Heart failure remains a highly prevalent condition with diverse etiology, yet the underlying signaling mechanisms are not fully understood. Despite the profound effects of post-translational protein modifications on downstream signaling, limited studies have investigated the cardiac phosphoproteome in human heart failure. We hypothesized that a combined proteomic and phosphoproteomic analysis of human dilated (DCM) and ischemic (ICM) cardiomyopathy would reveal novel etiology-associated disease pathways. Integrative analyses of left ventricular explants from DCM patients ( n =4) vs. non-failing controls ( n =4), and left ventricular infarct vs. non-infarct, and peri-infarct vs. non-infarct regions of ICM patients ( n =4) identified 5,570 unique proteins with 13,624 corresponding phosphorylation sites. Each pair-wise comparison revealed shared and etiology-specific signatures, with a unique DCM-associated enrichment of cell-cell adhesion pathways. We focused our attention on αT-catenin (CTNNA3) as a cardiomyocyte intercalated disc candidate phosphoprotein with a unique cluster of 4 hyperphosphorylated sites in DCM hearts ( P <0.0001). Overexpression of non-phosphorylatable hCTNNA3 in ex vivo isolated adult mouse cardiomyocytes showed internalized protein expression and weaker cell-cell adhesion vs. wildtype (WT) and phospho-mimetic forms. We established an in vivo mouse model using recombinant adeno-associated virus 9 (rAAV9) harboring hCTNNA3-WT, hCTNNA3-phospho-null, or empty rAAV9 control. Phospho-null CTNNA3 mice developed left ventricular dilation and contractile dysfunction (% EF; 51.25±1.17 phospho-null vs. 62.07±1.20 WT vs. 66.76±1.42 empty; n ≥10) with impaired left ventricular conduction velocity (cm/s; 36.83±1.10 phospho-null vs. 47.74±2.04 WT; n =6), by echocardiography and ex vivo optical mapping. Loss of CTNNA3 phosphorylation led to intercalated disc remodeling with internalization and dissociation of CTNNA3, connexin 43, N-cadherin, β-catenin, and plakophilin 2 from the adherens junction, using high-resolution confocal imaging. Together these findings reveal a compensatory role for αT-catenin phosphorylation in maintaining cardiomyocyte intercalated disc organization in human DCM.

Purpose: The purpose of this study was to report a case of spontaneous formation and resolution of a lamellar macular hole in a patient with diabetic macular edema treated with steroid implants. Methods: This study is a case report. Results: A 53-year-old man presented with blurry vision and was found to have diabetic macular edema that remained refractory to treatment despite multiple short-term intravitreal steroid implants. He was eventually treated with an intravitreal fluocinolone acetonide implant and was subsequently noted to have developed a lamellar macular hole that then resolved spontaneously without any additional therapy. Conclusion: There can be spontaneous formation and resolution of lamellar holes in the treatment of diabetic macular edema because of reorganization of the inner retinal layers, without significant impact on visual acuity. To the best of our knowledge, this finding has not been previously reported.

The prognosis and treatment outcomes of heart failure (HF) patients rely heavily on disease etiology, yet the majority of underlying signaling mechanisms are complex and not fully elucidated. Phosphorylation is a major point of protein regulation with rapid and profound effects on the function and activity of protein networks. Currently, there is a lack of comprehensive proteomic and phosphoproteomic studies examining cardiac tissue from HF patients with either dilated dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM). Here, we used a combined proteomic and phosphoproteomic approach to identify and quantify more than 5,000 total proteins with greater than 13,000 corresponding phosphorylation sites across explanted left ventricle (LV) tissue samples, including HF patients with DCM vs. nonfailing controls (NFC), and left ventricular infarct vs. noninfarct, and periinfarct vs. noninfarct regions of HF patients with ICM. Each pair-wise comparison revealed unique global proteomic and phosphoproteomic profiles with both shared and etiology-specific perturbations. With this approach, we identified a DCM-associated hyperphosphorylation cluster in the cardiomyocyte intercalated disc (ICD) protein, & alpha;T-catenin (CTNNA3). We demonstrate using both ex vivo isolated cardiomyocytes and in vivo using an AAV9-mediated overexpression mouse model, that CTNNA3 phosphorylation at these residues plays a key role in maintaining protein localization at the cardiomyocyte ICD to regulate conductance and cell-cell adhesion. Collectively, this integrative proteomic/phosphoproteomic approach identifies region and etiology-associated signaling pathways in human HF and describes a role for CTNNA3 phosphorylation in the pathophysiology of DCM.

