NPDR Patients Research Articles

Early and localized retinal dysfunction in patients with type 1 diabetes mellitus studied by multifocal electroretinogram.

To investigate the function of localized retinal areas in highly selected type 1 diabetes mellitus patients (DM1) with no or mild signs of diabetic retinopathy (NO DR and NPDR, respectively) and its correlation with age, diabetes duration and glycemic control. Multifocal electroretinograms (mfERG) were recorded in 35 eyes of 18 NO DR patients and 38 eyes of 19 NPDR patients. Thirty-one eyes of 17 normal subjects were enrolled as controls. N1-P1 response amplitude densities (RADs) and P1 implicit times (ITs) from isolated (R1: 0°-2.5°, R2: 2.5°-5°, R3: 5°-10°) and combined (R1 + R2, R2 + R3 and R1 + R2 + R3) annular rings and from four retinal sectors (nasal, N; temporal, T; superior, S and inferior, I) with increasing eccentricities up to 10° (S1, S2, S3, S1 + S2, S1 + S2 + S3) were measured. The statistical differences between DM1 groups and controls were tested by ANOVA. The electrophysiological data were correlated with age, duration of diabetes and glycated hemoglobin (HbA1c) level using the Pearson's test. MfERG RADs, but not ITs, from all isolated and combined rings and sectors up to 10° of foveal eccentricity were statistically different between DM1 groups compared to controls. No significant differences were found between NO DR and NPDR patients. The mfERG abnormalities of the central retinal areas were correlated significantly with age in both DM1 groups and with diabetes duration mainly in NPDR group. In DM1 patients, localized retinal dysfunction, described by reduced mfERG RAD, can be observed also in the absence of clinical signs of DR and it is related to aging.

Association of glycemic control with progression of diabetic retinopathy in type 2 diabetes mellitus patients in Malaysia

Abstract The risk of having microvascular complication is high among Type 2 Diabetes Mellitus (T2DM) patients. However, factors associated with the glycemic control and progression of diabetic retinopathy (DR) in T2DM patients is limited. This study aims to determine association between anti-diabetic agents, glycemic control and progression of diabetic retinopathy in a Malaysian population. A retrospective study conducted in a tertiary teaching hospital in Malaysia, from January 2009 until March 2014. This study enrolled 104 patients aged 40-84 years, with a mean age 63.12 ± 9.18 years. patients had non-proliferative diabetic retinopathy (NPDR, 77%) and 35% had proliferative diabetic retinopathy (PDR). Diabetic macula edema (DME) was present in 20% of NPDR patients, compared with 7% in PDR. Alpha-glucosidase inhibitor (p=0.012), age (p=0.014) and number of antidiabetic agents used (p=0.015) were significantly associated with stages of diabetic retinopathy. Family history of T2DM (p=0.039) was associated with DME. Identifying factors influencing the progression of diabetic retinopathy may aid in optimizing the therapeutic effects of anti-diabetic agents in T2DM patients.

Personalized analysis of foveal avascular zone with optical coherence tomography angiography

Aim. To investigate the relationship between the foveal avascular zone (FAZ) and inner nuclear layer (INL) free zone in order to provide a personalized approach for evaluation of the FAZ area with optical coherence tomography-angiography (OCTA).
 Material and methods.Thirty-six healthy individuals (36 eyes) and 9 patients (12 eyes) with nonproliferative diabetic retinopathy (nPDR) were included in this study. The FAZ area as well as INL-free zone were measured in superficial capillary plexus on OCTA images. The FAZ area, INL-free area, and the ratio of the INL-free area to the FAZ area were compared between healthy subjects and nPDR patients.
 Results. The mean FAZ area in healthy subjects and nPDR patients was 0.33 0.1 and 0.56 0.28 mm2 (p 0.05), respectively. The mean INL-free zone in healthy subjects and nPDR patients was 0.33 0.07 and 0.28 0.1 mm2 (p 0.05), respectively. The ratio of the INL-free area to the FAZ area in healthy subjects and nPDR patients was 1.08 0.25 and 0.57 0.2 (p 0.001), respectively. Receiver operating characteristic analysis showed that the ratio of the INL-free area to the FAZ area had the higher area under curve (0.98; 91.7% sensitivity and 97.2% specificity) compared to the FAZ area (0.8; 66.7% sensitivity and 87.1% specificity) for differentiating nPDR from healthy eyes.
 Conclusion. This study showed that personalized analysis of the FAZ area based on the relationship between the actual FAZ and INL-free zone has better diagnostic accuracy compared to the conventional FAZ area measurement on OCTA images.

