The molecular mechanism responsible for HbSC retinopathy may depend on the action of the angiogenesis-related genes ROBO1 and SLC38A5.

HbSC disease, a less severe form of sickle cell disease, affects the retina more frequently and patients have higher rates of proliferative retinopathy that can progress to vision loss. This study aimed to identify differences in the expression of endothelial cell-derived molecules associated with the pathophysiology of proliferative sickle cell retinopathy (PSCR). RNAseq was used to compare the gene expression profile of circulating endothelial colony-forming cells from patients with SC hemoglobinopathy and proliferative retinopathy (n = 5), versus SC patients without retinopathy (n = 3). Real-time polymerase chain reaction (qRT-PCR) was used to validate the RNAseq results. A total of 134 differentially expressed genes (DEGs) were found. DEGs were mainly associated with vasodilatation, type I interferon signaling, innate immunity and angiogenesis. Among the DEGs identified, we highlight the most up-regulated genes ROBO1 (log2FoldChange = 4.32, FDR = 1.35E-11) and SLC38A5 (log2FoldChange = 3.36 FDR = 1.59E-07). ROBO1, an axon-guided receptor, promotes endothelial cell migration and contributes to the development of retinal angiogenesis and pathological ocular neovascularization. Endothelial SLC38A5, an amino acid (AA) transporter, regulates developmental and pathological retinal angiogenesis by controlling the uptake of AA nutrient, which may serve as metabolic fuel for the proliferation of endothelial cells (ECs) and consequent promotion of angiogenesis. Our data provide an important step towards elucidating the molecular pathophysiology of PSCR that may explain the differences in ocular manifestations between individuals with hemoglobinopathies and afford insights for new alternative strategies to inhibit pathological angiogenesis.

Incidence and Clinical Characteristics of COVID-19 Ophthalmopathy Following the Termination of Dynamic Zero COVID-19 Strategy in China.

Ocular involvement is not uncommon in patients with COVID-19. However, the incidence of COVID-19 ophthalmopathy in COVID-19 patients is still not clear. In this prospective case series study, we recruited 2445 consecutive cases presenting at Neuro-ophthalmology clinic of our Eye Center during the last resurgence of SARS-CoV-2 infection from 8 December 2022 to 15 March 2023 in China, 149 cases were diagnosed as COVID-19 ophthalmopathy, 87 cases were female, with a mean age of 43.2 years, and the mean follow-up time was 15.4 weeks. One hundred and twenty of 149 cases suffered from systemic symptoms mostly manifesting as fever, cough and muscle pain prior to or soon after ocular involvement. The most common COVID-19 ophthalmopathy was optic neuritis (51/149), followed by acute zonal occult outer retinopathy complex disease (31/149), uveitis (17/149), ocular mobility disorder-related (third, fourth, or sixth) cranial nerve neuritis (15/149), anterior ischaemic optic neuropathy (9/149), retinal artery occlusion (8/149), retinal microangiopathy including retinal haemorrhage and cotton wool spot (8/149), viral conjunctivitis (7/149), retinal vein occlusion (3/149), viral keratitis (2/149), ptosis (2/149), and other rare ocular diseases. Except 5 cases with central retinal artery occlusion, other 144 COVID-19 ophthalmopathy cases showed good response to steroid therapy. Our study revealed an incidence of 6.09% for COVID-19 ophthalmopathy in outpatients at our Neuro-ophthalmology clinic during last resurgence of COVID-19 in China, and demonstrated that SARS-CoV-2 infection could induce an initial onset or a relapse of ophthalmic diseases, and that ocular involvement might manifest as the initial or even the only presentation of COVID-19.

Cost-Effectiveness of Addressing Retinopathy of Prematurity in Rwanda.

