Assessment of early macular microangiopathy in subjects with prediabetes using optical coherence tomography angiography and fundus photography.

AIMS: Early detection of retinal microangiopathy in patients with prediabetes may reduce diabetic retinopathy complications. The aim of this study was to assess early macular vascular changes in prediabetics before development of over diabetes using OCTA and fundus photography. METHODS: In this cross-sectional study, 66 prediabetic individuals and 66 normal controls underwent clinical, laboratory, and fundus photography evaluation followed by OCTA macular imaging to examine for the foveal avascular zone, and area of capillary non-perfusion, thickness, disorganization of vessels, and vessel density perfusion percentage of superficial capillary plexus and deep capillary plexus. RESULTS: Retinal microangiopathy was detected in 36.4% of prediabetics by OCTA and only in 10.6% by fundus photography. None of clinical or laboratory parameters had significant association with DR. Area of capillary non-perfusion and disorganization of SCP were detected in 53.8% and 56.8%, respectively, in prediabetics. VDP of SCP and DCP of whole image, parafoveal, and perifoveal areas was significantly lower in prediabetes group compared to normal control. VDP of DCP of perifoveal area (ß coefficient: - 0.10, OR: 0.91, 95% CI: 0.86-0.96, P < 0.001) and disorganization of DCP (ß coefficient: 1.93, OR: 6.89, 95% CI: 2.5-18.8, P < 0.001) were significant predictors of DR in prediabetics. There was no difference in FAZ in prediabetics with and without retinopathy. CONCLUSIONS: OCTA could detect early retinal vascular changes during the prediabetic state before developing diabetes. VDP was significantly reduced in prediabetic patients. Furthermore, VDP of DCP of perifoveal area and disorganization of DCP were the most important predictors of retinopathy in prediabetic patients.

Assessment of the association between genetic factors regulating thyroid function and microvascular complications in diabetes: A two-sample Mendelian randomization study in the European population.

Background: Observational studies have identified a possible link between thyroid function and diabetic microangiopathy, specifically in diabetic kidney disease (DKD) and diabetic retinopathy (DR). However, it is unclear whether this association reflects a causal relationship. Objective: To assess the potential direct effect of thyroid characteristics on DKD and DR based on Mendelian randomization (MR). Methods: We conducted an MR study using genetic variants as an instrument associated with thyroid function to examine the causal effects on DKD and DR. The study included the analysis of 4 exposure factors associated with thyroid hormone regulation and 5 outcomes. Genomewide significant variants were used as instruments for standardized freethyroxine (FT4) and thyroid-stimulating hormone (TSH) levels within the reference range, standardized free triiodothyronine (FT3):FT4 ratio, and standardized thyroid peroxidase antibody (TPOAB) levels. The primary outcomes were DKD and DR events, and secondary outcomes were estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR) in diabetes, and proliferative diabetic retinopathy (PDR). Satisfying the 3 MR core assumptions, the inverse-variance weighted technique was used as the primary analysis, and sensitivity analysis was performed using MR-Egger, weighted median, and MR pleiotropy residual sum and outlier techniques. Results: All outcome and exposure instruments were selected from publicly available GWAS data conducted in European populations. In inverse-variance weighted random-effects MR, gene-based TSH with in the reference range was associated with DKD (OR 1.44; 95%CI 1.04, 2.41; P = 0.033) and eGFR (ß: -0.031; 95%CI: -0.063, -0.001; P = 0.047). Gene-based increased FT3:FT4 ratio, decreased FT4 with in the reference range were associated with increased ACR with inverse-variance weighted random-effects ß of 0.178 (95%CI: 0.004, 0.353; P = 0.046) and -0.078 (95%CI: -0.142, -0.014; P = 0.017), respectively, and robust to tests of horizontal pleiotropy. However, all thyroid hormone instruments were not associated with DR and PDR at the genetic level. Conclusion: In diabetic patients, an elevated TSH within the reference range was linked to a greater risk of DKD and decreased eGFR. Similarly, decreased FT4 and an increased FT3:FT4 ratio within the reference range were associated with increased ACR in diabetic patients. However, gene-based thyroid hormones were not associated with DR, indicating a possible pathway involving the thyroid-islet-renal axis. However, larger population studies are needed to further validate this conclusion.

Development and validation of a predictive risk model based on retinal geometry for an early assessment of diabetic retinopathy.

