Proliferative Diabetic Retinopathy In Patients Research Articles

The Association of Sickle-Cell Disorders With Diabetic Retinopathy: A Large Database Study

PurposeTo evaluate the association of sickle-cell disease (SCD) and sickle-cell trait (SCT) disease with diabetic retinopathy (DR) in patients with diabetes mellitus (DM). DesignPopulation-based, retrospective cohort study utilizing data from the TriNetX Research Network, including 119 million patients across 80 healthcare organizations worldwide. ParticipantsDM patients (Type 1 (T1DM) or 2 (T2DM)), with or without SCD and SCT, were included. Three cohorts were analyzed, including (1) DM patients without SCD, SCT, or Sickle-cell/Hb-C; (2) DM with SCD; and (3) DM with SCT. MethodsAll patients with DM were categorized into three cohorts based on the presence of SCD and SCT. Each cohort underwent 1:1 propensity score matching for demographics, blood glucose levels, hemoglobin A1C, and other relevant comorbidities. Main Outcome MeasuresRisk of DR in DM patients with and without SCD or SCT. ResultsThere was no significant difference in the risk of any T1DR between those with and without SCD. However, for those with SCT, there was a notable 2-fold increased risk for T1-PDR (RR: 2.03; 95% CI: 1.33-3.01). In contrast, there was an elevated risk for any T2DR in patients with SCD (RR: 1.50; 95% CI: 1.19-1.88), particularly due to higher proliferative DR risks in T2DM patients (RR: 1.83; 95% CI: 1.29-2.60). The risk of mild to moderate T2DM non-proliferative DR was also found to be higher in patients with SCT. ConclusionsThe risk of any DR was increased in T2DM patients with SCD or SCT, with increased risks for proliferative DR in patients with SCT and T1DM. This indicates there may be a potential role of SC disorders in diabetic eye disease progression.

Subclinical Hypothyroidism in Patients with Diabetic Retinopathy: Role of Vascular Endothelial Growth Factor.

This study was conducted by considering the vital role of Vascular Endothelial Growth Factor (VEGF) in the development of Diabetic Retinopathy (DR) on the one hand and the frequent association between Subclinical Hypothyroidism (SCH) and DR on the other hand. The present study was proposed to explore the possible role of VEGF in the relation between SCH and DR; thus, we investigated the relationship between SCH and VEGF levels in patients with DR. Two hundred patients with DR were recruited in this study [100 patients with Proliferative Diabetic Retinopathy (PDR) and 100 patients with Non-Proliferative Diabetic Retinopathy (NPDR)]. Patients with DR were divided into 2 groups according to thyroid function, patients with SCH or those with euthyroidism. Patients were subjected to careful history taking and underwent clinical and ophthalmological examination. Fasting blood glucose, glycosylated hemoglobin, fasting insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), TSH, FT4, FT3, VEGF, and thyroid volume were assessed. Among all the studied patients, 21.5% (43/200) had SCH. DR patients with SCH had older age, longer diabetes duration, and higher HbA1c, HOMA-IR, and VEGF than those with euthyroidism. The frequency of PDR in patients with SCH was 72.1% (31/43) and 43.9% (69/157) in those with euthyroidism, whereas the frequency of NPDR in patients with SCH was 27.9 (12/43) and 56.1% (88/157) in those with euthyroidism (P 0.003). In multivariate analysis, PDR, HOMA- IR, and VEGF levels were the significant predictor variables of SCH. Increased VEGF levels may be implicated in the relationship between SCH and DR.

Long-term vision outcomes for patients with albinism and diabetic retinopathy.

