eye

1. Pathology of uvea
Azza Mohamed Ahmed Said
Ass. Prof. Of Ophthalmology
Ain Shams University

2. Uveal tract

3. 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

4. IRIS
• Most anterior part of uveal tract.
• Circular diaphragm e central hole.
• Forms posterior wall of anterior
chamber.
• Lies in front of crystalline lens.
• Colour differs acc. To melanin
concentration
in
melanocytes.
• Has 2 surfaces (ant &post).
ant.stromal

5. IRIS
• The iris is composed of 5 layers:
1-Anterior border layer
4-Anterior pigment epithelium
2-Stroma
3 - Muscular layer
5-Posterior pigment epithelium
Melanocytes
Clump cells
2 layers of
Cuboidal epith

6. CILIARY BODY
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

7. CHOROID
consists of 3 principal layers:
• lamina fusca (suprachoroid layer)
• stroma
• choriocapillaris
The choriocapillaris is the blood supply for (RPE) and the outer retinal
Layers.

8. Common pathological disorders
Congenital
Congenital
Inflammation
Inflammation
Neoplasms
Neoplasms
Degenerative
Degenerative
Vascular
Vascular
Traumatic
Traumatic
Primary
Metastasis

9. Iris pathology

11. Abnormal neural crest cell migration
Axenfeld anomaly
Rieger anomaly
Peter's anomaly
Sclerocornea

12. Abnormal neural crest cell proliferation
Iridocorneal Endothelial Syndrome
Iris naevus (Cogan-Reese) syndrome
Progressive iris atrophy
Chandler syndrome

13. Abnormal neural crest cell final
differentiation
Congenital hereditary endothelial dystrophy

14. Congenital and
developmental anomalies

15. Coloboma

16. Aniridia
Partial absence
Wilm’s
Tumor
Synechial angle-closure
glaucoma in 75%

17. Iris cysts

18. Unilateral
stationary

19. Primary epithelial cyst
Primary stromal cyst

22. Iris stromal cyst lined by stratified squamous
epithelium

23. Miotic cyst

24. Implantation cysts
Pearl cyst
Serous cyst

25. Iris nodules

26. Causes of iris nodules
• Cysts….
• Solid swellings:
1- Brushfield spots.
2- Lisch nodules.
3- Inflammatory:
• Koeppe's and Busacca's in nodules in granulomatous uveitis.
• FB granuloma.
• Juvenile xanthograuloma.
4- Neoplasms:
• Benign: naevus, leiomyoma, neurofibroma, hemangioma, adenoma of iris
pigment epithelium.
• Malignant:
– Primary :iris melanoma
– Secondaries : extension from CB melanoma, leukemic deposits.

27. Brushfield spots in Down syndrome
Relatively normal, or mildly hypercellular, iris
stroma (between arrows) surrounded by a hypoplastic
iris

28. Lisch nodules in NF1
Benign iris hamartomas

29. Koeppe'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

30. FB granuloma

31. 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

32. Juvenile Xanthogranuloma

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.

34. 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

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

36. Melanoma cytology
• Spindle-A cells have slender,
elongated nuclei with small
nucleoli.
• A central stripe may be present
down the long axis of the
nucleus

37. Melanoma cytology
• 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.

38. Melanoma cytology
• 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.

39. Histological classification of uveal melanoma
Spindle A cell
Spindle cell (45%)
Mixed cell (45%)
Spindle B cell
Pure epithelioid cell (5%)
Necrotic (5%)

40. 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)

41. Iris nevus
•
Benign tumor that arises in the
melanocytes in the iris stroma.
• Composed of low-grade spindletype cells.
• Asymptomatic pigmented, wellcircumscribed lesion in the iris
stroma .
• Flat or minimally elevated.

42. Iris leiomyoma
• Benign tumor, arises from smooth
muscles of iris.
• DD :
Iris amelanotic melanoma
– Location :may not present in inferior
half.
– Immunohistochemical analysis with
anti-muscle specific actin and electron
microscopy.

43. Adenoma 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.

44. Malignant infiltrates
Malignant hypopyon and
hyphema in leukemic patient
Retinoblastoma
infiltrates of iris

45. CB malignant melanoma invading the
iris

46. Ciliary Body tumors

47. Ciliary body tumors
• Stromal tumors:
– Benign : angioma, neurofibroma, leiomyoma.
– Malignant: malignant melanoma, metastatic carcinoma.
• Epithelial tumors:
– Benign: adenoma, pseudoadenomatous hyperplasia.
– Malignant : Medulloepithelioma, adenocarcinoma.

