Welsh MA, Taguchi A, Schaefer K, Van Tyne D, Lebreton F, Gilmore MS, Kahne D, Walker S. Identification of a Functionally Unique Family of Penicillin-Binding Proteins. J Am Chem Soc 2017;139(49):17727-17730.Abstract
Penicillin-binding proteins (PBPs) are enzymes involved in the assembly of the bacterial cell wall, a major target for antibiotics. These proteins are classified by mass into high-molecular-weight PBPs, which are transpeptidases that form peptidoglycan cross-links, and low-molecular-weight PBPs, which are typically hydrolases. We report a functionally unique family of low-molecular-weight PBPs that act as transpeptidases rather than hydrolases, but they do not cross-link peptidoglycan. We show that these PBPs can exchange d-amino acids bearing chemical tags or affinity handles into peptidoglycan precursors, including Lipid II, enabling biochemical studies of proteins involved in cell wall assembly. We report that, in two organisms, the PBPs incorporate lysine into cellular peptidoglycan and that, further, the PBPs have the unprecedented ability to transfer the primary ε-amine of lysine to peptidoglycan.
Yau GL, Silva PS, Arrigg PG, Sun JK. Postoperative Complications of Pars Plana Vitrectomy for Diabetic Retinal Disease. Semin Ophthalmol 2017;:1-8.Abstract
Despite recent advances in the medical management of diabetic retinal disease, there remain established indications for vitreoretinal surgery in the treatment of severe proliferative diabetic retinopathy. These include non-clearing vitreous hemorrhage and tractional retinal detachment. Advances in surgical instrumentation, technique, and experience have led to improved visual outcomes, as well as a corresponding decrease in the incidence of postoperative complications. However, the presence of systemic and ocular factors in diabetic patients increases the risk of adverse events compared to non-diabetic individuals. This review will focus on the most important postoperative complications following pars plana vitrectomy, with specific considerations for the diabetic patient.
Pineles SL, Kraker RT, VanderVeen DK, Hutchinson AK, Galvin JA, Wilson LB, Lambert SR. Atropine for the Prevention of Myopia Progression in Children: A Report by the American Academy of Ophthalmology. Ophthalmology 2017;124(12):1857-1866.Abstract
PURPOSE: To review the published literature on the efficacy of topical atropine for the prevention of myopic progression in children. METHODS: Literature searches were last conducted in December 2016 in the PubMed database with no date restrictions, but were limited to studies published in English, and in the Cochrane Library database without any restrictions. The combined searches yielded 98 citations, 23 of which were reviewed in full text. Of these, 17 articles were deemed appropriate for inclusion in this assessment and subsequently were assigned a level of evidence rating by the panel methodologist. RESULTS: Seventeen level I, II, and III studies were identified. Most of the studies reported less myopic progression in children treated with atropine compared with various control groups. All 8 of the level I and II studies that evaluated primarily myopic progression revealed less myopic progression with atropine (myopic progression ranging from 0.04±0.63 to 0.47±0.91 diopters (D)/year) compared with control participants (myopic progression ranging from 0.38±0.39 to 1.19±2.48 D/year). In studies that evaluated myopic progression after cessation of treatment, a rebound effect was noted. Several studies evaluated the optimal dosage of atropine with regard to myopic progression, rebound after treatment cessation, and minimization of side effects. Lower dosages of atropine (0.5%, 0.1%, and 0.01%) were found to be slightly less effective during treatment periods of 1 to 2 years, but they were associated with less rebound myopic progression (for atropine 0.01%, mean myopic progression after treatment cessation of 0.28±0.33 D/year, compared with atropine 0.5%, 0.87±0.52 D/year), fewer side effects, and similar long-term results for myopic progression after the study period and rebound effect were considered. The most robust and well-designed studies were carried out in Asian populations. Studies involving patients of other ethnic backgrounds failed to provide sufficient evidence of an effect of atropine on myopic progression. CONCLUSIONS: Level I evidence supports the use of atropine to prevent myopic progression. Although there are reports of myopic rebound after treatment is discontinued, this seems to be minimized by using low doses (especially atropine 0.01%).
