Natural History of Progression of Choroideremia (NIGHT) Study: Cross-Sectional Analysis of Baseline Characteristics

Abstract

Purpose : To report baseline characteristics of participants with Choroideremia (CHM) in the NIGHT prospective, multi-center, observational study (NCT03359551); the largest natural history study for CHM.

Methods : Males ≥18 years with a genetic diagnosis of CHM, clinically active disease within the macula, and best-corrected visual acuity (BCVA) better or equal to 20/200 (LogMar 1.0) in at least one eye were enrolled. Imaging data were assessed at a central reading center. Cross-sectional analysis of baseline characteristics is presented. Linear regression models estimated the associations between BCVA and age, and interocular symmetry analyses were performed.

Results : Of 219 patients enrolled to date across 17 sites globally, majority were Caucasian (97%), mean age ± SD of 47 ± 13.2 years. At baseline, BCVA was moderately impaired (63 ± 21.5 ETDRS letters, LogMar 0.5) with a mean sensitivity (MS) on microperimetry of 3.6 ± 4.83 dB. Similarly, the mean areas of preserved autofluorescence (PAF) and ellipsoid zone (PEZ) on SD-OCT were 5.4 ± 6.28 mm² and 2.4 ± 2.16 mm², respectively. Linear regression showed BCVA declines slowly with increasing age (average of -0.5 ETDRS letters/yr) although the linear correlation coefficient was low (-0.3). Bilateral asymmetry in BCVA was evident with a mean inter-eye difference of 19 ± 19.2 ETDRS letters (only 28% patients showed ≤5-letter difference), and a low ICC score of 0.23 (Figure 1A and 1B). In contrast, a high degree of bilateral symmetry was observed for MS, PAF and PEZ with high ICC scores of 0.90, 0.92 and 0.86, respectively.

Conclusions : Cross-sectional analysis of baseline characteristics indicates that during late-stage of CHM, when macular involvement is evident, visual acuity becomes asymmetrical due to the irregular pattern of macular atrophy in CHM and thus unpredictable onset of foveal involvement (Figure 1C). These findings have important implications for designs of future CHM interventional trials, whereby use of fellow-eye as a control is appropriate only in early-stage patients, if BCVA is used.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Figure 1. Bilateral symmetry in visual acuity of CHM patients (A)Baseline BCVA: Equality (grey) and orthogonal regression (red) lines. (B)Bland-Altman plot of difference between left and right eyes plotted against their average value. Mean difference (red) ± 2 SD (blue). (C) Preserved autofluorescence in a late-stage CHM patient.