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Intraocular Tumors – Melanocytic

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Differential Diagnosis of iris nodules

  • Iris pigment epithelial cysts -encompass both layers of iris and produce localized stromal elevation. May need B-scan or trans-illumination to see.
  • Iris pigment epithelial proliferation results from congenital or acquired (trauma/surgery) –composed of plaques of pigment epithelium –black, velvety color.
    • Juvenile xanthogranuloma -yellow/grey iris lesions with orange skin
    • Lesions in 1st yearof life.
    • Assoc. 1. with spontaneous hyphema
    • Secondary glaucoma
    • Diffuse granulomatous reaction with lipid filled histiocytes and touton giant cells Regress spontaneously
  • Leiomyoma
    • localized or diffuse, pedunculated or flat
    • Electron microscopy required to differentiate from amelanotic spindle cell melanoma
  • Leukemia -very rare
    • Nodularor diffuse milky lesions with intense hyperemia.
    • Pseudohypopyon
    • Iris loses architecture and becomes thickened.
  • Lisch Nodules
    • one of the diagnostic criteria for NF-1
    • Multiple flat or raised tan to brown lesions
    • Composed of collections of nevus cells
  • Malignant melanoma
    • Nodular of flat –usually peripheral
    • 80% inferior + inferotemporal
    • May have nutrient vessel, satellite pigmentation
    • Pupil may dilate irregularly
  • Melanocytosis
    • Unilateral, heterochromia irides
    • May have oculodermal form with eyelid + brow involved
    • Has malignant potential
  • Retinoblastoma
    • White foci on iris surface or in angle
    • May have pseudohypopyon
    • Retinoblastoma present in posterior chamber
  • Tapioca Melanoma
    • Often associated with unilateral glaucoma.
    • Tapioca-like nodules over part or all of iris
  • Metastatic Carcinoma
    • Gelatinous to white vascularized nodules on iris surface.
    • May be associated with anterior uveitis, glaucoma, rubeosis, and hyphema.

Iris Nevus:

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17.01 External slit lamp photo

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17.02 Spindle nevus

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17.03 Borderline spindle nevus

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17.04 Epithelioid nevus

  • Darkly pigmented lesion of iris stroma
  • minimal distortion of normal architecture
  • circumscribed > typically nodular + discrete
  • diffuse > may involve entire sector or even entire iris
  • increased incidence in NF –1
  • most common in Caucasian background (97%)(1)
  • ABCDEF guide for risk factors 1–risk of nevus transformation to melanoma increases for the following:
    • A –age –younger age is higher risk
    • B –blood –hemorrhage is common in melanoma
    • C –clock hour inferiorly –inferior location is higher risk
    • D –diffuse configuration –diffuse nevus more likely for malignant transformation
    • E–ectropion –ectropion uvea increases risk
    • F –feathery margin

Iris Melanocytoma:

  • Dark pigmented brown lesion –may have granular “mound of black sand” appearance.(1)
  • Usually stable and does not require intervention
  • May have spontaneous necrosis –which can liberate pigment into anterior chamber and cause glaucoma.
  • In one series of 47 patients, 48% showed mild growth and 63% showed new tumor seeds, but none (0%) showed malignant transformation(4).

Iris Melanoma:

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17.05 External slit lamp photo

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17.06 Spindle melanoma

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17.07 Epithelioid melanoma

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17.08 Mixed melanoma

Nick’s Tips: When small iris melanoma may be impossible to differentiate from nevus –may consider biopsy done through clear cornea.

  • Risk of metastasis is about 3%,(5) much less commonly fatal than other choroidal melanomas possibly due to
    • Earlier diagnosis and usually smaller at diagnosis
    • Most commonly spindle cell type(over 50%)
    • May have other unique features
  • Least common site of primary uveal melanoma (about 3-10%).(6)
  • Associated with: (6)
    • Light iris color
    • Inferior location
    • Average age 40 years old (younger than choroidal melanoma (age 50))
  • May appear circumscribed (melanotic nodule) or diffuse (heterochromia), with diffuse having a somewhat poorer prognosis.
  • Histopathologic features:
    • Typically spindle uveal melanoma cells –
      • Plump nucleus,
      • Eosinophilic nucleolus visible,
      • Mildly coarse chromatin
  • Some are mixed cell type (combination of spindle and epithelioid
  • Epithelioid –
    • Abundant eosinophilic cytoplasm and distinct cell borders
    • Large nucleus
    • Central nucleolus
    • Larger and more pleomorphic than spindle cells.
  • Signs of iris melanoma:
    • Ectropion iris
    • Prominent Vascularity
    • Sectoral cataract
    • Secondary glaucoma
    • Progressive growth
    • Extrascleral extension
    • Seeding of angle
    • Large size
    • ¾ of iris melanomas involve inferior iris
    • Unilateral glaucoma
    • Spontaneous hyphema
  • Treatment
    • Excision
    • Brachytherapy
    • Proton beam

