Search

Understanding tumor-induced angiogenesis is a challenging problem with important consequences for the diagnosis and treatment of cancer. In this study, we define a novel function for epithelial membrane protein-2 (EMP2) in the control of angiogenesis. EMP2 functions as an oncogene in endometrial cancer, and its expression has been linked to decreased survival. Using endometrial cancer xenografts, modulation of EMP2 expression resulted in profound changes to the tumor microvasculature. Under hypoxic conditions, upregulation of EMP2 promoted vascular endothelial growth factors (VEGF) expression through a HIF-1α-dependent pathway and resulted in successful capillary-like tube formation. In contrast, reduction of EMP2 correlated with reduced HIF-1α and VEGF expression with the net consequence of poorly vascularized tumors in vivo. We have previously shown that targeting of EMP2 using diabodies in endometrial cancer resulted in a reduction of tumor load, and since then we have constructed a fully human EMP2 IgG1. Treatment of endometrial cancer cells with EMP2-IgG1 reduced tumor load with a significant improvement in survival. These results support the role of EMP2 in the control of the tumor microenvironment and confirm the cytotoxic effects observed by EMP2 treatment in vivo.

Purpose: Programmed death-1 (PD-1) ligation downregulates active lymphocyte responses. The authors tested whether PD-1 or its ligands are expressed in the posterior segment during active intraocular inflammation.Methods: Experimental autoimmune uveitis (EAU) was induced using interphotoreceptor retinoid-binding protein (IRBP 161-180). Ocular inflammation was evaluated by histology and expression of PD-1 ligand tested by immunohistochemistry. PD-1 expression was evaluated by immunohistochemistry, RT-PCR, and Western immunoblotting.Results: Using immunohistochemistry, PD-1, but not its ligands, was constitutively expressed in retinal neurons of naive mouse retina. Both PD-1 and its ligands were observed, as expected, in sites of active inflammation.Conclusions: PD-1 and its ligands were expressed in sites of active inflammation, in accordance with many other models of inflammatory disease. Surprisingly, PD-1, not previously described outside the immune system, was constitutively expressed in retinal neurons, raising the possibility that PD-1 signaling may be important for neuronal function in the absence of an inflammatory insult. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors report no conflicts of interest.

Epithelial membrane protein-2 (EMP2) is upregulated in a number of tumors and therefore remains a promising target for mAb-based therapy. In the current study, image-guided therapy for an anti-EMP2 mAb was evaluated by PET in both syngeneic and immunodeficient cancer models expressing different levels of EMP2 to enable a better understanding of its tumor uptake and off target accumulation and clearance. The therapeutic efficacy of the anti-EMP2 mAb was initially evaluated in high- and low-expressing tumors, and the mAb reduced tumor load for the high EMP2-expressing 4T1 and HEC-1-A tumors. To create an imaging agent, the anti-EMP2 mAb was conjugated to p-SCN-Bn-deferoxamine (DFO) and radiolabeled with 89Zr. Tumor targeting and tissue biodistribution were evaluated in syngeneic tumor models (4T1, CT26, and Panc02) and human tumor xenograft models (Ramos, HEC-1-A, and U87MG/EMP2). PET imaging revealed radioactive accumulation in EMP2-positive tumors within 24 hours after injection, and the signal was retained for 5 days. High specific uptake was observed in tumors with high EMP2 expression (4T1, CT26, HEC-1-A, and U87MG/EMP2), with less accumulation in tumors with low EMP2 expression (Panc02 and Ramos). Biodistribution at 5 days after injection revealed that the tumor uptake ranged from 2 to approximately 16%ID/cc. The results show that anti-EMP2 mAbs exhibit EMP2-dependent tumor uptake with low off-target accumulation in preclinical cancer models. The development of improved anti-EMP2 Ab fragments may be useful to track EMP2-positive tumors for subsequent therapeutic interventions., (©2024 American Association for Cancer Research.)

Breast cancer (BC) remains among the most commonly diagnosed cancers in women worldwide. Triple-negative BC (TNBC) is a subset of BC characterized by aggressive behavior, a high risk of distant recurrence, and poor overall survival rates. Chemotherapy is the backbone for treatment in patients with TNBC, but outcomes remain poor compared to other BC subtypes, in part due to the lack of recognized functional targets. In this study, the expression of the tetraspan protein epithelial membrane protein 2 (EMP2) was explored as a predictor of TNBC response to standard chemotherapy. We demonstrate that EMP2 functions as a prognostic biomarker for patients treated with taxane-based chemotherapy, with high expression at both transcriptomic and protein levels following treatment correlating with poor overall survival. Moreover, we show that targeting EMP2 in combination with docetaxel reduces tumor load in syngeneic and xenograft models of TNBC. These results provide support for the prognostic and therapeutic potential of this tetraspan protein, suggesting that anti-EMP2 therapy may be beneficial for the treatment of select chemotherapy-resistant TNBC tumors.

Purpose: Research about academic medicine women faculty has focused on comparisons of men and women or specific groups who achieved leadership. To better understand the low percentages of women in academic medicine leadership, attention should be paid to the career continuum within genders. Study findings will inform policies and programs to support women in building careers and acquiring leadership positions. Materials and Methods: Association of American Medical Colleges (AAMC) StandPoint Faculty Engagement Survey data are used to describe and compare women assistant, associate and full professors' perceptions of (1) career development and advancement opportunities, and (2) a culture and climate that fosters diversity, equity, and inclusion. Specific similarities and differences with men are highlighted. Results: Fifty-nine percent of women respondents were assistant, 25% associate, and 16% full professors. Associate professors of both genders were the least satisfied on the main measures. Women were less satisfied than men at each career stage across the majority of variables. Among women, fewer than half of full and associate professors, and 52% of assistant professors believe they can express their opinions without fear of retribution. While the majority at all ranks (69%-75%) report feeling respected in the workplace, among those who did not, the highest percentage of disrespect based on gender was among associate professors. Conclusions: The perceptions of >7,500 academic medicine women faculty, representing different generations and ranks, underscore the need to broadly address gender inequity and sexism throughout the career continuum. It identifies the mid-career stage as a challenging experience for both men and women. Women, especially at the associate professor rank, remain a critically dissatisfied and underresourced group that is at risk for underutilization and potentially exit from academic medicine. All ranks of women need career development and equitable policies to support their sense of belonging and career advancement.

