Optic Neuritis¶

DIAGNOSIS: Optic Neuritis ICD-10: H46.9 (Optic neuritis, unspecified); H46.00 (Optic papillitis, unspecified eye); H46.10 (Retrobulbar neuritis, unspecified eye); G36.0 (Neuromyelitis optica - if NMOSD confirmed); H46.8 (Other optic neuritis) SYNONYMS: Optic neuropathy (inflammatory), retrobulbar neuritis, papillitis, demyelinating optic neuropathy, acute optic neuritis, ON, MS-associated optic neuritis, clinically isolated syndrome (CIS) - optic neuritis, optic perineuritis, MOGAD optic neuritis, NMOSD optic neuritis SCOPE: Acute evaluation and management of optic neuritis in adults. Covers typical demyelinating optic neuritis, atypical features requiring expanded workup, MS risk stratification, ONTT-based treatment, and NMO/MOG antibody evaluation. For established MS with optic neuritis as a relapse, can also use "MS - Exacerbation" template.

VERSION: 1.1 CREATED: January 27, 2026 REVISED: January 30, 2026

STATUS: Draft - Pending Review

PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

CLINICAL PEARL: The Optic Neuritis Treatment Trial (ONTT) established that IV methylprednisolone accelerates visual recovery but does not change final visual outcome. Oral prednisone alone at standard doses (1 mg/kg/day) was associated with increased recurrence rate and should NOT be used as monotherapy. Most patients (90%+) recover vision to 20/40 or better within 1 year.

SECTION A: ACTION ITEMS¶

1. LABORATORY WORKUP¶

1A. Essential/Core Labs¶

Test (CPT)	ED	HOSP	OPD	ICU	Rationale	Target Finding
CBC with differential (85025)	STAT	STAT	ROUTINE	-	Infection screen, baseline before steroids	Normal
CMP (80053)	STAT	STAT	ROUTINE	-	Metabolic screen, renal function for contrast	Normal
ESR (85652)	STAT	STAT	ROUTINE	-	Inflammatory/vasculitis screen; elevated in GCA	Normal (<20 mm/hr); elevated in GCA
CRP (86140)	STAT	STAT	ROUTINE	-	Inflammatory marker	Normal
Blood glucose (82947)	STAT	STAT	ROUTINE	-	Pre-steroid baseline	Normal
Urinalysis (81001)	STAT	STAT	ROUTINE	-	UTI screen before steroids	Negative

1B. Extended Workup (Second-line)¶

Test (CPT)	ED	HOSP	OPD	ICU	Rationale	Target Finding
Mayo CDS1 Panel - AQP4-IgG + MOG-IgG by FACS (86235)	URGENT	URGENT	ROUTINE	-	Combined NMO/MOGAD screen; critical for atypical cases	Both negative
ANA (86038)	URGENT	ROUTINE	ROUTINE	-	Lupus/connective tissue disease	Negative or low titer
TSH (84443)	-	ROUTINE	ROUTINE	-	Thyroid eye disease (Graves ophthalmopathy)	Normal
Vitamin B12 (82607)	-	ROUTINE	ROUTINE	-	Nutritional optic neuropathy	Normal (>300 pg/mL)
Folate (82746)	-	ROUTINE	ROUTINE	-	Nutritional optic neuropathy	Normal
RPR/VDRL (86592)	-	ROUTINE	ROUTINE	-	Neurosyphilis	Negative
HIV (86701)	-	ROUTINE	ROUTINE	-	HIV-associated optic neuropathy	Negative
ACE level (82164)	-	ROUTINE	ROUTINE	-	Neurosarcoidosis	Normal
Lyme serology (86618)	-	ROUTINE	ROUTINE	-	Endemic areas; Lyme optic neuropathy	Negative
HbA1c (83036)	-	ROUTINE	ROUTINE	-	Glycemic status before steroids	<5.7%

Note: Mayo CDS1 Panel preferred for combined AQP4 + MOG testing. Cell-based assay (FACS) is gold standard. If unavailable, order AQP4-IgG (Mayo NMOFS) and MOG-IgG (Mayo MOGFS) separately.

