Mild Non-proliferative Diabetic Retinopathy Group Research Articles

Rod photoreceptor activation and deactivation in early-stage diabetic eye disease.

To infer rod phototransduction activation and deactivation characteristics in diabetics who have mild or no clinically-apparent retinopathy. Fifteen non-diabetic controls, 15 diabetics with no clinically-apparent diabetic retinopathy (NDR), and 15 diabetics with mild non-proliferative diabetic retinopathy (MDR) participated. Dark-adapted flash electroretinograms (3.2 to 4.4 log scot td-s) were recorded to assess rod activation. The a-waves were fit with a Gaussian model to derive Rmp3 (maximum photoreceptor response amplitude) and S (phototransduction sensitivity). Rod deactivation was assessed with a paired flash paradigm, in which a-waves were measured for two flashes separated by inter-stimulus intervals (ISIs) of 0.125 to 16s. The ISI needed for the a-wave amplitude of the second flash to recover to 50% of the first flash (t50) was determined. The effect of stimulus retinal illuminance on activation and deactivation was evaluated in a subset of control subjects. Analysis of variance indicated that both diabetic groups had significant log S reductions compared to controls (p < 0.001). Mean S was reduced by approximately 49% and 78% for the NDR and MDR groups, respectively. In contrast, log Rmp3 and log t50 did not differ significantly among the groups (both p > 0.08). Reducing stimulus retinal illuminance significantly reduced S, but did not significantly affect Rmax or t50. Only phototransduction sensitivity was abnormal in this sample of diabetic subjects. The normal deactivation kinetics suggests that circulating rod current is normal. These findings begin to constrain possible explanations for abnormal rod function in early diabetic retinal disease.

The Correlation between the Level of Skin Advanced Glycation End Products in Type 2 Diabetes Mellitus and the Stages of Diabetic Retinopathy and the Types of Traditional Chinese Medicine Syndrome.

Objective We aimed to analyze the correlation between the level of skin advanced glycation end products (AGEs) in type 2 diabetes mellitus (T2DM) patients and the diabetic retinopathy (DR) staging in different traditional Chinese medicine (TCM) syndromes. Methods 416 T2DM patients were divided into normal group, nonproliferative diabetic retinopathy (NPDR) group (mild, moderate, and severe), and proliferative diabetic retinopathy (PDR) group according to the DR grade. Patients' height, weight, fasting blood glucose (FBG), hemoglobin A1C (HbA1c), blood lipid, renal function, and skin AGEs were measured. According to TCM syndrome differentiation criteria, 230 patients with T2DM and DR were divided into I. qi and yin deficiency, collateral stasis group; II. liver and kidney deficiency, eye collaterals loss group; and III. yin and yang deficiency, blood stasis, and phlegm coagulation group. Results The skin AGEs levels of different DR staging groups were statistically significant (P < 0.05), and the skin AGEs levels in the mild and moderate NPDR groups were significantly higher (P < 0.05) than those of the normal group. It was significantly higher (P < 0.05) in the severe NPDR group than in the normal group, mild and moderate NPDR groups. The skin AGEs levels of the PDR group were significantly higher (P < 0.05) than the normal group, mild and moderate NPDR groups. It was positively correlated with DR stage, HbA1c, total cholesterol (TC), low-density lipoprotein (LDL), and urine metal analysis (UMA) (r = 0.467, 0.411, 0.413, 0.503, 0.424, P < 0.05). The skin AGEs levels of the qi and yin deficiency and collaterals stasis syndrome group were significantly higher (P < 0.05) than in the liver and kidney deficiency and eye collaterals loss groups. It was also significantly higher (P < 0.05) in yin and yang deficiency, blood stasis, and phlegm coagulation syndrome groups than in qi and yin deficiency and collaterals stasis syndrome groups. Conclusion There is a positive correlation between skin AGEs and DR staging in T2DM patients. Skin AGEs level is predictive for the risk of DR complications in T2DM patients and is vital in assessing DR degree per TCM syndrome type.

Association of Resolved Paracentral Acute Middle Maculopathy Lesions with Diabetic Retinopathy.

