_optic neuritis treatment trial ontt 视神经炎治疗试验课件

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 loss 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 improving and continues to improve over the next 6 months. Typical Demyelinating Optic Neuritis Acute to subacute onset progressive over a few days to 2 weeks Young adult patient, typically less than 45 years of age, but may be of any age Periocular pain (90%), especially with eye movement preceding or coinciding with visual loss Unilateral loss of visual acuity variable severity Reduced contrast and colour vision out of proportion to loss of visual acuity Exacerbation of symptoms with increased body temperature (Uhthoffs phenomenon) Normal (65%) or swollen (35%) optic nerve head MS Typical Demyelinating Optic Neuritis Ipsilateral relative afferent pupillary defect Mild periphlebitis (venous sheathing) Visual field defect almost any type Spontaneous visual improvement in 90% starting within 23 weeks regardless of treatment No deterioration in vision when corticosteroids are withdrawn Pallor of the optic disc is seen within 46 weeks from onset of visual loss Ancillary investigations suggestive of MS Atypical Optic Neuritis Age 50 or 2 weeks from onset Painless visual loss Pain following onset of visual loss or persistent pain for 2 weeks from onset Severe pain that restricts eye movements or wakes patient from sleep Unusual 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 function Symptoms or signs of a systemic disorder other than MS African or Asian race Family history Corticosteroid-dependent optic neuropathy/ deterioration in vision when corticosteroids are withdrawn Previous history of neoplasia Ancillary investigations suggestive of a diagnosis other than MS (NMO, sarcoidosis, Behet syndrome) Atypical Optic Neuritis Differential Diagnosis of Optic Neuritis Corticosteroid-responsive optic neuropathies Sarcoidosis, systemic lupus erythematosus, Behet syndrome, autoimmune ON, NMO, chronic relapsing inflammatory optic neuropathy Other inflammatory conditions Post-infection, post-vaccination, neuroretinitis, acute disseminated encephalomyelitis Compressive optic neuropathies Primary tumours, gliomas, meningioma, pituitary tumours particularly craniopharyngioma in children, metastases, sinus mucocoeles, arterial aneurysms Ischaemic optic neuropathies Anterior and posterior 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 amblyopia, methanol intoxication, ethambutol toxicity Inherited conditions Leber hereditary optic neuropathy Ocular causes Posterior scleritis, maculopathy, retinopathy, big blind spot syndrome Periorbital infection Cellulitis, severe suppurative sinusitis Factitious visual loss Intentional or hysterical Differential 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 (PRMS) - 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 neuritis. 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 followed 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 ( Longitudinal optic neuritis study LONS ) Oral prednisone (1 mg/kg/day) for 14 days 156 patients randomised Intravenous methylprednisolone (250 mg every 6 hours) for 3 days, followed by oral prednisone (1 mg/kg/day) for 11 days 151 patients randomised Oral placebo for 14 days 150 patients randomised Follow up 7 follow 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 ) - Logmar for analysis Colour vision - Ishihara and FM-100 Hue Visual fields - Humphrey 30-2 and Goldman Contrast 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 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 defect 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 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 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% start 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 20/40 In classical monocular demyelinating ON, VA recovery occurs soon and most patients achieve normal or near normal vision. This is across all treatment groups with no statistical difference between groups The best predictor of EVENTUAL acuity was initial acuity Final 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 studies, 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 BILATERAL 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 group 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 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 MRI findings At 5 years - 37% with 1-2 lesions - 51% with 3 lesions At 10 years - 56% with 1 lesion At 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 peripapillary haemorrhages Retinal exudates Absent pain Vision no PL Brief Bibliography PN Shams, GT Plant. Optic Neuritis: A Review The International MS Journal 2009;