OCULAR SARCOIDOSIS

SIVATEJA CHALLA

• DEFINITION• EPIDEMIOLOGY• PATHOGENESIS• ETIOLOGY• HISTOPATHOLOGY• CLINICAL FEATURES• DIFFERENTILA DIAGONOSIS• INVESTIGATIONS• DIAGONOSTIC CRITERIA• TREATMENT• COMPLICATIONS• COURSE AND OUTCOME

Definition

• Multisystem chronic inflammatory disorder characterised by the presence of non caeseating granulomas in affected tissues• Main organs involved are lungs,lymph nodes, eyes,

skin, heart, liver,kidneys, muscles• Ocular involvement was first observed by schumaker

in patient with nodular iritis in the year 1909

EPIDEMIOLOGY

• World wide distribution• Prevance differs from region to region• Overall incidence 6-10/ 1 lakh• Japan 3.2/lakh and finland 28.2/lakh• Age common is 20-40 yrs (bimodal 20 to 30y and 50-60y)• Sex females>males• Ocular incidence is 25 to 60%• Earlier was disease of developed world,now d/t increased

diagnostic modalities seen in developing countries also

PATHOGENESIS

• Caused by antgenic stimulation• Antigen activates a cascade of reactions in genetically

susceptible individuals

Antigen presented by APC

Activation of CD4+T lymphocytes and cytokines

compartmentalisation at site of inflammation sealing the antigen L/T granuloma formation

ETIOLOGY

• ?BACTERIAL• ?VIRAL• ?ENVIRONMENTAL

• Mycobacterial- clinical radiological and histopath similarities of TB and sarcoidosis implicates mycobacterium as cause.

-studies demo M.TB DNA and RNA from sarcoid tissues,but was not able to isolate M.TB on culture

- recently high frequency of M.TB catalase peroxidase in sarcoid granulomas renewed interest

ANTIGEN STUDIES BUT CAUSE IS NOTPROVED

Cont…..

ETIOLOGY

• Other agentsProprionobacteriumHepatitis CHerpesEBVHelicobacter pyroli

HISTOPATHOLOGY

• HLADR 17 AND TNF play important role in disease severity and prognosis

• But no gene has been demonstrated responsible for sarcoidosis

• HPE classically shows typical NON CASEATING sarcoid granulomas

centre—epitheloidcells or macrophages

surrounded by –lymphocytes and fibroblasts• SARCOID and ASTEROID bodies are found

HISTOPATHOLOGY

CLINICAL FEATURES

• OCULAR FEATURES• SYSTEMIC FEATURES

PRESENTATION

ACUTE ONSETLOFGRENS SYNDROME-erythema nodosum, B/L hilar lymphadenopathy, arthritis

HEERFORDTS SYNDROME-fever, uveitis, parotid swelling, facial palsy

INSIDIOUS ONSET 5th decade with PUL involvement resulting in cough,dyspnoea along with extra pulmonary manifestations

OCULAR FEATURES

• Seen in 50% pts with systemic disease• m/c manifestation is uveitis• May be asymptomatic• May present with blurred vision floaters, redness and

discomfort• Ocular involvement is chronic and has insidious onset

Eye lids

• Small millet shaped to large nodules on eyelids• Lesions are non tender and rarely ulcerate

Lacrimal gland and drianage system

• 7% pts with sarcoidosis• 25% pts with ocular sarcoidosis• Usually B/L• Enlargement of lacrimal glands found• Loss of functionality may lead to keratoconjunctivitis sicca• NLD afected very rarely,dacrystenosis may occur secondary

to granulomatous inflammation• May L/T epiphora and acute or chronic dacrocyctitis

