Carolyn Choate has experienced eye tearing since cancer treatment. - PHOTO COURETESY CAROLYN CHOATE
CAROLYN CHOATE, A 15-YEAR survivor of stage 3b breast cancer, fully expects to live for a long time to come. However, an ongoing eye problem presents a daily reminder of her diagnosis and years of treatment.
“Shortly after I started chemotherapy treatment, my eyes started tearing 24 hours a day, seven days a week,” explains Choate, 60, a contributing essayist for CURE
®. “That has probably reduced by 30 to 40 percent over the last 10 years, but it’s still problematic.” An on-air television reporter, Choate says her daily life and career were affected by this issue that, despite her visits to several specialists, has not been explained.
Choate’s experience is not unique. Many cancer treatments, including chemotherapy, radiation, steroids and immunotherapies, are known to cause eye-related side effects such as dryness, tearing, cataracts, sensitivity to light, infection or altered vision. It’s even possible for eye color to change.
Patients with cancer “are frequently dealing with a devastating diagnosis and not thinking about keeping up with their routine medical care, like seeing an ophthalmologist or a dentist,” says Dan S. Gombos, M.D., professor and chief of the section ophthalmology at the University of Texas MD Anderson Cancer Center in Houston. “It is important to continue routine care because many adverse effects that might occur, if addressed early, can be treated effectively and have less impact.”
No good statistics reveal how commonly eye-related side effects occur in patients undergoing treatment for cancer, according to Gombos. “It is interesting, though, that if you look in a ‘Physicians’ Desk Reference’ at side effects from general drugs, you will often find that a very high percentage will say things like ‘blurry vision,’” he says, “so these things are not uncommon.”
Certain chemotherapeutic agents are known to affect the eyes. Fluorouracil, also called 5-FU, is used alone or in combination with other agents to treat breast, head and neck, gastrointestinal and genitourinary cancers. The mechanism that makes 5-FU effective at killing cancer cells can also negatively affect other organs. For example, it can cause rapid cell turnover on the eye surface or around the tear ducts, which may become clogged due to inflammation or scar tissue, blocking normal drainage of tears to the nasal cavity. “Because of these chemotherapeutic therapies, the eye may also become irritated, making a lot of tears, but with no place for the tears to go,” says Giacomina Massaro-Giordano, M.D., co-director of the Penn Dry Eye and Ocular Surface Center within the Scheie Eye Institute at the University of Pennsylvania in Philadelphia. “There is a dual mechanism producing tears (abnormally): the irritation and the physical blockage.”
If consulted early, an ophthalmologist can prevent blockage by surgically inserting temporary silicone tubes or stents to hold the tear ducts open during the period of treatment with 5-FU, Massaro-Giordano says.
The drug Taxotere (docetaxel) is also associated with eye-related side effects, including, in a limited number of cases, blocked tear ducts. As part of her chemotherapy regimen, Choate was treated with four rounds of Taxotere over an eight-week period. When her physicians tested her tear ducts to see if they were blocked, a filament passed through them freely, leaving her physicians stumped, she says. In fact, a 2013 study demonstrated that most cases of eye tearing due to Taxotere are not due to blocked ducts and eventually resolve on their own.
Many chemotherapy regimens also include a steroid. These drugs, which include prednisone, have a long list of associated toxicities, including some that affect the eye. “Steroids can change a patient’s glasses prescription by inducing diabetes and high blood sugar,” Gombos says. Dry eye is not uncommon, either, he says.
The drugs can cause other ophthalmological issues, as well. “Steroids can cause cataracts in the lens of the eye. A structure that is normally clear becomes opaque,” Massaro-Giordano says. They have also been known to induce glaucoma, a group of diseases that damage the eye’s optic nerve.
