- Email: [email protected]
Visual evoked potentials in successfully treated strabismic amblyopes and normal subjects
Visual Evoked Potentials in Successfully Treated Strabismic Amblyopes and Normal Subjects Patrick O. Watts, FRCOphth,a Magella M. Neveu, MSc, IPEM,b Graham E. Holder, MSc, PhD,b and John J. Sloper, DPhil, FRCS, FRCOphtha Purpose: To assess electrophysiological recovery in successfully treated strabismic amblyopes. Methods: Pattern reversal visual evoked potentials were recorded from 11 successfully treated strabismic amblyopes 7 to 11 years of age and 10 age-matched normal children using 12.5’ and 50’ checks. Results: Nine amblyopic eyes had recovered to a Snellen acuity of 6/6 or better, and the remaining 2 were 6/9 after patching. Comparison between the amblyopic and the fellow eyes showed significantly lower P100 amplitude for the amblyopic eyes with small checks (difference –16.7%; P ⬍ .02) and significantly longer latency with larger checks difference (⫹5.0%; P ⬍ .02). The P100 latencies to stimulation of both the amblyopic and fellow eyes by 12.5’ checks were markedly longer than in normal subjects (amblyopic eye, ⫹11.7%, P ⬍ .0001; fellow eye, ⫹7.7% P ⬍ .002). Conclusions: Successfully treated amblyopic eyes showed significantly longer latency than did normal eyes with small check stimulation. However, the nonamblyopic fellow eyes also showed significantly longer latency than did normal eyes, suggesting altered central processing. (J AAPOS 2002;6:389-92) attern visual evoked potentials (VEPs) recorded from human amblyopic eyes might show attenuated amplitudes and prolonged latencies.1,2 These abnormalities might recover in association with improvement in visual acuity when the amblyopia is treated.3 However, there is some evidence that the fellow eye in amblyopia may show VEP abnormalities2-4 and reduced contrast sensitivity.5 The present study examines VEPs in children who were successfully treated for strabismic amblyopia. Comparisons have been made not only between the amblyopic and the fellow eyes, but also between responses from both the amblyopic and the fellow eye, and between amblyopes and normal age–matched children to investigate the characteristics of the VEPs recorded after successful treatment.
P
SUBJECTS AND METHODS Pattern reversal VEPs were recorded from 11 successfully treated strabismic amblyopes 7 to 11 years of age and 10 normal subjects of similar age. Eight subjects in each group were boys. The amblyopes had completed their
From Moorfields Eye Hospital, London, United Kingdom. aStrabismus and Paediatric Service. bDepartment of Electrophysiology. Presented as a poster at AAPOS Annual Meeting, San Diego, California, 2000. Submitted February 4, 2002. Revision accepted July 28, 2002. Mr John Sloper, Moorfields Eye Hospital, City Road, London EC1V 2PD, United Kingdom; e-mail, [email protected]. Copyright © 2002 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2002/$35.00 ⫹ 0 75/1/129046 doi:10.1067/mps.2002.129046
Journal of AAPOS
amblyopia therapy at least a year before their recruitment to this study. Using a standard Snellen chart, all amblyopes had a best– corrected acuity of 6/9 or better in their amblyopic eye and 6/6 or better in their fellow eye. The 10 normal subjects had binocular single vision with a TNO stereoacuity (Lame´ris Ootech BV, Nieuwegein, The Netherlands) of 60 sec of arc or better and a corrected visual acuity of 6/6 or better in each eye. Pattern reversal VEPs were recorded with 12.5⬘ and 50⬘ checks, with white luminance more than 80 cdm⫺2, contrast of 80%, and a reversal rate of 1.1 Hz. The recording bandwidth was 1-100 Hz. Full refractive correction was used during recording. Peak-to-peak amplitudes and peak latency were measured from the midline P100 component for each check size for each eye. The active electrode was Oz and the reference Fz. Statistical analysis was performed with the Wilcoxon rank sum test for comparison of amblyopic and fellow eyes, and the Mann-Whitney U test for comparisons between amblyopes and normal subjects. Both were corrected for tied values. The study was approved by Moorfields Hospital’s ethical committee.
