Optic neuritisDr. Meenank

Optic Neuritis (ON)

• Inflammation of optic nerve - ON

• Associated with swollen disc – papillitis/ anterior ON

• Normal disc – retro bulbar ON/ neuritis

• Absence of any signs of M.S/ systemic illness –

monosymptomatic/ idiopathic/ Clinically isolated ON

• Subtle clinical signs + electrophysiological evidence –

asymptomatic ON

Two variants 1. Neuroretinitis – infla. Of intraocular + Peripapillary retina –>

disc swelling + retinal oedema + Hx + hard exudates + macular star

2. Optic peri-neuritis – infla. Of optic nerve sheet only –> disc swelling with out Vn complications + large blind spot

• D/D papilledema

Demographic • 2.2 -2.6 per 100,000 cases (or) 115 / 100,00 cases per year• white population • Northern latitude• Females ( 77%)• Age – 15 to 50yr , (children – 10 to 20 )• Mean age – 33yrs

Triad of symptoms • Vision loss• Ipsilateral eye pain• dyschromotopsia

initial attack – unilateral

Associated Symptoms

• Movement phosphens• Sound induced phosphens• Visual obscuration's in bright light • Uhthoff’s syndrome

Loss of vision• Rapid / abrupt loss of vision• According to ONTT • With in hrs – 29%• In 1 to 2 days – 20%• In 3 to 7 days – 23 %• In 1 to 2 weeks – 7 %

• Variant : • Ch. Demyelination of optic neuropathy characterized by slow

progressive vision loss – due to macro-plaques optic nerve – impairment of vision • Micro-plaques chiasma – chiasmal optic neuritis ( rare symptom)

Pain • Freq. of Ipsilateral eye pain in unilateral ON – 55% to 92%• Character – dull aching• ass. With generalized / periocular headache• aggravated by – EOM / touch • Pain precedes vision loss• Max severity – 24 to 36 hr subsides with in 48 to 72 hrs• Pain = vision loss• Pain in retro-bulbar > papillitis > AION ( 93%> 90% > 12% )• Atypical presentation = pain more than 7 days

Dyschromatopsia • Impaired color vision = 94%• Desaturation• – eg: red = dark/ beached

• Distinguishes b/w macular lesion

sparkles

Sound induced flashes

Motion induced flashes

Phosphens• Ring of light • ONTT = 30% positive • 3 observation • Sparkles • Due to disc oedema• Stimulation of Peripapillary retina

• Motion induced • Before / during / months after • Most common – dim illumination, horizontal gaze, closed eyes• Rapid eye movement's – decrease phosphens

• Cause : spontaneous discharge of the partially demyelinated spinal chord axons in min. stress condt.

• Sound induced • Loud noise at rest = phosphens• Pathological variant of hypnogogic hallucinations

Quick recovery

Transient blurring

Hot baths

/climate

Isolated ON (rare) /

M.S.

• Generalized blurring for 2- 20 min• Cool down vision back with in 5min to 24 hrs ( rare)• Not common in ON but seen in

compressive toxicinflammatoryLHON

In ½ of isolated ON Shows recurrence , sporadic

Uhthoff’s symptoms

Clinical Sign’s

• Acuity • Dyschomatopsia • Contrast sensitivity • Afferent pupillary defect• Optic disc• Retinal finding

• Acuity • Varying degree of visual acuity can be seen ranging from

6/9 to NLP

Dyschromatopsia

• Unilateral Dyschomatopsia with good V.A → ON• Can be detected using • Hardy Rand Ritter• Ishihara pseudo=isochomatic plates • Fans-worth Munsell 100-hue Test

• Ishihara - 20/280• Hardy Randy Ritter – 20/ 100 Dyschromatopsia

• Color sensitivity > V.A• Contrast sensitivity = V.A

Recovered ON with 6/6 but, imperfect Vn

Physiological test •Contrast sensitivity test – Pelli-Robson and Sloan low contrast

Contrast sensitivity

• Pelli- Robson Contrast chart (Sensitivity)• Distance – 1 - good for subclinical ON• Chart – 16 triplet of same letter• Contrast – 96% 10 1% - cannot diff. b/w

• Sloan low Contrast acuity Chart (acuity) ON/ maulopathy/ • Low contrast, light grey organic (or) non- organic

• Like snellen chart

Stereoacuity • Stereoacuity and snellen’s and in linear relationship• Normal Stereoacuity with impaired snellen’s • Snellen's incorrect • Non-organic vision loss

• Pulrich effect • Damaged optic nerve delays transmission to visual cortex from

the unilateral eye

• Oscillating target on the front plane is perceived as elliptical due to stereo –illumination due to impulse delay

• Magnitude of stereo – illumination • Velocity of target• Diff. between retinal illumination b/w two eyes• Basic level of retinal illumination • Distance between the observer and target

• Pulrich – more sensitive indicator of optic nerve dis.