OBJECTIVE:Surgical repair of complex tractional retinal detachments (TRDs) can be challenging due to the difficulty in delineating the fibroglial membranes from the underlying retinal surface. We describe the visual and retinal reattachment rate with the intraoperative use of trypan blue (TB) to visualize proliferative fibrous membranes in patients with TRDs. DESIGN:Retrospective study. PARTICIPANTS:Seventeen patients who underwent a pars plana vitrectomy for surgical TRD repair with TB use between January 1, 2005, and December 31, 2020. METHODS:Patient charts were retrospectively evaluated for surgical details, preoperative and postoperative logMAR best-corrected visual acuity (BCVA) and status of retinal attachment om days 30 and 90 and at the most recent follow-up visit. RESULTS:In the cohort of 17 patients, TRDs were found to be secondary to proliferative diabetic retinopathy, complications from endophthalmitis, open globe injury, and neovascularization secondary to a retinal vein occlusion. Mean ± SD preoperative BCVA was 1.7 ± 1.7 logMAR (Snellen, 20/1000), whereas postoperative BCVA at the most recent follow-up visit was 1.4 ± 1.2 logMAR (Snellen, 20/500). The use of TB was successful in delineating the proliferative preretinal membranes in 100% of patients, with no residual staining of posterior segment tissues or adverse reactions related to the dye noted at postoperative visits. Eighty-eight percent (15 of 17) and 76% of retinas (13 of 17) were attached at postoperative month 3 and 6 visits, respectively. CONCLUSION:TB can be a useful adjunct tool to visualize and allow for a thorough removal of tractional fibrous proliferative epiretinal membranes in patients with complex TRDs, possibly yielding better surgical and long-term reattachment outcomes.

To determine the association between pre-operative central subfield thickness (CST) and post-radiotherapy visual acuity (VA), cystoid macular edema (CME), and intravitreal anti-vascular endothelial growth factor (VEGF) requirement. Single-center retrospective study. Patients with plaque-irradiated extramacular choroidal melanoma treated between 11/11/2011 and 4/30/2021. Pre-operative CST difference between the affected and unaffected eye was used. Kaplan-Meier analysis and hazard ratios were calculated. Of 85 patients, pre-operative CST was greater in the melanoma-affected eye (vs. fellow eye) by mean of 20.4 μm (median 14.0, range − 60.0–182.0). Greater CST at presentation (vs. fellow eye) was associated with larger tumor diameter (p = 0.02), greater tumor thickness (p < 0.001), and more frequent tumor-related Bruch’s membrane rupture (p = 0.006). On univariate analysis of outcome data, greater CST at presentation (vs. fellow eye) was associated with higher 5-year risk (1.09 [1.02–1.17], p = 0.02) of VA 20/200 or worse and increased (1.10 [1.01–1.20], p = 0.03) likelihood for anti-VEGF injections after plaque irradiation. There was no significant association with CME. The association between CST and VA outcome remained significant on multivariate analysis accounting for impact of tumor thickness and radiation dose to optic disc, while tumor distance to fovea was the only significant factor on multivariate analysis for anti-VEGF injections. Greater CST at presentation (vs. fellow eye) was associated with worse VA outcome following plaque radiotherapy for choroidal melanoma. Large-sized tumors may contribute to a higher intraocular VEGF burden, potentially leading to greater preoperative CST, which correlates with poor VA outcome post-plaque radiotherapy.

