Objective To summarize the available clinical evidence on the treatment of non-proliferative diabetic retinopathy (NPDR). Methods Based on the basic methods and principles of evidence-based medicine, we searched and evaluated the NPDR-related evidence from the Cochrane Library(Issue 3,2007), PubMed (1966 to June 2007) and CBM(1979 to June 2007) Results We finally identified 1 systematic review and 20 randomized controlled trials. Clinical evidence showed that critical glycemic control and blood pressure control were essential in the treatment of NPDR, which might delay the progression of retinopathy. The effectiveness of other therapeutic measures needed to be further investigated. Conclusion NPDR is the early stage of diabetic retinopathy (DR). Relevant systematic reviews and high-quality randomized controlled trials have confirmed the effectiveness of critical control of blood glucose and blood pressure for NPDR. The effectiveness of other therapeutic measures needs to be confirmed by systematic reviews of high quality and rigorously designed randomized, multi-center and large-scale trials.
The erythrocytic membrane ATPase activity and intraerythrocytic cation levels have been measured in 20 noninsulin dependent diabetes mellitus(NIDDM)patients with retinopathy(DR group),20 NIDDM patients without retinopathy(DM group)and 20 normal subjects (C group)respectively.The activities of Na+- K+-ATPase and Ca2+-ATPase were significantly lower in both DR and DM groups than in C group.The levels of intraerythrocyte sodium and calcium were significantly higher,and of magnisium waws significantly lower in DR and DM groups than in C group.The above observed abnormalities especially decreased level of magnisium,were more significant in DR group than in DM group. （Chin J Ocul Fundus Dis,1994,10:11-13）
ObjectiveTo observe the safety and efficacy of Keluoxin capsules in the treatment of moderate to severe non-proliferative diabetic retinopathy (NPDR). MethodsAn open-label, multi-center, single-arm, phase Ⅱa clinical trial. From May 2014 to December 2016, the patients diagnosed with moderate to severe NPDR who received Keroxin treatment in General Hospital of Central Theater Command, Affiliated Eye Hospital to Nanchang University, Xiyuan Hospital of China Academy of Chinese Medical Sciences, and Eye Hospital China Academy of Chinese Medical Sciences were divided into moderate NPDR group and severe NPDR group. The baseline data of the patients were obtained, best-corrected visual acuity (BCVA), optical coherence tomography, fundus fluorescein angiography and fundus photography were performed. On the basis of maintaining the original diabetes treatment, all patients took Keluoxin capsules orally for 24 weeks; 24 weeks after treatment was used as the time point for evaluating the efficacy. BCVA letters, central macular thickness (CMT) and 6 mm diameter total macular volume (TMV), retinal vascular leakage area, and retinal non-perfusion (RNP) area within an average diameter of 6 mm were compared between the two groups at baseline and 24 weeks after treatment. Independent sample Mann-Whitney U test was used to compare continuous variables between groups. Categorical data were compared by χ2 test. ResultsA total of 60 NPDR patients and 60 eyes were included, 9 cases were lost to follow-up, and 51 cases and 51 eyes were finally included, including 37 eyes in the moderate NPDR group and 14 eyes in the severe NPDR group, respectively. At baseline, BCVA in moderate NPDR group and severe NPDR group were (80.1±6.8), (81.4±6.3) letters, respectively. CMT were (249.5±32.1), (258.9±22.2) μm, respectively. TMV were (8.79±1.09), (8.95±1.31) mm3, respectively. Retinal vascular leakage areas were (7.69±10.63), (10.45±7.65) mm2, respectively. RNP area were (2.48±5.74), (10.63±20.06) mm2, respectively. There were 11 (29.7%, 11/37) and 4 (28.6%, 4/14) eyes with diabetic macular edema (DME), respectively; 24 weeks after treatment, BCVA in moderate NPDR group and severe NPDR group increased by (1.3±5.2), (3.2±3.0) letters, respectively. Compared with baseline, there was a statistically significant difference in the severe NPDR group (t=－3.986, P=0.033). CMT were (252.1±45.6), (269.8±57.2) μm, respectively. There were no significant differences compared with baseline (t=－0.567, －0.925; P＞0.05). TMV were (9.96±1.16), (10.09±1.32) mm3, respectively. There were no significant differences compared with baseline (t=－0.996, －1.304; P＞0.05). Retinal vascular leakage area decreased (0.19±6.90), (1.98±7.52) mm2, respectively. There were no significant differences compared with baseline (t=0.168, 0.983; P＞0.05). RNP area were (3.01±6.47), (10.36±19.57) mm2, respectively. Compared with baseline, the differences were statistically significant (t=－1.267, 0.553; P＞0.05). There were 8 (21.6%, 8/37) and 3 (21.4%, 3/14) eyes with DME, respectively. Compared with baseline, the difference was statistically significant (χ2=11.919, 4.571; P=0.001, 0.033). ConclusionKeluoxin capsules can stabilize or improve BCVA, CMT, TMV and RNP area in patients with moderate and severe NPDR, and reduce the area of retinal vascular leakage.
