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Interferon May Offer First Drug Therapy for Diabetic Retinopathy

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Interferon May Offer First Drug Therapy for Diabetic Retinopathy CLINICAL NEWS he says, "studies of angiogenesis have led to a new understanding of some of the vascular complications of diabetes." Angiogenesis was first linked to Interferon May Offer First Drug interferon —10 yr ago. Until then, in- Therapy for Diabetic terferon has been known mainly for its ability to stimulate the production of T Retinopathy lymphocytes. Then studies showed that the protein could slow the migration of New Research Showing That a-Interferon endothelial cells during the growth of new blood vessels. Soon after, other re- Blocks New Blood Vessel Formation in the Iris searchers showed that a-interferon slows down blood vessel growth in of Monkeys May Point the Way to New mice. In 1989, Carl W. White and Treatment for Diabetes Retinopathy. colleagues at the University of Colorado Health Sciences Center in Denver used a-interferon to treat a child with a he- mangioma, a mass resulting from the proliferation of capillaries. Hemangio- ye researchers are looking to the sudden loss of vision. The scarring that mas can occur anywhere in the body, immune system for new ways to accompanies recurrent hemorrhaging and can be fatal when they occur in E prevent, treat, or reverse prolifera- can lead to permanent loss of vision. certain organs. White's patient had a tive retinopathy, the most serious form Approximately 700,000 people hemangioma in the lung, a rare and of diabetic retinopathy. in the United States have proliferative usually fatal condition. Treatment with Proliferative retinopathy is retinopathy, with —65,000 new cases interferon, however, caused the heman- marked by the development of new being diagnosed each year. Proliferative gioma to regress. blood vessels, or neovascularization, in retinopathy rarely develops within the In 1990, Folkman and several the retina. Joan Miller, William G. Stin- first 5 yr of diagnosis of insulin-depen- colleagues began a clinical trial of a-in- son, and Judah Folkman, all of Harvard dent diabetes mellitus, although —26% terferon treatment for hemangioma. Medical School and the Massachusetts of people diagnosed with insulin de- Their results validated Whites results; Har and Eye Infirmary in Boston, have pendent diabetes mellitus will develop the mortality rate fell from 60 to 5% for found that the lymphokine a-interferon proliferative retinopathy within 10 yr. those treated with a-interferon. delivered systemically can slow or stop Less than 4% of people with non-insu- the growth of new small vessels in the lin-dependent diabetes develop prolif- The positive results led Folkman irises of monkeys. erative retinopathy within the first 4 yr and colleagues to consider applying the So far the work has been per- of their diabetes diagnosis. After 15 yr treatment to neovascularization in the formed only in animals, and a-interfer- with the disease, from 5 to 20% of eye. "It turns out," he says, "that the on's effects have not been shown di- those diagnosed with non-insulin-de- new capillary blood vessels in hemangi- rectly on blood vessels in the retina. pendent diabetes will develop prolifera- oma grow at very similar rates and by However, controlled clinical trials on tive retinopathy. similar rules as do new vessels in the one form of neovascularization in the The new research is the by- eye." The same angiogenic molecules eye are being planned. The work could product of research into the formation appear in the same sequence to induce lead to a new mode of treatment for of new blood vessels, or angiogenesis. capillaries to grow. proliferative retinopathy, a major factor New blood vessel formation occurs nat- Folkman, Miller, and their col- behind the 12,000 new cases of blind- urally during development, but can also leagues blocked branch retinal veins in ness attributable to diabetes in the signal the progression of disease. At the the eyes of monkeys, a procedure that United States each year. International Diabetes Federation Con- induces intense capillary growth and In proliferative retinopathy, new gress and ADA Scientific Sessions held neovascularization in the iris. A total of blood vessels grow on the retina or on last June in Washington, DC, Folkman 11 eyes were studied. or near the optic disk. These blood noted that angiogenesis research started After the new blood vessels ap- vessels are fragile and rupture easily, some 20 yr ago "as an inquiry into how peared, eight were treated with a-inter- and a major hemorrhage can cause a tumors stimulate new vessels." Today, feron, while three were left untreated. 