Orbit

• Uncommon• Only involves in 1% pts with ocular sarcoidosis• Granulomatous infl of orbit may L/T U/L OR B/L proptosis• Involvement of EOM very rare,may lead to painful external

ophthalmoplegia

Conjunctiva

• 4-13% cases of sarcoidosis• 17-20% pts with ocular sarcoidosis• 25% pts with sarcoid uveitis have conj changes• M.C lesion is granuloma• Seen as small round yellow nodules• Usually present in infero palpebral conj and fornix• May be single,may be U/L OR B/L• In some cases cicatrial chnages and symblepheron can

occur

CONJUNCTIVA

Cornea

• M.C manifestation is band shaped keratopathy• Also nummular keratitis may be seen,bilateral,not

characteristic• May also seen as thickening and opacification of

descemets membrane and endothelium in inferior cornea due to fibrous metaplsia of endothelial cells,may be of chronic inflammation

• Presencce of inferior corneal opacification in patient with chronic iridocyclitis should raise the suspicion of sarcoid

CORNEA

Iris

• Nodules in 11% pts with ocular sarcoidosis• Koeppes and busaccas nodules• Not characteristic

Anterior uveitis• M.c manifestation

• Seen on 2/3rd cases• Typical chronic B/L Non caseating granulomatous uveitis

• Acute or chronic

ACUTE ANTERIOR UVETIS• Abrupt onset asso with pain redness and photophobia• Blurred vision

• Usually U/L,exam reveals cells,flare and fine KPs

• Likely to occur at the onset of systemic disease

• Well responds to treatment

Cont….

Anterior uveitis

CHRONIC ANTERIOR UVEITIS• Mutton fat KPs• Iris nodules• Trabecular meshwork nodules on gonio• Tent shaped PAS on gonio• May lead to glaucoma and cataract• Mor edifficult to treat and has higher incidence of

complaications and worst prognosis

ANTERIOR UVEITIS

ANTERIOR UVEITIS

Intermediate uveitis

• Inflammation of vitreous,pars plana and peripheral retina• Snow balls are seen• Some times snow banking may be seen• Least common form• In sarcoidosis anterior uveitis > posterior uveitis >

intermediate uveitis

Posterior uveitis

• 25% patients with ocular sarcoidosis have posterior segment involvement

• Although asso with ant uveitis 20% pts amy have isolated post sement involvment

CHARACTERISTIC FINDINGS• Candle wax dripping sign/taches de bouge,there is

periphlebitis with segmental cuffing with extensive sheatind and perivenous infiltrate

• Capillary closure and ischemia may L/T Neo vas and VH• Choroidal granulomas are seen,which resolve and form RPE

atrophy or scar formation• Cystoid macular oedema

OTHER RARE COMPLICATIONS

• RETINAL DETACHMENTS• OPTOCILIARY SHUNTS• ARTERIAL MACRO ANEURYSMS

• major concern is posterior segment sarcoid uvetis involvement associated with neurological involvement in 27% cases,SO careful fundus examination should be done

POSTERIOR UVEITIS

POSTERIOR UVEITIS

OPTIC NEUROPATHY

• Rare• Feared complication,may lead to rapid vn loss• Four types of optic nerve disease described

1.Papilloedema sec to severe raised ICP and CNS involvement

2.Infiltration of optic nerve by non caeseating granulomas

3.Retrobulbar neuritis

4.Glaucomatous optic atrophy secondary to raised IOP FOR long periods

OPTIC NEUROPATHY

SYSTEMIC FEATURES

• Predominantly affects

1. Lungs 90%

2. Thoracic lymph nodes

3. Skin

4. CNS

5. ARTHROPATHY

6. Hepatic involvement

7. Renal invlvement

8. Cardiac involvement

Lungs and thoracic lymphnodes

• Usually asymptomatic and discovered on CXR• Patient may also present with fever,malaise,fatigue,weight

loss,cough,dyspnoea,chest pain

SCADDING SCALE CXR and HRCT CHEST• Stage 1 (a) –Bilateral hilar lymphadenopathy (55-90%)

• Stage 2 (b) –Pulmonary infiltrates with BHL(40-70%)• Stage 3 (c) – Pulmonary infiltrate alone (10-20%)• Stage 4 (d) – extensive pulmonary fibrosis (10%)