Vascular responsiveness in type 2 diabetes mellitus (T2DM).

Diabetic retinopathy is used for staging of progression of micro and macro-vascular complications of patients with DM. Our hypothesis was that diabetic patients at different stages of retinopathy would have different vascular responsiveness that will be used as a surrogate marker of macro-vascular disease for risk assessment of cardiovascular complications. A prospective study enrolled 96 patients. Twenty-three healthy volunteers (44 ± 11 years), 25 diabetic patients without retinopathy (63 ± 11 years), 25 patients with non-proliferative retinopathy [NPDR] (62 ± 9 years) and 23 patients with proliferative diabetic retinopathy [PDR] (59 ± 10 years). All patients underwent an ophthalmologic examination to diagnose retinopathy staging, and vascular responsiveness evaluation that included endothelial function evaluation (using the brachial artery method to measure flow mediated diameter change (FMD%)) and measuring the ankle-brachial blood pressure ratio, a measure of arterial stiffness. Endothelial function was severely impaired in all diabetic patients. Patients with PDR had an FMD% of -3.1 ± 6.6%, patients with NPDR had -3.3 ± 9.2%, patients without retinopathy -1.9 ± 7.4% (P = NS between all groups of patients). Healthy controls had an FMD% of 16.5 ± 7.5% with a significant difference (P < 0.001) compared with each group of patients. No difference in FMD% was observed among patients (P = 0.93 between PDR and NPDR groups, P = 0.54 between NPDR and no retinopathy groups and P = 0.71 between patients without retinopathy and those with PDR).The ankle brachial (ABI) ratio was 1.03 ± 0.28 in the PDR group, 1.14 ± 0.24 in the NPDR group and 0.97 ± 0.18 in the no-retinopathy group. Healthy volunteers had an ABI of 1.07 ± 0.18. No difference was observed between ABI of PDR and NPDR patients (P = 0.17) and between patients without retinopathy and PDR patients (P = 0.91). However, a significant difference was observed between the NPDR and no-retinopathy groups (P = 0.008). No significant difference was found between ABI ratios when compared with the control group (P = 0.62 for PDR, P = 0.26 for NPDR and P = 0.07 for the no-retinopathy group). No difference was observed in age and BMI among all groups of patients (P = NS for all). Patients were older (P < 0.001) and had a higher BMI (P < 0.001). Interestingly there was no difference in height among groups of patients, but controls were significantly taller compared with each group of patients (P < 0.02). All patients with T2DM had severe endothelial dysfunction with no difference among the different retinopathy groups. In our patients, all patients had a normal arterial stiffness but patients without retinopathy who had the highest arterial stiffness. We could not distinguish vascular traits that would define diabetic patients at the highest risk to develop cardiovascular complications.

The Effect of Prophylactic Nepafenac 0.1% Eye Drops on Macular Changes after Phacoemulsification in Non- Proliferative Diabetic Retinopathy Patients Using Spectral Domain Optical Coherence Tomography (SD-OCT)

