1、The Optic Neuritis Treatment Trial ( ONTT ),R.R.Battu Narayana Nethralaya Bangalore,Classical Demyelinating Optic Neuritis,Young adults between 20 and 45 years F:M = 3:1 Monocular retro ocular pain particularly on eye movement (? Upward) Followed several hours or a few days later by rapid visual los
2、s occurring over a few days to a week Clinical examination : Dyschromatopsia (mostly red/green) and loss of contrast out of proportion to visual acuity loss. Afferent pupillary defect/RAPD Fundus shows either normal fundus or mild/moderate disc edema About 3 weeks later, visual acuity starts improvi
3、ng and continues to improve over the next 6 months.,Typical Demyelinating Optic Neuritis,Acute to subacute onset progressive over a few days to 2 weeksYoung adult patient, typically less than 45 years of age, but may be of any agePeriocular pain (90%), especially with eye movement preceding or coinc
4、iding with visual lossUnilateral loss of visual acuity variable severityReduced contrast and colour vision out of proportion to loss of visual acuityExacerbation of symptoms with increased body temperature (Uhthoffs phenomenon)Normal (65%) or swollen (35%) optic nerve head MS,Typical Demyelinating O
5、ptic Neuritis,Ipsilateral relative afferent pupillary defectMild periphlebitis (venous sheathing)Visual field defect almost any typeSpontaneous visual improvement in 90% starting within 23 weeks regardless of treatmentNo deterioration in vision when corticosteroids are withdrawnPallor of the optic d
6、isc is seen within 46 weeks from onset of visual lossAncillary investigations suggestive of MS,Atypical Optic Neuritis,Age 50 or 2 weeks from onsetPainless visual lossPain following onset of visual loss or persistent pain for 2 weeks from onsetSevere pain that restricts eye movements or wakes patien
7、t from sleepUnusual ocular findings: Marked anterior and/or posterior segment inflammation / Marked periphlebitis (venous sheathing) /Markedly swollen optic nerve head / Marked optic disc haemorrhages /Macular star,Lack of any visual recovery within 5 weeks or continued deterioration in visual funct
8、ionSymptoms or signs of a systemic disorder other than MSAfrican or Asian race Family historyCorticosteroid-dependent optic neuropathy/ deterioration in vision when corticosteroids are withdrawnPrevious history of neoplasiaAncillary investigations suggestive of a diagnosis other than MS (NMO, sarcoi
9、dosis, Behet syndrome),Atypical Optic Neuritis,Differential Diagnosis of Optic Neuritis,Corticosteroid-responsive optic neuropathies Sarcoidosis, systemic lupus erythematosus, Behet syndrome, autoimmune ON, NMO, chronicrelapsing inflammatory optic neuropathyOther inflammatory conditions Post-infecti
10、on, post-vaccination, neuroretinitis, acute disseminated encephalomyelitisCompressive optic neuropathies Primary tumours, gliomas, meningioma, pituitary tumours particularly craniopharyngioma in children, metastases, sinus mucocoeles, arterial aneurysmsIschaemic optic neuropathies Anterior and poste
11、rior ischaemic optic neuropathy, giant cell arteritis, diabetic papillopathy,Infective conditions Tuberculosis, syphilis, Lyme disease, viral ON, toxocariasis or helminthitis (usually visible retinal/optic head lesion)Toxic and nutritional optic neuropathy Vitamin B12 deficiency, tobacco-ethanol amb
12、lyopia, methanol intoxication, ethambutol toxicityInherited conditions Leber hereditary optic neuropathyOcular causes Posterior scleritis, maculopathy, retinopathy, big blind spot syndromePeriorbital infection Cellulitis, severe suppurative sinusitisFactitious visual loss Intentional or hysterical,D
13、ifferential Diagnosis of Optic Neuritis,Multiple Sclerosis ( MS ),Schumacher Criteria 1965 clinical Poser Criteria 1983 MRI and spinal taps McDonalds Criteria 2001 MRI and clinical,Multiple Sclerosis,Relapsing / Remitting Multiple Sclerosis ( RRMS) - 55%,Progressive Relapsing Multiple Sclerosis (PRM
14、S) - 5%,Secondary Progressive Multiple Sclerosis (SPMS) - 30%,Primary Progressive Multiple Sclerosis (PPMS) - 15%,The Optic Neuritis Treatment Trial,Interventional (drug), randomised single blind placebo controlled trial To determine the natural history of vision in patients who suffer optic neuriti
15、s. To assess the beneficial and adverse effects of corticosteroid treatment for optic neuritis. To identify risk factors for the development of multiple sclerosis in patients with optic neuritis.,Questions asked,(1) Does treatment with either oral prednisone or intravenous methylprednisolone followe
16、d by oral prednisone improve the visual outcome of acute optic neuritis? (2) Does either treatment speed recovery of vision? and (3) Are the complications of treatment insignificant in relation to the magnitude of the treatment effect?,Treatment phase ( ONTT ) Long term follow up phase ( Longitudina
17、l optic neuritis study LONS ),Oral prednisone (1 mg/kg/day) for 14 days 156 patients randomisedIntravenous methylprednisolone (250 mg every 6 hours) for 3 days, followed by oral prednisone (1 mg/kg/day) for 11 days 151 patients randomisedOral placebo for 14 days 150 patients randomised,Follow up,7 f
