type, the e x a c e r b a t i n g  - remitting  i s c h a r a c t e r i z e d by r e l a p s e s o c c u r r i n g at  the r a t e of one  every  s i x months to one  every  three  or four y e a r s . Such p a t i e n t s are able to f u n c t i o n i n an occupation  for about twenty years, a f t e r which  14 the m a j o r i t y develop a r e m i t t i n g - p r o g r e s s i v e course. The  t h i r d type, the r e m i t t i n g - p r o g r e s s i v e  p a t t e r n , i s d e f i n e d by the presence of one a t t a c k s followed by p e r i o d s of t o t a l or r e m i s s i o n . U n l i k e the benign course, p r o g r e s s i v e course patient  is cyclical  partial  the r e m i t t i n g -  in nature  until  reaches a stage where the d i s e a s e  progresses The  without  the  slowly  remission.  f o u r t h type,  in a m i n o r i t y of MS  or more  the p r o g r e s s i v e course,  p a t i e n t s (about  i d e n t i f i e d by the slow onset  10%)  and  occurs is  of motor weakness.  There i s no remission of symptoms, r e s u l t i n g i n severe  d i s a b i l i t y . Although r e l a p s e r a t e tends to be  a d i s t i n g u i s h i n g f e a t u r e of MS, & Linnemann, 1970; D i r d a & Deloch,  Lhermitte,  1973)  researchers  Fog  Marteau, Gazengel,  have not confirmed  (1953) r e p o r t s that there  (eg.  Thygeson's  is a significant  c o r r e l a t i o n between number of r e l a p s e s and s e v e r i t y of the  disease.  Despite MS,  the apparent a b i l i t y  c l i n i c i a n s find  course  i t impossible  the d i s e a s e w i l l take  to d e f i n e the course to p r e d i c t the  scales exist mobility  exact  i n a p a t i e n t . In a d d i t i o n ,  d i f f i c u l t i e s a r i s e with respect to diagnosing time of onset  of  the d i s e a s e at  as w e l l as i t s s e v e r i t y . Numerous c l i n i c a l f o r c a t e g o r i z i n g p a t i e n t s on the b a s i s of  (eg. Thygesen, 1949;  McAlpine and Compston,  1952;  15 Fog,  1964) or n e u r o l o g i c a l s i g n s ( d i s a b i l i t y )  1961;  Alexander, B e r k e l y & Alexander,  (eg. Kurtzke,  1958; Schumacher,  Beebe, K i b l e r , Kurland, Kurtzke, McDowell, Nagler, S i b l e y , T o u r t e l l o t t e & Willman, Bauer,  1965; McDonald & H a l l i d a y , 1977;  1980; Poser, Paty, Scheinberg et a l . ,  1983).  Although  these s c a l e s c l a s s i f y p a t i e n t s i n t o c a t e g o r i e s such as 'clinically  definite',  'probable' and ' p o s s i b l e ' , they  d i f f e r on which symptoms a r e i n d i c a t i v e of which category a c l a s s i f i c a t i o n problem  which makes i t d i f f i c u l t  r e s u l t s across studies using d i f f e r e n t diagnostic  to compare scales.  Moreover, d i f f e r e n c e s i n c l a s s i f i c a t i o n c r i t e r i a are r e l a t e d to  the time a t which d i a g n o s i s i s made. Thus I z q u i e r d o ,  Hauw, Lyon-Caen, Marteau, Lhermitte  E s c o u r o l l e , Buge, Castaigne and  (1985) r e p o r t e d that p a t i e n t s c l a s s i f i e d with  Poser's c r i t e r i a were diagnosed s i g n i f i c a n t l y e a r l i e r  than  with the c l a s s i f i c a t i o n of Bauer. However, there was no d i f f e r e n c e between c l a s s i f i c a t i o n s  f o r those p a t i e n t s  diagnosed as " p r o g r e s s i v e " . F u r t h e r c o m p l i c a t i n g attempts  t o study MS i s the  presence of s i l e n t c a s e s , those p a t i e n t s who are asymptomatic and are o n l y r e v e a l e d at autopsy. Georgi  (1961)  r e p o r t e d that of 66 a u t o p s i e d cases, 12 unexpectedly had MS. S i m i l a r r e s u l t s have been r e p o r t e d by A l t e r  (1962),  Castaigne, L h e r m i t t e , E s c o u r o l l d , Hauw, Gray & Lyon-Caen (1981) and G i l b e r t & S a d l e r (1981), r e v e a l i n g the presence of  widespread  demyelination among asymptomatic  patients.  Although the death r a t e among MS p a t i e n t s i s higher than  16 that of the g e n e r a l p u b l i c , e p i d e m i o l o g i c a l s t u d i e s tend to i n d i c a t e that over f i f t y percent of MS deaths are due t o c o m p l i c a t i o n s such as pulmonary i n f e c t i o n and c a r d i a c d i s e a s e and t h e r e f o r e may not be d e t e c t e d u n l e s s an autopsy i s performed  (eg. L e i b o w i t z , Kahana, Jacobson  & Alter;  1972).  C. MODE OF ONSET  As s t a t e d e a r l i e r , onset of MS i s extremely v a r i a b l e with symptoms d e v e l o p i n g over a matter of minutes, hours,  days,  or weeks. McAlpine et a l . (1955) r e p o r t e d that of 219 confirmed MS p a t i e n t s , 68.4% had symptoms which developed w i t h i n one week, 22.8% w i t h i n one year and 8.8% had t h e i r symptoms develop p r o g r e s s i v e l y over s e v e r a l y e a r s . Table 2 p r o v i d e s the f i n d i n g s of s e v e r a l s t u d i e s r e p o r t i n g the types of e a r l y symptoms found amoung MS p a t i e n t s . The m a j o r i t y of symptoms i n v o l v e the sensory system  (eg. p a r a e t h e s i a , o p t i c  n e u r i t i s ) with a smaller percent p r i m a r i l y motor i n e x p r e s s i o n . Although  i t i s tempting to assume that the type  of symptom expressed i s r e l a t e d t o the s i t e and extent of the d e m y e l i n a t i o n , such a c o r r e l a t i o n has not been conclusively established  (Field,  1977; G i l b e r t & S a d l e r ,  1983). Attempts  made at e s t a b l i s h i n g the presence of prodromal  f e a t u r e s unique to MS have been u n s u c c e s s f u l , g e n e r a l l y  17  TABLE 2 E a r l y Symptoms Found i n MS Symptoms  Poser et a l . (1978) (n=1271)  Kuroiwa et a l . (1975) (n=948)  McAlpine et a l . (1972) (n=241 )  Kurtzke et a l .(1968) (n=293)  1  Visual  36%  43%  Diplopia  13  11  12  22  Balance Problems  23  26  5  3  27  Paresis  43  22  40*  40  Paraesthesia  41  26  21  42  Micturation Di sturbance  10  s  22%  5  2  24%  8  5  F i g u r e s are d e r i v e d from a l i t e r a t u r e review Optic n e u r i t i s I n c l u d e s v o m i t i n g due to v e r t i g o * C l a s s i f i e d under a general category c a l l e d "motor weakness" I n c l u d e s d e f e c a t i o n and sexual d i s t u r b a n c e s 1  2  3  5  18 c h a r a c t e r i z i n g the pre-onset p e r i o d as being pseudo-rheumatic  (muscle or j o i n t p a i n s , or n e u r a l g i a s  without f e v e r ) or pseudo-neurasthenic irritable)  (eg. f a t i g u e d ,  (eg. Abb & Schaltenbrand, 1956). Although recent  r e s e a r c h e r s such as Bervoets & Delaet (1984) have commented upon the neurasthenic f e a t u r e of MS p a t i e n t s ,  psychological  r e s e a r c h has not been a b l e to f i n d an u n d e r l y i n g , u n i t a r y p r o f i l e of MS p a t i e n t s . P s y c h o l o g i c a l c h a r a c t e r i s t i c s of MS p a t i e n t s have ranged from that of euphoria (Sugar & N a d e l l , 1943;  S u r r i d g e , 1969), d e p r e s s i o n and h y s t e r i a (Canter,  1951;  Shontz,  1955; Whitlock & S i s k i n d ,  d e n i a l , a n x i e t y and somatic concern Poser,  1980)  t o that of  (Peyser, Edwards &  1980).  P a t h o l o g i c a l f i n d i n g s have revealed the m u l t i - f o c a l nature of the d i s e a s e . In an autopsy of 70 MS Ikuta and  patients,  Zimmerman (1976) found plaques i n 99% of the o p t i c  nerves, 97% i n the cerebrum,  87% i n the cerebellum, 84% i n  the m i d b r a i n , 98% i n the pons, the s p i n a l c o r d . S i m i l a r i l y ,  88% i n the medulla and 99% i n  s c l e r o t i c plaques have been  reported extensively  i n the o p t i c nerves, chiasm, and  (Walsh & Hoyt,  Lumsden, 1970;  1969;  tracts  P a t t e r s o n & Heron,  1980). H i s t o l o g i c a l work on the eyes of MS p a t i e n t s have i n d i c a t e d the presence of o p t i c nerve atrophy (Gartner, 1953)  and a b n o r m a l i t i e s i n the p e r i p a p i l l a r y nerve  layer  ( F e i n s o d & Hoyt, Imaging  fiber  1975).  techniques such as computed tomographic  scanning and magnetic  resonance  imaging  (MRI)  (CT)  have i n d i c a t e d  19 f o c a l decreased  b r a i n d e n s i t y , and abnormal enhancement with  the main area of involvement  being i n "the p e r i v e n t r i c u l a r  areas or w i t h i n the c e r e b r a l or c e r e b e l l a r white ( K i r s h n e r , T s a i , Runge & P r i c e ,  1985, p.860). D e s p i t e the  h i g h r a t e s obtained with imaging presence  matter"  of d e m y e l i n a t i v e plaques  techniques  i n d e t e c t i n g the  (about 85%), the  c o r r e l a t i o n between a p o s i t i v e scan and the d u r a t i o n as w e l l as s e v e r i t y of the d i s e a s e i s n o n s i g n i f i c a n t — some r e s e a r c h e r s have argued  that there i s a strong  c o r r e l a t i o n with CT c o n t r a s t abnormality c l i n i c a l exacerbation  although  (enhancement) and  (eg. B a r r e t t , Drayer  £< Shin,  1985).  Such f i n d i n g s , coupled with others to be d i s c u s s e d , appear to i n d i c a t e the s e n s i t i v i t y of the v i s u a l system to the degenerative e f f e c t s of m u l t i p l e s c l e r o s i s . Because of the apparent  s e n s i t i v i t y of the v i s u a l system, the f o l l o w i n g  d e s c r i p t i o n of symptomatology w i l l d e a l b r i e f l y with motor s i g n s and then focus p r i m a r i l y on sensory s i g n s .  D. MOTOR/BRAIN STEM INVOLVEMENT P a t i e n t s whose plaques appear to center upon the cerebellum or s p i n a l cord f r e q u e n t l y r e f e r t o themselves  as clumsy  their  limb i s  limbs as heavy,  i n v o l v e d , as dragging  stiff,  o r , when a lower  or flapping  or  (McAlpine et a l , 1972).  Depending upon the s i t e of involvement,  p a t i e n t s may  demonstrate d i p l o p i a , d e p r e s s i o n , absence of deep r e f l e x e s , f o c a l p a r e s i s , muscular wasting, v e r t i g o , a t a x i a , d y s a r t h i a  20 o r , r a r e l y , peripheral f a c i a l palsy  (Lumsden, 1970; McAlpine  et a l , 1972). In a d d i t i o n , MS p a t i e n t s with motor/brain stem involvement may e x h i b i t 5th c r a n i a l nerve resulting  (Trigeminal) loss  i n f a c i a l pain and l o s s of c o r n e a l r e f l e x .  Impaired h e a r i n g due t o p a r a l y s i s of the tensor tympanic a l s o occur, but i s r e l a t i v e l y  rare  may  (Chusid & McDonald,  1978). As the t h e s i s of t h i s study c e n t e r s e n t i r e l y upon the v i s u a l system,  the remainder  of t h i s s e c t i o n w i l l  focus on  motor d i s t u b a n c e s a f f e c t i n g the v i s u a l system. For a more indepth d i s c u s s i o n of motor/brain stem involvement, the reader i s r e f e r r e d to McAlpine et a l . , 1972).  Motor involvement of the v i s u a l system c e n t e r s p r i m a r i l y upon nystagmus and a b n o r m a l i t i e s i n smooth eye movement, both of which have been used as e a r l y s c r e e n i n g t e s t s f o r MS (eg. S o l i n g e n , Baloh, Myers & E l l i s o n , 1977; Sharpe, Goldberg, Lo & Herishanu,  1.  1980, 1981).  NYSTAGMUS  Nystagmus, which i s found i n 70% of cases (Newell, 1978)  i s e i t h e r of the j e r k or v e s t i b u l a r type. Jerk  nystagmus i n v o l v e s a q u i c k movement nasalward and a slow, c o r r e c t i v e move temporalward  (the o p p o s i t e i n the abducting  eye). A c c o r d i n g to Sharpe, Goldberg, Lo & Herishanu  (1981),  o p t i c o k i n e t i c nystagmus, a form of jerk nystagmus where the  21 slow phase r e s u l t s from f i x a t i n g on a moving o b j e c t  and the  f a s t phase from mediation by higher c o r t i c a l c e n t e r s , elicited  i n MS p a t i e n t s  in conditions  can be  where i t i s i n h i b i t e d  in normals ( f i x e d t a r g e t moves with the head) and i s s u g g e s t i v e of l e s i o n s i n the temporal and o c c i p i t a l (Newell,  lobes  1978).  V e s t i b u l a r nystagmus i s a r e f l e x i v e response t o "asymmetric s t i m u l a t i o n of the s e m i - c i r c u l a r c a n a l s  or t h e i r  c e n t r a l pathways" (Newell, 1978, p.537). Such p a t i e n t s it difficult  find  t o f i x a t e on some t a r g e t a f t e r movement i s  stopped, and, i f the d i r e c t i o n of the nystagmus changes with the d i r e c t i o n of the gaze, one may suspect v e s t i b u l a r n u c l e i involvement  extensive  (Newell, 1978).  2. SMOOTH EYE MOVEMENT  With respect  t o saccades and smooth p u r s u i t , MS  patients are characterized  by i n c r e a s e d  time, saccadic  and impaired smooth p u r s u i t ,  inaccuracy,  suggesting b r a i n stem and/or cerebellum (McAlpine et a l . , 1972; Solingen, 1977;  saccadic  reaction  involvement  Baloh, Myers & E l l i s o n ,  F i e l d et a l . , 1980). In a d d i t i o n , p a r e s i s of o c u l a r  muscles may occur  ( i n a t l e a s t 25% of cases a c c o r d i n g t o  Newell, 1978) as w e l l as d i p l o p i a due t o p a l s i e s of i n d i v i d u a l muscles or i n t e r n u c l e a r ophthalmoplegia. Reulen, Sanders and Hogenhuis (1984) reported  t h a t , i n a sample of  84 MS p a t i e n t s , s u b c l i n i c a l eye movement d i s o r d e r s were  22 found i n 80% of the ' d e f i n i t e ' cases, 74% of the  'probable',  and 60% of the ' p o s s i b l e ' . In a sample of 21 o p t i c  neuritis  p a t i e n t s , only 25% showed any eye movement d e f i c i t . Assessment procedures l i k e the P u l f r i c h , which i s p r i m a r i l y a t e s t of conduction l o s s i n one o p t i c nerve F r i s e n , Hoyt & B i r d ,  1973),  (eg.  r e q u i r e f i x a t i o n of both eyes;  and, are t h e r e f o r e a f f e c t e d by the lack of eye muscle c o n t r o l e v i d e n t in MS. most v i s u a l  Indeed,  f u n c t i o n assessment  t h i s i s undoubtedly procedures  t r u e of  requiring  f i x a t i o n - some of which w i l l be d i s c u s s e d l a t e r .  E. SENSORY INVOLVEMENT  1. GENERAL  According to McAlpine  e t . a l . (1972), roughly 35% of  MS  p a t i e n t s e x h i b i t some sensory a b n o r m a l i t y . U n f o r t u n a t e l y , from a d i a g n o s t i c s t a n d p o i n t , the sensory s i g n s may difficult  be  to e s t a b l i s h and are l e s s severe than the  expressed symptoms would seem to warrant. T h i s i n c o n g r u i t y between sensory sign and symptoms may  be due t o the poor  knowledge r e g a r d i n g the a e t i o l o g y and mechanism i n v o l v e d as w e l l as the s u b j e c t i v e nature of p a t i e n t s ' d e s c r i p t i o n s of their  sensory symptoms. Sensory  as 1876  involvement  i n MS  has been recognized as e a r l y  by Layden, and subsequently i n 1878  by Erb and  1887  by Oppenheim. The s i g n s , probably a s s o c i a t e d to some degree  23 with the s i t e of d e m y e l i n a t i o n , range from p a r a e s t h e s i a e (variously  d e s c r i b e d as a tingling  or pins  and  s e n s t a t i o n to a dead f e e l i n g ) , Lhermitte's sign s e n s a t i o n produced  needles  electric  (an  by f l e x i o n of neck muscles), bowl and  bladder d i s o r d e r s , a l t e r a t i o n  i n t a s t e s e n s i t i v i t i e s , as  w e l l as a decrement i n two-point  discrimination,  vibration  s e n s a t i o n , and p o s t u r a l s e n s a t i o n (Kurtzke, 1970; Fogg, 1977;  C a t a l a n o t t o , Dore-Duffy,  Donaldson, T e s t a , Paterson,  and Ostrom 1 984). Of p a r t i c u l a r involvement  i n t e r e s t are the symptoms  of the v i s u a l system. Such p a t i e n t s t y p i c a l l y  report t h e i r v i s i o n as misty, 1970;  indicating  blurred  or foggy  Moore, 1983). They r e p o r t t r a n s i t o r y  (Kurtzke,  fluctuations in  a c u i t y , depth p e r c e p t i o n impairment, the presence of phosphenes, d e t e r i o r a t i o n of l i g h t p e r c e p t i o n and d i f f i c u l t y a d j u s t i n g t o changes i n l i g h t Newell,  intensities  1978; Moore, 1983). The complaint  (Kurtzke, 1970; tends t o be  u n i l a t e r a l , , with the symptoms l a s t i n g anywhere from than one day t o two weeks or more. Discomfort p a i n may be present especially  i n or behind  less  (pressure) or  the a f f e c t e d eye,  i n eye movements i n v o l v i n g t r a c t i o n of an  inflamed o p t i c nerve  ( A l p i n e e t a l . , 1968; Lumsden,  1970;  Moore, 1983). The  symptoms, t y p i c a l of o p t i c n e u r i t i s and r e t r o b u l b a r  n e u r i t i s , may be presented s i n g l y or i n combination  with  other n e u r o l o g i c s i g n s (Kurtzke, 1970) and may be seen i n demyelinative d i s e a s e s (MS, n e u r o m y e l i t i s o p t i c a , S c h i l d e r ' s  24 disease), infections vascular diseases  (uveitis, meningitis, tuberculosis)  ( a r t e r i o s c l e r o s i s , giant c e l l  p u l s e l e s s d i s e a s e ) (Newell, It  should be  n e u r i t i s and  arteritis,  1978).  noted that the  retrobulbar  d i s t i n c t i o n between  neuritis  r e p r e s e n t i n g demyelination of the  nerve without  optic  v i s i b l e ophthalmoscopic changes and optic  others view o p t i c clinically the  neuritis  separate - o p t i c  changes i n the  optic  disc  ranges from 11.5% and  Eckert,  optic  to changes at  globe (eg.  neuritis  two to  MS.  1  in the  patients  literature  to 83%  1980). T h i s high i n c i d e n c e has Whitty  to  Kurtze,  these  percentage of MS  (Kurland et a l . , 1963)  authors such as Bradley and  as  retrobulbar n e u r i t i s  c l a s s i f i c a t i o n of  d e f i n e s i t , the  i n i t i a l l y exhibit  Patzld  referring  o p h t h a l m o l o g i c a l l i t e r a t u r e on  However one who  neuritis  neuritis  c o n d i t i o n s among authors makes i t d i f f i c u l t  a s s e s s the  the  Newell, 1978). Whereas  retrobulbar  and  as  therefore c l a s s i f y  nerve o u t s i d e the  1970). D i f f e r e n c e s i n the clinical  (eg.  n e u r i t i s and  nerve head or o p t i c  optic  n e u r i t i s appears to vary with  a u t h o r s . Some authors view r e t r o b u l b a r  pathology as  and  (Haller, led  (1968) to s p e c u l a t e that  1  A c c o r d i n g to Ebers and Feasby (1983), the relationship between o p t i c n e u r i t i s and MS i s a l s o confounded by the f a c t that c e n t r a l serous r e t i n o p a t h y (an accumulation of serous f l u i d between the r e t i n a and r e t i n a l pigment e p i t h e l i u m c a u s i n g a l e s i o n i n the r e t i n a ) and o p t i c n e u r i t i s are s i m i l a r i n p a t t e r n . As o p t i c n e u r i t i s , c e n t r a l serous r e t i n o p a t h y (CSR) tends to occur i n young a d u l t s "commonly under s t r e s s , has a seasonal p r e d i l i c t i o n , i s u n i l a t e r a l , produces v i s u a l b l u r r i n g and a r e l a t i v e c e n t r a l scotoma, improves spontaneously, but may r e c u r " (p.79). U n l i k e o p t i c n e u r i t i s however, CSR appears not to a f f e c t c o l o u r v i s i o n .  25 51% of p a t i e n t s with o p t i c n e u r i t i s are m a n i f e s t i n g first  clinical  be m i s l e a d i n g  signs of MS.  Such c l i n i c a l  g e n e r a l i t i e s may  in that only about 35% of MS  have v i s u a l complaints  p a t i e n t s tend  ( F i e l d et a l , 1980)  the d i a g n o s i s of o p t i c n e u r i t i s alone may  the  and  to  r e l i a n c e on  increase  the  chance of f a l s e p o s i t i v e s . Recent attempts to index o p t i c n e u r i t i s with other p o s i t i v e s i g n s f o r MS the e r y t h r o c y t e unsaturated still  by t e s t s such as  f a t t y a c i d (E-UFA) t e s t have  only i n d i c a t e d that 32% of p a t i e n t s have MS  Caputo, B e r t o n i and  Zibetti  (Cazzullo,  (1980).  2. SPECIFIC  As e a r l y as  1870  ( A l b u t t ) i t has  been shown that  o p t i c nerves and chiasm appear to be e s p e c i a l l y to  demylinating  ophthalmological atrophy  d i s e a s e s . Uhtoff  and  cases,  reported o p t i c  o p t i c n e u r i t i s in 5%.  (1954) r e p o r t e d o p t i c chiasmal and  Lehoczky  involvement in 11 p a t i e n t s  9 with o p t i c nerve a b n o r m a l i t i e s  from a t o t a l of 20  p a t i e n t s . S i m i l a r i l y , Lumsden (1970) reported involvement of the o p t i c nerves, 36 MS  vulnerable  (1889), in an  examination of 100  i n 40% of cases  the  MS  100%  chiasm, or o p t i c t r a c t in  p a t i e n t s . Computer tomography of o p t i c n e u r i t i s  (Howard, Osher, & Tomsak, 1980) Lodder, deWeerd, K o e t s i e r and  and MS  van  (Wuthrich,  der Lugt, 1984)  the use of nuclear magnetic resonance i n MS K i s t l e r , Davis,  Brady and  Buomanno, 1984)  1980; as w e l l as  (DeWitt, Wrag,  have confirmed  the  26 involvement  of the v i s u a l system i n e x c e p t i o n a l acute  stages  (20-33% of c a s e s ) . Examination  in vivo of  the r e t i n a l  l a y e r i n MS has  i n d i c a t e d d i f f u s e and f o c a l damage of r e t i n a l axons even among p a t i e n t s who have not r e p o r t e d any v i s u a l d i s t u r b a n c e s ( F r i s e n & Hoyt, 1974). F e i n s o l d and Hoyt  (1975) r e p o r t e d two  types of f u n d a l abnormality  f i b r e l a y e r of 17  i n the nerve  MS p a t i e n t s :  s l i t - l i k e d e f e c t s i n the arcuate nerve with d i f f u s e t h i n n i n g of the nerve d i f f u s e t h i n n i n g of temporal  f i b r e s combined  fibre  layer,  p e r i p a p i l l a r y bundles  with  a l e s s e r degree of t h i n n i n g i n the remaining s e c t o r s surrounding the o p t i c  disc.  In an e x t e n s i v e o p h t h a l m o l o g i c a l examination cases  of 1,728  (1,180 were confirmed MS p a t i e n t s ) , Bervoets and  DeLaet  (1984) r e p o r t e d the presence  of s e v e r a l a b n o r m a l i t i e s  i n c l u d i n g r e t i n a l v e i n sheathing, o p t i c atrophy, and nystagmus (see Table 3 ) . The presence  of venous sheathing (a  w h i t i s h segmental s t r u c t u r e o u t l i n i n g the vein) i s c o n t r o v e r s i a l with some authors c l a i m i n g that i t s appearance i s due to non-MS d i s e a s e s (eg. F i e l d & F o s t e r , 1962). Kurtzke  (1970), however, r e p o r t s that venous sheathing  occurs i n about 10% of MS p a t i e n t s and that 80% of p a t i e n t s with venous sheathing had MS. A s s o c i a t e d with the presence of r e t i n a l venous sheathing has been the non-pathognomonic  27  TABLE 3 Neuro-ophthalmological Diagnosis  T y p i c a l MS  F i n d i n g s i n MS and Non-MS P a t i e n t s Presumed  (n= 1 180)  MS (n = 270)  R e t i n a l Vein Sheathing  292  47  Optic Atrophy  522  Nystagmus  Uncertain MS (n = 53)  Non-MS Pat i e n t s (n = 225)  9  7  91 •  21  42  392  73  18  43  Anterior Internuclear Ophthalmoplegia  87  29  4  8  Convergence P a r e s i s or Palsy  98  19  5  24  Horner's Syndrome  13  3  0  9  Extracted  from Bervoets and De Laet  (1984)  28 sign of p e r i p h l e b i t i s r e t i n a e and  Klinken,  1985).  (Rucker, 1972;  1  Changes i n v i s u a l f u n c t i o n i n g due retinae  (PR)  reported  E n g e l l , Jensen  to p e r i p h l e b i t i s  alone appear to be unknown. Rucker (1945)  the presence of PR  i n MS,  which has  s i n c e been  confirmed through h i s t o l o g i c a l examination of MS Fog,  1965;  Toussaint,  1984). Rucker a l s o reported  presence of d o t - l i k e o p a c i t i e s , which has e s t a b l i s h e d as f o c i of c h r o n i c  eyes  (eg.  the  s i n c e been  inflammation  (Arnold  et a l . ,  1984) . More r e c e n t l y E n g e l l , Jensen and reported two  the presence of PR  confirmed MS  Klinken  (1985)  i n h i s t o l o g i c a l examination of  p a t i e n t s with reduced v i s u a l a c u i t y .  authors argued that p e r i p h l e b i t i c l e s i o n s in the were c l i n i c a l disruptions  signs of e a r l y plaque formation  i n the b l o o d - b r a i n  s i m u l t a n e o u s l y i n PR and  MS  (eg. Adams & Dath, 1977)  and  barrier  The  retinae  since  occurred  - a stance supported by some r e j e c t e d by others  (eg.  P e r i p h l e b i t i s r e t i n a e (PR), which may a l s o be found in t u b e r c u l o s i s , s y p h i l i s , s a r c o i d o s i s and more f r e q u e n t l y i n c h o r i o r e t i n i t i s (Newell, 1978) i s a n e o v a s c u l a r i z a t i o n of c o n n e c t i v e t i s s u e membrane extending i n t o the v i t r e o u s (Scheie & A l b e r t , 1977). PR both occurs and r e s o l v e s i t s e l f q u i c k l y , p r e s e n t i n g segmental, d i l a t e d , beaded occluded v e i n s with sheathing or exudation of lymphocytes and plasma cells. In an extensive h i s t o l o g i c a l examination of the eyes of 47 MS p a t i e n t s , Arnold, Pepose, Hepler and Foos (1984) reported the presence of PR in four cases (8.5%). PR was found to be segmental perivenous lymphoplasmacytic i n f i l t r a t i o n . The authors reported widespread v a s c u l a r changes in r e t i n a l areas among p a t i e n t s who had and d i d not have PR. A r n o l d et a l . f e l t that the v a s c u l a r changes were more widespread ( e s t a b l i s h e d through v e s s e l p e r m e a b i l i t y with immunoperoxidase) than c o u l d be c l i n i c a l l y d e t e c t e d . 1  29 Oppenheimer, 1976). Thus the o c u l a r changes found represent a primary  MS  f o l l o w i n g i s a d i s c u s s i o n of the major  employed in a s s e s s i n g v i s u a l first  techniques  f u n c t i o n in MS.  Although  the  procedure to be d i s c u s s e d , evoked p o t e n t i a l s , i s not a  p s y c h o p h y s i c a l procedure per  se,  i t represents the most  f r e q u e n t l y used method f o r a s s i s t i n g t h e r e f o r e needs to be The  i n the d i a g n o s i s of  argument to be developed  i s that the evoked  l a t e n c y ) . Such a procedure does not, unless  permit  one  (amplitude modified,  to assess the changes o c c u r r i n g i n the macular  r e g i o n s - ones which the w r i t e r f e e l s p r o v i d e s a more sensitive  i n d i c a t i o n of the presence and  s e v e r i t y of  MS.  F o l l o w i n g the d i s c u s s i o n of evoked p o t e n t i a l s , the major p s y c h o p h y s i c a l methods of s p a t i a l c o n t r a s t sensitivity,  temporal c o n t r a s t s e n s i t i v i t y , c o l o u r v i s i o n  assessment, and perimetry  MS  discussed.  p o t e n t i a l measures only gross f u n c t i o n a l changes and  may  demyelination.  3. PSYCHOPHYSICAL ASSESSMENT OF  and  i . e . PR,  p h l e b i t i c process which i n the c e n t r a l  nervous system leads to  The  i n MS,  w i l l be  discussed.  30 F. VISUAL EVOKED POTENTIALS  1. TECHNIQUE.  Since the c l a s s i c a l c l i n i c a l McDonald and Mushin  experiment of H a l l i d a y ,  (1972), v i s u a l evoked  responses (VERs)  have become one of the standard d i a g n o s t i c methods f o r a s s e s s i n g the presence  of MS,  i . e . f o r the d e t e c t i o n of some  abnormality of the v i s u a l system which, with the presence or absence of other c l i n i c a l The VER  s i g n s , may  r e s u l t s from changes  electroencephalogram  be i n d i c a t i v e of  MS.  i n the p o t e n t i a l s of an  (EEG) due to the p r e s e n t a t i o n of some  v i s u a l s t i m u l u s . As the EEG c o n s i s t s not only of summated e l e c t r o - c o r t i c a l a c t i v i t i e s but a l s o b i o - e l e c t r i c a l the  evoked  "noise",  response must be obtained by enhancing the  s i g n a l - t o - n o i s e r a t i o through mathematical  filtering  techniques such as a u t o r e g r e s s i v e moving averages (ARMA). As such, the v a l i d i t y and r e l i a b i l i t y r e g a r d l e s s of i t s s t i m u l u s o r i g i n somatosensory)  of an evoked (eg. v i s u a l ,  are h i g h l y dependent  potential auditory,  upon techniques  s e n s i t i v e to temporal s h i f t s and a c t i v i t y o u t s i d e the time window of i n t e r e s t  (Kay & Marple,  1981).  An evoked p o t e n t i a l can be c h a r a c t e r i z e d as being e i t h e r t r a n s i e n t or s t e a d y - s t a t e evoked p o t e n t i a l s r e s u l t  (Regan,  1982). T r a n s i e n t  from responses to abrupt  stimuli  such as f l a s h e s of l i g h t whereas s t e a d y - s t a t e are composed  31 of harmonics whose f r e q u e n c i e s are p r e c i s e l y d e f i n e d and  are  r e c o g n i z a b l e w i t h i n the b r a i n ' s background n o i s e . In essence, the onset  of a stimulus  results in a t r a n s i t o r y  response that e v e n t u a l l y becomes a s t e a d y - s t a t e Regardless steady-state  of whether one  i s examining a t r a n s i e n t or  response, v i s u a l l y evoked responses may  generated through two flash-evoked  potential.  b a s i c techniques.  responses,  result  The  be  first,  from the p r e s e n t a t i o n of  m u l t i p l e f l a s h e s ( g e n e r a l l y 50 to 100  t r i a l s ) of a d i f f u s e  achromatic l i g h t to the e n t i r e r e t i n a e . Luminance l e v e l s of the f l a s h appear to depend upon the equipment ray tube) used. F l a s h induced  VER  tend to c o n s i s t of complex  waveforms with peaks between 50 and to r e s u l t p r i m a r i l y from a c t i v i t y  (eg. cathode  150 msec., and are  felt  in the macula e s p e c i a l l y  in the case of the e l e c t r o r e t i n o g r a m  ( H i r o s e , Wolf & M a l i n ,  1972). F l a s h t r a n s i e n t VERs are b e l i e v e d to be the r e s u l t p r o c e s s i n g e i t h e r i n the r e t i n o - g e n i c u l o - o c c i p i t a l cortex or the b r a i n stem r e t i c u l a r  formation  t r a n s m i s s i o n to the o c c i p i t a l cortex The  f l a s h VER  relatively cortical  procedure i t s e l f  insensitive test  f u n c t i o n i n g . The  (Carlow,  of  striate  p r i o r to i t s 1980).  i s considered  to be a  f o r a s s e s s i n g normal-abnormal  generated l a t e n c y does not  be g r e a t l y a f f e c t e d by d i s e a s e onset s u f f e r s from l a r g e v a r i a b i l i t y  seem to  (unless s e v e r e ) ,  i n the l a t e n c y s h i f t  and  even  among n e u r o l o g i c a l l y i n t a c t normals (Duwaer & S p e k r e i j s e , 1978;  Neetens, Hendrata & van  Mushin, 1980;  Bodis-Wollner  Rompaey, 1979;  Halliday &  and O n o f r j , 1982). A d d i t i o n a l l y ,  32  though e q u a l l y true of a l l VER methods, f l a s h VERs are dependent  upon f a c t o r s such as luminance of background and  t a r g e t , stimulus frequency (time i n t e r v a l ) , and e l e c t r o d e placement and wavelength (Regan, Hintze,  1979; Carlow,  1977; White, White &  1980).  The second technique f o r g e n e r a t i n g VERs, p a t t e r n evoked responses, i s through the p r e s e n t a t i o n of a r e v e r s i n g grating  ( s i n e or square wave) or checkerboard p a t t e r n .  P a t t e r n s are presented at the r a t e of about second with the luminance being dependent being used, making  i t difficult  1 or 2 per  upon the equipment  to compare r e s u l t s across  s t u d i e s . The major advantages of p a t t e r n over f l a s h VER are that the former produces c o n s i s t e n t waveforms with a r e c o g n i z a b l e p o s i t i v e peak and a c o n s i s t e n t normal samples  (eg. H a l l i d a y , McDonald  Behrman, H a l l i d a y & McDonald, generated VERs are f e l t  l a t e n c y among  & Mushin,  1972;  1972). As with f l a s h ,  to r e s u l t  pattern  from the complex  i n t e r a c t i o n between the p e r i p h e r a l and c e n t r a l as higher and p o s s i b l y lower c o r t i c a l  fovea as w e l l  centres.  2. APPLICATION.  With respect to abnormality, the f l a s h and p a t t e r n VERs may  be examined  f o r changes i n l a t e n c y , amplitude, wave  form, and d i s t r i b u t i o n of the p o t e n t i a l s MS  (McDonald,  1980).  i s c h a r a c t e r i z e d by an i n c r e a s e i n l a t e n c y of the P100  while m a i n t a i n i n g a w e l l - p r e s e r v e d wave form u n l i k e  glaucoma  33 or Parkinson's d i s e a s e Changes  i n the waveform  (eg. Bodis-Wollner & O n o f r j ,  1982).  and r e d u c t i o n i n amplitude may  also  be seen, e s p e c i a l l y d u r i n g the acute stages of an a t t a c k of optic neuritis  (Adachi-Usami, Kellermann & Makabe,  1972;  F e i n s o d , Abramski & Auerbach, 1973; Feinsod & Hoyt,  1975).  Abnormal VERs have been found i n anywhere from 38 to 96% of MS cases ( H a l l i d a y , McDonald Low,  Galloway & Reeves,  & Mushin,  1973; Purves,  1-981; Kupersmith, Nelson, S e i p l e ,  Carr & Weiss, 1983). As i n d i c a t e d  i n Table 4, the d e l a y i n  VER occurs more o f t e n among "probable" and " d e f i n i t e " p a t i e n t s as compared  MS  with " p o s s i b l e " p a t i e n t s . Although  i n c r e a s e d l a t e n c i e s i n evoked p o t e n t i a l s may  be seen i n  other m o d a l i t i e s such as somatosensory (Purves e t . a l . , 1981; Haldeman, G l i c k , B h a t i a , Bradley & Johnson,  1982;  P h i l i p s , P o t u i n , Syndulko, Cohen, S t a n l e y , T o u r t e l l o t e & Potuin,  1983) and a u d i t o r y b r a i n stem (Kjaer,  et. a l . ,  1981; Green & Walcoff,  1983; J a v i d a n , McLean & Warren,  1980; Purves  1982; Quine, Regan & Murray, 1985), the v i s u a l system  appears to be more s e n s i t i v e to the e f f e c t s of m u l t i p l e sclerosis  (McDonald,  1980; Purves et a l . ,  1981).  A b n o r m a l i t i e s i n the VER have been reported a l s o among c l i n i c a l l y d e f i n i t e MS p a t i e n t s who do not e x h i b i t v i s u a l symptoms (McDonald, or may  any  1980). Moreover, the e f f e c t s  not appear b i l a t e r a l l y  may  i n the a f f e c t e d and u n a f f e c t e d  eye ( M i l n e r , Regan & Heron, 1974; K e t e l a e r ,  1980).  Recently Nuwer, V i s s c h e r , Packwood and Namerow  (1985)  demonstrated the presence of s i g n i f i c a n t l y delayed PlOO's i n  34  TABLE 4 Percentage of MS P a t i e n t s With Abnormal VEP's'  Study  Sample Size  Definite MS  Probable MS  Ghezzi et a l . (1984)  236  84.0%  65.0%  Green & Walcoff (1982)  115  82.0  NC  Purves e t a l . (1981)  112  91.0  76.0  Kjaer (1980)  99  100.0  70.0  Lowitzch (1980)  135  83.0  77.0  60.0  Franck & Middleton (1981)•  74  86  89  74  C o l l i n s et a l . (1978)  98  78  50  23  Hennerici et a l . ( 1 977)  57  94  94  78  Halliday et a l . (1973)  51  97  100  91  3  Possible MS  -  NC  14.0  38.0  ' I n c l u d e s a b n o r m a l i t i e s i n l a t e n c y and a m p l i t u d e No o p t i c n e u r i t i s NC - unable t o be computed from t h e a r t i c l e ' S t i m u l a t i o n w i t h r e d and b l a c k c h e c k e r b o a r d Foveal stimulation only 3  5  31.0%  NC  5  2  Suspected MS  2  35 the VEP's of n e u r o l o g i c a l l y normal  f i r s t degree  r e l a t i v e s of  confirmed MS p a t i e n t s . The authors argued that although the f i n d i n g s i n d i c a t e the presence of s u b c l i n i c a l d e m y e l i n a t i o n or  f o c a l changes i n some r e l a t i v e s , the f a c t that l e s s than  2% of the r e l a t i v e s w i l l  develop c l i n i c a l MS  the changes are not p r e d i c t i v e of MS  suggests that  onset.  D e s p i t e such r e l a t i v e l y high d e t e c t i o n r a t e s among MS p a t i e n t s , delay i n the f i r s t  major p o s i t i v e wave (P100) i s  not d i a g n o s t i c of the presence of MS.  Delays have been  r e p o r t e d i n glaucoma (Bobak, Bodis-Wollner, Harnois, M a f f e i , M y l i n , Podos & Thornton,  1983;  Regan & Neima,  Parkinson's d i s e a s e (Bodis-Wollner & O n o f r j , al.,  1983)  and amblyopia  (Chiappa, 1980)  1984), 1982;  Bobak e t .  as w e l l as numerous  other p a t h o l o g i e s . Depending upon the procedure and type of MS the one d i s t i n g u i s h i n g wave form as s t a t e d  f e a t u r e of MS may  patient,  be a w e l l preserved  earlier.  Kimura (1985) has r e c e n t l y argued that evoked procedures are used  indiscriminately  in c l i n i c a l  potential  settings.  A c c o r d i n g to Kimura, VERs are o n l y u s e f u l i n c l a s s i f y i n g known problems such as i n the case of d e f i n i t e s c l e r o s i s . The major reason f o r t h i s c o r r e l a t i o n between c l i n i c a l  multiple  i s that the  "temporal  and e l e c t r i c a l changes [due to  the e x i s t e n c e of some pathology] i s tenuous at b e s t " as the intertrial  reliability  than would be expected  of the evoked  p o t e n t i a l s are " g r e a t e r  from the changes due  to the d i s e a s e "  (p.78). S i m i l a r i l y McDonald (1980) and Aminoff, Davis and  36 Panitch  (1984), among o t h e r s , have p o i n t e d out that the VER  provides general  evidence of an abnormality  as w e l l as i t s p o s s i b l e  l o c a t i o n but can not i d e n t i f y the cause nor i t s  course.  3. MODIFICATIONS.  Attempts to remedy the lack of c l i n i c a l i n the VER have been numerous and f a l l general  approaches. The f i r s t  differentiation  w i t h i n one of three  i n v o l v e s the examination of  s e v e r a l m o d a l i t i e s . The procedure g e n e r a l l y i n v o l v e s the auditory,  somatosensory and v i s u a l systems i n the assumption  that t h e i r combination w i l l  l o c a t e the presence of l e s i o n s  i n e i t h e r the s p i n a l c o r d , brainstem, v i s u a l  system,  c e r e b r a l cortex or some combination t h e r e o f . R e s u l t s have i n d i c a t e d a higher  d e t e c t i o n r a t e of abnormality  among MS  p a t i e n t s than would be the case when only one modality examined (Green and Walcoff,  was  1982; Purves e t . a l . , 1983).  T h i s appears to be e s p e c i a l l y t r u e of d e f i n i t e MS where the d e t e c t i o n of an abnormality  may be about 80 ( K e t e l a e r , 1980)  to 97% (Purves e t . a l . , 1983). Such d e t e c t i o n r a t e s i n the presence of no other clinical 1977;  (physical) signs  (eg. H e n n e r i c i , Wenzel & Freund,  Small, Matthews & Small,  repeated  belief  i n the presence of s u b c l i n i c a l d e f e c t s , ones  to which techniques sensitive.  1978) has a f f i r m e d the o f t e n  l i k e the evoked p o t e n t i a l appear t o be  37 In a study by F e i n s o d and Hoyt MS p a t i e n t s  (including  demonstrated abnormal Seventeen  (1975), a l l 25 of t h e i r  10 with no v i s u a l signs or symptoms) l a t e n c i e s and wave form i n the  VER.  of the 25 p a t i e n t s had an abnormality of the  p e r i p a p i l l a r y nerve f i b r e l a y e r  ( s l i t - l i k e d e f e c t s i n the  arcuate nerve f i b r e s , d i f f u s e t h i n n i n g of the nerve  fibre  l a y e r , and d i f f u s e t h i n n i n g of temporal p e r i p a p i l l a r y  nerve  f i b r e b u n d l e s ) , s i x a l s o had temporal p a l l o r of the d i s c  due  to t h i n n i n g . Because  of the a s s o c i a t e d VER  abnormalities, Feinsod  and Hoyt s p e c u l a t e d that d i s t o r t i o n s i n the evoked p o t e n t i a l s were due to changes  i n the r e t i n a l nerve  l a y e r and axons i n the o p t i c pathways. The  fibre  non-uniform  e f f e c t s of MS a c r o s s p a t i e n t s with respect to the VER may reflected  i n the types of s u b c l i n i c a l changes  fibre layers may  i n the nerve  (eg. d i s t u r b a n c e s of the wave form and  latency  depend upon the width of the nerve f i b r e s i n v o l v e d as  w e l l as t h e i r  location).  However, p o s s i b l e abnormal VERs due to changes nerve f i b r e l a y e r are not s p e c i f i c a l s o has been demonstrated l a y e r changes  retina  to MS.  to be a s s o c i a t e d with nerve  ( A r i k s i n e n , Lakowski  1983: Regan & Neima,  i n the  Glaucoma, which  & Drance,  has y i e l d e d abnormal VERs (Schwartz & Sonty, al.,  be  1981;  fibre  1985) Bobak e t .  1984).  A c c o r d i n g to Bobak e t . a l . (1983), in comparing s t e a d y - s t a t e v i s u a l evoked p o t e n t i a l s and e l e c t r o r e t i n o g r a m s (ERGs) generated by s i n u s o i d a l g r a t i n g s (2.3 c y c l e s / d e g r e e ) ,  38 both glaucoma and MS  p a t i e n t s showed abnormal ERGs under  mesopic i l l u m i n a t i o n . The p a t i e n t s showed g r e a t e r of  authors claimed  that the  abnormality i n the VER  10 eyes) than with the ERG,  (2 of  10  MS  l a t e n c i e s (7  eyes).  However, a r e - a n a l y s i s by t h i s w r i t e r of t h e i r  data,  using a t - t e s t f o r unequal sample s i z e s , r e v e a l e d  no  s i g n i f i c a n t d i f f e r e n c e s between the two  VER  latency  (t= 0.19,  (t= 0.84,  df=  df=  groups on  11, p > 0.05), nor  13, £ > 0.05), nor  ERG  on VER  latency  amplitude  (t= 0.06,  df=  1 3, p_ > 0.05) . These unreported n o n s i g n i f i c a n t d i f f e r e n c e s between two  pathologies  underlying and  MS  strengthens the b e l i e f t h a t , although  processes i n v o l v e d  in diseases  the  the  such as glaucoma  are d i f f e r e n t , t h e i r r e s u l t i n g e f f e c t s on the VER  similar  i n that one  v i s u a l system - be some s p e c i f i c  d i p o l e due  i t at the r e t i n a or o c c i p i t a l  time. Indeed, one  multimodalities l a t e n c i e s may  i s viewing the summated a c t i v i t y of  the  lobes at  danger with approaches where  are examined i s that the reported  only be s h i f t s  are  shift  i n the o r i e n t a t i o n of  to the p o s i t i o n i n g of the measuring  in  the  electrodes  (Wood, 1982). The MS  second general  approach to improve VER  i s the m a n i p u l a t i o n of the stimulus  detection  p r e s e n t a t i o n . One  the most common i n v o l v e s the comparison between p a t t e r n f l a s h VER  (eg. Neetens, Hendrata & van  P a t t e r n VERs are apparently discussed  of of  and  Rompaey, 1980).  the most s e n s i t i v e f o r reasons  p r e v i o u s l y . S i m i l a r attempts with p a t t e r n  and  39 f l a s h s t i m u l i have been made with ERGs, r e s u l t s of which have been u n s a t i s f a c t o r y  (eg. Kirkham & Coupland, 1983).  