The impact of case complexity in resident-performed cataract surgery.

PURPOSE: To evaluate the association of capsular dye and/or a pupil expansion device (PED) usage on the rate of major complication in resident-performed cataract extraction. METHODS: Resident cataract surgeries between 2016 and 2019 were included. The primary outcomes were anterior or posterior vitrectomy (AVx and PPVx). Cases were grouped by the use of a PED and/or capsular staining along with additional preoperative risk factors. RESULTS: Of the 1,348 cases, 371 (27.5%) documented capsular staining ("Dye-only"), 91 (6.8%) required pupil expansion ("PED-only"), and 100 (7.4%) used both capsular stain and a PED ("Both"). The remainder of cases (n=786, 58.3%) were classified as "Routine." Compared to the "Routine" group, "PED-only" and "Both" had significantly higher odds of an AVx (OR=2.90, 95% CI 1.27-6.19, P=0.01) and/or a PPVx (OR=2.33, 95% CI 1.07-5.12, P=0.04). Among the PPVx cases, the "PED-only" group has significantly higher odds than "Routine" and "Dye-only" (OR=4.64, 95% CI 1.68-12.79, P=0.01; and OR=6.48, 95% CI 1.7-25.0, P=0.005, respectively). In case-control analysis, vision, intraocular pressure, anterior chamber depth, axial length, cataract type, or severity had no significant overall association with complication. When compared to nuclear sclerotic cataract, posterior subcapsular (OR=7.86, 95% CI 1.46-42.47, P=0.017) and white/mature cataracts (OR=3.05, 95% CI 1.1-8.43, P=0.032) had increased odds of complication. CONCLUSION: Resident-performed cataract surgery frequently required capsular staining and/or a PED, and intuitively, these cases had a higher overall complication rate compared to routine cases. However, the use of a PED independently was associated with significantly higher odds of a major complication requiring an unplanned vitrectomy independent of predisposing factors.

Dealing with floppy iris syndrome.

PURPOSE OF REVIEW: The aim of this study was to review and summarize recent findings and advancements regarding intraoperative floppy iris syndrome (IFIS). Although many improvements have been made for the management of IFIS, it remains a challenging condition for surgeons. An understanding of the syndrome as well as the multitude of tools to mitigate risk of complication is important for surgeons operating on high-risk patients. RECENT FINDINGS: A variety of management approaches have been modified and improved or further supported with new data, such as intracameral compounds, intraoperative devices and surgical techniques. SUMMARY: An understanding of risk factors is important for the identification of at-risk patients. A variety of approaches can greatly reduce incidence of IFIS complications. Multiple management strategies should be utilized to further reduce risk during these difficult surgeries.

Vision Loss Secondary to Facial and Periorbital Steroid Injection: A Systematic Review.

PURPOSE: The risk of ophthalmic and retinal artery occlusions following facial and periorbital steroid injection has not been explored. This systematic review examines the prevalence, risk factors, and treatment outcomes of steroid-induced vision losses. METHODS: A literature search in Evidence Based Medicine Reviews, MEDLINE, Embase, Pubmed, ClinicalTrials, and WHO ICTRP was performed for vision loss following facial and periorbital corticosteroid injections through July 2020. RESULTS: Of 35 case reports, series, and reviews, 49 patients (56 eyes) with steroid-induced vision loss were analyzed. Injection sites predominantly involved the nose (45%) and periocular regions (10%). The most common type of steroid is triamcinolone (54%). Most cases were unilateral, except 7 cases of bilateral vision losses, 4 of which resulted from unilateral steroid injection. Symptoms were reported during or immediately after injections in 49% of cases. Most occlusions occurred in the ophthalmic (53%) or central retinal artery (33%). Vision most commonly presented as no light perception (37%), and 90% were 20/200 or worse. Final visual outcomes varied from 20/200 or worse (56%), 20/40 or better (30%), to in between (13%). CONCLUSION: Most vision losses resulted from steroid injections in the nasal and periorbital area. Triamcinolone was the most common offending agent, likely due to large particle size, low solubility, and extensive particle aggregation. Dexamethasone has the opposite pharmacologic properties and has never been reported in association with vascular occlusion related vision loss. Careful steroid selection, injection techniques, and treatment strategies should be considered to prevent and treat artery occlusion.

Building Your Brand: Analysis of Successful Oculoplastic Surgeons on Social Media.