1C. Rare/Specialized (Refractory or Atypical)¶

Test (CPT)	ED	HOSP	OPD	ICU	Rationale	Target Finding
Anti-dsDNA (86225)	-	EXT	EXT	-	If ANA positive; SLE screen	Negative
Anti-SSA/SSB - Ro/La (86235)	-	EXT	EXT	-	Sjogren syndrome	Negative
ANCA panel (86039)	-	EXT	EXT	-	CNS/orbital vasculitis	Negative
Serum protein electrophoresis (86335)	-	EXT	EXT	-	Paraproteinemic optic neuropathy	No M-spike
Mitochondrial DNA testing (81401)	-	-	EXT	-	Leber hereditary optic neuropathy (LHON)	Normal
Copper, ceruloplasmin (82525, 82390)	-	-	EXT	-	Wilson disease	Normal
Paraneoplastic panel - anti-CRMP5/CV2 (86255)	-	EXT	EXT	-	Paraneoplastic optic neuropathy	Negative

2. DIAGNOSTIC IMAGING & STUDIES¶

2A. Essential/First-line¶

Study (CPT)	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
MRI orbits with contrast - fat-suppressed T1, STIR (70543)	URGENT	URGENT	ROUTINE	-	Within 24-48h	Optic nerve enhancement, swelling; enhancement >50% nerve length suggests atypical/NMOSD	GFR <30, gadolinium allergy
MRI brain with and without contrast - MS protocol (70553)	URGENT	URGENT	ROUTINE	-	With orbit MRI	Demyelinating lesions (periventricular, juxtacortical, infratentorial); determines MS risk	GFR <30, gadolinium allergy
MRI C-spine with and without contrast (72156)	-	ROUTINE	ROUTINE	-	Within 1 week if MS suspected	Cord lesions supporting MS diagnosis	GFR <30, gadolinium allergy

MS protocol should include: 3D FLAIR, 3D T1 pre/post-contrast, T2, DWI. For orbits: fat-suppressed T1 post-contrast, STIR/T2 coronal.

2B. Extended¶

Study (CPT)	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
Visual evoked potentials - VEP (95930)	-	ROUTINE	ROUTINE	-	During workup	Prolonged P100 latency (confirms optic nerve dysfunction)	None significant
OCT - Optical coherence tomography (92134)	-	-	ROUTINE	-	Baseline and at 3-6 months	RNFL thickening acutely; thinning at follow-up indicates axonal loss	None significant
Formal visual field testing - Humphrey 30-2 or 24-2 (92083)	-	ROUTINE	ROUTINE	-	At presentation and follow-up	Central/cecocentral scotoma typical; document baseline	Patient cooperation required

Note: OCT typically available only in outpatient neuro-ophthalmology. RNFL thickening >15% of fellow eye acutely suggests papillitis.

2C. Rare/Specialized¶

Study (CPT)	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
CT chest (71260)	-	EXT	EXT	-	If sarcoidosis suspected	Hilar lymphadenopathy	Contrast allergy
PET-CT (78816)	-	EXT	EXT	-	If malignancy/paraneoplastic suspected	FDG-avid lesions	Pregnancy, uncontrolled diabetes
CT orbits (70480)	STAT	-	-	-	Only if MRI unavailable/contraindicated	Optic nerve enlargement, orbital mass	Contrast allergy
Fluorescein angiography (92235)	-	-	EXT	-	If retinal/vascular pathology suspected	Disc leakage, vascular abnormality	Dye allergy

LUMBAR PUNCTURE¶

Indication: Not routinely required for typical optic neuritis. Consider if: (1) atypical features present, (2) need to support MS diagnosis (OCBs for dissemination in time), (3) concern for infectious or inflammatory etiology, (4) poor response to steroids.

