Retinitis Pigmentosa

Retinitis pigmentosa is a group of inherited rod cone dystrophies in which rod photoreceptors degenerate first, followed by cones. Prevalence is about 1 in 4000, with more than 80 causative genes. Inheritance is autosomal recessive in 50 to 60%, autosomal dominant in 30 to 40% and X-linked in 5 to 15% (X-linked is the most severe, commonly from RPGR variants).

About 20 to 30% of cases are syndromic:

• Usher syndrome: sensorineural deafness, the most common
• Bardet-Biedl syndrome: obesity, polydactyly, renal disease, learning difficulty
• Refsum disease: raised phytanic acid, neuropathy, ataxia, ichthyosis
• Abetalipoproteinemia: fat malabsorption, acanthocytes
• Kearns-Sayre syndrome: ophthalmoplegia, heart block

Night blindness begins in adolescence, peripheral field constricts over decades, and many reach legal blindness by age 40 to 50 while central acuity persists until late. Complications are cystoid macular edema (10 to 50%), posterior subcapsular cataract (about 50%), glaucoma, keratoconus, myopia and vitreous cells.

• Nyctalopia, delayed dark adaptation, glare
• Progressive peripheral field loss ("tunnel vision"), photopsias
• Later: reduced central acuity and color vision
• Fundus: bone spicule pigmentation in the mid-periphery, arteriolar attenuation, waxy disc pallor
• Variants: sectoral retinitis pigmentosa, retinitis pigmentosa sine pigmento, X-linked carrier tapetal reflex
• Red flags: hearing loss, polydactyly, obesity, ataxia or neuropathy, onset in infancy (suggesting a Leber congenital amaurosis phenotype), rapid unilateral progression (suggesting an alternative diagnosis)

• Dilated fundus examination and a family history to three generations.
• Full field electroretinography: rod specific responses reduced or extinguished first, with delayed 30 Hz flicker implicit time (above 32 ms) and later cone loss.
• OCT: ellipsoid zone loss with preserved central island, cystoid macular edema, epiretinal membrane.
• Fundus autofluorescence: hyperautofluorescent ring around the fovea.
• Goldmann or automated perimetry: ring scotoma then constricted field.
• Molecular genetic testing with a next generation sequencing panel, essential for therapy eligibility and counseling.
• Syndromic workup: audiometry, plasma phytanic acid, fasting lipids and vitamin E, ECG, renal function.

Differentials: syphilitic chorioretinitis, diffuse unilateral subacute neuroretinitis, drug toxicity (hydroxychloroquine, thioridazine), paraneoplastic retinopathy, vitamin A deficiency, congenital stationary night blindness, cone rod dystrophy, choroideremia.

There is no general cure. Management is supportive, with gene therapy for a defined subgroup.

Gene therapy: voretigene neparvovec for biallelic RPE65-related disease in patients with viable retinal cells on OCT.

• Dose 1.5 x 10^11 vector genomes in 0.3 mL, injected subretinally into each eye on separate days, 6 to 18 days apart, under vitrectomy.
• Oral prednisolone 1 mg/kg/day (maximum 40 mg) for 7 days starting 3 days before injection, followed by a 5 day taper.
• Complications: retinal tear, macular hole, cataract, raised intraocular pressure, endophthalmitis, retinal atrophy.

Medical:

• Vitamin A palmitate 15,000 IU orally daily may slow ERG decline in adults. Avoid in pregnancy, smokers and liver disease, and monitor liver enzymes and serum retinol yearly. Avoid high dose vitamin E.
• Cystoid macular edema: dorzolamide 2% three times daily, or acetazolamide 250 to 500 mg orally twice daily (monitor bicarbonate and potassium; contraindicated in sulfonamide allergy). Intravitreal steroid for refractory edema.

Surgical and optical:

• Cataract extraction for posterior subcapsular lens opacity, which yields useful visual gain.
• Tinted lenses for glare, and low vision aids, orientation and mobility training.
• Retinal prosthesis for end stage disease with bare light perception in selected centres.

Syndromic care: audiology with hearing aids or cochlear implant for Usher syndrome, dietary restriction of phytanic acid with plasmapheresis for Refsum disease, high dose vitamin E and fat soluble vitamins for abetalipoproteinemia, pacemaker assessment for Kearns-Sayre syndrome.

Follow up: annual acuity, visual fields, OCT and cataract and glaucoma review. Genetic counseling: autosomal recessive carriers have a 25% recurrence risk in each pregnancy, autosomal dominant disease 50%, and in X-linked disease all daughters of affected males are carriers. Offer testing to at risk relatives. Counsel on driving, occupational limits and psychological support.