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Finn AP, Borboli-Gerogiannis S, Brauner S, Peggy Chang H-Y, Chen S, Gardiner M, Greenstein SH, Kloek C, Miller JW, Chen TC. Assessing Resident Cataract Surgery Outcomes Using Medicare Physician Quality Reporting System Measures. J Surg Educ 2016;73(5):774-9.Abstract

OBJECTIVES: To assess resident cataract surgery outcomes at an academic teaching institution using 2 Physician Quality Reporting System (PQRS) cataract measures, which are intended to serve as a proxy for quality of surgical care. DESIGN: A retrospective review comparing cataract surgery outcomes of resident and attending surgeries using 2 PQRS measures: (1) 20/40 or better best-corrected visual acuity following cataract surgery and (2) complications within 30 days following cataract surgery requiring additional surgical procedures. SETTING: An academic ophthalmology center. PARTICIPANTS: A total of 2487 surgeries performed at the Massachusetts Eye and Ear Infirmary from January 1, 2011 to December 31, 2012 were included in this study. RESULTS: Of all 2487 cataract surgeries, 98.95% achieved a vision of at least 20/40 at or before 90 days, and only 0.64% required a return to the operating room for postoperative complications. Of resident surgeries, 98.9% (1370 of 1385) achieved 20/40 vision at or before 90 days follow-up. Of attending surgeries, 99.0% (1091 of 1102) achieved 20/40 vision at or before 90 days (p = 1.00). There were no statistically significant differences between resident and attending cases regarding postoperative complications needing a return to the operating room (i.e., 0.65%, or 9 of 1385 resident cases vs 0.64%, or 7 of 1102 attending cases; p = 1.00). CONCLUSIONS: Using PQRS Medicare cataract surgery criteria, this study establishes new benchmarks for cataract surgery outcomes at a teaching institution and supplemental measure for assessing resident surgical performance. Excellent cataract outcomes were achieved at an academic teaching institution, with results exceeding Medicare thresholds of 50%. There appears to be no significant difference in supervised trainee and attending cataract surgeon outcomes using 2 PQRS measures currently used by Medicare to determine physician reimbursement and quality of care.

Cestari DM, Gaier ED, Bouzika P, Blachley TS, De Lott LB, Rizzo JF, Wiggs JL, Kang JH, Pasquale LR, Stein JD. Demographic, Systemic, and Ocular Factors Associated with Nonarteritic Anterior Ischemic Optic Neuropathy. Ophthalmology 2016;123(12):2446-2455.Abstract

OBJECTIVE: Nonarteritic anterior ischemic optic neuropathy (NAION) is a devastating ocular condition causing permanent vision loss. Little is known about risk factors for developing this disease. We assessed demographic, systemic, and ocular factors associated with NAION. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Beneficiaries between 40 and 75 years old without NAION at baseline enrolled in a large U.S. managed care network. METHODS: Enrollees were monitored continuously for ≥2 years between 2001 and 2014 to identify those newly diagnosed with NAION (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 377.41). All persons were under ophthalmic surveillance and all cases had ≥1 confirmatory ICD-9-CM code for NAION during follow-up. MAIN OUTCOME MEASURES: Multivariable Cox regression modeling was used to generate hazard ratios (HRs) with 95% confidence intervals (CIs) to describe the statistical relationship between selected demographic characteristics, systemic and ocular conditions, and the hazard of developing NAION. RESULTS: Of 1 381 477 eligible enrollees, 977 (0.1%) developed NAION during a mean ± standard deviation (SD) follow-up of 7.8±3.1 years. The mean ± SD age for NAION cases at the index date was 64.0±9.2 years vs. 58.4±9.4 years for the remainder of the beneficiaries. After adjustment for confounding factors, each additional year older was associated with a 2% increased hazard of NAION (HR = 1.02; 95% CI: 1.01-1.03). Female subjects had a 36% decreased hazard of developing NAION (HR = 0.64; 95% CI: 0.55-0.74) compared with male subjects. Compared with whites, Latinos had a 46% decreased hazard of developing NAION (HR = 0.54; 95% CI: 0.36-0.82), whereas African ancestry was not significantly associated with NAION (HR = 0.91; 95% CI: 0.72-1.15). Systemic diseases associated with NAION included hypertension (HR = 1.62; 95% CI: 1.26-2.07) and hypercoagulable states (HR = 2.46; 95% CI: 1.51-4.00). Although diabetes mellitus (DM) was not significantly associated with NAION compared with those without DM (P = 0.45), patients with end-organ involvement from DM had a 27% increased hazard of NAION relative to those with uncomplicated DM (HR = 1.27; 95% CI: 1.01-1.59). Ocular diseases associated with NAION were age-related macular degeneration (HR = 1.29; 95% CI: 1.08-1.54) and retinal vein occlusion (HR = 3.94; 95% CI: 3.11-4.99). CONCLUSIONS: Our study identified several modifiable risk factors that may be associated with NAION. Should future studies confirm these findings, they may offer opportunities to prevent or treat this debilitating condition.