To evaluate the association between paracentral acute middle maculopathy (PAMM) lesions and diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). Thirteen diabetic patients without DR, 13 patients with mild nonproliferative DR (NPDR), 18 patients with moderate-to-severe NPDR, and 20 patients with proliferative DR (PDR) were included in this retrospective study. For each patient, 6 mm × 6 mm macular OCTA scans of both eyes were reviewed for the presence of acute and resolved PAMM lesions. Among diabetic patients with and without DR, 49 (94.9%) and 7 (53.8%) patients demonstrated small resolved PAMM lesions, respectively. The odds ratio for the presence of resolved PAMM lesions in the eye with DR compared to the eye of diabetic patient without DR was 21.8 (P < 0.001, 95% confidence interval 7.0-67.8). In the mild NPDR group, moderate-to-severe NPDR group, and the PDR group, 11 (84.6%), 18 (100.0%), and 20 (100.0%) patients demonstrated resolved PAMM lesions, respectively. There was a statistically significant increasing prevalence of PAMM lesions as the severity of DR increased (P < 0.001). Small resolved PAMM lesions are a common form of ischemic retinal lesions in DR.

The Assessment of Blood Flow Velocities in Retinal Collaterals in Diabetic Retinopathy.

Diabetic retinopathy (DR) is a microvascular disease characterized by capillary dropout and resultant retinal ischemia which then leads to retinal vascular remodeling. Our goal was to assess blood flow velocities in retinal collateral vessels in healthy and diabetic subjects with various stages of DR. In our pilot study, we enrolled five eyes of five healthy subjects (H), five eyes of four subjects with diabetes and no retinopathy (DM), three eyes of three subjects with mild non-proliferative diabetic retinopathy (MDR), and five eyes of four subjects with proliferative diabetic retinopathy (PDR). Following routine ophthalmic examination, all subjects were imaged using a retinal function imager (RFI; Optical Imaging Inc., Rehovot, Israel). The built-in software of the RFI was used to identify and segment retinal collaterals with measurement of the blood flow velocities (BFV). One-way ANOVA was performed for BFV, followed by Newman-Keuls post hoc test. The level of significance was set at 5%. The total number of collateral segments involved in the study was 30, 31, 21, and 39 in the H, DM, MDR, and PDR groups, respectively. The BFVs in the collaterals were significantly lower in PDR (H: 1.86 ± 0.67, DM: 1.91 ± 0.71, MDR: 1.71 ± 0.53, PDR: 1.37 ± 0.58 mm/s). The PDR group showed a statistically significant difference in the comparisons to all groups (p = 0.012, p = 0.008, and p = 0.043 for the H, DM, and MDR groups, respectively), while no other comparisons between the groups were significant. We observed decreased BFV in retinal collaterals in PDR that may be due to the extensive capillary dropout and retinal ischemia. Further studies are needed for the noninvasive functional assessment of retinal microvascular changes in DR to better understand the underlying pathophysiology.

