Purpose: To investigate the natural history of RHO-associated retinitis pigmentosa (RP). Methods: A multicenter, medical chart review of 100 patients with autosomal dominant RHO-associated RP.... Show morePurpose: To investigate the natural history of RHO-associated retinitis pigmentosa (RP). Methods: A multicenter, medical chart review of 100 patients with autosomal dominant RHO-associated RP. Results: Based on visual fields, time-to-event analysis revealed median ages of 52 and 79 years to reach low vision (central visual field <20 degrees) and blindness (central visual field <10 degrees), respectively. For the best-corrected visual acuity (BCVA), the median age to reach mild impairment (20/67 <= BCVA < 20/40) was 72 years, whereas this could not be computed for lower acuities. Disease progression was significantly faster in patients with a generalized RP phenotype (n = 75; 75%) than that in patients with a sector RP phenotype (n = 25; 25%), in terms of decline rates of the BCVA (P < 0.001) and V4e retinal seeing areas (P < 0.005). The foveal thickness of the photoreceptor-retinal pigment epithelium (PR + RPE) complex correlated significantly with BCVA (Spearman's rho = 0.733; P < 0.001). Conclusion: Based on central visual fields, the optimal window of intervention for RHO-associated RP is before the 5th decade of life. Significant differences in disease progression are present between generalized and sector RP phenotypes. Our findings suggest that the PR + RPE complex is a potential surrogate endpoint for the BCVA in future studies. Show less
Retinal dystrophies (RDs) comprise relatively rare but devastating causes of progressive vision loss. They represent a spectrum of diseases with marked genetic and clinical heterogeneity. Mutations... Show moreRetinal dystrophies (RDs) comprise relatively rare but devastating causes of progressive vision loss. They represent a spectrum of diseases with marked genetic and clinical heterogeneity. Mutations in the same gene may lead to different diagnoses, for example, retinitis pigmentosa or cone dystrophy. Conversely, mutations in different genes may lead to the same phenotype. The age at symptom onset, and the rate and characteristics of peripheral and central vision decline, may vary widely per disease group and even within families. For most RD cases, no effective treatment is currently available. However, preclinical studies and phase I/II/III gene therapy trials are ongoing for several RD subtypes, and recently the first retinal gene therapy has been approved by the US Food and Drug Administration for RPE65-associated RDs: voretigene neparvovec-rzyl (Luxturna). With the rapid advances in gene therapy studies, insight into the phenotypic spectrum and long-term disease course is crucial information for several RD types. The vast clinical heterogeneity presents another important challenge in the evaluation of potential efficacy in future treatment trials, and in establishing treatment candidacy criteria. This perspective describes these challenges, providing detailed clinical descriptions of several forms of RD that are caused by genes of interest for ongoing and future gene or cell-based therapy trials. Several ongoing and future treatment options will be described. Show less