Purpose: Foveal herniation occurs when neuroretinal tissue protrudes through and above the level of an epiretinal membrane. This study describes the visual symptoms and spectral domain optical coherence tomography findings associated with foveal herniation and evaluates the postoperative visual, anatomical, and surgical outcomes. Methods: A multicenter retrospective review of patients diagnosed with epiretinal membrane identified 59 patients with preoperative foveal herniation on spectral domain optical coherence tomography. Data regarding visual symptoms, preoperative and postoperative best-corrected visual acuity (BCVA), central retinal thickness, macular volume, and size of foveal herniation were collected, and statistical analysis was performed. Results: A total of 58 of the 59 patients with foveal herniation underwent surgical epiretinal membrane peeling, with foveal contour restored in 53.5% of patients after surgery. Average BCVA improved from 20/80 to 20/40 Snellen equivalent at most-recent postoperative visit (P < 0.0001). The average central retinal thickness decreased from 632 µm to 432 µm (P < 0.0001) and the average macular volume decreased from 11.3 mm3 to 9.5 mm3 (P < 0.0001) at 3 months postoperatively. Preoperatively, greater herniation height was associated with worse BCVA (P = 0.008), greater central retinal thickness (P = 0.01), retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone abnormality, and external limiting membrane abnormalities (P < 0.05). Postoperatively, there was a decrease in retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone, and external limiting membrane abnormality (P < 0.05) on spectral domain optical coherence tomography. Conclusion: Patients with larger foveal herniation height had greater preoperative central retinal thickness, worse preoperative and postoperative BCVA, and more intraretinal abnormalities on spectral domain optical coherence tomography. Surgical epiretinal membrane peeling in patients with foveal herniation resulted in a significant improvement in patients' BCVA and microstructural abnormalities.

BackgroundIron overload cardiomyopathy (IOC) is a major co-morbidity of genetic hemochromatosis and secondary iron overload with limited therapeutic options. We aim to investigate mechanisms of rescue action of amlodipine in the murine model of iron overload, characterize changes in human cardiac tissue due to IOC, and compare them to the changes in the animal model of IOC.Methods and resultsAs an animal model, we used male hemojuvelin knockout (HJVKO) mice, which lacked hemojuvelin (a co-receptor protein for hepcidin expression). The mice were fed a high-iron diet from 4 weeks to 1 year of age. As a rescue, iron-fed mice received the Ca2+ channel blocker, amlodipine, from 9 to 12 months. Iron overload resulted in systolic and diastolic dysfunctions and changes in the cardiac tissue similar to the changes in the explanted human heart with IOC. An IOC patient (β-thalassemia) with left-ventricular ejection fraction (LVEF) 25% underwent heart transplantation. The murine model and the explanted heart showed intra-myocyte iron deposition, fibrosis, hypertrophy, oxidative stress, remodeling of Ca2+ cycling proteins, and metabolic kinases typical of heart failure. Single-myocyte contractility and Ca2+ release were diminished in the murine model. The amlodipine-treated group exhibited normalization of cellular function and reversed fibrosis, hypertrophy, oxidative stress, and metabolic remodeling. We also report a clinical case of primary hemochromatosis successfully treated with amlodipine.ConclusionsThe aged HJVKO murine model on the iron-rich diet reproduced many features of the human case of IOC. The use of amlodipine in the murine model and clinical case reversed IOC remodeling, demonstrating that amlodipine is effective adjuvant therapy for IOC.

Epiretinal membrane with foveal herniation is a rare presentation of a common disease. Only 1 case without follow-up has been reported in the literature so far, and there are no reports on visual outcome following membrane peel. We present a patient with epiretinal membrane causing significant macular edema and foveal herniation through a round central hole within the epiretinal membrane. The patient underwent vitrectomy with epiretinal membrane peel and indocyanine green assisted wide internal limiting membrane peel, which resulted in substantial visual acuity gain and restoration of macular anatomy. The presence of severe foveal herniation does not preclude good visual and anatomic outcome.