Boron-nitrogen-containing heterocycles with extended conjugated π-systems such as polycyclic aromatic 1,2-azaborines, hold the fascination of organic chemists due to their unique optoelectronic properties. However, the majority of polycyclic aromatic 1,2-azaborines aggregate at high concentrations or in the solid-state, resulting in aggregation-caused quenching (ACQ) of emission. This practical limitation poses significant challenges for polycyclic aromatic 1,2-azaborines' use in many applications. Additionally, only a few solvatochromic polycyclic aromatic 1,2-azaborines have been reported and they all display minimal solvatochromism. Therefore, the scope of available polycyclic 1,2-azaborines needs to be expanded to include those displaying fluorescence at high concentration and in the solid-state as well as those that exhibit significant changes in emission intensity in various solvents due to different polarities. To address the ACQ issue, we evaluate the effect of a pre-twisted molecular geometry on the optoelectronic properties of polycyclic aromatic 1,2-azaborines. Specifically, three phenyl-substituted pyrrolidinone-fused 1,2-azaborines (PFAs) with similar structures and functionalized with diverse electronic moieties (-H, -NO 2 , -CN, referred to as PFA 1 , 2 , and 3 , respectively) were experimentally and computationally studied. Interestingly, PFA 2 displays two distinct emission properties: 1) solvatochromism, in which its emission and quantum yields are tunable with respect to solvent polarity, and 2) fluorescence that can be completely "turned off" and "turned on" via aggregation-induced emission (AIE). This report provides the first example of a polycyclic aromatic 1,2-azaborine that displays both AIE and solvatochromism properties in a single BN-substituted backbone. According to time-dependent density function theory (TD-DFT) calculations, the fluorescence properties of PFA 2 can be explained by the presence of a low-lying n-π* charge transfer state inaccessible to PFA 1 or PFA 3 . These findings will help in the design of future polycyclic aromatic 1,2-azaborines that are solvatochromic and AIE-active as well as in understanding how molecular geometry affects these compounds' optoelectronic properties., Competing Interests: Conflicts of interest The authors declare no competing financial interest.

Of Being a First Generation (First Gen) college graduate is an important intersectionality which impacts the lens through which First Gen students learn to become physicians. In this Perspective, we define the First Gen identity and review some of the salient First Gen literature as it applies to the medical school experience. We discuss the conception, design and execution of First Gen initiatives and program development at our medical school as a call to action and model for other institutions to create communities for their First Gen populations, focusing on inclusion and tailored support. We describe the framework through which we envisioned our programming for First Gen medical students, trainees, staff, and faculty at the David Geffen School of Medicine at UCLA.

Since 2011, use of immune checkpoint inhibitors (ICI) in cancer immunotherapy dramatically expanded, both alone and in combination with either a different cancer treatment or with two different ICIs. With this increase in use have come a myriad of adverse effects from enhanced immune activation, including ophthalmic and neurologic immune related adverse events (irAE). Neuro-ophthalmic immune related adverse events (NOirAE) associated with use of ICIs are increasingly recognized and their severity may actually limit use of potentially life-saving immunotherapy. NOirAEs comprise a wide variety of presentations involving both the central and peripheral nervous system. They cause afferent or efferent visual dysfunction, including among them optic neuropathy and edema, orbital inflammatory disease, and ocular myasthenia. While treatment for irAEs typically involves immunosuppression with corticosteroids, there is no expert consensus regarding best practices for treatment of NOirAEs and whether to stop ICI immunotherapy for the cancer or not. This state-of-the-art review explores the pathophysiologic basis for NOirAEs, provides a framework for categorizing them within neuro-ophthalmology, and discusses what is needed to close the current knowledge gaps in diagnosis and management of an increasing population of cancer patients requiring neuro-ophthalmic care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Winges and Gordon.)

Pathologic retinal neovascularization is a potentially blinding consequence seen in many common diseases including diabetic retinopathy, retinopathy of prematurity, and retinal vaso-occlusive diseases. This study investigates epithelial membrane protein 2 (EMP2) and its role as a possible modulator of angiogenesis in human retinal pigment epithelium (RPE) under hypoxic conditions. To study its effects, the RPE cell line ARPE-19 was genetically modified to either overexpress EMP2 or knock down its levels, and RNA sequencing and western blot analysis was performed to confirm the changes in expression at the RNA and protein level, respectively. Protein expression was evaluated under both normoxic conditions or hypoxic stress. Capillary tube formation assays with human umbilical vein endothelial cells (HUVEC) were used to evaluate functional responses. EMP2 expression was found to positively correlate with expression of pro-angiogenic factors HIF1α and VEGF at both mRNA and protein levels under hypoxic conditions. Mechanistically, EMP2 stabilized HIF1α expression through downregulation of von Hippel Lindau protein (pVHL). EMP2 mediated changes in ARPE-19 cells were also found to alter the secretion of a paracrine factor(s) in conditioned media that can regulate HUVEC migration and capillary tube formation in in vitro functional angiogenesis assays. This study identifies EMP2 as a potential mediator of angiogenesis in a human RPE cell line. EMP2 levels positively correlate with pro-angiogenic mediators HIF1α and VEGF, and mechanistically, EMP2 regulates HIF1α through downregulation of pVHL. This study supports further investigation of EMP2 as a promising novel target for therapeutic treatment of pathologic neovascularization in the retina., (© 2022. The Author(s).)

Health care teams are most effective at addressing complex problems and improving health outcomes for underserved populations when team members bring diverse life experiences and perspectives to the effort. With rates of visual impairment expected to increase in the United States by 2050, especially among minority populations, diversification of the ophthalmology workforce will be critical in reducing disparities in access to and quality of vision health care. Currently, ophthalmology is less diverse with respect to race, ethnicity, and gender than graduating medical classes and other medical specialties, as well as the general US population. In addition, data on diversity in sexual orientation and gender identity, socioeconomic status, and disability are lacking in ophthalmology. The Minority Ophthalmology Mentoring and Rabb-Venable Excellence in Ophthalmology Programs are examples of initiatives to increase racial and ethnic diversity in the workforce and can serve as models for increasing other aspects of inclusiveness. Other strategies for improving vision health care for all Americans include continuing to support existing diversity programs and creating new ones; addressing unconscious and implicit bias in medical school, residency, and faculty selections; conducting holistic reviews of medical school and residency applications; diversifying selection committees and leadership; and encouraging faculty development of underrepresented groups., (Published by Elsevier Inc.)

Competing Interests: The authors report no conflicts of interest.

