Non-proliferative Diabetic Retinopathy Cases Research Articles

Prevalence and associated factors of diabetic retinopathy among type 2 diabetes in Dongcheng District and Tongzhou District, Beijing City: a cross-sectional study

Objective: Diabetic retinopathy (DR) is the most common cause of adult blindness in China. Screening of DR is important for early detection, prevention, and treatment. However, there is still controversy in the research on the prevalence and risk factors of DR in China. This study was designed to evaluate the prevalence of DR and related risk factors in patients with type 2 diabetes mellitus in Beijing City. Methods: A cross-sectional survey was conducted in in Dongcheng District and Tongzhou District, Beijing City. Patients with type 2 diabetes aged 18-80 years were selected from four communities, and all subjects underwent questionnaires, physical examinations, laboratory examinations and fundus photography. The logistic regression model was used to analyze the associated factors of DR. Results: A total of 1 531 subjects were included, with the median age of 66 years old and the average age of (65.6±7.4) years old, and the glycosylated hemoglobin level in the subjects was 7.2%±1.3%, and the glycosylated hemoglobin compliance rate was 56.0%(857/1 531). A total of 254 patients with diabetic retinopathy were detected, and the prevalence of DR was 16.6%(254/1 531). Among them, there were 218 cases of non-proliferative diabetic retinopathy and 36 cases of proliferative diabetic retinopathy. Compared with the non-DR group, there were statistically significant differences in fasting blood glucose (Z=-3.74, P<0.001), glycosylated hemoglobin(Z=-10.664, P<0.001), urinary microalbumin excretion rate(Z=-7.767,P<0.001), low-density lipoprotein cholesterol(Z=-2.589, P=0.01), and duration of diabetes(Z=-10.189, P<0.001) between the DR group and the non-DR group. Multivariate regression analysis showed that the duration of diabetes (OR=1.08, 95%CI: 1.06-1.10, P<0.001), glycosylated hemoglobin (OR=1.38, 95%CI: 1.23-1.55, P<0.001), and FPG (OR=1.11, 95%CI: 1.03-1.19, P=0.008) were associated factors for DR. Conclusion: In this study, the prevalence of DR in 4 communities of type 2 diabetes in Beijing City was 16.6%. Besides, this study further confirmed that the duration of diabetes, fasting blood glucose levels, and glycosylated hemoglobin are associated factors for DR in patients with type 2 diabetes.

Retinal Transcriptome and Cellular Landscape in Relation to the Progression of Diabetic Retinopathy.

PurposePrevious studies that identify putative genes associated with diabetic retinopathy are only focusing on specific clinical stages, thus resulting genes are not necessarily reflective of disease progression.This study identified genes associated with the severity level of diabetic retinopathy using the likelihood-ratio test (LRT) and ordinal logistic regression (OLR) model, as well as to profile immune and retinal cell landscape in progressive diabetic retinopathy using a machine learning deconvolution approach.MethodsThis study used a published transcriptomic dataset (GSE160306) from macular regions of donors with different degrees of diabetic retinopathy (10 healthy controls, 10 cases of diabetes, 9 cases of nonproliferative diabetic retinopathy, and 10 cases of proliferative diabetic retinopathy or combined with diabetic macular edema). LRT and OLR models were applied to identify severity-associated genes. In addition, CIBERSORTx was used to estimate proportional changes of immune and retinal cells in progressive diabetic retinopathy.ResultsBy controlling for gender and age using LRT and OLR, 50 genes were identified to be significantly increased in expression with the severity of diabetic retinopathy. Functional enrichment analyses suggested these severity-associated genes are related to inflammation and immune responses. CCND1 and FCGR2B are further identified as key regulators to interact with many other severity-associated genes and are crucial to inflammation. Deconvolution analyses demonstrated that the proportions of memory B cells, M2 macrophages, and Müller glia were significantly increased with the progression of diabetic retinopathy.ConclusionsThese findings demonstrate that deep analyses of transcriptomic data can advance our understanding of progressive ocular diseases, such as diabetic retinopathy, by applying LRT and OLR models as well as bulk gene expression deconvolution.

Plasma miR-26a-5p is a biomarker for retinal neurodegeneration of early diabetic retinopathy.