Aims: This study aimed to develop and validate a risk nomogram prediction model based on the retinal geometry of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to investigate its clinical application value. Methods: In this study, we collected the clinical data of 410 patients with T2DM in the Second Affiliated Hospital of Chongqing Medical University between October 2020 and March 2022. Firstly, the patients were randomly divided into a development cohort and a validation cohort in a ratio of 7:3. Then, the modeling factors were selected using the least absolute shrinkage and selection operator (LASSO). Subsequently, a nomogram prediction model was built with these identified risk factors. Two other models were constructed with only retinal vascular traits or only clinical traits to confirm the performance advantage of this nomogram model. Finally, the model performances were assessed using the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis (DCA). Results: Five predictive variables for DR among patients with T2DM were selected by LASSO regression from 33 variables, including fractal dimension, arterial tortuosity, venular caliber, duration of diabetes mellitus (DM), and insulin dosage (P< 0.05). A predictive nomogram model based on these selected clinical and retinal vascular factors presented good discrimination with an AUC of 0.909 in the training cohort and 0.876 in the validation cohort. By comparing the models, the retinal vascular parameters were proven to have a predictive value and could improve diagnostic sensitivity and specificity when combined with clinical characteristics. The calibration curve displayed high consistency between predicted and actual probability in both training and validation cohorts. The DCA demonstrated that this nomogram model led to net benefits in a wide range of threshold probability and could be adapted for clinical decision-making. Conclusion: This study presented a predictive nomogram that might facilitate the risk stratification and early detection of DR among patients with T2DM.

Assessment of tear inflammatory cytokines concentration in patients with diabetes with varying severity of involvement.

Diabetic retinopathy (DR), as one of the most important causes of blindness in Western societies, is a common micro-vasculopathy associated with diabetes. There is growing evidence of the role of inflammation in its development. This study was designed to measure cytokines in patients with diabetes with different stages of retinopathy .In this study, tear concentrations of three types of cytokines with different angiogenic properties including IL-1RA, IL-8, and TNF-α were measured in patients with diabetes without retinopathy, with non-proliferative retinopathy, with proliferative retinopathy, and in a healthy control group. The results showed that concentrations of TNF-α and IL-8 were higher in the tear sample of diabetics than in the control group and the concentrations of these cytokines were higher in patients with more advanced stages of diabetes, while the tear level of IL-1RA was significantly lower in diabetics. Based on these findings, it can be concluded that diabetes and its progression of severity affects the tear levels of IL-1RA, IL-8, and TNF-α inflammatory cytokines.

Optimal Frequency of Retinopathy Screening in Adolescents With Type 1 Diabetes: Markov Modeling Approach Based on 30 Years of Data.

OBJECTIVE: Current guidelines recommend biennial diabetic retinopathy (DR) screening commencing at the age of 11 years and after 2-5 years' duration of type 1 diabetes. Growing evidence suggests less frequent screening may be feasible. RESEARCH DESIGN AND METHODS: Prospective data were collected from 2,063 youth with type 1 diabetes who were screened two or more times between 1990 and 2019. Baseline (mean ± SD) age was 13.3 ± 1.8 years, HbA1c was 8.6 ± 1.3% (70.1 ± 14.7 mmol/mol), diabetes duration was 5.6 ± 2.8 years, and follow-up time was 4.8 ± 2.8 years. DR was manually graded from 7-field retinal photographs using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Markov chain was used to calculate probabilities of DR change over time and hazard ratio (HR) of DR stage transition. RESULTS: The incidence of moderate nonproliferative DR (MNPDR) or worse was 8.6 per 1,000 patient-years. Probabilities of transition to this state after a 3-year interval were from no DR, 1.3%; from minimal DR, 5.1%; and from mild DR, 22.2%, respectively. HRs (95% CIs) for transition per 1% current HbA1c increase were 1.23 (1.16-1.31) from no DR to minimal NPDR, 1.12 (1.03-1.23) from minimal to mild NPDR, and 1.28 (1.13-1.46) from mild to MNPDR or worse. HbA1c alone explained 27% of the transitions between no retinopathy and MNPDR or worse. The addition of diabetes duration into the model increased this value to 31% (P = 0.03). Risk was also increased by female sex and higher attained age. CONCLUSIONS: These results support less frequent DR screening in youth with type 1 diabetes without DR and short duration. Although DR progression to advanced stages is generally slow, higher HbA1c greatly accelerates it.

Low prevalence of diabetic retinopathy in patients with long-term type 1 diabetes and current good glycemic control - one-center retrospective assessment.