Purpose: In recent decades, women have achieved greater representation in ophthalmology. Globally, women now constitute approximately 25%-30% of ophthalmologists and 35%-45% of trainees. Nevertheless, women remain under-represented in key areas, including positions of professional and academic leadership and ophthalmic surgical subspecialization. Furthermore, there is evidence that women in ophthalmology encounter more bias and discrimination across multiple domains than men, including a gender-pay gap that is wider than in many other surgical subspecialties. Women ophthalmologists and trainees report sharply differing training experiences from male peers, including fewer opportunities to operate, more bullying and harassment, less access to mentorship, and contrasting expectations around contributions to family life., Design: Perspective., Methods: An extensive literature search was undertaken to compile and review papers published with a focus on gender equity across ophthalmology, surgery, and medicine., Results: We identified 8 broad domains that were widely discussed: leadership, research and academics, income, surgical exposure and subspecialization, harassment, career satisfaction, mentorship, and family and marital differences. We have summarized the current research across each of these areas, and discussed possible solutions to reduce the inequities reported., Conclusions: This review draws on current research published around representation and experiences of women in ophthalmology and suggests that there are opportunities to improve gender inequity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Fatal overdoses involving cocaine (powdered or crack) and fentanyl have increased nationally and in Massachusetts. It is unclear how overdose risk and preparedness to respond to an overdose differs by patterns of cocaine and opioid use. Methods: From 2017 to 2019, we conducted a nine-community mixed-methods study of Massachusetts residents who use drugs. Using survey data from 465 participants with past-month cocaine and/or opioid use, we examined global differences ( p  < 0.05) in overdose risk and response preparedness by patterns of cocaine and opioid use. Qualitative interviews ( n  = 172) contextualized survey findings. Results: The majority of the sample (66%) used cocaine and opioids in the past month; 18.9% used opioids alone; 9.2% used cocaine and had no opioid use history; and 6.2% used cocaine and had an opioid use history. Relative to those with a current/past history of opioid use, significantly fewer of those with no opioid use history were aware of fentanyl in the drug supply, carried naloxone, and had received naloxone training. Qualitative interviews documented how people who use cocaine and have no history of opioid use are largely unprepared to recognize and respond to an overdose. Conclusions: Public health efforts are needed to increase fentanyl awareness and overdose prevention preparedness among people primarily using cocaine.

Background: In recent years, CTLA-4 and PD-1/PD-L1 checkpoint inhibitors have proven to be effective and have become increasingly popular treatment options for metastatic melanoma and other cancers. These agents work by enhancing autologous antitumor immune responses. Immune-related ophthalmologic complications have been reported in association with checkpoint inhibitor use but remain incompletely characterized. This study seeks to investigate and further characterize the neuro-ophthalmic and ocular complications of immune checkpoint blockade treatment., Methods: A survey was distributed through the secure electronic data collection tool REDCap to neuro-ophthalmology specialists in the North American Neuro-Ophthalmology Society listserv. The study received human subjects approval through the University of California at Los Angeles Institutional Review Board. The survey identified patients sent for neuro-ophthalmic consultation while receiving one or more of a PD-1 inhibitor (pembrolizumab, nivolumab, or cemiplimab); PD-L1 inhibitor (atezolizumab, avelumab, or durvalumab); or the CTLA-4 inhibitor ipilimumab. Thirty-one patients from 14 institutions were identified. Patient demographics, neuro-ophthalmic diagnosis, diagnostic testing, severity, treatment, clinical response, checkpoint inhibitor drug used, and cancer diagnosis was obtained., Results: The checkpoint inhibitors used in these patients included pembrolizumab (12/31), nivolumab (6/31), combined ipilimumab with nivolumab (7/31, one of whom also received pembrolizumab during their course of treatment), durvalumab (3/31), ipilimumab (2/31), and cemiplimab (1/31). Malignant melanoma (16/31) or nonsmall cell lung carcinoma (6/31) were the most common malignancies. The median time between first drug administration and the time of ophthalmological symptom onset was 14.5 weeks. Eleven patients had involvement of the optic nerve, 7 patients had inflammatory orbital or extraocular muscle involvement, 6 patients had ocular involvement from neuromuscular junction dysfunction, 4 patients had cranial nerve palsy, and 4 patients had non neuro-ophthalmic complications. Use of systemic corticosteroids with or without stopping the checkpoint inhibitor resulted in improvement of most patients with optic neuropathy, and variable improvement for the other ophthalmic conditions., Conclusion: This study describes the variable neuro-ophthalmic adverse events associated with use of immune checkpoint inhibitors and contributes a more thorough understanding of their clinical presentations and treatment outcomes. We expect this will increase awareness of these drug complications and guide specialists in the care of these patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.)

