雷珠单抗联合激光光凝治疗PDR及对房水中PAI、t-PA、VEGF水平的影响

目的:研究雷珠单抗联合激光治疗增殖性糖尿病视网膜病变(PDR)疗效及对患者房水纤溶酶原激活物抑制剂(PAI)、组织溶酶原激活物(t-PA)、血管内皮生长因子(VEGF)水平的影响。方法:选取2015-03/2017-03我院PDR患者76例76眼,根据治疗方法不同分为全视网膜光凝(PRP)治疗前行玻璃体腔注射雷珠单抗治疗组(观察组)和单纯PRP治疗组(对照组),比较两组患者治疗时所用激光能量和密度以及治疗后患者最佳矫正视力(BCVA)、黄斑中心凹厚度(CMT)、房水中PAI、t-PA、VEGF水平、术后并发症及预后情况。结果:观察组光斑数量、激光能量和能量密度均低于对照组(P<0.05);治疗后,两组BCVA逐渐升高,CMT逐渐降低,组内不同时间差异有统计学意义(P<0.05),且观察组同一时间BCVA高于对照组,CMT低于对照组(P<0.05);治疗后,两组患者房水中VEGF、t-PA和PAI水平逐渐升高,但均明显低于术前水平(P<0.05),组内不同时间差异有统计学意义(P<0.05),且观察组同一时间房水中VEGF、t-PA和PAI水平低于对照组(P<0.05);两组术后黄斑水肿发生率分别为17%和37%(P<0.05)。两组患者术后1a PDR复发率分别为6%和16%(P>0.05)。结论:雷珠单抗联合激光治疗PDR能明显降低房水中VEGF、t-PA和PAI表达水平,降低患者CMT,改善患者BCVA,同时联合治疗有利于减少激光治疗时光斑数量、激光能量和能量密度,降低激光对视网膜损害。     

Changes of Oscillatory Potentials and Photopic Negative Response in Patients with Early Diabetic Retinopathy

Purpose

To investigate the clinical significance of the oscillatory potentials (OPs) and photopic negative response (PhNR) of the electroretinogram (ERG) in patients with early diabetic retinopathy.

Methods

One hundred two diabetic patients with diabetic retinopathy at different stages were examined. Thirty-two age-matched normal controls were also studied. Full-field maximal and photopic cone ERGs were recorded. The amplitudes and implicit times of the OPs, cone b wave, and PhNR were compared at the different stages of diabetic retinopathy.

Results

The a and b wave amplitudes of the maximal scotopic ERGs remained unchanged despite advancing stages of retinopathy, but the OP amplitudes were significantly attenuated even at an early stage of diabetic retinopathy. The amplitudes of both the PhNR and cone b wave were reduced at an early stage of diabetic retinopathy. Analysis of the receiver operating characteristic curves demonstrated that the amplitudes and implicit times of the OPs were more sensitive and specific than those of the PhNR in detecting changes of retinal function in the early stages of diabetic retinopathy.

Conclusions

The amplitudes of the OPs and PhNR progressively decrease with the progression of diabetic retinopathy. The PhNR amplitudes were reduced along with the cone b wave, indicating that earlier change of the PhNR in diabetic patients reflects reduced input to the retinal ganglion cell from the distal retina. The amplitudes and implicit times of the OPs are better indicators than those of the PhNR in detecting functional decreases in patients with early diabetic retinopathy.?Jpn J Ophthalmol 2006;50:367–373 © Japanese Ophthalmological Society 2006     

Roles of tissue plasminogen activator and its inhibitor in proliferative diabetic retinopathy

AIM:To investigate the role of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in proliferative diabetic retinopathy (PDR) and to discuss the correlations among t-PA, PAI and vascular endothelial growth factor (VEGF) expressions.METHODS: A total of 36 vitreous samples were collected from 36 patients with PDR (PDR group), and 17 vitreous samples from 17 patients with idiopathic macular hole were used as control. The concentrations of t-PA, PAI and VEGF in samples were determined by ELISA method. The correlations among t-PA, PAI and VEGF expressions were discussed.RESULTS: The concentrations of t-PA, PAI and VEGF in the PDR group were significantly higher than those in the control group (P<0.001). The t-PA and PAI expressions were highly correlated with the VEGF expression (P<0.001).CONCLUSION:In addition to VEGF, a variety of bioactive substances, such as t-PA and PAI, are involved in the pathogenesis involved in the angiogenesis of PDR. VEGF can activate t-PA expression, resulting in collagen tissue degradation and angiogenesis. VEGF may also activate the mechanism for endogenous anti-neovascularization.     