Iris Cysts:

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17.09 Iris stromal cyst

  • Imaging:(2)
    • Ultrasound (UBM) –better at imaging posterior wall and overall imaging of structure
    • Anterior Segment OCT –better at imaging anterior surface of lesion
  • Types of iris cysts
    • Stromal cysts
      • may be congenital or acquired
      • usually smooth, translucent mass on in in the iris
      • may have debris inside cyst
      • may rupture –can cause iritis or glaucoma if ruptured
      • Congenital stromal cysts in children under age 10 tend to be more aggressive and may have poor visual outcome.
      • Treatment –may surgically remove or may aspirate cyst and sclerose with absolute alcohol.(3)
    • Pigmented epithelial cysts
      • Usually asymptomatic
      • Darkly pigmented –arising from posterior surface of the iris
      • May resemble ciliary body melanoma or iris pigmented epithelial adenoma, clinically.
      • UBM and anterior segment OCT may help demonstrate cystic nature of lesion.

Nevus of choroid / ciliary body

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17.10 Fundoscopic photoof nevus

Nick’s Tips: Although no single feature differentiates a malignant melanoma and a choroidal nevus, virtually all melanocytic tumors greater than 3mm thick are melanomas and virtually all melanocytic lesions less than 1mm thick are Nevi.

  • Choroid nevus –7% of population –flat or minimally elevated
  • May be amelanotic or grey-black
  • Differential diagnosis of a pigmented fundus Lesion
    • Nevus
    • Melanoma
    • Atypical disciform scar
    • Suprachoroidal hemorrhage
    • RPE hyperplasia
    • CHRPE
    • Melanocytoma
    • Choroidal osteoma
    • Hemangioma with RPE changes
    • Metastatic tumor with RPE changes
  • Risk of melanoma
    • Increased with thickness > 1 mm
    • Increased with diameter > 10mm
    • (<10mm almost always benign)
    • Visual symptoms
    • Orange pigment
    • Subretinal fluid
    • Large size >1mm thick, >10mm diameter
    • Juxtapapillary
    • Absence of drusen or RPE changes
    • Hot spots on FA
    • Homogeneity on ultrasound
    • Enlargement


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17.11 Ciliary body melanocytoma

  • Rare, large polyhedral shaped cells with small nuclei + melanin.
  • May seed A/C causing glaucoma
  • In choroid, they appear like nevis or melanoma on exam
  • May undergo malignant changes.
  • If growth is documented, treat as malignant.

Melanoma of ciliary body/choroid:

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17.12 Ciliary body melanoma

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17.13 External slit lamp photo

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17.14 Gross cross-section of globe

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17.15 Tumor arising from ciliary body

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17.16 Tumor arising in ciliary body coming into trabecular meshwork

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17.17 Choroidal Melanoma

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17.18 Spindle cell A choroid

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17.19 Spindle cell B choroid

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17.20 Epithelioid choroid

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17.21 Mixed melanoma choroid

Nick’s Tips:

Histopathology of Choroidal Melanoma/Nevus:

  • Six types:
    • Spindle nevus
    • Spindle nevus with plaque
    • Borderline spindle nevus
    • Spindle melanoma
    • Epithelioid nevus
    • Epithelioid melanoma
  • Prognosis from histological features –poor outcomes due to metastasis via scleral emissary channels
    • Pure spindle B –good prognosis
    • Mixed is intermediate prognosis
    • Epithelioid is poor prognosis

