tRNAleu A3243G Gene Mutation of Mitochondrial DNA as a Risk Factor for Diabetic Retinopathy in Type 2 Diabetes Mellitus in Bali

Introduction: Diabetic retinopathy is one of the chronic complications in patients with diabetes mellitus caused by progressive microangiopathy. Various types of risk factors can affect the occurrence of diabetic retinopathy, one of which is mitochondrial DNA mutations in the tRNAleu A3243G gene that is common in T2DM. This study was conducted with the aim to identify whether the mutation of the tRNAleu A3243G gene acts as a risk factor for diabetic retinopathy in T2DM patients in Bali. Material and Methods: This study used a case control design with 35 T2DM patients with diabetic retinopathy and 35 T2DM patients without diabetic retinopathy. The techniques used to identify these mutations are PCR and DNA sequencing. Results: Based on the results obtained, no mutations were found in the tRNAleu A3243G gene in the entire sample. Therefore, the relationship analysis of the two variables cannot be identified. Conclusions: Mutations of the tRNAleu A3243G gene that were not successfully identified in this study can be concluded not play a role as a risk factor for diabetic retinopathy. Keywords: Diabetic Retinopathy, Diabetes Mellitus, tRNAleu Gene Mutation, Mitochondrial DNA.

Diabetic Retinopathy Detection System

Diabetic Retinopathy is a diabetes problem that affects the eye. Injury to the blood vessels of the light sensitive tissue inside the rear of the eye (retina) is that the most reason for diabetic retinopathy. To begin with, Diabetic Retinopathy may have no symptoms or just cause minor vision problems. It has the potential to lead to blindness. Machine learning approaches can be used for the early detection of Diabetic Retinopathy. This paper proposes an automated Diabetic Retinopathy detection system that can detect the presence of Diabetic Retinopathy from retinal images. This work uses ResNet50 for the detection and classification of Diabetic Retinopathy. ResNet50 is a type of neural network used as a backbone for many computer-vision tasks. This paper proposes a machine learning model which is developed using ResNet50, then the model will be deployed as a user-friendly web application where the user can upload the retinal images as input to the system then system will detect the presence of Diabetic Retinopathy and classifies it into the stage or class which the particular image belongs to. Keywords: Diabetic Retinopathy, ResNet50, Proliferative diabetic retinopathy, non-proliferative diabetic retinopathy.

Intravitreal Anti-Vascular Endothelial Growth Factor Agents for the Treatment of Diabetic Retinopathy: A Review of the Literature

Background: Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population. The purpose of this review is to gather the existing literature regarding the use of the approved anti-vascular endothelial growth (anti-VEGF) agents in the treatment of DR. Methods: A comprehensive literature review in PubMed engine search was performed for articles written in English language up to 1 July 2021, using the keywords “diabetic retinopathy”, “ranibizumab”, “aflibercept”, and “anti-VEGF”. Emphasis was given on pivotal trials and recent robust studies. Results: Intravitreal anti-VEGF agents have been found to significantly improve visual acuity and reduce retinal thickness in patients with diabetic macular edema (DME) in a long-term follow-up ranging from 1 to 5 years and are considered the standard-of-care in such patients. Regarding DR, intravitreal anti-VEGF agents provided ≥2-step improvement in DR severity on color fundus photography in about 30–35% of patients with NPDR at baseline, in the majority of clinical trials originally designed to evaluate the efficacy of intravitreal anti-VEGF agents in patients with DME. Protocol S and CLARITY study have firstly reported that intravitreal anti-VEGF agents are non-inferior to panretinal photocoagulation (PRP) in patients with proliferative DR (PDR). However, the use of new imaging modalities, such as optical coherence tomography-angiography and wide-field fluorescein angiography, reveals conflicting results about the impact of anti-VEGF agents on the regression of retinal non-perfusion in patients with DR. Furthermore, one should consider the high “loss to follow-up” rate and its devastating consequences especially in patients with PDR, when deciding to treat the latter with intravitreal anti-VEGF agents alone compared to PRP. In patients with PDR, combination of treatment of intravitreal anti-VEGF agents and PRP has been also supported. Moreover, in the specific case of vitreous hemorrhage or tractional retinal detachment as complications of PDR, intravitreal anti-VEGF agents have been found to be beneficial as an adjunct to pars plana vitrectomy (PPV), most commonly given 3–7 days before PPV, offering reduction in the recurrence of vitreous hemorrhage. Conclusions: There is no general consensus regarding the use of intravitreal anti-VEGF agents in patients with DR. Although anti-VEGF agents are the gold standard in the treatment of DME and seem to improve DR severity, challenges in their use exist and should be taken into account in the decision of treatment, based on an individualized approach.

