Masquerade Syndrome

DR R PATEL

Name the common syndromes that masquerade as anterior and posterior uveitis and their diagnostic tests. 5+5 PAPER III DNB question Papers 2011 (June)

Masquerade Syndrome Group of disorders simulating/mimic Ant. Or Post. Uveitis in their

C/F but are having entirely diff. etiopathogenesis being usually neoplastic or occasionally ischaemic

1967 :Theodore : used the term "Masquerade Syndrome" in ophthalmology to describe a case of conjunctival carcinoma that manifested as chronic conjunctivitis

Many are malignant; prompt dx needed.

Uveitis Masquerade accounts for 5 % of patients with uveitis in a tertiary care centre

When to suspect ?

Masquerade syndromes should be considered : In the very young and in the elderly. with persistent idiopathic uveitis that is nonresponsive to corticosteroids

Masquerade Syndromes Anterior Segment

Retinoblastoma Leukemia IOFB Malignant Melanoma JXG (Juvenile

xanthogranuloma) Peripheral RD

Posterior Segment Retinitis pigmentosa Reticulum Cell

Sarcoma Lymphoma Malignant Melanoma MS

Masquerade syndromes Lymphoid malignancies

i. Lymphoma ii. Leukemia

Nonlymphoid malignancies i.Uveal melanoma i. Choroidal metastasis ii. Paraneoplastic syndromes

CAR(carcinoma-associated retinopathy)

MAR Bilateral diffuse uveal

melanocytic proliferation iv. Retinoblastoma v. Juvenile xanthogranuloma Vi .Medulloepitheliom

Nonneoplastic a. Chronic peripheral retinal

detachment b. Retinitis pigmentosa c. Intraocular foreign body d. Amyloidosis e. Vitreous hemorrhage f. Retinal vascular disease

i. Ocular ischemic syndrome ii. Hypertensive retinopathy iii. Diabetic retinopathy iv. Vascular occlusion

g. Coats diseasea

Frequency of masquerade syndromes upon referral

Malignancy type Lymphoma (13) Leukemia (3) Melanoma (1) Metastasis (1) Retinoblastoma (1)

Nonmalignancy Retinal vascular disease

(10) Retinal Detachment (2) Coats' Disease (1) Other (8)

INTRAOCULAR LYMPHOMA :INTRODUCTION

Synonyms : large B-cell lymphoma, reticulum cell sarcoma.

The most common neoplastic masquerader(68%) NHL involving eye is a rare cond. Which mimics ch.

Uveitis or post. Uveitis Ocular lymphomas occur in both primary &

secondary forms Site of origin of PCNSL is unknown Yet are able to grow only in these two

immunologically sequestered locations (CNS or eye)

CLASSIFICATION of Lymphoma

1 Hodgkin disease may cause anterior uveitis, vitritis, and multifocal fundus lesions

resembling chorioretinitis. 2 Non-Hodgkin lymphoma may cause

conjunctival involvement, orbital involvement, Mikulicz syndrome and uveal infiltration.

3 CNS B-cell lymphoma may be associated with intermediate uveitis and sub-RPE infiltrates.

4 Primary intraocular lymphoma (PIOL) represents a subset of primary central nervous system

lymphoma (PCNSL

Intraocular Lymphoma

Intraocular lymphoma can masquerade as a chronic infection and may be a sign of CNS malignancy.

Etiopathogenesis Malignant infiltration of choroid by

lymphomatous cells.

PRIMARY INTRAOCULAR LYMPHOMA

Demographics Fifty to sixty years of age.

Ocular manifestations – Presentation unilateral floaters blurred vision red eye photophobia, which frequently becomes

bilateral after a variable interval.

Intraocular Lymphoma :Signs

Mild anterior uveitis with cells, flare and keratic precipitates.

Vitritis: impede visualization of the fundus. Large solid multifocal subretinal infiltrates Occasionally coalescence of sub-RPE deposits may form a ring

encircling the equator Other features include

retinal vasculitis, vascular occlusion, exudative retinal detachment and optic atrophy.

Lack of CMO is an important diagnostic clue, since in true uveitis significant vitritis is almost always accompanied by CMO.

Anterior segment of the eye of a patient with biopsy-prove intraocular large-cell lymphoma demonstrating corneal keratitic precipitates

Slit-lamp biomicroscopy examination revealing sheets ofvitreous cells characteristic of intraocular lymphoma

Vitritis in patient with intraocular lymphoma. universal finding

Multifocal subretinal infiltrates Shallow retinal detachment

Infiltration of transformed peripheral T-cell lymphoma into the iris

Subretinal infiltration of lymphoma cells

Fundus photograph of patient with intraocular lymphomashowing retinal infiltrates and hemorrhage mimicking Cytomegalovirus retinitis.

Obstructive hydrocephalus and cerebral lymphoma

Optic disc edema in human immunodeficiency virus-positive patient

Chorioretinal infiltration of primary ocular and CNS large B-cell NHL

Masquerading as multifocal chorioretinitis

PATHOLOGY

Thickening of detatched retina ( Pizza-Pie appearance )

Subretinal pigment elevation Vitreous infiltration FA shows blockage with a

granular characteristic, due to the presence of sub-RPE accumulation of lymphomatous cells (leopard skin spots).

