Stanford Report Online

Stanford Report, November 1, 2000
Radiation safe, effective for eye disorder


Scientists recently concluded a 40-year study of radiation treatment for an eye disorder known as Graves' ophthalmopathy and pronounced the results big success. The researchers found no radiation-induced cancers as a result of the highly successful treatment, and reported that 98% of patient were satisfied with the results of the radiation therapy.

"The numbers are great," said Sheri D. Marquez, M.D. "We have not observed any malignant tumors develop in the area that was treated with radiation." Marquez said. "And this is true up to 29 years following radiation treatment." Marquez, previously a Stanford resident and now a radiation oncologist in Burbank, will present the data at the American Society for Therapeutic Radiation and Oncology meeting, October 22-26 in Boston.

The study, which followed 197 patients over four decades, carries the kind of conclusive heft -- -- that makes doctors' decisions easier and more certain. "The current controversy has been who to treat and who not to treat," said Marquez. "Studies have shown that radiation works well, but there was still a question of its safety. This study helps answer that question."

Doctors have been treating Graves' ophthalmopathy with radiation, if at first unintentionally, since the 1940s. The name for this condition comes from a precipitating disorder, called Graves' disease, in which the thyroid is over-active. Twenty to forty percent of people suffering from this and other thyroid abnormalities develop Graves' ophthalmopathy: a case of bulging, red eyes surrounded by swollen and highly irritated tissue. The condition can be debilitating and a source of severe depression due to disfigurement and pain.

The cause of the Graves' ophthalmopathy remains speculative. Theory holds that when humans' thyroid developed, a tract linking the lymphatic system to the thyroid included areas around the eyes. Patients who develop Graves' disease show an increased immune response in the eye area. The concentration of lymphocytes, or white blood cells, resulting from the immune response around the eye cause swelling and irritation.

In the 1940s, doctors irradiated patients' pituitary glands to control hormone production in an over-active thyroid. After such treatment they noticed that the radiation also helped diminish patients' bulging eyes. Soon these patients were offered radiation directed at the source of the bulging: muscles behind the eye that are inflamed and engorged with immune cells. The doctors later found out that the treatment worked by killing lymphocytes, which are highly sensitive to radiation.

"After radiation the muscles often retract nicely," said Marquez. "If you don't do anything about the inflammation and engorgement behind the eyes, scars form. When that happens the patient will usually have problems moving their eyes at all, and surgery is often warranted."

Another complication is that patients often can't close their eyes completely because the bulging is so severe. "Their eyes become constantly dry, and that's a danger to the cornea. It can even lead to visual loss," Marquez said.

The apparent effectiveness of radiation treatment for bulging eyes is supported by the study's findings. For all but one patient, radiation kept symptoms from worsening. Swelling and irritation around the eyes was improved for 75% of the patients, 53% of patients had reduction of the bulging, 68% were allowed increased mobility of their eyes, 95% showed improvement to cornea damage, and 40% had improved vision. "Fundamentally, our goal is stop things from getting worse," Marquez said. "Fortunately, we've also learned that in many patients radiation actually reverses symptoms and these improvements continue for a long time, which is icing on the cake."

"There's a lot of data supporting the benefit of radiation treatment for this disease," Marquez said, "but I understand there are also some other data out there might suggest that radiation doesn't work well, and I have to question that. After treating as many patients as we have, there's no doubt in my mind we're able to benefit these people."

The study also measured potential harmful effects of radiation. In addition to finding no tumors in the irradiated area, the researchers also failed to find any retinal damage due to radiation. About 12% of the subjects later developed cataracts requiring medical attention, although the researchers don't know if this 12% would have developed cataracts anyway, since the patients are around 60 years old, an age at which cataracts are more common. Ninety-eight percent of patients were very pleased with the results of radiation. Eighty-four percent reported that radiation helped them, and fourteen percent said it kept their eye problems from getting worse. Two percent thought radiation therapy worsened their conditions.

The definitive findings should be particularly helpful for selecting patients for treatment. This subject draws debate partly because some patients will heal without treatment, while others are too far advanced for radiation to help. Thus therapists aim to select patients who are "progressively symptomatic" -- where the disease is developed and worsening.

"The selection of patients for radiation is very important and admittedly rather subjective," said Marquez. "It depends on their overall picture -- how much this is disturbing them, how their symptoms have developed over time, how young they are, if they're diabetic, and if their thyroid disease has been addressed."

Marquez' colleagues, who were instrumental in bringing the study to fruition, include Sarah S. Donaldson, MD, professor of radiation oncology; Ross McDougall, MD, professor of nuclear medicine; Peter Levin, MD, clinical associate professor of ophthalmology; and Bert L. Lum, PhD, of the Clinical Cancer Center.