Becoming Endemic: Anaplasmosis Imported Across State Borders.

Anaplasma phagocytophilum is the causative agent of human granulocytic anaplasmosis (HGA), a tick-borne illness with increasing incidence since being described in the 1990s. Importantly, the presentation can be vague, yet prompt treatment is paramount. An 81-year-old Caucasian female was hospitalized in Cincinnati, Ohio, for fever and confusion following prolonged outdoor exposure in Emlenton, Pennsylvania. She initially was treated for sepsis from presumed community-acquired pneumonia; however, the combination of leukopenia, thrombocytopenia, and elevated liver enzymes prompted empiric tick-borne illness consideration and treatment with rapid resolution in symptoms. Early recognition of HGA can reduce unnecessary treatments and improve patient outcomes.

Ellipsoid Zone Integrity and Visual Function in Dry Age-Related Macular Degeneration.

In this longitudinal retrospective image analysis, conducted on patients diagnosed with dry age-related macular degeneration (AMD) and 5 years of follow-up imaging data, the study aimed to investigate the relationship between ellipsoid zone (EZ) integrity on spectral domain optical coherence tomography (SD-OCT) and visual acuity (VA). Using a machine learning-enabled feature extraction tool, quantitative EZ parameters were derived from SD-OCT images. The analysis revealed significant correlations between EZ integrity metrics and VA. Eyes with excellent VA (≥20/25 Snellen) exhibited higher EZ integrity, including less EZ attenuation, thicker ellipsoid zone-retinal pigment epithelium (EZ-RPE) thickness, and higher EZ intensity, in contrast to eyes with worse VA (≤20/40 Snellen). Additionally, eyes with geographic atrophy (GA) in the foveal region displayed compromised EZ integrity compared to those without GA. Notably, baseline EZ integrity metrics were predictive of future VA loss. These findings suggest that quantitative SD-OCT measurements of EZ integrity could potentially detect early changes in dry AMD and serve as valuable indicators for predicting future functional outcomes. Furthermore, these measurements hold promise for use in clinical trial screenings, offering insights into the progression of the disease and its impact on visual acuity. This study underscores the importance of EZ integrity assessment in understanding and managing dry AMD.

A Smooth Transition: Assessing Transition Readiness in Adolescents with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory Bowel Disease (IBD) is an early onset condition that affects individuals of all ages. Approximately 15%-25% of patients present before the age of 20 years, with peak onset occurring during adolescence. AIMS: To evaluate transition readiness among adolescents diagnosed with IBD and identify barriers to transition. METHODS: We conducted a cross-sectional study of patients with IBD aged 12-21 years. Patients were stratified by age into three groups: A (12-14 years), B (14-17 years), and C (17 + years). Patients were asked to complete a questionnaire which assessed patient knowledge in three areas of transition: 'Taking Charge,' 'My Health,' and 'Using Health Care.' Fisher's Exact and Chi-Square tests were used to evaluate the associations between age and transition readiness. RESULTS: A total of 127 participants (68 males and 59 females) with a mean age of 16.14 years were included. Transition readiness increased with age from 60.7% in Group A to 63.2% and 77.9% in Groups B and C, respectively (p < 0.001). Patient confidence and the importance of transition increased with age, with means of 5.51, 6.17, and 6.94 in Groups A, B, and C (p = 0.02). Patient-reported knowledge of their health condition was > 70%, with no statistical differences between the groups (p = 0.65). Patient knowledge regarding 'Using Health Care' increased from 52% in Group A to 79% in Group C (p < 0.001). The greatest barriers to transitioning were carrying health information for Group A (100%) and obtaining provider referrals for Groups B (75%) and C (51%). CONCLUSION: This study demonstrated that transition readiness increases with age in adolescents with IBD.

Thinner is better: Intentional weight loss and cardiovascular risk.

