Regular exams needed to detect ocular complications of cancer therapy

Although ocular complications from cancer therapy are uncommon, patients should see an ophthalmologist as a precautionary measure.

Reza Dana

Ocular side effects of cancer treatments are uncommon, even rare, but when they occur they can be serious and sight-threatening. Patients undergoing treatments for cancers in other parts of the body should be monitored by an ophthalmologist for ocular complications, according to experts.

“The key things here, as a rule, are examination before the treatment, periodic follow-ups and aggressive management of any complications,” Reza Dana, MD, MSc, MPH, explained to Ocular Surgery News. “A lot of patients, we have found, are not educated by the oncologist, particularly in bone marrow transplant cases, as to the severity of the eye complications.”

Dr. Dana and other ophthalmologists spoke to OSN about the management of ocular side effects of cancer treatments, including bone marrow and radiation treatments, tamoxifen and other chemotherapies, and combination therapies.

Radiation complications

A number of cancers, including many on the face and around the eye, are treated with radiation, which causes cell damage by destroying the nucleic acids of cells. Cells that divide rapidly, such as cancer cells, are particularly susceptible to radiation damage, Dr. Dana said.

Since radiation came into use decades ago, techniques have been developed to shield important and sensitive structures such as the eye, he said.

“Over the years, the field has advanced considerably in terms of shielding important structures, … but the shielding techniques are not perfect,” Dr. Dana said.

When shielding is ineffective and radiation reaches the eye, he explained, a variety of problems can occur, including toxicity to the retina, degeneration and atrophy of the retina, cataract development, bleeding, and damage to the ocular surface and adnexa, such as the lacrimal glands and the eyelids.

“The most common type of damage that we have seen is damage to the cornea and ocular surface,” Dr. Dana said. “The cornea can basically melt, and it is damaged two ways; one is by the direct effect of radiation, and the second is indirect, by the damage of the radiation therapy on the eyelids and on the lacrimal glands that sit behind the eyelids.”

Radiation can lead to scarring, malformations or deformities that prevent the closure of the lid. This makes the ocular surface prone to dryness and to scratching by the lids, he said.

“The combination of the direct damage to the eye, as well as the indirect damage to the lacrimal glands and the lids, leads to chronic changes” such as scarring, new blood vessel formation and corneal melting, Dr. Dana said.

Bone marrow complications

When patients receive bone marrow transplants, their own marrow is destroyed and replaced by that of a donor. That donor can be related or not, Dr. Dana explained, but there must be a match to prevent tissue rejection.

“The problem is that the match is rarely a perfect match,” he said. “There are still differences between the white blood cells and the marrow that is transfused back. That can work, but the problem is that the new immune system they get can attack their own tissues, leading to a condition called graft-vs.-host disease [GVHD].”

GVHD is one of the main complications in people who get bone marrow transplants, Dr. Dana said, and it can affect the gut, the liver and the skin, as well as the eyes.

“GVHD can cause a lot of problems for the eye surface,” he said. “It can lead to severe dryness, severe inflammation and even scarring and destruction of the surface of the eye, including the cornea. These people can develop very severe and chronic forms of dryness and inflammation.”

He explained that approximately 3 months after bone marrow transplant a significant number of patients develop chronic GVHD, a problem that leads to debility from ocular surface dryness and inflammation.

“These people are prone to developing infections of the eye and developing sloughing of the epithelium of the corneas,” Dr. Dana said. “They are best managed by cornea specialists.”

Such patients may require punctal occlusion and heavy artificial lubrication, as well as treatment with anti-inflammatory drugs, topical cyclosporine or other pharmaceutical treatments.

Chemotherapy complications

Chemotherapy, although it has been refined over many years of use, still presents some challenges to ocular health.

“Chemotherapy is basically poison,” Dr. Dana said. “These poisons work best on cells that are proliferating a lot, which are cancer cells, but they also damage other cells in the body.”

Although most of the toxicity seen as a side effect of chemotherapy is not ocular, there is a “cumulative toxicity” of all chemotherapy agents, he said.

This accumulation can add to a cancer patient’s likelihood of developing cataracts, a complication that will be more common due to the high doses of prednisone steroids used in conjunction with chemotherapy. The prednisone can also make patients more prone to glaucoma, he said.

“All of those things needs to be monitored closely,” Dr. Dana said.

