{Reference Type}: Journal Article
{Title}: Long-term natural history of ellipsoid zone width in USH2A-retinopathy.
{Author}: Heyang M;Warren JL;Ocieczek P;Duncan JL;Moosajee M;Del Priore LV;Shen LL;
{Journal}: Br J Ophthalmol
{Volume}: 0
{Issue}: 0
{Year}: 2024 Aug 5
{Factor}: 5.908
{DOI}: 10.1136/bjo-2024-325323
{Abstract}: <B>OBJECTIVE: </B>To investigate the long-term natural history of ellipsoid zone (EZ) width in USH2A-retinopathy.<BR><B>METHODS: </B>EZ width measurements from optical coherence tomography were retrospectively obtained from 110 eyes of 55 participants with molecularly confirmed biallelic USH2A-retinopathy. We used a hierarchical Bayesian method to construct and compare different mathematical models describing the long-term decline of EZ width.<BR><B>RESULTS: </B>Compared 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).<BR><B>CONCLUSIONS: </B>EZ width follows an exponential decline in USH2A-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.