PURPOSE: Despite progress in type 1 diabetes (T1DM) therapy, diabetic retinopathy (DR) is still a common complication. We analysed predictors and prevalence of DR in patients with T1DM lasting 10 years or more. All of the patients were considered to be currently in excellent glycemic control and treated using modern therapies. METHODS: Study included 384 (80.7% women) T1DM patients participating in the Program of Comprehensive Outpatient Specialist Care at the University Hospital in Krakow between the years 2014 and 2020. A retrospective analysis of medical records was conducted. RESULTS: The patients were on average 34 ± 9.2 years old, had a BMI 25.0 ± 3.9 and a T1DM duration of 20.5 ± 7.9 years. The mean level of HbA1c throughout the follow-up (mean duration 4.9 ± 1.4 years) was 6.9 ± 1%. The group included 238 (62.0%) patients treated with insulin pumps and 99 (25.8%) on multiple daily injections, 47 (12.2%) used both methods; almost all patients were on insulin analogues. DR was confirmed in 150 (39.1%) patients, from which 109 (28.4%) were diagnosed de novo. Severe DR was occurred in just 31 cases (8.1%). In the multivariate logistic regression, independent risk factors for the presence of DR were T1DM duration (OR 1.13; 95% CI, 1.09-1.19), HbA1c level (OR 1.41; 95% CI, 1.08-1.84), LDL level (OR 1.79; 95% CI, 1.16-2.87), and the combined presence of non-DR micro- and macrovascular chronic complications (OR 1.86; 95% CI, 1.16-3.03). CONCLUSIONS: In this highly-selected group of T1DM patients, mostly female, the prevalence of both DR at any stage and severe DR was lower than earlier reported results from other cohorts. Independent risk factors for the DR cohort did not differ from previously reported studies.

Retinografia como forma de rastreio de retinopatia diabética em hospital terciário do Sistema Único de Saúde / Color retinography as a means of screening for diabetic retinopathy in the tertiary hospital of Unified Health System

RESUMO Objetivo Avaliar o impacto da triagem de retinopatia diabética de paciente diabéticos realizada com retinografia colorida. Métodos Estudo retrospectivo, de caráter descritivo, avaliando laudos de retinografias realizadas desde a implementação do protocolo da triagem de retinopatia diabética de paciente diabéticos acompanhados no Ambulatório de Endocrinologia de um hospital terciário do Sistema Único de Saúde, de maio de 2018 até maio de 2020. Resultados Realizaram retinografia 727 pacientes diabéticos, que tinham entre 14 e 91 anos, sendo a maioria com 60 anos ou mais (53,2%), do sexo feminino (68%) e brancos (87,6%). Não apresentavam retinopatia diabética 467 (64,2%) pacientes, 125 (17,2%) tinham retinopatia diabética não proliferativa, 37 (5,1%) retinopatia diabética não proliferativa grave e/ou suspeita de edema macular, 65 (8,9%) retinopatia diabética proliferativa, 21 (2,9%) suspeita de outras patologias, e as imagens de 12 (1,7%) pacientes eram insatisfatórias. Foram considerados de alto risco (aqueles com retinopatia diabética não proliferativa grave e/ou edema macular, retinopatia diabética proliferativa ou imagem insatisfatória) 114 (15,68%) pacientes. Conclusão O rastreio de retinopatia diabética com retinografia colorida possibilitou a detecção de pacientes diabéticos de alto risco que necessitavam atendimento com brevidade, permitindo o acesso deles à consulta oftalmológica e diminuindo a morbidade da doença relacionada ao tratamento tardio. Os demais foram encaminhados à Atenção Primária para regulamentação, por meio do Sistema de Regulação.

ABSTRACT Objective To evaluate the impact of diabetic retinopathy (DR) screening using color retinography in diabetic patients. Methods Retrospective descriptive study, evaluating reports of all retinographs performed since the implementation of the protocol for screening for diabetic retinopathy in diabetic patients followed up at the endocrinology outpatient clinic of a tertiary hospital of the Unified Health System, from May 2018 to May 2020. Results 727 diabetic with age range from 14 to 91 years old, the majority being 60 years old or older (53.2%), female (68%) and white (87.6%), patients underwent retinography. Of the patients, 467 (64.2%) did not have DR, 125 (17.2%) had non-proliferative DR, 37 (5.1%) had severe non-proliferative DR and/or suspected macular edema, 65 (8.9%) had proliferative DR, 21 (2.9%) had suspicion signs of other pathologies and 12 (1.7%) had unsatisfactory images. A total of 114 (15.68%) patients were considered at high risk (those with severe non-proliferative NP and/or EM, proliferative DR or poor image) and were referred for comprehensive ophthalmic evaluation. Conclusion The screening of RD with color retinography enabled the detection of high-risk diabetic patients who needed assistance sooner and enabled their access to ophthalmologic consultation, which decreased disease morbidity. The others were referred to primary care for regulation through the Regulation System (SISREG).

