Macular and peripapillary retinal nerve fibre layer thickness in adults with amblyopia Randy A. Walker, MD*; Shehla Rubab, MBBS*; Alexandra R.L. Voll†; Vasudha Erraguntla, MBBS*; Paul H. Murphy, MD, FRCS(C)* ABSTRACT ● RÉSUMÉ Objective: To evaluate macular and peripapillary retinal nerve fiber layer (RNFL) thickness in amblyopic eyes compared to the fellow eye. Design: Cross-sectional study. Participants: 30 patients (60 eyes) older than 18 years of age with amblyopia. Methods: Inclusion criteria included individuals older than 18 years, amblyopia, and best-corrected visual acuity (BCVA) ⱕ20/40. A complete medical history was taken and an eye examination carried out. Optical coherence tomography (OCT) was carried out on both eyes of all patients. Exclusion criteria included intraocular pressure (IOP) ⬎23 mm Hg and eye pathology that may affect OCT measurements. The primary outcome measures were foveal thickness and average peripapillary RNFL thickness, which were compared using a paired t test. Quadrants in peripapillary scans and concentric rings in macular scans were analyzed. Results: The average age was 56 years (range ⫽ 33– 82 years). Visual acuity ranged from 20/40 to 20/4000 (mean ⫽ 20/275). The average peripapillary RNFL thickness was 90.6 m (SD ⫽ 9.6 m) in the amblyopic eye and 90.1 m (SD ⫽ 12.1 m) in the fellow eye (p ⫽ 0.64). The average macular thickness in amblyopic eyes was 260.1 m (SD ⫽ 32.0 m), and 254.7 m (SD ⫽ 32.5 m) in fellow eyes (p ⫽ 0.10). No statistical difference existed between peripapillary quadrants or macular concentric rings. These differences were smaller when the strabismic amblyopes were isolated. Conclusions: There does not seem to be a difference in peripapillary RNFL or macular thickness between the amblyopic eye and fellow eye. Objet : Évaluation de l’épaisseur maculaire et des couches de fibres nerveuses rétiniennes (CFNR) péripapillaires dans les yeux amblyopes comparativement à l’autre œil. Nature : Étude transversale. Participants : 30 patients (60 yeux) de plus de 18 ans atteints d’amblyopie. Méthodes : Les critères d’inclusion comprenaient des personnes de plus de 18 ans, l’amblyopie et la meilleure acuité visuelle corrigée (MAVC) égale à 20/40 ou moins. Les antécédents médicaux ont été relevés et un examen oculaire, effectué. La tomographie par cohérence optique (TCO) a été effectuée dans les deux yeux de tous les patients. Les critères d’exclusion comprenaient la pression intraoculaire (PIO) supérieure à 23 mmHg et la pathologie oculaire susceptible d’affecter les mesures de la TCO. Les résultats orimaires ont porté sur l’épaisseur fovéale et la moyenne d’épaisseur des CFNR péripapillaires, qui ont été comparées à des tests t appariés. Les quadrants des scintigraphies péripapillaires et les cercles concentriques de la scanographie maculaire ont été analysés. Résultats : La moyenne d’âge était 56 ans (écart ⫽ 33-82 ans). L’acuité visuelle variait de 20/40 à 20/4000 (moyenne ⫽ 20/275). La moyenne d’épaisseur des CFNR péripapillaires était de 90,6 m (ÉT ⫽ 9,6 m) dans l’œil amblyope et 90,1 m (ÉT ⫽ 12,1 m) dans l’autre œil (p ⫽ 0,64). La moyenne d’épaisseur maculaire des yeux myopes était 260,1 m (ÉT ⫽ 32,0 m), et 254,7 m (ÉT ⫽ 32.5 m) dans les autres yeux (p ⫽ 0,10). Il n’y avait pas de différence statistique entre les quadrants péripapillaires ou entre les cercles concentriques maculaires. Ces différences étaient plus petites lorsque les amblyopes strabiques étaient isolés. Conclusion : Il ne semble pas y avoir de différence CFNR péripapillaires ni d’épaisseur maculaire entre l’œil amblyope et l’autre œil.