Timing: ROUTINE if indicated; URGENT if infection suspected

Volume Required: 15-20 mL (standard diagnostic)

Study (CPT)	ED	HOSP	OPD	ICU	Rationale	Target Finding
Opening pressure (62270)	URGENT	ROUTINE	ROUTINE	-	Rule out elevated ICP (papilledema mimics)	10-20 cm H2O
Cell count - tubes 1 and 4 (89051)	URGENT	ROUTINE	ROUTINE	-	Inflammation, rule out infection	WBC <50 (mild pleocytosis acceptable); RBC 0
Protein (84157)	URGENT	ROUTINE	ROUTINE	-	Elevated in inflammation	Normal to mildly elevated (<100 mg/dL)
Glucose with serum glucose (82947)	URGENT	ROUTINE	ROUTINE	-	Low in infection	Normal (>60% serum)
Gram stain and culture (87205, 87070)	URGENT	ROUTINE	ROUTINE	-	Rule out infection	No organisms
Oligoclonal bands - CSF AND serum (83916)	-	ROUTINE	ROUTINE	-	Intrathecal IgG synthesis (supports MS)	>=2 CSF-specific bands (not in serum)
IgG index (86327)	-	ROUTINE	ROUTINE	-	Intrathecal antibody synthesis	>0.7 = elevated
Cytology (89050)	-	ROUTINE	ROUTINE	-	Rule out malignancy	Negative
VDRL - CSF (86593)	-	ROUTINE	ROUTINE	-	Neurosyphilis	Negative

Special Handling: OCBs stable at 4°C for days; send paired serum.

Contraindications: Elevated ICP without imaging, coagulopathy (INR >1.5, platelets <50K), skin infection at LP site

3. TREATMENT¶

3A. Acute/Emergent¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Methylprednisolone	IV	Acute optic neuritis - accelerates visual recovery per ONTT	1000 mg :: IV :: daily x 3 days :: 1000 mg IV daily for 3 days; infuse over 1-2 hours; followed by oral prednisone taper	Active untreated infection; uncontrolled diabetes; active psychosis; severe hypertension	Glucose q6h (target <180); BP; mood; sleep; I/O	STAT	STAT	-	-
Prednisone oral taper	PO	Following IV methylprednisolone per ONTT protocol	1 mg/kg :: PO :: daily x 11 days :: 1 mg/kg/day (max 80 mg) x 11 days following 3 days IV steroids; then discontinue or rapid taper	Same as IV steroids	Glucose; BP; mood; GI prophylaxis	-	ROUTINE	ROUTINE	-
Omeprazole	PO	GI prophylaxis during steroids	20 mg :: PO :: daily :: 20-40 mg daily during steroid course	PPI allergy; osteoporosis (long-term)	None routine	STAT	STAT	ROUTINE	-
Insulin sliding scale	SC	Steroid-induced hyperglycemia	Per protocol :: SC :: PRN :: Per institutional protocol if glucose >180 mg/dL	Hypoglycemia risk	Glucose q6h	STAT	STAT	-	-

IMPORTANT: Oral prednisone alone (without preceding IV steroids) should NOT be used. ONTT showed increased recurrence rate with standard-dose oral prednisone monotherapy.

3B. Symptomatic Treatments¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Acetaminophen	PO	Pain with eye movement	650-1000 mg :: PO :: q6h PRN :: 650-1000 mg PO q6h as needed for pain; max 3000 mg/day (2000 mg if liver disease)	Hepatic impairment; chronic alcohol use	LFTs if prolonged use	ROUTINE	ROUTINE	ROUTINE	-
Ibuprofen	PO	Pain with eye movement	400-800 mg :: PO :: q8h PRN :: 400-800 mg PO q8h as needed for pain; max 2400 mg/day; take with food	Renal impairment; GI bleeding; concurrent anticoagulation	Renal function if prolonged	ROUTINE	ROUTINE	ROUTINE	-
Gabapentin	PO	Persistent periorbital pain/neuropathic symptoms	300 mg :: PO :: qHS :: Start 300 mg qHS; increase by 300 mg every 1-3 days; target 900-1800 mg/day divided TID	Renal impairment (adjust dose)	Sedation; dizziness	-	ROUTINE	ROUTINE	-
Artificial tears	TOP	Dry eye secondary to reduced blink or lagophthalmos	1-2 drops :: TOP :: q2-4h PRN :: Preservative-free artificial tears 1-2 drops q2-4h as needed	None	None	ROUTINE	ROUTINE	ROUTINE	-