Katharina Schmid

Katharina Schmid, MD, cautioned that ophthalmologists and oncologists should be aware of any existing ocular problems in their patients that can be exacerbated by chemotherapy or combination treatments.

“The ophthalmologist also needs to be aware of the patient’s oncological situation, since malignancies and metastases can also simulate some symptoms,” she added in an e-mail interview with Ocular Surgery News.

Dr. Schmid noted that many chemotherapy agents, including 5-fluorouracil, cytosine arabinoside, methotrexate, cyclophosphamide, busulfan, deoxycoformycin, cisplatin, plant alkaloids and carmustine, can cause ocular side effects.

Those side effects range from keratoconjunctivitis sicca to periorbital edema to retinal hemorrhages and more. Most of these complications can be treated as they would be normally, Dr. Schmid said. Some treatments, though, must be modified around the cancer treatment.

In patients undergoing cytosine arabinoside therapy, glucocorticoid or 2-deoxycytidine eye drops or eye washing with physiological saline and instillation of 0.1% sodium betamethasone phosphate eye drops should be performed prior to therapy to prevent keratitis and corneal opacities, she said.

With 5-fluorouracil therapy, ocular ice packs for 30 minutes, starting 5 minutes before the cancer therapy, have been shown to prevent ocular complications. Tear substitutes should be given in advance with methotrexate therapy, Dr. Schmid said.

Symptomatic patients receiving weekly docetaxel therapy should be given early temporary silicone intubation in order to avoid closure of the lacrimal duct, she said.

Dr. Schmid advised that the ophthalmologist should perform a standard ophthalmological examination, including Schirmer testing and tear film breakup time.

“Then further examination of any pathologies should be performed,” Dr. Schmid said.

Complications generally appear within the first 2 weeks of treatment, Dr. Schmid said.

David I. Kaufman, DO, who participated in a study of the ocular side effects of tamoxifen, noted that, with tamoxifen specifically, there is a potential for patients to develop crystals in the retina, particularly the macular area. This side effect is uncommon, though, he said, and the drug itself is relatively safe.

“In looking at hundreds of patients, we found that the effects were quite low,” Dr. Kaufman said. “Nevertheless, in patients who take tamoxifen, it would be reasonable that if they have any visual complaints they be seen by an eye doctor, of course.”

General recommendations

Treatment of ocular complications of chemotherapy should be considered on a case-by-case basis, according to the physicians we talked to. Their general recommendation was that ophthalmologists should be accessible to cancer patients and ready to work with any complications.

“It really varies and depends on what the patient is getting and what they’re susceptible to because of that treatment,” Dr. Dana said. “We tend to emphasize how important it is to put these patients in touch with their ophthalmologists.”

David J. Kaufman

Dr. Kaufman said, “If there are changes in vision that the patient complains of, getting the patient to see an ophthalmologist could be of value to be sure it isn’t one of the side effects of treatment.”

On rare occasions, those we interviewed said, complications can become so severe that the cancer medications causing them may have to be discontinued.

That decision “would be up to a team effort through oncology, retina and the patient,” Dr. Kaufman said.

“The risk vs. benefits of the treatment strategy is always a team decision between oncology, ophthalmology, neurology, if needed, and of course the patient making the ultimate decision after being properly educated,” he continued.

Dr. Dana said the debate regarding whether to stop the treatment or manage the complication sometimes becomes a philosophical discussion.

“In general, unless it is a rare and unusual complication, we do not recommend that people stop the anticancer therapy or management due to the eye complication,” he said. “We simply manage the complication because the other alternatives are worse than ocular complications.”

For more information:

• Reza Dana, MD, MSc, MPH, is director of the cornea service at Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles St., Boston, MA 02114; 617-573-4331; fax: 617-573-4300; e-mail: reza_dana@meei.harvard.edu.
• David I. Kaufman, DO, can be reached at Michigan State University, 138 Service Road, Suite A-217, East Lansing, MI 48824; 517-353-8122; fax: 517-432-9414; e-mail: kaufmana@ht.msu.edu.
• Katharina Schmid, MD, can be reached at Ludwig-Boltzmann Institute for Retinology and Biomicroscopic Laser Surgery, Ophthalmology Department, Rudolfstiftung Hospital of Vienna, Juchgasse 25, A-1030 Vienna, Austria; 43-1-711-65-94674; fax: 43-1-711-65-4609; e-mail: katharina.schmid@wienkav.at.

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• Katrina Altersitz is an OSN Staff Writer who covers all aspects of ophthalmology.