Optic Neuritis

Definition and Pathophysiology

Etiology

• Goldman-Cecil Medicine, p. 1328
• Tintinalli's Emergency Medicine, p. 706

Clinical Features

• Monocular visual loss developing over hours to a few days (bilateral in NMOSD/MOGAD)
• Periorbital/brow pain worsening with lateral eye movement - present in ~90% of cases; typically lasts 3-5 days
• Decreased color vision and contrast sensitivity - often disproportionately more affected than acuity (red desaturation test)
• Visual field defects - diffuse or discrete scotomas (non-specific)

• Afferent pupillary defect (APD/RAPD) - commonly present
• Fundoscopy:
  • Normal in ~two-thirds (retrobulbar neuritis)
  • Mild disc edema (papillitis) in ~one-third - less prominent than papilledema
  • No hemorrhages or cotton-wool spots in typical ON (their presence suggests another diagnosis)
• OCT - atrophy of retinal nerve fiber layer (RNFL) and ganglion cell layer develops over weeks after acute episode; reliable structural marker

MOGAD vs. MS vs. NMOSD - Key Differentiating Features in Optic Neuritis

• Harrison's Principles 22E, p. 3001-3023
• Bradley & Daroff's Neurology, p. 3175-3182

Risk of Progression to MS

• Brain MRI with ≥1 characteristic lesion at onset: 72% risk of MS at 15 years
• Normal brain MRI at onset: 25% risk of MS at 15 years
• Atypical features (painless loss, severe disc edema, disc/peripapillary hemorrhages, macular exudate) = negligible MS risk
• Bradley & Daroff's Neurology, p. 3167

Differential Diagnosis

• Anterior ischemic optic neuropathy (AION): sudden onset, painless, age >50, pallid disc edema
• Papilledema: bilateral, painless, preserved visual acuity (early)
• Compressive optic neuropathy: orbital tumor (proptosis), intracranial tumor
• Hypertensive retinopathy
• Hereditary optic neuropathies: Leber hereditary optic neuropathy (LHON), Charcot-Marie-Tooth 2a
• Toxic/metabolic: alcohol, tobacco, heavy metals, chloroquine

Investigations

1. MRI brain and orbits - most important for prognosis and MS risk stratification; orbital MRI with fat suppression shows optic nerve signal change
2. Visual fields (Humphrey perimetry)
3. Color vision testing
4. OCT - RNFL and ganglion cell layer thinning
5. VEP (Visual Evoked Potentials) - delayed P100
6. Serum AQP4-IgG - screen for NMOSD
7. Serum MOG-IgG (cell-based assay) - screen for MOGAD; CSF MOG-IgG if seronegative but suspected
8. CSF - oligoclonal bands (supports MS), pleocytosis
9. Where indicated: ANA, ANCA, ACE (sarcoidosis), RPR/VDRL, Lyme serology, HIV

Treatment

Acute Phase

• High-dose IV methylprednisolone (1 g/day for 3 days) - hastens visual recovery but does not significantly affect long-term visual outcome
• Oral prednisone alone (1 mg/kg) - AVOID - associated with increased risk of recurrence of ON without providing benefit (ONTT finding)
• Plasmapheresis - may be beneficial in acute NMOSD/MOGAD unresponsive to steroids

Long-term

• MS disease-modifying therapy (interferon-beta, natalizumab, etc.) - indicated for high-risk patients (≥1 MRI lesion) to reduce risk of conversion to MS
• NMOSD (AQP4+): Immunosuppressants; FDA-approved agents include eculizumab, inebilizumab, and satralizumab
• MOGAD: Typically treated with steroids ± mycophenolate/azathioprine for relapsing disease; differs from MS - avoid MS DMTs
• Bradley & Daroff's Neurology, p. 3171-3173
• Goldman-Cecil Medicine, p. 1338

Prognosis

• Visual recovery begins within 1 month in typical ON
• Prognosis correlates with severity of initial deficit
• Post-episode: optic nerve pallor (temporal pallor) on fundoscopy is expected - reflects axonal loss
• NMOSD-associated ON carries a significantly worse visual prognosis than MS-associated or idiopathic ON

Recent Evidence (2024-2026)

Episcleritis

Note: AK Khurana's Comprehensive Ophthalmology is not available in this library. The following is compiled from Kanski's Clinical Ophthalmology (10th ed.) and the Wills Eye Manual - two leading ophthalmology references that cover this topic in the same depth as Khurana.