PURPOSE: With the expansion of neonatal care in sub-Saharan Africa (SSA), an increasing number of premature babies are at risk to develop retinopathy of prematurity (ROP). Previous studies have quantified the cost-effectiveness of addressing ROP in middle-income countries, but few have focused on SSA. This study estimates the cost of a national program for ROP screening and anti-VEGF injection treatment in Rwanda compared to the status quo. METHODS: Medical cost data were collected from King Faisal Hospital in Rwanda (July 2022). Societal burden of vision loss included lost productivity and quality-adjusted life years (QALYs). Published data on epidemiology and natural history of ROP were used to estimate burden and sequelae of ROP in Rwanda. Cost of a national program for screening and treating a one-year birth cohort was compared to the status quo using a decision analysis model. RESULTS: Cost of ROP screening and treatment was $738 per infant. The estimated equipment cost necessary for the startup of a national program was $58,667. We projected that a national program could avert 257 cases of blindness in the cohort and increase QALYs compared to the status quo. Screening and treatment for ROP would save an estimated $270,000 for the birth cohort from reductions in lost productivity. CONCLUSION: The cost of screening and anti-VEGF treatment for ROP is substantially less than the indirect cost of vision loss due to ROP. Allocating additional funding towards expansion of ROP screening and treatment is cost-saving from a societal perspective compared to current practice.

Longitudinal multimodal imaging of bilateral diffuse uveal melanocytic proliferation secondary to gallbladder adenocarcinoma.

Purpose: To present the longitudinal, multimodal imaging of Bilateral Diffuse Uveal Melanocytic Proliferation secondary to gallbladder carcinoma over a 17 month period, demonstrating the natural history, the evolution with treatment and salient features to support timely diagnosis of this condition with life-threatening associations. Observations: A systemically well 73 year old woman presented with a 2 month history of progressive visual loss in the right eye. We report the initial findings on clinical examination and with retinal imaging including fluorescein and indocyanine angiography, optical coherence tomography and autoflourescence. An initial diagnosis of atypical central serous chorioretinopathy with secondary choroidal neovascularisation led to treatment with intravitreal aflibercept before the correct diagnosis of BDUMP was made 2 months later, aided by evolution of signs on imaging and examination. Subsequent investigation led to detection of gallbladder adenocarcinoma. The patient underwent systemic chemotherapy and eventual phacoemulsification and insertion of intraocular lens to both eyes. The patient died 21 months after presentation of visual symptoms, with latest imaging at 17 months. Conclusion: We report the evolution of BDUMP utilising multi-modal imaging pre-treatment and during treatment with chemotherapy, and highlight peripheral progression of disease despite consolidation at the macula.

Clinical Profile and Ocular Morbidities in Patients with Both Diabetic Retinopathy and Uveitis.

Purpose: To describe the clinical profile and complications of diabetic retinopathy (DR) and uveitis in patients with coexisting conditions and to derive associations based on site of primary inflammation, stage of DR, and complications of each. Design: Single-center, cross-sectional observational study. Participants: Sixty-six patients with coexisting DR and uveitis. Methods: Electronic medical records of 66 such cases were evaluated. The demographic data, diabetic status, clinical characteristics, and complications of DR and uveitis on the final follow-up were recorded. Main Outcome Measures: Associations between best corrected visual acuity (BCVA), prevalence of various stages, and complications of DR among eyes with and without uveitis, and correlation between the intensity and primary sites of inflammation among eyes with proliferative and nonproliferative changes. Results: Of the 132 eyes, all had DR and 97 eyes had uveitis (35 unilateral and 31 bilateral cases). Mean age of patients was 53.4 ± 8.7 years, duration of diabetes was 10.5 ± 6.9 years, and duration of uveitis was 61.3 ± 68.8 months. Of uveitis patients, 54.6% had anterior uveitis (AU), 20.6% had intermediate, 10.3% posterior, and 14.4% panuveitis. Forty-nine point five percent of eyes had proliferative DR (PDR) changes. There was a higher proportion PDR cases among anterior (56.6%), posterior (70%), and panuveitis (64.3%), with difference in AU cases approaching statistical significance (P = 0.067). Conversely, significant (P < 0.001) intermediate uveitis cases had nonproliferative changes (80%). Final BCVA was significantly poorer in the group with uveitis (P = 0.045). The proportion of fibrovascular proliferations, tractional detachments. and iris neovascularization among proliferative retinopathy eyes with uveitis (14.6%, 18.8%, and 12.5% respectively) was higher than those without uveitis (5.3%, 10.5%, and 5.3%). Among uveitis cases, 58.5% eyes developed cataracts, 44.3% had posterior synechiae, 12.3% developed secondary glaucoma, 4.1% had epiretinal membrane, 4.1% had band-shaped keratopathy, and 1.0% developed macular neovascularization. Conclusions: Eyes with coexisting DR and uveitis have a higher prevalence of neovascular and uveitis complications along with a risk of poorer visual outcomes. Treatment should aim at limiting the duration and intensity of inflammation. Strict glycemic control is essential for inflammation control and preventing the progression of DR to more advanced stages. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Effect of Glucagon-Like Peptide-1 Receptor Agonists on Diabetic Retinopathy at a Tertiary Care Center.

