Assessing an Exposure Keratopathy Prevention Strategy in Mechanically Ventilated Patients: A Retrospective Study.

OBJECTIVE: Patients who are intubated and sedated are at risk for developing exposure keratopathy, which can lead to permanent vision loss. This retrospective study assesses the incidence of exposure keratopathy (EK) in intensive care unit (ICU) patients before and after implementation of an EK Prevention Order Set. METHODS: At one tertiary care hospital (Bronx, NY), an "Exposure Keratopathy Prevention Order Set" was implemented to ameliorate this risk which included the application of white petrolatum-mineral oil lubricating ointment every 6 hours in both eyes. This retrospective chart review study analyzed the incidence of EK diagnosis before and after implementation of this EK Prevention Order Set. Patients who were on mechanical ventilation at the time of ophthalmology consult request between January 1, 2021, and December 31, 2021, were included. Ophthalmology consult notes of patients with EK diagnosis were reviewed for details regarding the consult request, examination findings, diagnosis, and treatment plan. RESULTS: There were 247 and 361 ventilated ICU patients before and after the order set, respectively. The number of ophthalmology consults decreased slightly after the order set from 15 of 247 to 20 of 361 ventilated patients. In addition, the rate of EK among ventilated patients decreased from 4.5% (11 of 247 patients over 151 days) to 2.2% (8 of 361 patients over 212 days; P =0.154) with a risk ratio of 0.50 (95% CI 0.20-1.22). CONCLUSION: The number of patients diagnosed with EK trended down after implementation of the EK Prevention Order Set.

Implantable Electronic Cardiovascular Device Complications Related to Electrocautery During Ophthalmology Surgery: A Systematic Review.

PURPOSE: Implantable electronic cardiovascular device such as cardiac pacemakers and implantable defibrillators are common life-saving devices. Device-related complications can arise when undergoing surgical interventions with electrosurgical tools due to electromagnetic interference, based on electrocautery type, implantable electronic cardiovascular device type, electrocautery location, and a number of other factors. The risk of device-related complications due to electrocautery in oculoplastic surgery has not been established. This systematic literature review assesses prevalence, risk factors, and outcomes of electrocautery-related device complications in oculoplastic surgery. METHODS: Systematic literature review followed Preferred Reporting Items for Systematic and Meta-Analysis guidelines and used the search terms "pacemaker," "implantable cardioverter defibrillator," "electrocautery," "cautery," and "electrosurgery" through June 2022. Inclusion criteria were full-text articles, discussing ocular, oculoplastic, or other facial surgery. Exclusion criteria were non-English language or surgery focused on other parts of the body. Full-text manuscripts of identified articles were reviewed and relevant data were extracted. RESULTS: Twelve studies met inclusion criteria. Two studies were level I and II evidence, while 10 studies were level III or IV. There were no reports of electromagnetic interference with bipolar cautery use. With monopolar cautery use, cases of electromagnetic interference were reported, but without related significant morbidity or mortality. Safety recommendations to minimize electrical flow through the implantable electronic cardiovascular device are described. CONCLUSIONS: There were no reports of implantable electronic cardiovascular device-related complications from bipolar or thermocautery use in ophthalmic or oculoplastic surgeries. Monopolar have been associated with electromagnetic interference, but additional preoperative and perioperative measures can be taken to mitigate this risk.

Impact of the COVID-19 Pandemic on Quantity and Characteristics of Ophthalmology Consults.

Purpose: To assess the COVID-19 exposure risk to consulting ophthalmologists and the pandemic effect on consultations at one of the most impacted hospital systems in New York. Methods: In a retrospective, cross-sectional study, ophthalmology consult notes and COVID-19 test results were collected from the electronic medical record from February to May in 2019 and 2020. Results: Of 2,215 total notes analyzed, consults decreased from 1,374 to 841 between years (p = 0.0002). In 2020, 22.5% of all consults were COVID tested and 2.4% were positive within 2 weeks of in-person evaluation. In 2020, 1.8% of consults were electronic. Ventilated patients increased between years (7.5% to 10.8%; p = 0.04). Conclusions: Although consultations decreased during the Spring 2020 peak, the majority (98.2%) remained as in-person evaluations. While few patients tested COVID positive, this likely reflects the limited availability of testing early in the pandemic. Consulting ophthalmologists remained at high risk of COVID-19 exposure during the pandemic peak.

