Identification of epithelial membrane protein 2 (EMP2) as a molecular marker and correlate for angiogenesis in meningioma.

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 (R2 = 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.

Programmed cell death-1 is expressed in large retinal ganglion cells and is upregulated after optic nerve crush.

Programmed cell death-1 (PD-1) is a key negative receptor inducibly expressed on T cells, B cells and dendritic cells. It was discovered on T cells undergoing classical programmed cell death. Studies showed that PD-1 ligation promotes retinal ganglion cell (RGC) death during retinal development. The purpose of this present study is to characterize PD-1 regulation in the retina after optic nerve crush (ONC). C57BL/6 mice were subjected to ONC and RGC loss was monitored by immunolabelling with RNA-binding protein with multiple splicing (Rbpms). Time course of PD-1 mRNA expression was determined by real-time PCR. PD-1 expression was detected with anti-PD-1 antibody on whole mount retinas. PD-1 staining intensity was quantitated. Colocalization of PD-1 and cleaved-caspase-3 after ONC was analyzed. Real-time PCR results demonstrated that PD-1 gene expression was significantly upregulated at day 1, 3, 7, 10 and 14 after ONC. Immunofluorescent staining revealed a dramatic increase of PD-1 expression following ONC. In both control and injured retinas, PD-1 tended to be up-expressed in a subtype of RGCs, whose somata size were significantly larger than others. Compared to control, PD-1 intensity in large RGCs was increased by 82% in the injured retina. None of the large RGCs expressed cleaved-caspase-3 at day 5 after ONC. Our work presents the first evidence of PD-1 induction in RGCs after ONC. This observation supports further investigation into the role of PD-1 expression during RGC death or survival following injury.

89Zr-ImmunoPET for the Specific Detection of EMP2-Positive Tumors.

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.

EMP2 Serves as a Functional Biomarker for Chemotherapy-Resistant Triple-Negative Breast Cancer.

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.

A Systematic Review of Clinical Trials in Uveitis: Lessons Learned.

PURPOSE: Clinical trials in uveitis have led to the expansion of therapeutic options for the management of non-infectious uveitis. The purpose of this systematic review is to investigate why some clinical trials have yielded successful results and regulatory approval of new therapies, and some have not. METHODS: A systematic literature search of the Pubmed/MEDLINE database and clinicaltrials.gov was performed from 2006 to 2021, according to the PRISMA guidelines. Phase III clinical trials of systemic and local therapies in adults with non-infectious intermediate, posterior, and panuveitis were included. RESULTS: A total of 79 clinical trials were collected from ClinicalTrials.gov and PubMed/MEDLINE database search. Based on the inclusion and exclusion criteria, 14 clinical trials were included. CONCLUSION: This review summarizes the study design, outcome measures, and results of recent phase III trials in non-infectious uveitis, in the interest of understanding limitations and rethinking new methods of defining endpoints in clinical trial design.

Knowledge, attitudes and intention on fertility preservation among breast cancer patients.

Breast cancer is the most common cancer in reproductive age women. The aim of this study is to assess the knowledge, attitude and intention on fertility preservation among women diagnosed to have breast cancer. This is a multi-centre cross-sectional questionnaire study. Reproductive age women diagnosed with breast cancer attending Oncology, Breast Surgery and Gynaecology Clinics and support groups were invited to participate. Women filled in paper or electronic form of the questionnaire. 461 women were recruited and 421 women returned the questionnaire. Overall, 181/410 (44.1%) women had heard of fertility preservation. Younger age and higher education level were significantly associated with increased awareness of fertility preservation. Awareness and acceptance of the different fertility preservation methods in reproductive age women with breast cancer was suboptimal. However, 46.1% women felt that their fertility concerns affected their decision for cancer treatment in some way.

The impact of the multi-disciplinary molecular tumour board and integrative next generation sequencing on clinical outcomes in advanced solid tumours.