RESULTS Clinical data for the 11 strabismic amblyopes are shown in Table 1. Nine amblyopic eyes had recovered to a Snellen acuity of at least 6/6 after patching, and the other 2 were 6/9. All fellow eyes had an acuity of 6/6 or better (Table 1). The small residual difference in acuity between the treated amblyopic and the fellow eyes was statistically significant (P ⫽ .026; Wilcoxon signed rank test). There was no December 2002
389
390
Journal of AAPOS Volume 6 Number 6 December 2002
Watts et al
TABLE 1. Details of amblyopic patients Initial acuity of Final visual acuity Patching Duration of amblyopic Age started Type of patching eye Amblyopic Fellow Patient (years) Sex (months) patching (months) Diagnosis 1 2 3 4 5 6 7 8 9 10 11
8 11 9 10 8 7 9 11 9 10 7
M M F M M M M F M M F
12 18 18 4 20 60 36 48 48 48 24
PT FT/PT PT PT PT PT FT/PT PT PT FT/PT PT
24 30 12 12 18 12 36 8 16 36 6
L ET R ET L ET L ET L ET R ET L ET R ET L ET R ET L ET
6/36 6/24 6/24 Obj 6/12 6/24 3/60 6/24 6/18 1/60 6/12
6/6 6/5 6/9 6/6 6/5 6/9 6/9 6/6 6/5 6/6 6/6
6/6 6/5 6/6 6/4 6/5 6/5 6/5 6/4 6/4 6/6 6/6
Refraction Amblyopic
Fellow
⫹4.25/⫹0.25⫻170 ⫹2.00/⫺1.50⫻100 ⫹0.25 ⫹3.50/⫹3.00⫻90 ⫹2.00/⫹1.00⫻90 ⫹4.50/⫺0.50⫻100 ⫹4.00 ⫹7.00/⫺0.75⫻180 ⫹8.75/⫺1.75⫻5 ⫹5.00/⫺1.50⫻20 ⫹6.25/⫺0.50⫻60
⫹4.00/⫺0.25⫻170 ⫹1.50/⫺1.00⫻90 ⫹0.25 ⫹2.50/⫹2.00⫻95 ⫹2.00/⫹1.00⫻90 ⫹2.00/⫺0.25⫻100 ⫹3.00/⫺0.75⫻130 ⫹6.50/⫺1.00⫻180 ⫹7.75/⫺1.25⫻180 ⫹3.00 ⫹4.25
M, Male; F, female; FT, full time; PT, part time; R, right; L, left; ET, esotropia; Obj, objected to occlusion of fixing eye.
significant difference between fellow and normal eyes (P ⫽ .88; Mann-Whitney U test using 1 random normal eye). Seven subjects showed no evidence of binocular function after treatment, with a manifest squint and suppression of the deviating eye on testing with Bagolini striated glasses. Patient 6 initially showed evidence of central suppression but recovered to have a stereoacuity of 60 sec of arc after treatment; patient 8 had left suppression when amblyopic but recovered to have a fully accommodative squint with a TNO stereoacuity of 60 sec of arc; patient 9 recovered to have a fully accommodative squint with a TNO stereoacuity of 480 sec of arc, and patient 11 had convergence excess esotropia and recovered after occlusion and surgery to have a TNO stereoacuity of 60 sec of arc. There were no significant differences in either P100 latency or amplitude between those with and without binocular function, and they have been considered together. The median age at which patching was started was 24 months (range, 4-60 months). Eight patients had part-time occlusion of 2 to 4 hours a day; 3 patients also had periods of full-time occlusion of 2 weeks, 6 months, and 14 months. The median duration of patching was 16 months (range, 6-36 months) (Table 1). Electrophysiological Data Comparison of the electrophysiological data for the amblyopic and the fellow eyes showed small interocular differences between the VEPs, with the amplitudes slightly smaller and the latencies slightly longer from the amblyopic eyes. Statistically significant mean differences were present only for amplitude with the 12.5⬘ check (⫺16.7%; P ⬍ .02) and for latency with the 50⬘ check (⫹5.0%; P ⬍ .02) (Table 2). Significant differences between the eyes of the normal controls were not observed. However, the mean P100 latency was significantly longer than normal for both amblyopic and fellow eyes to the 12.5⬘ check stimulus (amblyopic eye, ⫹11.7%, P ⬍ .0001; fellow eye, ⫹7.7%, P ⬍.002) (Figure), but not to
