Cancer and the Eye: What you need to know

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1 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) 270 deaths Systemic cancers 1.65 million new cases each year 589,000 deaths iledguide/eye-cancer-key-statistics What we are going to talk about Cancer basics How can systemic cancer affect the eyes? What should I be thinking if I see a patient with cancer? What treatments are available for cancer and how can they affect the eyes? Surgery Radiation Chemotherapy 3 Definitions Cancer: A collection of diseases in which some of the body s cells begin to divide without stopping, grow out of control, and can become invasive Malignant Can spread into, or invade, nearby tissues Differentiated vs undifferentiated 4 Pre-cancerous changes Categories of cancer Carcinoma most common; formed by epithelioid cells Sarcoma form in bone and soft tissue Leukemia begin in bone marrow; abnormal WBCs Lymphoma begins in lymphocytes (B- or T- cell) Multiple Myeloma malignant plasma cells Melanoma Neuroendocrine - forms from cells that release hormones in response to a signal from the nervous system

2 Most common cancers Metastasis Process by which cancer spreads from the organ of origin (primary site) to distant tissues Disorganized and invasive-appearing tumors Cells generally look the same as cells of the original cancer Increased risk if tumor cells have aggressive traits on histopathology Poorly differentiated Invade beyond normal tissue boundaries Spread to regional lymph nodes is one of the early signs of met potential and/or distant spread 8 Ocular metastases Rare site due to the absence of a lymphatic system within the eye Spread is via blood, therefore parts of eye with greatest vascular supply most likely to be affected Uvea: choroid, esp perimacular choroid But still may be the most common intraocular malignant neoplasm Based on autopsy data; often not seen Optic nerve, retina, vitreous, conjunctiva, orbit can also be affected, but these are rare 9 Choroidal metastases Creamy yellow subretinal mass, often with subretinal fluid (73%) Plateau or dome configuration Unusually large amount of subretinal fluid for their size 10 Choroidal metastases Solitary (72%) Avg was 1.6; range 1-13 Posterior to the equator (92%) Tends to grow rapidly May double in size in a few weeks Iris Solid, usually white/yellow 74% solitary 42% inferior Can shed tumor cells that form a pseudohyopyon or clog TM and cause glaucoma

3 Ciliary body Yellow domeshaped; usually difficult to visualize clinically Inferior location 48% of the time May be associated with extensive RD and severe ocular pain 13 Management Treatment may help prolong the lives of some people with metastatic cancer. In general, though, the primary goal of treatments for metastatic cancer is to control the growth of the cancer or to relieve symptoms caused by it. Metastatic tumors can cause severe damage to how the body functions, and most people who die of cancer die of metastatic disease 14 Treatment/management Radiation The aim of treatment is to restore visual acuity and therefore improve the patients quality of life for their remaining life span Cohen VML (2013) External beam radiation Lung and breast are most common primary sites, and are radiosensitive Readily available Time consuming: 5 days/week 30 min For 2-10 weeks Plaque radiotherapy Can be completed in a few days Specialty centers Must be able to undergo surgery Other treatments Cancer of Unknown Primary Systemic chemotherapy May respond, especially to treatments for breast cancer PDT (Photodynamic therapy) Best for solitary metastases Intravitreal anti-vegf Best for small, well-circumbscribed mets without exudative RDs Especially good for colon cancer Clinical syndrome No primary site is identified after standard clinical and pathological evaluation Exact incidence is unknown, as many of the patient are assigned other diagnoses May account for 5% of all invasive cancers Usually present with advanced cancer. Primary site becomes obvious in only 5-10% of patients during their lifetime. At autopsy, primary site identified in ~ 75% of patients. Primary sites in the pancreas, lung, colorectum and liver account for 60% of cases. Breast, ovary, or prostate are rare Greco FA, Hainsworth JD,

4 Paraneoplastic syndromes Paraneoplastic syndromes Group of rare disorders (~10%) that are triggered by an abnormal immune system response to a cancerous tumor Disorders arise from tumor secretion of hormones, peptides, or cytokines OR immune cross-reactivity between tumor and normal host tissues Most common in individuals with lung, ovarian, lymphatic, or breast cancer 19 Symptoms may be endocrine, neuromuscular, musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, or renal May in part explain some of the most common symptoms of cancer, such as fatigue, anorexia, and weight loss. Rahimey E, Sarraf D (2013) Nervous and visual system are rare, affecting as few as 0.01% of patients Occurs when an immune response is mounted to cancer antigens; these cancer-fighting antibodies & T-cells mistakenly attack normal cells in the nervous system - including brain, spinal cord, peripheral nerves or muscle or the eye 20 Can cause a host of neurologic symptoms: Difficulty walking, swallowing, or talking Loss of muscle tone or fine motor ability Memory loss, dementia, seizures In the eye, they disrupt normal cellular function, and ultimately cause visual dysfunction. Rahimey E, Sarraf D (2013) Cancer-associated retinopathy Cancer-associated retinopathy Likely most common of the intraocular PNS Painless visual loss, developing over weeks to months Symptoms: photosensitivity, photopsia, glare, poor central and color vision (cones) OR nyctalopia, impaired dark adaptation, ring scotoma, or other peripheral field loss (rods) Fundus findings normal, or optic nerve pallor, attenuated retinal arterioles, and RPE thinning and mottling 21 Rahimey E, Sarraf D (2013) Precedes diagnosis of underlying cancer in about 50% of patients Diagnosis made by labs (anti-retinal antibody testing) and ERG (severely reduced to extinguished) No effective treatment - long-term immunosuppresion is the main therapy but visual prognosis is poor; vision loss is often rapid and relentless. Treatment of underlying malignancy does not appear to be effective 22 Rahimey E, Sarraf D (2013) Take home points Systemic cancer is prevalent in the population, and will continue to be increasingly prevalent Metastases to the eye are most common in the choroid, but can occur anywhere in the eye 75% of the time the primary site will be the lung or breast Patients with cancer and new complaints of blurred vision or eye pain should be evaluated Although rare, be aware of the clinical entities of paraneoplastic syndrome and CAR Basic Principles of Therapy Staging guides therapy TNM Multimodality treatment Cure versus Comfort Risk versus Benefit 23 4

