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Neal S Patel,1,* Jade Y Moon,1,* Raviv Katz,1 Karen M Wai,1 Lucia Sobrin,2 Demetrios G Vavvas,2 John B Miller1,2 1Harvard Retinal Imaging Lab, Mass Eye and Ear, Boston, MA, USA; 2Retina Service, Mass Eye and Ear, Boston, MA, USA*These authors contributed equally to this workCorrespondence: John B MillerRetina Service, Mass Eye and Ear, Department of Ophthalmology, Harvard Medical School, Harvard Retinal Imaging Lab, 243 Charles St, Boston, MA, 02114, USATel +617 573-3750Fax +617 573-3698Email john_miller@meei.harvard.eduPurpose: Since the start of the COVID-19 pandemic, numerous authors have published data demonstrating retinal changes found in patients with COVID-19. However, others have debated the significance of these findings and the effects of COVID-19 on the retina remain uncertain. This study aims to better understand retinal findings in patients with COVID-19.Patients and Methods: A retrospective review of patients with a history of a positive COVID-19 polymerase chain reaction test was performed between March 1st, 2020 and October 31st, 2020. Patients were included if they presented within 90 days of their first positive COVID-19 test and underwent color fundus photography and/or OCT of the macula. All images were reviewed by two independent graders who assessed the presence of retinal heme, cotton wool spots, vascular sheathing, and disc edema, as well as hyper-reflective changes, intra-retinal fluid, and sub-retinal fluid on OCT.Results: A total of 119 eyes from 61 patients were included. Among 83 eyes which underwent OCT of the macula, inner retinal hyper-reflective changes were seen in 16.9% (n=14), outer retinal hyper-reflective changes in 18.1% (n=15), intra-retinal fluid in 28.9% (n=24), and sub-retinal fluid in 14.5% (n=12). Among 48 eyes which underwent color fundus photography, retinal hemorrhage was seen in 27.1% (n=13), optic disc edema in 2.1% (n=1), and cotton wool spots in none of the eyes. Sub-analysis of 70 eyes from 41 patients with no alternative retinal pathology to potentially explain the above findings revealed none of the above exam findings on OCT of the macula (n=35), fundus photography (n=28), or documented exam (n=66).Conclusion: While a number of patients seen after COVID-19 infection demonstrated retinal findings, all could be explained by pre-existing retinal conditions. In a sub-group of eyes without pre-existing retinal disease, we did not identify any retinal findings that could be associated with COVID-19.Keywords: COVID-19, SARS-CoV-2, retina, optical coherence tomography, fundus photography

Epilepsy of infancy with migrating focal seizures (EIMFS), one of the most severe developmental and epileptic encephalopathy syndromes, is characterized by seizures that migrate from one hemisphere to the other. EIMFS is genetically heterogeneous with 33 genes. We report five patients with EIMFS caused by recessive BRAT1 variants, identified via next generation sequencing. Recessive pathogenic variants in BRAT1 cause the rigidity and multifocal seizure syndrome, lethal neonatal with hypertonia, microcephaly, and intractable multifocal seizures. The epileptology of BRAT1 encephalopathy has not been well described. All five patients were profoundly impaired with seizure onset in the first week of life and focal seizure migration between hemispheres. We show that BRAT1 is an important recessive cause of EIMFS with onset in the first week of life, profound impairment, and early death. Early recognition of this genetic aetiology will inform management and reproductive counselling. [ABSTRACT FROM AUTHOR]

Purpose: Patients with Crohn's disease (CD) and subsequent ocular manifestations may have worse outcomes when compared to matched patients with CD without ocular disease., Methods: In this retrospective cohort study, an aggregated electronic health records research network, TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with CD stratified by the presence or absence of ocular involvement with at least 1 year of follow-up. Propensity score matching (PSM) was performed to control for baseline demographics and medical comorbidities., Results: Patients with CD with ocular disease showed a greater risk of undergoing bowel resections (RR: 2.06, 95% CI: 1.48-2.85, p  < 0.001), developing other CD-related gastrointestinal complications (RR: 1.31, CI: 1.15-1.49, p  < 0.001), or acquiring Clostridioides difficile infections (RR: 2.19, CI: 1.89-2.54, p  < 0.001). Further, patients with CD with ocular sequelae had a greater risk of developing NASH (RR: 1.43, CI: 1.31-1.56, p  < 0.001), CD-related nutrient deficiencies (RR: 1.38, CI: 1.29-1.49, p  < 0.001), iron deficiency anemia (RR: 1.41, CI: 1.33-1.50, p  < 0.001), CD-related dermatological disease (RR: 1.84, CI: 1.65-2.05, p  < 0.001), osteoporosis (RR: 1.49, CI: 1.37-1.64, p  < 0.001) and primary sclerosing cholangitis (RR: 1.63, CI: 1.11-2.38, p  = 0.011). Among patients with CD with ocular involvement, there was an elevated risk of MI (RR: 1.36, CI: 1.14-1.63, p  < 0.001), stroke (RR: 1.42, CI: 1.18-1.70, p  < 0.001), VTE (RR: 1.37, CI: 1.22-1.54, p  < 0.001), and sepsis (RR: 1.53, CI: 1.37-1.71, p  < 0.001)., Conclusions: Patients who have CD and subsequent ocular involvement have an increased risk of local intestinal complications, extraintestinal morbidity, and cardiovascular complications when compared to patients with CD without ocular involvement.

Purpose: Assessing immune-related ocular toxicities from immune checkpoint inhibitors (ICIs) is crucial, though rare. This study, utilizing real-world data, examines the occurrence of ophthalmic immune-related adverse events (irAEs) after ICI treatment and their impact on overall survival., Design: A retrospective cohort study., Methods: Data were obtained from TriNetX, an aggregated electronic health records database. Patients who developed ophthalmic irAEs within 1 year after the first instance of ICI therapy were included. Participants with defined ocular toxicities 6 months before ICI treatment were excluded. Subjects were paired with controls using propensity scores derived from demographics and cancer type. A Cox proportional hazard model was used to determine hazard ratios. A Kaplan-Meier survival function was evaluated with the log-rank test based on the development of ophthalmic irAEs in a 12-month landmark analysis., Results: A cohort of 41,020 patients comprising 57.4% males with a mean age of 65.2 ± 11.9 years was included. The 5 most prevalent ophthalmic irAEs in this cohort were dry eye syndrome (2%), conjunctivitis (0.87%), blepharitis (0.51%), anterior uveitis (0.39%), and keratitis (0.38%). Dry eye syndrome was the most common irAE among all ICI classes. Subjects taking CTLA-4 inhibitor plus PD-1 inhibitor and CTLA-4 inhibitors had higher rates of anterior uveitis (1.39% and 1.29%, respectively) than PD-1 inhibitors (0.27%) and PD-L1 inhibitors (0.14%) within 1 year after taking ICI. After a 12-month landmark analysis, there was a significant decreased chance of survival for the following categories: any ophthalmic irAE (HR, 1.37; 95% CI, 1.20-1.56; P < .0001), neuro-ophthalmic irAE (HR, 1.53; 95% CI, 1.09-2.14; P = .0124), and cornea and ocular surface irAE (HR, 1.34; 95% CI, 1.15-1.56; P < .0001)., Conclusions: Ophthalmic irAEs involving the anterior segment are more frequent than the posterior segment, regardless of ICI class. Ophthalmic irAEs may also portend decreased survival. This insight could help guide clinicians aggressively manage irAEs and allow patients to continue ICI therapy despite having ocular issues., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objective: This study compares the ability of resident ophthalmologists to identify neovascularization (NV) in patients with proliferative diabetic retinopathy (PDR) using widefield swept-source optical coherence tomography angiography (SS-OCTA) and fluorescein angiography (FA)., Patients and Methods: Fluorescein angiography and SS-OCTA images were scrambled to create a grading set consisting of 1) early and late phase FA images, 2) B-scan videos, and 3) vitreoretinal interface (VRI) slab. Participants were asked to identify NV., Results: Twelve resident physicians participated in the study. Resident physicians correctly identified 75.6% of NV using FA, 65.3% of NV using SS-OCTA B-scans, and 90.7% of NV using the SSOCTA VRI slab. There was no statistically significant difference in participants' ability to detect NV across imaging modalities ( P = 0.08)., Conclusion: Detection rates of NV using SS-OCTA were comparable to that of using FA. Results suggest that SS-OCTA may be an appropriate imaging modality for detection of NV in PDR patients. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.] .