48. Ciliary body melanoma
 Clinical picture
 Asymptomatic.
 Blurring of vision.(lenticular
astigmatism, presbyopia)
 Cataract, sublaxation.
 Epibulbar mass
 Sentinel vs.
 Heterochromia, iris nodule.
 Uveitis
 Glaucoma
 Ch.detachment, ERD.

49. CB malignant melanoma
Ring melanoma

50. Malignant melanoma
• Melanomas of the ciliary body have a
similar
histologic
melanomas
in
the
appearance
choroid
to
and
demonstrate spindle- to epithelioidtype cells with variable pigmentation.
Mitotic figures may be seen.

51. 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.

52. 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
accumulation
of
cells
with
basement
membrane-like material.

53. 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.

54. Melanocytoma
• Heavily pigmented tumors with
large polygonal cells and small
vesicular nuclei with abundant
cytoplasm totally packed with
melanin granules.

55. Leiomyoma
• Leiomyoma
body.
The
of
the
ciliary
tumor
shows
bundles of eosinophilic spindle
cells. The neoplastic cells are
immunoreactive with musclespecific actin.

56. Choroidal pathological
changes

57. Age –related changes: Drusen
Histopathology
Hard
•
•
Small well-defined
spots
Usually innocuous
Soft
•
Larger, ill-defined spots
May enlarge and coalesce
•
Increased risk of AMD
•

58. CNVM
Type 2
In
CNVM
Type 1
In
ARMD
POHS

59. Aicardi syndrome
Very rare
• X-linked dominant which is lethal in utero for males
• Infantile spasms
• Developmental delay
• CNS malformations and early demise
•
Multiple ‘chorioretinal lacunae’
Disc coloboma and pigmentation

60. Hereditary choroidal dystrophies
1. Choroideremia
2. Gyrate atrophy
3. Central areolar choroidal dystrophy
4. Diffuse choroidal atrophy

61. Choroideremia
Inheritance - X-linked recessive
Presents - first decade with nyctalopia
Prognosis - good VA until late
ERG - reduced
Progression
• Circumscribed atrophy of RPE
and choroid
• Starting in periphery
• Gradual central spread
• Fovea spared until late

62. Female carriers of choroideremia
Central patchy atrophy and
mottling of RPE
Peripheral diffuse pigmentary
granularity

63. Gyrate atrophy
Cause - deficiency of ornithine keto-acid aminotransferase
Inheritance - autosomal recessive
Presents - first decade with axial myopia and nyctalopia
Prognosis - usually good VA until late
ERG - severely reduced
Progression
•
Mid-peripheral, circular patches
of chorioretinal atrophy
•
Enlargement and confluence
Central and peripheral spread
• Late retinal vascular attenuation
• Fovea spared until late
•

64. Central areolar choroidal dystrophy
Inheritance - dominant
Presents - fifth decade
Prognosis - poor
ERG - normal
•
•
Bilateral, circumscribed, atrophic maculopathy
Prominent large choroidal vessels

65. Diffuse choroidal atrophy
Inheritance - dominant
Presents - fourth to fifth decades
Prognosis - poor
ERG - reduced
•
•
Diffuse atrophy of RPE and choriocapillaris
Prominent large choroidal vessels

66. 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

67. Uveitis
• Def.: inflammation of the uveal tract.
• Classification:
a-a- Anatomical
Anatomical
b- Clinical
anterior intermediate posterior pan
Acute
symp.
iritis
pars planitis
c- Etiological
Chronic
Asymp.
choroditis
iridocyclitis
< 8 wks
>3m
(iris+ pars plicata )
Acute
Gradual

68. Uveitis
Specific
Fuch’s heterochromic
Non specific
25%

69. 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.

70. Inflammation
Categories (by type of cells in tissue or exudates)
• Acute
– Polymorphonuclear leucocytes.
– Mast cells and eosinophils.
• Chronic
– Non granulomatous
• Lymphocytes and plasma cells.
– Granulomatous
• Epithelioid,histiocytes ± giant cells.

74. Granulomatous inflammation
Three histologic patterns of granulomatous
inflammation
• Diffuse.
• Discrete.
• Zonal.

75. 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 VogtKoyanagi-Harada
(VKH)
disease.

76. 1- Diffuse granulomatous inflammation
• Sympathetic ophthalmitis
– Bilateral diffuse chronic granulomatous panuveitis
– There is an exciting eye (previously traumatized)
sympathizing eye.
– Anterior segment findings:
and
• Mutton fat KPS
– Posterior segment findings:
• Vitreous inflammatory cells
• Papillitis
• Dalen-Fuchs nodules (yellow-white lesions beneath the RPE),
choroidal granulomas
• ERD.