PURPOSE: To determine the impact of social media content from oculoplastic surgeon-held accounts on public engagement. METHODS: This study analyzed successful Instagram accounts (defined by >500 followers as of May 2019) held by American Society of Ophthalmic Plastic Reconstruction Surgery members. Each account's 20 most and 20 least successful posts (based on number of likes) were characterized by the post's subject, location, media type, and tag usage. Posts were then analyzed using a web-based application that calculates the engagement level of Instagram users with the selected post. RESULTS: A total of 4,812 posts were analyzed from 37 Instagram accounts. Of these American Society of Ophthalmic Plastic Reconstruction Surgery members, the majority were men (67.6%, n = 25) in private practice solely (70.3%, n = 26). Numerous post characteristics, like content and media type, impacted success in a statistically significant manner; for example, public engagement rose when featuring the posting doctor, especially when smiling and wearing a white coat. Meanwhile, posts featuring an office procedure had a negative effect. Formatting was also found to contribute to success. For example, photographs were preferred over videos, while multiple images were best presented sequentially as a carousel (with the viewer swiping through the series) rather than in a large collage. Use of tags (hashtags, accounts, and locations) were associated with increased engagement. CONCLUSIONS: Social media is an important communication and marketing tool, especially in esthetic fields like oculoplastics. Guidelines for success are presented in this study; content, location, subject, media type, and tags statistically significantly impact public engagement.The influence of social media is rapidly growing and can be strategically harnessed by oculoplastic surgeons to educate both patients and healthcare providers, collaborate with colleagues, and for referrals and marketing.Supplemental Digital Content is available in the text.

The influence of social media is rapidly growing and can be strategically harnessed by oculoplastic surgeons to educate both patients and healthcare providers, collaborate with colleagues, and for referrals and marketing. Supplemental Digital Content is available in the text.

A Systematic Analysis of the Impact of an Ambulatory Ophthalmology Urgent Care Clinic.

Importance A same-day ophthalmic urgent care clinic can provide efficient eye care, a rich educational environment, and can improve patient experience. Objective The aim of this study was to systematically evaluate volume, financial impact, care metrics, and the breadth of pathology of urgent new patient encounters based on their site of initial presentation. Design, Setting, and Participants A retrospective analysis was performed on consecutive urgent new patient evaluations in our same-day triage clinic at the Henkind Eye Institute at Montefiore Medical Center between February 2019 and January 2020. The cohort of patients who presented directly to this urgent care clinic were referred to as the "TRIAGE" group. Patients who initially presented to an emergency department (ED), and were subsequently referred to our triage clinic, are referred to as the "ED + TRIAGE" group. Main Outcomes and Measures Visits were evaluated on a variety of metrics, including diagnosis, duration, charge, cost, and revenue. Furthermore, return to the ED or inpatient admission was documented. Results Of 3,482 visits analyzed, 2,538 (72.9%) were in the "TRIAGE" group. Common presenting diagnoses were ocular surface disease ( n = 486, 19.1%), trauma ( n = 342, 13.5%; most commonly surface abrasion n = 195, 7.7%), and infectious conjunctivitis ( n = 304, 12.0%). Patients in the "TRIAGE" group, on average, were seen 184.6% faster (158.2 vs. 450.2 minutes) than patients in the "ED + TRIAGE" group ( p < 0.001). The "ED + TRIAGE" group were furthermore found to generate 442.1% higher charges ($870.20 vs. 4717.70) and were associated with 175.1% higher cost ($908.80 vs. 330.40) per patient. The hospital was found to save money when noncommercially insured patients with ophthalmic complaints presented to the triage clinic instead of the ED. Patients seen in the triage clinic had a low rate of readmission to the ED ( n = 42, 1.2%). Conclusions and Relevance A same-day ophthalmology triage clinic provides efficient care, while providing a rich learning environment for residents. Less wait time with direct access to subspecialist care can help improve quality, outcome, and satisfaction metrics.

Effect of simulated lenticular debris on corneal endothelial cells: experimental study in rabbit eyes.

PURPOSE: To evaluate mechanical damage of simulated lenticular debris on corneal endothelial cells during phacoemulsification. SETTING: University setting, Salt Lake City, Utah. DESIGN: Experimental study. METHODS: 12 New Zealand rabbits underwent bilateral surgery. After incision, 10 1.0 mm beads were injected into the anterior chamber of test eyes to simulate lenticular debris. A balanced salt solution was injected into the contralateral eyes with the same injector. The Intrepid Balanced Tip of the Centurion Ozil handpiece was inserted into the anterior chamber, and 60% torsional ultrasound was applied for 20 seconds with 50 mL/min flow, 70 mm Hg intraocular pressure, and 600 mm Hg vacuum. Cumulative dissipated energy (CDE) was noted. After euthanasia and enucleation, the corneas were removed, stained with trypan blue/alizarin red, and photographed in a standardized manner (×400 photographs from 5 specific areas and 1 overview photograph from each corneal button). The ImageJ program was used to evaluate cell damage and loss in the photographs. RESULTS: CDE was 4.64 ± 0.19 for test eyes with beads and 4.66 ± 0.17 for control eyes without beads ( P = .58). The percentage of intact cells was statistically higher in the control group ( P = .0005), whereas the percentages of damaged and lost cells were statistically higher in the test group ( P = .0010 and .0005, respectively). This was observed in the analysis of the ×400 photographs and overview photographs. CONCLUSIONS: This study suggests that lenticular debris swirling around the anterior chamber may cause significant damage to the corneal endothelium, providing further insight on mechanisms of damage during phacoemulsification.