Pediatric Diabetic Retinopathy: Updates in Prevalence, Risk Factors, Screening, and Management.

PURPOSE OF REVIEW: Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus and a major cause of vision loss worldwide. The purpose of this review is to provide an update on the prevalence of diabetic retinopathy in youth, discuss risk factors, and review recent advances in diabetic retinopathy screening. RECENT FINDINGS: While DR has long been considered a microvascular complication, recent data suggests that retinal neurodegeneration may precede the vascular changes associated with DR. The prevalence of DR has decreased in type 1 diabetes (T1D) patients following the results of the Diabetes Control and Complications Trial and implementation of intensive insulin therapy, with prevalence ranging from 14-20% before the year 2000 to 3.7-6% after 2000. In contrast, the prevalence of diabetic retinopathy in pediatric type 2 diabetes (T2D) is higher, ranging from 9.1-50%. Risk factors for diabetic retinopathy are well established and include glycemic control, diabetes duration, hypertension, and hyperlipidemia, whereas diabetes technology use including insulin pumps and continuous glucose monitors has been shown to have protective effects. Screening for DR is recommended for youth with T1D once they are aged ≥ 11 years or puberty has started and diabetes duration of 3-5 years. Pediatric T2D patients are advised to undergo screening at or soon after diagnosis, and annually thereafter, due to the insidious nature of T2D. Recent advances in DR screening methods including point of care and artificial intelligence technology have increased access to DR screening, while being cost-saving to patients and cost-effective to healthcare systems. While the prevalence of diabetic retinopathy in youth with T1D has been declining over the last few decades, there has been a significant increase in the prevalence of DR in youth with T2D. Improving access to diabetic retinopathy screening using novel screening methods may help improve detection and early treatment of diabetic retinopathy.

Volume rendered 3D OCTA assessment of macular ischemia in patients with type 1 diabetes and without diabetic retinopathy.

The aim of this study was to measure macular perfusion in patients with type 1 diabetes and no signs of diabetic retinopathy (DR) using volume rendered three-dimensional (3D) optical coherence tomography angiography (OCTA). We collected data from 35 patients with diabetes and no DR who had OCTA obtained. An additional control group of 35 eyes from 35 healthy subjects was included for comparison. OCTA volume data were processed with a previously presented algorithm in order to obtain the 3D vascular volume and 3D perfusion density. In order to weigh the contribution of different plexuses' impairment to volume rendered vascular perfusion, OCTA en face images were binarized in order to obtain two-dimensional (2D) perfusion density metrics. Mean ± SD age was 27.2 ± 10.2 years [range 19-64 years] in the diabetic group and 31.0 ± 11.4 years [range 19-61 years] in the control group (p = 0.145). The 3D vascular volume was 0.27 ± 0.05 mm3 in the diabetic group and 0.29 ± 0.04 mm3 in the control group (p = 0.020). The 3D perfusion density was 9.3 ± 1.6% and 10.3 ± 1.6% in diabetic patients and controls, respectively (p = 0.005). Using a 2D visualization, the perfusion density was lower in diabetic patients, but only at the deep vascular complex (DVC) level (38.9 ± 3.7% in diabetes and 41.0 ± 3.1% in controls, p = 0.001), while no differences were detected at the superficial capillary plexus (SCP) level (34.4 ± 3.1% and 34.3 ± 3.8% in the diabetic and healthy subjects, respectively, p = 0.899). In conclusion, eyes without signs of DR of patients with diabetes have a reduced volume rendered macular perfusion compared to control healthy eyes.

Barriers to retinopathy screening in youth and young adults with type 1 diabetes.