The relationship between overweight/obesity and cardiovascular events needs to be tackled. The SELECT trial earns praise in showing that using GLP-1 receptor agonists to reduce overweight/obesity itself, in patients without dysglycemia, has beneficial effects on cardiovascular risk factors and clinical outcomes.1.

Implementing evidence-based obesity management guidelines requires development of medical competencies: A commentary outlining future directions in obesity education in Canada.

Background: This commentary provides an overview of forthcoming activities by Obesity Canada (OC) to inform obesity competencies in medical education. Competencies in medical education refer to abilities of medical professionals to appropriately provide patients the care they need. A recognized Canadian framework for informing medical competencies is CanMEDs. Additionally, the Obesity Medicine Education Collaborative (OMEC) provides 32 obesity specific medical competencies to be integrated across medical education curriculum. OC released the first globally recognized Adult Obesity Clinical Practice Guideline (CPGs) in 2020 inclusive of 80 recommendations. Referring to the CanMEDs and OMEC competencies, OC is developing medical education competencies for caring for patients who have obesity in line with the recent CPGs that can be applied to health professions education programs around the world. Methods: Activities being completed by OC's Education Action Team include a scoping review to summarize Canadian obesity medical education interventions or programs. Next, with expert consensus a competency set is being developed by utilizing the CanMEDs Framework, OMEC and the CPGs. Following this, OC will initially survey undergraduate medical programs across the country and determine to what degree they are meeting the competencies in content delivery. These findings will lead to a national report card outlining the current state of obesity medical education in Canada within undergraduate medical education. Results: To date, OC has completed the scoping review and the competency set. The Education Action Team is in the process of developing the survey tools to assess the current delivery of obesity medical education in Canada. Conclusion: The evidenced-based report card will support advocacy to refine and enhance future educational initiatives with the overall goal of improving patient care for individuals living with obesity. The process being applied in Canada may also be applicable and modified for other regions to assess and better obesity medical education.

A scoping review of obesity education interventions for current and prospective medical professionals in Canada.

Background: Obesity is a prevalent chronic disease in Canada. Individuals living with obesity frequently interact with medical professionals who must be prepared to provide evidence-based and person-centred care options. The purpose of this scoping review was to summarize existing educational interventions on obesity in Canada for current and prospective medical professionals and to identify key future directions for practice and research. Methods: A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. The search strategy was conducted using Medline (via PubMed), Embase, Eric, CBCA, Proquest Education, and Proquest Theses. The inclusion criteria included delivery of an educational intervention on obesity for current medical professionals, medical undergraduate trainees, or residents administered in Canada. Data were extracted from the included studies to thematically summarize the intervention content, and main outcomes assessed. Future directions for research and practice were identified. Results: Eight studies met the inclusion criteria. The interventions ranged in terms of the mode of delivery, including interactive in-person workshops and seminars, online learning modules, webinars, and videos. The main outcomes assessed were attitudes towards patients living with obesity, self-efficacy for having sensitive obesity-related discussions, skills to assess obesity and provision of management options. All studies reported improvements in the outcomes. Future directions identified were the need to develop standardized obesity competencies for inclusion across medical education programs, further research on effective pedagogical approaches to integrating content into existing curricula and the need for broader awareness and assessment of the quality of obesity education resources. Conclusion: Although there have been few obesity-specific educational interventions for current and prospective medical professionals in Canada, existing evidence shows positive learning outcomes. These findings advocate for continued investment in the development of obesity medical training and educational interventions.

Proteomic investigations of adult polyglucosan body disease: insights into the pathobiology of a neurodegenerative disorder.