Anatomy Relevant to Episcleritis

• Kanski's Clinical Ophthalmology 10e, p. 306

Definition

• More common in females (except in children, where it is rare)
• Average patient is middle-aged

Etiology

Types of Episcleritis

1. Simple Episcleritis (75% of cases)

• More acute onset; features often peak within 24 hours, then gradually fade
• Recurs in ~60% of cases (frequency decreases with time)

• 50% of cases are simultaneously bilateral

• Redness is sectoral (triangular, base at limbus) or diffuse - interpalpebral distribution
• Symptoms range from absent (up to 50%) to moderate - grittiness, mild photophobia
• Visual acuity: normal
• Chemosis, raised IOP, anterior uveitis, keratitis - all rare

Episcleritis: diffuse sectoral injection of radially-oriented episcleral vessels - Wills Eye Manual Fig. 5.6.1

2. Nodular Episcleritis (25% of cases)

• Affects females > males; less acute onset, more prolonged course than simple variant
• Red eye first noted on waking; redness enlarges and becomes uncomfortable over 2-3 days
• Tender, red vascular nodule - almost always within the interpalpebral fissure; occasionally more than one nodule
• Slit lamp: flat anterior scleral surface (confirms no scleritis)
• IOP very occasionally elevated
• Anterior chamber reaction in ~10%
• After several episodes, inflamed vessels may become permanently dilated
• Must exclude: phlyctenulosis (phlycten is within the conjunctiva, not beneath it) and conjunctival granuloma

Key Examination Steps

1. History - rash, arthritis, venereal disease, recent viral illness
2. External exam in natural light - look for violaceous hue (suggests scleritis)
3. Slit lamp - anesthetize, move conjunctiva with cotton-tipped applicator to assess depth of vessels; check for corneal/AC involvement; measure IOP
4. Phenylephrine 2.5% test - instill and re-examine after 10-15 min:
   • Episcleral vessels blanch → episcleritis
   • Deep scleral vessels do not blanch → scleritis

Episcleritis vs. Scleritis - Key Differences

Investigations

• CBC, CMP
• ANA, RF, anti-CCP
• ESR, CRP
• Serum uric acid (gout)
• RPR/VDRL + FTA-ABS (syphilis)
• ANCA (vasculitis)
• Investigate for herpes zoster, Lyme, etc. as indicated
• Wills Eye Manual, p. 339

Treatment

Simple Episcleritis

Note: Many physicians prefer oral NSAIDs to topical NSAIDs or steroids as initial therapy. Oral prednisone alone is NOT preferred for episcleritis.

Nodular Episcleritis

Prognosis

• Benign and self-limiting
• Recurrences are common but decrease in frequency with time
• Does NOT progress to scleritis in the vast majority
• Vision is not at risk

Note on Davidson's: Davidson's Principles and Practice of Medicine is not available in this library. The answer below is drawn entirely from Harrison's Principles of Internal Medicine 22E (2025), which covers headache in equivalent (and more extensive) depth across Chapters 17 and 441.

Headache

Classification (ICHD-III Based)

• Primary headaches - headache and its features form the disorder itself
• Secondary headaches - caused by an exogenous/underlying disorder

Anatomy and Physiology of Headache

1. Large intracranial vessels and dura mater + peripheral terminals of the trigeminal nerve (trigeminovascular system)
2. Trigeminocervical complex (TCC) - caudal trigeminal nucleus extending into dorsal horns of C1-C2
3. Rostral pain-processing regions: ventroposteromedial thalamus, cortex
4. Pain-modulating systems: hypothalamus, dorsal raphe, locus coeruleus, nucleus raphe magnus

Clinical Evaluation of Acute, New-Onset Headache

• Sudden onset ("thunderclap") - worst headache of life → SAH until proven otherwise
• Fever + neck stiffness → meningitis
• New headache in patient >50 → temporal arteritis, mass lesion
• Progressive worsening headache
• Headache with exertion, bending, Valsalva → posterior fossa mass, Chiari, low CSF pressure
• Neurologic deficits
• Headache in known malignancy → metastases or carcinomatous meningitis

PRIMARY HEADACHE DISORDERS

1. MIGRAINE

• Trigeminovascular input from meningeal vessels → trigeminal ganglion → TCC → quintothalamic tract → thalamus
• CGRP (calcitonin gene-related peptide) is the key neuropeptide mediator
• Cortical spreading depression underlies the aura

Treatment of Migraine

• Identify and avoid triggers
• Regulated lifestyle: regular sleep, diet, exercise
• Avoid excess caffeine, alcohol
• Biofeedback, relaxation, yoga, meditation (adjuncts)

Key principle: Take an adequate dose as soon as possible after onset. If inadequate relief within 60 min, increase dose for next attack or switch class.

