2. Classification
• Uveal tumors can be classified according to their location,
etiopathology, histopathology, histogenesis, genotype, and
various other ontological methods.
• Etiopathologic and pathologic classification
11. Epithelial tumours
• Epithelial tumors of iris & ciliary body are relatively rare.
• As anterior layer of epithelium gives rise to smooth
muscles, all gradations of tumour may exists from
epithelioma to leiomyoma.
12. EPITHELIAL HYPERPLASIA
• Hyperplasia frequently takes the form of proliferation into
the cells of same type as those of parent epithelium
• The process may often be diffuse, it is frequently localised
so that a discrete plaque is formed having clinical
characters of true neoplasm
• Hyperplasia of pigment epithelium may be congenital in
origin.
13. EPITHELIAL HYPERPLASIA
• It usually appears as discrete, flat & deeply pigmented
lesion showing no tendency to grow, mainly seen on
pupillary margin.
• EPITHELIAL hyperplasia of IRIS: simple hyperplasia of
pigmented layer of posterior surface is particularly seen
after prolonged iridocyclitis, trauma (including
surgery), glaucoma or degenerated eyes.
14. IRIS CYST
• Iris cysts are
lesions arising
from the iris
epithelium
mainly or from
stroma rarely.
Epithelial cyst
STROMAL
15. JUVENILE XANTHOGRANULOMA
• Rare idiopathic granulomatous d/s
of childhood
• Involves skin,muscle,stomach,
salivary glands
• Iris involvement cause localised or
diffuse yellow lesion with
spontaneous hyphema, anterior
uveitis or glaucoma
• TOC: topical steroids.
16. BENIGN EPITHELIOMA
• M/C site is pupillary border, appears as black/ brown
masses with knobby or convulated surface, periphery of
iris near root is 2nd m/c site
• Histo: made up of masses of cells typical of pigment
epithelium with normal nuclei without mitotic activity,
stromal elements may be entirely absent, tumour may be
infiltrated by blood vessels
17. BENIGN EPITHELIOMA
• Difference between epithelioma & melanoma is dense
blackness of former & its usual sharp differentiation from
surrounding.
• Management: observation over sometime, preferably by
photography. If doubt iridectomy is done,many eyes
involved have been excised owing to the fear of
malignancy.
18. EPITHELIOMA OF CILIARY BODY
• First description of benign epithelioma was given by Fuch
in 1883 in the eye of 70 year female pt having absolute
glaucoma known as Fuch’s epithelioma
• Occurs in wide age group 10 to 90 years of age, no sex
prediction
• Prolonged irritations such as inflammation, trauma or
other intraocular tumour predisposes their formation
19. EPITHELIOMA OF CILIARY BODY
• Tumour is usually small around 1mm but occasionally
reaches to 5mm in diameter
• Gonioscopy in dilated pupils shows brown pigmented
mass oval or round in shape lying on the ridge of ciliary
process or in intervening valley
• Histo: high degree of differentiation, seperated from
stroma, may lose its pigment or become atrophied
20. MEDULLO EPITHELIOMA
• Fuch classically divided medullo epithelioma to two
groups
A) Resesmbling embryonic retina DICTYOMATA
B) Ciliary epithelium (malignant epithelioma of ciliary
body)
21. DICTYOMA
• A.k.a Embryonal medullo-epithelioma
• It is a tumour arising from non pigmented layer of ciliary
epithelium having structure of embryonic retina
• Never b/l, no multicentric in origin & no hereditary
tendency, young children, present as u/l
buphthalmos/glaucoma/ cataract
• Histo: made up of bands of cells arranged in one/ several
rows forming intricate convolutions
22. DICTYOMA
• Dictyoma should be suspected
in all cases of u/l buphthalmos,
glaucoma in child , staphyloma,
u/l catarctous or dislocated lens
or nay cyst formation in the Ac
• Management: only treatment of
choice is enucleation.
23. MUSCULAR TUMOUR
• Leiomyoma: Reported only in
caucasians, F>M, commonly on
lower half of iris , temporally &
on sphincteric region.
