Inherited, compressive, infiltrative and nutritional optic neuropathies

Progressive loss demands a broad differential

Optic neuropathy may be inflammatory, ischaemic, inherited, compressive, infiltrative, toxic or nutritional. Reduced colour vision and central or cecocentral field loss are useful clues but do not identify the cause. The tempo, symmetry, age, pain, systemic history and disc appearance guide investigation. A slowly progressive unilateral neuropathy should not be labelled recurrent demyelinating neuritis without excluding compression.

Document corrected acuity, colour, pupils, fields, disc and retinal imaging. Ask about medications, alcohol and nutrition, gastrointestinal surgery, occupational exposures and family history. Distinguish optic-nerve dysfunction from a macular disorder with examination and, where needed, electrophysiology. A family history is valuable, but its absence does not exclude inherited disease because penetrance, family size and unrecognized cases vary.

LHON and dominant optic atrophy

Leber hereditary optic neuropathy (LHON) is associated with mitochondrial DNA variants and often produces sequential or near-simultaneous central visual loss. Men are more often affected, but women can develop disease. Early disc hyperaemia, peripapillary telangiectatic changes or nerve-fibre swelling may precede atrophy; none is sufficient without the clinical and molecular context.

Mitochondrial inheritance is maternal. An affected man does not transmit his mitochondrial variant to his children. A woman can transmit it to children of either sex, but carrying the variant does not guarantee the same onset or severity; heteroplasmy adds complexity. Genetic counselling should explain penetrance and avoid assigning a universal disease probability from the variant alone. Advise avoidance of smoking and review excessive alcohol and other relevant exposures.

Idebenone, marketed as Raxone, has a European indication for visual impairment in LHON from age 12, under specialist supervision. This does not establish a guaranteed recovery or approval of every proposed gene therapy. Timely diagnosis, rehabilitation and counselling remain necessary.

Dominant optic atrophy, commonly associated with OPA1, often begins in childhood with bilateral central dysfunction and temporal pallor. Autosomal dominant transmission differs from LHON. Some patients have hearing or neurological features in an expanded phenotype. Assess relatives and consider genetic testing rather than inferring a mitochondrial pattern from bilateral disease alone.

Compression and infiltration

A tumour, aneurysm, orbital lesion or sellar mass may compress the nerve or chiasm. Progressive asymmetry, optic pallor, proptosis, motility abnormalities or a field respecting the vertical meridian can suggest localization. Optic-nerve sheath meningioma may produce a characteristic sheath-enhancement pattern, but imaging signs require specialist interpretation and differential consideration.

Infiltration can accompany lymphoma, leukaemia, granulomatous inflammation or infection. Disc swelling or a poorly responding neuropathy in a patient with malignancy needs appropriate imaging and systemic coordination. Tissue or cerebrospinal fluid sampling is selected according to safety and the suspected disease; empiric steroids can reduce diagnostic yield in some malignant conditions. Do not let a transient steroid response rule out a tumour.

Nutritional and toxic patterns

Deficiencies such as vitamin B12 or copper can cause optic neuropathy, especially with malabsorption or restrictive intake. Check relevant laboratory markers and the wider neurological picture. Correct the deficiency and its cause with the appropriate team. Folate-only treatment can conceal aspects of B12 deficiency; a nonspecific vitamin supplement is not a substitute for a confirmed diagnosis and replacement plan.

Toxic optic neuropathy often has bilateral central dysfunction, but onset and symmetry vary. Ethambutol, methanol and other exposures require cause-specific action. Methanol poisoning is a medical emergency requiring toxicology care, not an outpatient visual review. Coordinate medication changes with the prescribing team and avoid stopping essential systemic treatment without a replacement plan when the situation allows consultation.

Posterior ischaemic optic neuropathy can initially have a normal-looking disc, unlike many anterior ischaemic presentations. Radiation-related neuropathy can occur after a latency and requires exclusion of recurrent tumour or other causes. Traumatic optic neuropathy may coexist with orbital injury; treatment remains individualized, and routine high-dose steroids are not an established universal benefit.

Case answer

A young man with sequential central loss and affected maternal relatives needs LHON evaluation, but reversible causes still require consideration. Slowly progressive unilateral loss with pallor needs imaging for compression. Bilateral cecocentral loss after gastrointestinal surgery needs nutritional assessment. Link the pattern to a test that changes management and begin rehabilitation while the diagnostic pathway proceeds.

Sources: GeneReviews LHON and EMA Raxone.