New therapies are extending the lives of people with AIDS who, as they live longer, become more susceptible to opportunistic diseases. One of these diseases is cytomegalovirus eye disease, i.e., CMV retinitis, the incidence of which has more than doubled since 1985. The sight of an HIV-positive patient may be threatened by CMV at any time. But CMV retinitis most commonly occurs when the patient's immune system has markedly declined, as may be indicated by a CD4+ T cell count below 100.

Left unchecked, CMV can cause extensive damage to the inner eye. Bleeding, destruction of tissue, and progressive loss of vision occur in virtually all untreated patients; and eye tissues, once they are destroyed by CMV, never recover. Drug treatments are, therefore, essential for preventing or stopping such terrible damage.

Two drugs are used to treat and, also, may prevent CMV retinitis: ganciclovir (Cytovene), formerly known as DHPG, and foscarnet (Foscavir). Treatment often involves the permanent placement of intravenous lines and prolonged hospitalizations, and there can be multiple side effects. Cytovene, in lowering the white blood count, may leave the patient open to other opportunistic infections and less able to tolerate AZT, a drug used to suppress the growth of HIV. Foscarnet, although it does not usually suppress the white blood count, has other side effects, including nausea, kidney damage, and damage to the nervous system. Also, the development of resistance by CMV to these drugs is itself a problem.

Clearly, new approaches are needed. Recently, a third treatment for CMV retinitis was announced, and amfAR played a key role in its development. This treatment involves the injection of either ganciclovir or HPMPC (a experimental derivative of the antiherpes antibiotic, acyclovir) directly into the fluid of the inner eye. Dr. William Freeman of the University of California at San Diego helped develop this pioneering method, a form of intravitreal therapy, with funding support from amfAR. Articles published in newspapers, magazines, and journals, such as The New York Times and Science, have viewed this therapy as the way of the future to the prevention of blindness in AIDS.

An injection of HPMPC takes about five minutes and, alone, may arrest CMV retinitis for six to eight weeks. Repeated injections further limit the progression of eye damage. This procedure is a new addition to the field of localized therapies, which includes the ocular implant. In an ocular implant, a capsule containing an anti-CMV drug in time-release form is injected into the eye. One treatment may be effective for up to eight months. However, implants may have serious side effects, including short-term post-implant decreases in vision that are a major setback for people with limited life expectancies.

Dr. Freeman's study is a major step forward in addressing the issue of blindness in AIDS; however, it is not the ultimate answer. Every local therapy has limitations. Direct injections or eye implants leave the uninvolved eye, as well as other tissues of the body, susceptible to CMV disease. Methods for measuring exactly how much of the virus is in an infected eye and in the rest of the body would provide invaluable assistance in making decisions about whether the best treatment for a patient is by the local or intravenous delivery of drugs. A technique for measuring amounts of CMV is the focus of research by other amfAR-funded scientists. For example, Dr. Todd Margolis of the University of California at San Francisco Medical Center, with an amfAR grant from the Lion's Club, has developed a sensitive PCR-based assay to detect CMV in the blood and eye. This method currently is being tested in hospitals nationwide. Another investigator, Dr. Eliot Lazar of the University of Rochester (New York), has developed a unique experimental animal model for studying human CMV retinal infections.

We wanted you to know that amfAR funding is playing a leading role in the treatment and diagnosis of a sight-threatening complication of AIDS. We look forward to further advances in this critical area.