Importance: Curcuma-based nutritional supplements (CBNS) are natural anti-inflammatory and antioxidant agents that may confer benefits against age-related macular degeneration (AMD)., Objective: To examine the association between the use of CBNS and the risk of development or progression of AMD., Design, Setting, and Participants: This was a retrospective cohort study with data collection in June of 2024. Data were gathered from the aggregated electronic health records research network, TriNetX (Cambridge, Massachusetts). Patients without AMD were included in the study before propensity score matching (PSM); these included those taking and not taking CBNS. Patients with no history of AMD were stratified by instances of CBNS prescription records. Patients with a history of early nonexudative AMD stratified by instances of CBNS prescription records were also identified. PSM was performed to control for baseline demographics and medical comorbidities., Exposures: Patients were stratified by whether or not they were taking CBNS using RxNorm (National Library of Medicine) codes., Main Outcome Measures: Relative risk (RR) of developing nonexudative AMD, exudative AMD, advanced nonexudative AMD or geographic atrophy (GA), blindness, or requiring intravitreal anti-vascular endothelial growth factor (VEGF) therapy., Results: A total of 66 804 patients (mean [SD] age, 64.9 [10.1] years; 44 124 female [66.1%]) taking CBNS and 1 809 440 patients (mean [SD] age, 67.0 [9.5] years; 999 534 female [55.2%]) not taking CBNS were included in this study. Among patients without a history of AMD aged 50 years or older, CBNS use was associated with lower rates of developing nonexudative AMD (RR, 0.23; 95% CI, 0.21-0.26; P < .001), advanced nonexudative AMD or GA (RR, 0.11; 95% CI, 0.07-0.17; P < .001), exudative AMD (RR, 0.28; 95% CI, 0.24-0.32; P < .001), blindness (RR, 0.46; 95% CI, 0.36-0.59; P < .001), or requiring intravitreal anti-VEGF therapy (RR, 0.15; 95% CI, 0.13-0.17; P < .001) when compared with matched patients not taking CBNS. Results were consistent among subsets of patients 60 and 70 years or older, respectively. Among patients with early nonexudative AMD, subsequent instances of CBNS prescription records were associated with lower rates of developing advanced nonexudative AMD or GA (RR, 0.58; 95% CI, 0.41-0.81; P < .001) when compared with matched patients with early nonexudative AMD without a CBNS prescription record., Conclusion and Relevance: Results of this cohort study suggest that a reduced risk of developing AMD or progression to later stages of AMD was associated with subsequent use of CBNS. Further investigation to validate these findings, safety, and potential pharmacoprotective mechanisms of CBNS in AMD are suggested.

Importance: While combined treatment of anti-vascular endothelial growth factor (VEGF) injections plus panretinal photocoagulation (PRP) is a common approach for treating proliferative diabetic retinopathy (PDR) in the clinical practice setting, large randomized clinical trials typically use monotherapy. Subsequently, information is limited as to whether the order of treatment when combining PRP and anti-VEGF injections for PDR affects outcomes., Objective: To compare outcomes of patients with PDR treated with PRP and subsequent anti-VEGF injections with outcomes of matched patients treated with anti-VEGF injections and subsequent PRP., Design, Setting, and Participants: This retrospective cohort study used data from January 2003 to January 2024 in the TriNetX aggregated electronic health records network, with data analysis performed in January 2024. Patients with PDR treated with PRP and anti-VEGF injections were eligible for inclusion., Exposures: Patients with new PDR diagnoses stratified by therapy with PRP and subsequent anti-VEGF injections or anti-VEGF injections and subsequent PRP., Main Outcomes and Measures: The primary outcome was the need for pars plana vitrectomy (PPV), defined by Current Procedural Terminology codes 67040 or 67113. The secondary outcome included incidence of PPV, vitreous hemorrhage (VH), or tractional retinal detachment (TRD). Relative risk ratios, relative risk differences, and 95% CIs were all calculated for univariate comparison of the cohorts and the development of primary outcomes after matching., Results: Before propensity score matching (PSM), which controlled for baseline demographic characteristics and medical comorbidities, 2167 patients with PDR treated with PRP first and subsequent anti-VEGF injections and 1549 patients with PDR treated with anti-VEGF injections and subsequent PRP were included. Post-PSM, mean (SD) participant age was 63.0 (13.1) years in cohort 1 (PRP and subsequent anti-VEGF injection) and 63.0 (12.4) years in cohort 2 (anti-VEGF injection and subsequent PRP). Of 1377 total participants in each cohort, 641 patients (46.6%) and 663 patients (48.1%) in cohorts 1 and 2 were female, respectively. Treatment with PRP first and subsequent anti-VEGF injection was associated with higher rates of PPV at 5 years compared with patients treated with anti-VEGF injection and subsequent PRP (relative risk [RR], 1.88; 95% CI, 1.55-2.27; risk difference [RD], 8.93%; 95% CI, 6.31%-11.55%; P < .001), with similar associations at 6 months, 1 year, and 3 years. Treatment with PRP and subsequent anti-VEGF injection was associated with higher rates of VH at 5 years (RR, 1.40; 95% CI, 1.09-1.80; RD, 6.47%; 95% CI, 1.66%-11.29%; P < .001) and TRD at 5 years (RR, 1.85; 95% CI, 1.35-2.53; RD, 4.31%; 95% CI, 2.10%-6.52%; P < .001), with similar findings at 6 months, 1 year, and 3 years compared with patients treated with anti-VEGF injection and subsequent PRP., Conclusions and Relevance: In this retrospective cohort study, findings suggest that patients with PDR treated with PRP first then subsequent anti-VEGF injection are more likely to undergo PPV for VH and TRD compared with matched patients treated with anti-VEGF agents first, then PRP. These findings support the need for further investigations to determine if the order of PRP and anti-VEGF injections should be considered when treating patients with PDR.