CXR

SKIN

• ERYTHEMA NODOSUM– tender erythematous plaques on knees,shins,occasionally seen on thighs and forearms

• Granulomatous scattered plaques,nodules and papules• LUPUS PERNIO-- indurated violaceous lesions involving

nose cheeks fingers and ears

SYSTEMIC FEATURES

• Neurological involvement is seen on 5-10% pts. M.C is U/L 7th nerve palsy,

• Arthropathy is typically symmetrical and all types of joints involved

• Hepatic involvement subclinical and altered liver enzymes may be present

• Renal involvement may lead to hyper calcemia,hyper calciuria and increased risk for nephrocalcinosis and nephrolithiasis

• Cardiac seen on <5%,conduction defects occur.be careful In using beta blockers in these patients for glaucoma

• Peripheral lymphadenopathy in 30% pts

DIFFERENTIAL DIAGONOSIS

• Varied presentations and features it shares with other diseases offer many oppurtunities for misdiagonosis

• So history, clinical corse and associated systemic sgns and investigations proves clinical clues

DIFFERENTIAL DIAGONOSIS

GRANULOMATOUS UVEITIS Tb, Syphilis, leprosy, vkh, toxoplasmosis, herpetic uveitis

ISOLATED IRIS NODULES Iris neoplasms, metastatic carcinomas, leukemic infiltrates, seeding from retinoblastoma

INTERMEDIATE UVEITIS LYMES disease,multiple sclerosis,pars planitis

CHOROIDAL LESIONS tb, birdshot retinopathy, metastatic tumours, large cell lymphomas, vkh, serpigrnous choroidopathy, behcets disease , CMV retinitis, Sympathetic ophthalmia, histoplasmosis

INVESTIGATIONS

• Diagonosis of exclusion

1.ICG csn be done for dx of occult choroidal lesions

2.TUBERCULIN TEST is depressed in pts with sarcoid d/t cutaneous anergy and may be NEGATIVE

3.Serum ACE levels are elevated,if patient on ACE inhibitors then do serum LYSOZYME levels,not characteristic

4.LIVER ENZYMES,included in diagonostic criteria for ocular sarcoidosis (3* inc in ALP or 2* inc in sgot/sgpt)

INVESTIGATIONS

• RADIOLOGY CXR,HRCT for hilar lymphadenopathy and pul infiltrates,HRCT is more sensitive than CXR

• GALLIUM SCANNING• BRONCHOALVELOR LAVAGE shows lymphocytois,altered

CD4/CD8 ratio, smears and culture can be made to r/o TB• BIOPSY any clinically involved tissue can be

biopsied,usuallu lung parenchyma and hilar lymph nodes are biopsied to look for non caseating granulomas

• HYPERCALCEMIA occurs in <10% pts,is of limited value

GALLIUM SCANNING

DIAGONOSTIC CRITERIA

TREATMENT

• No standardized therapy• Main is corticosteroids• If mild then topical corticosteroids• If severe then start oral corticosteroids and taper• If not responding then immunosuppresants like MTX,

mycophenolate, azathioprine, cyclosporine and leflunomide

• If not controlled then anti TNF ALPHA agents like etanecept, infliximab and alalimumab can be tried

COMPLICATIONS

1.CME IN 76% CASES

2.CATARACT 49%

3.GLAUCOMA 36 %

4.RETINAL ISCEMIA 16%

5.NEO VASCULARISATION IN 11%

CATARACT AND GLAUCOMA TO BE TREATED APPROPRIATELY

IVTA can be given for CME

COURSE AND OUTCOME

• Overall good prognosis• Systemic features asso with poor outcome are\

1.Diffuse CNS disease

2.Lupus pernio

3.Nephrocalcinosis

4.Late stages of pulmonary disease

5.Bone abnormalities

6.Hepatosplenomegaly

7.Cardiac involvement

THANK YOU