Inadequate glycogen branching enzyme 1 (GBE1) activity results in different forms of glycogen storage disease type IV, including adult polyglucosan body disorder (APBD). APBD is clinically characterized by adult-onset development of progressive spasticity, neuropathy, and neurogenic bladder and is histologically characterized by the accumulation of structurally abnormal glycogen (polyglucosan bodies) in multiple cell types. How insufficient GBE1 activity causes the disease phenotype of APBD is poorly understood. We hypothesized that proteomic analysis of tissue from GBE1-deficient individuals would provide insights into GBE1-mediated pathobiology. In this discovery study, we utilized label-free LC-MS/MS to quantify the proteomes of lymphoblasts from 3 persons with APBD and 15 age- and gender-matched controls, with validation of the findings by targeted MS. There were 531 differentially expressed proteins out of 3,427 detected between APBD subjects vs. controls, including pronounced deficiency of GBE1. Bioinformatic analyses indicated multiple canonical pathways and protein-protein interaction networks to be statistically markedly enriched in APBD subjects, including: RNA processing/transport/translation, cell cycle control/replication, mTOR signaling, protein ubiquitination, unfolded protein and endoplasmic reticulum stress responses, glycolysis and cell death/apoptosis. Dysregulation of these processes, therefore, are primary or secondary factors in APBD pathobiology in this model system. Our findings further suggest that proteomic analysis of GBE1 mutant lymphoblasts can be leveraged as part of the screening for pharmaceutical agents for the treatment of APBD.

Assessing the performance of regular surgical nose masks as a sampling method for SARS-CoV-2 detection in a cross-sectional study.

Nose masks are widely worn for protection against respiratory pathogens, including SARS-CoV-2. They have been reported as possible substrates for viral sampling and testing for COVID-19 but, evaluations have so far been purposive; involving individuals known to have the infection and using improved materials on the nose masks to trap the virus. We investigated the feasibility of using the regular 3-ply surgical masks and, voluntary coughing as a mode of particle expulsion for detecting SARS-CoV-2 infections in a cross-sectional study at Ghana's first COVID-19 testing reference laboratory, the Noguchi Memorial Institute for Medical Research, University of Ghana. Paired samples of naso-oropharyngeal swabs and nose masks already worn by 103 consenting adult participants (retro masks) were collected. Participants were also required to produce three strong coughs into a newly supplied sterile surgical nose mask. Pre-wetted swabs in Viral Transport Media (VTM) were used in swabbing the inner lining of each nose mask. The swabs used were then stored in VTM to maintain the integrity of the samples. PCR results of SARS-CoV-2 detection from the nose masks were compared to those from naso-oropharyngeal swabs ('gold-standard'). Out of the 103 participants tested with all three methods, 66 individuals sampled with naso-oropharyngeal swabs were detected as positive, and the retro and new masks matched 9 and 4, respectively. Only 3 individuals were positive across all three sampling methods accessed. The retro nose masks performed better in matching the gold-standard results than the new mask + coughing method, with 90% vs 80% sensitivity, positive predictive value of 13.6% vs 6%, and a weak but significant linear relationship (adj. R2 = 0.1; P = 0.0004). Importantly, we also show that the nose masks would work for sampling whether individuals are symptomatic or asymptomatic since gold-standard PCR cycling threshold (Ct) values for positive individuals did not differ between the two groups (P< 0.05). We recommend including features such as talking during participant engagement, use of a spontaneous cough inducer and increased coughing bouts > 3, to improve the performance of sterile nose masks for SARS-CoV-2 detection.

Novel Fractal-Based Sub-RPE Compartment OCT Radiomics Biomarkers Are Associated With Subfoveal Geographic Atrophy in Dry AMD.

