Cancer and the Eye: Ocular Tumors, Malignancies, and Neoplasms Brad Sutton, OD, FAAO Clinical Associate Professor IU School of Optometry No financial conflicts

Cancer and the Eye: Cancer and the Eye: Ocular Tumors, Ocular Tumors,

Malignancies, and Malignancies, and NeoplasmsNeoplasms

Brad Sutton, OD, FAAOBrad Sutton, OD, FAAO

Clinical Associate ProfessorClinical Associate Professor

IU School of OptometryIU School of Optometry

No financial conflicts No financial conflicts

Cancer factoidsCancer factoids

Can affect any tissue Can affect any tissue or organ at any ageor organ at any age

All cancers begin with All cancers begin with a defect in a single a defect in a single cell (monoclonal)cell (monoclonal)

This is followed by This is followed by unrestrained growthunrestrained growth


A one cm. tumor A one cm. tumor contains one billion contains one billion cellscells

One trillion cells One trillion cells usually means a usually means a lethal tumorlethal tumor

BENIGN tumors may BENIGN tumors may damage local tissue damage local tissue by occupying space by occupying space but they do not but they do not spreadspread

MALIGNANT tumors MALIGNANT tumors invade surrounding invade surrounding tissue and may tissue and may metastasizemetastasize


Cell division is Cell division is controlled by genes controlled by genes that promote it and that promote it and genes that suppress itgenes that suppress it

Cancer is the result of Cancer is the result of some combination of some combination of defects in this genetic defects in this genetic functioningfunctioning

Recent studyRecent study

Study of a 43 year Study of a 43 year old with skin old with skin cancer found cancer found 23,000 genetic 23,000 genetic mutationsmutations

Study of a 55 year Study of a 55 year old with lung old with lung cancer found cancer found 33,000 genetic 33,000 genetic mutationsmutations

Cancer typesCancer types

General types of General types of cancer include……..cancer include……..

Adenocarcinoma: Adenocarcinoma: Glandular tissueGlandular tissue

Melanomas (melanin)Melanomas (melanin) Sarcomas Sarcomas

(connective tissue)(connective tissue) Carcinomas Carcinomas

(epithelial tissue)(epithelial tissue) Leukemias (bone Leukemias (bone

marrow)marrow) Lymphomas Lymphomas

(lymphoid tissue)(lymphoid tissue)

Leading cancers in US (2009)Leading cancers in US (2009)

Men…Men… 1) Prostate1) Prostate 2) Lung2) Lung 3) Colon3) Colon 4) Urinary4) Urinary 5) Skin melanoma5) Skin melanoma

But the most common But the most common malignancy in humans malignancy in humans is………….Basal Cell is………….Basal Cell Carcinoma!Carcinoma!

Women….Women…. 1) Breast1) Breast 2) Lung (90% use tob.)2) Lung (90% use tob.) 3) Colon3) Colon 4) Uterine4) Uterine 5) NH lymphoma5) NH lymphoma

P,B,L, and C make up 50% P,B,L, and C make up 50% of all non-skin cancerof all non-skin cancer

25% of people affected 25% of people affected during their lifetimeduring their lifetime

Skin cancerSkin cancer

In the US 50% of all cancer is skin In the US 50% of all cancer is skin cancer…………..and 80% of skin cancer cancer…………..and 80% of skin cancer is BCCis BCC

Did you know……….that patients that Did you know……….that patients that have had a kidney transplant are 20X have had a kidney transplant are 20X more likely to develop ocular squamous more likely to develop ocular squamous cell carcinoma?cell carcinoma?

Cancer mortality in the USCancer mortality in the US

1) lung1) lung 2) colorectal2) colorectal 3) breast3) breast 4) pancreatic (# 12 in frequency)4) pancreatic (# 12 in frequency) 5) prostate5) prostate

2012 American Cancer Society 2012 American Cancer Society ReportReport

Cancer expected to be diagnosed in 1.64 Cancer expected to be diagnosed in 1.64 million Americans in 2012, and it is million Americans in 2012, and it is expected to kill 577,000.expected to kill 577,000.

