A 48-Month, Prospective, Multicenter, Natural History Study of Choroideremia

Purpose: State-of-the-art testing modalities evaluated choroideremia (CHM) disease progression and examined the feasibility of measuring specific endpoints over time. Design: Prospective multicenter natural history study. Participants: gene. Participants had best-corrected visual acuity (BCVA) ≥20/200 (measured using the ETDRS letter score), a preserved paracentral foveal (within the central 10°) ellipsoid zone (EZ) and outer nuclear layer on spectral-domain OCT (SD-OCT). Methods: Participants at 5 centers in the United States and Canada consented to testing at 6-month intervals for 24 months. Participants who completed the trial (NCT02994368) at the month 24 visit were asked to participate in visits at months 30, 36, 42, and 48. Main Outcome Measures: Best-corrected visual acuity, static and kinetic visual fields, preserved fundus autofluorescence (PFAF), EZ width on SD-OCT, and Visual Function Questionnaire 25. The decrease/year in EZ length was greater in the vertical dimension (OD: 9.9%; OS: 10.4%) than in the horizontal dimension (OD: 5.9%; OS: 7.0%). Conclusions: Preserved fundus autofluorescence area has an advantage over EZ area as a clinical endpoint in CHM due to its ease and precision of measurement. Importantly, several functional measures of visual field correlated highly with PFAF area, supporting its validity as an outcome measure. The average annual decrease in PFAF area was ∼10%. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.