Ocular Melanoma Treatment
Peter G. Hovland MD PhD
7th Annual Eyes on a Cure: Ocular Melanoma Patient
and Caregiver Symposium
21 April 2018

Welcome!
• Patient advocacy can make a difference
• Your fundraising helps
– Improve understanding
– Promotes better communication
– Fosters focused research

Introduction
• Dr. Peter Hovland
• Ocular Oncologist and Retina Specialist
• Clinical practice with Colorado Retina Associates
for 12 years

Disclosure
• Castle Biosciences – Advisory Board

When you hear hoof steps…
• You think of horses not zebras!
• Common things are seen more commonly.
• This talk is about zebras however.
Common Rare

Ocular Melanoma
• Rare
– About 2000 new cases per year in US
– About 7000 new cases per year world
– “Orphan” disease
• Mostly affects adults
– M = F
– More common in Caucasians
• Especially Blue/hazel eyes
• Familial 1%
• Cause unknown
– Genetic mutations - random

Ocular Melanoma
Starts in the eye wall:
– Choroid - 90%
– Ciliary Body – 6%
– Iris – 4%

OM originates in the eye
– Some OM can spread to the body

Tangent: Other cancers can spread to the eye
• Adenocarcinomas
– Breast, Lung, Prostate, GI, GU
• Lymphoma
• Sarcoma
• Melanoma
• Carcinoid

Journey of a New patient
• Symptoms or Routine Eye exam
• Eye doctor -> Specialist -> Ocular Oncologist
• Diagnosis
• Evaluation of Body
• Treatment of Eye
• Wait for response to treatment

How do we know it’s melanoma?
• Diagnosis based on exam and testing
• Diagnosis may be made
– At initial presentation
– After a period of observation
• Tumor may grow

Intraocular Tumor Diagnosis

Diagnostic Testing
• Initial evaluation
• Periodic observation
• Monitor response to treatment
• Multimodal

Color Photography

Angiography
• Evaluation of blood flow in eye tissues

Ultrasound
• 3-dimensional evaluation of tumors
• Measured in millimeters

Other Imaging
• Laser scanning - OCT

Autofluorescence

Infrared Reflectance

Enhanced Depth Imaging
• Measures thickness of tumor in microns

Fine Needle Biopsy
• For genetic evaluation and cytology

Risk assessment for spread of disease
into body (metastasis)
High risk Low risk
Tumor size Large Small
Genetics Class 2 Class 1
Eye location Ciliary Body Iris

Phases of patient experience
• Phase 1 – Diagnosis
– “Shock and Awe”
– Unexpected and Unwelcome
– Anxiety
– Why me?
– Loss of Control
– Confusion
– Fear of Unknown
– Work up
• Systemic screen for metastatic disease

Discovery: you are unique
• Not all OM patients are the same
• Differ in
– Genetics
– Location in the Eye
– Impact of disease
• Sight
• Involvement of body – threat to health

Challenge for medical team:
Find the best solution for the patient
• Eliminate cancer
– Locally
– Systemically
• Preserve vision
• Preserve eye

• You choose, providers inform, guide
• Three principles
– Life
• highest priority
– Vision
• can be damaged by treatment
• Can be improved or stabilized with other treatment
– Quality of life
• Pain
• Anxiety
• Appearance
Decisions – what to do?

Treatments for OM
• Toolbox
– Enucleation
– Radiation
– Laser
– Cryotherapy
– Excision

Treatment recommendation
• Based on:
– Eye structure involvement
– Size
– General Medical condition
– Patient preferences

Phases of patient experience
• Phase 2 – Treatment of eye
– Accept diagnosis
– Determination to get
through it
– Endure discomfort

Standard treatment options for OM
• Radiation
– Proton beam
– Brachytherapy
• Laser
– Diode (TTT)
– PDT – photosensitized dye
– Argon
• Enucleation

Radiation treatment
• Brachytherapy
– Most common treatment
– Usually “medium” sized tumors
– Up to 98% effective in controlling the tumor in the
eye

Radiation: Brachytherapy
• Local application of radiation to tumor
• Iodine 125 is usually used
• Two surgeries
– Implantation
– Removal
• Reattach muscle if necessary

Plaque Brachytherapy Pre-op
– Anxiety due to recent
diagnosis
• Need for treatment
• Loss of vision
– Pain usually not an
issue

Uveal Melanoma Brachytherapy
• Radioactive iodine plaque placement

Ultrasound
localization

Radiation safety
• Requires coordination with radiation
department
– Radiation oncologist
– Radiation oncology physicist

Radiation Complications
• Retinal problems
• Vision loss
• Cataract
• Glaucoma
• Inflammation
• Pain

Laser treatment of tumors
• Smaller tumors
• Different types of lasers
– Tissue burning lasers
• Argon laser
• TTT – diode laser
– 85% effective
– Light activated dye (PDT)
• Better in light colored tumors

If the tumor is too big…
• Enucleation
– Salvage of the eye is impossible
– The eye may be painful
– The eye may be blind
– Psychology
• Mourn loss of limb

Enucleation
• Procedure
– General Anesthesia
• And a retrobulbar block
• About 1 hour
– The eye is removed in a standard fashion
• Muscles are disinserted
• Optic nerve is cut.
• Eye is processed for biopsy and pathology
– Implant is placed, eye muscles attached
– Layered closure with conformer

Prosthesis

Phases of patient experience
• Phase 3 - Recovery
• Healing from surgery
– Vision issues
• Adjusting to the “new” you
• May need additional treatments to eye
– Prosthesis
– Intraocular shots
– Laser
– Additional surgery

Intraoperative procedures
• Enucleation
• Plaque Brachytherapy
• Vitrectomy
• Cryothermy
• Laser
• Biopsy

Vitrectomy
• Micro-incisions, sutureless

Cryotherapy
• Application of freeze-thaw
– Through the eye wall
– Ice crystals destroy tumor

Are there a better ways to treat OM?

Research designed to improve
treatment of eye tumors
• Goal to replace radiation and it’s side effects

Clinical trial: Aura Biosciences
• AU-011
• Currently in phase 1b clinical trial
– Small to medium size melanoma

Experimental Treatment of UM
• AU-011 Aura Biosciences
– Photoreactive modified viral capsid protein
• Modeled on Human Papilloma Virus
– Tumor selective binding
– Intravitreal delivery
– Targeted activation
• Attached chromophore
• Light activation – 689nm wavelength laser (same as PDT)
– Local tissue necrosis
• Cell membrane disruption

Experimental Treatment of UM
• Iconic therapeutics
– Intravitreal injection
– Anti-tissue factor (TF) antibody
– TF expressed at high levels
• On tumor surface
• Tumor vasculature
• Associated with aggressive tumor behavior
• Trial now closed, awaiting analysis

Phases of patient experience
• Phase 4 – Long term issues
– Surveillance after treatment
• Body Imaging
– What kinds?
– How often?
– Genetic information from Biopsy
• Low risk
– Are you cured?
• High risk
– Adjuvant trials
» Is it right for you?
– What if you have metastatic disease?

Ocular Melanoma
• Is a chronic condition.
– After treatment of the eye, follow up is required.

Teamwork needed!
• Patient
– Unique
• Support team
– Family
– Social
• Providers
– Advise
– Treat

Enjoy the meeting!