Natural History of Macular Sensitivity in Best Vitelliform Macular Dystrophy: Microperimetry-Derived Outcome Measures in Preparation For Clinical Trials

Abstract

Purpose To characterize the longitudinal changes of macular sensitivity in best vitelliform macular dystrophy (BVMD) and explore microperimetry (MP)-derived outcome measures for clinical trials. Methods Natural history cohort study (IRDs-OSR, NCT07265895) on subjects with BVMD undergoing mesopic MP (68-point grid, central 10°; MAIA, CenterVue). Test points were classified relative to normative data as normal (P ≥ 5%), relative scotoma (P < 5%, sensitivity ≥ 1dB), or deep scotoma (sensitivity <1 dB). Per-eye annual rates of change (RoC) of mean sensitivity (MS) were computed globally and within point subsets, together with point counts. Results Twenty-three eyes of 13 patients with clinical BVMD, with a median age at baseline of 29.4 years, completed an average of three tests over a median of 4.4 years. The median MS at baseline was 21.4 dB, with 44% of points being normal, 54% relative scotomas, and 2% deep scotomas. Globally MS showed no significant decline (mean RoC = −0.16 dB/year; P = 0.21). Restricting analysis to normal points at baseline revealed small but significant decline (mean RoC = −0.36 dB/year; P = 0.006), steepest within 5° (mean RoC = −0.56 dB/year; P = 0.028). Average increase of deep scotoma points was ∼1 every five years (mean RoC = 0.22 points/year; P = 0.015), with no significant change in relative scotoma or normal point counts (all P > 0.05). Conclusions Macular sensitivity within the central 10° remained stable over four years in BVMD when averaged across several test points, reflecting the disease slow natural history. Restricting analysis to normal points unmasked measurable decline, which may serve as an MP-derived outcome measure for gene therapy trials.