Diabetic retinopathy is a vascular complication of diabetes, and homocysteine is an intermediate product of methionine metabolism. Hyperhomocysteinemia can directly or indirectly damage vascular endothelial cells, causing vascular endothelial cells dysfunction and participating in the occurrence and development of diabetic retinopathy. Uric acid is the final product of purine metabolism. Hyperuricemia can cause vascular endothelial dysfunction, oxidative metabolism, platelet adhesion and aggregation dysfunction, thus participating in the occurrence and development of diabetic retinopathy. In recent years, there have been many studies on the correlation between diabetic retinopathy and levels of homocysteine and uric acid. This article reviews the relevant literature at home and abroad in order to provide new information for the prevention and treatment of diabetic retinopathy.
Objective To observe the effect of bone forming protein 4 (BMP4) on the proliferation and migration of human retinal pigment epithelium (RPE) cells under oxidative stress, and to preliminarily explore its effect on epithelial-mesenchymal transition (EMT) of RPE cells. MethodsHuman RPE cells cultured in vitro were divided into normal group, pure 4-hydroxynonenal (HNE) group (4-HNE group), 4-HNE+NC group and 4-HNE+ small interfering BMP (siBMP4) group. The effect of 4-HNE on the proliferation of RPE cells was detected by thiazole blue colorimetry. The effects of 4-HNE and BMP4 on cell migration were determined by cell scratch test. The expression of BMP4 was detected by immunofluorescence staining, Western blot and real-time quantitative polymerase chain reaction. The transfection efficiency of siBMP4 was observed by fluorescence microscopy. Mitochondrial reactive oxygen species (MitoSOX) were detected by flow cytometry. The expression of EMT markers E-cadherin and Fibronection were detected by immunofluorescence assay. t-test was used for comparison between the two groups, and one-way analysis of variance was used for comparison between the three groups. ResultsCompared with normal group, cell proliferation and migration ability of 4-HNE group were significantly enhanced, with statistical significance (t=21.619, 24.469; P＜0.05). The expression of BMP4 in cells was significantly increased, and the difference was statistically significant (t=19.441, P＜0.05). The relative expression levels of BMP4 mRNA and protein were also significantly increased, with statistical significance (t=26.163, 37.163; P＜0.05). After transfection with siBMP4 for 24 h, the transfection efficiency of BMP4 in RPE cells was＞90%. Compared with 4-HNE group and 4-HNE+NC group, the relative expression levels of BMP4 protein (F=27.241), mRNA (F=36.943), cell mobility (F=46.723) and MitoSOX expression levels (F=39.721) in normal group and 4-HNE+siBMP4 group were significantly decreased. The differences were statistically significant (P＜0.05). The epithelial marker E-cadherin increased significantly, while the mesenchymal marker Fibronection decreased significantly, with statistical significance (F= 51.722, 45.153; P＜0.05). ConclusionsBMP4 inhibits RPE proliferation and migration under oxidative stress. BMP4 is involved in inducing EMT in RPE cells.
