Background/aims Best-corrected visual acuity (BCVA) is the most common primary endpoint in treatment trials for choroideremia (CHM) but the long-term natural history of BCVA is unclear.
Methods We searched in seven databases to identify studies that reported BCVA of untreated eyes with CHM. We sought individual-level data and performed segmented regression between BCVA and age. For eyes followed longitudinally, we introduced a horizontal translation factor to each dataset to account for different ages at onset of a rapid BCVA decline.
Results We included 1004 eyes from 23 studies. BCVA of the right and left eyes was moderately correlated (r=0.60). BCVA as a function of age followed a 2-phase decline (slow followed by rapid decline), with an estimated transition age of 39.1 years (95% CI 33.5 to 44.7). After the introduction of horizontal translation factors to longitudinal datasets, BCVA followed a 2-phase decline until it reached 0 letters (r2=0.90). The BCVA decline rate was 0.33 letters/year (95% CI −0.38 to 1.05) before 39 years, and 1.23 letters/year (95% CI 0.55 to 1.92) after 39 years (p=0.004).
Conclusion BCVA in eyes with CHM follows a 2-phase linear decline with a transition age of approximately 39 years. Future trials enrolling young patients may not be able to use BCVA as a primary or sole endpoint, but rather, may need to employ additional disease biomarkers that change before age 39. BCVA may still have utility as a primary endpoint for patients older than 39 years who have measurable BCVA decline rates.
- clinical trial
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Contributors Conception and design: LLS. Data collection: LLS, AA, MS andHKGN. Data Analysis: LLS. Data interpretation: LLS and LVDP. Obtained funding: LLS and LVDP. Manuscript writing: LLS, AA, MS, BKY, HKGN and LVDP.
Funding Research reported in this publication was supported by the Yale School of Medicine Medical Student Research Fellowship (Recipient: Shen).
Disclaimer The sponsor or funding organisation had no role in the design or conduct of this research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the institution or funder.
Competing interests LVDP, Astellas Institute for Regenerative Medicine (consultant), CavtheRx (scientific and clinical advisors), LambdaVision (consultant), and Tissue Regeneration Sciences (scientific advisory board).
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request. Data are available on reasonable request sent to the corresponding author.