Amblyopia is a reduction of best-corrected visual acuity with onset in young age that cannot be accounted for by structural causes, nor can it be improved with refractive correction. It affects an estimated 2%– 6% of the population.1–5 It is divided into 3 classes: strabismic, anisometropic, and deprivational. Atrophic changes have been shown in the lateral geniculate nucleus for amblyopic eyes,6,7 leading to the hypothesis that upstream retinal nerve fibre layer (RNFL) thickening may occur due to a limitation of the normal postnatal reduction of ganglion cells.8 Optical coherence tomography (OCT) is a noninva-
sive test that allows measurement of macular and peripapillary RNFL thickness. Few studies have investigated differences in peripapillary RNFL thickness between the amblyopic eye and the fellow eye,8 –13 and even fewer have evaluated macular thickness.11–14 Furthermore, the results have been inconclusive, with only 2 finding increased peripapillary RNFL thickness in the amblyopic eye,8,10 and 1 finding increased macular thickness.13 None of these studies have used spectral domain OCT, and strabismic amblyopia has been minimally represented. The purpose of this study was to evaluate
Poster presentation at Canadian Ophthalmology Society Annual Meeting in Quebec City, Q.C., June 26 –29, 2010. From the *Department of Ophthalmology, Saskatoon City Hospital, and † College of Medicine, University of Saskatchewan, Saskatoon, Sask.
Can J Ophthalmol 2011;46:425– 427
0008-4182/11/$-see front matter Crown Copyright © 2011 Published by Elsevier Inc on behalf of the Canadian Ophthalmological Society. All rights reserved. doi:10.1016/j.jcjo.2011.07.013
Originally received Sep. 14, 2010 Final revision Feb. 21, 2011 Accepted Apr. 26, 2011 Correspondence to Randy Walker, Eye Care Centre, Saskatoon City Hospital, 701 Queen Street Saskatoon, SK S7K 0M7;
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Macular and RNFL thickness in amblyopic adults—Walker et al. RESULTS
Fig. 1—Comparison of peripapillary RNFL thickness differences between amblyopic and fellow eyes in m. All patients are represented on the left side and only strabismic patients are represented on the right side. A positive value represents a thicker RNFL in the amblyopic eye whereas a negative value represents a thicker RNFL in the fellow eye. p values are represented in brackets.
macular and peripapillary RNFL thickness using spectral domain OCT in adult amblyopes.
METHODS Approval from the University of Saskatchewan Research Ethics Board was obtained. Amblyopic patients older than 18 years were identified through the Saskatoon City Hospital Eye Care Centre database. Informed consent was obtained before participation in the study. Amblyopia was defined as BCVA ⱕ20/40, not explained by any other eye or visual pathway abnormalities. Severe amblyopia was defined as BCVA of 20/100 or worse, and we defined anisometropia as a refractive difference of ⬎1.50 D between eyes. A medical history, ocular history, and a complete ophthalmic examination were completed on all participants. All participants classified as purely strabismic amblyopia had a manifest deviation or history of strabismus surgery and ⬍1.50 D difference in spherical equivalent between eyes. OCT (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, Calif) was carried out bilaterally using peripapillary RNFL and macular thickness protocol. The primary investigator assessed the quality of each scan, and unsatisfactory scans were repeated. Exclusion criteria included intraocular pressure ⬎23 mm Hg and eye pathology that may affect OCT measurements, including, but not limited to, glaucoma, pan-retinal photocoagulation, and macular degeneration. Average peripapillary RNFL and central macular thickness data were compared using a paired t test (significance level of p ⬍ 0.05). All peripapillary quadrants and macular concentric rings (broken into quadrants) were additionally analyzed. Statistical analysis was completed using Microsoft Office Excel 2003 (Microsoft Corporation, Redmond, Wa).