• Generally forms a sessile mass
on pupillary margin, pink/
greyish white in colour.
• Difficult to diagnose from a
sparsely pigmented malignant
melanoma.
24. VASCULAR TUMOUR
• Haemangiomas are more common in choroid as compare
to iris & ciliary body
• Iris: vascular tumour is localised on the iris surface, which
may give rise to periodic bleeding
• Choroidal haemangioma is divided into
– Circumscribed
– Diffuse
25. CIRCUMSCRIBED
•Not associated with any systemic
d/s
•Shows mass within the choroid,
composed of vascular channels
•Presents in 2nd-4th decades,
u/l blurring of vision, visual field
defect & metamorphopsia
26. CIRCUMSCRIBED
• Hypermetropia+
• An oval mass posterior pole.
• Lesion is 6mm in dia & 3mm
thick.
• Can cause RD, RPE degenration
& subretinal fibrosis
FA shows spotty
• hyperfluorescence in early arterial
phase.
• ICGA also showhyperflourescence
27. CIRCUMSCRIBED
• US shows acoustically solid lesion with sharp anterior
surface.
• Treatment: photodynamic therapy- may be repeated after
few months.
• Radiotherapy.
• Intravitreal anti-VEGF therapy.
28. DIFFUSE
• Affects over half of choroid
• Enlarges very slowly
• Exclusively seen in patients with
sturge webber syndm
• Presents in 2nd decade of life
despite its formation at birth
29. DIFFUSE
• Fundus appears as deep red tomato ketchup colour, most
marked at posterior pole
• Localised area of thickening is present, simulating a
circumscribed haemangioma
• USG: shows diffuse thickening
• Complictn: RD, neovascular glaucoma, retinal cystoid
degenratn
• Treatmnt: radiotherapy/ PDT
30. CHOROIDAL OSTEOMA
• Very rare benign,slow growing ossifying tumour.
• B/L in 25% cases, F>M.
• Mature cancellous bone which causes overlying RPE
atrophy.
• Presents in 2nd- 3rd decades , yellowish-white flat,
minimally elevated lesion near disc or posterior pole
present.
31. CHOROIDAL OSTEOMA
• FA shows mottled
hyperfluoresecnce & late
staining
• ICGA: early hypofluorescence
• USG: highly reflective antr
surface & orbital shadowing
• No malignant potential,
managemant is directed at
preservation of vision mainly
32. UVEAL NEVUS
• The uveal nevus is a benign tumour that arises from
melanocytic cells derived from the neural crest
• m/c in whites, aprox 20% develop at least one choroidal
nevus >50yrs of age, M=F
• 1 in 4000-5000 undergoes malignant changes
• Asymptomatic may cause visual loss in macular choroidal
nevi
34. IRIS NEVUS
• IRIS NEVUS :< 3mm in diameter, < 0.5mm thick,pupillary
peaking, focal ectropion iridis or both, abnormal iris
vasculature
• Choroidal nevus: small grey to brown choroidal tumour,
< 5mm in diameter, < 1mm in thickness
• Clinical Features
– blurred/distorted vision
– serous subretinal fluid,
– cystic degenration of retina involving macula or
choroidal neovascularization
35. MELANOCYTOMA
• Special type of nevus “melanocytoma”of optic disc
• Composed entirely of maximally pigmented polyhedral
nevus cells (magnocellular nevus cells)
• Lesion appears striated because of insinuation of pigment
cells between axons in the nerve fibrelayer which may
inturn causes visual field defect
• Magnocellular nevus can occur in choroid, ciliary body &
iris
37. DIAGNOSIS
• B-scan
• Fluoresceine angiogrphy & indocyanine green
angiography.
• Documented photography shortly after detection.
• FNAC can be used to determine larger tumours >1.5mm
thick using trans vitreal bent neddle technique.
