FP1133 : Changes in RNFL and Macular Thickness in Patients of Unilateral Amblyopia After Amblyopia Therapy

Dr. Rupak Brahma Choudhury, Dr. Kamlesh, Dr. Babita Karothiya, Dr.Anju Rastogi, Dr. Prolima Thacker

INTRODUCTION 

Amblyopia is defined as unilateral or bilateral reduction in best corrected central visual acuity caused by form vision deprivation and/or abnormal binocular interaction, without any visible organic cause to commensurate with visual loss¹. Probably, amblyopia is the most common cause of preventable uniocular vision loss in children and young adults² and affects nearly 2%-5% of the general population³ .This visual loss is correctable if appropriate measures are taken at an appropriate time⁴. While the mechanisms underlying amblyopia are yet to be fully understood, the underlying etiologies are generally thought to be associated with abnormal visual environments resulting from strabismus, refractive error and/or visual deprivation. Those affected with amblyopia usually experience poor visual acuity, reduced contrast sensitivity, and poor binocular vision and stereoacuity. The current treatment for amblyopia primarily involves refractive correction, occlusion and visual training. Occlusion of the better eye remains the gold standard for the treatment of amblyopia.Recent trends have shown the role of near vision activities like television watching and video games, reading books etc. as an adjunct to patching in the management of amblyopia.

The deleterious effects of amblyopia during the neonatal period have been well established in several animal species and in humans^5-7by quantitative histological studies.Visual deprivation has an effect on the growth of cells in the lateral geniculate body that receives input from the amblyopic eye and this causes a shift in the dominance pattern in the visual cortex⁸.

Several studies have suggested that there is no difference in macular or RNFL thicknesses in children with unilateral amblyopia^9,10. Other studies, however, have shown that thickening of the RNFL occurs in anisometropic and strabismic amblyopia^11,12. Huynh et al. and Pang et al. showed a thicker fovea in unilateral amblyopia^13,14, while Al-Haddad et al. found a thicker macula in anisometropic amblyopia¹⁵.

Optical coherence tomography (OCT) is a rapid, non-invasive,office-based imaging technique allowing objectivequantification of retinal structures with high resolution,including determination of peripapillary RNFL thickness and macular thickness.Our study is designed to evaluate the change in RNFL and macular thickness and its clinical correlation with visual outcome following amblyopia therapy using Ocular coherence tomography.

MATERIALS AND METHODS

The study was a prospective interventional comparative study. Patients of unilateral amblyopia who attended the outpatient department and squint clinic of Guru Nanak Eye Centre, New Delhi between October 2014 and January 2016 were included in the study. Study group comprised of 30 children with unilateral amblyopia of 5-12 years in age. Children with only strabismic or/and anisometropic amblyopia were included in the study. Amblyopia of Moderate to severe grade were included. Informed consent was taken from the parents of the patients after explaining the nature of the study, duration of study, the procedure, the follow up with its schedule, side effects of patching.

A detailed history was taken in each case regarding the chief complaint i.e. decrease of vision or deviation, age of onset, previous history of use of glasses, orthoptic exercises, any occlusion therapy, previous strabismic surgery, diplopia or any systemic illness. It was followed by a general physical examination and local examination. Local examination included noting down the bestcorrected visual acuity(BCVA), performing cycloplegic refraction, a detailed squint examination and full fundus assessment. All subjects were given optimum optical correction and then patching was prescribed. The sound eye was patched daily for the number of age years and the amblyopic eye for one day thereafter. In cases of moderate amblyopia, 6hrs of patching was done, whereas in cases of severe amblyopia 24hours of patching was done. Patching was done in the ratio of 6:1 for better: amblyopic eye. Patients with severe amblyopia wereswitched over to 6 hours of patching once their visual acuity improved to >6/24 during the courseof treatment. In addition to this, all patients were prescribed additional near activities like watchingtelevision (cartoons) and playing video games from an approximate distance of 1meter for30minutes/day while being patched. OCT of both amblyopic and better eye was done before the starting occlusion therapy.All patients were followed up at 1 week, 1 month, 3 months and 6 months interval. Follow up at 1 week was done to look for any incompliance or side effect of patching. After initiation of occlusion therapy visual assessment was done at 1 month, 3 months and 6 months and OCTwas done at 3 months and 6 months of follow up.

RESULTS

Our study consisted of 30 patients with 19 male and 11 female. The mean age of our study population was 9.37 ±1.67 years(range 5-12 years). 14 patients had anisometropic amblyopia, 11 had strabismic amblyopia and 5 had combination of both.

The mean baseline BCVAof amblyopic eyes on day 1 for distance in our study population was0.20± 0.08.At the end of 6 month follow up the mean baseline BCVAof amblyopic eyes was 0.53±0.24. (p value – 0.000).

The mean baseline BCVA for distance in better eye was 0.85± 0.20. There was no change in the mean BCVA for better eye at the end of study.

At the start of occlusion therapy, the mean baseline RNFL thickness in amblyopic eye was 111.13±4.62 µm and in better eye was 106.07±4.77 µm. The difference in mean RNFL thickness between amblyopic and better eye was statistically significant (p=0.0001).