Early detection of diabetic retinopathy (DR) is imperative; however, adherence to screening guidelines is poor. We hypothesized that youth and young adults with type 1 diabetes (T1D) who met American Diabetes Association criteria for recommended DR screening at the time of the study (10 years old or greater with diabetes duration of 5 years or more) would report multiple barriers to screening and that targeted barriers and subpopulations could be identified to improve access to care. 271 youth aged 10 to 26 years with T1D of at least 5 years duration were recruited from clinic, diabetes camp, and a diabetes conference and completed a patient-reported questionnaire. 113 (41.7%) reported at least one barrier to DR screening, with missed school and work being the most common (20.7%). Older participants (P = 0.007) and those with a longer diabetes duration (P = 0.018) were more likely to report barriers to screening. Recruitment location, sex, race and ethnicity, HbA1c, insulin regimen, and clinic visit frequency were not associated with reporting at least one barrier. Slightly less than two-thirds (62.1%) of participants who responded (n = 235 out of 271) adhered to recommended screening guidelines of the time and reported having an eye exam within the past year, 24.7% 12-23 months ago, 9.8% 2 years ago or more, and 3.4% had never had a DR exam. As older patients and those with longer duration of diabetes are more likely to have DR, targeted interventions to address barriers to care, such as, missed school and work should be implemented in these groups.

Assessment of a New Nanostructured Microemulsion System for Ocular Delivery of Sorafenib to Posterior Segment of the Eye.

Eye drop formulations allowing topical treatment of retinal pathologies have long been sought as alternatives to intravitreal administration. This study aimed to assess whether a novel nanostructured microemulsions system (NaMESys) could be usefully employed to deliver sorafenib to the retina following topical instillation. NaMESys carrying 0.3% sorafenib (NaMESys-SOR) proved to be cytocompatible in vitro on rabbit corneal cells, and well-tolerated following b.i.d. ocular administration to rabbits during a 3-month study. In rats subject to retinal ischemia-reperfusion, NaMESys-SOR significantly inhibited retinal expression of tumor necrosis factor-alpha (TNFα, 20.7%) and inducible nitric oxide synthase (iNos, 87.3%) mRNAs in comparison to controls. Similarly, in streptozotocin-induced diabetic rats, NaMESys-SOR inhibited retinal expression of nuclear factor kappa B (NFκB), TNFα, insulin like growth factor 1 (IGF1), IGF1 receptor (IGF1R), vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2) mRNAs by three-fold on average compared to controls. Furthermore, a reduction in TNFα, VEGFR1 and VEGFR2 protein expression was observed by western blot. Moreover, in mice subject to laser-induced choroidal neovascularization, NaMESys-SOR significantly inhibited neovascular lesions by 54%. In conclusion, NaMESys-SOR was shown to be a well-tolerated ophthalmic formulation able to deliver effective amounts of sorafenib to the retina, reducing proinflammatory and pro-angiogenic mediators in reliable models of proliferative retinopathies. These findings warrant further investigations on the full therapeutic potential of NaMESys-SOR eye drops, aiming to address unmet needs in the pharmacotherapy of retinal neovascular diseases.

Baseline Diabetes Knowledge Assessment Amongst Adults With Type 1 and Type 2 Diabetes Receiving Eye Care at a Tertiary Ophthalmic Centre in Canada.

OBJECTIVES: The aim of this work was to assess the current state of baseline knowledge of diabetes and diabetic retinopathy (DR) in new patients referred to a tertiary retina service from their primary eye care provider. METHODS: This single-centre, prospective, observational study included patients presenting to the retina clinic at the Hamilton Regional Eye Institute, a major tertiary referral centre, for their initial consultation for diabetes- or DR-associated complications. Upon recruitment into the study, patients were asked to complete a 35-item questionnaire regarding diabetes and associated complications. All data were coded and analyzed using statistical software. RESULTS: A total of 98 patients participated in the study, which included 50 men and 48 women. Seventy-eight patients (79.6%) were Caucasian. We found that 56.1% (n=55) of the patients did not know the meaning of "HbA1C" (glycated hemoglobin) and only 26.5% of patients sampled were aware of their DR status. Bivariate analysis revealed that patients who had postsecondary education (p<0.001) or those who had education on complications of diabetes (p<0.05) were more likely to know their DR status. More importantly, it was found that 56.1% of patients expressed interest in a future diabetes seminar. CONCLUSIONS: It is evident that a significant proportion of patients do not have adequate knowledge of diabetes or DR, and this is related to their level of education and lack of being taught about diabetes complications. Our findings may guide prevention initiatives by primary eye care providers and promote increased awareness about diabetes and DR for prevention of disease complications, including blindness.