Background: To evaluate the effect of prophylactic nepafenac eye drops on macular thickness changes after phacoemulsification surgery in mild to moderate NPDR patients. Method: This study is an open label randomized clinical trial. Thirty-six subjects who met the inclusion criteria underwent phacoemulsification. One group (18 subjects) were given nepafenac 0.1% eye drops and the rest were given placebo. Foveal thickness was measured by SD-OCT before surgery and the fourth week after phacoemulsification. Best corrected visual acuity (BCVA) and degree of inflammation in the anterior chamber were also being assessed. Result: There was a statistically significant increase foveal thickness in the placebo group 4 weeks after phacoemulsification (p=0.022). Clinically, percentage degree of inflammation in anterior chamber in placebo group was higher than nepafenac group (38.9% : 5.6%) but not significantly different between 2 groups (p=0.27). Nepafenac group achieved clinically better BCVA than the placebo group 4 weeks after phacoemulsification, although statistically there was no significant difference between 2 groups (p=0.991). Conclusion: Nepafenac 0.1% eye drops could prevent foveal thickening 4 weeks after phacoemulsification in mild to moderate NPDR patients. Clinically, nepafenac 0.1% eye drops could decrease the risk of inflammation in the anterior chamber, risk of CME, and vision deterioration although did not reach statistically significant. Keywords: Nepafenac, macular thickness, phacoemulsification, retinopathy diabetic

Changing Clinical Presentation, Current Knowledge-Attitude-Practice, and Current Vision Related Quality of Life in Self-Reported Type 2 Diabetes Patients with Retinopathy in Eastern India: The LVPEI Eye and Diabetes Study.

Purpose. To document the changing clinical presentation of diabetic retinopathy (DR) over a decade, the current knowledge-attitude-practice (KAP) of known type 2 diabetes mellitus (DM) patients, and the current vision related quality of life (VR-QOL) of patients with DR in a tertiary eye care center in Eastern India. Methods. Two hundred and forty patients with known type-2 DM were evaluated. The evaluation included status of DR (n = 240), KAP (n = 232), and VR-QOL (n = 75). International classification of DR was used in the study. The DR status was compared with another cohort (n = 472) examined a decade earlier, in year 2001. The KAP-25 questions were designed after literature review. The National Eye Institute Visual Function Questionnaire (NEI-VFQ; including optional items) was validated by Rasch analysis. Both KAP and VR-QOL were analyzed according to degree of DR, duration of known DM, and educational qualification. Results. Average age of the current cohort (n = 240) was 57.16 ± 9.03 years; there were 205 (85.4%) male patients and 143 (59.6%) patients had received less than graduate qualification. The mean duration of DM since diagnosis was 10 ± 7.8 months (range 8 months to 30 years); 118 (49.16%) patients had DR. In a decade time, 2001 to 2011, there was a change of retinopathy status at presentation (more often nonproliferative diabetic retinopathy, NPDR). One-third of NPDR patients had poor vision and half of them were hypertensive. KAP was better in patients with higher education and those having DR. VFQ score was higher in better seeing patients. Conclusion. Patients currently presenting at earlier stage of retinopathy are probably related to poor vision. Early detection and treatment of DR is likely to preserve and/or improve vision.

Elevated serum monocyte chemoattractant protein-1 levels and its genetic polymorphism is associated with diabetic retinopathy in Chinese patients with Type 2 diabetes.

Previous studies have reported that monocyte chemoattractant protein-1 (MCP-1) is involved in inflammatory and metabolic diseases. The purpose of this study is to investigate the role of MCP-1 in the pathogenesis of diabetic retinopathy (DR) in Han Chinese patients with Type 2 diabetes. Serum levels of MCP-1 protein in patients classified as diabetic without retinopathy (DWR) and DR, including NPDR and PDR, were assayed by enzyme-linked immunosorbent assay. Genomic DNA from 198 DWR patients, 176 NPDR patients and 143 PDR patients were genotyped by using a PCR restriction fragment length polymorphism (PCR-RFLP) assay. MCP-1 serum levels were significantly higher in NPDR and PDR patients than in the DWR patients. The frequencies of the GG genotype and G allele of the single nucleotide polymorphism (SNP) were significantly increased in DR patients compared with DWR patients. Further subgroup analysis was performed to test whether there was an association between the PDR or NPDR and DWR groups. Significantly higher frequencies of the GG genotype and G allele were observed in PDR and NPDR patients compared with DWR patients. Furthermore, the 25 patients with PDR were divided into three groups according to the genotype of the tested SNP. The expression of the MCP-1 gene was higher in the GG genotype group compared with the other two groups. The results suggested that the -2518 GG genotype and G allele of MCP-1 are associated with an increased risk of PDR in the Chinese Han population. This polymorphism may influence the expression of the MCP-1 gene, which may play an important role in the pathogenesis of DR.