增殖性糖尿病视网膜病变眼内组织纤溶酶原激活物及其抑制物的表达与VEGF表达的相关性研究

目的:探讨增殖性糖尿病视网膜病变(PDR)中组织纤溶酶原激活物(t-PA)及纤溶酶原激活物抑制剂(PAI)的表达以及与血管内皮生长因子(VEGF)表达的相关性.方法:于玻璃体手术中采集PDR 35眼玻璃体,同时采集因黄斑裂孔行玻璃体手术20眼玻璃体作为对照组,采用酶联免疫吸附法检测t-PA及PAI的表达浓度,并与VEGF的表达进行相关性分析.结果:PDR眼玻璃体中VEGF、t-PA及PAI的表达浓度均显著高于对照眼玻璃体(P＜0.001).t-PA及PAI的表达与VEGF的表达经统计学分析,均存在显著相关性(P＜0.001).结论:在PDR眼内视网膜新生血管的发生过程中不仅有VEGF,可能同时有多种生物活性物质的参与.     

Detection of Glutamate and -y-aminobutvric Acid in Vitreous of Patients with Proliferative Diabetic Retinopathy

Purpose:To study the levels of glutamate and γ-aminobutyric acid (GABA) in vitreous of patients with proliferative diabetic retinopathy(PDR) and to investigate their roles in retinal ischemia.Method: Vitreous samples were collected from 25 patients (27 eyes) with PDR and 14 patients (14 eyes) with idiopathic macular hole. Glutamate and GAB A detection were performed by high-performance liquid chromatography (HPLC).Results: Patients with PDR had significantly higher concentrations of glutamate and GA-BA than the control group. The glutamate level has a significantly positive correlation with GABA level.Conclusion: Detection of glutamate and GABA in vitreous provides biochemical support for the mechanism and treatment of ischemic retinal damage in patients with PDR. Eye Science 2000; 16: 199-202.     

Relation Between Plasma Nitric Oxide Levels and Diabetic Retinopathy

Purpose Nitric oxide (NO) plays an important role in homeostatic vasodilation and the regulation of blood flow. On the other hand, excess release of NO causes various vascular complications. There are only a few reports on the relationship between plasma NO levels and microvascular complications, especially diabetic retinopathy (DR) in patients with type 2 diabetes. The purpose of this study was to determine the relationship between plasma NO levels and DR. Methods In a prospective study, blood samples were obtained from 36 patients with diabetes and no diabetic retinopathy (NDR), 43 patients with nonproliferative diabetic retinopathy (NPDR), 18 patients with proliferative diabetic retinopathy (PDR), and 40 subjects without diabetes mellitus, who served as controls. The levels of plasma NO_x (nitrite and nitrate), the stable metabolites of NO, were measured by high-performance liquid chromatography with the Griess method. Results The plasma NO_x levels were 92.8 ± 16.0, 70.2 ± 6.8, 90.3 ± 9.1, and 53.8 ± 6.1 μmol/l in patients with NDR, NPDR, or PDR, and in the controls, respectively. The plasma NO_x levels in the three diabetic groups were significantly higher than those in the control group (P < 0.05 in each case). Conclusion The increased plasma NO levels in patients with type 2 diabetes indicate that NO may be associated with the pathogenesis of DR. Jpn J Ophthalmol 2006;50:465–468 ? Japanese Ophthalmological Society 2006     

糖尿病视网膜病变患者行全视网膜光凝术中的疼痛反应

目的：:观察并评估糖尿病视网膜病变（DR）患者行全视网膜激光光凝术（PRP）治疗时的疼痛反应。方法：:回顾性系列病例研究。选择台州市立医院眼科门诊于2019年7─12月进行PRP治疗的DR患者55例,年龄45~72（60.7±7.9）岁,每次PRP治疗后应用数字分级法（NRS）对疼痛反应进行评估。采用Spearman相...     