Background: The integration of next-generation sequencing (NGS) comprehensive gene profiling (CGP) into clinical practice is playing an increasingly important role in oncology. Therefore, the HKU-HKSH Multi-disciplinary Molecular Tumour Board (MTB) was established to advance precision oncology in Hong Kong. A multicenter retrospective study investigated the feasibility of the HKU-HKSH MTB in determining genome-guided therapy for treatment-refractory solid cancers in Hong Kong. Methods: Patients who were presented at the HKU-HKSH MTB between August 2018 and June 2022 were included in this study. The primary study endpoints were the proportion of patients who receive MTB-guided therapy based on genomic analysis and overall survival (OS). Secondary endpoints included the proportion of patients with actionable genomic alterations, objective response rate (ORR), and disease control rate (DCR). The Kaplan-Meier method was used in the survival analyses, and hazard ratios were calculated using univariate Cox regression. Findings: 122 patients were reviewed at the HKU-HKSH MTB, and 63% (n = 77) adopted treatment per the MTB recommendations. These patients achieved a significantly longer median OS than those who did not receive MTB-guided therapy (12.7 months vs. 5.2 months, P = 0.0073). Their ORR and DCR were 29% and 65%, respectively. Interpretation: Our study demonstrated that among patients with heavily pre-treated advanced solid cancers, MTB-guided treatment could positively impact survival outcomes, thus illustrating the applicability of NGS CGPs in real-world clinical practice. Funding: The study was supported by the Li Shu Pui Medical Foundation. Dr Aya El Helali was supported by the Li Shu Pui Medical Foundation Fellowship grant from the Li Shu Pui Medical Foundation. Funders had no role in study design, data collection, data analysis, interpretation, or writing of the report.

Neuronal programmed cell death-1 ligand expression regulates retinal ganglion cell number in neonatal and adult mice.

OBJECTIVES: During mouse retina maturation, the final number of retinal ganglion cells (RGCs) is determined by highly regulated programmed cell death. Previous studies demonstrated that the immunoregulatory receptor programmed cell death-1 (PD-1) promotes developmental RGC death. To identify the functional signaling partner(s) for PD-1, we identified retinal expression of PD-1 ligands and examined the effect of PD-1 ligand expression on RGC number. We also explored the hypothesis that PD-1 signaling promotes the development of functional visual circuitry. METHODS: Characterization of retinal and brain programmed cell death-1 ligand 1 (PD-L1) expression were examined by immunofluorescence on tissue sections. The contribution of PD-ligands, PD-L1, and programmed cell death-1 ligand 2 (PD-L2) to RGC number was examined in PD-ligand knockout mice lacking 1 or both ligands. Retinal architecture was assessed by spectral-domain optical coherence tomography, and retinal function was analyzed by electroretinography in wild-type and PD-L1/L2 double-deficient mice. RESULTS: PD-L1 expression is found throughout the neonatal retina and persists in adult RGCs, bipolar interneurons, and Müller glia. In the absence of both PD-ligands, there is a significant numerical increase in RGCs (34% at postnatal day 2 [P2] and 18% in adult), as compared to wild type, and PD-ligands have redundant function in this process. Despite the increased RGC number, adult PD-L1/L2 double-knockout mice have normal retinal architecture and outer retina function. CONCLUSION: This study demonstrates that PD-L1 and PD-L2 together impact the final number of RGCs in adult mice and supports a novel role for active promotion of neuronal cell death through PD-1 receptor-ligand engagement.

Publication bias, Open-Labeled Trials and Sky Rocketing Costs- Past, Present and Future of Repository Corticotropin Injection?

Repository corticotropin injection (RCI) has recently gained attention in the field of ocular inflammatory disease. Data supporting the use of RCI therapy in ocular inflammation are limited to case reports or small series subject to publication bias toward positive results. How this therapy differs significantly from oral corticosteroids, which are significantly cheaper, is unknown. Clinical trials to investigate the efficacy of RCI are currently limited to open-labeled non-comparative studies. Side effects of RCI are not insignificant, have been reported in other fields of medicine, and require further scrutiny. Finally, the price of RCI has skyrocketed with average yearly cost of therapy estimated to be between $480,000-$850,000 with allegations of the RCI manufacturing drug company providing remuneration to induce healthcare providers to prescribe RCIs but without any repercussions from a regulatory standpoint. The significant cost of RCI combined with lack of evidence-based guidance on efficacy, safety, and indications for use in ocular inflammation warrant caution in utilizing this therapy.

Validation of a fully automated chemiluminescent immunoassay for cattle serum and plasma progesterone measurement.