Serum and Vitreous Concentrations of Omentin-1 in Diabetic Retinopathy.

Objective. Omentin, a new discovered adipokine, is implicated to inhibit inflammation. Inflammation is one important mechanism of diabetic retinopathy (DR). The purpose of this work was to evaluate serum and vitreous concentrations of omentin-1 in patients with diabetic retinopathy (DR). Methods. This study enrolled 204 diabetic patients (60 without DR, 49 with NPDR, and 95 with PDR) and 65 control subjects. Results. Serum and vitreous omentin-1 levels in PDR patients were markedly decreased compared with those in the other three groups. NPDR patients showed reduced vitreous omentin-1 compared with patients without DR. In addition, control subjects had significantly higher levels of serum and vitreous omentin-1 compared with diabetic patients without DR, NPDR patients, and PDR patients. In addition, serum/vitreous omentin-1 ratio was positively correlated with the development and severity of DR. Conclusion. Serum and vitreous omentin-1 levels, as well as serum/vitreous omentin-1 ratio, are correlated with the presence and severity of DR.

Relation of Serum and Vitreous Concentrations of Fetuin-A with Diabetic Retinopathy.

BackgroundFetuin-A, a liver-derived glycoprotein, is correlated with diabetes. The aim of the present investigation was to evaluate serum and vitreous concentrations of fetuin-A in patients with diabetic retinopathy (DR).Material/MethodsWe randomly selected 224 diabetic patients and 68 control subjects for this study.ResultsThere were markedly higher serum and vitreous fetuin-A concentrations in proliferative diabetic retinopathy (PDR) patients than in the other three groups. NPDR patients exhibited elevated vitreous fetuin-A concentrations compared with patients without DR. However, no significant differences in serum fetuin-A concentrations were observed between NPDR patients and patients without DR. In addition, there were significantly lower concentrations of serum and vitreous fetuin-A in control subjects compared with the other three groups.ConclusionsThe occurrence and severity of DR is correlated with serum and vitreous fetuin-A concentrations.

Assessment of macular function using the SKILL Card in adults with type 2 diabetes mellitus.

To evaluate the impact of reduced contrast and reduced luminance on visual acuity (VA) using the Smith-Kettlewell Institute Low Luminance (SKILL) Card in patients with type 2 diabetes mellitus (T2DM). We studied adults aged 27 to 65 years, 32 with T2DM and no retinopathy (NoRet group), 22 with T2DM and nonproliferative diabetic retinopathy (NPDR group), and 38 healthy control subjects. Monocular high-contrast (SKILL light) and low-contrast, low-luminance (SKILL dark) near visual acuities were tested. The SKILL score was calculated as the difference between dark chart and light chart acuities and was corrected for age. Contrast sensitivity (CS) was also measured. Subject group differences were examined using ANOVA and Tukey honestly significant difference test. Receiver operating characteristic curve analysis was used to assess the ability of the SKILL Card and CS to discriminate the subject groups. The SKILL score and CS were significantly worse in both diabetes groups compared with the controls (P < 0.01). SKILL scores in the NPDR group were poorest (highest) and significantly worse than those in the NoRet group (P < 0.05). SKILL scores discriminated NPDR and NoRet patients from the controls with high accuracy (99% and 88%, respectively), which was significantly (P < 0.03) better than CS (78% and 74%, respectively). The SKILL Card demonstrated vision function changes in diabetes even in the absence of clinically evident retinopathy. Diabetic retinopathy led to a further increase in the SKILL score, while high-contrast VA remained unchanged.

