Long-term natural history of ellipsoid zone width inUSH2A-retinopathy

Abstract

AimsTo investigate the long-term natural history of ellipsoid zone (EZ) width inUSH2A-retinopathy.MethodsEZ width measurements from optical coherence tomography were retrospectively obtained from 110 eyes of 55 participants with molecularly confirmed biallelicUSH2A-retinopathy. We used a hierarchical Bayesian method to construct and compare different mathematical models describing the long-term decline of EZ width.ResultsCompared with linear and quadratic models, exponential decline best represented the long-term loss of EZ width based on the deviance information criterion score. Log-transformed EZ width declined linearly over 30 years of inferred disease duration (median: 0.063 (IQR: 0.040–0.086) log (µm)/year). Compared with the raw EZ width decline rate, the log-transformed EZ width decline rate required 48% fewer patients to achieve an identically powered 1-year trial (38 vs 73 participants). Log EZ width decline rate was uncoupled from baseline EZ width (Spearman ρ=−0.18, p=0.06) and age (ρ=−0.10, p=0.31). Eyes with Usher syndrome exhibited earlier median onset ages of macular EZ width loss (18.8 (IQR: 13.1–24.7) vs 28.1 (IQR: 18.5–35.8) years, p<0.001) but comparable log EZ width decline rates (0.060 (IQR: 0.035–0.100) vs 0.065 (IQR: 0.050–0.079) log (µm)/year; p=0.42).ConclusionsEZ width follows an exponential decline inUSH2A-retinopathy. Compared with raw EZ width decline rate, log-transformed EZ width decline rate may be a superior endpoint for clinical trials. Syndromic eyes exhibit an earlier onset of macular EZ width loss but progress at comparable rates to non-syndromic eyes.