What is retinitis pigmentosa?

What is Retinitis Pigmentosa

Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies characterized by degeneration of photoreceptor cells, leading to night blindness, progressive peripheral visual field loss, and eventual central vision loss, affecting approximately 1 in 4,000 people worldwide. 1, 2

Clinical Presentation and Natural History

Classic Symptoms and Progression:

• Night blindness (nyctalopia) is typically the first symptom, reflecting initial rod photoreceptor dysfunction 3, 2
• Progressive concentric visual field loss follows, creating "tunnel vision" as peripheral retina degenerates 3, 2
• Central vision loss occurs in advanced stages, potentially leading to bilateral blindness after several decades 3, 2
• RP is one of the leading causes of visual disability and blindness in people under 60 years old, affecting over 1.5 million people worldwide 3

Clinical Variants:

• The most common form is rod-cone dystrophy, where peripheral vision loss predominates 2
• Some cases present as cone-rod dystrophy, where decreased central visual acuity is more prominent than peripheral field loss 2
• Disease progression varies widely—some cases evolve rapidly over two decades while others progress slowly and never lead to complete blindness 2

Diagnostic Features

Fundoscopic Findings:

• Characteristic retinal pigment deposits visible on fundus examination, giving the disease its name 2
• Retinal pigment epithelial atrophy, hyperplasia, or fibrous metaplasia may be present 1

Functional Testing:

• Hypovolted (reduced amplitude) electroretinogram traces are diagnostic 2
• Progressive worsening of visual field defects on perimetry 2
• Decreased contrast sensitivity affecting ability to see steps or read newsprint 1

Genetic Complexity

Inheritance Patterns:

• RP can be inherited as autosomal dominant, autosomal recessive, X-linked, mitochondrial, or digenic forms 2, 4
• Sporadic cases also occur without family history 5
• To date, 45 causative genes/loci have been identified in non-syndromic RP 2
• Approximately 60% of RP cases still have no known genetic cause 5

Syndromic Forms:

• RP is usually non-syndromic, but many syndromic forms exist 2
• Usher syndrome (RP combined with hearing loss) is the most frequent syndromic presentation 2

Current Treatment Landscape

Limited Therapeutic Options:

• There is currently no curative treatment for RP, and only patients with confirmed RPE65 mutations are eligible for the only FDA-approved gene therapy (voretigene neparvovec) 3
• Current management is restricted to slowing disease progression through sunlight protection and vitamin A supplementation 3, 2
• Visual aids and rehabilitation services help patients adapt to progressive vision loss 1
• Medical and surgical interventions treat ophthalmic comorbidities like cataract and macular edema 2

Vision Rehabilitation Considerations:

• Glaucoma and retinitis pigmentosa typically affect peripheral vision first, unlike macular degeneration which affects central vision 1
• Patients benefit from improved lighting, task lamps, and pocket flashlights 1
• Magnification devices, large-print materials, and electronic reading aids help maximize remaining vision 1
• More than 20% of people with vision loss from RP may experience Charles Bonnet syndrome (visual hallucinations that patients recognize as unreal) 1

Emerging Therapeutic Approaches

Research Directions:

• Gene therapy targeting specific mutations shows promise beyond the single approved RPE65 therapy 3, 2
• Cell therapy and RPE transplantation are under investigation 3, 6
• Neuroprotective strategies targeting endoplasmic reticulum stress, apoptotic pathways, and oxidative stress are in preclinical development 3
• Retinal prosthesis systems (like the now-discontinued Argus II) demonstrated improved visual function in patients with profound vision loss from advanced RP 1

Clinical Pitfalls

Genetic counseling is always advised given the hereditary nature and genetic heterogeneity of RP 2. However, molecular diagnosis is not routinely performed due to the tremendous genetic complexity—no single mutation accounts for more than 10% of unrelated patients 5. The visual prognosis remains poor without disease-modifying therapies, making early referral to vision rehabilitation services critical for maintaining quality of life 1, 3.