Non-syndromic retinitis pigmentosa

Abstract

Retinitis pigmentosa (RP) encompasses a group of inherited retinal dystrophies characterized by the primary degeneration of rod and cone photoreceptors. RP is a leading cause of visual disability, with a worldwide prevalence of 1:4000. Although the majority of RP cases are non-syndromic, 20-30% of patients with RP also have an associated non-ocular condition. RP typically manifests with night blindness in adolescence, followed by concentric visual field loss, reflecting the principal dysfunction of rod photoreceptors; central vision loss occurs later in life due to cone dysfunction. Photoreceptor function measured with an electroretinogram is markedly reduced or even absent. Optical coherence tomography (OCT) and fundus autofluorescence (FAF) imaging show a progressive loss of outer retinal layers and altered lipofuscin distribution in a characteristic pattern. Over the past three decades, a vast number of disease-causing variants in more than 80 genes have been associated with non-syndromic RP. The wide heterogeneity of RP makes it challenging to describe the clinical findings and pathogenesis. In this review, we provide a comprehensive overview of the clinical characteristics of RP specific to genetically defined patient subsets. We supply a unique atlas with color fundus photographs of most RP subtypes, and we discuss the relevant considerations with respect to differential diagnoses. In addition, we discuss the genes involved in the pathogenesis of RP, as well as the retinal processes that are affected by pathogenic mutations in these genes. Finally, we review management strategies for patients with RP, including counseling, visual rehabilitation, and current and emerging therapeutic options.

Adeno-Associated Viral Gene Therapy for Inherited Retinal Disease

“…RP is thought to affect 1.5 million people worldwide (37), with a prevalence ranging from 1 in 3000 to 1 in 4000, in certain populations (38,39). As a progressive IRD, RP is characterized by the degeneration of rod photoreceptor cells in the early stages of disease, followed by cone cell death.…”

“…As a result, RP generally presents as night blindness in adolescence with ensuing loss of visual field from early adulthood. Visual acuity (VA) remains relatively well preserved until more advanced disease and the photoreceptor cell loss affects the macula, generally during middle age (37). …”

“…The heterogenous nature of patients with RP corresponds, at least in part, to the considerable number of mutations that have been associated with the disease (37). More than 90 genes have been implicated in the development of RP (see http://www.sph.uth.tmc.edu/RetNet/www.sph.uth.tmc.edu/RetNet/) (40), and each defect results in a gene-specific subtype of RP with particular clinical and symptomatic features (37).…”

“…More than 90 genes have been implicated in the development of RP (see http://www.sph.uth.tmc.edu/RetNet/www.sph.uth.tmc.edu/RetNet/) (40), and each defect results in a gene-specific subtype of RP with particular clinical and symptomatic features (37). The severity of RP has been associated with the inheritance pattern; XLRP tends to follow a more severe course than autosomal recessive RP (arRP), while patients with autosomal dominant RP (adRP) generally have the best prognosis in terms of maintaining VA (37). Approximately 20–30% of patients with RP present with the syndromic form, which is associated with additional abnormalities outside of the eye (37).…”

“…The severity of RP has been associated with the inheritance pattern; XLRP tends to follow a more severe course than autosomal recessive RP (arRP), while patients with autosomal dominant RP (adRP) generally have the best prognosis in terms of maintaining VA (37). Approximately 20–30% of patients with RP present with the syndromic form, which is associated with additional abnormalities outside of the eye (37). …”