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

Male participants (N = 57) were ≥14 years (range, 14-70 years) with a clinical diagnosis of CHM and a disease-causing variant in the CHM 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.

RESULTS

The estimated annual rate of decrease of BCVA in the right eye (OD) was 0.17 letters (P = 0.38) and 0.16 letters (P = 0.40) in the left eye (OS). Estimated rates of change for kinetic perimetry depended on spot size. Size 14e had the fastest decline, but many participants could not reliably perform the test. Sizes III4e and V4e had annual rates of change varying from 13.7% to 20.4%. The mean static perimetry sensitivity declined annually by 8.1% (P < 0.0001) OD and 9.6% (P < 0.0001) OS. Visual Function Questionnaire 25 composite scores decreased by an average of 4.2 points over the first 24 months of the study, which is clinically meaningful to participants. The rate of decrease for PFAF OD was 10.1% (P < 0.0001), and OS was 9.7% (P < 0.0001). 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.