Association Between Thr21Met and Ser89Asn Polymorphisms of the Urotensin-II (UTS2) Gene, Diabetes Mellitus, and Diabetic Retinopathy

Purpose: To evaluate possible role of the UTS2 gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to diabetic retinopathy (DR) in a Turkish population.Methods: Total number of 280 patients with DR (nonproliferative DR 170 and proliferative DR 110), 291 nondiabetic healthy controls, and 113 diabetic controls (without DR) were included to this study. The detection of UTS2 gene polymorphisms was achieved with PCR-RFLP technique. The Discovery Studio 2.1 program was used for molecular modeling analysis.Results: Thr21Met (T21M) and Ser89Asn (S89N) polymorphisms of the UTS2 gene were associated with the risk of developing diabetes and DR. M21M genotype frequencies were high in PDR (8.9% in diabetic control vs. 54.6% in PDR, P = 0.0092) group. Increases in 21M allele frequency (52.7% in diabetic control vs. 76.4% in PDR, P < 0.0001) frequency in PDR group were detected. However, there were no changes in genotype and allele frequencies for T21M in NPDR group. There were decreases in the S89N genotype (23.9% in diabetic control vs. 13.5%) and 89N allele frequencies (11.9% in diabetic control vs. 6.8%) in NPDR group. However, S89S genotype (76.1% in diabetic control vs. 86.4%) and 89S allele frequencies (88.1% in diabetic control vs. 93.2%) were high in NPDR group. Three haplotypes (MN, MS and TS) were associated with NPDR patients (P < 0.001), but only MN (P < 0.001) and TS haplotypes (P = 0.018) were associated in PDR group. Molecular modeling analysis showed that these two polymorphisms changed the 3D structure of UTS2, and provided interactions with neighboring residues.Conclusion: The associations between Thr21Met and Ser89Asn polymorphisms in the UTS2 gene and DR strongly suggest that these SNPs may be an important a risk factor for the development of DR in Caucasians, and could be candidate markers for earlier diagnosis and targets for DR therapy.

In early-stage diabetic retinopathy, risk of cardiac events after implantation of sirolimus-eluting stent is higher than after coronary artery bypass surgery

Patients with diabetic retinopathy (DR) have an increased risk of death from coronary heart disease and myocardial infarction. The purpose of this study was to compare the outcomes of revascularization strategies (sirolimus-eluting stent [SES] and coronary artery bypass surgery [CABG]) in patients with DR according to the stage of retinopathy: non-proliferative retinopathy (NPDR) and proliferative retinopathy (PDR). From April 2004 until February 2007, 627 patients including 51 NPDR and 62 PDR patients underwent SES implantation. For each retinopathy group, a historical comparison group at the same stages of retinopathy undergoing CABG was selected. Cardiac events were defined as a composite of cardiac death, myocardial infarction, and repeat revascularization. The average follow-up from the time of the initial revascularization was 27.7 ± 8.5 months for NPDR-SES patients, 69.6 ± 36.6 months for NPDR-CABG patients, 26.4 ± 9.7 months for PDR-SES patients, and 68.3 ± 44.2 months for PDR-CABG patients; and Kaplan-Meier estimates of the percentages of events at 24 months were 47.0%, 22.8%, 28.5%, and 26.0%. Kaplan-Meier curves for cardiac events differed significantly between the SES group and the CABG group in NPDR patients (p = 0.04), whereas the curves did not differ significantly between the two groups of PDR patients. The adjusted hazard ratio of SES implantation for cardiac events in the entire group of DR patients was 1.75 (95% confidence interval [CI] 1.02-3.00, p = 0.04). SES implantation is not a suitable method of revascularization in DR patients, especially in NPDR patients. CABG may become the first-choice revascularization technique for these patients.

Comparison of serum NO, TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels with grades of retinopathy in patients with diabetes mellitus.