Albinism defines a group of genetic diseases which result from disordered melanin biosynthesis. Proliferative diabetic retinopathy (PDR) results from poorly controlled type 1 or 2 diabetes mellitus (DM) and can lead to blindness due to progressive neovascularisation. However, the treatment of PDR in patients with ocular/oculocutaneous albinism may be more challenging. In this study, we compared a group of patients with albinism and PDR, to a group with albinism and diabetes mellitus but no PDR, to examine the long-term implications. Retrospective observational study included all patients with ocular albinism (OA) or oculocutaneous albinism (OCA) and DM who presented at a single specialist centre. Participants were allocated into either group 1 (eyes with PDR) or group 2 (all eyes without PDR). Statistical analysis was performed using SPSS V26.0. Between-group differences were investigated. Outcome data was available for 5 eyes from 3 participants in group 1 and 26 eyes from 13 participants in group 2. Despite interventions, a large and significant difference in vision at follow-up was observed between group 1 and group 2 (mean change in visual acuity: 1.11 (± 1.00) versus - 0.15 (± 0.46), respectively; p = < 0.0001). PDR is associated with poor long-term prognosis despite interventions for patients with albinism. Those without PDR appear to maintain stable vision. Alternative treatments for PDR and its complications may be required in this population. Measures to prevent the development of diabetic eye disease and progression towards PDR should be employed at an early stage.

Прогностическое значение показателей протеолиза в формировании диабетической ретинопатии

В статье приведены результаты исследований нарушений в системе протеолиза у больных сахарным диабетом (СД) 2-го типа и диабетической ретинопатией (ДР). Определяли уровни матриксной металлопротеиназы‑9 (ММП‑9) и тканевого ингибитора матриксной металлопротеиназы‑1 (ТИМП‑1) в крови и внутриглазной жидкости (ВГЖ) у больных СД 2-го типа иммуноферментным методом (Bender Medsystems, Австрия). Установлены изменения в системе протеолиза у больных ДР и СД 2-го типа, которые заключались в повышении уровня ММП‑9 и ТИМП‑1 в крови и ВГЖ как при отсутствии признаков ДР, так и при любой ее стадии в сравнении с уровнем этих показателей у больных без СД. Установлено, что уровень ММП‑9 во ВГЖ и давность СД 2-го типа влияют на вероятность развития диабетического макулярного отека (ДМО). При уровне ММП‑9 ≥ 105 нг/мл и длительности СД 2-го типа ≥ 10 лет вероятность развития ДМО составляет 100 %. На вероятность развития пролиферативной ДР у больных СД 2-го типа в течение четырех лет наблюдения влияют: уровень ММП‑9 во ВГЖ, стадия ДР в начале наблюдения и длительность СД 2-го типа. При уровне ММП‑9 ≥ 100 нг/мл, длительности СД 2-го типа ≥ 10 лет и отсутствии признаков ДР в начале наблюдения вероятность развития пролиферативной ДР составляет 85,9 %.

Proliferative diabetic retinopathy in patients with type 2 diabetes correlates with the presence of atherosclerosis cardiovascular disease

BackgroundAtherosclerosis cardiovascular disease (ASCVD) is the main cause of morbidity and mortality in type 2 diabetes mellitus (T2DM). As most diabetic patients with ASCVD are asymptomatic, it is most neglected in clinical practice. For this reason, identifying high-risk ASCVD population with intensified treatment is very important. In recent years, the relationship between diabetic retinopathy (DR) and ASCVD has caused much academic concern, but the results are inconsistent. Moreover, whether all grades of DR increase the risk of ASCVD remains controversial. Most importantly, very few data can be found in China.ObjectiveOur aim is to discuss whether all grades of DR increase the risk of ASCVD after adjustment for the traditional cardiovascular risk factors and to assess the independent contribution of DR to cardiovascular events in patients with T2DM, hoping to provide more evidence for early identification of ASCVD.Research design and methodsA total of 425 T2DM patients with complete physical and biochemical data were included in the study. The grade of DR was assessed with two 45 color digital retinal images. Based on the presence of history of ASCVD, 425 T2DM patients were divided into 2 groups: ASCVD group and non-ASCVD group.ResultsASCVD patients were older and had a significantly higher fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) and proportion of history of ASCVD. At the same time, they were more likely to be females, and had lower level of alcohol and calculated glomerular filtration rate (eGFR) than non-ASCVD patients. Their trend to develop DR with ASCVD was significantly higher than patients with non-ASCVD (χ2 = 5.805, P = 0.016). DR was an independent statistical indicator of the presence of ASCVD [odds ratio (OR) (95% CI): 2.321 (1.152–4.678), P = 0.018]. Furthermore, when DR was divided into non-proliferative retinopathy (NPDR) and proliferative retinopathy (PDR) according to its severity, only PDR was significantly associated with incident ASCVD [OR (95% CI): 8.333 (1.813–38.304), P = 0.006]. After adjusting for traditional ASCVD risk factors, such an association still existed [OR (95% CI): 7.466 (1.355–41.137), P = 0.021].ConclusionDR associates strongly with ASCVD in the Chinese population with T2DM. With the increasing severity of DR, the risk of ASCVD also increases. After adjustment for traditional risk factors, PDR is still an independent risk marker for ASCVD.

