25th June 2023

CNII – Optic Nerve

The optic nerve arises from the retina of each eye, passing through the optic canals and converging at the optic chiasm before continuing to the lateral geniculate body in the thalamus and into the cortex as optic radiations. There is bilateral innervation in that one half of each visual field is projected to the contralateral visual cortex, with the medial fibres of each optic nerve decussating at the optic chiasm to then travel to the contralateral cerebral hemisphere.

Relative Afferent Pupillary Defect – RAPD

Also known as a Marcus Gunn Pupil, a relative afferent pupillary defect (RAPD) is a condition where there is an asymmetric response to the same light stimuli as a result of unilateral damage to the optic afferent pathway involving the retina and optic nerve. This can be elicited by the swinging flashlight test (Marcus Gunn Test), where a pen torch is shone at one eye before moving to the other and alternating between the two to observe the pupils’ response. In RAPD, the affected optic afferent nerve would be less responsive to the light stimuli than the unaffected side and lead to a competition between the direct pupillary light reflex of that eye and the consensual pupillary light reflex of the contralateral eye. In the affected eye, the direct pupillary light reflex would be impaired by pathology, causing a paradoxical pupillary dilation in response to light stimuli.

Pathology that can cause RAPD can be divided into :

• Retinal causes
  • Vascular causes –Ischaemic retinal disease and ocular disease
  • Mechanical – Retinal detachment
  • Infection
  • Tumour

• Optic nerve causes
  • Demyelination – Multiple sclerosis, neuromyelitis optica spectrum disorder
  • Vascular –Ischaemia to the optic nerve, giant cell arteritis
  • Inflammatory – Sarcoidosis, SLE
  • Hereditary – Leber’s hereditary optic neuropathy
  • Pressure – Glaucoma, Tumours

Optic Neuritis

Optic neuritis is an umbrella term for inflammation of the optic nerve, which can have many different aetiologies. A hallmark of optic neuritis is the presence of pain. It should be distinguished from optic neuropathy, which is a general term for any damage to the optic nerves. Optic neuritis is characterised by a rapid onset, painful ophthalmic condition associated with visual symptoms of dyschromatopsia, visual field defect or pupillary reflex abnormality.

There are several different conditions that can cause an optic neuritis:

• Demyelination:
  • Multiple sclerosis
  • Neuromyelitis optica spectrum disorders, which are a large spectrum of conditions exhibiting optic neuritis with myelitis, including:
    • Anti-Aquaporin-4 IgG (Anti-AQP4) positive neuromyelitis optica
    • Anti-AQP4 negative, Anti Myelin Oligodendrocyte Glycoprotein (anti-MOG) positive neuromyelitis optica.
    • Anti-Glial Fibrillary Acidic protein positive neuromyelitis

• Autoimmune:
  • Systemic Lupus Erythematosus
  • Paraneoplastic
  • Sarcoidosis
  • Vasculitis, e.g. granulomatosis with polyangiitis

• Infective causes – Syphilis, Lyme disease

Treatment is with high dose IV methylprednisolone tapering onto oral prednisolone. As with all treatment with steroids, a PPI and bone protection should always be considered, and glycaemic control in patients with impaired glucose metabolism, e.g. diabetes, should also be considered. With antibody mediated optic neuritis, there is a role for plasma exchange (PLEX) or intravenous immunoglobulin (IVIg). Neuro-ophthalmology follow-up is essential.

Optic Neuropathy

Optic neuropathy is a very general term for any damage to the optic nerves, which also encompasses optic neuritis. The causes of optic neuropathy can broadly be divided into:

• Rapid onset – secondary to ischaemia, trauma, and autoimmune or inflammatory conditions.
• Gradual onset – secondary to toxins, e.g. lead toxicity-induced demyelination, drugs, e.g. ethambutol, compressive causes, e.g. glaucoma, metabolic, or mitochondrial causes.

Idiopathic Intracranial Hypertension – commonly affects the optic nerves

Idiopathic intracranial hypertension (IIH) commonly affects the optic nerves. IIH manifests as raised intracranial pressure without any obvious structural cause observed on imaging, with common associated clinical signs of vision loss and headache. Papilloedema can be found on fundoscopy.

Risk factors:

• Raised BMI
• Oral contraceptive pill use
• Tetracycline antibiotics
• Female

Treatment:

• Weight loss
• Acetazolamide
• Therapeutic lumbar puncture

Space occupying lesions can cause similar symptoms and should always be excluded before a diagnosis of IIH is made.

Leber’s hereditary optic neuropathy

Mitochondrially inherited defects in NADH-ubiquinone oxidoreductase chains interfere with glutamate transport and protection from reactive oxygen species, resulting in the loss of retinal ganglion cells and demyelination in the optic nerves, chiasm, and tracts. This manifests as acute progressive vision loss (both field and acuity) progressing from unilateral to bilateral, in young adults of 20 to 24 years old, with a preponderance for males. A key hallmark here is that it is painless and affects one eye before the other. It can be associated with extraocular neurological symptoms of dystonia and tremor and cardiac conduction defects, which if present, is termed LHON Plus.

Wolfram syndrome

Wolfram syndrome is a childhood onset autosomal-recessive genetic disorder that manifests as a combination of both diabetes insipidus and diabetes mellitus, with optic atrophy and deafness (the acronyms of which result in it being also known as DIDMOAD). It is caused by a mutation in the WFS-1 or WFS-2 gene which are responsible for the production of a protein called wolframin thought to regulate calcium metabolism. Not all the components of the syndrome may occur at once, but most sufferers of Wolfram syndrome will develop optic atrophy with diabetes mellitus.