Purpose: To examine the effects of glucagon-like peptide-1 receptor (GLP-1) agonists compared to SGLT-2 inhibitors on diabetic retinopathy., Design: Retrospective clinical cohort study using TriNetX, a federated electronic health records network comprising multiple healthcare organizations., Methods: Patients with an International Classification of Diseases, Tenth Revision (ICD-10) code of nonproliferative diabetic retinopathy (PDR) and monotherapy treatment, excluding insulin, with GLP-1 agonists or SGLT-2 inhibitors. Patients with a history of PDR prior to initiation of treatment were excluded. The rate of progression to PDR and rate of development of diabetic macular edema (DME) were compared between patients on GLP-1 agonists compared to those on SGLT-2 inhibitors. The groups were propensity score matched for age, gender, ethnicity, race, type of diabetes, and severity of PDR. Main outcomes included rate and relative risk (RR) of progression to PDR and risk of DME in the GLP-1 agonist group versus the SGLT-2 inhibitor group., Results: A total of 6481 patients were identified in the GLP-1 cohort and the SGLT-2 inhibitor cohort after propensity score matching. At 1 and 3 years after initiation of therapy, a higher rate of progression of PDR was noted (RR: 1.26, CI 1.04-1.51, P = .017 at 1 year, RR: 1.284, CI 1.1-1.499, P = .002 at 3 years) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort. There was a higher rate of DME noted at 3 months (RR: 1.192, CI 1.059-1.276, P = .002), 6 months (RR: 1.22, CI 1.13-1.32, P < .001), 1 year (RR: 1.24, CI 1.15-1.33, P < .001), and at 3 years (RR: 1.29, CI 1.21-1.38, P < .001) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort., Conclusions: A higher rate of progression of PDR and risk of new-onset DME was observed in patients on monotherapy with GLP-1 agonists compared to those on SGLT-2 inhibitors. It is important for clinicians to be aware of these potential effects and to consider the current retinopathy status when initiating treatment with newer hypoglycemic agents to ensure these patients are appropriately monitored for developing potential vision-threatening complications., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To evaluate associations between ocular manifestations of Marfan syndrome and cardiovascular complications., Design: Retrospective cohort study., Methods: The TriNetX Analytics platform, a federated health research network of aggregated deidentified electronic health record data of more than 119 million patients, was used to identify patients diagnosed with Marfan syndrome. Univariate logistic regression models were used to evaluate the association of ocular manifestations of Marfan syndrome (such as retinal tears/detachment, lens dislocation, and myopia), with cardiovascular comorbidities. Additional sensitivity analyses were performed using propensity matching. Odds ratios and 95% CIs were calculated for incidence of cardiovascular comorbidities (including aortic dissection, valvular disease, and arrhythmias) following diagnosis of Marfan syndrome., Results: A total of 19,105 patients were identified who were diagnosed with Marfan disease without ocular manifestations, and an additional 3887 Marfan patients with ocular comorbidities. Patients who were diagnosed with ocular disease included 883 with ectopic lens, 417 with retinal tear or detachment, 683 with aphakia, 534 with pseudophakia, and 2465 with myopia. Patients with any ocular manifestations of Marfan were significantly more likely to be diagnosed with all cardiovascular comorbidities modeled including aortic aneurysm and dissection (OR 2.035; P < .0001), mitral valve prolapse (OR 2.725; P < .0001), tricuspid valve disorders (OR 2.142; P < .0001), cardiac arrhythmias (OR 1.836; P < .0001), and all cardiovascular outcomes combined (OR 2.194; P < .0001)., Conclusions: In a large and diverse cohort of patients with Marfan syndrome, ocular manifestations of the disorder appear strongly associated with cardiovascular comorbidities., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the risk of diabetic retinopathy progression and systemic vascular events, including death, in patients with nonproliferative diabetic retinopathy (NPDR) with obstructive sleep apnea (OSA)., Design: Retrospective cohort study., Methods: Electronic chart query using TriNetX, an electronic health records network comprising data from over 124 million patients. Patients with NPDR with and without OSA were identified. Patients were excluded if they had a history of proliferative disease (proliferative diabetic retinopathy), diabetic macular edema, or prior ocular intervention (intravitreal injection, laser, or pars plana vitrectomy). Propensity score matching was performed to control for baseline demographics and comorbidities. The rate of progression to vision-threatening complications, need for ocular intervention, and systemic events was measured at 1, 3, and 5 years., Results: A total of 11 931 patients in each group were analyzed after propensity score matching. There was an elevated risk of proliferative diabetic retinopathy in the OSA cohort at 1 (risk ratio [RR]: 1.34, P < .001), 3 (RR: 1.31, P < .001), and 5 years (RR: 1.28, P < .001). There was an elevated risk of diabetic macular edema in the OSA group at all time points: 1 (RR: 1.31, P < .001), 3 (RR: 1.19, P<.001), and 5 years (RR: 1.18, P < .001). With respect to ocular interventions, there was an increased risk of intravitreal injection in patients with OSA at 1 (RR: 1.59, P < .001), 3 (RR: 1.58, P < .001), and 5 years (RR: 1.54, P < .001), and similar trends were noted with laser photocoagulation, but not vitrectomy. Regarding systemic events, patients with NPDR with OSA had a greater risk of stroke (1 year RR: 1.80, P < .001; 3 years RR: 1.56, P < .001; and 5 years RR: 1.49, P < .001), myocardial infarction (1 year RR: 1.51, P < .001; 3 years RR: 1.46, P < .001; and 5 years RR: 1.43, P < .001), and death (1 year RR: 1.31, P < .001; 3 years RR: 1.19, P < .001; and 5 years RR: 1.15, P < .001)., Conclusions: There is an increased rate of diabetic retinopathy progression to vision-threatening complications, need for ocular intervention, and systemic complications, including death, for patients with OSA. We emphasize the need for improved screening measures of patients with NPDR and potential OSA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: The Diabetic Retinopathy Clinical Research Network Protocol S suggested that vitrectomy for vitreous hemorrhage (VH) or tractional retinal detachment (TRD) was more common among eyes assigned initially to panretinal photocoagulation (PRP) vs anti-vascular endothelial growth factor (anti-VEGF) for proliferative diabetic retinopathy (PDR). These clinical implications warrant further evaluation in the clinical practice setting., Objective: To explore outcomes of PDR treated with PRP monotherapy compared with matched patients treated with anti-VEGF monotherapy., Design, Setting, and Participants: Retrospective cohort study using an aggregated electronic health records research network. Patients with PDR who received PRP or anti-VEGF monotherapy between January and September 2023 were included before propensity score matching. Patients were excluded with 6 or fewer months' follow-up after monotherapy or with a combination of PRP and anti-VEGF. Data were analyzed in September 2023., Exposures: Patients with new PDR diagnoses stratified by monotherapy with PRP or anti-VEGF agents using Current Procedural Terminology code., Main Outcome Measures: Incidence of pars plana vitrectomy (PPV), VH, or TRD., Results: Among 6020 patients (PRP cohort: mean [SD] age, 64.8 [13.4]; 6424 [50.88%] female; 3562 [28.21%] Black, 6180 [48.95%] White, and 2716 [21.51%] unknown race; anti-VEGF cohort: mean [SD] age, 66.1 [13.2]; 5399 [50.52%] male; 2859 [26.75%] Black, 5377 [50.31%] White, and 2382 [22.29%] unknown race) who received treatment, PRP monotherapy was associated with higher rates of PPV when compared with patients treated with anti-VEGF monotherapy at 5 years (RR, 1.18; 95% CI, 1.05-1.36; RD, 1.37%; 95% CI, 0.39%-2.37%; P < .001), with similar associations at 1 and 3 years. PRP monotherapy was associated with higher rates of VH at 5 years (relative risk [RR], 1.72; 95% CI, 1.52-1.95; risk difference [RD], 7.05; 95% CI, 5.41%-8.69%; P < .001) and higher rates of TRD at 5 years (RR, 2.76; 95% CI, 2.26-3.37; RD, 4.25%; 95% CI, 3.45%-5.05%; P < .001), with similar magnitudes of associations at 6 months, 1 year, and 3 years, when compared with patients treated with anti-VEGF monotherapy., Conclusions and Relevance: These findings support the hypothesis that patients with PDR treated with PRP monotherapy are more likely to develop VH, TRD, and undergo PPV when compared with matched patients treated with anti-VEGF monotherapy. However, given the wide range in relative risk, confounding factors may account for some of the association between PRP vs anti-VEGF monotherapy and outcomes evaluated.

Purpose: Pre-eclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome have been previously implicated with ophthalmic complications including serous retinal detachments and disorders of the choroidal vasculature. Herein, we report a case of macular serous detachment associated with HELLP syndrome in which wide field swept-source optical coherence tomography angiography (WF SS-OCTA) was used., Methods: Retrospective case report of a patient who developed HELLP syndrome. The patient underwent multimodal retinal imaging and wide field swept-source OCT angiography (WF SS-OCTA) (PLEX® Elite 9000, Carl Zeiss Meditec Inc.)., Results: A 36-year-old female patient diagnosed with HELLP syndrome presented with bilateral blurry vision. At presentation, dilated fundus exam revealed localized subretinal fluid in the macula. WF SS-OCTA showed areas of peripapillary and subfoveal flow signal attenuation in the choroid OD, consistent with choroidal infarction., Conclusions: These findings support the hypothesis that HELLP syndrome is associated with vascular changes that lead to choroidal dysfunction and subsequent serous retinal detachments. Furthermore, this case highlights a role for the non-invasive WF SS-OCTA technology in diagnosing and further characterizing the pathophysiology without the use of dye-based angiography.