Reddy DN, Yonekawa Y, Thomas BJ, Nudleman ED, Williams GA. Long-term surgical outcomes of retinal detachment in patients with Stickler syndrome. Clin Ophthalmol 2016;10:1531-4.Abstract

PURPOSE: The aim of the study was to present the long-term anatomical and visual outcomes of retinal detachment repair in patients with Stickler syndrome. PATIENTS AND METHODS: This study is a retrospective, interventional, consecutive case series of patients with Stickler syndrome undergoing retinal reattachment surgery from 2009 to 2014 at the Associated Retinal Consultants, William Beaumont Hospital. RESULTS: Sixteen eyes from 13 patients were identified. Patients underwent a mean of 3.1 surgical interventions (range: 1-13) with a mean postoperative follow-up of 94 months (range: 5-313 months). Twelve eyes (75%) developed proliferative vitreoretinopathy. Retinal reattachment was achieved in 100% of eyes, with ten eyes (63%) requiring silicone oil tamponade at final follow-up. Mean preoperative visual acuity (VA) was 20/914, which improved to 20/796 at final follow-up (P=0.81). There was a significant correlation between presenting and final VA (P<0.001), and patients with poorer presenting VA were more likely to require silicone oil tamponade at final follow-up (P=0.04). CONCLUSION: Repair of retinal detachment in patients with Stickler syndrome often requires multiple surgeries, and visual outcomes are variable. Presenting VA is significantly predictive of long-term VA outcomes.

Gilbert AL, Heidary G. Update on the evaluation of pediatric idiopathic intracranial hypertension. Curr Opin Ophthalmol 2016;Abstract

PURPOSE OF REVIEW: Papilledema associated with idiopathic intracranial hypertension (IIH) may result in irreversible, progressive visual loss. The development of tools for the evaluation of pediatric patients with IIH is particularly relevant as many patients may not be able to comply with the detailed clinical evaluation utilized in adults for the treatment and management of this disease. The purpose of this review is to summarize relevant articles on the diagnostic tools used in evaluation and management of pediatric IIH. RECENT FINDINGS: Studies suggest that characteristic pediatric IIH MRI findings include empty sella turcica, decreased pituitary gland size, optic nerve tortuosity, perioptic subarachnoid space enlargement, posterior globe flattering, and intraocular protrusion of the optic nerve head. On optical coherence tomography (OCT), increased retinal nerve fiber layer and macular thickness may be observed in children with IIH compared with controls. The retinal nerve fiber layer thickness seems to coincide with the severity of papilledema and may be more sensitive than funduscopy for detecting optic nerve head elevation. Research on ultrasound of the optic nerve shows increased size of the optic nerve sheath diameter in pediatric IIH patients, and this may correlate with increased opening pressure on lumbar puncture. SUMMARY: There appears to be characteristic findings on MRI, OCT, and ultrasound studies in pediatric IIH patients. Although ultrasound is rarely used for monitoring these patients nowadays, MRI and OCT can be useful in the evaluation and management of these individuals.