Study of Clinical Correlation between Diabetic Retinopathy and Diabetic Nephropathy - A Cross-Sectional Observational Study in Eastern India

BACKGROUND In diabetes mellitus microvascular damages at various end-organ frequently occurs and leads to development of diabetic nephropathy as well as diabetic retinopathy. Diabetic nephropathy ultimately causes end stage renal disease. Diabetic retinopathy even at its earlier stage is easily suspected by simple clinical examination in any ophthalmological clinic. We wanted to study the relationship between various stages of diabetic retinopathy with diabetic nephropathy. METHODS 1209 diagnosed patients of diabetic mellitus were screened for presence of diabetic retinopathy. First comprehensive ophthalmological examination including slit-lamp bimicroscopy and indirect ophthalmoscopy were done and then clinically typing of diabetic retinopathy according to ETDRS classification was done. Then all diagnosed case of diabetic retinopathy further examined for blood Glycosylated haemoglobin, blood urea and serum creatinine to detect diabetic nephropathy. RESULTS 273 patients were included in this study. Average age of patients was 64.6 years with mean duration of diabetes mellitus was 7.4 years. Patients suffering from severe NPDR and PDR had association with poor control of blood glycosylated haemoglobin. Patients with mild NPDR 31.1 %, Moderate NPDR 52.3 %, severe NPDR 67.4 % and in PDR 65.2 % patient had blood urea more than 40 mg / dl. In mild NPDR group 32.2 %, moderate NPDR 55.4 %, severe NPDR 67.4 % and in PDR group 63.9 % patients had serum creatinine more than 1.5 mg / dl. We have found statistically significant correlation between HbA1c level and severity of diabetic retinopathy. Prevalence of nephropathy increased with increments in the grade of retinopathy. CONCLUSIONS A significant number of patients with severe NPDR or PDR had increased blood urea and serum creatinine level. Clinical grading of diabetic retinopathy gives us a clue about the presence of diabetic nephropathy. As diagnosis of diabetic retinopathy is simple and straight forward clinical procedure and it can be done all ophthalmological se up, we recommend all patient with diabetic retinopathy must be screened for nephropathy. KEYWORDS Diabetic Retinopathy, Diabetic Nephropathy, Glycosylated Haemoglobin, Blood Urea, Serum Creatinine

PREVALENCE, PATHOGENESIS, CLASSIFICATION, IMAGING, SCREENING AND MANAGE-MENT OF DIABETIC RETINOPATHY- A CRITICAL REVIEW

Diabetic retinopathy is that the leading reason for sightlessness among people between twenty-five and seventyfour years older within the industrialised world. Diabetes mellitus (DM) includes a heterogeneous cluster of disorders of carbohydrate, protein, and metastasis manifesting hyperglycemia. Diabetic retinopathy could be microangiopathy ensuing from the chronic effects of the disease, and shares similarities with the microvascular alterations that occur in different tissues at risk of DM equivalent to the kidneys and also the peripheral nerves. Diabetic retinopathy is assessed into nonproliferative and proliferative stages. Nonproliferative diabetic retinopathy (NPDR) involves progressive intraretinal microvascular alterations that may result in, and a lot of advanced proliferative stages outlined by extraretinal neovascularization. Imaging modalities in common clinical use for the management of NPDR and DME embrace structure photography, fluorescein angiography (FA), and optical coherence tomography (OCT). The suggested schedule for screening and surveillance for NPDR reflects data concerning the epidemiology and natural history of the disease. Diabetic retinopathy could be a leading explanationfor vision loss in working-age Americans and a major cause of sightlessness worldwide. The International Diabetes Federation estimates that as several as 592 million individuals worldwide can have DM in 2035, a rise from or so 387 million people calculable to possess the disease in 2014. Here, we tend to present a review of the presentunderstanding and new insights into biochemical mechanisms within the pathological process in DR, classification, furthermore as clinical treatments for DR patients. Keywords: Diabetic retinopathy, diabetes mellitus, retinal degeneration, fluoresces in angiography, optical coher- ence tomography, VEGF, focal/grid laser photocoagulation.