Objective To observe the clinical efficacy of pars plana vitrectomy (PPV) combined with dexamethasone intravitreal implant (DEX) in the treatment of proliferative diabetic retinopathy (PDR). MethodsA prospective randomized controlled study. A total of 57 PDR patients with 79 eyes diagnosed by Department of Ophthalmology of The First Affiliated Hospital of Nanjing Medical University from May 2021 to February 2023 were included in the study. Best corrected visual acuity (BCVA) and optical coherence tomography (OCT) were performed in all affected eyes. Central macular thickness (CMT) was measured by OCT. The patients were randomly divided into control group and experimental group, with 27 cases and 35 eyes and 30 cases and 44 eyes, respectively. All eyes were treated with routine 25G PPV and intraoperative whole-retina laser photocoagulation. At the end of the operation, the experimental group was given 0.7 mg DEX intravitreal injection. At 1, 4, 12, and 24 weeks after operation, the same equipment and methods were used for relevant examinations. The improvement after surgery was assessed according to the diabetic retinopathy severity score (DRSS). Mixed analysis of variance was used to compare logarithm of the minimum angle of resolution BCVA and CMT between the two groups and within the two groups before and after operation. ResultsAt 1, 4, 12 and 24 weeks after surgery, BCVA was significantly improved at different time points after surgery, and the differences were statistically significant (P＜0.001). At different time after operation, BCVA and CMT in experimental groups were significantly better than that in control group, with statistical significance (P＜0.05). Compared with the CMT before surgery, the CMT at all time point after surgery in experimental group were significantly decreased, and the difference were statistically significant (P＜0.05). There was no significant difference one week after eye operation in control group (P=0.315). At 4, 12 and 24 weeks after operation, CMT decreased in control group, and the differences were statistically significant (P＜0.05). Compared with before surgery, DRSS increased two steps higher at 1, 4, 12 and 24 weeks after surgery in 20 (45.45%, 20/44), 26 (59.10%, 26/44), 32 (72.73%, 32/44) and 31 (70.45%, 31/44) eyes in the experimental groups, respectively. The control group consisted of 15 (42.86%, 15/35), 15 (42.86%, 15/35), 16 (45.71%, 16/35) and 18 (51.43%, 18/35) eyes, respectively. There was no significant difference in DRSS at 1, 4 and 24 weeks after operation between the control group and the experimental group (P=0.817, 0.178, 0.105). At 12 weeks after surgery, the difference was statistically significant (P=0.020). ConclusionPPV combined with intravitreal injection of DEX in the treatment of PDR can improve postoperative visual acuity, alleviate postoperative macular edema and improve the severity of DR.
Objective Mendelian randomization (MR) was used to analyze the potential relationship between blood pressure and proliferative diabetic retinopathy (PDR). MethodsTwo-sample MR analysis was performed using summary statistics from genome-wide association studies. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were selected as the exposure, PDR as the outcome. The instrumental variable of SBP and DBP came from the publicly available data of the the UK Medical Research Council Comprehensive Epidemiology Unit and Neale Laboratory; the outcome data (8 681 cases in the case group, 204 208 cases in the control group, European population) are from the FinnGen database. Inverse variance weighting (IVW) and weighted median (WM) were used to analyze the potential relationships between SBP, DBP and PDR. ResultsMR analysis showed that IVW [SBP: odds ratio (OR)=1.36, 95% confidence interval (CI) 1.17-1.57, P=4.22E-05; DBP: OR=1.29, 95%CI 1.11-1.51, P=8.6E-04], WM (SBP: OR=1.33, 95%CI 1.07-1.66, P=0.009; DBP: OR=1.28, 95%CI=1.03-1.59, P=0.002). The results showed that elevated SBP and DBP increased the risk of PDR. ConclusionBlood pressure (SBP, DBP) change is positively correlated with the risk of PDR.