Bowers AR. Driving with homonymous visual field loss: a review of the literature. Clin Exp Optom 2016;99(5):402-18.Abstract

Driving is an important rehabilitation goal for patients with homonymous field defects (HFDs); however, whether or not people with HFDs should be permitted to drive is not clear. Over the last 15 years, there has been a marked increase in the number of studies evaluating the effects of HFDs on driving performance. This review of the literature provides a much-needed summary for practitioners and researchers, addressing the following topics: regulations pertaining to driving with HFDs, self-reported driving difficulties, pass rates in on-road tests, the effects of HFDs on lane position and steering stability, the effects of HFDs on scanning and detection of potential hazards, screening for potential fitness to drive, evaluating practical fitness to drive and the efficacy of interventions to improve driving of persons with HFDs. Although there is clear evidence from on-road studies that some people with HFDs may be rated as safe to drive, others are reported to have significant deficits in skills important for safe driving, including taking a lane position too close to one side of the travel lane, unstable steering and inadequate viewing (scanning) behaviour. Driving simulator studies have provided strong evidence of a wide range in compensatory scanning abilities and detection performance, despite similar amounts of visual field loss. Conventional measurements of visual field extent (in which eye movements are not permitted) do not measure such compensatory abilities and are not predictive of on-road driving performance. Thus, there is a need to develop better tests to screen people with HFDs for visual fitness to drive. We are not yet at a point where we can predict which HFD patient is likely to be a safe driver. Therefore, it seems only fair to provide an opportunity for individualised assessments of practical fitness to drive either on the road and/or in a driving simulator.

Selleck EM, Gilmore MS. Oxygen as a Virulence Determinant in Polymicrobial Infections. MBio 2016;7(4)Abstract

Infections caused by multiple organisms, or polymicrobial infections, are likely more common than is broadly appreciated. Interaction among microbial communities (and with their host) can change the infection landscape by subverting immunity, providing nutrients and inhibiting competing microbes. Stacy et al. (A. Stacy, D. Fleming, R. J. Lamont, K. P. Rumbaugh, and M. Whiteley, mBio 7:e00782-16, 2016, http://dx.doi.org/10.1128/mBio.00782-16) described a novel mechanism that results in synergistic growth of oral microbes Aggregatibacter actinomycetemcomitans and Streptococcus gordonii The authors used whole-genome fitness profiling by transposon sequencing (Tn-seq) to identify genes differentially required for growth in vitro versus in a mono- or coinfection in a thigh abscess model. They found that coinfection with S. gordonii allowed A. actinomycetemcomitans to shift from an anaerobic to an aerobic mode of growth. This shift involved the production of a terminal electron acceptor H2O2 by S. gordonii and increased A. actinomycetemcomitans persistence-an interaction termed "cross-respiration."

Ciolino JB, Ross AE, Tulsan R, Watts AC, Wang R-F, Zurakowski D, Serle JB, Kohane DS. Latanoprost-Eluting Contact Lenses in Glaucomatous Monkeys. Ophthalmology 2016;123(10):2085-92.Abstract

PURPOSE: To assess the ability of latanoprost-eluting contact lenses to lower the intraocular pressure (IOP) of glaucomatous eyes of cynomolgus monkeys. DESIGN: Preclinical efficacy study of 3 treatment arms in a crossover design. PARTICIPANTS: Female cynomolgus monkeys with glaucoma induced in 1 eye by repeated argon laser trabeculoplasty. METHODS: Latanoprost-eluting low-dose contact lenses (CLLO) and high-dose contact lenses (CLHI) were produced by encapsulating a thin latanoprost-polymer film within the periphery of a methafilcon hydrogel, which was lathed into a contact lens. We assessed the IOP-lowering effect of CLLO, CLHI, or daily latanoprost ophthalmic solution in the same monkeys. Each monkey consecutively received 1 week of continuous-wear CLLO, 3 weeks without treatment, 5 days of latanoprost drops, 3 weeks without treatment, and 1 week of continuous-wear CLHI. On 2 consecutive days before initiation of each study arm, the IOP was measured hourly over 7 consecutive hours to establish the baseline IOP. Two-tailed Student t tests and repeated-measures analysis of variance were used for statistical analysis. MAIN OUTCOME MEASURES: Intraocular pressure. RESULTS: Latanoprost ophthalmic solution resulted in IOP reduction of 5.4±1.0 mmHg on day 3 and peak IOP reduction of 6.6±1.3 mmHg on day 5. The CLLO reduced IOP by 6.3±1.0, 6.7±0.3, and 6.7±0.3 mmHg on days 3, 5, and 8, respectively. The CLHI lowered IOP by 10.5±1.4, 11.1±4.0, and 10.0±2.5 mmHg on days 3, 5, and 8, respectively. For the CLLO and CLHI, the IOP was statistically significantly reduced compared with the untreated baseline at most time points measured. The CLHI demonstrated greater IOP reduction than latanoprost ophthalmic solution on day 3 (P = 0.001) and day 5 (P = 0.015), and at several time points on day 8 (P < 0.05). CONCLUSIONS: Sustained delivery of latanoprost by contact lenses is at least as effective as delivery with daily latanoprost ophthalmic solution. More research is needed to determine the optimal continuous-release dose that would be well tolerated and maximally effective. Contact lens drug delivery may become an option for the treatment of glaucoma and a platform for ocular drug delivery.