Alport syndrome is characterized by type IV collagen network disruptions leading to renal, auditory, and ocular manifestations. This case report details a 24-year-old man with Alport syndrome who developed a rhegmatogenous retinal detachment following macular hole repair. The patient underwent a successful vitrectomy and internal limiting membrane peel for macular hole repair but returned with vision loss due to retinal detachment five weeks later, which necessitated a combined scleral buckle and vitrectomy. This is the first case describing rhegmatogenous retinal detachment post-macular hole repair in Alport syndrome. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:289-292.] .

Exposure to environmental heavy metals is associated with telomere length (TL) alteration. Available information regarding the effect of prenatal exposure to environmental pollutants on newborn TL is controversial. The aim of this study is to systematically review and conduct a meta-analysis of the existing epidemiological studies on the associations between prenatal metal exposure and newborn TL. A comprehensive literature search was performed using the online databases of PubMed, Web of Science, and ScienceDirect from their inception to December 1, 2023. Thirteen eligible studies were included from the overall initial identification of 3559 records. The effect size was expressed as standardized beta coefficients with 95% confidence intervals (CIs) by the restricted maximum-likelihood approach with a weighted random-effects model. Prenatal exposure to environmental heavy metals was associated with a shorter newborn TL (standardized beta = -0.04; 95% CI: -0.08, 0.00; p = 0.05). Subgroup analysis showed that prenatal exposure to cadmium was significantly, negatively associated with TL in newborns (standardized beta = -0.05; 95% CI: -0.10, -0.01; p = 0.021). Heavy metal exposure during the third trimester was significantly associated with a shorter TL in newborns (standardized beta = -0.05; 95% CI: -0.11, -0.01; p = 0.045). No significant association was found between the newborn's sex and exposure sample type. This study provides evidence for the negative effect of prenatal exposure to heavy metals on newborn TL. In particular, cadmium exposure and exposure during the third trimester of pregnancy are critical factors associated with heavy metal-induced TL shortening., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Futibatinib is an irreversible inhibitor of fibroblast growth factor receptors and is currently the subject of phase II clinical trials for the treatment of metastatic carcinomas. We report a case of a 59-year-old woman with metastatic malignant breast cancer who developed acute symptomatic subretinal fluid (SRF) accumulation after two weeks of futibatinib therapy. The SRF resolved within two weeks after futibatinib cessation. The medication was subsequently restarted at a lower dose, and SRF recurred within two weeks. To our knowledge, this is the first case depicting rapidly reversible SRF accumulation with the use of futibatinib in a real-world clinical setting. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:109-111.] .

Purpose: To examine rates of stroke, myocardial infarction (MI), deep vein thrombosis (DVT), pulmonary embolism (PE), and death in patients after retinal vein occlusion (RVO) compared to controls., Design: Retrospective cohort study., Methods: An aggregated electronic health records research network, TriNetX, was used to identify patients with diagnosis of RVO and a control group of patients with cataract. Patients were excluded if they had history of stroke, MI, DVT, or PE within 2 years of diagnosis of RVO or cataract. Propensity score matching was performed to control for baseline demographics and medical comorbidities. Main outcomes included relative risk (RR) of death, stroke, MI, DVT, and PE after RVO compared to those in matched controls., Results: A total of 45,304 patients were included in each cohort. There was elevated risk of death in the RVO cohort compared to the control cohort at 1 year (RR = 1.30, P < .01), 5 years (RR = 1.22, P < .01), and 10 years (RR = 1.08, P < .01). There was elevated risk of stroke at 1 year (RR = 1.61, P < .01), 5 years (RR = 1.31, P < .01), and 10 years (RR = 1.18, P < .01). There was elevated risk of MI at 1 year (RR = 1.26, P < .01) and 5 years (RR = 1.13, P < .01), but not at 10 years (RR = 1.06, P = .12). There was mildly elevated risk of DVT at 1 year (RR = 1.65, P < .01) but not at 5 years (RR = 0.94, P = .94) or 10 years (RR = 1.05, P = .37). There was no elevated risk of PE at 1 year (RR = 0.98, P = 0.80), 5 years (RR = 0.95, P = .42), or 10 years (RR = 0.85, P =.40)., Conclusions: There is an increased rate of death, stroke, and MI after RVO compared to those in matched controls. We emphasize the need for long-term systemic evaluation after RVO., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Patients with retinal artery occlusions (RAOs) are recommended to have emergent stroke workup, although the true risk of death and subsequent vascular events post-RAO is not clear., Objective: To determine short-term and long-term rates of stroke, myocardial infarction (MI), and death in patients after RAO compared with a control cohort., Design, Setting, and Participants: This retrospective cohort study used aggregated electronic health records from January 1, 2003, through April 14, 2023, from TriNetX, a network with data from more than 111 million patients. Patients with RAO and a cataract control group were identified and matched for age, sex, race, and comorbidities, including hypertension, diabetes, hyperlipidemia, and smoking status. Patients were excluded if they had a stroke or MI within 2 years before the diagnosis of RAO or cataract., Exposure: International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis code for RAO or age-related cataract., Main Outcomes and Measures: Rate of death, stroke, and MI at 2 weeks, 30 days, 1 year, 5 years, and 10 years after RAO compared with matched controls., Results: There were a total of 34 874 patients with at least 1 year of follow-up in the RAO cohort. The mean (SD) age at the RAO event was 66 (15.2) years. The rate of death after RAO diagnosis was higher than after cataract diagnosis at 2 weeks (0.14% vs 0.06%; relative risk [RR], 2.45; 95% CI, 1.46-4.12; risk difference [RD], 0.08%; 95% CI, 0.04%-0.13%; P < .001), 30 days (0.29% vs 0.14%; RR, 2.10; 95% CI, 1.49-2.97; RD, 0.15%; 95% CI, 0.08%-0.22%; P < .001), 1 year (3.51% vs 1.99%; RR, 1.78; 95% CI, 1.61-1.94; RD, 1.41%; 95% CI, 1.17%-1.66%; P < .001), 5 years (22.74% vs 17.82%; RR, 1.28; 95% CI, 1.23-1.33; RD, 4.93%; 95% CI, 4.17%-5.68%; P < .001), and 10 years (57.86% vs 55.38%; RR, 1.05; 95% CI, 1.02-1.07; RD, 2.47%; 95% CI, 1.25%-3.69%; P < .001). Risk of stroke after RAO was higher at 2 weeks (1.72% vs 0.08%; RR, 21.43; 95% CI, 14.67-31.29; RD, 1.64%; 95% CI, 1.50%-1.78%; P < .001), 30 days (2.48% vs 0.18%; RR, 14.18; 95% CI, 10.94-18.48; RD, 2.31%; 95% CI, 2.14%-2.47%; P < .001), 1 year (5.89% vs 1.13%; RR, 5.20; 95% CI, 4.67-5.79; RD, 4.64%; 95% CI, 4.37%-4.91%; P < .001), 5 years (10.85% vs 4.86%; RR, 2.24; 95% CI, 2.09-2.40; RD, 6.00%; 95% CI, 5.50%-6.50%; P < .001), and 10 years (14.59% vs 9.18%; RR, 1.59; 95% CI, 1.48-1.70; RD, 5.41%; 95% CI, 4.62%-6.21%; P < .001). Risk of MI after RAO was higher at 2 weeks (0.16% vs 0.06%; RR, 3.00; 95% CI, 1.79-5.04; RD, 0.11%; 95% CI, 0.06%-0.16%; P < .001), 30 days (0.27% vs 0.10%; RR, 2.61; 95% CI, 1.78-3.83; RD, 0.17%; 95% CI, 0.10%-0.23%; P < .001), 1 year (1.66% vs 0.97%; RR, 1.72; 95% CI, 1.51-1.97; RD, 0.59%; 95% CI, 0.42%-0.76%; P < .001), 5 years (6.06% vs 5.00%; RR, 1.21; 95% CI, 1.12-1.31; RD, 1.07%; 95% CI, 0.64%-1.50%; P < .001), and 10 years (10.55% vs 9.43%; RR, 1.12; 95% CI, 1.04-1.21; RD, 1.13%; 95% CI, 0.39%-1.87%; P = .003)., Conclusions and Relevance: This study showed an increased risk of death, stroke, and MI in patients with RAO at both short-term and long-term intervals after RAO compared with a matched control population diagnosed with cataract. These findings suggest a potential need for multidisciplinary evaluation and long-term systemic follow-up of patients post-RAO.