The mean RNFL thickness in amblyopic eye at 6 months of follow up was 107.96±3.77 µm. while in the better eye it was 105.77±4.57 µm. The difference in RNFL thickness was significant (p value- 0.04)

At the start of occlusion therapy, the mean baseline macular thickness in amblyopic eye in our studypopulation was 227.06±10.89 µm and in better eye was 218.43±7.45 µm. The difference in mean macular thickness between amblyopic and better eye was significant (p=0.0006).

The mean macular thickness in amblyopic eye at 6 months of follow up was 226.80±10.82 µm. and in better eye at 6 months of follow up was 218.03±7.26 µm. The difference in macular thickness was significant (p value- 0.0005)

The mean baseline RNFL thickness in amblyopic eye at start of study was 111.13±4.62 µmand at 6 months of follow up was 107.96±3.77 µm. The difference was statistically significant (p value- 0.0001,)The RNFL thickness was found to be thicker before the amblyopia therapy.

The mean baseline RNFL thickness in better eye at start of study was 106.07±4.77 µm and at 6 months of follow up was 105.77±4.57 µm. The changes in mean RNFL thickness of better eye at6 months were not significant (p value- 0.08).

The mean baseline macular thickness in amblyopic eye at start of study was 227.07±10.89 µm. while at 6 months of follow up was 226.80±10.82 µm. The change in mean macular thickness at 6 month was statistically not significant (p value- 0.11)

The mean baseline macular thickness in better eye at start of study was 218.43±7.45µm.While at 6 months of follow up was 218.03±7.26µm.The change in mean macular thickness at 6 month was statistically not significant (p value- 0.13, paired t –test)

DISCUSSION

 Although amblyopia is the most common cause of visual impairment in children, the role of the retina in the amblyopic process is not yet fully understood. Amblyopia may have different effects at various levels of the visual pathway. Receiving input from the amblyopic eye causing atrophy for the cells in the lateral geniculate nucleus has been reported¹⁶. OCT has been used to evaluate macular and RNFL thickness in amblyopic eyes. However, such efforts to detect morphological changes in the retina have produced inconsistent results.

In our study, we found significant improvement in visual acuity in both distant vision (p value – 0.000) and near vision (p value – 0.000)after occlusion therapy along with near activities like watching TV and video games.Visual acuity was found to be progressively improving with the effect of therapy.

The mean RNFL thickness in amblyopic eye in our studypopulation before starting occlusion therapy was 111.13±4.62 µm.while in the better eye it was 106.07±4.77 µm. This difference in mean RNFL thickness between amblyopic and better eye was statistically significant (p=0.0001). The mean macular thickness in amblyopic eye was 227.06±10.89 µm and the mean macular thickness in better eye was 218.43±7.45 µm. This difference in mean macular thickness between amblyopic and better eye was also significant (p=0.0006), therefore the amblyopic eye had thicker RNFL and macular thickness.

Wu SQ et al¹⁷. in 2013 conducted a study in which macular thickness, macular foveolar thickness, and peripapillary RNFL thickness were compared between the amblyopic eyes and the contralateral sound eye using OCT. The mean peripapillary RNFL thickness was 113.9±7.2µm and 109.2±6.9µm in the amblyopic eye and the normal eye, respectively, reaching statistical significance (P = 0.02). The mean macular foveola thickness was significantly thicker in the amblyopic eyes than the contralateral sound eyes (181.4±14.2µm vs 175.2±13.3µm, P < 0.01). They concluded eyes with hyperopic anisometropic amblyopia had thicker macular foveola and peripapillary RNFL than contralateral eyes.They speculated that due to visual deprivation and binocular competing role, blurred vision led to no enough stimulation in the amblyopic eye, affecting the normal maturation of the macula, including movement of Henle’s fibers away from the fovea and a decrease in foveal cone diameter, which would result in increased foveola thickness.

Alotaibi AGet al¹⁸ in 2011 measured the mean macular retinal thickness was 259.3 μm and 255.6 μm, and the mean RNFLthickness was 112.16 μm and 106 μm, in the amblyopic eye and the normal eye, respectively. The RNFL thickness in amblyopic eye was significantly thicker (P < 0.0001), but no statistically significant difference was found in macular retinal thickness(P = 0.195). They concluded that the amblyopic process may involve the RNFL, but not the macula. They concluded that the cause of this difference was not clear, though it may have been due to the slow-down of the normal postnatal reduction of ganglion cells. However, further evaluation is needed.

Al-Haddad CEet al¹⁵in 2011 studied RNFL and macular thickness in amblyopia. The mean central macular thickness (CMT) in the amblyopic eyes (273.8± 30.8 mm) was significantly greater than that of the fellow eyes (257.9 ± 21.5 mm), (p=0.001). The difference was only significant for the anisometropicamblyopes but not the strabismic group. The mean RNFL thickness in the amblyopic eyes (95.4±39.2 mm) was not significantly different from that of the fellow eyes (94.0±19.2 mm) (p=0.8).Possible hypothesis by them was that ageing affects the normal and amblyopic eye differentially, with normal eye being more affected, producing thinner macula. They concluded CMT was significantly increased in anisometropic amblyopia.