Thanos S, Oellers P, Meyer Zu Hörste M, Prokosch V, Schlatt S, Seitz B, Gatzioufas Z. Role of Thyroxine in the Development of Keratoconus. Cornea 2016;Abstract

PURPOSE: Keratoconus (KC) is a corneal ectasia whose pathophysiology is still mostly unknown. We investigated whether thyroid gland dysfunction (TGD) is associated with the development of KC. METHODS: We first conducted an epidemiological study, examining the prevalence of TGD among patients with KC. Then, we compared tear thyroxine (T4) in TGD and immunohistochemical staining of its receptors (T4Rs) between patients with KC and controls. The significance of T4 for corneal metabolism was studied in organotypic tissue cultures from monkey corneas. RESULTS: We found that TGD prevalence among patients with KC is 13.6%, which is higher than its prevalence in the general population (about 2%). Tear T4 was higher in KC, and keratocyte T4Rs were elevated in KC compared with controls. Furthermore, core proteins such as collagen and cytokeratins were equally altered both in KC and in the cultured corneas substituted with T4. CONCLUSIONS: Our data implicate a crucial role of T4 in KC pathophysiology, which is most likely mediated by T4Rs.

Rajagopal M, Martin MJ, Santiago M, Lee W, Kos VN, Meredith T, Gilmore MS, Walker S. Multidrug Intrinsic Resistance Factors in Staphylococcus aureus Identified by Profiling Fitness within High-Diversity Transposon Libraries. MBio 2016;7(4)Abstract

UNLABELLED: Staphylococcus aureus is a leading cause of life-threatening infections worldwide. The MIC of an antibiotic against S. aureus, as well as other microbes, is determined by the affinity of the antibiotic for its target in addition to a complex interplay of many other cellular factors. Identifying nontarget factors impacting resistance to multiple antibiotics could inform the design of new compounds and lead to more-effective antimicrobial strategies. We examined large collections of transposon insertion mutants in S. aureus using transposon sequencing (Tn-Seq) to detect transposon mutants with reduced fitness in the presence of six clinically important antibiotics-ciprofloxacin, daptomycin, gentamicin, linezolid, oxacillin, and vancomycin. This approach allowed us to assess the relative fitness of many mutants simultaneously within these libraries. We identified pathways/genes previously known to be involved in resistance to individual antibiotics, including graRS and vraFG (graRS/vraFG), mprF, and fmtA, validating the approach, and found several to be important across multiple classes of antibiotics. We also identified two new, previously uncharacterized genes, SAOUHSC_01025 and SAOUHSC_01050, encoding polytopic membrane proteins, as important in limiting the effectiveness of multiple antibiotics. Machine learning identified similarities in the fitness profiles of graXRS/vraFG, SAOUHSC_01025, and SAOUHSC_01050 mutants upon antibiotic treatment, connecting these genes of unknown function to modulation of crucial cell envelope properties. Therapeutic strategies that combine a known antibiotic with a compound that targets these or other intrinsic resistance factors may be of value for enhancing the activity of existing antibiotics for treating otherwise-resistant S. aureus strains. IMPORTANCE: Bacterial resistance to every major class of antibiotics has emerged, and we are entering a "post-antibiotic era" where relatively minor infections can lead to serious complications or even death. The utility of an antibiotic for a specific pathogen is limited by both intrinsic and acquired factors. Identifying the repertoire of intrinsic resistance factors of an antibiotic for Staphylococcus aureus, a leading cause of community- and hospital-acquired infections, would inform the design of new drugs as well as the identification of compounds that enhance the activity of existing drugs. To identify factors that limit the activity of antibiotics against S. aureus, we used Tn-Seq to simultaneously assess fitness of transposon mutants in every nonessential gene in the presence of six clinically important antibiotics. This work provides an efficient approach for identifying promising targets for drugs that can enhance susceptibility or restore sensitivity to existing antibiotics.