Some hormonal regimens, such as tamoxifen, which is commonly used to treat hormone receptor-positive breast cancer after chemotherapy, surgery and radiation, can cause neuropathies that lead to inflammation or damage of the optic nerve or pigmentary changes in the retina, creating a different eye color, Massaro-Giordano said. In many cases, eye damage related to cancer treatment can be reversed or stopped. Cataracts, for example, are routinely surgically removed and replaced with artificial lenses. Glaucoma, if caught early, can be treated with eyedrops, though some cases require laser or incisional surgery. If these eye conditions are caught soon enough, their impact on vision is limited, but in advanced cases, permanent vision loss can occur, Gombos says.
In addition, many of the eye-related side effects of chemotherapy or hormonal agents can be treated or reversed by stopping the drug that is causing them, or adjusting its dose. The idea of any change to cancer treatment might be intimidating for patients, Massaro- Giordano says, but they should disclose these symptoms to their physicians anyway. “Of course, the primary goal is always to keep the patient alive,” she says. “But sometimes there is some ‘leg room’ to help quality of life.”
Gombos agrees. “There are times when we do have to stop drugs if they are causing serious, sight-threatening problems,” he says. Ophthalmologists always work closely with oncologists to find appropriate treatment alternatives, he adds.
Reporting symptoms also might lead to the diagnosis and appropriate treatment of an unrelated eye problem. Another reason it’s important to disclose eye problems: Rarely, they may be due to tumor progression in areas such as the optic nerve, choroid (the vascular layer behind the retina) or orbit (the area outside the eye) and require prompt evaluation.
Treatment with radiation to the head or neck for certain cancers can also affect the eyes. “With proton beam radiation, simply because of the placement of the markers, eyelashes will suffer and often fall out,” says Sapna Patel, M.D., assistant professor in the department of melanoma medical oncology at the University of Texas MD Anderson Cancer Center. “This could be a permanent loss.” Radiation to the back of the eye can also damage the retina or the optic nerve.
“Radiation to the head and neck can affect the eyelid, the drainage system and also the tear film, as well, and how these structures are integrated,” Gombos says.
Some cases of damage may be more severe, such as radiation-induced optic neuropathy, a complication in patients with nasopharyngeal carcinoma who have undergone external beam radiation therapy. This can damage the optic nerve, resulting in irreversible vision loss.
However, in some settings, using certain forms of radiation, such as proton beam therapy or brachytherapy, can mitigate and reduce that risk, Gombos says. The risk of eye-related side effects from radiation is also higher in patients who already have vascular problems.
For example, “We would be worried about a diabetic patient with a long-standing history of diabetes who is now receiving radiation to the back of the eye,” Gombos says. “That patient is more likely to have problems because they are already at risk for problems by virtue of their diabetes.”
One of the most exciting recent advances for patients with melanoma has been the use of immunotherapies, which harness the body’s own immune system to fight cancer cells. However, “Immunotherapy causes immune response, and that can cause inflammation in the eye,” Patel says.
Ocular complications reported in patients taking the immunotherapy Yervoy (ipilimumab) include conjunctivitis, scleritis, intraocular inflammation and Graves’ ophthalmopathy. Though rare, intraocular inflammation has been reported with Keytruda (pembrolizumab) and Opdivo (nivolumab). Topical anti-inflammatory drugs or steroids typically can treat many of these problems, but surgery may be needed for Graves’ ophthalmopathy. Targeted agents used to treat melanoma in the clinic and in clinical trials also have been associated with certain ocular side effects. Specifically, agents designed to inhibit MEK protein, which plays an important role in the proliferation of malignant tumors, have been linked with central serous retinopathy (fluid buildup under the retina), retinal vein occlusion (small vein blockage) and periorbital edema (swelling around the eyes). “These will manifest as blurry vision in the patient but can be associated with multiple clinical diagnoses,” Patel says. Laser treatments may be helpful in retinopathy or vein occlusion. Similar to the way antibiotics make some people’s skin more prone to sunburn, some targeted therapies or immunotherapies can affect the eyes and make some individuals photosensitive, or sensitive to light. “Patients need to be aware of this and should safeguard themselves with sunglasses (that have) lenses (with) ultraviolet protection,” Patel says.
