Modeling dose-response in amblyopia: toward a child-specific treatment plan.

PURPOSE This article describes an empirically derived mathematical model of the treatment dose-response of occlusion therapy for amblyopia based on outcome data obtained from the Monitored Occlusion Treatment for Amblyopia Study (MOTAS). METHODS The MOTAS protocol comprised three discrete phases: baseline, refractive adaptation, and occlusion. Only data from the occlusion phase were used in this dose-response model. Seventy-two participants, 3 to 8 years of age, mean +/- SD age 5.2 +/- 1.4 years (anisometropia [n = 18]); strabismus [n = 22]); both anisometropia and strabismus [n = 32]) completed the occlusion phase. All participants were prescribed 6-h/d patching, which was objectively monitored by an occlusion dose monitor (ODM). RESULTS Simple normal linear regression modeling of the data on an interval-by-interval basis (interval between clinic visits) indicates that increasing cumulative dose within interval (hours) yields an increase in visual acuity (R2 = 0.918; 684 data points). Most of the children achieved their best visual acuity with 150 to 250 hours' cumulative dose. Specific patient characteristics (especially age) modify the steepness of this function. For example, a 0.20-logMAR (2-line logarithm of the minimum angle of resolution) gain in visual acuity requires a cumulative dose of 170 hours for children at age 48 months and 236 hours at age 72 months. CONCLUSIONS Mathematical modeling of amblyopia therapy is a novel approach that elucidates the kinetics of the therapeutic response in humans. This response is age-influenced so that older children require a greater dose to achieve the same outcome--evidence of altered plasticity of the visual system. Fine-tuning the dose-response in amblyopia therapy will facilitate the development of child-specific, evidence-based treatment plans.