Gaier ED, Torun N. The enigma of nonarteritic anterior ischemic optic neuropathy: an update for the comprehensive ophthalmologist. Curr Opin Ophthalmol 2016;Abstract

PURPOSE OF REVIEW: Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute optic nerve injury, and frequently presents to comprehensive ophthalmologists. We review the typical and atypical clinical features and current literature on various treatment modalities for NAION. RECENT FINDINGS: The epidemiology and clinical presentation of this disease can be variable, making a definitive diagnosis difficult in many cases. In addition, the differential diagnoses for this disorder, although comprising much less prevalent entities, are quite broad and can have substantial systemic implications if these alternatives go unrecognized. NAION has many systemic associations and comorbidities that deserve inquiry when the diagnosis is made. There are currently no widely accepted, evidence-based treatments for NAION. All recommendations made to patients to reduce their risk of sequential eye involvement, including avoidance of potential nocturnal hypotension, erectile dysfunction medication, and treatment of obstructive sleep apnea, have theoretical bases. SUMMARY: NAION is a common cause of acute vision loss in adult and older patients, and thus, comprehensive ophthalmologists need to be able to diagnose and appropriately manage this disorder. We anticipate fruitful results from current and future trials aimed at neuroprotection in the affected eye and prevention of sequential eye involvement.

Saeed HN, Chodosh J. Ocular manifestations of Stevens-Johnson syndrome and their management. Curr Opin Ophthalmol 2016;Abstract

PURPOSE OF REVIEW: Recent advances and outcomes data in the management of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) demonstrate the need for a universal standard of care for patients admitted with the disease. RECENT FINDINGS: Amniotic membrane transplantation, aggressive topical corticosteroids, and lubrication in the acute stage are necessary to prevent or mitigate long-term ocular sequelae. If chronic ocular disease does occur, several interventions can be employed to prevent progressive vision loss and discomfort. The earliest interventions are the ones most likely to prevent chronic complications. SUMMARY: The literature overwhelmingly describes acute intervention for ocular involvement in SJS/TEN as improving long-term outcomes. All patients admitted for SJS/TEN or suspicion of SJS/TEN should be evaluated and then closely followed by ophthalmologists. As the disease progresses, the interventions needed for visual rehabilitation become more invasive and higher risk.

Gromova A, Voronov DA, Yoshida M, Thotakura S, Meech R, Dartt DA, Makarenkova HP. Lacrimal Gland Repair Using Progenitor Cells. Stem Cells Transl Med 2016;Abstract