Of p a r t i c u l a r i n t e r e s t with the p a t t e r n procedure been the use  of c o n t r a s t  Maffei,  1982;  spatial  frequencies  (2 and  (eg.  lower Regan  abnormality among some MS  stimulus-check s i z e (11 minutes of  abnormalities  were a l s o found among some p a t i e n t s  f o r l a r g e stimulus-checks  (45 minutes of a r c ) r e g a r d l e s s  of  frequency. These r e s u l t s p a r a l l e l Regan's e a r l i e r  work demonstrating n o n - s e l e c t i v e MS  VERs  6 c y c l e s / degree) Neima and  g r e a t e r VER  p a t i e n t s f o r a small  spatial  i n generating  Kuppersmith e t . a l . , 1983). In using  (1984) reported  a r c ) . VER  gratings  has  s p a t i a l frequency l o s s for  i n that p a t i e n t s v a r i e d as to which s p a t i a l  demonstrated the g r e a t e s t VER  changes due  periphery  are  frequency  loss.  to s t i m u l a t i o n of the  fovea  or  i n t e r e s t i n g when taken i n t o c o n s i d e r a t i o n  with  the r e s u l t s on nerve f i b r e l a y e r l o s s . H e n n e r i c i , Wenzel Freund  (1977) reported  small-size rectangle  greater  delays  i n VERs f o r f o v e a l  s t i m u l a t i o n than f o r normal  checkerboard s t i m u l a t i o n of the e n t i r e r e t i n a among p a t i e n t s . The  MS  authors suggested that f o v e a l s t i m u l a t i o n  more s e n s i t i v e and  and  r e l i a b l e than the  standard  p r a c t i c e of s t i m u l a t i n g the e n t i r e eye, r e s u l t i n g abnormality was  due  and  clinical  that  to demyelination  was  of  the foveal  f ibres. From the r e s u l t s by H e n n e r i c i p l a u s i b l e that  et a l . i t would appear  i f the nerve f i b r e l a y e r i s a f f e c t e d e a r l i e r  40 in MS, and i f one can image a stimulus areas,  to s p e c i f i c damaged  then s t i m u l a t i o n of these p o s s i b l e pre-symptomatic  s t r u c t u r a l changes may a f f o r d one with a technique not only for the documentation of e a r l y onset of some d i s e a s e , but a l s o an index of s e v e r i t y (greater greater  the nerve f i b r e l o s s , the  the VER or ERG a b n o r m a l i t y ) .  The l i m i t a t i o n of such  a method f o r c h a r t i n g s e v e r i t y may be that there  i s a limit  to changes i n an abnormal evoked response once a c e r t a i n amount of area  (nerve f i b r e l a y e r ) has been  With respect MS, others but  destroyed.  to f o v e a l versus p e r i p h e r a l s t i m u l a t i o n i n  have found s i m i l a r r e s u l t s to H e n n e r i c i  f e e l that d e t e c t i o n  (confirmation)  et. a l .  of an abnormality i s  improved when the r e s u l t s from both f o v e a l and p e r i p h e r a l s t i m u l a t i o n are combined Caltagirone,  (eg. R o s s i n i , P i r c h i o , S o l l a z z o &  1979; Diener and S c h e i b l e r ,  1980).  Although luminance i s an important f a c t o r there a r e no a v a i l a b l e s t u d i e s on how such a v a r i a b l e may a f f e c t VERs of MS p a t i e n t s . With respect Franck and Middleton  to c o l o u r , only one study by  (1981) appears to have examined the  r e l a t i o n s h i p between c o l o u r and VERs. By using black and white squares as w e l l as red (X625 nm) and black the authors reported  squares,  b e t t e r d e t e c t i o n with the red and  b l a c k . The r e s u l t s , u n f o r t u n a t e l y ,  are d i f f i c u l t to  interpret  patterns  i n that the two stimulus  were not equated  for luminance; t h e r e f o r e one i s u n c e r t a i n  as to whether the  improved d e t e c t i o n was due to the c o l o u r  (red) or luminance  per se.  41 In a p r e l i m i n a r y on-going  study by Kozak, King and  Drance (1985), r e t i n a l s t i m u l a t i o n at the f o v e a l r e g i o n on a single  i n d i v i d u a l produced  similar  F i g u r e 3, the red cinemoid f i l t e r w e l l d e f i n e d waveform that was of 81.0  r e s u l t s . As i n d i c a t e d i n (XD unknown) produced  s l i g h t l y more l a t e n t  msec) when compared to the VER  produced  a  (average  by a white  (achromatic) stimulus (79.3 msec). In a d d i t i o n , the red produced  a wave form with g r e a t e r amplitude than the white.  Although the two  s t i m u l i were of the same s i z e  the red - d e s p i t e the c l a i m s by the instrument - had  l e s s luminance  the two  manufacturer  than the white and t h e r e f o r e the  were not p h o t o m e t r i c a l l y equated and thus may the s h i f t  (Goldmann V),  i n the l a t e n c y . The  similarity  two  have caused  i n the r e s u l t s of  s t u d i e s would suggest that the d i f f e r e n c e s r e p o r t e d  by Franck and Middleton may luminance  have been due to d i f f e r e n c e s i n  e q u i v a l e n c e rather than d i f f e r e n c e s i n wavelength.  The t h i r d and  f i n a l approach  i n attempting to  improve  VERs has been the manipulation of the p h y s i c a l s t a t e of the p a t i e n t . Although symptom p r o d u c t i o n i n MS p a t i e n t s has been done with methods such as the hot bath (eg. Rolak Ashizawa, VER  and  1984), only f a t i g u e seems to have been done with  as the dependent v a r i a b l e . Persson and Sachs (1981)  fatigued prior  15 MS p a t i e n t s and 5 normals  on a b i c y c l e  ergometer  to t h e i r VERs v i a standard p a t t e r n - r e v e r s a l  s t i m u l a t i o n . When compared to p r e - e x e r c i s e VERs, e x e r c i s e produced VERs d i d not d i f f e r with r e s p e c t to l a t e n c y . only n o t i c e a b l e e f f e c t was  The  a short l a s t i n g r e d u c t i o n i n the  42  Figure VEP  3  from f o v e a l s t i m u l a t i o n w i t h r e d and a c h r o m a t i c source.  a  43 VER amplitude and v i s u a l a c u i t y of the MS p a t i e n t s . If  i t i s p o s s i b l e to g e n e r a l i z e  from s t u d i e s v a r y i n g i n  p a t i e n t c h a r a c t e r i s t i c s and procedures, i t appears that v i s u a l f u n c t i o n i s a h i g h l y s e n s i t i v e measure of p a t h o l o g i c a l c o n d i t i o n s , and that cones may be i n v o l v e d earlier  than the rods. Moreover, i t appears that any attempt  to focus upon the involvement of the v i s u a l system i n MS should  i n v o l v e methodology o u t l i n e d by v i s u a l psychophysics  i n order  to assess changes at e i t h e r the r e t i n a l  versus cones) or c e n t r a l p r o c e s s i n g would enforce  (eg. rods  l e v e l . Such a paradigm  s t r i c t e r m e t h o d o l o g i c a l c o n t r o l (eg. stimulus  c o n t r o l ) , one s o l e l y l a c k i n g i n many s t u d i e s . For a more d e t a i l e d d i s c u s s i o n on VERs the reader i s r e f e r r e d t o Desmedt (1977), Nakayana (1982), and Petsche, Pockberger and Rappelsberger  (1984).  G. SPATIAL CONTRAST SENSITIVITY  1. TECHNIQUE  Spatial contrast  sensitivity  involves assessing  the a b i l i t y  of the v i s u a l system t o r e s o l v e s i n u s o i d a l or square wave forms v a r y i n g  from 0.5 to 100% c o n t r a s t . The s e n s i t i v i t y of  the v i s u a l system t o r e s o l v e such wave forms i s r e f e r r e d to as  "contrast  sensitivity  defined  form (see F i g u r e  spatial  frequencies  function"  (CSF). The CSF has a w e l l  4) with "a maximum value f o r  of about 0.15 t o 0.6 c y c l e s per  001  1000  O o  > 100  o  •01  f o  10  o  •  •  . 1 <->  t  0.1  1.0  0 I  001  c/m 10  1.0  Figure  il.O  rad  c/deg.  4  Contrast sensitivity for sine wave. From Lakowski (1982, p.6)  45 milliradian and  (c/m rad) or 2.5 t o 10 c y c l e s per degree  decreases at both higher and lower  (c/deg)  frequencies"  (Lakowski, 1982, p . 6 ) . Blurring due  at higher  frequencies  to o p t i c a l a b n o r m a l i t i e s  e r r o r s ) and eye  (1983), l o s s e s a t lower  f r e q u e n c i e s appear t o be r e l a t e d  variations  from a t t e n u a t i o n  (eg. r e f r a c t i v e  movement. As noted by Lakowski spatial  results  to luminance  i n the g r a t i n g s or r e t i n a l s i z e  (demonstrated by  Regan, S i l v e r and Murray, 1977). The that  advantage of examining CSF i s based upon the b e l i e f  i t permits  of o p t i c theorists  the researcher  to i d e n t i f y  nerve f i b r e s - a b e l i e f  central  such as Regan (1982) who h o l d that the v i s u a l information  Such an approach assumes that one can evaluate  s p e c i f i c ganglion  cells  i n the s p a t i a l channel by  s t i m u l a t i n g r e c e p t i v e f i e l d s with t h e i r f r e q u e n c i e s , although exists  groups  to channel  system i s comprised of p a r a l l e l p r o c e s s i n g channels.  specific  for this  respective  no e l e c t r o p h y s i o l o g i c a l  i n humans.  spatial  evidence  46 2.  APPLICATION  Regardless been  found to  (Regan,  of  the  theoretical  be h i g h l y  Silver  sensitive  and M u r r a y ,  Mylin  & Thornton,  1979;  Regan, W h i t l o c k , Murray  Raymond, changes  (eg.  Lakowski,  (Lakowski,  Typically, low  loss  only  correspond to  higher  the  with a p r i o r  blurring  o r washing in  itself,  as  measure  (eg.  1981).  Regan, Results  possible occur  typical  of  being  of  as  test,  visual  & Wilkinson,  1980;  well  as  Regan, age-related  & Owsley,  1982)  and  loss  clinical  with  to  lower  visual is  not  provide a  in v i s i o n testing.  between t h e spatial  contrast  be d e t e c t e d a t  the  can  The  or L a n d o l t Ring  by L a k o w s k i ( 1 9 8 1 ) , at  to  frequencies  testing  100% c o n t r a s t  tend  setting,  in s p a t i a l  Snellen  -  However,  through acuity the  a  r e p o r t e d by MS  why d i s t u r b a n c e s  s u c h as  showing  neuritis  vision.  loss  intermediate  losses  acuity  sensitivity  to  in both  These  optic  i n the  a r e d e t e c t e d more s e n s i t i v e l y for  of  their  detected  b a c k g r o u n d . As n o t e d  Indeed,  of MS  some p a t i e n t s  in v i s u a l  visual  Charts are constructed and  with  tested  explanantion  acuity  as  i n MS o c c u r  from c o n t r a s t  without  & Beverly,  Sekuler  history  out  a sensitive  presence  Campbell  frequencies.  changes  patients  acuity  CSF has  1981).  frequencies  i n the  the  taken,  Bodis-Wollner, Hendley,  1981)  1981;  CSF l o s s e s  spatial  to  Zimmerern,  Ginsberg & Murray,  glaucoma  and  1979;  1972;  stance  a high  figure losses  levels. contrast  47 l e v e l of 100% one would probably  r e q u i r e e x t e n s i v e cone and  rod damage t o have a l r e a d y o c c u r r e d . E a r l y d e t e c t i o n of v i s u a l l o s s would t h e r e f o r e n e c e s s i t a t e t e s t i n g at lower contrast  levels.  Unfortunately,  f o r d i a g n o s t i c purposes, l o s s e s i n the  intermediate and low s p a t i a l  f r e q u e n c i e s a r e not s p e c i f i c t o  MS as s i m i l a r l o s s e s have been r e p o r t e d i n other s t a t e s such as glaucoma (Wolkstein, A t k i n & 1980;  Lakowski,  disease  Bodis-Wollner,  1982).  More r e c e n t l y , Kuppersmith, S e i p l e , Nelson  and Carr  (1984) r e p o r t e d l o s s e s f o r three s p a t i a l f r e q u e n c i e s and  (1, 4  8 c y c l e s / degree) and four o r i e n t a t i o n s (0, 45, 90 and  135 degrees) among 15 MS cases with v i s u a l a c u i t i e s of 20/40 or b e t t e r . The l o s s e s tended to be spotty or m u l t i f o c a l and involved d i f f e r e n t  eyes.  H. TEMPORAL CONTRAST SENSITIVITY  I. TECHNIQUE  Assessment of temporal s e n s i t i v i t y of the r a t e i n which a stimulus  i n v o l v e s the manipulation  i s being presented  while  c o n s t a n t l y maximizing or v a r y i n g the c o n t r a s t , c r e a t i n g the critical  flicker  frequency  where a f l i c k e r i n g  light  (CFF). The CFF i s that t h r e s h o l d  i s p e r c e i v e d as becoming  constant  and can be obtained by one of two general procedures. by f l i c k e r i n g a l i g h t of constant  One,  luminance and background  48 to some part of the v i s u a l  f i e l d , and secondly, i n the de  Lange method, by mixing a steady l i g h t to a set f l i c k e r frequency  (Lakowski',  Temporal  1982).  s e n s i t i v i t y has been shown to be a f f e c t e d not  only by d i s e a s e s such as glaucoma (eg. Kozousek, 1968) retrobulbar n e u r i t i s  (Heron, Regan & M i l n e r ,  1974)  and  but a l s o  by v a r i a b l e s such as luminance, e c c e n t r i c i t y , wavelength age  and  (Lakowski, 1982). The lack of s t i m u l u s s p e c i f i c a t i o n i n  the l i t e r a t u r e makes i t extremely d i f f i c u l t  to compare  findings across studies.  2. APPLICATION  With respect to MS, seen as r e s u l t i n g  changes i n temporal t h r e s h o l d s are  from the e f f e c t s of demyelination on the  conduction rate of a n e u r a l s i g n a l . As noted by B r u s s e l l , White, M u s t i l l o & Overbury t h r e s h o l d s may  result  (1983), changes i n temporal  from an i n c r e a s e i n "conduction  v e l o c i t y and r e f r a c t o r y p e r i o d s , l o s s of synchrony between s t i m u l a t i o n and f i r i n g  rates,  c r o s s - t a l k between f i b r e s "  Regan,  & Willison,  1961;  and  (p.2). Research t y p i c a l l y  reduced CFF among MS p a t i e n t s Titcombe  impulse r e f l e c t i o n ,  (Parsons & M i l l e r ,  reports  1957;  Daley, Swank & E l l i s o n ,  1979;  1981).  In a recent a r t i c l e by Mason, Snelgar, F o s t e r , Herron & Jones  (1982), CFF l o s s e s among 20 MS p a t i e n t s were r e p o r t e d  for s t i m u l i v a r y i n g i n luminance and c h r o m a t i c i t y .  The  49 authors claimed that temporal luminance  l o s s e s were g r e a t e r i n the  r a t h e r than chromatic channel as has been claimed  by o t h e r s (eg. F a l l o w f i e l d & Krauskopf,  1984). S i m i l a r  f i n d i n g s have been reported by A l v a r e z , King-smith & Bhargara  (1972). On the b a s i s of t h e i r r e s u l t s , Mason et a l .  concluded that demyelination was e f f e c t s on nerve the experiment literature,  non-selective regarding i t s  f i b r e s i n the v i s u a l system.  the authors assumed t h a t , on the b a s i s of the  " a b n o r m a l i t i e s i n temporal  a s s o c i a t e d with the short wavelength (p.247),  In conducting  response  [was]  s e n s i t i v e mechanism"  the blue cone system. Then, i n e x p l i c a b l y , they  a red (630 nm) subtending  and green  (560 nm)  light-emitting  diode  10 minutes of arc on a white background of  290  cd/m . T h e i r f i n d i n g s with long and middle wavelength  LEDs  2  can not be used to r e j e c t the h y p o t h e s i s that  chromatic  channels are s e l e c t i v e l y a f f e c t e d . Inorder to r e j e c t h y p o t h e s i s , the authors should have used a short LED. may  The  used  the  wavelength  f a c t that Mason et a l . d i d not use a blue s t i m u l u s  be due  wavelength  to the present u n a v a i l a b i l i t y of r e l i a b l e short LED.  What can be concluded from the Mason et a l . study i s that at h i g h background luminances f o r both chromatic and luminance evident  i n the red system,  there are d e f i c i t s  i n CFF  channels. Since l o s s e s are  which might i n d i c a t e severe or  q u i t e progressed damage (eg. P i n c k e r s , Pokorny, Smith & Verriest,  1979)  chromatic and  the n o n - s i g n i f i c a n t d i f f e r e n c e between  luminance  CFF may  be r e i n t e r p r e t e d  as  50 i n d i c a t i n g that the cone system had a l r e a d y been a f f e c t e d to the extent  that any subsequent damage would r e s u l t i n  minimal f u n c t i o n a l l o s s e s . In examining the e f f e c t s of myelin n e u r i t i s , Alvarez  (1985) r e p o r t e d l o s s e s i n s p e c t r a l  d e t e c t i o n , chromatic no  loss i n retrobulbar  f u n c t i o n , and v i s u a l a c u i t y .  flicker  Although  i n f o r m a t i o n was provided on the i n s t r u m e n t a t i o n nor types  of l o s s  (hues) A l v a r e z argued that myelin  l o s s was  c h a r a c t e r i z e d by moderate to severe damage t o the c o l o u r opponent system as w e l l as conduction  block.  Other attempts to measure temporal changes i n MS have centered upon p e r c e p t u a l delay whereby the p e r c e i v e d delay in the onset  of two synchronously  s t i m u l i are assessed  presented  under photopic  the subject i s to a d j u s t the onset  achromatic  c o n d i t i o n s . The task of of one of the two s t i m u l i  u n t i l they appear synchronous. MS and r e t r o b u l b a r n e u r i t i s p a t i e n t s both demonstrate g r e a t e r delay times msec.) necessary  (at l e a s t 30  f o r p e r c e i v i n g the two s t i m u l i as  synchronous than normals (Heron, Regan & M i l n e r , 1974; Regan, M i l n e r & Heron, 1976). With the use of a 0.3 degree t a r g e t , r e s u l t s from the technique  r e f e r r e d t o as delay campimetry can be graphed so  as to c r e a t e temporal delay f i e l d s of the r e t i n a . The results typically  reveal greater i r r e g u l a r i t i e s  temporal f i e l d s of MS p a t i e n t s than As demyelination f o r the conduction  i n the  normals (see F i g u r e 5 ) .  does not appear to account  entirely  l o s s e s seen i n MS p a t i e n t s (eg. McDonald  Figure 5 Delay campimetry f i e l d s on a MS p a t i e n t . The darker the area, the g r e a t e r the d e l a y . M o d i f i e d from M u s t i l l o , B r u s s e l l & White (1984)  52 & Sears, 1970; Bodis-Wollner & O n o f r j ,  1982), Regan (1983)  has argued that the r e s u l t s obtained i n d e l a y campimetry (temporal) demonstrate but a l s o d i f f e r e n t i a l ganglion l e v e l  not only n e u r a l conduction response  (Regan,  (temporal) a t the r e t i n a l  1983). The i m p l i c a t i o n s of Regan's  f i n d i n g s f o r the r e t i n a are d i f f i c u l t variability  problems  to i n t e r p r e t as great  i n temporal ranges a c r o s s the r e t i n a e x i s t s  even  among normals. What needs to be examined i s p o s s i b l y not the mean temporal d i f f e r e n c e s but the range of the v a r i a n c e s under  s p e c i f i c psychophysical conditions  (eg. l e v e l of  luminance). M o d i f i c a t i o n s of delay campimetry, m u l t i - f l a s h and d o u b l e - f l a s h campimetry, where the subject responds to detect the presence of f l i c k e r the same r e t i n a l  i n two s t i m u l i presented a t .  l o c a t i o n , has y i e l d e d s i m i l a r  results in  demonstrating g r e a t e r l a t e n c i e s among MS, r e t r o b u l b a r n e u r i t i s , glaucoma and r e t i n i t i s pigmentosa G a l v i n , Regan & Herron, Borenstein, Mustillo,  1976; White,  p a t i e n t s (eg.  Bross, M u s t i l l o &  1982; Regan, 1983; White, B r u s s e l , Overbury &  1983). Both m u l t i - f l a s h and d o u b l e - f l a s h  campimetry y i e l d  temporal f i e l d s with i s l a n d s of impaired  temporal s e n s i t i v i t y ,  shown i n F i g u r e 6.  Recently, i n a comparison techniques, Overbury,  of s p a t i a l versus temporal  B r u s s e l l , White, Jackson & Anderson  (1983), r e p o r t e d that the temporal channel  demonstrated  greater l o s s e s than s p a t i a l f o r p a t i e n t s having amblyopia, c a t a r a c t , o p t i c n e u r i t i s or macular d e g e n e r a t i o n . Although  Figure  6  M o d i f i e d from Regan (1981, pp. 240-241)  Y  *  54 they claimed m u l t i - f l a s h campimetry was more s e n s i t i v e Goldmann perimetry  than  i n d e t e c t i n g l o s s e s , the c o n c l u s i o n i s  unsupported i n that the k i n e t i c perimetry method employed was done at d i f f e r e n t  luminance values than  Moreover, the two techniques  the temporal.  are so d i f f e r e n t i n  methodology, s u b j e c t b i a s (eg. greater a n t i c i p a t o r y in  k i n e t i c perimetry,  f o r once a stimulus i s sensed i t s  d i r e c t i o n and presence  i s always known) and p s y c h o p h y s i c a l  f u n c t i o n being assessed that i t i s d i f f i c u l t why the authors similar  felt  effects  the two procedures  to understand  should have p r o v i d e d  results.  F i n a l l y , one other temporal  technique  used t o assess  v i s u a l delay i n MS has been the P u l f r i c h Phenomenon (eg. F r i s e n , Hoyt, B i r d & Weale, 1973; E l l & Gresty, 1982) wherein there i s a g r e a t e r delay among MS p a t i e n t s than normals f o r p e r c e i v i n g an e l l i p t i c a l  movement of a stimulus  presented  unexpectedly,  Gresty  i n a f r o n t a l plane. Rather  E l l and  (1982) r e p o r t e d the phenomenon i n the eye of a  monocular MS p a t i e n t . As the e f f e c t r e q u i r e s b i n o c u l a r v i s i o n , the f i n d i n g of E l l and Gresty may be e i t h e r an i n d i c a t i o n of some gross r e t i n a l anomaly i n t h e i r p a t i e n t u n r e l a t e d to the MS or a methodological  problem.  55  I.  COLOUR V I S I O N  Of  the  possible  assess, stage  colour  by  direct  treatment  vision  vision  pathologies  involvement the  sensory  have  of  qualities  appears  to  involving  as  in  visual  neuritis  Thus,  reported  in  such as glaucoma  (Flammer  & Drance,  Lakowski,  (Roy,  McCulloch,  1980;  Lakowski,  arthritis  Moreland, Due t o  the  losses  have a l s o 1962,  Jayle  & Daud,  Aiken  1964),  Pinckers, vision  1963)  are  in  in  colour  & Lakowski, diabetes  Begg & L a k o w s k i , rheumatoid 1968),  retinitis  Robertson  retinal  & Oliver,  &  cone  aging  system,  (Lakowski,  (Ourgaud,  1973),  intake  1982).  Vola,  luminanace  (Aiken,  1982;  1982).  (Pokorny,  viewed  as  conditions  1979),  diameter  may b e c l a s s i f i e d  abnormalities  acqui red.  normal  When c l a s s i f i e d  that  (Dubois-Poulson,  in  and drug  be  losses  1980;  the  pupil  may  earlier  indirect  1972),  of  Lagerlof,  performance  1979).  in  Lakowski  1982;  vision or  reported  changes  1972;  1984;  lesions  an  Drance  & Partridge,  sensitivity  been  & Schnabel,  mechanism,  & Drance,  one  at  clinical  & Paschke,  and c e r e b r a l  (Verriest,  Colour  Haining  or  1984;  & Kinnear,  Scheiber  extreme  1958,  Lakowski  Aspinall  (Wolf, 1980)  numerous  Hanna & M o r t i m e r ,  (Lakowski,  pigmentosa  contrast  1981;  that  system-  acquired  been  1983;  vision  be a f f e c t e d  the  optic  arthritis.  of  according Smith,  according as e i t h e r  to  origin,  Verriest to  &  origin,  congenital  colour or  56 1. SYSTEMS OF CLASSIFICATION  a. I . C l a s s i f i c a t i o n By O r i g i n  a) C o n g e n i t a l : C o n g e n i t a l c o l o u r v i s i o n l o s s e s a r e due to  the presence of some d e f e c t  i n the cone system at the  time of b i r t h , the assumption being that the cone system never f u n c t i o n e d normally throughout that  individual's  development. C o n g e n i t a l d e f e c t s include the red-green and yellow-blue v a r i e t y  ( d i s c u s s e d i n s e c t i o n I I I on  C l a s s i f i c a t i o n by Performance) as well as the achromatopsias. Achromatopsia or monochromacy r e f e r s to the c o n d i t i o n whereby e i t h e r the cone or rod system i s m i s s i n g e n t i r e l y . Rod monochromats are c h a r a c t e r i z e d by their  inability  to d i f f e r e n t i a t e s t i m u l i on the b a s i s of  hue a l o n e - r e s u l t i n g i n the s o - c a l l e d "colour  blind"  i n d i v i d u a l . In a d d i t i o n , rod monochromats tend t o be photophobic, have poor a c u i t y , and s u f f e r from nystagmus.  Although post mortem examination of a rod  monochromat has r e v e a l e d the presence of cones ( G l i c k s t e i n and Heath, the  1975), i t i s g e n e r a l l y f e l t  that  photopigments of achromatopsia s u b j e c t s have  s p e c t r a l a b s o r p t i o n c h a r a c t e r i s t i c s s i m i l a r t o that of rhodopsin  (Boynton, 1979). The presence of  r h o d o p s i n - l i k e photopigments may r e s u l t s c o t o p i z a t i o n mechanism f e l t  by V e r r i e s t  i n the (1964) t o  57 c h a r a c t e r i z e a l l forms of  achromatopsia.  Cone monochromacy may type or the Blue  be e i t h e r of the red (R) cone  (B) cone type. Although not d i s c u s s e d  here, Weale (1953) has presented evidence f o r a green cone monochromat. R cone monochromats have s p e c t r a l s e n s i t i v i t y curves s i m i l a r to the of deuteranopes  except  below 500 nm where the R monochromats show h i g h e r sensitivity  ( A l p e r n , 1974).  B cone monochromats are the most frequent type of cone monochromats. A c c o r d i n g to Boynton (1979) they have r e l a t i v e l y poor a c u i t y , photopic s p e c t r a l  sensitivity  s i m i l a r to the blue cones i n normals, and a Stiles-Crawford effect other f o v e a l  "normal"  - suggesting the presence  of  cones.  C o n g e n t i a l c o l o u r l o s s e s tend to be expressed p r e d i c t a b l e manner (Lakowski,  1969). The  l o s s e s are  t y p i c a l l y b i l a t e r a l and r e l a t i v e l y s t a b l e over Discrimination  in a  time.  l o s s e s are s p e c i f i c with w e l l d e f i n e d  axes and tend not to be a s s o c i a t e d with any other v i s u a l c o m p l a i n t s . Colour naming i s c h a r a c t e r i z e d by c o n f u s i o n s (eg. the protanope  classical  c o n f u s i n g red f o r  b l u e - g r e e n ) . According to P i n c k e r s , Pokorny, Smith  and  Verriest  less  (1979), c o n g e n i t a l c o l o u r l o s s e s are a l s o  a f f e c t e d than a c q u i r e d dyschromatopsias and  by t a r g e t  size  i l l u m i n a n c e . Smith and Pokorny (1977) have  demonstrated  that dichromats  (acquired) perform  like  anomalous t r i c h r o m a t s when t a r g e t s i z e i s i n c r e a s e d .  58 b) A c q u i r e d : A c q u i r e d c o l o u r v i s i o n l o s s e s are based upon the assumption that at one time of the i n d i v i d u a l ' s development  his/her colour v i s i o n  normal. The subsequent changes to e i t h e r normal  was  i n colour v i s i o n are due  (eg. ageing) or abnormal  (eg. glaucoma)  p r o c e s s e s . C l a s s i f i c a t i o n of the type of a c q u i r e d depending upon whether  loss,  one assesses c o l o u r v i s i o n on the  b a s i s of c o l o u r matching performance or wavelength and/or hue d i s c r i m i n a t i o n , t y p i c a l l y show red-green and y e l l o w - b l u e a x i s l o s s . Losses may  a l s o be n o n - s p e c i f i c ,  or i n the case of the Farnsworth-Munsell 100 Hue  Test  a n a r c h i c . A c q u i r e d l o s s e s tend not to a f f e c t both eyes e q u a l l y . Colour v i s i o n  f u n c t i o n i s unstable over time i n  t h a t , depending upon the pathology, i t may  either  worsen  or improve. There i s no c l e a r l y d e f i n e d a x i s and c o l o u r naming i s u s u a l l y good  (Lakowski, 1969). A c q u i r e d  d e f e c t s are o c c a s i o n a l l y accompanied a c u i t y and/or v i s u a l  field  loss  with reduced v i s u a l  (eg. o p t i c  neuritis).  b. I I . C l a s s i f i c a t i o n By Mechanism  If c l a s s i f i e d by mechanism, c o l o u r v i s i o n are seen as r e s u l t i n g  from e i t h e r  defects  absorption,  a l t e r a t i o n , or r e d u c t i o n p r o c e s s e s . Based upon the e a r l y work of von K r i e s  (1905), the type of mechanism  r e s p o n s i b l e f o r the l o s s i s assumed from c o l o u r matches that p r e d i c t the l o s s .  59  b) A b s o r p t i o n : absorption  In the f i r s t p o s s i b l e mechanism, the  system, the r e t i n a  i s f u n c t i o n a l l y normal and  the c o l o u r d e f e c t s are due t o p r e - r e c e p t o r a l changes i n the l e n s and cornea ( V e r r i e s t ,  1964; Lakowski,  1962).  Although most c o l o u r matches w i l l agree with the normal t r i c h r o m a t , some c o l o u r v i s i o n the yellow-blue  l o s s e s w i l l be e v i d e n t i n  axis.  b) A l t e r a t i o n : The second mechanism, the a l t e r a t i o n system, i s due to d i f f e r e n c e s i n one or more of the v i s u a l photopigments as compared to the normal trichromat. Abnormalities  are detected  in photopigment a b s o r p t i o n  spectra  through changes  (eg. Wald, 1966; Vos  and Walraven, 1971; Ruddock and Naghshineh, 1974). c) Reduction:  The r e d u c t i o n system, the t h i r d  mechanism, i s c h a r a c t e r i z e d by_colour d i s c r i m i n a t i o n much worse than those  found i n the normal  trichromat  while at the same time a c c e p t i n g any matches made by normals. The r e d u c t i o n system may occur  through the l o s s  of one of the normal receptor mechanisms (the Konig mechanism) or by a c o l l a p s e or f u s i o n of two r e c e p t o r mechanisms (the L i b e r - F i c k or A i t k e n - L i b e r F i c k mechanism). For a f u r t h e r d i s c u s s i o n of t h i s t o p i c the reader and  i s r e f e r r e d to P i c k f o r d (1958), Lakowski,  (1969),  Pokorny et a l . , (1979). d) C l a s s i f i c a t i o n by V e r r i e s t : V e r r i e s t (1964) has  employed three other mechanisms f o r d e f i n i n g a c q u i r e d c o l o u r v i s i o n l o s s , which a r e :  (1) mesopization,  (2)  60 s c o t o p i z a t i o n , and (3) e c c e n t r a t i o n . Mesopization, Etienne that  o r i g i n a l l y discussed  (1961), d e s c r i b e s  those colour  r e s u l t from t h e i n c r e a s e  causing  a reduction  mesopic  to that  i n photopic  losses  thresholds, illuminance.  discrimination (shift  seen i n normal o b s e r v e r s  i n VX  under  adaptation.  Scotopization activity  i n colour  efficiency  o c c u r s from t h e i n t r u s i o n o f r o d v i s i o n . The p h o t o p i c  luminosity  f u n c t i o n does not c h a r a c t e r i z e t h e r e t i n a l  sensitivity  of t h e observer.  extreme c a s e , have c o l o u r  Such o b s e r v e r s ,  conditions. Unfortunately,  i nthe  discrimination losses s i m i l a r  t o t h a t of normals under f u l l y  scotopic  adapted  i t i s presently  what r o l e t h e r o d s m i g h t p l a y colour  vision  i n the l e v e l of r e t i n a l  H e r e , t h e change i n c o l o u r is equivalent  by O u r g a u d a n d  unclear  as t o  i n c o n t r i b u t i n g t o such  v i s i o n matches both f o r normals as w e l l as  i n d i v i d u a l s s u f f e r i n g f r o m some f o r m o f c o n e degenerat ion. V e r r i e s t ' s t h i r d mechanism, e c c e n t r a t i o n , colour the  refers to  v i s i o n l o s s e s r e s u l t i n g from the e x c i t a t i o n of  parafoveal  r e t i n a by p h o t o p i c  stimuli.  Such  i n d i v i d u a l s , as i n the case of s t r a b i s m i c amblyopia, a r e u n a b l e t o f i x a t e due t o e y e movement p r o b l e m s . of  t h e e y e movement, t h e image i s f o c u s s e d  parafoveal According  region,  Because  onto the  r e s u l t i n g i n poorer d i s c r i m i n a t i o n .  t o V e r r i e s t (1964) and L a s z c z y k and S z u b i n s k a  61 (1973) there with  i s no s p e c i f i c c o l o u r d e f e c t  associated  eccentration.  c. I I I . C l a s s i f i c a t i o n By Performance  The  f i n a l method f o r c l a s s i f y i n g c o l o u r  anomalies, and  by  f a r the most e x t e n s i v e l y used, i s that  through performance. Performance can be according  to the a x i s of l o s s and  moderate, and tests  vision  categorized  s e v e r i t y (mild,  severe) or on chromatic d i s c r i m i n a t i o n  (Lakowski, 1969). However, the c l a s s i f i c a t i o n most  widely  used i s that based upon c o l o u r matching  performance with  three p r i m a r i e s ,  three general  c l a s s i f i c a t i o n s of  dichromat, and  (c) monochromat.  from which are (a) t r i c h r o m a t ,  derived (b)  a) Trichromatism: In the case of the t r i c h r o m a t , normal observer,  a l l three p r i m a r i e s  s h o r t , middle, and  long wavelengths of of the  spectrum) are r e q u i r e d to match any under photopic  with  one  c o n d i t i o n s . In the Wright  the three p r i m a r i e s are the three 650X nm  (representing  ( r ) , 530X nm  (g), and  the t r i c h r o m a t i c c l a s s i f i c a t i o n  the  visual  s p e c t r a l colour (1946) system,  spectral stimuli  460X nm  of  (b). Associated i s the l a r g e s t  group of c o l o u r v i s i o n d e f e c t s known as anomalous trichromatism. Anomalous trichromatism  or  r e f e r s to the  condition  where three p r i m a r i e s are needed to match a s p e c t r a l c o l o u r except that the r a t i o of the mixtures are  62 different  from normals Lakowski, (1969). The d e f e c t  may  be e i t h e r protanomolous, deuteranomalous, or tritanomalous  (to be d i s c u s s e d  shortly).  According to Lakowski, the incidence f o r the protan defect  i s 1.5%  (male and female) and 4.0 - 5.0%  f o r the  deutan. The protan d e f e c t i s c h a r a c t e r i z e d by a luminous efficiency  i n v o l v i n g long wavelengths (Judd & Wyszecki,  1963). Table 5 from Wyszecki and S t i l e s  (1982) p r o v i d e s  i n f o r m a t i o n on the s a l i e n t c h a r a c t e r i s t i c s of the v a r i o u s d e f e c t s d i s c u s s e d here. b) Dichromatism: Dichromats r e q u i r e only  two  p r i m a r i e s to match s p e c t r a l c o l o u r s and belong to that group t y p i c a l l y r e f e r r e d to as c o l o u r (Lakowski, 1969). The d e f e c t may  deficient  be c l a s s i f i e d  into  p a i r s a c c o r d i n g to the type of c o l o u r c o n f u s i o n mani f e s t e d . The f i r s t  p a i r l i e s along the red-green a x i s and i s  r e f e r r e d to as protanopia and d e u t e r a n o p i a . The terms, l i t e r a l l y meaning ' f i r s t '  and  'second' d e f e c t  r e s p e c t i v e l y were thus named by von K r i e s not  (1924) so as  to i n f e r any p h y s i o l o g i c a l mechanisms i n t o the  terms. As can be seen i n Table 5, protanopia ( r e d d e f e c t ) i s c h a r a c t e r i z e d by reduced luminous e f f i c i e n c y at  long wavelengths  (Wyszecki & S t i l e s ,  wavelength d i s c r i m i n a t i o n Walraven,  1982). Best  i s at about 490 nm  (Vos &  1971). Of males, about 1.0% are protanopes  whereas only 0.02%  of females a r e .  Table 5 Distinguishing  Chjfm  Icnslic  PIKIKIHIIIIJI.UIS  features  nil miiiMn.iloiis  I r,  of  the  major  INriitaiuirH-  l)<  colour  defects  IriUimpv  III«I.IMO|K'  Rod-  M i i i K K h r m i M l  C o l o r discrimination  Materially reduced front red to  Absent front the ted  At'M'iil f r o m the led  Absent in the  N o color dis-  through the spectrum  yellowish green hin lo a vatving  lo ahoul S ' O mil  lo j h o u i 5 <il m n  giei nish blue lo  criinlnalion  degree in difleient u s e s Neutral point (i e ,  None  None  l>lue 400  4S>5 nm  4 J^  Mrt n m  <  | , i 4 X 0 nm)  <hK and J 7 0 n m  A l l wavelength?.  No  Yes  wavelength of monochromatic stimulus that male h e a fined " w h i t e " stimulus)' Shortening of the red  Yes  .  No  Yes  No  MM) nm  <4t>nm  5M) mn  >,, ^ 0 2.V.  y  {! c . reduced luminous efficientv of long wavelengths) Wavelength of the maximum  Un  nm  nm  V»7 n m  of luminous efficiency curve C ' l h IV3I c h r o t n j l i c i l y of  x  the confusion point  ••• 1 OHO  Jt  Jt  =  «„  0.171  - tl IIKO  ( u V h r o n u t s only) Percentage frequency of occurence among males  1 0  4 V  1 (1  1 1  om:  among females  0 02  OJH  <Hl2  DDI  II lull  Modified  from Wyszecki  £, S t i l e s  (1982,  p.464)  0 t M) 1  64  The  c o l o u r c o n f u s i o n l o c i and n e u t r a l a x i s f o r  p r o t a n o p i a , and other dichromats to be d i s c u s s e d , can found  i n f i g u r e 7. The  isochromatic  lines  d e f e c t . Provided  c o n f u s i o n l o c i d e f i n e d by  be  the  ( s t r a i g h t l i n e s ) c h a r a c t e r i z e the  there are no luminance d i f f e r e n c e s , two  c h r o m a t i c i t i e s f a l l i n g along a s p e c i f i c l i n e w i l l be confused  isochromatic  by the c o l o u r d e f i c i e n t  while a normal observer  observer  would see them as d i f f e r e n t  as  long as there i s some minimum d i f f e r e n c e between the  two  c h r o m a t i c i t i e s . A l i n e drawn p e r p e n d i c u l a r to the n e u t r a l a x i s i n d i c a t e those c o l o u r s that the dichromat is l i k e l y  to d i s c r i m i n a t e .  In the second d e f e c t , deuteranopia, reduced  there i s no  luminous e f f i c i e n c y of long wavelengths.  The  n e u t r a l p o i n t occurs at about X495 nm.  and the peak  r e l a t i v e luminous e f f i c i e n c y  i s at 560  nm.  r a t e s are  0.01%  The  1.1%  f o r males and  for  Incidence  females.  second major p a i r of c o l o u r v i s i o n d e f e c t s i s  determined from the c o n f u s i o n along the a x i s , t r i t a n o p i a and  yellow-blue  tertartanopia. Tritanopia is  c h a r a c t e r i z e d by an absence of d i s c r i m i n a t i o n between 445  to 480  reduced  nm  (Wyszecki & S t i l e s ,  1982). There i s no  luminous e f f i c i e n c y at long wavelengths and  maximum luminous e f f i c i e n c y & Stiles,  i s at about 555  1982). Roughly 0.002% of males and  females have t h i s type of d e f e c t .  nm  (Wyszecki  0.001% of  65  Confusion l o c i , c e n t r e of c o n f u s i o n , and n e u t r a l axes f o r dichromats. From Lakowski (1969, p.187)  66  Little  i s known about t e r t a r t a n o p i a . Some have  argued that such a c o n d i t i o n does not e x i s t 1979). However, others (1949) and  such as M u l l e r  (Boynton,  (1924), Judd  Lakowski, (1969) have presented t h e o r e t i c a l  evidence f o r t e r t a r t a n o p i a . Loss i n the yellow-blue  axis  i n v o l v e s two  465  nm  neutral points  (blue) and  575  (1969), c o l o u r s in F i g u r e  nm  i n the  spectrum, one  at  ( y e l l o w ) . As noted by Lakowski  f a l l i n g along  the confusion  l i n e s shown  7 would not be d i s c r i m i n a t e d by such an  i n d i v i d u a l . T h e o r e t i c a l l y , there in luminous e f f i c i e n c y a v a i l a b l e f o r the  should  be no  reduction  f o r long wavelengths. No data i s  incidence  c) Monochromatism: The  of  tetartanopia.  l a s t major c l a s s i f i c a t i o n  by  c o l o u r matching performance i s monochromatism. Monochromats, be they rod or cone, need only one (as w e l l as luminance information) c o l o u r under photopic d i s c r i m i n a t e any  by e i t h e r t h e i r photopic  are  identified  (cone) or s c o t o p i c  f u n c t i o n s . The  defect  females. No  0.003% amoung males and  data i s a v a i l a b l e on the  only  (rod) i s extremely  r a r e . Information on rod monochromats estimates frequency to be  spectral  c o n d i t i o n s . They are unable to  c o l o u r at a l l and  r e l a t i v e luminousity  to match any  primary  the  0.002% among  frequency of cone  monochromats. In a l l , defects  i t needs to be s t r e s s e d that c o l o u r v i s i o n  should  not be  seen as separate c a t e g o r i e s  dichromat versus t r i c h r o m a t )  but  (eg.  i n s t e a d as a continuum  ranging from e x c e l l e n t discrimination better vision.  colour  discrimination  to  at a l l . Only by doing so does one  understanding of the process known as  no get  colour  68 2.  ASSESSMENT OF COLOUR VISION  The assessment of c o l o u r v i s i o n may be done  through  c o l o u r matching and hue or wavelength d i s c r i m i n a t i o n (AX). Another approach,  that of determining the photopic  e f f i c i e n c y of the cone system t o s p e c t r a l energy  (EX),  will  be d e a l t with i n the s e c t i o n on p e r i m e t r y .  a. Colour  Matching  Colour matching i n v o l v e s the mixing of s p e c t r a l c o l o u r s to produce a s p e c i f i c match to some r e f e r e n c e . The procedure,  t y p i c a l l y done l a b o r i o u s l y on a  c o l o r i m e t e r such as Wright's determine  C o l o r i m e t e r , i s used to  what r a t i o s of the three p r i m a r i e s ( r , g, b)  are r e q u i r e d to match a given wavelength. Normal t r i c h r o m a t s are a b l e to match a l l hues with an a p p r o p r i a t e mixture in  of the three p r i m a r i e s . D e v i a t i o n s  the type of p r i m a r i e s and t h e i r r a t i o s needed provide  an e s t i m a t i o n of the type and s e v e r i t y of c o l o u r v i s i o n loss. Colour matching performance can be assessed r e l a t i v e l y e a s i e r on c o l o r i m e t e r s c a l l e d anomaloscopes (eg.  the P i c k f o r d - N i c o l s o n Anomaloscope). S u b j e c t s view  a b i p a r t i t e f i e l d and match one h a l f of the f i e l d  with  the other on the b a s i s of b r i g h t n e s s and s p e c t r a l composition. Colour v i s i o n may be examined on red-green,  69 y e l l o w - b l u e , and green-blue  ratios.  Anomaloscopes e v a l u a t e an i n d i v i d u a l on matches or equations i n v o l v i n g the matching  specific of  two  s p e c t r a l c o l o u r s . There are three such equations used to assess c o l o u r v i s i o n d e f i c i e n c e s , which a r e : 1) the R a y l e i g h Equation, 2) the Pickford-Lakowski Equation, and  3) the E n g e l k i n g Trendelenburg  E q u a t i o n . The  R a y l e i g h and Pickford-Lakowski Equations are the most frequently  used.  The R a y l e i g h Equation d i s c r i m i n a t e s between c o n g e n i t a l red-green c o l o u r d e f e c t s . Depending upon the anomalscope used matching  (eg. the Nagel), the task i n v o l v e s  a spectral light  of about  X589 nm  of s p e c t r a l l i g h t s of X670 nm and X545 nm. range of r a t i o s between X670 nm and uses to match to X589 nm  to a mixture The  X545 nm a s u b j e c t  i s r e f e r r e d to as the  range, p r o v i d i n g the c l i n i c i a n  possible  matching  with an index as to the  type and extent of the s e v e r i t y . The median p o i n t w i t h i n a range  i s known as the midmatching p o i n t .  The Pickford-Lakowski Equation i n v o l v e s determining the matching X585 nm  range and midmatching p o i n t of X470 nm  filtered  equation was  l i g h t s to a white  developed  to t e s t  (tungsten) l i g h t .  f o r age  in the y e l l o w - b l u e range and has proven  1972).  The  r e l a t e d changes particularly  useful in detecting early acquired losses in various ophthomological d i s e a s e s (Lakowski,  and  1969,  Lakowski,  70 The f i n a l equation, the Engelkinq Trendelenburg Equation, was developed to assess blue-green l o s s e s . The task f o r the s u b j e c t  i s to match a mixture of X470 nm  and X517 nm to a l i g h t of X490 nm. F i g u r e 8 from Lakowski  (1981) shows the l o c a t i o n of the v a r i o u s  equations on the C.I.E c h r o m a t i c i t y diagram as determined from c o l o r i m e t r i c Pickford-Nicolson  information form the  Anomaloscope.  