the 50⬘ check (Table 2). The amplitude of the fellow eye response to 12.5⬘ checks was also greater than normal, but there was considerable intersubject variability. The onset of amblyopia was recorded in the hospital notes as before 18 months of age in patients 1 to 5 and after 18 months of age in patients 6 to 11. Separate analyses of these subgroups showed that the latency changes were similar, and both were significantly different from normal for amblyopic and fellow eyes (both, P ⬍ .02; Mann-Whitney U test). However, the residual amplitude difference between amblyopic and fellow eyes for 12.5’ checks was much larger in the late onset group than in the early onset group (early onset mean difference –7.0%, P ⫽ .35; late onset mean difference –25.4%, P ⬍ .05; difference between early and late onset significant, P ⬍ .05, MannWhitney U test). There were no significant correlations between the interocular P100 latency asymmetry and either the age of onset of patching, the duration of patching, or the initial acuity of the amblyopic eye.
DISCUSSION Although visual acuity had returned to normal after successful patching, there were still small differences in acuity and small mean VEP differences between amblyopic and fellow eyes. However, the most notable feature in these patients was that the P100 latency with small-check stimulation of both amblyopic and fellow eyes was significantly prolonged compared with normal subjects. This largely masked the increased latency in their amblyopic eyes when interocular comparisons were made. The central visual pathways serving both the amblyopic and the fellow eyes of these children thus remained affected after clinically “successful” patching. Several previous studies have examined the VEP from the fellow eye in amblyopes.1-4 Using a pattern reversal stimulus with a large check and lower contrast, Arden and Barnard3 found that the latency of the fellow eye response
Journal of AAPOS Volume 6 Number 6 December 2002
Watts et al
TABLE 2. Electrophysiological data for 11 successfully treated strabismic amblyopes 12.5ⴕ check P100 latency (ms) Patient 1 2 3 4 5 6 7 8 9 10 11 Mean ⫾ SD % difference Amblyopic v fellow Significance* Normal mean ⫾ SD† % difference compared with normal Significance‡
391
50ⴕ check
P100 amplitude (V)
P100 latency (ms)
P100 amplitude (V)
Fellow
Amblyopic
Fellow
Amblyopic
Fellow
Amblyopic
Fellow
Amblyopic
118 111 120 108 124 120 120 112 116 114 114 116.1 ⫾ 4.8
116 124 116 115 123 124 120 116 123 113 117 118.8 ⫾ 4.1
37.1 15 37.8 32.4 17.1 11.5 28.7 31.6 20.5 32.2 32.2 26.9 ⫾ 9.2
30.9 13.0 43.2 27.2 15.4 9.2 21.9 20.9 13.2 23.4 28.3 22.4 ⫾ 9.8
105 104 105 102 111 116 104 102 104 103 104 105.4 ⫾ 4.3
108 130 104 102 114 130 108 105 104 105 108 110.7 ⫾ 10.1
36.5 11.8 35.7 22.2 22.9 11.8 33.1 18.8 19.7 20.3 34.7 24.3 ⫾ 9.2
29.8 9.2 34.7 23.6 20.7 7.7 24.8 24.2 16.5 21.9 26.0 21.7 ⫾ 8.1
107.8 ⫾ 4.0 ⫹7.7%
⫹2.4% NS 106.2 ⫾ 5.1 ⫹11.7%
18.9 ⫾ 8.7 ⫹42.4%
⫺16.7% P⬍.02 20.0 ⫾ 10.0 ⫹12.2%
106.3 ⫾ 3.6 ⫺0.8%
⫹5.0% P⬍.02 105.4 ⫾ 3.6 ⫹5.0%
23.6 ⫾ 8.9 ⫹3.3%
⫺10.6% NS 22.1 ⫾ 7.5 ⫺1.4%
P⬍.002
P⬍.0001
P⬍.05
NS
NS
NS
NS
NS
*Wilcoxon signed rank test v fellow eye; †Fellow eyes are compared with normal right eyes and amblyopic eyes with normal left eyes; ‡Mann-Whitney U test v corresponding normals; NS, not significant.
