Intravitreal bevacizumab has initial clinical benefit lasting eight weeks in eyes with neovascular age-related macular degeneration

P William Conrad, David N Zacks, Mark W JohnsonDepartment of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USAPurpose: To determine whether the effect of a single initial intravitreal injection of bevacizumab for neovascular age-related macular degeneration (AMD) persists for 8 weeks.Methods: We reviewed the records of 25 consecutive patients with neovascular AMD treated with intravitreal bevacizumab. Patients were included (n = 15) if follow up data were available from 4 and 8 week visits after a single initial injection. Additionally, optical coherence tomography (OCT) images were graded qualitatively in a masked fashion by a single reader.Results: Baseline mean visual acuity was 20/200, improving to 20/125 at 4 weeks (p = 0.0153) and 20/100 at 8 weeks (p = 0.0027). Mean central retinal thickness was 316 ± 107 µm at baseline and decreased to 223 ± 70 µm and 206 ± 45 µm at 4 and 8 weeks post-injection, respectively (p = 0.0003 and 0.0005). By masked OCT grading, macular fluid was resolved in 10/15 (66.7%) and 11/15 (73.3%) eyes at 4 and 8 weeks, respectively, and 3/15 (20%) eyes had continued reduction in residual macular fluid between 4 and 8 weeks.Conclusions: A single initial bevacizumab injection has persistent clinical benefit lasting 8 weeks in most eyes with neovascular AMD. Results of prospective randomized studies are needed before changes in treatment regimens can be recommended.Keywords: age-related macular degeneration, bevacizumab, choroidal neovascular membrane, optical coherence tomograph

Adjunctive intravitreal dexamethasone in the treatment of acute endophthalmitis following cataract surgery

Edward F Hall1, Garrett R Scott1, David C Musch1,2, David N Zacks11Department of Ophthalmology and Visual Sciences, Medical School; 2Department of Epidemiology, School of Public Health; University of Michigan, Ann Arbor, MI, USAPurpose: Controversy exists regarding the use of intravitreal dexamethasone (IVD) as an anti-inflammatory adjunct to intravitreal antibiotics in patients with acute endophthalmitis following cataract surgery. The purpose of this project was to evaluate our experience regarding the effect of adjunctive IVD use on visual outcomes in such patients.Design: Retrospective, comparative case series.Methods: Study population: Patients treated for acute endophthalmitis following cataract surgery from 1995–2004. Intervention: In addition to standard intravitreal antibiotic treatment, some patients also received a single adjunctive injection of IVD. Primary outcome measures: Median visual acuity at last follow-up and percentage of patients achieving a ≥3-line improvement in visual acuity. Secondary outcome measures: Inflammatory index scoring, including amount of cell and flare, height of hypopyon, and presence of fibrin as a function of time after treatment.Results: Twenty-six eyes were treated with and 38 eyes without adjunctive IVD. Median presenting visual acuity was Hand Motion in both groups. Median visual acuity at last followup measured 20/40 in the IVD group and 20/50 in the No-IVD group (p = 0.75). Seventy-three percent of patients in the IVD group and 82% of patients in the No-IVD group achieved a ≥3-line improvement in visual acuity (p = 0.42). No significant difference was detected between the IVD and No-IVD groups for any of the three measures of inflammation.Conclusion: The use of IVD did not significantly improve the final median visual acuity, the chance of achieving a ≥3-line improvement in visual acuity, or the amount of intraocular inflammation. Based on these findings, and the possible detrimental effect of IVD on visual outcomes previously reported in the literature, the use of IVD does not appear to be warranted as a routine adjunctive treatment in postoperative endophthalmitis.Keywords: endophthalmitis, dexamethasone, intravitreal injectio

Understanding Everyday Events: Predictive Looking Errors Drive Memory Updating

peer reviewedMemory-guided predictions can improve event comprehension by guiding attention and the eyes to the location where an actor is about to perform an action. But when events change, viewers may experience predictive looking errors and need to update their memories. In two experiments (Ns = 38 and 111), we examined the consequences of mnemonic predictive looking errors for comprehending and remembering event changes. University students watched movies of everyday activities with actions that repeated exactly and actions that repeated with changed features—for example, an actor reached for a paper towel on one occasion and a dish towel on the next. Memory guidance led to predictive looking errors that were associated with better memory for subsequently changed event features. These results indicate that retrieving recent event features can guide predictions during unfolding events, and that error signals derived from mismatches between mnemonic predictions and actual events contribute to new learning.Mind-wandering in everyday event comprehension: Memory, attention, and the brai