3C. Second-line/Refractory¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Plasmapheresis (PLEX)	PLEX	Steroid-refractory or severe vision loss	5-7 exchanges :: PLEX :: qod :: 5-7 exchanges every other day; typical volume 1-1.5 plasma volumes	Hemodynamic instability; sepsis; line contraindication	BP; electrolytes; coags; fibrinogen; line infection	-	URGENT	-	-
IVIG	IV	Steroid-refractory (alternative to PLEX)	0.4 g/kg :: IV :: daily x 5 days :: 0.4 g/kg/day for 5 days (total 2 g/kg); infuse slowly day 1	IgA deficiency; renal failure; thrombosis risk	Renal function; headache; thrombosis	-	URGENT	-	-
Extended IV steroids	IV	Incomplete response to 3-day course	1000 mg :: IV :: daily :: Extend to 5-7 total days if inadequate response	Same as initial course	Same as initial course	-	ROUTINE	-	-

3D. Disease-Modifying Therapies (If MS/NMOSD/MOGAD Confirmed)¶

DMT initiation requires confirmed diagnosis and specialist involvement. Not initiated in ED or ICU. See specific disease templates for detailed DMT options.

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
MS DMT (various)	Variable	If MS diagnosed based on MRI + clinical criteria	See MS - New Diagnosis template :: - :: - :: See MS - New Diagnosis template	Per specific DMT	Per specific DMT	Per specific DMT	-	-	ROUTINE	-
Rituximab	IV	NMOSD (AQP4-IgG positive)	1000 mg :: IV :: q2wk x 2 then q6mo :: 1000 mg IV days 1 and 15; maintenance 1000 mg q6 months	Hepatitis B serology; TB test; immunoglobulins	Active Hep B; active infection	CD19/20; immunoglobulins annually	-	-	ROUTINE	-
Eculizumab (Soliris)	IV	NMOSD (AQP4-IgG positive) - FDA approved	900 mg :: IV :: weekly x 4 then q2wk :: 900 mg weekly x 4; then 1200 mg at week 5; then 1200 mg q2 weeks	Meningococcal vaccination (2 weeks prior)	Unresolved Neisseria infection	CBC; LFTs; signs of meningococcal infection	-	-	ROUTINE	-
Immunosuppression (MOGAD)	Variable	MOGAD (MOG-IgG positive) with relapsing course	Per agent :: Variable :: - :: Rituximab, azathioprine, or mycophenolate per specialist	Per specific agent	Per specific agent	Per specific agent	-	-	ROUTINE	-

4. OTHER RECOMMENDATIONS¶

4A. Referrals & Consults¶

Recommendation	ED	HOSP	OPD	ICU
Neuro-ophthalmology referral for comprehensive evaluation and follow-up	URGENT	URGENT	ROUTINE	-
Neurology/MS specialist referral if brain MRI shows demyelinating lesions	URGENT	URGENT	ROUTINE	-
Ophthalmology referral if neuro-ophthalmology unavailable or alternate diagnosis suspected	URGENT	URGENT	ROUTINE	-
MS specialist/Neuroimmunology for DMT discussion if MS criteria met	-	ROUTINE	ROUTINE	-
Low vision rehabilitation if significant persistent visual impairment	-	-	ROUTINE	-
Occupational therapy for ADL adaptation if functional visual impairment	-	ROUTINE	ROUTINE	-
Social work for disability resources if visual impairment affects employment	-	-	ROUTINE	-

