Prevention Of Diabetic Retinopathy Research Articles

Periodontal Disease May be Associated With the Occurrence of Diabetic Retinopathy: A Subgroup Analysis of The Survey of the Diabetes Coordination Notebook in Gifu.

A questionnaire survey of the prevalence of diabetic retinopathy was recently conducted in Japan. A subgroup analysis to examine the association of periodontal disease with diabetic retinopathy in subjects with diabetes and prediabetes was conducted. The association of the presence of periodontal disease with the occurrence of diabetic retinopathy was examined using multivariate logistic regression analysis. Of 27 016 subjects who completed a survey at 217 community pharmacies, 5 572 had diabetes or prediabetes, among whom 522 and 1 421 had retinopathy or periodontal disease, respectively. Therapy duration≥10 years (OR: 2.73, 95% CI: 2.17-3.43, P<0.001), periodontal disease (OR: 2.10, 95% CI: 1.68-2.62, P<0.001) and glycated hemoglobin (HbA1c) ≥ 7.0% (OR: 1.64, 95% CI: 1.32-2.04, P<0.001) were significantly associated with the occurrence of retinopathy, while retinopathy (OR: 2.11, 95% CI: 1.: 69-2.63, P<0.001) and therapy duration ≥10 years (OR: 1.24, 95% CI: 1.06-1.46, P=0.007) were significantly associated with the occurrence of periodontal disease. The prevalence of retinopathy was much higher in diabetic subjects with periodontal disease than in those without it (15.1% vs. 7.8%, P<0.001). Notably, the difference of prevalence of retinopathy between subjects with and without periodontal disease was statistically significant even at HbA1c 6.0-6.9% (15.2% vs. 7.3%, P<0.01). These findings indicate that the target HbA1c level for diabetes patients with periodontal disease may be set lower than for those without it, and that regular dental visits should be prescribed for the management of periodontal disease and the prevention of diabetic retinopathy.

Physical activity and risk of diabetic retinopathy: a systematic review and meta-analysis

Diabetic retinopathy (DR) is an important microvascular complication of diabetes mellitus (DM) and a leading cause of visual impairment and blindness among people of working age. Physical activity (PA) or exercise is critical and beneficial for DM patients, whereas studies evaluating the relationship between PA and DR have yielded inconsistent and inconclusive results. The American Diabetes Association's "Standards of Medical Care in Diabetes" has also pointed out the indeterminate roles of PA in DR prevention. The purpose of this systematic review and meta-analysis was to explore the association between PA and DR risk. Medline (accessed by PubMed), EmBase, and Cochrane Library were systematically searched for studies up to June 2018, and the reference lists of the published articles were searched manually. The association between PA and DR risk was assessed using random-effect meta-analysis. Twenty-two studies were included in this meta-analysis. PA was found to have a protective association with DR [risk ratio (RR) = 0.94, 95% confidence interval (95% CI) 0.90-0.98, p = 0.005] in diabetic patients, and the impact was more pronounced on vision-threatening DR (RR = 0.89, 95% CI 0.80-0.98, p = 0.02). Sedentary behavior could increase the risk of DR (RR = 1.18, 95% CI 1.01-1.37, p = 0.04). Moderate-intensity PA was likely to have a slight protective effect (RR = 0.76, 95% CI 0.58-1.00, p = 0.05). PA is associated with lower DR risk, and more studies should focus on the causality between them.

Global prevalence of diabetic retinopathy: protocol for a systematic review and meta-analysis

IntroductionWith increasing diabetes trends worldwide, morbidity, mortality and associated costs due to diabetes-related complications are a global public health concern. Diabetic retinopathy (DR) is among the leading causes of vision...

Diabetic Retinopathy as a Risk Factor for Chronic Kidney Disease Progression: A Multicenter Case⁻Control Study in Taiwan.