Association of UCP1 and UCP2 variants with diabetic retinopathy susceptibility in type-2 diabetes mellitus patients: a meta-analysis

BackgroundGenetic association of uncoupling proteins (UCPs) variants with the susceptibility of diabetic retinopathy (DR) in diabetes mellitus (DM) patients has been reported but with controversy. Here we aimed to conduct a meta-analysis to confirm the association of different UCPs variants with DR.MethodsThree databases (Medline Ovid, Embase Ovid and CENTRAL) were applied in the literature search. Five genetic models, including allelic, homozygous, heterozygous, dominant and recessive models, were evaluated. Odds ratios (OR) were estimated under the random or fixed-effects models. Subgroup analyses, publication bias and sensitivity analyses were also conducted.ResultsEleven studies on 2 UCPs variants (UCP1 rs1800592 and UCP2 rs659366) were included. Our meta-analysis showed that UCP1 rs1800592 was not associated with DR in type-2 DM patients, and UCP2 rs659366 also showed no association with DR. In the subgroup analyses on the stage of DR, allele G of UCP1 rs1800592 significantly increased the susceptibility of proliferative diabetic retinopathy (PDR) in type-2 DM patients in the allelic (OR = 1.26, P = 0.03) and homozygous models (OR = 1.60, P = 0.04). Subgroup analysis on ethnicity did not found any significant association of rs1800592 and rs659366 with DR.ConclusionOur meta-analysis confirmed the association of UCP1 rs1800592 variant with PDR in patients with type-2 DM, suggesting its potential as a genetic marker for PDR prediction in population screening.

Commentary: Vitrectomy for proliferative diabetic retinopathy in patients with type 1 diabetes mellitus.

Commentary: Vitrectomy for proliferative diabetic retinopathy in patients with type 1 diabetes mellitus.

Can nasal septum deviation be one of the factors affecting diabetic retinopathy?

Aim: Information on the extraocular causes of diabetic retinopathy is limited. Therefore, when researching etiology in a patient with diabetic retinopathy, if glucose, blood pressure and cholesterol are normal, other reasons must be investigated. Our aim was to evaluate the effect of nasal septum deviation (NSD) on the presence and severity of diabetic retinopathy in patients with diabetes mellitus. Methods: This prospective case-control study included 100 eyes of 50 patients with only diabetes mellitus (DM+ NSD-, control group) and 120 eyes of 60 patients with DM and nasal septum deviation (DM+NSD+, NSD group). After evaluation of NSD patients using a nasal obstruction symptom evaluation scale (NOSE scale), 22 patients were classified as mild, 21 as moderate, and 17 as severe. Anterior segment and dilated fundus examinations were performed in all patients. Diabetic retinopathy (DR) was classified as mild, moderate, and severe non-proliferative DR and proliferative DR (PDR). Results: The mean age of patients in the NSD and control groups was 58.7 (15.2) years (range: 41–69) and 59.6 (8.1) years (range: 44–67), respectively. The prevalence of DR and PDR were 70% (n=14) and 30% (n=6), respectively, in the severe NSD group (P=0.045 and P=0.035, respectively). The relationship between PDR and other factors in patients with NSD were evaluated, and a correlation was detected with DM duration (P=0.024, OR=1.272), HbA1c (P=0.032, OR=3.085), and NOSE scale severity (P=0.040, OR=2.566). Conclusion: The results of the present study show an increased risk of DR and PDR in patients with severe NSD. In addition to other risk factors in PDR etiology, NSD should also be considered.