The incidence of the four most common The incidence of the four most common cancers……….lung, colon, breast, and cancers……….lung, colon, breast, and prostate………….is decreasing for all fourprostate………….is decreasing for all four

The incidence is increasing for cancer The incidence is increasing for cancer involving the pancreas, liver, thyroid and involving the pancreas, liver, thyroid and kidney as well as melanomaskidney as well as melanomas

Cancer in the futureCancer in the future

By 2020, the number By 2020, the number of cancer patients and of cancer patients and cancer survivors will cancer survivors will increase by over 50% increase by over 50% to an estimated 18.2 to an estimated 18.2 millionmillion

There will be a There will be a projected shortage of projected shortage of 4000 oncologists4000 oncologists

Cancer epidemiologyCancer epidemiology

Cancer screenings Cancer screenings are driven by several are driven by several factors…………factors…………

1) Is it a common 1) Is it a common cancer ?cancer ?

2) Can we detect it ?2) Can we detect it ? 3) Can we treat it ?3) Can we treat it ? 4) How much does 4) How much does

the screening cost?the screening cost?

Cancer epidemiologyCancer epidemiology

It is worth screening It is worth screening for prostate, colon, for prostate, colon, breast, cervical, and breast, cervical, and skin cancerskin cancer

Cancer increases with Cancer increases with age due to increased age due to increased length of exposure to length of exposure to carcinogenscarcinogens

Cancer screeningsCancer screenings

1) Blood tests1) Blood tests 2) Bone scans2) Bone scans 3) Biopsies3) Biopsies 4) X-ray, CT, MRI and other imaging4) X-ray, CT, MRI and other imaging 5) Observation5) Observation

Cancer Cancer

Leading cause of Leading cause of death worldwidedeath worldwide

It accounts for ¼ of It accounts for ¼ of deaths in the deaths in the US…….one death per US…….one death per minute! Only heart minute! Only heart disease kills more.disease kills more.

Economic toll of $895 Economic toll of $895 billion…….not counting billion…….not counting the cost of treatment!the cost of treatment!

Cancer treatmentCancer treatment

CHEMOTHERPY:CHEMOTHERPY:

Drugs that interfere Drugs that interfere with cell divisionwith cell division

Multiple drugs Multiple drugs available, oral and IVavailable, oral and IV

RADIATION:RADIATION:

Damages cellular Damages cellular DNADNA

SURGERY:SURGERY: Removes the tumorRemoves the tumor


Chemotherapy targets all cells in the body Chemotherapy targets all cells in the body that are actively dividing…………abnormal that are actively dividing…………abnormal and normal!and normal!

Hair follicles > loss of hairHair follicles > loss of hair Intestinal mucosa > diarrhea, vomiting, Intestinal mucosa > diarrhea, vomiting,

nauseanausea Bone marrow > anemiaBone marrow > anemia


Radiation results in the damage of cellular Radiation results in the damage of cellular DNA > cell deathDNA > cell death

Need to be focal with treatment because Need to be focal with treatment because all cells are affectedall cells are affected

Both radiation and chemotherapy can lead Both radiation and chemotherapy can lead to retinal complications to retinal complications


Treatment often Treatment often consists of a consists of a combination of combination of surgery, radiation and surgery, radiation and chemotherapychemotherapy

This depends on This depends on many factors many factors (location, metastases, (location, metastases, etc.)etc.)

Help from a tree?Help from a tree?

Beta-lapachone from Beta-lapachone from the South American the South American lapacho treelapacho tree

Cyctotoxic effects Cyctotoxic effects shown (due to shown (due to induced apoptosis) to induced apoptosis) to cancer cells: cancer cells: retinoblastoma, lung, retinoblastoma, lung, breast, prostate, breast, prostate, many othersmany others

Beta LapachoneBeta Lapachone

Usefulness in humans limited thus far by Usefulness in humans limited thus far by toxicitytoxicity

Also has antibacterial and antiviral Also has antibacterial and antiviral properties, including activity against HIVproperties, including activity against HIV

Did you know……….Did you know……….

