Pathology of uvea

Azza Mohamed Ahmed Said

Ass. Prof. Of Ophthalmology

Ain Shams University

Uveal tract

• Uveal tract is embryologically derived from mesoderm and neural crest.

• Firm attachments between the uveal tract and the sclera exist at only 3 sites:

– Scleral spur

– Exit points of the vortex veins

– Optic nerve

Uveal tract

• Most anterior part of uveal tract.Most anterior part of uveal tract.

• Circular diaphragm e central hole.Circular diaphragm e central hole.

• Forms posterior wall of anterior Forms posterior wall of anterior

chamber.chamber.

• Lies in front of crystalline lens.Lies in front of crystalline lens.

• Colour differs acc. To melanin Colour differs acc. To melanin

concentration in ant.stromal concentration in ant.stromal

melanocytes.melanocytes.

• Has 2 surfaces (ant &post).Has 2 surfaces (ant &post).

IRIS

• The iris is composed of 5 layers:1-Anterior border layer 2-Stroma 3 - Muscular layer

4-Anterior pigment epithelium 5-Posterior pigment epithelium

IRIS

Melanocytes

Clump cells

2 layers ofCuboidal epith

6.0- 6.5 mm wide.6.0- 6.5 mm wide.

Inner surface:2parts• pars plicata ant.1/3• pars plana post.2/3

• Lined by double layer of epith.cells: inner non pig. and outer pig

CILIARY BODY

consists of 3 principal layers:• lamina fusca (suprachoroid layer)

• stroma

• choriocapillaris

The choriocapillaris is the blood supply for (RPE) and the outer retinal

Layers.

CHOROID

Common pathological disorders

Inflammation Inflammation

Neoplasms Neoplasms Primary

Metastasis

Congenital Congenital

Degenerative Degenerative

Vascular Vascular

Traumatic Traumatic

Iris pathology

Axenfeld anomaly Rieger anomaly

Peter's anomaly Sclerocornea

Abnormal neural crest cell migration

Abnormal neural crest cell proliferation

Iridocorneal Endothelial Syndrome

Progressive iris atrophy

Iris naevus (Cogan-Reese) syndrome

Chandler syndrome

Abnormal neural crest cell final differentiation

Congenital hereditary endothelial dystrophy

Congenital and developmental anomalies

Coloboma

Synechial angle-closure glaucoma in 75%

Partial absence

Aniridia

Wilm’sTumor

Iris cysts

Unilateralstationary

Primary epithelial cyst Primary stromal cyst

Iris stromal cyst lined by stratified squamous epithelium

Miotic cyst

Implantation cysts

Pearl cyst Serous cyst

Iris nodules

Causes of iris nodules• Cysts….Cysts….

• Solid swellings:Solid swellings:

1- Brushfield spots. 1- Brushfield spots.

2- Lisch nodules. 2- Lisch nodules.

3- Inflammatory: 3- Inflammatory: • Koeppe's and Busacca's in nodules in granulomatous uveitis.

• FB granuloma.

• Juvenile xanthograuloma.

4- Neoplasms:4- Neoplasms:• Benign: naevus, leiomyoma, neurofibroma, hemangioma, adenoma of iris

pigment epithelium.

• Malignant: – Primary :iris melanoma– Secondaries : extension from CB melanoma, leukemic deposits.

..

Brushfield spots in Down syndromeBrushfield spots in Down syndrome

Relatively normal, or mildly hypercellular, iris stroma (between arrows) surrounded by a hypoplastic

iris

Lisch nodules in NF1Lisch nodules in NF1

Benign iris hamartomas

Koeppe's and Busacca's in nodulesKoeppe's and Busacca's in nodules

Busacca’s nodules: on the surface of iris

Koeppe’s nodules: at pupillary margin

Aggregates of epithelioid cells & mononuclear cells

FB granuloma

Juvenile Xanthogranuloma Juvenile Xanthogranuloma

Pediatric skin disorder of non-langerhan's cell histiocytosis. (benign)

Skin lesions

Firm, slightly raised papulonodules Several millimeters in diameter Tan-orange in color

Extracutaneous… 1- The uveal tract, is the m/f site:

Iris nodules Heterochromia Uveitis Spontaneous hyphema Secondary glaucoma

2- Eyelid: typical cutaneous lesions.