in children ages 4 to 11 was delayed during patching but had returned to normal in most eyes by a year after patching had been discontinued. This agrees with the results found here with a large check. Sokol1 found no difference between the fellow eyes of amblyopes and normal subjects, with younger subjects ranging in age from 3 to 7.5 years. Shawkat et al2 found reduced P100 amplitude in the fellow eyes of amblyopes compared with normal eyes and suggested that this might be due to patching. A more recent study of treated anisometropic amblyopes ages 4 to 12 years showed increased P100 latencies to small checks from both amblyopic and fellow eyes, paralleling the results found here with strabismic amblyopes.4 The ages of the patients in the present study—7 to 11 years—facilitated better patient compliance and less variability than would have been found in a younger group. This increased the sensitivity of the study to detect significant group mean differences compared with previous reports where younger children, with higher variability, formed the patient group.1,3 It might also be relevant that animal experiments have shown that changes in LGN cells continue after the initial deprivation,6,7 and it is possible that latency differences from normal become apparent only late in development, perhaps by failure of the normal shortening of latency seen with age.8 The patching-related latency changes observed by Arden and Barnard3 had mostly resolved within a year, even though many patients had full–time occlusion. In the present study, at least a year had elapsed from the end of patching, and, in most children, patching had been part
FIG. Pattern reversal VEP to 12.5’ checks for patient 1 compared with group mean normal response. Responses from both amblyopic and fellow eyes are delayed compared with normal.
time. Furthermore, there was no correlation between duration of patching or initial acuity of the amblyopic eye and the latency change, which would be anticipated if patching was the cause of the delay. Although comparisons between LGN cell size changes caused by visual deprivation in nonhuman primates and VEP latencies in human strabismic amblyopes must be treated with caution, anatomical studies in monocularly deprived primates have shown shrinkage of those parvocellular LGN cells that receive input from both the deprived and the fellow eye
392
Journal of AAPOS Volume 6 Number 6 December 2002
Watts et al
even when the fellow eye had no deprivation.6 This shrinkage of all parvocellular LGN cells persists after reverse suture, even when the sizes of the deprived and the fellow eye cells have equalized.7 Because smaller neurons generally have smaller and more slowly conducting axons, the latency changes described here might relate to similar structural changes in man. It could also be significant that in man it is the latency to small checks that is affected, and in primates it is the parvocellular LGN laminae that show the most change. Further studies on the fellow eyes of strabismic amblyopes who have never been patched might help to clarify the situation. The present study reports electrophysiological features that affect not only the amblyopic eye but also the fellow eye of strabismic amblyopes long after successful occlusion therapy has ceased. Because most strabismic amblyopes rely on their fellow eyes and suppress their amblyopic eyes, these fellow-eye changes are potentially of clinical importance.
References 1. Sokol S. Abnormal evoked potential latencies in amblyopia. Br J Ophthalmol 1983;67:310-4. 2. Shawkat FS, Kriss A, Timms C, Taylor DSI. Comparison of pattern– onset, –reversal and – offset VEPs in treated amblyopia. Eye 1998;12: 863-9. 3. Arden GB, Barnard WM. Effect of occlusion on the visual evoked response in amblyopia. Trans Ophthal Soc UK 1979;99:419-26. 4. Li S, Cai H, Guo J. The visual evoked potentials of non-amblyopic eyes in children with amblyopia. Chin J Ophthalmol 1995;31:422-5. 5. Leguire LE, Rogers GL, Bremer DL. Amblyopia: the normal eye is not normal. J Pediatr Ophthalmol Strabismus 1990;27:32-8. 6. Sloper JJ. Edridge-Green Lecture. Competition and cooperation in visual development. Eye 1993;7:319-31. 7. Sloper JJ, Headon MP, Powell TPS. Experiments to study recovery of lateral geniculate nucleus cell size following monocular lid closure and reverse suture in infant monkeys. Brain Res 1988;468:47-59. 8. Sloper JJ, Collins AD. Reduction in binocular enhancement of the visual-evoked potential during development accompanies increasing stereoacuity. J Pediatr Ophthalmol Strabismus 1998;35:154-8.