Incidence and Risk for Developing Proliferative Diabetic Retinopathy after Photocoagulation for Diabetic Maculopathy

ABSTRACT Purpose Diabetic maculopathy (DM) treated with photocoagulation may subsequently progress to proliferative diabetic retinopathy (PDR). However, there is insufficient knowledge about the incidence and risk factors for the development of PDR in patients previously treated for DM. Materials and methods Survival data was used to analyze prospectively collected epidemiological and clinical data to describe the incidence and risk factors for the occurrence of PDR in all 1,235 patients photocoagulation treated for DM in a defined population from the Aarhus area, Denmark, from January 1. 1993 until December 31. 2016. Results Among 1,204 (97.5%) of the patients in whom the subsequent clinical history was known, 536 (44.5%) had died and 131 (10.9%) had received panretinal photocoagulation for PDR. The cumulative incidence of developing PDR after photocoagulation for diabetic maculopathy increased with time to reach a plateau around 13% after approximately 15 years. Earlier age at diagnosis of diabetes and higher HbA1c at the time of macular treatment were significant risk factors for the development of PDR, whereas gender, diabetes type, body mass index, known diabetes duration at the time of macular photocoagulation and blood pressure were not significant risk factors. Conclusions In patients treated with retinal photocoagulation for DM, a tight metabolic control is accompanied with a reduced risk for subsequent progression to PDR. In the treated patients who do not develop PDR, the control interval can be gradually increased with time.

Surgical outcomes of vitrectomy surgery for proliferative diabetic retinopathy in patients with abnormal renal function.

To analyse the influence of renal function on the outcomes of vitrectomy for tractional-related complications in cases of severe proliferative diabetic retinopathy (PDR). Retrospective consecutive case series of 109 eyes that underwent vitreoretinal interventions for traction-related complications of severe PDR from 2014 to 2017. Data collected included patient demographics, best-corrected visual acuity (BCVA), surgical complications, and systemic markers including HbA1c and estimated glomerular filtration rate (eGFR). Renal function categories were defined as low (eGFR < 30mL/min/1.73m2), medium (eGFR 30-60mL/min/1.73m2), and normal (eGFR > 60mL/min/1.73m2). A total of 109 eyes (56% (n = 61) female) were included in the study. Overall, mean baseline BCVA improved from 1.33 logMAR to 0.91 logMAR (p < 0.001) postoperatively. Patients with low eGFR had significantly worse baseline BCVA (p = 0.039) and demonstrated greater improvement in mean BCVA (p = 0.059). Multivariate regression analysis indicated that seven predictors explained 65.5% of the variance (R2 = 0.655, F(11,97) = 16.7, p < 0.01). Reduced renal function does not adversely affect visual outcomes of vitrectomy for traction-related complications of PDR.

531-P: Weight Change and the Incidences of End-Stage Renal Disease and Proliferative Diabetic Retinopathy in Patients with Newly Diagnosed Diabetes Mellitus: A Nationwide Cohort Study

Aims/Hypothesis: This study aimed to investigate the impact of weight changes on the clinical outcomes of diabetic nephropathy and retinopathy among patients with newly diagnosed diabetes. Methods: Using nationally representative data from the Korean National Health Insurance System, 181,872 patients newly diagnosed with diabetes who were free of end-stage renal disease (ESRD) and proliferative diabetic retinopathy (PDR) during 2007-2012 were followed to the end of 2016. Weight change was defined as the difference in body weight from the time of diabetes diagnosis to 2 years later. Results: There were 180 cases of ESRD (0.10%) and 780 cases of PDR (0.43%) followed-up for a median of 5.5 years from the index year at 2 years after diagnosis. Those with moderate weight gain (+5% to +10%) showed a significantly higher hazard ratio (HR) for ESRD, compared with those with modest weight changes (−5% to +5%) after adjusting for several confounding factors, including the baseline estimated glomerular filtration rate (HR, 1.732; 95% CI 1.125-2.667). Those with severe weight loss (−5% to −10%) showed the lowest HR for PDR (HR, 0.591; 95% CI 0.372-0.938), whereas those with severe weight gain (> +10%) showed the highest HR for PDR (HR, 1.732; 95% CI 1.125-2.667). Conclusion: This study provides direct evidence that a change in body weight affects the risk of diabetic microvascular complications. Strategies to control body weight may reduce the risk of ESRD and PDR in patients with newly diagnosed diabetes. Disclosure H. Kwon: None. K. Song: None.