Thus depending upon the equation used, the anomaloscope  can, with a h i g h degree of r e l i a b i l i t y and  v a l i d i t y , assess an i n d i v i d u a l ' s c o l o u r v i s i o n . many have r e f e r r e d to the anomaloscope colour vision tests 41,  (eg. Boynton,  Indeed,  as the "queen" of  1979; Working  Group  1981). With respect to assessment using red-green matches,  an i n d i v i d u a l may be c l a s s i f i e d as a normal trichromat (normal, red-green weak, colour-weak), as a simple anomalous t r i c h r o m a t who may be protonomalous  (uses a  higher r a t i o of red to green than the t r i c h r o m a t ) or deuteranomalous  (more green to r e d ) , as an extreme  anomalous t r i c h r o m a t who may be e i t h e r an extreme protonomalous matches  (accepts a l a r g e range of red-green  and has a reduced s e n s i t i v i t y to the red end of  the spectrum) or extreme deuteranomalous red-green r a t i o matches  (wide range f o r  i n c l u d i n g the green p r i m a r y ) , or  f i n a l l y as a dichromat (protanope or deuteranope). For a more e x t e n s i v e d i s c u s s i o n on c o l o u r  vision  Figure  Colorimetric b a s e d upon  8  i n f o r m a t i o n on a n o m a l o s c o p e e q u a t i o n s the P-N a n o m a l o s c o p e . M o d i f i e d from L a k o w s k i (1981, p.22)  72 c l a s s i f i c a t i o n s a c c o r d i n g to anomaloscopes as w e l l as technique, b. Colour  the reader  i s r e f e r r e d to Lakowski(1969).  Confusion  Although  the term c o l o u r c o n f u s i o n can  g e n e r a l i z e d to c o l o u r matching or hue  be  (as on the anomaloscope)  or wavelength d i s c r i m i n a t i o n , i t i s d e a l t with  s e p a r a t e l y here i n o r d e r to i n d i c a t e c o l o u r  vision  assessment as done with pseudoisochromatic  plates.  Colour c o n f u s i o n occurs when an  i n d i v i u d a l mistakes  primary  c o l o u r f o r that of another.  nature  of the mistake made. When one  of  t h i s mistake  (how  It r e f l e c t s  u n d e r l y i n g c o l o u r c o n f u s i o n can best  understood  two  how  i s . The be  i n r e l a t i o n to the C.I.E. c h r o m a t i c i t y  diagram p r e v i o u s l y shown i n F i g u r e 7. The confuse  extent  r e f e r s to  poor the matching r a t i o s of t h a t i n d i v i d u a l concept  the  d i s c u s e s the  extreme i t i s ) , one  one  dichromat  will  c h r o m a t i c i t i e s t h a t l i e on a s p e c i f c a x i s  with a minimal d i s t a n c e between them, u n l i k e a normal who  may  p e r c e i v e the two  l u m i n o s i t i e s of the two dichromat may if  as d i f f e r e n t . However i f the c h r o m a t i c i t i e s are the same, the  not be able to d i s c r i m i n a t e the two  the d i s t a n c e between them are g r e a t .  even  The  d i s c r i m i n a t i n g f a c t o r here i s whether the c h r o m a t i c i t i e s fall The  along the  isochromatic  isochromatic  confusion l o c i  l i n e s f o r a given dichromat.  l i n e s seen i n F i g u r e 7 are  the  f o r that p a r t i c u l a r dichromat. I t i s  73  important to note that although the confusion d i r e c t i o n s of the l i n e s may  vary  slightly  i n d i v i d u a l to another, the c o n f u s i o n s d e f e c t s are  systematic  and  loci  from  for the  and  one various  d i r e c t i o n a l (Lakowski, 1982).  Pseudoisochromatic p l a t e s such as the Dvorine, I s h i h a r a , and  Ichikawa's Standard Pseudoisochromatic  P l a t e s are c o n s t r u c t e d confusion.  The  on the p r i n c i p l e of  plates contain  made up of hues that  f i g u r e and  f a l l along  colour  ground images  a p a r t i c u l a r confusion  a x i s , ones which are confused by an  i n d i v i d u a l with a  s p e c i f i c d e f e c t . Thus the pseudoisochromatic p l a t e s grossly categorize confusions.  i n d i v i d u a l s on the b a s i s of  the a x i s would not  a x i s . Colours  falling  be confused and  thereby  i n v a l i d a t i n g the d i a g n o s t i c d i s c r i m i n a b i l i t y of t e s t , as has  been shown f o r example with the  (Lakowski, Young and c. Hue  the  Ichikawa  Kozak, 1981).  or Wavelength D i s c r i m i n a t i o n  The  term " c o l o u r " d i s c r i m i n a t i o n r e f e r s to  a b i l i t y of the observer to d i s c r i m i n a t e e i t h e r p e r c e p t i b l e d i f f e r e n c e s in surface c o l u r s Farnsworth-Munsell lights  be  c l o s e the hues on the p l a t e s a l i g n  themselves to the c o n f u s i o n outside  their  Indeed, the v a l i d i t y of these t e s t s can  assessed by how  can  100  Hue  the small,  (eg.  Test) or s p e c t r a l or  filtered,  (eg. Koning-Helmoholtz monochromator). U n l i k e  c a t e g o r i c a l approach in c o l o u r  confusion  tests  the  74 (excluding  the anomaloscope), the  i n t e r v a l - l i k e approach  in c o l o u r  discrimination  existence  of ranges of d i s c r i m i n a t i o n  U t i l i z i n g the confusion,  procedures r e c o g n i z e s  abilities.  range (magnitude of e r r o r ) and  i n d i v i d u a l s can  q u a l i t a t i v e l y assessed on  the  the a x i s  be q u a n t i t a t i v e l y their ability  to  of  and  discriminate  colours. Colour d i s c r i m i n a t i o n wavelength d i s c r i m i n a t i o n  may  be assessed through  (AX),  matching ranges based  metameric matches on the anomaloscope, and discrimination The  most e x t e n s i v e l y  discrimination and,  involving surface  The  hue  colours.  used t e s t  for assessing  i s the Farnsworth-Munsell 100  as mentioned above, i t r e q u i r e s  discriminate  differences  FM-100 Hue  Hue  hue test,  the observer  between s u r f a c e  to  colours.  c o n s i s t s of four boxes c o n t a i n i n g  moveable caps. Each cap c o n s i s t s of Munsell c o l o u r s are  of equal s a t u r a t i o n  and  d i f f e r e n c e being in hue.  brightness,  The  from p u r p l e to v i o l e t . The  on  with the  85 that  only  boxes cover hues ranging  caps i n each box  are  presented in a predetermined "randomized" order and  the  task of the observer i s to rearrange them a c c o r d i n g  to  their  hues. Error  which are  scores are c a l c u l a t e d then p l o t t e d  misplacements,  in either a c i r c u l a r  frequency-by-cap graph form. The discrimination  from the  (shown by  the  or  degree of lack  s i z e of the e r r o r  of score)  75 and  the  l o c a t i o n of the e r r o r s helps d i s t i n g u i s h the  type of d i s c r i m i n a t i o n problems and 9 shows the  idealized discrimination  c h a r a c t e r i s t i c of the major c o l o u r As  i t s severity.  the d i s c u s s i o n  exceeds the  of c o l o u r  vision defects.  v i s i o n t e s t i n g far  reader i s r e f e r r e d to the e x t e n s i v e 1969,  Sharpe  here,  the  reviews by Lakowski  1982), Boynton (1979), Pokorny,  Smith, V e r r i e s t and Mollon and  losses  rather b r i e f o u t l i n e provided  (1966, 1968,  Figure  Pinckers  (1979), Mollon  (1982),  and  (1982).  3. APPLICATION  With respect  to MS,  colour  v i s i o n l o s s e s are  prominent  among p a t i e n t s with a h i s t o r y of o p t i c n e u r i t i s and be of the Vola,  red-green v a r i e t y (Cox,  1961;  R i s s , J a y l e , Gosset & Tassy,  Thronberend, 1974;  Serra,  Although the d e f e c t K o l l n e r ' s Law acquired defect  1982;  Grutzner,  1972;  tend to 1972;  Scheibner &  Kupersmith e t . a l . , 1983).  i s of the protan v a r i e t y as p r e d i c t e d  (diseases  by  of the o p t i c nerve r e s u l t in an  red-green d e f e c t ) , i t i s not  classical  i n that  the  tends to have a deutan component to i t (Birch-Cox,  1976). By  f a r , the m a j o r i t y  focused upon the use I s h i h a r a . T h i s has r o l e colour  of research  of confusion  in c o l o u r  p l a t e s such as  vision  has  the  probably l e d to an underestimation of  d i s c r i m i n a t i o n may  play  in assessing  both  the  the  ANARCHIC  SCOTOPIC  Figure 9 D i s c r i m i n a t i o n l o s s e s on the FM 100-Hue of the major c o l o u r v i s i o n d e f e c t s . From Lakowski (1969, p.274)  77 presence and  s e v e r i t y of o p t i c involvement i n MS  i n that  pseudo-isochromatic p l a t e s are not p a r t i c u l a r l y u s e f u l in measuring a c q u i r e d This  i s e s p e c i a l l y true when one  standard  colour  confusion  and  It has has  focussed  colours  t e s t s done on MS  recognizes  only been w i t h i n the  upon c o l o u r d i s c r i m i n a t i o n - mainly  (1980) reported  100  Hue  (FM  surface  100  Hue).  t o t a l e r r o r score  the p a t i e n t was  presently  n e u r i t i s . I t i s unclear  increased  Mascia are not  i n a s t a t e of acute o p t i c  whether p a t i e n t s with a h i s t o r y of from those who by Serra  i n agreement with t h e i r reported  had  no  and  sample s i z e s  groups.  Wildberger and  van  Lith  (1976) reported  that  i n the  acute phase of o p t i c n e u r i t i s (as assessed on the FM Farnsworth Panel D-15), 6 of 12 eyes blue-yellow,  12 eyes had and  4 of  14 of 20 eyes on the FM  100-Hue and  100  Hue  a red-green  12 eyes were  u n c l a s s i f i a b l e . Four to twenty-four months a f t e r the  D-15  FM  significantly if  o p t i c n e u r i t i s i n that the t a b l e s provided  d e f e c t , 2 of  their  type of l o s s e s on the  optic n e u r i t i s d i f f e r e d s i g n i f i c a n t l y  and  Thus  (with or without o p t i c n e u r i t i s ) showed e i t h e r  100  for the two  colour  that v i r t u a l l y a l l of  red-green or a n a r c h i c  The  the  l a s t decade that a t t e n t i o n  yellow-blue, Hue.  that  patients involved  i n the Farnsworth-Munsell  patients  (Lakowski, 1981).  not c o l o u r d i s c r i m i n a t i o n .  Serra and Mascia MS  colour v i s i o n losses  17 of 20 on the  were normal. In the case of r e t r o b u l b a r  attack, Panel  n e u r i t i s (RBN),  G r i f f i n and Wray (1978) found that a l l t h i r t y a f f e c t e d  and  78 ten n o n a f f e c t e d  (no RBN) eyes, had abnormal scores on the  FM-100 Hue even though the p a t i e n t s had a recovery  in their  v i s u a l a c u i t y . No i n f o r m a t i o n was made a v a i l a b l e by the authors  as t o the nature  of the d e f e c t s . According to  R i g o l e t , M a l l e c o u r t , LeBlanc and Chain  (1979) and Pokorny  e t . a l . (1979), the major d e f e c t i n RBN i s of a red-green v a r i e t y and that t h i s d e f e c t i s h i g h l y c o r r e l a t e d with clinical  s i g n s such as abnormal VEP's. S i m i l a r f i n d i n g s have  been reported by Scheibner The  other  interesting  and Thranbevend  (1974).  f e a t u r e of MS i s t h a t , although  i t is  a s s o c i a t e d with o p t i c n e u r i t i s , MS p a t i e n t s tend not t o show a recovery  i n c o l o u r v i s i o n . The p e r s i s t e n c e of the d e f e c t  over time i s equal Serra (repeated one  to that found with  RBN.  (1982) r e p o r t e d that i n a f a t i g u e design t e s t i n g of the FM 100-Hue under an i l l u m i n a t i o n of  Lux) MS p a t i e n t s had worse e r r o r scores p r i o r to t e s t i n g  than d i d the normals. Moreover, the c o l o u r d e f e c t was more f r e q u e n t l y of a t r i t a n e r r o r scores but  type. Fatique tended to increase the  i n MS and non-MS p a t i e n t s with o p t i c n e u r i t i s ,  not normals. T h i s was a l s o true of a f f e c t e d versus  unaffected  ( c o n t r a l a t e r a l ) eyes of MS p a t i e n t s (see Figure  10). One i n t r i g u i n g  f i n d i n g was the presence of c o l o u r  d e f e c t s i n c o n t r a l a t e r a l eyes - a f i n d i n g that had been r e p o r t e d with RBN (eg. Scheibner In one of the only  & Thranbevend, 1974).  i n v e s t i g a t i o n s on c o l o u r  d i s c r i m i n a t i o n of s p e c t r a l c o l o u r s incremental  (other s t u d i e s using  t h r e s h o l d procedures w i l l be d i s c u s s e d  i n the  79  150H  total JOOH  score 50H Affected  2b  To  30  76  50  60  MINUTES  Figure  10  ° * 9 °n PM 100-Hue e r r o r scores for an MS p a t i e n t ( a f f e c t e d versus una?fected eye) M o d i f i e d from Serra (1982, p.447) f ^  E  f  f  6  £ c  f  a t i  u e  Y  80 subsequent  s e c t i o n ) , Lakowski,  H a r r i s o n and S t e l l  (1985)  reported that 70% of MS p a t i e n t s (7 of 10 p a t i e n t s ) had c o l o u r v i s i o n d e f e c t s as assessed on the P i c k f o r d - N i c o l s o n anomaloscope. A l l were c h a r a c t e r i z e d as y e l l o w - b l u e with h a l f having an a d d i t i o n a l green-blue  l o s s . Red-green l o s s e s  were present and showed the g r e a t e s t d i f f e r e n c e between MS p a t i e n t s with o p t i c n e u r i t i s versus MS p a t i e n t s with no o p t i c n e u r i t i s . When compared t o o c u l a r h y p e r t e n s i v e s , the MS p a t i e n t s with o p t i c n e u r i t i s had s i g n i f i c a n t l y g r e a t e r red-green  l o s s e s . MS p a t i e n t s with o p t i c n e u r i t i s were found  to be s i m i l a r  i n t h e i r anomaloscope equations to  glaucomatous p a t i e n t s , p o s s i b l y  suggesting some s i m i l a r  s t r u c t u r a l - f u n c t i o n a l pathology  i n the two c l i n i c a l  e n t i t i e s . With r e s p e c t t o the FM 100-Hue, l o s s e s among the MS p a t i e n t s were found t o be a n a r c h i c with no d e f i n e d a x i s . A b n o r m a l i t i e s i n c o l o u r v i s i o n through the use of s p e c t r a l c o l o u r s has a l s o been assessed with the Gunkel Chromograph (Matthews, K o l l a r i t i s , Mehelas & Calderone  Kollaritis,  Robinson,  (1983), which i n v o l v e s f i n d i n g the  n e u t r a l p o i n t s f o r green, magenta, t u r q u o i s e , red, yellow and blue viewed  on a VDT s c r e e n . In e f f e c t , the Gunkel  Chromograph may be viewed  as an automated yet i n s t r u m e n t a l l y  poorer v e r s i o n of an anomaloscope. MS p a t i e n t s with a p r e v i o u s h i s t o r y of o p t i c n e u r i t i s were found to have enlarged n e u t r a l areas ( l a r g e r r e g i o n s of c o l o u r s were seen as having no c o l o u r ) than normals even when v i s u a l was 20/20. In another  acuity  study, Chu, Reingold, Cogan, Hunt and  81 Young (1983) reported the presence of enlarged  neutral  areas  on the Gunkel f o r MS p a t i e n t s much g r e a t e r than those f o r other p a t i e n t s (see Table  6 ) . They a l s o r e p o r t e d  sector  d e f e c t s among MS p a t i e n t s f o r "orange", "cyan", and "turquoise"  (no wavelengths  specified).  With a rather unique method known as F l i g h t of Colours (FOC), where s u b j e c t s d e s c r i b e the c o l o u r and b r i g h t n e s s of a p o s i t i v e afterimage,  differences in perceived  noted between MS and normals. A f t e r the i n i t i a l with a c o l o u r e d l i g h t  source  b l i n d f o l d e d and requested  (about  30 Lux),  " c o l o u r " was stimulation  the subject i s  to report on the afterimage  ten seconds f o r a p e r i o d of about ten minutes. Rolak  every (1984)  r e p o r t e d that MS p a t i e n t s with o p t i c n e u r i t i s had a shorter duration  f o r the presence of the afterimage  that the FOC c o r r e c t l y information the  regarding  identified  than normals and  126 of 134 eyes. No  the a c t u a l d u r a t i o n s were provided by  author. S i m i l a r r e s u l t s have been reported by Minderhoud,  Smits,  Kuks, and t e r Steege (1984) i n MS p a t i e n t s with a  h i s t o r y of r e t r o b u l b a r n e u r i t i s . In a d d i t i o n t o the shortened  l i f e of the afterimages  ( l e s s than 175 sec. f o r MS  compared to 278.5 sec. f o r normals),  Minderhoud et a l .  r e p o r t e d that f o r MS p a t i e n t s the afterimage  d u r a t i o n was  e s p e c i a l l y short f o r the c o l o u r s red, p u r p l e , and blue. T h i r t y - o n e percent  of the p a t i e n t s had t h e i r  afterimages  r e s t r i c t e d to only one c o l o u r or reported none at a l l . Unfortunately,  no i n f o r m a t i o n was provided  as to wavelengths  82 TABLE 6 N e u t r a l Colour Area of P a t i e n t Groups As Determined by the Gunkel Chromograph Diagnosi s  Mean Neutral Area Increase ( r e l a t i v e to normals)  Retinitis Pi gmentosa (n=38)  Area  Marked y e l l o w , moderate blue  14.50  Macular Degenerat i on (n = 8l )  Major Colour Involved  6.54  Marked y e l l o w , moderate blue  6.08  M i l d orange, m i l d cyan  5.54  Moderate orange  Rheumatoid Arthritis (n=l9)  3.46  Mild  yellow  Systemic Lupus Erythematosis (n=68)  2.00  Mild  yellow  Optic N e u r i t i s Atrophy (n=20) Multiple (n=28)  or  Sclerosis  Modified  from Chu  et a l . (1983)  83  nor  their s p e c i f i c durations. It i s apparent, t h e r e f o r e , that  a b n o r m a l i t i e s are a s s o c i a t e d i n MS and  prevalent  are  longitudinally  study has  nor  similar  to that  (eg. Lakowski,  been p u b l i s h e d as  neuritis of  disease. either  to how  colour  - a change which may  observed in d i f f e r e n t  are  indicative  of the  cross-sectionally  change over time in MS  of o p t i c  possibly  a longer d u r a t i o n or s e v e r i t y  U n f o r t u n a t e l y , no  vision  Red-green d e f e c t s  p a t i e n t s with a h i s t o r y  r e t r o b u l b a r n e u r i t i s and  either  may  i n MS.  colour  vision  hopefully  stages of  be  glaucoma  1981).  J . PERIMETRY Attempts at a s s e s s i n g v i s u a l vision The  i n the  peripheral  researcher must be  decrease in a c u i t y  adaption  factors  with i n c r e a s i n g  such as  the  eccentricity  (Troxler's  causing b l u r r e d  e f f e c t ) , changes due  colour v i s i o n defects  1969;  target  rapid  images with  to aging  local (eg.  Verriest  & Uvijls,  1977a, 1977b),  (eg. V e r r i e s t  & Uvijls,  1977b;  Lakowski, Wright & O l i v e r ,  1977), and  as p r e v i o u s experience of the to name j u s t a  colour  (Aulhorn,  (Aulhorn & Harms, 1972), r a p i d  Lakowski & A s p i n a l l ,  1972)  especially  r e t i n a c r e a t e s numerous problems.  aware of  1960), r e f r a c t i v e e r r o r reduced i n t e n s i t y  functioning,  few.  subject  poor f i x a t i o n as (Aulhorn & Harms,  well  84 Of p a r t i c u l a r problematic, and  importance,  and p o s s i b l y one  of the most  i s the q u e s t i o n of the e f f e c t of stimulus area  stimulus luminance on a b s o l u t e t h r e s h o l d s . T h i s e f f e c t ,  known under the g e n e r a l heading  of s p a t i a l summation depends  upon numerous f a c t o r s such as stimulus d u r a t i o n and c h r o m a t i c i t y , and w i l l be d i s c u s s e d Despite these "light  sense"  later.  i n t r a v e n i n g v a r i a b l e s , the assessment of  (Wentworth, 1930)  through  s t a t i c and  kinetic  (dynamic) perimetry has become one of the most v a l u a b l e methods i n both experimental  and c l i n i c a l  application.  Perimetry has advanced over the years from a p u r e l y s u b j e c t i v e e v a l u a t i o n of a p a t i e n t ' s response presence  to the  or absence of c o l o u r e d s t i m u l i presented  examiner to t h e i r  by  the  s t r i c t e r e v a l u a t i o n of rod, cone, and  rod/cone f u n c t i o n i n g under s p e c i f i e d background and t a r g e t luminances/wavelenghs (Lakowski  & Dunn, 1981;  Dunn &  Lakowski, 1981). Indeed some r e s e a r c h e r s as Enoch (1978) f e e l that s t a t i c perimetry allows one l a y e r - b y - l a y e r , p r o v i d i n g a completely  to examine the  retina  noninvasive method  for l o c a l i z i n g and d i f f e r e n t i a t i n g v a r i o u s  retinal/visual  pathologies. As mentioned e a r l i e r , are k i n e t i c and  the two  b a s i c p e r i m e t r i c methods  s t a t i c . K i n e t i c perimetry d i f f e r s  from  static  i n that the former i n v o l v e s a s s e s s i n g where i n the  visual  field  the s u b j e c t senses a stimulus while  luminance  (among other v a r i a b l e s ) remains constant. T h i s process of moving a stimulus from unseen to seen i s repeated on v a r i o u s  85  meridians, r e s u l t i n g  i n h o r i z o n t a l bearings  ( i s o p t e r s ) of  what T r a q u a i r (1949) r e f e r r e d to as the " h i l l " (see F i g u r e  of v i s i o n  11).  S t a t i c perimetry i n v o l v e s choosing some r e t i n a l p o s i t i o n to which a stimulus i s presented  i n d e c r e a s i n g and  i n c r e a s i n g l e v e l s of luminanace u n t i l a t h r e s h o l d i s determined. veritical hill  These t h r e s h o l d s (Figure 11) represent the  soundings  of v i s i o n  or p r o f i l e s of the three dimensional  (Anderson,  1982). Isopter perimetry p r o v i d e s  i n f o r m a t i o n r e g a r d i n g the shape of v i s u a l c a p a c i t y as w e l l as c h a r t i n g the presence  of l a r g e , deep d e p r e s s i o n s  (scotomas) whereas p r o f i l e perimetry enables one determine  the a l t i m e t r y of a h i l l ,  to  r e g a r d l e s s of shape as  w e l l as small shallow d e p r e s s i o n s along a s p e c i f i c Although  p r o f i l e perimetry c o u l d be used to map  meridian.  out  the  v i s u a l f i e l d as i n i s o p t e r p e r i m e t r y , the process would be too time consuming as i t would n e c e s s i t a t e measuring t h r e s h o l d s f o r a number of e c c e n t r i c i t i e s along a l a r g e number of m e r i d i a n s . Thus each method, k i n e t i c versus s t a t i c , p r o v i d e s the researcher with a s p e c i f i c  ( i s o p t e r versus  assessment of the v i s u a l f i e l d being determined further  profile)  - the method of  interest  by the problem under i n v e s t i g a t i o n . For  i n f o r m a t i o n regarding the two  techniques the reader  i s r e f e r r e d to Reed and Drance (1971), Aulhorn and Harms (1972), Tate and Lynn (1977) and Anderson  (1982).  86  Figure  11  Isopter and p r o f i l e perimetry p l o t s i n r e l a t i o n to the r e t i n a . M o d i f i e d from Anderson (1982).  87 U n l i k e s t a t i c perimetry, k i n e t i c perimetry  i s limited  in that the speed at which the stimulus i s brought f i e l d complicates t h r e s h o l d i n t e r p r e t a t i o n . Both and  s p a t i a l summation f a c t o r s i n t e r a c t  thereof  temporal  in a h i g h l y complex  manner, which, along with the response make i t d i f f i c u l t  i n t o the  speed of the s u b j e c t ,  t o assess which v a r i a b l e or  combination  i s a f f e c t i n g the t h r e s h o l d . Moreover, as  kinetic  perimetry uses s t i m u l i at s u p r a t h r e s h o l d v a l u e s , i t i s not p o s s i b l e to e x p l o r e p o i n t s between two r e l a t i v e scotoma are d i f f i c u l t Israel,  1956;  Sloan,  1961;  isopters, i . e . ,  to assess (eg. V e r r i e s t &  Aulhorn  & Harms, 1972).  Conversely, s t a t i c perimetry, with i t s use of s t i m u l u s d u r a t i o n , c o n t r o l s confounding temporal  e f f e c t s due  summation. By m a n i p u l a t i n g stimulus s i z e ,  summation e f f e c t s at d i f f e r e n t e c c e n t r i c i t i e s can evaluated  (eg. Sloan & Brown, 1962;  Of g r e a t e r importance, perimetry enables one for  invariant  specific  stimuli  to spatial  be  Dunn & Lakowski,  from a c l i n i c a l  standpoint,  1981).  static  to examine f i e l d l o s s e s ( t h r e s h o l d s such as wavelength and s i z e ) under  c o n t r o l l e d c o n d i t i o n s (eg. s c o t o p i c vs. p h o t o p i c ) . As  such,  s t a t i c perimetry a f f o r d s one with an e x c e l l e n t method f o r a s s e s s i n g r e t i n a l change. As the c l i n i c a l  l i t e r a t u r e on MS  appear to  indicate  that the f u n c t i o n i n g of the macula i s the e a r l i e s t  and  p o s s i b l y most a f f e c t e d of the v i s u a l systems, i t i s the b e l i e f of the w r i t e r that the assessment of s e n s i t i v i t y to chromatic  stimuli  retinal  under s p e c f i c l e v e l s of  88  preadapatation w i l l provide the most s e n s i t i v e measure of the presence sections w i l l  and s e v e r i t y of MS.  Therefore the f o l l o w i n g  focuss p r i m a r i l y upon chromatic  static  perimetry.  1. CHROMATIC PERIMETRY Chromatic perimetry was e a r l y as  1857  first  introduced by Aubert  wherein he and F o r e s t e r s t u d i e d the  d i s t r i b u t i o n of space and c o l o u r p e r c e p t i o n i n the field  as  (Aulhorn & Harms, 1972). Aubert  visual  b e l i e v e d that  space and c o l o u r p e r c e p t i o n were r e l a t e d to  both  "light  p e r c e p t i o n " , a b e l i e f which became the b a s i s f o r using s t i m u l i of v a r y i n g s i z e s and c o l o u r s . Hess (1889), Engelking and E c k s t e i n (1920),  and  Feree  and Rand (1924) employed pigmented t a r g e t s i n examining c o l o u r s e n s i t i v i t y and c o l o u r d e f e c t i v e s . Due difficulty  i n equating pigments, Lauber  the use of i n t e r f e r e n c e f i l t e r s  to the  (1932) i n t r o d u c e d  i n a p r o j e c t i o n pathway.  These techniques, however, focussed upon k i n e t i c and  i t was  not u n t i l Sloan  (1939) that ' s t a t i c '  were used to assess l i g h t p e r c e p t i o n at s p e c i f i c  perimetry procedures retinal  posit ions. The  s t a t i c method enabled Goldmann (1945a, 1945b) to  develop and o u t l i n e the v a r i a b l e s important  i n modern  e x p e r i m e n t a l / c l i n i c a l s t a t i c p e r i m e t r y . Despite these gains, Dubois-Poulsen's  (1952) c r i t i c i s m s of chromatic  perimetry,  89  that  i t d i d not p r o v i d e any more i n f o r m a t i o n than using  achromatic s t i m u l i , e f f e c t i v e l y a decade. I t was  the r e s e a r c h by V e r r i e s t and h i s a s s o c i a t e s  (eg. V e r r i e s t & I s r a e l ,  1965; F r a n c o i s , V e r r i e s t & I s r a e l ,  1966; V e r r i e s t & U v i j l s , re-examine  stopped r e s e a r c h f o r almost  1977) which began t o s e r i o u s l y  the use of c o l o u r e d s t i m u l i  and abnormal v i s u a l  (1981), Lakowski, Wright  (1977) and Lakowski, Drance and Carsh (1980) have  e x t e n s i v e l y s t u d i e d wavelength s e n s i t i v i t y abnormal  normal  f u n c t i o n i n g . Since then, o t h e r s such as  Hansen (1974), Genio and Friedman and O l i v e r  i n studying  i n normal and  eyes with other techniques such as dark a d a p t a t i o n .  2. THRESHOLD ESTIMATION  T h r e s h o l d d e t e r m i n a t i o n i n s t a t i c perimetry f o r chromatic s t i m u l i can be done through one of three ways: 1) luminance, 2) hue, and 3) f l i c k e r  (luminance p r o v i d i n g 1. Of the t h r e e ,  only luminance and hue w i l l be d i s c u s s e d . F i r s t , as i n achromatic p e r i m e t r y , chromatic perimetry t h r e s h o l d s can be based upon the luminance of the s t i m u l u s . Here, where the stimulus i s of some s p e c i f i c wavelength, the s u b j e c t responds when he f i r s t d e t e c t s the presence of the s t i m u l u s . The d e t e c t i o n i s based upon luminance alone and not the wavelength. In the second method, t h r e s h o l d s are determined from the d e t e c t i o n of the hue of the stimulus a l o n e . T h i s second approach, the chromatic t h r e s h o l d , i s the most d i f f i c u l t  due  90 to  i n t r a - s u b j e c t v a r i a b i l i t y . Large v a r i a b i l i t y e x i s t s i n  t h r e s h o l d s found through the chromatic d e t e c t i o n method due to p s y c h o l o g i c a l v a r i a b l e s such as knowledge of the wavelengths d u r i n g t e s t i n g as w e l l as the s a t u r a t i o n  level  of which the c o l o u r must be. T h i s alone, the problem of saturation,  i s a source of great i n t r a s u b j e c t v a r i a b i l i t y .  Equally  important, the e s t a b l i s h m e n t of t h r e s h o l d s  based upon hue are c o m p l i c a t e d by the photochromatic interval size,  which depends upon wavelength,  r e t i n a l area, target  exposure time, and a d a p t a t i o n l e v e l as a s t i m u l u s  s h i f t s from achromatic to chromatic (Aulhorn & Harms, 1972).  1  The time d u r a t i o n of the photochromatic  interval  depends upon the wavelength, with long wavelengths having the  shortest  interval  and being n e a r l y n o n e x i s i t e n t  fovea. As noted by Aulhorn and Harms, even  i n the  i f one were able  to e s t a b l i s h r e l i a b l e chromatic t h r e s h o l d s , they c o u l d not be equated to " l i g h t p e r c e p t i o n p e r i m e t r y " (luminance t h r e s h o l d ) . The reason f o r t h i s be seen even when luminance  i s that hue d i f f e r e n c e s can  i s constant between two hues. At  most, i n the case where background and t a r g e t luminance i s c o n s t a n t , one not  light  i s detecting hue-difference s e n s i t i v i t y  and  sensitivity.  Because of these d i f f i c u l t i e s ,  research i n chromatic  p e r i m e t r y has c e n t e r e d p r i m a r i l y upon the luminance t h r e s h o l d method i n steady s t a t e c o n d i t i o n s  (non  flicker).  The photochromatic i n t e r v a l r e f e r s to the range from a b s o l u t e rod t h r e s h o l d to the d e t e c t i o n of a hue. 1  91  Although susceptable outlined  i n Table  carefully, yield  7,  to numerous f a c t o r s as  briefly  luminance t h r e s h o l d s , when done  r e l i a b l e r e s u l t s with i n t e r - s u b j e c t  v a r i a b i l i t y g r e a t e r than i n t r a - s u b j e c t v a r i a b i l i t y . much e a s i e r task to detect the presence light  than i t s presence p l u s hue.  discussion w i l l differing  The  It i s a  ( i n t e n s i t y ) of a  remainder of  focus upon achromatic p e r c e p t i o n  the  of  wavelengths.  Luminance t h r e s h o l d r e f e r s to the n o t i c e a b l e c o n t r a s t between the luminance of a t a r g e t and photometric be expressed  i t s background. T h i s  d i f f e r e n c e between the two  luminance l e v e l s  may  as;  AL/L  Where,  AL = D i f f e r e n c e between stimulus and  background  luminance L = Background Luminance  The  r e c i p r o c a l of the AL/L  differential  p r o v i d e s a measure of  s e n s i t i v i t y . When speaking  of t h r e s h o l d s i n  terms of i n t e n s i t i e s as p e r c e i v e d by the observer, equation  the  can be r e w r i t t e n i n t o a form d e s c r i b e d by Weber's  Law:  AI/I  Where,  TABLE 7  Factors E f f e c t i n g Parlmetry  Methodological  1>  Fixation  Control  2) P r e a d a p t a t i o n L u m i n a n c e Laval » Duration 3) B a c k g r o u n d * S t i m u l u s Luminance L e v e l  4) B a c k g r o u n d ft S t i m u l u s Wavelength  S) Stimulus  Size  6)  Stimulus Duration (On » O f f I n t e r v a l s )  7)  Threshold Estimation Procedure (eg. Ascending veraua Oeacendlng)  PraracaotoraI  I) P u p i l  1 ) Retinal  Size  a) V t a u a l (Iris)  4) O c u l a r S t r u c t u r e (eg. tmmetropla) 9) C o r n e a l 6)  and  Batinal  a) O c u l a r M e d i a 3) P i g m e n t a t i o n  (Kinetic  Poat  Adaptation Angle  3) P i g m e n t a t i o n  Static)  (Retinal)  4) R e t i n a l  Eccentricity  9)  Spatial  Interactions  6>  Temporal I n t e r a c t i o n s  Receotoral  Statua 1) C M S . -1 e a 1 one - I n f e c t lone -tumora -chemicals -inflammatlone  7) P h y s i o l o g i c a l S t a t u s ( e g . P r e s e n c e of n e r v e F i b r e Layer O e f e c t s )  from Committee on V i s i o n  (1975).  Mot 1 v a t Ion Experience  (Learning) Level  a) l e c h e m t c  Problema  4) Dec l a Ion C r i t e r i o n  3) Movement  Sensitivity  S) R e a c t i o n Time  4) O l f f e r e n c e e  In I n f o r m a « ) P e r s o n a l 1ty t i o n P r o c e s s i n g (eg. S p a t i a l v e r s u s Temporel1)  8) Cone/Rod S t a t u s ( a g . Rod Monochromat)  Modified  1>  a) P a a t  3) A t t e n t Ion  Aberrations  Eye Movement ( O r b i t a l Muscle Involvement)  Psychological  p. 10.  93 AI = D i f f e r e n c e between stimulus  and background  intensity I = I n t e n s i t y of the background  AI/I  r e f e r s to the j u s t n o t i c e a b l e d i f f e r e n c e r e q u i r e d  in e s t a b l i s h i n g the r e l a t i v e t h r e s h o l d f o r a s p e c i f i c stimulus  s i z e , wavelength, and e c c e n t r i c i t y . The smaller the  obtained  v a l u e , the more s e n s i t i v e i s that p a r t i c u l a r  retinal  eccentricity.  P r i o r to d i s c u s s i n g s p e c i f i c v a r i a b l e s r e l e v a n t to establishing r e l a t i v e thresholds, d i s c u s s the problem of equating  i t i s necessary t o b r i e f l y  coloured  stimulus  intensities. Coloured  s t i m u l i may  be matched e i t h e r r a d i o m e t r i c a l l y  or p h o t o m e t r i c a l l y . The r a d i o m e t r i c method  involves  s p e c i f y i n g s t i m u l i by t h e i r p h y s i c a l energy c h a r a c t e r i s t i c s whereas photometric e n t a i l s c o r r e c t i n g and matching on the b a s i s of VX  ( s p e c t r a l s e n s i t i v i t y of the f o v e a ) .  Radiometric matching views v i s u a l  f u n c t i o n i n g as being  to the p h y s i c a l c h a r a c t e r i s t i c s of the organ l i g h t . Proponents of the r a d i o m e t r i c photometric method  i s not a p p r o p r i a t e  that  equal  (the eye) and  approach argue that the as VX i s not  r e p r e s e n t a t i v e of the e n t i r e r e t i n a (Aulhorn The d i f f i c u l t y with  stimuli  & Harms,  1972).  the r a d i o m e t r i c approach, however, i s  i t i s an instrumental  - p h y s i c a l method of s p e c i f y i n g  s t i m u l i . I t removes from the researcher  the only human  94 standard a v a i l a b l e to him, In the photometric  a psychophysical  adjustment,  stimuli  the  i s able to e s t a b l i s h d i f f e r e n c e s between  observers and  not remove them as i n the r a d i o m e t r i c method.  In perimetry typically  invariant foveal threshold.  method where one matches s p e c t r a l  on the b a s i s of VX, researcher  the  result  i n v o l v i n g r a d i o m e t r i c matches, f i n d i n g s i n high f o v e a l t h r e s h o l d s f o r red and  s t i m u l i as compared to achromatic  and  green s t i m u l i  (Aulhorn  and Harms, 1972). These r e l a t i v e d i f f e r e n c e s , as noted Lakowski and Dunn (1981), r e s u l t e n t i r e l y  from VX  blue  by  . By  removing the e f f e c t s of VX by p h o t o m e t r i c a l l y equating  the  s t i m u l i , a p s y c h o p h y s i c a l method, the f o v e a l t h r e s h o l d s would be s t a n d a r d i z e d  f o r luminance, a l l o w i n g one  chromatic  i n the r e t i n a  Oliver,  sensitivity  to assess  (eg. Lakowski, Wright &  1976).  Photometric  equivalence  a l s o p l a y s an important  role in  the p e r i p h e r y . If not p h o t o m e t r i c a l l y equated, t h r e s h o l d s i n the p e r i p h e r y  f o r chromatic  s t i m u l i may  vary  in s e n s i t i v i t y  as w e l l as r e l a t i v e luminous e f f i c i e n c y - a problem which effected earlier  r e s e a r c h e r s d i s c u s s e d by Aulhorn  and Harms.  3. ADAPTATION  The  luminance l e v e l to which the eye has become adapted  g r e a t l y e f f e c t s the increment t h r e s h o l d s f o r chromatic achromatic  s t i m u l i . The  effect  i s presumably due  complex i n t e r a c t i o n between luminance, cones and  to the rods.  and  95 U n f o r t u n a t e l y , due t o e a r l y experimenter b i a s and problems, very  few s t u d i e s have been done with  s t i m u l i and adaptation One of the f i r s t  chromatic  levels. examinations of chromatic  increment  t h r e s h o l d s and luminance background was Wentworth Using monochromatic s t i m u l i of X672.5,  X581.5,  nm under s c o t o p i c c o n d i t i o n s , Wentworth differential  (1930).  X522 and X468  reported  s e n s i t i v i t i e s across the r e t i n a  degrees meridian)  instrument  (0 to 180  f o r the v a r i o u s s t i m u l i . As seen in F i g u r e  12, the increment t h r e s h o l d s were higher than green or yellow  f o r red and blue  i n the p e r i p h e r y . S i m i l a r r e s u l t s to  Wentworth have been r e p o r t e d by Sloan  (1939) and Nolte  (1962). With respect to the fovea, a s i m i l a r r e l a t i o n s h i p found except  that there was l i t t l e  d i f f e r e n c e between the  green and yellow. The i m p l i c a t i o n s behind f i n d i n g s are d i f f i c u l t  was  Wentworth's  to s t a t e i n that the d i f f e r e n c e i n  the f o v e a l t h r e s h o l d s may have been due t o ; (1) her use of r a d i o m e t r i c u n i t s , and (2) the p o s s i b i l i t y of poor under s c o t o p i c c o n d i t i o n s r e s u l t i n g in the parafovea  i n higher  fixation  sensitivites  ( s t i m u l i were 1' 16" of v i s u a l a n g l e ) .  Under photopic  c o n d i t i o n s using s t i m u l i of equal  i n t e n s i t i e s but not s i z e , Nolte  (1974), V e r r i e s t and I s r a e l  (1965) and Ronchi and G a l a s s i (1976) among others the presence of a c e n t r a l scotoma f o r increment  reported  thresholds  with a "blue" s t i m u l u s . No such scotoma, however, was by Lakowski and Dunn (1979) when the chromatic  and  found  Figure  12  Achromatic t h r e s h o l d s at 0 asb background f o r 4 monochromatic l i g h t s . Stimulus s i z e = 1° 16' M o d i f i e d from Aulhorn & Harms (1972, p.122)  97 achromatic s t i m u l i were p h o t o m e t r i c a l l y equated and kept c o n s t a n t .  T h i s f i n d i n g was  of matching but probably  not due  size  was  j u s t to the method  more so to the f a c t that the  "blue"  scotoma i s found with small t a r g e t s o n l y . In a d d i t i o n to the method by which s t i m u l i were equated, the f i n d i n g of a "scotoma" f o r short wavelengths may problems with  shift  adjacent  to  f i x a t i o n . Under s c o t o p i c c o n d i t i o n s , such as  that used by N o l t e , Any  have been due  f i x a t i o n becomes d i f f i c u l t  in fixation w i l l  result  i n higher  p a r a f o v e a l areas, thereby  to  maintain.  s e n s i t i v i t i e s at  creating a relative  scotoma. Again p h o t o m e t r i c a l l y equating  t h e i r s t i m u l i , Lakowski  and Dunn (1981) reported that d i f f e r e n c e s in the for a blue  (475  nm),  achromatic stimulus adaptation  (0 cd/m  2  red (630 nm)  and  i n the p e r i p h e r y  increased as  the  an  g r e a t e s t at the f u l l y - s c o t o p i c  (rod)  cd/m , the g r a d i e n t s were l e s s  f o r the s c o t o p i c l e v e l was  Purkinje s h i f t , a s h i f t  separated  2  to the l u m i n o s i t i e s being photometric  larger s h i f t  13,  ). When i n c r e a s e d to the f u l l y - p h o t o p i c  (cone) l e v e l of 250 due  nm),  luminance decreased. As can be seen in F i g u r e  the s e p a r a t i o n was level  green (582  gradients  equated.  probably  The  due  to the  i n s e n s i t i v i t y towards the blue  end  of the spectrum under s c o t o p i c c o n d i t i o n s . T h i s d i f f e r e n c e in r e l a t i v e l u m i n o s i t y e f f i c i e n c y (510-512 nm)  ( s e n s i t i v i t y ) f o r rods  and cones (550-555 nm),  became the f i r s t  psychophysical  shown i n F i g u r e  evidence  f o r a dual  system ( D u p l i c i t y Theory) i n the r e t i n a . Photopic  14, receptor  (VX)  and  98  -3.0 -a  .O  -2.0 O 1  1  -a  Scotopic  -1.0  u  o  o  > t— m  I  1.0  Mesopic  Z  UJ  <J~>  2.0  3.0  a  •  '  «i0'  '  I  N  A • •  1  I  •  •  I  I  I  i  •  3 •  c  O  O  CNl  Photopic  f  0'  40'  F i g u r e 13 S t a t i c t h r e s h o l d s f o r f u l l y - p h o t o p i c , m e s o p i c , and f u l l y - s c o t o p i c c o n d i t i o n s . S t i m u l u s s i z e = 6.8' v i s u a l angle, blue (•), green ( o ) , red ( A ) , and a c h r o m a t i c (A) From L a k o w s k i & Dunn ( 1 9 8 1 , p . 1 9 6 )  Standard r e l a t i v e s p e c t r a l luminous e f f i c i e n c y f u n c t i o n s f o r photopic and s c o t o p i c v i s i o n . From Lakowski, Dahl & Rawicz (1982, p.1).  100 scotopic  (VX')  sensitivity greatly effects  t h r e s h o l d s f o r chromatic  s t i m u l i as seen i n the q u e s t i o n of  r a d i o m e t r i c versus photometric p o s s i b i l i t y of rod a c t i v i t y Although  increment  (VX)  (VX')  e q u i v a l e n c e s and  i n Wentworth's  the  study.  r e s e a r c h e r s such as Wentworth (1930) Wooten  and F u l d & Spillman  (1975), and Verdun Lunel and  (1974) have r e p o r t e d d i f f e r e n t i a l r e t i n a f o r chromatic  Crone  s e n s i t i v i t y a c r o s s the  s t i m u l i under v a r y i n g background  luminance l e v e l s , the r e s u l t s by Lakowski and Dunn (1981) are of extreme importance with respect to the In a d d i t i o n to the accepted b e l i e f inverse r e l a t i o n s h i p between increment  fovea.  that there i s an sensitivity  and  background a d a p t a t i o n even at the fovea, Lakowski and Dunn r e p o r t e d no d i f f e r e n t i a l  sensitivity  a d a p t a t i o n l e v e l s except  at the mesopic l e v e l  having  lower  t h r e s h o l d s than the green and  s t i m u l i ) as w e l l as the photopic earlier,  for the fovea w i t h i n  t h i s f i n d i n g was  Verriest  l e v e l . As d i s c u s s e d  o p p o s i t e to that of  earlier use of  e q u i v a l e n c e . Thus, c o n t r a r y to Hedin  (1980),  increment  red  achromatic  r e s e a r c h and can be a t t r i b u t e d to the author's photometric  (blue and  and  t h r e s h o l d s under photopic  a d a p t a t i o n do not vary g r e a t l y with e c c e n t r i c i t y for d i f f e r e n t wavelengths whereas they do i n the p e r i p h e r y f o r red under f u l l y - s c o t o p i c c o n d i t i o n s . D e s p i t e d i f f e r e n c e s i n the f o v e a l area, N o l t e ' s under mesopic and  (1962) r e s u l t s i n the  parafovea  s c o t o p i c a d a p t a t i o n agreed with Lakowski  and Dunn (see F i g u r e  13).  101 4. SPATIAL SUMMATION  In a d d i t i o n t o a d a p t a t i o n  luminance, the s i z e of the  stimulus e f f e c t s increment t h r e s h o l d s . Increment depending upon stimulus tend to decrease with  thresholds,  s i z e , c h r o m a t i c i t y and d u r a t i o n ,  i n c r e a s i n g stimulus  size.  