OBJECTIVE: The purpose of this study was to quantitatively characterize the shape of the sub-retinal pigment epithelium (sub-RPE, i.e., space bounded by RPE and Bruch's membrane) compartment on SD-OCT using fractal dimension (FD) features and evaluate their impact on risk of subfoveal geographic atrophy (sfGA) progression. METHODS: This was an IRB-approved retrospective study of 137 subjects with dry age-related macular degeneration (AMD) with subfoveal GA. Based on sfGA status at year five, eyes were categorized as "Progressors" and "Non-progressors". FD analysis allows quantification of the degree of shape complexity and architectural disorder associated with a structure. To characterize the structural irregularities along the sub-RPE surface between the two groups of patients, a total of 15 shape descriptors of FD were extracted from the sub-RPE compartment of baseline OCT scans. The top four features were identified using minimum Redundancy maximum Relevance (mRmR) feature selection method and evaluated with Random Forest (RF) classifier using three-fold cross validation from the training set (N = 90). Classifier performance was subsequently validated on the independent test set (N = 47). RESULTS: Using the top four FD features, a RF classifier yielded an AUC of 0.85 on the independent test set. Mean fractal entropy (p-value = 4.8e-05) was identified as the most significant biomarker; higher values of entropy being associated with greater shape disorder and risk for sfGA progression. CONCLUSIONS: FD assessment holds promise for identifying high-risk eyes for GA progression. SIGNIFICANCE: With further validation, FD features could be potentially used for clinical trial enrichment and assessments for therapeutic response in dry AMD patients.

Longitudinal analysis of aqueous humour cytokine expression and OCT-based imaging biomarkers in retinal vein occlusions treated with anti-vascular endothelial growth factor therapy in the IMAGINE study.

BACKGROUND/OBJECTIVES: Retinal vein occlusion (RVO) is the second most common retinal vascular disorder. Despite promising advances with anti-VEGF therapy, select patients are unresponsive to therapy. A precision medicine-based approach for therapeutic decision-making based on underlying biomarkers may facilitate treatment based on the underlying pathway. This study aims to identify the baseline and longitudinal cytokine profiles of RVO-related macular oedema and correlating these expression profiles with higher order OCT features using a novel retinal segmentation and feature extraction platform. SUBJECTS/METHODS: The IMAGINE study is a post-hoc assessment of aqueous humour cytokines with correlation to higher level analysis of imaging studies. OCT scans underwent machine learning enhanced segmentation of the internal limiting membrane (ILM), ellipsoid zone (EZ) and retinal pigment epithelium (RPE), as well as evaluating volumetric fluid metrics. Samples of aqueous humour were obtained at baseline, as well as months 4 and 9 prior to treatment. These samples were analysed for the expression of multiple cytokines. Patients were divided into Responders and Non-Responders based on OCT profiles. Additionally, patients were categorised as a Rebounder if their CST increased by 50% after initial improvement. RESULTS: Twenty-six eyes were included. The OCT-based response schema identified 21 Responders (81%) and 5 Non-Responders (19%). VEGF levels directly correlated with intraretinal fluid volume and angiogenin was inversely correlated with fluid indices. Multiple cytokines, including ANGPTL4, were directly correlated with ellipsoid zone disruption. The baseline VEGF levels were significantly higher in all responders compared to Non-Responders (p = 0.02). Rebounders tended to have significantly decreased levels of angiogenin and TIMP-1 (p = 0.019, p = 0.015). CONCLUSIONS: Cytokine expression was linked to specific OCT features and treatment response in RVO. Identification of an imaging phenotype that could serve as a surrogate for underlying active disease pathways could enhance treatment decision-making and precision medicine.

Meta-Analysis on Invasive Versus Conservative Strategy in Patients Older Than Seventy Years With Non-ST Elevation Myocardial Infarction.

Management of non-ST elevation myocardial infarction (NSTEMI) has evolved over the years, but most published data are from younger patients. Data on the NSTEMI management in older patients remain limited. We performed a meta-analysis of randomized controlled trials to evaluate the long-term outcomes of invasive versus conservative strategies in older patients (>70 years old) with NSTEMI. Of 1,550 reports searched, 4 randomized controlled trials (1,126 patients) were included in the analysis, with a median follow-up of 1.25 years (range: 1 to 2.5 years). The median age of included patients was 83.6 (interquartile range: 2.8 years). The invasive strategy was associated with significantly lower risk of major adverse cardiac and cerebrovascular event (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.40 to 0.91, I2 = 54%; 3 trials] and unplanned revascularization (OR 0.31, 95% CI 0.15 to 0.64, I2 = 1.7%; 3 trials] than was the conservative strategy. There was no difference in all-cause mortality (OR 0.88, 95% CI 0.65 to 1.18, I2 = 0%; 4 trials], myocardial infarction (OR 0.70, 95% CI 0.42 to 1.19, I2 = 54.7%; 4 trials], or bleeding (OR 0.87, 95% CI 0.39 to 1.93, I2 = 0%; 3 trials] between the strategies. In conclusion, the use of initial invasive strategy in older patients presenting with NSTEMI was associated with a significantly lower risk of major adverse cardiac and cerebrovascular event and unplanned revascularization than that of the initial conservative strategy without increased bleeding.

