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)

Definition
Involvement 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%)

Classification
Ophthalmoscopic

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

Symptoms
Triad :

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.

PHOSPHENES
Movement 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.

SIGNS
I.

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 DISC
60 % - normal disc 20 % - swollen disc 20 % - blurred, hyperemic

Recovered pts. 40 % normal disc 20 % total disc pallor

RETINAL CHANGES
Retinal venous sheathing
o

Round/confluent white exudates on a peripheral vein, with posterior vitreous cells 28 % cases
Can resolve completely & then recur All pts. with MS will have venous sheathing at some point of their lives.

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 TRIAL

i.

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 criteria

Age 18 46 yrs. <=8 days of symptoms of acute unilateral optic neuritis. Presence of RAPD and a visual field defect in the involved eye. No previous episodes of optic neuritis in the affected eye No previous corticosteroid treatment for optic neuritis or multiple sclerosis No systemic disease other than multiple sclerosis that might be the cause of the optic neuritis

Three following treatment groups at 15 clinical centers

Oral prednisone (1 mg/kg/day) for 14 days
Intravenous methylprednisolone (250 mg every 6 hours) for 3 days, followed by oral prednisone (1 mg/kg/day) for 11 days with 4 day taper Oral placebo for 14 days

i.
ii.

iii.

Visual acuity & contrast sensitivity were primary visual outcome measures in ONTT Development of MS was endpoint

MAJOR RESULTS

Iv MP hastened recovery of visual function but DID NOT affect long term visual outcome after 6 months 5+ years compared to placebo or oral steroids

This benefit was greatest within the first 15 days

II RESULT

Patients treated with oral steroid ALONE showed INCREASED rate of recurrence as compared to placebo

30% / 2yrs = oral 16% / 2 yrs = placebo 13% / 2ys = Iv MP

III result

Monosypmtomatic patients given Iv MP had REDUCED rate of development of MS in first 2 yrs of follow up, but this benefit did not last after that

Other conclusions
i.

Median visual acuity improved to 20/25 by 4 days of i.v. treatment. Iv steroid pts. have a significant benefit in contrast sensitivity, color vision and visual fields but not in VA at 6 mths. I.v. methyl prednisolone followed by oral steroids accelerated visual recovery, but offered no long term benefit.

ii.

iii.

v.

Visual recovery begins rapidly (within 2 weeks) in most optic neuritis patients without any treatment & then improvement continues for up to 1 year.

vi. Treatment was well tolerated with few major side effects. vii. Standard dose oral prednisolone alone should not be used as It does not improve visual outcome. associated with a higher incidence of recurrence.

viii.

Investigations like lumbar puncture, laboratory tests are not necessary for typical cases.
Presence of brain MRI lesions is strongest predictor of developing multiple sclerosis ----->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.

Aim
Interferon 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-A
While those in the second group were treated with placebo. Interferon therapy was initiated during the prednisone taper.

RESULTS
I.

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 = <.002)

II.

At the end of three years, the cumulative probability of CDMS was 50% in the placebo-treated group and 35% in the interferon 1-A-treated group.

III.

At 18 months, treatment with Avonex was associated with a significant reduction of new T2 lesions, gadolinium enhanced lesions and T2 lesion volume. Among placebo-treated patients, 82% had developed a new subclinical MRI signal abnormality by the eighteenth month after study entry.

IV.

CHAMPIONS
Controlled High Risk AVONEX Multiple Sclerosis Prevention Study In Ongoing Neurological Surveillance

To assess if early treatment with AVONEX in delaying relapses and reducing the accumulation of MS brain lesions was sustained for up to five years.

Patients who began treatment with Avonex immediately after their first attack had a 43% decrease in the risk of developing a second attack compared to those who began treatment on placebo

Current treatment protocol

Patient with typical clinical course & findings for acute monosymptomatic ON T2 enhanced MRI ( >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

BENEFIT
Betaferon 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 neuritis

Autoimmune 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 neuritis

Distinct 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 neuritis

Imaging 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