Dominant optic atrophy: inherited optic nerve loss explained

The optic nerve carries visual information from the retina to the brain. In dominant optic atrophy the retinal ganglion cells whose fibres make up the nerve gradually degenerate. The review published in the Orphanet Journal of Rare Diseases says DOA belongs to the group of inherited optic neuropathies and is a mitochondrial disease in the sense that the genes involved encode proteins located in the inner membrane of mitochondria, the energy-producing parts of cells.

The term dominant refers to the inheritance pattern. A person with a single changed copy of the gene can be affected, and each child of an affected parent has a chance of inheriting it. The review gives the penetrance as around 70% on average, varying between families, so some people who carry the change have no symptoms. It says the prevalence is about 3 in 100,000 in most populations, but can reach 1 in 10,000 in Denmark because of a founder effect.

The review says DOA usually presents as a bilateral optic neuropathy diagnosed in school-aged children who complain of reading problems, though it can manifest later in adult life. Vision loss is slow and insidious, irreversible, usually moderate and highly variable between and within families, with acuity typically in a range from 6/10 to 2/10 but from normal to legal blindness.

The visual field typically shows a central or caecocentral scotoma while peripheral vision remains normal. Colour vision is affected in a characteristic way: the review describes tritanopia, a blue-yellow confusion axis, as strongly indicative of the condition when found. Pupil reflexes and circadian rhythms are not affected. Loss of vision may progress during puberty into adulthood, with very slow progression afterwards in most cases.

• Reduced central vision in both eyes, not corrected by glasses.

• Difficulty with reading and fine detail.

• Colour vision problems, especially blue-yellow confusion.

• A central blind spot, with normal side vision.

• In DOA plus, hearing loss and other neurological symptoms.

The review explains that diagnosis is usually made in early childhood because of bilateral, mild, otherwise unexplained visual loss with optic disc pallor or atrophy, typically in the context of a family history of DOA. On examination the optic disc shows pallor, often on the temporal side, and optical coherence tomography (OCT) shows non-specific thinning of the retinal nerve fibre layer with normal photoreceptor layers. Visual evoked potentials and pattern electroretinography may also show dysfunction of the ganglion cells and their axons.

Molecular diagnosis is provided by identifying a mutation in OPA1 (about 75% of patients) or OPA3 (about 1%). Because the pattern can look like other optic neuropathies, such as Leber hereditary optic neuropathy, which is passed on through the mitochondrial DNA by the maternal line, genetic testing helps to confirm the type and guide counselling.

About 20% of people with a DOA-causing gene change develop additional features, called DOA plus. The review lists neurosensory hearing loss, and less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. The Newcastle and Cardiff study found that people with DOA plus had significantly worse visual acuity and visual function scores, and higher depression scores, than those with isolated optic atrophy.

If you have DOA, new symptoms such as hearing loss, weakness or numbness should be mentioned to your clinicians, since they may be part of the picture and can be supported.

The review states that to date there is no preventative or curative treatment in DOA, and that severely visually impaired patients may benefit from low vision aids. Genetic counselling is commonly offered. It also reports that patients are advised to avoid alcohol and tobacco and medicines that may interfere with mitochondrial metabolism, and that gene and pharmacological therapies are under investigation.

The wellbeing side matters too. The Newcastle and Cardiff study of 38 people with confirmed OPA1 mutations found borderline or definite anxiety symptoms in 50% and depression symptoms in 18.4%, with scores significantly higher than in the general adult population, and a link between worse visual function and higher anxiety and depression scores. In practice, access to eye clinic liaison officers, low vision services, education and workplace adjustments, and mental health support are all part of good care.

On the NHS, children are usually seen by paediatric ophthalmology or neuro-ophthalmology after an optometrist or GP notices reduced vision, with referral to clinical genetics for testing and counselling. Adults are seen in ophthalmology, neuro-ophthalmology or a specialist mitochondrial or inherited eye disease service.

Private neuro-ophthalmology can provide a quicker appointment, OCT or visual field testing, but genetic testing and long-term follow-up for a rare condition are best coordinated with the NHS genetics service, which will also be able to test relatives where appropriate.