18、ollow up visits during the first 6 months Primary outcome at 6 months At one year Yearly upto 1997 2001 2002 2006,Baseline and Follow up tests,Neurological evaluation Visual Acuity Contrast Colour Fields Vision specific quality of life questionnaire,Parameters assessed Visual acuity ( BCVA ) - Logma
19、r for analysisColour vision - Ishihara and FM-100 HueVisual fields - Humphrey 30-2 and GoldmanContrast Sensitivity - Pelli Robson Chart,Classification of Changes on Brain Magnetic Resonance Images,Graded 0 to 4 based on the following criteria Number of lesions Size and shape of lesions: 3 mm, 20 mm
20、Location of lesions: periventricular, peripheral white matter, grey matter, brainstem, cerebellum and corpus callosum,Baseline characteristics,Eligibility criteria: 8 to 45 years unilateral optic neuritis, with visual symptoms of 8 days duration or less relative afferent pupillary defect field defec
21、t in the affected eye,Ancillary Tests,neurologic examination MRI glucose,antinuclear antibody ANA, and fluorescent treponemal antibody absorption FTAABS1 tests CXR MS classification by Posers classification,CSF evaluation and MRI,The presence of oligoclonal bands in the CSF strongly correlated with
22、the future development of MS However, the presence of oligoclonal bands strongly correlated with an MRI positive for one or more lesions THERE IS NO NEED TO DO A CSF ANALYSIS IN CLASSICAL DEMYELINATING ON, HOWEVER, AN MRI WOULD BE MANDATORY TO ASSESS PROGNOSIS,Results,448 patients at entry 300 at 15
23、 year f.u. M: F = 22.8% : 77.2% 1: 3 Age : 31.8 +/- 6.7 years,The Clinical Profile of Optic Neuritis Experience of the Optic Neuritis Treatment Trial Optic Neuritis Study Group,(Arch Ophthalmol. 1991;109:1673-1678),Visual Acuity in ON,Course of VA recovery 79% start recovering in 3 weeks and 96% sta
24、rt recovery in 5 weeks At 1 year: 93% had VA 20/40 and 69% had achieved 20/20 At 15 years: 92% had VA 20/40 and 72% had achieved 20/20 85% of patients with VA 20/200 at presentation had EVENTUAL VA of 20/40In classical monocular demyelinating ON, VA recovery occurs soon and most patients achieve nor
25、mal or near normal vision. This is across all treatment groups with no statistical difference between groupsThe best predictor of EVENTUAL acuity was initial acuityFinal VA was worse in patients EVENTUALLY diagnosed as MS,The role of steroid,THERE IS NO ROLE OF ORAL STEROID In the 5 year outcome stu
26、dies, oral steroid use was significantly associated with recurrent optic neuritis THERE IS A ROLE FOR IV METHYLPREDNISOLONE AND THIS IS TO SHORTEN THE PERIOD OF RECOVERY THIS DOES NOT AFFECT FINAL VISUAL ACUITY THE INDICATIONS FOR IVMP IN CLASSICAL DEMYELINATING ON MONOCULAR PATIENTS SEVERE BILATERA
27、L VISUAL LOSS OCCUPATIONAL REQUIREMENTS * REVIEW VA AFTER A MONTH LACK OF IMPROVEMENT MANDATES EVALUATION FOR OTHER CAUSES OF ON,Recurrence of ON,28% develop recurrence in 5 years, 35% develop recurrence in 10 years At 5 (10) years, higher in the oral pred group 41% (44%), than in the placebo/IVMP g
28、roup 25% (29%) More likely in patients who subsequently diagnosed as MS,Risk of MS,OVERALL AT 10 YEARS - 38% AT 15 YEARS - 50%The influence of gender 35% of males and 75% of females ultimately develop MS ( a non ONTT observation ) The 2 year follow up study showed that IVMP has a protective role in
29、the development of MS, but this was not significant after the 3rd year,MRI and risk of developing MS,CIS Clinically isolated event monocular optic neuritis CDMS Clinically definite MS,Without MRI findings,At 5 years - 16% At 10 years - 22%At 15 years - 25%,Only 3% increased risk after 10 years,With
30、MRI findings,At 5 years - 37% with 1-2 lesions- 51% with 3 lesions At 10 years - 56% with 1 lesionAt 15 years - 75% with 1 lesion,20% increased risk after 10 years,Protective factors,Male gender Optic nerve head swelling papillitis Atypical presentation severe optic disc swelling Disc or peripapilla
31、ry haemorrhages Retinal exudates Absent pain Vision no PL,Brief Bibliography,PN Shams, GT Plant. Optic Neuritis: A ReviewThe International MS Journal 2009; 16: 8289Multiple Sclerosis Risk after Optic Neuritis: Final Optic Neuritis Treatment Trial Follow-Up. The Optic Neuritis Study Group*. Arch Neur
32、ol. 2008 June ; 65(6): 727732.The Clinical Profile of Optic Neuritis. Experience of the Optic Neuritis Treatment Trial. Optic Neuritis Study Group. Arch Ophthalmol. 1991;109:1673-1678Roy W. Beck, Robin L. Gal, Treatment of Acute Optic Neuritis. A Summary of Findings From the Optic Neuritis Treatment
33、 Trial. ARCH OPHTHALMOL/VOL 126 (NO. 7), JULY 2008Long-term Brain Magnetic Resonance Imaging Changes After Optic Neuritis in PatientsWithout Clinically Definite Multiple Sclerosis Optic Neuritis Study Group. Arch Neurol. 2004;61:1538-1541,ONTT,The results of the ONTT are applicable to monocular demyelinating typical optic neuritis Beware of applying these results to all cases presenting with “optic neuritis” In general, the visual outcome is usually good irrespective of treatment The MRI (T-2 weighted 1.5 Tesla ) is an extremely important prognosticator for future MS,