Five-Year Visual Acuity Outcomes of Fovea-Involving Rhegmatogenous Retinal Detachments Following Pars Plana Vitrectomy (PPV) or Combined PPV/Scleral Buckle.

BACKGROUND AND OBJECTIVE: Macular involvement is considered a poor prognostic factor for visual recovery after rhegmatogenous retinal detachment (RRD) repair. Few prior studies report outcomes longer than 2 years after repair with pars plana vitrectomy (PPV) or combined PPV/scleral buckle (SB). The purpose of this study is to evaluate long-term (at least 5 years) visual outcomes following fovea-involving RRD repair with PPV or PPV/SB. PATIENTS AND METHODS: This retrospective case series evaluated eyes that underwent fovea-involving RRD repair with PPV or PPV/SB. Eyes with single surgery anatomic success and 5 years or more of follow-up were included. Eyes with other ophthalmic pathology affecting central vision were excluded. Paired analysis compared changes in best visual acuity (BVA) between two timepoints. RESULTS: Fifty-one eyes were included. Median (interquartile range, IQR) time to final follow-up was 7 (IQR: 3) years. Median pre-operatively BVA was 19.95 (IQR: 41.25) letters and improved to 80.15 (IQR:15.05) letters and 80.16 (IQR: 8.80) letters at the 1-year and final follow-up, respectively (P < 0.001). Thirteen of 45 eyes (28.89%) had an improvement in BVA of at least 10 letters from the 1-year to the final follow-up. Average BVA was 20/40 or better in 35/45 eyes (75.56%) at 1-year and 45/51 eyes (88.24%) at final follow-up. No eye had an average BVA of 20/200 or worse at final follow-up. CONCLUSIONS: Patients with fovea-involving RRD successfully repaired with PPV or PPV/SB have favorable long-term visual acuity outcomes. BVA may continue to significantly improve even beyond 1 year after surgery. The majority of patients have a BVA of 20/40 or better 5 years after surgery. [Ophthalmic Surg Lasers Imaging Retina 2022;53:674-680.].

Computational Imaging Biomarker Correlation with Intraocular Cytokine Expression in Diabetic Macular Edema: Radiomics Insights from the IMAGINE Study.

Purpose: Various pathways and cytokines are implicated in pathogenesis of diabetic macular edema (DME). Computational imaging biomarkers (CIBs) of vessel tortuosity from ultra-widefield fluorescein angiography (UWFA) and texture patterns from OCT images have been associated with anti-vascular endothelial growth factor (VEGF) therapy treatment response in DME. This analysis was a radiogenomic assessment of the association between underlying cytokines, UWFA, and OCT-based DME CIBs. Design: Biclustering analysis based on UWFA and OCT CIBs to identify a common imaging phenotype across patients with subsequent assessment of underlying cytokine signatures and treatment response attributes. Participants: The IMAGINE DME study was a post hoc study of cytokine expressions that included 24 eyes with sufficient baseline aqueous humor samples and an in-depth assessment of the imaging studies obtained during the phase I/II DmeAntiVEgf study (DAVE) that measured different cytokine expressions. Methods: A total of 151 graph or morphologic features quantifying leakage shape, size, density, interobject distance, and architecture of leakage spots and 5 vessel tortuosity features were extracted from the baseline UWFA scans, and 494 texture-based radiomics features were extracted from each of the fluid and retinal tissue compartments of OCT images. Biclustering enables simultaneous clustering of patients and features and was used to aggregate patients in terms of their commonality of phenotypes (based on similar imaging attributes) and to identify commonality in terms of cytokine expression and treatment response to anti-VEGF therapy. Main Outcome Measures: Identification of eyes with similar imaging phenotypes to evaluate commonalities of patterns and underlying cytokine expression. Results: Strong correlations between VEGF and 7 UWFA leakage morphologic features (Pearson correlation coefficient [PCC], 0.45-0.51; P < 0.05), 1 vascular tortuosity-based UWFA feature (PCC, 0.45; P = 0.00016), and 2 OCT-derived intraretinal fluid texture features (PCC, 0.58-0.63; P < 0.05) were identified. Strong correlation between intraretinal fluid features and other cytokines (PCC, 0.41-0.59; P < 0.05) were also observed. Conclusions: This study identified groups of eyes with similar imaging phenotypes as defined by UWFA and OCT CIBs that demonstrated similar treatment response patterns and cytokine expression, including a strong association between VEGF with UWFA-derived leakage morphologic and vessel tortuosity features.