Vitreal interleukin (IL)-1beta (IL-1beta), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels have previously been determined in patients with proliferative diabetic retinopathy (PDR). However, at present there is no cohort study linking serum levels of NO and many inflammatory cytokines such as TNF-alpha, IL-1beta, soluble IL-2 receptor (sIL-2R), IL-6 and IL-8 to the grade of the microvascular complications. To determine the relation between the stages of DR and the levels of serum NO, TNF-alpha, IL-1beta, sIL-2R, IL-6 and chemokine IL-8 in patients with diabetes compared with healthy controls. Fifty-three consecutive patients with diabetes (25 men, 28 women) with or without DR and 15 non-diabetic healthy subjects (seven men, eight women) as controls were included in this prospective study. As an indicator for NO, serum total nitrite (NO2- + NO3-) levels (end-product of NO) were measured by the Griess reaction. Serum TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels were determined by a spectrophotometric technique using an Immulite chemiluminescent immunometric assay. The patients with diabetes were classified into three groups according to the stage of DR: no DR (NDR; n = 16), non-proliferative DR (NPDR; n = 18) and PDR (n = 19). The data were analysed using a Mann-Whitney U-test and the results were expressed as mean +/- SE (range). The levels of IL-1beta and IL-6 were below the detection limits of the assay (for each, <5.0 pg/ml) in all patients with diabetes and controls. Soluble IL-2R levels ranged from 260 to 958 U/ml, with the highest values observed in the patients with PDR. In 47 of the 53 samples (89%) tested for diabetic patients, IL-8 levels were above the detection limits of the assay (5.0 pg/ml). IL-8 levels ranged from <5.0 to 25.0 pg/ml, with the highest mean values observed in PDR patients. TNF-alpha was detectable in 46 of 53 patients with diabetes (87%), ranging from <4.0 to 26.4 pg/ml, with again the highest values obtained in the patients with PDR. Serum NO levels ranged from 80 to 188 micromol/l, with the highest values obtained in patients with PDR. Taken together, the mean serum NO, sIL-2R, IL-8 and TNF-alpha levels increased with the stage of DR and the highest levels were found in patients with PDR. The PDR patients had significantly (for each, P < 0.001) higher serum NO (166.8 +/- 3.2 micromol/l), sIL-2R (807.9 +/- 33.3 U/ml), IL-8 (17.9 +/- 0.4 pg/ml) and TNF-alpha (15.0 +/- 0.8 pg/ml) levels compared with NPDR patients (149.5 +/- 2.1, 659.4 +/- 23.4, 12.9 +/- 1.1, 11.5 +/- 0.6, respectively), NDR patients (115.9 +/- 5.8, 373.8 +/- 15.0, 8.3 +/- 1.0, 6.6 +/- 0.9, respectively) and controls (116.6 +/- 2.3, 392.4 +/- 16.6, 7.2 +/- 0.3, 7.3 +/- 0.5, respectively). Serum levels of these parameters for NPDR patients were also significantly (for each, P < 0.01) higher compared with those of NDR patients and controls. On the other hand, serum NO, sIL-2R, IL-8 and TNF-alpha levels of patients with NDR were comparable with those of controls (for each, P > 0.05). The results of the present study suggest that NO, sIL-2R, IL-8 and TNF-alpha may play important roles in the pathophysiology and progression of DR. We think that these potentially inflammatory cytokines and NO with their endothelial implications may act together during the course and progression of DR. These molecules may serve as therapeutic targets for the treatment and/or prevention of diabetes with its systemic and ocular microvascular complications.

Human Lymphocyte Antigen DR7 Protects Against Proliferative Retinopathy with Type II Diabetes Mellitus

Background This study was undertaken in order to analyze the genetic incidence of human lymphocyte antigen diabetic retinopathy (HLA-DR) and its influence in proliferative diabetic retinopathy (PDR). Methods We designed a case-control study in which 127 mestizo Mexican patients with DM II and diabetic retinopathy were studied. DNA was extracted and HLA-DR regions were amplified using PCR. Alleles were determined by DNA hybridization. Diagnosis was assessed clinically and by fluorescein angiography. Incidence of HLA-DR alleles in patients was compared with an ethnically matched control group of healthy subjects ( n = 98). Statistical significance was established with non-parametric tests. Results Patients with diabetic retinopathy showed less frequency of HLA-D11 compared with the control group ( p = 0.043). NPDR patients with 10 or more years of DM II showed an increase of HLA-DR7 ( p = 0.01). Conclusions Our results suggest that the presence of HLA-DR7 protects against the development of proliferative disease in the diabetic Mexican population.