An Eye on the Arts – The Arts on the Eye
When Aaron lifts his eyes to the sky, he looks for a soft pulsing glow, nothing too dramatic or everyone would notice. He knows not to expect too much. Even Moses only got to see God once in a while. He decides that maybe God can only be seen from the sky. He begins saving his weekly quarter until he learns that it would take sixteen years of saved allowances to afford even a cheap round-trip fare. If there is to be another sighting, God will have to come to him after all. He widens the scope of his God-watch accordingly. If God can be in a cloud or a burning bush, there’s no reason to think God can’t be in a car or a cookie. The intensity with which Aaron begins looking at the world gives him headaches. Concerned, Saul takes him to get his eyes tested. Aaron is a little disappointed to learn that his vision is fine. He had begun to hope that all he needed to see God was a pair of glasses. —Myla Goldberg (from Bee Season)
P
SUBJECTS AND METHODS Pattern reversal VEPs were recorded from 11 successfully treated strabismic amblyopes 7 to 11 years of age and 10 normal subjects of similar age. Eight subjects in each group were boys. The amblyopes had completed their
From Moorfields Eye Hospital, London, United Kingdom. aStrabismus and Paediatric Service. bDepartment of Electrophysiology. Presented as a poster at AAPOS Annual Meeting, San Diego, California, 2000. Submitted February 4, 2002. Revision accepted July 28, 2002. Mr John Sloper, Moorfields Eye Hospital, City Road, London EC1V 2PD, United Kingdom; e-mail, [email protected]. Copyright © 2002 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2002/$35.00 ⫹ 0 75/1/129046 doi:10.1067/mps.2002.129046
Journal of AAPOS
amblyopia therapy at least a year before their recruitment to this study. Using a standard Snellen chart, all amblyopes had a best– corrected acuity of 6/9 or better in their amblyopic eye and 6/6 or better in their fellow eye. The 10 normal subjects had binocular single vision with a TNO stereoacuity (Lame´ris Ootech BV, Nieuwegein, The Netherlands) of 60 sec of arc or better and a corrected visual acuity of 6/6 or better in each eye. Pattern reversal VEPs were recorded with 12.5⬘ and 50⬘ checks, with white luminance more than 80 cdm⫺2, contrast of 80%, and a reversal rate of 1.1 Hz. The recording bandwidth was 1-100 Hz. Full refractive correction was used during recording. Peak-to-peak amplitudes and peak latency were measured from the midline P100 component for each check size for each eye. The active electrode was Oz and the reference Fz. Statistical analysis was performed with the Wilcoxon rank sum test for comparison of amblyopic and fellow eyes, and the Mann-Whitney U test for comparisons between amblyopes and normal subjects. Both were corrected for tied values. The study was approved by Moorfields Hospital’s ethical committee.