COVID-19 Therapeutics: Improvise-Adapt-Learn.

"In the midst of chaos, there is also opportunity"-Sun Tzu, The Art of War [...].

Impact of Baseline Quantitative OCT Features on Response to Risuteganib for the Treatment of Dry Age-Related Macular Degeneration: The Importance of Outer Retinal Integrity.

OBJECTIVE: The purpose of the study was to perform a post hoc analysis to explore the effect of baseline anatomic characteristics identified on OCT on best-corrected visual acuity (BCVA) responses to risuteganib from the completed phase II study in subjects with dry age-related macular degeneration (AMD). DESIGN: Post hoc analysis of a randomized, double-masked, placebo-controlled, phase II study. SUBJECTS: Eyes with intermediate dry AMD with BCVA between 20/40 and 20/200. Patients with concurrent vision-influencing or macula-obscuring ocular pathologies were excluded. METHODS: Patients were randomized to receive a 1-mg intravitreal risuteganib injection or a sham injection at baseline. A second 1-mg intravitreal injection of risuteganib was given at week 16 to those in the treatment arm. Two independent, masked reading centers evaluated the baseline anatomic characteristics on OCT to explore features associated with positive responses to risuteganib. MAIN OUTCOME MEASURES: Treatment response was defined as a gain of ≥ 8 letters in BCVA from baseline to week 28 in the treatment arm, compared with baseline to week 12 in the sham group. Anatomic parameters, measured by retinal segmentation platforms, including measures of retinal thickness were compared between the responders and nonresponders to risuteganib. RESULTS: Thirty-nine patients completed the study and underwent analysis. In the treatment arm, 48% of eyes demonstrated treatment responses, compared with 7% in the sham group. In the quantitative anatomic assessment, enhanced ellipsoid integrity, greater outer retinal thickness, and decreased geographic atrophy were associated with increased BCVA gains to risuteganib. CONCLUSIONS: This post hoc analysis demonstrated that baseline OCT features may help determine the likelihood of a functional response to risuteganib. The characterization of higher-order OCT features may provide important information regarding biomarkers for treatment response and could facilitate optimized clinical trial enrollment and enrichment.

Survivability of Clostridioides difficile spores in fermented pork summer sausage during refrigerated storage.