Expression of Pigment Epithelium-Derived Factor and Vascular Endothelial Growth Factor in Fibrovascular Membranes from Patients with Proliferative Diabetic Retinopathy

Purpose

The expression of pigment epithelium-derived factor (PEDF), a strong inhibitor of angiogenesis, has not been examined in human ocular fibrovascular membranes, to the best of our knowledge. The purpose of this study was to determine whether PEDF is expressed in the fibrovascular membranes in eyes of patients with proliferative diabetic retinopathy (PDR), and to compare the expression of PEDF with that of vascular endothelial growth factor (VEGF).

Methods

The expression of PEDF and VEGF in the fibrovascular membranes excised during vitreous surgery in eight cases of PDR was determined by immunohistochemistry.

Results

VEGF was strongly expressed in the endothelial cells of newly formed vessels in the fibrovascular membranes. In contrast, PEDF was weakly expressed in the endothelial cells and was prominently expressed in the extracellular matrix and fibrous tissue surrounding the new vessels.

Conclusions

Our results suggest that PEDF, along with VEGF, may modulate the formation of fibrovascular membranes in patients with PDR.?Jpn J Ophthalmol 2006;50:116–120 © Japanese Ophthalmological Society 2006     

视网膜内新生血管——糖尿病性视网膜病变115例眼底荧光血管造影分析

就115例(217只限)糖尿病性视网膜病变的眼底荧光血管造影进行分析。发现46例(86只限)有视网膜内新生血管,集中发生在Ⅲ期以后。并就其表现形式,与视网膜前新生血管的关系进行了研究。认为视网膜内新生血管可以成为诊断糖尿病性视网膜病变增殖前期的标志,视网膜内界膜的健康状况是视网膜内新生血管转变为视网膜前新生血管的关健。     

Plasma and Vitreous Metabolomics Profiling of Proliferative Diabetic Retinopathy

PurposeTo determine the differences of metabolites and metabolic pathways between patients with proliferative diabetic retinopathy (PDR) and without diabetes (nondiabetic controls) in plasma and vitreous, respectively, and to characterize the relationship between plasma and vitreous metabolic profiles.MethodsLiquid chromatography/tandem mass spectrometry technology was performed to distinct metabolite profiles of plasma and vitreous. A total of 139 plasma samples from 88 patients with PDR and 51 nondiabetic controls, as well as 74 vitreous samples from 51 patients with PDR and 23 nondiabetic controls, were screened. Pathway analysis was performed using MetaboAnalyst 5.0. Pearson correlation analysis was used to investigate the correlation of metabolites in vitreous and plasma.ResultsAfter adjusting for age, fasting blood glucose, and urea, in vitreous metabolomes, a total of 76 features distinguished patients with PDR from controls. Fifteen differential metabolites were found in plasma metabolites. Pantothenate and CoA biosynthesis was the common metabolic pathway altered in both plasma and vitreous. Aromatic amino acid metabolism pathways were dysregulated in vitreous of PDR. For four metabolic features, there were positive correlations between vitreous and plasma.ConclusionsDespite great differences between the metabolic profiles of plasma and vitreous in PDR cases, there are also similarities in the change of metabolites and metabolic pathways. Exploring the relationship of metabolomics between vitreous and plasma may help provide new understanding of the mechanism of PDR.     

激活T淋巴细胞与增生性糖尿病性视网膜病变关系的研究

目的:研究免疫介导过程对增生性糖尿病性视网膜病变(proliferative diabetic retinopathy PDR)的发生发展的潜在作用。方法:应用特异性的抗辅助T淋巴细胞(CD4)、抗白细胞介素-2(interleukin-2 IL-2)及其受体的单克隆抗体(interleukin-2 receptor IL-2R),对经扁平部玻璃体切割术获得的15例PDR视网膜前膜标本进行了研究。结果:在15例标本中,12例(80%)呈CD4阳性;12例(80%)发现有IL-2,且其中11例也呈CD4阳性;10例(67%)发现有IL-2R,其中9例呈CD4阳性并有释放的IL-2。大多数IL-2R阳性的前膜都来自Ⅰ型糖尿病患者,其中40%的患者小于40岁。结论:研究证实了半数以上的糖尿病视网膜前膜中有激活的免疫细胞和释放的淋巴因子,揭示了免疫反应过程和淋巴因子的生物效应对PDR视网膜前膜的形成起重要作用,尤其在青年患者和Ⅰ型糖尿病患者。眼科学报1999;15:229-232。     