Intraocular Lymphoma Systemic Findings

Behavioral changes hemiparesis Ataxia

Special Tests MRI. Lumbar puncture. Vitreous biopsy for cytology, flow cytometry, interleukin-6 and -10, immunoglobulin heavy chain gene rearrangement.

Treatment and Management Radiation therapy. Chemotherapy (intrathecal methotrexate or cytosine arabinoside [ara-C]) . Biologic agents involving specific anti-B cell monoclonal antibodies (such as rituximab

Initial workup may be negative, but maintain a high clinical suspicion in uveitis refractory to treatment.

MR image showing a hypointense multifocal lesion

SYSTEMIC LYMPHOMA

Epidemiology Rare intraocular involvement, older adults

Ocular Manifestations: Vitreitis, retinal vasculitis, necrotizing retinitis, diffuse

choroiditis, focal uveal masses, AU, hypopyon Systemic Associations:

Lymphadenopathy, involvement of retroperitoneum, paranasal sinuses, orbits, meninges, bone marrow

Comments: ocular involvement may be initial sign average longevity of 31 months following ocular diagnosis

RETINOBLASTOMA

Most common primary, malignant, intraocular tumour of childhood (1:20,000)

No sexual predilection Presents before age of 3 years (average 3

months) Heritable (40%) or non-heritable (60%) Predisposing gene (RPE 1) on 13q14 AU(1–3%), vitreitis, shifting white hypopyon

Leukocoria - 60% Strabismus - 20% Secondary glaucoma

• Anterior segment invasion • Orbital inflammation • Orbital invasion

Presentations of retinoblastoma

Early endophyliticretinoblastoma

White flat lesion Placoid lesion

More advanced endophytic retinoblastoma

Friable white mass Cottage cheese appearance

Fine surface blood vessels Vitreous seedings

Exophytic retinoblastoma

Multiglobulated white mass withoverlying retinal detachment

May be difficult to visualize through deep detachment

Occasionally, tumor necrosis may produce significant inflammation.

Right eye showing pseudo-hypopyon and tumour infiltrating the iris.

Pseudohypopyon was an unusual first sign of retinoblastoma in a 6-year-old girl without a positive family history

RETINOBLASTOMA

Investigations Ultrasound, aqueous tap USG, CT, MRI, Bonemarrow aspiration, lumbar

puncture Calcification(75%) on ultrasonography and CT

scan may help to differentiate retinoblastoma from various forms of childhood uveitis (toxoplasmosis, toxocariasis, cysticercosis, and pars planitis)

CT diagnosis of retinoblastoma

Calcification

• Optic nerve involvement

• Orbital and CNS extension

• Pinealoblastoma

Treatment Options of Retinoblastoma1. Small tumours

• Laser photocoagulation• Transpupillary thermotherapy• Cryotherapy

2. Medium tumours • Brachytherapy• Chemotherapy• External beam radiotherapy

3. Large tumours • Chemotherapy followed by local treatment• Enucleation

4. Extraocular extension• External beam radiotherapy

5. Metastatic disease• Chemotherapy

CILIARY BODY MELANOMA

10% of uveal melanomas C/F 6 th decade Dilated episcleral vessels in same quadrants

(Sentinel vessels ) Astigmatism, Subluxation, Cataract RD Necrotic tumors may elicit an intense inflammatory

response associated with seeding of tumor cells into the vitreous cavity and anterior segment

Ciliary body melanoma

• Rare - 12% of uveal melanomas

• Presentation - 6th decade

• May be discovered by chance

• Prognosis - guarded

Signs of ciliary body melanoma

• Sentinel vessels • Extraocular extension

• Erosion through iris root • Lens subluxation or cataract• Retinal detachment

CILIARY BODY MELANOMA

C/F Ant. Uveitis Investigations –

Tripple mirror contact lens, Transillumination, Ultrasonic biomicroscopy, Biopsy

Infiltration of malignant melanoma into the iris

Keratic precipitates, occasional intraocular cells, and posterior synechiae

Treatment options of ciliary body melanoma

1. Iridocyclectomy - small or medium tumours

2. Enucleation - large tumours

3. Radiotherapy - selected cases

Uveal melanoma

Epidemiology: 4.9% of 450 enucleation specimens had ocular

inflammation initially Ocular Manifestations:

Episcleritis, AU, PU, endophthalmitis, panophthalmitis

Systemic Associations: May have features of metastatic melanoma

Choroidal melanoma• Most common primary intraocular tumour in adults

• Most common uveal melanoma - 80% of cases

• Presentation - sixth decade

• Prognosis - usually good

Choroidal melanoma (1)

• Brown, elevated, subretinal mass• Occasionally amelanotic• Double circulation

• Secondary retinal detachment • Choroidal folds

Choroidal melanoma (2)

• Surface orange pigment (lipofuscin) is common• Mushroom-shaped if breaks through Bruch’s membrane

• Ultrasound - acoustic hollowness, choroidal excavation and orbital shadowing

Treatment of choroidal melanoma

1. Brachytherapy - less than 10 mm elevation and 20 mm diameter

2. Charged particle irradiation - if unsuitable for brachytherapy

3. Transpupillary thermotherapy - selected small tumours

4. Trans-scleral local resection - carefully selected tumours less than 16 mm in diameter

5. Enucleation - very large tumours, particularly if useful vision lost

6. Exenteration - extraocular extension

LEUKAEMIAS :INTRODUCTION

Gp. Of neoplastic disorders ch. By abnormal proliferation of WBC.

