B.D. Kuppermann

Vitreous VEGF clearance is increased after vitrectomy.

Purpose. Pars plana vitrectomy (PPV) has been reported to reduce macular thickness and improve visual acuity in patients with diabetic macular edema (ME). The hypothesis for the study was that after PPV, clearance is accelerated and VEGF concentrations are reduced. To test this hypothesis, hVEGF(165) injections were performed in rabbit eyes, with and without PPV, and vitreous VEGF levels were measured as a function of time. Methods. The PPV group rabbits had a bilateral 25-gauge PPV, and in the no-PPV group, rabbits had intact vitreous. Intravitreal injections of hVEGF(165) were performed, and the animals were euthanatized at time points up to 7 days. The vitreous was isolated and an enzyme-linked immunosorbent assay was used to measure the VEGF levels. Pharmacokinetic parameters were determined in a noncompartmental analysis approach. Results. Mean vitreous VEGF levels decreased more rapidly in eyes subjected to PPV than in no-PPV eyes. The vitreous VEGF half-life (t([)(1/2)(])) in PPV eyes was 10 times shorter than that in normal eyes. In addition, mean clearance and mean area under the curve (AUC) increased and decreased, respectively, in eyes that underwent PPV. Conclusions. VEGF clearance is increased after PPV. Reducing VEGF concentrations in the vitreous post-PPV may partially explain the improvement in macular thickness in some patients with ME. Unexpectedly, the half-life of VEGF in the vitreous, even in no-PPV eyes, was <3 hours, whereas compounds of similar molecular weight typically have longer vitreous half-lives. The back of the eye may be uniquely adapted with rapid-clearance mechanisms to regulate vitreous VEGF levels. Further study is suggested.

Emergence of Drug-Resistant Cytomegalovirus Retinitis in the Contralateral Eyes of Patients with AIDS Treated with Ganciclovir

The purpose of the present study was to examine the emergence of ganciclovir-resistant virus in the contralateral eyes of patients who received treatment for cytomegalovirus retinitis with either a ganciclovir implant plus oral placebo, a ganciclovir implant plus oral ganciclovir, or intravenous (iv) ganciclovir. Viral DNA was amplified from vitreous specimens and was assayed for UL97 and UL54 resistance mutations. Resistant viral genotypes were found in the contralateral eyes of 0 of 28 patients treated with a ganciclovir implant plus oral placebo, in 5 of 23 patients treated with a ganciclovir implant plus oral ganciclovir, and in 1 of 6 patients treated with iv ganciclovir. All resistance mutations were in codons 591, 592, or 594 of the UL97 gene. Treatment of unilateral cytomegalovirus retinitis with systemic ganciclovir decreases the risk of development of secondary sites of infection, but, in contralateral eyes that develop retinitis, this approach to treatment is associated with a higher prevalence of drug resistance, compared with treatment with the ganciclovir implant alone (P p ; Fisher’s exact test). .023