Various  attempts have been made to q u a n t i f y the r e l a t i o n s h i p as an index  of s p a t i a l summation would provide one with  i n f o r m a t i o n on r e c e p t i v e f i e l d Aulhorn  size.  and Harms (1972) s t a t e that luminance and  stimulus area are i n v e r s e l y r e l a t e d f o r t h r e s h o l d s based upon small t a r g e t s . In the fovea,  summation f o r small  t a r g e t s l e s s than 10' appears to f o l l o w R i c c o ' s Law of Complete S p a t i a l Summation  (Luminance x Stimulus  summation c o n s t a n t ) . However, i n the p e r i p h e r y r e t i n a , P i p e r ' s Law of P a r t i a l Summation Stimulus  Area'  stimuli  5  = summation constant)  Area =  of the  (Luminance x  appears t o be true f o r  up to 1° (Baumgardt, 1972). Although k i n e t i c i s o p t e r  perimetry  has been used t o determine summation  coefficients  (Goldmann, 1945a, 1945b), i t should be p o i n t e d out that summation r a t i o s should only be e s t a b l i s h e d by v a r y i n g stimulus  s i z e at one s p e c i f i c  temporal e f f e c t s , static  i . e . they  retinal location,  should be e s t a b l i s h e d through  perimetry.  In h i s research on k i n e t i c perimetry, the r e l a t i o n s h i p between luminance and area as  removing any  Goldmann d e f i n e d f o r thresholds  'k', the exponent of summation. The summation exponent  102 was d e f i n e d by Goldmann as:  $ = (F /F)  where  0  where $ i s the transmitance filter  t o maintain a f i e l d  r e q u i r e d from a n e u t r a l d e n s i t y s i z e with a stimulus of s i z e F , 0  using a stimulus with a s i z e of F. The k exponent can vary from no summation Goldmann  (k=0) to complete summation ( k = l ) .  r e p o r t e d t h a t , f o r the k i n e t i c perimeter, a k value  of 0.84 expressed  the r e l a t i o n s h i p i n h i s d a t a . Since i t i s  assumed t h a t there i s an i n v e r s e r e l a t i o n s h i p between luminance and stimulus area, the c o e f f i c i e n t of s p a t i a l summation can be r e w r i t t e n a s : L x A  To d e s c r i b e a change i n k with a change i n stimulus area, the above may be r e w r i t t e n a s :  Although  k = Log L  1  Log A  2  - Log L _  2  Log a.  the above may be used to provide a measure of  s p a t i a l summation, i t a p p l i e s only to a b s o l u t e t h r e s h o l d s r a t h e r than levels  increment  t h r e s h o l d s f o r photopic and mesopic  (Baumgardt, 1972). To estimate the  increment  t h r e s h o l d s f o r s t i m u l i of d i f f e r e n t area, i t i s necessary to  103 s u b s t i t u t e AL f o r L. In the s i t u a t i o n where increment t h r e s h o l d s are obtained at d i f f e r e n t adaptation AL/L  luminances,  c o u l d r e p l a c e L as AL i s p r o p o r t i o n a l to a d a p t a t i o n  luminance. T h e r e f o r e , using e i t h e r AL or AL/L, k values obtained  f o r a b s o l u t e t h r e s h o l d s may be estimated f o r  increment t h r e s h o l d s by:  1  k = Log ALj - Log A L Log A  2  2  - Log A,  a. Relevant L i t e r a t u r e C a l c u l a t i n g the summation c o e f f i c i e n c t b a s i s of the slope and s e p a r a t i o n between g r a d i e n t s , Fankhauser and Schmidt  (K) on the  sensitivity  (1958, 1960) and  Dannheim and Drance (1971) r e p o r t e d i n c r e a s e d summation in the p e r i p h e r y of the r e t i n a when compared to the fovea, and that summation decreased stimulus s i z e . Moreover, they summation with  with i n c r e a s i n g  r e p o r t e d an i n c r e a s e i n  i n c r e a s i n g background luminances  (0.013-12.7 cd/m ). 2  Similarily,  Sloan  (1961) and Sloan and Brown (1962)  r e p o r t e d an i n v e r s e r e l a t i o n s h i p f o r achromatic  stimuli  between stimulus s i z e and increment t h r e s h o l d s using Goldmann s i z e s of I-V (1/4,1 4,16,64 mm.).  P l o t t i n g 'k'  Note: k here expresses the r e l a t i o n s h i p found under c o n d i t i o n s of constant adaptation i l l u m i n a t i o n . 1  104 from:  LogL + kLogA Where,  L = Luminance t h r e s h o l d A = Stimulus  area  Sloan and Brown found that the summation c o e f f i c i e n t v a r i e d g r e a t l y f o r normals and p a t i e n t s with c e n t r a l serous r e t i n o p a t h y . As with Fankhauser and Schmidt (1958) and Gourgnard (1961), Sloan r e p o r t e d i n c r e a s i n g summation i n the p e r i p h e r y . Dunn and Lakowski summation f o r chromatic  (1981) i n v e s t i g a t e d stimuli  spatial  (red and blue) with  Goldmann s i z e s I, I I , I I I , and IV (1/4, 1, 4, and 16 mm)  under f u l l y - p h o t o p i c , mesopic, and s c o t o p i c  a d a p t a t i o n . Summation c o e f f i c i e n t the red (617 nm),  blue  (474 nm)  'K' was  similar for  and achromatic  stimuli  in the f u l l y - p h o t o p i c and mesopic c o n d i t i o n s . The summation c o e f f i c i e n t s  f o r red and blue i n c r e a s e d with  e c c e n t r i c i t y and stimulus s i z e . S p a t i a l summation f o r red and blue, however, v a r i e d under s c o t o p i c a d a p t a t i o n in that n e i t h e r changed i n a c o n s i s t e n t manner f o r e i t h e r e c c e n t r i c i t y nor s t i m u l u s s i z e . Moreover, the red under s c o t o p i c a d a p t a t i o n gave l a r g e r values f o r 'K' than d i d the blue. As noted by the authors, t h i s f i n d i n g was probably due to the f a c t that the two  last  105 s t i m u l i were p h o t o p i c a l l y and As with p r e v i o u s  not  scotopically  s t u d i e s , Dunn and  reported large variances  Lakowski  i n the summation c o e f f i c i e n t s  l e a d i n g them to argue that research should designs  employing e q u i v a l e n t experimental  r a t h e r than seeking  conditions  (Dunn & Lakowski, 1981,  p.  Thus keeping in mind that i n t r a v e n i n g v a r i a b l e s  such as age  (general r e d u c t i o n  & Aspinall,  1969;  (Aulhorn (Hedin  focus upon  " s i g n i f i c a n c e " in i t s [summation  c o e f f i c i e n t ] absolute v a l u e " 205).  equated.  Verriest & Uvijls,  1977a), r e f r a c t i o n  & Harms, 1972), c o l o u r v i s i o n  & V e r r i e s t , 1980), and  position  in s e n s i t i v i t y - Lakowski  (Engel,  t h r e s h o l d s and i s indeed  1971)  knowledge of  can a f f e c t  the  stimulus  increment  t h e r e f o r e the summation c o e f f i c i e n t , i t  difficult  summation as i t may sensitivity  abnormalities  to e v a l u a t e  the s i g n i f i c a n c e of  only r e f l e c t v a r i a n c e s  in l i g h t  alone.  5. APPLICATION With respect to MS, ( k i n e t i c and  v i r t u a l l y a l l perimetric studies  s t a t i c ) report the presence of small  scotoma both in the p e r i p h e r y and  fovea. Serra and  (1982), using an achromatic stimulus  in a Goldmann  relative Mascia perimeter  ( s i z e II/2) with an u n s p e c i f i e d background found c e n t r a l scotoma i n a l l of t h e i r p a t i e n t s with MS. d e f e c t s were found among those  The  p a t i e n t s with a  m a j o r i t y of previous  106 h i s t o r y of o p t i c n e u r i t i s - a f i n d i n g found other r e s e a r c h . P r o f i l e perimetry  c o n s i s t e n t l y in  r e s u l t s with  their  p a t i e n t s i n d i c a t e d higher t h r e s h o l d s among recent  MS  p a t i e n t s i n both the a f f e c t e d and u n a f f e c t e d eye. T h i s i s e q u a l l y true of o p t i c n e u r i t i s alone 1984). U n f o r t u n a t e l y , r e s u l t s as no  i t is difficult  visual  to evaluate  the  i n f o r m a t i o n i s provided regarding stimulus  background s p e c i f i c a t i o n s Van  (eg. Johnson & K e l t n e r ,  Dalen,  levels).  Spekreyse and Greve (1981) assessed  f i e l d s of 29 MS  f i e l d analyzer,  (eg.luminance  p a t i e n t s by  (1) Friedmann  (2) k i n e t i c perimetry,  and  and  (3)  the  visual  static  p e r i m e t r y . F o r t y - s i x eyes of 58 showed abnormal v i s u a l f i e l d s as w e l l as abnormal VERs. Although made of stimulus  (presumably achromatic) nor  s p e c i f i c a t i o n s , the authors eyes, a c e n t r a l d e f e c t and visual  field"  intermediate  no mention  background  reported a c e n t r a l d e f e c t i n s i x "a d e f e c t in the  intermediate  (p.80) i n 28, and a d e f e c t only i n the field  i n 12. The  d e f e c t s tended to occur  between 10 degrees to 30 degrees e c c e n t r i c i t y . perimetry  (Figure 15)  45-225 degree meridian Although patchy,  Van  shows a reduced  only  Static  t h r e s h o l d along  as compared to a normalized  the  curve.  Dalen e t . a l . r e p o r t the presence of  small scotoma 10- 20 degrees temporally,  i n t e r p r e t a t i o n s of t h i s i s l i m i t e d adaptation  was  the  i n that no stimulus  s p e c i f i c a t i o n s were provided nor was  there  mention of c o r r e c t i n g f o r r e f r a c t i v e e r r o r . As MS  nor any  patients  with o p t i c n e u r i t i s have lowered a c u i t y , one would need to  107  45°  -  225'  Figure  eye  Meridian  15  Static thresholds (45° - 225°) of the right (asymptomatic) o f a n MS p a t i e n t . M o d i f i e d f r o m Van D a l e n , S p e k r e y s e & G r e v e (19.81, p.81 )  108 know i f they were a c c o r d i n g l y c o r r e c t e d i n the s t u d i e s mentioned. Moreover, s i n c e t h e i r f i g u r e was with the r i g h t eye, the patchy 20 degrees  temporally may  difficulties nerve  of a p a t i e n t  scotoma i n the r e g i o n of 10 -  have been caused  by  fixation  s h i f t i n g the area of the l i g h t onto the o p t i c  (blind spot). One  c o n s i s t e n t f i n d i n g i n t h i s study that has been  r e p o r t e d elsewhere  (Lowitzsch, 1980)  perimetry, involving s t a t i c d e f e c t s i n MS  i s that Friedman  t h r e s h o l d s , detected more  p a t i e n t s than k i n e t i c perimetry. Provided  there are no other methodological  reasons  (luminance  of background e t c . ) , t h i s d i f f e r e n c e between s t a t i c k i n e t i c perimetry i s undoubtedly  due  levels and  to the i s s u e s r a i s e d  earlier. Meienberg, Flammer and Ludin d e f i n i t e MS automatic  p a t i e n t s and  (1982) examined  14  17 normals with the Octopus, an  p e r i m e t e r . Using a t a r g e t s i z e of 0.43  a background luminance of 1.27  degrees  cd/m , s u b j e c t s who 2  on  were  c o r r e c t e d f o r a c u i t y were examined with programs 33 and  34  ( c e n t r a l f i e l d with a r a d i u s of 30 degrees). Eleven of the t h i r t e e n p a t i e n t s had abnormal f i e l d s , with the center being spared and  l o s s e s i n s e n s i t i v i t y o c c u r r i n g i n the p e r i p h e r y .  The d e f e c t s tended and  30 degrees  Similar  to be patchy  r e l a t i v e scotoma between  e c c e n t r i c i t y and were shallow  15  i n depth.  f i n d i n g s with manual perimeters have been reported  by F r i s e n and Hoyt  (1974).  109 P a t t e r s o n and Heron (1980), using a tangent  screen  a background luminance of 2.4 cd/m , r e p o r t e d v i s u a l 2  with  field  d e f e c t s among 46 of 53 MS p a t i e n t s and 12 of 13 o p t i c n e u r i t i s p a t i e n t s with no MS. Using an achromatic (1 mm) moved " c e n t r i p e t a l l y at r a d i a l at  stimulus  i n t e r v a l s of 30° and  a speed of about 1.5°/sec (p. 205), the authors  field  defects f o r suprathresholds  reported  ( t a r g e t luminance at 172  cd/m ) among 100% of d e f i n i t e MS p a t i e n t s (9/9), 94% of the 2  probable of  MS (15/16), 81% of the p o s s i b l e MS (13/16), and 75%  the MS p a t i e n t s with no h i s t o r y of v i s u a l complaints. Of  the d e f e c t s , 76% were arcuate depression,  scotoma, 14% l o c a l i z e d  13% g e n e r a l i z e d d e p r e s s i o n , and 4% a p a r a c e n t r a l  scotoma. The high percent  of v i s u a l  field  d e f e c t s among MS  p a t i e n t s with no h i s t o r y of v i s u a l complaints c o n t r a d i c t s the r e s u l t s by E l l e n b e r g e r and Z i e g l e r  (1977) who were  unable t o f i n d any among 25 s i m i l a r MS p a t i e n t s . P a t t e r s o n and Heron argue that the negative and  f i n d i n g s of E l l e n b e r g e r  Z i e g l e r was due to t h e i r use of the Goldmann  which they c l a i m can not e a s i l y d e t e c t narrow scotoma. E a r l i e r  r e s e a r c h u s i n g tangent  perimeter,  relative  screen have a l s o  r e p o r t e d small r e l a t i v e scotoma ( c e n t r a l or p a r a c e n t r a l ) among MS p a t i e n t s (Paton, Beck, Savino,  1924; S c o t t , 1957).  Schatz,  Smith and Sergott  (1982) r e p o r t e d  homonymous hemianopea among MS p a t i e n t s , c o n f i r m i n g the earlier  r e s u l t s of Kurtzke,  Beebe, Nagler, Auth, Kurland and  Nefzger  (1968). U n f o r t u n a t e l y , n e i t h e r study  provided  i n f o r m a t i o n as t o the c o n d i t i o n s nor s p e c i f i c a t i o n s under  110 which the p a t i e n t s were examined on the Goldmann. Only one  study  i n the l i t e r a t u r e appears to have  focussed  itself  Lakowski  (1968) examined the t h r e s h o l d s of an MS  two  chromatic  other at 495  upon increment t h r e s h o l d s  s t i m u l i , one nm  at 570  nm  for c o l o u r s . p a t i e n t to  (cone v i s i o n ) and  (rod v i s i o n ) . When dark adapted on a  Goldmann/Weekers adaptometer, rod f u n c t i o n i n g was only d u r i n g the i n i t i a l phase of dark a d a p t a t i o n any  evidence  of s l i g h t  h o r i z o n t a l meridian (9.87  2  receptor  l o g u n i t s and  v i s i o n was  who  losses  sensitivity  r e s t r i c t e d to  e f f e c t s of MS.  the achromatic  (0.4  the  This i s  by the work of F o l l o w f i e l d and Krauskopf  channel (wavelengths not  10  the  systems, the cones (photopic) appear to be  r e p o r t e d greater t h r e s h o l d l o s s e s for MS  chromatic  threshold  a d a p t a t i o n . Thus of  most s e n s i t i v e to the demyelination supported  retinal  c o n d i t i o n s . Foveal  degrees e c c e n t r i c i t y f o r photopic two  the  16, t h r e s h o l d s r e v e a l e d  photopic  reduced by two  there  (0 - 180 degrees) under normal l e v e l s of  l o s s e s . As seen i n F i g u r e  was  was  and  f o r s t a t i c p r o f i l e s along a  cd/m ) r e v e a l e d e x t e n s i v e  under mesopic and  normal  impairment. Examination of  p a t i e n t on a Goldmann perimeter  adaptation  the  (1984)  p a t i e n t s in the  s p e c i f i e d ) as compared to  l o g u n i t s versus  0.2  f o r the  latter).  Subjects were r e q u i r e d to respond to changes i n c h r o m a t i c i t y from white on a background of 300 i n f o r m a t i o n was  provided  regarding  cd/m . Although 2  their respective  wavelengths, l o s s e s occurred a c r o s s the four hues Figure  no  (see  17), with the yellow p o s s i b l y showing more of a l o s s  Ill  Figure  16  Mesopic and photopic t h r e s h o l d s f o r an MS p a t i e n t . From Lakowski (1968, p.97)  112  Figure  17  Thresholds of c o l o u r s generated on a t e l e v i s o n screen f o r normals and MS p a t i e n t s ( a f f e c t e d and u n a f f e c t e d eyes. M o d i f i e d from F a l l o w f i e l d & Krauskopf (1984, p.773)  113 than the other  three.  Although F o l l o w f i e l d and Krauskopf employed a d i f f e r e n t method ( t e l e v i s i o n monitor generating wavelengths), t h e i r reported  their  l o s s e s under  unspecified photopic  c o n d i t i o n s as well as Lakowski's (1968) f o r photopic and mesopic c l e a r l y functioning  i n d i c a t e the importance of a s s e s s i n g  i n MS.  Similar threshold varying  cone  l o s s e s f o r a red LED stimulus  under  luminance backgrounds having been reported by  Patterson,  F o s t e r and Heron (1980). F i v e MS p a t i e n t s were  preselected  on the b a s i s of having had abnormally  visual  thresholds  screen  (no s p e c i f i c a t i o n s p r o v i d e d ) .  filters,  variable  as p r e v i o u s l y assessed on an unknown Wearing n e u t r a l  density  the p a t i e n t s were adapted to a background with  e i t h e r 0, 1.0, 2.0, or 3.0 l o g cd/m  2  luminance. Thresholds  were e s t a b l i s h e d f o r a r e d LED (625 nm) subtending 11 degrees and presented i n the c e n t r e lights  of four small  ( i n t e n s i t i e s unknown). P l o t t e d i n terms of  of Seeing  curves  variance 2  i n their thresholds  adaptation  across  greater  the 1.0, 2.0 and 3.0 l o g  c o d i t i o n s . A l l of the MS t h r e s h o l d s  s i g n i f i c a n t l y higher of the a d a p t a t i o n  Frequency  (assumes that the u n d e r l y i n g d i s t r i b u t i o n  of AI i s normal), the MS p a t i e n t s demonstrated  cd/m  white  were  than those f o r f i v e normals across a l l  conditions.  Thus i t appears t h a t , with respect l o s s e s appear to be g r e a t e r c o n d i t i o n s . Less v a r i a b i l i t y  t o perimetry,  under photopic  MS  and mesopic  from normals appear under pure  1 14 rod f u n c t i o n i n g , that  i s s c o t o p i c v i s i o n . Though such a  statement needs to be c a r e f u l l y guarded due to the lack of precise perimetric specifications  i n v i r t u a l l y a l l of the  s t u d i e s reviewed, these r e s u l t s a l o n g with the changes seen in c o l o u r v i s i o n d i s c u s s e d e a r l i e r would appear  to suggest  that s t a t i c p e r i m e t r y on cone f u n c t i o n i n g under mesopic photopic c o n d i t i o n s might p r o v i d e the means through both the presence and s e v e r i t y of MS may  and  which  be e v a l u a t e d .  6 . HYPOTHESIS A review of the l i t e r a t u r e has i n d i c a t e d that MS i s c h a r a c t e r i z e d by both s t r u c t u r a l and f u n c t i o n a l changes i n the r e t i n a . S t r u c t u r a l l y , MS has shown the presence of o p t i c atrophy, o p t i c n e u r i t i s , r e t i n a l venous sheathing, and d e f e c t s i n the r e t i n a l nerve f i b r e l a y e r . In a d d i t i o n , imaging techniques (eg CT scans) have r e v e a l e d the e x t e n s i v e presence of plaques i n the white matter. More i m p o r t a n t l y , post mortem examinations have shown a high degree of plaque involvement i n the o p t i c nerves. F u n c t i o n a l l y , MS p a t i e n t s have shown abnormal p o t e n t i a l s with respect to i n c r e a s e d l a t e n c i e s and  evoked reduced  amplitudes -- a f i n d i n g which appears to be h i g h l y consistent  f o r v i s u a l l y evoked  p o t e n t i a l s . Attempts made at  d i f f e r e n t i a t i n g c e n t r a l versus p e r i p h e r a l v i s u a l with evoked p o t e n t i a l s appears to improve  stimulation  d e t e c t i o n of  MS.  1 15 In a d d i t i o n l o s s e s have been found f o r s p a t i a l sensitivity  i n the low and intermediate  some MS p a t i e n t s showing high  frequencies,  chromatic, there processing  delay  with MS p a t i e n t s  than normals. Of luminance and  i s some evidence to suggest that  of c o l o u r  with  s p a t i a l frequency l o s s .  Temporal l o s s e s have a l s o been r e p o r t e d , e x h i b i t i n g greater  contrast  temporal  i s the most a f f e c t e d of the two.  Probably the most s e n s i t i v e i n d i c a n t s of the e f f e c t s of demyelination  has been v i s u a l assessment through c o l o u r  v i s i o n t e s t i n g and p e r i m e t r y . have been reported  Extensive  colour v i s i o n losses  among MS p a t i e n t s , with red-green  being  the most predominant l o s s as assessed by the anomaloscope. Assessment on the FM-100 Hue has t y p i c a l l y shows the l o s s as anarchic. Perimetric  ( k i n e t i c and s t a t i c ) s t u d i e s with achromatic  s t i m u l i have demonstrated the presence of c e n t r a l and p e r i p h e r a l scotoma as w e l l as an o v e r a l l l o s s i n s e n s i t i v i t y . T h i s appears t o be e s p e c i a l l y t r u e when one examines photopic  and mesopic  adaptation.  Because of these f i n d i n g s , i t i s proposed that changes in v i s u a l p r o c e s s i n g  due to MS be s t u d i e d  e s t a b l i s h i n g luminance t h r e s h o l d s chromatic s t a t i c perimetry postulated  through  f o r achromatic and  on an automated p e r i m e t e r . I t i s  that MS p a t i e n t s w i l l e x h i b i t g r e a t e r  s e n s i t i v i t y than normals, and that the t h r e s h o l d would be dependent upon the a d a p t a t i o n a l system. E a r l i e r t h r e s h o l d  losses in losses  s t a t e of the v i s u a l  l o s s would be found among MS  116 patients  under p h o t o p i c or mesopic l e v e l s than  under  photopic. The  t y p e s of  reduction  threshold  in overall sensitivity  s c o t o m a s . From t h e the  l o s s expected are  clinical  foveal threshold  may  as w e l l as  literature,  The  to p e r i p h e r a l  presence  show t h e most v a r i a b i l i t y  i m p o r t a n c e of  thresholds,  f u n c t i o n a l a r e a s may  the  general  i t i s expected  when c o m p a r e d t o n o r m a l s d e p e n d i n g upon t h e adaptation.  a  that  in loss of  t h i s a s s u m p t i o n , when c o m p a r e d  i s that  explain  state  of  the  AI/I  subjective  between the  two  c o m p l a i n t s such  as  glare. Thus i t i s p r o p o s e d t h a t demyelination by  ( i t s p r e s e n c e and  e f f e c t s due  severity)  examining luminance thresholds  achromatic perimeter  s t i m u l i on  provide  establishing obtained  f a s t and  highest with  the  closely associated  neuritis.  of  and  be  for chromatic  assessed  and automatic  three  MS  r e l i a b l e means f o r Luminance t h r e s h o l d s  and  F 2 2 5 . As  w i t h MS,  categories  by  t h e MS  3) p o s s i b l e MS.  differentiate patients  without a h i s t o r y  C l i n i c , Health  the  basis  into  probable  made t o  of c l i n i c a l  MS  Sciences  d e f i n i t e , 2) be  the of  h a v e been c l a s s i f i e d  Attempts w i l l on  be  o p t i c n e u r i t i s appears  i t i s proposed that  t h o s e w i t h and patients w i l l  will  lowest background bowl  C e n t r e H o s p i t a l , U . B . C : 1) c l i n i c a l l y MS,  i n MS  a u t o m a t e d p e r i m e t e r . The  thresholds.  at both the  p a t i e n t s c o n s i s t of optic  a  static  luminances p o s s i b l e t o be  an  to  i s Synemed's Fieldmaster® F225 m o d e l , w h i c h i t i s  hoped w i l l  one  the  stability  1 17 and  frequency  of episodes  (acute phase).  To summarize, i t i s hypothesized 1.  that:  R e l a t i v e t h r e s h o l d s w i l l be s i g n i f i c a n t l y between MS  different  and v i s u a l l y normal s u b j e c t s and  that  this  d i f f e r e n c e w i l l be h i g h l y dependent upon background preadaptation. elevated  S p e c i f i c a l l y , MS  patients will  have  (higher) t h r e s h o l d s than normals and  that  t h r e s h o l d d i f f e r e n c e s between MS  and  normals w i l l  greater under b r i g h t e r background adaptation 2.  Threshold  d i f f e r e n c e s between MS  g r e a t e r at and 3.  and  Cone t h r e s h o l d s as determined by red and will  be  levels.  normals w i l l  near the fovea than i n the  the  be  periphery. blue  filters  show more s e l e c t i v e l o s s than t h r e s h o l d s determined  by the achromatic f i l t e r compared to normals.  f o r the MS  s u b j e c t s when  118  I I . INSTRUMENTATION  1. APPARATUS  The  Fieldmaster® Model 2 2 5 i s an a u t o m a t i c  i n i t i a l l y designed  perimeter  t o p r o v i d e t h e c l i n i c i a n w i t h t h e means  to c o n d u c t a thorough,  s t a n d a r d i z e d assessment o f a  p a t i e n t ' s v i s u a l f i e l d s . The F 2 2 5 i s equipped w i t h a D i g i t a l LSI-11  s i x t e e n - b i t computer w i t h 17 f a c t o r y - i n s t a l l e d  s t a n d a r d programs and one u s e r - d e f i n e d program. In a d d i t i o n , t h e r e i s memory c a p a c i t y f o r an a d d i t i o n a l 81 o p t i o n a l programs t h a t can be f a c t o r y programmed.  2. PHYSICAL SPECIFICATIONS  The  F 2 2 5 c o n s i s t s of an u p r i g h t h e m i s p h e r i c a l bowl, a  power s u p p l y , and a m o t o r i z e d , h e i g h t v a r i a b l e t a b l e . The bowl i s e n c l o s e d w i t h t h e LSI-11 computer and c o n t r o l p a n e l , weighing  i n t o t a l 58.1 kg. The d i m e n s i o n s o f t h e i n s t r u m e n t  a r e 8 8 . 9 cm i n l e n g t h , 6 4 . 8 cm i n w i d t h , and 119.4 cm i n h e i g h t . The power s u p p l y , d i r e c t l y under t h e t a b l e upon which t h e instrument  s i t s , weighs 28.1 kg and i s 9 1 . 4 cm by  52.1 cm by 16.5 cm. The t a b l e i t s e l f weighs 6 3 . 6 kg and i s 88.9  cm by 71.1 cm by 7 4 . 9 cm. More d e t a i l e d i n f o r m a t i o n  1 19 r e g a r d i n g the LSI-11 may  be found i n Appendix A.  The hemispheric bowl has a diameter  of 62 cm  i n c l u d e s 149 l o c a t i o n s where a stimulus may  and  be presented.  Each stimulus l o c a t i o n c o n s i s t s of the p o l i s h e d ends of 1 mm diameter  fibre optics  selectively  ( v i s u a l angle = .19°) that can  be  i l l u m i n a t e d with one achromatic and four  chromatic s t i m u l i of v a r y i n g i n t e n s i t i e s . Stimulus p o s i t i o n s w i t h i n the bowl are not i n a s e q u e n t i a l order and t h e r e f o r e when presented to a s u b j e c t they appear to be  'random'.  C o n t r o l over p r e s e n t a t i o n and bowl background are c o n t r o l l e d by the operator through the LSI-11 computer. As i s shown i n figure  18, the p o s s i b l e p o s i t i o n s that can be examined  70° h o r i z o n a t a l l y and +55° to -65°  range  vertically.  3. CONTROL FUNCTIONS  The  o p e r a t i o n of the F225 i s c o n t r o l l e d through a panel  on the s i d e of the instrument  shell  (see F i g u r e 1 8 ) ,  which  enables the r e s e a r c h e r to c o n t r o l both stimulus and background c o n d i t i o n s as w e l l as monitor  the responses of  the s u b j e c t . The c o n t r o l panel c o n s i s t s of touch  sensitive  pads and LED d i s p l a y windows f o r each c o n t r o l l a b l e The  s t i m u l u s address d i s p l a y window (#1  p r e s e n t s which stimulus p o s i t i o n  running of a standard programme), the LED f l a s h . S t i m u l i may  in Figure  18)  in the bowl i s being  presented to the s u b j e c t . During automatic  (#4) w i l l  function.  testing  (the  on the s h u t t e r key  be presented manually  by  **STIMULUS ADDRESS«|  p-ATTENTION MONITOR—|  - MANUAL-  •SENSITIVITY•  |  STIMULUS FILTERS  flB i>9  1  ^9  TESTING KTIST i o n  •ACKGROUND |—INTENSITY—|  •STIMULUS INTENSITY-  •DISPLAY-  B3 0  3 15  f—CHART —||  |—PROGRAM —j  AUTO TEST-  -TIMING-  OUIATION  INTElVAl  lRO«iajEnr.cMjF.tt&A,  ® ®  11 @  13,  14)  FIGURE 18 F225 CONTROL PANEL MODIFIED FROM THE SYNEMED FIELDMASTER F225 MANUAL (P.8)  112,  121 p r e s s i n g numbers 1 t o 149 on the input keyboard  (#14) and  then p r e s s i n g the s h u t t e r s e l e c t key (#4). When the s e l e c t e d position  i s shown on the stimulus address window (#1), the  operator  may then press the s h u t t e r key t o present the  s t i m u l u s . The s h u t t e r w i l l remain open as long as the operator  depresses the key, i . e . the stimulus w i l l be  presented  as long as the key i s depressed. I t i s extremely  important  that the operator  observes that the p o s i t i o n he  chooses i s a c t u a l l y d i s p l a y e d i n the address window. Although the s h u t t e r l i g h t  should come on when the s h u t t e r  i s open, a t times i t w i l l not; and, t h e r e f o r e , the operator should not r e l y upon the s h u t t e r l i g h t  d u r i n g automatic  t e s t i n g . I f d u r i n g t e s t i n g the s h u t t e r l i g h t  i s not on and  the subject responds, the computer w i l l a u t o m a t i c a l l y  record  the response as p o s i t i v e only i f a stimulus has indeed  been  presented.  The type of response recorded  depends upon the choice  (seen or missed)  s e l e c t e d by the operator  (#11). The  s u b j e c t s response i s shown as a s e r i e s of dashes i n the d i s p l a y window (#8). When o p e r a t i n g the perimeter should take care fifteen  manually the operator  i n t h a t , a f t e r a p e r i o d of more than  minutes of t e s t i n g , the F225 w i l l not permit the  p r e s e n t a t i o n of any more s t i m u l i and w i l l  automatically  p r i n t out r e s u l t s . Although t h i s does not occur time, i t w i l l cause the operator  a l l the  t o l o s e c o n t r o l of the  t e s t i n g s i t u a t i o n and f o r c e him t o begin a g a i n .  Discussions  with Synemed as t o why the computer o v e r r i d e s the operator  122 d u r i n g manual mode have not The  a t t e n t i o n monitor  of the eye.  The  r e s o l v e d t h i s problem. (#2)  records the general p o s i t i o n  monitor operates  on a c o r n e a l  reflection  method, compensating f o r both the c o l o u r of the p a t i e n t ' s i r i s and  background bowl luminance. A photodetector  the p o s i t i o n of the s u b j e c t ' s eye To f i x a t e the eye, chin rest u n t i l  the two  monitors  (see Appendix A ) .  the s u b j e c t  i s asked to a d j u s t  red h o r o z o n t a l  and v e r t i c a l  the  l i n e s in  the a t t e n t i o n monitor are p e r f e c t l y c r o s s e d . T h i s i s done by having  the subject p l a c e h i s head on the c h i n r e s t , with h i s  forehead  pressed  a g a i n s t the head r e s t . The  i n s t r u c t e d to adjust adjust s l i d e ,  tilt,  (or the operator and  may  s i d e clamps. The  subject  i s then  do t h i s ) the operator  should  make c e r t a i n t h a t the l a t e r a l canthus of the t e s t e d  eye  l i n e s up with the edge of the bowl. T h i s i s done to ensure that the eye e i t h e r ask  the subject to press h i s forehead  the headrest aligned  i s p r o p e r l y in the f i e l d of the bowl. I f not,  or adjust the t i l t  (see F i g u r e  Once the subject  (#2)  the l a t e r a l canthus i s  i s p r o p e r l y a l i g n e d , the a t t e n t i o n  the c r o s s e d red l i n e s and  Monitor Zero Key  against  19).  monitor i s c a l i b r a t e d by having at  until  harder  the subject f i x a t e  directly  then p r e s s i n g the A t t e n t i o n  f o r a few  seconds (a green l i g h t  on  the Zero key w i l l come on). Making c e r t a i n that the  stimulus  address window shows that p o s i t i o n one  the  operator  then presses  i s in place,  the manual s h u t t e r button  and  requests  that the s u b j e c t s h i f t s h i s gaze to the p o s i t i o n i l l u m i n a t e d  123  ALIGNMENT OF SUBJECT MODIFIED FROM THE SYNEMED FIELDMASTER F225 MANUAL (P.19)  1 24  i n the bowl ( 5 ° ) .  Immediately  press the Auto  Sensitivity  Monitor Key. T h i s causes the a t t e n t i o n monitor to be readied f o r subsequent  t e s t i n g , p e r m i t t i n g a 5 ° movement. Anything  beyond 5 ° w i l l cause an alarm t o be emitted, which  remains  on u n t i l the subject r e f i x a t e s . For s u b j e c t s who have l o s t or are unable to maintain f i x a t i o n , the operator may reset the a t t e n t i o n monitor by j u s t p r e s s i n g the a t t e n t i o n zero key. When the auto s e n s i t i v i t y monitor  monitor  key i s pressed,  a value i s shown i n the a t t e n t i o n d i s p l a y monitor. T h i s v a l u e , which v a r i e s from subject t o s u b j e c t , p r o v i d e s the operator with a b a s e l i n e from which he may e i t h e r  increase  or decrease the s e n s i t i v i t y of the a t t e n t i o n monitor to movement i n f i x a t i o n by e i t h e r p r e s s i n g the "+" or "-" (decrease) s e n s i t i v i t y keys  (increase)  respectively.  Although a 5 ° movement i s l a r g e f o r s t a t i c p e r i m e t r y , many manufacturers of automated p e r i m e t e r s (eg. Octopus) have adopted the 5 ° as an a c c e p t a b l e d e v i a t i o n d u r i n g t e s t i n g . Despite the p s y c h o p h y s i c a l dubiousness of assuming that such an a l l o w a b l e degree of movement w i l l enable the examiner  to v a l i d l y and r e l i a b l y a s s e s s r e t i n a l  at some s p e c i f i c  sensitivity  r e t i n a l e c c e n t r i c i t y , the 5 ° was probably  agreed upon due to i n s t r u m e n t a l f a c t o r s  (eg. m o n i t o r i n g  f i x a t i o n through gross techniques as c o r n e a l r e f l e c t i o n ) and subject c h a r a c t e r i s t i c s  (eg. the strenuous demand of good  f i x a t i o n and c o n c e n t r a t i o n i n standard p s y c h o p h y s i c a l paradigms).  125 The a t t e n t i o n monitor i n that  i n the F225 has s e v e r a l  problems  i t r e g i s t e r s any gross head movement or b l i n k as a  l o s s of f i x a t i o n yet permits a 5° eye movement, one makes i t d i f f i c u l t Moreover,  to e s t a b l i s h r e l i a b l e s t a t i c  as the a t t e n t i o n monitor  reflection,  which  thresholds.  r e l i e s on c o r n e a l  i t i s not p o s s i b l e to do p u r e l y  scotopic  adapation as the monitor r e q u i r e s a minimal l e v e l of The monitor illumination  f u n c t i o n s b e t t e r with higher  light.  background  (10 to 35 a s b ) .  The a t t e n t i o n monitor p r e s e n t s another problem the red f i x a t i o n  i n that  l i n e s f l a s h from time to time, which  a c c o r d i n g to Synemed was  done p u r p o s e f u l l y so as to keep the  s u b j e c t ' s a t t e n t i o n t r a i n e d onto the monitor. Although there i s no c o r r e l a t i o n between s t i m u l u s onset and f l a s h i n g of the l i n e s , s u b j e c t s do however press the response chord a c c i d e n t l y when the f i x a t i o n l i n e s f l a s h . To a v o i d problem, monitor  this  s u b j e c t s must be i n s t r u c t e d before t e s t i n g that the f l a s h e s and not to respond to i t . The  monitor may  be turned o f f by removing  attention  p i n 6 (Appendix  from i t s socket. To accomplish t h i s task, the  A)  interface  board with the three c o n n e c t o r s must be removed from the backplane  i n the instrument. T h i s w i l l  f i x a t i o n target  leave the c e n t r a l  i l l u m i n a t e d while power i s a p p l i e d to the  instrument. The a t t e n t i o n monitor w i l l never b l i n k a f t e r p i n 6 has been removed. However, the b r i g h t n e s s of the target w i l l intensity  still  remain a f u n c t i o n of the  (as i n the unmodified c o n d i t i o n ) .  fixation  background  126 4. STIMULUS CHARACTERISTICS AND  PRESENTATION  Stimulus f i l t e r s are chosen filter  key  (#3), which causes a f i l t e r  the stimulus l i g h t p o s i t i o n . The filters,  wheel to r o t a t e over  the s e l e c t e d f i l t e r  wheel c o n s i s t s of f i v e  #29  red f i l t e r  # 8 yellow f i l t e r  (XD  The  1.0),  (XD 633.73), 3) Kodak  5) Kodak Wratten  #61  #38A blue  1  XD values are presented f o r i l l u m i n a n t  stimulus l i g h t  (NDF  (XD 581.2), 4) Kodak Wratten  (XD 535.86), and  489.73).  i s in  cinemoid  which a r e : 1) a n e u t r a l d e n s i t y f i l t e r  green f i l t e r filter  source u n t i l  filter  2) Kodak Wratten Wratten  by p r e s s i n g the a p p r o p r i a t e  source i s a 16 watt  'A' as the  tungsten b u l b . The  advantages of a tungsten source are s t a b i l i t y ,  chief  continuous  s p e c t r a l output, a v a i l a b i l i t y , and high output at about 2854°K f o r i l l u m i n a n t e f f i c i e n c y due high-wattage  'A'.  to a problem  Inorder to minimize  low  of heat d i s s i p a t i o n  from  sources, the F225 u t i l i z e s a low wattage  watt) bulb. Thus the a c t u a l o p e r a t i n g temperature  (16  of the  tungsten bulb w i l l be w e l l below 3000°K. The C.I.E. c h r o m a t i c i t y c o o r d i n a t e s f o r the v a r i o u s chromatic  f i l t e r s as w e l l as t h e i r T r i s t i m u l u s values and  dominant wavelengths may  be found  illuminants  A l s o presented are the  'A' and  'C.  i n Table 8 f o r both  s p e c i f i c a t i o n s f o r i l l u m i n a n t D65, source with more u l t r a v i o l e t energy 1  XD = Dominant Wavelength  a standard l a b o r a t o r y than i l l u m i n a n t  'C.  127  TABLE 8 COLORIMETRIC SPECIFICATION OF F225 FILTERS ACHROMATIC FILTER (NDF) ILLUMINANT A C  D65  CHROMATICITY CO-ORDINATES x  455 321 323  y  .414 .332 .345  TRISTIMULUS VALUES X Y  DOMINANT WAVELENGTH  22.34 20.35 6.46 19.53 20.22 21.12 18.96 20.22 19.48  .45 ntn, 572.22 571.79  581  RED FILTER (WRATTEN #29) ILLUMINANT  CHROMATICITY CO-ORDINATES x  A C D65  709 699 699  y  289 289 290  DOMINANT WAVELENGTH  TRISTIMULUS VALUES X Y 27.25 11.11 15.50 6.41 14.88 6.18  0.08 0.25 0.23  633.73 nm, 632.91 632.49  BLUE FILTER (WRATTEN # 38A) ILLUMINANT  CHROMATICITY CO-ORDINATES x  A C D65  .215 .168 .168  y  .339 .190 .205  TRISTIMULUS VALUES X Y  Z  8.19 12.93 17.04 15.20 17.26 58.27 14.28 17.45 53.42  DOMINANT WAVELENGTH 489.73 nm. 479.31 480.44  GREEN FILTER (WRATTEN #61) ILLUMINANT  CHROMATICITY CO-ORDINATES x  A C D65  .262 .234 .228  y  .684 .688 .694  TRISTIMULUS VALUES X Y 3.88 10.15 4.17 12.26 4.16 12.65  DOMINANT WAVELENGTH Z  0.80 1.40 1.41  535.86 nm. 538.47 537.48  128 F i g u r e 20 provides the C.I.E. L o c i of the v a r i o u s for  i l l u m i n a n t 'A'.  The  each of the f i l t e r s may  r e l a t i v e t r a n s m i t t a n c e values f o r be found  i n F i g u r e 21. As can  seen from F i g u r e 21, the red f i l t e r  broad  chromatic  nm.  The  f i l t e r s , however, are r e l a t i v e l y more  (eg. the blue c o n t a i n i n g some of the  f r e q u e n c i e s ) . The achromatic absorbs  be  i s a cut o f f f i l t e r  r e s t r i c t e d to the long wavelength region beyond 600 remaining  filters  filter  (NDF)  middle t r a n s m i t s and  evenly a c r o s s the spectrum.  Attempts to p h o t o m e t r i c a l l y measure the i n t e n s i t y of the presented the c r i t i c a l  s t i m u l i have not been s u c c e s s f u l because of angle at which the measurement has to be made  with respect to the head of the f i b r e o p t i c . T h i s was prime concern  because e a r l i e r  of  r e s e a r c h with the Fieldmaster  101-PR by Johnson and K e l t n e r (1980) i n d i c a t e d that the luminance meter readings were "lower luminances by a constant  than a c t u a l stimulus  f a c t o r of 4.7."  (p.  732).  D i s c u s s i o n s with Synemed® about t h i s r e v e a l e d that F225  was  corrected for t h i s  the  (see Appendix A). Moreover, although  F225 does equate f o r luminance d i f f e r e n c e s between (see Appendix A), t h i s has yet to be photometrically. Visual, filters  filters  confirmed  s u b j e c t i v e comparison of the  does i n d i c a t e the red to be l e s s b r i g h t , i . e .  t r a n s m i t t l e s s l i g h t than the other Stimulus  intensity  filters.  i n the F225, a c c o r d i n g the the  documentation p r o v i d e d by Synemed, v a r i e s from 8.00 100,000 asb.  i n 10.00  asb. to  asb. steps (or 1 d e c i b e l s t e p s ) . The  129  FIGURE  20  C.I.E. CHROMATICITY COORDINATES FOR THE F225 CHROMATIC FILTERS  1  0.9-  A - A - A - A - A - A -  - A - A - A - A - A - A  0.8-  UJ  o ^  0.7-  0.6-  (/)  < > P  ,130.5  • / 0.4-  (3  0.3 H  -H-  0.2-  0.1X 400  - H - H-ffi-ffi-S  X  S  0  ffi^ffi-ffi-'X-B-S--S--H-E/--H-a  Legend  /  /  A  YELLOW wrotton #8  X  GREEN wrotton #61  •  RED wrotton #29  Bl BLUE wrotton #380 ffi  ACHROMATIC ncJf  A-A-A-A-A^A-X^OnD-D-O-M-D-O^Xt*E=R-S=S=S=B 450  500  550  600  650  700  WAVELENGTH nm. FIGURE  21  VALUES  OF  CO  o TRANSMITTANCE  F225  FILTERS  131 maximum i n t e n s i t y that may a c t u a l l y be obtained asb.  f o r the achromatic f i l t e r ,  i s 88,731  70,985 asb. f o r the yellow,  17,746 asb. f o r the r e d , 8,873 asb. f o r the blue, and 6,212 asb.  f o r the g r e e n . The  1  d u r a t i o n d u r i n g which a stimulus may be  presented  ranges from 100 msec, to 9.9 sec. i n .1 sec. i n t e r v a l s , and i s c o n t r o l l e d by e n t e r i n g the d e s i r e d time through the d u r a t i o n key on the c o n t r o l panel interval  (#10). I n t e r s t i m u l u s  (ISI) i s a l s o v a r i a b l e , ranging  from 100 msec, to  9.9 sec a t .1 sec. i n t e r v a l s . As with the d u r a t i o n , ISI i s c o n t r o l l e d by e n t e r i n g the d e s i r e d time with the i n t e r v a l key on the c o n t r o l panel  (#10). I t should be noted that the  ISI chosen by the operator running  i s not the a c t u a l one d u r i n g the  of a t h r e s h o l d or screening programme. The ISI  i n c r e a s e s as the d i s t a n c e between stimulus p o s i t i o n s i n c r e a s e s . For example, the examiner may choose to t e s t e i g h t l o c a t i o n s i n the s u p e r i o r n a s a l f i e l d . d e s i r e d stimulus  Once the  i n t e n s i t y , background luminance,  filter,  a t t e n t i o n monitor s e t t i n g , and stimulus d u r a t i o n and ISI has been s e l e c t e d , the F225 a u t o m a t i c a l l y begins  to t e s t the  p r e s e l e c t e d l o c a t i o n s . The ISI remains constant all  as long as  e i g h t p o s i t i o n s are being examined. When a t h r e s h o l d i s  determined f o r a given p o s i t i o n , that p o s i t i o n i s no longer 1 a p o s t i l b = 0.3183 cd/m . In experimental v i s u a l psychophysics one t r a d i t i o n a l l y r e p o r t s luminance values i n terms of c a n d e l l a s (cd/m ). However, as the m a j o r i t y of c l i n i c a l l i t e r a t u r e i n perimetry r e f e r s to luminance i n terms of a p o s t i l b s , the present study w i l l r e f e r t o a p o s t i l b s to reduce p o s s i b l e c o n f u s i o n when d i s c u s s i n g the 1iterature. 1  2  2  132  t e s t e d and, t h e r e f o r e , the ISI between the preceeding and f o l l o w i n g stimulus l o c a t i o n s i n c r e a s e s . The reason i s that stimulus l o c a t i o n  i s processed  s e q u e n t i a l l y . Even i f  a t h r e s h o l d f o r some l o c a t i o n has been determined, must s e q u e n t i a l l y run through  for this  that l o c a t i o n  the F225  (without  p r e s e n t i n g i t t o the s u b j e c t ) i n order t o reach the subsequent l o c a t i o n . Thus the g r e a t e r the number of l o c a t i o n s whose t h r e s h o l d s a l r e a d y are determined l i e between two l o c a t i o n s s t i l l  being t e s t e d , the g r e a t e r  be the ISI between the two. T h i s can be observed examiner when viewing the stimulus address control  will  by the  window on the  panel.  