Retinal neurodegeneration is an early pathological change in diabetic retinopathy (DR). Early-stage retinal neurodegeneration is usually asymptomatic. This study aims to identify circulating microRNAs (miRNAs) as sensitive biomarkers for early retinal neurodegeneration. We profiled the plasma miRNA expression in three mild nonproliferative diabetic retinopathy (NPDR) cases and three matched non-DR patients using RNA sequencing. The differential miRNAs were validated with qRT-PCR. The retinal nerve fibre layer (RNFL) thickness of the eyes was measured using spectral-domain Optical coherence tomography (SD-OCT). The association between differential miRNAs and RNFL thickness was analysed using the Pearson correlation analysis. Bioinformatics tools were used to predict potential targets of miRNA associated with RNFL thickness and investigate the functions of the potential target genes. RNA sequencing identified 69 differential miRNAs and eight of them were reported to be associated with DR. The qRT-PCR for these eight miRNAs validated the down-regulation of circulating miR-26a-5p and miR-126-5p in a larger validating cohort. A positive correlation between plasma miR-26a-5p level and the RNFL thickness of the superior quadrant of both eyes was identified in another cohort, including 33 mild NPDR cases, 33 matched non-DR patients and 20 healthy controls. Furthermore, 367 candidate targets of miR-26a-5p were predicted. The functional studies revealed that these target genes are profoundly involved in various cellular functions and signalling pathways. Circulating miR-26a-5p is a potential biomarker for early-stage retinal neurodegeneration and it may be involved in the development of DR via profoundly influencing the functions of retinal cells.

Study on the correlation between the level of bioactive factors in the blood and severity of diabetic retinopathy

Objective To analyse the correlation between the level of related bioactive factors in the blood and severity of diabetic retinopathy(DR). Methods The data of 100 patients with DR admitted in Traditional Chinese Medical Hospital of Huangdao District from Jun.2016 to Dec.2018 were selected in the prospective study. There were 50 cases of non-proliferative DR and 50 cases of proliferative DR. At the same time, 50 non-DR diabetic patients and 50 healthy people were selected as the healthy control group. The levels of Apelin, TNFR and MK in the blood were detected and the correlation between the level of bioactive factors and severity of the disease was analyzed. Results The difference in levels of Apelin, TNFR and Midkine in the blood were statistically significant among the four groups (P<0.05), and the levels of Apelin, TNFR and Midkine were the highest in the proliferative DR group; the levels of Apelin, TNFR and Midkine were positively correlated with the severity of DR patients (P<0.05). The specificity of DR and the area under the receiver operating characteristic curve were significantly higher than those of Apelin, TNFR and Midkine alone (P<0.05). Conclusion The levels of Apelin, TNFR and Midkine increase with the aggravation of DR. The combined detection of Apelin, TNFR and Midkine can help to improve the diagnostic value of DR. Key words: Apelin; TNFR; Midkine; Diabetic retinopathy; Severity

Efficacy of the ranibizumab combined with panretinal photocoagulation for the treatment of diabetic retinopathy

Objective To evaluate the clinical efficacy of intravitreal injection of ranibizumab combined with panretinal photocoagulation for the treatment of nonproliferative diabetic retinopathy(DR). Methods The data of 104 eyes of 65 cases of nonproliferative DR were retrospectively analyzed.All cases received intravitreal injection of ranibizumab combined with panretinal photocoagulation.The followed-up time was 6 months. Results The visual acuity improved in 42 eyes, no changed in 55 eyes. The efficacy rate was 93.37%.The results of FFA showed markedly effective in 42 cases (40.38%), effective in 34 cases (32.69%) and ineffective in 24 cases (22.93%). The results of OCT showed that, the macular retinal thickness were (367.56±78.34)μm before treatment and(225.12±35.78)μm half a year after treatment. The difference was statistically significant (P<0.05). Conclusion Intravitreal injection of ranibizumab combined with panretinal photocoagulation for the treatment of nonprotiferative DR is effective. Key words: Retinopathy, diabetic, nonproliterative; Ranibizumab, intravitreal injection; Photocoagulation, panretinal

OUTER RETINAL LAYER THICKNESS AS GOOD VISUAL PREDICTOR IN PATIENTS WITH DIABETIC MACULAR EDEMA.

To evaluate the relationship between outer retinal layer (ORL) thickness in diabetic macular edema to visual acuity (VA). Ninety-five eyes were included in this prospective nonrandomized case-control study. They divided into 30 cases of healthy normal subjects and 65 cases of nonproliferative diabetic retinopathy with diabetic macular edema. Complete ophthalmic examination and spectral domain-optical coherence tomography were done for all cases and analyzed to measure central foveal point thickness (CFT), ORL thickness at fovea, and subfoveal choroidal thickness. The ORL thickness was significantly thinner in diabetic macular edema group (85.3 μm) than controls (99.9 μm) (P = 0.002). There was higher significant correlation between ORL thickness and logMAR VA (r = -0.87, P < 0.001) than correlation between CFT and VA (r = 0.18, P = 0.16). The cutoff point of the relationship between ORL thickness and VA was 88 μm with moderate sensitivity (81%) and high specificity (88%), below which vision is affected. Outer retinal layer thickness is significantly related to subfoveal choroidal thickness but not CFT. This study revealed reduction in ORL thickness in diabetic macular edema. There is a higher and stronger correlation between ORL thickness and vision than that between CFT and vision.