Autophagy in the eye:from physiology to pathophysology

Autophagy is a catabolic self-degradative pathway that promotes the degradation and recycling of intracellular material through the lysosomal compartment. Although first believed to function in conditions of nutritional stress, autophagy is emerging as a critical cellular pathway, involved in a variety of physiological and pathophysiological processes. Autophagy dysregulation is associated with an increasing number of diseases, including ocular diseases. On one hand, mutations in autophagy-related genes have been linked to cataracts, glaucoma, and corneal dystrophy; on the other hand, alterations in autophagy and lysosomal pathways are a common finding in essentially all diseases of the eye. Moreover, LC3-associated phagocytosis, a form of non-canonical autophagy, is critical in promoting visual cycle function. This review collects the latest understanding of autophagy in the context of the eye. We will review and discuss the respective roles of autophagy in the physiology and/or pathophysiology of each of the ocular tissues, its diurnal/circadian variation, as well as its involvement in diseases of the eye

Hypopyon uveitis associated with systemic lupus erythematosus and antiphospholipid antibody syndrome

To report a case of hypopyon uveitis associated with systemic lupus erythematosus and antiphospholipid antibody syndrome.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47393/1/417_2004_Article_1022.pd

Worldwide Argus II implantation: recommendations to optimize patient outcomes

Abstract Background A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation. Methods Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined. Results Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon’s capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical. Conclusions Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.http://deepblue.lib.umich.edu/bitstream/2027.42/134581/1/12886_2016_Article_225.pd

Caspase Inhibition with XIAP as an Adjunct to AAV Vector Gene-Replacement Therapy: Improving Efficacy and Prolonging the Treatment Window

AAV-mediated gene therapy in the rd10 mouse, with retinal degeneration caused by mutation in the rod cyclic guanosine monophosphate phosphodiesterase β-subunit (PDEβ) gene, produces significant, but transient, rescue of photoreceptor structure and function. This study evaluates the ability of AAV-mediated delivery of X-linked inhibitor of apoptosis (XIAP) to enhance and prolong the efficacy of PDEβ gene-replacement therapy.Rd10 mice were bred and housed in darkness. Two groups of animals were generated: Group 1 received sub-retinal AAV5-XIAP or AAV5-GFP at postnatal age (P) 4 or 21 days; Group 2 received sub-retinal AAV5-XIAP plus AAV5- PDEβ, AAV5-GFP plus AAV5- PDEβ, or AAV- PDEβ alone at age P4 or P21. Animals were maintained for an additional 4 weeks in darkness before being moved to a cyclic-light environment. A subset of animals from Group 1 received a second sub-retinal injection of AAV8-733-PDEβ two weeks after being moved to the light. Histology, immunohistochemistry, Western blots, and electroretinograms were performed at different times after moving to the light.Injection of AAV5-XIAP alone at P4 and 21 resulted in significant slowing of light-induced retinal degeneration, as measured by outer nuclear thickness and cell counts, but did not result in improved outer segment structure and rhodopsin localization. In contrast, co-injection of AAV5-XIAP and AAV5-PDEβ resulted in increased levels of rescue and decreased rates of retinal degeneration compared to treatment with AAV5-PDEβ alone. Mice treated with AAV5-XIAP at P4, but not P21, remained responsive to subsequent rescue by AAV8-733-PDEβ when injected two weeks after moving to a light-cycling environment.Adjunctive treatment with the anti-apoptotic gene XIAP confers additive protective effect to gene-replacement therapy with AAV5-PDEβ in the rd10 mouse. In addition, AAV5-XIAP, when given early, can increase the age at which gene-replacement therapy remains effective, thus effectively prolonging the window of opportunity for therapeutic intervention

Shattered pellet injection experiments at JET in support of the ITER disruption mitigation system design

A series of experiments have been executed at JET to assess the efficacy of the newly installed shattered pellet injection (SPI) system in mitigating the effects of disruptions. Issues, important for the ITER disruption mitigation system, such as thermal load mitigation, avoidance of runaway electron (RE) formation, radiation asymmetries during thermal quench mitigation, electromagnetic load control and RE energy dissipation have been addressed over a large parameter range. The efficiency of the mitigation has been examined for the various SPI injection strategies. The paper summarises the results from these JET SPI experiments and discusses their implications for the ITER disruption mitigation scheme

New H-mode regimes with small ELMs and high thermal confinement in the Joint European Torus

New H-mode regimes with high confinement, low core impurity accumulation, and small edge-localized mode perturbations have been obtained in magnetically confined plasmas at the Joint European Torus tokamak. Such regimes are achieved by means of optimized particle fueling conditions at high input power, current, and magnetic field, which lead to a self-organized state with a strong increase in rotation and ion temperature and a decrease in the edge density. An interplay between core and edge plasma regions leads to reduced turbulence levels and outward impurity convection. These results pave the way to an attractive alternative to the standard plasmas considered for fusion energy generation in a tokamak with a metallic wall environment such as the ones expected in ITER.& nbsp;Published under an exclusive license by AIP Publishing