When a f i l t e r density f i l t e r  i s s e l e c t e d by the operator, a n e u t r a l  s i t u a t e d above the f i l t e r  wheel a u t o m a t i c a l l y  compensates f o r the change i n luminance due t o f i l t e r density  ( r e f e r t o Appendix A ) . In a d d i t i o n , a c o r r e c t i o n  factor for non-linearity  i s a p p l i e d to the stimulus  luminance a u t o m a t i c a l l y by the LSI-11. I t should be noted that high stimulus i n t e n s i t i e s unobtainable  with c e r t a i n  (above 50,000 asb) are  filters,  such as the red. I f t h i s  occurs, the stimulus i n t e n s i t y d i s p l a y (#7) w i l l s e r i e s of dashes. The  1  automatic  problem. testing lights  s t a t u s of the perimeter the proceed  button  show a  (#5) show the operator the  when being run a u t o m a t i c a l l y . When  (#12) i s pressed, the t e s t i n g auto  light  I t should be noted that any e r r o r by the operator or m a l f u n c t i o n by the F 2 2 5 w i l l r e s u l t i n dashes i n the d i s p l a y i n window q u e s t i o n . 1  133 comes on and remains on u n t i l a l l the chosen  stimulus  p o s i t i o n s have been run once, at which time the r e t e s t  light  (#5) becomes l i t i n d i c a t i n g that the p o s i t i o n s a r e to be r e t e s t e d . I f the pause key i s pressed  (#12), the perimeter  a u t o m a t i c a l l y stops t e s t i n g and remains i n a c t i v e  (idle  light  w i l l b l i n k ) u n t i l the proceed button i s pressed a g a i n . The r e s e t button a u t o m a t i c a l l y r e s e t s the perimeter to the beginning stimulus p o s i t i o n  i t began.  5. BACKGROUND LUMINANCE  Background  intensity  i n the bowl i s c o n t r o l l e d by  e n t e r i n g the d e s i r e d luminance l e v e l  on the input keyboard  and then p r e s s i n g the enter button on the background i n t e n s i t y s e c t i o n of the c o n t r o l panel (#7). The d e s i r e d level  w i l l be r e g i s t e r e d i n the background i n t e n s i t y  display  (#6).  I f an e r r o r has o c c u r r e d , dashes w i l l appear i n the  d i s p l a y and the operator w i l l have to reenter the background v a l u e . I f the dashes s t i l l  appear, the background  illuminant  w i l l have to be r e p l a c e d . The i l l u m i n a n t 211-2  f o r the background i s a General E l e c t r i c  bulb. The background bowl luminantion may be s e t  anywhere from 5 asb to 45 asb (1.59 cd/m Bowl l u m i n a t i o n  2  to 14.32 cd/m ). 2  i s c o n s t a n t l y monitored and a d j u s t e d during  t e s t i n g by a photodiode (Appendix A ) . As mentioned  earlier,  bowl luminantion f o r the a t t e n t i o n monitor i s best between 10 and 35 a p o s t i l b s . An attempt was made to disengage the  134 background i l l u m i n a n t so that  f u l l y scotopic  thresholds  c o u l d be o b t a i n e d . U n f o r t u n a t e l y t h i s was u n s u c c e s s f u l i n that the stimulus l i g h t  source (a tungsten bulb) i l l u m i n a t e s  the i n s i d e back of the bowl, c a u s i n g a l l of the 149 stimulus p o s i t i o n s to appear b r i g h t background  i n c o n t r a s t w i t h the darkened  bowl.  Photometric measurements of bowl luminance conducted with a Spectra® Pritchard®  was  Photomter Model  1980A.  Measurements were conducted 2 meters from the bowl with a 6 minute measuring f i e l d . Three measurements each were done for 20 bowl p o s i t i o n s under 8 background luminances. The background luminances were: 1) 2 asb., 2) 5 asb., 3) 10 asb., 4) 15 asb., 5) 30 asb., 6) 45 asb., 7) 50 asb., and 8) 45 asb. F i g u r e 22 shows the photometric r e s u l t s i n l o g a p o s t i l b s u n i t s f o r 5 asb., 10 asb., 15 asb., 30 asb., 45 asb., and 50 asb. R e s u l t s f o r the 2 and 55 asb. c o n d i t i o n s were not i n c l u d e d as they d i d not d i f f e r  from the 5 and 50  asb. c o n d i t i o n s r e s p e c t i v e l y . The a c t u a l values f o r a l l e i g h t c o n d i t i o n s may The  be found i n Appendix  B.  1 to 20 p o s i t i o n s found i n F i g u r e 23 represent the  p o i n t s measured  i n the bowl, as shown i n F i g u r e  23.  P o s i t i o n s 9 to 20 represent the 15° - 195° m e r i d i a n . As can be seen i n F i g u r e 22, t h i s region i s r e l a t i v e  consistent  with r e s p e c t to background luminance. The nasal p o s i t i o n of the bowl  (13 - 15) i s s l i g h t l y darker than the temporal  r e g i o n . However, as the d i f f e r e n c e i s l e s s than a l o g u n i t , the lower luminance l e v e l  i s not s e r i o u s . The luminance i s  < O Q  O  Z <  z  D  21.91.81.71.61.51.41.31.21.110.90.80.70.60.5 0.4 0.3 0.2 0.10 -0.1 -0.2 -0.3 -0.4 -0.5 -0.6 -0.7 -0.8 -0.9 -1 -1.1 -1.2 -1.3 -1.4 -1.5  -n—n ta—ta-  -ta—si- -Ei—si- -ta—ta — t a — t a — B — t a - gj  -ia—EL  _ X — X — X — - X — X ~  A —  A  X  X - - X - - X - - X - - X - - X  -  — A — A — — - A  A  A-  Legend  T 2  -r3  -r 5  -r6  T 8  9  -r—  ~r-  10  11  I  I  12  13  BOWL POSITION  —r14  i  15  16  FIGURE 22 BOWL POSITION AND BACKGROUND LUMINANCE (FOR BOWL POSITION REFER TO FIGURE 23)  17  18  I  1  19  20  A  5 ASB.  X  10 ASB.  D  15 ASB.  El  30 ASB.  H  49 ASB. _  M  50 ASB.  FIGURE 23 BOWL POSITIONS MEASURED BY THE PRITCHARD PHOTOMETER  1 37 g r e a t l y reduced  at the p o i n t of f i x a t i o n  (position 5),  i n d i c a t i n g , c o n t r a r y to the manual, the f i x a t i o n c r o s s h a i r s are not c o r r e c t l y a d j u s t e d  f o r background luminance. T h i s  c o n t r a s t d i f f e r e n c e i n luminance may e f f e c t the determination  of t h r e s h o l d s , but s i n c e no p o i n t i s t e s t e d  with 5°s of t h i s area  i t may not be of consequence.  U n f o r t u n a t e l y , there i s no way of overcoming t h i s problem given the p h y s i c a l c o n f i g u r a t i o n of the bowl.  6. THRESHOLD ESTIMATION  Both s u p r a t h r e s h o l d and t h r e s h o l d p r o f i l e s may be obtained with the F225. A d d i t i o n a l programmes may be s t o r e d in the computer  (#13 on the d i s p l a y p a n e l ) . Ten standard  programmes are a v a i l a b l e f o r determining  s u p r a t h r e s h o l d s at  v a r i o u s l o c a t i o n s i n the v i s u a l  f i e l d . The programmes, shown  in the programme d i s p l a y window  (#9), i n c l u d e an  of  the f u l l v i s u a l f i e l d  examination  (149 p o s i t i o n s ) , a c e n t r a l 30°, a  glaucoma screen, a c e n t r a l - c e c a l , as w e l l as a t e s t of the macula. Appendix C c o n t a i n s the l o c a t i o n s f o r these and other programmes. The a c t u a l s u p r a t h r e s h o l d s a r e p r i n t e d i n terms of i s o p t e r s s i m i l a r t o that of the Goldmann. R e s u l t s may be presented  as i n d i c a t i n g at which i n t e n s i t y the  s t i m u l i were seen or not seen. Suprathresholds  are based upon s i n g l e p r e s e n t a t i o n of a  stimulus at some given l o c a t i o n computer i n the perimeter  ( i . e . e c c e n t r i c i t y ) . The DEC  s t o r e s the s u b j e c t ' s responses and  138 l a t e r p r i n t s out the values upon completion of the examination. As noted by Anderson suprathreshold testing  (1985), t h i s type of  is primarily  d e t e c t i n g and e s t a b l i s h i n g  adequate  for rapidly  types of v i s u a l f i e l d  defects.  The procedure, however, n e i t h e r permits the c l i n i c i a n to establish  the d e n s i t y of the d e f e c t nor allows him to  compensate f o r changes i n r e t i n a l s e n s i t i v i t y due to eccentricity may  ( M i l l s , 1985). Moreover, p e r i m e t r i c  be inadequate  assessment  f o r a given s u b j e c t i n that the  s u p r a t h r e s h o l d value (eg. 50 asb.) chosen may  not be optimal  for that s u b j e c t . Synemed® p r o v i d e s three t h r e s h o l d i n g procedures to t r y to overcome the above problems.  The  first,  t e s t i n g , a l l o w s the examiner to determine  threshold the  initial  i n t e n s i t y by predetermining the s u b j e c t ' s a c t u a l at some given l o c a t i o n . T h i s i n t e n s i t y determine The  related  threshold  i s then used to  the s u p r a t h r e s h o l d p r o f i l e . second procedure a v a i l a b l e  i s what Synemed®  refers  to as contour p e r i m e t r y . T h i s procedure, more c o r r e c t l y referred  to by M i l l s (1985) and Anderson  " e c c e n t r i c i t y compensated" t e s t i n g , adjustment stimuli  of stimulus i n t e n s i t y  (1985) as  i n v o l v e s the automatic  for eccentricity, i . e . ,  i n the p e r i p h e r y are presented at a higher  than s t i m u l i presented  intensity  centrally.  The F225 has four contour programmes (see Appendix D), each d i f f e r i n g as to the " m u l t i p l i c a t i o n compensate the luminance  l e v e l . The  factor"  greater the  used to  139 " m u l t i p l i c a t i o n f a c t o r " , the more the luminance  level i s  c o r r e c t e d f o r change i n e c c e n t r i c i t y . The f o u r t h contour programme  (programme #4) i s the most d e s i r a b l e as i t i s the  most s e n s i t i v e to e c c e n t r i c i t y , thus reducing examination time q u i t e a p p r e c i a b l y . Each of the four contour programmes may be run i n c o n j u n c t i o n with any of the F225 s u p r a t h r e s h o l d or t h r e s h o l d programmes a v a i l a b l e  (except f o r programme  #10 on the  macula). Work with the v a r i o u s programmes has l e d t o the c o n c l u s i o n that contour programme  #4 should be used whenever  possible. The t h i r d s u p r a t h r e s h o l d i n g procedure used by Synemed® i s r e f e r r e d to by M i l l s The procedure  (1985) as "defect d e n s i t y "  testing.  i n v o l v e s s t a r t i n g a t some predetermined  suprathreshold l e v e l  (eg. 50 asb.) and, when not seen by the  s u b j e c t , i n c r e a s i n g the i n t e n s i t y u n t i l  i t i s seen. R e s u l t s  p r o v i d e the examiner with a crude r e c o r d of the p o s s i b l e d e n s i t y of a d e t e c t e d d e f e c t . The p r o f i l e of the d e f e c t i s crude i n that the e c c e n t r i c i t y one can t e s t problem  i s limited. This  occurs i n both f i b r e o p t i c perimeters (eg. the  F i e l d m a s t e r F225) and LED perimeters (eg. the Dicon 2000 or the F i e l d m a s t e r 50). Apart from s u p r a t h r e s h o l d examination, the F225 a l s o p r o v i d e s f o r assessment a t the t h r e s h o l d l e v e l .  Four  meridonal p r o f i l e s are a v a i l a b l e , and these a r e : 1) 105 285°, 2) 75 -255°, 3) 165 - 345°, and 4) 15 - 195°. The a c t u a l s t i m u l u s l o c a t i o n s f o r these four p r o f i l e s may be  140  found  i n Appendix E. I t should be noted  that n e i t h e r of  four t h r e s h o l d programmes exceeds 4 0 ° . According  the  to  Synemed®, the programmes were r e s t r i c t e d to 4 0 ° i n order shorten t e s t i n g time as SYNEMED® "found beyond 4 0 ° was 19,  1 9 8 2 ) .  that the  information  not needed." (personal communication, J u l y  Whereas l i m i t i n g the examination  appropriate for c l i n i c a l  r e s e a r c h s i n c e one  to  40°  may  be  s c r e e n i n g , i t i s of great  importance to go beyond t h i s e c c e n t r i c i t y  be  to  in  experimental  does not know whether an abnormality  i n the p e r i p h e r y or c e n t r a l regions of the v i s u a l In a d d i t i o n to the above four meridonal  may  field.  thresholds, a  user d e f i n e d programme (programme # 9 9 ) provided by Synemed® enables  the examiner to determine a t h r e s h o l d f o r a s p e c i f i c  i n the p e r i m e t r i c bowl. Programme # 9 9 , however, i s  point  limited  i n the number of stimulus l o c a t i o n s that may  assessed  be  during a s i n g l e t e s t i n g s e s s i o n .  Thresholds  are determined through a b r a c k e t i n g  s t a i r c a s e method. The  a l g o r i t h m , shown in F i g u r e 2 4 ,  i n v o l v e s the i n i t i a l p r e s e n t a t i o n of a stimulus at some p r e - s e l e c t e d l e v e l of i n t e n s i t y . The  subject's  based upon p r e s s i n g or not p r e s s i n g a button chord,  i s t e m p o r a r i l y s t o r e d by the DEC  the presented next  stimulus l e v e l . The  F 2 2 5  response,  on a response  computer along  with  then proceeds to the  stimulus p o s i t i o n , s t o r i n g the i n t e n s i t y value  with the s u b j e c t ' s response (button pressed or not  along pressed).  When a l l of the stimulus l o c a t i o n s have been t e s t e d once, the  F 2 2 5  r e t u r n s to the stimulus l o c a t i o n s i t i n i t i a l l y  PRESENT STIMULUS  FIGURE 2 4 THRESHOLD TESTING ALGORITHM  I—»  142 began with and  commences to r e t e s t  Depending upon the intensity w i l l either o r i g i n a l test  a l l the  s u b j e c t ' s response, the  be  10.00  asb.  higher or  recorded and  the  intensity  i f a subject saw at 76 asb., be  78 asb.  the  are  computed. A  twice p r i o r to c a l c u l a t i o n . The  stimulus was  average of the seen with the  a stimulus 15°  intensity  level a  l e v e l i t was  nasally  at 80  actual  not.  asb.  f i n a l t h r e s h o l d f o r that' e c c e n t r i c i t y  Thresholds may  be  l e v e l at which the  found through e i t h e r  examiner commences  P i l o t work with the r e v e a l e d two  asb. large  for increasing when t e s t i n g Secondly, and  method used by  the  i n the  more s e r i o u s l y ,  monitor t e m p o r a r i l y h a l t s  month  algorithm  v i s u a l steps of  the  bracketing  t h r e s h o l d a l g o r i t h m . When  or movement i n f i x a t i o n , the  i n c r e a s e s the  eight  10.00 is  too  staircase  F225 i s i n a p p r o p r i a t e because of a  attention  that  intensity  fovea.  f a u l t i n the  assumes that  would  the  or d e c r e a s i n g stimulus i n t e n s i t y  technical  blink  initial  major f a u l t s with such an the  not  testing.  F225 over an  for computing t h r e s h o l d s . F i r s t ,  Thus,  and  ascending or descending method depending upon the  p e r i o d has  and  s u b j e c t to miss a stimulus at a  t h r e s h o l d value i s the specific  level  the  e n t i r e process i s  repeated u n t i l t h r e s h o l d s for a l l l o c a t i o n s t h r e s h o l d r e q u i r e s the  retest  lower than  i n t e n s i t y . Again, both i n t e n s i t y  s u b j e c t response are  specific  points.  i n t e n s i t y was  t e s t i n g because of a DEC  "not  i n t e n s i t y d u r i n g the  the  computer seen" and  incorrectly therefore  r e t e s t phase. Instead of  143  retesting  that l o c a t i o n  increased i n t e n s i t y  with the same i n t e n s i t y , the  falsely raises  As a t h r e s h o l d i s c a l c u l a t e d intensity  the s u b j e c t ' s  a f t e r not seeing a given  l e v e l twice, t h i s lack of r e t e s t i n g  missed i n t e n s i t y  threshold.  i s not s e r i o u s among those  a falsely  subjects  good or moderate f i x a t i o n . I t does become problematic s u b j e c t s with poor f i x a t i o n or those who b l i n k P r e s e n t l y , one can only exclude as they  w i l l have a r t i f i c a l l y  among  excessively.  such s u b j e c t s from  raised  with  thresholds. A  testing solution  to the probelm i s to provide one's own a l g o r i t h m based upon retesting  of missed p o i n t s and smaller  i n c r e a s e s and  decreases i n i n t e n s i t y . As the DEC does not permit flexibility  i n programming, one w i l l have to i n t e r f a c e the  F225 with a p e r s o n a l computer capable various  such  f u n c t i o n s of the perimeter.  how the i n t e r f a c e  should  be done.  of c o n t r o l l i n g the  Appendix F b r i e f l y l i s t s  144 7. INSTRUMENTAL MODIFICATIONS  As shown i n F i g u r e 25 from the F i e l d m a s t e r Synemed® c l a i m s that the F225 was capable meridian  brochure,  of p r o v i d i n g four  t h r e s h o l d p r o f i l e c u t s up to 70° e c c e n t r i c i t y  both  n a s a l l y and t e m p o r a l l y . Moreover the luminance t h r e s h o l d f o r the fovea  (0° e c c e n t r i c i t y ) was shown to be about 3 asb.  ( A I / I ) , p r o v i d i n g one an e x c e l l e n t cone p r o f i l e . When replicated,  i t was d i s c o v e r e d that the t h r e s h o l d s d i d not  exceed 40° e c c e n t r i c i t y , that the i n i t i a l  threshold  luminance was set at 50 asb., that the AI/I value d i d not approach 3 asb., and that t h r e s h o l d s were unobtainable f o r any  of the chromatic  f i l t e r s other than  in suprathreshold  t e s t i n g . F i g u r e 26 p r o v i d e s an example of our r e s u l t s when t r y i n g to r e p l i c a t e Synemed's®. Contact  with the company  r e v e a l e d that the F225 a c t u a l l y d i d not provide t h r e s h o l d p r o f i l e s as they  i m p l i e d i n F i g u r e 25 and that the f i g u r e  was only an i d e a l i z e d v e r s i o n of what they perimeter  intended  their  to do i n the f u t u r e .  As the above problems rendered  the perimeter  u s e l e s s f o r r e s e a r c h , the V i s u a l Laboratory  virtually  entered a long  p e r i o d of i n t e r a c t i o n between Synemed® of C a l i f o r n i a , U.S.A. and  their  r e p r e s e n t a t i v e s i n Canada, C a r l Z e i s s Canada L t d .  A f t e r eighteen months of r e p e a t e d l y modifying  the  instrument,  we were able to have the F225 do the f o l l o w i n g :  1.  s t i m u l i as low as 8 asb. (we were never a b l e to  Present  go lower than  t h i s due to a programming problem with  145  1 -j i  10-  70  55  40  30 25  15  5  0 5'  15 =25 30 40  55 70  ECCENTRICITY  FIGURE 25 STATIC THRESHOLD PROFILE PROVIDED BY THE FIELDMASTER F225 SALES BROCHURE (MODIFIED FROM THE SYNEMED FIELDMASTER BROCHURE)  FIGURE 26 REPLICATED FIELDMASTER  F225 THRESHOLD PROFILE  147 Synemed®). 2.  Conduct t h r e s h o l d t e s t i n g up to 70° e c c e n t r i c i t y  both  n a s a l l y and temporally on a h o r i z o n t a l m e r i d i a n . 3.  Obtain t h r e s h o l d s f o r the v a r i o u s chromatic with assurances  4.  stimuli,  that they were p h o t o m e t r i c a l l y equated.  To be a b l e to programme any l o c a t i o n i n the bowl t o be examined f o r t h r e s h o l d s e n s i t i v i t y .  D e s p i t e these m o d i f i c a t i o n s t o the perimeter, the f o l l o w i n g problems s t i l l 1.  exist:  Maximum stimulus i n t e n s i t y must be s e t at a lower  level  than the perimeter  from  i s capable of a c h i e v i n g . Apart  reducing t e s t i n g time f o r determining a p r o f i l e , the major reason  f o r doing so i s that a f t e r about  minutes of continuous  fifteen  t e s t i n g the machine s t a l l s and  never c o n t i n u e s the t e s t . Indeed, upon s t a l l i n g , the examiner l o s e s a l l the data that has been s t o r e d up to that time. The reason  f o r the s t a l l i n g  a l g o r i t h m i s attempting i n t e n s i t y to a l e v e l  i s that the  to i n c r e a s e the s t i m u l u s  i t can never  reach, causing the  perimeter to i n t e r r u p t t e s t i n g . By s e t t i n g the i n t e n s i t y to some l e v e l below i t s maximum p r i o r to t e s t i n g , one a v o i d s the problem of s t a l l i n g and the eventual l o s s of data. 2.  T h r e s h o l d data i s presented  i n graphic form o n l y . To  o b t a i n the a c t u a l t h r e s h o l d one must i n t e r p o l a t e the graph with a p p r o p r i a t e adjustments l a t e r ) . Although  from  (to be d i s c u s s e d  the p r i n t o u t does provide one with an  1 48 index  of r e l i a b i l i t y  ( r a t i o of c o r r e c t l y seen p o i n t s  over the number presented), intensity level,  i n d i v i d u a l data  regarding  subject response, and eye movement f o r  each stimulus p o s i t i o n throughout the t e s t i n g s e s s i o n i s not p r o v i d e d . To o b t a i n the data, one w i l l to  be r e q u i r e d  i n t e r f a c e the LSI-11 to another computer which  will  r e t r i e v e and s t o r e the r e l e v a n t i n f o r m a t i o n . P r e s e n t l y , final  t h r e s h o l d values are o b t a i n a b l e by connecting a  t e r m i n a l v i a a RS232-C to the perimeter the i n f o r m a t i o n through ODT ODT provides  and a c c e s s i n g  ( O c t a l Debugging  two sets of o c t a l values  not seen), which must be transformed  Technique).  ( l e v e l seen and i n t o the d e c i b e l  system p r i o r t o computation of the t h r e s h o l d values (see Appendix F ) . 3.  D i s t r a c t i o n of s u b j e c t ' s by the f l a s h i n g a t t e n t i o n monitor and l a c k of repeat monitor t e m p o r a r i l y During  stops  t e s t i n g when the a t t e n t i o n testing.  the m o d i f i c a t i o n s to the perimeter,  v i s u a l l y normal s u b j e c t s  three  (mean age of 20.3 years) with 20/20  a c u i t y or b e t t e r and no known h i s t o r y of r e t i n a l were r e p e a t e d l y E).  pathology  t e s t e d with programmes #11 and 14 (Appendix  T e s t i n g was done under a v a r i e t y of background and  stimulus c o n d i t i o n s . O v e r a l l r e l i a b i l i t y detection  i n terms of  ( c o r r e c t i d e n t i f i c a t i o n of a stimulus)  the achromatic s t i m u l u s ,  was .93 f o r  .91 f o r the red and green, .90 f o r  the blue, and .83 f o r the y e l l o w . The r a t e s a r e comparable to  those  reported  f o r other  f i b r e o p t i c perimeters  provided  149 by Synemed®  (eg. Johnson & K e l t n e r ,  Steinhauser & K r i e g l s t e i n ,  1982).  1980a, 1980b; Gramer,  150  I I I . PILOT STUDY  1. PURPOSE The purpose of the p i l o t or  study was to determine whether  not the m o d i f i c a t i o n s t o the perimeter, d i s c u s s e d  i n the  p r e v i o u s s e c t i o n , would permit one to conduct an assessement of  retinal  t h r e s h o l d s among MS p a t i e n t s under low (5 asb.)  and h i g h (45 asb.) background red,  and blue  luminance  f o r the a c h r o m a t i c ,  filters.  2. SUBJECTS  Subjects c o n s i s t e d of one probable (male) and f i v e clinically definite Clinic  (females) MS p a t i e n t s r e f e r r e d by the MS  i n the Acute Care Unit of the H e a l t h S c i e n c e s Centre  H o s p i t a l at the U n i v e r s i t y of B r i t i s h Columbia.  Seven  a d d i t i o n a l p a t i e n t s were excluded because of e i t h e r the presence of a l a r g e c e n t r a l scotoma  1  or s p a s t i c movements  making i t impossible t o p o s i t i o n the head and respond. The mean age of the p a t i e n t s was 34.3 years (a = 11.4). The average d i s e a s e d u r a t i o n from the time of diagnosed onset was 12.33 years (a = 12.53). Four of the s u b j e c t s had a h i s t o r y of o p t i c  neuritis.  The F i e l d m a s t e r ® F225 cannot be used r e l i a b l y with p a t i e n t s whose scotoma i n c l u d e the fovea and exceed 5°'s temporally or n a s a l l y . 1  151 3. METHOD  Subjects were preadapted f o r ten minutes under 5 asb. and  45 asb. background luminance c o n d i t i o n s p r i o r to  testing.  The order of the background p r e a d a p t a t i o n  condition  was randomized a c r o s s s u b j e c t s . T e s t i n g , i n the case of o p t i c n e u r i t i s , was done with the a f f e c t e d eye. F o l l o w i n g a p r a c t i c e s e s s i o n to f a m i l i a r i z e  them with  the task, s u b j e c t s were t e s t e d with programme #98 r e c t a n g l e s found i n F i g u r e 27) to determine thresholds  f o r a 15° - 195° m e r i d i a n .  (dark  relative  Eccentricities  examined ranged from 40° n a s a l l y t o 70° temporally. meridian  was chosen because i t p r o v i d e d  eccentricities  near to the t r a d i t i o n a l  the most 0 - 180° meridian  p r o f i l e done i n p e r i m e t r i c r e s e a r c h . Thresholds e s t a b l i s h e d f o r the achromatic,  r e d , and blue  order of p r e s e n t a t i o n of the f i l t e r s background c o n d i t i o n f o r every Foveal  thresholds  completing  thresholds subject  at  subject.  the 15° - 195° meridian  filters,  with  separately  p r o f i l e s . The  f o r the fovea were e s t a b l i s h e d by having the  f i x a t e at a p o i n t 5° n a s a l l y i n the bowl. F i x a t i o n  to normal f i x a t i o n  the a t t e n t i o n monitor  (fixation  the f i x a t i o n t a r g e t ) . Thresholds  repeated  The  was randomized f o r each  f o r each of the three  c o u l d be monitored by a c t i v a t i n g similar  were  filters.  t h e i r p r e s e n t a t i o n randomized, were determined after  This  set at 5° rather than were determined by the  p r e s e n t a t i o n of v a r i o u s i n t e n s i t i e s at that s i n g l e  FIGURE 27  153 5° p o i n t . The  a c t u a l p r e s e n t a t i o n was  automatic and  by programming the LSI-11 as d i s c u s s e d  achieved  i n the Synemed®  manual. There were two achromatic,  reasons f o r l i m i t i n g t e s t i n g to only  red, and blue f i l t e r s . F i r s t ,  i n d i c a t e d that the short (i.e.  ( i . e . blue) and  red) are the most important  spectrum to assess  research  regions of the  visual  f u n c t i o n a l l o s s in the cone system.  background c o n d i t i o n s was  under  and  even for a t r a i n e d s u b j e c t .  The filter  stimulus d u r a t i o n f o r the p r e s e n t a t i o n of each  was  200  msec, (nearest to the IPS  125 m s e c ) . I n t e r s t i m u l u s recommended). Thresholds p r i n t e r and  i n t e r v a l was  recommendation of  800  msec. (Synemed®  were p r i n t e d by a thermal graph  the a c t u a l values were i n t e r p o l a t e d from an  o v e r l a i d graph. Each t h r e s h o l d had  to be s c a l e d a c c o r d i n g  the region of the graph on which they were found. Table provide a VDT  the  three hours. Any a d d i t i o n a l  f i l t e r s would have made the t e s t i n g more d i f f i c u l t tiring  has  long wavelengths  Secondly, the t e s t i n g time for the three f i l t e r s two  the  the s c a l a r values  4. RESULTS AND  that the procedure of  s c a l i n g were c o r r e c t .  DISCUSSION  R e s u l t s are only presented background c o n d i t i o n . The  9  r e q u i r e d . Subsequent i n t e r f a c e of  to the LSI-11 confirmed  i n t e r p o l a t i o n and  to  f o r the low  5 asb.  45 asb. c o n d i t i o n w i l l  be  TABLE 9 SCALAR VALUES FOR OBTAINING THRESHOLDS THRESHOLD POSITION (Y CO-ORDINATE) 5 8 14 23 39 65 108 180 300 500 834  TO TO TO TO TO TO TO TO TO TO TO  8 14 23 39 65 108 180 300 500 834 1000  SCALAR VALUE 0.33 0.67 1 .00 1 .78 2.89 4.78 8.00 13.33 22.22 37. 1 1 18.44  155 discussed  l a t e r . Table  achromatic,  10 p r o v i d e s  blue, and red f i l t e r s  the means and a's f o r the f o r the v a r i o u s  e c c e n t r i c i t i e s . F i g u r e 28 shows the l o g s e n s i t i v i t y gradients  f o r each of the r e s p e c t i v e f i l t e r s . The o v e r a l l  reliability The  ( c o r r e c t responses) was never below .90.  r e s u l t s i n d i c a t e d t h a t the lowest  i n t e n s i t y that c o u l d be presented  stimulus  was 8 asb. I t i s apparent,  t h e r e f o r e , that the 5 asb. background does not permit e s t a b l i s h the r e l a t i v e t h r e s h o l d s the  field  f o r the c e n t r a l region of  (15° n a s a l to 10° temporal).  s u b j e c t s reached the lower l i m i t  More importantly, the  of the stimulus  intensity  (8 asb.) w i t h i n t h i s c e n t r a l r e g i o n . T e s t i n g with normal s u b j e c t s l e d t o s i m i l a r lower l i m i t  extended i t s e l f  one t o  visually  f i n d i n g s except that the  f u r t h e r from the fovea  than  among the MS p a t i e n t s . R e s u l t s f o r a s i n g l e normal subject may be found i n F i g u r e 29. The  l i m i t a t i o n of the perimeter  to present  stimuli  lower than 8 asb. g r e a t l y e f f e c t s any examination of f o v e a l f u n c t i o n i n g . P e r i m e t r i c r e s e a r c h on f o v e a l f u n c t i o n i n g t y p i c a l l y has found the 0° e c c e n t r i c i t y , under  photopic  c o n d i t i o n s , to have a t h r e s h o l d l e s s than 1 cd/m upon the stimulus incremental  2  depending  (eg Lakowski & Dunn, 1980). Moreover,  steps f o r a s s e s s i n g f o v e a l s e n s i t i v i t y are  g e n e r a l l y at .10 l o g u n i t s t e p s . With respect to the F225, n e i t h e r the machine l i m i t of 8 asb. nor the l a r g e incremental assessment.  steps of 10 asb. permit  accurate  foveal  TABLE 10 THRESHOLD VALUES (APOSTILB) FOR MS PATIENTS BY ECCENTRICITY AND FILTER FOR A 5 APOSTILB BACKGROUND ACHROMATIC  RED  ECCENTRICITY  MEAN  S.D  MEAN  NASAL 40 30 20 15 10 5  93. 10 40. 55 31 .39 27. 63 12. 02 9.07  76,. 5 1 9,.26 1 8 . .94 20,.17 1 ,.90  8. 00 8. 00 16. 45 40. 16 23. 17 17. 88 40. 16 59. 10  FOVEA 0 TEMPORAL 5 10 20 30 40 55 70  BLUE S.D  MEAN  139..14 59..23 120..10 34..75 18..17 14.. 5 1  44..69 0..10 77..92 1 .00 . 14..38 6..36  302..03 99,.50 48..98 8..00 8..84 8..00  405 .92 1 13.84 57 .95 0 .00 1 .19 0 .00  0,.00  8..00  0..00  8..00  0 .00  0,.00 3,.46 31 .06 , 7,.31 5,.83 31 .06 , 43..50  8..00 19..50 45..34 41 .09 . 55..34 71 .47 . 140.,80  0..00 2..12 27..81 39..22 40..70 24..66 46.,39  8..00 14.,80 37..70 37..70 20.,95 38..89 .99 1 54.  0 .00 9 .62 42 .00 42 .00 2 .76 43 .69 193 .73  1 ,. 5 1  S.D.  ///  A'  X  r  ~ ^ r  <»  i  1  JO  1 1 1 1 1 1 1 1 1 1 20  15  10  5  0  5 10 20 ECCENTRICITY  1—-i  1 1 1  SO  40  i 55  FIGURE 28 SENSITIVITY GRADIENTS FOR MS SUBJECTS AT 5 APOSTILB BACKGROUND  —  r  V  Legend A  f~i  r—'  n  i  '  i  i — ' — i — i — i — i — i — i  -40  30  20  '5  <0  9  0  5  10 20 ECCENTRICITY  30  1 40  1  1  1  1  55  ACHROMATIC  1 1 70  FIGURE 29 SENSITIVITY GRADIENTS FOR A NORMAL SUBJECT AT 5 APOSTILB BACKGROUND  ,  »  159 5. MODIFICATION  TO ADAPTATION  In an attempt to approach the q u e s t i o n of a d a p t a t i o n , 6 v o l u n t e e r MS s u b j e c t s agreed t o p a r t i c i p a t e i n a m o d i f i c a t i o n of the experimental procedure which allowed the s u b j e c t s to become readapted at a lower l i g h t  level  (below  45 a s b . ) . T h r e s h o l d s were determined f o r the 0° e c c e n t r i c i t y both a u t o m a t i c a l l y and manually. In the automated determined as o u t l i n e d  mode, f o v e a l t h r e s h o l d s were i n the method s e c t i o n of the P i l o t  Study. In the manual mode, s u b j e c t s were i n s t r u c t e d to f i r s t adapt to the 45 asb. background  f o r ten minutes, a f t e r  they were presented with a stimulus below background (40 a s b . ) . The s u b j e c t s were then asked to c l o s e  which  level  their  examined eye f o r a p e r i o d of 2 minutes and not t o reopen i t u n t i l asked. E a r l i e r attempts with s h o r t e r time p e r i o d s had shown that a d a p t a t i o n was not complete. When i n s t r u c t e d t o reopen the eye, the subject ( h i m / h e r s e l f ) at the 0° e c c e n t r i c i t y again and was with e i t h e r a higher or lower s t i m u l u s i n t e n s i t y .  fixated retested  Testing  always o c c u r r e d with a 45 asb. background. The procedure was repeated u n t i l a f o v e a l t h r e s h o l d was o b t a i n e d . A f t e r adapting by c l o s i n g  the eye, t h r e s h o l d s were  obtained through the descending method of l i m i t s . Catch t r i a l s of a s k i n g the s u b j e c t s t o open h i s / h e r eye and not p r e s e n t i n g a stimulus were randomly s e s s i o n . Because  of time c o n s t r a i n t s  i n s e r t e d i n each t e s t (an a d d i t i o n a l  average  160 of 20 minutes t o the a l r e a d y  3 hour p e r i o d ) , only  c o u l d be examined f o r each s u b j e c t — e x c e p t  1 filter  f o r 1 subject who  agreed t o 2 t e s t i n g s . The in Table  r e s u l t s f o r the 2 t e s t i n g c o n d i t i o n s a r e presented 11. A l l of the f o v e a l t h r e s h o l d s , except f o r 1  s u b j e c t , c o u l d be reduced to a lower l e v e l from that initially  determined i n the automatic mode. A dependent  «-test between the automatic and manual, 2 minute re-adaptation was  phase revealed that the decrease i n t h r e s h o l d  significant  (t = 2 . 37 ,df = 6, p_=.05). Because of the small  sample, no comparisons c o u l d be made of the 3 f i l t e r s and the e f f e c t changes i n adaptation When the 2 minute adaptation  had on them. was t r i e d on normals,  there was no d i f f e r e n c e at a l l between the automated and manual mode. In both s i t u a t i o n s , the normals reached the intensity  l i m i t of the perimeter  (8 asb.),  i . e . they reached  the l i m i t of the machine. To examine whether or not the drop i n f o v e a l t h r e s h o l d a f t e r the 2 minute adaptation change i n adaptation  and not r e s t ( f a t i g u e i s known to play  a major r o l e i n p s y c h o h p y s i c a l 3 p a t i e n t s were repeatedly eccentricities  p e r i o d was a c t u a l l y due to a  examinations of MS p a t i e n t s ) ,  t e s t e d at 2 temporal  (30° and 40°) with an achromatic stimulus f o r  a p e r i o d of 30 minutes with no r e s t . The 2 temporal e c c e n t r i c i t i e s were chosen as there was l e s s chance of f i n d i n g a scotoma at those p o s i t i o n s . A dependent J - t e s t between the i n i t i a l  t h r e s h o l d and t h r e s h o l d at the l a s t  TABLE 11 FOVEAL THRESHOLD VALUES (APOSTILB) FOR MS PATIENTS DURING ADAPATATION  SUBJECT M.P. P.P. R.C. L.B. T.M. S.E.  ACHROMATIC  RED  BLUE  NORMAL ADAPTED*  NORMAL ADAPTED  NORMAL ADAPTED  28.34 8.00 14.00 28.34  36.35 -  8.00 8.00 8.00 8.00  Note: * - 2 MINUTE ADAPTATION CHANGE  8.00 -  8.00  8.00  70.74  8.00  162 t e s t i n g r e v e a l e d no s i g n i f i c a n t d i f f e r e n c e P>.05) between the f i r s t 40°  (t=-0.29, df = 2,  and  and  l a s t t e s t at 30° as w e l l as at  2 >.05). The mean t h r e s h o l d at 40°  226.83 asb. f o r the f i r s t Similarily,  (t=-3.57, DF=2,  t e s t and  250.20 f o r the  the f i r s t mean t h r e s h o l d f o r 30° was  249.76 asb. f o r the l a s t .  then one would have expected  was  last. 168.00 asb.  If f a t i g u e d i d p l a y a r o l e the t h r e s h o l d s to have become  s i g n i f i c a n t l y worse, i . e . become higher over time. According to  the means, there was  an  i n c r e a s e i n the t h r e s h o l d s over  repeated t e s t i n g . However, the l a c k of a s i g n i f i c a n t d i f f e r e n c e i n the repeated t e s t i n g s e s s i o n would  indicate  that the improvement seen a f t e r having the s u b j e c t s c l o s e t h e i r eyes f o r 2 minutes was  p r i m a r i l y due  to a change i n  a d a p t a t i o n l e v e l . F u r t h e r e l a b o r a t i o n on t h i s p o i n t w i l l presented  be  i n the d i s c u s s i o n .  Although a d a p t a t i o n does appear to play a major r o l e i n determining t h r e s h o l d s i n MS  s u b j e c t s , i t was  d i s c a r d the i n v e s t i g a t i o n on the e f f e c t s of a d a p t a t i o n from the present study. The decision  decided to lowered  reason  for this  i s that the a d a p t a t i o n f o r the " c l o s e d eye"  c o n d i t i o n would never  be known and  therefore introduce a  methodological c o n s t r a i n t on the d a t a . Moreover, by  manually  t r y i n g to i n v e s t i g a t e the fovea, the F225 c o n t i n u a l l y a f t e r a p e r i o d of 10 minutes.  T h i s r e s u l t s i n the LSI  computer p r i n t i n g an empty thermal  graph, a f t e r which the  operator must r e s t a r t t e s t i n g . P e r i o d i c a l l y the completely  stalls  perimeter  stops f u n c t i o n i n g , r e q u i r i n g the perimeter to be  163 turned o f f and r e s t a r t e d . These problems add unduly t o the time r e q u i r e d f o r a s u b j e c t to remain motivated and prepared for  testing. a. Revised Hypothesis  Based upon the r e s u l t s of the p i l o t demonstrated  the i n a b i l i t y  p e r i p h e r a l s e n s i t i v i t y due  study that  to examine f o v e a l  and  to machine l i m i t a t i o n ,  i t was  decided to remove the a d a p t a t i o n v a r i a b l e and modify initial 1.  hypothesis as  2.  follows:  R e l a t i v e t h r e s h o l d s w i l l be s i g n i f i c a n t l y between MS  the  and v i s u a l l y normal  different  subjects.  T h r e s h o l d d i f f e r e n c e s between MS and normals  will  be  g r e a t e r at and near the fovea than in the p e r i p h e r y . 3.  As a consequence of f o v e a l involvement, cone t h r e s h o l d s f o r the MS  s u b j e c t s , as determined  red  will  and blue f i l t e r s ,  by the  show more s e l e c t i v e  than t h r e s h o l d s determined by the achromatic  loss  filter.  164  IV.  1.  SUBJECTS  Subjects consisted by  t h e MS  Clinic  of  Sciences Hospital 30  of  22 v o l u n t e e r  MS  patients  the Acute Care U n i t  of  the  at the  a g e - m a t c h e d n o r m a l s w i t h no was  mean age  32.67 y e a r s  and  was  for  independent groups with  27.50 y e a r s  significant  (t=1.63, df=49, p Of 7 of  the  t h e MS  patients  Fisher's  (X = 3 . 3 3 , d f - 1 , £ 2  Ten  of  and  14 had  the  ages of  the not.  MS  2 >«05) n o r  df=l9,  (x =0.02, d f = 1 . 2  >.05).  11  normals. A t - t e s t  the  two  no  groups  were f e m a l e w h e r e a s  14 were f e m a l e .  normals w i t h  A  respect  to  gender  2  p a t i e n t s had  those with  patients,  E x a c t T e s t f o u n d no s i g n i f i c a n t  and  T h e r e was  problems.  1  were male and  b e t w e e n MS  and  unequal sample s i z e s r e v e a l s  n o r m a l s , 20 were male and  chi-square using differences  (o = 10.86) f o r t h e  between the a g e s of  >.05).  Health  h i s t o r y of m e d i c a l  (a = 11.30) f o r t h e  difference  referred  U n i v e r s i t y of B r i t i s h C o l u m b i a  The  two  STUDY  no  a h i s t o r y of  optic neuritis  significant difference  between  o r w i t h o u t o p t i c n e u r i t i s (_t = 0.90,  was  there  2  >.05).  a sex  difference  between  the  A l l t ^ - t e s t s r e f e r r e d t o a r e b a s e d upon t w o - t a i l e d t e s t s of probability. The F i s h e r ' s E x a c t T e s t s i s Computed f o r 2 x 2 contingency t a b l e s when a c e l l e n t r y has l e s s t h a n 20 c a s e s . 1  2  165  Fourteen clinically based  o f t h e MS p a t i e n t s  definite  and eight  upon a n e u r o l o g i s t ' s  modified version difference  as p r o b a b l e .  r a t i n g of the p a t i e n t  o f t h e Rose  a difference  T h e r e was no d i f f e r e n c e or w i t h o u t (x =2.05,  optic  e t . a l . (1976)  neuritis  the demographic  i n gender  years  average  2  and t h e i r  probable.  deviations  since  Table  Table  duration  diagnosis  2.  group  14 p r o v i d e s  df=20,  since  d i a g n o s i s was  patient  g r o u p . The  f o r the c l i n i c a l l y and 7.43 y e a r s t h e means  definite  (a=6.35) f o r  and s t a n d a r d  from d i a g n o s i s .  T h e r e was  between t h e two c l i n i c a l g r o u p s on p >.05).  PROCEDURE  Subjects place  their  against  aligned  were s e a t e d a t t h e p e r i m e t e r  c h i n on t h e c h i n - r e s t  that  with  cornea  the l a t e r a l  canthus  their  o f t h e head  to  forehead in  this  o f t h e eye was p r o p e r l y  t h e edge o f t h e bowl a n d t h a t  to the stimulus  and i n s t r u c t e d  and p r e s s  a restraining bar. Positioning  way e n s u r e d  the  (o=9.82)  difference  (t=1.04,  with  12 a n d 13 p r o v i d e a summary  f o r d u r a t i o n of i l l n e s s  no s i g n i f i c a n t  d f - 1 , p_ > . 0 5 ) .  MS d i a g n o s t i c  f o r the e n t i r e  g r o u p was 1 1 . 8 5 y e a r s the  df = 1, p_ >.05)  data.  (<x=8.63)  length  using a  c r i t e r i a . No age  (x =.03,  The mean d u r a t i o n o f t h e d i s e a s e 10.03  were  between t h e number o f p a t i e n t s  df=1, p >.05).  2  as b e i n g  Diagnoses  was f o u n d between t h e two ( t = 0 . 2 3 ,  n o r was t h e r e  of  were d i a g n o s e d  the distance  was h e l d c o n s t a n t  a t 30 c m .  from  TABLE 12 MEAN AND STANDARD DEVIATION FOR SUBJECTS CATEGORIES BY AGE (YEARS) AGE SUBJECTS  N  MEAN  S.D.  NORMALS MS  30 22  27.50 32.67  11.30 10.86  CLINICALLY DEFINITE  14  32.15  7.60  PROBABLE  8  33.50  15.37  OPTIC NEURITIS  8  30.25  7.34  NO OPTIC NEURITIS  14  34.15  12.59  TABLE 13 DIAGNOSTIC NORMAL  DEMOGRAPHICS  CLINICALLY DEFINITE  PROBABLE  MALE  20  5  2  FEMALE  11  9  6  OPTIC NEURITIS  OF SUBJECTS  NO OPTIC NEURITIS  CLINICALLY DEFINITE  7  7  PROBABLE  1  7  TABLE 14 DURATION (YEARS) FROM DIAGNOSIS DURATION DIAGNOSIS  N  MEAN  S.D.  CLINICALLY DEFINITE  14  1 1 .85  9.82  PROBABLE  8  7.43  6.35  22  10.03  8.63  TOTAL  169  Once  positioned,  cross-hairs either  the  table)  or  An eye.  A  of  height the  gauze  responding occluder  and  swung  eye.  As  easily used. the  into  was  reduce  the  by  eye  of  tested,  do  to  the  subject  for  10  always  the  either the  the  in  a  the  with  the  left and  were  are  not  neuritis,  one of  with  or  properly  Only  the  head-rest  right  optic  sample  of  equipped to  eye  the  subject  periphery is  rest.  non-tested  the  occluders  examined.  head  between  of  attached  cover  resulting  over  the  F225  MS p a t i e n t s  testing,  was  the  room  preadapted  to  The  subject  the  and  not  bowl  area.  When instructed attention  be  subject,  minutes.  fixation  in  adjusting  motorized the  inserted  The  cover  not  the  was  may  a  by  of  p o s s i b i l i t y  eye.  to  the  placed  perceived  that  position  (through  was  the  aligned  position  was  pad  was  on  eye  22  of  each  MS e y e s  and  darkened  and  eyes.  Prior  on  eye  non-tested  case  affected  normal  occluder  occluders  the  vertical  stimulus  displaced In  around  to  fixation  monitor  perimeter  or  occluders  the  subject 30  a  the  rubber  the  white  eye  to  by  of  protective  and  subject's  fixation  lateral  opaque  occluder  soft  the  the  In  this  to  to  fixate  monitor  was  Instrumentation.  upon set  the  was  asb.  bowl  move  his  gaze  dark  central  after-images  were  avoided.  the  on  to  background  the  was  as  45  completely  instructed  fixate  way,  pre-adaptation  was  completed, center  the  subject  cross-hairs  described  earlier  in  and  was the  Chapter  II  170 Programme 98 was of  14 p o i n t s on the  10°,  15°, 20°,  40°,  55°, and  1mm.,  20°, 70°  s t o r e d i n the LSI-11 f o r the t e s t i n g  15°-195° meridian, 30°, and  40°  temporally.  which were: 0°,  n a s a l l y ; 5°,  The  5°,  10°, 20°,  30°,  s i z e of each stimulus  was  subtending a v i s u a l angle of 0.19'. During f o v e a l t e s t i n g , s u b j e c t s were i n s t r u c t e d to  f i x a t e at bowl p o s i t i o n #59,  which i s 10° n a s a l on  15°-195° meridian.  