Introduction: Pregnant and postpartum women experience significant sleep disruption, but the role of perinatal sleep disturbances in breastfeeding is understudied., Methods: In this observational cohort study, we used mixed methods to examine associations between perinatal sleep and breastfeeding. Forty-eight women (mean age 28.2 ± 4.9 years) who were euthymic at enrollment but had a history of major depression (n = 43) or bipolar disorder (n = 5) had sleep recorded with wrist actigraphy. We determined feeding status through daily diaries and used semi-structured interviews to identify themes regarding participants' experiences, breastfeeding decisions, and behaviors. To examine whether sleep disturbance during pregnancy predicted breastfeeding (BF) rates, we defined "lower sleep efficiency" (LSE) and "higher sleep efficiency" (HSE) groups based on the median split of actigraphic SE at 33 weeks' gestation (cutoff SE = 84.9%) and classified mothers as No-BF, Mixed-BF (BF + formula), and Exclusive-BF at 2 weeks postpartum., Results: Percentages of women who did any breastfeeding were: Week 2 = 72.3%, Week 6 = 62.5%, Week 16 = 50%. LSE mothers were less likely than HSE mothers to initiate breastfeeding (percent No-BF: LSE = 45.8%, HSE = 16.7%, P < .05). Average actigraphic sleep onset, sleep offset, time in bed, sleep duration, and SE did not differ based on breastfeeding status at any time point. Qualitative themes included insufficient preparation for the demands of breastfeeding, interrupted and nonrestorative sleep, and unrelenting daytime tiredness., Conclusions: In our sample, preserved actigraphic SE during pregnancy was associated with initiation and continuation of breastfeeding. Future work should examine whether improving sleep in pregnancy improves mothers' feeding experiences., (Copyright © 2021 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Detailed study of ophthalmic immune-related adverse events (AEs), including determination of incidence and recurrence rates, is of integral importance in cancer immunotherapy to inform management and treatment guidelines., Design: Retrospective registry study., Participants: Patients newly diagnosed with ophthalmic immune-related AEs between January 1, 2013, and December 31, 2017, in the American Academy of Ophthalmology's Intelligent Research in Sight (IRIS®) Registry., Methods: Data were collected from electronic health records of IRIS® Registry participating ophthalmology practices. Patients with select ophthalmic immune-related AEs were identified by International Classification of Diseases diagnosis codes. The primary exposure of interest was prior initiation of immune checkpoint inhibitors (ICIs)., Main Outcome Measures: Incidence of ophthalmic immune-related AEs within 1 year after initiation of ICI therapy was determined. Incidence rate ratios (IRRs) were derived by comparing incidence of ophthalmic immune-related AEs after ICIs versus rates of the same ocular complications in patients not taking ICIs in the entire registry population. Rates of ophthalmic immune-related AEs in patients with a past history of ocular inflammation or other specific ophthalmic condition before initiation of ICIs were examined further., Results: A total of 3123 patients who received anti-CTLA-4 or anti-programmed cell death 1 (PD-1) therapy were identified, 112 of whom demonstrated an ophthalmic immune-related AE. Incidence rates for anterior uveitis, the most common ophthalmic immune-related AE, were 8209 per 100 000 for ipilimumab (anti-CTLA-4), 2542 per 100 000 for nivolumab (anti-PD-1), 2451 per 100 000 for pembrolizumab (anti-PD-1), 5556 per 100 000 for ipilimumab plus nivolumab, and 3740 per 100 000 among all ICIs. Rates of ophthalmic immune-related AEs among patients receiving ICI therapy were higher compared with baseline rates in the general registry population (anterior uveitis IRR, 13.9; other uveitis IRR, 43.0; papilledema IRR, 38.3). Patients with a history of uveitis or other ocular inflammatory condition demonstrated high recurrence rates of ophthalmic immune-related AEs after initiating ICIs (up to 51.1%)., Conclusions: For patients initiating ICI therapy, early coordination with ophthalmic subspecialist care is important because rates of ophthalmic immune-related AEs are elevated compared with ocular complication rates in the entire registry population and patients with a history of prior autoimmune ocular disease are at high risk of recurrence of ocular complications., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: The clinical utility of most antiretinal antibodies (retina antibodies) currently available for testing remains unclear and unproven. Despite this, the presence of retinal antibodies is included in current diagnostic autoimmune retinopathy criteria., Objective: To evaluate the clinical significance of comprehensive retinal antibody evaluations currently offered in North America., Design, Setting, and Participants: In this cross-sectional study, 14 patients without autoimmune retinopathy were recruited into the Mayo Clinic Neuroimmunology Biorepository for this study between January 1, 2019, and October 1, 2019. These serum samples without autoimmune retinopathy were sent in masked fashion to a Clinical Laboratory Improvement Amendments-certified laboratory. Using similar methods, the Mayo Clinic Neuroimmunology Research Laboratory independently assessed the same sample to ascertain reproducibility of the findings., Main Outcomes and Measures: Results of the autoimmune retinopathy and cancer-associated retinopathy panels., Results: Thirteen of 14 (93%; 95% CI, 66%-100%) serum samples tested positive for retinal antibodies, with a median of 5 retinal antibodies (range, 0-8) per patient at the Clinical Laboratory Improvement Amendments-certified laboratory, which provides a specificity of 7% (95% CI, 0%-34%). Confirmatory immunohistochemistry staining in human retina was present in 12 of 14 samples (86%). α-Enolase was found in 9 (64%). The only retinal antibody not present was recoverin. These nonspecific retinal antibody results were replicated at the Mayo Clinic Laboratory on Western blot using pig retina proteins as substrate., Conclusions and Relevance: The presence of retinal antibodies in 93% of the patients without autoimmune retinopathy indicates a lack of specificity and that most detectable retinal antibodies have limited clinical relevance in the evaluation of patients for suspected autoimmune retinopathy. Current retinal antibody testing, other than recoverin, should be interpreted with caution, especially for cases of low clinical suspicion. The poor specificity is important to recognize to prevent the potentially unnecessary commencement of systemic immunosuppressants that may result in significant extraocular adverse effects. Identification of biomarkers that have a high predictive value for inflammatory or autoimmune retinal diseases is needed to move the field forward.