Background and Aim: Clostridioides difficile is a spore-forming pathogen that causes serious enteric disease in humans. Strains have been isolated from food animals and meat, including pork, which suggest a potential for foodborne transmission. Pork summer sausage is a popular fermented meat product, which is consumed cooked or cooked to a lower internal temperature due to acidification of the product. The effect of acidity and cooking on the viability of C. difficile spores in a fermented meat product has not been determined. Therefore, the aim was to study the survivability of C. difficile spores in fermented pork summer sausage. Materials and Methods: Fermented pork sausages were prepared according to a commercial recipe with or without starter culture and C. difficile spores followed by fermentation at 37°C for ~12 h under 85% relative humidity until pH 5.0 was reached and further processed as cooked (>57°C) or uncooked (≤57°C) and stored at 4°C. C. difficile spores in sausages were enumerated at 1 h following inoculation and on days 0, 1, 7, 14, 21, 30, 60, and 90 of storage. Results: It was observed that C. difficile spore viability in control unfermented treatment was significantly different on day 0 from the fermented, fermented cooked, and control unfermented cooked treatments (p<0.05); however, there was no significant difference among the latter three treatment groups throughout 90 days of storage (p>0.05). On day 90 of storage, the unfermented control sausages yielded ~4.0 log colony-forming unit (CFU)/g of C. difficile spores compared to ~3.5 log CFU/g recovered from fermented samples and the unfermented cooked control samples identifying spore viability in all treatment groups. Conclusion: C. difficile spores were found to survive the acidity and cooking of fermented pork summer sausage and storage at 4°C for 3 months, thereby highlighting the need for effective intervention strategies to reduce the risk of C. difficile contamination in pork products.

Risk Classification for Progression to Subfoveal Geographic Atrophy in Dry Age-Related Macular Degeneration Using Machine Learning-Enabled Outer Retinal Feature Extraction.

BACKGROUND AND OBJECTIVE: To evaluate the utility of spectral-domain optical coherence tomography biomarkers to predict the development of subfoveal geographic atrophy (sfGA). PATIENTS AND METHODS: This was a retrospective cohort analysis including 137 individuals with dry age-related macular degeneration without sfGA with 5 years of follow-up. Multiple spectral-domain optical coherence tomography quantitative metrics were generated, including ellipsoid zone (EZ) integrity and subretinal pigment epithelium (sub-RPE) compartment features. RESULTS: Reduced mean EZ-RPE central subfield thickness and increased sub-RPE compartment thickness were significantly different between sfGA convertors and nonconvertors at baseline in both 2-year and 5-year sfGA risk assessment. Longitudinal change assessment showed a significantly higher degradation of EZ integrity in sfGA convertors. The predictive performance of a machine learning classification model based on 5-year and 2-year risk conversion to sfGA demonstrated an area under the receiver operating characteristic curve of 0.92 ± 0.06 and 0.96 ± 0.04, respectively. CONCLUSIONS: Quantitative outer retinal and sub-RPE feature assessment using a machine learning-enabled retinal segmentation platform provides multiple parameters that are associated with progression to sfGA. [Ophthalmic Surg Lasers Imaging. 2022;53:31-39.].

A CASE REPORT OF CHRONIC ENDOPHTHALMITIS SECONDARY TO AQUAMICROBIUMterrae.

PURPOSE: Chronic postoperative endophthalmitis is a known complication of cataract surgery. Here, we report a case of chronic endophthalmitis following uncomplicated cataract surgery secondary to the atypical bacterium Aquamicrobium terrae . METHODS: Retrospective case report of a single patient with endophthalmitis secondary to A. terrae. RESULTS: A 61-year-old healthy patient presented with recurrent iridocyclitis following uncomplicated cataract surgery. Repeated attempts to taper off topical steroid eyedrops were unsuccessful. Anterior chamber paracentesis cultures and vitrectomy cultures grew the same gram-negative bacillus, A. terrae , on six different occasions. The patient was treated initially with a series of intravitreal ceftazidime injections and adjuvant oral minocycline with recurrence of inflammation necessitating pars plana vitrectomy with intraocular lens removal and total capsulectomy. Inflammatory episodes recurred until residual capsule fragments were ablated using endoscopic vitrectomy. Since ablation over 18 months ago, no further recurrences have occurred and the patient has excellent visual outcome. CONCLUSION: A. terrae is a gram-negative bacillus recovered from polluted soil. This is the first case of postoperative endophthalmitis secondary to A. terrae and the first description of human infection caused by this newly identified microbe.