Patients undergoing bone marrow transplant for cancer also may be at risk of eye-related side effects as a result of graft-versus-host disease, which occurs when the donor’s immune cells mistakenly attack the transplant recipient’s normal cells. Ocular complications include acquisition of the donor’s allergic disorders, lost pigmentation in the eyebrows or lashes, lost eyelashes and a variety of issues related to the cornea, or the front of the eye. Some of these complications can be treated with immunosuppression and local therapy; others may require surgery.
The main manifestation, however, is dry eye. “Severe dry eye in ocular graft-versus-host disease can be very severe and lead to permanent visual loss,” Gombos says. “But we can sometimes use drops or contact lenses to mitigate or reduce the symptoms and side effects.”
People diagnosed with certain cancer types are also more likely to experience problems in the eye and surrounding areas due to the tumor itself. Intraocular or uveal melanoma is a rare form of melanoma but the most common primary form of intraocular malignancy in adults. As uveal melanoma grows, patients often experience symptoms including blurred vision or decreased visual acuity because of retinal detachment.
“When patients are treated for eye melanoma, they become monocular, or have only one functioning eye,” Patel says, noting that this is a permanent condition. Treatment for uveal melanoma involves either enucleation (removal of the eye) or radiation, which damages the retina and leads to vision loss in the affected eye.
In contrast to skin melanoma, which is associated with ocular side effects in up to 10 percent of patients, the rate of these issues rises to as high as 30 to 40 percent in uveal melanoma, according to Patel. “People are primarily functioning out of one eye, and if that one eye becomes blurry, they are more likely to notice than someone with two eyes to help compensate for the difference,” she says.
Patients should tell their doctors or nurses about changes to their eyes or ability to see, including blurred vision, seeing halos, loss of areas of sight, headaches, dry eyes, tearing, light sensitivity or itching. Some problems might be eased by simple measures: eyelid massage, steroid/ antibiotic combinations, ice packs, artificial tears, warm compresses and electing not to wear contact lenses. “It is never a bad idea to be assessed by an ophthalmologist,” says Gombos, emphasizing the need for this type of physician. These specialists in eye and vision care are licensed to practice medicine and surgery and have received a high level of training in the diagnosis and treatment of all eye diseases. An optometrist, on the other hand, provides primary vision care but is not a medical doctor, while an optician is a technician trained to design, verify and fit devices to correct eyesight. “An optometrist might do a cursory evaluation but not a detailed medical evaluation,” Massaro-Giordano says.
Those who do not already see an ophthalmologist as part of routine health care should ask their oncologists to recommend one, Massaro-Giordano says. An ophthalmologist will perform a detailed medical examination of the front of the eye (including the surface, using special stains) and also the back part. This will involve dilating the pupils and using sophisticated instruments. Specialized tests (visual field and optical coherence tomography) and pictures will measure overall function of the retina and optic nerve.
“Even before you start treatment, it is a good idea to consult with an ophthalmologist for baseline measurements and close monitoring,” Massaro-Giordano says.
Ideally, she continues, patients should have their eyes examined every three to 12 months, depending on the aggressiveness of their treatment, or every 12 months if there are no known side effects.
Patients should come to each visit prepared to discuss their type and stage of cancer, as well as what therapies they are taking and at what dosages, Gombos says.
“The bottom line is that some patients will think, ‘My eye is not a priority. I need to stay alive,’” Massaro-Giordano says. “But with good screening and communication with their oncologists, effects on the eye can be halted, diminished or slowed down.”
Choate said that her cancer diagnosis completely altered her life and definitely changed her eyes, which also were stripped of pigment during her treatment — they went from brown to blue. She hopes that by bringing awareness to eye-related side effects, she might help prevent problems similar to hers in other people.
“The loss of pigment is not a big deal, but the tearing situation can be difficult,” Choate says. “We are surviving for longer and longer now but are still plagued by side effects long after our treatment. We definitely need more answers and options for survivors like me.”