Metformin (Type II DBM drug) is proving to Metformin (Type II DBM drug) is proving to be very protective against lung cancerbe very protective against lung cancer

It activates an enzyme…….. that inhibits a It activates an enzyme…….. that inhibits a protein…….. that is needed for the growth protein…….. that is needed for the growth of cancer cellsof cancer cells

Paraneoplastic syndromeParaneoplastic syndrome

CARCAR Rare: antibody mediatedRare: antibody mediated Associated with many Associated with many

types of cancertypes of cancer Photopsia and Photopsia and

progressive bilateral progressive bilateral vision lossvision loss

Normal fundus Normal fundus appearance then RPE appearance then RPE changes, etc.changes, etc.

Confirm with ERGConfirm with ERG

MARMAR Rare, more common in Rare, more common in

malesmales Associated with Associated with

cutaneous melanomacutaneous melanoma Photopsia, night Photopsia, night

blindness, loss of visionblindness, loss of vision Normal fundus Normal fundus

appearance then RPE appearance then RPE changes, etc.changes, etc.

Antibodies target rodsAntibodies target rods

Interferon chemotherapyInterferon chemotherapy

Cancer itself can CWS too…….Cancer itself can CWS too…….

Case ReportCase Report

A 55 year-old white female reported to our A 55 year-old white female reported to our clinic with a complaint of blurry vision in clinic with a complaint of blurry vision in her left eye for about one monthher left eye for about one month

She also complained of dizziness, nausea, She also complained of dizziness, nausea, and a “pressure” behind her left earand a “pressure” behind her left ear

Her medical history was significant only for Her medical history was significant only for a family history of colon cancera family history of colon cancer


An eye exam performed in our clinic three An eye exam performed in our clinic three years prior was remarkable only for years prior was remarkable only for refractive errorrefractive error

Entering acuity with correction was 20/20 Entering acuity with correction was 20/20 OD, 20/40 OS and BCVA was 20/20 OD, OD, 20/40 OS and BCVA was 20/20 OD, 20/25 “-” OS20/25 “-” OS

Entrance testing was unremarkable as Entrance testing was unremarkable as was the anterior segment OUwas the anterior segment OU


DFE OD was remarkable for an isolated DFE OD was remarkable for an isolated cotton-wool spot in the superior arcadecotton-wool spot in the superior arcade

All other fundus findings OD were normalAll other fundus findings OD were normal DFE OS revealed a large (2.5 disc DFE OS revealed a large (2.5 disc

diameter) cream colored mass infero-diameter) cream colored mass infero-temporal to the macula which was temporal to the macula which was encroaching on the foveal region but did encroaching on the foveal region but did not involve the foveal centernot involve the foveal center

Amelanotic Lesion OS (whitening in Amelanotic Lesion OS (whitening in arcades is a camera artifact)arcades is a camera artifact)


Screening and threshold Matrix FDT VF Screening and threshold Matrix FDT VF results were normal OUresults were normal OU

B-scan ultrasound of the left eye revealed B-scan ultrasound of the left eye revealed a solid lesion with 1.5-2.0mm of elevation a solid lesion with 1.5-2.0mm of elevation and moderately high internal reflectivity and moderately high internal reflectivity with no evidence of overlying retinal with no evidence of overlying retinal detachmentdetachment

Threshold VF OSThreshold VF OS

B-Scan of lesion (note elevation B-Scan of lesion (note elevation and internal reflectivity)and internal reflectivity)

Systemic Work-upSystemic Work-up

Due to the appearance of the retinal Due to the appearance of the retinal lesion, metastatic disease was strongly lesion, metastatic disease was strongly suspectedsuspected

