Rahman SI, Turalba A. Anticoagulation in Glaucoma Surgery. Semin Ophthalmol 2017;:1-4.Abstract
Anticoagulation medications are used commonly, particularly in an elderly population. There are many systemic diseases and scenarios that require modulation of coagulation to prevent serious adverse outcomes. While there is some consensus about their use in cataract surgery, there is less certainty about their management with glaucoma surgery. Glaucoma surgery presents a unique challenge when considering anticoagulation. Currently, there is great diversity in surgeon practices regarding anticoagulation in glaucoma surgery. Based on available evidence, it is unclear whether it is beneficial to hold anticoagulation, with or without bridging therapy, leading up to a planned surgery. Considering the potential serious adverse outcomes related to holding anticoagulation therapy, altering these medications for glaucoma surgery should be done sparingly and in consultation with the primary prescriber of such medications.
Rahmani S, Eliott D. Postoperative Endophthalmitis: A Review of Risk Factors, Prophylaxis, Incidence, Microbiology, Treatment, and Outcomes. Semin Ophthalmol 2017;:1-7.Abstract
Postoperative endophthalmitis is one of the most feared complications of intraocular surgery. The most common types of intraocular surgeries performed worldwide are cataract extraction, glaucoma drainage implants/trabeculectomy, and pars plana vitrectomy. This review will focus on the clinical features, risk factors, prophylaxis, and treatment of endophthalmitis in these three main intraocular surgeries.
Rami HE, Barham R, Sun JK, Silva PS. Evidence-Based Treatment of Diabetic Retinopathy. Semin Ophthalmol 2017;32(1):67-74.Abstract

Diabetic retinopathy (DR) is the most frequent microvascular complication from diabetes and requires annual screening and at least annual follow-up. A systemic approach to optimize blood glucose and blood pressure may halt progression to severe stages of DR and obviate the need for ocular treatment. Although there is evidence of benefit from fenofibrate or intravitreous antiVEGF treatment for eyes with nonproliferative DR (NPDR), these therapies are not standard care for NPDR at this time. Some patients with severe NPDR, especially those with type 2 diabetes, benefit from early panretinal photocoagulation (PRP). Once DR progresses to proliferative DR (PDR), treatment is often necessary to prevent visual loss. PRP remains mainstay treatment for PDR with high-risk characteristics. However, intravitreous antiVEGF injections appear to be a safe and effective treatment alternative for PDR through at least two years. Vitreoretinal surgery is indicated for PDR cases with non-clearing vitreous hemorrhage and/or tractional retinal detachment.

Ramke M, Lee JY, Dyer DW, Seto D, Rajaiya J, Chodosh J. The 5'UTR in human adenoviruses: leader diversity in late gene expression. Sci Rep 2017;7(1):618.Abstract

Human adenoviruses (HAdVs) shut down host cellular cap-dependent mRNA translation while initiating the translation of viral late mRNAs in a cap-independent manner. HAdV 5' untranslated regions (5'UTRs) are crucial for cap-independent initiation, and influence mRNA localization and stability. However, HAdV translational regulation remains relatively uncharacterized. The HAdV tripartite leader (TPL), composed of three introns (TPL 1-3), is critical to the translation of HAdV late mRNA. Herein, we annotated and analyzed 72 HAdV genotypes for the HAdV TPL and another previously described leader, the i-leader. Using HAdV species D, type 37 (HAdV-D37), we show by reverse transcription PCR and Sanger sequencing that mRNAs of the HAdV-D37 E3 transcription unit are spliced to the TPL. We also identified a polycistronic mRNA for RID-α and RID-β. Analysis of the i-leader revealed a potential open reading frame within the leader sequence and the termination of this potential protein in TPL3. A potential new leader embedded within the E3 region was also detected and tentatively named the j-leader. These results suggest an underappreciated complexity of post-transcriptional regulation, and the importance of HAdV 5'UTRs for precisely coordinated viral protein expression along the path from genotype to phenotype.