Visual fields • ONTT = all patients show V.F abnormalities in acute phase• Vn loss – central ⁺⁺⁺, peripheral⁺, particular region⁺ • If Vn severely impaired – confrontation test • Vision improved – • Multi-isotropic kinetic Goldman Perimetry ( only central scotoma)• Computer Assisted automated static Perimetry ( Diffused and focal )• Octopus Perimetry

• Focal defect – • Altitudinal • Arcate 42%• Nasal step defect

Afferent pupillary defect • In the absence of an optic nerve lesion in the fellow eye RAPD

can be demonstrated by swinging flash light • RAPD can be graded by neutral density filters – 0.3, 0.6, 0.9,

1.2• -ve RAPD in recurrent attacks

Optic disc • Normal – ⅔• Oedematous - ½ • Temporal pallor – 10% , suggestive of preceding attack• Disc Oedema is without Hx / lipids/ cotton wool • Disc changes α multiple sclerosis • Recovered ON – optic disc • Normal 40%• Temporal pallor 30%• Total pallor 20%

• M.S without ON can have pale optic nerves

Optic disc oedema

Retinal Findings

• Retinal venous sheathing • Small ill-defined/ round confluent white exudates along the

peripheral veins• Most common – systemic illness ( M.S. , sarcoidosis)• Also in asymp. Eye of M.S as an isolated B/l finding • Recurrence – post complete resolution

• RNFL atrophy • Disc atrophy is seen in all types of optic neuropathy• M.S – incidious RNFL atrophy with visual symptoms of optic nerve

dysfuntion • RNFL defects in ON/ M.S – from axonal atrophy

• Seen as a slit in the nerve fiber striation in the arcate fiber bundle• Slits – M.S 70% - normal eye of ON – 2 sub-clinical optic nerve lesions

• RNFL defects – focal / diffused atrophy Diagnosed through 1. monochromatic red free ophthalmoscopy 2. Red free light magnifying fungus photography3. OCT4. Heidelberg retinal tomography

• RNFL thickness - α neurological function test - ⅟α contrast sensitivity test

RNFL

Normal RNFL

Loss of RNFL

Differential diagnosis• Unilateral ON• NAION• Infectious/ inflammatory

• Neuroretinitis• Viral • Post- viral• Fungal• Syphilis• Toxoplasmosis• Lyme• Herpes zoster• Sarcoidosis• T.B.• Collagen vascular disease• Autoimmune ON

• Leber’s hereditary ON• Compressive

• Meningioma• Glioma• Metastasis• PNS mass

• Infiltrative• Multiple myeloma• Leukemia• Cā meningitis

• Retinopathies• Paraneoplastic ON• Cone dystrophy

• M.C occurring optic neuropathies AION and idiopathic ON• Difficult to distinguish on the basis of • Age, initial presentation, progression, V.F defects, optic nerve

Optic neuritis AION

demographicsMean age, yrs

33 ( 5- 70) 66 ( 11 – 90 )

Gender, % female 70% 45%

Annual incidence, per 100,000

2 -6 1- 6

SymptomsPain 92% 10%

Progression 70% 30% - 45%

Improvement >90% >40%

SignsAcuity 6/6 to NPL 6/6 to NPL

Field defects Central scotoma Inferior altitudinal

Disc oedema 35% 100%

Rhinogenous ON

• From the sinus – posterior ethmoidal (or) sphinodal

• Mimics unilateral idiopathic ON

• Seen in – recurrent attacks of Vn loss with sever head-ach/

febrile illness

• Diff. diagnosis –

• Rx – steroids

• Can lead to steroid sensitive ON

Lyme disease

• Lyme borreliosis

ehrlichosis rarely cause optic neuropathy

• Early stages – optic nerve swollen

• Lyme meningitis- disc swelling – papilledema/ optic

perineuritis

• Diagnosis – serological test (imp. In endemic cases)

• Rx – oral / I.V steroids

Acute syphilitic neuritis• Manifestation of 2⁰ syphilis – uni/ bi lateral Vn loss• Acc. by intraocular inflammation – uveitis , retinal vasculits