The patient was counseled earnestly The patient was counseled earnestly regarding this fear and referred for a regarding this fear and referred for a consultation with a retinal oncologist consultation with a retinal oncologist

Systemic work-upSystemic work-up

A systemic work-up revealed previously A systemic work-up revealed previously undiagnosed large cell carcinoma of the undiagnosed large cell carcinoma of the lung with multiple lesionslung with multiple lesions

There were metastases detected in the There were metastases detected in the liver, spleen, and kidneysliver, spleen, and kidneys

Chemotherapy was begun at this timeChemotherapy was begun at this time

TherapyTherapy

The ocular lesion in the left eye continued The ocular lesion in the left eye continued to be problematic despite chemotherapy to be problematic despite chemotherapy and the vision deteriorated to 20/100 over and the vision deteriorated to 20/100 over the course of one monththe course of one month

The retinal surgeon decided to proceed The retinal surgeon decided to proceed with a course of external beam radiation with a course of external beam radiation ocular therapy in addition to the ocular therapy in addition to the chemotherapy. Ultimately successful with chemotherapy. Ultimately successful with acuity recovery to 20/25acuity recovery to 20/25

Another example……Another example……

The following set of pictures represent The following set of pictures represent another patient another patient

Once again, the patient reported with a Once again, the patient reported with a complaint of blurry vision OS and no complaint of blurry vision OS and no known cancerknown cancer

Multiple Metastatic Lesions OUMultiple Metastatic Lesions OU

Early IVFA OSEarly IVFA OS

Note blocking of the Note blocking of the background background hyperflouresence in hyperflouresence in multiple areas multiple areas including large central including large central lesionlesion

Late IVFALate IVFA

Note late staining of Note late staining of large central lesion large central lesion secondary to leakage secondary to leakage from lesion’s blood from lesion’s blood supplysupply

Another Example……..Another Example……..

In this case systemic evaluation revealed In this case systemic evaluation revealed multiple, subcutaneous adenocarcinomas with multiple, subcutaneous adenocarcinomas with several intracranial metastases and lymph node several intracranial metastases and lymph node involvementinvolvement

No primary tumor site was able to be identifiedNo primary tumor site was able to be identified Management with radiation and chemotherapy Management with radiation and chemotherapy

was undertaken and the ocular lesions was undertaken and the ocular lesions responded well but ultimately the patient did not responded well but ultimately the patient did not survivesurvive

Several weeks later….systemic Several weeks later….systemic chemo and radiationchemo and radiation

Uveal Metastatic LesionsUveal Metastatic Lesions

Most common Most common intraocular tumorintraocular tumor

Number one primary Number one primary site in women is the site in women is the breast, in men it is the breast, in men it is the lunglung

Choroid around 90%, Choroid around 90%, ciliary body about 8%, ciliary body about 8%, iris 1-2%iris 1-2%

Up to 10% of cancer Up to 10% of cancer patients get uveal patients get uveal metastases: often not metastases: often not diagnoseddiagnosed

Primary site is often Primary site is often never determinednever determined

Uveal MetastasesUveal Metastases

Located in posterior pole Located in posterior pole (blood supply)(blood supply)

Unilateral or bilateral Unilateral or bilateral (unilateral 3 to 1)(unilateral 3 to 1)

Breast metastases most Breast metastases most likely to be bilateral: lung likely to be bilateral: lung unilateralunilateral

Single lesion or multiple Single lesion or multiple lesionslesions

RPE detachments RPE detachments

Creamy yellow in color Creamy yellow in color (may have orange hue)(may have orange hue)

Oval to placoidOval to placoid Relatively flat (rarely Relatively flat (rarely

break through Bruch's break through Bruch's membrane)membrane)

High internal reflectivity High internal reflectivity on ultrasoundon ultrasound

Management of Metastatic TumorsManagement of Metastatic Tumors

Metastatic lesions Metastatic lesions tend to be detected tend to be detected sooner because their sooner because their posterior pole location posterior pole location leads to earlier leads to earlier symptomssymptoms

