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Correction of amblyopia in cats and mice after the critical period.

ABSTRACT: Monocular deprivation early in development causes amblyopia, a severe visual impairment. Prognosis is poor if therapy is initiated after an early critical period. However, clinical observations have shown that recovery from amblyopia can occur later in life when the non-deprived (fellow) eye is removed. The traditional interpretation of this finding is that vision is improved simply by the elimination of interocular suppression in primary visual cortex, revealing responses to previously subthreshold input. However, an alternative explanation is that silencing activity in the fellow eye establishes conditions in visual cortex that enable the weak connections from the amblyopic eye to gain strength, in which case the recovery would persist even if vision is restored in the fellow eye. Consistent with this idea, we show here in cats and mice that temporary inactivation of the fellow eye is sufficient to promote a full and enduring recovery from amblyopia at ages when conventional treatments fail. Thus, connections serving the amblyopic eye are capable of substantial plasticity beyond the critical period, and this potential is unleashed by reversibly silencing the fellow eye.

SUBMITTER: Fong MF

PROVIDER: S-EPMC8456712 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Correction of amblyopia in cats and mice after the critical period.

Fong Ming-Fai MF Duffy Kevin R KR Leet Madison P MP Candler Christian T CT Bear Mark F MF

eLife 20210831

Monocular deprivation early in development causes amblyopia, a severe visual impairment. Prognosis is poor if therapy is initiated after an early critical period. However, clinical observations have shown that recovery from amblyopia can occur later in life when the non-deprived (fellow) eye is removed. The traditional interpretation of this finding is that vision is improved simply by the elimination of interocular suppression in primary visual cortex, revealing responses to previously subthres ...[more]

PMID: 34464258

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Project description:IntroductionAmblyopia therapy appears to be most effective in children under the age of 7 years, but results from randomized control trials (RCTs) have shown that occlusion therapy and/or atropine penalization therapy may improve visual acuity in an older age group. Which of these two therapies is the most effective with fewer adverse effects in an older age group has not yet been agreed upon.MethodsWe systematically searched the literature for RCTs that compared atropine penalization therapy and occlusion therapy in terms of their visual acuity outcomes and adverse events and performed a meta-analysis on the visual acuity data obtained. The adverse effects reported and their implications for clinical practice are discussed.ResultsTwo RCTs were identified, with the authors of both concluding that there was no detectable difference between the two therapies for the age groups they studied. The mean difference between atropine penalization and occlusion therapies was calculated to be - 0.01 logMAR (95% confidence interval - 0.07 to 0.03 logMAR) in favor of occlusion therapy, and no statistical difference between the two groups was detected (P = 0.45). Neither study detected a marked difference in terms of reported adverse effects from the two interventions.ConclusionBased on the results of our meta-analysis we conclude that there is no difference in visual acuity outcomes between atropine penalization therapy and occlusion therapy after 17 to 24 weeks of treatment in children aged 7-12 years. Further evidence to determine the efficacy of amblyopia therapy for an older patient population is required before studies comparing atropine penalization and occlusion therapy in patients older than 12 years can be performed. Atropine penalization therapy may cause more frequent minor adverse effects, such as light sensitivity, but in the clinical setting this needs to be balanced with the potential practical benefits of twice-weekly eye drops versus daily occlusion.FundingThe funding for this study was provided by the National Institute for Health Research (NIHR) and Health Education England (HEE). A plain language summary is available for this article.

Project description:Dichoptic movie viewing has been shown to significantly improve visual acuity in amblyopia in children. Moreover, short-term occlusion of the amblyopic eye can transiently increase its contribution to binocular fusion in adults. In this study, we first asked whether dichoptic movie viewing could improve the visual function of amblyopic subjects beyond the critical period. Secondly, we tested if this effect could be enhanced by short-term monocular occlusion of the amblyopic eye. 17 subjects presenting stable functional amblyopia participated in this study. 10 subjects followed 6 sessions of 1.5 hour of dichoptic movie viewing (nonpatched group), and 7 subjects, prior to each of these sessions, had to wear an occluding patch over the amblyopic eye for two hours (patched group). Best-corrected visual acuity, monocular contrast sensitivity, interocular balance, and stereoacuity were measured before and after the training. For the nonpatched group, mean amblyopic eye visual acuity significantly improved from 0.54 to 0.46 logMAR (p < 0.05). For the patched group, mean amblyopic eye visual acuity significantly improved from 0.62 to 0.43 logMAR (p < 0.05). Stereoacuity improved significantly when the data of both groups were combined. No significant improvement was observed for the other visual functions tested. Our training procedure combines modern video technologies and recent fundamental findings in human plasticity: (i) long-term plasticity induced by dichoptic movie viewing and (ii) short-term adaptation induced by temporary monocular occlusion. This passive dichoptic movie training approach is shown to significantly improve visual acuity of subjects beyond the critical period. The addition of a short-term monocular occlusion to the dichoptic training shows promising trends but was not significant for the sample size used here. The passive movie approach combined with interocular contrast balancing even over such a short period as 2 weeks has potential as a clinical therapy to treat amblyopia in older children and adults.

Project description:The aim of this study was to assess the effect of wearing optical correction on the choroidal structure in eyes of children with anisohypermetropic amblyopia. This study was conducted at the Nara Medical University Hospital and at the Tokushima University Hospital. Twenty-nine anisohypermetropic amblyopic eyes and their fellow eyes of 29 amblyopic patients (mean age, 5.7 ± 1.7 years, range 3- to 8-years) and twenty eyes of 20 age-similar control children (4.9 ± 0.8 years, range 4- to 6-years) were studied. All patients wore optical correction and 15 patients had both optical correction and patching. The values at the baseline were compared to that at one year later. The binarization method was used to determine the total, luminal, and stromal areas of the choroid in the enhanced depth imaging optical coherence tomographic images. The best-corrected visual acuity (BCVA) of the amblyopic eyes was significantly improved after the one-year period. A large luminal area was characteristic of the amblyopic eye at the baseline, and it was significantly reduced after the optical treatment. The stromal area widened significantly in the amblyopic and fellow eyes after one year whereas there were no significant changes in the choroid of the control eyes after one year. After one-year of optical correction, the luminal/stromal ratios in the amblyopic and fellow eyes were decreased and were then not significantly different from that of the normal control eyes. There was a significant and positive correlation between the improvement of the BCVA and the stromal area at the baseline (r = 0.64, P = 0.001). Wearing corrective lenses on the amblyopic eyes improves the BCVA, and the choroidal structure of the amblyopic eye becomes closer to that of the control eyes. The narrowed luminal area is a specific response of the amblyopic eye associated with the correction of the refractive error. The larger stromal area in the amblyopic eyes at the baseline is a predictive factor for improvements of the BCVA.

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Correction of amblyopia in cats and mice after the critical period.

Publications

Correction of amblyopia in cats and mice after the critical period.

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