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Log in Main page Articles Getting Started Help Recent changes Demyelinating Optic Neuritis Original article contributed by: All contributors: Assigned editor: Review: Guy V. Jirawuthiworavong, M.D., M.A. Aaron M. Miller, MD, MBA, FAAP, Dale Fajardo, Ed.D., M.B.A., Guy V. Jirawuthiworavong, M.D., M.A. and WikiWorks Team Guy Jirawuthiworavong Assigned status Update Pending by Guy V. Jirawuthiworavong, M.D., M.A. on February 3, 2015. Demyelinating optic neuritis in an adult is one of the most common reasons why a patient may seek consultation with a neuro-ophthalmologist. This brief guide will help the general ophthalmologist to understand: 1. optic neuritis is a clinical diagnosis, thus MRI of the orbit with gadolinium looking for optic nerve enhancement, blood testing for inflammatory or infectious etiologies, and lumbar puncture are not needed for the diagnosis, 2. typical (unilateral vision decrease, pain with eye movement) optic neuritis will recover with good visual prognosis by 6-12 months, 3. the final amount of vision recovery is independent of treatment with or without IV steroids, (IV STEROIDS DO NOT IMPROVE VISUAL OUTCOME, THE NATURAL HISTORY AND PROGNOSIS OF TYPICAL OPTIC NEURITIS IS VERY FAVORABLE WITH OR WITHOUT IV STEROID TREATMENT), 4. oral prednisone alone is CONTRAINDICATED because it has been shown to cause more recurrences to the affected eye or new episodes in the contralateral eye compared to placebo or IV steroids followed by oral prednisone, 5. MRI of the brain is a must after an initial episode of optic neuritis because the number of lesions will stratify patients’ risk for developing clinically definite multiple sclerosis (CDMS) after a clinically isolated syndrome (CIS), and 6. the ophthalmologist can play a vital role to decrease morbidity from multiple sclerosis (MS) by understanding the role of early treatment with disease modifying drugs (DMD). This article will focus on adults, 18 years and older who present with optic neuritis. Disease Entity Optic neuritis ICD 377.3 Retrobulbar neuritis (acute) ICD 377.32 Optic neuritis unspecified, ICD 377.30 Disease Optic nerve inflammation that is accompanied with decreased vision, optic nerve dysfunction (decreased peripheral vision, decreased color vision, decreased contrast/brightness sense, relative afferent papillary defect (RAPD)) and tends to be associated with periorbital pain, especially with eye movement. Prevalence roughly estimated to be 1-5/100,000 depending upon geography and ethnicity. Etiology Unknown cause, felt to be an autoimmune process Risk Factors 3:2-female:male ratio Young age (20-45 years old) A prodromal flu like illness commonly accompanies the event but does not always occur Multiple Sclerosis-up to 75% of patients with CDMS will have at least one episode of optic neuritis in their lifetime. Autopsies of patients with CDMS show up to 90% optic nerve involvement. General Pathology Immune-mediated inflammatory demyelination of the optic nerve. The myelin undergoes destruction causing axons to poorly conduct impulses. With recurrences, the damage to the retinal ganglion cell becomes irreparable. Pathophysiology After myelin destruction occurs, the retinal ganglion cell axons starts to degenerate. Monocytes localize along blood vessels, and macrophagaes follow to remove myelin. Astroctyes then proliferate with deposition of glial tissue where axons may have been present before. These gliotic (sclerotic) areas can be multiple in number througout the brain and spinal cord, hence the term mutliple sclerosis. Diagnosis Optic Neuritis is a clinical diagnosis that is made when a patient presents with unilateral decreased visual acuity pain with eye movement and/or periorbital discomfort RAPD visual field defect optic nerve swelling (35% anterior disc edema, 65% retrobulbar) Patients recruited in the Optic Neuritis Treatment Trial (ONTT) were selected based on decreased unilateral vision loss for 8 days or less, but the presence of a RAPD or a visual field defect were not required. An enhancing optic nerve seen on MRI post-gadolinium is helpful but not required to make the diagnosis. Less commonly, patients may present with absence of eye pain, absence of orbital discomfort, bilateral vision loss, no light perception vision, severe disc swelling with hemorrhages of the optic disc or retinal exudates. These are considered more atypical signs and symptoms of optic neuritis. 