It has rarely been studied whether the presence and severity of diabetic retinopathy (DR) could influence the renal disease progression among all chronic kidney disease (CKD) diabetic patients. This study investigates the characteristics of diabetic patients, with different stages of chronic kidney disease (CKD), according to the occurrence of diabetic retinopathy and determines the influence of retinopathy in the deterioration of renal function. We conduct a multicenter, longitudinal cohort study based on the Epidemiology and Risk Factors Surveillance of the CKD project (2008–2013) and the National Health Insurance Research Database (NHIRD) (2001–2013). A total of 4050 diabetic patients with CKD, 20–85 years of age, from 14 hospitals and the community are included in this study. As compared to CKD patients without DR, CKD patients with DR have a lower baseline estimated glomerular filtration rate (eGFR) (39.17 ± 30.36 mL/min per 1.73 m2 vs. 54.38 ± 33.67 mL/min per 1.73 m2 ); poorer glycemic control (higher glycated hemoglobin (HbA1c) 7.85 ± 4.97 vs. 7.29 ± 4.02, p < 0.01); higher proteinuria (urine protein-to-creatinine ratio (UPCR )1.94 ± 2.96 g/dL vs. 0.91 ± 2.11 g/dL, p < 0.01); more anemia (Hb 11.22 ± 2.43 g/dL vs. 12.39 ± 3.85 g/dL, p < 0.01), and more hypoalbuminemia (3.88 ± 0.95 g/dL vs. 4.16 ± 1.74 g/dL, p < 0.01). Later stage (stage 3b–5) CKD patients with DR had significantly higher CKD progression compared with patients without DR (OR (odds ratio) 1.66 (1.36–2.02)). Patients with proliferative DR had significantly higher CKD progression events compared to patients with non-proliferative DR (OR 2.18 (1.71–2.78)). The presence and severity of DR is a risk factor for CKD progression among our Taiwanese CKD patients with diabetes. Prevention and early detection of DR are important and DR should be routinely screened as early as possible among diabetic CKD patients.

Associations of renal function with diabetic retinopathy and visual impairment in type 2 diabetes: A multicenter nationwide cross-sectional study.

BACKGROUNDDiabetic retinopathy (DR) separately has been noted as a major public health problem worldwide as well. Currently, many studies have demonstrated an association between diabetic nephropathy and DR in type 1 diabetes mellitus (T1DM) patients, but this association is less strong in T2DM. The evidence for an association between renal function and DR and visual impairment among T2DM patients is limited, particularly in the Asian population.AIMTo assess the association between glomerular filtration rate (GFR) and DR, severe DR, and severe visual impairment among T2DM patients in Thailand.METHODSWe conducted a nationwide cross-sectional study based on the DM/HT study of the Medical Research Network of the Consortium of Thai Medical Schools. This study evaluated adult T2DM patients from 831 public hospitals in Thailand in the year 2013. GFR was categorized into ≥ 90, 60-89, 30-59 and < 30 mL/min/1.73 m2. The association between GFR and DR, severe DR, and severe visual impairment were assessed using multivariate logistic regression.RESULTSA total of 13192 T2DM patients with available GFR were included in the analysis. The mean GFR was 66.9 ± 25.8 mL/min/1.73 m2. The prevalence of DR, proliferative DR, diabetic macular edema, and severe visual impairment were 12.4%, 1.8%, 0.2%, and 2.1%, respectively. Patients with GFR of 60-89, 30-59 and < 30 mL/min/1.73 m2 were significantly associated with increased DR and severe DR when compared with patients with GFR of ≥ 90 mL/min/1.73 m2. In addition, increased severe visual impairment was associated with GFR 30-59 and < 30 mL/min/1.73 m2.CONCLUSIONDecreased GFR was independently associated with increased DR, severe DR, and severe visual impairment. GFR should be monitored in diabetic patients for DR awareness and prevention.

Carnosine improves diabetic retinopathy via the MAPK/ERK pathway.

Diabetic retinopathy (DR) is one of the most common causes of blindness in developed countries. Due to its asymptomatic onset and progressive disease course, DR is typically diagnosed at a late stage when treatment options are limited and therefore often results in irreversible blindness. Studies have demonstrated that carnosine may prevent and treat DR. In a previous study, the positive effect of carnosine on DR was determined and it was revealed that there may be an association between carnosine and the mitogen-activated protein kinase (MAPK)/extracellular signal related kinase (ERK) signaling pathway. To assess the interaction between carnosine and the MAPK/ERK signaling pathway, changes in PKC, ERK and p-ERK expression was assessed in diabetic rats following treatment with carnosine, PD98059 or U46619 via reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that the expression of ERK and p-ERK were significantly suppressed following treatment with carnosine, but no significant effect on the expression of PKC was identified, which indicates that suppressing the activation of the MAPK/ERK signaling pathway may serve an important role in carnosine-induced DR prevention and treatment.