Clinical Features of Choroidal Melanoma

  • Most common primary intraocular malignancy in adults 6-7 cases per million.
  • Primary affects patients aged 50’s-60’s
  • Risk factors:
    • Light complexion, light irides
    • Ocular melanocytic conditions
    • Melanosis oculi, oculodermal melanocytosis
    • Genetic predisposition (dysplastic nevus syndrome)
    • Cigarette smoking
  • May be clinically silent + large when detected.
  • Symptoms may include
    • Vision loss or decreased vision
    • Changes in or decreased visual field
    • Photopsias
    • May have no symptoms
  • Appearance:
    • May rarely erode through sclera or iris + become visible on external exam
    • Initial sign of ciliary body melanoma may be dilated episcleral sentinel vessels.
    • Ring Melanoma → 360° -180° melanoma of ciliary body.
    • Pigmented, elevated dome shaped.
    • May be amelanotic to dark brown.
    • May erupt through Bruch’s membrane + make mushroom shape.
    • Orange pigment clumps may form @ RPE level.
    • Serous detachment of retina is common
    • Neovascularization, hemorrhage, lens subluxation are late complications
    • Vitreous hemorrhage only if penetrated through Bruch’s
  • Diagnostic Evaluation:
    • Indirect ophthalmoscopic evaluation-#1 technique.
    • Gonioscopy –best method for establishing anterior involvement
    • High-frequency ultrasound for iris + ciliary body evaluation
    • B-scan u/s →for tumor measurement, extrascleral extension
    • A-scan u/s →for internal reflectivity (characteristic low internal reflectance –homogenous)
    • Transilluminationmay help identify tumor
    • Wide angle fundus photography.
    • FA does NOT have characteristic appearance.
    • CT + MRI may help in opaque media
  • Differential diagnosis:
    • choroidal nevus: usually flatter + smaller
    • ARMD with pigmented scar –fluorescein angiographypathognomic –hemorrhage rare in melanoma
    • CHRPE –well defined, flat dark lesion-histology → tall melanin containing RPE cells that are histologically identical to bear tracks.
    • Melanocytoma of the optic disc.
      • Has minimal malignant potential
      • Lesion is located peripapillarily.
      • 10% will show growth over 5 years
      • May produce vision and visual field defects due to nerve fiber layer disruption
    • Suprachoroidal Detachments:
      • May be hemorrhagic orserous.
      • Associated with hypotony.
      • Often dome shaped, associated with breakthrough vitreous hemorrhage.
      • Usually located in multiple quadrants
      • Usually treated with observation
    • Choroidal Osteoma:
      • Benign bony tumors. Yellow to orange, well defined
      • Arise from juxtapapillary choroid
      • Adolescent to young adults
      • High amplitude echo on u/s from bony plate with shadowing behind lesion.
      • Calcification on CT scan.
      • Typically slow growing over years
      • May affect vision if in macula or nearby
      • Etiology unknown, may be related to low-grade inflammation
      • Subretinal neovascularization common

Classification of Melanomas:

Nervus <5mm diameter <2mm thick
Small 5-10mm 2-3mm thick
Medium 10-15mm 3-5mm
Large 15-20mm 5-10mm
Extra Large >20mm >10mm


  • Metastasis up to 50% at 25yrs, 25% at 5yrs, 34% at 10yrs (COMS Study)Less than 2% have clinically detectable metastatic disease at time of diagnosis. Median survival less than 6months with metastatic disease.Liver 1st site of metastasis, 89% on clinical exam 100% on autopsy. Lung, 24% on clinical exam 50% on autopsy; skin, 12% on clinical exam 50% on autopsy; bone possible later 17% on clinical exam 50% on autopsy.

    • Clinical Evaluation: (yearly follow-up)
      • Liver ultrasound
      • Liver function tests (LFTs)
      • Chest X-ray (low yield)
      • If any are positive tests, then Tri-phasic liver CT, CT or MRF of chest + abdomen.
      • Metastases can develop up to 20 years after treatment.
    • Treatment: little evidence of natural history exists.
      • If metastasis found, then enucleation is NOT appropriate.
      • Much of the treatment protocols were developed from the results of the COMS trial –a randomized prospective treatment study of choroidal melanoma.
      • Methods of treatment depend on
        • Size, location, extent
        • vision of affected + fellow eye
        • age + general health
    • Treatment Protocols:
      • Observation:
        • small melanoma <1mm thick
        • Elderly or otherwise short life expectancy
      • Enucleation: Gold-standard for treatment
        • Does NOT disseminate tumor secondary to manipulation.
        • Appropriate for all medium to extra-large tumors
      • Brachytherapy: most common method of treating uveal melanoma.
        • High dose, localized radiation. Usually I125, Ruthenium106 plaques
        • Local control rates >96%
        • Optic neuropathy + radiation retinopathy in 50%-Location + dose dependent complications
    • Charged particle radiation: proton beam.
      • Requires tantalum localization clips.
      • Up to 98% local control. Increased radiation dose to anterior segment.
    • External Beam Radiation: can be used in conjunction with enucleation or brachytherapy.
    • Other Alternative Treatments:
      • Photoablation + hyperthermia → subretinal fluid treated with grid laser: leads to increase in tumor growth due to rupture of Bruch’s membrane
      • Transpupillary Thermotherapy –associated with decrease in tumor volume.
      • Cryotherapy –not thought to be effective
      • Transcleral diathermy –contraindicated–provides route for extrascleral extension
      • Surgical excision: may have success, but difficult + margins are very important.
      • Chemotherapy: Not effective for treatment, but may be palliative
      • Immunotherapy: under investigation
      • Exenteration: rarely employed, but may be used in cases with extrascleral extension.
    • Prognosis: 5yr mortality:
      • 50% for large
      • 30% for medium
      • 12% for small
    • Risk factors for mortality:
      • Large tumor
      • Growth
      • Anterior tumor location
      • Extraocular extension
      • Older age
      • Tumor regrowth after ocular conservation therapy
      • Rapid decrease in size after globe conserving treatment
      • Juxtapapillary tumors.
      • Histopathological Features associated with increased mortality
        • Epithelioid cells
        • High mitotic index
        • Complex microvascular patterns
        • Large nuclei
        • Tumor infiltrating lymphocytes
        • Monosomy 3
        • Trisomy 8
    • Collaborative Ocular Melanoma Study.
      • 1003 patients with large or extra-large choroidal melanomas
        • Greater than 16mm diameterand/or greater than 10mm thick
        • Comparedenucleation to enucleation + external beam
        • 5-yr survival 57%with enucleation versus 62% with external beam
        • No improvement with radiation over enucleation alone.
      • 1317 patients with medium-sized choroidal melanoma
        • Tumor size: 6mm-15mm diameter and/or 2.5-10mm thick. Compared enucleation with brachytherapy
        • No difference in mortality (18% for enucleation and 19%for brachytherapy)
        • 43% had visual acuity worse than 20/200 with brachytherapy
        • Small ↑ in mortality with tumor recurrence
      • 204 patients with small choroidal melanoma
        • 4-8mm wide x 1-2.5mm thick
        • Mortality 1% at 5 years
      • COMS Study risk factors for growth
        • Increased thickness + diameter @ presentation
        • Orange pigment
        • No drusen or RPE changes
        • Pinpoint hyperflourescence on FA