: In humans, the lacrimal gland (LG) is the primary contributor to the aqueous layer of the tear film. Production of tears in insufficient quantity or of inadequate quality may lead to aqueous-deficiency dry eye (ADDE). Currently there is no cure for ADDE. The development of strategies to reliably isolate LG stem/progenitor cells from the LG tissue brings great promise for the design of cell replacement therapies for patients with ADDE. We analyzed the therapeutic potential of epithelial progenitor cells (EPCPs) isolated from adult wild-type mouse LGs by transplanting them into the LGs of TSP-1(-/-) mice, which represent a novel mouse model for ADDE. TSP-1(-/-) mice are normal at birth but progressively develop a chronic form of ocular surface disease, characterized by deterioration, inflammation, and secretory dysfunction of the lacrimal gland. Our study shows that, among c-kit-positive epithelial cell adhesion molecule (EpCAM(+)) populations sorted from mouse LGs, the c-kit(+)dim/EpCAM(+)/Sca1(-)/CD34(-)/CD45(-) cells have the hallmarks of an epithelial cell progenitor population. Isolated EPCPs express pluripotency factors and markers of the epithelial cell lineage Runx1 and EpCAM, and they form acini and ducts when grown in reaggregated three-dimensional cultures. Moreover, when transplanted into injured or "diseased" LGs, they engraft into acinar and ductal compartments. EPCP-injected TSP-1(-/-) LGs showed reduction of cell infiltration, differentiation of the donor EPCPs within secretory acini, and substantial improvement in LG structural integrity and function. This study provides the first evidence for the effective use of adult EPCP cell transplantation to rescue LG dysfunction in a model system. SIGNIFICANCE: In humans, the lacrimal gland is the primary contributor to the aqueous layer of the tear film. Damage or inflammation of the lacrimal gland may lead to severe aqueous-deficiency dry eye and corneal disease. Endogenous lacrimal gland epithelial cell progenitors (EPCPs) injected into the gland of mouse model of human Sjögren's syndrome TSP-1(-/-) mice resulted in long-term engraftment and markedly improved structure and function of "diseased" lacrimal gland. This study demonstrates, for the first time, that EPCPs can mediate functional recovery of the lacrimal gland in a Sjögren's syndrome mouse model. These data establish proof of concept that endogenous stem/progenitor cell transplantation may be used to treat human lacrimal gland chronic inflammation.

Chun BY, Rizzo JF. Dominant optic atrophy: updates on the pathophysiology and clinical manifestations of the optic atrophy 1 mutation. Curr Opin Ophthalmol 2016;Abstract

PURPOSE OF REVIEW: Review recent advances in clinical and experimental studies of dominant optic atrophy (DOA) to better understand the complexities of pathophysiology caused by the optic atrophy 1 (OPA1) mutation. RECENT FINDINGS: DOA is the most commonly diagnosed inherited optic atrophy, causing progressive bilateral visual loss that begins early in life. During the past 25 years, there has been substantial progress in the understanding of the clinical, genetic, and pathophysiological basis of this disease. The histopathological hallmark of DOA is the primary degeneration of retinal ganglion cells, preferentially in the papillomacular bundle, which results temporal optic disc pallor and cecocentral scotomata in patients with DOA. Loss of OPA1 protein function by OPA1 gene mutations causes mitochondrial dysfunction because of the loss of mitochondrial fusion, impaired mitochondrial oxidative phosphorylation, increases in reactive oxygen species, and altered calcium homeostasis. These factors lead to apoptosis of retinal ganglion cells by a haploinsufficiency mechanism. SUMMARY: Improved understanding of the pathophysiology of DOA provides insights that can be used to develop therapeutic approaches to the DOA.

Shekhar K, Lapan SW, Whitney IE, Tran NM, Macosko EZ, Kowalczyk M, Adiconis X, Levin JZ, Nemesh J, Goldman M, McCarroll SA, Cepko CL, Regev A, Sanes JR. Comprehensive Classification of Retinal Bipolar Neurons by Single-Cell Transcriptomics. Cell 2016;166(5):1308-1323.e30.Abstract

Patterns of gene expression can be used to characterize and classify neuronal types. It is challenging, however, to generate taxonomies that fulfill the essential criteria of being comprehensive, harmonizing with conventional classification schemes, and lacking superfluous subdivisions of genuine types. To address these challenges, we used massively parallel single-cell RNA profiling and optimized computational methods on a heterogeneous class of neurons, mouse retinal bipolar cells (BCs). From a population of ∼25,000 BCs, we derived a molecular classification that identified 15 types, including all types observed previously and two novel types, one of which has a non-canonical morphology and position. We validated the classification scheme and identified dozens of novel markers using methods that match molecular expression to cell morphology. This work provides a systematic methodology for achieving comprehensive molecular classification of neurons, identifies novel neuronal types, and uncovers transcriptional differences that distinguish types within a class.

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