3% of patients in the ONTT presented with no light perception vision. History A prodromal viral illness may occur. Patients often experience orbital pain and pain with eye movement prior to visual changes. The pain can be excruciating or very mild like a foreign body sensation. The visual change is often acute and typically worsens over a few days and nadirs around 2 weeks prior to improvement. Physical examination Snellen visual acuity with best correction for distance and/or near vision Color vision and/or Contrast measurement (Pelli-Robson or VisTech) Swinging flashlight test for RAPD Evaluation of extraocular movement Confrontation visual fields Amsler grid with best correction central visual field defects (be aware that this test may also be abnormal in macular disease) Biomicroscopy/direct ophthalmoscopy of the optic nerve and retina SignsDecreased visual acuity Decreased color vision (red desaturation) and/or decreased contrast/brightness sense RAPD unless both eyes are affected or RAPD was present prior in contralateral eye Ocular dysmetria of internuclear ophthalmoplegia Any scotoma on Amsler grid and/or confrontation visual fields or formal visual field testing Disc edema (only 35% noted in ONTT, thus lack of disc edema does not rule out acute optic neuritis) Retinal vascular sheathing, pars planitis (periphlebitis occurs in 5-10% of multiple sclerosis patients) Symptoms acute vision loss that tends to worsen over days eye discomfort or pain particularly with eye movement (mild to severe) phosphenes (flashes of lights) vision becomes blurry when body temperature rises during exercise or bathing in warm to hot water (Uhthoff's phenomenon) "washed out" color vision dimmed vision (contrast on t.v. is turned down) dark vision loss of central vision or part of the peripheral/side vision altered perception of motion (Pulfrich phenomenon) Clinical diagnosis Optic neuritis is diagnosed clinically by symptoms of acute unilateral decrease in vision, eye painespecially with movement and signs of a RAPD, decreased color vision/contrast/brightness sense and documentation of a visual field defect. A MRI depicting enhancement of the optic nerve after administration of gadolinium is helpful but not required to make the clinical diagnosis and neither is disc swelling required to be present. Relative recovery of vision at 6 months from onset tends to be the natural progression of the disease. However, 12% of patients may not recover 20/40 or better vision, and the ones that do recover, have residual vision changes such as decreased contrast. Diagnostic procedures MRI is a must to help risk stratify patients for the development of MS after the acute initial onset of optic neuritis. Multiple sclerosis plaques are seen as white matter lesions on MRI scans. MRI of the brain with FLAIR sequences of axial, coronal and sagittal planes can help identify lesions >3mm in size, or large (>6mm) ovoid lesions abutting the lateral ventricles. "Dawson's Fingers" (periventricular white matter lesions on mid-sagittal FLAIR sequences that involve the corpus collosum) are highly suggestive of MS. Not all high-signal abnormalities in white matter are diagnostic of MS, thus one must use caution when considering these findings in the assessment for MS. The lesions can be present in healthy patients over age 50 who have hypertension, atherosclerosis, as well as other diseases such as vasculitis. Optical coherence tomography (OCT) of the nerve fiber layer (NFL) is helpful as an adjunctive measurement of nerve function in patients with optic neuritis. OCT is a diagnostic technique introduced into clinical practice in 1997 and widely utilized by retina specialists. It's use in glaucoma and neuroophthalmology is currently evolving and still at its formative stages. OCT uses the principal of reflection of low coherence radiation from tissue