Introduction: Monitoring circulating progesterone concentration ([P4]) is an important component of basic and applied reproduction research and clinical settings. IMMULITE® 2000 XPi (Siemens Healthineers, Cary, NC) is a newly upgraded fully automated immunoassay system marketed for human use to measure concentrations of different measurands including P4. Objectives: Our objective was therefore to characterize the analytical performance of the IMMULITE® 2000 XPi P4 immunoassay (IPI) across the reportable range in serum and plasma of cattle. Methods: The IPI validation protocols included characterization of the method linearity, within-run, and between-run precision through calculation of the coefficient of variation (CV). The method accuracy was assessed through the calculation of the spiking-recovery (SR) bias across the reportable range (0.2-40.0 ng/mL). Passing-Bablok regression and Bland-Altman plots were used to determine the interlaboratory bias for two laboratories. Three types of observed total error (TEo) were calculated based on the considered type of bias, TEoSR (spiking-recovery), TEoRB (range-based bias), and TEoAB (average-based bias). Results: The IPI was linearly related to the true value (R 2 = 0.997) across the reportable range. The within-run and between-run precision (CV%) of the IPI for both serum and plasma [P4] of clinical relevance (1, 2, 5, and 10 ng/mL) were <5 and <10%, respectively. The TEo reported here for serum and plasma at [P4] of 1 and 5 ng/mL was ~20 and 25%, respectively. Of interest, the three types of TEo were relatively similar regardless of the considered bias. Conclusions: We concluded that the automated IPI provides a precise, accurate, reliable, and safe method for measuring [P4] in both serum and plasma of cattle. Consistent with the manufacturer's recommendations, the serum matrix is more accurate than plasma.

Analytical Validation of the IMMULITE® 2000 XPi Progesterone Assay for Quantitative Analysis in Ovine Serum.

Monitoring circulating progesterone (P4) concentration is an important component of basic and applied reproduction research and clinical settings. IMMULITE® 2000 XPi (Siemens) is a newly upgraded fully automated immunoassay system marketed for human use to measure concentrations of different analytes including P4. Our objective was therefore to characterize the analytical performance of the IMMULITE® 2000 XPi P4 immunoassay across the reportable range in ovine serum. This validation of analytical performance included determining (1) linearity, (2) precision through within-run, and between-run coefficient of variation (CV) calculations, (3) accuracy through bias calculations for spiking-recovery bias and interlaboratory (range and average based) bias for two laboratories across the reportable range (0.2−40 ng/mL). The average within-run and between-run precision (CV%) across the reportable range of the IMMULITE® 2000 XPi P4 immunoassay for serum P4 concentration were both <5%, ranging between 2−8%. The average Observed Total Analytic Error (TEo) reported here for serum P4 concentration across the reportable range was ~30%, ranging from 14.8−59.4%, regardless of the considered bias. Based on these data we conclude that the automated IMMULITE® 2000 XPi P4 immunoassay provides a precise, accurate, reliable, and safe method for measuring P4 concentration ovine serum.

Patient Adherence to Immunosuppressive Therapy in Treatment of Chronic Inflammatory Eye Disease.

TITLE: Patient Adherence to Immunosuppressive Therapy for Chronic Inflammatory Eye Disease. PURPOSE: To investigate adherence rates to immunosuppressive therapy (IMT) for treatment of noninfectious inflammatory eye disease (IED), adherence and disease control, and factors associated with nonadherence. METHOD: Retrospective review of medical charts from 2015 to 2020 was conducted on patients with IED at 6 months, 1 and 2 years after initiation of IMT. RESULTS: Of 183 patients, adherence rates at 6 months and 1 year were 70% and 58% by 2 years. Eighty-two percent, 78%, and 65% of patients with disease quiescence were adherent at 6 months, 1 and 2 years, respectively. Adherent patients have 1.86 (95% CI 1.09, 3.20) times greater likelihood for disease control compared to nonadherent. Primary reason for nonadherence was patient self-discontinuation. No specific factors were associated with nonadherence. CONCLUSION: Patients on IMT for IED had steady adherence rates up to 1 year, with decreased adherence at 2 years. Adherence to IMT significantly correlates with disease quiescence.

Epithelial membrane protein 2 (EMP2) regulates hypoxia-induced angiogenesis in the adult retinal pigment epithelial cell lines.

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.

Outcomes of Repository Corticotropin Gel for Ocular Sarcoidosis.

PURPOSE: To evaluate the utility and side effect profile of subcutaneous repository corticotropin gel (RCI) in ocular sarcoidosis. METHODS: Retrospective chart review. RESULTS: Among six identified patients on RCI therapy, 4 had uveitis, one had optic neuritis and one had uveitis and optic neuritis secondary to sarcoidosis. The average follow-up was 43.5 months. RCI therapy was continuous in 4 patients (average 7.7 months) and intermittent in 2 patients (24 and 12 months). Five of the 6 patients continued with local and/or systemic corticosteroids for ocular inflammation control while on RCI therapy.  Two-thirds of patients experienced adverse effects including hyperpigmentation, alopecia, and severe hypertension. RCI therapy was discontinued in 5 of the 6 patients due to continued inflammation and side/adverse effects (4 patients) and loss of follow-up (1 patient). CONCLUSION: In this small cohort, the majority of patients failed to achieve adequate steroid-sparing ocular inflammation control and experienced side effects while on RCI therapy. Additional studies are needed to elucidate the role of RCI in ocular inflammation.