HomeStrokeVol. 53, No. 7Thrombosed Developmental Venous Anomaly as a Rare Cause of Brain Stem Venous Infarction Free AccessCase ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCase ReportPDF/EPUBThrombosed Developmental Venous Anomaly as a Rare Cause of Brain Stem Venous Infarction Stephanie B. Syc-Mazurek, Nathan A. Seven, Saumya M. Shah, John J. Chen and Zafer Keser Stephanie B. Syc-MazurekStephanie B. Syc-Mazurek Correspondence to: Stephanie B. Syc-Mazurek, MD, PhD, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Email E-mail Address: [email protected] https://orcid.org/0000-0002-9549-6648 Department of Neurology (S.B.S.-M., N.A.S., J.J.C., Z.K.), Mayo Clinic, Rochester, MN. , Nathan A. SevenNathan A. Seven Department of Neurology (S.B.S.-M., N.A.S., J.J.C., Z.K.), Mayo Clinic, Rochester, MN. , Saumya M. ShahSaumya M. Shah Department of Neurology (S.B.S.-M., N.A.S., J.J.C., Z.K.), Mayo Clinic, Rochester, MN. , John J. ChenJohn J. Chen Department of Neurology (S.B.S.-M., N.A.S., J.J.C., Z.K.), Mayo Clinic, Rochester, MN. Department of Ophthalmology (S.M.S., J.J.C.), Mayo Clinic, Rochester, MN. and Zafer KeserZafer Keser https://orcid.org/0000-0001-6415-0874 Department of Neurology (S.B.S.-M., N.A.S., J.J.C., Z.K.), Mayo Clinic, Rochester, MN. Originally published6 May 2022https://doi.org/10.1161/STROKEAHA.122.038314Stroke. 2022;53:e253–e254Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: May 6, 2022: Ahead of Print Key PointDevelopmental venous anomalies are typically asymptomatic variations occurring in 2% to 3% of the population; however, thrombosis of these veins is a rare cause of venous infarction.1,2A 62-year-old man presented with acute-onset left gaze deviation and diplopia. Exam demonstrated partial right horizontal gaze palsy not overcome with vestibulo-ocular reflex, exotropia, right hypertropia from a skew deviation, and vertical gaze-evoked nystagmus. Exam findings localized to the right abducens nucleus with the vertical gaze-evoked nystagmus pattern indicating involvement of the medial longitudinal fasciculus and paramedian tracts. Magnetic resonance imaging demonstrated an acute infarct in the right ventral dorsal tegmentum and linear hypointensity on susceptibility images with surrounding edema consistent with a thrombosed developmental venous anomaly (Figure [A through D]). Hypercoagulable workup was negative. He was started on apixaban. His symptoms slowly resolved. At 3-month follow-up, extraocular movements were normal and magnetic resonance imaging showed resolved vasogenic edema with midbrain linear enhancement suggestive of recanalization of the thrombosed vessel, and thus apixaban was transitioned to low-dose aspirin (Figure [E and F]).Download figureDownload PowerPointFigure. Imaging findings of a brain stem thrombosed developmental venous anomaly. Magnetic resonance imaging of the brain demonstrating an acute infarct (indicated by black arrow) in the right dorsal pons with diffusion restriction (A) and apparent diffusion coefficient correlate (A, inset) with midline linear susceptibility (B) consistent with a thrombosed venous anomaly. On initial presentation, there was a midline T2/fluid-attenuated inversion recovery hyperintensity consistent with vasogenic edema (C), which had resolved at 3-mo follow-up (E). T1-weighted postgadolinium images demonstrated more prominent linear enhancement (white arrow) at follow-up (F) when compared with initial imaging (D).Article InformationSources of FundingNone.Disclosures Dr Chen is a consultant for Roche and UCB. The other authors report no conflicts.FootnotesFor Sources of Funding and Disclosures, see page e254.Correspondence to: Stephanie B. Syc-Mazurek, MD, PhD, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Email syc-mazurek.[email protected].eduReferences1. Ruíz DS, Yilmaz H, Gailloud P. Cerebral developmental venous anomalies: current concepts.Ann Neurol. 2009; 66:271–283. doi: 10.1002/ana.21754CrossrefGoogle Scholar2. Hon JM, Bhattacharya JJ, Counsell CE, Papanastassiou V, Ritchie V, Roberts RC, Sellar RJ, Warlow CP, Al-Shahi Salman R; SIVMS Collaborators. The presentation and clinical course of intracranial developmental venous anomalies in adults: a systematic review and prospective, population-based study.Stroke. 2009; 40:1980–1985. doi: 10.1161/STROKEAHA.108.533034LinkGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails July 2022Vol 53, Issue 7 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.122.038314PMID: 35514283 Originally publishedMay 6, 2022 Keywordsthrombosisdiplopiabrain steminfarctionPDF download Advertisement