The Association of CEP135 rs4865047 and NPY2R rs1902491 Single Nucleotide Polymorphisms (SNPs) with Rapid Progression of Proliferative Diabetic Retinopathy in Patients with Type 1 Diabetes Mellitus

BackgroundDiabetic retinopathy has a varied prevalence, severity, and rate of progression. The aim of this study was to determine whether the single nucleotide polymorphisms (SNPs) of the gene encoding a 135-kD centrosomal protein CEP135 rs4865047 and the gene encoding the type 2 NPY protein NPY2R rs1902491 were associated with the development of rapidly progressive proliferative diabetic retinopathy in patients with type 1 diabetes mellitus.Material/MethodsPatients with rapidly progressive proliferative diabetic retinopathy (n=48) were included in the study group. The control group (n=84) consisted of diabetes mellitus patients who had no proliferative diabetic retinopathy up to 15 years of diabetes duration. The reference group (n=90) included non-diabetic individuals who matched the study group by age and gender. The SNPs in the three groups were analyzed using real-time polymerase chain reaction (PCR) amplification.ResultsThe analysis of the distribution of genotypes in CEP135 rs4865047 and NPY2R rs1902491 detected significant differences only in the single nucleotide polymorphism rs4865047 genotype between the case and control group in comparison to the reference group. The co-dominant model showed that CEP135 rs4865047 was significantly associated with patients with rapidly progressive proliferative diabetic retinopathy (OR 7.2, 95% CI, 2.28–22.74, p=0.001). No significant association was found for the NPY2R SNP rs1902491 genotype.ConclusionsOur study reports a significant association of the CEP135 single nucleotide polymorphism rs4865047 genotype with rapidly progressive proliferative diabetic retinopathy and the control group. No significant association was found of the NPY2R single nucleotide polymorphism rs1902491 genotype.

Clinical efficacy of vitrectomy for proliferative diabetic retinopathy in patients with chronic renal failure

Objective To evaluate the efficacy of vitrectomy for the treatment of proliferative diabetic retinopathy in patients with chronic renal failure. Methods Clinical data of 21 eyes of 21 cases with chronic renal failure and proliferative diabetic retinopathy were analyzed retrospectively. All cases underwent vitrectomy. Results The follow-up time was 3 months. The postoperative BCVA were improved in 20 eyes (95.24%), and decreased in 1 eye (4.76%). The average BCVA(logMAR) was 2.05±0.78 before operation and 0.68±0.66 after operation. The difference in BCVA was statistically significant between pre-operation and post-operation (t=6.103, P=0.000). During perioperative period blood pressure was elevated in 18 patients. Blood pressure was increased after establishment of the three scleral cannulas in 17 patients. The increase of blood pressure repeatedly occurred in 11 patients during operation. All patients with high blood pressure were treated with appropriate treatment. All the proliferative membrane and vitreous hemorrhage were removed, retina was reattached. The postoperative complications included temporary intraocular pressure elevation in 3 eyes, pre-retinal hemorrhage in 4 eyes, ischemic optic neueopathy in 3 eyes, endogenous fungal endophthalmitis after hemodialysis deep vein catheterization in 1 eye, and heart failure caused by respiratory tract infection in 1 eye. Conclusion Carefully conducted perioperative treatment and relatively stable systemic conditions, a well-designed minimally invasive vitrectomy can effectively treat proliferative diabetic retinopathy in patients with chronic renal failure, improving visual acuity and quality of life. Key words: Vitrectomy; Renal failure, chronic; Retinopathy, diabetic, proliferative

Regional differences in the prevalence of diabetic retinopathy: a multi center study in Brazil