Prevalência e fatores de risco para retinopatia diabética em pacientes diabéticos atendidos por demanda espontânea: um estudo transversal / Prevalence and risk factors of diabetic retinopathy in patients with diabetes seen by unscheduled demand: a cross-sectional study

RESUMO Objetivo: Estimar a prevalência da retinopatia diabética em pacientes diabéticos de uma capital brasileira e correlacioná-la com fatores de risco presentes na população estudada. Métodos: Estudo observacional transversal, realizado a partir do relatório de atendimentos prestados em mutirão ocorrido em 2018. O relatório foi preenchido pelos médicos oftalmologistas durante a campanha, com informações referentes a sexo do paciente, idade, classificação do diabetes mellitus, tempo de doença, uso de insulina, índice de massa corporal, hábitos de vida (tabagismo e atividade física) e história de hipertensão arterial sistêmica, dislipidemia, infarto agudo do miocárdio e acidente vascular cerebral, além de exame clínico oftalmológico realizado na ação. Resultados: Dentre os 219 participantes do estudo, a prevalência da retinopatia diabética foi de 31,96%. As variáveis que se apresentaram como fator de risco com significância estatística foram sexo masculino, idade de 51 a 70 anos, mais de 10 anos de diabetes mellitus, insulinoterapia, índice de massa corporal ≥40kg/m2 e história prévia de infarto agudo do miocárdio. Atividade física mostrou-se como fator protetor significativo. Conclusão: Estudos populacionais ao longo dos anos comprovaram a variabilidade geográfica na prevalência da retinopatia diabética justificada pela diferente exposição aos fatores de risco. Dentro de tal conjuntura, ressalta-se o quão fundamental é o conhecimento das características regionais, de modo a orientar as políticas de saúde pública, permitindo atuar com impacto na redução das estatísticas de cegueira evitável.

ABSTRACT Objective: To estimate the prevalence of diabetic retinopathy in patients with diabetes, from a Brazilian capital city, and to correlate with the risk factors present in the studied population. Methods: A cross-sectional observational study, based on the report of care provided by a campaign, in 2018. The report was filled out by ophthalmologists during the joint effort, with information on patient's gender, age, classification of diabetes mellitus, duration of illness, use of insulin, body mass index, lifestyle (smoking and physical activity), history of hypertension, dyslipidemia, myocardial infarction, stroke, and the clinical ophthalmic examination. Results: Among the 219 study participants, the prevalence of diabetic retinopathy was 31.96%. The variables considered risk factors with statistical significance were male sex, age 51-70 years, diabetes mellitus for over 10 years, insulin therapy, body mass index ≥40 kg/m2, and previous history of myocardial infarction. The physical activity proved to be a significant protective factor. Conclusion: Over the years, population studies have proven the geographical variability in prevalence of diabetic retinopathy justified by different exposure to risk factors. Therefore, knowledge of regional characteristics is crucial and emphasized in the text, since it can guide public health policies, aiming to have an impact on reduction of preventable blindness statistics.

Socioeconomic deprivation and development of diabetic retinopathy in patients with type 1 diabetes mellitus.

INTRODUCTION: Very little is known about the influence of socioeconomic status on type 1 diabetes mellitus (T1DM) complications. Our aim was to determine whether socioeconomic level is a risk factor for the development of diabetic retinopathy (DR) in patients with T1DM. RESEARCH DESIGN AND METHODS: A cohort of 150 patients with T1DM were studied prospectively over 9 years. Socioeconomic status was assessed using a neighborhood-level measure based on an index of deprivation. The contribution of other variables such as hypertension, dyslipidemia, diabetic nephropathy and smoking habit was evaluated. Cox proportional hazards models were used to quantify the associations. RESULTS: The incidence of DR was 21.6 cases per 1000 patient-years. Multivariable analyses showed that for each percentage point increase in glycated hemoglobin (HbA1c), the risk of developing DR increased by 58% (HR 1.58, 95% CI 1.19 to 2.10).Patients with T1DM onset >18 years of age and resident in areas of lower socioeconomic levels presented with almost triple the risk of developing DR (HR 2.95, 95% CI 1.08 to 8.00) compared with those with onset <18 years of age and resident in less deprived areas. We did not find significant relationships with other variables studied such as hypertension, dyslipidemia, diabetic nephropathy and smoking habit. CONCLUSIONS: Low socioeconomic level is a risk factor, independent of glycemic control, in the development of DR in patients with T1DM when the onset of diabetes is in adulthood. This finding indicates that socioeconomic status and age of onset need to be considered in population screening for DR in patients with T1DM.

