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