Choroidal Thickness Change in Patients With Diabetic Macular Edema.

To evaluate subfoveal choroidal thickness (SFCT) in diabetic macular edema (DME) and its relationships. One hundred and six eyes were included in this prospective, nonrandomized case control study. They were divided into 37 cases of healthy, normal subjects and 69 cases of nonproliferative diabetic retinopathy (NPDR) with DME. Spectral-domain optical coherence tomography was done for all cases and analyzed to measure SFCT and central foveal thickness (CFT). The SFCT was significantly thinner in the DME group (193.4 μm) than in the control group (282.6 μm) (P = .001). In the DME group, SFCT was significantly related to CFT and vision (P < .05). The cutoff point for the relationship between SFCT and vision was 228 μm below the point at which vision is affected. DME is associated with a significant decrease in SFCT. SFCT is directly related to vision and foveal thickness, but it is inversely correlated to age. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:970-977.].

Proliferative retinopathy during hyperbaric oxygen treatment

A 43-year-old male with type 2 diabetes mellitus, treated with insulin for 28 years and with an HbA1c of 7.9% six months prior, suffered from bilateral plantar ulcers refractory to specialised wound care. He underwent a planned 40 sessions of treatment (HBOT) at 243 kPa for 90 minutes. Consent was given for this report. The patient's ophthalmic history included bilateral proliferative diabetic retinopathy (PDR) identified on routine diabetic eye screening three years previously. This was treated with pan-retinal photocoagulation (PRP). Three months before starting HBOT, he underwent phacoemulsification and intra-ocular lens insertion of his left eye, having had the same procedure done to his right eye a year prior, without complication. He was reviewed again one week prior to his first HBOT and fundoscopy confirmed non-proliferative diabetic retinopathy (NPDR) without evidence of PDR. The patient had a routine follow up by the ophthalmologist following his fifth HBOT when fundoscopic examination revealed pre-retinal a form of PDR, in his left eye. This was treated with PRP at the time. His visual acuity, 6⁄9 bilaterally, had not changed, nor did he describe any changes in his visual field despite these findings. He was seen three weeks later (following 12 further HBOT) when fundoscopy showed worsening proliferative changes, this time in both eyes. Bevacizumab was injected at the time and fill-in PRP performed the following week. His visual acuity remained unchanged in both eyes. At this point, HBOT was withheld to allow the proliferative phase of the patients' retinopathy to remit. The potentially effects of to the retinal vasculature of diabetic patients was postulated in 1994 following a similar experience, albeit without a baseline fundoscopic examination. In particular, the concern was of accelerating the proliferative process of retinopathy with subsequent irreversible loss of vision. Thereafter, routine screening and treatment of all diabetic patients for PDR was adopted at our facility. Until now, there have been no further cases of NPDR evolving into PDR at three-month review following HBOT. Indeed, a brief literature search using the terms retinopathy, complications, adverse effects, vitreous, hemorrhage, haemorrhage, hyperbaric and oxygen has not found any other cases described. In a double blind, randomised trial (meeting abstract only) of 15 diabetic patients with both NPDR and PDR, patients in neither the HBOT (243 kPa for 90 min) nor the control arm had evidence of neovascularisation nor worsening of their proliferative retinopathy at three-month follow up. The significance of PDR following cataract surgery has also been considered. A review article consistently found that NPDR progression occurred in up to a third of such patients. Despite this, there were no cases of NPDR progressing to PDR at 12-month follow up. Whether this patient's sudden progression to PDR was related to HBOT, recent cataract surgery or another unknown factor is unclear. However, the temporal relationship to 17 HBOT is difficult to explain and appears more rapid than available data regarding vascular regrowth in wound healing would suggest.

