UCSF

Purpose

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.

Design

Prospective natural history study.

Participants

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

Methods

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).

Main outcome measures

Best-corrected visual acuity, FST, and ERG.

Results

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.

Conclusions

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.

Financial disclosures

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.