to measure layers of the retina and nerve fiber layer at a resolution of <10 microns with spectral-domain OCT. OCT can quantify the onset of optic atrophy and pallor that ensues 6-8 weeks post onset of optic neuritis. Optic atrophy can be subtle on biomicroscopy, thus OCT is useful for detection and quantification of the optic atrophy. OCT of the NFL also serves in patient education and documentation. A lumbar puncture is not required for the diagnosis of optic neuritis. However, presence of CSF levels of oligoclonal bands and elevated IgG synthesis are data that is considered in the McDonald diagnostic criteria for MS. A spinal tap can also help to rule out elevated intracranial pressure in cases of atypical bilateral optic neuritis with bilateral anterior disc edema. The CSF can also be examined for infectious and inflammatory conditions as well in atypical cases of optic neuritis. Laboratory test Typical optic neuritis (unilateral, pain with eye movment, no uveitis) does not require any blood testing. Bilateral optic neuritis with poor visual recovery is atypical and a blood test for neuromyelitis optica (Devic's disease) should be entertained. The test is the neuromyelitis optica (NMO) antibody which is available commercially. If vision loss has occurred in a young male with a significant family history of maternally-related males with bilateral vision loss, genetic consulting and testing should be entertained for Leber's hereditary optic neuropathy. Leber’s hereditary optic neuropathy patients are much less likely to recover vision and the contralateral eye is often affected within weeks to months of the first eye. Differential diagnosis Differential Diagnosis for Retrobulbar Optic Neuritis (normal appearance of optic nerve and vision loss)[edit source] Of note, the conditions noted below tend to be painless in nature, whereas 92% of patients with demyelinating optic neuritis present with some form of eye pain and/or eye pain with movement. With a relative Afferent Pupillary Defect Compressive lesion Central serous chorioretinopathy (OCT of the macula can help to rule out macular etiology) Central retinal artery occlusion Posterior ischemic optic neuropathy Infiltrative lesion Toxic/metabolic (early without optic atrophy, tends to be more symmetric) No relative Afferent Pupillary Defect Visual field defects from brain infarct, tumor, lesion Retinal degeneration such as retinitis pigmentosa Macular disease (OCT of the macula helpful) o Age-related macular degeneration o Macular edema (post-cataract surgery, diabetic) o Central serous chorioretinopathy o Macular hole (traumatic, idiopathic) o Epiretinal membrane/surface wrinkling maculopathy o Documented apriori contralateral eye RAPD Differential Diagnosis of Optic Neuritis (unilateral optic nerve edema, vision loss) Anterior ischemic optic neuropathy (tends to be painless in nature) Pending central retinal vein occlusion (painless) Optic papillitis in patient with uveitis (Vogt-Koyanagi-Harada (VKH) syndrome, sarcoidosis) Diabetic papillopathy (painless) Compressive lesion along the anterior pathway of the optic nerve (up to and including optic chiasm) Disc drusen (pseudodisc edema, visual field defects common due to crowding of the disc, painless) Infectious optic neuritis (syphilis, lyme, herpes viradae (HSV, VZV); Bartonella-often with macular star in neuroretinitis) Vasculitis (SLE, granulomatous) Malignant hypertension (tends to be bilateral) Infiltrative-CNS leukemia, CNS lymphoma, metastatic lesion Posterior scleritis (pain with eye movement, decreased vision, B-scan with thickened choroid and fluid-"T-sign") Mutiple evanescent white dot syndrome (MEWDS)-(painless, "wreath sign" on fluorescein angiography) Leber's hereditary optic neuropathy (painless, telangiectatic disc vessels) Vascular lesion-(juxtapapillary hemangioblastoma, combined hamartoma of the retina and RPE) Radiation induced optic neuropathy Management Optic Neuritis Treatment Trial (ONTT) Multi-centered, randomized, prospective, controlled clinical trial that was designed to evaluate the efficacy and safety of oral prednisone vs. intravenous methylprednisolone followed by oral prednisone as compared with oral placebo for the treatment of acute optic neuritis. Patients were recruited from July, 1988 to June, 1991. 