Pars plana modified Baerveldt implant versus neodymium:YAG cyclophotocoagulation in the management of neovascular glaucoma

OBJECTIVE: To determine the relative effectiveness of neodymium:YAG cyclophotocoagulation (NCYC) and pars plana modified Baerveldt implant (PPBI) surgery on intraocular pressure (IOP) control in eyes with neovascular glaucoma (NVG). PARTICIPANTS: In this retrospective comparative group study, 30 patients with NVG treated with contact NCYC were compared with 18 patients who underwent PPBI. Patients groups were not statistically dissimilar with respect to the underlying disorder-causing angle and iris neovascularization, intraocular pressure, and patient's age. RESULTS: During a follow up of 6 months, an IOP control of > or = 6 and < or = 21 mm Hg was achieved in 23 eyes (76.6%) treated with NCYC compared with 17 eyes (94.4%) receiving PPBI (P = 0.13). Among eyes that had unsuccessful outcome in both groups, the proportions with persistently high IOP or hypotony were greater in the NCYC group than in the PPBI group. Based on our criteria, the cumulative proportion of failure in the NCYC group was 23.3% at 6 months as compared to 5.6% in the PPBI group. Seven eyes (23.3%) in the NCYC group lost light perception versus 1 eye (5.6%) in the PPBI group. The incidence of postoperative choroidal effusion (36%) was higher in the PPBI group. CONCLUSIONS: This study suggests that in the management of NVG, PPBI surgery more frequently controls IOP in a medically acceptable range with less hypotony and greater preservation of visual acuity than NCYC.     

Chronic acetaminophen attenuates age-associated increases in cardiac ROS and apoptosis in the Fischer Brown Norway rat

There is a growing need for pharmacological agents to manage cardiovascular disease in the rapidly growing elderly population. Here, we determine if acetaminophen is efficacious in decreasing age-related increases in cardiac reactive oxygen species (ROS) and apoptosis in aging Fischer 344 X Brown Norway rats. Compared to 6-month control animals, indices of oxidative (superoxide anion [O2 ^?–] and 4-hydroxy-2-nonenal [4-HNE]) and nitrosative (protein nitrotyrosylation) stress were markedly increased in 33-month-old rat hearts. 33-month animals that had been treated with acetaminophen (30 mg/kg/day p.o. for 6 months) exhibited diminished age-related increases in cardiac ROS levels and TUNEL positive nuclei and these changes were accompanied by improvements in the Bax/Bcl2 ratio, diminished evidence of caspase-3 activation and increased phosphorylation of protein kinase B, ERK1/2, p70S6K and GSK-3β. Taken together these results suggests that acetaminophen may attenuate the age-associated increases in the cardiomyocyte apoptosis, possibly via diminishing age associated elevation in ROS production.     

Prophylactic circumferential intraoperative laser retinopexy decreases the risk of retinal detachment after macular hole surgery

Purpose. Pars plana vitrectomy with peeling of the internal limiting membrane is a well-established technique for the treatment of idiopathic macular holes with high success rates. Complications such as retinal tears may result from vitreous incarceration at the sclerotomy sites. Prophylactic laser retinopexy (LR) has recently been shown to decrease incidence of postvitrectomy rhegmatogenous retinal detachment but its efficacy in macular hole repair has not been established. In this study we evaluated the safety and efficacy of prophylactic LR and compared the patients to a control group that did not receive prophylactic treatment. Methods. A retrospective, consecutive chart review was conducted comparing patients who underwent macular hole repair with LR to without LR. Patient demographics were collected and the number and time interval of retinal detachment in the 2 groups were compared. Statistical analysis was conducted between the 2 groups. Results. A total of 144 eyes underwent macular hole repair during the study period. A total of 76 eyes underwent LR and 68 eyes did not undergo LR. There were no significant differences in baseline characteristics between the 2 groups. At 1 year, RD occurred in 1 eye (1.31%) in the LR group and in 8 eyes (8.82%) without LR group (p<0.01). Conclusions. Prophylactic LR decreases the incidence of postoperative retinal detachment a potentially disabling complication of macular hole repair surgery.     

T Cells Redirected to EphA2 for the Immunotherapy of Glioblastoma

Outcomes for patients with glioblastoma (GBM) remain poor despite aggressive multimodal therapy. Immunotherapy with genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL)-13Rα2, epidermal growth factor receptor variant III (EGFRvIII), or human epidermal growth factor receptor 2 (HER2) has shown promise for the treatment of gliomas in preclinical models and in a clinical study (IL-13Rα2). However, targeting IL-13Rα2 and EGFRvIII is associated with the development of antigen loss variants, and there are safety concerns with targeting HER2. Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) has emerged as an attractive target for the immunotherapy of GBM as it is overexpressed in glioma and promotes its malignant phenotype. To generate EphA2-specific T cells, we constructed an EphA2-specific CAR with a CD28-ζ endodomain. EphA2-specific T cells recognized EphA2-positive glioma cells as judged by interferon-γ (IFN-γ) and IL-2 production and tumor cell killing. In addition, EphA2-specific T cells had potent activity against human glioma-initiating cells preventing neurosphere formation and destroying intact neurospheres in coculture assays. Adoptive transfer of EphA2-specific T cells resulted in the regression of glioma xenografts in severe combined immunodeficiency (SCID) mice and a significant survival advantage in comparison to untreated mice and mice treated with nontransduced T cells. Thus, EphA2-specific T-cell immunotherapy may be a promising approach for the treatment of EphA2-positive GBM.     

Chronic paracetamol treatment influences indices of reactive oxygen species accumulation in the aging Fischer 344 X Brown Norway rat aorta

Previous reports have demonstrated that increased levels of reactive oxygen species (ROS) and alterations in cell signaling characterize aging in the Fischer 344 X Brown Norway (FBN) rat aorta. Other work has suggested that increases in ROS may be related to vascular wall thickening and the development of hypertension. Paracetamol (acetaminophen) is a potent antioxidant that has been found to diminish free radicals in ischemia-reperfusion studies. However, it remains unclear whether chronic paracetamol administration influences signaling or ROS accumulation in the aging aorta. FBN rats (27 months old; n=8) were subjected to 6 months of treatment with a therapeutic dose of paracetamol (30 mg/kg/day) and compared to age-matched untreated FBN rat controls (n=8). Compared to measurements in the aortae of 6-month old animals, tunica media thickness, tissue superoxide levels, and protein oxidation levels were 38 ± 7%, 92 ± 31%, and 7 ± 2% higher in the aortae of 33-month control animals (p ≤0.05). Chronic paracetamol treatment decreased tunica media thickness and the amount of oxidized protein by 13 ± 4% and 30 ± 1%, respectively (p ≤0.05). This finding of diminished aortic thickening was associated with increased phosphorylation (activation) of the mitogen activated protein kinases and diminished levels of the anti-apoptotic protein Bcl-2. Taken together, these data suggest that chronic paracetamol treatment may decrease the deleterious effects of aging in the FBN rat aorta.