Multimodal assessment of choroideremia patients defines pre-treatment characteristics.

ABSTRACT

PURPOSE: 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 resolution multi-modal approach. METHODS: 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. RESULTS: We evaluated 98 data points of BCVA [0.34 ± 0.06 (logMAR); mean ± 95 % confidence interval], 80 of IOP (14.6 ± 0.6 mmHg), 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 ± 1.91 mm(2) (range 0.30-38.5 mm(2)), while mean neuroretinal volume (n  = 42) was found to be 1.76 ± 0.12 mm(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). CONCLUSION: 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.