A Study to Assess the Effectiveness of Planned Teaching Program on Knowledge regarding Prevention of Diabetic Retinopathy

Background: Diabetes Mellitus is chronic systematic disease characterized by either deficiency of insulin or decease ability of the body to use insulin. Diabetes Mellitus is sometimes referred as “High sugar” by both clients and health care provider. Aims and Objective: To assess the knowledge regarding Prevention of diabetic Retinopathy among the diabetic mellitus patients, To assess the effectiveness of Planned Teaching Program on knowledge regarding prevention of diabetic retinopathy among the diabetes mellitus patients, To find the association of the knowledge with their selected demographic variables. Methods-a quantitative approach using pre experimental one group pre test-post test design. 60 patients were selected using non probability convenience sampling in various hospital. Planned teaching programme was given. Self structure questionnaire will prepare and used to assess the knowledge. Results In this study overall the highest percentage in the demographic data including the Age group 31.66% (61-65y), Gender 95% (Male), marital status 83.33% (married), types of family 75% (joint), Education status 55% (other), occupation 43.66% (other) monthly income 53.33% (above 15000), types of diet (66.66%) vegetarian, and since how long you are diabetic 75% (less than 4 year)and family history of diabetic mellitus (83.33%) YES. During Pre-test, only 18 (30%) of workers had Poor level (0–10 score) of knowledge on prevention of diabetic retinopathy, 42 (70%) of patients had average (11–20 score) level of knowledge on prevention of diabetic retinopathy and no one had good knowledge (21–30) on prevention of diabetic retinopathy. During Post-test, No one of workers had Poor level (0–10 score) of knowledge on prevention of diabetic retinopathy.35(58.33%) of patients had average (11–20 score) level of knowledge on prevention of diabetic retinopathy and 25(41.66%) had good knowledge (21–30) on prevention of diabetic retinopathy. During pre-test, the mean score of level of knowledge was 10.33and the standard deviation was 1.9096. During post-test, the mean score of level of knowledge was 16.9and the standard deviation was 1.6492. The obtained‘t’ value for level of knowledge was20.27which is significant at p<0.05 level. Thus, it rejects the null hypothesis (H01) and accepts the research hypothesis (H1).

Prostaglandin E2/EP2 receptor signalling pathway promotes diabetic retinopathy in a rat model of diabetes.

Diabetic retinopathy is a common microvascular complication of diabetes mellitus and is initiated by inflammation and apoptosis-associated retinal endothelial cell damage. Prostaglandin E2 (PGE2) has emerged as a critical regulator of these biological processes. We hypothesised that modulating PGE2 and its E-prostanoid receptor (EP2R) would prevent diabetes mellitus-induced inflammation and microvascular dysfunction. In a streptozotocin (STZ)-induced rat model of diabetes, rats received intravitreal injection of PGE2, butaprost (a PGE2/EP2R agonist) or AH6809 (an EP2R antagonist). Retinal histology, optical coherence tomography, ultrastructure of the retinal vascular and biochemical markers were assessed. Intravitreal injection of PGE2 and butaprost significantly accelerated retinal vascular leakage, leucostasis and endothelial cell apoptosis in STZ-induced diabetic rats. This response was ameliorated in diabetic rats pre-treated with AH6809. In addition, pre-treatment of human retinal microvascular endothelial cells with AH6809 attenuated PGE2- and butaprost-induced activation of caspase 1, activation of the complex containing nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like protein containing a C-terminal caspase-activation and recruitment domain (ASC), and activation of the EP2R-coupled cAMP/protein kinase A/cAMP response element-binding protein signalling pathway. The PGE2/EP2R signalling pathway is involved in STZ-induced diabetic retinopathy and could be considered as a potential target for diabetic retinopathy prevention and treatment.

Intermittent Fasting and Prevention of Diabetic Retinopathy: Where Do We Go From Here?