3- Orbit: Infiltrative soft tissue tumors cause proptosis.

Juvenile Xanthogranuloma Juvenile Xanthogranuloma

Iris melanoma Iris melanoma

Color: Pigmented or non pigmented.

Site : inferior half.

Size : ›1mm X3mm.

Shape:– Nodular

– Diffuse (ring sarcoma)

Associated features:

Pupil distortion, ectropion uvea, localized cataract, angle invasion, glaucoma, uveitis

Iris melanoma Iris melanoma

Iris mass completely replacing the normal iris stroma, extending into the anterior chamber, touching the posterior cornea, and occluding

the angle.

Melanoma cytology

• Spindle-A cells Spindle-A cells have slender, elongated nuclei with small nucleoli.

• A central stripe may be present down the long axis of the nucleus

• Spindle-B cells Spindle-B cells demonstrate a higher nuclear to- cytoplasmic ratio; more coarsely granular chromatin; and plumper, large nuclei.

• Nucleoli are prominent and mitoses are present. though not in large numbers.

Melanoma cytology

• Epithelioid cells Epithelioid cells resemble epithelium because of abundant eosinophilic cytoplasm and enlarged oval to polygonal nuclei.

• Nuclei have a conspicuous nuclear membrane, very coarse chromatin, and large nucleoli.

Melanoma cytology

Histological classification of uveal melanoma

Spindle cell (45%) Pure epithelioid cell (5%)

Mixed cell (45%) Necrotic (5%)

Spindle A cell Spindle B cell

Iris Melanoma

1. Very rare - 8% of uveal melanomas

2. Presentation - fifth to sixth decades

3. Very slow growth

4. Low malignancy (spindle type)

5. Excellent prognosis (early detection, low grade malignancy, late metastasis)

•  Benign tumor that arises in the melanocytes in the iris stroma.

• Composed of low-grade spindle-type cells.

• Asymptomatic pigmented, well-circumscribed lesion in the iris stroma .

• Flat or minimally elevated.

Iris nevus Iris nevus

• Benign tumor, arises from smooth muscles of iris.

• DD :DD :

Iris amelanotic melanomaIris amelanotic melanoma

– Location :may not present in inferior half.

– Immunohistochemical analysis with anti-muscle specific actin and electron microscopy.

Iris leiomyoma Iris leiomyoma

Adenoma of iris pigment epitheliumAdenoma of iris pigment epithelium

Benign Pigmented friable nodule in the angle due to proliferation of iris pigment epithelium or pig. or non-pig. epith. Of CB.

Malignant infiltratesMalignant infiltrates

Malignant hypopyon and hyphema in leukemic patient Retinoblastoma

infiltrates of iris

CB malignant melanoma invading the CB malignant melanoma invading the irisiris

Ciliary Body tumorsCiliary Body tumors

Ciliary body tumorsCiliary body tumors

• Stromal tumors:Stromal tumors:

– Benign : angioma, neurofibroma, leiomyoma.– Malignant: malignant melanoma, metastatic carcinoma.

• Epithelial tumors:Epithelial tumors:– Benign: adenoma, pseudoadenomatous hyperplasia.– Malignant : Medulloepithelioma, adenocarcinoma.

Clinical picture

Asymptomatic. Blurring of vision.(lenticular

astigmatism, presbyopia) Cataract, sublaxation. Epibulbar mass Sentinel vs. Heterochromia, iris nodule. Uveitis Glaucoma Ch.detachment, ERD.

Ciliary body melanoma

CB malignant melanoma

Ring melanoma

Malignant melanoma

• Melanomas of the ciliary body have a

similar histologic appearance to

melanomas in the choroid and

demonstrate spindle- to epithelioid-

type cells with variable pigmentation.

Mitotic figures may be seen.

Medulloepithelioma (Diktyoma)

• Affects children between 6 months and 5 years.• Aises from inner layer of optic cup.• Teratoid or non teratoid, both subdivied into benign or malignant.• Multi-layered sheets or cords of immature neuroepithelial

cells/rosettes.