Haleem MS, Han L, van Hemert J, Li B, Fleming A, Pasquale LR, Song BJ. A Novel Adaptive Deformable Model for Automated Optic Disc and Cup Segmentation to Aid Glaucoma Diagnosis. J Med Syst 2017;42(1):20.Abstract
This paper proposes a novel Adaptive Region-based Edge Smoothing Model (ARESM) for automatic boundary detection of optic disc and cup to aid automatic glaucoma diagnosis. The novelty of our approach consists of two aspects: 1) automatic detection of initial optimum object boundary based on a Region Classification Model (RCM) in a pixel-level multidimensional feature space; 2) an Adaptive Edge Smoothing Update model (AESU) of contour points (e.g. misclassified or irregular points) based on iterative force field calculations with contours obtained from the RCM by minimising energy function (an approach that does not require predefined geometric templates to guide auto-segmentation). Such an approach provides robustness in capturing a range of variations and shapes. We have conducted a comprehensive comparison between our approach and the state-of-the-art existing deformable models and validated it with publicly available datasets. The experimental evaluation shows that the proposed approach significantly outperforms existing methods. The generality of the proposed approach will enable segmentation and detection of other object boundaries and provide added value in the field of medical image processing and analysis.
Wang S, Woods RL, Costela FM, Luo G. Dynamic gaze-position prediction of saccadic eye movements using a Taylor series. J Vis 2017;17(14):3.Abstract
Gaze-contingent displays have been widely used in vision research and virtual reality applications. Due to data transmission, image processing, and display preparation, the time delay between the eye tracker and the monitor update may lead to a misalignment between the eye position and the image manipulation during eye movements. We propose a method to reduce the misalignment using a Taylor series to predict the saccadic eye movement. The proposed method was evaluated using two large datasets including 219,335 human saccades (collected with an EyeLink 1000 system, 95% range from 1° to 32°) and 21,844 monkey saccades (collected with a scleral search coil, 95% range from 1° to 9°). When assuming a 10-ms time delay, the prediction of saccade movements using the proposed method could reduce the misalignment greater than the state-of-the-art methods. The average error was about 0.93° for human saccades and 0.26° for monkey saccades. Our results suggest that this proposed saccade prediction method will create more accurate gaze-contingent displays.
Costela FM, Kajtezovic S, Woods RL. The Preferred Retinal Locus Used to Watch Videos. Invest Ophthalmol Vis Sci 2017;58(14):6073-6081.Abstract
Purpose: Eccentric viewing is a common strategy used by people with central vision loss (CVL) to direct the eye such that the image falls onto functioning peripheral retina, known as the preferred retinal locus (PRL). It has been long acknowledged that we do not know whether the PRL used in a fixation test is also used when performing tasks. We present an innovative method to determine whether the same PRL observed during a fixation task was used to watch videos and whether poor resolution affects gaze location. Methods: The gaze of a group of 60 normal vision (NV) observers was used to define a democratic center of interest (COI) of video clips from movies and television. For each CVL participant (N = 20), we computed the gaze offsets from the COI across the video clips. The distribution of gaze offsets of the NV participants was used to define the limits of NV behavior. If the gaze offset was within this 95% degree confidence interval, we presumed that the same PRL was used for fixation and video watching. Another 15 NV participants watched the video clips with various levels of defocus blur. Results: CVL participants had wider gaze-offset distributions than NV participants (P < 0.001). Gaze offsets of 18/20 CVL participants were outside the NV confidence interval. Further, none of the 15 NV participants watching the same videos with spherical defocus blur had a gaze offset that was decentered (outside the NV confidence interval), suggesting that resolution was not the problem. Conclusions: This indicates that many CVL participants were using a PRL to view videos that differed from that found with a fixation task and that it was not caused by poor resolution alone. The relationship between these locations needs further investigation.
Wu W, Duan Y, Ma G, Zhou G, Windhol C, D'Amore PA, Lei H. AAV-CRISPR/Cas9-Mediated Depletion of VEGFR2 Blocks Angiogenesis In Vitro. Invest Ophthalmol Vis Sci 2017;58(14):6082-6090.Abstract
Purpose: Pathologic angiogenesis is a component of many diseases, including neovascular age-related macular degeneration, proliferation diabetic retinopathy, as well as tumor growth and metastasis. The purpose of this project was to examine whether the system of adeno-associated viral (AAV)-mediated CRISPR (clustered regularly interspaced short palindromic repeats)-associated endonuclease (Cas)9 can be used to deplete expression of VEGF receptor 2 (VEGFR2) in human vascular endothelial cells in vitro and thus suppress its downstream signaling events. Methods: The dual AAV system of CRISPR/Cas9 from Streptococcus pyogenes (AAV-SpGuide and -SpCas9) was adapted to edit genomic VEGFR2 in primary human retinal microvascular endothelial cells (HRECs). In this system, the endothelial-specific promoter for intercellular adhesion molecule 2 (ICAM2) was cloned into the dual AAV vectors of SpGuide and SpCas9 for driving expression of green fluorescence protein (GFP) and SpCas9, respectively. These two AAV vectors were applied to production of recombinant AAV serotype 5 (rAAV5), which were used to infect HRECs for depletion of VEGFR2. Protein expression was determined by Western blot; and cell proliferation, migration, as well as tube formation were examined. Results: AAV5 effectively infected vascular endothelial cells (ECs) and retinal pigment epithelial (RPE) cells; the ICAM2 promoter drove expression of GFP and SpCas9 in HRECs, but not in RPE cells. The results showed that the rAAV5-CRISPR/Cas9 depleted VEGFR2 by 80% and completely blocked VEGF-induced activation of Akt, and proliferation, migration as well as tube formation of HRECs. Conclusions: AAV-CRISRP/Cas9-mediated depletion of VEGFR2 is a potential therapeutic strategy for pathologic angiogenesis.
