AIDS TREATMENT UPDATE, Issue 27 - March 1995
Keith Alcorn

CMV can cause retinitis _ damage to the retina that leads to blindness if it is not treated. It tends to emerge only in severely immunosuppressed people with CD4 counts below 50. Currently CMV retinitis can only be prevented or treated by the use of intravenous (IV) ganciclovir or foscarnet, which have to be administered through a catheter. There is a significant chance that the catheter will be a route of bacterial infection, and catheters are uncomfortable and restrictive for those who need to use them. Last December an oral (capsule-form) of ganciclovir was approved for use in the UK in people who cannot safely tolerate a catheter yet risk worsening retinitis if they do not have ganciclovir treatment.

Implant trials

The Chiron Corporation, manufacturers of the implant, presented evidence on the safety and effectiveness of the implants at slowing the progression of CMV retinitis. The implants are tiny pellets which release ganciclovir into the eye for approximately eight months. They are implanted under the surface of the eye beneath the lower eyelid.

This trial recruited people who had very slight retinitis that could be detected by eye examinations but was not noticeable to the individual. They were randomised to receive immediate treatment or to defer treatment until evidence of slight progression had emerged from photographs of the retina. All progression in this study was evaluated by photographic readers, not by the treating physicians. The study showed that people who received the implants experienced no worsening of their CMV retinitis for an average of 226 days, compared with only 15 days in those not given implants.

The drawback of the method, as compared with IV or oral ganciclovir, is that it only delivers ganciclovir to the eye in which the implant has been made, when CMV is a systemic disease that can affect both eyes as well as causing disease in other parts of the body. A study comparing the implants with IV ganciclovir found that the IV drug is more effective. On average, people who already had mild retinitis in one eye took 50 days longer to develop retinitis in the other eye if they were treated with intravenous ganciclovir compared with those who received implants (254 vs 204 days). People who were receiving IV ganciclovir were also slightly less likely to develop CMV-related disease in other parts of the body, although this wasn't statistically significant (i.e. it could simply have been chance).

However, this study also raised the possibility that an implant in one eye also provides some protection for the other eye. When the chance of developing retinitis in one eye, irrespective of whether it contained an implant, was calculated, the IV group developed retinitis twice as fast (60 vs 120 days). This suggests either that an implant in one eye exerts some protective effect on the other eye as well, or that the risk of progression in the eye first diagnosed with retinitis is much greater than the risk of CMV developing in the other eye, and that in these circumstances an implant is a much more effective way of preventing progression.

Side-effects

Ganciclovir implants may reduce the need to use high doses of the drug, possibly reducing the side-effects and the cost of treating CMV retinitis. Unfortunately, the implants carry the risk of several side-effects which are not otherwise seen with ganciclovir treatment. The most common is the danger of detachment of the retina, in effect producing the very problems the implants are meant to prevent _ blurred vision, spots in the eye and eventual blindness. Retinal detachments occur when the retina is damaged or torn, but in some cases can be repaired. However, the eyesight in that eye may not be as good as before, and if the damage is severe, sight may be lost or seriously impaired.

In the study comparing the implant with IV ganciclovir, nearly 10% of implant recipients suffered retinal detachments, and in the safety study the 26 participants suffered retinal detachments in 7 out of 30 eyes treated with implants. Detachments were most likely to occur between 30 and 64 days after the implant was done.

Another significant side-effect was vitreous haemorrhage _ bleeding in the jelly of the eye. Some patients also reported a slight blurring of sight, especially in the weeks following the implant. It is aso unclear how easily the implant can be renewed without causing damage to the eye.

The use of implants opens up new possibilities in the treatment of CMV retinitis. In particular they may offer another way of reducing the use of devices such as Portacaths, with all their risks of infection, as a means of delivering anti-CMV drugs. Researchers in Washington suggested that a possible future treatment protocol for the prevention of CMV disease might go as follows:

- Intravenous induction therapy for 2 to 4 weeks in order to reduce CMV levels quickly

- Implants, first in one eye then in the second eye 2-4 weeks later

- Alongside this, oral ganciclovir to prevent CMV disease in other organs

Currently, the implants are in use on an experimental basis only, and their uptake is likely to depend on their acceptability to people at risk of developing retinitis. Many people are likely to prefer to continue with IV ganciclovir treatment rather than undergo an eye operation.

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