4B. Patient Instructions¶

Recommendation	ED	HOSP	OPD
Vision typically improves over 2-4 weeks; 90%+ recover to 20/40 or better within 1 year	ROUTINE	ROUTINE	ROUTINE
Return immediately if vision worsening after initial improvement (may indicate new attack or alternate diagnosis)	STAT	STAT	ROUTINE
Return if new symptoms: weakness, numbness, imbalance, bladder problems (may indicate MS)	STAT	STAT	ROUTINE
Do not drive if vision in affected eye prevents safe driving; check with state DMV regarding vision requirements	ROUTINE	ROUTINE	ROUTINE
Heat may temporarily worsen symptoms (Uhthoff phenomenon) - this is not a new attack or permanent worsening	ROUTINE	ROUTINE	ROUTINE
Expect temporary steroid side effects: insomnia, mood changes, increased appetite, metallic taste during IV infusion	ROUTINE	ROUTINE	-
Do not stop oral prednisone abruptly if on taper (adrenal suppression risk)	-	ROUTINE	ROUTINE
Monitor blood sugars if diabetic - steroids elevate glucose	ROUTINE	ROUTINE	ROUTINE
Avoid sick contacts while on high-dose steroids (immunosuppression)	ROUTINE	ROUTINE	-
Keep follow-up appointments - important to monitor for MS development	-	ROUTINE	ROUTINE
Contact physician if fever, new headache, or worsening vision on steroids	STAT	STAT	ROUTINE

4C. Lifestyle & Prevention¶

Recommendation	ED	HOSP	OPD
Smoking cessation - smoking increases MS conversion risk and worsens outcomes	ROUTINE	ROUTINE	ROUTINE
Vitamin D supplementation 2000-5000 IU daily (target serum 25-OH vitamin D >40 ng/mL) - low levels associated with MS risk	-	ROUTINE	ROUTINE
Avoid prolonged heat exposure (hot tubs, saunas, exercising in heat) which can temporarily worsen vision (Uhthoff)	-	ROUTINE	ROUTINE
Use sunglasses if photophobia present	ROUTINE	ROUTINE	ROUTINE
Regular aerobic exercise as tolerated once acute symptoms resolve	-	-	ROUTINE
Adequate sleep (7-8 hours nightly) and stress management	-	ROUTINE	ROUTINE
Eye protection during activities if monocular vision (loss of depth perception)	ROUTINE	ROUTINE	ROUTINE

SECTION B: REFERENCE¶

5. DIFFERENTIAL DIAGNOSIS¶

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
NMOSD-associated optic neuritis	Severe vision loss (often <20/200); bilateral simultaneous or sequential; poor recovery; longitudinally extensive optic nerve enhancement (>50% nerve length)	AQP4-IgG positive (Mayo CDS1 or NMOFS); MRI pattern
MOGAD-associated optic neuritis	Often bilateral; anterior optic nerve involvement; perineural enhancement ("optic nerve sheath sign"); disc edema more prominent; better steroid response; tends to relapse	MOG-IgG positive (Mayo CDS1 or MOGFS)
Anterior ischemic optic neuropathy (AION)	Sudden painless vision loss; altitudinal field defect; disc edema with hemorrhages; age >50; vascular risk factors (hypertension, diabetes)	ESR/CRP for GCA; fluorescein angiography; cardiovascular risk assessment
Giant cell arteritis (GCA)	Age >50; headache; jaw claudication; scalp tenderness; elevated ESR/CRP; bilateral risk	ESR, CRP, temporal artery biopsy; prompt treatment to prevent fellow eye
Papilledema	Bilateral disc edema; transient visual obscurations; headache worse lying down; no RAPD unless asymmetric	LP with elevated opening pressure; MRI/MRV for venous sinus thrombosis
Compressive optic neuropathy	Progressive vision loss; proptosis; may have disc pallor or edema; optic canal mass	MRI orbits showing mass lesion; CT for bony detail
Leber hereditary optic neuropathy (LHON)	Painless; young males; sequential bilateral (weeks to months); central scotoma; no enhancement on MRI	Mitochondrial DNA testing (mutations: 11778, 3460, 14484)
Toxic/nutritional optic neuropathy	Bilateral symmetric; ethambutol, methanol, B12/folate deficiency; cecocentral scotoma	B12, folate, medication history, alcohol use
Neurosyphilis	May mimic optic neuritis; other neurologic signs; risk factors	RPR/VDRL, FTA-ABS, CSF VDRL
Sarcoidosis	Granulomatous optic neuropathy; uveitis; other systemic involvement	ACE, chest CT, tissue biopsy
Idiopathic intracranial hypertension (IIH)	Bilateral disc edema; obese young female; headache; transient visual obscurations	LP with elevated opening pressure; normal MRI/MRV