Epidemiology and Risk Factors in Non-infectious Uveitis: A Systematic Review.

Purpose: Non-infectious uveitis is a leading cause of vision loss in the developed world. The purpose of this systematic review is to investigate the epidemiology and risk factors of non-infectious uveitis over the last 50 years. Methods: A systematic literature search of Pubmed/MEDLINE database was performed in the 50-year period from January 1971 to January 2021, according to the PRISMA guidelines. Studies that assessed the epidemiology and risk factors for non-infectious uveitis were included. Results: Few epidemiologic studies focus specifically on non-infectious uveitis. In the Unites States, the estimated prevalence of non-infectious uveitis is 121/100,000. The incidence and prevalence varies considerably worldwide. Females and the working age group (20-50 years) appear to be the most affected. Smoking and vitamin D deficiency are the biggest risk factors for non-infectious uveitis, while pregnancy appears to be protective. Additional risk factors include presence of other autoimmune diseases (thyroid disease, diabetes, celiac), pre-eclampsia/eclampsia, psychological stress, and certain medications (bisphosphonates, immune checkpoint inhibitors, female hormone therapy, and etanercept). Discussion: Our systematic review summarizes the incidence and prevalence of non-infectious uveitis and associated modifiable and non-modifiable risk factors.

Regulation of particle morphology of pH-dependent poly(epsilon-caprolactone)-poly(gamma-glutamic acid) micellar nanoparticles to combat breast cancer cells.

The advantage of polymeric drug carriers lies in the uptake of the polymer nanoparticles by cancer cells before they release the drug, thereby reducing its toxic effects on healthy cells. A poly(gamma-glutamic acid)-b-poly(epsilon-caprolactone)-b-poly(gamma-glutamic acid) block copolymer was synthesized to encapsulate the anti-cancer drug doxorubicin in the treatment of wild type human breast cancer cells (MCF-7/WT). This pH-controllable carrier is negatively-charged in the presence of healthy tissues leading to lower cellular uptake. On the other hand, it becomes more hydrophobic in the acidic environment of cancer tissues, increasing its cellular uptake through the lipid bilayer. The block copolymer was characterized using Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, differential scanning calorimetry and dynamic light scattering. The micelles formed at a critical concentration range of 62-130 microg/mL depending on the composition of poly(gamma-glutamic acid) and poly(epsilon-caprolactone) chains. The nano-sized micelles were found to have pH-dependent sizes in the range of 90-200 nm. The role of poly(gamma-glutamic acid) was to increase the hydrophilicity and decrease the particle size of the copolymer. The structures of micelles that were more compact and less anionic showed better stability in plasma. It was found that the drug loading content and drug loading efficiency were 12.14% and 97.22% respectively. The copolymer showed shrinking and aggregation at low pH which led to a slower drug release. These nano-sized micelles showed potential as effective drug delivery carriers for doxorubicin because of its accumulation and slow release inside the MCF-7/WT cells.

EMP2 Is a Novel Regulator of Stemness in Breast Cancer Cells.

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 ALDHhigh 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 ALDHhigh 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.

Epithelial Membrane Protein-2 (EMP2) Antibody Blockade Reduces Corneal Neovascularization in an In Vivo Model.

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.

Perioperative Management of Uveitic Cataracts.

Uveitis patients represent a unique subset of the population undergoing cataract surgery and pose several challenges that require special consideration and strategy. Maintenance of disease quiescence for at least three months prior to surgery maximizes postoperative outcomes, though these patients remain at increased risk for pseudophakic cystoid macular edema, which can be refractory to the traditional steroid treatments. In this review, we detail the pillars of preoperative optimization, intraoperative considerations, and postoperative management of uveitic cataracts, with special attention on the evidence surrounding prevention and treatment of refractory postoperative cystoid macular edema.

Cytomegalovirus Retinitis in HIV and Non-HIV Individuals.

Cytomegalovirus retinitis (CMVR) is a severe, vision-threatening disease that primarily affects immunosuppressed patients. CMVR is the most common ocular opportunistic infection in human immunodeficiency virus (HIV) infected patients and is the leading cause of blindness in this group; however, the incidence of CMVR in HIV patients has dramatically decreased with antiretroviral therapy. Other causes of immunosuppression, including organ transplantation, hematologic malignancies, and iatrogenic immunosuppression, can also lead to the development of CMVR. Herein, we describe the pathogenesis of CMVR and compare clinical features, epidemiology, and risk factors in HIV and non-HIV infected individuals with CMVR.