Clinical Characteristics and Natural History of Rho-Associated Retinitis Pigmentosa

Abstract

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. 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°) and blindness (central visual field ,10°), 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 r = 0.733; P , 0.001). Conclusion: Based on central visual fields, the optimal window of intervention for RHOassociated 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.

Retinitis Pigmentosa: Current Clinical Management and Emerging Therapies

“…High myopia (refractive error of −6 diopters or more) may be associated with a more rapid disease progression, for instance in RPGR -associated X-linked RP [ 69 , 71 , 72 ]. In contrast, patients with adRP (e.g., due to RHO mutations) mostly demonstrate a relatively mild disease course compared to arRP or XLRP, and they may even retain considerable central and peripheral visual function up until the eighth decade of life [ 73 , 74 , 75 ]. The disease course of RP is best understood in the most prevalent genes associated with RP (e.g., RHO and RPGR ) as more extensive retrospective and prospective studies have been performed in these genes; thus, their visual prognosis can be more accurately estimated [ 23 , 68 , 71 , 73 , 74 , 76 , 77 , 78 ].…”

“…The onset and presentation of the aforementioned fundus findings differ highly between individuals and may even present in atypical forms. Sector RP is considered an atypical, mild form of RP, which is more common in patients with adRP [ 69 , 73 , 83 , 84 , 85 ]. Degeneration in sector RP has a predilection for the inferior nasal hemisphere of the retina with corresponding superior visual field defects [ 58 ].…”

“…Degeneration in sector RP has a predilection for the inferior nasal hemisphere of the retina with corresponding superior visual field defects [ 58 ]. A widespread, generalized disease similar to classic RP may develop with time, although this is not necessarily the case for all patients with sector RP [ 73 ].…”

Genes and Gene Therapy in Inherited Retinal Disease

“…Recent longitudinal studies have suggested visual acuity declines at a rate of −1.8% to −3.8% per year in RHO-RP. 138 There are several challenges to developing gene therapy for RHO-RP. While autosomal recessive IRDs may be treated by simply correcting for the absence of functional protein, dominant negative RHO variants, such as the common P23H mutation in RHO-adRP, additionally require suppression of deleterious mutant protein expression.…”

“…Low vision often does not develop until the third decade of life, and patients frequently avoid blindness until the eighth decade or later. Recent longitudinal studies have suggested visual acuity declines at a rate of −1.8% to −3.8% per year in RHO-RP 138…”