微循环在糖尿病视网膜病变发展中的作用

自身对照检查83例糖尿病视网膜病变患者甲皱微循环改变。直线回归分析表明微循环管袢数、管径、流速、细胞聚集、白色微血栓在糖尿病视网膜病变发展中起一定作用，并进一步探讨糖尿病视网膜病变的发病机理。     

Vitreous Proteomics and Diabetic Retinopathy

Diabetic retinopathy is the major cause of acquired blindness in working-age adults. Studies of the vitreous proteome have provided insights into the etiology of diabetic retinopathy and suggested potential molecular targets for treatments. Further characterization of the protein changes associated with the progression of this disease may suggest additional therapeutic approaches as well as reveal novel factors that may be useful in predicting risk and functional outcomes of interventional therapies. This article provides an overview of the various techniques used for proteomic analysis of the vitreous and details results from various studies evaluating vitreous of diabetic patients using the proteomic approach.     

Mini Review: Changes in the Incidence of and Progression to Proliferative and Sight-Threatening Diabetic Retinopathy Over the Last 30 Years

Purpose: Diabetic retinopathy is a leading cause of blindness worldwide. The last 3 decades have seen major improvements in glycemic and blood pressure control as well as the introduction of national screening programs, and we sought to determine if rates of proliferative diabetic retinopathy have changed as a result.

Methods: We conducted a systematic review to determine whether the incidence and progression rates of proliferative diabetic retinopathy and sight-threatening retinopathy have changed, focusing on large population-based studies with objective assessment of diabetic retinopathy.

Results: Comparisons across different studies is problematic due to different baseline retinopathy severity, different reported outcomes and different follow-up periods, but within these constraints certain trends could be identified. This review provides evidence that the incidence and progression of these conditions has reduced by approximately 2–3 fold over the last 3 decades.

Conclusion: These results have implications for current diabetic retinopathy screening guidelines and has identified future areas where research could be improved.     

Higher Serum Uric Acid Levels Are Associated With an Increased Risk of Vision-Threatening Diabetic Retinopathy in Type 2 Diabetes Patients

PurposeTo investigate the association between serum uric acid (SUA) levels and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes.MethodsThis cross-sectional study evaluated 3481 patients with type 2 diabetes from four communities in China between 2016 and 2019. VTDR was defined as severe nonproliferative, proliferative diabetic retinopathy, or clinically significant macular edema evaluated by fundus photography and optical coherence tomography. Potential association between SUA and VTDR was examined using multivariable logistic regression. Sub-group analyses based on sex were constructed.ResultsA total of 305 participants had VTDR. Both higher SUA (odds ratio [OR], 1.22 per 100 µmol/L; 95% confidence interval [CI], 1.04–1.44; P = 0.013) and hyperuricemia (OR, 1.47; 95% CI, 1.07–2.04; P = 0.019) were positively associated with VTDR after adjustment for relevant covariates. Compared with those in the lowest SUA quartile, participants in the third (OR, 1.60; 95% CI, 1.07–2.39; P = 0.022) and fourth (OR, 2.05; 95% CI, 1.37–3.08; P = 0.001) sex-specific SUA quartiles showed a significantly increased risk of VTDR after adjustment. No sex-related difference was observed.ConclusionsHigher SUA levels were associated with an increased risk of VTDR in patients with type 2 diabetes in both sexes, although females seemed to be more sensitive to high SUA than males. Prospective cohort studies are needed to verify SUA as a biomarker for predicting the risk of VTDR. Whether decreased SUA levels could decrease the risk of VTDR also requires further investigation.     

Population-Based Study of Nonproliferative Diabetic Retinopathy Among Type 2 Diabetic Patients in Kinmen, Taiwan

Purpose

This study was conducted to assess the prevalence and associated factors of nonproliferative diabetic retinopathy among type 2 diabetic patients in Kinmen, Taiwan.

