Optic Atrophy

Pallor and loss of axons of the optic nerve, the end result of damage to retinal ganglion cells or their axons from many diseases. It is irreversible.

• Classification by cause and pattern:
  • Primary (descending, no preceding swelling): compressive lesions, optic neuritis, hereditary neuropathies (dominant optic atrophy, Leber), toxic and nutritional neuropathies, trauma, and glaucoma (cupped atrophy).
  • Secondary: after prolonged disc swelling (papilloedema, ischaemic optic neuropathy), with blurred margins and glial scarring.
  • Consecutive: retinal disease (central retinal artery occlusion, retinitis pigmentosa), with waxy pallor and thin vessels.
  • Ascending: after retinal ganglion cell loss from retinal disease; descending: from lesions behind the globe.
  • Other causes: syphilis, radiation optic neuropathy, retinal vascular disease, hydrocephalus, increased intracranial pressure for long periods, and genetic syndromes (Wolfram syndrome).
• Temporal pallor suggests papillomacular bundle loss (toxic, nutritional, Leber, dominant optic atrophy, demyelination); generalised pallor suggests widespread damage.

• Reduced visual acuity (variable), colour desaturation (red), contrast sensitivity loss, visual field defects (central, cecocentral, arcuate, altitudinal, or bitemporal, depending on cause), and relative afferent pupillary defect in unilateral or asymmetric disease (absent in symmetrical bilateral disease).
• Optic disc: pale (white or chalky), with sharp margins, reduced capillary vasculature (loss of the small vessels on the disc), and loss of retinal nerve fibre layer reflexes; cupping in glaucomatous atrophy; pseudo-cupping in compressive atrophy.
• Associated features by cause: proptosis, motility restriction, headaches, hearing loss, diabetes, pituitary signs, or neurological deficits.

• Clinical diagnosis by fundoscopy; quantify with optical coherence tomography (retinal nerve fibre layer and ganglion cell layer thinning), colour vision testing, visual fields, and visual evoked potentials (reduced amplitude and delayed latency).
• Find the cause: MRI brain and orbits with contrast (compression, demyelination, hydrocephalus), blood tests (full count, ESR, CRP, glucose, vitamin B12, folate, copper, thiamine, syphilis serology, HIV, ANA, ANCA, aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies, angiotensin-converting enzyme, thyroid function, lead and heavy metals, methanol if relevant).
• Genetic testing for suspected hereditary atrophy (OPA1, mitochondrial DNA mutations 11778, 3460, 14484, WFS1); toxicology screen; lumbar puncture if inflammatory disease suspected.
• Intraocular pressure and gonioscopy to exclude glaucoma.

• Optic atrophy cannot be reversed; the goal is to find and treat the cause to prevent further loss and to protect the fellow eye.
  • Compressive lesions: surgery, radiotherapy, or medical therapy (pituitary tumours: cabergoline 0.25 mg twice weekly).
  • Demyelination: disease-modifying therapy after neurological assessment.
  • Nutritional: hydroxocobalamin 1000 micrograms IM, thiamine, folate, and copper replacement.
  • Toxic: stop the toxin (ethambutol, linezolid, amiodarone, alcohol, tobacco).
  • Raised intracranial pressure: acetazolamide, weight loss, surgery.
  • Glaucoma: pressure-lowering therapy.
  • Syphilis: benzylpenicillin 18 to 24 million units daily for 10 to 14 days.
  • Hereditary: idebenone 900 mg daily in Leber hereditary optic neuropathy, genetic counselling.
• Supportive care: low-vision aids, magnifiers, contrast enhancement, orientation and mobility training, certification and registration of visual impairment, occupational and educational support, and driving advice.
• Neuroprotection and regeneration therapies remain experimental.
• Follow-up every 6 to 12 months with acuity, fields and optical coherence tomography.