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Torun N, Laviv Y, Jazi KK, Mahadevan A, Bhadelia RA, Matthew A, Strominger M, Kasper EM. Schwannoma of the trochlear nerve-an illustrated case series and a systematic review of management. Neurosurg Rev 2018;41(3):699-711.Abstract
Schwannomas of cranial nerves in the absence of systemic neurofibromatosis are relatively rare. Among these, schwannomas of the trochlear nerve are even less common. They can be found incidentally or when they cause diplopia or other significant neurological deficits. Treatment options include observation only, neuro-ophthalmological intervention, and/or neurosurgical management via resection or sterotactic radiosurgery (SRS). In recent years, the latter has become an attractive therapeutic tool for a number of benign skull base neoplasm including a small number of reports on its successful use for trochlear Schwannomas. However, no treatment algorithm for the management of these tumors has been proposed so far. The goal of this manuscript is to illustrate a case series of this rare entity and to suggest a rational treatment algorithm for trochlear schwannomas, based on our institutional experience of recent cases, and a pertinent review of the literature. Including our series of 5 cases, a total of 85 cases reporting on the management of trochlear schwannomas have been published. Of those reported, less than half (40 %) of patients underwent surgical resection, whereas the remainder were managed conservatively or with SRS. Seventy-six percent (65/85) of the entire cohort presented with diplopia, which was the solitary symptom in over half of the cases (n = 39). All patients who presented with symptoms other than diplopia or headaches as solitary symptoms underwent surgical resection. Patients in the non-surgical group were mostly male (M/F = 3.5:1), presented at an older age and had shorter mean diameter (4.6 vs. 30.4 mm, p < 0.0001) when compared to the surgical group. Twelve patients in the entire cohort were treated with SRS, none of whom had undergone surgical resection before or after radiation treatment. Trochlear schwannoma patients without systemic neurofibromatosis are rare and infrequently reported in the literature. Of those, patients harboring symptomatic trochlear Schwannomas do not form a single homogenous group, but fall into two rather distinct subgroups regarding demographics and clinical characteristics. Among those patients in need of intervention, open microsurgical resection as well as less invasive treatment options exist, which all aim at safe relief of symptoms and prevention of progression. Both open microsurgical removal as well as SRS can achieve good long-term local control. Consequently, a tailored multidisciplinary treatment algorithm, based on the individual presentation and tumor configuration, is proposed.
Kaufman AR, Nosé RM, Lu Y, Pineda R. Phacoemulsification with intraocular lens implantation after previous descemetorhexis without endothelial keratoplasty. J Cataract Refract Surg 2017;43(11):1471-1475.Abstract
A 58-year-old woman with bilateral Fuchs endothelial corneal dystrophy presented with predominantly central guttata in the left eye causing visually significant stromal edema. A 4.0 mm descemetorhexis without endothelial keratoplasty was performed. At the 6-week follow-up, the central cornea had cleared completely and the central endothelial cell density (ECD) was 541 cells/mm2. The central corneal clearing remained stable for 2 years after the procedure; however, vision declined because of a visually significant cataract in the left eye. Uneventful phacoemulsification with intraocular lens implantation was performed with a target refraction of -0.50 diopters. At 1.5 months postoperatively, the uncorrected distance visual acuity was 20/20 with a manifest refraction of -0.25 -0.25 × 60 and the central ECD was 2373 cells/mm2 (increased from 1471 cells/mm2 prior to phacoemulsification). Cataract surgery by phacoemulsification years after descemetorhexis without endothelial keratoplasty appears to be well-tolerated, with good clinical and predictive refractive outcomes.
Sheppard JD, Foster SC, Toyos MM, Markwardt K, Da Vanzo R, Flynn TE, Kempen JH. Difluprednate 0.05% versus Prednisolone Acetate 1% for Endogenous Anterior Uveitis: Pooled Efficacy Analysis of Two Phase 3 Studies. Ocul Immunol Inflamm 2017;:1-13.Abstract
PURPOSE: To analyse pooled data from 2 similar phase 3 noninferiority studies comparing difluprednate 0.05% versus prednisolone acetate 1% in patients with endogenous anterior uveitis. METHODS: Patients received difluprednate alternating with vehicle or prednisolone acetate for 14 days (8 drops/day in both groups), followed by tapering from day 14 to 28. All patients were observed until day 42. RESULTS: More patients on difluprednate than on prednisolone acetate were cleared of anterior chamber cells on day twenty one (71.3% vs 54.7%; p = 0.02); results were similar at the other time points. Treatment withdrawals were higher with prednisolone acetate than difluprednate (19.8% vs 7.4%; log-rank p = 0.02). Study discontinuation due to lack of efficacy was also higher with prednisolone acetate than difluprednate (14.0% vs 0%; p = 0.0002 [pre-specified exploratory analysis]). CONCLUSIONS: More difluprednate-treated eyes were quiet following 21 days of treatment, and difluprednate-treated patients were much less likely to be withdrawn from the study because of treatment failure.
Wolkow N, Jakobiec FA, Yoon MK. Intratarsal Keratinous Eyelid Cysts in Gorlin Syndrome: A Review and Reappraisal. Surv Ophthalmol 2017;Abstract
A 38-year-old woman presented with multiple bilateral recurrent eyelid cysts. Her medical history was notable for Gorlin (nevoid basal cell carcinoma) syndrome. Histopathologic and immunohistochemical examinations revealed that the lesions were intratarsal keratinous cysts. They were similar in appearance to sporadic intratarsal keratinous cysts and closely resembled odontogenic keratocysts of the jaw. Eyelid cysts occur in up to 40 percent of patients with Gorlin syndrome; however, their description has been cursory and for the most part, outside of the ophthalmic literature. Although ophthalmologists are familiar with the periocular basal cell carcinomas that occur in patients with Gorlin syndrome, up to 10 percent of patients never develop a basal cell carcinoma, but may manifest other ophthalmic findings. Awareness of these other features may contribute to the earlier diagnosis of the syndrome. We discuss the clinical and histopathologic features of intratarsal keratinous cysts in Gorlin syndrome, comparing them to sporadic intratarsal keratinous cysts, other eyelid cysts, and jaw cysts that also characterize this syndrome. We briefly review the ocular and systemic manifestations of Gorlin syndrome and recent genetic and therapeutic developments so that the eyelid cysts may be appreciated within the appropriate context of Gorlin syndrome as a whole.
Sanguansak T, Morley KE, Morley MG, 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.Abstract
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.
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.
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.

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