300 DIABETES CARE, VOLUME 15, NUMBER 2, FEBRUARY 1992 Clinical news The a-interferon was given twice a day terms of what a-interferon is doing in vision. "In the age-related macular de- at twice the normal human dose. After an animal system, it's probably much generation area, the current treatment is 14 days, new blood vessel growth be- more complicated than that," she says. substantially less satisfactory," he notes, gan to slow in the eyes treated with A more immediate question is and a new drug potentially more im- a-interferon. Within 3 wk, the disease whether a-interferon treatment for portant. regressed in all of the treated eyes. some forms of diabetic retinopathy will Indeed, at the meeting of the Among the eyes that had not been represent an improvement over treat- American Academy of Ophthalmology treated, however, the disease progressed ment now available. Currently, patients last October, Wayne Fung, a San Fran- steadily. with proliferative retinopathy are cisco ophthalmologist, reported some Although the researchers specu- treated with scatter laser photocoagula- positive, but preliminary, findings on late that a-interferon may have a simi- tion. In this treatment, laser burns on treating macular degeneration with in- lar effect on the retina as on the iris, the retina are used to arrest neovascu- terferon. "In general, I'm seeing visual that remains difficult to prove. Cur- larization, possibly by stopping the improvement in at least half the pa- rently, there is no good animal model production of angiogenic factors. Laser tients and stabilization of the condition of diabetic retinopthy, says Miller. "It's photocoagulation can reduce the risk of in all the patients." hard to get new vessels to grow from severe vision loss by as much as 60% Another important question to be answered concerns a-interferon's the retina of animals," she says. "There Matthew Davis, professor of toxicity. In this area, a-interferon has a are other models in other parts of the ophthalmology at the University of track record. The Food and Drug Ad- eye—the cornea, for example—but it's Wisconsin at Madison School of Medi- ministration has approved its use for a bigger leap from treating that to treat- cine, points out that laser treatment is a hairy cell leukemia and AIDS-related ing diabetic retinopathy." very satisfactory therapy for diabetic Kaposi's sarcoma. In general, a-inter- retinopathy. "I doubt that any pharma- Still, on the strength of the feron produces a flulike response, in- cologic treatment that presumably studies on irises, Miller, along with cluding fatigue, muscle aches and Tony Adamis, David Guyer, Evangelos would have to be kept up for a year or pains, and low-grade fevers. But Miller Gragoudas of the Massachusetts Eye two . might be useful in eyes that added that it can also decrease the and Ear Infirmary, and Larry Yanuzzi of failed photocoagulation." number of lymphocytes and affect liver the Manhattan Eye, Ear, and Throat Miller counters that although enzymes Hospital in New York are now planning photocoagulation is effective, it has side Although those side effects are a pilot study involving people with effects that may make drug therapy at- controllable for many people, "the more choroidal neovascularization, in which tractive. "You end up having to destroy medical problems people have, the new blood vessels grow in the vascular tissue that, if not totally normal, is more difficult the drug is to use," Miller later between the retina and the sclera functional," she says. "If you had a says. It may prove difficult to treat the of the eye. treatment that could stop the vessels sickest people with diabetes who could The researchers hope to uncover from growing without having to destroy benefit most. Other inhibitors of angio- the mechanism by which a-interferon the tissue, it would be a preferred treat- genesis that are more effective and less reverses neovascularization. Miller spec- ment." toxic than a-interferon, may be devel- ulates that a-interferon may work both Davis argues that a-interferon oped, she says. by inhibiting the growth of endothelial could actually have greater clinical use- cells and by suppressing their migra- fulness in the treatment of age-related —Joe Wakelee-Lynch, Associate Editor tion; both processes are necessary for degeneration of the macula, the central for Diabetes Forecast and the growth of blood vessels. "But in area of the retina responsible for final Peter Banks, Editorial Director DIABETES CARE, VOLUME 15, NUMBER 2, FEBRUARY 1992 301.
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