Background: Limited research has explored risk factors for opioid pain medication misuse, concomitant substance misuse, and the unmet behavioral health treatment (BHTx) needs of transgender and gender diverse (TGD) adults., Methods: In 2019, TGD adults (N = 562) in Massachusetts and Rhode Island were purposively recruited and completed a psychosocial and behavioral health survey (95 % online; 5% in-person). Multivariable logistic regression was used to examine factors associated with past 12-month opioid pain medication misuse and unmet BHTx needs., Results: Overall, 24.4 % of participants were trans women; 32.0 % trans men; and 43.6 % were non-binary. Past-year substance misuse included: marijuana (56.8 %), hazardous drinking (37.5 %), hallucinogens (9.8 %), benzodiazepines (8.2 %), and opioid pain medication (8.0 %). Among participants with past-year substance misuse and BHtx need (n = 326), 81.3 % received BHtx and 18.7 % had unmet BHtx needs. Being a trans woman, having HIV, stigma in healthcare, and number of substances misused were associated with increased odds of past-year opioid pain medication misuse; high social connectedness was associated with decreased odds of opioid pain medication misuse (p-values<0.05). Younger age, stigma in healthcare, and misusing opioid pain medications were associated with increased odds of unmet BHTx needs; post-traumatic stress disorder and family support were associated with decreased odds of unmet BHtx needs (p-values<0.05)., Conclusions: Addressing disparities in opioid pain medication misuse among TGD people requires systematic improvements in healthcare access, including efforts to create TGD-inclusive BHtx environments with providers who are equipped to recognize and treat the social and structural drivers of TGD health inequities, including opioid pain medication misuse., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To examine the frequency of ophthalmic immune-related adverse events (OirAEs) in melanoma, other cancers, and after immune checkpoint inhibitor (ICI) treatment., Design: Retrospective clinical cohort study., Methods: This study identified patients diagnosed with OirAEs between January 1, 2011, and December 31, 2018, in the Kaiser Permanente Southern California electronic health records. The primary exposures of interest were prior initiation of ICIs and underlying cancer diagnosis. Risk-adjusted prevalence of OirAEs was evaluated in patients with melanoma, with nonmelanoma cancer, and without cancer. The 1-year incidence of OirAEs and recurrence of prior ophthalmic disease were identified in ICI-receiving patients with melanoma and nonmelanoma., Results: Among 4,695,669 unique patients identified, 9.9% had a cancer diagnosis, of whom 2.8% had a diagnosis of melanoma. Overall prevalence for uveitis and selected neuro-ophthalmic diagnoses was 341.8/100,000 patient-years in patients with melanoma and 369.6/100,000 patient-years in patients with nonmelanoma cancer regardless of ICI treatment, compared with 142.2/100,000 patient-years in patients without cancer. A total of 2,911 unique patients received ICI therapy. Compared with patients with nonmelanoma cancer, patients with melanoma on any ICI had elevated 1-year incidence rates of uveitis (1.2% vs 0.2%; risk-adjusted odds ratio, 6.45). High 1-year recurrence rates for uveitis in ICI patients with a prior uveitis history were also observed., Conclusions: The prevalence of all OirAEs was substantially higher in patients with cancer, with ICI-related uveitis risk specifically increased in patients with melanoma compared with patients with nonmelanoma cancer. Evidence-based guidelines for ophthalmic monitoring of patients undergoing ICI treatment may require different risk stratifications based on underlying cancer diagnosis, specific ICI used, and prior history of uveitis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Discrimination, bullying and sexual harassment (DBSH) impact the psychological well-being of doctors and contribute to poor health outcomes. The Royal Australian and New Zealand College of Ophthalmologists (RANZCO) commissioned independent surveys to evaluate DBSH among members/trainees., Methods: Anonymous online surveys by Best Practice Australia were undertaken in 2015 and 2018. Cross-sectional analysis was prevalence of perceived DBSH, rates of reporting, intervention and resolution undertaken. Response rate was 50% (658/1319) in 2015 and 40% (557/1401) in 2018. In both surveys, 29% were female. This is representative of the distribution of the RANZCO members., Results: In a 2015 survey, 37.6% of respondents experienced DBSH, with prevalence being the highest for females (62.3%; N = 104 cf males 27.7%; N = 167) and trainees (49.2%; N = 61). In 2018, 49.2% of respondents reported DBSH with rates low for all forms of DBSH (22%-29%). Sexual harassment was reported by 12% and the least discussed or reported. Respondents strategy for taking action included draw on personal support network (25-43%), official complaints to supervisors (16-22%), human resources (2%-10%) and RANZCO (0%-6%). Reasons for not taking action included fear of impact of future career options (54.1%-60.7%), fear of victimization (35.7%-50.4%) and afraid of not being believed (31.9%-52.4%). Satisfactory resolution rates were 6% to 25%. A majority of respondents (77%) were positive about RANZCO initiatives., Conclusions: DBSH is commonly reported by RANZCO members with female ophthalmologists more than two times more likely to experience any one of the four behaviours, three times more likely to experience discrimination and six times for sexual harassment. Fear of compromising personal and career progression contribute to low levels of reporting., (© 2021 Royal Australian and New Zealand College of Ophthalmologists.)

Introduction: Murine models provide microvascular insights into the 3-D network disarray seen in retinopathy and cardiovascular diseases. Light-sheet fluorescence microscopy (LSFM) has emerged to capture retinal vasculature in 3-D, allowing for assessment of the progression of retinopathy and the potential to screen new therapeutic targets in mice. We hereby coupled LSFM, also known as selective plane illumination microscopy, with topological quantification, to characterize the retinal vascular plexuses undergoing preferential obliteration. Method and Result: In postnatal mice, we revealed the 3-D retinal microvascular network in which the vertical sprouts bridge the primary (inner) and secondary (outer) plexuses, whereas, in an oxygen-induced retinopathy (OIR) mouse model, we demonstrated preferential obliteration of the secondary plexus and bridging vessels with a relatively unscathed primary plexus. Using clustering coefficients and Euler numbers, we computed the local versus global vascular connectivity. While local connectivity was preserved ( p > 0.05, n = 5 vs. normoxia), the global vascular connectivity in hyperoxia-exposed retinas was significantly reduced ( p < 0.05, n = 5 vs. normoxia). Applying principal component analysis (PCA) for auto-segmentation of the vertical sprouts, we corroborated the obliteration of the vertical sprouts bridging the secondary plexuses, as evidenced by impaired vascular branching and connectivity, and reduction in vessel volumes and lengths ( p < 0.05, n = 5 vs. normoxia). Conclusion: Coupling 3-D LSFM with topological quantification uncovered the retinal vasculature undergoing hyperoxia-induced obliteration from the secondary (outer) plexus to the vertical sprouts. The use of clustering coefficients, Euler's number, and PCA provided new network insights into OIR-associated vascular obliteration, with translational significance for investigating therapeutic interventions to prevent visual impairment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose : To review the broad spectrum of clinical neuro-ophthalmic presentations associated with human immunodeficiency virus (HIV) infection. Methods : Critical review of the literature regarding neuro-ophthalmic consequences of HIV infection and its sequelae. Results : Neuro-ophthalmological diseases are common in both asymptomatic HIV-positive patients and those who profound immunosuppression with acquired immune deficiency syndrome (AIDS). Neuro-ophthalmic manifestations of HIV infection can involve the afferent or efferent visual pathway. Common clinical presentations include headache, papilledema, chorioretinitis, optic nerve involvement, meningitis, and cranial nerve palsies. Other neuro-ophthalmic manifestations include involvement of the visual pathway in the brain producing visual field defects such as occur in progressive multifocal encephalopathy. Pupil abnormalities have also been reported. Discussion : Neuro-ophthalmic consequences of HIV are important to recognize as it is critical to identify underlying neoplastic or infectious diseases which could be amenable to treatment.