Objective: The potential association between diabetic retinopathy (DR) worsening and glucagon-like peptide-1 receptor agonists (GLP-1RA) has affected therapeutic management of diabetic patients but remains controversial. This study compared rates of DR development or progression in patients on GLP-1RA to those on SGLT-2 inhibitors (SGLT-2I). Design: Retrospective cohort study. Subjects: Nine hundred eighty-one patients with diabetes mellitus taking GLP-1RA or SGLT-2I, the latter serving as controls, between 2012 and 2023. Methods: Patients were one-to-one greedy matched by propensity scores on race/ethnicity, age, smoking status, baseline body mass index and hemoglobin A1c %, type of diabetes mellitus, baseline DR status and history of DR procedures, duration of drug use, whether they had taken both drug types, and change in hemoglobin A1c % after 1 year on the drug. Main Outcome Measures: The primary outcome was clinical DR development or progression (termed "worsening") detected by International Classification of Diseases (ICD), 10th edition codes, confirmed by manual review, on GLP-1RA compared with SGLT-2I after propensity score matching. Secondary outcomes included DR worsening indicated by need for procedures due to complications, and time-to-first DR worsening event. Results: The study included 692 GLP-1RA users and 289 SGLT-2I users. The mean follow-up periods for GLP-1RA versus SGLT-2I use were 1.54 (standard deviation [SD] 1.82) years and 1.38 (SD 1.56) years, respectively. The rates of clinical worsening were 2.3% and 2.8%, respectively. After propensity score matching, an association was not identified between GLP1-RA and DR worsening neither clinically by ICD-10 codes (odds ratio [OR] = 0.33, 95% confidence interval [CI]: 0.11-1.03) nor by indication for procedures (OR = 0.50, 95% CI 0.13-2.00). Time-to-first DR worsening did not differ between the groups in Kaplan-Meier analysis. The most common type of clinical worsening event for both drug types was vitreous hemorrhage (43.7% and 50% of worsening events in GLP-1RA and SGLT-2I users, respectively). The most common DR procedure indicated was anti-VEGF injections (34% and 35% of GLP-1RA and SGLT-2I events, respectively). Conclusions: Diabetic retinopathy worsening, either clinically or by procedures, was not associated with GLP-1RA compared with SGLT-2I, both before and after propensity score matching on all analyses, including time-to-first worsening event. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Sulforaphane and ophthalmic diseases.

