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December 14, 1994
A National Eye Institute (NEI) clinical trial reported today that a new, drug-releasing device was effective in treating cytomegalovirus (CMV) retinitis, a sight-threatening disease that affects one out of four people with AIDS. The 4 millimeter-diameter device, called a ganciclovir implant, is surgically placed into the eye, where it releases the anti-viral drug ganciclovir over a period of several months.
Today's findings, published in the Archives of Ophthalmology, show that AIDS patients had no progression of newly diagnosed CMV retinitis for about eight months using the ganciclovir implant. Among those who received no immediate treatment, the eye infection worsened in about 15 days.
"These findings provide strong scientific evidence that this experimental device can help to improve the treatment and potentially the quality of life for thousands of AIDS patients worldwide with CMV retinitis," said Carl Kupfer, M.D., director of the NEI, part of the National Institutes of Health.
CMV retinitis is a chronic, sight-threatening infection of the retina, the light-sensing tissue that lines the back of the eye. It is caused by cytomegalovirus, an usually benign virus that may infect the eye, colon, lung, and other organs of those with weakened immune systems, such as people with AIDS.
Currently, CMV retinitis is controlled through intravenous treatment with the drugs ganciclovir or foscarnet. Because people with AIDS are never cured of CMV retinitis, they must undergo daily intravenous treatment for the rest of their lives. To improve the treatment and quality of life for these people, researchers have sought alternative therapies for CMV retinitis, such as the ganciclovir implant, that would prove safe and effective and spare them the daily inconvenience of intravenous treatment.
Although patients must have surgery to use the implant, the procedure is performed under local anesthesia, takes less than one hour, and can be done on an outpatient basis.
The Food and Drug Administration (FDA) has not yet approved the ganciclovir implant. To receive FDA approval, clinical trials, such as this NEI study, are essential to determine the device's safety and effectiveness.
The Ganciclovir Implant Study for Cytomegalovirus Retinitis evaluated the safety and efficacy of the sustained-release ganciclovir implant as the primary treatment for newly diagnosed, peripheral CMV retinitis. It evaluated 26 patients, of which 30 eyes were randomly assigned to either immediate treatment (patients received an implant within 48 hours of study enrollment) or deferred treatment (patients were evaluated until progression of CMV retinitis was noted).
The study found that in people who received immediate treatment (within 48 hours of enrollment), the ganciclovir implant eliminated all signs of active infection for a median of 226 days, or about eight months. Among study participants in the deferred treatment group, the median time to CMV retinitis progression was 15 days.
The optimal time for replacement of the implant is unknown. "We calculated that the implant should be exchanged at 32 weeks to minimize the patient's chance of having a relapse," said Daniel F. Martin, M.D., the study's co-principal investigator and an assistant professor of ophthalmology at the Emory University School of Medicine. "But we found that the implants released the drug into the eye at variable rates, making it hard to know when the device actually needed to be replaced."
Dr. Martin and his colleagues reported that most participants enjoyed good vision with the implant. By the final followup eye examination, 34 of the 39 eyes treated with the implant had nearly perfect vision (20/25).
But the scientists also noted that nearly all affected eyes had blurred vision immediately after receiving the ganciclovir implant. Normal vision returned on average within 4 weeks.
Retinal detachment, a common problem for AIDS patients with CMV retinitis, occurred in 18 percent of the eyes. The researchers said that it was unclear whether the detachments were caused by the implant or CMV retinitis.
Because the implant releases ganciclovir into the eye only, there is concern that those who receive the treatment may develop CMV infections in their unaffected eye and elsewhere in the body. In this study, the researchers reported a high rate of infection in the second eye. Of the 21 patients who entered the study with only one eye affected, 14 developed CMV retinitis in the other eye. Doctors treated 11 of these patients with ganciclovir implants in their second eye with similar results.
In addition, eight of the 26 study participants developed CMV infections in other organs. These patients were treated with either intravenous ganciclovir or foscarnet.
Robert Nussenblatt, M.D., co-principal investigator and NEI scientific director, said that because the Ganciclovir Implant Study did not evaluate intravenous therapy for CMV retinitis, it is difficult to compare the effectiveness of the two treatments. But Dr. Nussenblatt added, "Based on our study and previous clinical trial results, the ganciclovir implant may be more effective at controlling CMV retinitis than intravenous therapy." A previous NEI study reported that intravenous ganciclovir and foscarnet on average stopped CMV retinitis from progressing for about two months, some six months less than today's finding.
Currently, two industry-sponsored clinical trials are underway to evaluate the ganciclovir implant for CMV retinitis. Enrollment in these studies is limited to patients who meet certain eligibility criteria. For more information on these studies, contact the Professional Services Group at Chiron Corporation, the implant's manufacturer. The number is 1-800-C-H-I-R-O-N-8 (1-800-244-7668), select "2."
The National Eye Institute is the Federal government's lead agency for vision research.
The Ganciclovir Implant Study for Cytomegalovirus Retinitis sought to assess the safety and effectiveness of the sustained-release ganciclovir implant as the primary treatment for CMV retinitis.
Between October 1992 and December 1993, study sites in Bethesda, Maryland and Atlanta, Georgia enrolled 26 patients, from which 30 eyes with newly diagnosed CMV retinitis were evaluated. Each eye was randomly assigned to one of two groups:
Immediate treatment: Patients underwent surgery to implant the ganciclovir device within 48 hours of enrollment. Patients were evaluated the day after surgery, weekly for two weeks, and then every two weeks until the CMV retinitis had progressed. Fourteen eyes were randomly assigned to this group.
Deferred treatment: Patients were followed every two weeks until progression of CMV retinitis was noted. At this point, patients were offered a ganciclovir implant. Sixteen eyes were assigned to this group, of which 14 later received a ganciclovir implant.
Because many patients developed CMV retinitis in their unaffected eye during the study, 11 additional ganciclovir implants were evaluated as the primary treatment for this disease. Twelve implants were replaced during the course of the study.
Surgery consisted of a 5-6 mm incision into the pars plana, near the cornea, and removal of a small portion of the eye's vitreous gel. The implant was placed through the wound and sutured into place. The wound was then closed and a saline solution injected into the eye to return it to normal pressure. The surgery, which is performed under local anesthesia, lasted less than one hour. At the start of the study, researchers planned to replace the implant at 32 weeks or earlier if CMV progression occurred.
All patients had AIDS, as defined by the Centers for Disease Control and Prevention, and peripheral CMV retinitis. Patients had not been previously treated with intravenous ganciclovir or foscarnet. They did not have any evidence of CMV infection in other organs.
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