RESULTS Clinical data for the 11 strabismic amblyopes are shown in Table 1. Nine amblyopic eyes had recovered to a Snellen acuity of at least 6/6 after patching, and the other 2 were 6/9. All fellow eyes had an acuity of 6/6 or better (Table 1). The small residual difference in acuity between the treated amblyopic and the fellow eyes was statistically significant (P ⫽ .026; Wilcoxon signed rank test). There was no December 2002
389
390
Journal of AAPOS Volume 6 Number 6 December 2002
Watts et al
TABLE 1. Details of amblyopic patients Initial acuity of Final visual acuity Patching Duration of amblyopic Age started Type of patching eye Amblyopic Fellow Patient (years) Sex (months) patching (months) Diagnosis 1 2 3 4 5 6 7 8 9 10 11
8 11 9 10 8 7 9 11 9 10 7
M M F M M M M F M M F
12 18 18 4 20 60 36 48 48 48 24
PT FT/PT PT PT PT PT FT/PT PT PT FT/PT PT
24 30 12 12 18 12 36 8 16 36 6
L ET R ET L ET L ET L ET R ET L ET R ET L ET R ET L ET
6/36 6/24 6/24 Obj 6/12 6/24 3/60 6/24 6/18 1/60 6/12
6/6 6/5 6/9 6/6 6/5 6/9 6/9 6/6 6/5 6/6 6/6
6/6 6/5 6/6 6/4 6/5 6/5 6/5 6/4 6/4 6/6 6/6
Refraction Amblyopic
Fellow
⫹4.25/⫹0.25⫻170 ⫹2.00/⫺1.50⫻100 ⫹0.25 ⫹3.50/⫹3.00⫻90 ⫹2.00/⫹1.00⫻90 ⫹4.50/⫺0.50⫻100 ⫹4.00 ⫹7.00/⫺0.75⫻180 ⫹8.75/⫺1.75⫻5 ⫹5.00/⫺1.50⫻20 ⫹6.25/⫺0.50⫻60
⫹4.00/⫺0.25⫻170 ⫹1.50/⫺1.00⫻90 ⫹0.25 ⫹2.50/⫹2.00⫻95 ⫹2.00/⫹1.00⫻90 ⫹2.00/⫺0.25⫻100 ⫹3.00/⫺0.75⫻130 ⫹6.50/⫺1.00⫻180 ⫹7.75/⫺1.25⫻180 ⫹3.00 ⫹4.25
M, Male; F, female; FT, full time; PT, part time; R, right; L, left; ET, esotropia; Obj, objected to occlusion of fixing eye.
significant difference between fellow and normal eyes (P ⫽ .88; Mann-Whitney U test using 1 random normal eye). Seven subjects showed no evidence of binocular function after treatment, with a manifest squint and suppression of the deviating eye on testing with Bagolini striated glasses. Patient 6 initially showed evidence of central suppression but recovered to have a stereoacuity of 60 sec of arc after treatment; patient 8 had left suppression when amblyopic but recovered to have a fully accommodative squint with a TNO stereoacuity of 60 sec of arc; patient 9 recovered to have a fully accommodative squint with a TNO stereoacuity of 480 sec of arc, and patient 11 had convergence excess esotropia and recovered after occlusion and surgery to have a TNO stereoacuity of 60 sec of arc. There were no significant differences in either P100 latency or amplitude between those with and without binocular function, and they have been considered together. The median age at which patching was started was 24 months (range, 4-60 months). Eight patients had part-time occlusion of 2 to 4 hours a day; 3 patients also had periods of full-time occlusion of 2 weeks, 6 months, and 14 months. The median duration of patching was 16 months (range, 6-36 months) (Table 1). Electrophysiological Data Comparison of the electrophysiological data for the amblyopic and the fellow eyes showed small interocular differences between the VEPs, with the amplitudes slightly smaller and the latencies slightly longer from the amblyopic eyes. Statistically significant mean differences were present only for amplitude with the 12.5⬘ check (⫺16.7%; P ⬍ .02) and for latency with the 50⬘ check (⫹5.0%; P ⬍ .02) (Table 2). Significant differences between the eyes of the normal controls were not observed. However, the mean P100 latency was significantly longer than normal for both amblyopic and fellow eyes to the 12.5⬘ check stimulus (amblyopic eye, ⫹11.7%, P ⬍ .0001; fellow eye, ⫹7.7%, P ⬍.002) (Figure), but not to
the 50⬘ check (Table 2). The amplitude of the fellow eye response to 12.5⬘ checks was also greater than normal, but there was considerable intersubject variability. The onset of amblyopia was recorded in the hospital notes as before 18 months of age in patients 1 to 5 and after 18 months of age in patients 6 to 11. Separate analyses of these subgroups showed that the latency changes were similar, and both were significantly different from normal for amblyopic and fellow eyes (both, P ⬍ .02; Mann-Whitney U test). However, the residual amplitude difference between amblyopic and fellow eyes for 12.5’ checks was much larger in the late onset group than in the early onset group (early onset mean difference –7.0%, P ⫽ .35; late onset mean difference –25.4%, P ⬍ .05; difference between early and late onset significant, P ⬍ .05, MannWhitney U test). There were no significant correlations between the interocular P100 latency asymmetry and either the age of onset of patching, the duration of patching, or the initial acuity of the amblyopic eye.