Pseudoadenomatous hypeplasia (Fuchs' adenoma)

• A glistening, white irregular

tumor arising from the ciliary

body. It consists of a benign

proliferation of non-pigmented

ciliary epithelial cells with

accumulation of basement

membrane-like material.

Adenoma and adenocarcinoma

• Adenoma shows tubular proliferation

of pigment epithelium of the ciliary

body.

• Adenocarcinomas are composed of

gland-like accumulations of cells with

prominent nuclei, nucleoli and marked

pleomorphism.

• Pigmented or non-pigmented.

Melanocytoma

• Heavily pigmented tumors with

large polygonal cells and small

vesicular nuclei with abundant

cytoplasm totally packed with

melanin granules. 

Leiomyoma

• Leiomyoma of the ciliary

body. The tumor shows

bundles of eosinophilic spindle

cells. The neoplastic cells are

immunoreactive with muscle-

specific actin.

Choroidal pathological changes

Age –related changes: DrusenHistopathology

• Small well-defined spots• Usually innocuous

• Larger, ill-defined spots• May enlarge and coalesce

SoftHard

• Increased risk of AMD

CNVM Type 1

In

ARMD

CNVM Type 2

In

POHS

Aicardi syndrome

• CNS malformations and early demise

• Very rare• X-linked dominant which is lethal in utero for males

Multiple ‘chorioretinal lacunae’ Disc coloboma and pigmentation

• Infantile spasms• Developmental delay

Hereditary choroidal dystrophies

1. Choroideremia

2. Gyrate atrophy

3. Central areolar choroidal dystrophy

4. Diffuse choroidal atrophy

ChoroideremiaInheritance - X-linked recessive

• Circumscribed atrophy of RPE and choroid• Starting in periphery

• Gradual central spread

• Fovea spared until late

Presents - first decade with nyctalopiaPrognosis - good VA until lateERG - reduced

Progression

Female carriers of choroideremia

Peripheral diffuse pigmentary granularity

Central patchy atrophy and mottling of RPE

Gyrate atrophy

• Mid-peripheral, circular patches of chorioretinal atrophy

• Enlargement and confluence

• Central and peripheral spread• Late retinal vascular attenuation

Inheritance - autosomal recessivePresents - first decade with axial myopia and nyctalopia

Prognosis - usually good VA until lateERG - severely reduced

Cause - deficiency of ornithine keto-acid aminotransferase

• Fovea spared until late

Progression

Central areolar choroidal dystrophy

• Bilateral, circumscribed, atrophic maculopathy• Prominent large choroidal vessels

Inheritance - dominantPresents - fifth decadePrognosis - poorERG - normal

Diffuse choroidal atrophy

• Diffuse atrophy of RPE and choriocapillaris• Prominent large choroidal vessels

Inheritance - dominantPresents - fourth to fifth decadesPrognosis - poorERG - reduced

Elschnig's spots

• Elschnig's spots are ischemic infarcts of the choroid and RPE that appear in the posterior pole.

• Causes:– Malignant hypertension.

– Temporal arteritis.

– Sickle cell disease.

– Toxemia of pregnancy.

– Disseminated intravascular coagulopathy

• Def.: inflammation of the uveal tract.• Classification:

a- Anatomical

anterior intermediate posterior pan Acute Chronic

symp. Asymp.

iritis pars planitis choroditis

iridocyclitis < 8 wks >3m

(iris+ pars plicata ) Acute Gradual

a- Anatomical

Uveitis

b- Clinical c- Etiological

Uveitis

SpecificSpecificFuch’s heterochromic Fuch’s heterochromic

Non specific Non specific 25%25%

Inflammation

A reaction of microcirculation ccc. By movement of fluid and cells into the extravascular tissues in response to foreign particles, micro-oganisms or antigens.

Categories (by type of cells in tissue or exudates)

• AcuteAcute– Polymorphonuclear leucocytes.– Mast cells and eosinophils.

• ChronicChronic– Non granulomatous

• Lymphocytes and plasma cells.

– Granulomatous• Epithelioid,histiocytes ± giant cells.

Inflammation

Granulomatous inflammation

Three histologic patterns of granulomatous

inflammation

• Diffuse.