Purpose: New-onset persistent diplopia has become a common complication after glaucoma drainage device (GDD) placement. Understanding the orbital anatomy of such patients may provide information regarding risk of diplopia, GDD selection, and post-operative management. The purpose of this study was to examine the orbital anatomic differences in diplopic and non-diplopic patients after GDD implantation using high-resolution MRI. Methods: Seven eyes (N = 4 with diplopia and N = 3 without diplopia after GDD placement) of seven patients that had undergone placement of Baerveldt 250 (B250), Baerveldt 350 (B350), or Ahmed FP7 (FP7) GDD were prospectively enrolled at a single institution. All patients underwent a 3.0T orbital MRI with 3D volumetric T1 and T2 weighted sequence. Images were analyzed for orbital volume, axial length, orbital distances, presence of superior rectus-lateral rectus (SR-LR) band, position of GDD, and SR-LR angles. Results: Patients with diplopia had smaller mean ± SD orbital axial (911.5 ± 111.8 mm3 vs 931.7 ± 79.7 mm3) and coronal volumes (1162.5 ± 145.5 mm3 vs 1180 ± 34.6 mm3) compared to non-diplopic patients. Average orbital rim distances were larger for the diplopic group. The SR-LR displacement angle for diplopic patients was larger (101.6° ± 8.1 vs 94.7° ± 17.6) while the SR-LR quadrantic angle (86.6° ± 4.2 vs 89.1° ± 4.3) was smaller. SR-LR band was present and intact in all patients. GDD malpositioning was not evident in any patient. Conclusion: The decreased orbital axial and coronal volumes as well as increased orbital rim distances in diplopic patients suggests the need for further studies to understand the role of orbital anatomy in occurrence of diplopia. Dynamic MRI imaging may be helpful in identifying differences in extraocular muscle function that reveal an etiology of diplopia in patients with GDD implantation.

Left ventricular assist device (LVAD) use in patients with dilated cardiomyopathy (DCM) can lead to a differential response in the LV and right ventricle (RV), and RV failure remains the most common complication post-LVAD insertion. We assessed transcriptomic signatures in end-stage DCM, and evaluated changes in gene expression (mRNA) and regulation (microRNA/miRNA) following LVAD. LV and RV free-wall tissues were collected from end-stage DCM hearts with (n = 8) and without LVAD (n = 8). Non-failing control tissues were collected from donated hearts (n = 6). Gene expression (for mRNAs/miRNAs) was determined using microarrays. Our results demonstrate that immune response, oxygen homeostasis, and cellular physiological processes were the most enriched pathways among differentially expressed genes in both ventricles of end-stage DCM hearts. LV genes involved in circadian rhythm, muscle contraction, cellular hypertrophy, and extracellular matrix (ECM) remodelling were differentially expressed. In the RV, genes related to the apelin signalling pathway were affected. Following LVAD use, immune response genes improved in both ventricles; oxygen homeostasis and ECM remodelling genes improved in the LV and, four miRNAs normalized. We conclude that LVAD reduced the expression and induced additional transcriptomic changes of various mRNAs and miRNAs as an integral component of the reverse ventricular remodelling in a chamber-specific manner.