Systemic work-up is Systemic work-up is criticalcritical

Average survival time Average survival time of 9 months after Dxof 9 months after Dx

Systemic Systemic chemotherapychemotherapy

Radiation via external Radiation via external beam (outpatient) or beam (outpatient) or plaque (hospital)plaque (hospital)

PBT (protons)PBT (protons) PhotocoagulationPhotocoagulation EnucleationEnucleation Must consider life Must consider life

expectancyexpectancy

Differential Diagnoses of Metastatic Differential Diagnoses of Metastatic TumorsTumors

Primary uveal Primary uveal melanomasmelanomas

HemangiomasHemangiomas OsteomasOsteomas Posterior scleritisPosterior scleritis Inflammatory Inflammatory

disordersdisorders

Other Examples of Ocular Other Examples of Ocular NeoplasmsNeoplasms

Choroidal neviChoroidal nevi Primary Choroidal / Primary Choroidal /

CB MelanomasCB Melanomas MelanocytomasMelanocytomas Iris melanomasIris melanomas

Choroidal neviChoroidal nevi

Possibly present in up to Possibly present in up to 30% of general population 30% of general population (? clinical) 6.5% of whites (? clinical) 6.5% of whites in 2011 st.in 2011 st.

Flat or minimally elevated Flat or minimally elevated (< 1.5 mm)(< 1.5 mm)

< 6 mm in diameter: 95% < 6 mm in diameter: 95% are less than 2ddare less than 2dd

Melanotic or amelanoticMelanotic or amelanotic Overlying drusen: usually Overlying drusen: usually

indicate longstanding indicate longstanding inactivity: lipofuscin?inactivity: lipofuscin?

Possible overlying serous Possible overlying serous RDRD

RPE disturbance / RPE disturbance / atrophy over timeatrophy over time

Conversion to uveal Conversion to uveal melanoma : 1 in 4000melanoma : 1 in 4000

10% will grow without 10% will grow without undergoing malignant undergoing malignant conversion. Recent 2011 conversion. Recent 2011 study showed growth in study showed growth in 31% over 15 years. 31% over 15 years.

Choroidal NeviChoroidal Nevi

PhotodocumentPhotodocument B-scanB-scan If small follow If small follow

annuallyannually If suspicious, more If suspicious, more

frequent observationfrequent observation Significant elevation Significant elevation

rare with nevirare with nevi

Choroidal NeviChoroidal Nevi

Choroidal nevusChoroidal nevus

Peripheral choroidal nevusPeripheral choroidal nevus

Longstanding, Large Choroidal Longstanding, Large Choroidal NevusNevus

Overlying PED / RDOverlying PED / RD B-scan revealed no B-scan revealed no

growth compared to growth compared to baseline : retinal baseline : retinal oncologist chose to oncologist chose to monitor closelymonitor closely

B-ScanB-Scan

MelanomaMelanoma

Later, decision was Later, decision was made that malignant made that malignant transformation had transformation had occurredoccurred

Treatment was Treatment was undertaken with undertaken with brachytherapybrachytherapy

Primary Uveal TumorsPrimary Uveal Tumors

Unilateral & solitaryUnilateral & solitary Pigmented but may be Pigmented but may be

amelanoticamelanotic Relatively elevatedRelatively elevated Can break though Can break though

Bruch’s Bruch’s membrane…”Collar membrane…”Collar Button”Button”

Rare in non-caucasions Rare in non-caucasions (C 19 X AA; H 5x AA)(C 19 X AA; H 5x AA)

Low internal Low internal reflectivity with reflectivity with ultrasoundultrasound

Can be located Can be located anywhere…….no anywhere…….no posterior pole posterior pole predilectionpredilection

About 2000 new About 2000 new cases per year in UScases per year in US

Melanoma vs. nevusMelanoma vs. nevus

Important risk factors Important risk factors for possible malignant for possible malignant transformation….transformation….