Corneal endothelium protection provided by ophthalmic viscosurgical devices during phacoemulsification: experimental study in rabbit eyes.

PURPOSE: To compare the protection of the corneal endothelium provided by a cohesive and a dispersive ophthalmic viscosurgical device (OVD) against damage from torsional ultrasound and simulated lenticular debris during phacoemulsification. SETTING: University setting, Salt Lake City, Utah. DESIGN: Experimental study. METHODS: 15 New Zealand rabbits were included. After incision, each eye received cohesive or dispersive OVD (ProVisc or Viscoat). 10 1.0 mm beads were injected to simulate lenticular debris. The Intrepid Balanced tip (Centurion Ozil handpiece) was inserted into the anterior chamber, and 60% torsional ultrasound with 50 mL/min flow, 70 mm Hg intraocular pressure, and 600 mm Hg vacuum was applied (20 seconds). Cumulative dissipated energy (CDE) was noted. After euthanasia and enucleation, corneas were removed, stained with trypan blue/alizarin red, and photographed (5 ×400 magnification photos and 1 overview photograph from each cornea). ImageJ was used to evaluate cell damage and loss. RESULTS: CDE was 4.70 ± 0.26 and 4.64 ± 0.10 in the cohesive and dispersive OVD groups, respectively ( P = .8647). The analysis of the ×400 photographs showed that the percentage of intact cells was statistically higher in the dispersive OVD group ( P = .0002), whereas the percentages of damaged and lost cells were statistically higher in the cohesive OVD group ( P = .0002 and .0059, respectively). Overview photographs revealed the presence of residual OVD on the endothelium, especially in the dispersive group. CONCLUSIONS: In this experimental study using a rabbit model, the corneal endothelium protection provided by the dispersive OVD was superior to that provided by the cohesive OVD.

Fgd5 is a Rac1-specific Rho GEF that is selectively inhibited by aurintricarboxylic acid.

Rho proteins are signalling molecules that control cellular dynamics, movement and morphological changes. They are activated by Rho guanine-nucleotide exchange factors (Rho GEFs) that transduce upstream signals into Rho-mediated activation of downstream processes. Fgd5 is a Rho GEF involved in angiogenesis and its target Rho protein for this process has been linked to Cdc42 activation. Here, we examined the function of purified Fgd5, specifically, which Rho proteins it activates and pinpoint the structural domains required for enzymatic activity. Using a GEF enzyme assay, we found that purified Fgd5 showed preferential activation of Rac1 and direct binding of Rac1 in pull-down and co-immunoprecipitation assays. Structural comparisons showed that the Fgd5 DH domain is highly similar to the Rac1 GEF, TrioN, supporting a role for Fgd5 as a Rac1 GEF. Compounds that bind to purified Fgd5 DH-PH protein were identified by screening a small molecule library via surface plasmon resonance. The effects of eleven ligands were further examined for their ability to inhibit the Fgd5 GEF enzymatic activity and Rac1 interaction. From these studies, we found that the compound aurintricarboxylic acid, and to a lesser extent mitoxantrone dihydrochloride, inhibited both Fgd5 GEF activation of Rac1 and their interaction. Aurintricarboxylic acid had no effect on the activity or binding of the Rac1 GEF, TrioN, thus demonstrating the feasibility of selectively disrupting Rho GEF activators. Abbreviations: a.a.: amino acid; ATA: aurintricarboxylic acid; DH: Dbl homology; DOCK: dictator of cytokinesis; Fgd: faciogenital dysplasia; GEF: guanine-nucleotide exchange factor; GST: glutathione S-transferase; LOPAC: library of pharmacologically active compounds; PH: pleckstrin homology; PDB: protein data bank; s.e.m.: standard error of the mean; SPR: surface plasmon resonance.

Expression of immune checkpoints on circulating tumor cells in men with metastatic prostate cancer.