BackgroundDiabetic retinopathy has a significant impact in every healthcare system. Despite that fact, there are few accurate estimates in the prevalence of DR in Brazil’s different geographic regions, particularly proliferative DR and diabetic macular edema. This study aims to determine the prevalence of diabetic retinopathy in Brazil’s five continental regions and its determinant factors.MethodsThis multi center, cross-sectional, observational study, conducted between August 2011 and December 2014, included patients with type 1 diabetes from the 5 Brazilian geographic regions (South, Southeast, North, Northeast and Midwest). During a clinical visit, a structured questionnaire was applied, blood sampling was collected and each patient underwent mydriatic binocular indirect ophthalmoscopy evaluation.ResultsData was obtained from 1644 patients, aged 30.2 ± 12 years (56.1% female, 54.4% Caucasian), with a diabetes duration of 15.5 ± 9.3 years. The prevalence of diabetic retinopathy was 242 (36.1%) in the Southeast, 102 (42.9%) in the South, 183 (29.9%) in the North and Northeast and 54 (41.7%) in the Midwest. Multinomial regression showed no difference in the prevalence of non-proliferative diabetic retinopathy in each geographic region, although, prevalence of proliferative diabetic retinopathy (p = 0.022), and diabetic macular edema (p = 0.003) was higher in the Midwest. Stepwise analyses reviled duration of diabetes, level of HbA1c and hypertension as independent variables.ConclusionsThe prevalence of non proliferative diabetic retinopathy in patients with type 1 diabetes was no different between each geographic region of Brazil. The Midwest presented higher prevalence of proliferative diabetic retinopathy and diabetic macular edema. Duration of DM and glycemic control is of central importance to all. Hypertension is another fundamental factor to every region, at special in the South and Southeast. Glycemic control and patients in social and economic vulnerability deserves special attention in the North and Northeast of Brazil.

Diabetic Retinopathy in Patients with Dyslipidemia: Development and Progression

To investigate the association of dyslipidemia with the development of diabetic retinopathy (DR). A prospective cohort from the Longitudinal Health Insurance Database in Taiwan. Patients with diabetes mellitus (DM) aged ≥18 years from this cohort. A logistic regression model considering age, sex, and adapted Diabetes Complication Severity Index (aDCSI) including diabetic retinopathy, diabetic neuropathy, diabetic nephropathy cardiovascular disease, cerebrovascular disease, peripheral arteriolar disease, and metabolic disease. We estimated the propensity score for disease assignment probability for each included patient with DM and dyslipidemia. For each patient, a comparison patient without dyslipidemia was matched with a propensity score using a greedy algorithm. The standardized mean differences method was used to measure the difference in means or proportions divided by the pooled standard deviation of a variable. We calculated the incidence densities of nonproliferative DR (NPDR), diabetic macular edema (DME), and proliferative DR (PDR) as total events divided by the sum of follow-up duration, and the incidence curves were measured using the Kaplan-Meier method. The log-rank test was applied to test the differences of incidence curves. Hazard ratios (HRs) for DR. Our results demonstrated that the cumulative incidence of NPDR, DME, and PDR significantly increased in patients with DM and dyslipidemia compared with those without before adjustment for covariates (P< 0.001). Adjusted HRs for NPDR, DME, and PDR in patients with dyslipidemia were 1.77 (95% confidence interval [CI]= 1.63-1.92), 2.34 (95% CI= 1.24-4.41), and 1.07 (95% CI= 0.91-1.27), respectively. The risks of NPDR, DME, and PDR increased in patients who had underlying complications according to the aDCSI. Only statin use had a protective effect against the development of NPDR (HR= 0.83; 95% CI= 0.76-0.90), but it had no effect on DME and PDR. The protective effect was not significantly different between patients with and without dyslipidemia. Dyslipidemia is involved in the development of DR at an earlier stage, but the role of lipid-modulating agents in DR requires additional study.