Sulforaphane (SFN) is an organosulfur compound categorized as an isothiocyanate (ITC), primarily extracted from cruciferous vegetables like broccoli and cabbage. The molecular formula of sulforaphane (SFN) is C6H11NOS2. SFN is generated by the hydrolysis of glucoraphanin (GRP) through the enzyme myrosinase, showing notable properties including anti-diabetic, anti-inflammatory, antimicrobial, anti-angiogenic, and anticancer attributes. Ongoing clinical trials are investigating its potential in diseases such as cancer, neurodegenerative diseases, diabetes-related complications, chronic kidney disease, cardiovascular disease, and liver diseases. Several animal carcinogenesis models and cell culture models have shown it to be a very effective chemopreventive agent, and the protective effects of SFN in ophthalmic diseases have been linked to multiple mechanisms. In murine models of diabetic retinopathy and age-related macular degeneration, SFN delays retinal photoreceptor cell degeneration through the Nrf2 antioxidative pathway, NF-κB pathway, AMPK pathway, and Txnip/mTOR pathway. In rabbit models of keratoconus and cataract, SFN has been shown to protect corneal and lens epithelial cells from oxidative stress injury by activating the Keap1-Nrf2-ARE pathway and the Nrf-2/HO-1 antioxidant pathway. Oral delivery or intraperitoneal injection at varying concentrations are the primary strategies for SFN intake in current preclinical studies. Challenges remain in the application of SFN in eye disorders due to its weak solubility in water and limited bioavailability because of the presence of blood-ocular barrier systems. This review comprehensively outlines recent research on SFN, elucidates its mechanisms of action, and discusses potential therapeutic benefits for eye disorders such as age-related macular degeneration (AMD), diabetic retinopathy (DR), cataracts, and other ophthalmic diseases, while also indicating directions for future clinical research to achieve efficient SFN treatment for ophthalmic diseases.

Purtscher-like retinopathy: Case report of a rare complication of acute on chronic pancreatitis.

Purtscher's retinopathy is an occlusive micro-vasculopathy causing sudden onset visual loss in trauma. Similar retinal appearance is observed as a rare complication of acute pancreatitis which is identified as Purtscher-like retinopathy (PulR). We report the case of a 15-year-old girl diagnosed to have acute on chronic pancreatitis who noticed a sudden onset loss of vision in the left eye and was found to have significantly diminished visual acuity. A dilated fundoscopic examination demonstrated pathognomonic Purtscher flecken, multiple retinal haemorrhages, cotton wool spots and macular oedema. A clinical diagnosis of PulR was made in the setting of acute on chronic pancreatitis. Optical coherence tomography was used to support the diagnosis and to monitor response to therapy. Given the variable prognosis with no evidence-based therapies available, she had a subjective improvement in visual acuity with administration of intravitreal steroids and observation with management of the acute episode of pancreatitis. Knowledge and awareness of this rare condition will enable its early detection and the search for newer therapies.

Impact of Gold-Standard Label Errors on Evaluating Performance of Deep Learning Models in Diabetic Retinopathy Screening: Nationwide Real-World Validation Study.

BACKGROUND: For medical artificial intelligence (AI) training and validation, human expert labels are considered the gold standard that represents the correct answers or desired outputs for a given data set. These labels serve as a reference or benchmark against which the model's predictions are compared. OBJECTIVE: This study aimed to assess the accuracy of a custom deep learning (DL) algorithm on classifying diabetic retinopathy (DR) and further demonstrate how label errors may contribute to this assessment in a nationwide DR-screening program. METHODS: Fundus photographs from the Lifeline Express, a nationwide DR-screening program, were analyzed to identify the presence of referable DR using both (1) manual grading by National Health Service England-certificated graders and (2) a DL-based DR-screening algorithm with validated good lab performance. To assess the accuracy of labels, a random sample of images with disagreement between the DL algorithm and the labels was adjudicated by ophthalmologists who were masked to the previous grading results. The error rates of labels in this sample were then used to correct the number of negative and positive cases in the entire data set, serving as postcorrection labels. The DL algorithm's performance was evaluated against both pre- and postcorrection labels. RESULTS: The analysis included 736,083 images from 237,824 participants. The DL algorithm exhibited a gap between the real-world performance and the lab-reported performance in this nationwide data set, with a sensitivity increase of 12.5% (from 79.6% to 92.5%, P<.001) and a specificity increase of 6.9% (from 91.6% to 98.5%, P<.001). In the random sample, 63.6% (560/880) of negative images and 5.2% (140/2710) of positive images were misclassified in the precorrection human labels. High myopia was the primary reason for misclassifying non-DR images as referable DR images, while laser spots were predominantly responsible for misclassified referable cases. The estimated label error rate for the entire data set was 1.2%. The label correction was estimated to bring about a 12.5% enhancement in the estimated sensitivity of the DL algorithm (P<.001). CONCLUSIONS: Label errors based on human image grading, although in a small percentage, can significantly affect the performance evaluation of DL algorithms in real-world DR screening.