38. DIAGNOSIS
• Neurofibromatosis 1 patients come with multiple uveal
nevi in both eyes, become evident at 10-15 yrs of age
• Histo: spindle nevus cells are fusiform melanocytes that
typically have a relatively small nucleus
• Magnocellular nevus: plump polyhedral melanocytes
containing numerous large intra cytoplasmic melanin
granules
39. MANAGEMENT
• Photographic documentation/ usg documentation &
periodic evaluation
• For every small tumours 1-2 yearly followup, slightly larger
6-12 months followup, mal changes 1-3 months
• Focal laser therapy can be given in nevi causing blurred
visison
• In choroidal neovascularisation focal obliterative laser
therapy/ photodynamic therapy can be given
40. Course / outcome
In IRIS LESION consider benign if:
– Small size <3mm in dia, 0.5mm thick
– cohesive surface
– Absence of pig dispersion
– lack of pupillary peaking.
– Absence of ectropion iridis.
– Absence of cataract, vascularity.
– Lack of symptoms & enlargement.
41. Course / Outcome
• In choroidal lesion consider benign if:
– Small size <5mm dia, 1mm thick
– Homogenous gray brown surface
– Feathered margins blends into surrounding normal
choroid
– Drusen/retinal pigment clumping & migration
– Ab of lipofuscin pig on surface lesion/ subretinal fluid
– No sudden increase in size
42. MALIGNANT MELANOMA
• Malignant neoplasm arising from neuroectodermal
melanocytes. m/c intraocular tumour in whites.
• Key features are metastasize hematogenously, m/c involve
liver, choroid is commonly involved.
• Incidence is 1 in 2000-5000 white individuals, 15 to 50
times less common in blacks, m/c in men.
43. MALIGNANT MELANOMA
• Uveal tumours confined to iris appear to be substantially
less malignant as compare to choroidal melanomas
• Extent of tumour & management is different for iris
melanoma & ciliary body/ choroidal melanomas
• For this reason these two general forms are discussed
seperately
44. IRIS MELANOMA
• Presents as an spot on the iris with no symptoms
• >1mm thick is main concern for its malignancy
• Dispersion of tumour cells, pigments, may cause increase
in IOP, pupillary peaking ectropion iridis , iris splinting
may present
46. IRIS MELANOMA
• Histo: composed of atypical melanocytic cells, larger
nuclear to cytoplasmic ratio
• Tumour cells have a fusiform shape & mild atypical spindle
melanoma cells
• Those that have more spherical & more pronounced
anaplasia are called as epithelioid melanoma cells
47. MANAGEMENT
• Small melanomas should be observed without
intervention
• Excision: iridectomy/ irideocyclectomy is done
• Plaque radiotherapy/ photon beam irridiation performed
in small number of cases but appears to be effective in
short term followup
• Enucleation: for large iris melanomas, extensive seeding,
transcleral spread, blind painful eye
48. COURSE
• Iris tumour grows relatively slowly
• Replaces porportion of iris & ciliary body
• Can cause secondary glaucoma
• Post excision patient must be followed for every 6 months
for first 2-3 years & yearly there after
50. CHOROIDAL/CILIARY
MELANOMAS
• 20% of choroidal melanomas breaks through bruch’s
membrane & RP to form a nodular eruption
• They exhibits prominenet clumps of orange lipofuscin
pigment on their surface
• May be associated with non rhegmatogenous RD clear,
serous, shifting subretinal fliud
• VH may be present
52. Clinical features
• Asymptomatic
• Incidentally during ophthalmoscopy
• In general, the more anterior their origin, the longer the
delay of any symptoms
• Blurred visual acuity
• Growth of the melanoma into the subfoveal retina
53. Clinical features
• cystoid macular edema causes disruption of choroidal
circulation ischemia degeneration of retinal
photoreceptors
• The retina overlying the tumor separates into cystoid
spaces and larger schisis cavities
• Retinal detachment - Exudation of fluid into the subretinal
space retinal detachment enlarge the field loss can
lead to total retinal detachment
54. • Vitreous hemorrhage - Erosion of the melanoma into
blood vessels in adjacent tissues, or areas of necrosis
within the tumor
• Cataract – involvement of lens
• Paracentral scotoma
• If the tumor affects the perifoveal retina
• Visual field loss Painless and progressive as peripheral
melanoma grows
Clinical features
55. • Floaters when areas of necrosis within the tumor or
adjacent structures produce vitreous hemorrhage or
hyphema
• Severe ocular pain Occasionally when they impinge into
posterior ciliary nerves
• can also cause pain secondary to high intraocular pressure
from acute angle-closure glaucoma
Clinical features
56. IMPORTANT
• History of weight loss, marked fatigue, cough, or change in
bowel or bladder habits, should prompt consideration of
primary non-ocular malignancy with choroidal metastasis
57. DIAGNOSIS
• A-scan ultrasound
– Tumors more than 2-3 mm thick
– Characteristically shows an initial prominent spike,
followed by low-to-medium internal reflectivity.