457 patients (85% Caucasian, range of 18-60 years old) at 15 different medical centers with presentation of symptoms of decreased vision at 8 days or less without any prior episodes of optic neuritis, not currently on any prednisone, and without any significant systemic diseases were randomized to either: 1) oral placebo, 2) 250mg IV solumedrol q6hrs for 3 days then 1mg/kg of prednisone for 11 days, or 3) 1mg/kg of PO prednisone alone for 14 days. Primary outcome measures were contrast sensitivity and visual field and secondary measures were vision and color. The patients were followed for a minimum of 6 months. ONTT Outcomes 1. IV steroid treated patients recovered faster within the first 4-6 weeks post onset. However at 6 months to 10 years out, there was no statistical difference in final visual outcome between IVsteroid treated patients and placebo. 2. ORAL STEROIDS ALONE ARE CONTRAINDICATED FOR ACUTE OPTIC NEURITIS BECAUSE OF HIGHER RATE OF RECURRENCES OF OPTIC NEURITIS. Practically speaking, physicians may vary in the implementation of the ONTT. Some physicians give 1gm IV bolus daily for 3 to 5 days as outpatient infusion. Furthermore, some physicians may or may not give the 11 day oral prednisone taper that follows. There still may exist among physicians the misconception that IV steroids improve visual outcome by 6 months out. This is not the case. It is given to hasten recovery the first 4-6 weeks after onset. Ultimate visual outcome is the same with or without the administration of IV steroids in typical optic neuritis. Medical therapy -Side effects of IV steroids should be fully discussed, especially in diabetics. -Oral steroids are contraindicated in patients who have acute optic neuritis especially in patients that carry a diagnosis of MS Medical follow up Visual acuity, (color vision and/or contrast can elucidate subtle changes not seen on Snellen acuity testing) Visual field testing upon onset if possible (Humphrey visual field or Goldmann visual field) and repeat at follow up visual fields at 3, 6 and 12 months. OCT of the NFL at onset, at 6-8 week visit, and at 6 month follow up for quantitation of optic atrophy. Complications Visual prognosis is excellent with normal to near normal recovery. Patients may still complain of decreased brightness sense, contrast deficit, and loss of steropsis. It is important to forewarn them at the beginning that eventhough visual recovery is the norm, they still have the possibility of: permanent visual loss either mild (20/30) to severe (20/200 or worse) permanent scotomas that may limit driving recurrences IV steroids at high dosages for the treatment of optic neuritis according to the ONTT can cause insomnia, mood changes, dyspepsia, weight gain, flushing, nausea, vomiting, and elevated blood pressure. Patients should be advised to take a proton pump inhibitor such as omeprazole and may need to seek medical attention for anxiety and insomnia. Diabetics may be at risk for episodes of hyperglycemia and also for diabetic ketoacidosis. Co-management with the patient's primary physician, internist or endocrinologist is a must. Prognosi 94% recover 20/40 or better at 5 years out in the ONTT. 20/200 or worse visual outcome occurred in 3% of patients at 5 years out in the ONTT. Visual recovery tends to occur by 1 month after onset and the majority recover by 1-3 months time. At 6 months, patients tend to have similar visual outcomes no matter if they were treated with IV steroids or placebo. Vision improvement can take up to one year. Prolonged pain with eye movement, lack of recovery, recurrence within 2 months would alert the physician to re-evaluate for atypical causes of optic neuritis such as sarcoidosis, syphilis or an idiopathic autoimmune optic neuritis that is steroid-responsive. 