    Pigmented Epithelial Tumors of Uvea + Retina:

    • Adenoma:
      • (benign) very rare
      • Oval, deeply melanotic tumors arising abruptly from RPE
      • Rarely undergo malignancy change.
    • Adenocarcinoma:
      • very, very rare
      • Malignantpotential very low.
    • Ciliary Cysts
      • Opacified ciliary cysts associated with multiple myeloma and macroglobulinemia

    Fuchs’ Adenoma

    Mamalis Tumor 22 unlabeled  Mamalis Tumor 22 labeled

    17.22 Fuch’s adenoma

      • Usually incidental finding @ autopsy.
      • Glistening white irregular tumor from ciliary crest.
      • Benign proliferation of non-pigmented epithelium
    • Acquired Hyperplasia: RPE + ciliary pigmented epithelium may
      • Proliferate in response to trauma or surgery.
      • may mimic choroidal melanoma
      • Treatmentis to observe.
    • Combined Hamartoma:
      • Rare–occurs at the disc margin. Dark pigmented, minimally invasive lesion
      • Proliferation of RPE, glial, + blood vessels
      • May cause retinal traction.
      • May have more or less pigment
      • May be mistaken for melanoma.

    Angiomatous Tumors

    Choroidal Hemangioma

    • Circumscribed choroidal hemangiomas are not associated with systemic disorders
    • Red/orange tumor, often in macula
    • Often produces secondary retinal detachment
    • Often affect overlying RPE with degeneration of outer retina.
    • Differential diagnos is
      • Amelanotic choroidal melanoma
      • Choroidal osteoma
      • Metastatic carcinoma
      • Granuloma of choroid.

    Diffuse choroidal Hemangioma associated with Sturge –Weber Syndrome

    • Diffuse reddish-orange thickening of retina
    • Tomato catsup fundus.
    • Retinal detachmentcommon
    • Glaucoma common.
    • FA shows large choroidal vessels, in pre arterial + arterial phases and late staining of tumor. NOT pathognomonic. U/S shows high internal reflectivity, acoustic heterogeneity. No shadowing. CT scan can be helpful in differentiating from osteoma. Treatment:
      • observation if asymptomatic
      • Serous detachment (including fovea) → photocoagulation
        • Treating withlight laser to adhere retina + ↓ serous fluid.
        • Recurrent detachments common.
        • PDT → to entire lesion may involute tumor + ↓ fluid.
        • Brachytherapy, Proton Beam, Gamma Knife have been used to involute tumor as well.
        • Periocular + intraocular avastin is being investigated.

