Autosomal Dominant Optic Atrophy

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Synonyms

Kjer optic atrophy, Kjer-type optic atrophy, Optic atrophy, juvenile, Optic atrophy type 1 , OPA1, Dominant optic atrophy, DOA, Autosomal dominant optic neuropathy, ADOA,

Overview

Autosomal Dominant Optic Atrophy (ADOA) is the most common inherited optic neuropathy, causing slow, progressive, and often symmetric vision loss in both eyes, typically starting in childhood (4-6 years old). It is primarily caused by mutations in the OPA1 gene, leading to dysfunction of retinal ganglion cells and mitochondrial dysfunction. While often restricted to the eye (non-syndromic), some cases (ADOA-plus) involve neurological issues like hearing loss.

Symptoms

Autosomal Dominant Optic Atrophy (ADOA) typically presents in early childhood with slowly progressive, bilateral vision loss, often leading to blurred vision, central field defects (scotoma), and color vision deficiencies (especially blue-yellow). It is caused by genetic mutations, most commonly OPA1, leading to retinal ganglion cell degeneration.

Causes

Autosomal Dominant Optic Atrophy (ADOA) is primarily caused by genetic mutations that lead to mitochondrial dysfunction and the death of retinal ganglion cells. Over 75% of cases are linked to mutations in the OPA1 gene, with OPA3 mutations causing a rarer form associated with cataracts. These mutations cause a progressive, hereditary loss of vision.

Prevention

Currently, there is no cure or established medical treatment to prevent or reverse vision loss from Autosomal Dominant Optic Atrophy (ADOA), a genetic condition typically caused by OPA1 gene mutations. Management focuses on supporting existing vision through low-vision aids, regular eye exams, and avoiding mitochondrial toxins like tobacco. Research is ongoing into gene therapy and antioxidants.

Diagnosis

Autosomal Dominant Optic Atrophy (ADOA) is diagnosed by an ophthalmologist based on slow, bilateral vision loss, characteristic temporal optic disc pallor, and positive family history. Key diagnostic tools include Optical Coherence Tomography (OCT) to detect nerve fiber layer thinning, color vision tests, and visual field testing. Confirmation is achieved via genetic testing, most commonly identifying mutations in the OPA1 gene.

Prognosis

Autosomal Dominant Optic Atrophy (ADOA) typically presents in early childhood as a slowly progressive, bilateral, and irreversible loss of central vision, often resulting in legal blindness in about 46% of cases by age 50. While most patients maintain a functional level of vision (better than 20/200) and have a normal life span, the prognosis varies widely in severity, ranging from mild vision impairment to, rarely, complete blindness.

Treatment

Currently, there is no FDA-approved, disease-modifying treatment or cure for Autosomal Dominant Optic Atrophy (ADOA), a hereditary, progressive, and typically irreversible vision-loss condition caused by OPA1 gene mutations. Management relies on supportive measures like low-vision aids, with emerging, experimental therapies (such as STK-002 and PYC-001) in early-stage clinical trials.