Decline of visual function and risk of legal blindness with age in patients with RPGR-associated retinal degeneration, a multicenter study

Abstract

Purpose : Understanding the trajectory of best recorded visual acuity (VA) and visual field (VF) loss over time for patients with RPGR-associated retinal degeneration can be helpful in identifying patients who could most benefit from novel therapies for this condition.

Methods : Using retrospective medical data from 7 sites in the Sight Outcomes Research Collaborative (SOURCE) Ophthalmology Big Data consortium, 282 patients with a genetic diagnosis of RPGR-associated retinal degeneration were identified. All VAs and Goldmann VFs (isopters I4e, III4e, V4e) were captured for both eyes of each patient at each clinical encounter. Patients were classified phenotypically as rod-cone (RC) or cone/cone-rod (CR) degeneration in affected males, and female carriers, based on a combination of the following evaluations: full-field ERGs (photopic and scotopic), VF, and genetic test results. For each phenotype, scatterplots of VA vs. age and VF vs. age were created and overlaid with local polynomial smoothers to show the trajectory of VA and VF loss. The distribution of age of first record of legal blindness (VA < 20/200 or GVF constricted to within the central 20 degrees for both eyes) was modeled.

Results : Of 282 patients with RPGR-associated retinal degeneration, VF was analyzed in 108 RC, 35 CR, and 31 female carriers; VA was analyzed in 141 RC, 42 CR, and 60 female carriers. In the RC phenotype, VF area rapidly declined by 50% every 17y, on average, from 60° of central field to below 20° (VF criteria for legal blindness). The steepest decline was between ages 25 and 40y (Figure 1). 47% RC reached VF criterion for legal blindness; the estimated median age of first VF blindness was 31y (95% CI: 27-35y). 25% reached legal blindness by VA; the estimated median age was 48y (44-52y) (Figure 2). In the CR phenotype, VF area declines slowly. 21% CR reached VA blindness; median age 60y (27-51y).

Conclusions : In patients with RC phenotype, rapid decline of VF in the 3rd decade of life was observed. In patients with CR phenotype however, VA deteriorates earlier than VF. Clinicians can use our times to legal blindness projections to help decide on an appropriate time to intervene with emerging novel therapies in RPGR-associated retinal degeneration, and to try to do so in a time window when visual function is still preserved.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.