The Progression of Stargardt Disease using Volumetric Hill of Vision Analyses Over 24 Months: ProgStar Report No.15.

Abstract

PURPOSE\nTo report the yearly rate of change in macular function in patients with Stargardt disease type 1 (STGD1) over 24 months and to establish a new volumetric visual function index for use in clinical trials investigating the efficacy on retinal sensitivity.\n\n\nDESIGN\nInternational, multicenter, prospective cohort study with five study visits every 6 months over 24 months.\n\n\nPARTICIPANTS AND MAIN OUTCOME MEASURES\nA total of 233 individuals with genetically confirmed STGD1 (≥ 1 disease-causing ABCA4 variant). The total volume (VTOT) beneath the sensitivity surface of a 3-D model of the hill of vision and mean sensitivity (MS) derived from mesopic microperimetry performed with a white stimulus. Changes of VTOT over time and its correlation with the ABCA4 genotype and baseline features.\n\n\nRESULTS\nAt baseline, 440 eyes (233 patients) with a mean (SD) age of 33.7 (15.0) years, mean (SD) visual acuity of 46.08 (16.03) ETDRS letters were analyzed with an average VTOT of 0.91 dB-sr and an MS of 10.73 dB. The overall mean rate of decrease in sensitivity [95% CI] was 0.077 [0.064, 0.090] dB-sr/yr for VTOT and 0.87 [0.72, 1.02] dB/year for MS. The progression rate of VTOT depended on baseline visual function (0.029 dB-sr/year for low and 0.120 dB-sr/year for high baseline VTOT; p<0.001) and exhibited a difference in the first vs. second year of follow up (0.065 dB-sr/year vs. 0.089 dB-sr/year, respectively; p<0.001). The absence of pigmentary abnormalities of the retinal pigment epithelium at baseline was found to be associated with a faster progression rate (p<0.001), whereas a significant association with the genotype was not detected (p=0.7).\n\n\nCONCLUSION\nIn STGD1, both microperimetric outcomes demonstrate statistically significant and clinically meaningful changes after relatively short follow-up periods. Volumetric modeling may be useful in future interventional clinical trials that aim to improve retinal sensitivity or to slow down its decline and for structure-function correlations.