Evaluation of choroidal thickness in different stages of diabetic retinopathy

Purpose: to assess changes of choroidal thickness (CT) in diabetic patients in different stages of diabetic retinopathy and diabetic macular edema using spectral domain optical coherence tomography. Patients and methods: One hundred and sixty three subjects were enrolled: 113 diabetic patients (186 eyes) and 50 normal individuals as controls. Eyes were divided into two groups according to age; group A from 35 to 50 years and group B from 51 to 65 years. Both groups classified according to retinopathy grade: DR1 (no DR), DR2 (mild- moderate nonproliferative diabetic retinopathy (NPDR)), DR3 (severe NPDR), DR4 (untreated proliferative diabetic retinopathy (PDR)) and DR5 (previously treated PDR). All participants underwent full ophthalmic examination, stereoscopic color fundus photography, and spectral domain optical coherence tomography (RS-3000; Nidek). Spectral domain optical coherence tomography examination consisted of linear scans, 6 mm in length, centered onto the fovea, and macula multi scans. Choroidal thickness was measured manually at the fovea and at 500, 1000, and 1500 um distance along all scans in the macula. Results: Mean age was not significantly different between patients with diabetes and controls. In the macular area, CT was significantly lower in the nasal quadrant versus all other quadrants (P, 0.0001), in both groups. No significant CT difference was found between controls and diabetic eyes without detectable DR. Diabetic macular edema did not influence CT. In early NPDR (mild and moderate) and treated PDR the mean choroidal thickness was significantly decreased than control. In severe NPDR and treated PDR, the mean subfoveal choroidal thickness was not different than control. There was a statistically significant increase in choroidal thickness in PDR when compared with the mild NPDR group (P=0.027). DME was associated with a non-statistically significant increase in choroidal thickness compared with eyes without DME (P=0.13). Conclusion: Choroidal thickness is reduced in diabetic eyes. Subfoveal choroidal thickness increased with the severity of diabetic retinopathy but showed no statistically significant association with the presence of DME. Spectral domain optical coherence tomography clearly confirms in vivo previously reported histopathologic observations. The role of choroid in the pathophysiology of DR needs to be adequately investigated.

Reduced Contrast Sensitivity is Associated With Elevated Equivalent Intrinsic Noise in Type 2 Diabetics Who Have Mild or No Retinopathy.

PurposeTo evaluate explanations for contrast sensitivity (CS) losses in subjects who have mild nonproliferative diabetic retinopathy (NPDR) or no diabetic retinopathy (NDR) by measuring and modeling CS in luminance noise.MethodsTen diabetic subjects with NDR, 10 with mild NPDR, and 10 age-equivalent nondiabetic controls participated. Contrast threshold energy (Et) was measured for letters presented in the absence of noise (Et0) and in four levels of luminance noise. Data were fit with the linear amplifier model to estimate inferred noise level within the visual pathway (Neq) and sampling efficiency (ability to use stimulus information optimally). Et0, Neq, and efficiency were compared to clinical characteristics.ResultsNeq was correlated with Et0 for the diabetic subjects (r = 0.93, P < 0.001) and ranged from normal to 12-times the upper limit of normal. ANOVA indicated significant differences among the subject groups for Et0 and Neq (both F > 11.92, P < 0.001). Et0 and Neq were elevated for the mild NPDR group compared to the control and NDR groups (all t > 3.89, P ≤ 0.001); the NDR and control groups did not differ significantly (all t < 0.61, P > 0.55). There were no significant efficiency differences among the groups (F = 1.29, P = 0.29). Neq was correlated significantly with disease duration, microperimetric sensitivity, and Pelli-Robson CS.ConclusionsElevated contrast threshold may be associated with increased intrinsic noise in early-stage diabetic subjects. Results suggest that noise-based CS measurements can provide important information about early neural dysfunction in these individuals.

Correlation of peripapillary retinal nerve fiber layer thickness and ganglion cell complex thickness with the severity of diabetic retinopathy

Purpose The aim of this study was to verify the role of peripapillary retinal nerve fiber layer thickness (RNFLT) and ganglion cell (GC) complex thickness in early detection of diabetic retinopathy (DR) using spectral domain optical coherence tomography (SD-OCT). Patients and methods This was a cross-sectional, case–control study. Twenty-nine eyes of patients with type 2 diabetes mellitus, either with no DR (16 eyes, group 1) or mild nonproliferative DR (13 eyes, group 2), and 14 eyes of healthy controls (group 3) were enrolled in the present study. All participants had a complete ophthalmic examination, including SD-OCT. Ganglion cell inner plexiform layer (GCIPL) and RNFLT values were calculated after automated segmentation of SD-OCT scans. Results Significantly reduced GCIPL and RNFLT values were demonstrated in both diabetic patients’ groups compared with healthy controls. Mean GCIPL thickness was 97.5 µm in group 1, 96.9 µm in group 2, and 107.9 µm in group 3 (P=0.04 and 0.04 compared with healthy controls, respectively). Average RNFLT was 104.12±9.6 µm in diabetes patients with no DR (group 1), 100.46±12.86 µm in group 2, and 111.35±6.15 µm in controls (P=0.02 and 0.009 compared with healthy controls, respectively). Conclusion Significantly reduced GCIPL and RNFLT values were demonstrated in both no DR and mild nonproliferative DR groups compared with healthy controls. This indicates that retinal neuronal degeneration occurs in the early stages of DR, even before microvascular abnormalities are visible.

