Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of...

To describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the USH2A-related Retinal Degeneration study and to assess their suitability as clinical trial endpoints.

Prospective natural history study.

Participants (n = 105) with biallelic disease-causing sequence variants in USH2A and BCVA letter scores of ≥54 were included.

BCVA, FST, fundus-guided microperimetry, static perimetry, and spectral domain OCT were performed annually and ERG at baseline and 4 years only. Mixed effects models were used to estimate annual rates of change with 95% confidence intervals. Associations of change from baseline to 4 years between BCVA, FST, ERG, and other metrics were assessed with Spearman correlation coefficients (r_s).

Best-corrected visual acuity, FST, and ERG.

The annual rate of decline in BCVA was 0.83 (95% confidence interval: 0.65-1.02) letters/year. For FST, the change was 0.09 (0.07-0.11) log cd.s/m²/year for white threshold, 0.10 (0.08-0.12) log cd.s/m²/year for blue threshold, and 0.05 (0.04-0.06) log cd.s/m²/year for red threshold. Changes were 22.6 (17.4-28.2)%/year for white threshold, 26.0 (20.3-32.1)%/year for blue threshold, and 12.3 (8.7-16.0)%/year for red threshold. The high percentage of eyes with undetectable ERGs at baseline limited assessment of change.

Best-corrected visual acuity was not a sensitive measure of progression over 4 years. Full-field stimulus threshold was a more sensitive measure; however, additional information on the clinical relevance of changes in FST is needed before this test can be adopted as an endpoint for clinical trials.

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