Type 2 diabetes represents one of the most significant global health threats of the 21st century owing to its constantly increasing prevalence and long-term debilitating complications (1). In addition to accelerated macrovascular disease in poorly controlled diabetes that is responsible for increased cardiovascular morbidity and mortality, microvascular complications, such as diabetic nephropathy, neuropathy, and retinopathy, cause a significant burden and may markedly impair not only life expectancy but also quality of life of patients with diabetes (2). Diabetic retinopathy is the most common cause of blindness in developed countries and one of the most feared diabetes complications (3). Significant progress has been made in our understanding of the etiopathogenesis of type 2 diabetes with numerous novel contributing mechanisms identified in the past couple of years (4). Both experimental and clinical studies have demonstrated that gut represents a vital organ with respect to regulation of glucose metabolism and modulation of the risk of type 2 diabetes development (5). Multiple facets of the gut–glucose metabolism interconnection have been uncovered in particular by studying the changes induced by weight loss associated with bariatric surgery or endoscopic methods mimicking bariatric surgery. The possible mechanisms of gut-driven improvements in glucose metabolism after surgical or endoscopic interventions include restriction of food amount, enhanced passage of chymus into distal parts of small …

Loss of Angiotensin-Converting Enzyme 2 Exacerbates Diabetic Retinopathy by Promoting Bone Marrow Dysfunction.

Angiotensin-converting enzyme 2 (ACE2) is the primary enzyme of the vasoprotective axis of the renin angiotensin system (RAS). We tested the hypothesis that loss of ACE2 would exacerbate diabetic retinopathy by promoting bone marrow dysfunction. ACE2-/y were crossed with Akita mice, a model of type 1 diabetes. When comparing the bone marrow of the ACE2-/y -Akita mice to that of Akita mice, we observed a reduction of both short-term and long-term repopulating hematopoietic stem cells, a shift of hematopoiesis toward myelopoiesis, and an impairment of lineage- c-kit+ hematopoietic stem/progenitor cell (HS/PC) migration and proliferation. Migratory and proliferative dysfunction of these cells was corrected by exposure to angiotensin-1-7 (Ang-1-7), the protective peptide generated by ACE2. Over the duration of diabetes examined, ACE2 deficiency led to progressive reduction in electrical responses assessed by electroretinography and to increases in neural infarcts observed by fundus photography. Compared with Akita mice, ACE2-/y -Akita at 9-months of diabetes showed an increased number of acellular capillaries indicative of more severe diabetic retinopathy. In diabetic and control human subjects, CD34+ cells, a key bone marrow HS/PC population, were assessed for changes in mRNA levels for MAS, the receptor for Ang-1-7. Levels were highest in CD34+ cells from diabetics without retinopathy. Higher serum Ang-1-7 levels predicted protection from development of retinopathy in diabetics. Treatment with Ang-1-7 or alamandine restored the impaired migration function of CD34+ cells from subjects with retinopathy. These data support that activation of the protective RAS within HS/PCs may represents a therapeutic strategy for prevention of diabetic retinopathy. Stem Cells 2018;36:1430-1440.

Entering New Golden Era in the Management and the Prevention of Diabetic Retinopathy

Diabetes mellitus is one of the first diseases defined, with the oldest known description being an Egyptian manuscript from 1500 BCE [1]. Throughout history, different terms and tests were used to describe this disease; often referring to the sweet taste it gives urine.

An Overview of Dietary Approaches to Prevent the Development of Diabetic Retinopathy

Various researchers suggest that in up to 50% of patients with type 1 diabetes and 30% of those with type II diabetes, potentially vision-threatening retinal changes develop over time. Diabetic retinopathy is a common micro-vascular complication of diabetes mellitus. The present review outlines the dietary strategies to manage these complications of diabetes mellitus and studies the relationship between diet and retinopathy-associated risk factors in the development and progression of diabetic retinopathy. Though retinopathy therapy is currently limited to invasive procedures like laser photocoagulation and vitrectomy but there is a paradigm shift in favor of a preventive and protective, natural and safe dietary approach which can be used in treatment or prevention of diabetic retinopathy. Dietary carbohydrates, fats, proteins, dietary fibers, vitamins, antioxidants, minerals, phyto-estrogens, exogenous advanced glycation end-products, herbs, spices and protective dietary approaches play a role in development of diabetic retinopathy. This rationale can be applied to food interventions e.g. changing the composition of diet which favors metabolic improvements in type II diabetes and diabetic retinopathy. The ophthalmologists should encourage an interdisciplinary approach with endocrinologists and dietitian for optimal care of diabetic patient so as to prevent the development of diabetic retinopathy.