center dot PURPOSE: To report outcomes of patients presenting to the emergency department (ED) with new-onset visual flashes and/or floaters following implementation of a for-malized triage protocol allowing eligible patients to be dis-charged for prompt outpatient ophthalmic examination. center dot DESIGN: Retrospective consecutive case series. center dot METHODS: Patient characteristics, protocol eligibility, and clinical outcomes were recorded for adult patients triaged within a formal "flashes and floaters" protocol at a single academic ED. center dot RESULTS: A total of 457 patients presented for 471 unique ED encounters with a chief complaint of vi-sual flashes and/or floaters between October 2014 and May 2018. In all, 61% of patient encounters (287/471) met protocol criteria for prompt outpatient ophthalmic examination, of whom 94% (269/287) were exam-ined within 48 hours. Final diagnoses of protocol -eligible patients were posterior vitreous detachment only (73%, 197/269), retinal break(s) (10%, 26/269), mi-graine (5%, 14/269), and no cause or new cause found (10%, 27/269). No protocol-eligible patients had reti-nal detachment or diagnoses requiring emergent diag-nostic or therapeutic care (0%, 95% CI = 0%-1.1%). Final diagnoses following 175 encounters not meet-ing criteria for deferred examination included poste-rior vitreous detachment only (25%, 43/175), retinal break(s) (19%, 33/175), macula-involving retinal de-tachment (13%, 22/175), macula-sparing retinal detach-ment (11%, 19/175), retinal arterial occlusion (2%, 3/175), and stroke (0.6%, 1/175). The Cohen kappa for agreement on protocol eligibility between the ED physi-cian and ophthalmologist was 0.85. center dot CONCLUSIONS: A formalized ED "flashes and floaters" triage protocol may help identify patients for whom prompt outpatient ophthalmic examination may be more safely considered. (Am J Ophthalmol 2022;242: 125-130. (c) 2022 Elsevier Inc. All rights reserved.)

PURPOSE: To examine the risk, prevalence, and progression of glaucoma development in age-related macular degeneration (AMD) eyes receiving intravitreal anti -vascular endothelial growth factor (anti-VEGF) injections compared to controls. DESIGN: Retrospective clinical cohort study. METHODS: Retrospective review of eyes receiving intravitreal anti-VEGF injections from January 1, 2004, to December 31, 2013, for exudative AMD. Age-and sex -matched control groups of eyes included eyes with nonexudative AMD (NEAMD) and no AMD. Eyes with a diagnosis of glaucoma or glaucoma suspect were reviewed for injection details, type and date of glaucoma diagnosis, glaucoma treatments, standard automated perimetry (SAP), and spectral domain optical coherence tomography (SD-OCT). Qualitative progression was determined by indication of glaucoma progression in provider notes. Quantitative progression was assessed based on change in mean deviation (MD) on SAP, retinal nerve fiber layer thickness on SD-OCT, and intraocular pressure (IOP). RESULTS: There were 707 eyes of 504 patients treated with anti-VEGF injections and 1008 eyes in the NEAMD and no-AMD cohorts. There was no difference in glaucoma or suspect prevalence at initial presentation be-tween eyes treated with injections and NEAMD (6.9% vs 9.7%, P = .22) or no-AMD controls (vs 8.5%, P = .55). There was no difference in cumulative 5-year probability of new glaucoma diagnosis after anti-VEGF injections compared to NEAMD (1.9% vs 1.0%, P = .69) or no-AMD controls (vs 1.6%, P = .88). There was no difference in qualitative progression of glaucoma in the injection cohort vs NEAMD ( P = .19) or no-AMD controls ( P = .61). The rate of MD change in injection eyes was similar to NEAMD eyes ( P = .74) but greater than no-AMD eyes ( P = .02). Eyes receiving injections required more topical glaucoma medications compared with NEAMD ( P = .03) and more glaucoma laser treatments compared with no-AMD controls ( P = .009). Eyes receiving injections did not require more frequent incisional glaucoma surgery compared with NEAMD (21.0% vs 15.0%, P = .95) or no-AMD controls (vs 10.0%, P = .10). CONCLUSION: Eyes treated with intravitreal anti-VEGF injections for exudative AMD did not have in-creased risk of developing glaucoma compared with controls. Of those with a glaucoma diagnosis, exudative AMD eyes receiving injections required a greater number of topical glaucoma medications compared with NEAMD eyes and had a greater rate of MD loss than no-AMD controls.