Association of Glycated Haemoglobin and Serum Apolipoproteins with Diabetic Retinopathy: An Indian Overview.

India is presently facing an epidemic of diabetes mellitus and the risks of chronic complications from the disease are associated with the duration of the disease as well as the degree of hyperglycaemia. Diabetic retinopathy is a known microvascular complication of diabetes mellitus and is the most common cause of blindness in the western countries.Apolipoproteins are the protein component of lipoproteins. Apart from acting as structural proteins, they also act as cofactors to various enzymes. To measure the levels of serum apolipoproteins and glycated haemoglobin in cases of diabetic retinopathy and to assess their association with the stages of diabetic retinopathy. The 135 diabetic cases [with (110) and without (125) retinopathy] attending the Ophthalmology OPD of this tertiary care hospital were included in the present study. Following retinoscopy, the patients were classified as Non-Proliferative Diabetic Retinopathy (NPDR) (n=75) and Proliferative Diabetic Retinopathy (PDR) (n=35). The controls (n=100) were age and sex matched patients who did not have diabetes. The cases and controls were assessed for HbA1c, total cholesterol, triglycerides, HDL cholesterol, Apo A-I and Apo B-100. The HbA1c was found to be higher in diabetics without retinopathy (7.02%) as compared to controls (5.58%) (p<0.05) and the highest value was seen in the mild NPDR group (8.82%). The mean value of Apo A-I was found to be lowest in the diabetics without retinopathy at 88 mg/dl and the highest in severe NPDR at 167 mg/dL. The mean value of Apo B-100 was found to be highest in severe NPDR at 114 mg/dL. The mean value of HDL cholesterol was lowest in moderate NPDR at 36.6 mg/dl. Total cholesterol was highest in severe NPDR at 280.88mg/dl while triglyceride was highest in severe NPDR at 286.4mg/dl. In our study, the level of HbA1c was found to range from 5.58% in non-diabetic to 8.82% in mild NPDR. There was a clear association between Apo B-100 and total cholesterol, triglycerides with the highest value of each parameter seen in the severe NPDR group. There was a discordance noted in the levels of HDL and Apo A-I in various groups. Apo B-100 values may be of value in prognosis of diabetic retinopathy as higher values may result in progression of the disease. Further studies involving Lp(a) and homocysteine may be required in cases of diabetic retinopathy.

Subfoveal choroidal thickness in patients with diabetic retinopathy and diabetic macular oedema.

PurposeTo investigate the relationship between subfoveal choroidal thickness, severity of diabetic retinopathy (DR), and the presence of diabetic macular oedema (DMO) using enhanced depth imaging spectral domain optical coherence tomography (EDI-OCT) in patients with type 2 diabetes.MethodsA retrospective study of 145 eyes from untreated, type 2 diabetic patients who attended clinic at the Oxford Eye Hospital between January 2012 and February 2013, and underwent fundus photography and EDI-OCT imaging. Eyes were divided into two groups based on the presence or absence of foveal involving DMO and classified according to retinopathy grade: R1 (mild non-proliferative diabetic retinopathy (NPDR), R2 (moderate-severe NPDR), and R3 (proliferative diabetic retinopathy (PDR). Subfoveal choroidal thickness was measured on the EDI-OCT images and statistically analysed using Student's t-test.ResultsIn mild NPDR (n=87), the mean subfoveal choroidal thickness was 217.7 microns. In moderate-severe NPDR (n=37), the mean subfoveal choroidal thickness was 221.7 microns. In PDR (n=21), the mean subfoveal choroidal thickness was 242.1 microns. There was a statistically significant increase in choroidal thickness in PDR when compared with the mild NPDR group, P=0.027. DMO was associated with a non-statistically significant increase in choroidal thickness (225.4 microns) compared with eyes without DMO (209.3 microns), P=0.13.ConclusionSubfoveal choroidal thickness increased with the severity of diabetic retinopathy but showed no statistically significant association with the presence of DMO. This suggests that the choroidal layer is responsive to retinal vascular changes.