Cost-effectiveness of Autonomous Point-of-Care Diabetic Retinopathy Screening for Pediatric Patients With Diabetes.

Importance: Screening for diabetic retinopathy is recommended for children with type 1 diabetes (T1D) and type 2 diabetes (T2D), yet screening rates remain low. Point-of-care diabetic retinopathy screening using autonomous artificial intelligence (AI) has become available, providing immediate results in the clinic setting, but the cost-effectiveness of this strategy compared with standard examination is unknown. Objective: To assess the cost-effectiveness of detecting and treating diabetic retinopathy and its sequelae among children with T1D and T2D using AI diabetic retinopathy screening vs standard screening by an eye care professional (ECP). Design, Setting, and Participants: In this economic evaluation, parameter estimates were obtained from the literature from 1994 to 2019 and assessed from March 2019 to January 2020. Parameters included out-of-pocket cost for autonomous AI screening, ophthalmology visits, and treating diabetic retinopathy; probability of undergoing standard retinal examination; relative odds of undergoing screening; and sensitivity, specificity, and diagnosability of the ECP screening examination and autonomous AI screening. Main Outcomes and Measures: Costs or savings to the patient based on mean patient payment for diabetic retinopathy screening examination and cost-effectiveness based on costs or savings associated with the number of true-positive results identified by diabetic retinopathy screening. Results: In this study, the expected true-positive proportions for standard ophthalmologic screening by an ECP were 0.006 for T1D and 0.01 for T2D, and the expected true-positive proportions for autonomous AI were 0.03 for T1D and 0.04 for T2D. The base case scenario of 20% adherence estimated that use of autonomous AI would result in a higher mean patient payment ($8.52 for T1D and $10.85 for T2D) than conventional ECP screening ($7.91 for T1D and $8.20 for T2D). However, autonomous AI screening was the preferred strategy when at least 23% of patients adhered to diabetic retinopathy screening. Conclusions and Relevance: These results suggest that point-of-care diabetic retinopathy screening using autonomous AI systems is effective and cost saving for children with diabetes and their caregivers at recommended adherence rates.

Diabetic eye screening with variable screening intervals based on individual risk factors is safe and effective in ophthalmic practice.

PURPOSE: To test in a 'real world' diabetic eye-screening programme, a computer-based personal risk evaluation for progression to sight-threatening diabetic retinopathy. Screening intervals were individualized, and clinical outcomes, safety and cost-effectiveness documented. METHODS: The RETINARISK algorithm was used in an ophthalmology clinic in Norway. The diabetes cohort was divided on voluntary basis into two groups: one with variable screening intervals based on their personal risk profile and the other group with conventional fixed interval diabetic eye screening. Compliance, clinical outcomes, safety and health economics were evaluated. A total of 843 diabetic patients participated in the program 2014-2019. A total of 63 had type 1 and 780 type 2 diabetes. A total of 671 patients had no diabetic retinopathy at baseline and 171 had retinopathy. RESULTS: A total of 444 (53%) diabetic patients were included in the personal risk profile program and 399 in the fixed interval group. The RETINARISK algorithm calculated 563 screening intervals for the variable interval group, which was 23 ± 16 months (mean ± SD), compared to 14 ± 5 months for the group with fixed screening intervals. Due to selection bias, the two groups could not be directly compared. We did not experience any delay in detecting diabetic retinal changes when using the personal risk profile program. CONCLUSION: The RETINARISK algorithm was safe and effective in a diabetic screening program in an ophthalmology clinic over 5 years. The use of the program reduces the mean frequency of screening visits and liberates valuable time in ophthalmic practice to be used on high-risk diabetic patients or other patient groups.

Assessment of diabetic retinopathy in type 1 diabetes in a diabetes care center in South India-Feasibility and awareness improvement study.