• Discrete.

• Zonal.

1- Diffuse granulomatous inflammation

• Epithelioid histiocytes are scattered throughout the involved uveal tissue. There may be an accompanying background of lymphocytes and plasma cells.

• Seen in sympathetic ophthalmitis and Vogt-Koyanagi-Harada (VKH) disease.

• Sympathetic ophthalmitis– Bilateral diffuse chronic granulomatous panuveitis

– There is an exciting eye (previously traumatized) and sympathizing eye.

– Anterior segment findings:Anterior segment findings:• Mutton fat KPS

– Posterior segment findings:Posterior segment findings:• Vitreous inflammatory cells

• Papillitis

• Dalen-Fuchs nodules Dalen-Fuchs nodules (yellow-white lesions beneath the RPE), choroidal granulomas

• ERD.

1- Diffuse granulomatous inflammation

• Sympathetic ophthalmitis

– Histologically, both the traumatized and sympathizing eyes show diffuse granulomatous inflammation made up of nests of epithelioid cells and giant cells mixed with lymphocytes. This inflammation does not extend to does not extend to involve the choriocapillaris. involve the choriocapillaris. XVKHXVKH

– Dalen-Fuchs nodules are composed of:

Nodular clusters of epithelioid cells lying between the RPE and Bruch's membrane .

1- Diffuse granulomatous inflammation

1- Diffuse granulomatous inflammation

• Well-circumscribed areas of epithelioid histiocytes

• Seen in :

Sarcoidosis: Non caseating granuloma of of the lungs, liver, lymph nodes, skin, and even the central nervous system.

2- Discrete granulomatous inflammation

• The classic sarcoid nodule is composed of noncaseating granulomas. These are collections of epithelioid histiocytes, sometimes accompanied by multinucleated giant cells, that have a surrounding cuff of lymphocytes.

• The multinucleated giant cells may demonstrate:

– Asteroid bodies

• (star-shaped, acidophilic bodies)

– Schaumann bodies

• (spherical, basophilic, calcified bodies).

2- Discrete granulomatous inflammation

• A central zone of necrosis and/or polymorphonuclear leukocytes surrounded by epithelioid histiocytes which is in turn surrounded by a zone of non-granulomatous inflammation consisting of granulation tissue, lymphocytes and plasma cells.

• Seen in:

Phacoanaphylactic uveitis

3- Zonal granulomatous inflammation

Typical choroidal nevus

• Common - 2% of population

• Round slate-grey with indistinct margins

• Surface drusen

• Flat or slightly elevated

• < 2 mm X 5 mm

• Location - anywhere

• Asymptomatic

Nevus cells

Four types of nevus cells:

• Plump polyhedral: Plump polyhedral: abundant cytoplasm filled with pigment and a small, round to oval nucleus with bland appearance.

• Slender spindle : Slender spindle : cytoplasm contains scant pigment and a small, dark, elongated nucleus.

• Plump fusiform dendritic: Plump fusiform dendritic: morphology is intermediate between plump polyhedral and slender spindle.

• Balloon cells: Balloon cells: abundant, foamy cytoplasm that lacks pigment and has a bland nucleus.

Choroidal melanoma• Most common primary intraocular tumour in adults.

• Most common uveal melanoma - 80% of cases

• Presentation - sixth decade

• More common in males , white race

Predisposing factors

• Diameter more than 5 mm

• Elevation 2 mm or more

• Surface lipofuscin

• Posterior margin within 3 mm of disc

• May have symptoms due to serous fluid

Suspicious choroidal nevus

Oculodermal melanocytosisNevus of Ota

Course of malignant melanoma of the choroid(knapp’s classification)

1.1. Quiescent stage:Quiescent stage:

Tumor starts in the outer layers of

choroid. ( lens –shaped) deep to Bruch’s

membrane--- the membrane then raised

by tumor and resists invasion----then

Broken and tumor extends through hole –

-collar -stud appearance which is formed

of :

A- Broad base in choroid.

B- Neck embraced by Bruch’s membrane.

C- Head internal to Bruch’s membrane.