Progress in Experimental and Clinical Research of the Diabetic Retinopathy Treatment Using Traditional Chinese Medicine.

Diabetic retinopathy (DR), one of the most common microvascular complications of diabetic mellitus, is currently the main cause of adult-acquired blindness. The pathogenesis of DR is complex and the current clinical application of various treatment methods cannot completely prevent the development of this disease. Many reports have been published regarding the treatment of DR with Traditional Chinese Medicine (TCM), which has received increasing attention from medical practitioners worldwide. Studies published between 1994 and April 2017 were collected from the CNKI, VIP, Medline and Web of Science databases, as well as from Chinese traditional books and Chinese Pharmacopoeia, subsequently obtaining more than 550 studies. Thereafter, the status quo of DR treatment using TCM had been summarized according to four aspects- compound formula therapy, Chinese herbal medicine extracts and monomer therapy, integrated traditional Chinese and Western medicine therapy, and Chinese medicine external treatment. According to the literature reviewed herein, TCM has had definite effects on the prevention and treatment of DR, especially when used in combination with modern medical methods. However, the lack of a unified standard on the syndrome differentiation of DR and the lack of support of evidence-based medicine theory in clinical practice have been consistent concerns in previous research studies and needs to be addressed in subsequent studies.

Strategies to Improve Prevention and Management in Diabetic Retinopathy: Qualitative Insights from a Mixed-Methods Study.

Nonproliferative and proliferative diabetic retinopathy (DR) are common, progressive complications of diabetes with a rising incidence. Over time, patients with nonproliferative DR may progress to more advanced stages of DR, with an increased risk of vision-threatening conditions such as diabetic macular edema (DME). DME is the most frequent cause of vision loss in patients with diabetes and eventually can lead to blindness. Early-stage DR is asymptomatic; therefore, a coordinated management strategy is crucial to prevent or limit the progression of DR. Such a strategy includes regular screening for DR risk factors, glycemic control, and prompt diagnosis of DR. Preventive care should include a comprehensive dilated eye exam, ancillary tests, and patient education involving a multidisciplinary team composed of ophthalmologists, retina specialists, and primary diabetes care providers, including primary care providers and endocrinologists/diabetologists. However, although guideline recommendations for regular screening and patient education are well disseminated, many people with diabetes are not receiving ophthalmological care that could prevent visual impairment and blindness. We designed a mixed-methods study to explore the impact of patient-focused education on patient knowledge and self-efficacy in relation to DR prevention and management and to assess how online education can help to change patient knowledge, competence, and practice. Analysis of in-depth, qualitative data involving people with diabetes with or without DR collected 5–16 weeks after education participation shows that online patient education is an effective tool in building patient knowledge and awareness about DR and in motivating action in DR self-care.

Cost-Effectiveness of Community Pharmacists' Intervention For Patients With Type 2 Diabetes In Prevention of Diabetic Retinopathy

Cost-Effectiveness of Community Pharmacists' Intervention For Patients With Type 2 Diabetes In Prevention of Diabetic Retinopathy

Omega-3 fatty acids in prevention of diabetic retinopathy.

To review the competence of Omega-3 fatty acids in restricting the progression, thereby leading to prevention of diabetic retinopathy. Owing to their anti-inflammatory and anti-angiogenic properties, Omega-3 fatty acids alleviate major aetiological agents. These fatty acids are renowned for their beneficial effects in various cardiovascular and other disorders; however, their potential to prevent the progression of diabetic retinopathy remains least explored. Utilizing this potential, we may develop effective prophylactic agents which markedly inhibit the advent of retinal angiogenesis and prevent the apoptosis of retinal endothelial and neuronal cells, thereby averting retinal degeneration, hence safeguarding diabetic patients from this sight-threatening complication.

