Photoreceptor imaging in USH2A-related non-syndromic retinitis pigmentosa and Usher Syndrome type 2A patients

Abstract

Purpose : Although non-syndromic autosomal recessive retinitis pigmentosa (ARRP) and Usher syndrome type 2A (ARRP with congenital, moderate hearing loss) can both result from USH2A variants, the retinal phenotypes may differ. We used high resolution retinal imaging to ask if clinically significant differences in retinal structure exist in these patient populations.

Methods : This cross-sectional study enrolled patients with ARRP and Usher syndrome type 2A with at least 2 likely pathogenic or pathogenic USH2A variants. Eligible patients had clear media, stable fixation, visual acuity better than 20/50, and <6 diopters of myopia. 20 degree horizontal spectral domain optical coherence tomography scans through the fovea were segmented to measure outer segment (OS) and total retina (TR) thickness where cone spacing was measured. Cone structure was studied with confocal and split detector adaptive optics scanning laser ophthalmoscopy (AOSLO) in the central 5.5 degrees of the macula. Regions of interest were chosen at 1-degree intervals and cones were counted by an independent investigator. Cone spacing was compared with data from 37 age-similar normal eyes and converted to Z-scores to normalize for eccentricity-dependent changes. An exact permutation test was performed at the level of the individual patient to compare Z-scores between ARRP and Usher syndrome patients.

Results : 17 eyes of 9 ARRP patients (mean age 49±8 years) and 7 eyes of 4 Usher Syndrome patients (mean age 41 ±19 years) with at least 2 pathogenic or likely pathogenic USH2A variants were studied. Cone spacing Z-scores were correlated with OS (r = -0.78, P=0.001) and TR (r = -0.77, P=0.001) thickness. Mean cone spacing Z-scores were significantly greater than normal in Usher syndrome patients (3.60, 95% CI 2.1–5.1), but not greater than normal in ARRP patients (0.77, 95% CI 0.25–1.3). Cone spacing mean Z-scores were significantly higher in Usher syndrome compared to ARRP patients (P = 0.022).

Conclusions : Usher syndrome patients have significantly increased cone spacing compared to normal and to ARRP patients due to disease-causing USH2A variants, demonstrating retinal degeneration is more severe in Usher syndrome type 2A than ARRP. AOSLO is a valuable tool in studying the retinal structure of patients with retinal degeneration and may be helpful for prospectively studying the natural history of these diseases.

This is a 2020 ARVO Annual Meeting abstract.