5 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 Rad = unit of absorbed energy in tissue Gray (Gy) = 100 Rad the latest unit 1 Gy = 100 cgy Chest X-Ray is < 1 cgy Cancer treatment may be 6000 cgy Radiation Therapy: Treatment Considerations 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 Radiation Therapy: Treatment Considerations High radiosensitivity High mitotic activity Highly vascularized Tissue Brain Spinal Cord Heart Intestine Liver Lung Kidney Bone Marrow Dose, cgy

6 Radiation Therapy: Acute Radiation Sickness GI upset N/v Diarrhea Anemia Depends on area radiated Skin rashes Alopecia - localized Fatigue 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 Radiation Complications: Eyelid Epiphora Telangiectasia Madarosis Transient Permanent (>50 gy) Erythema Usually resolves in several weeks Entropion Ectropion Trichiasis Causes secondary to radiation: KCS Pseudo-epiphora Ectropion Nasolacrimal duct obstruction Management Prophylaxis with silicone tubes Dcr 6

7 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 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 Cataracts Conjunctival flap Tarsorraphy Enucleation 12/30 patients PSC most common Can get ASC Can develop in infant if mom receives radiation during first trimester Let s move to the posterior segment... Acta Ophthalmol Scand 2007: 85:

8 Radiation Retinopathy 6-36 months after radiation Damage because of occlusive microangiopathy Increased incidence if: Chemotherapy DM or HTN Collagen vascular disease Radiation Retinopathy: Signs Capillary nonperfusion: hallmark Intraretinal hemorrhages Microaneurysms Retinal NFL infarcts Exudates Vessel sheathing Clinical and Experimental Optometry 2007; 90(6) 44 YOM Referred for evaluation of HTN retinopathy Gradual reduced vision OS>OD Radiation Retinopathy: Further Complications Macular Edema NVE NVD NVI more likely in the angle? Radiation Retinopathy: Management Neovascular Glaucoma R/O other causes of retinopathy Laser PRP Focal Intravitreal Injections Anti-VEGF Steroid Preventive? Incidence 14% if >50 G 7% overall May not have retinopathy! Average time of onset years post-radiation 8

9 Radiation Optic Neuropathy 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 Radiation Induced Cerebral Necrosis Visual pathway is highly susceptible Optometrist may detect Onset 3-22 years!! Usually irreversible and progressive Radiation Induced Cerebral Necrosis Often diagnosis of exclusion Rule out: Neoplasm Abscess Cva MRI Diagnostic imaging of choice Orbit Bony structures Hypoplasia Soft tissue Enophthalmos Prosthetic fit is difficult Biological Response Modifiers Interferons Inhibit transcription of a number of oncogenes Alter cytokine secretion from normal cells Results in regulation of tumor growth Adjuvant Cutaneous melanoma Leukemia Lymphoma Interferon-Induced Retinopathy Often asymptomatic Prospective study of chronic hepatitis C patients Up to 57% incident May be subclinical Intraretinal hemorrhages, cotton wool spots Rule out other causes Resolution often after d/c interferon therapy 9

10 Chemotherapy: The Basics Disseminated malignancy Neoadjuvant Combo drugs Routes: Local Regional Systemic: IV., P.O. Conventional Targeted Tamoxifen Selective estrogen receptor modulator Interferes with binding of estradiol to its target tissues Indications Breast Prophylactic through metastic 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 Location is debatable: NFL, RPE, IPL, OPL Superficial to vasculature Macular edema Crystals usually do not resolve with discontinuation of therapy Specific Examples with known OADR Docetaxel (taxotere ) Epiphora Canalicular stenosis Cme Increased IOP Specific Examples with known OADR Epidermal growth factor receptors (EGFR) inhibitors Dry eye Trichomegaly Trichiasis Persistent corneal erosions Imatinib (gleevec ) Periorbital edema Epiphora Subconjunctival hemorrhage 10

11 Our Role Role of Optometrist Prevention Encourage appropriate behavior Encourage screenings Early Detection If in doubt, refer it out During Cancer Treatment Educate yourself! Educate patient Treat if symptomatic Depending on treatment consider prophylactic management Role of Optometrist After Ocular lubricants Patient WILL have dry eye Good case history Radiation? Fraction Dose Chemotherapy agents? Refer as needed for ocular sequelae We have an important role to play on the cancer patient s management team. 11

Cancer and the Eye: What You Need to Know

Cancer and the Eye: What You Need to Know Disclosure Nothing to disclose Tammy Pifer Than, MS, OD, FAAO tammythan@bellsouth.net 1 2 Systemic vs ocular cancers for 2016 Ocular cancers 2,810 new cases in