The Hippo signaling pathway: a potential therapeutic target is reversed by a Chinese patent drug in rats with diabetic retinopathy

BackgroundThe Hippo signaling pathway is reported to be involved in angiogenesis, but the roles of the Hippo pathway in diabetic retinopathy have not been addressed. Fufang Xueshuantong Capsule has been used to treat diabetic retinopathy in China; however, the effect of Fufang Xueshuantong Capsule on the Hippo pathway has not been investigated.MethodsIn this study, diabetes was induced in Sprague-Dawley rats with intraperitoneal injection of streptozotocin. Twenty weeks later, Fufang Xueshuantong Capsule was administered for 12 weeks. When the administration ended, the eyes were isolated for western blot and immunohistochemistry analyses. The levels of P- mammalian sterile 20-like (MST), large tumor suppressor homolog (Lats), P- yes-associated protein (YAP), transcriptional co-activator with PDZ binding motif (TAZ) and TEA domain family members (TEAD) were measured.ResultsDiabetic rats had a decreased P-MST level in the inner plexiform layer and reduced expression of P-YAP in the photoreceptor layers of their eyes. In addition, diabetic rats displayed remarkable increases in Lats, TAZ and TEAD in their retinas. Furthermore, Fufang Xueshuantong Capsule restored the changes in the Hippo pathway.ConclusionsThe Hippo signaling pathway is important for the progression of diabetic retinopathy and will hopefully be a targeted therapeutic approach for the prevention of diabetic retinopathy.

Imbalance between pro-apoptotic and pro-survival factors in human retinal pericytes in diabetic-like conditions.

Loss of pericytes is one the key events in the pathogenesis of diabetic retinopathy. We have previously demonstrated that human retinal pericytes (HRP) are more vulnerable to intermittent than stable high glucose concentrations, with an increase in apoptosis. Our aim was to explore the expression of molecules involved in pro-apoptotic and survival pathways in pericytes cultured in stable/intermittent high glucose and/or hypoxia, to clarify the mechanisms of action of these diabetic-like stressing stimuli. Human retinal pericytes (HRP) were exposed intermittently at 48-hr intervals to high/physiological glucose for 8days (intHG) and/or hypoxia over the last 48hr. Control cells were kept in stable physiological and high glucose. Cell proliferation and apoptosis were assessed. The expression of pro-apoptotic and pro-survival molecules was evaluated by Western blotting. Caspase-8 translocation from the cytoplasm into the nucleus was checked by Western blotting of nuclear versus cytoplasmic fractions and immunofluorescence. Hypoxia, alone and combined with intHG, increased HRP apoptosis and decreased proliferation. Pro-apoptotic molecules increased in HRP cultured in these conditions, while some survival markers decreased. Conversely, in stable HG, pro-apoptotic molecules were stable or even decreased, and survival factors increased. Translocation of caspase-8 from cytoplasm into nucleus indicates a primary role for this molecule in inducing apoptosis. Diabetic-like conditions are able to stimulate pericyte apoptosis through activation of pro-apoptotic molecules, leading to an imbalance between pro-apoptotic and survival signalling pathways, with caspase-8 playing a pivotal role. Our identification of such intermediates could help finding new therapeutic approaches for the prevention of diabetic retinopathy.

AB001. Vision impairment &amp; repairment in diabetes

: With the development of global industrialization, urbanization and changes of people’s lifestyle, Diabetes Mellitus, DM has become a serious worldwide health issue. The prevalence of diabetes in China is more than 10%. Due to the huge population base, China has surpassed the U.S. and India, becoming the country with the largest diabetic population in the world. Diabetic retinopathy (DR) is one of the most common complications of DM. The latest epidemiological survey shows that 17.8–29.2% of China’s diabetes patients developed DR, and it has become the leading cause of blindness in adults over the age of 40. Despite the continued emergence of new medicine and treatment in the past ten years, and a large number of global clinical trials have been carried out, we still couldn’t prevent the occurrence and development of DR. Microvascular damage caused by DM has been a top priority in the prevention and treatment of diabetic complications. Chinese government attaches great importance to the prevention and treatment of DR and has included it into China’s plan of the prevention and treatment of blindness. In this presentation, I’m going to focus on the pathogenesis of DR, especially the relationship between immune inflammatory response and DR. Major challenges and solutions in clinical treatment were discussed as well.

Abstract # PO-3: Diabetic Retinopathy Screening: An Example of How Primary Healthcare Can Truly Make A Difference in Diabetic Retinopathy Prevention

Abstract # PO-3: Diabetic Retinopathy Screening: An Example of How Primary Healthcare Can Truly Make A Difference in Diabetic Retinopathy Prevention