Retinal thickness and visual acuity in early-onset Stargardt disease follow a non-linear progression curve: implications for clinical trials.

Abstract

Introduction: We retrospectively evaluated early-onset, autosomal recessive Stargardt disease in younger siblings from affected sibships using longitudinal analysis of visual acuity and multimodal imaging.

Methods: Between 2002 and 2022, two sibships (n = 4, n = 2) with molecularly-confirmed Stargardt disease had younger affected siblings with clinical data obtained prior to the onset of vision loss. Measurement of best-corrected visual acuity and acquisition of color fundus photographs, autofluorescence, SLO, and OCT imaging were performed as part of routine clinical care.

Results: Both sibships presented with early-onset vision loss between 5-9 years old. Fundus autofluorescence changes and a thickened external limiting membrane on OCT were the first biomarkers observed in the youngest siblings. Decline in visual acuity and total thickness in the fovea followed a distinct, three-phase course (initial, acute, slow/stable). The timing of the second (acute) phase of acuity loss differed by up to 5 years between siblings within a sibship. Loss of total retinal thickness in the fovea preceded the greatest drop in visual acuity.

Discussion: Clinical trials must account for interrelationship between structure and function and the heterogeneity among patients sharing the same genotype, which suggests the action of unidentified modifiers.