Cancer and the Eye: What You Need to Know

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Cancer and the Eye: What You Need to Know Disclosure Nothing to disclose Tammy Pifer Than, MS, OD, FAAO tammythan@bellsouth.

1 Cancer and the Eye: What You Need to Know Disclosure Nothing to disclose Tammy Pifer Than, MS, OD, FAAO 1 2 Systemic vs ocular cancers for 2016 Ocular cancers 2,810 new cases in 2016 (primarily melanomas) 280 deaths Systemic cancers 1.68 million new cases each year 595,000 deaths 1630 people a day 3 Cancer Prevalence Second only to heart disease as the leading cause of death Accounts for nearly 1 in 4 deaths In the US the lifetime risk for developing cancer is: 42% for men 38% for women 86% of all cancers are diagnosed in people age 50 or older Median age of diagnosis is 65 4 How many cancer survivors are there? Basic Principles of Therapy As of Jan 1, 2016, nearly 15.5 million Americans with a history of cancer were alive By January 1, 2024, the population of cancer survivors will increase to almost 20.3 million Staging guides therapy TNM Multimodality treatment Cure versus Comfort Risk versus Benefit 5 1

Surgery Radiation Therapy: The Basics Localized malignancy Surgery alone for ~25% of patients May be palliative Ocular complications can occur Dependent upon tissue excised Spectacle considerations

$Fractionation Schedule 5 days / week for 2-7 weeks beam is on for 1-2 minutes Hyperfractionation Fraction size is key!$

2 Surgery Radiation Therapy: The Basics Localized malignancy Surgery alone for ~25% of patients May be palliative Ocular complications can occur Dependent upon tissue excised Spectacle considerations Administration Teletherapy Brachytherapy I-125, Sr-90, Ru-106 Targets DNA - impairs division free radicals generated Intensity Modulated Radiation Therapy (IMRT) Radiation Therapy: The Basics Radiation Therapy: Treatment Considerations Gray = absorption of 1 Joule of energy / kg 1 Gy = 100 cgy Chest X-Ray is < 1 cgy Cancer treatment may be 6000 cgy Fraction Size < 225 cgy / day Fractionation Schedule 5 days / week for 2-7 weeks beam is on for 1-2 minutes Hyperfractionation Fraction size is key! Radiation Therapy: Tumors to Treat High radiosensitivity High mitotic activity Highly vascularized Radiation Therapy: Treatment Considerations Tissue Brain Spinal Cord Heart Intestine Liver Lung Kidney Bone Marrow Dose, cgy

Radiation Therapy: Acute Radiation Sickness GI upset N/v Diarrhea Anemia Depends on area radiated Skin

Signs Retinal edema Retinal hemorrhages Acute vascular occlusion rare papilledema responds well to

$treatment Incidence increases with: More fractions Larger fractions Higher total dose Radiation$ to bone marrow transplantation 13% (N=397) had posterior segment complications Hemibody irradiation

to bone marrow transplantation 13% (N=397) had posterior segment complications Hemibody irradiation

Complications: Anterior Segment Eyelids Conjunctiva Lacrimal system Cornea Iris Sclera Lens Eyelids

3 Radiation Therapy: Acute Radiation Sickness GI upset N/v Diarrhea Anemia Depends on area radiated Skin rashes Alopecia - localized Fatigue Acute Radiation Retinopathy Rare Usually no clinical consequence Signs Retinal edema Retinal hemorrhages Acute vascular occlusion rare papilledema responds well to corticosteroids Radiation Therapy: Long Term Complications Tend to be progressive Can occur years after treatment Incidence increases with: More fractions Larger fractions Higher total dose Radiation Complications: Diagnosis and Management Focal radiation Head/neck delivery Total body irradiation Prior to bone marrow transplantation 13% (N=397) had posterior segment complications Hemibody irradiation Decreases diffuse bone pain Treats multiple disease sites May require treatment of other half Radiation Complications: Anterior Segment Eyelids Conjunctiva Lacrimal system Cornea Iris Sclera Lens Eyelids Telangiectasia Madarosis Transient Permanent (>50 Gy) Erythema Usually resolves in several weeks Entropion Ectropion Trichiasis 3

Epiphora / Pseudo-Epiphora Causes secondary to radiation: KCS Ectropion Nasolacrimal duct obstruction Management

to dry eye Symptomatic in 1 month Opacification in 9-10 months More likely if >30 Gy Dry Eye: Management Aggressive

Off-labeled for severe, recalcitrant dry eye Evoxac (Cevimiline) 30 mg tid (Sjögren s associated xerostomia) Dry

common Can get ASC Can develop in infant if mom receives radiation during first trimester 6-36 months after

4 Epiphora / Pseudo-Epiphora Causes secondary to radiation: KCS Ectropion Nasolacrimal duct obstruction Management Prophylaxis with silicone tubes DCR Dry Eye Int J Radiation Oncology 30(4) % had severe decrease in VA due to dry eye Symptomatic in 1 month Opacification in 9-10 months More likely if >30 Gy Dry Eye: Management Aggressive lubrication Punctal Plugs Medical Management Salagen (pilocarpine) Xerostomia post head/neck radiation 5-10 mg tid Off-labeled for severe, recalcitrant dry eye Evoxac (Cevimiline) 30 mg tid (Sjögren s associated xerostomia) Dry Eye: Management Conjunctival flap Tarsorrhaphy Enucleation 12/30 patients Cataracts Radiation Retinopathy PSC most common Can get ASC Can develop in infant if mom receives radiation during first trimester 6-36 months after radiation Damage because of occlusive microangiopathy Increased incidence if: Chemotherapy DM or HTN Collagen vascular disease 4

Radiation Retinopathy: Signs Capillary nonperfusion: hallmark Intraretinal hemorrhages

Complications Macular Edema NVE NVD NVI more likely in the angle?