Rao R, Borkar DS, Colby KA, Veldman PB. Descemet Membrane Endothelial Keratoplasty After Failed Descemet Stripping Without Endothelial Keratoplasty. Cornea 2017;36(7):763-766.Abstract
PURPOSE: To describe the clinical course, surgical experience, and postoperative outcomes of 3 patients with Fuchs endothelial dystrophy who underwent Descemet membrane endothelial keratoplasty (DMEK) after failed Descemet stripping without endothelial keratoplasty. METHODS: Three patients who underwent DMEK for management of persistent corneal edema after deliberate Descemet stripping in the setting of Fuchs endothelial dystrophy were identified. Patients were examined at day 1, week 1, and months 1, 3, and 6 after DMEK. Visual acuity, central corneal thickness (CCT), and evaluation of central corneal endothelial cell counts were recorded. RESULTS: Two women and one man, aged 56, 72, and 68 years, were included. The time interval between primary Descemet stripping and DMEK ranged from 3.5 to 8 months. Preoperative visual acuities were 20/200, 20/300, and 20/80. Immediately before DMEK, no patients had countable central endothelial cells, and CCTs were 825, 1034, and 878 μm. After DMEK, all patients had improvement in visual acuity to 20/70, 20/20, and 20/20 with CCTs of 529, 504, and 528. The postoperative period in the first case was notable for the immediate development of a pigmented pupillary membrane with posterior synechiae, as well as cystoid macular edema, of uncertain chronicity, noted 1 month postoperatively. The second case also developed posterior synechiae. Two cases completed 6-month endothelial cell counts totaling 2200 and 3114 cells per square millimeter (endothelial cell loss of 13% and 5.3%). CONCLUSIONS: DMEK is a reliable procedure to facilitate corneal rehabilitation and visual recovery in the event of poor corneal clearance after Descemet stripping without endothelial keratoplasty.
Riau AK, Venkatraman SS, Dohlman CH, Mehta JS. Surface Modifications of the PMMA Optic of a Keratoprosthesis to Improve Biointegration. Cornea 2017;36 Suppl 1:S15-S25.Abstract
Biointegration of a keratoprosthesis (KPro) is critical for the mitigation of various long-term postoperative complications. Biointegration of a KPro occurs between the haptic skirt (corneal graft) and the central optic [poly(methyl methacrylate) (PMMA)]. Various studies have highlighted common problems associated with poor bonding and biointegration between these 2 incompatible biomaterials. Resolution of these issues could be achieved by surface modification of the inert material (PMMA). A calcium phosphate (CaP) coating deposited on dopamine-activated PMMA sheets by simulated body fluid incubation (d-CaP coating) was shown to improve adhesion to collagen type I (main component of corneal stroma) compared with untreated PMMA and PMMA with other surface modifications. However, the d-CaP coating could easily undergo delamination, thereby reducing its potential for modification of KPro optical cylinders. In addition, the coating did not resemble the Ca and P composition of hydroxyapatite (HAp). A novel dip-coating method that involves the creation of cavities to trap and immobilize HAp nanoparticles on the PMMA surface was introduced to address the problems associated with the d-CaP coating. The newly obtained coating offered high hydrophilicity, resistance to delamination, and preservation of the Ca and P composition of HAp. These advantages resulted in improved adhesion strength by more than 1 order of magnitude compared with untreated PMMA. With respect to biointegration, human corneal stromal fibroblasts were able to adhere strongly and proliferate on HAp-coated PMMA. Furthermore, the new coating technique could be extended to immobilization of HAp nanoparticles on 3-mm-diameter PMMA cylinders, bringing it closer to clinical application.
Richarme G, Liu C, Mihoub M, Abdallah J, Leger T, Joly N, Liebart J-C, Jurkunas UV, Nadal M, Bouloc P, Dairou J, Lamouri A. Guanine glycation repair by DJ-1/Park7 and its bacterial homologs. Science 2017;357(6347):208-211.Abstract
DNA damage induced by reactive carbonyls (mainly methylglyoxal and glyoxal), called DNA glycation, is quantitatively as important as oxidative damage. DNA glycation is associated with increased mutation frequency, DNA strand breaks, and cytotoxicity. However, in contrast to guanine oxidation repair, how glycated DNA is repaired remains undetermined. Here, we found that the parkinsonism-associated protein DJ-1 and its bacterial homologs Hsp31, YhbO, and YajL could repair methylglyoxal- and glyoxal-glycated nucleotides and nucleic acids. DJ-1-depleted cells displayed increased levels of glycated DNA, DNA strand breaks, and phosphorylated p53. Deglycase-deficient bacterial mutants displayed increased levels of glycated DNA and RNA and exhibited strong mutator phenotypes. Thus, DJ-1 and its prokaryotic homologs constitute a major nucleotide repair system that we name guanine glycation repair.
Roberto SA, Bayes J, Karner PE, Morley MG, Nanji KC. Patient Harm in Cataract Surgery: A Series of Adverse Events in Massachusetts. Anesth Analg 2018;126(5):1548-1550.Abstract
Massachusetts state agencies received reports of 37 adverse events (AEs) involving cataract surgery from 2011 to 2015. Fifteen were anesthesia related, including 5 wrong eye blocks, 3 cases of hemodynamic instability, 2 retrobulbar hematoma/hemorrhages, and 5 globe perforations resulting in permanent loss of vision. While Massachusetts' reported AEs likely underrepresent the true number of AEs that occur during cataract surgery, they do offer useful signal data to indicate the types of patient harm occurring during these procedures.
Roh M, Lee NG, Miller JB. Complications Assoicated with MIRAgel for Treatment of Retinal Detachment. Semin Ophthalmol 2017;:1-6.Abstract
MIRAgel (MIRA, Waltham, MA) is a hydrogel buckle that was introduced in 1979 as a new scleral implant for the treatment of retinal detachment. Long-term follow-up of more than 10 years revealed that the hydrolysis of the synthetic hydrophilic material leads to marked expansion of the substance, causing complications such as buckle extrusion and intrusion, eye motility disorder, cosmetic deformities, and periocular infections. Removal of the implant is the treatment of choice in cases with complications, but it is technically difficult due to the friability of the implant, severe scleral ectasia, and relatively high rate of redetachment after removal.
Rong SS, Ma STU, Yu XT, Ma L, Chu WK, Chan TCY, Wang YM, Young AL, Pang CP, Jhanji V, Chen LJ. Genetic associations for keratoconus: a systematic review and meta-analysis. Sci Rep 2017;7(1):4620.Abstract
Genetic associations for keratoconus could be useful for understanding disease pathogenesis and discovering biomarkers for early detection of the disease. We conducted a systematic review and meta-analysis to summarize all reported genetic associations for the disease. We searched in the MEDLINE, Embase, Web of Science, and HuGENET databases for genetic studies of keratoconus published from 1950 to June 2016. The summary odds ratio and 95% confidence intervals of all polymorphisms were estimated using the random-effect model. Among 639 reports that were retrieved, 24 fulfilled required criteria as eligible studies for meta-analysis, involving a total of 53 polymorphisms in 28 genes/loci. Results of our meta-analysis lead to the prioritization of 8 single-nucleotide polymorphisms (SNPs) in 6 genes/loci for keratoconus in Whites. Of them 5 genes/loci were originally detected in genome-wide association studies, including FOXO1 (rs2721051, P = 5.6 × 10(-11)), RXRA-COL5A1 (rs1536482, P = 2.5 × 10(-9)), FNDC3B (rs4894535, P = 1.4 × 10(-8)), IMMP2L (rs757219, P = 6.1 × 10(-7); rs214884, P = 2.3 × 10(-5)), and BANP-ZNF469 (rs9938149, P = 1.3 × 10(-5)). The gene COL4A4 (rs2229813, P = 1.3 × 10(-12); rs2228557, P = 4.5 × 10(-7)) was identified in previous candidate gene studies. We also found SNPs in 10 genes/loci that had a summary P value < 0.05. Sensitivity analysis indicated that the results were robust. Replication studies and understanding the roles of these genes in keratoconus are warranted.
Roohipoor R, Yaseri M, Teymourpour A, Kloek C, Miller JB, Loewenstein JI. Early Performance on an Eye Surgery Simulator Predicts Subsequent Resident Surgical Performance. J Surg Educ 2017;Abstract

