Optic neuropathy

Summary

Optic neuropathy refers to damage to the second cranial nerve. This can be due to inflammatory, glaucomatous, ischaemic, hereditary, nutritional, traumatic and papilloedematous causes - to name a few! In this article, we delve in to the various forms of optic neuropathy.

Clinical features

Clinical features of optic nerve dysfunction include:

• Reduced visual acuity for distance and near vision

• RAPD: relative afferent pupillary defect

• Dyschromatopsia - impairment of colour vision, often seen as red desaturation

• Diminished light brightness sensitivity

• Diminished contrast sensitivity

• Visual field defects

Classification of optic neuritis

Optic neuritis refers to inflammation of the optic nerve. We can classify this according to cause, for example, demyelinating or infectious, but also by appearance on ophthalmoscopy.

Retrobulbar neuritis: The optic nerve behind the globe is affected, and the optic nerve head is spared resulting in a normal looking disc on fundoscopy. This is most associated with Multiple Sclerosis.

Papillitis: Optic nerve head is affected. This type is common in children (especially in post-viral infections). Characteristic features include hyperaemia and oedematous optic disc, with peripapillary flame shaped haemorrhages

Neuroretinitis: Papillitis plus retinal involvement. Occurs with cat scratch disease + Lyme disease. A see a ‘macular star’ is characteristic.

Neuroretinitis with (a) swelling of optic nerve head,(b) subretinal exudates, (c) dilated and tortuous veins and (d) classic macular star. Image courtesy of Narayan et al.

Demyelinating optic neuritis

💡 Demyelinating optic neuritis is the commonest cause of optic neuritis.

Demyelinating disease is any disease which results in damage to the protective myelin sheath insulating our nerve fibres. Myelin is phagocytosed by microglia and macrophages, following which astrocytes lay down fibrous tissue in plaques. The end result is a disruption of nervous conduction within the white matter.

Multiple Sclerosis

The commonest cause of demyelinating optic neuritis (remember, demyelinating disease is the commonest cause of optic neuritis to start with!)

Multiple sclerosis is a condition well covered in medical school. It has a female predominance, often occuring in the 3rd/4th decade of life.

• Acute unilateral retrobulbar pain exacerbated by eye movements

• Retrobulbar neuritis

• Internuclear ophthalmoplegia

• Nystagmus

• General features of optic nerve dysfunction as described above

• Spontaneous resolution after a few weeks

• MRI: demyelinated plaques disseminated in time and space, lumbar puncture: oligoclonal bands in CSF

Management: IV methylprednisolone (3 days) + oral prednisolone (11 days)

Neuromyelitis Optica

Also known as Devic’s disease, and more recently as neuromyelitis optica spectrum disorders (NMOSD), is an inflammatory, antibody mediated demyelinating disorder characterized by an IgG antibody against the astrocytic aquaporin 4 (AQP4) water channel (aka, the aquaporin-4 autoantibody). The AQP4 water channel membrane protein is concentrated in the optic nerve, but also in areas of the spinal cord, which results in a specific presentation of the disease. Features include:

• Retrobulbar neuritis

• Transverse myelitis in 3 or more vertebral columns, resulting in muscle weakness, increased tone + spasms

Schilder disease

A very rare condition characterised by bilateral optic neuritis, with onset before the age of 10 and progression to death within 1-2 years.

Anterior ischaemic optic neuropathy

Anterior ischaemic optic neuropathy refers to optic nerve damage due to ischaemia. The vast majority of cases are non-arteritic, with the most common cause being idiopathic. Around 5-10% of cases are arteritic.

Non-arteritic ischaemic optic neuropathy

Non-arteritic anterior ischaemic optic neuropathy (NAION) is caused by occlusion of the short posterior ciliary arteries, resulting in infarction within the retrolaminar portion of the optic nerve head. Some of the associated conditions include:

• Hypertension

• Structural crowding of the optic nerve head resulting in a small optic cup

• Diabetes mellitus

• Hyperlipidaemia

• Sleep apnoea syndrome

• Erectile dysfunction

Essentially, conditions that may contribute to vaso-occlusion commonly co-exist, and the treatment relies on treating the underlying cause. Investigation should include blood pressure, a fasting lipid profile and blood glucose, however the important thing is to exclude giant cell arteritis (see below).