Three types ALL- Children are affected AML- Worse prognosis,Adults more affected Chronic leukaemias – Elderly affected

Ocular findings in 28–75% with acute leukemia less with chronic

LEUKAEMIAS OCULAR FEATURES

SCH Iritis & Hypopyon Diffuse & Nodular iris thickening Hyphaema Orbital involvement Optic neuropathy

Anterior segment infiltration in acute myeloid leukemia (AML) presenting as hypopyon uveitis

Relapsing acute myeloid leukemia presenting as hypopyon uveitis Sapna P Hegde1, Atul T Ursekar2, Ajay A Chitale3

LEUKAEMIAS Retinopathy

Venous tortuosity & dilatation

Flame shaped H’ge & ROTH SPOTS Cotton wool spots Peripheral retinal

neovascularisation LEOPARD SPOT

RETINA

Leukemic infiltration of the retina

Masquerading as infectious chorioretinitis

Diagnostic Tests

Bone marrowperipheral blood smearaqueous cytology

JUVENILE XANTHOGRANULOMA

Vascular Tm. Affecting skin & eye

Important cause spontaneous hyphaema & seconary glaucoma

Epidemiology: 85% of skin lesions present before 1

year of age

Ocular Manifestations: Yellowish iris nodule or diffuse

thickening, heterochromia, spontaneous hyphema

Systemic Associations:Raised, reddish-yellowish skin lesions

Diagnosis iris biopsy or by finding similar lesions on the skin

Metastatic tumors Epidemiology :

Most common intraocular malignancy in adults

Ocular Manifestations: Usually bilateral, multifocal,

plateau-shaped, yellow posterior segment lesions with SRF; anterior segment: AU, iris nodules, NVI

Systemic Associations : Lung and breast carcinoma most

common primary sites Cutaneous melanoma most

common metastasis to retina

Long-standing peripheral rhegmatogenous retinal detachment

May produce a cellular reaction in the anterior or posterior chamber as well as PS.

Diagnostic Tests Ophthalmoscopy Ultrasound

Retained intraocular foreign body

Retained intraocular foreign body associated with trauma may cause persistent anterior and/ or posterior segment inflammation.

Diagnostic Tests: X-ray Ultrasound CT scan( should demonstrate the abnormality)

Retinitis pigmentosa

May present with vitreous cells and posterior subcapsular cataract The ‘‘bone spicule’’ pigment deposition in the retina,

attenuated retinal vessels, mottling and atrophy of the RPE, and waxy pallor of the optic nerve help to distinguish this disease from other disorders.

The diagnosis can be confirmed with an extinguished electroretinogram and ring scotoma on visual field testing.

Kruckenberg’s spindle in a patient with pigment dispersion syndrome that masqueraded as anterior uveitis.

Ocular ischemicsyndrome

Age (yr):50+ Signs of Inflammation

Cell Flare Redness

Diagnostic Tests: IVFA Carotid Doppler

Ocular Ischemic Syndrome

What percent carotid obstruction is typically required to cause OIS? 90%

Describe the symptoms Gradual visual loss Aching pain Prolonged recovery following bright light exposure

What are anterior segment findings? Iris neovascularization (67%) AC cellular reaction (20%)

Ocular Ischemic Syndrome Describe the posterior segment findings

Narrowed arteries Dilated, non-tortuous veins Mid-peripheral retinal hemorrhages, microaneurysms Neovascularization

What are the fluorescein angiographic findings? Delayed choroidal filling (60%) Delayed arteriovenous transit (95%) Vascular staining (85%)

What is the 5-year mortality rate and what is the most common cause of death? 40% Cardiovascular disease

85yo chronic pain and redness OD

Coats’ disease

Aspecific uveitis Vitreous infiltrates Fluorescein angiography

Presentation of Coats disease• First decade, more common in boys• Always unilateral

Visual loss and strabismus White fundus reflex (leukocoria)

Progression of Coats disease

• Retinal and subretinal hard exudation• Overlying vascular dilatation and tortuosity

• Slow progresssion of exudation• Exudative retinal detachment and retrolental mass

• May benefit from photocoagulation

• Treatment not beneficial • May mimic retinoblastoma

• Severe visual loss

FA of Coats disease

Vascular malformations are highlighted

Uveitis associated with medications

CONCLUSION

It is clear that a number of entities can masquerade as idiopathic uveitis, and in the absence of a correct diagnosis inappropriate therapy may be prescribed.

The diagnosis of a masquerade syndrome should therefore be considered in the evaluation of all patients with undiagnosed inflammatory eye disease

Thanks for your attention