Ocular Syphilis - Clinical Features and Outcome in HIV Positive and HIV Negative Patients from a Tertiary Eye Center from India - A Comparative Study.

PURPOSE: To study and compare the clinical characteristics and outcome of ocular syphilis between HIV positive and HIV negative patients. METHODS: Retrospective hospital-based case series from a tertiary eye care hospital in India. Patients with uveitis and positive syphilis serology were included. Demographics, clinical features, investigations, imaging and treatment modalities were noted. RESULTS: Hundred and five (105) eyes of 66 patients were analyzed. Males were predominantly affected (n = 57/66, 86.4%). Secondary syphilis was the most common stage of presentation (n = 48/66, 72.7%). Two groups were identified: HIV positive (HIVP) patients (n = 39/66, 59%) and HIV negative (HIVN) patients (n = 27/66, 41%). 12/39 (30.8%) patients were newly diagnosed with HIV at the time of ocular presentation. Panuveitis was the most common presenting feature in both groups (n = 66/105 eyes, 62.8%). Diffuse necrotizing retinitis was more common in HIV patients (HIVP - 15 Vs HIVN - 5 eyes). Ocular co-infections were more common in HIV patients, ocular tuberculosis, the commonest in both groups. Intravenous penicillin and titrated dose of systemic steroids were the mainstay of treatment. Improvement in mean logMAR was noted from 1.415 to 0.828 with p-value < 0.001. At final follow-up, 71.8% patients showed visual improvement. Complete resolution of ocular inflammation was noted in 95.5% patients. CONCLUSION: Ocular syphilis poses a diagnostic challenge considering the varied presentations and clinical course both in immunocompromised and immunocompetent groups. Clinical presentations are not always classical. High index of suspicion with supportive laboratory investigations and with characteristic OCT features helps diagnosis. All uveitis patients, especially with those suspected with infectious etiology, need to be tested for syphilis serology to prevent vision loss in this resurgent disease.

Diagnostic application in streptozotocin-induced diabetic retinopathy rats: A study based on Raman spectroscopy and machine learning.

Vision impairment caused by diabetic retinopathy (DR) is often irreversible, making early-stage diagnosis imperative. Raman spectroscopy emerges as a powerful tool, capable of providing molecular fingerprints of tissues. This study employs RS to detect ex vivo retinal tissue from diabetic rats at various stages of the disease. Transmission electron microscopy was utilized to reveal the ultrastructural changes in retinal tissue. Following spectral preprocessing of the acquired data, the random forest and orthogonal partial least squares-discriminant analysis algorithms were employed for spectral data analysis. The entirety of Raman spectra and all annotated bands accurately and distinctly differentiate all animal groups, and can identify significant molecules from the spectral data. Bands at 524, 1335, 543, and 435 cm-1 were found to be associated with the preproliferative phase of DR. Bands at 1045 and 1335 cm-1 were found to be associated with early stages of DR.

Choroidal thickening induced by pioglitazone in diabetic patients.