28% of patients developed recurrent optic neuritis which was associated with oral prednisone. As a result, oral steroids is contraindicated in the management of acute optic neuritis. Since optic neuritis is common among patients who have MS, (up to 75% have at least one episode of optic neuritis in their life time), these patients are at risk for developing CDMS. The ONTT showed that even without any lesions present on MRI, there still was a 16% chance of developing MS in 5 years and 22% in 10 years. Patients are counseled about the importance of getting a brain MRI as well as watchful waiting of other peripheral or central neurological deficits in the future. At 10 years, the overall risk of MS was 38% after an initial episode of optic neuritis. That risk is 56% if the MRI had 1 or more lesions. The risk is lower if the patient is male, disc swelling is present, pain is absent, vision is no light perception, severe optic disc swelling with hemorrhages are seen, or macular exudates such as a retinal star pattern occur. In patients with CDMS, the median time to diagnosis was 3 years and 34% of the diagnoses were made in the first 2 years whereas 72% were made within 5 years. In MS, clinically isolated syndromes (CIS) such as optic neuritis have been a focus for clinical trials. Is there a role for disease modifying drugs (DMD) in the postponement of developing CDMS when patients present initially with CIS optic neuritis and are at high risk for CDMS due to the presence of 2 or more lesions on MRI? Three randomized prospective clinical trials have examined this question. Controlled High-Risk Avonex Multiple Sclerosis Prevention Study (CHAMPS) Early Treatment of Multple Sclerosis Study (ETOMS) Betaseron in Newly Emerging Multple Sclerosis for Initial Treatment Trial (BENEFIT). The DMD in these studies were as follows: IM weekly interferon beta-1a (Avonex) in CHAMPS SC weekly interferon beta-1a (Rebif) in ETOMS SC every other day interferon beta-1b (Betaseron) in BENEFIT. Patients were recruited and randomized to DMD or placebo. In CHAMPS, ETOMS, and BENEFIT, DMDs were shown to reduce the probability of CIS converting to CDMS compared to placebo. MRI scans showed less new lesions in DMD treated groups as compared to patients receiving placebo in CHAMPS and ETOMS. Thus, patients with signs and symptoms of acute optic neuritis (CIS) require prompt MRI brain imaging for lesions (>3mm) to determine if they are at high risk for the development of CDMS. Early treatment with interferon-beta can effectively reduce the risk of developing CDMS by up to 50% in patients with CIS. Thus, the ophthalmologist plays a pivotal role on the front lines when a patient presents to their office with acute optic neuritis. Additional Resources www.nanos-web.org References 1.Miller NR, Newman NJ, et al, eds. Walsh & Hoyt's Clinical Neuro-ophthalmology. 6th ed. Lippincott Williams & Wilkins; 2005:3460-3497. 2.Neuro-Ophthalmology, Section 5. Basic and Clinical Science Course, AAO, 2003. 3.Cleary PA, Beck RW, Anderson MM Jr, et al. Design, methods, and conduct of the Optic Neuritis Treatment Trial. Control Clin Trials. 1993;14(2):123-42. 4.Optic Neuritis Study Group. The 5-year risk of MS after optic neuritis. Experience of the Optic Neuritis Treatment Trial. Neurology. 1997;49:1404-1413. 5.Trobe JD, Sieving PC, Guire KE, et al. The impact of the optic neuritis treatment trial on the practices of ophthalmologists and neurologists. Ophthalmology. 1999;106(11):2047-53. 6.Jacobs LD, Beck RW, Simon JH, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med.2000;343:898-904. 7.McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol.2001;50(1):1217. 8.Comi G, Filippi M, Barkhof F,et al.; Early Treatment of Multiple Sclerosis Study Group. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet. 2001;357(9268):1576-82. 9.Optic Neuritis Study Group. High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis. Arch Ophthalmol. 2003;121:944-949. 10.Fisher JB, Jacobs DA, Markowitz CE, et al. Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology. 2006;113(2):324-32. Epub 2006 Jan 10. 11.Kappos L, Freedman MS, Polman CH, et al. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. BENEFIT Study Group. Lancet Neurol. 2009;8(11):987-97. Epub 2009 Sep 10. 12.Comi G. Shifting the paradigm toward earlier treatment of multiple sclerosis with interferon beta. Clin Ther. 2009;31(6):1142-57.