Arteritic ischaemic optic neuropathy

Arteritic ischaemic optic neuropathy complicates around 30-50% of untreated giant cell arteritis, a granulomatous uveitis that has a predilection for large and medium-size arteries, (in particular, the major aortic branches and the superficial temporal (STA), ophthalmic, posterior ciliary and proximal vertebral arteries!).

AAION has a poor prognosis, and urgent treatment with IV methylprednisolone is indicated on suspicion to prevent blindness in the fellow eye.

	Non-arteritic ischaemic optic neuropathy	Arteritic ischaemic optic neuropathy
Clinical features and examination/investigation findings	Vision loss is sudden, painless, unilateral, with a VA > 6/60	Vision loss is sudden, painful, unilateral (but risk of progression), with a VA < 6/60. Scalp tenderness, headache, jaw claudication may be present.
Features on fundoscopy	Segmental hyperaemic disc swelling + peripapillary splinter haemorrhages	‘Chalky-white’ diffuse swollen disc
Management	Treatment of underlying cause	High dose IV-methylpred + oral pred

Leber’s hereditary optic neuropathy

💡 Leber’s hereditary optic neuropathy is the commonest inherited mitochondrial disorder

• A rare ganglion cell degeneration

• Caused by mitochondrial DNA point mutations, most frequently at nucleotide position 11778 (G to A) in the MT-ND4 gene

• Typically affects males between the ages of 15 and 35 years

• A triad of signs pathognomonic for LHON are circumpapillary telangiectatic microangiopathy, swelling of the nerve fiber layer around the disc (disc pseudo-oedema), and absence of leakage from the disc or papillary region on fluorescein angiography (distinguishing it from true disc oedema)

• Generally however, signs of optic nerve dysfunction may be subtle with the disc appearing normal

• No effective treatment

Nutritional optic neuropathy

Also known as ‘tobacco-alcohol’ amblyopia, thought to affect individuals with high alcohol and tobacco consumption in western countries.

• Deficiency in the B-complex vitamins, e.g. cyanocobalamin (B12) and thiamine (B1), but also riboflavin (B2), niacin (B3) and pyridoxine (B6)

• In impoverished parts of the world, inadequate dietary intake can be the cause

• However, the underlying mechanism is thought to be deficient mitochondrial function (similar to the heritable optic neuropathies)

• Insidious onset of painless bilateral central blurring associated with abnormal colour vision (the reduction in colour vision is often disproportionate to the reduction in acuity)

• Visual field defects are bilateral and relatively symmetrical

• Investigation includes blood tests (B12 and folate, B1 (thiamine) and B2, an FBC and film (macrocytic anaemia) and serum protein levels) as well as assessing for LHON mutations. MRI can help rule out any intracranial pathology.

• Treatment is with dietary changes (increased fruit and leafy veg), smoking and alcohol cessation, and daily multivitamins (+ thiamine and folate!) Response to treatment may be slow, however complete vision loss is uncommon

💡 Pernicious anaemia sufferers may develop the condition due to reduced vitamin B12 absorption

Papilloedema

💡 Papilloedema is swelling of the optic nerve head secondary to raised intracranial pressure (ICP). Remember, ‘disc swelling’ and ‘disc oedema’ are non specific terms that may relate to a swollen disc from causes other than raised ICP!

Causes of raised ICP:

• Idiopathic intracranial hypertension (a diagnosis of exclusion!)

• Tumours or haemorrhages

• An obstruction of the ventricular system (CSF is formed by the choroid plexus in the ventricles, draining into the subarachnoid space from the fourth ventricle!)