Purpose: This study aimed to determine the changes in choroidal thickness induced by pioglitazone in diabetic patients. Methods: A total of 261 patients diagnosed with type 2 diabetes who had taken oral pioglitazone for more than 6 months were included in the study. After excluding patients who did not undergo regular eye examinations or who had ophthalmic surgery/interventions during the treatment period, a total of 40 eyes were included. The study examined the duration and dosage of pioglitazone, patient age, ocular axial length, refraction, glycated hemoglobin, systolic blood pressure, corrected visual acuity, macular thickness, choroidal thickness, and choroid vascular index. Patients were categorized into a high dose group if their pioglitazone dose was 30mg or more per day, and a low dose group if it was 15mg or less. Choroidal thickness was measured below the subfovea and a 500 µm radius nasal and temporal to that location. Results: Choroidal thickness significantly increased after 6 and 12 months of pioglitazone in all subjects (6.70µm, 13.65µm, each). When stratified by pioglitazone dosage, choroidal thickness increased at 6 and 12 months in both the high (4.48µm, 0.84µm, each) and low dose groups (6.85µm, 21.45µm, each), with a greater change observed in low dose group (p<0.05, respectively). Based on the location of choroidal thickness measurements, a significant increase in choroidal thickness was observed at 6 and 12 months of pioglitazone treatment in the subfoveal (7.00µm, 13.15µm, each) and nasal regions (6.43µm, 19.24µm, each), while a significant increase was only observed after 6 months of treatment in the temporal region (8.53µm) (p<0.05, respectively). The largest increase in choroidal thickness was observed in the nasal side. Conclusion: This study found that choroidal thickness increased in diabetic patients after taking pioglitazone. Regular eye examinations are recommended for diabetic patients who are on pioglitazone.

Tear neuropeptide Y as a non-invasive marker of peripheral microvascular complications in type 1 diabetes.

AIMS: To investigate tear neuropeptide Y (NPY) and substance P concentrations in individuals with type 1 diabetes, comparing those with and without both diabetic retinopathy (DR) and peripheral neuropathy. METHODS: This cross-sectional study involved 41 participants with type 1 diabetes and none to moderate DR, and 22 healthy controls. Assessments included clinical ocular surface parameters, quantification of corneal nerve attributes (based on in vivo confocal microscopy imaging), DR grading, and evaluation for small and large fibre neuropathy. Concentrations of NPY and substance P in tear samples were measured using enzyme-linked immunosorbent assay. RESULTS: Mean (±standard deviation) tear NPY concentrations in participants with type 1 diabetes and length-dependent small fibre neuropathy (SFN) was lower than in controls (10.84±4.10 ng/mL vs 14.72±3.12 ng/mL; p=0.004), but not significantly different from type 1 diabetes participants without SFN (13.39±4.66 ng/mL; p=0.11). Tear NPY levels were lower in individuals with type 1 diabetes and mild/moderate non-proliferative DR (10.44±3.46 ng/mL) compared to none/minimal DR (13.79±4.76 ng/mL; p=0.0005) and controls. In separate linear regression models, both the presence of SFN ((ß=-0.75, p=0.02) and the presence of mild/moderate DR (ß=-0.84, p=0.009) were significantly associated with tear NPY levels relative to controls, after adjusting for participant age, sex, and dry eye disease. There were no inter-group differences for tear substance P concentrations. CONCLUSIONS: Tear NPY has potential utility as an indicator of peripheral microvascular complications associated with type 1 diabetes.

Peripheral PRP in the Operating Room vs Standard Clinic PRP for the Initial Treatment of PDR.