Telomeres, repeated TTAGGG sequences at chromosomal ends, shorten with age and indicate cellular lifespan. Zinc can protect against telomere damage through its anti-oxidative effect. Meanwhile, telomere shortening was correlated with metabolic diseases of hypertension and type 2 diabetes. The objective of this study was to investigate whether the association between zinc and telomere length differs by the presence or absence of hypertension/type 2 diabetes. This is a cross-sectional study with 1064 participants of the Iwaki area, Japan. Multiple linear regression models were performed to test the hypothesis. A higher serum zinc concentration was significantly associated with a longer G-tail length (β = 48.11, 95% confidence intervals [CI]: 25.69, 70.54, p < 0.001). By multivariate linear regression analysis, there was a significant positive association between zinc and G-tail length in both hypertensive (β = 46.84, 95%CI: 9.69, 84.0, p = 0.014) and non-hypertensive groups (β = 49.47, 95%CI: 20.75, 78.18, p = 0.001), while the association was significant only in the non-diabetes group (β = 50.82, 95%CI: 27.54, 74.11, p < 0.001). In conclusion, higher zinc concentration was significantly associated with longer G-tail length. The protective effect of zinc on G-tail did not differ by hypertension status; however, it disappeared in individuals with type 2 diabetes.

A critical challenge in translational research is establishing a viable and efficient interface between patient care in the operating room (OR) and the research laboratory. Here, we developed a protocol for acquiring high-quality liquid biopsies for molecular analyses from the aqueous humor and the vitreous from patients undergoing eye surgery. In this workflow, a Mobile Operating Room Lab Interface (MORLI) cart equipped with a computer, a barcode scanner, and lab instruments, including onboard cold storage, is used to obtain and archive human biological samples. A web-based data privacy-compliant database enables annotating each sample over its lifetime, and a cartesian coordinate system allows tracking each barcoded specimen in storage, enabling quick and accurate retrieval of samples for downstream analyses. Molecular characterization of human tissue samples not only serves as a diagnostic tool (e.g., to distinguish between infectious endophthalmitis and other non-infectious intraocular inflammation) but also represents an important component of translational research, allowing the identification of new drug targets, development of new diagnostic tools, and personalized therapeutics.

Depression is a leading cause of disease worldwide. The association between gut microbiota and depression has barely been investigated in the Japanese population. We analyzed Iwaki health check-up data collected from 2017 to 2019 and constructed generalized linear mixed models. The independent variable was the relative abundance of each of the 37 gut microbiota genera that were reported to be associated with depression. The dependent variable was the presence of depression assessed by the Center for Epidemiologic Studies Depression Scale. Potential confounders, including grip strength, gender, height, weight, smoking, and drinking habits, were adjusted in the regression models. Nine genera's regression coefficients ( Alistipes , Blautia , Coprococcus , Dorea , Faecalibacterium , Holdemania , Lactobacillus , Mitsuokella , and Oscillibacter ) showed statistical significance after multiple comparisons adjustment. Among these nine gut bacteria genera, Alistipes , Blautia , Coprococcus , Dorea , Faecalibacterium , and Oscillibacter were reported to be associated with butyrate production in the intestine. Our results indicate that gut microbiotas may influence the depression condition of the host via the butyrate-producing process.

Background: Anemia and stunting in children are detrimental to the prospects of a normal, healthy upbringing. Having similar risk factors and serious consequences, the syndemic aspect of these two ailments is mostly underrated, and positive deviant (PD) factors that ensure non-anemic status in stunted children have not been studied to date., Methods: This study aimed to identify PD factors that have potential to prevent syndemic anemia among stunted children aged 6-59 months in Myanmar. This was a cross-sectional secondary analysis of the Myanmar Demographic and Health Survey (DHS) data conducted in 2016, applying the PD concept, where children who were stunted without anemia were considered as PDs., Results: Among 1248 stunted children, those who had the syndemic condition were compared with their PD peers in terms of maternal characteristics as well as socioeconomic and health-related factors. Multivariable logistic regression analyses were used to identify the determinants of syndemic state. The results showed that three out of every five stunted children were anemic. The syndemic risk was decreased among children of maternal age groups 20-34 years and 35-44 years: [aOR] = 0.19, 95% CI = 0.05-0.69; p = 0.012, and aOR = 0.19, 95% CI = 0.05-0.75; p = 0.018, respectively. Moderately stunted children (aOR = 0.53, 95% CI = 0.34-0.81; p = 0.004) and children who were not currently breastfed (aOR = 1.56, 95% CI = 1.01-2.41; p = 0.044) were less likely to develop the syndemic condition., Conclusion: Maternal age, stunting severity, breastfeeding duration, and maternal anemic status are strong predictors in determining hemoglobin concentrations among stunted children. This study suggests that nutritional interventions targeting PD factors could represent syndemic action in improving child health., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: To report a series of fundus photographs taken for retinopathy of prematurity (ROP) screening that contain artifacts with imaging characteristics mimicking a notch, a recently refined classification metric in the International Classification of Retinopathy of Prematurity, third edition., Design: Retrospective case series., Participants: Infants requiring ROP screening in neonatal intensive care units from the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) and TeleROP telemedicine screening programs., Methods: Preterm infants meeting ROP examination criteria were screened with 130° wide-angle imaging systems. The images were taken by a trained nurse in the neonatal intensive care unit and transferred to an ROP specialist using a Health Insurance Portability and Accountability Act-compliant picture archiving and communication system for interpretation., Main Outcome Measures: Presence of an artifact that appeared consistent with a notch., Results: We identified a total of 17 cases in ROP screening with artifact findings that had imaging characteristics similar to a notch. The artifactual appearance of the pseudo-notch was created by the camera illumination system within the gel-lens interface when the lens was not well apposed to the cornea. In telemedicine screening for ROP, we present fundus images of eyes with a pseudo-notch appearance; review of overlapping images can help differentiate between notch and artifact., Conclusions: Pediatric retinal specialists need to be aware that artifacts play a confounding role in screening for ROP, that can be mitigated through the use of overlapping and redundant images., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2023. Published by Elsevier Inc.)

