Retinal dystrophies are hereditary disorders that can cause progressive and severe vision loss. Retinal dystrophies can be classified into three main groups based on the affected tissue: photoreceptor dystrophies, macular and RPE dystrophies, and choroidal dystrophies.
Achromatopsia: Characterized by severe color vision impairment and photophobia due to dysfunction of cone photoreceptors. Visual acuity is very low, and nystagmus may be present. It follows an autosomal recessive inheritance pattern.
Blue-Cone Monochromacy: Results from dysfunction of red and green cone photoreceptors, causing color vision defects, reduced visual acuity, photophobia, and nystagmus. It follows an X-linked recessive inheritance pattern.
Leber’s Congenital Amaurosis (LCA): A retinal disorder presenting with severe vision loss from infancy. Associated features may include photophobia, nystagmus, strabismus, enophthalmos, and keratoconus. A typical sign is the patient pressing their eyes with fingers or fists (oculodigital sign). Gene therapy has been FDA-approved for patients with biallelic RPE65 mutations.
Retinitis Pigmentosa (RP): A progressive retinal dystrophy caused by the loss of rod photoreceptors. It manifests with night blindness and visual field constriction. Fundus examination may reveal mild peripheral retinal pigment epithelium atrophy, narrowing of arterioles, intraretinal pigmentation, and optic disc pallor. In advanced stages, macular edema and atrophic maculopathy can worsen the condition. RP can follow autosomal dominant, autosomal recessive, or X-linked inheritance patterns.
Stargardt Disease: A progressive disorder that presents with central vision loss between the ages of 10 and 20. As the disease progresses, patients may experience difficulty with night vision and color perception. It is usually caused by mutations in the ABCA4 gene and follows an autosomal recessive inheritance pattern.
Best Disease: A disorder primarily affecting the retinal pigment epithelium, with an autosomal dominant inheritance pattern. In the early stages, vision may be normal or only mildly reduced. In advanced stages, visual acuity can decrease to 0.2–0.4.
Gyrate Atrophy: A progressive chorioretinal degeneration characterized by early-onset cataracts and myopia, inherited in an autosomal recessive pattern. It typically presents within the first 10 years of life with night vision difficulties, areas of chorioretinal atrophy on fundus examination, and progressive peripheral vision loss. The disorder is caused by various mutations in the ornithine aminotransferase (OAT) gene. Reducing serum ornithine levels through a low-protein and arginine-restricted diet, and in some patients Vitamin B6 supplementation, can slow disease progression.
Choroideremia: A diffuse, progressive chorioretinal degeneration affecting the retinal pigment epithelium, photoreceptors, and choriocapillaris. It is caused by mutations in the CHM gene and follows an X-linked inheritance pattern. It typically presents in the first decade of life with night blindness, followed by progressive constriction of the peripheral visual field over the years. Central vision and visual acuity are generally preserved until adulthood. Because it results from mutations in a single gene, choroideremia is a candidate for gene therapy, and studies in this area are ongoing.