6. MONITORING PARAMETERS¶

Parameter	Frequency	Target/Threshold	Action if Abnormal	ED	HOSP	OPD	ICU
Visual acuity	Daily inpatient; each visit OPD	Improvement by 3+ Snellen lines	If no improvement by 2 weeks, reconsider diagnosis or escalate treatment	STAT	ROUTINE	ROUTINE	-
Color vision (Ishihara or HRR plates)	Baseline and follow-up	Normal or improving	Persistent dyschromatopsia suggests residual dysfunction	-	ROUTINE	ROUTINE	-
Pupillary exam (RAPD)	Daily inpatient; each visit OPD	RAPD diminishing	Persistent or worsening RAPD concerning	STAT	ROUTINE	ROUTINE	-
Blood glucose	Q6h during IV steroids	<180 mg/dL	Insulin sliding scale; endocrine consult if persistent >250	STAT	ROUTINE	-	-
Blood pressure	Q shift during steroids	<160/100 mmHg	Antihypertensives PRN	STAT	ROUTINE	-	-
Mood and sleep	Daily during steroids	No psychosis, mania, severe insomnia	Psychiatry consult; consider dose reduction	-	ROUTINE	-	-
Visual field (formal)	Baseline, 1 month, 3 months, 6 months	Improving or stable	Worsening field concerning for progression	-	-	ROUTINE	-
OCT (RNFL thickness)	Baseline, 3 months, 6 months	Thinning plateaus by 6 months	>20 micron loss associated with poorer outcome	-	-	ROUTINE	-
MRI brain (follow-up)	3-6 months after initial; annually if MS risk	No new lesions	If new lesions: MS diagnosed, start DMT	-	-	ROUTINE	-
NMO/MOG antibodies (recheck)	Repeat at 3-6 months if initially negative but atypical features	Remain negative	If seroconversion: diagnosis changes, different treatment	-	-	ROUTINE	-

7. DISPOSITION CRITERIA¶

Disposition	Criteria
Discharge home	Mild-moderate vision loss with stable exam; able to perform ADLs safely; IV steroids completed or not indicated; reliable follow-up within 1-2 weeks with neuro-ophthalmology or neurology; understands return precautions
Admit to floor	Severe vision loss (20/200 or worse); bilateral involvement; diagnostic uncertainty requiring expedited workup; unable to care for self safely at home due to vision loss; IV steroids indicated and outpatient infusion not available
Admit to ICU	Not typically required for isolated optic neuritis; consider if concurrent severe neurologic involvement (e.g., NMOSD with myelitis and respiratory compromise)
Transfer to higher level	Neuro-ophthalmology or MS specialist not available; PLEX needed but unavailable; MRI unavailable for urgent imaging