The  f i x a t i o n and  log-unit neutral density  a two  a t t e n t i o n monitor was  placed over the opening of the The  LSI-11 was  the  set f o r t h i s filter  was  f i b r e o p t i c at p o s i t i o n  then programmed to t e s t only at that  #59.  one  point. The was  purpose of the two  to allow  f o r the p r e s e n t a t i o n  the machine l i m i t of 8.0 filter,  log-unit neutral density  filter  of a f o v e a l stimulus  below  asb. With the n e u t r a l d e n s i t y  f o v e a l s t i m u l i c o u l d be presented  as low  as  0.08  asb. For trial  f o v e a l t e s t i n g , a c u i t y was  lenses  head-rest.  i n t o a lens holder  Refractions  which i s connected to  for the p a t i e n t s were obtained  an opthalmic t e c h n i c i a n at the Eye Unit of the Health  c o r r e c t e d by p l a c i n g  Sciences  Clinic  the from  i n the Acute care  Centre H o s p i t a l at  the  U n i v e r s i t y of B r i t i s h Columbia. P a t i e n t s with a c u i t i e s worse than 20/40 were excluded. S i m i l a r l y , normal s u b j e c t s were c o r r e c t e d when necessary for f o v e a l t e s t i n g . A c u i t y assessed only.  with the Near V i s i o n A c u i t y Test  was  f o r the normals  171 Although pupil perimetry, two  the  diameter  reasons. F i r s t ,  traditionally pupil  prior  uses to  configuration artificial  of  monitored pupil  Because  without  important  of  the  would  greatly  variable  during  diameter,  an a r t i f i c i a l  F225, i t  pupil  p r e s e n c e of  dilation  a medically  medical  technician,  normals  difficult.  of  control  either  the  an  pupil  in  testing  for  one or  dilates  the  physical  be d i f f i c u l t  affecting  the  to  use  an  detection  of  stimuli.  Secondly,  issue  to  is  was n o t  testing.  pupil  peripheral  the  diameter  whether  was n o t  trained  which would Moreover,  the  use of  chosen as  supervisor  it or  approved  h a v e made t e s t i n g  r e s e a r c h has yet a dilator  affects  requires  to  of  the  resolve  the  retinal  sensitivity. Prior  to  familiarize  testing,  themselves with  trial  and a c t u a l  press  the  of  respond to  the  halt  test  the  trials,  received a practice task.  its  colour.  flashing  and were  the  in  were  were  the  to  practice to  flash,  requested  not  c r o s s - h a i r s on t h e  s h o w n how b l i n k s  trial  instructed  saw a l i g h t  Subjects  of  Both  subjects  r e s p o n s e c h o r d when t h e y  regardless  monitor  subjects  to  attention  and head movements  would  testing. The o r d e r  randomized  for  examinations. acuity, Subjects  always  of  presentation  each subject The  foveal  followed  in  of  the  both  the  examination, completion  received a five-minute  three  of  rest  filters  15°-195°  with the after  was  and  correction 15°-195° the  foveal for  exam.  completion  of  1 72 each 15°-195° p r o f i l e and two minutes a f t e r the f o v e a l examination. The average l e n g t h of time f o r e s t a b l i s h i n g thresholds  f o r the 15°-195° p r o f i l e was  minutes f o r the fovea.  12 minutes and 1.5  T o t a l t e s t time averaged two hours,  depending upon the d i f f i c u l t y encountered i n e s t a b l i s h i n g the  thresholds. Thresholds were e s t a b l i s h e d through the ascending  method of l i m i t s with the LSI-11 a u t o m a t i c a l l y c o n t r o l l i n g stimulus  duration  (200 m s e c ) , i n t e r s t i m u l u s  i n t e r v a l (800  m s e c ) , and luminance i n t e n s i t y i n 10 asb. s t e p s . was a l s o c o r r e c t e d contour programme The highest  Intensity  f o r e c c e n t r i c i t y through the use of #4.  i n t e n s i t y l e v e l presented by the F225 was  set at 1,000 asb. i n order t o reduce t e s t i n g time and the l o s s of data by having the perimeter If the t h r e s h o l d i n t e n s i t y , the subject  stall.  l e v e l was not o b t a i n e d a t the h i g h e s t was given  a value of 1,000 asb. f o r  that e c c e n t r i c i t y . The lowest i n t e n s i t y obtained i n the 15°-195° c o n d i t i o n was 8.00 asb. and 0.08 asb. i n the f o v e a l condition. Thresholds were p r i n t e d , upon completion of t e s t i n g , i n a bar c h a r t threshold  format on the thermal p r i n t e r and the a c t u a l  values were i n t e r p o l a t e d as d e s c r i b e d  Study s e c t i o n .  i n the P i l o t  173 3. RESULTS  The for  mean r e l i a b i l i t y  of response  ( c o r r e c t responses)  normals was 0.93 (o=0.09) f o r the achromatic f i l t e r ,  0.91 U=0.11) f o r the red, and 0.90 (CT=0.11) f o r the b l u e . For the MS s u b j e c t s , the mean r e l i a b i l i t y for  the achromatic  was 0.92 (a=0.l0)  f i l t e r , 0.92 (a=0.l2) f o r the red, and  0.93 (ff=0.07) f o r the blue. Tables standard  15 t o 17 provide  the mean t h r e s h o l d s and  d e v i a t i o n s f o r the 3 groups by f i l t e r and  e c c e n t r i c i t y . Tables  18 to 20 p r o v i d e  s u b j e c t s with and without  similar  r e s u l t s f o r MS  optic n e u r i t i s .  F i g u r e s 30 t o 32 show the l o g a p o s t i l b s e n s i t i v y gradients  f o r the achromatic,  r e d , and blue  filters  r e s p e c t i v e l y by s u b j e c t group. F i g u r e s 33 t o 35 show the l o g a p o s t i l b s e n s i t i v y g r a d i e n t s f o r the achromatic, blue  filters  r e s p e c t i v e l y by d i a g n o s i s of o p t i c n e u r i t i s .  F i g u r e s 36 and 37 provide gradients  r e d , and  the l o g a p o s t i l b s e n s i t i v i t y  f o r a s i n g l e MS p a t i e n t and normal s u b j e c t  r e s p e c t i v e l y . The g r a d i e n t s o b t a i n e d  from the MS p a t i e n t  r e v e a l h i g h l y i r r e g u l a r f l u c t u a t i o n s a c r o s s the e c c e n t r i c i t i e s examined u n l i k e that f o r the normal. These f l u c t u a t i o n s are c h a r a c t e r i s t i c a l l y  r e f e r r e d to i n the  l i t e r a t u r e as Swiss cheese f i e l d s . An i n t e r e s t i n g shown i n F i g u r e 36 i s the r e l a t i v e y red  intact p r o f i l e  finding f o r the  f i l t e r as compared to e i t h e r the achromatic or blue.  T h i s trend i s c l e a r l y evident  i n the mean t h r e s h o l d s f o r the  TABLE 15 MEAN AND STANDARD DEVIATIONS FOR THRESHOLD VALUES (APOSTILBS) BY ECCENTRICITY AND GROUP FOR THE ACHROMATIC FILTER NORMALS ECCENTRICITY NASAL 40 30 20 15 10 5 FOVEA 0 TEMPORAL 5 10 20 30 40 55 70  MEAN 287.87 173.87 100.63 99.34 74.51 58.64 0.13 61 .58 91.11 135.85 162.28 135.06 179.90 421.84  CLINICALLY DEFINITE  PROBABLE  S.D  MEAN  244.48 116.42 45.88 72.28 20.35 21 .23  527.15 477.13 375.72 302.99 354.35 291.40  302.85 274.25 295.60 329.85 372. 13 385.34  701 . 19 610.96 499.13 443.42 434. 10 432. 1 9  381.98 428.39 425.37 461 . 14 469.14 470.75  375.14  483.66  73.69  95.99  302.39 352.17 410.68 303.60 348.44 415.93 716.92  380. 11 366.09 365.44 272.23 302.85 321 .38 317.45  431.73 469.91 581.03 534.70 538.43 596.09 893.09  470.79 440.85 379.51 358.07 388.79 351.81 197.96  0.09 22.68 34.33 82.60 134.64 67. 18 53.74 231.07  S.D  MEAN  S.D.  TABLE 16 MEAN AND STANDARD DEVIATIONS FOR THRESHOLD VALUES (APOSTILBS) BY ECCENTRICITY AND GROUP FOR THE RED FILTER NORMALS ECCENTRICITY NASAL 40 30 20 15 10 5 FOVEA 0 TEMPORAL 5 10 20 30 40 55 70  MEAN 659.41 488.76 268.27 219.74 113.83 62.87  CLINICALLY DEFINITE  PROBABLE  S.D  MEAN  242.02 260.26 162.97 132.46 44. 15 29.81  861.64 798.57 705.80 532.14 414.39 341.21  214.94 229.31 335.07 354.84 350.73 371.27  947.71 913.04 745.75 666.56 527.13 488.63  147.91 165.38 319.10 319.90 403.77 430.72  S.D  MEAN  S.D.  0. 12  0.15  304.51  457.01  58.87  73.88  61 .66 177.48 373.88 341.20 390.07 549.65 848.95  30.81 87.71 190.30 174.71 158.95 214.86 179.08  328.45 449.33 449.33 589.18 679.60 744.99 763.36  378.00 318.64 296.09 294.77 251.04 303.46 229.17  500.20 579.20 821.31 719.97 765.56 790.32 967.65  428.70 394.31  261.85 324. 18 323.83 298.28 91 .49  TABLE 17 MEAN AND STANDARD DEVIATIONS FOR THRESHOLD VALUES (APOSTILBS) BY ECCENTRICITY AND GROUP FOR THE BLUE FILTER NORMALS ECCENTRICITY NASAL 40 30 20 15 10 5 FOVEA 0 TEMPORAL 5 10 20 30 40 55 70  CLINICALLY DEFINITE MEAN  S.D  PROBABLE  MEAN  S.D  273 .81 201 .97 96 .45 87 .31 64 .21 33 .57  183. 17 174. 97 46. 23 54. 22 32. 38 16. 14  0 .09  0. 03  370. 38  487. 30  54. 09  102 .01  32 .84 1 13.57 104 .55 140 .85 171 .39 234 .92 520 .67  22. 37 170. 33 69. 90 60. 25 1 1 982 . 143. 35 270. 62  254. 34 290. 34 359. 26 324. 60 329. 95 493. 50 724. 12  404. 76 385. 96 385. 12 271 .46 277. 43 353. 76 327. 06  401 .48 446. 49 688. 75 494. 28 649. 61 634. 17 91 1 .19  495 .79 460 .62 399 .32 370 .71 388 .37 394 .91 193 .06  623. 94 3 1 8 . 54 506. 88 365. 77 317. 03 309. 57 237. 4 1 273. 49 319. 77 388. 36 257. 56 403. 06  MEAN 768. 06 679. 70 672. 71 555. 75 424. 68 406. 50  S.D. 359 .52 442 .44 451 .97 395 . 1 4 476 .86 491 .87  177  TABLE 18 MEAN AND STANDARD DEVIATIONS FOR THRESHOLD VALUES ( A P O S T I L B S ) BY ECCENTRICITY AND GROUP FOR THE ACHROMATIC F I L T E R OPTIC NEURITIS ECCENTRICITY NASAL 40 30 20 15 10 5 FOVEA 0 TEMPORAL 5 10 20 30 40 55 70  MEAN  NO OPTIC NEURITIS  S.D  MEAN  58 47 85 47 56 16  279.94 286.07 296.20 323.49 402. 17 423.15  669.21 591.70 463.30 384.68 398.09 358.27  348.67 352.30 371.66 414.61 414.42 422.42  514.86  519.02  123.04  263.25  331.64 362.29 472.52 297.40 339.87 379.86 699.67  413.63 402.98 384.06 234.40 240.40 252.61 338.50  359.59 413.67 472.69 439.20 461.90 539.50 827.44  421.85 394.50 378.20  452 410 345 300 357 315  S.D  355.81  387.67 371.89 256.78  178  TABLE 19 MEAN AND STANDARD DEVIATIONS FOR THRESHOLD VALUES (APOSTILBS) BY ECCENTRICITY AND GROUP FOR THE RED FILTER OPTIC NEURITIS ECCENTRICITY NASAL 40 30 20 15 10 5  MEAN  S.D  NO OPTIC NEURITIS MEAN  S.D  878.60 770.07 804.36 596.83 466.94 393.45  199.20 221.33 281.34 317.15 348.56 386.03  901.13 880.26 672.31 571.99 448.78 395.60  198.28 203.24 343.92 365.63 387.59 407.43  FOVEA 0  399.46  497.95  109.89  262.83  TEMPORAL 5 10 20 30 40 55 70  422.97 544. 19 682.03 664.52 723.16 743.61 878.72  388.05 332.81 319.78 362.89 318.00 303.36 226.80  372.58 469.34 668.77 711.29 769.22 790.06 924.42  413.91 360.58 300.93 268.98 253.71 299.80 178.82  179  TABLE 20 MEAN AND STANDARD DEVIATIONS FOR THRESHOLD VALUES (APOSTILBS) BY ECCENTRICITY AND GROUP FOR THE BLUE FILTER OPTIC NEURITIS ECCENTRICITY NASAL 40 30 20 15 10 5 FOVEA 0 TEMPORAL 5 10 20 30 40 55 70  MEAN  S.D  NO OPTIC NEURITIS MEAN  S.D  521.05 487.85 300.04 226.66 343.33 297.07  305.35 407.02 303.35 205.10 416.98 434.44  765.09 616.51 529.98 425.46 366.26 320.09  325.07 393.95 430.25 400.54 428.66 446.75  514.62  519.32  107.22  268.39  296.37 320.79 437.30 337.42 340.41 433.90 636.77  435.01 420.59 390.72 221.82 217.03 333. 13 318.38  314.40 362.17 502.94 414.23 506.63 607.94 880.93  450.16 420.52 439.09 360.77 402.51 381.12 250.62  THRESHOLD: LOO APOS7H.es CO  w  z > z CO D  TJ W  O  •X  -3  >  <  Cd  >< > oa  o w  f  TJ  w• o  > a i—«  3  > tu w -3 — z >-3 *« 5C CO tn cn > CO  CO  CO  o  >  "0 > O o w o Cd  ?:  O » O G z o  o>  o -  o  TJ G O tfl » CO c_,Z  •-< o r -9  o  — i« O G W  TO  m  CO  o  > i—t Zz t-t  > o o X r> f  o  •<  a  w n  z  >-i  i—i -3  tr  1  w w n o •—  •  X o  z  a>  0  <Q  1 cl 3  & o  C81  -2 -1.5  3  -0.5  < 0.5  9 o  5 1.5-  Legend 2.5 3  J  -I  1  1  1  1  20 - 15 10 5 0  1  A  NORMALS n=30  X  C0n=14  •  Pfln=8  '  r-  5 10 20 ECCENTRICITY  FIGURE 31 SENSITIVITY GRADIENTS FOR NORMAL, CLINICALLY DEFINITE (CD), AND PROBABLE (PB) MS SUBJECTS FOR A RED FILTER AT 45 APOSTILB BACKGROUND  00  FIGURE 32 SENSITIVITY GRADIENTS FOR NORMAL, CLINICALLY DEFINITE (CD), AND PROBABLE (PB) MS SUBJECTS FOR A BLUE FILTER AT 4 5 APOSTILB BACKGROUND  S  -2 -1.5-  2 »-  -0.5-  o <  o Q  0.5-  O I uJ  a: i  1.5-  A  U 2" 2.5-  A  • -A" -X-  x—•• i  40  i  -i 30  Legend A ON n=8 X  r  -i  20  1  1  15  10  r~ 5 0  1  - i —  — i —  10 20 ECCENTRICITY  30  40  55  70  FIGURE 33 SENSITIVITY GRADIENTS FOR OPTIC NEURITIS (ON) AND NON-OPTIC NEURITIS (NON) SUBJECTS FOR AN ACHROMATIC FILTER AT 45 APOSTILB BACKGROUND  N0Nn=U  -2  -1.5 H  -0.5  OH  O  °,  O  0.5  H  or  r  1.5  A  2.5 H  Legend A ON n=8 X  ^y^A 3-1  1  7 — .  40  30  1  1  1  1—  .  20  15  10  5  0  5  10  20  ECCENTRICITY  FIGURE 34 SENSITIVITY GRADIENTS FOR OPTIC NEURITIS (ON) AND NON-OPTIC NEURITIS (NON) SUBJECTS FOR A RED FILTER AT 45 APOSTILB BACKGROUND  N0Nn=U  X  Legend  / \  A ON n=8  A  -X"*  A-  X  x40-  30  20  15 10  5  0  5 10 20 ECCENTRICITY  30  40  55  70  FIGURE 35 SENSITIVITY GRADIENTS FOR OPTIC NEURITIS (ON) AND NON-OPTIC NEURITIS (NON) SUBJECTS FOR A BLUE FILTER AT 45 APOSTILB BACKGROUND  N0Nn=14  CLINICALLY DEFINITE MALE, AGE 20  X *  I  1  40  I  30  I  I  I  I  I  20  15  10  -5  1 0  1  1  5  10  1  1  20  1  1  30  1  1  40  1  1  1  55  ECCENTRICITY  FIGURE 36 SENSITIVITY GRADIENTS FOR A MS PATIENT  1  1  I  70  THRESHOLD: LOG APOSTILBS  188 various f i l t e r s for  shown i n Tables  15 t o 17. A l l of the f i l t e r s  the normals show a good p r o g r e s s i o n of l e a s t  in the p e r i p h e r y to high s e n s i t i v i t y t h r e s h o l d s f o r the probable relatively  sensitivity  at the fovea. The  MS p a t i e n t s a l s o demonstrate a  c o n s i s t e n t p r o g r e s s i o n from low s e n s i t i v i t y i n  the p e r i p h e r y to high s e n s i t i v i t y  at the fovea. T h i s  progession  i s more c h a r a c t e r i s t i c  of the red than the  achromatic  and b l u e . As f o r the c l i n i c a l l y  definite  p a t i e n t s , the mean t h r e s h o l d s have an i r r e g u l a r for  the achromatic  clinically  definite  and b l u e . Again, i s relatively  r e g u l a r p r o g r e s s i o n of l e a s t  MS  progression  the red f o r the  c o n s i s t e n t i n showing a  sensitivity  to high  sensitivity. Examination of Tables  18 t o 20 r e v e a l s a  similar  p a t t e r n i n that the mean t h r e s h o l d s f o r the red f i l t e r show a r e g u l a r p a t t e r n of l e a s t high s e n s i t i v i t y  sensitivity  i n the p e r i p h e r y to  at the fovea. A poor p r o g r e s s i o n  t h r e s h o l d s are found among the o p t i c n e u r i t i s for  the achromatic  non-optic  neuritis  i n the  MS p a t i e n t s  and blue f i l t e r s , u n l i k e that f o r the patients.  As can be seen from F i g u r e s 30 to 35, the g r e a t e s t d i f f e r e n c e between the normals and MS groups appears t o be in the fovea and l e s s  so i n the p e r i p h e r y . Foveal  depression  among the MS groups appears to occur more prominently the blue and achromatic sensitivity probable  with  f i l t e r s as compared t o the red. The  g r a d i e n t s f o r the c l i n i c a l l y  groups t y p i c a l l y  d e f i n i t e and  show a g r e a t e r d i f f e r e n c e i n the  189 f o v e a l and adjacent r e g i o n s as compared to the p e r i p h e r y . A s i m i l a r t r e n d i s evident i n the f i g u r e s f o r MS p a t i e n t s with and without o p t i c n e u r i t i s . P a t i e n t s with o p t i c  neuritis  tend to demonstrate a f o v e a l d e p r e s s i o n f o r the blue achromatic appears  and  f i l t e r s . L i t t l e d i f f e r e n c e between the two  groups  to be found i n the p e r i p h e r y as compared to the  center. To determine  i f there was  an o v e r a l l  significant  d i f f e r e n c e between the three groups of normal, M S - c l i n i c a l l y d e f i n i t e , and MS-probable, a repeated measures M u l t i v a r i a t e A n a l y s i s of Variance groups) and two  (MANOVA)  1  within factors  e c c e n t r i c i t i e s ) was  conducted.  with one between f a c t o r (3 f i l t e r s and The  (3  14  3x3x14 repeated MANOVA i s  a g e n e r a l case of the S p l i t - P l o t ANOVA design  (Winer,  1971).  As shown i n Table 21, there were many s i g n i f i c a n t i n t e r a c t i o n s and main e f f e c t s i n the d a t a . Due of  to the lack  o r t h o g o n a l i t y (independence) between the v a r i a b l e s ,  actual  the  i n t e r p r e t a t i o n of s i g n i f i c a n t main e f f e c t s becomes  problemmatic.  T h i s i s e s p e c i a l l y t r u e with the group  v a r i a b l e as almost  a l l of the other v a r i a b l e s  interact  s i g n i f i c a n t l y with i t . N e v e r t h e l e s s , the a n a l y s i s r e v e a l e d a s i g n i f i c a n t main e f f e c t due  to groups (F(2,49)=19.96, 2 « <  Honestly S i g n i f i c a n t D i f f e r e n c e s (HSD)  0  0  0  1  )'  were c a l c u l a t e d  upon the harmonic mean f o r s u b j e c t s ' of 13.06 d i f f e r e n c e value of 1 27 .93. 1 2  2  Tukey's  and a  Using t h i s c r i t i c a l  based  critical  v a l u e , the  A11 MANOVA's were performed u s i n g BMDP4V (Dixon, 1981). Using a B o n f e r r o n i adjustment to c o r r e c t f o r p o s s s i b l e  TABLE 21 MULTIVARIATE ANALYSIS OF VARIANCE BETWEEN NORMALS (n*30) CLINICALLY DEFINITE (n=14), AND PROBABLE (n=8) MS PATIENTS  SOURCE  SS  51329111 . 04 GROUP (G) FILTER (F) 11418434. 62 ECCENTRICITY (E) 40283074. 88 G G F G X  X X X F  F E E X E  df 2,49 2,98 13,637  296655. 38 2 .79,68. 45 3781798. 22 7 .15,175 .17 4029295. 62 1 1.72,574 .19 2024808. 96 23 .44,574 .19  MS 25664555. 52 5709217. 31 3098698. 07 74163. 85 145453. 78 154972. 91 38938. 63  F  P-  19. 96 86. 86 50. 42  .0000 .0000 .0000  1 .1 3 2. 37 72 11 . 2. 94  .3417* .0237* .0000* .0000*  Note: * Denotes p r o b a b i l i t y a f t e r degees of freedom have been a d j u s t e d by Greenhouse-Geisser.  191 o v e r a l l mean t h r e s h o l d s f o r the normals found t o be s i g n i f i c a n t l y d i f f e r e n t definite  (205.11 asb.) was  from the c l i n i c a l l y  (460.71 asb.) as w e l l as the probable (583.79 asb.)  MS groups at the .0001 l e v e l of s i g n i f i c a n c e . There was no s i g n i f i c a n t d i f f e r e n c e between the mean t h r e s h o l d s f o r the c l i n i c a l l y d e f i n i t e and probable groups. T a b l e s 22 and 23 p r o v i d e the means and a b s o l u t e mean d i f f e r e n c e s between the 3 groups. Thus, the Tukey's HSD i n d i c a t e s that the normals have s i g n i f i c a n t l y  lower t h r e s h o l d s than the two MS groups,  and that the two p a t i e n t groups a r e s i m i l a r with respect to their overall  thresholds.  An o v e r a l l s i g n i f i c a n t d i f f e r e n c e was a l s o between f i l t e r s  (F(2,98)=86.86,  found  p<.0l), e c c e n t r i c i t y  (F(13,637)=50.42, p<.01) as w e l l as the i n t e r a c t i o n s between e c c e n t r i c i t y x group eccentricity  (F(7.15,175.17)=2.37, £<.02)  r  filter x  (F(11.72,574.19)=11.72, P<.01), and f i l t e r x  e c c e n t r i c i t y x group  (F(23.44,574.19)=2.94, p<.01).  1  Tukey's HSD were c a l c u l a t e d f o r each f i l t e r a g a i n s t one another. Using a c r i t i c a l  value of 122.97, the a b s o l u t e  ( c o n t ' d ) experment-wise e r r o r due to the l a r g e number of mean comparisons, a c r i t i c a l value was computed f o r a p r o b a b i l i t y l e v e l of .01/42. The a c t u a l c r i t i c a l value a s s o c i a t e d with a ;t value of .9999 was found through the U.B.C. Computing Centre f o r t r a n s u b r o u t i n e programme known as UBC P r o b a b i l i t y (1981). When the orthogonal polynomials were found not to be independent or to have equal v a r i a n c e s , i n d i c a t i n g a problem of symmetry due t o o u t l i e r s or some c a r r y over e f f e c t from one w i t h i n f a c t o r l e v e l to the next, Greenhouse-Geisser adjustments were computed. The Greenhouse-Geisser i s a c o n s e r v a t i v e t e s t f o r r e j e c t i n g the n u l l h y p o t h e s i s by reducing the degrees of freedom through an e p s i l o n (e) f a c t o r . By s e t t i n g e to i t s lower bound, the Greenhouse-Geisser r a i s e s the c r i t i c a l value necessary f o r s i g n i f i c a n c e (Winer, 1962). 1  1  192  TABLE 22 MEAN THRESHOLDS (APOSTILBS) FOR NORMALS (n=30) CLINICALLY DEFINITE (n=14), AND PROBABLE (n=8) MS PATIENTS ACROSS FILTERS AND ECCENTRICITIES  GROUP  MEAN  NORMALS  205., 1 1  CLINICALLY DEFINITE  460,,71  PROBABLE  583.,79  193  TABLE 23 ABSOULTE MEAN THRESHOLD DIFFERENCE (APOSTILBS) FOR NORMALS (n=30) CLINICALLY DEFINITE (n=14), AND PROBABLE (n=8) MS PATIENTS ACROSS FILTERS AND ECCENTRICITIES  COMPARISON  MEAN DIFFERENCE  NORMAL VS. PB  378.,68 *  NORMAL VS. CD  255.,60 *  PB VS. CD  123..08  Note: PB - PROBABLE CD - CLINICALLY DEFINITE * - SIGNIFICANT AT THE .0001 LEVEL  194 difference filter  (Table 24) between the mean of the achromatic  (mean=268.06 asb.) and the red f i l t e r  (453.33 asb.)  was s i g n i f i c a n t l y d i f f e r e n t at the .0001 l e v e l . The a b s o l u t e d i f f e r e n c e s between the mean t h r e s h o l d value f o r the red and blue  (275.15 asb.)  filters  were a l s o s i g n i f i c a n t l y  d i f f e r e n t . There was no s i g n i f i c a n t d i f f e r e n c e between the achromatic  and blue  filters.  Thus, o v e r a l l , the r e d f i l t e r  had a s i g n i f i c a n t l y  higher t h r e s h o l d than e i t h e r the achromatic  or b l u e . The  l a c k of a s i g n i f i c a n t d i f f e r e n c e between the achromatic and blue may have been due t o the l a c k of blue i n the red filter. filter  The n o n s i g n i f i c a n t F f o r the i n t e r a c t i o n between and group would suggest  blue, red > achromatic,  that the p a t t e r n of red >  and blue = achromatic  i s consistent  a c r o s s the three groups. The  main e f f e c t of e c c e n t r i c i t y  2<.01) i s a t r i v i a l  (F(13,637)=50.42,  one i n that i t only r e f l e c t s a change i n  s e n s i t i v i t y across the fovea as does the s i g n i f i c a n t i n t e r a c t i o n of f i l t e r  x eccentricity  (F(11.72,574.19)=11.72,  p_<.0l). Table 25 p r o v i d e s the mean t h r e s h o l d values a c r o s s the three f i l t e r s  f o r each of the 14 e c c e n t r i c i t i e s . Tukey's  HSD were c a l c u l a t e d using a c r i t i c a l  value of 118.69 f o r a  s i g n i f i c a n c e l e v e l of .0001, and the r e s u l t i n g a b s o l u t e mean d i f f e r e n c e s are presented the t a b l e , the fovea different 10°  i n Table 26. As can be seen from  (0°) i s c o n s i s t e n t l y  from e c c e n t r i c i t i e s past  significantly  10°. The 0° and the two  ( n a s a l and temporal) e c c e n t i c i t i e s have the lowest mean  195  TABLE 24 ABSOLUTE MEAN THRESHOLD DIFFERENCE (APOSTILBS) FOR NORMALS (n=30) CLINICALLY DEFINITE (n=14), AND PROBABLE (n=8) MS PATIENTS BY FILTERS  COMPARISON  MEAN DIFFERENCE  RED VS. ACHROMATIC  185.27*  RED VS. BLUE  178.28*  ACHROMATIC VS. BLUE  6.99  Note: * - SIGNIFICANT AT THE .0001 LEVEL  196  TABLE 25 MEAN THRESHOLDS (APOSTILBS) FOR ALL GROUPS AND FILTERS BY ECCENTRICITY  ECCENTRICITY  MEAN  NASAL  40 30 20 15 10 5  539.40 439.25 313.34 259.83 217.32 177.77  FOVEA  0  103.87  5 10 20 30 40 55 70  177.84 248.17 347.34 330.96 361.87 439.22 694.39  TEMPORAL  TABLE 26 ABSOLUTE MEAN THRESHOLD DIFFERENCE (APOSTILBS) BY ECCENTRICITY ACROSS GROUPS AND FILTERS  40 NASAL  30  20  15  5  O  5  10  20  30  40  30  IOO.15  20  226.06*  125.91*  15  279.57*  179.42*  53.51  10  322.08*  221.93*  96.02  42.51  361.63* 261.48*  135.57*  82.06  39.55  O  435.53*  335.38*  209.47*  155.96*  113.45  TEMPORAL 5  361.56*  261.41*  135.50*  8 1.99  39.48  0.07  73.97  10  291.29*  191.08*  65.17  11.66  30.85  70.40  144.30*  20  192.06*  91.91  34 . OO  87.51  130.02*  169 57* 2 4 3 . 4 7 *  169.50*  99.17  30  208.44*  108.29  17.62  71.13  113.64  153.19* 227.09*  153.12*  82.79  16 38  40  177 5 3 *  77.38  48.53  102.04  144.55*  184.10* 258.OO*  184.03*  113.70  14.53  SO.91  55  100.18  0.03  125.88*  179.39*  22 1 9 0 * 2 6 1 . 4 5 *  261.38*  191.05*  91.88  108.26  70  154.99*  255.14*  NOTE:  70  40  5 FOVEA  85  * - SIGNIFICANT  3 8 1 . 0 5 * 434 56* 4 7 7 . 0 7 *  AT THE .0001  LEVEL  73.90  335.35*  70.33  5 1 6 . 6 2 * 5 9 0 . 5 2 * 516 5 5 * 4 4 6 . 2 2 * 3 4 7 . 0 5 * 3 6 3 . 4 3 *  77.35 332.52*  255.17*  198 t h r e s h o l d values compared with t h e i r p e r i p h e r y . Adjacent peripheral eccentricities different  tend not to be s i g n i f i c a n t l y  from each other except  eccentricity,  f o r the temporal 70°  which i s s i g n i f i c a n t l y d i f f e r e n t  t h r e s h o l d ) than any other  eccentricity.  To e v a l u a t e the s i g n i f i c a n t and e c c e n t r i c i t y  interaction  between  (F(11.72,574.19)=11.72, p_<.000l),  HSD were computed between the f i l t e r s a c r o s s the 3 f i l t e r s  f o r each  u s i n g the c r i t i c a l  value of .0001). The r e s u l t i n g  Tukey's  eccentricity  value of 118.69 (p  i n Table 27.  As s t a t e d e a r l i e r , the s i g n i f i c a n t  interaction  and f i l t e r r e f l e c t s the d i s t r i b u t i o n  cones and rods a c r o s s the r e t i n a . The l a r g e s t d i f f e r e n c e s as c a l c u l a t e d  filter  a b s o l u t e mean d i f f e r e n c e s  between the 3 f i l t e r s may be found  eccentricity  (higher  between  of the  significant  i n Table 27 occur i n the p e r i p h e r y  (beginning from 20° temporally and 15° n a s a l l y ) between the achromatic  and red f i l t e r s  (higher t h r e s h o l d s f o r the r e d ) ,  f o l l o w e d by the d i f f e r e n c e s between the red and blue (higher t h r e s h o l d s f o r the r e d ) . There were no s i g n i f i c a n t mean d i f f e r e n c e s between the blue and achromatic The p a t t e r n found  filters.  i n Table 27 t y p i c a l l y demonstrates  the l a c k of s e n s i t i v i t y i n the p e r i p h e r y f o r the r e d ,  i.e.  the red show a higher t h r e s h o l d i n the p e r i p h e r y than the other f i l t e r s . Though n o n s i g n i f i c a n t , the mean d i f f e r e n c e s between the achromatic found  and blue r e f l e c t a s i m i l a r  trend as  i n the red, i . e . , the blue has a higher t h r e s h o l d i n  the p e r i p h e r a l e c c e n t r i c i t i e s  when compared to the  199  TABLE 27 ABSOLUTE MEAN THRESHOLD (APOSTILBS) DIFFERENCE BETWEEN FILTERS BY ECCENTRICITY  ECCENTRICITY NASAL  40 30 20 15 10 5  FOVEA  0 5 10 20 30 40 55 70  TEMPORAL  RED VS. ACHROMATIC 352.17* 318.09* 231.18* 172.97* 59.42 29.56  RED VS. BLUE  BLUE VS. ACHROMATI<  342.58* 288.37* 221.60* 184.64* 76.24 57.56  9.59 29.72 9.58 1 1 .67 16.75 28.00  19.50  15.47  4.03  23. 1 3 97.08 231.20* 230.67* 298.09* 353.20* 317.64*  56.49 105.89 251.68* 248.99* 265.18*  299.64* 263.02*  Note: * - SIGNIFICANT AT THE .0001 LEVEL  33.36 8.81 20.48 18.32 32.91 53.56 54.62  200 achromatic.  The  i n c r e a s e i n t h r e s h o l d f o r the red and  as one moves away from the fovea p o p u l a t i o n reduces periphery  i s expected  as the cone  d r a s t i c a l l y when moving toward the  (0sterberg,  1935). The  finding  of red y i e l d i n g  s i g n i f i c a n t l y higher t h r e s h o l d than an achromatic s t i m u l u s has been confirmed and Dunn  a  or blue  with normal s u b j e c t s by Lakowski  (1981).  In order to examine the s i g n i f i c a n t eccentricity HSD  blue  interaction  and group (F(7.15,175.17)=2.37, Q<.02),  between Tukey's  were computed a c r o s s f i l t e r s using a c r i t i c a l value of  120.00. Table 28 provides the a b s o l u t e mean d i f f e r e n c e s between the 3 groups by e c c e n t r i c i t y . s i g n i f i c a n t mean d i f f e r e n c e s at the the normal and probable the fovea  The .0001  largest  number of  l e v e l were between  groups. A l l e c c e n t r i c i t i e s ,  except  (0°), were s i g n i f i c a n t l y d i f f e r e n t . A l l  eccentricities  were s i g n i f i c a n t l y d i f f e r e n t  normal and c l i n i c a l l y  definite  comparison between the two MS ( e x c l u d i n g the 10° n a s a l and significantly different  between the  groups. With r e s p e c t to the groups, a l l e c c e n t r i c i t i e s  55° temporal) were  at the  .0001  l e v e l . For a l l of the  group comparisons, the n a s a l p a r t of the f i e l d  typically  y i e l d e d g r e a t e r mean d i f f e r e n c e s than the temporal Thus both MS  groups have s i g n i f i c a n t l y  region.  higher  t h r e s h o l d s than the normals a c r o s s a l l e c c e n t r i c i t i e s , except at the fovea between the probable  and normal groups.  The magnitude of t h i s d i f f e r e n c e appears to be g r e a t e r i n the n a s a l f i e l d ,  suggesting a d i f f e r e n t i a l e f f e c t  (due to  TABLE 28 ABSOLUTE MEAN THRESHOLD (APOSTILBS) DIFFERENCE BETWEEN GROUPS BY ECCENTRICITY  ECCENTRICITY NASAL  40 30 20 15 10 5  FOVEA  0  TEMPORAL  5 10 20 30 40 55 70  NORMAL VS. PB  NORMAL VS. CD  PB VS. CD  398.62* 446.37* 484.08* 419.78* 377.79* 390.75*  263.88* 305.99* 311.06* 222.06* 278.66* 245.03*  134.74* 140.38* 173.02* 197.72* 99. 1 3 145.72*  62.1 0  349.89*  287.79*  392.42* 371.14* 492.27* 368.20* 419.03* 352.04* 326.83*  243.03* 236.56* 248.28* 221.15* 242.29* 236.1 1* 174.40*  149.39* 134.58* 243.99* 1 47.05* 176.74* 115.93 152.43*  Note: PB - PROBABLE MS CD - CLINICALLY DEFINITE MS * - SIGNIFICANT AT THE .0001 LEVEL  202 the p o s s i b l e  d i s e a s e pathology) a c r o s s the r e t i n a . As with  the normals,  the probable and c l i n i c a l l y d e f i n i t e  differ  s i g n i f i c a n t l y at the fovea with the l a t t e r  having s i g n i f i c a n t l y higher t h r e s h o l d s . A p o s s i b l e contributing  groups group factor  to the f i n d i n g of a lack of s i g n i f i c a n c e at the  fovea between the normal  and probable groups may be found i n  the s e c t i o n e n t i t l e d O p t i c N e u r i t i s . To examine the s i g n i f i c a n t 3 way i n t e r a c t i o n between group x f i l t e r  x e c c e n t r i c i t y (F( 23.44,574.19)=2.94 ,  P_<.0001 ), Tukey's HSD were c a l c u l a t e d by group and f i l t e r .  The c r i t i c a l  f o r each e c c e n t r i c i t y  value used was 118.69  (.0001 l e v e l of p r o b a b i l i t y ) . Tables 29, 30, and 31 provide the a b s o l u t e mean d i f f e r e n c e s blue f i l t e r s  respectively.  Examination differences  f o r the achromatic, r e d , and  of the t a b l e s  reveals  that  the l a r g e s t mean  tended to be between the normal and probable  groups a c r o s s a l l e c c e n t r i c i t i e s except at the fovea. A l l e c c e n t i c i t i e s were s i g n i f i c a n t l y d i f f e r e n t between the normal  and c l i n i c a l l y  definite  Although the red f i l t e r the blue or or achromatic blue f i l t e r  groups.  was s i g n i f i c a n t l y higher than  filters  (discussed  e a r l i e r ) , the  had the g r e a t e r number of l a r g e mean d i f f r e n c e s  (300 or above). Although t h i s may not be s i g n i f i c a n t , the l a r g e r number of mean d i f f e r e n c e s  may i n d i c a t e a g r e a t e r  s u s c e p t a b i l i t y of the blue cones over the r e d . I t i s i n t e r e s t i n g t o note that differences  the r e d has s l i g h t e r l a r g e r mean  than the achromatic. Though any i n t e r p r e t a t i o n  TABLE 29 ABSOLUTE MEAN THRESHOLD (APOSTILBS) DIFFERENCE BETWEEN GROUPS BY ECCENTRICITY FOR THE ACHROMATIC FILTER  ECCENTRICITY  NORMAL VS. PB  NORMAL VS. CD  PB VS. CD  NASAL  40 30 20 15 10 5  413.32* 437. 10* 398.51* 344.08* 359.59* 373.55*  239.28* 303.26* 275.10* 203.66* 279.84* 232.76*  174.04* 1 33.84* 123.41* 140.42* 79.75 140.79*  FOVEA  0  73.56  375.01*  301.45*  370.15* 378.80* 445.18* 372.41* 403.37* 416.19* 472.08*  240.81* 261.06* 274.83* 141.32* 213.38* 236.03* 295.08*  129.34* 117.74 170.35* 231.09* 189.99* 180.16* 177.00*  TEMPORAL  5 10 20 30 40 55 70  Note: PB - PROBABLE MS CD - CLINICALLY DEFINITE MS * - SIGNIFICANT AT THE .0001 LEVEL  204  TABLE 30 ABSOLUTE MEAN THRESHOLD (APOSTILBS) DIFFERENCE BETWEEN GROUPS BY ECCENTRICITY FOR THE RED FILTER  ECCENTRICITY NASAL  40 30 20 15 10 5  FOVEA  0  TEMPORAL  5 10 20 30 40 55 70  NORMAL VS. PB  NORMAL VS. CD  PB VS. CD  288.30* 424.28* 477.48* 446.82* 413.30* 425.76*  202.23* 309.81* 437.53* 312.40* 300.56* 278.34*  86.07 1 14.47 39.95 134.42* 112.74 147.42*  58.86  304.50*  245.64*  438.54* 401.72* 447.42* 378.77* 354.93* 240.68* 118.70*  266.79* 271.85* 215.30* 338.40* 375.48* 213.71* 246.50*  17 1.75* 129.87* 232.14* 40.37 20.56 26.97 94.05  Note: PB - PROBABLE MS CD - CLINICALLY DEFINITE MS * _ SIGNIFICANT AT THE .0001 LEVEL  205  TABLE 31 ABSOLUTE MEAN THRESHOLD (APOSTILBS) DIFFERENCE BETWEEN GROUPS BY ECCENTRICITY FOR THE BLUE FILTER  ECCENTRICITY NASAL  FOVEA TEMPORAL  NORMAL VS. PB  NORMAL VS. CD  PB VS. CD  40 30 20 15 10 5  494.24* 477 .74* 576.26* 468.44* 360.47* 372.93*  350.13* 304.91* 220.57* 150.10* 255.56* 223.99*  144.12* 172.82* 355.68* 318.34*  0  54.00  370.29*  316.29*  368.64* 332.92* 584.20* 354.44* 478.22* 399.25* 390.53*  221.51 * 176.77* 254.71* 183.75* 158.56* 258.58* 203.45*  147.13* 156.15* 329.49* 169.69* 319.66* 140.67* 187.07*  5 10 20 30 40 55 70  Note: PB - PROBABLE MS CD - CLINICALLY DEFINITE MS * - SIGNIFICANT AT THE .0001 LEVEL  104.91  148.94*  206 of  t h i s d i f f e r e n c e i s rather questionable,  tempting  to speculate that the f i n d i n g of g r e a t e r mean  d i f f e r e n c e s among the blue and red f i l t e r s the achromatic system over The  i t would be  as compared to  r e s u l t e d from the s e n s i t i v i t y of the cone  the rod to the e f f e c t s of MS.  n a s a l e c c e n t r i c i t i e s t y p i c a l l y r e v e a l e d greater  mean t h r e s h o l d d i f f e r e n c e s than comparisons f o r each f i l t e r .  the temporal f o r a l l group  T h i s t r e n d may p o s s i b l y be  i n d i c a t i v e of some s e l e c t i v e p a t h o l o g i c a l process in  occuring  the eyes of the MS p a t i e n t s . At 30° e c c e n t r i c i t y , the t h r e s h o l d s f o r v i r t u a l l y a l l  of  the comparisons becomes much lower than the 20°  e c c e n t r i c i t y . From Tables  15 t o 17, which c o n t a i n e d the  standard d e v i a t i o n s f o r each group by f i l t e r and eccentricity, variability of 1.  eccentricity  i n r e t i n a l t h r e s h o l d s as a r e s u l t  i n d i c a t e s the f o l l o w i n g :  Among the normals, t h r e s h o l d v a r i a b i l i t y e c c e n t r i c i t y except  i n c r e a s e s with  a t 20° and 30° t e m p o r a l l y . I r r e g u l a r  i n c r e a s e s may a l s o be seen at and past 30° e c c e n t r i c i t y for  the achromatic  filter  o n l y . The i n c r e a s e i n  v a r i a b i l i t y among normals i s i n agreement with investigations  (eg. Aulhorn  previous  & Harms, 1972; Lakowski &  Dunn, 1981). 2.  For the c l i n i c a l l y d e f i n i t e group, the v a r i a b i l i t y i n t h r e s h o l d s i s highest at the fovea. The remaining e c c e n t r i c i t i e s a l s o demonstrate great v a r i a b i l i t y the 3 f i l t e r s ,  e s p e c i a l l y near the fovea.  across  207 3.  For the probable  group, higher v a r i a b i l i t y  i n the  t h r e s h o l d s tends to occur near the p e r i p h e r y but not at the fovea  itself.  The drop i n v a r i a b i l t y at 20° temporal eccentricity  i s interesting  and 30° n a s a l  i n that one would have  the reverse to have been t r u e . Greater v a r i a b i l i t y have o c c u r r e d at 20° temporal  expected should  eccentricity resulting  from  i t s p r o x i m i t y to the b l i n d spot. S i m i l a r f i n d i n g s r e g a r d i n g the drop i n v a r i a b i l i t y  i n the p e r i p h e r y has been r e p o r t e d  by Dunn (1981) f o r 40° nasal and  30° temporal  eccentricity  under photopic c o n d i t i o n s . a. Fovea  To examine more c l o s e l y the involvement  of  fovea with respect to the other e c c e n t r i c i t i e s ,  the Pearson  Product-Moment c o r r e l a t i o n s were computed for the f o v e a l t h r e s h o l d a g a i n s t the other e c c e n t r i c i t i e s . p r o v i d e s the c o r r e l a t i o n s d e f i n i t e , and probable Tables 33 and  2  1  Table  32  f o r the normal, c l i n i c a l l y  groups f o r the achromatic  34 provide s i m i l a r  filter.  r e s u l t s for the red  and  blue f i l t e r s  r e s p e c t i v e l y . C o r r e l a t i o n s for the normal  group tended  to be n o n s i g n i f i c a n t with the fovea.  The  d i r e c t i o n of the c o r r e l a t i o n t y p i c a l l y became negative after  5° f o r the red and at 5° f o r the blue  achromatic.  This functional pattern r e f l e c t s  and the  The c o r r e l a t i o n s were computed using the S t a t i s t i c a l Package f o r the S o c i a l S c i e n c e s , v e r s i o n X (1983). S i g n i f i c a n c e i s based upon a t w o - t a i l e d t e s t . 1  2  TABLE 32 CORRELATIONS BETWEEN THE FOVEA AND ECCENTRICITIES BY GROUP FOR THE ACHROMATIC FILTER  CLINICALLY ECCENTRICITY  NORMALS  PROBABLE  DEFINITE  NASAL 40 30 20 15 10 5  .09 .03 -.10 -.11 -.11 .04  .48 .47 .53 .50 .50 .51  .30 .65* .65* .71** .68** .69**  TEMPORAL 5 10 20 30 40 55 70  .16 -.06 -.16 -.08 -.12 .22 .08  .50 .52 .49 -.23 -.07 -.11 .27  .72** .72** .85** .79** .81** .83** .58  Note: * - .05 LEVEL OF SIGNIFICANCE ** - .01 LEVEL OF SIGNIFICANCE  209  TABLE 33 CORRELATIONS BETWEEN THE FOVEA AND ECCENTRICITIES BY GROUP FOR THE RED FILTER  ECCENTRICITY  CLINICALLY DEFINITE  NORMALS  PROBABLE  NASAL 40 30 20 15 10 5  -.09 -.13 -.07 -.19 -.14 -.17  .32 .43 .54 .72* .74* .74*  .48 .45 .57* .77** .71** .76**  TEMPORAL 5 10 20 30 40 55 70  .26 -.06 -.22 .05 -.13 -.37* .25  .72* .65 .54 -.47 -.27 -.35 .32  .78** .73** .51 .40 .47 .34 .40  Note: * - .05 LEVEL OF SIGNIFICANCE ** - .01 LEVEL OF SIGNIFICANCE  210  TABLE 34 CORRELATIONS BETWEEN THE FOVEA AND ECCENTRICITIES BY GROUP FOR THE BLUE FILTER  CLINICALLY ECCENTRICITY  NORMALS  PROBABLE  NASAL 40 30 20 15 10 5  .26 .16 -.25 -.20 -.13 -.11  .37 .41 .41 .61 .64 .64  .41 .76** .64* .73** .71** .72**  TEMPORAL 5 10 20 30 40 55 70  -.29 -.10 -.15 -.07 .31 .14 .39*  .64 .64 .44 .54 .36 .37 .26  .73** .72** .89** .84** .81** .73** .27  NOTE: * - .05 LEVEL OF SIGNIFICANCE ** _ .01 LEVEL OF SIGNIFICANCE  DEFINITE  21 1 d i s t r i b u t i o n of cones and rods i n the r e t i n a , i n d i c a t i n g the e x i s t e n c e of two d i f f e r e n t systems as has been demonstrated by numerous With respect  researchers.  t o the c l i n i c a l l y d e f i n i t e and  probable groups, the c o r r e l a t i o n s between the f o v e a l threshold  and other e c c e n t r i c i t i e s were p o s i t i v e . The  only exception t o t h i s trend  was between 30° and 55°  temporally f o r the probable s u b j e c t s . the c o r r e l a t i o n s  The m a j o r i t y of  f o r the c l i n i c a l l y d e f i n i t e group were  significant. To examine more r i g o r o u s l y  the p o s s i b l e  differences  in the c o r r e l a t i o n s between the v a r i o u s f i l t e r s and groups, the c o r r e l a t i o n s were transformed i n t o Standard e r r o r of the d i f f e r e n c e s filter  Z'.  were computed f o r each  by group. The normal curve was then examined to  determine i f the d i f f e r e n c e s  between the Z' were  statistically significant. R e s u l t s of the a n a l y s i s filter  revealed  that  the blue  f o r both the c l i n i c a l l y d e f i n i t e and probable MS  patients  had s i g n i f i c a n t l y more (>.01) l a r g e  positive  c o r r e l a t i o n s than d i d e i t h e r the achromatic or r e d . Moreover, the achromatic had s i g n i f i c a n t l y more  positve  c o r r e l a t i o n s than the red at the .01 l e v e l of s i g n i f i c a n c e . For the normals, only the red demonstrated s i g n i f i c a n t l y l a r g e r negative c o r r e l a t i o n s .  This  confirms the d e s c r i p t i v e o b s e r v a t i o n s noted e a r l i e r .  212 b. O p t i c  Neuritis  To examine the p o s s i b l e (ON)  r o l e that o p t i c n e u r i t i s  may have had on the t h r e s h o l d  patients,  the data was r e a n a l y z e d . A repeated measures  MANOVA f o r 1 between group f a c t o r 2 within done.  factors  (3 f i l t e r s ,  (MS-ON, MS-no ON) and  14 e c c e n t r i c i t i e s ) was  1  The 35.  r e s u l t s from the MS  r e s u l t s of the a n a l y s i s a r e presented i n Table  There was no s i g n i f i c a n t main e f f e c t f o r groups  (F(1 , 20)=0.13, p >.05), nor f o r f i l t e r x group (F( 1 .36,27.23) = 2.69,  p_ >.05), nor e c c e n t r i c i t y x group  (F(3.09,61 .85) = 2. 1 9, p_ >.05). The f i l t e r x e c c e n t r i c i t y x group i n t e r a c t i o n was a l s o  nonsignificant  (F(8.04,160.31)=1.21, p > . 0 5 ) . A s i g n i f i c a n t main e f f e c t was obtained f o r f i l t e r (F(2,40)=42.73, p_< . 0 1 ) . Using a c r i t i c a l  value of  166.51, Tukey's HSD were computed between the mean thresholds asb.),  f o r the achromatic  and blue f i l t e r s  differences  (Table  achromatic f i l t e r s  (443.97 asb.),  red (632.66  (453.83). The a b s o l u t e mean  36) between the red and the blue and r e s p e c t i v e l y were both s i g n i f i c a n t a t  the  .0001 l e v e l . The mean d i f f e r e n c e between the blue  and  r e d f i l t e r s were not s i g n i f i c a n t . These f i n d i n g s are  i d e n t i c a l t o that  reported  i n the main study, i n d i c a t i n g  An a n a l y s i s i n c l u d i n g the normal group was a l s o done. As the r e s u l t s were s i m i l a r t o the one reported i n the main study, i t was not d i s c u s s e d . The MANOVA r e s u l t s f o r t h i s a n a l y s i s may be found i n Appendix G. 1  TABLE 35 MULTIVARIATE ANALYSIS OF VARIANCE BETWEEN OPTIC NEURITIS AND NON OPTIC NEURITIS (N=8) MS PATIENTS  SOURCE  SS  df  MS  GROUP (G) 1 ,20 421653. 76 421653. 76 FILTER (F) 7353989. 75 2, 40 3676994. 87 ECCENTRICITY (E) 16685914. 32 1 3.09,61 .85 1 283531 .87 G G F G X  X X X F  F E E X E  1.36,27 .23 463532. 58 3 .09,61 .85 3344496. 91 2808966. 91 8. 04,160 .31 530210. 39 8. 04,160 .31  231766. 29 257268. 99 108037. 19 20392. 71  (n=14)  F  P-  0. 1 3 42 .73 10 .94  .7199 .0000 .0000*  2 .69 2 .19 6 .42 1 .21  .0799* .0960* .0000* .2954*  NOTE: * Denotes p r o b a b i l i t y a f t e r degrees of freedom were a d j u s t e d by the Greenhouse-Gei s s e r .  214  TABLE 36 ABSOLUTE MEAN THRESHOLD DIFFERENCE (APOSTILBS) FOR OPTIC NEURITIS AND NON OPTIC NEURITIS MS PATIENTS BY FILTER  COMPARISON  MEAN DIFFERENCE  RED VS. ACHROMATIC  188.69*  RED VS. BLUE  178.83*  ACHROMATIC VS. BLUE  9.86  NOTE: * - SIGNIFICANT AT THE .0001 LEVEL  215 that the t h r e s h o l d s were higher the achromatic  f o r the red f i l t e r  and b l u e . Although  over  the mean t h r e s h o l d f o r  the blue was s l i g h t l y higher than that of the achromatic, of  the d i f f e r e n c e was not s i g n i f i c a n t . The lack  s i g n i f i c a n c e was seen as r e s u l t i n g from the l a r g e  c o n t r i b u t i o n of blue energy i n white (achromatic)  light.  