Background: Ferritin is associated with an increased prevalence of diabetes mellitus. Moreover, the ferritin levels differ across the body compositions. Although there were studies reporting the association of ferritin and diabetes, the alteration in ferritin-diabetes association by body composition differences is rarely explained. Thus, the aim of this study is to identify the effects of body compositions on the association between ferritin and diabetes parameters among the Japanese population., Methods: This study analyzed the data of a cross-sectional study with 1065 subjects aged over 19 years in the Iwaki area, Japan. Independent variables were ferritin and body compositions, while dependent variables were blood sugar, HbA1c, and diabetes mellitus. Correlations between serum ferritin and blood sugar and HbA1c were analyzed using Spearman's Rank Correlation. Multivariate linear or logistic regressions were used to investigate the effects of body compositions (body fat percentage, muscle mass, or visceral fat level) on the ferritin-diabetes associations by adjusting the confounders., Results: There were significant positive correlations between ferritin and blood sugar in both sexes (p < 0.05), while a significant correlation between ferritin and HbA1c was found only in females (p < 0.001). Higher ferritin was significantly associated with an increase in blood sugar in individuals with normal body fat percentage (lowest vs. highest quartile group, coefficient=5.07, 95 % confidence intervals [CI]: 1.48-8.65), normal visceral fat level (lowest vs. highest quartile group, coefficient=4.84, 95 % CI: 1.74-7.94), and very high muscle mass (lowest vs. highest quartile group, coefficient=14.14, 95 % CI: 5.00-23.29)., Conclusions: By our study findings, individuals' body composition notably influenced the associations of serum ferritin and diabetes parameters, and the association was attenuated in obese individuals., Competing Interests: Declaration of Competing Interest We have no conflict of interest to declare., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Purpose: We compare the ability of resident physicians to identify retinal breaks on ultra-widefield color fundus photos using the traditional image compared to an image with a green filter overlay., Methods: Residents were shown fundus photos of 10 eyes with either a retinal tear or hole. Participants were shown each photo twice-once with traditional color settings and once with a green filter overlay. Participants were scored on whether the break was correctly identified and timed on how long it took to identify the pathology., Results: Residents were able to correctly identify more retinal breaks on fundus photos with a green filter overlay compared to photos with traditional settings (P = 0.02). Residents were also able to identify breaks on fundus photos more quickly on images with a green filter overlay compared to the traditional images (P < 0.001)., Conclusions: The application of a green filter overlay may help in identifying retinal breaks., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Affordable and accessible behaviour-based interventions that do not overwhelm or demoralise overweight/obese individuals are needed. Combining clothing with behaviour change techniques might be an option. This is because clothing is a social norm, and clothing and motivation for weight loss are associated with the common desire to look better. Therefore, we conducted a single-blind randomised controlled trial to examine the effect of an intervention that combined behaviour change techniques, including simplified goal setting and self-monitoring, with a body compression corrective garment (BCCG), which exerts continuous but minimal tactile pressure on the hips and abdomen. We enrolled healthy community-dwelling adults with a body mass index ≥ 25 kg/m 2 and assigned 35 and 34 participants to the intervention and control groups, respectively. The reduction in body weight was 1.3 kg more in the intervention group than in the control group after the 12-week intervention period ( p < 0.05, repeated-measures mixed model). In addition, eating behaviour and body appreciation showed significant improvement in the intervention group compared with the control group. Our newly developed intervention improved eating behaviour and body appreciation and reduced the body weight of overweight/obese participants. Wearing a BCCG seems to facilitate behavioural changes and lead to weight loss.

Background and Objective: Newer hypoglycemics such as dipeptidyl peptidase 4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists have been increasingly used in diabetes. This study aimed to assess the relationship between usage of these hypoglycemic agents and effect on diabetic retinopathy (DR)., Materials and Methods: Using the Vestrum Health Retina Database, patients with DR with 1 year follow-up after use of a hypoglycemic agent were included and stratified by agent, including no pharmacotherapy., Results: Of 60,649 eyes, in 1 year after hypoglycemic agent usage, progression rates from severe nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) were the following: DPP-4 (17%), SGLT-2 (12%), GLP-1 (21%), metformin (18%), and none (20%). Progression rates from moderate NPDR to severe NPDR or PDR were the following: DPP-4 (11%), SGLT-2 (10%), GLP-1 (11%), metformin (10%), none (13%). Progression rates from mild NPDR to moderate/severe NPDR or PDR were the following: DPP-4 (6%), SGLT-2 (9%), GLP-1 (9%), metformin (7%), and none (10%)., Conclusions: Within a large real-world database, patients prescribed GLP-1 agonists were found to have DR progression rates comparable to those of patients receiving no hypoglycemic agents. [ Ophthalmic Surg Lasers Imaging Retina 2023; 54(3):158-165.] .

Urban air pollution has aroused growing attention due to its associated adverse health effects. A model which could promptly predict urban air quality with considerable accuracy is, therefore, important and will benefit the development of smart cities. However, only a computational fluid dynamics (CFD) model could better resolve the dispersion behavior within an urban canyon layer. A machine learning (ML) model using the Artificial Neural Network (ANN) approach was formulated in the current study to investigate vehicle-derived airborne particulate (PM 10 ) dispersion within a compact high-rise-built environment. Various measured meteorological parameters and PM 10 concentrations were adopted as the model inputs to train the ANN model. A building-resolved CFD model under the same environmental settings was also set up to compare its model performance with the ANN model. Our results showed that the ANN model exhibited promising performance (r = 0.82, fractional bias = 0.002) when comparing the > 1000 h PM 10 measurements. When comparing the diurnal hourly measured PM 10 variations in a clear-sky day, both the ANN and CFD models performed well (r > 0.8). The good performance of the CFD model relied on the knowledge of the in situ diurnal traffic profile, the adoption of suitable mobile source emission factor(s) (e.g., from MOBILE 6 and COPERT4), and the use of urban thermal and dynamical variables to capture PM 10 variations in both neutral and unstable atmospheric conditions. These requirements/constraints make it impractical for daily operation. On the contrary, the ML (ANN) model adopted here is free from these constraints and is fast (less than 0.1% computational time relative to the CFD model). These results demonstrate that the ANN model is a superior option for a smart city application.

Recent attempts to classify adult-onset diabetes using only six diabetes-related variables (GAD antibody, age at diagnosis, BMI, HbA1c, and homeostatic model assessment 2 estimates of b-cell function and insulin resistance (HOMA2-B and HOMA2-IR)) showed that diabetes can be classified into five clusters, of which four correspond to type 2 diabetes (T2DM). Here, we classified nondiabetic individuals to identify risk clusters for incident T2DM to facilitate the refinement of prevention strategies. Of the 1167 participants in the population-based Iwaki Health Promotion Project in 2014 (baseline), 868 nondiabetic individuals who attended at least once during 2015-2019 were included in a prospective study. A hierarchical cluster analysis was performed using four variables (BMI, HbA1c, and HOMA2 indices). Of the four clusters identified, cluster 1 (n = 103), labeled as "obese insulin resistant with sufficient compensatory insulin secretion", and cluster 2 (n = 136), labeled as "low insulin secretion", were found to be at risk of diabetes during the 5-year follow-up period: the multiple factor-adjusted HRs for clusters 1 and 2 were 14.7 and 53.1, respectively. Further, individuals in clusters 1and 2 could be accurately identified: the area under the ROC curves for clusters 1and 2 were 0.997 and 0.983, respectively. The risk of diabetes could be better assessed on the basis of the cluster that an individual belongs to.

Maintaining telomere length plays a crucial role in regulating cellular life span. Telomere lengthening or shortening is one of the important biomarkers which could predict the preceding or present diseases. Meanwhile, the impact of environmental arsenic exposure on telomere length has increasingly concerned. Although previous studies demonstrated the effects of arsenic on telomere length, the findings were unclear on whether telomere shortens or lengthens by arsenic exposure. Thus, this manuscript summarized and discussed the telomere length alteration following arsenic exposure and the possible does-response effect of arsenic on telomere length. The present review suggested that different age groups may respond differently to arsenic exposure, and the dose-response effect of arsenic could be a critical factor in its effect on telomere length. Moreover, speciation analysis of arsenic could be more informative in identifying the effect of arsenic on telomere length., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wai, Swe, Myar, Aisyah and Hninn.)