8. EVIDENCE & REFERENCES¶

Recommendation	Evidence Level	Source
IV methylprednisolone accelerates visual recovery but does not change final outcome	Class I, Level A	Beck RW et al. NEJM 1992 (ONTT)
Oral prednisone alone (1 mg/kg) increases recurrence rate - avoid as monotherapy	Class I, Level A	Beck RW et al. NEJM 1992 (ONTT)
Visual prognosis excellent: 90%+ recover to 20/40 or better by 1 year	Class I	Beck RW et al. Arch Ophthalmol 1993
Brain MRI lesions predict MS: 50% at 15 years with >=1 lesion vs 25% with normal MRI	Class I	Beck RW et al. NEJM 2003 (ONTT 10-year); Optic Neuritis Study Group 2008 (15-year)
Cell-based assay (FACS) preferred for AQP4/MOG antibody testing	Class II, Level B	Pittock SJ et al. Neurology 2019; Waters P et al. J Neurol Neurosurg Psychiatry 2014
MOG-IgG associated with better visual recovery and relapsing course	Class II	Jarius S et al. J Neuroinflammation 2018
PLEX beneficial for steroid-refractory demyelinating optic neuritis	Class II, Level B	Roesner S et al. J Neurol 2012
VEP shows prolonged P100 latency in optic neuritis	Class I	Halliday AM et al. Lancet 1972
OCT RNFL thinning correlates with visual outcomes	Class II	Trip SA et al. Brain 2005
Vitamin D deficiency associated with increased MS risk after optic neuritis	Class II	Munger KL et al. JAMA 2006
Smoking increases MS conversion risk after CIS	Class II, Level B	Hedstrom AK et al. Brain 2013

CHANGE LOG¶

v1.1 (January 30, 2026) - Standardized lab tables (1A, 1B, 1C) to Test (CPT) | ED | HOSP | OPD | ICU | Rationale | Target Finding format with CPT codes - Added CPT codes to imaging tables (2A, 2B, 2C) - Standardized LP studies table with CPT codes and ICU column - Fixed structured dosing first fields to starting_dose :: route :: frequency :: full_instructions format - Standardized priority markers from checkmarks to STAT/ROUTINE in patient instructions, lifestyle, and monitoring tables - Fixed section header formatting to use ## SECTION format - Fixed 3D table separator formatting - Added ICD-10 code H46.8 - Added additional clinical synonyms - Bumped version to 1.1

v1.0 (January 27, 2026) - Initial creation - Comprehensive coverage of typical and atypical optic neuritis - ONTT-based treatment protocol with structured dosing - MS risk stratification based on brain MRI lesions - NMO-IgG and MOG-IgG testing recommendations - Emphasis on oral prednisone monotherapy avoidance - Visual prognosis and monitoring parameters - PubMed citations for all major recommendations

APPENDIX A: Typical vs Atypical Optic Neuritis Features¶

Feature	Typical (MS-Associated)	Atypical (Consider NMOSD/MOGAD/Other)
Age	20-45 years	<15 or >50 years
Pain	Present, mild-moderate, worse with eye movement	Absent OR severe
Vision loss severity	Mild-moderate (usually >20/200)	Severe (<20/200 or NLP)
Laterality	Unilateral	Bilateral simultaneous
Disc appearance	Normal (retrobulbar) or mild edema	Marked disc edema, hemorrhages
MRI optic nerve	Short segment enhancement	Longitudinally extensive (>50% nerve length) or posterior involvement to chiasm
Recovery	Good (>90% to 20/40)	Poor or incomplete
Steroid response	Responds then relapses off steroids	Highly steroid-dependent or refractory
Brain MRI	White matter lesions (MS pattern)	Normal or atypical lesion pattern

If ANY atypical features present: Order AQP4-IgG and MOG-IgG testing (Mayo CDS1 Panel preferred)

APPENDIX B: MS Risk Stratification Based on Brain MRI¶

Brain MRI Finding	5-Year MS Risk	15-Year MS Risk	Recommendation
Normal (no lesions)	~16%	~25%	Close clinical follow-up; MRI at 3-6 months then annually x 5 years
1-2 lesions	~37%	~50%	MS specialist referral; consider early DMT discussion
>=3 lesions	~51%	~78%	MS specialist referral; strongly consider DMT if McDonald criteria met

Data from ONTT long-term follow-up studies