Project Details

Valproate for the treatment of residual amblyopia

Eric Gaier, MD, PhD

Summary

BACKGROUND: Amblyopia (“lazy eye”) is a common neurodevelopmental disorder affecting up to 3% of children and remains the leading cause of preventable lifelong visual impairment. Treatment effectiveness declines sharply after early childhood due to closure of experience-dependent cortical plasticity, leaving many older children with residual deficits. GAP: Despite strong preclinical evidence that critical-period plasticity can be pharmacologically reopened, no clinical trial has successfully translated this strategy to improve visual outcomes in older children with amblyopia. As a result, there are no approved treatments for residual amblyopia beyond the traditional critical period. HYPOTHESIS: We hypothesize that valproate, a histone deacetylase inhibitor, can transiently reopen visual cortical plasticity and enable clinically meaningful and durable recovery from amblyopia when combined with standard patching therapy. METHODS: We are conducting a randomized, double-blind, placebo-controlled, cross-over clinical trial enrolling children aged 8–17 years with residual amblyopia, comparing patching combined with oral valproate versus patching with placebo. The primary outcome is improvement in amblyopic-eye visual acuity, with secondary outcomes including stereoacuity, durability of response, quality of life, and safety. RESULTS: Pending. IMPACT: If successful, this study would establish the first effective therapy for residual amblyopia in older children, redefining treatment windows and improving lifelong visual and functional outcomes. By repurposing a widely available medication, this approach has the potential for rapid clinical adoption and broad global impact on pediatric vision health. Optional/Additional Comments: This project translates decades of foundational neuroscience into a rigorously controlled pediatric clinical trial and may provide a generalizable framework for treating other neurodevelopmental disorders limited by reduced plasticity later in life.