Progressive Loss of Rod Sensitivity in Patients with Autosomal Dominant Retinitis Pigmentosa (adRP) due to RHO Pro23His Mutation

Abstract

Purpose : Although longitudinal clinical characterization of patients having RHO mutations has been reported, there has been insufficient quantitative characterization of rod photoreceptor loss to enable the design of therapeutic clinical trials for this form of adRP. As part of an ongoing multi-center 2-year natural history study, patients with a confirmed RHO Pro23His mutation were evaluated for clinical and retinal endpoints every 6 months at 4 sites in the US. Testing included measures of visual acuity, visual fields, dark-adapted fundus perimetry, ERG and spectral domain optical coherence tomography. Here we report preliminary rod sensitivity data obtained from a subset of study participants over one year follow-up.

Methods : A total of 27 adRP patients (8- 66 yr age; BCVA of -0.1 to +0.5 logMAR) having a confirmed P23H RHO mutation were enrolled. Following pupil dilation and at least 30 minutes of dark adaptation, sensitivity was measured with an MP-1S (Nidek USA) at 64 locations within the vessel arcades but excluding the fovea. Blue stimuli (spot-size V) were used to obtain sensitivity values, and red stimuli in the same locations were used to identify locations where sensitivity was mediated by rods. Subjects with no detectable rod sensitivity were excluded. For those retaining rod-mediated sensitivity, average change was calculated for each patient over 6 and 12 months at locations that were rod mediated at baseline.

Results : Preliminary data were available from 16 patients followed through one year. In the right eye, mean (± 1 s.e.) sensitivity at rod-mediated locations was 28.8 (± 1.6) dB at baseline, 27.3 (± 1.8) dB at 6 months, and 24.2 (±2.2) dB at 12 months. In the left eye, mean (± 1 s.e.) sensitivity at rod-mediated locations was 29.5 (± 1.7) dB at baseline, 26.1 (± 1.8) dB at 6 months, and 23.8 (±1.8) dB at 12 months. Repeated measures analyses of variance indicated significant progression over 1 year for OD (F=8.9; p=0.0009) and for OS (F=15.4; p<0.0001).

Conclusions : Preliminary results suggest that rod sensitivity loss can be detected with scotopic fundus perimetry over 1 year in adRP patients with RHO Pro23His mutation.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.