Background: Antiangiogenic therapy with bevacizumab has failed to provide substantial gains in overall survival. Epithelial membrane protein 2 (EMP2) is a cell surface protein that has been previously shown to be expressed in glioblastoma, correlate with poor survival, and regulate neoangiogenesis in cell lines. Thus, the relationship between bevacizumab and EMP2 was investigated., Methods: Tumor samples were obtained from 12 patients with newly diagnosed glioblastoma at 2 time points: (1) during the initial surgery and (2) during a subsequent surgery following disease recurrence post-bevacizumab treatment. Clinical characteristics and survival data from these patients were collected, and tumor samples were stained for EMP2 expression. The IVY Glioblastoma Atlas Project database was used to evaluate EMP2 expression levels in 270 samples by differing histological areas of the tumor., Results: Patients with high EMP2 staining at initial diagnosis had decreased progression-free and overall survival after bevacizumab ( median progression-free survival 4.6 months vs 5.9 months; log-rank P = .076 and overall survival 7.7 months vs 14.4 months; log-rank P = .011 ). There was increased EMP2 staining in samples obtained after bevacizumab treatment in both unpaired ( mean H-score 2.31 vs 1.76; P = .006 ) and paired analyses ( mean difference 0.571; P = .019 ). This expression increase correlated with length of bevacizumab therapy ( R 2   = 0.449; Pearson P = .024 )., Conclusions: Bevacizumab treatment increased EMP2 protein expression. This increase in EMP2 correlated with reduced mean survival time post-bevacizumab therapy. We hypothesize a role of EMP2 in clinical bevacizumab resistance and as a potential antiangiogenic therapeutic target in glioblastoma., (© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Little is known about the role of epithelial membrane protein-2 (EMP2) in breast cancer development or progression. In this study, we tested the hypothesis that EMP2 may regulate the formation or self-renewal of breast cancer stem cells (BCSC) in the tumor microenvironment. In silico analysis of gene expression data demonstrated a correlation of EMP2 expression with known metastasis-related genes and markers of cancer stem cells (CSC) including aldehyde dehydrogenase (ALDH). In breast cancer cell lines, EMP2 overexpression increased and EMP2 knockdown decreased the proportion of stem-like cells as assessed by the expression of the CSC markers CD44 + /CD24 - , ALDH activity, or by tumor sphere formation. In vivo , upregulation of EMP2 promoted tumor growth, whereas knockdown reduced the ALDH high CSC population as well as retarded tumor growth. Mechanistically, EMP2 functionally regulated the response to hypoxia through the upregulation of HIF-1α, a transcription factor previously shown to regulate the self-renewal of ALDH high CSCs. Furthermore, in syngeneic mouse models and primary human tumor xenografts, mAbs directed against EMP2 effectively targeted CSCs, reducing the ALDH + population and blocking their tumor-initiating capacity when implanted into secondary untreated mice. Collectively, our results show that EMP2 increases the proportion of tumor-initiating cells, providing a rationale for the continued development of EMP2-targeting agents., (©2020 American Association for Cancer Research.)

Purpose: National medical specialty societies speak for their respective fields in policy debates, influence research, affect trainees' specialization decisions, provide career development opportunities, and confer awards and recognitions. This study provides a comprehensive overview of the gender demographics of society members and leaders., Method: In 2016, the Group on Women in Medicine and Science (of the Association of American Medical Colleges) sought to characterize the gender of members and leaders of specialty societies from 2000 to 2015. This report provides descriptive data, including how many of the responding societies (representing each of 30 major medical specialties) had substantial (> 10%) increases in women's representation among leadership between the first and second halves of the study period., Results: The average proportion of full members who were female in responding societies was 25.4% in 2005 and 29.3% in 2015. The proportion of women among those serving as the highest-ranking elected leader between 2000 and 2015 in each specialty ranged from 0% to 37.5% (mean, 15.8%). The mean proportion of women on governing boards ranged from 0% to 37.3% (mean of means, 18.8%) in 2000-2007 and from 0% to 47.6% (mean of means, 25.2%) in 2008-2015. In 9 specialties, the mean percentage of women serving on governing boards increased by over 10% from the first to the second half of the study period., Conclusions: Although many women are full members of specialty societies, women still constitute a minority of leaders. This report establishes a baseline from which to evaluate the effect of societies' efforts to improve diversity, equity, and inclusion.

Purpose: Although intracranial meningiomas are the most common primary brain tumor in adults, treatment options are few and have traditionally been limited to surgical resection and radiotherapy. Additional targeted therapies and biomarkers are needed, especially as complete surgical resection is frequently not feasible in many patients., Methods: Non-pathologic brain tissue from 3 patients undergoing routine autopsies and tumor specimens from 16 patients requiring surgical resection for meningioma were collected. EMP2 protein expression was evaluated by immunohistochemistry and western blot analysis. EMP2 mRNA expression was also investigated using surgical specimens and validated by analysis of several independent NCBI GEO databases., Results: EMP2 mRNA expression levels were found to be higher in meningioma relative to non-pathologic meninges (P = 0.0013) and brain (P = 0.0011). Concordantly, strong EMP2 protein expression was demonstrated in 100% of meningioma specimens from all 16 patients, with no observable protein expression in normal brain tissue samples from 3 subjects (P < 0.001). EMP2 expression was confirmed by western blot analysis in five samples, with EMP2 protein intensity positively correlating with histologic staining score (R 2  = 0.780; P = 0.047). No association was found between EMP2 mRNA or protein levels and WHO grade or markers of proliferation. However, EMP2 expression was positively associated with an angiomatous pattern on histologic evaluation (P = 0.0597), VEGF-A mRNA expression (P < 0.001), and clinical markers of tumor vascularity such as operative blood loss (P = 0.037)., Conclusions: EMP2 is not found in normal brain tissue, yet has shown consistently high mRNA and protein expression in meningiomas, and may serve as a useful molecular marker for these tumors.

Purpose : To investigate the link between treatment with CTLA-4 and PD-1 checkpoint blockade inhibitors and the development of noninfectious uveitis. Methods : A survey was distributed to uveitis specialists to identify patients who developed uveitis while receiving either PD-1 inhibitors pembrolizumab and nivolumab; PD-L1 inhibitors atezolizumab, avelumab, and durvalumab; or the CTLA-4 inhibitor ipilimumab. Results : Fifteen patients from seven institutions were identified. The most common cancer diagnosis (13/15) was malignant melanoma. Fourteen patients had a new uveitis diagnosis following checkpoint blockade administration (six anterior uveitis, six panuveitis, one posterior uveitis, one anterior/intermediate combined); one patient developed optic neuritis. Uveitis was diagnosed within 6 months after drug initiation for 11/12 patients (median 63 days). Corticosteroid treatment was effective for most patients, although two patients had permanent loss of vision. Conclusions : Patients on checkpoint inhibitor therapy should be educated to seek care if they develop ocular symptoms, and prompt referral to specialists should be incorporated into oncology protocols.

