Mobility and Postural Testing in Patients with Rod-Cone Dystrophy Enrolled in the Prospective Natural History Study PHENOROD2

Abstract

Purpose : Rod-cone dystrophy (RCD) is a rare inherited retinal disorder whose etiology and clinical manifestations are heterogeneous. RCD gravely burdens the patient’s quality of life, and the disease impact on functional vision is not well characterized. PHENOROD2 is an ongoing prospective natural history study assessing RCD progression, to help select relevant clinical efficacy endpoints for the evaluation of novel therapies.

Methods : A subset of 30 patients enrolled in the PHENOROD2 study performed mobility and postural tests using the Artificial Street platform at the Streetlab facility (Paris, France). The locomotion test consisted of a modular maze including two obstacles on the floor and five suspended obstacles. The mobility course was performed under binocular and monocular conditions, at five different light levels. A performance score was computed considering trial duration and mobility errors. The postural test consisted of the Sensory Organization Test, performed on the Opal Mobility Lab System (APMD Wearable Technologies). Four conditions were tested at 400 lux: eyes closed or open, on firm floor or foam.

Results : The subset included 21 patients with a RHO mutation, 6 in PDE6A, and 3 in PDE6B. At study enrollment, mean (SD) age was 46.9 (12.5) years, mean BCVA was 0.15 (0.17) LogMAR in OD and 0.18 (0.24) LogMAR in OS, foveal sensitivity was 19.1 (6.2) dB in OD and 18.2 (6.8) dB in OS, and mean mobility performance score was 69 (21) in OD, 68 (24) in OS, and 75 (19) in OU. The mean change from baseline of the performance score was 0 (5) in OD, 0 (7) in OS, and 2 (6) in OU at Year 1; and 1 (11) in OD, 0 (12) in OS, and 1 (7) in OU at Year 2. The mobility performance score correlated mildly with patient’s age (r = -0.29), but more strongly with foveal sensitivity (r = 0.77) and BCVA (r = -0.67). For the postural test, the Romberg ratio showed a mild impact of vision on sway and movement fluidity (jerk), that did not change over time.

Conclusions : Overall, no substantial change was reported for mobility or postural assessment after two years of follow-up. These findings indicate that disease evolution is slow and difficult to assess over the course of a standard clinical trial. However, variability among patients could have impacted the analysis, and individual disease evolution should be considered.

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