DISCUSSION Although visual acuity had returned to normal after successful patching, there were still small differences in acuity and small mean VEP differences between amblyopic and fellow eyes. However, the most notable feature in these patients was that the P100 latency with small-check stimulation of both amblyopic and fellow eyes was significantly prolonged compared with normal subjects. This largely masked the increased latency in their amblyopic eyes when interocular comparisons were made. The central visual pathways serving both the amblyopic and the fellow eyes of these children thus remained affected after clinically “successful” patching. Several previous studies have examined the VEP from the fellow eye in amblyopes.1-4 Using a pattern reversal stimulus with a large check and lower contrast, Arden and Barnard3 found that the latency of the fellow eye response
Journal of AAPOS Volume 6 Number 6 December 2002
Watts et al
TABLE 2. Electrophysiological data for 11 successfully treated strabismic amblyopes 12.5ⴕ check P100 latency (ms) Patient 1 2 3 4 5 6 7 8 9 10 11 Mean ⫾ SD % difference Amblyopic v fellow Significance* Normal mean ⫾ SD† % difference compared with normal Significance‡
391
50ⴕ check
P100 amplitude (V)
P100 latency (ms)
P100 amplitude (V)
Fellow
Amblyopic
Fellow
Amblyopic
Fellow
Amblyopic
Fellow
Amblyopic
118 111 120 108 124 120 120 112 116 114 114 116.1 ⫾ 4.8
116 124 116 115 123 124 120 116 123 113 117 118.8 ⫾ 4.1
37.1 15 37.8 32.4 17.1 11.5 28.7 31.6 20.5 32.2 32.2 26.9 ⫾ 9.2
30.9 13.0 43.2 27.2 15.4 9.2 21.9 20.9 13.2 23.4 28.3 22.4 ⫾ 9.8
105 104 105 102 111 116 104 102 104 103 104 105.4 ⫾ 4.3
108 130 104 102 114 130 108 105 104 105 108 110.7 ⫾ 10.1
36.5 11.8 35.7 22.2 22.9 11.8 33.1 18.8 19.7 20.3 34.7 24.3 ⫾ 9.2
29.8 9.2 34.7 23.6 20.7 7.7 24.8 24.2 16.5 21.9 26.0 21.7 ⫾ 8.1
107.8 ⫾ 4.0 ⫹7.7%
⫹2.4% NS 106.2 ⫾ 5.1 ⫹11.7%
18.9 ⫾ 8.7 ⫹42.4%
⫺16.7% P⬍.02 20.0 ⫾ 10.0 ⫹12.2%
106.3 ⫾ 3.6 ⫺0.8%
⫹5.0% P⬍.02 105.4 ⫾ 3.6 ⫹5.0%
23.6 ⫾ 8.9 ⫹3.3%
⫺10.6% NS 22.1 ⫾ 7.5 ⫺1.4%
P⬍.002
P⬍.0001
P⬍.05
NS
NS
NS
NS
NS
*Wilcoxon signed rank test v fellow eye; †Fellow eyes are compared with normal right eyes and amblyopic eyes with normal left eyes; ‡Mann-Whitney U test v corresponding normals; NS, not significant.
in children ages 4 to 11 was delayed during patching but had returned to normal in most eyes by a year after patching had been discontinued. This agrees with the results found here with a large check. Sokol1 found no difference between the fellow eyes of amblyopes and normal subjects, with younger subjects ranging in age from 3 to 7.5 years. Shawkat et al2 found reduced P100 amplitude in the fellow eyes of amblyopes compared with normal eyes and suggested that this might be due to patching. A more recent study of treated anisometropic amblyopes ages 4 to 12 years showed increased P100 latencies to small checks from both amblyopic and fellow eyes, paralleling the results found here with strabismic amblyopes.4 The ages of the patients in the present study—7 to 11 years—facilitated better patient compliance and less variability than would have been found in a younger group. This increased the sensitivity of the study to detect significant group mean differences compared with previous reports where younger children, with higher variability, formed the patient group.1,3 It might also be relevant that animal experiments have shown that changes in LGN cells continue after the initial deprivation,6,7 and it is possible that latency differences from normal become apparent only late in development, perhaps by failure of the normal shortening of latency seen with age.8 The patching-related latency changes observed by Arden and Barnard3 had mostly resolved within a year, even though many patients had full–time occlusion. In the present study, at least a year had elapsed from the end of patching, and, in most children, patching had been part
FIG. Pattern reversal VEP to 12.5’ checks for patient 1 compared with group mean normal response. Responses from both amblyopic and fellow eyes are delayed compared with normal.
