Metaplasticity: a key to visual recovery from amblyopia in adulthood?

PURPOSE OF REVIEW: We examine the development of amblyopia and the effectiveness of conventional and emerging therapies through the lens of the Bienenstock, Cooper, and Munro (BCM) theory of synaptic modification. RECENT FINDINGS: The BCM theory posits metaplastic adjustment in the threshold for synaptic potentiation, governed by prior neuronal activity. Viewing established clinical principles of amblyopia treatment from the perspective of the BCM theory, occlusion, blur, or release of interocular suppression reduce visual cortical activity in the amblyopic state to lower the modification threshold and enable amblyopic eye strengthening. Although efficacy of these treatment approaches declines with age, significant loss of vision in the fellow eye by damage or disease can trigger visual acuity improvements in the amblyopic eye of adults. Likewise, reversible retinal inactivation stimulates recovery of amblyopic eye visual function in adult mice and cats. SUMMARY: Conventional and emerging amblyopia treatment responses abide by the framework of BCM theory. Preclinical studies support that the dramatic reduction in cortical activity accompanying temporary retinal silencing can promote recovery from amblyopia even in adulthood, highlighting a promising therapeutic avenue.

Spontaneous recovery from amblyopia following fellow eye vision loss: a systematic review and narrative synthesis.

BACKGROUND: The effectiveness of traditional amblyopia therapies is largely restricted to childhood. However, spontaneous recovery in adulthood is possible following vision loss in the fellow eye due to enucleation, injury, or disease. The twofold purpose of this study was (1) to define the incidence of recovery and (2) to elucidate the clinical features associated with greater amblyopic eye gains. METHODS: A systematic review of three databases yielded 24 reports containing 110 cases of patients ≥18 years old with unilateral amblyopia and vision-limiting fellow eye pathology. RESULTS: Our analysis revealed that 25 of 42 of adult patients (59.5%) gained ≥2 logMAR lines in the amblyopic eye after fellow eye vision loss. The degree of improvement is clinically meaningful (median, 2.6 logMAR lines). Recovery occurs within 12 months of initial loss of fellow eye vision. Regression analysis demonstrated that younger age, worse baseline visual acuity in the amblyopic eye, and worse vision in the fellow eye independently conferred greater gains in amblyopic eye visual acuity. Recovery occurs across amblyopia types and fellow eye pathologies, although disease entities affecting fellow eye retinal ganglion cells demonstrate shorter latencies to recovery. CONCLUSIONS: Amblyopia recovery after fellow eye injury demonstrates that the adult brain harbors the neuroplastic capacity for clinically meaningful recovery, which could potentially be harnessed by novel approaches to treat adults with amblyopia.

Recovery from Amblyopia in Adulthood: A Meta-Analysis.

Purpose: The effectiveness of traditional amblyopia therapies is largely restricted to childhood. However, recovery in adulthood is possible following removal or vision-limiting disease of the fellow eye. Study of this phenomenon is currently limited to isolated case reports and a few case series, with reported incidence ranging from 19-77% 1-5 . We set out to accomplish two distinct goals: (1) define the incidence of clinically meaningful recovery and (2) elucidate the clinical features associated with greater amblyopic eye gains. Methods: A systematic review of 3 literature databases yielded 23 reports containing 109 cases of patients ≥18 years old with unilateral amblyopia and vision-limiting fellow eye pathology. Results: Study 1 revealed 25/42 (59.5%) of adult patients gained ≥2 logMAR lines in the amblyopia eye after FE vision loss. The overall degree of improvement is clinically meaningful (median 2.6 logMAR lines). Study 2 showed that for cases with amblyopic eye visual acuity improvement, recovery occurs within 12 months of initial loss of fellow eye vision. Regression analysis revealed that younger age, worse baseline acuity in the amblyopic eye, and worse vision in the fellow eye independently conferred greater gains in amblyopic eye visual acuity. Recovery occurs across amblyopia types and fellow eye pathologies, although disease entities affecting fellow eye retinal ganglion cells demonstrate shorter latencies to recovery. Conclusions: Amblyopia recovery after fellow eye injury demonstrates that the adult brain harbors the neuroplastic capacity for clinically meaningful recovery, which could potentially be harnessed by novel approaches to treat adults with amblyopia.

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

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.