Thickness > 2mmThickness > 2mm SymptomsSymptoms Orange PigmentOrange Pigment

New onset of New onset of subretinal fluid / serous subretinal fluid / serous RD, especially in the RD, especially in the absence of drusenabsence of drusen

Ultrasound hollowness Ultrasound hollowness / no halo/ no halo

Location within 3mm of Location within 3mm of ONHONH

Diameter of 12mm or Diameter of 12mm or moremore

Primary uveal tumorsPrimary uveal tumors

Can metastasize, but rarely have by the time they Can metastasize, but rarely have by the time they are detected in the eyeare detected in the eye

Gene mutation that causes metastasis has been Gene mutation that causes metastasis has been discovered (Dr. Harbour, Washington University)discovered (Dr. Harbour, Washington University)

Systemic work-up a must, but not common to find Systemic work-up a must, but not common to find metastases at time of diagnosismetastases at time of diagnosis

Most frequent site……..75%.........is the liverMost frequent site……..75%.........is the liver 2X risk of colon cancer compared to general 2X risk of colon cancer compared to general

populationpopulation

PathologyPathology

Three main tumor Three main tumor types based upon cell types based upon cell morphology….morphology….

Spindle (relatively Spindle (relatively benign)benign)

Epithelioid (most Epithelioid (most large tumors)large tumors)

MixedMixed

Small Choroidal Melanoma with Small Choroidal Melanoma with Lipofuscin and ElevationLipofuscin and Elevation

Choroidal Melanoma With Choroidal Melanoma With Intravitreal ExtensionIntravitreal Extension

Early choroidal melanomaEarly choroidal melanoma

““Collar Button” MelanomaCollar Button” Melanoma

Bile Duct Liver Cancer?Bile Duct Liver Cancer?

Lesion edgeLesion edge Atrophic area and borderAtrophic area and border

??

Treatment options for tumorsTreatment options for tumors

Systemic radiation / chemo if metastatic Systemic radiation / chemo if metastatic disease involveddisease involved

Brachytherapy (radioactive plaque) : requires Brachytherapy (radioactive plaque) : requires two surgeries and sometimes a hospital staytwo surgeries and sometimes a hospital stay

PhotocoagulationPhotocoagulation CryotherapyCryotherapy EnucleationEnucleation TTTTTT

Treatment options for tumorsTreatment options for tumors

EBRT (external beam EBRT (external beam radiation therapy)radiation therapy)

3-4 weeks of daily 3-4 weeks of daily treatmenttreatment

PBT (proton beam PBT (proton beam therapy)therapy)

Two treatment Two treatment sessions onlysessions only

Less readily availableLess readily available One at IUB One at IUB

(cyclotron)(cyclotron)

PBTPBT

PBT at IU cyclotronPBT at IU cyclotron

PBT in ScotlandPBT in Scotland

2012 retrospective 2012 retrospective studystudy

147 patients who had 147 patients who had medium and large medium and large uveal (most all uveal (most all choroidal) melanomaschoroidal) melanomas

Treated with PBT Treated with PBT between 1993 and between 1993 and 2008 2008

23% eventually 23% eventually required enucleationrequired enucleation

Disease specific 5 Disease specific 5 year survival rate of year survival rate of 88%88%

Most common Most common reasons for eventual reasons for eventual enucleation were enucleation were tumor recurrence and tumor recurrence and NVGNVG

Treatment side effectsTreatment side effects

Main side effect of Main side effect of focal ocular treatment focal ocular treatment is…………is…………

Radiation retinopathy!Radiation retinopathy!

NVD / NVENVD / NVE Exudative changesExudative changes Macular edemaMacular edema

Occurs several weeks Occurs several weeks to months after to months after therapytherapy

Treatment optionsTreatment options

Rapid shrinkage of Rapid shrinkage of the tumor with the tumor with treatment may be bad treatment may be bad news………indicates news………indicates substantial malignant substantial malignant (and metastatic) (and metastatic) potentialpotential

COMS and other studiesCOMS and other studies

Five year survival rates Five year survival rates for……….for……….

