High-resolution Imaging of Retinal Structure in Retinitis Pigmentosa and Usher Syndrome

Abstract

Purpose: Retinitis Pigmentosa (RP) and Usher Syndrome (USH) are progressive retinal degenerations that are clinically and genetically heterogeneous. This study aims to use reflectance Adaptive Optics Scanning Light Ophthalmoscopy (AOSLO) to examine the photoreceptor mosaic in RP and USH.

Methods: Eighteen subjects were recruited (4 USH, 14 RP), with 11 subjects having clinically detectable Cystoid Macular Edema (CME). In 6 subjects, total, Outer Nuclear + Henle’s Fiber layer (ONL+HFL), and inner retinal thickness were measured using SD-OCT images acquired through the fovea. Subjects were imaged using an AOSLO, and the integrity of the photoreceptor mosaic was assessed in regions with no CME. In 7 subjects without central CME, parafoveal cone density was measured using semi-automated cone counting software. DNA samples were acquired for 15 subjects.

Results: DNA testing identified mutations in 6 of the RP subjects. Consistent with previous findings, subjects with RP and USH had near-normal retinal thickness centrally with significant thinning in the perifovea. The ONL+HFL width was diminished with normal inner retinal thickness. On average, the subjects with USH had a greater reduction in retinal thickness than did the subjects with RP. In images of the parafoveal cone mosaic, subjects with USH had many presumed non-waveguiding cones, while subjects with RP had contiguous cone mosaics. Average cone density in the subjects with RP at 0.65 degrees from the fovea was 63,865 cones/mm² (n=3), comparable to previously reported normative values (72,528 cones/mm²). In contrast, the average cone density in the subjects with USH was 45,475 cones/mm² (n=4). All subjects imaged had areas devoid of visible photoreceptors where the RPE mosaic could be visualized in reflectance. The mean spacing of the RPE cells was 17.6μm, which agrees with previous findings in AOSLO and histologic estimates. Follow-up images in a subject with RP revealed no change in parafoveal cone density over a period of 16 months.

Conclusions: AOSLO imaging reveals different photoreceptor phenotypes in USH and RP. Though cone density varied, no differences in acuity or visual sensitivity were seen. While issues like CME and cataract remain barriers to imaging many individuals with RP and USH, the ability to repeatedly image single locations with AO will allow longitudinal tracking necessary for clinical trials of treatments for RP and USH.

Keywords: 696 retinal degenerations: hereditary • 551 imaging/image analysis: non-clinical • 648 photoreceptors