There was a s i g n i f i c a n t main e f f e c t f o r eccentricity  (F (3 . 09, 61 .85) = 1 0. 94, p_<'0l). As i n the  main study, the s i g n i f i c a n t e f f e c t seen as r e s u l t i n g  from d i f f e r e n t i a l  f o r e c c e n t r i c i t y was sensitivity  across  the r e t i n a . Threshold v a l u e s were the lowest at the fovea  (0°) and i n c r e a s e d i n the p e r i p h e r y . Table 37  p r o v i d e s the mean t h r e s h o l d values f o r the e c c e n t r i c i t i e s averaged  a c r o s s the 3 f i l t e r s .  Tukey's HSD were c a l c u l a t e d using a c r i t i c a l of  value  153.43 and the a b s o l u t e mean d i f f e r e n c e s are shown i n  Table 38. Again as i n the main r e s u l t s , the g r e a t e s t s i g n i f i c a n t d i f f e r e n c e s (at the .0001 l e v e l ) were between the p e r i p h e r y and c e n t r a l areas of the fovea. The  g r e a t e s t d i f f e r e n c e s tended  to be found when  comparing the fovea. A significant eccentricity  i n t e r a c t i o n was found  for f i l t e r x  (F(8.04,160.31)=6.42, p_< . 0 1 ) . Table 39  p r o v i d e s the mean t h r e s h o l d values f o r each of the 3 filters.  Tukey's HSD, u s i n g a c r i t i c a l  value of 152.34,  were computed. Table 40 shows the a b s o l u t e mean d i f f e r e n c e s between the f i l t e r s  by e c c e n t r i c i t i e s .  216  TABLE 37 MEAN THRESHOLDS (APOSTILBS) FOR OPTIC NEURITIS AND NON OPTIC NEURITIS PATIENTS ACROSS FILTERS BY ECCENTRICITY  ECCENTRICITY  MEAN  NASAL  40 30 20 15 10 5  717.55 645.16 542.13 444.15 413.16 362.77  FOVEA  0  255.38  5 10 20 30 40 55 70  361.07 425.50 559.62 488.63 527.57 580.69 818.74  TEMPORAL  TABLE 38 ABSOLUTE MEAN THRESHOLD DIFFERENCE (APOSTILBS) BY ECCENTRICITY ACROSS OPTIC NEURITIS PATIENTS AND NON OPTIC NEURITIS PATIENTS AND FILTERS  NASAL 40 NASAL  30  FOVEA 5  15  20  0  10  5  1  40  30  20  55  70  40 30  72 . 39 102 . 0 3  20  175  42*  15  273 . 4 0 *  201 . 0 1 *  97 .98  10  304  232 . 0 0 *  128 .97  30  282 . 3 9 *  179 . 3 6 *  81 , 38  389 . 7 8 *  286 . 7 5 *  188 . 7 7 *  157 . 7 8 *  39*  99  5  354 . 7 8 *  FOVEA  O  462  TEMPORAL  5  356 . 4 8 *  284  09*  18 1 . 0 6 *  83 . 08  52 . 0 9  1 . 70  10  292  05*  219  66*  1 16 63  18 . 65  12 . 34  62 . 73  20  157  93*  30  228 . 9 2 *  156  40  189 . 9 8 *  55  136  70  NOTE:  TEMPORAL  *  -  17*  85 .54  49  1 15. 47  53*  53 . 5 0  44 . 48  75 . 4 7  117  59  14 56  8 3 . 42  86  64  47  38  56  101 . 19  173  61*  SIGNIFICANT  58*  AT THE  17  5 0 . 39  276  .0001  146 . 4 6 *  107 . 39 105  69  170 . 12*  196 . 8 5 * 304 . 2 4 *  64 . 4 3 198 . 5 5 *  134  12  63  13  70.99  125 .86  233 . 2 5 *  127 .56  1 14 . 4 1  164 . 8 0 *  272 . 19*  166  50*  102  07  32 . 0 5  38  136 . 54  167 . 5 3 *  2 17 . 9 2 *  325 . 3 1 *  2 19 6 2 *  155  19*  2 1 .07  92.06  5 3 . 12  374 . 5 9 *  405 . 5 8 *  455  393  24*  330.11*  291.17*  LEVEL  97*  563 . 3 6 * 457  67*  259  12*  94  238  05  218  TABLE 39 MEAN THRESHOLDS (APOSTILBS) FOR OPTIC NEURITIS AND NON OPTIC NEURITIS PATIENTS BY FILTERS AND ECCENTRICITY  ECCENTRICITY  ACHROMATIC  RED  BLUE  NASAL  40 30 20 15 10 5  591.21 523.49 429.64 365.78 394.86 353.77  887.84 832.58 737.49 600. 12 471.85 410.18  673.61 579.39 459.28 366.55 372.77 324.36  FOVEA  0  275.89  224.07  266.17  5 10 20 30 40 55 70  357.49 408.65 489.99 394.99 402.47 456.75 770.55  405.40 509.35 692. 14 679.73 740.69 762.36 903.41  320.31 358.51 496.74 391 . 17 439.56 522.97 782.25  TEMPORAL  219  TABLE 40 ABSOLUTE MEAN THRESHOLD (APOSTILBS) DIFFERENCE BETWEEN FILTERS BY ECCENTRICITY  ECCENTRICITY NASAL  40 30 20 1 5 10 5  FOVEA  0  TEMPORAL  NOTE:  * -  5 10 20 30 40 55 70  RED V S . ACHROMATIC 296.63* 309.09* 307.85* 234.34* 76.99 56.41  RED V S . BLUE  BLUE V S . ACHROMATIC  214.23* 253.19* 278.21 * 233.57* 99.00 85.82  82.40 55.90 29.64 0.77 22.09 29.41  51 .82  42. 1 0  9. 72  47.91 100.70 202.15* 284.74* 338.22* 305.61* 132.86*  85.09 150.84 195.40* 288.56* 301 . 1 3 * 239.39* 121.16  37. 18 50. 1 4 6.75 3.82 37.09 66.22 1 1 .70  SIGNIFICANT AT THE .0001  LEVEL  220 The l a r g e s t number of s i g n i f i c a n t d i f f e r e n c e s (at the  .0001 l e v e l ) are found between the red and  achromatic f i l t e r s ,  followed by the red and blue. There  were no s i g n i f i c a n t d i f f e r e n c e s between the achromatic and  blue  filters.  As with the s i g n i f i c a n t e c c e n t r i c i t y x f i l t e r i n t e r a c t i o n found i n the main study, the s i g n i f i c a n t d i f f e r e n c e s tends t o begin  at and past  10° n a s a l l y and  temporarily.  T h i s trend i s seen as r e s u l t i n g from the  differential  s e n s i t i v i t y of the r e t i n a to the red versus  blue and achromatic f i l t e r s .  Again, the lack of  s i g n i f i c a n c e between the achromatic and blue was seen as r e s u l t i n g from the presence of short wavelength l i g h t i n white  light.  c. D i s c r i m i n a n t  Analysis  To examine how a c c u r a t e l y the normals and MS p a t i e n t s c o u l d be c l a s s i f i e d by the t h r e s h o l d s , a stepwise d i s c r i m i n a n t a n a l y s i s was done f o r the three filters.  Both the t h r e s h o l d s  f o r the nasal and temporal  p e r i p h e r i e s were c o l l a p s e d i n t o a mean t h r e s h o l d f o r each inorder to p r o t e c t the degrees of freedom. Thus three d i s c r i m i n a n t analyses  using  three measures of  thresholds  (fovea, n a s a l , and p e r i p h e r y )  were conducted  separately  f o r the achromatic, red, and blue  The r e s u l t s of the a n a l y s i s are shown i n Table  filters. 41.  221  TABLE 41 PERCENT CLASSIFICATION OF SUBJECTS BY DIAGNOSIS (NORMAL VS. MS) AND FILTER ACHROMATIC PREDICTED GROUP  GROUP NORMAL  (n=30)  MS (n=22)  NORMAL  MS  100%  0%  52.4%  47.6%  OVERALL CORRECT CLASSIFICATION = 78.43%  RED PREDICTED GROUP  GROUP  NORMAL  NORMAL  (n=30)  MS (n=22)  MS  96.7%  3.3%  28.6%  71.4%  OVERALL CORRECT CLASSIFICATION = 86.27%  BLUE PREDICTED GROUP  GROUP  NORMAL  NORMAL MS  (n=30)  (n=22)  MS  96.7%  3.3%  47.6%  52.4%  OVERALL CORRECT CLASSIFICATION = 78.43%  222 In terms of o v e r a l l c l a s s i f i c a t i o n ,  the red f i l t e r  c o r r e c t l y c l a s s i f i e d 86.27% of the normals and p a t i e n t s as compared  MS  to 78.43% f o r both the blue and  achromatic. Both of these r a t e s are f a r above  that  expected by chance. The red f i l t e r c o r r e c t l y c l a s s i f i e d  96.7% of the  normals and 71.4% of the MS p a t i e n t s . Only 28.6% of the p a t i e n t s were i n c o r r e c t l y c l a s s i f i e d as normals whereas 3.3% of the normals were i n c o r r e c t l y i d e n t i f i e d as belonging to the MS group. With respect  to the  achromatic and blue f i l t e r s , more of the MS were c l a s s i f i e d as normal  (52.4% and  r e s p e c t i v e l y ) . The MS p a t i e n t s  patients  47.6%  incorrectly identified  were the probable p a t i e n t s . That i s , the probable p a t i e n t s tended to be m i s c l a s s i f i e d as normals. In terms of o v e r a l l group p r e d i c t i o n as w e l l as low f a l s e p o s i t i v e s f o r not having MS,  the red f i l t e r  appears to p r o v i d e the best r e s u l t s . d. T h r e s h o l d  Classification  Inorder to provide a t h r e s h o l d clinically  l e v e l that  i d e n t i f y an abnormal t h r e s h o l d  would  from a normal  one, l o g d i f f e r e n c e s between the fovea and 30° n a s a l e c c e n t r i c i t y were computed. Both the probable and c l i n i c a l l y d e f i n i t e p a t i e n t s were c o l l a p s e d i n t o one group as the q u e s t i o n centered upon which  threshold  would d i f f e r e n t i a t e between MS and normals.  223 The l o g d i f f e r e n c e s were then used t o compute cummulative  f r e q u e n c i e s i n an ascending manner f o r the  normals and descending f o r the MS p a t i e n t s . The t h r e s h o l d at which most of the MS p a t i e n t s and normals c o u l d be d i s c r i m i n a t e d from one another was found. T h i s was done f o r each of the three f i l t e r s For  the achromatic f i l t e r ,  separately.  a log apostilb  d i f f e r e n c e c u t - o f f value of -2.60 c o r r e c t l y all  of the MS p a t i e n t s and a l l but one of the normals.  Similarily, for  identified  the l o g a p o s t i l b d i f f e r e n c e value of -2.45  the blue i d e n t i f i e d a l l but one of the MS p a t i e n t s  as being d i f f e r e n t  from the normals. No normal  i d e n t i f i e d as having an abnormal  was  t h r e s h o l d using the  value of -2.45. With respect to the red f i l t e r ,  a log apostilb  t h r e s h o l d value of -2.25 c o r r e c t l y separated a l l of the normals from a l l but one of the MS p a t i e n t s .  224  V. DISCUSSION  The  r e s u l t s of the a n a l y s i s supported  the hypothesis  t h a t t h e r e would be a d i f f e r e n c e between t h e MS p a t i e n t s and normals w i t h r e s p e c t t o t h e i r r e l a t i v e t h r e s h o l d s f o r a r e d , b l u e , and a c h r o m a t i c  f i l t e r . MS p a t i e n t s have s i g n i f i c a n t l y  h i g h e r t h r e s h o l d s a c r o s s a l l e c c e n t r i c i t i e s when compared t o age-matched normals. Although  t h e t h r e s h o l d s f o r the r e d a r e  s i g n i f i c a n t l y g r e a t e r than e i t h e r t h e b l u e o r  achromatic  f i l t e r s , t h e r e i s no o v e r a l l group d i f f e r e n c e by f i l t e r . T h i s would argue t h a t the f u n c t i o n a l l o s s i n cone/rod f u n c t i o n i n g i s so great among t h e MS p a t i e n t s , a t t h e i r present  s t a t e i n the d i s e a s e , t h a t a l l of t h e f i l t e r s were  a f f e c t e d . Such a c o n c l u s i o n needs t o be guarded i n t h a t the magnitude of t h e d i f f e r e n c e between the 3 f i l t e r s all  groups) needs t o be r e a s s e s s e d  photometric  (across  once the a c t u a l  measures f o r s t i m u l u s i n t e n s i t y i s a c h i e v e d .  U n t i l t h e n , assuming that Synemed® i s c o r r e c t i n s t a t i n g t h a t t h e F225 f i l t e r s a r e p h o t o m e t r i c a l l y equated, the r e l a t i v e d i f f e r e n c e between the f i l t e r s r e p o r t e d here a r e v a l i d . Support f o r the r e l a t i v e p o s i t i o n of the r e d t h r e s h o l d f o r normals comes from Lakowski and Dunn (1981) who r e p o r t e d t h a t the red (XD 532 nm.) y i e l d e d a " g r a d i e n t from 1 and 1/2 t o 2 l o g u n i t s below the o t h e r s [ a c h r o m a t i c , b l u e , and g r e e n ] "  (p. 195). S i m i l a r r e s u l t s were r e p o r t e d by  Aulhorn  (1972).  and Harms  225  However, relative  as  pointed  out  threshold gradients  b a c k g r o u n d bowl a d a p t a t i o n reported the  that  2.  the  patients  MS-clinically  across  fovea,  the  the  clinically at  patients fovea  all  and Dunn (250  filters  cd/m ) 2  become  very  x  higher  thresholds  except  the  fovea,  had s i g n i f i c a n t l y  higher  eccentricities patients  eccentricities  and a c h r o m a t i c  mean t h r e s h o l d s  greatest  definite  the  the  between g r o u p x f i l t e r  from 2 0 ° t e m p o r a l l y t o  normals,  occur  all  blue  significant  center  various  had s i g n i f i c a n t l y  definite  thresholds  red,  the  conditions  upon  that:  normals a c r o s s  for  photopic  interaction  revealed  MS-probable  Thus L a k o w s k i  the  fovea.  significant  eccentricity  than  fully  and D u n n ,  a r e h i g h l y dependent  leve.  between t h e  except at The  1.  under  separation  small  by L a k o w s k i  including  filters  were  Thus t h e  had s i g n i f i c a n t l y  when compared t o  the  the the  the  the  tended  to  definite  thresholds  normals or  in  As w i t h  between  clinically  higher  For  found o n l y  and p r o b a b l e p a t i e n t s  fovea.  only.  15° nasally.  mean d i f f e r e n c e  the  in  the  MS-probable  pat i e n t s . 3.  Losses  i n the  rather  than temporal  slightly various The groups  is  field  tended  regions,  more s i g n i f i c a n t groups than  differences  to  the  with  with  the  i n the  blue  mean d i f f e r e n c e s  nasal  showing between  the  red.  in r e t i n a l  i n agreement  be g r e a t e r  the  sensitivity  f o u n d i n t h e MS  few  that  studies  have  been  226 done u s i n g s t a t i c t h r e s h o l d perimetery. Serra and r e p o r t e d the presence fovea of MS presence  of a small r e l a t i v e scotoma i n the  p a t i e n t s using an achromatic  of a c e n t r a l d e f e c t and  temporally through by Van Dalen,  Mascia  s t i m u l u s . The  small scotoma  10 -20° 0  s t a t i c perimetry has a l s o been r e p o r t e d  Spekreyse  and Greve (1981). The  the present study are i n agreement with these  results  from  findings.  Losses tend to be great at the fovea as w e l l as at e c c e n t r i c i t i e s adjacent to the fovea. However, the differ  findings  from the others i n that the l o s s i n MS appears  occur a c r o s s a l l e c c e n t r i c i t i e s except  to  i n the fovea of  probable p a t i e n t s . A p o s s i b l e e x p l a n a t i o n f o r t h i s w i l l discussed  be  shortly.  S u p r a t h r e s h o l d s t u d i e s t y p i c a l l y have r e v e a l e d the presence  of abnormal f i e l d s such as arcuate scotoma  ( P a t t e r s o n and Heron, 1980), c e n t r a l and p a r a c e n t r a l d e f e c t s (Paton,  1924;  1979), and  S c o t t , 1957;  K e l t n e r , Johnson & B a l e s t r e r y ,  small scotoma i n the p e r i p h e r y between 15°  30° e c c e n t r i c i t y  (Meienberg,  and  Flammer & Hans-Peter, 1982).  Again, the f i n d i n g s of the present study tend to agree with those  from the s u p r a t h r e s h o l d s t u d i e s i n showing a l o s s  in the v i s u a l  field.  It d i f f e r s  i n that the l o s s  a c r o s s the f i e l d , with the fovea showing l o s s e s . Moreover, the l o s s found  occurs  identifiable  i n the present study i s  much more pronounced f o r the chromatic  filters.  As  perimetric  s t u d i e s have focused upon the standard use of  achromatic  stimuli  (due to i n s t r u m e n t a l d i f f i c u l t i e s i n  227 p r e s e n t i n g chromatic s t i m u l i ) the involvement of the cone system al.  i n MS has not been a p p r e c i a t e d . Thus Meienberg e t .  (1982), i n u s i n g achromatic s t i m u l i  i n standard  s u p r a t h r e s h o l d t e s t i n g , s t a t e that abnormality i n MS i s b e t t e r d e t e c t e d with VEP s i n c e the d e f e c t s found through the Octopus Automated Perimeter are not i n the c e n t e r but p e r i p h e r y . By not d i f f e r e n t i a t i n g r e t i n a l r e c e p t o r functioning  (rod/cone), however, important i n f o r m a t i o n  r e g a r d i n g b a s i c as w e l l as p a t h o l o g i c a l f u n c t i o n i n g i s l o s t . Understanding  the involvement of the 2 r e t i n a l systems has  considerable t h e o r e t i c a l  implications regarding  symptomatology such as the f l u c t u a t i o n i n v i s u a l a c u i t y or g l a r e r e p o r t e d by p a t i e n t s . The  r e s u l t s from the present study do d i f f e r  from those  conducted by Younge (1985) on an automated p e r i m e t e r : the Octopus.  Younge r e p o r t e d that the mean t h r e s h o l d s f o r MS  p a t i e n t s overlapped with the mean t h r e s h o l d s f o r normals d e s p i t e the f a c t that  i n d i v i d u a l t h r e s h o l d v a l u e s were lower  f o r the MS p a t i e n t s . He concluded that the reason f o r the o v e r l a p was due to no cases of subacute o p t i c  nerve  involvement. The present study, however has shown s i g n i f i c a n t mean d i f f e r e n c e s i n the t h r e s h o l d s of MS p a t i e n t s from normals,  both among p a t i e n t s with and without  o p t i c n e u r i t i s . The reason f o r the d i f f e r e n c e s i n the two s t u d i e s c e n t e r s upon the p s y c h o p h y s i c a l c o n d i t i o n s of the t e s t i n g s i t u a t i o n . In Younge's study, p a t i e n t s were t e s t e d with an achromatic s t i m u l u s at mesopic l e v e l s . In the  228  present  s t u d y , however, the  chromatic  filters,  f u n c t i o n . One  one  s u b j e c t s were e x a m i n e d w i t h  more s u i t e d  s e r i o u s drawback  f o r a s s e s s i n g cone  i n the p r e s e n t  study  that  l i m i t s any  c o m p a r i s o n w i t h s t u d i e s s u c h a s Younge i s t h e  difference  i n the p s y c h o p h y s i c a l  itself.  The  I n s t r u m e n t a l P r o b l e m s , makes i t e x t r e m e l y  t o t r y and  compare the p r e s e n t  other p e r i m e t r i c f i n d i n g difference perimetry The  i n MS.  results with  any  T h i s , t h e p r o b l e m of  i n instumentation, i s a s e r i o u s problem i n in general.  r e s u l t s of the p r e s e n t  study a l s o d i f f e r  p r e v i o u s p e r i m e t r i c s t u d i e s w i t h respect to the fluctuations  i n the  i n the  p e r i m e t r i c r e s e a r c h on MS  the presence  of i r r e g u l a r  eccentricities,  resulting  the swiss cheese f i e l d .  f o v e a . As has  observed  thresholds across i n the p r o f i l e  b l u e and  filters.  The  profile  revealed  the  known c l i n i c a l l y  R e s u l t s of the p r e s e n t  threshold v a r i a b i l i t y  i s o n l y found f o r the red  sensitivity  i n c r e a s i n g a s one  the fovea. I t would  i n c o r r e c t , t h e r e f o r e , t o s t a t e t h a t MS  with  filter  gradient be  i s c h a r a c t e r i z e d by  swiss cheese f i e l d s .  This  i s only true for  (typically  blue  s t i m u l i . A red s t i m u l u s  u s e d ) and  an e n t i r e l y d i f f e r e n t p e r i m e t r i c p r o f i l e ,  achromatic  one  as  study  i s c o n s i s t e n t l y good, w i t h the moves t o w a r d  in  stated  typically  indicates that this achromatic  from  s e n s i t i v i t y p r o g r e s s i o n from l e a s t  the p e r i p h e r y to the h i g h e s t earlier,  instrument  d i f f e r e n c e , d i s c u s s e d i n t h e s e c t i o n on  M e t h o d o l o g i c a l and difficult  f u n c t i o n of the  provides  peculiar  to  229 the  red cone involvement i n MS. The  involvement of the cone system i n MS can be seen i n  the c o r r e l a t i o n between the fovea and other e c c e n t r i c i t i e s . For  the normals, the c o r r e l a t i o n s between the fovea and  remaining e c c e n t r i c i t i e s were n o n s i g n i f i c a n t n e g a t i v e . Though n o n s i g n i f i c a n t , could  i n d i c a t e the d i f f e r e n c e  fovea and cone/rod f u n c t i o n i n g  and g e n e r a l l y  the negative d i r e c t i o n  i n cone f u n c t i o n i n g  a t the  i n the p e r i p h e r y . An  i n t e r e s t i n g f i n d i n g with the normals i s the presence of p o s i t i v e c o r r e l a t i o n s , again n o n s i g n i f i c a n t  except f o r 70°  temporal e c c e n t r i c i t y f o r the blue f i l t e r , are found i n the far  nasal  and temporal p e r i p h e r i e s  f o r the red and blue  f i l t e r s . T h i s would seem to argue f o r a f u n c t i o n a l s i m i l a r i t y between the fovea and f a r p e r i p h e r y , p o s s i b l y due to the presence of cones i n the p e r i p h e r y  (eg. C u r c i o ,  1985). The  involvement of the cone system i n MS r e v e a l s  dramatically  i n the c o r r e l a t i o n s between the fovea and  remaining e c c e n t r i c i t i e s . Both i n the c l i n i c a l l y and  itself  definite  probable MS groups, the c o r r e l a t i o n s with the fovea are  generally The  s i g n i f i c a n t and p o s i t i v e . pattern  of the c o r r e l a t i o n s among the two MS groups  appears to r e s u l t from e x t e n s i v e damage to the cone system, making i t f u n c t i o n a l l y i n d i s t i n c t i s surported  from the rod system. T h i s  by the f a c t that the l a r g e s t p o s i t i v e  c o r r e l a t i o n s are found among the blue and achromatic f i l t e r s . U n f o r t u n a t e l y , there a r e no published  s t u d i e s on  230 dark a d a p t a t i o n and the e f f e c t s of MS. Among the normals, the c o r r e l a t i o n s blue f i l t e r s for  f o r the red and  tend t o be higher i n a negative d i r e c t i o n than  the achromatic, a l b e i t n o n s i g n i f i c a n t .  change f o r the blue f i l t e r highly  The dramatic  among the MS s u b j e c t s to become  p o s i t i v e with the other e c c e n t r i c i t i e s suggests  that  the blue cone system may have become more f u n c t i o n a l l y a f f e c t e d . As the c o r r e l a t i o n s patient the  f o r the red f i l t e r  f o r the 2  groups show fewer s i g n i f i c a n t c o r r e l a t i o n s  blue and achromatic, one might argue that  than do  the red cones  are more r e s i s t e n t and tend to be the l a s t of the cone system to be a f f e c t e d . Although i n t r i g u i n g i n that  the r e s u l t s from the  c o r r e l a t i o n s would argue that  the blue cones are more  s e n s i t i v e to the p a t h o l o g i c a l  e f f e c t s of MS, i t needs to be  p o i n t e d out that  this interpretation  upon the a d a p t a t i o n l e v e l and f i l t e r a d a p t a t i o n l e v e l i s increased,  i s highly  dependent  c h a r a c t e r i s t i c s . As the  the c o r r e l a t i o n between the  fovea and p e r i p h e r y w i l l decrease. Since i t i s assumed that the normals had no p a t h o l o g i c a l retinal (be that  functioning,  condition  affecting their  the lack of a s i g n i f i c a n t c o r r e l a t i o n  i t p o s i t i v e or negative) i s not s u r p r i s i n g  considering  the background bowl luminance was at the lower end of  the photopic range (45 a s b . ) . I f the a d a p t a t i o n l e v e l was lowered, one would have expected to have found s i g n i f i c a n t correlations periphery.  (hopefully  negative) between the fovea and  231 T h i s i n t e r p r e t a t i o n r e g a r d i n g the r o l e of a d a p t a t i o n has  theoretical  i m p l i c a t i o n s f o r the MS  groups. As  the  c o r r e l a t i o n s between the fovea and p e r i p h e r y f o r both p a t i e n t s became s i g n i f i c a n t l y p o s i t i v e , one might be able to argue that the c o r r e l a t i o n s were due  to a f u n c t i o n a l change  i n the cone system r e s u l t i n g from a change i n the a d a p t a t i o n a l s t a t e of the MS over  eye,  time. T h i s f l u c t a t i o n may  observed The  result  by other r e s e a r c h e r s i n one  one which may  fluctuate  from conduction  losses  MS.  problemmatic f i n d i n g  i n the present  study i s  the l a c k of a s i g n i f i c a n t d i f f e r e n c e at the fovea between the normal and probable MS would have expected between the two of MS  groups. T h i s i s unexpected as  the fovea to demonstrate a d i f f e r e n c e  groups. Although  p a t i e n t s who  one  there was  a g r e a t e r number  d i d not have o p t i c n e u r i t i s as compared  to the c l i n i c a l l y d e f i n i t e significantly different  (whose f o v e a l t h r e s h o l d s were  from both the normals and  probable),  o p t i c n e u r i t i s does not appear to p l a y a r o l e i n that there was  no s i g n i f i c a n t d i f f e r e n c e i n the t h r e s h o l d s between  those p a t i e n t s with or without  optic  neuritis.  A p o s s i b l e i n t e r p r e t a t i o n of the lack of a s i g n i f i c a n t d i f f e r e n c e at the fovea between the probable groups i s as f o l l o w s . In the i n i t i a l the e f f e c t s of demyelination  and  normal  stages of the d i s e a s e ,  occurs j u s t o u t s i d e the  e c c e n t r i c i t y . T h i s i s supported  0°  by the e a r l i e r p e r i m e t r i c  r e s u l t s of acurate scotoma or l o s s e s i n the near p e r i p h e r y . However, as the d i s e a s e p r o g r e s s e s , to the p o i n t where a  232 patient  i s clearly  i d e n t i f i e d as being c l i n i c a l l y  definite,  the l o s s e s have extended i n t o the 0° e c c e n t r i c i t y . Thus although  the cone system may be i n v o l v e d e a r l i e r  fovea i t s e l f  may be r e l a t i v e l y  i n MS, the  spared u n t i l the l a t t e r  stages of the d i s e a s e . T h e o r e t i c a l support  f o r t h i s may come  from the r e s e a r c h on s p a t i a l f r e q u e n c i e s and the d i s t r i b u t i o n of r e t i n a l ganglion  cells.  MS has been reported to a f f e c t  the intermediate and low  s p a t i a l f r e q u e n c i e s more so than the high f r e q u e n c i e s (eg. Regan, S i l v e r & Murrary, 1972; Bodis-Wollner, & Thornton, The  1979; Regan, Raymond, Ginsberg  robustness  of the higher s p a t i a l  Hendley, M y l i n  & Murrary,  1981).  f r e q u e n c i e s may r e s u l t  from the d i s t r i b u t i o n of the 3 r e t i n a l ganglion c e l l s x , and w. According Leventhal  (1980),  distributed  to Lennie  y,  (1980) and Stone, Dreher &  the w r e t i n a l ganglion c e l l s a r e maximally  i n and near the fovea and a r e f e l t  to be  r e s p o n s i b l e f o r s p a t i a l d i s c r i m i n a t i o n . As t h i s would  imply  that input t o these c e l l s may come from the cone system, the robutness  may be e x p l a i n e d by the f a c t that high  spatial  r e s o l u t i o n would r e q u i r e e x t e n s i v e cone damage before any l o s s i s found at that frequency. present c o r r e l a t i o n a l  I d e a l l y , based upon the  f i n d i n g t h a t the red e x h i b i t e d l e s s  l a r g e mean d i f f e r e n c e s than the blue, one would hope that the high s p a t i a l  resolution  ( f i n e a c u i t y ) was a f u n c t i o n of  the red cone system as i t i s t y p i c a l l y the l a s t t o be affected  i n d i s e a s e s (eg. B i r c h , Chisholm,  P i n c k e r s , Porkorny,  Smith & V e r r i e s t ,  Kinnear,  Marre',  1979). Thus i f the red  233  cone system was r e s p o n s i b l e f o r the r e s o l u t i o n of high s p a t i a l f r e q u e n c i e s , the higher spared  f r e q u e n c i e s tend to be  because of the r e s i l i a n c e of the red cones t o the  p a t h o l o g i c a l p r o c e s s e s . Although t h i s e n t i r e l i n e of argument assumes that s p a t i a l f r e q u e n c i e s are not the r e s u l t of c o r t i c a l  f u n c t i o n i n g , i t d e r i v e s some support  from the  f i n d i n g that the blue cone system can not mediate high s p a t i a l f r e q u e n c i e s u n l i k e the r e d (Boynton, With respect t o the s i g n i f i c a n t  1979).  1  i n t e r a c t i o n s between  e c c e n t r i c i t y as w e l l as between e c c e n t r i c i t y and f i l t e r i n d i c a t e d that the r e t i n a has a d i f f e r e n t i a l  sensitivity  across  Greater mean  i t s receptor d i s t r i b u t i o n  (rod/cone).  s i g n i f i c a n t d i f f e r e n c e s occurred between the p e r i p h e r y and the fovea. S i g n i f i c a n t d i f f e r e n c e s a l s o occurred between the c e n t r a l region and the p e r i p h e r y . Examination of the mean thresholds  i n d i c a t e that the fovea has the lowest  (highest s e n s i t i v i t y ) , thresholds  threshold  followed by the c e n t r a l r e g i o n . The  i n c r e a s e when moving towards the p e r i p h e r y .  In a d d i t i o n , there i s a s e l e c t i v e d i f f e r e n c e between filter  and e c c e n t r i c i t y , with the l a r g e s t s i g n i f i c a n t mean  d i f f e r e n c e s found between the r e d and blue as w e l l as red and achromatic.  The s i g n i f i c a n t d i f f e r e n c e s tended t o begin  The importance of the cone system i n s p a t i a l c o n t r a s t s e n s i t i v i t y with respect to t h e i r d i s t r i b u t i o n across the r e t i n a may e x p l a i n why the upper hemiretina i s more s e n s i t i v e t o s p a t i a l f r e q u e n c i e s than the lower (Skrandies, 1985). According to a recent study by C u r c i o (1985), there i s a higher p r o p o r t i o n of rods i n the lower r e t i n a . In e i t h e r some i n h i b i t o r y r o l e or j u s t due to t h e i r l a c k of s e n s i t i v i t y , the rods may a c t u a l l y decrease the s e n s i t i v i t y of the lower hemiretina to s p a t i a l f r e q u e n c i e s . 1  234 past  15° n a s a l and 20° e c c e n t i c i t y . There was no s i g n i f i c a n t  mean d i f f e r e n c e s between the achromatic In a l l , the s i g n i f i c a n t  i n t e r a c t i o n s between  e c c e n t r i c i t y and e c c e n t r i c i t y functional  relationship  and b l u e .  and f i l t e r  reflect a  based upon cone/rod d i s t r i b u t i o n . I t  has g e n e r a l l y been accepted  since  Osterberg  (1935) that the  cone p o p u l a t i o n i s a t i t s g r e a t e s t a t 0° e c c e n t r i c i t y and falls  rapidly  i n t o the p e r i p h e r y . The i n v e r s e i s f e l t  to be  t r u e with the rods, none at 0° e c c e n t r i c i t y and progressively  i n c r e a s i n g as moving i n t o the p e r i p h e r y .  Maximum rod d e n s i t y i s t r a d i t i o n a l l y  felt  to be at about 20°  e c c e n t r i c i t y . The r e s u l t s obtained tend t o agree f u n c t i o n a l l y with t h i s d i s t r i b u t i o n . Highest the f i l t e r s  i s found  sensitivity for  i n the p e r i p h e r y . Moving i n t o the  p e r i p h e r y , higher t h r e s h o l d s are found  f o r the red as  compared to the achromatic  or b l u e . T h i s i s f e l t as being  the r e s u l t of fewer c o n e s  i n the p e r i p h e r y of the r e t i n a ,  resulting red.  and blue i s problemmatic  i n that the d i s t r i b u t i o n  cones should have r e s u l t e d i n a f u n c t i o n a l p a t t e r n  s i m i l a r to the red, as has been found Verriest & Israel, for  i n d e t e c t i n g the  The l a c k of a s i g n i f i c a n t mean d i f f e r e n c e between the  achromatic of  i n the need f o r g r e a t e r i n t e n s i t y  t h i s negative  by others (eg.  1965, Lakowski & Dunn, 1981). The reason finding  i s that the achromatic  stimulus  used i n the F225 c o n t a i n s blue and that the s i m i l a r i t y i n wavelengths between the 2 r e s u l t e d i n n o n s i g n i f i c a n t t h r e s h o l d d i f f e r e n c e s . However, by i n c r e a s i n g the background  235 a d a p t a t i o n l e v e l to f u l l y  photopic  (250 cd/m ) a s e p a r a t i o n 2  between the achromatic and blue f i l t e r s  should be a c h i e v e d .  a. T h e o r e t i c a l Mechanism  As noted by Drance  (1985a, 1985b), l o s s i n f o v e a l  f u n c t i o n i n g tends t o occur p r i o r to the c l i n i c a l d e t e c t i o n of v i s u a l f i e l d d e f e c t s . Thus Lakowski has argued and demonstrated through a v a r i e t y of p s y c h o p h y s i c a l techniques t h a t c o l o u r v i s i o n  losses,  mediated through the cones, can occur i n a wide of  d i s e a s e s before the onset of recognized  defects  (eg. Lakowski, B r y e t t & Drance,  Begg, 1976; Lakowski & Drance, Carsh,  variety  visual  1972; Lakowski &  1978; Lakowski, Drance &  1980).  The present study i s i n agreement  with the f i n d i n g  on cone s e n s i t i v i t y , as i s evident from the c o r r e l a t i o n s between the fovea and remaining e c c e n t r i c i t i e s f o r the 3 groups (normal, M S - c l i n i c a l l y d e f i n i t e , MS-probable). A c c o r d i n g to the c o r r e l a t i o n s , the g e n e r a l i z e d l o s s a t the  fovea and adjacent e c c e n t r i c i t i e s would argue the  presence of f u n c t i o n a l damage to the cone system as w e l l as the r o d . The f u n c t i o n a l l o s s among the cones, one which appears to be s l i g h t l y g r e a t e r f o r the blue, makes it d i f f i c u l t  t o d i f f e r e n t i a t e between the rods and cones  ( i n t e r p r e t e d from the p o s i t i v e c o r r e l a t i o n s ) . That i s , demyelination has d i s r u p t e d the normal  functional  d i f f e r e n c e between the rod and cone systems.  236 U n f o r t u n a t e l y , what has not been e s t a b l i s h e d by present  study  i s which of the two  the  receptor systems i s  a f f e c t e d e a r l i e r . Because of the l o s s at the fovea, i t i s assumed by the author  that the cone system may  been a f f e c t e d e a r l i e r than the r o d s .  1  case then p s y c h o p h y s i c a l  such as dark  procedures  have  If t h i s i s the  a d a p t a t i o n would be of great importance to use in studying  MS.  Throughout t h i s d i s c u s s i o n , the l o s s i n cone f u n c t i o n i n g has not been assumed to be s t r u c t u r a l -- at l e a s t not  i n the e a r l y stages of the d i s e a s e . The  f o r t h i s comes from the attempted p i l o t modifying  a d a p t a t i o n t h r e s h o l d . By having MS  c l o s e t h e i r t e s t e d eye thereby  study  reason  on subjects  f o r a p e r i o d of 2 minutes,  a l t e r i n g the s t a t e of r e t i n a l a d a p t a t i o n , f o v e a l  t h r e s h o l d s were d r a m a t i c a l l y lowered. As t h i s change in t h r e s h o l d d i d not appear to be due fatigue, was  to a change i n  i t i s assumed that the i n i t i a l  not due  higher t h r e s h o l d  to the presence of s t r u c t u r a l damage,i.e.,  at l e a s t not permanent s t r u c t u r a l change. If the damage was  permanent, one  would not have expected  improvement  i n the t h r e s h o l d . S i m i l a r r e s u l t s regarding the of v a r i a b l e background luminances on MS  has been  r e p o r t e d by P a t t e r s o n , F o s t e r and Heron  (1980).  effects  P a t t e r s o n e t . a l . reported that t h r e s h o l d v a r i a b i l i t y 'Although the mean t h r e s h o l d d i f f e r e n c e at the fovea between the normals and MS-probables was not s i g n i f i c a n t , i t i s f e l t that i f the fovea was analyzed s e p a r a t e l y a s i g n i f i c a n t d i f f e r e n c e would have been found.  237 i n c r e a s e d with i n c r e a s i n g background luminance i n MS but not  normal c o n t r o l s u b j e c t s . ,  suggesting  some type of  f l u c t u a t i n g i n t e r f e r e n c e with the v i s u a l s i g n a l . T h i s i s i n agreement with the present deviations  study i n that the standard  f o r the 2 MS groups under the 45 asb.  background c o n d i t i o n  i s much greater  than that of the  normals. Fluctuations the p i l o t  i n cone f u n c t i o n i n g , as evidenced i n  study, may e x p l a i n temporary l o s s e s seen i n MS  p a t i e n t s with respect More importantly, one  to complaints about v i s u a l a c u i t y .  by a l t e r i n g the a d a p t a t i o n a l  state,  may be able to e s t a b l i s h which of the receptor  systems was a f f e c t e d the e a r l i e s t process.  Thus, by examining receptor  f u l l y photopic able  and f u l l y  scotopic  f u n c t i o n i n g under  l e v e l s , one should  be  to i s o l a t e which of the systems i s i n v o l v e d . As the  present asb.)  i n the disease  study used a background luminance l e v e l (45  a t the lower end of the photopic  have expected b e t t e r cone f u n c t i o n i n g was not a f f e c t e d . As the reverse argue that  range, one would the cone system  was t r u e , the r e s u l t s  i t i s the cone system which i s a f f e c t e d the  most. As the course of the disease damage becomes more e x t e n s i v e ,  progresses,  and the  the cone system becomes  i n d i s t i n g u i s h a b l e from the rod i n the former's s e n s i t i v i t y t o chromatic The  question  stimuli.  that a r i s e s i s what may be  responsible  f o r the observed t h r e s h o l d d i f f e r e n c e s . Because of the  238 r e l a t i o n s h i p o f o p t i c n e u r i t i s (ON) possible The to  1.3  t h a t ON  may  provide  million  nerve f i b r e s as  (Newell,  anatomical  2.  orbital,  3.  i n t r a c a n a l i c u l a r , and  4.  intracranial.  The  intraocular section  pathological  c a s e s ) and  the  cup  the  eye.  to the  known as  that  the  Inside  p a s s e s i n and  into 4  c o n s i s t s of the  inner  the  outer s c l e r a l .  optic disk  the  the  physiologic  cup  are  juncture out  of  the  blood vessels  t o the  innermost surface  The  inner  optic  disk.  cup.  I t i s through  vein enter  pore l i k e the  and  leave  structures  scleral  o p t i c nerve  foramen. itself  i s c o m p r i s e d of  afferent  c e l l s c o l l e c t i v e l y c a l l e d nerve  bundles are  c e l l s are  the  retina,  eye.  o p t i c nerve i t s e l f  b u n d l e s . The  small  where t h e  as  in  is a central  that connect with  axons of g a n g l i o n  ganglion  1.1  surportive  (except  c e n t r a l a r t e r y and  cribosa)  i s at t h i s  The  divided  i s viewed ophthalmoscopically  depression  other  i s unmyelinated  m i d d l e c h o r o i d a l , and  Concentric  It  be  roughly  sections:  intraocular,  (lamina  explanation.  w e l l as  1 9 7 8 ) . I t may  1.  retina  a partial  i t is  o p t i c nerve i s e s t i m a t e d to c o n t a i n  elements  the  t o MS,  n e r v e . The  spread of  s e p a r a t e d by  the  a x o n s of  in a radial retinal  septa that the  fashion  fibre carry  retinal around  layer, converging  at  the  239 the o p t i c d i s c . Normally, t h i s r e t i n a l nerve f i b r e l a y e r (RNFL) i s s l i g h t l y opaque and appear as f i n e s t r i p e d striations  i n the temporal and nasal r e t i n a  & Nieminen, 1985). In d i s e a s e s  (Airaksinen  such as glaucoma,  however, d i f f u s e and l o c a l i z e d l o s s e s i n v a r i o u s can  be detected  regions  p r i o r to any measureable changes i n the  optic disc i t s e l f  ( A i r a k s i n e n & Alanko, 1983). The  l o s s e s themselves a r e found as t h i n i n g of the RNFL due to damage of the axon l a y e r . Recently,  RNFL l o s s has  been shown to be h i g h l y c o r r e l a t e d with c o l o u r d i s c i m i n a t i o n l o s s e s on the anomalscope i n glaucomatous patients  ( A i r a k s i n e n , Lakowski & Drance, 1986).  In o p t i c neuropathies, Tagami (1979) reported central  f i e l d depression  on the Tiibinger perimeter  c o r r e l a t e d h i g h l y with the degree of observed atrophy i n maculopapillar retrobulbar  bundles. Although Tagami t e s t e d  n e u r i t i s p a t i e n t s with an achromatic  stimulus,  the c e n t r a l l o s s observed i s i n t e r e s t i n g as  it,  with the f i n d i n g s on glaucoma, suggests that  along  the m a c u l o p a p i l l a r  region  visual  such as c o l o u r v i s i o n and a c u i t y back  information  i s responsible  f o r conveying  to the o p t i c d i s c . Moreover, i t i s t h i s region  which  appears to be the most s e n s i t i v e to p a t h o l o g i c a l processes. In the case of MS, examination of the r e t i n a l has  revealed  layer  the presence of d i f f u s e and f o c a l damage,  e s p e c i a l l y of the temporal p e r i p a p i l l a r y bundles  240 ( F e i n s o l d & Hoyt, 1975). In a d d i t i o n , there tends t o be slit-like  d e f e c t s i n the arcuate  nerve f i b r e s . As t h i s  d e f e c t p a t t e r n i s s i m i l a r t o the ones r e p o r t e d by Tagami (1979) and A i r a k s i n e n e t . a l . (1986), i t would seem likely study  that the t h r e s h o l d l o s s e s observed i n the present were p a r t i a l l y due t o RNFL l o s s i n the  maculopapillar correspond  r e g i o n . The l o s s w i t h i n t h i s region would  to the l a r g e c e n t r a l depressions  among the MS p a t i e n t s f o r the v a r i o u s If  t h i s i s the case, a q u e s t i o n  observed  filters. then a r i s e s about  the l o s s e s reported  i n MS as r e l a t e d to that  p r o g r e s s i o n . Tagami  (1979) argued that RNFL l o s s tended  to  occur  o u t s i d e the fovea  disease's  i n the temporal region of the  r e t i n a . The f i n d i n g from the present  study  thresholds  (temporal  i n the n a s a l v i s u a l  field  of i n c r e a s e d s i d e of  the r e t i n a ) would appear to i n d i c a t e a s i m i l a r l o s s i n MS. I f t h i s i s the case, cones may provide  the d i s t r i b u t i o n of the v a r i o u s  some answer t o t h i s f i n d i n g . I t has  long been accepted,  based upon k i n e t i c perimetry,  the r e l a t i v e frequency  d i s t r i b u t i o n s of the v a r i o u s  cones d i f f e r s at the r e t i n a . I t i s t y p i c a l l y the fovea  itself  that  (1/8°) i s blue b l i n d  felt  that  ( A d l e r , 1975) and  that the red s e n s i t i v e cones are maximally s i t u a t e d t h e r e . The blue and green wavelength s e n s i t i v e cones are d i s t r i b u t e d away from t h i s r e g i o n . T r i c h r o m a t i c itself  extends about 20° t o 30° from f i x a t i o n  1975). As RNFL l o s s appears to spare  the fovea  vision  (Adler, i n the  241 e a r l y stages of d i s e a s e , red cone f u n c t i o n i n g remains relatively  i n t a c t u n t i l the r e t i n a l system i s s t r e s s e d  as i n c o n d i t i o n s of i n c r e a s e d background i l l u m i n a t i o n . Once i n such s t r e s s f u l v i s u a l s i t u a t i o n s , in red cone f u n c t i o n i n g appear. As the red cone system may  i t would appear that  p l a y a part i n the r e s o l u t i o n of  high s p a t i a l f r e q u e n c i e s , one disturbances  abnormalities  would t h e o r e t i c a l l y  expect  i n v i s u a l a c u i t y under such s t r e s s f u l  c o n d i t i o n s . I t i s i n t e r e s t i n g to note that a common clinical  symptom reported about MS  i s e a r l y , temporary  f l u c t u a t i o n s i n a c u i t y . These f l u c t u a t i o n s may from abnormal p r o c e s s i n g at the cone l e v e l and,  i f Lennie  i n the  fovea,  (1980) i s c o r r e c t i n h i s statement that w  r e t i n a l ganglion the fovea,  result  c e l l s are maximally found at and  around  i t i s p o s s i b l e that the w c e l l s ( c a r r y i n g  i n f o r m a t i o n mostly from the red cone system) are  least  s u s c e p t i b l e to s t r u c t u r a l damage. I t must be s t r e s s e d that t h i s does not mean there  i s no p s y c h o p h y s i c a l  f o r e v i d e n t l y l o s s e s do occur  (eg. presence of  l o s s e s as noted by Lakowski, H a r r i s o n and Because an area appears to be a n a t o m i c a l l y does not  loss  red-green  Stell  (1985).  