Purpose The purpose of this study is to compare the use of metformin in patients with both exudative and non-exudative age-related macular degeneration (AMD) versus control populations. Design Retrospective review of three age- and sex-matched cohorts from 1/1/2004 to 12/31/2013: patients with exudative AMD, a cohort of dry AMD patients, and a cohort of patients without AMD. The primary endpoint was the incidence of metformin use in all of the cohorts. Results There were 1512 patients, with 504 in each of the three cohorts. There was no difference in the prevalence of diabetes between cohorts. Compared to patients with dry AMD, patients with no AMD had increased likelihood of metformin use ( p = 0.0168, OR 1.66 (1.09–2.51). There was no difference in the likelihood of metformin use between exudative AMD patients and non-AMD controls. Conclusions There appears to be an increased incidence of metformin use in patients without AMD compared to patients with dry AMD. Metformin’s current role in the treatment of anti-aging diseases makes it a plausible target for use in the treatment of AMD, particularly dry AMD.

Esthesioneuroblastoma is a rare neoplasm originating from the olfactory neuroepithelium at the cribriform plate. The superior nasal cavity is primarily affected. Morbidity and mortality are related to locally destructive growth as well as metastatic potential. Orbital involvement is associated with decreased survival. The authors describe a case of advanced esthesioneuroblastoma with bilateral orbital involvement, presenting with a rare constellation of orbital hypertelorism and Foster-Kennedy Syndrome.

PURPOSE: To describe the newer predatory movement within academia: predatory conferences and its associated characteristics. DESIGN: Perspective METHODS: Literature review of currently published lit-erature regarding the topic RESULTS: Although ophthalmology and vision science are often spared from falling prey to predatory organi-zations, it is important for scientists of all levels, from trainees to senior faculty, to be aware of the existence of for-profit conferences and their characteristics. CONCLUSION: We discuss the details of predatory con-ferences and provide resources to help identify such meet-ings for all scientists and professionals. (Am J Ophthal-mol 2021;230: 178-180. (c) 2021 Elsevier Inc. All rights reserved.)

Myocardial infarction (MI) accounts for a significant proportion of death and morbidity in aged individuals. The risk for MI in females increases as they enter the peri-menopausal period, generally occurring in middle-age. Cytochrome (CYP) 450 metabolizes N-3 and N-6 polyunsaturated fatty acids (PUFA) into numerous lipid mediators, oxylipids, which are further metabolised by soluble epoxide hydrolase (sEH), reducing their activity. The objective of this study was to characterize oxylipid metabolism in the left ventricle (LV) following ischemic injury in females. Human LV specimens were procured from female patients with ischemic cardiomyopathy (ICM) or non-failing controls (NFC). Female C57BL6 (WT) and sEH null mice averaging 13–16 months old underwent permanent occlusion of the left anterior descending coronary artery (LAD) to induce myocardial infarction. WT (wild type) mice received vehicle or sEH inhibitor, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (tAUCB), in their drinking water ad libitum for 28 days. Cardiac function was assessed using echocardiography and electrocardiogram. Protein expression was determined using immunoblotting, mitochondrial activity by spectrophotometry, and cardiac fibre respiration was measured using a Clark-type electrode. A full metabolite profile was determined by LC–MS/MS. sEH was significantly elevated in ischemic LV specimens from patients, associated with fundamental changes in oxylipid metabolite formation and significant decreases in mitochondrial enzymatic function. In mice, pre-treatment with tAUCB or genetic deletion of sEH significantly improved survival, preserved cardiac function, and maintained mitochondrial quality following MI in female mice. These data indicate that sEH may be a relevant pharmacologic target for women with MI. Although future studies are needed to determine the mechanisms, in this pilot study we suggest targeting sEH may be an effective strategy for reducing ischemic injury and mortality in middle-aged females.