• 2⁰ syphilis –> meningeal inflammation –> syphilitic optic perineuritis inflammation of the optic nerve sheet swelling of the optic disc

• 2⁰ syphilis – tertiary syphilis Slow prog. Vn loss with optic atrophy without inflammation

• Check for – palmar and truncal rash ( 2⁰ syphilis)

• Diagnosis• VDRL positive for 2⁰ syphilis• PRP (plasma rapid reagent) normal for tertiary syphilis

• Immunocompetent + syphilis = +ve for life for• Microhemaglutten assay for treponema pallidum (MHA-TP)• Florescent treponemal antibody absorption test ( FTA-AB)

• CSF – normal / inc. WBC

Neuro-retinitis

• ON + swollen disc + macular oedema (ME)

• Resolved ME –> macular star

• Vitreous cells ± mid peripheral choroditis

• Neuroretinitis due to infec./ infla

• Cat-scratch dis

• Syphilis

• Lyme

• Toxoplasmosis

• Sarcoidosis

• Prognosis – good

CancerParaneoplastic • Acute and sub-acute – Vn loss• Auto-antibodies –> retina / &, optic nerve – uni/bi Vn loss with

in 1 week • Optic disc – normal to swollen, vitreous cells • Neurological defects – ataxia, peripheral neuropathy,

movement disorders• Optic nerve – show (CRMP-5) IGg• Antibodies to Collapsing response mediated protein -5

• Tumors associated with Paraneoplastic optic neuropathy • Small cell Ca. lung• Thymoma • Thyroid Ca.

Bilateral (or) Simultaneous• Leber’s hereditary ON (LHON)• Chiasmal syndrome• Nutritional • B₁₂ deficiency

• Tobacco – alcohol amblyopia • Toxic • Linezolid• Ethambutol• Amiradone• Tumor necrosis alpha inhibitors

• Neuromylitis optica (NMO)

• Papilledema

Neuromylitis Optica (NMO)• AKA Devic’s diseases • Rare, all ages, bilateral (91%)• Inflammatory CNS demyelinating diseases• Optic nerve • Spinal chord ( only 3 vertebrae )

• In NMO, ON –> transverse myelitis ( weeks)• Acute stage – CSF proteins – CSF pleocytosis• Pleocytosis – predictor of out come • Don’t show oligoclonal bands• No white matter lesions• Incomplete neurological recovery • NMO IGg antibodies – 70% sensitive , 100% specific to NMO

SLE• Affinity - 1%• Vision loss • Acute progressive • Corticosteroid Rx – sub-acute to slow prog. – steroid dependent

and suggestive of collagen vascular disorder• Lab – ANA , anti-cardiolopin (increased)• Biopsy of non-exposed tissue• Peri-vascular infiltrates• Immune-complex deposits in the dermis

• Rx – prolong steroid thx

Tobacco – alcohol amblyopia • AKA Tobacco/ ON of chronic alcohol/ malnutrition ON• Vision loss – slow progressive• Visual field defect – B/L centro-coecal scotoma• Dietary deficiency • Rx – thiamine, B₁₂, folate• Vision imp. Inspite of abuse

Jamaican optic neuropathy • Vn 6/60 ↓, B/l dense central scotoma, W. Africa &

Carrabinan immigrant's • Patient – well nourished, non-toxic, VDRL non-reactive• Rx – no Tx relief, no spontaneous recovery • Cause – unknown

Leber’s hereditary ON (LHON)• 1st disease to inherit mitochondrial mutation in DNA • Maternally inherited • 1 young men, white ( 80% -90% ) with 50% Vn loss• Japanese's • Symptoms • Sub-acute painless bilateral Vn loss• Central (or) ceco-central scotoma• Onset- all ages

• Most common -12 yr to 30 yrs• Vn loss –permanent profound , with in weeks -1 month - 8yrs• Rare – monocular Vn loss • Uhthoff's symptoms ⁺

• Nadir of visual acuity, commonly 6/60 and ↑• Fundus – depending on the stage / normal • Acute• circumpapillary telangiectic microangiopathy with disc hyperemia• Swelling of Peripapillary NFL• Vascular tortuosity • F.A – absence of leak from disc

• Late • Telangiectic microangisums –resolved• Optic atrophy• Loss of NFL striations in papillomacular bundle

• Associated with cardiac anomalies• Diagnosis – DNA analysis• Rx – L-carnitine, Succinate, Vit. B, Vit. E, co-enzyme Q₁₀, idebenon