BACKGROUND: A subset of men with metastatic prostate cancer (mPC) responds to immune checkpoint inhibitors, and there is an unmet need to predict those most likely to benefit. We characterized circulating tumor cells (CTCs) for expression of immune checkpoint ligands in men with mPC as a non-invasive biomarker of immune evasion and immunotherapy benefit. METHODS: Three cohorts of patients were enrolled: 1) men with mCRPC starting abiraterone acetate/prednisone or enzalutamide (pre-ARSI), 2) men with mCRPC who were progressing on enzalutamide or abiraterone acetate/prednisone (post-ARSI), and 3) men with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy. CTCs were captured using the CellSearch® system and stained for PD-L1, PD-L2, B7-H3, and CTLA-4 at baseline, on treatment, and disease progression. Summary statistics on mean CTCs per cohort, as well as rates of ligand positivity were used to analyze CTCs by cohort and by timepoint. RESULTS: Men in all cohorts and timepoints had prevalent CTC B7-H3 expression (> 80%). We found evidence for CTC PD-L1 expression across disease states, in which > 1 positive CTC or > 50% of CTCs were positive for PD-L1 in 40 and 30% of men with mHSPC, respectively, 60 and 20% of men with mCRPC pre-ARSI, and 70 and 30% of men with mCRPC post-ARSI. CTC PD-L2 expression was present in 20-40% of men in each disease state, while CTC CTLA-4 expression was rare, present in 20% of men with mCRPC pre-ARSI and 10% of men with mCRPC post-ARSI or with mHSPC. CTC immune checkpoint expression was heterogeneous within/between men and across disease states. CONCLUSIONS: We have identified that CTCs from men with mPC heterogeneously express immune checkpoints B7-H3, PD-L1, PD-L2, and CTLA-4, and the detection of these immune checkpoints may enable monitoring on immunotherapy.

Persistent Endocrine-Disrupting Chemicals and Fatty Liver Disease.

PURPOSE OF REVIEW: Non-alcoholic fatty liver disease (NAFLD) is the most prominent chronic liver disease in Western countries, affecting approximately 25% of the population worldwide. Sex-specific differences in the development of NAFLD are apparent. While obesity and insulin resistance are major contributors to the increasing prevalence of NAFLD, a growing body of literature suggests that exposure to persistent endocrine-disrupting chemicals (pEDCs) may also play a role. This review summarizes recent (2011 and later) scientific literature investigating exposures to pEDCs, specifically persistent organic pollutants (POPs), and NAFLD, with a focus on sex-specific associations. RECENT FINDINGS: The overwhelming majority of studies were conducted in single-sex animal models and provide biological evidence that exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin polychlorinated biphenyls, and other POPs or POP mixtures are negatively associated with liver health. There were four cross-sectional epidemiological studies in humans that reported associations for several POPs, including polychlorinated biphenyls and perfluorinated chemicals, with elevated liver enzymes. Only one of these studies, using a sample of gastric bypass surgery patients, examined sex-specific associations of POPs and liver enzymes, finding adverse associations among women only. The noticeable lack of studies investigating how differences (i.e., biochemical, physiological, and behavioral) between men and women may influence associations of pEDCs and NAFLD represents a large research gap in environmental health. Sexual dimorphism in metabolic processes throughout the body, including the liver, is established but often overlooked in the designs and analyses of studies. Other factors identified in this review that may also act to modulate associations of environmental chemicals and NAFLD are reproductive status and dietary nutrient intakes, which also remain understudied in the literature. Despite knowledge of sexual dimorphism in the actions of pEDCs, as well as in metabolic processes related to NAFLD development, few experimental or epidemiological studies have investigated sex-dependent associations. Future studies, especially those in humans, should be designed to address this research need. Consideration of other factors, such as reproductive status, dietary intakes, and mixtures of chemicals with varying endocrine-disrupting capabilities, should be explored.

Snail promotes resistance to enzalutamide through regulation of androgen receptor activity in prostate cancer.

Treatment with androgen-targeted therapies can induce upregulation of epithelial plasticity pathways. Epithelial plasticity is known to be important for metastatic dissemination and therapeutic resistance. The goal of this study is to elucidate the functional consequence of induced epithelial plasticity on AR regulation during disease progression to identify factors important for treatment-resistant and metastatic prostate cancer. We pinpoint the epithelial plasticity transcription factor, Snail, at the nexus of enzalutamide resistance and prostate cancer metastasis both in preclinical models of prostate cancer and in patients. In patients, Snail expression is associated with Gleason 9-10 high-risk disease and is strongly overexpressed in metastases as compared to localized prostate cancer. Snail expression is also elevated in enzalutamide-resistant prostate cancer cells compared to enzalutamide-sensitive cells, and downregulation of Snail re-sensitizes enzalutamide-resistant cells to enzalutamide. While activation of Snail increases migration and invasion, it is also capable of promoting enzalutamide resistance in enzalutamide-sensitive cells. This Snail-mediated enzalutamide resistance is a consequence of increased full-length AR and AR-V7 expression and nuclear localization. Downregulation of either full-length AR or AR-V7 re-sensitizes cells to enzalutamide in the presence of Snail, thus connecting Snail-induced enzalutamide resistance directly to AR biology. Finally, we demonstrate that Snail is capable of mediating-resistance through AR even in the absence of AR-V7. These findings imply that increased Snail expression during progression to metastatic disease may prime cells for resistance to AR-targeted therapies by promoting AR activity in prostate cancer.