ObjectiveTo observe and evaluate the predictive value of serum cystatin C (Cys-C) on the risk of sight-threatening diabetic retinopathy (STDR). MethodsA non-randomized controlled cross-sectional clinical study. Ninety-two patients with type 2 diabetes mellitus (T2DM) who were admitted to Department of Ophthalmology of Beijing Tsinghua Changgung Hospital from January 2022 to October 2022 were included in the study. Among them, 50 were male, 42 cases were female, with the mean age of (58.24±12.49) years. The mean duration of T2DM was (13.18±8.35) years, of which 38 cases had a duration of ≥10 years. Twenty-nine cases complicated with hypertension, of which 16 cases had a duration of ≥10 years. Seventeen cases complicated with chronic kidney disease stage 2 and 23 cases were treated with lipid-lowering drugs. Hemoglobin Alc, serum Cys-C, serum lipids and renal function were tested, and urinary microalbumin/creatinine ratio (ACR) was calculated. According to the 2003 American Academy of Ophthalmology "Clinical Guidelines for Diabetic Retinopathy (DR)" and international clinical DR severity grading standards, the patients were divided into STDR and non-STDR groups, with 44 and 48 cases in each group, respectively. STDR was defined as severe non-proliferative DR, proliferative DR, and macular edema. Logistic regression was used to analyze the independent risk factors of STDR in T2DM patients. Receiver operating characteristic curve (ROC curve) was used to calculate and analyze the area under ROC curve (AUC) and the predictive value of serum Cys-C and ACR in predicting STDR in T2DM patients. ResultsSerum Cys-C levels in STDR and non-STDR groups were 1.10 (0.94, 1.28) and 0.91 (0.83, 1.02) mg/L, respectively, with ACR of 4.29 (1.05, 21.89) and 1.39 (0.77, 3.80) mg/mmol, respectively. Compared with non-STDR group, serum Cys-C and ACR in STDR group were higher, and the difference was statistically significant (Z=－3.984, －3.280; P＜0.05). Multivariate logistic regression analysis showed that serum Cys-C was an independent risk factor for STDR (odds ratio=1.337, 95% confidence interval 1.145-2.090, P=0.033), and the risk of STDR increased by 33.7% for every 0.1 mg/L increase in serum Cys-C. ROC analysis results showed that serum Cys-C＞1.065 mg/L combined with ACR＞5.84 mg/mmol predicted the AUC of STDR in T2DM patients was 0.661, with the specificity of 95.8%. ConclusionsThe high serum Cys-C level is an independent risk factor for STDR in T2DM patients. Serum Cys-C has high predictive value for the occurrence of STDR.
Proliferative diabetic retinopathy (PDR) is more advanced stage in diabetic retinopathy (DR), often with vitreous hemorrhages and traction retinal detachment which seriously affects patients' vision and even leads to severe visual impairment. Pars plana vitrectomy is an effective treatment for PDR. However, the operation procedure is quite complexed. Inadequate management can negatively impact postoperative vision or even lead to complications. Therefore, it is very important to clarify the surgical indications and standardize the operating procedures of PDR. To this end, Fundus Disease Group of Ophthalmological Society of Chinese Medical Association, Fundus Disease Group of Ophthalmologist Branch of Chinese Medical Doctor Association, Expert Group of Expert consensus for pars plana vitrectomy treatment of type 2 diabetic retinopathy focus on 9 key clinical issues, based on the latest evidence-based medical evidence, combined with international guidelines and China's social and economic development. Recommendations were made on the selection of DR Surgery timing, perioperative blood glucose management, surgical mode selection, formulation of surgical operation plan, drug combination or laser therapy, etc., which formed China's expert consensus on pars plana vitrectomy in the treatment of type 2 DR. This consensus is applicable to Chinese doctors specializing in fundus diseases and doctors engaged in fundus diseases, aiming to provide scientific guidance for vitreous surgery treatment of PDR patients, assist clinical decision-making, and further improve the level of surgical treatment of DR in China.