Multimodal assessment of choroideremia patients defines pre-treatment characteristics.

Abstract

Choroideremia (CHM) is a X-chromosomal disorder leading to blindness by progressive degeneration of choroid, retinal pigment epithelium (RPE), and retinal neurons. A current clinical gene therapy trial (NCT01461213) showed promising safety and efficacy data in a carefully selected patient population. The present study was performed to shed light on pre-treatment characteristics of a larger cohort of CHM patients using a high resolutionmulti-modal approach. In a retrospective cross-sectional study, data from 58 eyes of 29 patients with clinically confirmed CHM were analysed including best-corrected visual acuity (BCVA), refractive error, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), perimetry, and tonometry. Residual retinal volume, area of residual RPE, and foveal thickness were quantified to further define natural disease progression and assess symmetry. We evaluated 98 data points of BCVA [0.34 ± 0.06 (logMAR); mean ± 95% confidence interval], 80 of IOP (14.6 ± 0.6mmHg), and 98 of refraction (-2.16 ± 1.08 spherical equivalent). Visual fields (n = 76) demonstrated variable degrees of concentric constriction (54% <10°, 25% 10-30°, 21% >30°). Mean residual RPE area on FAF (n = 64) measured 8.47 ± 1.91mm(2) (range 0.30-38.5mm(2)), while mean neuroretinal volume (n = 42) was found to be 1.76 ± 0.12mm(3). Age at examination was exponentially associated with BCVA, while logarithmic functions best described progressive loss of retinal area and volume. A high degree of left to right symmetry was found in all modalities with structural markers showing the best correlation (r (2) area = 0.83; r (2) volume = 0.75). Analysis of these widely available clinical data defines the natural disease characteristics of a relevant patient population eligible for gene therapeutic intervention. In the wake of preliminary reports on safety and efficacy of CHM gene therapy (NCT01461213), this multi-modal assessment of a cohort of CHM patients provides important evidence of the natural rate of disease progression and degree of symmetry between eyes.