Gay Men's Health Crisis "Treatment Issues" Vol. 8, No. 11 - December 1994
Kevin Robert Frost

CMV retinitis is a sight-threatening condition that occurs in approximately twenty percent of people with AIDS. The standard regimen, involving daily infusions of either ganciclovir or foscarnet, is difficult for patients and has limited benefit in treating CMV retinitis. The data from the NEI study offer the hope that the Chiron implant will significantly improve the ability to treat CMV retinitis.

What are Intraocular Implants?

The implant consists of a tiny device (about half the size of a peppercorn) surgically placed directly into the eye and designed to deliver a steady dose of ganciclovir over an extended period of time. The implants, which are manufactured by Chiron Vision of Irvine, California, provide a higher concentration of drug to the area of the eye that is affected by CMV.

The Study

The small phase II study randomized 26 patients to receive either the implant or deferred therapy. Patients with newly diagnosed untreated CMV retinitis were entered into the study, provided that the retinitis was considered peripheral and non-sight-threatening. Studies in which patients are randomized to an "observational" arm have long been controversial in CMV retinitis trials since those patients not receiving treatment will suffer some tissue damage, though usually not an actual loss of vision. Most ophthalmologists believe that deferred therapy trials are ethical since they place the least number of patients at risk.

Trial participants assigned to the immediate treatment arm were given the implant. If a patient entered the study with disease in both eyes, then one eye served as the control (and received no treatment) while the other eye was immediately treated with the implant. All patients were examined on a biweekly schedule, and fundus photographs (the "gold standard" for CMV retinitis) were taken at each visit. Patients with clinical signs of CMV disease outside the eyes (extraocular CMV) were excluded. However, if a patient on the study developed extraocular CMV, systemic IV therapy with either ganciclovir or foscarnet was given.

Results

The median time to progression of retinitis was fifteen days in the delayed treatment arm compared to 226 days in the implant group (statistically a highly significant difference). While it is difficult to compare results from different studies, the Studies of Ocular Complications of AIDS (SOCA) study, which compared the standard CMV drugs intravenous ganciclovir and foscarnet, showed that the median time to progression on these drugs was 47 and 53 days, respectively.[1]

Possible Toxicities

Seven of the eyes in the trial developed a complication known as retinal detachment, a condition in which the retinal tissue becomes separated from the inner wall of the eye. Retinal detachment can rapidly lead to vision loss, but is treatable with silicone oil injections. It is unclear whether the detachments seen in the trial were attributable to the implant since the overall rate of detachments was only eighteen percent, when all 39 eyes that received an implant at some point in the study (including those originally randomized to deferred therapy) are included. This overall rate appears similar to the incidence of retinal detachments typically found in patients with CMV retinitis who have not been given implants. One study, by Jabs, et al, found that approximately twenty percent of individuals with CMV retinitis developed retinal detachments.[2]

Spread of CMV

The rate of CMV disease outside the eyes was 31 percent (eight of 26 patients) and the median time to this extraocular disease was 248 days. The estimated risk of developing disease in the unaffected eye was 50 percent at six months. Taken together, these findings suggest that physicians may consider using some systemic therapy with the implants. Reduced dosing and frequency of standard intravenous therapy is one possibility.

Looking Beyond The Study

Some researchers believe that achieving control of CMV retinitis would make the need for daily infusions obsolete. Currently, Syntex, of Palo Alto, California, is conducting a study comparing oral ganciclovir combined with the Chiron implant to both intravenous ganciclovir alone and the implant alone.

As of August 1994, fifteen of the 26 patients in the NEI study had died (median survival time of 295 days). The need is paramount to understand how this survival time differs from that obtained with the current standard of care. The Syntex study, as well as the still unreleased results from a phase III study of the implants by Chiron, may provide that information.

Access to the Implants

Currently, the Chiron implant is an experimental therapy, although the company plans to seek FDA approval in 1995. The Syntex study of the implant plus oral ganciclovir is now enrolling patients with CMV retinitis. For more information, call Lynda Thomas of Syntex at 415/855-6021. In addition, Chiron is making the implant available to patients that have failed or are intolerant to both ganciclovir and foscarnet. For more information on centers able to provide the implants, call 800/CHIRON-8.

References

1. SOCA-ACTG Study. Ophthalmology. Jul 1994; 101(7):1250-61.

2. Jabs DA et al. Archives of Ophthalmology. Jun 1991; 109(6): 794-9.

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