Long-term natural history of visual acuity in eyes with choroideremia: a systematic review and meta-analysis of data from 1004 individual eyes

Br J Ophthalmol. 2021 Feb;105(2):271-278. doi: 10.1136/bjophthalmol-2020-316028. Epub 2020 May 29.


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.

Keywords: clinical trial; degeneration; genetics; retina; vision.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adult
  • Choroideremia / physiopathology*
  • Databases, Factual
  • Female
  • Fluorescein Angiography
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Tomography, Optical Coherence
  • Visual Acuity / physiology*