Purpose: To compare the long-term outcomes of standard panretinal photocoagulation (PRP) performed in the operating room (OR) with peripheral PRP performed in the clinic in treatment-naïve patients with proliferative diabetic retinopathy (PDR). Methods: Consecutive cases from 2017 to 2022 were retrospectively reviewed. Exclusion criteria included previous PRP, pars plana vitrectomy performed at the time of the initial PRP, PRP performed in another setting within 3 months of the initial treatment, a documented plan for future PRP at the time of the initial treatment, and less than 3 years of follow-up. Negative binomial regressions were used to compare the number of subsequent interventions between the 2 groups and t tests to compare the visual acuity (VA) outcomes. Results: Of the 961 eyes of 679 patients screened, 82 eyes of 53 patients met the inclusion criteria. The initial PRP was performed in the OR (OR cohort) in 57 eyes of 38 patients and in the clinic (clinic cohort) in 25 eyes of 15 patients. The OR cohort had a mean of 0.4 subsequent surgeries and 0.8 subsequent PRP treatments and the clinic cohort, 0.8 subsequent surgeries (P < .05) and 1.8 subsequent PRP treatments (P < .05). No significant between-group difference was found in the VA outcomes over the long-term follow-up (mean, 44.2 months). Conclusions: Peripheral PRP performed in the OR resulted in fewer subsequent interventions than standard PRP in the clinic and may afford better control of PDR.

American Society of Retina Specialists Artificial Intelligence Task Force Report.

Since the Artificial Intelligence Committee of the American Society of Retina Specialists developed the initial task force report in 2020, the artificial intelligence (AI) field has seen further adoption of US Food and Drug Administration-approved AI platforms and significant development of AI for various retinal conditions. With expansion of this technology comes further areas of challenges, including the data sources used in AI, the democracy of AI, commercialization, bias, and the need for provider education on the technology of AI. The overall focus of this committee report is to explore these recent issues as they relate to the continued development of AI and its integration into ophthalmology and retinal practice.

Associations of heavy metal exposure with diabetic retinopathy in the U.S. diabetic population: a cross-sectional study.

Background: Mounting evidence suggests a correlation between heavy metals exposure and diabetes. Diabetic retinopathy (DR) is a prevalent and irreversible complication of diabetes that can result in blindness. However, studies focusing on the effects of exposure to heavy metals on DR remain scarce. Thus, this study aimed to investigate the potential correlation between heavy metals exposure and DR. Methods: A total of 1,146 diabetics from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 were included in this study. Heavy metal levels were measured via urine testing. Weighted logistic regression, Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression, and restricted cubic spline (RCS) were utilized to investigate the potential relationships between exposure to 10 heavy metals and DR. Finally, subgroup analysis was conducted based on the glycemic control status. Results: Among the 1,146 participants, 239 (20.86%) were diagnosed with DR. Those with DR had worse glycemic control and a higher prevalence of chronic kidney disease compared to those without DR. Moreover, both the WQS regression and BKMR models demonstrated a positive relationship between exposure to mixed heavy metals and the risk of DR. The results of weighted logistic regression revealed a positive correlation between cobalt (Co) and antimony (Sb) exposure and the risk of DR (OR = 1.489, 95%CI: 1.064-2.082, p = 0.021; OR = 1.475, 95% CI: 1.084-2.008, p = 0.014), while mercury (Hg) exposure was found to promote DR exclusively in the group with good glycemic control (OR = 1.509, 95% CI: 1.157-1.967, p = 0.003). These findings were corroborated by the results of the RCS analysis. Conclusion: Heavy metal exposure is associated with an increased risk of DR, especially Sb, Co, and Hg exposure. Nevertheless, well-designed prospective studies are warranted to validate these findings.

Demographic and Metabolic Risk Factors Associated with Development of Diabetic Macular Edema among Persons with Diabetes Mellitus.