    Retinal Angiomas:

    Capillary Hemangioma

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    17.23 Capillary hemangioma in Von Hippel –Lindau syndrome

    • Rare, autosomal dominant (1 in 40,000)
    • Diagnosis at age 10-30.
    • Orange/red tumor arising in retina with tortuous vessels.
    • Subretinal exudates common + often in fovea.
    • Exudate detachment common.
    • “Von Hippel disease”
      • familial in 20%
      • Bilateral in 50%
    • Von Hippel–Lindau Syndrome choroidal hemangioma with associated with cerebellar hemangioblastoma
    • Genetics
      • Gene located on chromosome 3
      • Associated tumors
        • Retinal capillary hemangioma
        • Cerebellar hemangioblastoma
        • Renal Cell Carcinoma
        • Pheochromocytoma
      • Genetic screening can help determine risk of tumors,
    • FA shows feeding arteriole, massive network + draining venule.
    • Treatment:
      • Photocoagulatesmall lesions.
      • Cryotherapy for larger, peripheral lesions.
      • Penetrating diathermy for very large lesions.
      • Avastin isbeing investigated.

    Cavernous Hemangioma

    Mamalis Tumor 24 unlabeled  Mamalis Tumor 24 labeled

    17.24 Cavernous hemangioma

    • Uncommon, cluster of grapes lesion.
    • Generally not associated with exudates.
    • Small hemorrhages + gliosis may appear on surface.
    • May occur on optic disc.
    • FA is diagnostic–fills slowly fluorescein + RBCs separate.
    • No vitreous leakage (unlike Coats Disease or capillary hemangioma)
    • No treatment necessary for cavernous hemangioma.
    • Composed of dilated, thin walled vessels, interconnected

    A-V malformation

    A-V malformation:

    • Racemose Hemangioma (congenital retinal A-V malformation)
    • Range from small vascular communication near disc or periphery
    • To large tangle of tortuous vessels throughout fundus.


    • Racemose hemangioma + midbrain A-V malformation.
    • Associated A-V malformations possible in orbit+ mandible


    Mamalis Tumor 25 unlabeled  Mamalis Tumor 25 labeled

    17.25 Retinoblastoma

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    17.26 Gross cross-section globe of RB

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    17.27 Exophytic growth pattern of RB

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    17.28 Endophytic growth pattern

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    17.29 Necrosis

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    17.30 Dystrophic calcification

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    17.31 Flexner-Wintersteiner rosettes

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    17.32 Alcian blue stain

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    17.33 Fleurette

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    17.34 Vitreous seeding

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    17.35 Tumor invading optic nerve

    Nick’s Tips: The differential diagnosis of leukocoria in a child and specifically the details of retinoblastoma is one of the most high yield study subject for the Boards. In addition, this material may enable you to save a child life someday.


    • #1 most common primary malignancy of childhood.
    • 2nd most common primary malignancy (behind uveal melanoma) in all age groups.
    • 1 in 14,000-20,000, 300 new cases/year in USA.
    • No gender predilection
    • 30% to40%bilateral.
    • Age @ diagnosis:
      • Family history of known retinoblastoma→ 4months
      • Bilateral disease → 14 months
      • Unilateral disease →24 months
      • 90% by age 3.
    • Genetics: mutation in retinoblastoma tumor suppressor gene.
      • 6% familial
        • 98% chance of germline mutation in bilateral disease.
        • Children of retinoblastoma survivor have 45% chance of having retinoblastoma (50% transmission, 90% penetrance)
      • 94% sporadic.
        • About 60% have unilateral disease
          • No germline mutation
          • Most have unifocal tumor
        • 40% have new germline mutation + multifocal disease.
      • About 95% chance of finding germline mutation with genetic testing.
    • Presentation:
      • Leukocoria = most common presentation
      • Strabismus + ocular inflammation also possible.
    • Clinical Appearance
      • Begins as grey/translucent intraretinal tumor with dilated feeder vessels
      • Becomes chalky white as calcification occurs.
      • Serous retinal detachment may occur as tumor grows + cause ↓ vision + difficulty visualizing tumor.
      • Exophytic tumors: grow beneath retina → retinal detachment
      • Endophytic tumors:
        • Grow on retinal surface into vitreous.
        • Vitreous seeding more common
        • May seed Anterior chamber leading to
          • Pseudohypopyon
          • Rubeosis + secondary to glaucoma in 50%
      • Diffuse –infiltrating retinoblastoma:
        • Appears like intermediate uveitis with diffuse vitreous cells,
        • Poor view of retina.
      • Metastatic
        • Most common metastasis is through direct extension via optic nerve.
        • May extend into subarachnoid space.
        • May also erode through sclera or emissary veins into orbit.
        • In A/C, may invade trabecular meshwork + lymphatics.
        • Metastatic to:
          • Skull bones, distant bones
          • Brain, spinal cord
          • Lymph nodes (preauricular/cervical)
          • Abdominal viscera
      • Clinical Exam:
        • Need exam under anesthesia with scleral depression.
        • Document clearly location + size of multiple tumors.
        • Ultrasound may show calcifications
        • MRI is imaging modality of choice for globe, ON, brain.
        • Systemic evaluation not necessary if no signs of extraocular extension.
        • LP if extensionvia ON thought to have occurred
        • Examine siblings + parents
      • Differential Diagnosis of Leukocoria:
        • Retinoblastoma
        • Coats disease
        • Astrocytic hamartoma –tuberous sclerosis
        • Retinal capillary hemangiomatosis
        • Granulomas (especially associated with nematode endophthalmitis) -toxocariasis
        • Coats
        • Persistent fetal vasculature
        • Ocular toxocariasis
        • Retinopathy of prematurity
        • Retinal detachment
        • Coloboma
        • Myelinated nerve
        • Toxoplasmosis
        • Retinal dysplasia
        • Trisomy13 → cartilage in ciliary body
        • Norrie’s disease
        • Retinoschisis
        • Cataract (torch, congenital)
        • Cyclitic membrane
        • Medulloepithelioma
        • Incontinenti pigmenti