Course of malignant melanoma of the choroid(knapp’s classification)

Course of malignant melanoma of the choroid

2.2. Glaucomatous stage:Glaucomatous stage:

a) Obstruction of venous outflow.

b) Pusching of iris lens dighragm forward closing the angle of Ach.

c)c) Melanomalytic glaucoma.Melanomalytic glaucoma.Angle blocked by large number of macrophages containing

phagocytosed melanin pigments.

d) Iris neovascularization.

Course of malignant melanoma of the choroid

3.3. Extraocular stage:Extraocular stage:

a) Scleral foramina… epibular mass

b) direct sclera invasion: late..

c) Along optic nerve and sheaths: not common.

d) Orbit ----Proptosis

Course of malignant melanoma of the choroid

4.4. Metastasis stage:Metastasis stage:

Hematogenous spread to liver, lung, bone.

Histological classification of uveal melanoma

Spindle cell (45%) Pure epithelioid cell (5%)

Mixed cell (45%) Necrotic (5%)

Spindle A cell Spindle B cell

Malignant melanoma of choroidMalignant melanoma of choroid

• Clinical picture Asymptomatic. Photopsia or floaters. Painless visual loss. Pain….Glaucoma, uveitis. Epibulbar mass.

Unilateral / Unifocal Unilateral / Unifocal collar collar button shaped button shaped pigmentedpigmented or or non pigmented non pigmented (amelanotic)(amelanotic)

± Exudative RD± Exudative RD

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

Poor Prognostic Factors of Uveal Melanomas

1. Histological• Epithelioid cells

• Closed vascular loops

• Lymphocytic infiltration

2. Large size

3. Extrascleral extension

4. Anterior location

5. Age over 65 years

6. Chromosomal abnormalities

Cell type 5ys mortality

Spindle A 5% Spindle B 25%Necrotic and mixed 50%Epithelioid 60%

Differential diagnosis of choroidal melanoma

Large choroidal naevus Metastatic tumour Localized choroidal haemangioma

Choroidal detachment Choroidal granuloma Dense sub-retinal or

sub-RPE haemorrhage

Circumscribed choroidal haemangioma• Presentation - adult life

• Dome-shaped or placoid, red-orange mass

• Commonly at posterior pole

• Between 3 and 9 mm in diameter

• May blanch with external globe pressure

• Surface cystoid retinal degeneration

• Exudative retinal detachment

• Treatment - radiotherapy if vision threatened

It is composed of cavernous spaces filled with red blood cells and is usually demarcated from normal choroid

Circumscribed choroidal haemangioma

Diffuse choroidal haemangioma Typically affects patients with Sturge-Weber syndrome

Diffuse thickening, most marked at posterior pole

Can be missed unless compared with normal fellow eye as shown here

Choroidal metastatic carcinoma Most frequent primary site is breast in women and bronchus in both sexes

• Fast-growing, creamy-white, placoid lesion• Most frequently at posterior pole

• Deposits may be multiple

• Bilateral in 10-30%

Choroidal osseous choristoma

• Very rare, benign, slow-growing ossifying tumor.

• Typically affects young women

• Orange-yellow, oval lesion.

• Well-defined, scalloped, geographical borders.

• Most commonly peripapillary or at posterior pole.

• Diffuse mottling of RPE.

• Bilateral in 25%.

Compact bone contain osteocytes, and intratrabecular spaces are filled with loose connective tissue containing large and small blood vessels.

Melanocytoma (Magnocellular nevus)

• Affects dark skinned individuals

• Usually asymptomatic

• Most frequently affects optic nerve head (inferotemporal)

• Black lesion with feathery edges.

• Deeply pigmented Deeply pigmented polyhedral cells with a small polyhedral cells with a small nuclei. nuclei.

Choroidal ruptures

• Blunt trauma.

• Semicircular lines circumscribing the optic nerve head in the peripapillary region.

• Sub retinal NV can occur as a late complication.

• More severe injury may cause rupture of both the choroid and the retina, a condition termed chorioretinitis sclopetaria.

Choroidal detachment

• - Associated with hypotony.

• - Unilateral, brown, smooth, solid and immobile.

Heterochromia iridisDifferent colours of the two irides

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