Relationship of Skin Autofluorescence to Severity of Retinopathy in Type 2 Diabetes

Purpose: To evaluate the relationship between skin autofluorescence (SAF), which reflects the accumulation of advanced glycation end products (AGEs), and the severity of diabetic retinopathy (DR) in patients with type 2 diabetes.Methods: Sixty-seven eyes of 67 patients with type 2 diabetes were enrolled. Sixty-seven age-matched non-diabetic subjects served as controls. Diabetic patients were classified by the severity of their DR: no DR (NDR), non-proliferative DR (NPDR), and proliferative DR (PDR). SAF was measured with an autofluorescence reader.Results: SAF in the diabetes patients was significantly higher than in the controls (median 2.5 (interquartile range 2.3–2.7) and 1.8 (1.6–2.3) arbitrary unit (AU), respectively, p < 0.001). There was a statistically significant increase in SAF along with the increasing severity of DR (from NDR to NPDR: p = 0.034; NPDR to PDR: p < 0.01). Logistic regression analysis revealed that SAF (OR, 17.2; p < 0.05) was an independent factor indicating the presence of PDR.Conclusions: SAF has an independent relationship with PDR in patients with type 2 diabetes. SAF measurement with an autofluorescence reader is a non-invasive way to assess the risk of DR. SAF may, therefore, be a surrogate marker candidate for the non-invasive evaluation of DR.

Angiotensin-converting enzyme gene variants interact with the renin-angiotensin system pathway to confer risk and protection against type 2 diabetic retinopathy.

The angiotensin‐converting enzyme (ACE) gene has been found to be associated with pathogenesis and progression of diabetic retinopathy (DR). A recent meta‐analysis comprising 2,224 Chinese patients showed moderate evidence of a relationship between the ACE insertion/deletion (I/D) polymorphism and proliferative diabetic retinopathy (PDR)1; however, the role of other renin–angiotensin system (RAS) polymorphisms and their possible interactions with ACE I/D genotypes are less clearly defined. Thus, we investigated the association and interaction between RAS gene polymorphisms and the development and progression of DR in 1,446 north Indian type 2 diabetic patients. DR patients were divided into two groups, non‐proliferative diabetic retinopathy (NPDR) and PDR. DR was diagnosed by dilating the pupils with mydriatics and then carefully examining the retina. Retinal photography or fluorescein angiography tests were also carried out. A total of 1,720 type 2 diabetic patients were screened for the presence of DR, of which, 1,446 patients were finally included for the present study. Patients receiving antihypertensive drug treatment, with any retinopathy other than DR, cataracts and cataract surgery, and age‐related macular degeneration were excluded from the study. All the participants in both the cohorts were age (≥35 years), sex and ethnicity matched. Significant deviation from the Hardy–Weinberg equilibrium of genotype distribution in the present population in ACE I/D and angiotensinogen (AGT) variant rs5050 might be a result of the moderate population size or the rare allele, which can cause a random change in allele frequencies. Furthermore, we excluded the possibility of a typing error (logarithmic odds ratio score >0). The present sample size had the power of 90% at a small effect size (0.1) and alpha level (0.05). In both the cohorts, we observed a consistently higher prevalence and increased risk of PDR in patients with the DD genotype of ACE I/D, TT genotype of AGTrs699 and the CC genotype of angiotensin II receptor type 1 A1166C (Table 1). Table 1 Genotype frequencies of the renin–angiotensin system variants in type 2 diabetes patients (diabetes mellitus vs non‐proliferative diabetic retinopathy vs proliferative diabetic retinopathy) The biological mechanism through which the ACE I/D polymorphism might be related to an increased risk of PDR is unclear. Serum ACE concentrations are significantly higher in those carrying the DD genotype2. Also, the final component of RAS, which is converted by ACE, has a vasoconstrictive effect, promotes the accumulation of extracellular matrix and induces plasminogen activator inhibitor‐1 production in endothelial cells3. Furthermore, DR is associated with impaired balance of retinal RAS. Increased expression of ACE/AGT overcomes this imbalance and confers protection against DR4. The present results suggest RAS polymorphism as a significant risk factor for DR in Asian Indians.