77. 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
involve the choriocapillaris. XVKH
– Dalen-Fuchs nodules are composed of:
Nodular clusters of epithelioid cells lying
between the RPE and Bruch's membrane .

78. 1- Diffuse granulomatous inflammation

79. 2- Discrete 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.

80. 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).

81. 3- Zonal granulomatous inflammation
• A central zone of necrosis and/or
polymorphonuclear
leukocytes
surrounded
by
epithelioid
histiocytes which is in turn
surrounded by a zone of nongranulomatous
inflammation
consisting of granulation tissue,
lymphocytes and plasma cells.
• Seen in:
Phacoanaphylactic uveitis

82. 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

83. Nevus cells
Four types of nevus cells:
• Plump polyhedral: abundant cytoplasm filled with pigment and a
small, round to oval nucleus with bland appearance.
• Slender spindle : cytoplasm contains scant pigment and a small,
dark, elongated nucleus.
• Plump fusiform dendritic: morphology is intermediate between
plump polyhedral and slender spindle.
• Balloon cells: abundant, foamy cytoplasm that lacks pigment and
has a bland nucleus.

84. 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

85. Predisposing factors
Suspicious choroidal nevus
• Diameter more than 5 mm
• Elevation 2 mm or more
• Surface lipofuscin
• Posterior margin within
3 mm of disc
Oculodermal melanocytosis
Nevus of Ota
• May have symptoms due
to serous fluid

86. Course of malignant melanoma of the choroid
(knapp’s classification)
1. 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.

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

88. Course of malignant melanoma of the choroid
2. Glaucomatous stage:
a) Obstruction of venous outflow.
b)
Pusching of iris lens dighragm forward closing the angle of Ach.
c) Melanomalytic glaucoma.
Angle blocked by large number of macrophages containing
phagocytosed melanin pigments.
d)
Iris neovascularization.

89. Course of malignant melanoma of the choroid
3. Extraocular stage:
a) Scleral foramina… epibular mass
b) direct sclera invasion: late..
c) Along optic nerve and sheaths: not common.
d) Orbit ----Proptosis

90. Course of malignant melanoma of the choroid
4. Metastasis stage:
Hematogenous spread to liver, lung, bone.

91. Histological classification of uveal melanoma
Spindle A cell
Spindle cell (45%)
Mixed cell (45%)
Spindle B cell
Pure epithelioid cell (5%)
Necrotic (5%)

92. Malignant melanoma of choroid
• Clinical picture





Asymptomatic.
Photopsia or floaters.
Painless visual loss.
Pain….Glaucoma, uveitis.
Epibulbar mass.


Unilateral / Unifocal collar
button shaped pigmented or
non pigmented
(amelanotic)
± Exudative RD

93. Choroidal melanoma (1)
• Brown, elevated, subretinal mass
• Secondary retinal detachment
• Occasionally amelanotic
• Double circulation
• Choroidal folds

94. 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

95. 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
Necrotic and mixed
Epithelioid
25%
50%
60%

96. Differential diagnosis of choroidal melanoma
Large choroidal naevus
Choroidal detachment
Metastatic tumour
Choroidal granuloma
Localized choroidal
haemangioma
Dense sub-retinal or
sub-RPE haemorrhage

97. 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 externa
globe pressure
• Surface cystoid retinal
degeneration
• Exudative retinal
detachment
• Treatment - radiotherapy
if vision threatened

98. Circumscribed choroidal haemangioma
It is composed of cavernous spaces filled with red blood
cells and is usually demarcated from normal choroid

99. Diffuse choroidal haemangioma
Typically affects patients with Sturge-Weber syndrome
Can be missed unless compared with normal
fellow eye as shown here
Diffuse thickening, most marked at
posterior pole

100. 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%

101. Choroidal osseous choristoma
Compact bone contain osteocytes, and intratrabecular
spaces are filled with loose connective tissue containing
large and small blood vessels.
• Very rare, benign, slowgrowing 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%.

102. Melanocytoma (Magnocellular nevus)
• Affects dark skinned
individuals
• Usually asymptomatic
• Most frequently affects
optic nerve head
(inferotemporal)
• Black lesion with feathery
edges.
• Deeply pigmented
polyhedral cells with a small
nuclei.

103. 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.

104. Choroidal detachment
• - Associated with hypotony.
• - Unilateral, brown, smooth,
solid and immobile.

105. Heterochromia iridis
Different colours of the two irides

106. THANK YOU