Park-Windhol C, Ng YS, Yang J, Primo V, Saint-Geniez M, D'Amore PA. Endomucin inhibits VEGF-induced endothelial cell migration, growth, and morphogenesis by modulating VEGFR2 signaling. Sci Rep 2017;7(1):17138.Abstract
Angiogenesis is central to both normal and pathologic processes. Endothelial cells (ECs) express O-glycoproteins that are believed to play important roles in vascular development and stability. Endomucin-1 (EMCN) is a type I O-glycosylated, sialic-rich glycoprotein, specifically expressed by venous and capillary endothelium. Evidence has pointed to a potential role for EMCN in angiogenesis but it had not been directly investigated. In this study, we examined the role of EMCN in angiogenesis by modulating EMCN levels both in vivo and in vitro. Reduction of EMCN in vivo led to the impairment of angiogenesis during normal retinal development in vivo. To determine the cellular basis of this inhibition, gain- and loss-of-function studies were performed in human retinal EC (HREC) in vitro by EMCN over-expression using adenovirus or EMCN gene knockdown by siRNA. We show that EMCN knockdown reduced migration, inhibited cell growth without compromising cell survival, and suppressed tube morphogenesis of ECs, whereas over-expression of EMCN led to increased migration, proliferation and tube formation. Furthermore, knockdown of EMCN suppressed VEGF-induced signaling as measured by decreased phospho-VEGFR2, phospho-ERK1/2 and phospho-p38-MAPK levels. These results suggest a novel role for EMCN as a potent regulator of angiogenesis and point to its potential as a new therapeutic target for angiogenesis-related diseases.
Bains U, Hoguet A. Aqueous Drainage Device Erosion: A Review of Rates, Risks, Prevention, and Repair. Semin Ophthalmol 2017;:1-10.Abstract
Aqueous drainage device tube erosions require prompt intervention to prevent endophthalmitis. As the use of drainage devices in glaucoma surgery continues to increase, recognizing and managing tube erosions is a pertinent issue. This review provides a comprehensive overview of tube erosions, including the rates of erosion with various types of patch grafts, the risk factors associated with erosion, and approaches to repair in order to counsel and treat our patients to prevent endophthalmitis.
Sharma M, Hunter DG. Diplopia after Strabismus Surgery. Semin Ophthalmol 2017;:1-6.Abstract
Diplopia is a disappointing and, at times, unanticipated consequence of what might otherwise be considered anatomically successful strabismus surgery. In this study, we review the existing literature regarding diplopia after strabismus surgery in the context of the senior author's experience. We divide postoperative diplopia types into cases that occur in the setting of normal binocular vision (or "normal" suppression) vs. cases that are the consequence of rare or anomalous sensorial adaptations. We then discuss how to identify patients at greatest risk based on history and preoperative testing, and we offer strategies for managing these sometimes-challenging cases.
Learned D, Eliott D. Management of Delayed Suprachoroidal Hemorrhage after Glaucoma Surgery. Semin Ophthalmol 2017;:1-5.Abstract
PURPOSE: To review the most current treatment recommendations and outcomes for delayed suprachoroidal hemorrhages. METHODS: Article review of management and outcomes of suprachoroidal hemorrhages, with emphasis on delayed suprachoroidal hemorrhages in the setting of glaucoma surgery. CONCLUSION: Time of drainage of suprachoroidal hemorrhages remains controversial. Earlier drainage should be considered with high intraocular pressure, expulsion of intraocular content, or retinal detachment. In clinically stable eyes with suprachoroidal hemorrhage, recommendations range from observation to immediate drainage. Clot lysis occurs at roughly 14 days.