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Thirty patients with amblyopia were recruited. The average age was 56 years (range ⫽ 33– 82 years). Twenty-two patients (73%) had strabismic amblyopia, 2 (7%) had anisometropic amblyopia, and 6 (20%) had a mixed-type amblyopia. Visual acuity ranged from 20/40 to 20/4000 (mean ⫽ 20/275). Fifty percent had BCVA ⱕ20/100. The average spherical equivalent was 1.29 D in amblyopic eyes and 0.71 D in fellow eyes. This difference was less in the strabismic group, with the average spherical equivalent being 1.82 D in the amblyopic eye and 1.55 D in the fellow eye. All patients had satisfactory peripapillary RNFL scans but macular data was only usable in 27 of 30 patients. The average peripapillary RNFL thickness was 90.6 m (SD ⫽ 9.6 m) in the amblyopic eye and 90.1 m (SD ⫽ 12.1 m) in the fellow eye (p ⫽ 0.64). In strabismic amblyopes, the average peripapillary RNFL thickness was 90.2 m (SD ⫽ 10.6 m) in the amblyopic eye and 89.8 m (SD ⫽ 12.3 m) in the fellow eye (p ⫽ 0.91). Neither group reached statistical significance comparing peripapillary quadrants or clock hours (Fig. 1). The average macular thickness in amblyopic eyes was 260.1 m (SD ⫽ 32.0 m), and 254.7 m (SD ⫽ 32.5 m) in fellow eyes (p ⫽ 0.10). Regarding strabismic amblyopes, the values for the amblyopic and fellow eye, respectively, were 257.4 m (SD ⫽ 34.9 m) and 255.0 m (SD ⫽ 34.1 m) (p ⫽ 0.84). Cube volume, cube average, and 2 concentric annular rings were also evaluated, not reaching statistical significance (Fig. 2). Subgroup analysis was carried out on severe amblyopes. There was no statistical significance in any anatomical location.
DISCUSSION This study did not find any difference in either macular or peripapillary RNFL thickness between the amblyopic eye and fellow eye in all amblyopes, severe amblyopes, or strabismic amblyopes.
Fig. 2—Comparison of macular thickness differences between amblyopic and fellow eyes in m. All patients are represented on the left side and only strabismic patients are represented on the right side. A positive value represents greater macular thickness in the amblyopic eye whereas a negative value represents greater macular thickness in the fellow eye. p values are represented in brackets.
Macular and RNFL thickness in amblyopic adults—Walker et al. Our results concur with the results of the majority of previous studies using OCT to investigate these parameters in amblyopia. In 2005, Altintas et al.11 carried out OCT on 14 strabismic amblyopic patients between 5 and 18 years of age and no difference was seen in macular and peripapillary RNFL thickness or macular volume. Kee et al.12 in 2006 enrolled 26 amblyopic children (6 strabismic amblyopes), and found no difference in peripapillary and macular thickness between the amblyopic eye and fellow eye, nor between amblyopes and normal control children. Repka et al.9,15 completed studies in 2006 and 2009 evaluating 17 patients aged 5–28 years and subsequently 37 amblyopic children, with neither finding a statistically significant difference. Park et al.14 investigated 44 children with ocular dominance in intermittent exotropia and also found no statistically significant difference. Conversely, in 2001 Baddini-Caramelli et al.16 carried out laser scanning polarimetry in 21 children, finding thicker RNFL in the amblyopic eye. However, amblyopia type was not differentiated. In 2005, Yen et al.8 enrolled 38 amblyopes, aged 6 –75 years, with 20 having strabismic amblyopia. They found a thicker peripapillary RNFL in the amblyopic eye in anisometropic amblyopia but no difference in strabismic amblyopes. Yoon et al.10 had similar findings in a 2005 study of 31 hyperopic anisometropic children regarding peripapillary RNFL thickness but found no difference in macular thickness. On the contrary, the Sydney Childhood Eye Study evaluated 48 amblyopic children (17 strabismic) and found increased central macular thickness in the amblyopic eye, but no difference in peripapillary thickness.13 This was especially notable in younger patients and in those with more severe amblyopia. In 2006, Salchow et al.17 reported that each diopter of hyperopia results in an increased RNFL thickness of approximately 1.67 m, suggesting the difference in RNFL thickness found in patients with anisometropic amblyopia may be related to the refractive error difference rather than amblyopia. This study is the largest cohort of strabismic amblyopes in a study of its kind in the English literature next to the study from Park et al.14 on intermittent exotropia. Additionally, this is the only study using spectral-domain OCT to compare amblyopic eyes to fellow eyes. A further strength of this study is the proportion of severe amblyopia in the cohort. Fifty percent of the patients in this study had BCVA ⱕ20/100 in their amblyopic eye versus the study by Repka9 in 2009 where 11% had BCVA worse than 20/100 in the amblyopic eye. Nonetheless, there are limitations to this study. The small sample size limits the power of the study. However, the number of participants in this study is similar to other studies. One could argue that refractive error may have affected the results. However, amblyopic eyes were only 0.58 D more hyperopic than fellow eyes, and strabismic amblyopic eyes were only 0.27 D more hyperopic than fellow eyes. Based on the study by Salchow,17 this would only create an increase of 0.97 m in the total cohort of amblyopes and 0.46 m in the strabismic subset. Accordingly, refraction is unlikely to be a significant
source of error. Finally, the anisometropic and mixed groups are not large enough for subgroup analysis and the results of this study cannot be applied to deprivational amblyopia. In summary, the findings of this study suggest that in adults with amblyopia, there does not appear to be a difference in the peripapillary RNFL or macular thickness between the amblyopic eye and the fellow eye.