– Vascular pulsations can be seen as fine oscillations of
the internal spiking pattern within the tumor.
– Standardized ultrasonography has a diagnostic accuracy
of more than 95%.
58. DIAGNOSIS
• B-scan ultrasound to help establish the diagnosis, to
evaluate possible extraocular extension, and to estimate
tumor size for periodic observation and plan therapeutic
intervention
– Low-to-medium reflectivity
– Excavation of underlying uveal tissue
– Internal vascularity
– An acoustic quiet zone at the base of the tumor called
acoustic hollowing
59. DIAGNOSIS
• Fluorescein angiography do not show pathognomonic signs
of choroidal melanoma but can help point to its diagnosis
• Small choroidal melanomas may show fluorescein
angiographic changes similar to some choroidal nevi, as
– normal angiography to hypofluorescence secondary to
blockage of background fluorescence.
60. DIAGNOSIS
• Larger melanomas may show a patchy pattern of early
hypofluorescence and hyperfluorescence followed by late
intense staining.
• Intrinsic vascularization, visible throughout the
angiogram.
• The angiographic sign called "double circulation" pattern
refers to simultaneous fluorescence of retinal and
choroidal circulation within the tumor. When it occurs, it
is fairly distinctive of choroidal melanomas
62. CT scan orbit
– Is more expensive than ultrasound and not as sensitive
– It is useful to see extraocular extension
– may help differentiate between choroidal or retinal
detachment and a solid tumor
– Choroidal melanoma shows enhancement with
contrast, where as exudation does not
– Very sensitive detecting calcium, a feature of some
tumors that are different than uveal melanoma
(characteristically choroidal osteoma)
63. Fine needle and incisional biopsy
• Usually are not required
• Distinguish amelanotic melanomas from metastatic
tumors
• Accuracy of more than 95% in tumors larger than 3 mm
• Incisional biopsy is more invasive and may have more
associated complications, but it has less false-negative and
false-positive results
64. Histological evaluation
• Three distinct cell types are recognized:
• Spindle A - elongated nuclei and uncommonly have
mitotic figures
• Spindle B - prominent nucleolus
– found more commonly,
– have an elongated profile but are slightly larger than
spindle A cells
• Epithelioid – most aggressive behavior
– poorer prognosis for the patient's long-term survival
– highly anaplastic, poorly cohesive, and have
considerable frequent mitotic figures
65. Modified callender classification
• Histologically can be divided into 3 types;