OBJECTIVE: To examine early performance on an eye surgery simulator and its relationship to subsequent live surgical performance in a single large residency program. DESIGN: Retrospective study. SETTING: Massachusetts Eye and Ear, Harvard Medical School, Department of Ophthalmology. METHODS: In a retrospective study, we compared performance of 30 first-year ophthalmology residents on an eye surgery simulator to their surgical skills as third-year residents. Variables collected from the eye surgery simulator included scores on the following modules of the simulator (Eyesi, VRmagic, Mannheim, Germany): antitremor training level 1, bimanual training level 1, capsulorhexis level 1 (configured), forceps training level 1, and navigation training level 1. Subsequent surgical performance was assessed using the total number of phacoemulsification cataract surgery cases for each resident, as well as the number performed as surgeon during residency and scores on global rating assessment of skills in intraocular surgery (GRASIS) scales during the third year of residency. Spearman correlation coefficients were calculated between each of the simulator performance and subsequent surgical performance variables. We also compared variables in a small group of residents who needed extra help in learning cataract surgery to the other residents in the study. MAIN OUTCOME MEASURES: Relationships between Eyesi scores early in residency and surgical performance measures in the final year of residency. RESULTS: A total of 30 residents had Eyesi data from their first year of residency and had already graduated so that all subsequent surgical performance data were available. There was a significant correlation between capsulorhexis task score on the simulator and total surgeries (r = 0.745, p = 0.008). There was a significant correlation between antitremor training level 1 (r = 0.554, p = 0.040), and forceps training level 1 (r = 0.622, p = 0.023) with primary surgery numbers. There was a significant correlation between forceps training level 1 (r = 0.811, p = 0.002), and navigation training level 1 (r = 0.692, p =0.013) with total GRASIS score. There was a significant inverse correlation between total GRASIS score and residents in need of extra help (r = -0.358, p =0.003). CONCLUSION: Module scores on an eye surgery simulator early in residency may predict a resident׳s future performance in the operating room. These scores may allow early identification of residents in need of supplemental training in cataract surgery.