The relationship between serum adiponectin concentration (S-Adipo) and various diseases, such as type 2 diabetes (T2D) is conflicting. We hypothesized that the extent of kidney damage in patients with T2D may be responsible for this inconsistency and, thus, examined association between S-Adipo and T2D after consideration for the extent of kidney damage present. Of the 1816 participants in the population-based Iwaki study of Japanese people, 1751 participants with a complete dataset were included. Multivariate logistic regression analyses revealed that low S-Adipo was independently associated with T2D (<0.001), as was high urinary albumin to creatinine ratio (uACR) (<0.001). Principal components analysis showed that the relative value of S-Adipo to uACR (adiponectin relative excess) was significantly associated with T2D (odds ratio: 0.49, p < 0.001). Receiver operating curve analyses revealed that an index of adiponectin relative excess the ratio of S-Adipo to uACR was superior to S-Adipo per se as a marker of T2D (area under the curve: 0.746 vs. 0.579, p < 0.001). This finding indicates that the relationship between S-Adipo and T2D should be evaluated according to the extent of kidney damage present and may warrant similar analyses of the relationships between S-Adipo and other medicalconditions, such as cardiovascular disease.

Purpose: Medication samples of anti-VEGF agents can represent a good option for retina specialists to provide timely treatment for newly converted neovascular age-related macular degeneration (nvAMD) while prior-authorizations (PA) are pending. Our study examines the effect of medication sample use (ranibizumab or aflibercept) on future anti-vascular endothelial growth factor (VEGF) agent selection in nvAMD., Design: Retrospective cohort study., Participants: nvAMD patients who underwent an initial anti-VEGF injection with a sample medication were compared to nvAMD control patients who never received a medication sample., Methods: Charts from 2017 through 2020 were reviewed for data regarding demographics, anti-VEGF agent selection, and visual acuity outcomes for both groups. The utilization of different anti-VEGF agents in each group was compared at various time points using chi-square tests for independence of proportions., Main Outcome Measures: Anti-VEGF agent selection for the first four injections and at one year were examined., Results: Adherence to the initial agent was high between first and subsequent injections (2 nd , 3 rd , 4 th injection, and 1 year) in sample (96.2%, 95.9%, 91.9%, 93.4%, respectively), and control groups (98.1%, 94.2%, 94.9%, 87.8%, respectively). Bevacizumab usage was significantly lower among eyes receiving samples relative to controls at the second (1.9% vs. 38.7%, p < .001), third (3.1% vs. 41.3%, p < .001), fourth injections (4.7% vs. 40.4%, p < .001), and at 1 year (0% vs. 33.8%, p < .001). Aflibercept usage was significantly higher in sample eyes relative to controls at the second (78.3% vs. 43.4%, p < .001), third (76.3% vs. 41.5%, p < .001), and fourth injections (76.7% vs. 43.4%, p < .001), and at 1 year (77.0% vs. 52.7%, p < .001)., Conclusions: Sample medications in nvAMD may be initiated for many reasons, including awaiting PA approval. Our study found that eyes receiving a sample anti-VEGF agent (ranibizumab or aflibercept) for their initial injection were less likely to receive bevacizumab at future visits relative to eyes that did not receive an anti-VEGF sample, even after one year of treatment. Given the persistent use of more expensive medications at subsequent injections for patients who were initiated on samples, insurance payors may consider waiving PA requirements for bevacizumab to avoid a paradoxical increase in health-care costs.

Purpose: To review the clinical features, microbiology, management, and incidence of bacterial dacryoadenitis at our institution., Methods: This was a case series examining patients with bacterial dacryoadenitis from 2004 to 2020. Charts were reviewed for demographics, comorbidities, presenting symptoms and signs, radiology, microbiology, and management. Main outcomes included need for surgical intervention or inpatient admission., Results: Forty-five patients with bacterial dacryoadenitis had a mean age of 46.1 years. Presenting symptoms included eyelid edema (100%), extraocular motility restriction (53.3%), and purulent discharge (75.5%). Based on computed tomography or magnetic resonance imaging, 9 (20.5%) patients presented with definite abscess and 15 (34%) presented with a phlegmon or early abscess. Eleven patients (24.4%) required surgical drainage. Twenty patients (44.4%) required admission, for an average stay of 4 days (range 2-8 days). Common organisms included Haemophilus influenzae, Streptococcus pneumoniae , and Staphylococcus aureus . Presence of an early abscess or phlegmon correlated with need for drainage (p < 0.01). Extraocular motility restriction correlated with need for drainage (p = 0.02) and admission (p = 0.05). The incidence of bacterial dacryoadenitis at our institution increased as a percentage of confirmed dacryoadenitis cases; from 2004 to 2010 the incidence was 0 to 9.1% per year, while from 2010 to 2019 the incidence ranged from 7.7 to 36.2%. In 2019, our institution had 17 cases (incidence 36.2%) of bacterial dacryoadenitis., Conclusions: Bacterial dacryoadenitis is a major cause of dacryoadenitis, and its incidence may be increasing. It can resolve with minimal complications if managed appropriately, although some patients may require surgical drainage or admission for intravenous antibiotics.

Objectives: Little is known about loneliness in lower- and middle-income countries. This study investigates loneliness in the older population of Myanmar using a mixed-methods approach., Methods: To identify predictors of loneliness, hierarchical regression models were used to analyze data from the Myanmar Aging Survey 2012 (N = 3,618, 57% women). In a mixed-methods sequential explanatory design, quantitative data were integrated with qualitative data from semi-structured interviews with older adults in Myanmar in 2019., Results: The prevalence of loneliness varied by between-person characteristics. Health impairments, lower income, being widowed, not having children, and living with fewer household members were each associated with loneliness. Qualitative findings suggested that the physical presence of family members was especially protective against loneliness. Religion had mixed associations with loneliness, depending on the type of religious practice, demographic characteristics, health status, and community engagement., Discussion: The findings contribute to a better understanding of individuals' experiences of loneliness and may inform the design of interventions to prevent loneliness in Myanmar and globally., (© 2022. The Author(s).)

This study aimed to investigate the gut microbial genera associated with skeletal muscle mass, using a large-scale survey from the standpoint of preventing sarcopenia. A total of 848 participants were included in the analysis. The mean (SD) ages of men ( n = 353) and women ( n = 495) were 50.0 (12.9) years and 50.8 (12.8) years, respectively. Body composition was assessed using appendicular skeletal muscle mass/body weight (ASM/BW), ASM, and BW. Additionally, the relationship between gut microbial genera and body composition was analyzed. The means (SD) of ASM/BW were 34.9 (2.4) % in men and 29.4 (2.9) % in women. Blautia and Bifidobacterium were positively associated with ASM/BW only in men ( Blautia : β = 0.0003, Bifidobacterium : β = 0.0001). However, Blautia was negatively associated with BW (β = -0.0017). Eisenbergiella was positively associated with ASM/BW (β = 0.0209) and negatively associated with BW (β = -0.0769) only in women. Our results indicate that Blautia , Bifidobacterium and Eisenbergiella , which are positively associated with ASM/BW, might help increase skeletal muscle mass. ASM/BW may clarify the relationship between gut microbiota and skeletal muscle mass without being affected by obesity or excess body fat mass.