• Impairment of CSF absorption (it is absorbed into the cerebral venous system via arachnoid villi), which can occur due to meningitis, or a subarachnoid haemorrhage

• Cerebral venous sinus thrombosis (preventing absorption into the cerebral venous system)

Symptoms of raised ICP

• Headaches: early morning, which get progressively worse over time and are triggered by head movement, bending or coughing

• Nausea

• Visual symptoms are usually absent in initial/mild raised ICP, however transient episodes of visual loss lasting up to 30 seconds are a characteristic feature of papilloedema, commonly precipitated by coughing/bending/Valsalva

• Horizontal diplopia due to sixth nerve palsy caused by stretching abducens over the petrous tip is a false localising sign

Optic disc appearance

• Early features include mild disc hyperaemia with preservation of the optic cup

• With progression, hyperaemia worsens, with blurring of optic disc margins and an enlarged optic nerve head

• Venous engorgement, peripapillary flame haemorrhages cotton wool spots may all be present

• With chronic papilloedema, disc elevation is seen

Congenital optic disc abnormalities

Tilted disc: a common anomaly, where there is oblique entry of the optic nerve into the globe. On examination, this is seen as a small or ‘D’ shaped disc, tilted inferonasally

Torsional disc: this is when the long axis is inclined at > 15 degrees from the vertical meridian, (which is a line 90° to a horizontal line connecting the foveola to the centre of the optic disc)

Optic disc pit: A greyish round or oval pit in the optic disc, usually temporal but occasionally central or elsewhere; pits are bilateral in 10–15% of cases. Complications include macular detachment.

Optic disc drusen: Disc drusen are calcified deposits composed of axonal metabolic products, which are present within the substance of the optic nerve head in around 2% of the population - thought to be sporadic but some have an AD inheritance pattern. Have a strong association with Alagille syndrome

Optic disc coloboma: A coloboma results due to incomplete closure of the embryonic fissure: which extends from the optic nerve to the margin of the pupil. When this affects the optic disc, one can see a ‘glistening white’ bowl-shaped excavation decentred inferiorly. The defect may be unilateral or bilateral, and most commonly occurs sporadically in otherwise normal individuals. However, it may also be present as part of wider chromosomal abnormalities (CHARGE syndrome, Goldenhar syndrome) and an AD variety by a mutation in the PAX6 gene.

Morning glory anomaly: A rare unilateral condition, which can be associated with PAX6 like coloboma. The characteristic features in exams is a ‘funnel-shaped excavation’, with the retinal vessels emerging from the peirphery of the optic nerve head rather than the centre. Although systemic features are rare, remember the association with frontonasal dysplasia.

Optic nerve hypoplasia: An underdeveloped optic nerve. The double-ring sign is characteristic (a white ring of visible sclera surrounding a pigmented band of migrated pigment epithelium). It is a rare condition, thought to be associated with a variety of developmental midline brain defects.

The morning glory anomaly characterized by a funnel-shaped, excavated optic disc surrounded by chorioretinal pigmentary disturbance. Image Courtesy of Safari et al.

References

1. Salmon, John F., and Jack J. Kanski. Kanski’s Clinical Ophthalmology: A Systematic Approach. Ninth Edition, Elsevier, 2020.

2. Shemesh, Ari, et al. ‘Leber Hereditary Optic Neuropathy (LHON)’. StatPearls, StatPearls Publishing, 2022. PubMed, http://www.ncbi.nlm.nih.gov/books/NBK482499/.

3. Narayan, Sunil K., et al. ‘Neuroretinitis, a Great Mimicker’. Annals of Indian Academy of Neurology, vol. 11, no. 2, 2008, pp. 109–13. PubMed Central, https://doi.org/10.4103/0972-2327.41879.

4. Safari, Anahid, et al. ‘Morning Glory Syndrome Associated with Multiple Sclerosis’. Iranian Journal of Neurology, vol. 13, no. 3, July 2014, pp. 177–80. PubMed Central, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240937/