LONGITUDINAL ELLIPSOID ZONE AND OUTER RETINAL INTEGRITY DYNAMICS AFTER EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To quantify ellipsoid zone (EZ) changes in integrity after epiretinal membrane (ERM) surgery, correlate findings to visual acuity, and determine predictors for prognosis. METHODS: A post hoc analysis of eyes undergoing ERM surgery pooled from the prospective DISCOVER intraoperative optical coherence tomography study and eyes undergoing conventional ERM surgery without intraoperative optical coherence tomography. Quantitative EZ features were extracted using a multilayer machine learning enabled automated segmentation platform after image analyst review/correction for segmentation accuracy. Visual acuity and EZ integrity were quantitatively assessed and correlated before and after ERM surgery. Multiple linear regression was performed to assess preoperative visual acuity and EZ features as predictors for improvement in visual acuity or EZ integrity. RESULTS: There were 177 eyes from 177 subjects that underwent ERM surgery from the DISCOVER and conventional arms. Improvement in visual acuity and multiple EZ integrity features was noted after ERM surgery, including EZ partial attenuation and EZ-retinal pigment epithelium (RPE) volume (P < 0.05). A reduction in EZ partial attenuation and increase in EZ-RPE central subfield thickness (EZ-RPE CST) was significantly correlated with improved visual acuity after ERM surgery (P < 0.05). More robust EZ-RPE CST at baseline predicted visual acuity improvement after ERM peel in regression modeling (ß = 0.005, P < 0.05). CONCLUSIONS: Longitudinal assessment of EZ features demonstrates significant postoperative improvement in multiple EZ integrity metrics after ERM surgery. Improving EZ integrity was correlated to improving the visual acuity. Ellipsoid zone integrity and visual acuity were significant predictors in regression modeling and may have value in clinical prognostication.

Exploring the angiographic-biologic phenotype in the IMAGINE study: quantitative UWFA and cytokine expression.

BACKGROUND: This study investigates the association of intraocular cytokine expression and ultrawide-field fluorescein angiography (UWFA) quantitative imaging biomarkers and their association with angiographical feature response after antivascular endothelial growth factor (VEGF) therapy in diabetic macular oedema (DME). METHODS: The IMAGINE DME study is a post hoc imaging biomarker and intraocular cytokine assessment from the DAVE study, a prospective DME clinical trial that included aqueous humour sampling and UWFA imaging. Fifty-four cytokines associated with inflammation and angiogenesis were evaluated through multiplex arrays. UWFA parameters were assessed using an automated feature analysis platform to determine ischaemic and leakage indices and microaneurysm (MA) count. Eyes were classified into UWFA responder or non-responder groups based on longitudinal quantitative UWFA parameter improvement. Cytokine expression was correlated with UWFA metrics and evaluated in the context of therapeutic response. RESULTS: Twenty-one eyes were included with a mean age of 55±10 years. Increased panretinal leakage index correlated with VEGF (r=0.70, p=0.0005), angiopoietin-like 4 (r=0.77, p=4.6E-5) and interleukin (IL)-6 (r=0.64, p=0.002). Panretinal ischaemic index was associated with tissue inhibitor of metalloproteinases 1 (TIMP-1, r=0.49, p=0.03) and peripheral ischaemia correlated with VEGF (r=0.45, p=0.05). MA count correlated with increased monocyte chemotactic protein-4 (MCP-4, r=0.60, p=0.004) and platelet and endothelial cell adhesion molecule 1 (PECAM-1, r=0.58, p=0.005). Longitudinal MA reduction was associated with decreased baseline VEGF and urokinase receptor (uPAR) (p<0.05). High baseline VEGF and IL-6 were associated with dramatic reduction in macular leakage (p<0.05). CONCLUSIONS: Baseline and longitudinal quantitative UWFA imaging parameters correlated with multiple aqueous humour cytokine concentrations, including VEGF and IL-6. Further research is needed to assess the possible implications of using these findings for evaluating treatment response.