28-day intraocular pressure reduction with a single dose of brimonidine tartrate-loaded microspheres.

Treatment of glaucoma by intraocular pressure (IOP) reduction is typically accomplished through the administration of eye drops, the difficult and frequent nature of which contributes to extremely low adherence rates. Poor adherence to topical treatment regimens in glaucoma patients can lead to irreversible vision loss and increased treatment costs. Currently there are no approved treatments for glaucoma that address the inherent inefficiencies in drug delivery and patient adherence. Brimonidine tartrate (BT), a common glaucoma medication, requires dosing every 8-12 h, with up to 97% of patients not taking it as prescribed. This study provides proof-of-principle testing of a controlled release BT formulation. BT was encapsulated in poly(lactic-co-glycolic) acid microspheres and drug release was quantified using UV-Vis spectroscopy. For in vivo studies, rabbits were randomized to receive a single subconjunctival injection of blank (no drug) or BT-loaded microspheres or twice daily topical 0.2% BT drops. The microspheres released an average of 2.1 ± 0.37 µg BT/mg microspheres/day in vitro. In vivo, the percent decrease in IOP from baseline was significantly greater in the treated eye for both topical drug and drug-loaded microspheres versus blank microspheres throughout the 4-week study, with no evidence of migration or foreign body response. IOP measurements in the contralateral, untreated eyes also suggested a highly localized effect from the experimental treatment. A treatment designed using the release systems described in this study would represent a vast improvement over the current clinical standard of 56-84 topical doses over 28 days.

Incidence of Glaucoma or Ocular Hypertension After Repeated Anti-Vascular Endothelial Growth Factor Injections for Macular Degeneration.

PURPOSE: To estimate the risk of glaucoma or sustained ocular hypertension (OHT) related to anti-vascular endothelial growth factor (VEGF) injections for age-related macular degeneration (AMD). DESIGN: Retrospective chart review. SUBJECTS: Patients who received unilateral anti-VEGF injections for AMD at the Wheaton Eye Clinic (IL). METHODS: Chart analysis was performed on 1095 patients, without prior glaucoma or OHT, who received unilateral anti-VEGF injections for AMD from 2005 to 2012, with data collected through 2013. Data collection included demographics, lens status, date and medication type of each injection, and the date of diagnosis of glaucoma or OHT by a treating glaucoma specialist, which was the main outcome measure. Rare events logistic regression was performed to determine the risk of disease development based on sex, lens status, and injection frequency. RESULTS: Unilateral glaucoma or sustained OHT developed in 42 patients over the course of follow-up, with 40 events in the injected eye only, 2 in the contralateral eye only. Statistical modeling predicted elevated risk for onset of glaucomatous disease with a higher maximum frequency of injections (p < 0.0001, odds ratio [OR] 2.18 for each additional injection over the most injection-intense 6 months for a given subject) and with phakic lens status (p = 0.0009, OR 0.33 for pseudophakia). CONCLUSION: Our results show a significant risk for glaucoma or OHT development in patients undergoing repeated treatments with intravitreal anti-VEGF injections for AMD, establishing the first reliable connection between disease development and a period of high-frequency injections. In addition, we show a significantly increased risk of disease development in phakic patients, which we believe points to a mechanical explanation for this type of secondary glaucoma.

Critical appraisal of bepotastine in the treatment of ocular itching associated with allergic conjunctivitis.

Bepotastine besilate 1.5% solution is an H(1)-antihistamine recently approved by the Food and Drug Administration for the topical treatment of ocular itching associated with allergic conjunctivitis. Several clinical studies have demonstrated its safety as well as its efficacy versus placebo. This review finds that bepotastine besilate 1.5% solution is a suitable alternative to other agents within the class of H(1)-antihistamines, but there are no clinical trial data to suggest that it holds any specific advantages over other agents.

Induction of HIV-specific T and B cell responses with a replicating and conditionally infectious lentiviral vaccine.

The development of an HIV vaccine that induces broad and potent immunity is critically needed. Viruses, including lentiviruses, have been used as vectors for ex vivo transduction of antigens into dendritic cells (DC). We hypothesized that DC transduced with a vector that allows selective infection of DC could induce potent immunity by continually priming DC. A lentiviral vector encoding HIV gag-pol without env would form viral cores in transduced DC, but would release non-infectious particles by budding into endosomes and releasing apoptotic bodies or exosomes containing viral cores. DC function by endocytosing DC-derived apoptotic bodies, and they are specialized in their ability to move endocytic contents into the cytoplasm. We postulated that endocytosis of vector cores could lead to transduction of a second round of DC. In this report, we demonstrate accumulation of viral cores inside transduced DC and show second-round transduction of immature DC that endocytose transduced DC in vitro. The effectiveness of immunization of mice with transduced DC to induce specific lymphocyte activation was assessed. Mice developed antigen-specific T cell responses and specific antibodies after immunization. Transduction of DC with a replication-competent but conditionally infectious lentivirus could be a novel vaccine strategy for HIV.