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A National Eye Institute (NEI) clinical trial reported today that anew, drug-releasing device was effective in treating cytomegalovirus(CMV) retinitis, a sight-threatening disease that affects one out offour people with AIDS. The 4 millimeter-diameter device, called aganciclovir implant, is surgically placed into the eye, where itreleases the anti-viral drug ganciclovir over a period of severalmonths.
Today’s findings, published in the Archives of Ophthalmology,show that AIDS patients had no progression of newly diagnosed CMVretinitis for about eight months using the ganciclovir implant. Amongthose who received no immediate treatment, the eye infection worsenedin about 15 days.
“These findings provide strong scientific evidence that thisexperimental device can help to improve the treatment and potentiallythe quality of life for thousands of AIDS patients worldwide with CMVretinitis,” said Carl Kupfer, M.D., director of the NEI, part ofthe National Institutes of Health.
CMV retinitis is a chronic, sight-threatening infection of theretina, the light-sensing tissue that lines the back of the eye. It iscaused by cytomegalovirus, an usually benign virus that may infect theeye, colon, lung, and other organs of those with weakened immunesystems, such as people with AIDS.
Currently, CMV retinitis is controlled through intravenous treatmentwith the drugs ganciclovir or foscarnet. Because people with AIDS arenever cured of CMV retinitis, they must undergo daily intravenoustreatment for the rest of their lives. To improve the treatment andquality of life for these people, researchers have sought alternativetherapies for CMV retinitis, such as the ganciclovir implant, thatwould prove safe and effective and spare them the daily inconvenienceof intravenous treatment.
Although patients must have surgery to use the implant, theprocedure is performed under local anesthesia, takes less than onehour, and can be done on an outpatient basis.
The Food and Drug Administration (FDA) has not yet approved theganciclovir implant. To receive FDA approval, clinical trials, such asthis NEI study, are essential to determine the device’s safety andeffectiveness.
The Ganciclovir Implant Study for Cytomegalovirus Retinitisevaluated the safety and efficacy of the sustained-release ganciclovirimplant as the primary treatment for newly diagnosed, peripheral CMVretinitis. It evaluated 26 patients, of which 30 eyes were randomlyassigned to either immediate treatment (patients received an implantwithin 48 hours of study enrollment) or deferred treatment (patientswere 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 eliminatedall signs of active infection for a median of 226 days, or about eightmonths. Among study participants in the deferred treatment group, themedian time to CMV retinitis progression was 15 days.
The optimal time for replacement of the implant is unknown. “Wecalculated that the implant should be exchanged at 32 weeks tominimize the patient’s chance of having a relapse,” said DanielF. Martin, M.D., the study’s co-principal investigator and anassistant professor of ophthalmology at the Emory University School ofMedicine. “But we found that the implants released the drug intothe eye at variable rates, making it hard to know when the deviceactually needed to be replaced.”
Dr. Martin and his colleagues reported that most participantsenjoyed good vision with the implant. By the final followup eyeexamination, 34 of the 39 eyes treated with the implant had nearlyperfect vision (20/25).
But the scientists also noted that nearly all affected eyes hadblurred vision immediately after receiving the ganciclovir implant.Normal vision returned on average within 4 weeks.
Retinal detachment, a common problem for AIDS patients with CMVretinitis, occurred in 18 percent of the eyes. The researchers saidthat it was unclear whether the detachments were caused by the implantor CMV retinitis.
Because the implant releases ganciclovir into the eye only, there isconcern that those who receive the treatment may develop CMVinfections in their unaffected eye and elsewhere in the body. In thisstudy, the researchers reported a high rate of infection in the secondeye. Of the 21 patients who entered the study with only one eyeaffected, 14 developed CMV retinitis in the other eye. Doctors treated11 of these patients with ganciclovir implants in their second eyewith similar results.
In addition, eight of the 26 study participants developed CMVinfections in other organs. These patients were treated with eitherintravenous ganciclovir or foscarnet.
Robert Nussenblatt, M.D., co-principal investigator and NEIscientific director, said that because the Ganciclovir Implant Studydid not evaluate intravenous therapy for CMV retinitis, it isdifficult to compare the effectiveness of the two treatments. But Dr.Nussenblatt added, “Based on our study and previous clinicaltrial results, the ganciclovir implant may be more effective atcontrolling CMV retinitis than intravenous therapy.” A previousNEI study reported that intravenous ganciclovir and foscarnet onaverage 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 toevaluate the ganciclovir implant for CMV retinitis. Enrollment inthese studies is limited to patients who meet certain eligibilitycriteria. For more information on these studies, Contact theProfessional Services Group at Chiron Corporation, the implant’smanufacturer. 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 agencyfor vision research.
The Ganciclovir Implant Study for Cytomegalovirus Retinitis soughtto assess the safety and effectiveness of the sustained-releaseganciclovir 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 eyeswith newly diagnosed CMV retinitis were evaluated. Each eye wasrandomly assigned to one of two groups:
Immediate treatment: Patients underwent surgery to implant theganciclovir device within 48 hours of enrollment. Patients wereevaluated the day after surgery, weekly for two weeks, and then everytwo weeks until the CMV retinitis had progressed. Fourteen eyes wererandomly assigned to this group.
Deferred treatment: Patients were followed every two weeks untilprogression of CMV retinitis was noted. At this point, patients wereoffered a ganciclovir implant. Sixteen eyes were assigned to thisgroup, of which 14 later received a ganciclovir implant.
Because many patients developed CMV retinitis in their unaffectedeye during the study, 11 additional ganciclovir implants wereevaluated as the primary treatment for this disease. Twelve implantswere replaced during the course of the study.
Surgery consisted of a 5-6 mm incision into the pars plana, near thecornea, and removal of a small portion of the eye’s vitreous gel. Theimplant was placed through the wound and sutured into place. The woundwas then closed and a saline solution injected into the eye to returnit to normal pressure. The surgery, which is performed under localanesthesia, lasted less than one hour. At the start of the study,researchers planned to replace the implant at 32 weeks or earlier ifCMV progression occurred.
All patients had AIDS, as defined by the Centers for Disease Controland Prevention, and peripheral CMV retinitis. Patients had not beenpreviously treated with intravenous ganciclovir or foscarnet. They didnot have any evidence of CMV infection in other organs.
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- Martin DF, Parks DJ, Mellow SD, Ferris FL, Walton RC, Remaley NA, Chew EY, Ashton P, Davis MD, Nussenblatt RB. Treatment of Cytomegalovirus Retinitis With An Intraocular Sustained-Release Ganciclovir Implant. A Randomized Controlled Trial. Arch Ophthalmol. 1994 Dec. PubMed