Sunir J. Garg
• Group of hereditary, progressive retinal diseases that result in the degeneration of rod (mainly) and cone photoreceptors; the degeneration starts in the mid-periphery and advances toward the macula.
• Significant phenotypic and genotypic diversity
• 1 in 3,000—5,000 persons
• 60% of affected people have associated genetic mutations
• Inherited forms could be autosomal dominant (30–40%), autosomal recessive (50–60%), or X-linked (5–15%).
• Even with the same genotype, patients can present with different manifestations.
• In non-syndromic retinitis pigmentosa (RP), more than 45 genes/loci have been isolated
• Most common genes (30% of RP cases):
– Rhodopsin gene (RHO): 25% of autosomal dominant RP
– USH2A gene: 20% of recessive disease
– RPGR gene: 70% of X-linked RP
• Controversial: Use of dark glasses to slow progression of retinal damage.
• Primary degeneration of rod photoreceptors, and secondary degeneration of cone photoreceptors.
• The exact mechanism has not been established.
• Genetic inheritance in 60%
COMMONLY ASSOCIATED CONDITIONS
• 20–35% of cases are associated with non-ocular disease (about 30 syndromes)
• Usher’s Syndrome (10–20% of RP cases): Congenital or early deafness followed by RP in teenage years
• Bardet-Biedel syndrome (5% of RP cases): RP, obesity present in childhood, renal failure, hypogonadism, polydactyly, mental retardation, or mild psychomotor delay.
• Variable; some have symptoms starting in childhood, while others have symptom onset during young adulthood.
• Nyctalopia (night blindness) is the most common symptom and presents earlier in autosomal recessive form; median age of onset 24 years.
• Constricted mid-peripheral visual fields in early adulthood, which leads to tunnel vision in advanced cases.
• Although many patients have good central acuity for decades, a number eventually develop significant vision loss.
• Photophobia, especially in diffuse light (e.g., overcast days) – difficulty with reading, due to the narrow window between too much and insufficient light.
• Photopsia (35%) – late sign
• Anterior segment
– Posterior subcapsular cataract (50%)
• Posterior segment
– Waxy pallor of the optic nerve head
– Attenuated retinal vessels
– Retinal hypo- and hyper-granularity
– Bone spicule formation around intraretinal vessels (mid to far periphery)
– Cystoid macular edema
– Optic nerve head drusen (10%)
– Vitreous cells
• Sectoral RP: Variant of RP; only 1 or 2 quadrants are affected
• Color vision testing can be normal, or show blue cone dysfunction in advanced RP (acquired tritanopia)
• Decreased contrast sensitivity (Pelli-Robson chart)
DIAGNOSTIC TESTS & INTERPRETATION
Initial lab tests
• Genetic tests, if available
Follow-up & special considerations
• Optical coherence tomography (OCT) is useful to measure retina thickness, assess the photoreceptor layer, and to assess the presence and degree of cystoid macular edema.
Follow-up & special considerations
• OCT imaging in subsequent follow-ups.
• Electroretinogram (ERG) is critical to confirm the diagnosis and assess degree of visual impairment: Diminuted a- and b-wave amplitude and delayed timing during scotopic and photopic conditions are seen even in early stages.
• Visual field tesing initially shows patchy loss of peripheral vision; progresses to mid-peripheral field loss; in advanced cases, only far peripheral and central island of vision remains (“tunnel vision”). Goldmann (kinetic) perimetry is more useful to assess peripheral vision changes.
• Rod and cone degeneration
• Bone spicule pattern is due to hyperplasia and migration of RPE cells into the neurosensory retina in response to photoreceptor cell loss.
• Waxy pallor of the nerve: Indicates axonal loss and overlying gliosis
• Leber congenital amaurosis – when visual loss is present from birth or first 5 years of life.
• Cancer/melanoma associated retinopathy
• Congenital stationary night blindness
• Fundus albipunctatus
• Vitamin A deficiency
• Congenital infections: Rubella, syphilis
• X-linked disorders: Choroideremia, ocular albinism
• Mitochondrial disease: Kearns-Sayre syndrome
• Gyrate atrophy
• Hereditary vitreoretinopathies: Familial exudative vitreoretinopathy, Wagner disease, Stickler syndrome
• Inflammatory disorders: Birdshot choroidoretinopathy, serpiginous retinopathy, multifocal placoid pigment epitheliopathy, sarcoidosis
• Maculopathies: Stargardt disease, Cone dystrophies, Sorsby disease
• Vitamin A Palmitate 15,000 units daily
• Omega 3 fatty acids (1400 mg daily)
• Lutein 12 mg daily
• If prescribing high dose Vitamin A, need to monitor serum levels for retinol, triglyceridemia, and liver enzymes.