High-resolution Imaging of Photoreceptor Structure in Choroideremia

Abstract

Purpose: : To use high-resolution retinal imaging tools to examine photoreceptor structure in patients with choroideremia (CHM).

Methods: : We recruited 8 males with CHM (average age = 47 yrs) and 4 obligate female carriers (average age = 55 yrs). Patients were screened for mutations of the CHM gene. SD-OCT was used to obtain volumetric cross-sectional images of the macula, and C-scans were extracted to visualize specific layer disruption. Images of the photoreceptor mosaic were obtained using a flood-illumination adaptive optics (AO) camera and an AO scanning light ophthalmoscope (AOSLO).

Results: : SD-OCT showed foveal thickening in 1 male subject. Asymmetrical parafoveal thinning was observed in 4 of the males. The youngest patient (17 yrs) showed a relative thickening of the nasal retina, with preserved IS/OS structure throughout the central retina. Preserved IS/OS structure was observed in 5 additional males, though there was substantial variation in this feature. Outer retinal tubulation was observed in 5 males; C-scans demonstrated these tubules were inter-connected. On SD-OCT, the female carriers ranged from entirely normal to having clinically significant macular changes. We found significant variation in photoreceptor structure across the 8 males. AO flood-illuminated images of the youngest patient showed a normal foveal cone mosaic with a low-frequency structure across the image. On follow-up, the cone density remained constant but the arrangement of the low-frequency structures changed. Images with the AOSLO also showed a normal cone mosaic, but the low-frequency structures were not visible, suggesting an origin in the RPE or choriocapillaris. The other 5 patients with preserved IS/OS structure showed disrupted cone mosaics on AOSLO. In the carrier with skewed X-inactivation, we observed patchy disruption of the rod, but not cone mosaic in the mid-peripheral retina. The remaining carriers had normal photoreceptor mosaics.

Conclusions: : Our data are consistent with retinal remodeling in CHM (Jacobson et al, 2006 IOVS;47:4113). In particular, we observed retinal thickening in the youngest patient, though the cone mosaic appeared normal at the same location. Differences in flood-illuminated versus scanning ophthalmoscopes should be considered when applying this imaging technology to this disease. The cellular phenotype of CHM takes on additional relevance as gene therapy trials emerge for the condition, and more patients at various disease stages are needed to better characterize disease progression.

Keywords: photoreceptors • imaging/image analysis: non-clinical • retina