#OculoplasticsandSocialMedia: a review of social media in oculoplastics and relevant subspecialties.

The permeation of social media into life almost goes without bounds and medicine is no exception. While social media holds great potential for physicians and medicine, it also comes with concurrent spread of disinformation. This increases the importance of evidence-based information from qualified physicians on social media.Although the definition of social media is broad, in general, it refers to the use of web-based platforms to connect one human to another. In oculoplastic surgery, these relationships can be physician to physician, physician to patient, patient to patient, and vendor to physician. These relationships mostly involve education, social support, and advertising, but can also include research and government advocacy. The purpose of this review is to evaluate the current utilization of social media in oculoplastic surgery and relevant subspecialties.

Benign fibrous histiocytoma of the medial rectus muscle.

We report the case of a healthy 17-year-old girl who underwent surgery for excision of a painless, rapidly enlarging subconjunctival mass. The mass was found to be tightly adherent to the medial rectus muscle of the left eye, requiring extensive dissection. Histopathology revealed a mass of bland and foamy spindle cells in a storiform pattern that was positive for CD68, PGM1, and factor XIIIA and negative for S-100. The clinical and histopathologic findings are consistent with benign fibrous histiocytoma.

Expanding Understanding of Thyroid Eye Disease Manifestations to Include Hispanic and Black Patients.

PURPOSE: Knowledge of thyroid eye disease (TED) is based on predominantly Caucasian populations. To date, no studies in the United States examine the presentation in Black and Hispanic patients. The purpose of this study is to introduce the presentation of TED in two previously undescribed populations. METHODS: This is a retrospective, cross-sectional, chart review study of patients with TED at a tertiary center using the Strengthening the Reporting of Observational Studies in Epidemiology checklist. The main outcome measure for severity was the European Group on Graves' Orbitopathy 2016 Severity Scale. RESULTS: Of the 2905 charts reviewed, 99 met the inclusion criteria. The mean age was 51 (standard deviation 16) years with 78% women. Race was 49.4% Black, 39.1% Hispanic, 9.2% Caucasian, and 2.3% Asian. Smoking rates were 25% current smokers and 14% former smokers. Manifestations were proptosis (94% Hispanic and 91% Black), eyelid retraction (85% Hispanic and 79% Black), extraocular muscle (EOM) restriction (79% Hispanic and 63% Black), eyelid edema (41% Hispanic and 30% Black), chemosis (24% Hispanic and 14% Black), and optic neuropathy (18% Hispanic and 9% Black). Overall, disease severity was 22% mild, 65% moderate to severe, and 13% sight-threatening. Older patients had increased rates of optic neuropathy (P = 0.04). Younger patients had increased rates of proptosis (P = 0.02). Socioeconomic status was not associated with disease severity (P = 0.67). CONCLUSION: Hispanic and Black patients with TED presented with higher than previously established rates of proptosis, EOM restriction, and optic neuropathy. Including research of different races broadens understanding of presentation and management, improving patient outcomes.

A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution.

Combinatorial inhibition of effector and feedback pathways is a promising treatment strategy for KRAS mutant cancers. However, the particular pathways that should be targeted to optimize therapeutic responses are unclear. Using CRISPR/Cas9, we systematically mapped the pathways whose inhibition cooperates with drugs targeting the KRAS effectors MEK, ERK, and PI3K. By performing 70 screens in models of KRAS mutant colorectal, lung, ovarian, and pancreas cancers, we uncovered universal and tissue-specific sensitizing combinations involving inhibitors of cell cycle, metabolism, growth signaling, chromatin regulation, and transcription. Furthermore, these screens revealed secondary genetic modifiers of sensitivity, yielding a SRC inhibitor-based combination therapy for KRAS/PIK3CA double-mutant colorectal cancers (CRCs) with clinical potential. Surprisingly, acquired resistance to combinations of growth signaling pathway inhibitors develops rapidly following treatment, but by targeting signaling feedback or apoptotic priming, it is possible to construct three-drug combinations that greatly delay its emergence.