Background: To determine whether gender-based differences may be present in letters of recommendation written for ophthalmology residency applicants., Methods: All applications submitted through SF Match to the UCLA Stein Eye Institute Residency Training Program from the 2017-2018 application cycle were analyzed using validated text analysis software (Linguistic Inquiry and Word Count (Austin, TX)). The main outcome measures were differences in language use in letters of recommendation by gender of applicant., Results: Of 440 applicants, 254 (58%) were male and 186 (42%) were female. The two gender groups had similar United States Medical Licensing Exam (USMLE) Step 1 scores, undergraduate grade point averages (uGPA's), proportions of underrepresented minority (URM) applicants and Gold Humanism Honor Society members, numbers of academic and service activities listed, and gender distributions of their letter writers (all P values > 0.05). However, letters written for male applicants were determined to use more "authentic" words than those written for female applicants (mean difference, 0.800; 95% CI, 0.001-1.590; P = 0.047). Letters written for male applicants also contained more "leisure" words (mean difference, 0.056; 95% CI, 0.008-0.104; P = 0.023) and fewer "feel" words (mean difference, 0.033; 95% CI, 0.001-0.065; P = 0.041) and "biological processes" words (mean difference, 0.157; 95% CI, 0.017-0.297; P = 0.028)., Conclusions: There were gender differences detected in recommendation letters in ophthalmology consistent with prior studies from other fields. Awareness of these differences may improve residency selection processes.

Purpose: Pathologic corneal neovascularization is a major cause of blindness worldwide, and treatment options are currently limited. VEGF is one of the critical mediators of corneal neovascularization but current anti-VEGF therapies have produced limited results in the cornea. Thus, additional therapeutic agents are needed to enhance the antiangiogenic arsenal. Our group previously demonstrated epithelial membrane protein-2 (EMP2) involvement in pathologic angiogenesis in multiple cancer models including breast cancer and glioblastoma. In this paper, we investigate the efficacy of anti-EMP2 immunotherapy in the prevention of corneal neovascularization., Methods: An in vivo murine cornea alkali burn model was used to study pathologic neovascularization. A unilateral corneal burn was induced using NaOH, and subconjunctival injection of either anti-EMP2 antibody, control antibody, or sterile saline was performed after corneal burn. Neovascularization was clinically scored at 7 days postalkali burn, and eyes were enucleated for histologic analysis and immunostaining including VEGF, CD31, and CD34 expression., Results: Anti-EMP2 antibody, compared to control antibody or vehicle, significantly reduced neovascularization as measured by clinical score and central cornea thickness, as well as by histologic reduction of neovascularization, decreased CD34 staining, and decreased CD31 staining. Incubation of corneal limbal cells in vitro with anti-EMP2 blocking antibody significantly decreased EMP2 expression, VEGF expression and secretion, and cell migration., Conclusions: This work demonstrates the effectiveness of EMP2 as a novel target in pathologic corneal neovascularization in an animal model and supports additional investigation into EMP2 antibody blockade as a potential new therapeutic option.

While more women are in leadership positions in academic medicine now than ever before in U.S. history, evidence from recent surveys of women and graduating medical students demonstrates that sexual harassment continues in academic health centers. Academic medicine's ability to change its culture is hampered by victims' fear of reporting episodes of harassment, which is largely due to fear of retaliation. In this Perspective, the authors describe efforts in scientific societies to address the issue of sexual harassment and to begin to establish safe environments at national meetings. The authors contend that each institution must work to make it safe for individuals to come forward, to provide training for victims and for bystanders, and to abolish "locker room" talk that is demeaning to women.

Epithelial membrane protein-2 (EMP2) expression is noted in many human cancers. We evaluated EMP2 as a biomarker in gliomas. A large tissue microarray of lower grade glioma (WHO grades II-III, n = 19 patients) and glioblastoma (GBM) (WHO grade IV, n = 50 patients) was stained for EMP2. EMP2 expression was dichotomized to low or high expression scores and correlated with clinical data. The mean EMP2 expression was 1.68 in lower grade gliomas versus 2.20 in GBMs (P = 0.01). The percentage of samples with high EMP2 expression was greater in GBMs than lower grade gliomas (90.0 vs. 52.6%, P = 0.001). No significant difference was found between median survival among patients with GBM tumors exhibiting high EMP2 expression and survival of those with low EMP2 expression (8.38 vs. 10.98 months, P = 0.39). However, EMP2 expression ≥2 correlated with decreased survival (r = -0.39, P = 0.001). The EMP2 expression level also correlated with Ki-67 positivity (r = 0.34, P = 0.008). The mortality hazard ratio for GBM patients with EMP2 score of 3 or higher was 1.92 (CI 0.69-5.30). Our findings suggest that elevated EMP2 expression is associated with GBM. With other biomarkers, EMP2 may have use as a molecular target for the diagnosis and treatment of gliomas.

Purpose: We investigated the effect of exogenously administered human embryonic stem cell-derived mesenchymal stromal cells (hESC-MSCs) in experimental autoimmune uveitis (EAU) in B10.RIII mice, a murine model of severe uveitis., Methods: B10.RIII mice were immunized with an uveitogenic peptide, and intraperitoneal injections of 5 million hESC-MSCs per animal were given on the same day. Behavioral light sensitivity assays, histological evaluation, cytokine production, and regulatory T cells were analyzed at the peak of the disease., Results: Histological and behavioral evidence demonstrated that early systemic treatment with hESC-MSCs decreases the development of severe EAU in B10.RIII mice. hESC-MSCs suppress Th17 and upregulate Th1 and Th2 responses as well as IL-2 and GM-CSF in splenocytes from hESC-MSC-treated mice., Conclusions: MSCs that originate from hESC decrease the development of severe EAU in B10.RIII mice, likely through systemic immune modulation. Further investigation is needed to determine any potential effect on active EAU.

Previous studies have suggested that overexpression of the oncogenic protein epithelial membrane protein-2 (EMP2) correlates with endometrial carcinoma progression and ultimately poor survival from disease. To understand the role of EMP2 in the etiology of disease, gene analysis was performed to show transcripts that are reciprocally regulated by EMP2 levels. In particular, EMP2 expression correlates with and helps regulate the expression of several cancer stem cell associated markers including aldehyde dehydrogenase 1 (ALDH1). ALDH expression significantly promotes tumor initiation and correlates with the levels of EMP2 expression in both patient samples and tumor cell lines. As therapy against cancer stem cells in endometrial cancer is lacking, the ability of anti-EMP2 IgG1 therapy to reduce primary and secondary tumor formation using xenograft HEC1A models was determined. Anti-EMP2 IgG1 reduced the expression and activity of ALDH and correspondingly reduced both primary and secondary tumor load. Our results collectively suggest that anti-EMP2 therapy may be a novel method of reducing endometrial cancer stem cells.