The mean RNFL thickness in amblyopic eye in our studypopulation before starting occlusion therapy was 111.13±4.62 µm. The mean RNFL thickness in amblyopic eye after 6 months of follow up was 107.96±3.77 µm. The RNFL thickness was significantly thinner after the amblyopia therapy (p value- 0.00001). To the best of our knowledge, no study has been done to see RNFL thickness in pre and post occlusion therapy.

The mean macular thickness in amblyopic eye in our studypopulation before starting occlusion therapy was 227.07±10.89 µm. The mean macular thickness in amblyopic eye after 6 months of follow up was 226.80±10.82 µm. The difference in macular thickness was not significant after the amblyopia therapy (p value- 0.11). While there was progressive improvement in the visual acuity with the start of occlusion therapy the RNFL thickness was found to be significantly thicker in amblyopic eye and also before the occlusion therapy. However there were no significant difference in macular thickness in amblyopic eye and better eye. There was no significant difference found after the occlusion therapy on macular thickness.

In view of above results we can give a hypothesis that if amblyopia affects the process of postnatal reduction of ganglion cells in the amblyopic eye, the occlusion therapy can result in restoring the postnatal reduction of ganglion cells. However our study has few drawbacks like small study group, small period of follow up and in our study we didn’t have any control group. So further studies having long term follow up and larger sample size is required to further establish the results.

REFERENCES

1. Von NoordenGK,Campos EC. Binocular vision and ocular motility: Theory and management of strabismus. 6^th ed St. louis: Mosby: 2002. P.246-97
2. Hills A, Flynn JT,Hawkins BS. The evolving concept of amblyopia: a challenge to epidemiologists. Am J Epidemiol. 1983;118:192-205
3. Attebo K, Mitchell P, Cumming R. Prevalence and causes of Amblyopia in an adult population. Ophthalmology 1998;105:154-9
4. Von Noorden GK. Mechanism of amblyopia: Doc Ophthalmol.1977;34:93
5. Headon MP, Powell TP. Cellular changes in the lateral geniculate nucleus of infant monkeys after sutures of the eyelids. J Anat 1973;116:135-45
6. Sherman SM, Wilson JR. Behavioral and morphological evidence for binocular competition in the postnatal development of the dog’s visual system. J Comp Neurol 1975;161:183-95
7. Von Noorden GK, Crawford ML. The lateral geniculate nucleus in human strabismic amblyopia. Invest Ophthalmol Vis sci 1992;33:2729-32
8. Alotaibi AG, Enazi BA. Unilateral amblyopia: Optical coherence tomography findings. Saudi journal of Ophthalmology 2001;25:405-9
9. Altintas O, Yuksel N, Ozkan B, Caglar Y. Thickness of theretinal nerve fiber layer, macular thickness, and macularvolume in patients with strabismic amblyopia. J PediatrOphthalmol Strabismus 2005;42:216–221.
10. Kee SY, Lee SY, Lee YC. Thicknesses of the fovea andretinal nerve fiber layer in amblyopic and normal eyes inchildren. Korean J Ophthalmol 2006;20:177–181
11. Yen MY,ChengCY,Wang AG. Retinal nerve fibre layer thickness in unilateral amblyopia. Invest Ophthalmol Vis Sci 2004;45(7):2224-30
12. Yoon SW, Park WH, Baek SH, Kong SM. Thicknesses ofmacular retinal layer and peripapillary retinal nerve fiberlayer in patients with hyperopic anisometropic amblyopia.Korean J Ophthalmol 2005;19:62–67.
13. Huynh SC, Samarawickrama C, Wang XY, Rochtchina E, Wong TY, Gole GA, et al. Macular and nerve fiber layer thickness in amblyopia: the Sydney Childhood Eye Study. Ophthalmology. 2009 Sep;116(9):1604–9.
14. Pang Y, Goodfellow GW, Allison C, Block S, Frantz KA.A prospective study of macular thickness in amblyopicchildren with unilateral high myopia. Invest OphthalmolVis Sci 2011;52:2444–2449.
15. .Al-Haddad CE, Mollayess GMEL, Cherfan CG, Jaafar DF, Bashshur ZF. Retinal nerve fibre layer and macular thickness in amblyopia as measured by spectral-domain optical coherence tomography. Br J Ophthalmol. 2011 Dec;95(12):1696–9.
16. Wiesel TN, Hubel DH. Effects of visual deprivation on morphology and physiology of cells in the cat’s lateral geniculate body. J Neurophysiol. 1963;26(6):978-93
17. Wu S-Q, Zhu L-W, Xu Q-B, Xu J-L, Zhang Y. Macular and peripapillary retinal nerve fiber layer thickness in children with hyperopic anisometropic amblyopia. Int J Ophthalmol. 2013;6(1):85–9.
18. Alotaibi AG, Al Enazi B. Unilateral amblyopia: Optical coherence tomography findings. Saudi J Ophthalmol Off J Saudi Ophthalmol Soc. 2011 Oct;25(4):405–9.