Acknowledgements: The authors thank Dr. Ralph Schneider and the Andrews Ophthalmology Training and Research Endowment for help in providing honoraria to participants, and Jocelyn Zurevinsky, O.C.(C.) for her help in identification of eligible patients. Disclosure: The authors have no proprietary or commercial interest in any materials discussed in this article. Support: Honoraria for participants in this study was provided by the Andrews Ophthalmology Training and Research Endowment. The purpose of this endowment is to help fund education and research opportunities for residents completing their training in ophthalmology. REFERENCES 1. Flyn JT. Amblyopia revisited. J Pediatr Ophthalmol Strabismus. 1991; 28:183-201. 2. Kiorpes L, McKee SP. Neural mechanisms underlying amblyopia. Curr Opin Neurobiol. 1999;9:480-6. 3. France LW. Evidence-based guidelines for amblyogenic risk factors. Am Orthopt J. 2006;56:7-14. 4. Graham PA. Epidemiology of strabismus. Br J Ophthalmol. 1974;58: 224-31. 5. Roper-Hall G. Current concepts of amblyopia: a neuro-ophthalmology perspective. Am Orthopt J. 2007;57:2-11. 6. Von Noorden GK, Middleditch PR. Histology of the monkey lateral geniculate nucleus after unilateral lid closure and experimental strabismus: further observations. Invest Ophthalmol. 1975;14:674-83. 7. Kiorpes L, Kiper DC, O’Keefe LP, et al. Neuronal correlates of amblyopia in the visual cortex of macaque monkeys with experimental strabismus and anisometropia. J Neurosci. 1998;18:6411-24. 8. Yen MY, Cheng CY, Wang AG. Retinal nerve fiber layer thickness in unilateral amblyopia. Ophthalmol Vis Sci. 2004;45:2224-30. 9. Repka MX, Kraker RT, Tamkins SM, et al. Retinal nerve fiber layer thickness in amblyopic eyes. Am J Ophthalmol. 2009;48:143-7. 10. Yoon SW, Park WH, Baek SH, Kong SM. Thicknesses of macular retinal layer and peripapillary retinal nerve fiber layer in patients with hyperopic anisometropic amblyopia. Korean J Ophthalmol. 2005;19:62-7. 11. Altintas O, Yuksel N, Ozkan B, Caglar Y. Thickness of the retinal nerve fiber layer, macular thickness, and macular volume in patients with strabismic amblyopia. J Pediatr Ophthalmol Strabismus. 2005;42:216-21. 12. Kee SY, Lee SY, Lee YC. Thickness of the fovea and retinal nerve fiber layer in amblyopic and normal eyes in children. Korean J Ophthalmol. 2006;20:177-81. 13. Huynh SC, Samarawickrama C, Wang XY, et al. Macular and nerve fiber layer thickness in amblyopia: The Sydney Childhood Eye Study. Ophthalmology. 2009;116:1604-9. 14. Park SW, Lee SH, Heo H, Park YG. Macular nerve fiber layer thickness. Ophthalmology. 2010;117:1053-53.e1. 15. Repka MX, Goldenberg-Cohen N, Edwards AR. Retinal nerve fiber layer thickness in amblyopic eyes. Am J Ophthalmol. 2006; 142:247-51. 16. Baddini-Caramelli C, Hatanaka M, Polati M, et al. Thickness of the retinal nerve fiber layer in amblyopic and normal eyes: A scanning laser polarimetry study. J AAPOS. 2001;5:82-4. 17. Salchow DJ, Oleynikov YS, Chiang MF, et al. Retinal nerve fiber layer thickness in normal children measured with optical coherence tomography. Ophthalmology. 2006;113:786-91.
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