Longitudinal phenotypic changes in PRPH2-associated Retinal Disease

Abstract

Purpose : There is currently a lack of longitudinal phenotypic data on PRPH2-associated retinal disease (PRPH2-ARD). To address this, we investigated longitudinal multimodal imaging in PRPH2-ARD patients.

Methods : Patients with confirmed pathogenic variants of PRPH2 who underwent macular spectral-domain optical coherence tomography (SD-OCT) and ultra-widefield (UWF) fundus autofluorescence (FAF) were included. Macular thickness and choroidal volume measurements were manually segmented and recorded from the HEYEX software, and baseline SD-OCT measurements were compared to controls. Areas of atrophy from the UWF FAF were measured manually using the OptosAdvance software. Patients with multiple imaging visits were evaluated longitudinally for the area of atrophy, retinal thickness, and choroidal volume.

Results : Fifteen PRPH2-ARD patients and 14 controls were included, with mean ages of 53 and 63 years, respectively. Mean retinal thickness was lower in the PRPH2 cohort than in controls, with the superior inner ETDRS sector being significantly different (288.8 vs. 323.1 µm, p=0.045). The mean total choroidal volume measurements were lower in the PRPH2 cohort, though not significantly different (7.28 mm³ vs. 7.32 mm³).
Eight patients had longitudinal retinal thickness and choroidal volume measurements with a . mean follow-up of 39.96 (range 2.5-102.1) months. A general decline in retinal thickness was noted at a mean of -4.54 µm/year. The mean retinal thickness at baseline and last follow-up was 276.73 µm and 264.14 µm, respectively, which was significantly reduced (p<0.001).
The mean total choroidal volume measurement was noted to have decreased, though not significantly (-0.220 mm³/year).
In nine patients, who had atrophic disease, the mean baseline atrophic area was 21.6 mm³. Three patients had longitudinal data, with mean follow-up of 25.7 (range 12-45) months. These patients had a mean baseline atrophy of 25.67 mm³ and a mean follow-up atrophy increase of 14.87 mm³; an increase of 7.3 mm³/year (p<0.001).

Conclusions : Patients with PRPH2-ARD had progressive macular thinning and increased atrophy over a relatively short follow up. These multimodal imaging measures may potentially be useful as short/medium-term markers of progression to understand prognosis and for treatment trials for PRPH2-ARD. Work is currently underway to replicate these findings in a larger multicenter cohort.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.