Abstract
PURPOSE: To assess the reproducibility of retinal measurements from optical coherence tomography (OCT) in ABCA4-related Stargardt disease (STGD1). METHODS: The international multicenter Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study enrolled 259 STGD1 patients. OCT images were graded by the study reading center (RC). Semiautomatic segmentation with manual adjustments was used to segment the layers of retinal pigmentation epithelium, outer segments, inner segments (ISs), outer nuclear layer (ONL), inner retina, and the total retina (TR). The images were overlaid to the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. For each layer, the thickness and the intact area of the ETDRS central subfield, inner ring, and outer ring were recorded, respectively. A different set of RC graders regraded 30 independent ProgStar images to evaluate measurement reproducibility. Reproducibility was assessed graphically and using statistics including intraclass correlation (ICC) and relative absolute difference (RAD). RESULTS: Across all layers, measurements of the ETDRS central subfield had low ICC and/or large RAD. The outer-ring region was not fully captured in some images. For inner ring, good reproducibility was observed for intact area in the IS (ICC = 0.99, RAD = 4%), thicknesses of the ONL (ICC = 0.93, RAD = 6%), and TR (ICC = 0.99, RAD = 1%). CONCLUSIONS: STGD1's complex morphology made outer retina segmentation challenging. Measurements of the inner ring, including the intact area of IS (i.e., the ellipsoid zone [EZ]) and ONL and TR thicknesses, had good reproducibility and showed anatomical impairment. TRANSLATIONAL RELEVANCE: ONL and TR thicknesses and the EZ intact area in the ETDRS inner ring hold potential as structural endpoints for STGD1 trials. Structure-function relationships need to be further established.