Injections Anti-VEGF Steroid Preventive?

2 years post-radiation May not have retinopathy!

Cerebral Necrosis Onset: 2 months - 7 years Average: 1 year Sudden, painless, unilateral loss of

5 Radiation Retinopathy: Signs Capillary nonperfusion: hallmark Intraretinal hemorrhages Microaneurysms Retinal NFL infarcts Exudates Vessel sheathing Radiation Retinopathy: Further Complications Macular Edema NVE NVD NVI more likely in the angle? Radiation Retinopathy: Management R/O other causes of retinopathy Laser PRP Focal Intravitreal Injections Anti-VEGF Steroid Preventive? Neovascular Glaucoma Incidence 14% if >50 Gy 7% overall Average time of onset years post-radiation May not have retinopathy! Clinical and Experimental Optometry; 2007: 90(6) Radiation Optic Neuropathy Radiation Induced Cerebral Necrosis Onset: 2 months - 7 years Average: 1 year Sudden, painless, unilateral loss of vision (+) APD Possible prodrome reported Acute presentation (two variations) Anterior ischemic optic neuropathy Retrobulbar optic neuropathy Chronic presentation Optic atrophy Visual pathway is highly susceptible Optometrist may detect Onset 3-22 years!! Usually irreversible and progressive 5

Radiation Induced Cerebral Necrosis Orbit Often diagnosis of exclusion Rule out: Neoplasm Abscess Cva MRI Diagnostic imaging of choice Bony structures

Regional Systemic: IV, PO Conventional Targeted Tamoxifen Selective estrogen receptor modulator Interferes with binding of estradiol to its target tissues

opacities Retinopathy +/- Macular edema Cataracts ASC Optic neuropathy Rare Macular holes?

6 Radiation Induced Cerebral Necrosis Orbit Often diagnosis of exclusion Rule out: Neoplasm Abscess Cva MRI Diagnostic imaging of choice Bony structures Hypoplasia Soft tissue Enophthalmos Prosthetic fit is difficult Chemotherapy: The Basics Disseminated malignancy Neoadjuvant Combo drugs Routes: Local Regional Systemic: IV, PO Conventional Targeted Tamoxifen Selective estrogen receptor modulator Interferes with binding of estradiol to its target tissues Indications Breast Prophylactic through metastatic Ovarian Pancreatic Malignant melanoma Tamoxifen: Ocular Effects Keratopathy White-yellow subepithelial opacities Retinopathy +/- Macular edema Cataracts ASC Optic neuropathy Rare Macular holes? International ophthalmology 2005; 26(3) Tamoxifen Retinopathy Bilateral yellow-white crystals in ring-like pattern microns ± Macular edema Cystoid changes Crystals usually do not resolve with discontinuation of therapy 6

Tamoxifen Retinopathy Pseudocystic foveal cavitation With or without edema With or without crystalline retinopathy Low daily doses Am Journal of Ophthal 167(6) June 2014 Am J Ophthalmol.

2014 Jun;157(6):1291-1298 39 40 http://www.cancer.org/acs/groups/content/@research/docum ents/document/acspc-047079.

7 Tamoxifen Retinopathy Pseudocystic foveal cavitation With or without edema With or without crystalline retinopathy Low daily doses Am Journal of Ophthal 167(6) June 2014 Am J Ophthalmol Jun;157(6): Managing Patients on Tamoxifen OCT Baseline Annually Pseudocystic Foveal Cavitation Macular Edema Oral CAI Topical NSAID Am J Ophthalmol Jun;157(6): ents/document/acspc pdf Specific Examples with Known OADR Docetaxel (Taxotere ) Epiphora Canalicular stenosis CME Increased IOP Specific Examples with Known OADR Epidermal Growth Factor Receptor (EGFR) Inhibitors Dry eye Trichomegaly Trichiasis Persistent corneal erosions Imatinib (Gleevec ) Periorbital edema Epiphora Subconjunctival hemorrhage Survey of Ophthal 59(2014)

8 Identifying OADR Resources Clinical Ocular Toxicology Fraunfelder, Fraunfelder, Chambers Drug Induced Ocular Side Effects Fraunfelder, Fraunfelder, Chambers Report It! MedWatch Our Role Prevention Encourage appropriate behavior Encourage screenings Early Detection If in doubt, refer it out Modifiable risk factors for the development of breast cancer Weight gain (~50% risk) Especially post-menopausal Physical inactivity (~20% risk) Alcohol consumption >4 drinks/week (~35% risk) Depends on age of drinking 2 drinks/day (~50% increased risk) Overall, it is estimated that >50% of all breast cancers could be prevented through healthy behaviors and chemoprevention (i.e. tamoxifen and raloxifene) 28 Role of Optometrist Role of Optometrist During Cancer Treatment Educate yourself! Educate patient Treat if symptomatic Depending on treatment consider prophylactic management After Ocular lubricants Patient WILL have dry eye Good case history Radiation? Fraction Dose Chemotherapy agents? Refer as needed for ocular sequelae 8

Cancer and the Eye: What you need to know

Cancer and the Eye: What you need to know Tammy P. Than OD, MS, FAAO University of Alabama Birmingham School of Optometry Systemic vs ocular cancers Ocular cancers 2580 new cases each year (primarily melanomas)