    Coats Disease:

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    17.36 Fundoscopic photo

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    17.37 Gross cross-section globe

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    17.38 Telangiectasic vessels leak into retina and under retina

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    17.39 Processed specimen leaving sickle shaped cholesterol plaques

    • male>female (10:1)
    • poor visual prognosis
    • Unilateral retinal telangiectasias, yellow exudates.
    • No distinct mass, (cholesterol rich sickle shaped spaces)
    • Fluid leakage may lead to serous retinal detachment which may be large
    • Ultrasound documents absence of retinal tumor.
    • Treat with laser or cryo of vascular anomalies to decrease serous detachments

    Persistent Fetal Vasculature (Persistent hyperplastic primary vitreous):

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    17.40 External slit lamp photo

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    17.41 Mass in the lens pulls and contracts ciliary processes forward.

    Mamalis Tumor 42  Mamalis Tumor 42 labeled

    17.42 Remnant hyaloid artery

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    17.43 Bergmeister papillae

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    17.44 Gross cross-section glob

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    17.45 PHPV

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    17.46 Remnant Hyaloid artery

    • Typically recognized in 1st few weeks of life
    • Unilateral in 2/3
    • Associated with
      • Microphthalmos.
      • Shallow anterior chamber
      • Hypoplastic iris
      • Retrolenticular mass of fibrovascular tissue
    • Vascular stalk may be seen arising from nerve.
    • May have closed funnel retinal detachment
    • Ultrasound shows no tumor, short axial length +/-calcification
    • Treatment is vitrectomy/lensectomy.

    Ocular Toxocariasis:

Mamalis Tumor 47 unlabeled  Mamalis Tumor 47 labeled


17.47 Toxocariasis

    • Most patients have a history of soil ingestion or exposure to puppies.
    • Posterior mass + peripheral granulomas + uveitis.
    • Ultrasound shows vitritis, granuloma, retinal traction, NO calcification
  • Astrocytoma: (astrocytic hamartoma)
    • Small, white, glistening tumor of nerve fiber layer
    • Sometimes large, mulberry appearance with calcification.
    • Usually arise from optic disc (termed “giant drusen”)
    • Common in tuberous sclerosis + may occur in neurofibromatosis
    • Usually ∅assoc. with phakomatosis.
  • Retinocytoma: clinically indistinguishable from retinoblastoma
    • Histologically benign.
    • Same genetic implications as retinoblastoma
    • Unclear developmental biology.
  • Reece-Ellsworth classification of intraocular retinoblastoma.
  • Predicts eye preservation when treated with external beam radiation.
Group I (very favorable) solitary tumor <4DD multiple tumors
II 4-10DD multiple 4-10DD
III at equator or anterior >10DD posterior
IV multiple tumors, some >10DD anteriorto ora serrata
V(least favorable) massive tumor > ½ retina vitreous seeding

International Classification

A Small(<3mm) >3mm from fovea >1.5mm from optic nerve
B (>3mm) confined to retina
C Localizedvitreous or subretinal seeding. <6mm from tumor
D Diffuse vitreous or subretinal seeding. >6mm from primary
E No visual potential or tumor in anteriorsegment, in or onciliary body, neovascular glaucoma,vitreous hemorrhage, phthisical eye, orbital extension/proptosis.