2. TENSION-TYPE HEADACHE (TTH)

• Most common headache (69% of all headaches)
• Bilateral, pressing/tightening (non-pulsating), mild-moderate intensity
• No nausea/vomiting; no aggravation by routine physical activity
• Featureless headache - migraine is headache WITH features; TTH is headache WITHOUT features

• Acute: acetaminophen, aspirin, NSAIDs
• Behavioral: relaxation therapy
• Triptans NOT effective in pure TTH (effective only if patient also has migraine)
• Chronic TTH: amitriptyline is the only proven preventive treatment
• SSRIs, benzodiazepines - NOT proven effective
• Botulinum toxin A - negative in controlled trials for chronic TTH

3. TRIGEMINAL AUTONOMIC CEPHALALGIAS (TACs)

Comparison Table:

Cluster Headache - Key Features

• Population frequency ~0.1%; men affected 3x more than women
• Deep, retroorbital, excruciating, nonfluctuating, explosive pain
• Periodicity - attacks recur at the same hour daily for a cluster bout (8-10 weeks/year)
• Pain-free interval averages ~1 year
• Nocturnal onset in ~50%
• Patients pace and rock during attacks (contrast: migraine patients lie still)
• Ipsilateral autonomic features: conjunctival injection, lacrimation, rhinorrhea, ptosis
• Involves central pacemaker neurons in posterior hypothalamic region

• 100% O₂ at 10-12 L/min for 15-20 min (very effective)
• Sumatriptan 6 mg SC - shortens attack to 10-15 min; no tachyphylaxis
• Sumatriptan 20 mg nasal spray or zolmitriptan 5 mg nasal spray
• Non-invasive vagus nerve stimulation (nVNS) - FDA cleared for episodic cluster headache
• Oral sumatriptan NOT effective for cluster headache

4. OTHER PRIMARY HEADACHE DISORDERS

SECONDARY HEADACHE - Important Causes

Meningitis

• Acute severe headache + stiff neck + fever → LP mandatory
• Pain accentuated by eye movement; can mimic migraine (photophobia, nausea, vomiting)

Intracranial Hemorrhage (SAH)

• Sudden onset, maximal in <5 min, severe, lasting >5 min + stiff neck without fever → SAH until proven otherwise
• CT head; if CT negative → LP required (small or infraforamen magnum bleeds can be CT-negative)

Brain Tumor

• ~30% of brain tumor patients report headache as chief complaint
• Usually intermittent, deep, dull, moderate intensity; worsens with exertion/position change
• Vomiting preceding headache by weeks = highly characteristic of posterior fossa tumor
• Headache disturbs sleep in ~10%
• Brain tumor is a rare cause of headache; migraine far more common

Temporal (Giant Cell) Arteritis

• Annual incidence 77/100,000 in age ≥50; average onset age 70; women 65%
• Dull, boring head pain - unilateral or bilateral; temporal in 50%
• Jaw claudication, scalp tenderness, fever, weight loss, polymyalgia rheumatica
• ESR usually elevated (but normal ESR does NOT exclude it)
• 50% risk of blindness if untreated - ischemic optic neuropathy is the major cause of rapid bilateral blindness in >60 years
• Treat promptly with prednisone 80 mg/day for 4-6 weeks; temporal artery biopsy

Glaucoma (Acute Angle Closure)

• Prostrating headache + nausea/vomiting + severe eye pain
• Red eye, fixed, moderately dilated pupil

Chronic Daily Headache (CDH)

• Headache on ≥15 days/month
• Not a single diagnosis - encompasses chronic migraine, chronic TTH, medication-overuse headache, new daily persistent headache
• Medication-overuse headache: regular use of any acute headache medication on >10 days/month leads to chronic daily headache