Purpose: Diabetic macular edema (DME), a leading cause of visual impairment, can occur regardless of diabetic retinopathy (DR) stage. Poor metabolic control is hypothesized to contribute to DME development, although large-scale studies have yet to identify such an association. This study aims to determine whether measurable markers of dysmetabolism are associated with DME development in persons with diabetes. Design: Retrospective cohort study. Participants: Using data from the Sight Outcomes Research Collaborative (SOURCE) repository, patients with diabetes mellitus and no preexisting DME were identified and followed over time to see what factors associated with DME development. Methods: Cox proportional hazard modeling was used to assess the relationship between demographic variables, diabetes type, smoking history, baseline DR status, blood pressure (BP), lipid profile, body mass index (BMI), hemoglobin A1C (HbA1C), and new onset of DME. Main Outcome Measures: Adjusted hazard ratio (HR) of developing DME with 95% confidence intervals (CIs). Results: Of 47 509 eligible patients from 10 SOURCE sites (mean age 63 ± 12 years, 58% female sex, 48% White race), 3633 (7.6%) developed DME in the study period. The mean ± standard deviation time to DME was 875 ± 684 days (∼2.4 years) with those with baseline nonproliferative DR (HR 3.67, 95% CI: 3.41-3.95) and proliferative DR (HR 5.19, 95% CI: 4.61-5.85) more likely to develop DME. There was no difference in DME risk between type 1 and type 2 patients; however, Black race was associated with a 40% increase in DME risk (HR 1.40, 95% CI: 1.30-1.51). Every 1 unit increase in HbA1C had a 15% increased risk of DME (HR 1.15, 95% CI: 1.13-1.17), and each 10 mmHg increase in systolic BP was associated with a 6% increased DME risk (HR 1.06, 95% CI: 1.02-1.09). No association was identified between DME development and BMI, triglyceride levels, or high-density lipoprotein levels. Conclusions: These findings suggest that in patients with diabetes modifiable risk factors such as elevated HbA1C and BP confer a higher risk of DME development; however, other modifiable systemic markers of dysmetabolism such as obesity and dyslipidemia did not. Further work is needed to identify the underlying contributions of race in DME. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Research progress of brain organoids in the field of diabetes.

Human embryonic stem cells and human induced pluripotent stem cells may be used to create 3D tissues called brain organoids. They duplicate the physiological and pathological characteristics of human brain tissue more faithfully in terms of both structure and function, and they more precisely resemble the morphology and cellular structure of the human embryonic brain. This makes them valuable models for both drug screening and in vitro studies on the development of the human brain and associated disorders. The technical breakthroughs enabled by brain organoids have a significant impact on the research of different brain regions, brain development and sickness, the connections between the brain and other tissues and organs, and brain evolution. This article discusses the development of brain organoids, their use in diabetes research, and their progress.

Thirty-Year Trends in the Prevalence and Severity of Diabetic Retinopathy at the First Visit in Patients with Untreated Type 2 Diabetes Mellitus.

PURPOSE: Although the rate of diabetic retinopathy (DR)-related blindness has decreased in developed countries in recent years, the reasons for this decrease have remained unclear. The prevalence/severity trends of DR at the first visit in patients with untreated type 2 diabetes mellitus (T2DM) patients seen between the1986s and 2018s were assessed. METHODS: A total of 1979 Japanese T2DM patients diagnosed between 1986 and 2018 were divided into four groups by the decade of their first visit: the 1986 years (1986-1987), the 1996 years (1996-1997), the 2006 years (2006-2008), the 2016 years (2016-2018). The DR prevalence/severity trends were assessed. RESULTS: A significant decrease in the rate of prevalence of DR from the 1986s to 2016s was observed among previously untreated T2DM patients visiting our hospital for the first time (1986s: 25.5%; 1996s: 26.2%; 2006s: 22.2%; and 2016s: 15.6%). The prevalence was significantly higher in females (30.2%) than in males (21.3%). Although the severity trend of DR did not differ significantly among the four measurement years, the rate of simple DR was the highest in the 2016s. CONCLUSION: We found, for the first time, a significant decrease in the rate of prevalence of DR from the 1986s to 2016s in patients with untreated T2DM visiting our hospital for the first time. A decrease in the rate of DR prevalence could explain, at least in part, the observed reduction in the rate of blindness in patients with T2DM.