time. Furthermore, there was no correlation between duration of patching or initial acuity of the amblyopic eye and the latency change, which would be anticipated if patching was the cause of the delay. Although comparisons between LGN cell size changes caused by visual deprivation in nonhuman primates and VEP latencies in human strabismic amblyopes must be treated with caution, anatomical studies in monocularly deprived primates have shown shrinkage of those parvocellular LGN cells that receive input from both the deprived and the fellow eye
392
Journal of AAPOS Volume 6 Number 6 December 2002
Watts et al
even when the fellow eye had no deprivation.6 This shrinkage of all parvocellular LGN cells persists after reverse suture, even when the sizes of the deprived and the fellow eye cells have equalized.7 Because smaller neurons generally have smaller and more slowly conducting axons, the latency changes described here might relate to similar structural changes in man. It could also be significant that in man it is the latency to small checks that is affected, and in primates it is the parvocellular LGN laminae that show the most change. Further studies on the fellow eyes of strabismic amblyopes who have never been patched might help to clarify the situation. The present study reports electrophysiological features that affect not only the amblyopic eye but also the fellow eye of strabismic amblyopes long after successful occlusion therapy has ceased. Because most strabismic amblyopes rely on their fellow eyes and suppress their amblyopic eyes, these fellow-eye changes are potentially of clinical importance.
References 1. Sokol S. Abnormal evoked potential latencies in amblyopia. Br J Ophthalmol 1983;67:310-4. 2. Shawkat FS, Kriss A, Timms C, Taylor DSI. Comparison of pattern– onset, –reversal and – offset VEPs in treated amblyopia. Eye 1998;12: 863-9. 3. Arden GB, Barnard WM. Effect of occlusion on the visual evoked response in amblyopia. Trans Ophthal Soc UK 1979;99:419-26. 4. Li S, Cai H, Guo J. The visual evoked potentials of non-amblyopic eyes in children with amblyopia. Chin J Ophthalmol 1995;31:422-5. 5. Leguire LE, Rogers GL, Bremer DL. Amblyopia: the normal eye is not normal. J Pediatr Ophthalmol Strabismus 1990;27:32-8. 6. Sloper JJ. Edridge-Green Lecture. Competition and cooperation in visual development. Eye 1993;7:319-31. 7. Sloper JJ, Headon MP, Powell TPS. Experiments to study recovery of lateral geniculate nucleus cell size following monocular lid closure and reverse suture in infant monkeys. Brain Res 1988;468:47-59. 8. Sloper JJ, Collins AD. Reduction in binocular enhancement of the visual-evoked potential during development accompanies increasing stereoacuity. J Pediatr Ophthalmol Strabismus 1998;35:154-8.
An Eye on the Arts – The Arts on the Eye
When Aaron lifts his eyes to the sky, he looks for a soft pulsing glow, nothing too dramatic or everyone would notice. He knows not to expect too much. Even Moses only got to see God once in a while. He decides that maybe God can only be seen from the sky. He begins saving his weekly quarter until he learns that it would take sixteen years of saved allowances to afford even a cheap round-trip fare. If there is to be another sighting, God will have to come to him after all. He widens the scope of his God-watch accordingly. If God can be in a cloud or a burning bush, there’s no reason to think God can’t be in a car or a cookie. The intensity with which Aaron begins looking at the world gives him headaches. Concerned, Saul takes him to get his eyes tested. Aaron is a little disappointed to learn that his vision is fine. He had begun to hope that all he needed to see God was a pair of glasses. —Myla Goldberg (from Bee Season)