1. Spindle cell melanoma- good prognosis.
2. Mixed cell melanoma- intermediate.
3. Epitheloid cell melanoma- worst prognosis.
66. Prognosis
• 30-50% of patients with choroidal melanoma will die
within 10 years from diagnosis and treatment
• Tumor features found to correlate with increased
mortality:
– larger size
– anterior location
– transscleral extension
– growth through Bruch's membrane
– optic nerve extension
– lack of pigmentation, and
– histologic characteristics such as mitotic activity and cell
type
67. Surgical Care
• Enucleation -large (basal diameter >15 mm and height >10
mm) and complicated tumors, which compromise visual
function, and where other therapies tend to fail
• Because of potential release of malignant cells into the
bloodstream, manipulation of the globe should be kept to a
minimum
• Particular care has to be taken to avoid perforation of the
globe during surgery. If transcleral extension is found, the
tumor should be removed in one piece, pre enucleation
radiotherapy is given, followed by cryotherapy of the
involved orbital soft tissues
68. Plaque brachytherapy
• Alternative to enucleation for medium size posterior
uveal melanomas (<10 mm in height and <15 mm in
diameter)
• Iodine 125(USA), preferred because of its
• lower energy emission (lack of alpha and beta rays)
• good tissue penetration, and its commercial availability
• Mechanism damage of DNA in cancerous cells and tumor
vessels, with consequent tumor necrosis and regression
• A computerized calculation is used to determine the dose
and duration of plaque application for a radiation delivery
of approximately 400 Gy to the base and 80-100 Gy to the
apex of the tumor.
69. Plaque brachytherapy
• A margin of 2 mm over the largest tumor basal dimension
is adequate
• Postoperative imaging confirmation of correct plaque
localization is required. Radioactive plaques are left in
place for 3-7 days
• The goal of successful treatment is to achieve arrest of
tumor growth or regression in size
• Local recurrence, usually requiring enucleation, occurs at
a rate of about 12-16%.
70. COMPLICATIONS
– Cataract,
– Rubeosis,
– Scleral necrosis,
– Keratopathy,
– Radiation retinopathy, and
– Optic neuropathy but at a reduced rate compared with
external beam irradiation
71. External Beam Irradiation
• using charged particles, either protons or helium to treat
medium size choroidal melanomas (<10 mm in height and
<15 mm in diameter
• It has similar indications and success rates to plaque
brachytherapy
• Radiopaque tantalum rings usually are sutured to the
sclera to serve as reference markers for alignment of the
radiation beam. A collimated beam delivers about 70 Gy,
divided usually in 5 sessions
72. External Beam Irradiation
• Vital ocular structures are avoided through careful
positioning of the head and eye
• Irradiation causes damage of DNA in cancerous cells and
tumor vessels
• There may be consequent tumor necrosis and regression
• Survival rate comparable to those treated by enucleation
73. • Small choroidal melanomas, when they are located
away from the fovea and are less than 3 mm in thickness
– Laser photocoagulation - to seal off the blood supply to
the tumour and destroy it
– Transpupillary thermotherapy
– Photodynamic Treatment
• Animal study
• melanin precursors become extremely phototoxic in
melanoma tumor cells when activated with certain
light sources
• No additional phototoxic agents are administered
• differs from conventional photodynamic therapy in
that it uses pulsed, longer wavelength light
74. The Collaborative Ocular Melanoma
Study
• Initiated in 1986
• Long-term, multicenter, randomized controlled trials
• Conducted in 43 clinical centers located in major
population areas of the United States and Canada
75. SMALL MEDIUM LARGE
Type of study Nonrandomized,
prospective
follow-up
study
Prospective
randomized
clinical trial
Prospective
randomized
clinical trial
Number of
patients
204 1317 1003
Size of
melanomas
included in
study
Apical height:
1.0 to 2.5mm
Largest basal
diameter: 5mm
Apical
height: 2.5 to
10.0mm
Largest basal
diameter: 5 to
16 mm
Apical height:
10.0 mm or
larger
Largest basal
diameter:
16 mm or
larger
76. Findings of study
• Baseline characteristics associated with growth of small
tumors
– 21% grew by 2 years
– 31% grew by 5 years
– Characteristics associated with growth: initial tumor, thickness and
diameter, presence of orange pigment, absence of drusen, absence of RPE
changes
• No clinically or statistically significant difference in survival
rates between I125 Brachytherapy vs enucleation for
treatment of medium tumors for up to 12 years after treatment
77. FINDINGS CONTD..
• No significant difference in survival rates between Pre-
enucleation radiation vs. enucleation alone for treatment of
large tumors . 5-year survival rates - 60 percent
• Age and largest basal diameter of the tumor are the only factors
that affect prognosis