Clinical Study on Correlation of HbA1c with Different Grades of Diabetic Retinopathy at S.V.R.R.G.G.H, Tirupati – A Hospital Based Descriptive Correlative Study

BACKGROUND Patients with diabetic retinopathy (DR) are 25 times more likely to become blind than non-diabetics.1 One of the main difficulties in establishing a relationship between the degree of hyperglycemia and the long-term complications of diabetes is the lack of a reliable and objective method for the assessment of diabetic control. Recordings of glycated proteins, serum proteins, and primary hemoglobin, have added a new dimension to glycemia assessment. HbA1c has been known to be a marker to assess the long-term control of diabetes mellitus. Few studies have shown the correlation between HbA1c and different grades of DR in the past. The purpose of this study was to determine the correlation of HbA1c with different grades of diabetic retinopathy. METHODS A descriptive correlative study was conducted among 100 diabetic patients attending the Department of Ophthalmology in S.V.R.R.G.G. Hospital, Tirupathi, for a duration of one year. Relevant history regarding their diabetes was noted. The status of diabetic retinopathy in each patient was diagnosed by comprehensive ophthalmologic examination and classified according to the early treatment diabetic retinopathy study (ETDRS) system. Patients were evaluated for their HbA1c levels. RESULTS Out of 100 patients, 43 % of participants were females, and the remaining 57 % were males. A statistically significant correlation was found between different grades of diabetic retinopathy and HbA1c levels. The other factor which had a significant correlation was the duration of diabetes and grade of retinopathy (P – value < 0.05). Age of the patient, gender of the patient, did not significantly correlate when compared in different grades of diabetic retinopathy (P - value > 0.05). CONCLUSIONS A statistically significant correlation was found between HbA1c levels and the severity of diabetic retinopathy. Higher the level of HbA1c (indicating poor glycaemic control), the more severe is the grade of DR in those set of patients. KEYWORDS Diabetic Retinopathy, HbA1c, CSME

Effects of refraction and axial length on the development and progression of diabetic retinopathy

Eye disorders have a special place in diabetes since visual impairment has a significant effect on the quality of life. Therefore, determining risk factors and prognostic criteria for disease course are essential for developing strategies for early prevention of diabetic retinopathy (DR). This paper addresses studies on various aspects of DR in patients with myopia. It was demonstrated that DR arises, develops, and progresses in different ways under various axial lengths (AL). Thus, many authors report that DR barely occurs in high myopia. Some of them account for this phenomenon for poor blood circulation in a long myopic eye. Others refer to a significantly lower vascular endothelial growth factor (VEGF) concentration in longer eyes or eyes with myopic refraction. The third authors argue a focal disintegration of retinal pigment epithelium to eliminate metabolic end products through the choroid and sclera. As a result, neither acidosis nor venous congestion develops, and endothelial barrier function remains unaffected Keywords: diabetic retinopathy, myopia, axial length, vascular endothelial growth factor, emmetropia, hyperopia, diabetes. For citation: Bikbov M.M., Orenburkina O.I., Babushkin A.E., Fakhretdinova A.A. Effects of refraction and axial length on the development and progression of diabetic retinopathy. Russian Journal of Clinical Ophthalmology. 2021;21(4):205–209 (in Russ.). DOI: 10.32364/2311-7729- 2021-21-4-205-209.