Matrix Metalloproteinase-1 and Matrix Metalloproteinase-9 in the Aqueous Humor of Diabetic Macular Edema Patients.

PurposeTo assess the concentrations of matrix metalloproteinase (MMP)-1 and MMP-9 in the aqueous humor of diabetic macular edema (DME) patients.MethodThe concentrations of MMP-1 and MMP-9 in the aqueous humors of 15 cataract patients and 25 DME patients were compared. DME patients were analyzed according to the diabetic retinopathy (DR) stage, diabetes mellitus (DM) duration, pan-retinal photocoagulation (PRP) treatment, recurrence within 3 months, HbA1C (glycated hemoglobin) level, and axial length.ResultsThe concentrations of MMP-1 and MMP-9 of the DME groups were higher than those of the control group (p = 0.005 and p = 0.002, respectively). There was a significant difference in MMP-1 concentration between the mild non-proliferative diabetic retinopathy (NPDR) group and the proliferative diabetic retinopathy (PDR) group (p = 0.012). MMP-1 concentrations were elevated in PRP-treated patients (p = 0.005). There was a significant difference in MMP-9 concentrations between the mild NPDR group and the PDR group (p < 0.001), and between the moderate and severe NPDR group and the PDR group (p < 0.001). The MMP-9 concentrations in PRP treated patients, DM patients with diabetes ≥ 10 years and recurrent DME within 3months were elevated (p = 0.023, p = 0.011, and p = 0.027, respectively). In correlation analyses, the MMP-1 level showed a significant correlation with age (r = -0.48, p = 0.01,), and the MMP-9 level showed significant correlations with axial length (r = -0.59, p < 0.01) and DM duration (r = 049, p = 0.01).ConclusionsConcentrations of MMP-1 and MMP-9 were higher in the DME groups than in the control group. MMP-9 concentrations also differed depending on DR staging, DM duration, PRP treatment, and degree of axial myopia. MMP-9 may be more important than MMP-1 in the induction of DM complications in eyes.

High-Resolution Imaging of Parafoveal Cones in Different Stages of Diabetic Retinopathy Using Adaptive Optics Fundus Camera.

PurposeTo assess cone density as a marker of early signs of retinopathy in patients with type II diabetes mellitus.MethodsAn adaptive optics (AO) retinal camera (rtx1™; Imagine Eyes, Orsay, France) was used to acquire images of parafoveal cones from patients with type II diabetes mellitus with or without retinopathy and from healthy controls with no known systemic or ocular disease. Cone mosaic was captured at 0° and 2°eccentricities along the horizontal and vertical meridians. The density of the parafoveal cones was calculated within 100×100-μm squares located at 500-μm from the foveal center along the orthogonal meridians. Manual corrections of the automated counting were then performed by 2 masked graders. Cone density measurements were evaluated with ANOVA that consisted of one between-subjects factor, stage of retinopathy and the within-subject factors. The ANOVA model included a complex covariance structure to account for correlations between the levels of the within-subject factors.ResultsTen healthy participants (20 eyes) and 25 patients (29 eyes) with type II diabetes mellitus were recruited in the study. The mean (± standard deviation [SD]) age of the healthy participants (Control group), patients with diabetes without retinopathy (No DR group), and patients with diabetic retinopathy (DR group) was 55 ± 8, 53 ± 8, and 52 ± 9 years, respectively. The cone density was significantly lower in the moderate nonproliferative diabetic retinopathy (NPDR) and severe NPDR/proliferative DR groups compared to the Control, No DR, and mild NPDR groups (P < 0.05). No correlation was found between cone density and the level of hemoglobin A1c (HbA1c) or the duration of diabetes.ConclusionsThe extent of photoreceptor loss on AO imaging may correlate positively with severity of DR in patients with type II diabetes mellitus. Photoreceptor loss may be more pronounced among patients with advanced stages of DR due to higher risk of macular edema and its sequelae.