Anemia as a factor related to the progression of proliferative diabetic retinopathy after photocoagulation

ObjectiveThis study aimed to investigate factors that could be related to the progression of proliferative diabetic retinopathy in patients treated with photocoagulation. MethodsIn this case-control study, a total of 106 patients with diabetic retinopathy participated who were treated with photocoagulation. We analyzed glycaemia, serum cholesterol, triglycerides, hemoglobin, platelet levels, blood pressure measurement, diabetes duration, diabetes and hypertension treatment, sex, and age. The statistical analysis was done with t test, χ2 test, odds ratio (OR), and simple linear regression. ResultsWe found statistical significance in blood glucose level(P=.038), cholesterol level (P<.001), and hemoglobin level (P<.001). The simple linear regression was significant with blood glucose level (P<.05) and hemoglobin level (P=.001). Hemoglobin had a significant result: OR=2.432, 95% CI 1.902–3.115; Pearson χ2=16.812; P<.001. ConclusionsAnemia is an important finding in diabetic patients. Anemia is a relevant factor related to the progression of proliferative diabetic retinopathy, which can be treated with photocoagulation.

Enhanced Circulating Soluble LR11 in Patients With Diabetic Retinopathy

To investigate the relationship of circulating levels of soluble form of LR11 (sLR11; also called SorLA or SORL1), with the progression of proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus. Cross-sectional study. Fifty-four patients with type 2 diabetes mellitus were divided into 2 sex- and age-matched groups: one with PDR (n = 29) and the other with nonproliferative diabetic retinopathy (n = 25). The serum sLR11 levels were measured with an immunodetection system followed by chemifluorescence quantification. The serum sLR11 levels were higher in the PDR group than in the nonproliferative diabetic retinopathy group (5.8 ± 1.2 U vs 3.7 ± 1.3 U; P < .01). A multivariate regression analysis showed that circulating sLR11 is a factor contributing to the prediction of PDR independent of other classical risk factors, and an area under the receiver operating characteristic curve analysis revealed that the sensitivity and the specificity were equivalent to or more than those of other factors. Among the classical risk factors for PDR, glycosylated hemoglobin levels showed the highest correlation coefficient (P < .01) for the sLR11 concentrations. Serum sLR11 concentration may reflect the progression of PDR in patients with type 2 diabetes mellitus. sLR11, released from immature vascular cells and indicating the development of atherosclerosis, is expected to be a novel candidate biomarker indicating diabetic retinopathy in patients with type 2 diabetes mellitus.

Axial Length and Proliferative Diabetic Retinopathy

To determine the correlation between axial length and diabetic retinopathy (DR) in patients with diabetes mellitus for 10 years or more. This study was a prospective, observational, cross-sectional study. Patients with diabetes for 10 years or more were included. We excluded eyes with any other significant ocular disease or any prior intraocular surgery, except uncomplicated cataract surgery. Only one eye of each patient was included as the study eye. The severity of DR was graded as no DR, non-proliferative DR (NPDR), or proliferative DR (PDR). Axial length was measured by A-scan ultrasound (10 MHz Transducer, AL-2000 Biometer/Pachymeter; Tomey, Phoenix, AZ). Univariate logistic regression models were used to evaluate the relationship between the dependent variables (any DR, PDR) and all potential risk factors. Axial length and other factors with p value <0.1 were included in multivariate logistic regression models. Backward selection based on the likelihood ratio statistic was used to select the final models. We included 166 eyes from 166 patients (93 female and 73 male; mean age, 68.8 years). The mean diabetes duration was 15.4 years. Fifty-four (32.5%) eyes had no DR, 72 (43.4%) eyes had NPDR, and 40 (24.1%) eyes had PDR. In univariate analysis, hypertension (p = 0.009), renal impairment (p = 0.079), and insulin use (p = 0.009) were associated with developing any DR. Hypertension (p = 0.042), renal impairment (p = 0.014), insulin use (p = 0.040), pseudophakia (p = 0.019), and axial length (p = 0.076) were associated with developing PDR. In multivariate analysis, hypertension (p = 0.005) and insulin use (p = 0.010) were associated with developing any DR. Hypertension (p = 0.020), renal impairment (p = 0.025), pseudophakia (p = 0.006), and axial length (p = 0.024) were associated with developing PDR. This observational study suggests an inverse relationship between axial length and the development of PDR in patients with diabetes for 10 years or more. No relationship was found between axial length and the development of any DR.