  • Trilateral Retinoblastoma:
    • bilateral intraocular retinoblastoma + ectopic intracranial retinoblastoma.
    • Ectopic foci usually in pineal gland. (pinealoblastoma)
    • Occurs in 2-5% with germline mutation.
    • Usually pineal
    • blastoma presents years after retinoblastoma, but may present before.
    • Often show Flexner-Wintersteiner rosettes on histology.
    • Embryological evidence for photoreceptor differentiation in pineal glando
    • All retinoblastoma patients should undergo neuroimaging.
    • Serial MRI with and without contrast = best (No radiation exposure)
    • Decreased incidence of trilateral retinoblastoma with chemo –may be prophylactic.
    • Median survival 8 month with CNS involvement.
  • Prognosis:
    • 95% survival if contained in eye
    • Less than 50% survival if extraocular spread.
  • Treatment:
    • Goals
      • #1 preserve life,
      • #2 preserve eye,
      • #3 preserve vision.
    • Enucleation: definitive treatment. Usually enucleate if any of the following:
      • Tumor >50% of eye
      • Orbitalor ON involvement suspected
      • Anterior segment involved
    • Chemotherapy:
      • carboplatin, vincristine, etoposide, cyclosporine
      • IV treatment Q3-4 weeks in 4-9 cycles.
      • Decrease tumor volume + finish treatment with laser, cryo, radiation.
    • Periocular Chemo: in phase 1 + 2 trials, shows promise.
    • Photocoagulation + hyperthermia:
      • May kill tumor blood supply
      • Cytotoxic effect of heat.
      • Small tumors.
    • Cryotherapy
      • Small tumors <10mm diameter, <3mm thick.
      • Anterior location (laser for posterior)
      • Repetitive treatment+ close follow up.
    • External Beam:
      • retinoblastomais radiation responsive.
      • 4,000 –4,500 cGy over 4-6 wks.
      • Typically are bilateral not amenable to cryo or laser.
      • 85% of globes retained.
      • Visual function limited only by tumor location and secondary complications.
    • Concerns:
      • Retinoblastoma mutation associated with lifelong increased risk of osteosarcoma
      • Risk of osteosarcoma is exacerbated by exposure to external beam radiation
      • Midface hypoplasia
      • Cataract
      • Radiation optic
      • Neuropathy + other radiation side effects.
    • Combination therapy may decrease radiation and its secondary complications.
  • Brachytherapy: salvage therapy for some eyes
  • Primary treatment for amenable eyes with small-medium tumors.
  • Adenovirus targeted gene therapy in trials → makes tumor susceptible to ganciclovir –via Thymidine Kinase transfection
  • Spontaneous Regression:
    • May undergo complete necrosis + regression.
    • Sometimes seen in phthisical eyes.
    • Vitreous filled with islands of calcified cells in mass of fibrovascular connective tissue.
    • Associated with exuberant proliferation of RPE + ciliary body
    • Ghost contours of tumor cells.
  • Prognosis:
    • Survival greater than 95% with access to modern care.
    • Extraocular extension is the most important poor prognostic factor
    • Bilateral diseasemay have decreased survival secondary to optic intracranial foci
    • Bilateral retinoblastoma leads to increased incidence of other tumors
    • Mean time = 9 years
    • 26% develop another tumor in 50 yrs.
    • External beam radiation decreased latency and increased head + neck tumors.
    • Most common secondary tumor = osteogenic sarcoma
    • Also pinealoma, brain tumor, melanoma, sarcoma, primitive tumors
      • 10-20% will develop tumor in 20 years
      • 30-40% will develop 3rd tumor in 30 years
      • Survival <50% in those who develop 2° osteogenic sarcoma.

Secondary Tumors

Metastaticintraocular tumors:

Mamalis Tumor 48 unlabeled  Mamalis Tumor 48 labeled

17.48 Fundoscopic photo

Mamalis Tumor 49 unlabeled  Mamalis Tumor 49 labeled

17.49 Lung cancer metastasized to choroid

Nick’s Tips:

  • Metastases are the most common intraocular tumors in adults
  • Metastases are the most common orbital tumors in adults

Mets to Eye

Males Females
Lung 40% Breast 68%
Unknown 29% Lung 12%
GI 9% Unknown 12%
Kidney 6% Others 4%
Prostate 6% GI 2%
Skin 4% Skin 1%
Others 4% Kidney<1%