Epithelial membrane protein 2 (EMP2) is a cell surface protein that has recently emerged as an object of neuro-oncological interest due to its potential to be utilized as a biomarker and target for antibody therapies. Preclinical studies have demonstrated that EMP2 is associated with disease prognosis in a number of human cancers, including glioblastoma. The four large extracellular domains of EMP2 and its association with the extracellular matrix makes it an attractive target for future cancer therapies. Translational research suggests that EMP2 may be targeted with antibodies to improve tumor control and survival in a variety of murine models and cancer types. However, in order to translate these preclinical findings into the clinic, future research will need to focus on elucidating the role EMP2 in the normal human body by better understanding its molecular and chemical interactions. The focus of this review is to provide a comprehensive insight into current research endeavors, discuss the potential for clinically translatable applications, and predict the future directions of such research., (Copyright © 2017. Published by Elsevier Ltd.)

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and is associated with an extremely poor clinical prognosis. One pathologic hallmark of GBM is excessive vascularization with abnormal blood vessels. Extensive investigation of anti-angiogenic therapy as a treatment for recurrent GBM has been performed. Bevacizumab, a monoclonal anti-vascular endothelial growth factor A (VEGF-A), suggests a progression-free survival benefit but no overall survival benefit. Developing novel anti-angiogenic therapies are urgently needed in controlling GBM growth. In this study, we demonstrate tumor expression of epithelial membrane protein-2 (EMP2) promotes angiogenesis both in vitro and in vivo using cell lines from human GBM. Mechanistically, this pro-angiogenic effect of EMP2 was partially through upregulating tumor VEGF-A levels. A potential therapeutic effect of a systemic administration of anti-EMP2 IgG1 on intracranial xenografts was observed resulting in both significant reduction of tumor load and decreased tumor vasculature. These results suggest the potential for anti-EMP2 IgG1 as a promising novel anti-angiogenic therapy for GBM. Further investigation is needed to fully understand the molecular mechanisms how EMP2 modulates GBM pathogenesis and progression and to further characterize anti-EMP2 therapy in GBM.

Background: The time of onset of optic disc swelling in non-arteritic anterior ischaemic optic neuropathy (NAION) is not known, and it is commonly assumed to arise simultaneously with vision loss. Our goal is to report the presence and persistence of optic disc swelling without initial vision loss and its subsequent evolution to typical, symptomatic NAION., Methods: Clinical case series of patients with optic disc swelling and normal visual acuity and visual fields at initial presentation who progressed to have vision loss typical of NAION. All subjects underwent automated perimetry, disc photography and optic coherence tomography and/or fluorescein angiography to evaluate optic nerve function and perfusion., Results: Four patients were found to have sectoral or diffuse optic disc swelling without visual acuity or visual field loss; the fellow eye of all four had either current or prior NAION or a 'disc at risk' configuration. Over several weeks of clinical surveillance, each patient experienced sudden onset of visual field and/or visual acuity loss typical for NAION., Conclusions: Current treatment options for NAION once vision loss occurs are limited and may not alter the natural history of the disorder. Subjects with NAION may have disc swelling for 2-10 weeks prior to the occurrence of visual loss, and with the development of new therapeutic agents, treatment at the time of observed disc swelling could prevent vision loss from NAION., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Importance: The number of women in ophthalmology is rising. Little is known about their clinical activity and collections., Objective: To examine whether charges, as reflected in reimbursements from the Centers for Medicare & Medicaid Services (CMS) to ophthalmologists, differ by sex and how disparity relates to differences in clinical activity., Design, Setting, and Participants: Retrospective review of the CMS database for payments to ophthalmologists from January 1, 2012, through December 31, 2013. The dates of the analysis were February 1 through May 30, 2016. After exclusion of J and Q codes, the total payments to and the number of charges by individual ophthalmologists were analyzed. The mean values were compared using a single t test, and the medians were compared by the nonparametric Wilcoxon rank sum test., Main Outcomes and Measures: Primary outcome measures were the mean and median CMS payments to male and female ophthalmologists in outpatient, non-facility-based settings. Secondary outcome measures included the number of charges submitted by men and women and the types of charges most commonly submitted by men and women., Results: This study included 16 111 ophthalmologists (3078 women [19.1%] and 13 033 men [80.9%]) in 2012 and 16 179 ophthalmologists (3206 women [19.8%] and 12 973 men [80.2%]) in 2013. In 2012, the average female ophthalmologist collected $0.58 (95% CI, $0.54-$0.62; P < .001) for every dollar collected by a male ophthalmologist; comparing the medians, women collected $0.56 (95% CI, $0.50-$0.61; P < .001) for every dollar earned by men. Mean and median collections were similar when comparing female vs male ophthalmologists in 2013 (P < .001). The mean payment per charge was the same for men and women, $66 in 2012 and $64 in 2013. There was a strong association between collections and work product, with female ophthalmologists submitting fewer charges to Medicare in 2012 (median, 1120 charges; difference -935; 95% CI, -1024 to -846; P < .001) and in 2013 (median, 1141 charges; difference -937; 95% CI, -1026 to -848; P < .001) than male ophthalmologists. When corrected by comparing men and women with similar clinical activity, renumeration was still lower for women. In both years, women were underrepresented among ophthalmologists with the highest collections., Conclusions and Relevance: Remuneration from the CMS was disparate between male and female ophthalmologists in 2012 and 2013 because of the submission of fewer charges by women. Further studies are necessary to explore root causes for this difference, with equity in opportunity and parity in clinical activity standing to benefit the specialty.

Optic nerve diseases arise from many different etiologies including inflammatory, neoplastic, genetic, infectious, ischemic, and idiopathic. Understanding some of the characteristics of the most common optic neuropathies along with therapeutic approaches to these diseases is helpful in designing recommendations for individual patients. Although many optic neuropathies have no specific treatment, some do, and it is those potentially treatable or preventable conditions which need to be recognized in order to help patients regain their sight or develop a better understanding of their own prognosis. In this chapter several diseases are discussed including idiopathic intracranial hypertension, optic neuritis, ischemic optic neuropathies, hereditary optic neuropathies, trauma, and primary tumors of the optic nerve. For each condition there is a presentation of the signs and symptoms of the disease, in some conditions the evaluation and diagnostic criteria are highlighted, and where possible, current therapy or past trials are discussed.

Purpose: To develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts., Design: Modified Delphi process., Methods: A survey of uveitis specialists in the American Uveitis Society, a face-to-face meeting (AIR Workshop) held at the National Eye Institute, and 2 iterations of expert panel surveys were used in a modified Delphi process. The expert panel consisted of 17 experts, including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75% of experts in agreement., Results: There was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy and melanoma-associated retinopathy. Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as first- or second-line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a 2-tier design and that Western blot and immunohistochemistry should be the methods used to identify antiretinal antibodies., Conclusions: Consensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study., (Published by Elsevier Inc.)