Natural History of Visual Dysfunction in ABCA4 Retinopathy and Its Genetic Correlates

Two- and five-year ability-to-detect-change based on the Eta-squared statistic RESULTS: A total of 134 eyes from 67 participants with a mean follow-up of 3.65 years were included. In the two-year interval, the microperimetry-derived peri-lesional sensitivity (η of 0.73 [0.53, 0.83]; -1.79 dB/yr [-2.2, -1.37]) and mean sensitivity (η of 0.62 [0.38, 0.76]; -1.28 dB/yr [-1.67, -0.89]) showed most change over time, but could only be recorded in 71.6 % of the participants. In the five-year interval, the dark-adapted ERG a- and b-wave amplitude showed marked change-over-time as well (e.g., DA 30 a-wave amplitude with an η of 0.54 [0.34, 0.68]; -0.02 Log10(µV)/yr [-0.02, -0.01]). The genotype explained a large fraction of variability in the ERG-based age-of-disease-initiation (adj. R of 0.73) CONCLUSIONS AND RELEVANCE: Microperimetry-based clinical outcome assessments were most sensitive to change but could only be acquired in a subset of participants. Across a 5-year interval, the ERG DA 30 a-wave amplitude was sensitive to disease progression, potentially allowing for more inclusive clinical trial designs encompassing the whole ABCA4-retinopathy spectrum.