What are the symptoms, epidemiology, and causes of optic neuritis, particularly in young adults with a potential history of autoimmune disorders such as multiple sclerosis?

Optic Neuritis: Symptoms, Epidemiology, and Causes

Epidemiology

Optic neuritis is the most common cause of subacute optic neuropathy in young adults, with an incidence of 5 cases per 100,000 persons per year in central Europe, predominantly affecting individuals aged 20-40 years with a female predominance. 1, 2, 3

• Peak age of onset is 30-40 years 4
• Women are disproportionately affected compared to men 4
• Represents the most frequent cause of acute visual loss due to optic nerve dysfunction in this age demographic 3

Clinical Symptoms

Cardinal Features

The classic triad of optic neuritis consists of sudden vision loss developing over hours to days, periocular pain worsening with eye movement, and red-green color desaturation (dyschromatopsia). 5, 2

• Visual impairment: Subacute onset over 1-10 days, progressing from hours to days 5, 3
• Periocular pain: Present in the majority of cases, characteristically exacerbated by eye movements 5, 4
• Color vision defects: Red-green dyschromatopsia is a hallmark feature 5, 4
• Photophobia: Common associated symptom 5

Objective Clinical Findings

• Afferent pupillary defect (Marcus Gunn pupil): Weaker direct pupillary light reflex in the affected eye in unilateral cases 2, 3, 4
• Visual field defects: Central scotomas are most characteristic, though centrocecal and arcuate defects can occur 5, 4
• Optic disc appearance: One-third of patients demonstrate mild optic disc edema (30-40%); the remainder have retrobulbar neuritis with normal-appearing disc 6, 2

Red Flags for Atypical Optic Neuritis

Bilateral simultaneous involvement, severe vision loss with poor recovery after steroids or steroid dependence, prominent optic disc edema, posterior optic nerve involvement extending to the chiasm, and long optic nerve lesions mandate urgent serologic testing for AQP4-IgG and MOG-IgG antibodies. 7, 1

• Bilateral simultaneous presentation suggests neuromyelitis optica spectrum disorders (NMOSD) or MOG-antibody disease (MOGAD) 5, 7
• Childhood or late adult onset (outside typical 20-40 year range) 1
• Painless vision loss, though this can occasionally occur even in MS-associated cases 8

Causes and Underlying Etiologies

Demyelinating Disorders (Most Common)

Multiple sclerosis is the most common underlying cause of typical optic neuritis, with optic neuritis often serving as the initial presenting manifestation of MS. 1, 2, 4

• MS-associated optic neuritis: Idiopathic demyelination with lesions similar to MS plaques; even one clinically silent T2 hyperintense brain lesion on MRI is highly associated with eventual MS diagnosis (hazard ratio 5.1 for 1-3 lesions, 11.3 for ≥10 lesions) 5, 4
• Neuromyelitis optica spectrum disorders (NMOSD): AQP4-antibody positive disease frequently presents with bilateral optic neuritis, more severe vision loss, and poorer recovery than MS-related cases; characterized by posterior optic nerve involvement extending to chiasm and longitudinally extensive lesions 5, 7
• MOG-antibody disease (MOGAD): Characterized by long optic nerve lesions, bilateral simultaneous involvement, and soft tissue enhancement extrinsic to the nerve affecting orbit, orbital apex, or cavernous sinus 7

Autoimmune and Inflammatory Conditions

• Systemic lupus erythematosus: Can cause inflammatory optic neuritis (both inflammatory and ischemic/thrombotic mechanisms), associated with poor visual outcomes with only 30% maintaining visual acuity >20/25; may present bilaterally 6, 7
• Glial fibrillary acidic protein (GFAP) autoimmunity: Rare cause presenting as bilateral painless optic neuropathy with optic disc edema 1
• Collapsin response-mediator protein 5 (CRMP5) autoimmunity: Another rare autoimmune cause with similar bilateral painless presentation 1

Infectious Causes

• Measles (rubeola): Can cause bilateral optic neuritis, particularly in unvaccinated individuals 7
• Epstein-Barr virus: Associated with follicular conjunctivitis and optic neuritis 7
• Zika virus: Reported to cause bilateral non-purulent conjunctivitis and optic neuritis 7

Granulomatous and Other Causes

• Granulomatous disease: Suggested by perioptic nerve sheath enhancement and soft tissue enhancement extrinsic to the nerve 7
• Sarcoidosis: Can present with optic nerve involvement 9

Prognosis and Natural History

Visual disturbance resolves in 95% of typical optic neuritis cases, with recovery usually occurring regardless of treatment, though high-dose intravenous methylprednisolone expedites recovery without improving final outcome. 2

• MS-associated typical optic neuritis generally has good visual prognosis 2, 8
• NMOSD-related optic neuritis has significantly poorer visual outcomes and requires aggressive immunosuppression to prevent devastating relapses 7
• MOGAD has a 50-60% relapse rate during corticosteroid taper, necessitating maintenance immunosuppressive therapy 6, 7
• SLE-related optic neuritis carries poor prognosis with only 30% maintaining good visual acuity 6

Critical Diagnostic Considerations

Brain MRI is critical for MS risk stratification even in isolated optic neuritis; absence of brain lesions strongly predicts monophasic illness, while CSF oligoclonal bands combined with brain MRI lesions dramatically reduce the likelihood of monophasic disease. 5

• Treatment delay beyond 2 weeks is an unfavorable prognostic factor, particularly in SLE-related cases 6, 7
• Cell-based assays using full-length human MOG are the gold standard for MOG-IgG testing 7
• Serum antibody testing for AQP4-IgG and MOG-IgG should be performed immediately in atypical presentations, as these have significant therapeutic consequences requiring different treatment approaches than MS 7