The Ganciclovir Intraocular Implant

There are multiple advantages offered by the implant including the longest length of effective control of CMV retinitis compared to the other therapies, lack 

Use of the ganciclovir implant and eventual discontinuation of systemic therapy may be possible in selected patients with improved immunity due to HAART and this approach may result in better long-term visual outcomes (100,106,107). In patients who have not yet received HAART when the CMV retinitis is treated with an implant, systemic therapy for CMV is indicated until the CD4+ count has stabilized appropriately at an elevated level. In patients who develop their initial episode of CMV retinitis while undergoing HAART therapy, this is a sign of progressive immune dysfunction and reassessment of the antiretroviral therapy is indicated. Use of the implant may be especially useful in these patients who are undergoing readjustment of HAART or who have failed HAART as longer term CMV control can be provided by the implant. 

Relapsed CMV retinitis while undergoing HAART may be a sign of progressive immune dysfunction and requires reassessment of HAART and other medications. Individuals treated with HAART may experience reactivation of CMV retinitis when their CD4 count decreases (108). The threshold CD4 count below which reactivation of CMV retinitis occurred in patients for whom HAART was not successful is approximately 50cells/mm3. Thus, despite an initial response to HAART, there is a risk for CMV retinitis reactivation when the CD4 count decreases below 50cells/mm3. The HIV viral load does not appear to predict CMV reactivation. 

Each eye should be considered independently in individuals with bilateral disease. Simultaneous implant surgery is not usually indicated although only a few days are required between operating on each eye. 

---

Ganciclovir may be administered intravenously, orally, or via intraocular implant. The bioavailability of oral ganciclovir is poor. Cerebrospinal fluid concentrations are approximately 50% of those in serum. The elimination half-life is 4 hours, and the intracellular half-life is prolonged at 16-24 hours. Clearance of the drug is linearly related to creatinine clearance. Ganciclovir is readily cleared by hemodialysis. 

In a rare cytomegalovirus comparison trial, a ganciclovir insert (an intraocular implant) plus oral ganciclovir was compared with intravenous cidofovir (18). Based on data from 61 patients (the trial was stopped early owing to low recruitment), cidofovir was associated with a raised serum creatinine concentration of 142 pmol/l (1.6 mg/dl) or greater (0.48 per person-year), 3+ or greater proteinuria (0.29 per person-year), uveitis (0.35 per person-year), and neutropenia (0.11 per person-year). 

In advanced HIV disease, oral ganciclovir (1000 mg three times daily) may reduce the risk of CMV disease, and possibly mortality, in those not receiving didanosine. The addition of oral high-dose ganciclovir (1500 mg three times daily) to the intraocular ganciclovir implant further delays the time to retinitis progression and reduces the risk of new CMV disease and, possibly, the risk of Kaposi s sarcoma. 

---