Interocular progression in retinitis pigmentosa: A 10-year follow-up study

Abstract

Purpose : Emerging clinical trials for inherited retinal disease require an understanding of long-term progression and interocular symmetry, particularly when using the fellow eye as a control. This longitudinal observational study investigated the genetic diagnosis and change in retinal structure and function over 10 years in individuals diagnosed with retinitis pigmentosa (RP).

Methods : Individuals who participated in our previous RP study between 2010-2013 with VA 1.6 LogMAR or better in either eye attended a follow-up assessment, including best corrected visual acuity (VA), Goldmann visual field (GVF), multimodal retinal imaging, and panel-based genetic testing. Interocular symmetry of disease progression was compared using intraclass correlation coefficients (ICC). Linear mixed models were used to investigate disease progression measured using VA, GVF area, and ellipsoid zone (EZ) width and factors associated with progression rate.

Results : For the 23 participants (mean age at baseline: 53±15 years; 48% female), diagnoses include autosomal dominant RP (n=7; PRPF31, RHO, RP1), autosomal recessive RP (n=6; USH2A, EYS, BBS1, CLN1) and X-linked RP (n=2; RPGR). Three RP cases were reclassified to cone-rod dystrophy upon genetic diagnosis (n=3, ABCA4, PROM1, CRX), and five remain genetically unsolved. In participants with RP, the estimated change in VA was 0.68 (95% confidence interval [CI]: 0.44-0.92) LogMAR at 10-year follow-up. Using the Food and Drug Administration's minimal clinically important difference criteria, seven of 20 RP participants lost 15 letters or more in each eye over the 10 years, and eight did not meet the criteria in either eye. EZ width was estimated to decrease by 757 [562-949] μm, and GVF area by 38% [95% CI: 29% to 45%], at 10 years. Between the eye with poorer versus better VA at baseline, high interocular symmetry in disease progression was observed for GVF area (ICC=0.87 [95% CI: 0.68-0.95]), and moderate interocular symmetry in disease progression was observed for VA (R=0.50 [95% CI: 0.07-0.77]) and EZ width (ICC=0.64 [95% CI: 0.25-0.85]). Disease progression rate in each of VA, GVF, and EZ width was associated with initial baseline measurement.

Conclusions : RP progression rate is related to residual visual function. Clinical trials using the fellow eye as control should consider the implications of interocular symmetry on study outcomes and the most appropriate measure to use.

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