optic neuritis
TRANSCRIPT
OPTIC NEURITIS
Dr Rishi Jhalani
Anatomy
Axons of ganglion cells converge to form the optic nerve The optic nerve contains 1,000,000 axons The nerves hemidecussate at the chiasm and end at the lateral geniculate body
47-50 mm
Parts:i. ii. iii. iv.
Intraocular part (1mm) Intraorbital part (30mm) Intracanalicular part (69mm) Intracranial part (1cm)
DefinitionInvolvement of any part of the optic nerve by a disease process that impairs nerve conduction, as indicated by loss of visual acuity and changes in field of vision
Age : 20-50yrs (30yr) Rare in children More common in females(77%)
ClassificationOphthalmoscopic
Aetiological
Retrobulbar neuritis Papillits Neuroretinitis
Demyelinating Parainfectious Infectious Non infectious
Retrobulbar neuritis
Nl appearance of optic disc No involvement of optic nerve head Most common type
Frequently associated with MS
Papillitis
Characterized by disc hyperemia & edema
Peripapillary hemorrhages Most common type in children
Neuroretinitis
Papillitis associated with inflammation of retinal nerve fibre layer & macular star figure
MS & ON
15-20% of MS present with ON ON seen at some point in time in 50% cases
10 yr risk of MS after acute attack of ON : 38%Even if MRI lesions are present, clinical MS DOES NOT develop in 44% cases Risk of MS is increased in winters & HLADR2 in ON patients
SymptomsTriad :
Loss of vision Ipsilateral eye pain Dyschromatopsia
Associated :
Movement phosphenes Sound induced phosphenes Visual obscuration in bright light Uhthoffs symptom
LOSS OF VISION
PAIN
Typically deteriorates over
hours to days Reaches a trough 1 week
post onset Subtle or profound
Unilateral loss(70%)
Deep orbital, retroocoular,brow pain May precede decrease in visual acuity. Aggravated with eye movement Increased on globe pressure Reaches maximal severity in 24 36 hrs & spontaneously resolves in 48 72 hrs. Does not correlate with severity of visual loss or enlargement of optic nerve
DYSCHROMATOPSIA
VISUAL OBSCURATION IN BRIGHT LIGHT Patient sees better in dim light Vision becomes more impaired as background luminance increases. Objects appear to flicker off and on flicker scotoma.
Reduced vividness of saturated colors. In absence of a macular lesion, color desaturation is highly sensitive indicator of optic nerve disease.
PHOSPHENESMovement ph
Sound ph
Can occur without prev hx of ON Before/with the attack Occurs with horizontal eye movements. Are best perceived in dark with eyes closed.
Precipitated by sudden noise when patient is resting in dark.
UHTHOFFS SYMPTOMS~ Episodic transient obscuration of vision with
exertion, high core temperature.~ Blurred vision &color desaturation in the affected eye 5
20 minutes after exposure to the provoking factor recovery in 5 60 minutes~ Provoking factors ~ physical exertion, hot bath, hot weather, hot drinks, stress, tiredness.
~
Correlates with higher incidence of recurrent optic neuritis Correlates significantly with the presence of multifocal white matter lesions in brain& conversion to MS.
~
SIGNSI.
II.III. IV. V. VI.
Reduced visual acuity RAPD Impaired contrast sensitivity Decreased stereoacuity Visual field defects Optic disc changes
STEREOACUITY 20/20 + binocular fixation = 40 sec of arc Titmus 3D stereoacuity test Pulfrich effect
IMPAIRED CONTRAST SENSITIVITY
Measurement of peak contrast sensitivity is an effective indicator of sub clinical ON. Abnormal contrast sensitivity was present in 99% in ONTT.
RAPD
Present in almost all unilateral cases Acute ON= 44% Recovered ON = 17- 55%
OPTIC DISC60 % - normal disc 20 % - swollen disc 20 % - blurred, hyperemic
Recovered pts. 40 % normal disc 20 % total disc pallor
RETINAL CHANGESRetinal venous sheathingo
Round/confluent white exudates on a peripheral vein, with posterior vitreous cells 28 % casesCan resolve completely & then recur All pts. with MS will have venous sheathing at some point of their lives.
o
o
o
NERVE FIBRE DEFECTS
Present in 70% of cases Gradual progressive nature without visual symptoms Slits in nerve fiber striations
If slits are present in normal eye of a patient with contra lateral ON : secondary sub clinical optic nerve lesions.
VISUAL FIELDS
Generalized depression of sensitivity(48%) Centrocecal scotoma Plotting the field of the contralateral eye is important --- subtle temporal depression sellar mass Present in 48% of fellow eyes.
CT SCAN
Enlargement and contrast enhancement of the affected nerve
MRI~ With or without gadoilinium scan~ Abnormalities seen in 55-70 % cases with ON and 90-98% cases of clinically definite MS ~ Lesions are hypertense, round or ovoid.
Most commonly distributed in a perpendicular pattern around the ventricles following a perivascular course
ONTT follow up :>2 lesions of white matter : highly predictive of development of MS in monosynptomatic patients (50%)
Axial MRI scan
VEP
Technique of choice to objectively confirm weak clinical evidence & to detect subclinical abnormality
Pattern shift VEP
2 types Pattern electroretinogram
Pattern VEP
Pattern VEP tests the central and perifoveal visual fields Prolongation of P100 latency Difference in interocular P100 latency Disadvantage nonspecific.
PERG
Monitors the integrity of central retinal ganglion cell layer Reqd : delay in pVEP is not due to maculopathy or anterior visual dysfunction
TREATMENT & TRIALS
ROLE OF CORTICOSTEROIDS
OPTIC NEURITIS TREATMENT TRIALi.