Small melanomas (< 10 Small melanomas (< 10 mm) : 94%mm) : 94%

Medium melanomas (10-Medium melanomas (10-15 mm): 70-90%15 mm): 70-90%

Large melanomas ( > 15 Large melanomas ( > 15 mm): 40-60%mm): 40-60%

Enucleation does NOT Enucleation does NOT appear to increase appear to increase metastatic riskmetastatic risk

Choroidal Melanoma (“George”) Choroidal Melanoma (“George”) Post Photocoagulation TherapyPost Photocoagulation Therapy

MelanomaMelanoma

MelanomaMelanoma

Radiation retinopathyRadiation retinopathy

Avastin may be Avastin may be effective at reducing effective at reducing retinopathy and retinopathy and stabilizing visionstabilizing vision

What about silicone What about silicone oil?oil?

Another example of RRAnother example of RR

What if……….What if……….

Wash U and other locations (Dr. William Wash U and other locations (Dr. William Harbour)Harbour)

Fine needle biopsies of melanomas are yielding Fine needle biopsies of melanomas are yielding amazing info with RNA transcriptomic profilingamazing info with RNA transcriptomic profiling

Essentially two types of tumors that can be Essentially two types of tumors that can be identified with over 90% accuracyidentified with over 90% accuracy

Class one signature: almost never metastasizes: Class one signature: almost never metastasizes: Class two almost always doesClass two almost always does

What are the implications of this?What are the implications of this?

Possible interventionPossible intervention

New research by Dr. New research by Dr. Harbour indicates that Harbour indicates that a certain class of a certain class of seizure drugs……seizure drugs……HDAC HDAC inhibitors……..may inhibitors……..may help help

Cancer cells that Cancer cells that have metastasized have metastasized from the eye to other from the eye to other sites are inhibited and sites are inhibited and made less aggressive made less aggressive by these drugs. May by these drugs. May be able to keep be able to keep disease “at bay” for disease “at bay” for an extended periodan extended period

More genetics…….More genetics…….

80% of uveal melanoma patients have 80% of uveal melanoma patients have mutations in either GNA11 or GNAQmutations in either GNA11 or GNAQ

But……………this mutation alone does But……………this mutation alone does not result in melanoma formation. Must not result in melanoma formation. Must have mutation plus other factors (as of have mutation plus other factors (as of now not known)now not known)

Iris MelanomasIris Melanomas

Around 5% of all uveal Around 5% of all uveal tumorstumors

Located inferiorly Located inferiorly secondary to sun secondary to sun exposureexposure

Only metastasize in < 5% Only metastasize in < 5% of casesof cases

Found almost exclusively Found almost exclusively in light colored iridesin light colored irides

Can have satellite lesionsCan have satellite lesions Can seed tumor cells in Can seed tumor cells in

to the TM causing to the TM causing elevated IOPelevated IOP

May be melanotic or May be melanotic or amelanoticamelanotic

Can irradiate, but Can irradiate, but complete excision is the complete excision is the treatment of choicetreatment of choice

Differential diagnosesDifferential diagnoses

NeurolemmomaNeurolemmoma XanthogranulomaXanthogranuloma Nevus Nevus Iris cystIris cyst Lisch noduleLisch nodule MelanocytomaMelanocytoma

Be suspicious Be suspicious if………..if………..