Rossi A, Gnesi M, Montomoli C, Chirico G, Malerba L, Merabet LB, Merabet LB, Fazzi E. Neonatal Assessment Visual European Grid (NAVEG): Unveiling neurological risk. Infant Behav Dev 2017;49:21-30.
Saavedra JT, Schwartzman JA, Gilmore MS. Mapping Transposon Insertions in Bacterial Genomes by Arbitrarily Primed PCR. Curr Protoc Mol Biol 2017;118:15.15.1-15.15.15.Abstract

Transposons can be used to easily generate and label the location of mutations throughout bacterial and other genomes. Transposon insertion mutants may be screened for a phenotype as individual isolates, or by selection applied to a pool of thousands of mutants. Identifying the location of a transposon insertion is critical for connecting phenotype to the genetic lesion. In this unit, we present an easy and detailed approach for mapping transposon insertion sites using arbitrarily-primed PCR (AP-PCR). Two rounds of PCR are used to (1) amplify DNA spanning the transposon insertion junction, and (2) increase the specific yield of transposon insertion junction fragments for sequence analysis. The resulting sequence is mapped to a bacterial genome to identify the site of transposon insertion. In this protocol, AP-PCR as it is routinely used to map sites of transposon insertion within Staphylococcus aureus, is used to illustrate the principle. Guidelines are provided for adapting this protocol for mapping insertions in other bacterial genomes. Mapping transposon insertions using this method is typically achieved in 2 to 3 days if starting from a culture of the transposon insertion mutant. © 2017 by John Wiley & Sons, Inc.

Sadaka A, Durand ML, Sisk R, Gilmore MS. Staphylococcus aureus and its Bearing on Ophthalmic Disease. Ocul Immunol Inflamm 2017;25(1):111-121.Abstract

PURPOSE: To review antibiotic resistance associated with S. aureus endophthalmitis and the virulence of S. aureus. METHODS: Review of the current and prospective approaches for treating S. aureus endophthalmitis. RESULTS: Bacterial endophthalmitis remains to be a major threat for vision. S. aureus endophthalmitis specifically, carries a poor visual prognosis making early diagnosis and treatment crucial. Methicillin resistant Staphylococcus aureus (MRSA) endophthalmitis represents a significant number of S. aureus endophthalmitis cases. MRSA with reduced susceptibility to glycopeptide antibiotics such as vancomycin (vancomycin intermediate S. aureus, VISA) have also emerged in the ocular infections, and there has been a rise in S. aureus resistance to new and old generation fluoroquinolones that are commonly used for prophylaxis after intravitreal injections and intraocular surgeries. CONCLUSIONS: With the rise in the number of penetrating procedures in the ophthalmology practice and the parallel rise in antibiotic resistance, prophylaxis and awareness of the antimicrobial resistance profiles remain crucial and the identification of novel antimicrobials is essential.