Melanoma Therapeutic Strategies that Select against Resistance by Exploiting MYC-Driven Evolutionary Convergence.

Diverse pathways drive resistance to BRAF/MEK inhibitors in BRAF-mutant melanoma, suggesting that durable control of resistance will be a challenge. By combining statistical modeling of genomic data from matched pre-treatment and post-relapse patient tumors with functional interrogation of >20 in vitro and in vivo resistance models, we discovered that major pathways of resistance converge to activate the transcription factor, c-MYC (MYC). MYC expression and pathway gene signatures were suppressed following drug treatment, and then rebounded during progression. Critically, MYC activation was necessary and sufficient for resistance, and suppression of MYC activity using genetic approaches or BET bromodomain inhibition was sufficient to resensitize cells and delay BRAFi resistance. Finally, MYC-driven, BRAFi-resistant cells are hypersensitive to the inhibition of MYC synthetic lethal partners, including SRC family and c-KIT tyrosine kinases, as well as glucose, glutamine, and serine metabolic pathways. These insights enable the design of combination therapies that select against resistance evolution.

Targeting MCL-1/BCL-XL Forestalls the Acquisition of Resistance to ABT-199 in Acute Myeloid Leukemia.

ABT-199, a potent and selective small-molecule antagonist of BCL-2, is being clinically vetted as pharmacotherapy for the treatment of acute myeloid leukemia (AML). However, given that prolonged monotherapy tends to beget resistance, we sought to investigate the means by which resistance to ABT-199 might arise in AML and the extent to which those mechanisms might be preempted. Here we used a pathway-activating genetic screen to nominate MCL-1 and BCL-XL as potential nodes of resistance. We then characterized a panel of ABT-199-resistant myeloid leukemia cell lines derived through chronic exposure to ABT-199 and found that acquired drug resistance is indeed driven by the upregulation of MCL-1 and BCL-XL. By targeting MCL-1 and BCL-XL, resistant AML cell lines could be resensitized to ABT-199. Further, preemptively targeting MCL-1 and/or BCL-XL alongside administration of ABT-199 was capable of delaying or forestalling the acquisition of drug resistance. Collectively, these data suggest that in AML, (1) the selection of initial therapy dynamically templates the landscape of acquired resistance via modulation of MCL-1/BCL-XL and (2) appropriate selection of initial therapy may delay or altogether forestall the acquisition of resistance to ABT-199.

PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation.

Therapies that efficiently induce apoptosis are likely to be required for durable clinical responses in patients with solid tumors. Using a pharmacological screening approach, we discovered that combined inhibition of B cell lymphoma-extra large (BCL-XL) and the mammalian target of rapamycin (mTOR)/4E-BP axis results in selective and synergistic induction of apoptosis in cellular and animal models of PIK3CA mutant breast cancers, including triple-negative tumors. Mechanistically, inhibition of mTOR/4E-BP suppresses myeloid cell leukemia-1 (MCL-1) protein translation only in PIK3CA mutant tumors, creating a synthetic dependence on BCL-XL This dual dependence on BCL-XL and MCL-1, but not on BCL-2, appears to be a fundamental property of diverse breast cancer cell lines, xenografts, and patient-derived tumors that is independent of the molecular subtype or PIK3CA mutational status. Furthermore, this dependence distinguishes breast cancers from normal breast epithelial cells, which are neither primed for apoptosis nor dependent on BCL-XL/MCL-1, suggesting a potential therapeutic window. By tilting the balance of pro- to antiapoptotic signals in the mitochondria, dual inhibition of MCL-1 and BCL-XL also sensitizes breast cancer cells to standard-of-care cytotoxic and targeted chemotherapies. Together, these results suggest that patients with PIK3CA mutant breast cancers may benefit from combined treatment with inhibitors of BCL-XL and the mTOR/4E-BP axis, whereas alternative methods of inhibiting MCL-1 and BCL-XL may be effective in tumors lacking PIK3CA mutations.