To assess the beneficial and adverse effects of corticosteroid treatment for optic neuritis. To determine the natural history of vision in patients who suffer optic neuritis. To identify risk factors for the development of multiple sclerosis in patients with optic neuritis.
ii.
iii.
Major eligibility criteriaAge 18 46 yrs. 2 white matter lesions : 51% risk of MS/5yrs 1-2 lesions : 37 Normal MRI : 16%
ix.
x.
MRI of the brain could be a good predictor of MS and could be used for making treatment decisions and prognostication.
CHAMPS (Controlled High Risk Avonex MS Prevention Study)
383 patients between April 1996 and April 1998.
AimInterferon beta 1alpha (Avonex) treatment would benefit:
i.
Patients who had experienced a first acute demyelinating event involving the optic nerve, brain stem/cerebellum, or spinal cord Displayed MRI brain signal abnormalities that predicted a high likelihood of future MS-like events. (defined as > or = 2 T2 weighted hyperintense lesions, 1 of which was periventricular or ovoid, on unenhanced MRI scans)
ii.
All patients received intravenous methylprednisolone 1 g per day for three days within 14 days of the onset of their neurologic symptoms.
An oral prednisone taper beginning with 1mg/kg for 11 days and ending with a 4-day oral taper
Patients in the first group were treated with a onceweekly intramuscular injection of interferon beta 1-AWhile those in the second group were treated with placebo. Interferon therapy was initiated during the prednisone taper.
RESULTSI.
The cumulative probability of developing clinically definite multiple sclerosis was significantly lower in patients receiving interferon beta 1-A than in those receiving placebo (P = 2 white matter lesions)
I.
IV Methyl prednisonlone 1 G/day 3 days Oral prednisolone ( 1mg/kg/day 11 days),4 day taper
II.
Avonex 30mcg IM once a week
BENEFITBetaferon in Newly Emerging Multiple Sclerosis for Initial Treatment
CONCLUSION
The results show that IFN B 1 beta 250 mcg reduces the risk of developing clinically definite multiple sclerosis (MS) by 50 percent compared with placebo
VISION PROTECT (AUG 2006- DEC 2008)Safety and Efficacy Study of Erythropoietin as Add-on Therapy of Methylprednisolone to Treat Acute Optic Neuritis
Both Treatment group Mpred 1000 mg/250 ml normal saline i.v. once daily for 3 days
Add-on regimen E
Placebo controlled group S Normal saline given i.v.once daily for 3 days as a bolus injection
3.3 x 104 IU recombinant human Epo given i.v. OD for 3 days as a bolus injt
Primary Outcome Measures:
Secondary Outcome Measures
nerve fiber loss in the optical nerve head determined by OCT at weeks 4,8 and 16 compared to baseline measurements at baseline
Visual acuity and visual field perception determined at weeks 1, 4, 8, 16 compared to baseline
MRI measurements of optic nerve atrophy performed at weeks 4, 8 and 16 compared to baseline
PPAR-gamma
Peroxisome proliferator-activated receptorgamma Control the response of microglial cells found in brain parenchyma, and limit the inflammation
hypothesis that PPAR-gamma might be targeted to modulate degenerative brain diseases in which inflammation is recognized as a significant component
VISUAL PROGNOSIS
Prognosis for visual recovery is good. Recovery in pts. without treatment tends to begin 2 3 wks after onset 65-80% regain 20/30 or better 45% of these recover rapidly within the first 4 months 35% recover normal to near normal; acuity within 1 year
Poorer visual outcome correlated with recurrent episodes, patients with CDMS The probability of a recurrence of optic neuritis in either eye within 5 years is 28 %. Visual recovery after a second episode in the same eye is generally very good.
Differential diagnosis of optic neuritisAutoimmune Steroid-sensitive MS Optic neuritis (Devic) Sarcoidosis SLE Behets disease CRION (chronic relapsing inflammatory optic neuropathy) Borrelia Lues Tbc Viral Post-infectious (ADEM) Primary Tumor (Meningeoma, glioma) Metastasis Thyroid ophthalmopathy AION/PION Arteriitis temporalis Diabetic Methanol Tobacco-Alcohol amblyopathy Vit. B12 Ethambutol toxicity Maculopathy/retinopathy Posterior scleritis
Infectious
Compressive Ischemic
Toxic-metabolic Ocular causes
"Red flags" in optic neuritisDistinct vision impairment No pain Ischemic Infectious CRION Ischemic Compressive Hereditary Toxic/nutritive (Vit. B12/methanol) Compressive Ischemic Hereditary Collagenosis/Vasculitis Devic Post-infektious (ADEM) Toxic LHON
Optic atrophy
Bilateral
Strong oedema Exacerbation after stopping steroid treatment
Infectious (Lues, Tbc, borrelia, viruses) Ischemic Collagenosis/vasculitis CRION (chronic relapsing inflammatory optic neuropathy)
Workup of optic neuritisImaging CSF MRI orbital (lesion load) cerebral (MS) spinal (Devic)
Pleocytosis (Borreliosis/infection) Oligoclonal bands Serology (borrelia/Lues/HIV) ANA, ANCA, antiphospholipid, anti-dsDNA (collagenosis/vasculitis) Vitamin B12/alcohol/methanol ACE BSR (arteriitis ?) AQP4 Ab (Devic ?) VEP ERG Sarcoidosis?
Laboratory
Neurophysiology Chest xray
Management of isolated optic neuritis
optic neuritis positive cerebral MRI negative Low risk to develop MS
Suspected MS, discussed probability to develop MS
Steroid treatment Offer immunomodulatory treatment, like interferonbeta
Steroid treatment Clinical course and MRI in 3 to 6 months