Publications

2017

Sanguansak T, Morley K, Morley M, Thinkhamrop K, Thuanman J, Agarwal I. Two-Way Social Media Messaging in Postoperative Cataract Surgical Patients: Prospective Interventional Study. J Med Internet Res. 2017;19(12):e413.
BACKGROUND: Social media offers a new way to provide education, reminders, and support for patients with a variety of health conditions. Most of these interventions use one-way, provider-patient communication. Incorporating social media tools to improve postoperative (postop) education and follow-up care has only been used in limited situations. OBJECTIVE: The aim of this study was to determine the feasibility and efficacy of two-way social media messaging to deliver reminders and educational information about postop care to cataract patients. METHODS: A total of 98 patients undergoing their first eye cataract surgery were divided into two groups: a no message group receiving usual pre- and postop care and a message group receiving usual care plus messages in a mobile social media format with standardized content and timing. Each patient in the message group received nine messages about hand and face hygiene, medication and postop visit adherence, and links to patient education videos about postop care. Patients could respond to messages as desired. Main outcome measures included medication adherence, postop visit adherence, clinical outcomes, and patients' subjective assessments of two-way messaging. The number, types, content, and timing of responses by patients to messages were recorded. RESULTS: Medication adherence was better in the message group at postop day 7, with high adherence in 47 patients (96%, 47/49) versus 36 patients (73%, 36/49) in the no message group (P=.004), but no statistically significant differences in medication adherence between the groups were noted at preop and postop day 30. Visit adherence was higher at postop day 30 in the message group (100%, 49/49) versus the no message group (88%, 43/49; P=.03) but was 100% (49/49) in both groups at postop day 1 and 7. Final visual outcomes were similar between groups. A total of 441 standardized messages were sent to the message group. Out of 270 responses generated, 188 (70%) were simple acknowledgments or "thank you," and 82 (30%) responses were questions that were divided into three general categories: administrative, postop care, and clinical issues. Out of the 82 question responses, 31 (11%) were about administrative issues, 28 (10%) about postop care, and 23 (9%) about clinical symptoms. All the messages about symptoms were triaged by nurses or ophthalmologists and only required reassurance or information. Patients expressed satisfaction with messaging. CONCLUSIONS: Two-way social media messaging to deliver postop information to cataract patients is feasible and improves early medication compliance. Further design improvements can streamline work flow to optimize efficiency and patient satisfaction.
Haleem MS, Han L, Hemert J, Li B, Fleming A, Pasquale L, Song B. A Novel Adaptive Deformable Model for Automated Optic Disc and Cup Segmentation to Aid Glaucoma Diagnosis. J Med Syst. 2017;42(1):20.
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.
Park-Windhol C, Ng YS, Yang J, Primo V, Saint-Geniez M, D’Amore P. Endomucin inhibits VEGF-induced endothelial cell migration, growth, and morphogenesis by modulating VEGFR2 signaling. Sci Rep. 2017;7(1):17138.
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.
Pineles S, Kraker R, VanderVeen D, Hutchinson A, Galvin J, Wilson L, Lambert S. Atropine for the Prevention of Myopia Progression in Children: A Report by the American Academy of Ophthalmology. Ophthalmology. 2017;124(12):1857–1866.
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%).
Sharma M, Hunter D. Diplopia after Strabismus Surgery. Semin Ophthalmol. 2017;:1–6.
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.
Wang S, Woods R, Costela F, Luo G. Dynamic gaze-position prediction of saccadic eye movements using a Taylor series. J Vis. 2017;17(14):3.
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.
Welsh M, Taguchi A, Schaefer K, Van Tyne D, Lebreton F, Gilmore M, Kahne D, Walker S. Identification of a Functionally Unique Family of Penicillin-Binding Proteins. J Am Chem Soc. 2017;139(49):17727–17730.
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.
Wu W, Duan Y, Ma G, Zhou G, Windhol C, D’Amore P, Lei H. AAV-CRISPR/Cas9-Mediated Depletion of VEGFR2 Blocks Angiogenesis In Vitro. Invest Ophthalmol Vis Sci. 2017;58(14):6082–6090.
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.