Scanning laser edema index: A reliable tool to correlate with diabetic retinopathy and systemic risk factors?

To correlate Heidelberg Retina Tomograph (HRT) derived macular edema (DME) index with severity of diabetic retinopathy and systemic factors.A total of 300 diabetic patients were recruited for the study for each of them a value for the macular edema index was obtained using the HRT II. Patients' age, gender, duration and type of diabetes mellitus, latest HbA1c result and presence or absence of co-morbid factors (hypertension, ischemic heart disease, nephropathy) were recorded together with the stage of diabetic retinopathy. These were correlated with DME.Out of 300 patients, HRT defined macula edema was seen in 68 patients (22.6%). There is a wider and higher range (95% percentile) of macula edema index in the severe non proliferative diabetic retinopathy (NPDR) group. Independent samples t test showed significant difference between the severe NPDR group and no DR group (p<0.001), mild NPDR group (p<0.05) and moderate NPDR group (p<0.05). A higher macula edema index was also found to have a low degree of correlation with more advanced stages of retinopathy (r=0.310; p<0.001). Also nephropathy showed a strong and significant correlation with DME. Hypertension had moderately significant correlation with DME. This study found no correlation between ischemic heart disease and DME.HRT derived scanning laser edema index is a reliable objective tool to evaluate diabetic retinopathy and systemic risk factors.

Association Between Diabetic Retinopathy and Flow-Mediated Vasodilation in Type 2 DM

Objective: Retinal endothelial dysfunction is a key in the etiogenesis of diabetic retinopathy (DR), in patients with type 2 diabetes mellitus (DM). Brachial artery flow-mediated vasodilation (FMD) is a marker of endothelial function associated with production of endogenous nitric oxide. Using FMD, we investigated the relationship between macrovascular function and DR.Methods: We studied 74 patients with type 2 DM, including non-DR (NDR) (n = 30); mild nonproliferative DR (NPDR) (n = 16); moderate NPDR (n = 10); severe NPDR (n = 10); and proliferative DR (PDR) (n = 8); and 21 age-matched controls. We measured FMD in each group. Retinal blood flow and pulsatility ratios were measured using laser Doppler velocimetry.Results: FMD decreased significantly in patients with DM compared with healthy control subjects. No significant differences were found in FMD among the NDR, mild NPDR, and moderate NPDR groups. FMD decreased significantly in the severe NPDR and PDR groups compared with the NDR group. FMD was significantly and negatively correlated with duration of DM and pulsatility ratio.Conclusion: Systemic endothelial dysfunction appears to be associated with DR and vascular abnormalities in patients with type 2 DM.

Impaired Retinal Circulation in Patients with Type 2 Diabetes Mellitus: Retinal Laser Doppler Velocimetry Study

To evaluate the differences in retinal circulation in eyes of patients with type 2 diabetes with no or early-stage diabetic retinopathy compared with control eyes. Seventy-five nondiabetic eyes and 194 eyes with type 2 diabetes mellitus were evaluated. The type 2 diabetic eyes were classified into two groups: 139 eyes (139 patients) without diabetic retinopathy (NDR) and 55 eyes (55 patients) with mild nonproliferative diabetic retinopathy (NPDR). The retinal circulatory parameters were measured with laser Doppler velocimetry, and the factors that affect retinal hemodynamics were determined in a cross-sectional population of patients with type 2 diabetes. The group-averaged blood velocity (V) and retinal blood flow (RBF) in the NDR and mild NPDR groups were significantly (P < 0.01) lower than in the non-DM group. The diameter and wall shear rate were also significantly (P < 0.05) lower in the NDR group than in the nondiabetic control eyes. Multiple regression analysis showed that the RBF was independently and negatively correlated with serum low-density lipoprotein and creatinine. HbA1c was significantly (P < 0.05) higher in participants in the lowest RBF quartile than in the highest quartiles. The results indicate that the RBF may decrease in patients with type 2 diabetes without retinopathy and in those with mild retinopathy.