ON in children Adults ⅓

• Disc oedema Children (50% - 75%) bilateral + optic nerve swelling

• MRI - normal to large enhance white matter lesions• Acute disseminated encephalomyelitis

• Rx – IVMP 1-4 gm./ kg/ day x 3-5 day oral prednisolone 1mg/ kg/ day (taper @ 4 wks)

• Child with ant ON – relapse with steroid• Progress – 80% • Pediatric ON –> M.S, very low (4yrs to 9yrs)

Investigations

Visual evoke potential • ON detects • Sub-clinical abnormalities• Difference between organic and non-organic origin

• Test the central and para-foveal visual field• Flash VEP – areas 17, 18, 19• Wave form VEP – triphasic

• P100 - +ve peak • N75 with N45 - -ve peaks

• Prolong P100 (latency) => changes with ON• P100 (amplitude) => visual acuity, not reliable

• Absolute latency @ P100, > 9 ms = optic nerve dysfunction• Delay in P100 permanent after an attack• Prolong latency in VEP • Compression• Glaucoma• Dopamine def. in central neurodegenerative dis.

• Altered amplitude and latency in normal individuals• Defocusing• Looking away

Pattern Electro-retino-gram • PERG is used to evaluate the function of the macula or central

retina• PERG refines VEP’s abnormal interpretations • To R/o the cause isn’t from a ant. Lesion • Waves – P50 (+ve), N95( large –ve), N35 ( small early –ve)• In ON –• Delayed VEP P100 latency • Near-normal PERG N50 amplitude • Small/ absent PERG N95 amplitude

• Ant. Visual pathway dysfunction/ maculopathy – • Delayed/ small P100 • Reduced P50 • Normal N95

Magnet Resonance Imaging

• Not always imp. but, help R/o other disorders• MRI brain and orbit with fat suppression and gadolinium• In ON – • Optic nerve – abr STIR signals• Gadolinium enhancements• Single white matter lesion in AMON – high risk for M.S

• Abnormality > 3mm, oval, in peri-ventricular white matter, radially oriented towards the ventricular spaces on a unenhanced MRI

DISSEMINATION IN SPACE DISSEMINATION IN TIME

One or more gadolinium enhanced lesions/ 9 hyper intense white matter lesion

Gadolinium enhanced lesion > 3month post initial evaluation

One or more infra-tentorial lesion New T2 lesion > 30 days after baseline MRI

Three/ more prei-ventricular lesions

A spinal chord lesion can substitute for one infra-tentorial lesion

Revised McDonalds Criteria

Need to fulfill atleast 3Lesion should be 3mm or more

Prognosis and Recurrence

Prognosis • although 85% show irreversible nerve damage• Visual out come is in 92% - 6/9

• Recurrence• Two group’s • Existing M.S – 45%• People using oral prednisolone

Multiple Sclerosis• MS is an inflammatory demyelinating disorder of the CNS white

matter• Ophthalmic presentation • ON, inter-nuclear ophthalmaoplegia, nystagmus • Uncommon presentation – homonymous V.F loss, gaze palsy, isolated

ocular motor palsy• Diagnostic –• Two or more lesions in nervous system in separate locations

occurring at diff. time – separation of time and space, with no explanation

• MRI - New gadolinium enhancement > 3months after ON attack• CSF - oligoclonal bands in the gamma-globulin region of the

fractioned protein • Also seen in – neurosyphilis, neurosarcoidosis, meningitis

• Abnormal IGg index

Treatment

Corticosteroid's

• ONTT (optic neuritis treatment trial) 3 groups1. Oral prednisolone (1mg/kg) daily for 14 days2. Oral placebo (1mg/kg) daily for 14 days 3. IVMP (1gm/d) for 3 days followed by oral prednisolone (1mg/kg) for 11 days

• Faster recovery with IVMP, but no diff. in final result• Recurrence with oral prednisolone• IVMP – 50% reduction in development to M.S

Interferon therapy

• CHAMPS – Controlled High Risk Subjects Avonex M.S. prevention• Multicenter , randomized, double-blinded, placebo-controlled

clinical trial • Inclusion – abnormal MRI + 2 white matter lesions • Rx – systemic corticosteroids + weekly IM (interferon beta 1a)

IFNβ1-a (or) placebo • Result @ 3yrs – 35% of IFNβ developed MS , no progression in

MRI abnormalities

• BENEFIT – Beteferon in Newly Emerging MS for Initial Treatment• Subcutaneous IFNβ1b reduces conversion ( 45%)