> 3mm> 3mm Increased IOPIncreased IOP Distorted pupilDistorted pupil Rapid growthRapid growth Secondary cataractSecondary cataract

Amelanotic Iris MelanomaAmelanotic Iris Melanoma

Another iris melanomaAnother iris melanoma

MelanocytomasMelanocytomas

Jet black lesion consisting of melanocytesJet black lesion consisting of melanocytes Most often on ONH, but can rarely affect Most often on ONH, but can rarely affect

the conjunctiva or uveal tractthe conjunctiva or uveal tract Usually involves less than half of the disc Usually involves less than half of the disc

but may cover the entire ONHbut may cover the entire ONH Can have concomitant juxtapapillary Can have concomitant juxtapapillary

choroidal nevuschoroidal nevus

MelanocytomaMelanocytoma

Very little potential for malignant Very little potential for malignant transformationtransformation

Very slow growingVery slow growing Usually little or no effect on vision but can Usually little or no effect on vision but can

cause VF defects including an enlarged cause VF defects including an enlarged blind spotblind spot

May also cause an APDMay also cause an APD

Differential diagnosesDifferential diagnoses

Malignant melanomaMalignant melanoma Juxtapapillary choroidal nevusJuxtapapillary choroidal nevus Optic disc meningiomaOptic disc meningioma

MelanocytomasMelanocytomas

MelanocytomaMelanocytoma

Multiple CHRPE / Bear tracksMultiple CHRPE / Bear tracks

A ticket for…………..A ticket for…………..

Familial Adenomatous Familial Adenomatous PolyposisPolyposis

FAPFAP 1 / 8000 people1 / 8000 people Associated with RPE Associated with RPE

hypertrophyhypertrophy Colon polyps with a Colon polyps with a

chance for malignant chance for malignant transformationtransformation

Gardner’s SyndromeGardner’s Syndrome A variant of FAP, but also A variant of FAP, but also

has….has…. Osteomas of the jawOsteomas of the jaw Soft tissue benign tumorsSoft tissue benign tumors Dental abnormalitiesDental abnormalities Polyps have nearly 100% Polyps have nearly 100%

chance of malignant chance of malignant trans.trans.

1 / 1,000,0001 / 1,000,000

What’s this?What’s this?

Or this?Or this?

How about this? How about this?

Photo Courtesy Dr. Mark DunbarPhoto Courtesy Dr. Mark Dunbar OCTOCT

RetinoblastomaRetinoblastoma

Malignant, congenital Malignant, congenital tumortumor

Derived from Derived from retinoblasts retinoblasts

Most common Most common intraocular tumor in intraocular tumor in infants / childreninfants / children

70 % unilateral70 % unilateral 1 / 15,000 children1 / 15,000 children

No racial or sexual No racial or sexual predilectionpredilection

Two types……Two types…… 1) Inherited (AD). 1) Inherited (AD).

Less than 10% of Less than 10% of cases. Frequently cases. Frequently multifocal and multifocal and bilateralbilateral

2) Sporadic. Usually 2) Sporadic. Usually unilateralunilateral


Can metastasize and Can metastasize and be fatal if detected too be fatal if detected too latelate

Survival rate 90+% if Survival rate 90+% if detected early (typical detected early (typical age of diagnosis is age of diagnosis is around 18 months)around 18 months)

LEUKOCORIALEUKOCORIA StrabismusStrabismus Poor VA Poor VA Involvement of ONH Involvement of ONH

is ominousis ominous Many treatment Many treatment

options depending on options depending on multiple factorsmultiple factors

IV chemo? IV chemo?

GeneticsGenetics

RB survivor with inherited type: 50% RB survivor with inherited type: 50% chance of transmitting to their childrenchance of transmitting to their children

Healthy parents: one child with RB; 6% Healthy parents: one child with RB; 6% chance of another : two or more children chance of another : two or more children with RB; 50% of anotherwith RB; 50% of another

Leukocoria differentialsLeukocoria differentials

RetinoblastomaRetinoblastoma Coat’s diseaseCoat’s disease ToxocariasisToxocariasis ToxoplasmosisToxoplasmosis Congenital cataractCongenital cataract PHPVPHPV colobomacoloboma

ColobomaColoboma



Documents

Cancer and the Eye: Ocular Tumors, Malignancies, and Neoplasms Brad Sutton, OD, FAAO Clinical Associate Professor IU School of Optometry No financial conflicts