Comparative Regional Pupillography as a Noninvasive Biosensor Screening Method for Diabetic Retinopathy

We describe infrared regional pupillometry as an objective comparative assessment of midperipheral to central retinal sensitivity and to correlate with midperipheral retinal ischemia in diabetic subjects. We tested 12 normal and 17 diabetic subjects using bilateral infrared pupillometry. The diabetic cohort included seven subjects without, five with mild, three with moderate, and two with severe non-proliferative diabetic retinopathy (NPDR). Central and annular stimuli of varying intensity were presented to one eye, and pupillary amplitude and constriction velocity were measured from both eyes. Light stimulus of increasing intensity was presented as 20 consecutive trials (stimulus duration of 300 ms with 3000 ms intervals). The ratio of central to peripheral responses (Q values) was calculated for each stimulus configuration. Average responses with respect to the stimulus strength were regressed with Gompertz sigmoid function. Control and moderate/severe NPDR cases comparison showed statistically significant differences in amplitude (Q(A)) and constriction velocity (Q(CV)) (Wilcoxon rank sum test P = 0.002, respectively). Age difference for these groups was not statistically significant (Wilcoxon rank sum test P = 0.15). The comparison of control and diabetic subjects without NPDR/mild NPDR was statistically significant for Q(A) and Q(CV) (Wilcoxon rank sum test P = 0.0002 and P = 0.001, respectively). Q(A) and Q(CV) differences were statistically significant between moderate/severe NPDR cases and subjects without or mild NPDR cases (Wilcoxon rank sum test P = 0.013). Q(A) and Q(CV) values correlated highly with the severity of diabetic retinopathy, but not with the duration of diabetes.

Increased protein carbonylation of red blood cell membrane in diabetic retinopathy

We investigated the protein carbonylation of red blood cell (RBC) membrane in type 2 diabetic patients and the potential implication of carbonyl/oxidative stress in reflecting disease severity. Sixty-four diabetic patients with or without retinopathy of variable clinical severity (Groups DR and DM, respectively) and 20 healthy controls were included in the study. Protein carbonyls were determined in RBC membranes by immunoblotting. Compared to healthy volunteers, the RBC membranes of diabetic patients were characterized by significantly increased levels of carbonylated proteins. The carbonylation of Group DR was higher compared to that of Group DM. The subgroup of patients with proliferative retinopathy exhibited a trend towards a significant increase in protein carbonyls, compared to both free-of-retinopathy diabetic cases and non-proliferative diabetic retinopathy cases. The correlation between the chemical modifications of the erythrocyte membrane proteins and the clinical severity of diabetic retinopathy suggests a potential utility of membrane carbonylation as a marker and risk factor in the development of retinopathy.

MEDICARE EXPENDITURES ASSOCIATED WITH DIABETES AND DIABETIC RETINOPATHY

To estimate the expenditures for diabetic retinopathy in the United States by Medicare. Retrospective data analysis using the 1997 through 2004 5% Medicare claims data. A case control design was used; eligible beneficiaries were 65 or older and without major ophthalmic conditions (cataract, cataract surgery, and macular degeneration) during the study period. Controls had diabetes but no evidence of diabetic retinopathy. There were two diabetic retinopathy case groups: beneficiaries with nonproliferative diabetic retinopathy (NPDR) and beneficiaries with proliferative diabetic retinopathy (PDR). Analyses quantified annual Medicare payments for case and control groups. A total of 178,383 controls, 33,735 NPDR cases, and 6,138 PDR cases were identified. After adjusting for age, sex, and race, annual average Medicare payments for all care were significantly higher for case groups compared to the control group, as were average payments for ophthalmic care only (all P < 0.0001). In addition, average payments for all care and for ophthalmic care were substantially higher for PDR cases compared to NPDR cases. These findings demonstrate substantial expenditures associated with diabetic retinopathy, and with PDR in particular, only part of which is due to ophthalmic care. Delaying progression may be associated with decreased Medicare expenditures.

Can digitised colour 35 mm transparencies be used to diagnose diabetic retinopathy?

Retinal photography is an adjunct to ophthalmoscopy in screening for diabetic retinopathy (DR). Digital retinal cameras allow a retinal image to be displayed immediately on a high resolution video display monitor. We conducted a pilot study to investigate the agreement in retinopathy grading from digitized images in comparison to original colour transparencies as 35 mm slides. One hundred and fifty macula-centred, 45 degree, non-stereoscopic retinal images were digitized onto CD ROM by Kodak at base resolution of 768 x 512 pixels. The anonymized images were displayed on a 17" monitor running Windows at 800 x 600 resolution in 64,000 colours (PC images) and graded in random order. Alternatively the transparencies were graded on a Slidex viewer. A quality control set were also graded with exact agreement in 93% of cases (91% (73/80) of PC images and 94% (75/80) of slide images). Compared to colour transparencies, 95% (84/88) of sight threatening diabetic retinopathy (STDR) and 100% (62/62) of non-STDR cases were diagnosed using the PC. One case of pre-proliferative DR and three cases of non-proliferative DR were graded as non-STDR from the PC. There was good agreement between PC displayed digitized retinal images and 35 mm colour transparencies.