Saint-Geniez M, Rosales MAB. Eyeing the Fountain of Youth. Cell Stem Cell 2017;20(5):583-584.Abstract
Stem cell-based disease modeling is an emerging technology for the mechanistic study and therapeutic screening of complex ocular pathologies. In this issue of Cell Stem Cell, Saini et al. (2017) show that iPSC-derived RPE cells from age-related macular degeneration patients express increased levels of pro-inflammatory factors that can be normalized by the anti-aging drug nicotinamide.
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.
Satitpitakul V, Kheirkhah A, Crnej A, Hamrah P, Dana R. Determinants of Ocular Pain Severity in Patients With Dry Eye Disease. Am J Ophthalmol 2017;179:198-204.Abstract
PURPOSE: To quantify the severity of ocular pain in patients with dry eye disease (DED) and evaluate factors associated with pain severity. DESIGN: Cross-sectional study. METHODS: Eighty-four patients with DED were asked to score their severity level of ocular pain using a 10-point scale, with 10 indicating the most severe pain. All patients also had a comprehensive ophthalmic assessment including a detailed history, Ocular Surface Disease Index (OSDI) questionnaire, and ocular surface examination. Regression analysis was used to determine the factors associated with ocular pain severity. RESULTS: The mean OSDI score was 45.6 ± 23.1. At least some degree of ocular pain (score >1) was reported by 88.1% of patients, including mild pain (scores 2-4) in 46.4%, moderate pain (scores 5-7) in 34.5%, and severe pain (scores 8-10) in 7.1% of patients. Ocular pain levels significantly correlated with the OSDI score (rs = 0.49, P < .001). Regression analysis showed that the severity of ocular pain had a significant association with use of antidepressant medications (P = .045) but not with tear breakup time, corneal fluorescein staining, or ocular medications used by patients. In patients without pain, a significant correlation was seen between OSDI and corneal fluorescein staining scores (rs = 0.67, P = .01). However, such a correlation was not observed in those with ocular pain. CONCLUSIONS: A majority of patients with DED report some degree of ocular pain, which correlates only moderately with the OSDI score. Severity of ocular pain correlates with nonocular comorbidities such as use of antidepressant medications rather than with clinical signs of DED.
Schuerch K, Woods RL, Lee W, Duncker T, Delori FC, Allikmets R, Tsang SH, Sparrow JR. Quantifying Fundus Autofluorescence in Patients With Retinitis Pigmentosa. Invest Ophthalmol Vis Sci 2017;58(3):1843-1855.Abstract

Purpose: Using quantitative fundus autofluorescence (qAF), we analyzed short-wavelength autofluorescent (SW-AF) rings in RP. Methods: Short-wavelength autofluorescent images (486 nm excitation) of 40 patients with RP (69 eyes) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference. Mean qAF was measured in eight preset segments (qAF8) and in region of interest (ROI)-qAF (200-700 μm) within and external to the borders of the rings at superior, temporal, and inferior sites relative to the ring. For both groups, qAF in patients with RP was compared to age-similar and race/ethnicity-matched healthy eyes at equivalent retinal locations. Results: In 71% of eyes of RP patients, qAF8 acquired internal to the inner border of the ring, was within the 95% confidence interval (CI) for healthy eyes, while in the remaining RP eyes qAF8 was either higher or lower than the CI. Measured external to the ring, qAF8 values were within the CI in 47% of RP eyes with the other eyes being higher or lower. In 28% of sites measured by ROI-qAF within the SW-AF ring, values were above the 95% CI of healthy controls. Region of interest-qAF measured just external to the ring was within the CI of healthy eyes in 74% of locations. The average local elevation in qAF within the ring was approximately 15%. In SD-OCT scans, photoreceptor-attributable reflectivity bands were thinned within and external to the ring. Conclusions: Increased fluorophore production may be a factor in the formation of the SW-AF rings in RP.

Scott NL, Stryjewski TP, Rizzo JF. A Young Woman With Headaches and Blurry Vision. JAMA Ophthalmol 2017;135(6):663-664.
Shaikh M, Miller JB, Papakostas TD, Husain D. The Efficacy and Safety Profile of Ocriplasmin in Vitreomacular Interface Disorders. Semin Ophthalmol 2017;32(1):52-55.Abstract

Vitreomacular adhesion (VMA) describes the adhesion of the posterior hyaloid face to the inner retina in any part of the macula. This can arise after incomplete separation of the posterior vitreous cortex from the macula during vitreous liquefaction. While the VMA may resolve spontaneously, a strong and persistent adhesion can lead to a variety of anatomical changes, including vitreomacular traction (VMT) and macular hole (MH). Both conditions can present with metamorphopsia and decreased vision. In cases of symptomatic VMT and full-thickness macular hole, pars plana vitrectomy has long been the standard of care. However, due to the possible surgical complications and need for postoperative care, many have searched for non-surgical options via pharmacologic vitreolysis. Ocriplasmin (Jetrea, Thrombogenics USA, Alcon/Novartis EU) is a recombinant protease approved in October 2012 for the treatment of symptomatic vitreomacular adhesion (VMA). There have been conflicting views on the safety of Ocriplasmin with changes in the ellipsoid zone seen on OCT and changes seen on ERG indicating photoreceptor damage. This publication reviews the efficacy and safety of ocriplasmin injection for VMA based on previously published data.