The prevalence of youth-onset diabetes, both type 1 diabetes (T1D) and young-onset type 2 diabetes (YT2D) are gradually increasing in India. Early and repetitive screening for diabetic retinopathy (DR) is essential to provide timely management, and thereby prevent visual impairment due to the silent sight-threatening microvascular complication of diabetes. A study was undertaken at a diabetes care center in Chennai, south India, to assess the feasibility of screening for DR in T1D in a diabetes clinic and determine the burden of sight-threatening DR (STDR) in individuals with T1D. 315 people with T1D were screened for DR (mean age at onset of diabetes 12.3 ± 6.4 years) by digital retinal color photography, at the urban diabetes center, in a semi-urban and rural diabetes clinic. Counseling about diabetes and the importance of annual screening for retinopathy was provided by diabetes educators. Participants were reviewed after 6 months/1 year based on ophthalmologist's advice. DR was detected in 37.1% (n = 117), 42 (13%) of whom had STDR.Three-quarter participants were compliant with the annual follow-up retinal examination. The peer support group was established for participants with T1D and their families to foster interactions with service providers. The peer group meetings helped to increase the awareness of retinopathy among the parents and individuals with T1D. This narrative provides details of the study that shows that screening for DR among individuals with T1D in a diabetes clinic is a feasible model, irrespective of its location.

Assessment of Circulating Biomarkers in Relation to Various Stages of Diabetic Retinopathy in Type 2 Diabetic Patients-A Cross Sectional Study.

AIM: The aim of this study is to examine the relationship between inflammatory markers, and diabetic retinopathy in type II diabetic patients. METHODS: The study was a cross-sectional study included 150 type 2 diabetic patients who were divided into 3 groups. 50 in each group are divided as Diabetic patients without retinopathy (DM, n=50), nonproliferative diabetic retinopathy patients (NPDR, n=50), proliferative diabetic retinopathy patients (PDR, n=50). All the patients were subjected to complete clinical examination and laboratory investigations, such as fasting and postprandial blood glucose, serum creatinine, lipid profile tests, glycosylated haemoglobin (HbA1c), fasting insulin, serum inflammatory markers (TNF-alpha, C-reactive protein) and serum VEGF. RESULTS: The study revealed from the multivariate analysis that age, duration and WHR (waist-hip ratio) are potent risk factors responsible for the risk of Diabetic retinopathy. Similarly, serum creatinine, CRP, TNF- alpha and VEGF are significantly higher in diabetic patients with retinopathy compared to diabetic patients without retinopathy. CONCLUSION: The study concluded that inflammation was associated with severe diabetic retinopathy in patients with well-controlled diabetes. A possible relationship was provided between the risk factors and biomarkers which are responsible for Diabetic retinopathy. Hence, modifying the risk factors risk and development of severe diabetic retinopathy can be reduced.

Dose-response analysis of ranibizumab as-needed regimens for visual improvement in patients with diabetic macular edema using a modelling approach.

BACKGROUND: Ranibizumab and aflibercept are anti-vascular endothelial growth factor therapies for diabetic macular edema (DME) but have only been directly compared in one study: the Protocol T study, a 24-month randomized controlled trial which compared the safety and efficacy of three anti-VEGF agents (ranibizumab 0.3 mg, aflibercept 2.0 mg and bevacizumab 1.25 mg). The ranibizumab dose used in Protocol T is not licensed for use outside of the US, where a higher ranibizumab dose of 0.5 mg is approved. Therefore, the relevance of the head-to-head Protocol T study findings to healthcare providers in Europe is limited. The purpose of this research was to predict the visual outcomes that may have been achieved in Protocol T with ranibizumab 0.5 mg. METHODS: A simplified dose-response model was constructed to describe the relationship between average monthly dose and one-year best corrected visual acuity (BCVA) change from baseline. A linear mixed effects model was evaluated and Bayesian Monte-Carlo Markov chains method was used to estimate the model parameters. RESULTS: If ranibizumab 0.5 mg PRN had been studied in Protocol T, it would have resulted in a BCVA gain of 14-15 early treatment diabetic retinopathy study (ETDRS) letters; 3-4 letters more than the actual BCVA gain reported with ranibizumab 0.3 mg PRN. In Protocol T patients with poor baseline BCVA (<69 letters), a similar additional letter gain would have been achieved. CONCLUSION: The relevance of the Protocol T study findings are limited due to the use of ranibizumab 0.3 mg PRN which, based on the modelling approach reported herein, resulted in sub-optimal visual gains.

Visual acuity assessment in diabetes.

Optometric or visual acuity assessment is an essential part of ophthalmologic examination. Visual acuity measurement serves as a tool for screening of ophthalmic disorders, as well as diagnosis and monitoring of refractive errors and other causes of reduced acuity. Persons with diabetes may experience situations which impair visual acuity, or which impact the utility of refractive visual acuity assessment. This communication shares guidance as to when and when not to perform visual acuity charting in persons with diabetes.