Role of MMP-9 in Diabetic Retinopathy

Diabetic retinopathy is a common neurovascular complication of diabetic that strike a third of diabetic patients worldwide. Complex mechanism of biomolecules including enzyme and cytokines is related to oxidative stress of constant hyperglycaemia. Vascular permeability damage resulting from endothelial leakage and apoptosis of Muller cell is the main mechanism of retinal damage. MMPs as endopeptidases have an important role in angiogenesis process of retinopathy by working with various molecules of growth factors, chemokines, cytokines and cell adhesion molecules. MMP-9 has been widely shown to be associated with inflammation, blood-retinal barrier disruption, cell apoptosis and neovascularization in the diabetic retinopathy pathomechanism. Keywords: Diabetic retinopathy; MMP; MMP-9; Blood-retinal barrier

Diabetic Dermopathy (Shin Spots) and Diabetic Retinopathy - Are They Associated?

BACKGROUND Diabetes mellitus (DM) is a major cause of avoidable blindness in the developing and the developed countries. Diabetic patients have 25 times more chance of becoming blind than the non-diabetics.1 According to the WHO, the number of people in India affected with Diabetes Mellitus in the year 2000 was 31.7 million which is estimated to rise to 79.4 million by 2030, which would be higher than any other country in the world. 75 percent of all Type 2 diabetics and almost all Type 1 diabetics are expected to develop diabetic retinopathy (DR) over a period of time.2 Diabetic dermopathy or shin spots are the commonest dermatological manifestation in patients with Diabetes Mellitus. It is also known as pigmented pretibial patches, spotted leg syndrome or diabetic dermangiopathy.3 Both diabetic retinopathy and dermopathy are manifestations of diabetic microangiopathy. We wanted to study the association between diabetic retinopathy and diabetic dermopathy. METHODS 182 patients (between 40 - 70 years of age) having diabetes mellitus for at least five years were included in the study and were examined for retinal changes and skin changes. The study period was six months. RESULTS Of the 182 diabetic patients included in this study, 106 (58.2 %) had diabetic retinopathy. Shin spots were seen in 158 cases (86.8 %). 100 (94.3 %) cases with diabetic retinopathy had shin spots. The mean duration of diabetes mellitus in patients with diabetic retinopathy was 11.85 years and it was 8.16 years in those without diabetic retinopathy. The mean duration of diabetes mellitus in patients with shin spots was 14.88 years and it was 10.70 years in those without shin spots. CONCLUSIONS There is significant association between diabetic retinopathy and diabetic dermopathy. KEYWORDS Diabetic Retinopathy, Shin Spots, Diabetic Dermopathy

Deep Learning untuk Klasifikasi Diabetic Retinopathy menggunakan Model EfficientNet

ABSTRAKDiabetic Retinopathy merupakan penyakit yang dapat mengakibatkan kebutaan mata yang disebabkan oleh adanya komplikasi penyakit diabetes melitus. Oleh karena itu mendeteksi secara dini sangat diperlukan untuk mencegah bertambah parahnya penyakit tersebut. Penelitian ini merancang sebuah sistem yang dapat mendeteksi Diabetic Retinopathy berbasis Deep Learning dengan menggunakan Convolutional Neural Network (CNN). EfficientNet model digunakan untuk melatih dataset yang telah di pre-prosesing sebelumnya. Hasil dari penelitian tersebut didapatkan akurasi sebesar 79.8% yang dapat mengklasifikasi 5 level penyakit Diabetic Retinopathy.Kata kunci: Diabetic Retinopathy, Deep Learning, CNN, EfficientNet, Diabetic Classification ABSTRACTDiabetic Retinopathy is a diseases which can cause blindness in the eyes because of the complications of diabetes mellitus. Therefore, an early detection for this diseases is very important to prevent the diseases become severe. This research builds the system which can detect the Diabetic Retinopathy based on Deep Learning by using Convolutional Neural Network (CNN). EfficientNet model is used to trained the dataset which have been pre-prossed. The result shows that the system can clasiffy the 5 level of Diabetic Retinopathy with accuracy 79.8%. Keywords: Diabetic Retinopathy, Deep Learning, CNN, EfficientNet, Diabetic Classification