Effect of anti-cytomegalovirus therapy on the incidence of immune recovery uveitis in AIDS patients with healed cytomegalovirus retinitis.

PURPOSE: To determine the association between anticytomegalovirus (CMV) maintenance therapy after immune recovery and immune recovery uveitis in acquired immunodeficiency syndrome (AIDS) patients on highly active antiretroviral therapy (HAART). DESIGN: Observational cohort study. METHODS: Data were obtained on AIDS patients with CMV retinitis followed up at the AIDS Ocular Research Unit of University of California San Diego from November 1995 to October 1999. Immune recovery was defined as CD4 count greater than 50 cells/microl for more than 3 months. Patients with immune recovery uveitis presented with vitritis, cystoid macular edema, or epiretinal membrane. Statistical analyses were conducted to determine the risk of continued use of anti-CMV therapy after immune recovery and the relationship of developing immune recovery uveitis with the type of anti-CMV therapy. RESULTS: Forty-three patients (64 eyes) had healed CMV retinitis and had achieved immune recovery. Thirty-one patients (48 eyes) received anti-CMV therapy after immune recovery, and 20 patients (29 eyes) developed immune recovery uveitis. Per-eye analyses revealed a 3.8-fold increase in the odds of developing immune recovery uveitis with anti-CMV therapy compared with no treatment (P =.02). If treated with cidofovir the odds were 3.3 greater than if treated with an alternative regimen (P =.04), 4.1 greater if treated intravenously (P =.01), and 5.2 greater than if not treated (P =.004). If not treated with cidofovir, a nonsignificant increase in the risk (2.4) of immune recovery uveitis was found (P =.15). Neither the potency nor the use of implants for noncidofovir treatment was related to the risk of recovery uveitis (P >.62). CONCLUSIONS: The use of cidofovir is a primary risk factor in the subsequent development of immune recovery uveitis. Ongoing treatment of healed CMV retinitis after immune recovery does not appear to protect against the development of immune recovery uveitis.

Human immunodeficiency virus type 2 (HIV-2) vector-mediated in vivo gene transfer into adult rabbit retina.

PURPOSE: To evaluate the potential usefulness of HIV-2 viral vector in in vivo retinal gene therapy. METHODS: An HIV-2 virus based viral vector was constructed and administered subretinally and intravitreally into rabbit eyes. After viral vector administration, the eyes were closely monitored for any adverse effects by slit lamp, indirect ophthalmoscopy, and fundus photography. Eyes were enucleated at specified times after injection, and reporter gene expression was identified within cell types and graded by the pattern and distribution of staining cells using fluorescent microscopy. RESULTS: The HIV-2 viral vector demonstrated efficient gene transfer into many types of retinal cells without apparent cytotoxicity. Notably with subretinal injection, the HIV-2 vector resulted in higher efficiency of transduction of photoreceptor cells than of the other cell types (p < 0.05). With the intravitreal administration of HIV-2 viral vectors, cellular transduction and transgene expression in the ganglion cell layer was the dominant finding. CONCLUSIONS: HIV-2 viral vector may be a useful gene delivery vehicle for retinal photoreceptor cells and ganglion cells. It deserves further exploration to investigate its potential merit in long term gene therapy protocols and in other animal species.

Effects of preoperative and postoperative epiretinal membranes on macular hole closure and visual restoration.

OBJECTIVE: To investigate the effects of epiretinal membranes (ERMs) on macular hole surgical results and postoperative visual restoration. DESIGN: A subgroup analysis arising from a multicenter, controlled, randomized clinical trial. PARTICIPANTS: Ninety-one phakic eyes with an idiopathic macular hole that underwent standard vitrectomy for macular hole repair with or without ERM peeling. METHODS: Preoperative, intraoperative, and postoperative data of macular status, ERM status, and visual function status were recorded, and their relationships were analyzed. MAIN OUTCOME MEASURES: Visual acuity and clinical features of macular hole and ERM on baseline examination and scheduled follow-ups. RESULTS: ERM peeling was associated with greater anatomic hole closure success rates (67% of the ERM peeled vs. 35% of nonpeeled, P = 0.03) but not associated with visual improvement in eyes with anatomic hole closure (2.9 lines improvement vs. 3.6 lines improvement, P > 0.5). Macular hole reopening was associated with excessive ERM growth (P = 0.005). Postoperative ERMs were more common in the eyes that underwent cataract surgery after vitrectomy (77% in aphakic and 36% in phakic eyes, P = 0.02). Macular hole edge approximation or hole appearance after initial vitrectomy for hole repair was stable over the average 18-month period in 89% of the eyes; only approximately 10% of the eyes underwent changes in their hole appearance. The hole edge approximation or hole appearance was associated with preoperative hole size and postoperative visual acuity. Preoperative hole size was found to be the major predictor of postoperative visual acuity (P < 0.005). CONCLUSIONS: Surgical ERM peeling increases the anatomic hole closure rate. The presence of postoperative ERMs was not associated with postoperative visual acuity; however, excessive ERM growth contributed to hole reopening. Preoperative hole size was the most sensitive predictor for postoperative visual acuity. Surgical intervention during the early stages of macular hole before ERM formation is strongly recommended.

Treatment or prevention of herpes simplex virus retinitis with intravitreally injectable crystalline 1-O-hexadecylpropanediol-3-phospho-ganciclovir.

PURPOSE: To evaluate an intraocular drug delivery system consisting of the crystalline ammonium salt of 1-O-hexadecylpropanediol-3-phospho-ganciclovir (HDP-P-GCV) as a slow-release form of the drug. METHODS: A dosage of 0.885, 1.57, 2.8, 4.486, or 8.85 micromol of ammonium salt HDP-P-GCV in 0.1 mL was intravitreally injected into rabbit vitreous. The toxicity and safety were evaluated with ophthalmoscopy, electroretinography, and pathology. Drug vitreous levels were determined at various time intervals by means of HPLC. The treatment efficacy and duration of efficacy were tested in a herpes simplex virus (HSV)-1 retinitis rabbit model. RESULTS: Intravitreal injections of the compound revealed clear vitreous of optic axis, a desirable drug depot in the inferior vitreous cavity, and no clinical toxicity, except for variable mild local posterior subcapsular cataract and local retinal toxicity with high doses. HPLC analysis showed free ammonium salt of HDP-P-GCV in the upper vitreous at a level of 0.2 microM 12 weeks after the 2.8-micromol initial intravitreal dose. Drug concentration was still 1.95 microM 20 weeks after the 8.85-micromol initial intravitreal dose. These concentrations (0.2 and 1.95 microM) were 10 and 100 times higher, respectively, than the median inhibitory concentration (IC(50)) of HSV-1 (0.023 microM). Treatment with the highest nontoxic dose (2.8 micromol) and the highest dose (8.85 micromol) showed significant protection from HSV-1 infection (P < 0.05) and provided sustained antiviral effect after a single intravitreal drug injection. CONCLUSIONS: The crystalline ammonium salt of HDP-P-GCV may be a very useful local therapy for herpes family viral retinitis.