Retinal Dystrophies

A group of genetically determined disorders causing progressive photoreceptor and retinal pigment epithelial degeneration, with more than 300 genes implicated. Collectively they affect about 1 in 3000 people.

• Main types:
  • Rod-dominant: retinitis pigmentosa and its syndromic forms (Usher syndrome, Bardet-Biedl syndrome), congenital stationary night blindness, choroideremia, gyrate atrophy.
  • Macular dystrophies: Stargardt disease (ABCA4, autosomal recessive, onset in childhood and teens), Best vitelliform macular dystrophy (BEST1), adult-onset vitelliform dystrophy, pattern dystrophies, Sorsby dystrophy, X-linked retinoschisis.
  • Cone and cone-rod dystrophies, achromatopsia.
  • Early-onset: Leber congenital amaurosis (RPE65, CEP290, CRB1 and others).
• Inheritance: autosomal recessive, dominant, X-linked, and mitochondrial.

• Night blindness and peripheral field loss (rod dystrophies); central visual loss, colour defects, photophobia, and glare (cone and macular dystrophies); nystagmus and poor vision from infancy (Leber congenital amaurosis, achromatopsia).
• Fundus: bone-spicule pigment, attenuated vessels, waxy disc (retinitis pigmentosa); yellow flecks with a "beaten bronze" macula and dark choroid on angiography (Stargardt disease); egg-yolk lesion (Best disease); bull's-eye maculopathy (cone-rod dystrophy); peripheral chorioretinal atrophy with preserved fovea (choroideremia); foveal schisis with spoke-wheel pattern (X-linked retinoschisis).
• Associated findings: cataract (posterior subcapsular), cystoid macular oedema, keratoconus, hearing loss (Usher), obesity and polydactyly (Bardet-Biedl), and learning disability.

• Detailed family history and pedigree; visual acuity, colour vision (Farnsworth D-15, Ishihara), visual fields (Goldmann, Humphrey), dark adaptometry.
• Full-field electroretinogram (rod and cone responses, flicker amplitude) and multifocal electroretinogram; electro-oculogram (reduced Arden ratio in Best disease).
• Optical coherence tomography: ellipsoid zone loss, foveal thinning, cystoid oedema, schisis, vitelliform material; fundus autofluorescence for hypoautofluorescent atrophy and hyperautofluorescent rings.
• Genetic testing (targeted panel or exome sequencing) with genetic counselling; carrier testing for relatives; audiometry for Usher syndrome; metabolic screen (plasma ornithine for gyrate atrophy, phytanic acid for Refsum).

• Genetic counselling and family screening (inheritance risk, reproductive options including preimplantation diagnosis).
• Gene therapy: voretigene neparvovec (subretinal injection of 1.5 x 10^11 vector genomes per eye, each eye separately, at least 6 days apart) for biallelic RPE65-related retinal dystrophy, improves functional vision. Other gene therapies are under investigation.
• Cystoid macular oedema: topical dorzolamide 2 percent three times daily or oral acetazolamide 250 to 500 mg twice daily, intravitreal steroid or anti-VEGF in resistant cases.
• Avoid high-dose vitamin A in Stargardt disease and Best disease (accelerates lipofuscin accumulation); protect against bright light with tinted lenses and ultraviolet-blocking glasses. Vitamin A palmitate 15,000 IU daily is considered for retinitis pigmentosa only after discussion with a specialist, with liver function monitoring.
• Cataract surgery when visually significant; keratoconus management; hearing aids or cochlear implants (Usher).
• Dietary management (low phytanic acid diet for Refsum disease, arginine-restricted diet and pyridoxine for gyrate atrophy).
• Low vision rehabilitation: magnifiers, electronic aids, high-contrast materials, orientation and mobility training, schooling support, and certification of visual impairment; psychological support for patients and families.
• Retinal prosthesis (epiretinal implants) in profound retinitis pigmentosa; cell and gene therapies under investigation; regular follow-up every 6 to 12 months for fields, acuity, and complications.
• Counsel on realistic prognosis: most progress slowly, with stable useful vision into middle age in many.