Purpose: To study the wider field swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, especially non-perfusion area (NPA), in the diagnosing and staging of DR., Design: Cross-sectional observational study (November 2018-September 2020)., Participants: 473 eyes of 286 patients (69 eyes of 49 control patients and 404 eyes of 237 diabetic patients)., Methods: We imaged using 6mm×6mm and 12mm×12mm angiograms on WF SS-OCTA. Images were analyzed using the ARI Network and FIJI ImageJ. Mixed effects multiple regression models and receiver operator characteristic analysis was used for statistical analyses., Main Outcome Measures: Quantitative metrics such as vessel density (VD); vessel skeletonized density (VSD); foveal avascular zone (FAZ) area, circularity, and perimeter; and NPA in DR and their relative performance for its diagnosis and grading., Results: Among patients with diabetes (median age 59 years), 51 eyes had no DR, 185 eyes (88 mild, 97 moderate-severe) had non-proliferative DR (NPDR); and 168 eyes had proliferative DR (PDR). Trend analysis revealed a progressive decline in superficial capillary plexus (SCP) VD and VSD, and increased NPA with increasing DR severity. Additionally, there was a significant reduction in deep capillary plexus (DCP) VD and VSD in early DR (mild NPDR), but the progressive reduction in advanced DR stages was not significant. NPA was the best parameter to diagnose DR (AUC:0.96), whereas all parameters combined on both angiograms efficiently diagnosed (AUC:0.97) and differentiated between DR stages (AUC range:0.83-0.97). The presence of diabetic macular edema was associated with reduced SCP and DCP VD and VSD within mild NPDR eyes, whereas an increased VD and VSD in SCP among moderate-severe NPDR group., Conclusions: Our work highlights the importance of NPA, which can be more readily and easily measured with WF SS-OCTA compared to fluorescein angiography. It is additionally quick and non-invasive, and hence can be an important adjunct for DR diagnosis and management. In our study, a combination of all OCTA metrics on both 6mm×6mm and 12mm×12mm angiograms had the best diagnostic accuracy for DR and its severity. Further longitudinal studies are needed to assess NPA as a biomarker for progression or regression of DR severity.

Introduction: Contrast sensitivity function (CSF) may better estimate a patient's visual function compared with visual acuity (VA). Our study evaluates the quick CSF (qCSF) method to measure visual function in eyes with macular disease and good letter acuity., Methods: Patients with maculopathies (retinal vein occlusion, macula-off retinal detachment, dry age-related macular degeneration and wet age-related macular degeneration) and good letter acuity (VA ≥20/30) were included. The qCSF method uses an intelligent algorithm to measure CSF across multiple spatial frequencies. All maculopathy eyes combined and individual macular disease groups were compared with healthy control eyes. Main outcomes included area under the log CSF (AULCSF) and six CS thresholds ranging from 1 cycle per degree (cpd) to 18 cpd., Results: 151 eyes with maculopathy and 93 control eyes with VA ≥20/30 were included. The presence of a maculopathy was associated with significant reduction in AULCSF (β: -0.174; p<0.001) and CS thresholds at all spatial frequencies except for 18 cpd (β: -0.094 to -0.200 log CS, all p<0.01) compared with controls. Reductions in CS thresholds were most notable at low and intermediate spatial frequencies (1.5 cpd, 3 cpd and 6 cpd)., Conclusion: CSF measured with the qCSF active learning method was found to be significantly reduced in eyes affected by macular disease despite good VA compared with healthy control eyes. The qCSF method is a promising clinical tool to quantify subtle visual deficits that may otherwise go unrecognised by current testing methods., Competing Interests: Competing interests: Dr JWM is a consultant for Genentech, Kalvista Pharmaceuticals, Sunovion and Valeant Pharmaceuticals. Dr JBM is a consultant for Alcon, Allergan, Zeiss, Heidelberg and Genentech. The remaining authors report no relevant financial disclosures., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We describe the development and management of choroidal neovascularization (CNV) in a patient with acute syphilitic posterior placoid chorioretinitis (ASPPC)., Methods: A retrospective case review is presented., Results: A 66-year-old man presented with unilateral blurry vision. He had a history of systemic syphilis infection twice, the last diagnosed 15 years before presentation and treated with intravenous ceftriaxone, resulting in seroreversion of an initially positive rapid plasma reagin (RPR). Examination revealed ASPPC with subfoveal CNV. Repeat testing revealed an RPR titer of 1:16 384. He was treated with 6 monthly intravitreal injections of bevacizumab and systemic antibiotics, resulting in resolution of his ASPPC and regression of his CNV., Conclusions: CNV is a rare complication of ASPPC. Multimodal imaging can be useful to suggest the diagnosis, and prompt treatment with systemic antibiotics and intravitreal anti-vascular endothelial growth factor agents can lead to resolution of ASPPC and regression of CNV, respectively., Competing Interests: Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: The authors declare that they have no conflicts of interest to disclose.

We describe a case of a 29-year-old man with a history of intravenous drug use and vague history of eye trauma who presented with a hypopyon and white cataract in the right eye. He underwent pars plana vitrectomy and lensectomy; his anterior chamber aspirate revealed a single helminth on calcofluor stain. We suspect that his helminth infection may be secondary to unsanitary eating and drinking practices. As overall hygiene and dietary habits have improved during the years, parasitic helminth infections are relatively rare in nonendemic areas, especially in the nonpediatric population. [ Ophthalmic Surg Lasers Imaging Retina . 2022;53:168-171.] .

Hypertension (HT) is an important risk factor for mortality and morbidity. Previous studies showed that cadmium (Cd) was associated with increased blood pressures and the prevalence of HT. This study hypothesized that Cd, regardless of its level, may increase blood pressures/HT. The objective of this study was to examine the associations between a low level of serum Cd concentration and blood pressures/HT among a general population in the Iwaki area, Japan. This was a cross-sectional study, conducted in the Aomori prefecture with 1144 volunteers aged over 19 years old, who were participants of the Iwaki health check-up in 2014. The study assessed questionnaire survey, body composition, and serum Cd concentrations. Median serum Cd concentration was 0.06 ng/mL (interquartile range 0.05-0.08 ng/mL) among our study population. Compared to the lowest quintile of serum Cd concentration group, the highest quintile of serum Cd concentration group had 4.9 mmHg higher systolic blood pressure (SBP) (95% confidence interval [CI] 1.53-8.31, p < 0.01) and 2.4 mmHg higher diastolic blood pressure (DBP) (95% CI 0.36-4.34, p < 0.05), compared to the lowest quintile group. Similarly, the highest quintile of serum Cd concentration group had 1.7 times higher prevalence of HT (95% CI 1.10-2.51, p < 0.05) than the lowest quintile group. This study identified that higher serum Cd concentration was significantly, positively, associated with SBP and DBP and HT prevalence. This study provided evidence for the associations between environmental exposure to Cd and blood pressures/HT which should be considered for future preventive measures., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Telomere (TL) is a biomarker of biological aging, and its shortening is associated with major risk factors for cardiovascular diseases (CVD). This study aimed to identify whether TL is associated with arterial stiffness as reflected by brachial-ankle pulse wave velocity (baPWV). This population-based cross-sectional study involved 1065 individuals in the Iwaki area, Japan. Total TL length and TL G-tail length were measured by hybridization protection assay. The baPWV was measured on the right and left sides using a non-invasive vascular screening device. The associations between TL and baPWV were assessed by multivariate linear regression. Compared with the shortest total TL tertile, the longest total TL group showed a significant decrease in baPWV (lowest vs. highest tertile: adjusted beta: -41.24, 95% confidence interval (CI): -76.81, -5.68). The mean baPWV decreased with a longer TL (TL G-tail length: p trend < 0.001, total TL: p trend < 0.001). TL G-tail and total TL lengths were inversely associated with baPWV, implicating TL shortening in the development of CVD. This study provides evidence of the factors influencing CVD risks at a very early stage when individuals can still take necessary precautions before CVD gives rise to a symptomatic health outcome.

Age-related macular degeneration (AMD) affects various aspects of visual function compromising patients' functional vision and quality of life. Compared to visual acuity, contrast sensitivity correlates better with vision-related quality of life and subjectively perceived visual impairment. It may also be affected earlier in the course of AMD than visual acuity. However, lengthy testing times, coarse sampling and resolution, and poor test-retest reliability of the existing contrast testing methods have limited its widespread adoption into routine clinical practice. Using active learning principles, the qCSF can efficiently measure contrast sensitivity across multiple spatial frequencies with both high sensitivity in detecting subtle changes in visual function and robust test-retest reliability, emerging as a promising visual function endpoint in AMD both in clinical practice and future clinical trials.