Natural History of the Central Structural Abnormalities in Choroideremia: Insights from a Cross-sectional Study

Abstract

Purpose : To increase understanding of the retinal structure and function in choroideremia (CHM).

Methods : Patients with CHM, ages 6 to 71 years were evaluated by ocular examination. Retinal imaging was performed with spectral domain optical coherence tomography (SD-OCT) and near infrared reflectance (NIR-REF). SD-OCT cross sections were quantified along the horizontal meridian and related in a subset of patients to NIR-REF images and co-localized visual thresholds measured with automated static perimetry.

Results : Eighty nine patients carrying the diagnosis of CHM were included. Youngest patients showed abnormalities of the photoreceptor outer segment (OS) - retinal pigmented epithelium (RPE) interdigitation layers, outer nuclear layer (ONL) thinning and central rod photoreceptor dysfunction. Most patients retained visual acuities better than 20/40 until the fifth decade of life. Visual acuity decline coincided with the approximation to the foveal center of transitional zones (TZs) of structural change from relatively preserved or thickened retina to severe thinning accompanied by vision loss. Photoreceptor loss was associated with a remodeling response that included thickening, the presence of interlaminar bridges and the formation of tubular structures. The lateral extent of the outer retinal sublaminae approximated the extent of relative preservation of RPE melanin by NIR-REF imaging. RPE disease generally paralleled or followed photoreceptor degeneration although there were frequent examples of photoreceptor survival in regions with severe RPE depigmentation and thinning of the choroid.

Conclusions : Early CHM showed photoreceptor OS-apical RPE abnormalities. There was preservation of the central retinal function and structure until relatively late in the course of the disease. Proximity of TZs to the foveal center and the presence of a structurally disorganized or thin fovea heralded central vision loss. The results have implications for the planning of future gene therapy trials that intend to target the central retina.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.