intact, i t  f o l l o w that i t i s f u n c t i o n a l l y i n t a c t . Given  the c o r r e c t v i s u a l c o n d i t i o n s adaptation)  and  (eg. chromatic  (eg. higher  background  the a p p r o p r i a t e p s y c h o p h y s i c a l  procedure  f l i c k e r p e r i m e t r y ) , changes i n s p e c i f i c  types of v i s u a l f u n c t i o n i n g may  become apparent.  242  If the l i n e of reasoning here i s v a l i d , one might be a b l e to h y p o t h s i z e respect to r e t i n a l  on the p r o g r e s s i o n of MS with  f u n c t i o n i n g . The present  study  found  that there were s l i g h t l y more s i g n i f i c a n t c o r r e l a t i o n s with the blue f i l t e r  than the r e d , keeping  i n mind  however that such a t r e n d depends h i g h l y upon the a d a p t a t i o n a l s t a t e . Such a p a t t e r n c o u l d be i n t e r p r e t e d as meaning that the blue system was a f f e c t e d the most.  1  As the blue cones tend to be t y p i c a l l y  just  o u t s i d e 0° e c c e n t r i c i t y , the t h i n n i n g of the RNFL i n the temporal p a r t of the m a c u l o p a p i l l a r r e g i o n may disturbance  i n blue cone conduction.  represent  I t i s conceivable  that e a r l y blue cone f u n c t i o n l o s s may p r e d i c t RNFL l o s s in t h i s r e g i o n . The r e d cone system, though a l s o a f f e c t e d by MS, tends not to show f u n c t i o n a l change e a r l y unless the system i s p l a c e d i n a v i s u a l l y stressful  situation  c o n d i t i o n s found  (eg. high background luminance  i n g l a r e ) . As the d i s e a s e  the red cone system becomes more inmpaired  progresses, until  permanent d y s f u n c t i o n s such as l o s s i n v i s u a l a c u i t y i s seen. The damage c o n t i n u e s longer  u n t i l the cone system i s no  functionally distinct  than the rods,  both  r e q u i r i n g l a r g e i n c r e a s e s i n i n t e n s i t y . As noted l i t e r a t u r e , disturbances observed  i n the  i n luminance p e r c e p t i o n i s a l s o  i n the p r o g r e s s i o n of MS, suggesting p o s s i b l e  higher c o r t i c a l  involvement  than has been  suggested  Yellow-blue l o s s e s have been r e p o r t e d by Lakowski, H a r r i s o n and S t e l l (1985). 1  243  here. Further r e s e a r c h i n v o l v i n g f l i c k e r perimetry  will  be needed to i n v e s t i g a t e the p o s s i b l e r o l e of higher c o r t i c a l centres. b. Methodological and Instrumental  Problems  Several problems a f f e c t the r e s u l t s and i n t r e p r e t a t i o n s presented here. F i r s t and foremost i s the psychophysics  of the Fieldmaster® bowl. U n l i k e the  m a j o r i t y of p e r i m e t e r s whereby a stimulus i s p r o j e c t e d onto a bowl that has some constant  l e v e l of  i l l u m i n a t i o n , the background luminance l e v e l i n the F 2 2 5 does not appear t o p l a y a s i g n i f i c a n t  r o l e . The reason  f o r t h i s i s that the f i b e r o p t i c system does not p r o j e c t a stimulus onto the bowl but d i r e c t l y t o the eye. Thus, u n l i k e other p e r i m e t e r s , the f o v e a l t h r e s h o l d obtained with the F 2 2 5 was much lower  than normally  seen.  Moreover as the c e n t e r of the f i b r e o p t i c , when not being  i l l u m i n a t e d , was darker than  the bowl, s u b j e c t s  were not only d e t e c t i n g changes i n stimulus luminance but luminance c o n t r a s t d i f f e r e n c e s between the f i b r e o p t i c p o s i t i o n and adjacent  surround. As p h o t o m e t r i c a l l y  the bowl was shown not to be e q u i v a l e n t i n luminance, e s p e c i a l l y at the p o i n t of f i x a t i o n , the changes i n the center of the v i s u a l t h r e s h o l d f o r the MS p a t i e n t s may have been due to an abnormal l a t e r a l by the luminance c o n t r a s t . Aulhorn r e p o r t e d reduced  inhibition  caused  and Harms ( 1 9 7 2 )  t h r e s h o l d s due to the presence  have  of such  244  luminance border c o n t r a s t s . T h i s however would appear unlikely conduct  i n the present study as the p o i n t used to the f o v e a l examination,  as w e l l as the other  e c c e n t r i c i t i e s occurred away from the regions of differing  l u m i n a t i o n . I f the luminance d i f f e r e n c e  between the f i b r e o p t i c and surround played a significant  role,  a c r o s s the r e t i n a  i t s e f f e c t s should have been constant (only i f , of course, i n h i b i t i o n  i s the  same a c r o s s the r e t i n a ) . Because of the f i b r e o p t i c system used, the background bowl l e v e l may f u n c t i o n only to "ready" the r e t i n a at some general l e v e l of a d a p t a t i o n (here the lower photopic range). I t does not play a r o l e i n determining t h r e s h o l d l e v e l s , and, as such, normal p s y c h o p h y s i c a l laws as the Weber f r a c t i o n which i s based on background l e v e l probably do not apply. Thus i t makes it  extremely  difficult  to compare the present  results  with those reported with other perimeters such as the Goldmann. Another problem with the r e s u l t s i s the manner i n which t h r e s h o l d s are determined  by the F225. I f a b l i n k  occurs d u r i n g t e s t i n g , the computer a l g o r i t h m i n c r e a s e s the i n t e n s i t y l e v e l  f o r that e c c e n t r i c i t y . Instead of  r e t e s t i n g that e c c e n t r i c i t y with the same luminance level,  the programme s t o r e s the b l i n k as not seen at  that t h r e s h o l d . Although  not a problem e a r l i e r  t e s t sequence, t h i s does become extremely  i n the  important  near  245 the end of t e s t i n g  f o r i t w i l l provide the operator  a f a l s e l y r a i s e d t h r e s h o l d . The  only way  with  of overcoming  t h i s problem i s to redesign the computer programme to r e - t e s t a p o i n t where f i x a t i o n has changed  (eye  movement, b l i n k e t c . ) with the same luminance Problems a l s o arose with respect to the  level. treatment  1 , 0 0 0 asb. Because of time  of t h r e s h o l d s exceeding  c o n s t r a i n t s with the p a t i e n t s , the maximum i n t e n s i t y s t i m u l i were presented that l e v e l ,  at was  1 , 0 0 0 asb.  the p a t i e n t or normal was  maximum v a l u e . T h i s i n e f f e c t may  If not seen at  assigned  have b i a s e d  that the  r e s u l t s by reducing the range of the a c t u a l t h r e s h o l d difference. In a d d i t i o n to a l t e r i n g how a missed p o i n t due  the perimeter r e - t e s t s  to a problem i n f i x a t i o n , changes  need to be made i n the incremental stimulus about  steps used to change  i n t e n s i t y . For the fovea the steps should  .1 cd/m , which i s much s m a l l e r than the 2  be  1 decibel  step p r e s e n t l y used. Fixation  i s another  major problem. Although  the  r e l i a b i l i t i e s were high with the F225, the allowed  5°  eye movement i s too great f o r r e s e a r c h purposes. More control  i s r e q u i r e d in monitoring  the eye p r i o r to any  f u r t h e r r e s e a r c h . In the case of the F225 t h i s require adaptating perimeter.  some e x t e r n a l monitor to the  will  246 In c o n t r o l l i n g the perimeter,  i t i s recommended to  bypass the LSI computer by i n t e r f a c i n g the F225 with another, more f l e x i b l e computer. T h i s w i l l permit r e s e a r c h to c o l l e c t  the  i n v a l u a b l e data such as the a c t u a l  a p o s t i l b l e v e l presented, one which i s only presented i n graph  form. The  thermal graph used  i s both  time  consumming when t r y i n g to i n t e r p o l a t e v a l u e s as w e l l as problemmatic f o r storage: the thermal graph time or exposure to any  heat.  Other methodological problems may i n t e r p r e t a t i o n of the r e s u l t s . F i r s t , severity important  fades with  index f o r the MS  have a f f e c t e d  the  there i s no  p a t i e n t s . I t would have been  to have some e x t e r n a l s e v e r i t y score as to the  d i s a b i l i t y of the MS  i f c o n c l u s i o n s about the  p r o g r e s s i v e e f f e c t s of the s e v e r i t y of the d i s e a s e are to be made. Moreover, i t would have been d e s i r a b l e to have i n c l u d e d a group of p a t i e n t s who suspected of having MS  were j u s t  and compare these to p a t i e n t s  have been c l i n i c a l l y v e r i f i e d as having  who  i t f o r a long  p e r i o d of time. In f a c t , what i s needed i s a l o n g i t u d i n a l p s y c h o p h y s i c a l study on Another problem was  MS.  the i n a b i l i t y t o a l t e r  r i g o r o u s l y the a d a p t a t i o n a l s t a t e . Without doing so, i t i s impossible to draw any  systematic c o n c l u s i o n s about  the r o l e of rods and cones i n MS. d i d not allow f o r a c o n t r o l l e d e f f e c t s of a d a p t a t i o n .  U n f o r t u n a t e l y the F225  investigation  i n t o the  247  c. Future Research  The r e s u l t s of the study suggest s e v e r a l r e s e a r c h avenues i n s t u d y i n g the e f f e c t s of MS. intensive investigation  First,  a more  i s needed r e g a r d i n g  p s y c h o p h y s i c a l f u n c t i o n i n g of the r e t i n a . Inorder to i s o l a t e the r e l a t i v e c o n t r i b u t i o n s of the two r e c e p t o r systems,  i t will  be necessary to a l t e r  background  i n t e n s i t i e s from the f u l l y photopic to the scotopic. This w i l l  fully  a l s o r e q u i r e the use of  p h o t o m e t r i c a l l y equated chromatic and achromatic stimuli. Secondly, to understand temporal p r o p e r t i e s , the i n v e s t i g a t i o n should examine s p e c i f i c cone f u n c t i o n i n g (for  the red, blue, and green systems) through the  chromatic f l i c k e r  t h r e s h o l d technique using low  r a t e s . The procedure may  be done under  flicker  selective  chromatic a d a p t a t i o n so as to understand cone functioning  i n g r e a t e r d e t a i l than has ever been  p o s s i b l e b e f o r e . By doing so, i n f o r m a t i o n r e g a r d i n g temporal p r o c e s s i n g i n the r e t i n a w i l l be o b t a i n e d . S i m i l a r i l y , temporal p r o c e s s i n g i n the cone system can be s t u d i e d by measuring  achromatic  changes through the chromatic f l i c k e r technique at high f l i c k e r  rates  functional threshold  (eg. 24 Hz). Data  obtained from such a procedure w i l l  provide i n f o r m a t i o n  on the luminance c h a n n e l . A l l of the r e s e a r c h suggested  248 here, of course, w i l l populations  need t o be done on normal  i n order t o determine o v e r a l l normal  psychophysical  f u n c t i o n i n g p r i o r to studying MS and i t s  effects. In c o n j u n c t i o n with the p s y c h o p h y s i c a l  approach,  data regarding s t r u c t u r a l changes i n the r e t i n a (eg. RNFL) needs to be c o l l e c t e d . I t would be valuable c l i n i c a l l y  to c o r r e l a t e p s y c h o p h y s i c a l  with the anatomical, change probably  extremely changes  e s p e c i a l l y s i n c e the p s y c h o p h y s i c a l  occurs p r i o r to any s t r u c t u r a l change.  Moreover, the noninvasive  nature of p s y c h o p h y s i c a l  assessment makes i t a more d e s i r a b l e procedure t o use clinically.  Using c u t - o f f l o g a p o s t i l b t h r e s h o l d values  such as -2.45 f o r the blue, -2.25 f o r the r e d , and -2.50 for  the achromatic  clinical  one may be able t o t o examine  ( v i s u a l ) changes i n the p r o g r e s s i o n of MS more  p r e c i s e l y than was p r e v i o u s l y p o s s i b l e . That i s , these values may be used t o develop v i s u a l t h r e s h o l d p r o f i l e s , which i n turn c o u l d be used not only f o r a s s i s t i n g i n the d i a g n o s i s of MS but a l s o s e r v i n g as the b a s i s of a 'visual'  s e v e r i t y index.  As the cone system appears to be the most s e n s i t i v e to  the presence of a p a t h o l o g i c a l s t a t e , here MS,  further c l i n i c a l  and experimental  r e s e a r c h needs to  focus upon macular f u n c t i o n i n g . V i s u a l evoked p o t e n t i a l procedures, chromatic  f o r example, may be improved by u s i n g  s t i m u l i a t photopic  adaptation  levels  inorder  249 to improve the d e t e c t i o n  r a t e of an a b n o r m a l i t y . In a l l ,  what i s need, i s an e x t e n s i v e  prospective  at  through t h e i r  r i s k p a t i e n t s are  h i s t o r y with an  followed  i n t e n s i v e examintion of  f u n c t i o n i n g . It i s s t r o n g l y f e l t  invaluable  clinical  rod/cone  that the  gained through such an approach would not something about the nature of MS  study whereby  but a l s o  information only  tell  provide  insight into v i s u a l functioning.  us  250  VI. SUMMARY  Through the use of chromatic s t a t i c perimetery, i t was e s t a b l i s h e d that t h r e s h o l d l o s s e s occur a c r o s s the r e t i n a i n MS p a t i e n t s . The l o s s e s appear system  t o be g r e a t e r f o r the cone  r a t h e r than the rod, as i n f e r r e d  from the g r e a t e r  l o s s e s w i t h the chromatic rather than achromatic  filters.  S i g n i f i c a n t d i f f e r e n c e s were found a t the 0 ° e c c e n t r i c i t y between the normal  and c l i n i c a l l y  d e f i n i t e p a t i e n t s but not  the probable and normal. T h i s may have i n d i c a t e d the s p a r i n g of  the 0 ° e c c e n t r i c i t y  i n n o n e s t a b l i s h e d cases of MS. Such  an i n t e r p r e t a t i o n needs to be guarded  due t o problems i n  m o n i t o r i n g eye movement as w e l l as the l a c k of a s e v e r i t y index. D i f f e r e n c e s were found i n the f i l t e r s ,  with the blue  showing s l i g h t l y more s i g n i f i c a n t mean d i f f e r e n c e s than the red  or achromatic between the 3 s u b j e c t groups. Both the  comparison  of mean d i f f e r e n c e s as w e l l as c o r r e l a t i o n s  between the fovea and remaining e c c e n t r i c i t i e s r e v e a l e d e x t e n s i v e involvement of the r e t i n a among the MS p a t i e n t s as compared t o the normals. Threshold d i f f e r e n c e s between the filters  due t o e c c e n t r i c i t y was a l s o noted a c r o s s groups,  and was f e l t rod/cone  to r e f l e c t  system  the s e l e c t i v e s e n s i t i v i t y of the  t o chromatic s t i m u l i . An i n v e s t i g a t i o n of  p a t i e n t s with and without o p t i c n e u r i t i s r e v e a l e d no o v e r a l l s i g n i f i c a n t d i f f e r e n c e s except f o r the d i f f e r e n t i a l s e n s i t i v i t y a c r o s s the r e t i n a to chromatic and achromatic  251 stimuli. The  typical  threshold  swiss cheese f i e l d  s e n s i t i v i t y across  the c l i n i c a l  r e s u l t i n g from i r r e g u l a r  the e c c e n t r i c i t i e s reported  l i t e r a t u r e appears to be true only  achromatic and  blue  s t i m u l i . No  for a red s t i m u l u s . As d e s c r i p t i o n of MS  in  for  such i r r e g u l a r i t y appears  such, the  ophthalmological  c o n s i s t i n g of patchy r e l a t i v e scotoma  l e a d i n g to the swiss cheese f i e l d d e f e c t needs to  be  qualified. The perimetry  importance of a s s e s s i n g MS was  through chromatic  a l s o demonstrated by the a b i l i t y  c l a s s i f y 86.27% of the normals and  MS  to c o r r e c t l y  p a t i e n t s by the  f i l t e r . T h i s high l e v e l of d i a g n o s t i c accuracy along the a b i l i t y  to examine s p e c i f i c cone/rod  i n d i c a t e s the chromatic  invaluable  information  static  red with  functioning  a v a i l a b l e through  perimetry.  Results  from a p i l o t  study i n d i c a t e d that  s t a t e p l a y s a major r o l e in d e t e c t i n g l o s s e s i n MS.  Unfortunately,  relative  the present  adaptation threshold  s t a t e of the F225  d i d not permit f u r t h e r i n v e s t i g a t i o n i n t o the e f f e c t s of adaptational In a l l ,  state. retinal  Fieldmaster® F225 has changes due  f u n c t i o n i n g as assessed with  been shown to be h i g h l y s e n s i t i v e to  to the presence of MS  n e u r i t i s ) . 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Contrast s e n s i t i v i t y i n r e t i n a l d i s e a s e . Ophthalmology, 87, 140-149. Wolman, M. (1970). H i s t o c h e m i s t r y of m y e l i n a t i o n and d e m y e l i n a t i o n . In P.J. Vinken & G.W. Bruyn, (eds.) Handbook of c l i n i c a l neurology. V o l . 9, M u l t i p l e s c l e r o s i s and other d e m y e l i n a t i n g d i s e a s e s . American E l s e v i e r P u b l i s h i n g Co., Inc.: New York, 23-44. Wood, C C . (1982). A p p l i c a t i o n of d i p o l e l o c a l i z a t i o n methods to source i d e n t i f i c a t i o n of human evoker p o t e n t i a l s . Annals of the New York Academy of S c i e n c e s , 338, 139-155. Wooten, B.R., F u l d , K. & S p i l l m a n , L. (1975). Photopic s p e c t r a l s e n s i t i v i t y of the p e r i p h e r a l r e t i n a . J o u r n a l of the O p t i c a l S o c i e t y of America, 65, 334-342. Working Group 41 (1981). Procedures f o r t e s t i n g c o l o r v i s i o n . 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S p e c t r a l s e n s i t i v i t i e s of a c q u i r e d c o l o r d e f e c t s analyzed i n terms of c o l o r opponent t h e o r y . Modern Problems i n Ophthalmology, 19, 254. Zweifach, P.H. (1978). S t u d i e s on hyperthermia i n o p t i c neuropathy: C o n s i d e r a t i o n of a humoral f a c t o r . A r c h i v e s of Ophthalmology, 96, 1831-1834.  284  V I I . APPENDIX A  285 1. POWER SUPPLY  The F225 has four are:  separate power supply u n i t s . These  (1) the thermal p r i n t e r power supply,  power supply,  (2) the computer  (3) the analog power supply, and (4) the  Fieldmaster® power supply. a. Thermal P r i n t e r  Power  Supply  The power source t o the thermal p r i n t e r s w i t c h i n g power supply rated which i s s u i t a b l e The  supply  is a  a t 15 v o l t s and 15 amps,  f o r the Synemed TP640 Thermal  Printer.  (Lambda Model No. LYS-W-15) i s p r e s e t t o  p r o v i d e the proper v o l t a g e f o r the i n d i v i d u a l  printheads  on the p r i n t e r . There are two p r i n t h e a d s , each c o l o u r coded so as t o i d e n t i f y them both on the thermal  printer  and power supply u n i t . The two p r i n t h e a d s a r e :  a. Blue coded -- 16.0 v o l t s b. Brown coded —  b. Computer Power  The  17.0 v o l t s  Supply  power supply  (Lambda Model No. LYS-W-15) to the  computer operates the b a s i c including  functioning  of the F225  background and s t i m u l u s i n t e n s i t y  control,  286 visual  field  s c r e e n i n g , and  r e l a t i v e threshold  e s t i m a t i o n . The power supply has  three d i f f e r e n t  outputs  that are f a c t o r y p r e s e t , which a r e :  a. +5.05 v o l t s b. +12.0  volts  c. -12.0  volts.  c. Analog Power Supply  The  analog  power supply  p r o v i d e s power to the analog analog  (Model No.  HAA-15-0.8)  s e c t i o n of the F225.  The  board, d i s c u s s e d elsewhere, i s a s i g n a l  p r o c e s s i n g board  that b u f f e r s and a m p l i f i e s analog  s i g n a l s . I t i s f a c t o r y preset to produce two  voltages  at:  a. +15.0  volts  b. -15.0  volts.  d. Fieldmaster® Power Supply  The  Fieldmaster® power supply  i s c o n s t r u c t e d to  provide v o l t a g e to the background luminance, luminance, and  stimulus  stepper motor. I t i s housed i n a moveable  s e c t i o n under the t a b l e of the F225. The  bowl of  the  287 F22f perimeter i s connected pin or  to the power supply v i a a 37  connector, which must be disconnected when removing connecting the F225 bowl from the t a b l e . The F225 power supply i s s h i e l d e d from  f l u c t u a t i o n s i n the A.C. circuit.  Examination  transient  power l i n e by a L-C  filter  of the power supply i t s e l f  done by l o o k i n g at the i n d i c a t o r LED's found  can  be  i n the  instrument s h e l l on the Monitor c a r d (to be d i s c u s s e d ) . When f u n c t i o n i n g normally, the LED's w i l l  be a l l l i t .  The power supply outputs a r e :  a. 0 to +13.0 b. +5.8  v o l t s f o r the background bulb  v o l t s f o r the stimulus bulb  c. +12.0  v o l t s f o r the stepper motor.  2. INSTRUMENT SHELL  The F225 i s operated by an LSI-11/2 D i g i t a l Equipment Corporation  (DEC)  computer. The LSI-11/2 i s found i n a c a r d  cage f i x e d to the lower r i g h t hand s i d e of the s h e l l when viwed x).  instrument  from the back of the perimeter  The c a r d cage i t s e l f  c o n s i s t s of a backplane  (see F i g u r e (DEC  No.  H9275A) that has four dual and two quad height p.c.  boards.  The  connects  backplane  i s b a s i c a l l y a s k e l e t a l s t u c t u r e that  the v a r i o u s c.p. boards  to one another and to s e c t i o n s of  the p e r i m e t e r . Power i s s u p p l i e d through a source l o c a t e d i n  288 the  back of  For  a discussion  reader  is  the  c a r d c a g e on t o p o f of  referred  the to  terms  used  the  backplane  in this  L a b o r a t o r y computer  M i c r o c o m p u t e r s and memories  published  itself.  section  the  handbook  and  by the  Digital  Equipment C o r p o r a t i o n . The  following  are  the  various  boards  found  i n the  F225  per i m e t e r . a.  1.  Central  Processing  The c e n t r a l height the  p.c.  Unit  processing  b o a r d found  in  the  c a r d c a g e marked "1B".  floating  point  contains  the  programmes). CPU i s Test  described  under  o r CPU b o a r d i s  lower is  hand c o r n e r the  optimal  (DEC N o . KEV11)  set  and  processor  functions  the  left  a dual  used w i t h  computer  The d i f f e r e n t  section  of  (stored  possible  with  the  r e f e r r e d to  as  Visual  Functions. The CPU i s  address  in s l o t  Grant  Extender.  160-11519) permits  j u m p e r - c o n f i g u r e d t o jump  "0" when t h e  card,  cage.  It  instruction  actual  unit,  the  power  "1A", i s  another  The G r a n t  passes  is  of  p.c.  Extender  backplane  cooling  turned on.  signals  various  p.c.  to  address  Above t h e CPU  b o a r d known as (Synemed to  No.  other  boards  the  boards  i n the  and  card  289 b.  Serial/Memory  The the  card  serial/memory  board  cage.  dual  MXV11-AA) memory the  and  (RAM)  octal  port,  a  rate  177560,  it  c.  use  two  port of  1,  300.  is  found  the  port  0  140000  to  dual  height  any  board  random  RS232  a  (DEC N o .  The  from  f i r s t  interface  with  location  (25  case.  of  addressed  memory  DB25  "2B"  access  157776.  the  instrument for  slot  RAM i s  standard  on  located  in  pin)  The  does  F225  operation.  fixed  and  "8A".  (ROM).  The  information  header  Output  labels  Information  a to  4k  byte  16776.  the  end  The  of  as  in  may  be  each  in  this  found  is  board  ROM c a r d  used  "window"  board  such  information  the  operator.  p.c.  slot  at  160000  of  ports.  through  in  p.c.  bytes  Addressed at  automatically  through  8k  a  found  height  serial  connected  other  contains  output.  of  locations  read-only-memory  lines,  a  is  Board  The board,  and  serial  Image  is  consists  is  connector not  It  memory  serial baud  Board  the  consists  (DEC N o .  box  lines,  generating either run  image of  MRV11-C) degree printer  obtained  or  by  request  board  is  processed  memory  locations  in  of  290 d.  Printer  Control  The p r i n t e r quad h e i g h t to  the  board. the  In  "5B"),  cool  e.  cycle  Next  the  and  to  f.  boards  right  various  the  the  This  Grant  the  to  "4A",  board for  a  data  drive interfaces  generating the  Extenders  card  is  transfer  from  p a s s bus  of  board, the  the  Grant  image  (slots  signals  "5A"  as well  as  cage.  Extenders  (eg.  board,  (slots  DEC L S I - 1 1 / 2  stimulus  is  "6A" computer  control)  and  parts.  Convertor  to  analog convertor  including  level  drive  interface  the  in  going  a c c o m p l i s h e d by  the to  (DAC) c o n s i s t s  a DAC1220 t w e l v e  T h e DAC e n a b l e s  {12).  background  is  in  following  circuits  background  two  F225 f u n c t i o n s  The d i g i t a l  convertor  time  (information  slot  printer  control  board connects  Digital-Analog  various  is  the  and off  used to  quad p . c .  This  of  through  in  Board  the  consists  function  (on  are  are  various  "6B").  with  this  found  printer  control  which  Another found  Its  the  timing  to  Interface  board,  printheads  and p r i n t  board). and  board.  addition,  print  plots)  control  p.c.  thermal  Board  bowl  Fieldmaster®  LSI-11/2  bit  LSI-11/2  perimetry  the  the  the  of  to  control  through Power  sending  the  Supply.  twelve  bit  291 s i g n a l s to the DAC, thereby producing an analog d r i v e s i g n a l f o r the Fieldmaster® Power Supply. The DAC i t s e l f i s powered by a v o l t a g e r e g u l a t o r  (Z10) that a l l o w s the  analog output to range from 0 to +10.24 v o l t s . g. A n a l o g - D i g i t a l Convertor  The analog to d i g i t a l c o n v e r t o r (ADC) i s comprised of an ADC1210 twelve b i t c o n v e r t o r (Z5), which enables the computer t o r e c o r d and monitor analog i n f o r m a t i o n from e i g h t channels. The analog s i g n a l s from the e i g h t channels a r e d i r e c t e d  i n t o an analog m u l t i p l e x e r  (Z7) t o  the DAC.  Channel  1 Stimulus l e v e l  Channel  2 Stimulus l e v e l X 22.1  Channel  3 Background  Channel  4 A t t e n t i o n monitor  (x plane)  Channel  5 A t t e n t i o n monitor  (y plane)  Channel  6 A t t e n t i o n monitor common mode  Channel  7 Analog ground  1  level  Channel 8 Analog ground  The m u l t i p l i c a t i o n value of 22.1 i n the second channel i s to i n c r e a s e r e s o l u t i o n a t lower l i g h t l e v e l s so as t o be a b l e t o a c c u r a t e l y record s t i m u l u s i n t e n s i t y . Both channels 1 and 2 o v e r l a p , making i t p o s s i b l e to p r o v i d e measures of l e v e l s c o n t i n u o u s l y from h i g h (30,000 asb) to low (x asb) stimulus i n t e n s i t i e s . 1  292 h. Permanent Memory  Permanent memory c o n s i s t s of a RAM c h i p byt).  (1k by 4  In a d d i t i o n , there are two b a t t e r i e s s e r v i n g as  power back-up i n case of power f a i l u r e from the Fieldmaster® Power Supply. The permanent memory stores test information i.  chip  obtained from a t e s t run.  A t t e n t i o n Monitor Targets  Both the a t t e n t i o n monitor and macula (discussed  target  elsewhere) are monitored f o r i n t e n s i t i e s . The  montiors are powered by s i g n a l s from the background preamplifier  (BGLVL) and are adjusted  by the c h i p s R70  (macula t a r g e t ) and R71 ( a t t e n t i o n m o n i t o r ) . j.  Alarm  Alarms are produced when e i t h e r the a t t e n t i o n monitor d e t e c t s  gross changes i n the s u b j e c t ' s  position  or when t e s t i n g i s completed. An alarm i s a l s o a c t i v a t e d during  t e s t i n g when there  perimeter i t s e l f  i s some problem with the  (discussed  i n the s e c t i o n on e r r o r  feedback -- Appendix x ) . The alarm i t s e l f  i s produced by  a timer and can be a m p l i f i e d by the Z14 c h i p and adjusted  by the R71.  293 k. Stepper D r i v e  There are three steper motors, i s on the i n t e r f a c e board. The f i r s t  the d r i v e f o r which stepper motor  operates the s e l e c t o r arm ( s e l e c t s s t i m u l u s p o s i t i o n ) and the d r i v e output f o r i t i s found on p i n s 9, 10, 11, and  12 on the P8 connector. The second stepper motor  c o n t r o l s the stimulus i n t e n s i t y wedge, which i s done throug p i n s 7, 8, 13, and 14. The f i n a l operates the s t i m u l u s c o l o u r f i l t e r  stepper motor  through p i n s 3, 4,  5, and 6. 1. Programme Board  The programme board i s below the serial/memory in  slot  card  "2k". I t i s read-only-memory (ROM) and s t o r e s  the o p e r a t i n g programmes a v a i l a b l e on the F225. The board  (DEC No. MRV11-C) has 48 bytes comprised of 12  I n t e l 2732 EPROM's. The EPROM's c n t a i n the a c t u a l programmes from Synemed. When s t a r t e d , the programme board a u t o m a t i c a l l y i s c o n f i g u r e d t o s t a r t at address 0. To the r i g h t of the board are two Grant Extenders for  used  cooling.  m. Monitor  Board  The monitor  board i s found on the l e f t  of the c a r d  cage, and i s r e c o g n i z a b l e by ten LED's (eight green, one  294 red,  and one y e l l o w ) . The red LED, when on, i d i c a t e s the  presence of a f a u l t at which time the instrument  powers  down stopping a l l t e s t i n g . See Appendix D f o r a l i s t of p o s s i b l e e r r o r s . The yellow LED i n d i c a t e s normal f u n c t i o n i n g , and turns o f f when e i t h e r a f a u l t i s d e t e c t e d or the RUN/HALT switch  (discussed s h o r t l y ) i s  toggled. The  e i g h t green LEDs i n d i c a t e the f u n c t i o n i n g of  t h r e s h o l d comparators that monitor power v o l t a g e s i n the v a r i o u s areas of the p e r i m e t e r . A green LED w i l l be turned o f f when i t s a s s o c i a t e d v o l t a g e comparator a drop i n the v o l t a g e of a s p e c i f i c  senses  power supply. At the  same time a drop i n v o l t a g e i s sensed, the red f a u l t LED will  be turned on and the cpu c a r d begins t o power down  the perimeter  immediately.  The f o l l o w i n g i s a l i s t of  what t h r e s h o l d v o l t a g e s a r e a s s o c i a t e d with a s p e c i f i c green LED.  a. LED #1 v o l t a g e = -15 V., t h r e s h o l d v o l t a g e = -12.2 V. b. LED #2 v o l t a g e = +12 V. (Fieldmaster® Power Supply), t h r e s h o l d v o l t a g e = +11.0 V. c. LED #3 v o l t a g e = +17 V. (Thermal P r i n t e r  Power  Supply), t h r e s h o l d v o l t a g e = +14.0 V. d. LED #4 v o l t a g e = +15 V., t h r e s h o l d v o l t a g e = +12.2 V. e. LED #5 v o l t a g e = +5.8 V. (Stimulus  Supply),  295 t h r e s h o l d v o l t a g e = +4.99 V. f. LED #6 v o l t a g e = -12.0 V., v o l t a g e = -11.0 V. g. LED #7 v o l t a g e = +5.0 V. (Computer Power Supply), v o l t a g e = +4.42 V. h. LED #8 v o l t a g e = +12.0 V. (Computer Power Supply), v o l t a g e = +11.0 V.  In a d d i t i o n to the sensing of a change i n the power voltage f o r sections l i k e  the power supply t o the  computer  (3), wherein i f the t h r e s h o l d  (8,9) or p r i n t e r  voltages l i s t e d  above are reached  a power down sequence  commences, two buss s i g n a l s (BPOK and BDCOK) monitor v o l t a g e changes from the A.C. l i n e . The  monitor board  a l s o c o n t a i n s two t o g g l e  switches  used to e i t h e r power down or power up the perimeter d u r i n g t r o u b l e s h o o t i n g . Both switches  d u r i n g normal  o p e r a t i o n are i n the down p o s i t i o n . The f i r s t switch on the l e f t hand s i d e , the RUN/HALT switch, i s used to power down the perimeter. T h i s i s done by t o g g l i n g the RUN/HALT switch i n t o the up p o s i t i o n , causing the yellow LED  to go o f f and, at the same time,  The  second switch on the r i g h t hand s i d e of the monitor  board  i s the INIT switch  (initialize  switch i s used t o i n i t i a l i z e mode. To i n i t i a l i z e ,  the red to go on.  s w i t c h ) . The INIT  the LSI-11/2 i n t o  running  the RUN/HALT switch must be i n the  down p o s i t i o n and the INIT switch t o g g l e d f i r s t up and then down. I f done c o r r e c t l y , the yellow  (running  light)  296 LED w i l l  be on. When c o n n e c t i n g any minicomputer or  other p e r i p h e r a l t o the perimeter f o r the purpose of debugging  problems  or i n c r e a s i n g the c a p a b i l i t i e s (eg.  storage) of the 225 , i t i s extremely u s e f u l to remove the  back p l a t e of the perimeter so as to have access to  the  switches and observe the LEDs on the monitor  board.  n. Analog Board  The analog board i s found on the l e f t monitor board. I t s f u n c t i o n  near to the  i s to b u f f e r and a m p l i f y  s i g n a l s coming from the a t t e n t i o n monitor, the background  p r e a m p l i f i e r , and the s t i m u l u s p r e a m p l i f i e r .  Input to the analog board a r r i v e on a 26 p i n Berg connector the  (P6) and e x i t  through a 10 p i n f l a t  c a b l e to  m u l t i p l e x e r . A l l s i g n a l s from the analog board go  directly  to the i n t e r f a c e board through the m u l t i p l e x e r .  o. A t t e n t i o n Monitor  Board  The monitor c o n s i s t s of a photodetector that doubles as an a m p l i f i e r . R e f l e c t i o n o f f the cornea i s imaged onto four quadrants of a photodector housed o p t i c a l t e l e s c o p e assembly.  Quadrants  i n an  1 and 3 of the  photodetector c r e a t e c u r r e n t s whose v a l u e s represent changes i n the r e f l e c t e d l i g h t changes,  from the cornea. These  r e p r e s e n t i n g eye movements, are then summed and  passed onto the analog board. S i m i l a r i l y , quadrants 2  297  and  4 pass t h e i r produced c u r r e n t changes whose sum  sent to the analog  board. The  quadrants are converted  values  from the  to v o l t a g e s p r i o r  is  various  to  transmission. p. Background P r e a m p l i f i e r  A photodiode c o n s t a n t l y measures the background illumination  i n the bowl. The  photodiode c r e a t e s a  c u r r e n t that i s d i r e c t l y p r o p o r t i o n a l to the level  i n the hemisphere. Through a v o l t a g e  (Z1),  the c u r r e n t  that  i s processed  luminance  convertor  i s then changed i n t o a v o l t a g e to the analog  value  board. S i g n a l s from the  p r e a m p l i f i e r are enhanced by a "background a m p l i f i e r " that  i n c r e a s e s the c u r r e n t value by a f a c t o r of  2.2.  T h i s i s done so as to i n c r e a s e the " s e n s i t i v i t y " of photodiode, i . e . small f l u c t u a t i o n s in the c u r r e n t  the are  registered. q. Stimulus  Preamplifier  Stimulus filtered  light  intensity  i s monitored by sampling  the  from the main p r o j e c t i o n beam. The  actual  i n t e n s i t y , monitored by a photodiode, i s a m p l i f i e d through two for  voltage convertors  n o n - l i n e a r i t y . Two  a d j u s t the stimulus  (Z1,  Z2)  and  i s corrected  other photodiodes are used to  intensity calibration.  c a l i b r a t i o n adjustment occurs  The  i n c o n j u n c t i o n with  the  298 non-linear  c o r r e c t i o n of luminous i n t e n s i t y . The  on the F225 r e f e r s to the adjustment of  manual  stimulus  i n t e n s i t y as slope c o r r e c t i o n p r e a m p l i f i c a t i o n . Output from the  stimulus  preamplifies  goes d i r e c t l y to  the  Analog board wherein the v a r i o u s  signals  monitor, background and  i n t e n s i t y l e v e l s ) are  processed toward the r.  the  stimulus  Interface  (attention  board.  P r o j e c t o r / S h u t t e r / F i l t e r Assembly  T h i s u n i t , s i t u a t e d on top of the S e l e c t o r converges the p r o j e c t e d arm  l i g h t conduit.  the LSI-11, two  Board,  beam of l i g h t onto a s e l e c t o r  Through stepper motors c o n t r o l l e d by  (2) f i l t e r  wheels r o t a t e around an  aperature from which the p r o j e c t e d  beam i s passed  through the  fibre optics.  filter for  filter  wheels onto the  wheel c o n s i s t s of n e u t r a l d e n s i t y  c o n t r o l l i n g stimulus  filter  filters  i n t e n s i t y whereas the  One used  other  wheel i s comprised of 4 Kodak Wratten F i l t e r s  632.7, 581.2, 533.8, 489.3 nm.) latter  filter,  and  one  achromatic  filter.  The  colour,  i s operated through a separate stepper motor  than the n e u t r a l d e n s i t y c o n t r o l l e d by the  r e f e r e d to as the wedge  filter.  Interface  Both f i l t e r  shutter  for stimulus  wheels are  Board.  In a d d i t i o n , the assembly c o n t a i n s responsible  (X  photodiodes  preamplifications  f o r c o n t r o l l i n g stimulus  as w e l l as a  presentation.  299 s. S e l e c t o r  The  Board  board i s l o c a t e d c e n t r a l l y on the bottom of the  instrument housing. I t c o n t a i n s that  form a c i r c u l a r p a t t e r n  d r i v e n arm. A l i g h t conduit  149 f i b r e o p t i c  radially  from a motor  on the arm p r o j e c t s a l i g h t  beam, o r i g i n a l l y d i r e c t e d t o the center r o t a t i o n , to s p e c i f i c operator defined  strands  of the arm's  o p t i c f i b r e s as determined by the  programme. The a c t u a l p o s i t i o n of the  motor d r i v e n arm i s c o n t r o l l e d by a stepper motor operated by the I n t e r f a c e  board.  VIII.  Photometric  Bowl  APPENDIX B  Measurements  PHOTOMETRIC MEASUREMENTS IN APOSTILBS (ABS.) AND CANDELLA/METER (CD/M-2) OF BACKGROUND INTENSITIES BY STIMULUS POSITION IN THE FIELDMASTER F225 PERIMETER* BACKGROUND INTENSITY (APOSTILBS)  Note:  STIMULUS POSITION 1  2  3  4  5  6  7  8  9  10  2  0 .81 ABS. CD/M- 2 ' 0 . 26  0 .83 O .26  0 .88 0 .28  0 .87 0 . 28  0 . 75 0 . 24  0 .05 O .02  0 .69 O . 22  0 .94 O .30  0 .80 O .25  0 .85 O . 27  5  ABS. CD/M- 2  4 .75 1 .51  4 .59 1 .46  4 .39 1 .40  4 . 56 1.45 ,  3 . 19 1 .01  0 .69 0 .22  2 .56 0 81  4 .27 1 . 36  4 .51 1 .44  4 . 53 1 . 44  10  ABS. CO/M- 2  10 .58 3 .31  10 43 10 . 16 10 , 39 3 . 32 3 23 3 .31  7 29 2 . 32  1 . 79 0 .57  5. , 75 1 .83  9. 64 3 07  15  ABS. CD/M- 2  16 .83 5 .08  16 48 5 .25  16 . 39 1 139. 5. 22 3 63  2 98 0 .95  9. 10 15. 37 4 . 89 2. 90  30  ABS . CD/M- 2  35 28 34 .61 34 . 15 34 . 12 24 .. 12 1 1 , 14 . 1 102. 10. 87 10. 86 7. 68  6 . 16 19. 09 32 . 27 34 . 42 33 .83 1 96 6. 08 10. 37 10. 96 10 .77  45  ABS. CD/M- 2  53 78 53. . 38 52. 69 52 . 76 36. 68 16. 88 16. 99 16. 77 16. 79 1 168.  8 .73 29. 08 49. 53 52 . 76 52 . 25 2. 78 9. 26 15. 77 16. 79 16 .63  50  ABS. CD/M- 2  59. 75 58. 95 58 . 09 58. 49 40. 74 18. 83 18. 76 18. 49 18. 62 12 . 97  9. 49 32 . 26 54 . 95 58 . 29 57 .42 3. 02 10. 27 17 . 49 18. 56 18 .28  55  ABS. CD/M- 2  61 . 04 59. 79 58. 89 58 . 65 40. 68 19. 18 19. 03 18 . 75 18. 67 12. 95  9. 49 32 . 22 54 . 85 58 . 28 57 . 42 3. 02 10. 26 17. 46 18. 55 18 .23  16 .41 5 .22  * - Values p r e s e n t e d are based on the mean of stimulus p o s i t i o n .  10 . 29 10 . 25 3 .28 3 . 26 16 39 5 . 22  16 .20 5 . 16  3 measurements done on each  PHOTOMETRIC MEASUREMENTS IN APOSTILBS (ABS.) AND CANDELLA/METER (CD/M-2) OF BACKGROUND INTENSITIES BY STIMULUS POSITION IN THE FIELDMASTER F225 PERIMETER* STIMULUS POSITION BACKGROUND INTENSITY (APOSTILBS)  11  12  13  14  15  16  17  18  19  20  2  ABS. CD/M- 2  0 .81 0 .26  0 .85 0 .27  0 .78 0 .25  0 .85 0 .27  0 .85 0 .27  0 .89 0 .28  0 .78 0 .25  0 .84 0 .27  0 .93 0 .81 0 . 30 0 . 26  5  ABS. CD/M- 2  4 .43 1 .41  4 .39 1 .40  4 . 34 4 .52 1 .44 1 .38  4 .56 1 .45  4 .37 1 .39  4 .04 1 .30  4 .47 1 .42  4 . 36 4 .24 1 .39 1 .35  10  ABS. CO/M- 2  9 .49 9 .92 10 .09 10 .21 10 . 12 9 .99 9 .29 10 .29 10 .23 3 . 17 3 . 16 3 .21 3 .25 3 .22 3 . 18 2 .96 3 .28 3 .26  15  15 .95 15 .74 15 .89 16 . 24 16 .21 15 .93 14 .89 16 . 35 16 . 13 15 . 53 ABS. CD/M- 2 5 .08 5 .01 5 .06 5 . 17 5 . 16 5 .07 4 .74 5 .20 5 . 13 4 .94  30  ABS . 33 .69 33 .05 33 .52 34 .09 34 .21 33 . 30 31 . 30 34 . 25 34 . 1 132 . 15 CD/M- 2 10 .72 10 .52 10 .67 10 .85 10 .89 10 .60 9 .96 10 .90 10 .86 10 .23  45  ABS. 50 .99 50 .71 51 . 1 152 .06 52 .64 51 .59 47 .65 52 .84 52 .59 49 . 57 CD/M- 2 16 .23 16 . 14 16 .27 16 .57 16 .76 16 .42 15 .26 16 .82 16 .74 15 .78  50  55 .91 55 . 10 55 .51 56 .77 56 .85 55 .66 51 .74 56 . 73 56 .63 53 . 19 ABS. CD/M- 2 17 .80 17 .54 17 .67 18 .07 18 . 10 17 .72 16 .47 18 .06 18 .03 16 .93  55 \  9 .82 3 . 13  ABS. 55 .82 CD/M-2 17 .77  Note: * - Values p r e s e n t e d are based on the mean of 3 measurements done on each stimulus p o s i t i o n .  303 IX. APPENDIX C  F225  Automatic V i s u a l F i e l d Programmes  304  1. CONTENTS  The v i s u a l available  f i e l d programmes are copywrited and are  from Synemed upon w r i t t e n  request.  X. APPENDIX D  Automatic Contour Programmes  306 1 . CONTENTS  The contour programmes are copywrited and are a v a i l a b l e from Synemed upon w r i t t e n  request.  XI. APPENDIX E  F225 Automatic M e r i d i a n Programmes  308  1 . CONTENTS  The meridian programmes are copywrited and are available  from Synemed upon w r i t t e n  request.  309 X I I . APPENDIX F  310 1. COMPUTER INTERFACE The Fieldmaster® F225 uses a D i g i t a l LSI 11/2 microcomputer both with another  f o r programme execution and communicating  host. The LSI can be used i n a s p e c i a l  debugging mode known as O c t a l Debugging Technique  (ODT). The  system to be connected through a s e r i a l l i n k with the F225 must appear as a t e r m i n a l to the LSI 11/2. The s e r i a l l i n k i s through a RS-232c a l r e a d y found  i n the F i e l d m a s t e r .  The communications p o r t on the host computer connect  to i t s c o u n t e r p a r t  on the F i e l d m a s t e r  will  through p i n s  2, 3, and 7 on the RS-232. S i g n a l s from any of the other p i n s w i l l be ignored. The host computer must be s e t on the following  specifications:  1.  8 b i t s , no p a r i t y  2.  1 stop b i t  3.  300 Baud rate  Once connected, t h r e s h o l d i n f o r m a t i o n may be obtained in o c t a l values for  intensity  transforming averaging  from two memory l o c a t i o n s s t a r t i n g a t 144650  seen and 144742 f o r i n t e n s i t y not seen. By the o c t a l values  i n t o the decimal  system and  the seen/not seen i n t e n s i t y v a l u e s , one o b t a i n s  the t h r e s h o l d f o r each e c c e n t r i c i t y  tested.  311  -I  X I I I . APPENDIX G  MULTIVARIATE ANALYSIS OF VARIANCE BETWEEN NORMALS (n=30) OPTIC NEURITIS (n=8), AND NON OPTIC NEURITIS (n=14) MS PATIENTS  SOURCE  SS  48511962. 29 GROUP (G) FILTER (F) 13381983. 78 ECCENTRICITY (E) 33959267. 43 G G F G X  X X X F  F E E X E  df  MS  F  2,49 18 .06 24255981. 1 4 2,98 6690991. 89 104 .52 42 .85 3. 70,181 .54 2612251. 34  464663. 53 2. 86,70. 01 4099006. 93 7. 41,181 .54 57,567 .06 4878008. 39 1 1 . 1929719. 1 1 23. 14,567 .06  116165. 88 1 57654.1 1 187615. 71 37109. 98  1 .81 2 . 59 1 4. 1 1 2 .79  NOTE: * Denotes p r o b a b i l i t y a f t e r degees of freedom have been a d j u s t e d by the Greenhouse-Geisser.  P.0000 .0000* .0000* .1550* .0128* .0000* .0000*  

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