Adaptive Optics Scanning Laser Ophthalmoscopy and High Resolution Imaging in Autosomal Dominant Retinitis Pigmentosa Caused by a Novel PRPF31 Nonsense Mutation

Abstract

Purpose: To study cone photoreceptor density and retinal ultrastructure in autosomal dominant retinitis pigmentosa (adRP) using adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography (OCT) and to compare the results with clinical findings and genetic characterization.

Methods: Exome sequencing was carried out in individuals negative for previously known mutations causing adRP. The DNA variants were confirmed in CLIA labs. Patients underwent ophthalmic examination, visual acuity (VA), Humphrey and Goldman visual field testing. Retinal images at several locations within 1.5mm of fixation were obtained using an AOSLO developed by Canon, Inc. Infrared and color fundus photos, OCT and autofluorescence (AF) images were also obtained.

Results: For all patients, peripheral pigmentary clumping and bone spicule retinopathy were observed on ophthalmic examination. One individual was followed in the clinic for over 35 years. His VA went from 20/200 at age 36 to 20/500 OD and hand motion OS at age 73. VA was reduced: 20/60, 20/40, 20/25 for patients aged 44, 16 and 11 respectively in the second family. Goldman visual fields showed restricted peripheral fields with remaining central vision. Humphrey visual field showed no reduction of visual threshold in the central retina for the 16 and 11 y.o., but reduced sensitivity in the 44 y.o. OCT for the 11 y.o. revealed central intact photoreceptors with peripheral thinning. The 16 y.o. had macular edema OU. AF revealed a hyper-AF ring within the macula region. As well, the 44 y.o. exhibited clumps of hypo-AF in the periphery corresponding to regions of degenerated retinal pigment epithelium. AOSLO imaging of the central macula revealed intact cone photoreceptor mosaics, and cone density fell within normal limits. Results of genetic testing (in both families) revealed a PRPF31 c.1060 C>T mutation (p.Arg354Stop) which segregated with the phenotype and was consistent with the diagnosis of adRP.

Conclusions: Here we report a novel PRPF31 mutation causing adRP in two apparently unrelated families. AOSLO imaging allows visualization of the cone mosaic within the remaining central retina in patients with adRP. AOSLO in combination with other imaging modalities will be useful for studying the mechanisms of disease progression for degenerations including adRP.

Keywords: 696 retinal degenerations: hereditary • 550 imaging/image analysis: clinical • 648 photoreceptors