  • Choroid is 10-20 x more likely location for metastases, due to higher blood supply than iris or ciliary body
  • Metastases to the retina + optic disc rare
  • Bilateral in 20-25%
  • Metastases are often yellow/white/grey, may have RPE changes
  • Metastases to the posterior pole may cause decreased visual acuity
  • Rarely break through Bruch’s membrane
  • May cause retinal detachment over tumor
  • Necrosis + uveitis possible
  • Diagnosis:
    • FA pattern of double circulation + early filling seen in choroidal melanomas is rare in metastatic tumors
    • Ultrasound is helpful,
      • A-scan shows moderate to high reflectivity (melanoma = low)
    • Fine needle aspiration biopsy may help, but metastases may be too poorly differentiated to identify.
  • Metastases to retina are very rare:
    • Appear as white, non-cohesive lesions
    • May appear similar to cotton wool spots
    • May vitreous seed + appear like retinitis.
  • Previous diagnosis versus unknown cancer diagnosis:
    • Breast cancer
      • 70-90% with metastatic ocular or orbital breast tumor to uvea have a history of breast CA diagnosis + treatment.
      • If no prior diagnosis of breast cancer, then refer for breast exam
    • Lung cancer
      • Lung metastases often do not have prior diagnosis.
      • Poor prognosis if uveal metastasis. Mean survival 1-67 mo
  • Prognosis: Depends on primary tumor.
    • Lung + GI is worst prognosis
    • Carcinoma+ breast cancer is better prognosis
  • Treatment: depends on many factors
    • Goals
      • Maintain vision
      • Palliate pain.
    • Types:
      • Systemic chemo or hormone treatment
      • Laser, cryo, beam radiation, etc….
      • Enucleation with unrelenting pain.
  • Avenue of entrance to the orbit or globe
    • Hematogenous inoculation is by far the most common
      • Breast, lung, GI, and others
    • Direct intraocular extension is rare because the sclera is a good barrier.
      • Squamous cell carcinoma from conj. = most common
      • Conj. Melanoma
      • Basal cell of eyelid possible

Lymphomatous Tumors

Intraocular lymphoma:

Mamalis Tumor 50 unlabeled  Mamalis Tumor 50 labeled

17.50 Lymphoma

  • Type:
  • Almost always Non-Hodgkin, B-cell, large cell.
  • T-cell = rare.
  • May invade any part of eye/orbit.
  • Source:
  • Most common = primary CNS lymphoma (25% have intraocular involvement) Vitreous + retina involved
  • Rarely Systemic/visceral/nodal lymphoma: usually uveal tract + choroid.
  • Making the diagnosis
  • Any bilateral or chronic uveitis age over 50 should consider lymphoma.
  • Diffuse vitreous cells, headlight in fog appearance.
  • Complete neuro exam will be positive of deficiencies in 10% of patients
  • 60% will have central nervous system involvement –should do
  • CT
  • MRI
  • LP
  • Diagnostic vitrectomy.
  • Pathology
  • Flow cytometry
  • PCR
  • Immunohistochemical stains
  • Treatment
  • Limited by blood-ocular barrier.
  • Irradiation with external beam –tumor invariably reoccurs.
  • Intraocular methotrexate → good response, low recurrence
  • CNS treatment by oncologist
  • Prognosis: poor, requires close f/u

Uveal Lymphoid Infiltration:

  • Uveal Lymphoid Infiltration: (reactive lymphoid hyperplasia) –unknown etiology
  • May occur at any site. –benign lymphoid infiltration
  • Painless progressive vision loss
  • Diffuse amelanotic thickening of choroid
  • Exudative retinal detachment+ glaucoma in 85%, proptosis 15% due to orbit infiltration
  • Treatment: high dose steroid, fractionated radiation
  • Excellent prognosis


  • Ocular involvement common –up to 80% on autopsy
  • Up to 40% at diagnosis.
  • Retinal lesions most commonly found, choroid is most common site.
  • Choroid may act as sanctuary for leukemic cells
  • Eye may be 1st sentinel of reactivation
  • Ultrasound may be better than indirect ophthalmoscopy.
  • May involve iris with small nodules @ pupil margin or diffuse thickens
  • May have pseudohypopyonor 2° glaucoma.
  • Retinal findings include:
    • hard exudates
    • CWS
    • Pseudo-Roth spots.
    • Yellow deposits in retina,
    • Grey nodules in CML
    • Perivascular streaks
  • Vitreous involvement rare –use diagnostic vitrectomy if suspected
  • Optic Nerve infiltration is anophthalmic emergency, treatment required immediately –treat with systemic + intrathecal chemo. +/-radiation
  • Proptosis possible if orbital soft tissue infiltrates.
  • May have opportunistic infections secondary to immunocompromise.
  • Treatment = low dose radiation, systemic chemotherapy


  • Meulloepithelioma (diktyoma)
    • Tumor of non-pigmented Ciliary Body epithelium
    • Has benign + malignant forms
    • Congenital
    • Clinical diagnosis usually around age 4-12 years old. Sometimes diagnosed in adults
    • Variably pigmented mass arising from ciliary body (rarely on orinretina)
    • May erode into anterior chamber
    • Treatment
      • Observe
      • Metastasisis RARE
      • May treat small lesions with brachy therapy (I-125 plaque)

Leiomyomas, Neurilemomas, Neurofibromas:

VERY RARE: Usually misdiagnosed as amelanotic primary uveal melanomaand discovered on histopathology


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