Methods

From 1991 to 1993, 971 type 2 diabetic patients in Kinmen underwent diabetic retinopathy screening performed by a panel of ophthalmologists using indirect ophthalmoscopy and 45° color fundus retinal photographs.

Results

Of the 971 patients screened in 1991–1993, 578 (59.5%) were examined for this study. Diabetic retinopathy was diagnosed in 127 patients (22.0%), including nonproliferative diabetic retinopathy in 13.3%, proliferative diabetic retinopathy in 1.4%, legal blindness in 1.4%, and ungradable diabetic retinopathy in 5.9%. Significant associated factors of nonproliferative diabetic retinopathy based on multiple logistic regression analysis were fasting plasma glucose (FPG) at baseline [≥126?mg/dl vs. <126?mg/dl; odds ratio (OR) = 2.89; 95% confidence interval (CI), 1.01–9.09], 2-h postload at baseline (≥200 vs. <200?mg/dl; OR = 1.48; 95% CI, 1.09–2.07); HbA_1c at follow-up (≥7% vs. <7%; OR = 6.54; 95% CI, 3.01–14.20), duration of diabetes (≥15 years vs. <10 years; OR = 6.72; 95% CI, 2.13–21.18), and incremental systolic blood pressure between baseline and follow-up (OR = 1.02; 95% CI, 1.00–1.04).

Conclusions

In addition to the longer duration of type 2 diabetes, FPG at baseline, poorly controlled glucose concentration, and altered blood pressure may increase the risk of nonproliferative diabetic retinopathy in type 2 diabetic patients. Jpn J Ophthalmol 2006;50:44–52 © Japanese Ophthalmological Society 2006     

Two-year Course of Visual Acuity in Severe Proliferative Diabetic Retinopathy with Conventional Management: Diabetic Retinopathy Vitrectomy Study (DRVS) Report #1

Seven hundred forty-four eyes with very severe proliferative diabetic retinopathy (PDR) were followed with conventional management over a two-year period. Decreases in visual acuity were more frequent during the first year of follow-up than during the second, and were related to baseline visual acuity level and retinopathy severity. After two years, visual acuity was less than 5/200 in 45% of eyes with more than four disc areas of new vessels and visual acuity of 10/30 to 10/50 at baseline, but in only 14% of eyes with traction retinal detachment not involving the center of the macula and without active new vessels or fresh vitreous hemorrhage at baseline. Vitrectomy, which was undertaken only if retinal detachment involving the center of the macula occurred or if severe vitreous hemorrhage failed to clear after a one-year waiting period, had been carried out in 25% of eyes after two years of follow-up.     

Role of Steroids in the Management of Diabetic Macular Edema and Proliferative Diabetic Retinopathy

Diabetic retinopathy is the most common microvascular complication of diabetes. Early clinical trials have established the efficacy and safety of laser in the treatment of proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). Despite timely and appropriate use of laser, some patients continue to experience visual loss. The pathogenesis of PDR and DME is multifactorial involving both angiogenic and inflammatory processes. Recent trials have shown that the anti-inflammatory and anti-angiogenic properties of corticosteroids may provide benefit in treating PDR and DME. The exact role of steroids in the treatment for diabetic retinopathy and macular edema remains to be fully elucidated.     

糖尿病视网膜病变患者全视网膜光凝后角膜上皮基底神经丛和朗格汉斯细胞的改变及其相关性

目的：利用结构拼图观察糖尿病（DM）患者全视网膜光凝（PRP）前后角膜上皮基底神经丛（SNP）和 朗格汉斯细胞（LC）的变化,并分析二者的相关性。方法：前瞻性临床研究。选取2019年4─11月 就诊于山西省眼科医院准备行PRP治疗且双眼糖尿病视网膜病变Ⅳ期的2 型DM患者,选择病情 较重的眼为治疗眼,对侧眼为对照眼,分别于PRP治疗前、每次光凝后1周和PRP完成后1个月行 角膜共焦显微镜检查,观察涡状结构及其周围2～3 mm区域SNP和LC的变化,并测量涡状区神经纤维长度（NFL）值和LC密度。采用重复测量方差分析比较不同观察时间点LC密度和NFL值,并 采用SAS软件的MIXED模型分析重复测量的NFL值和LC密度之间的相关性。结果：共纳入患者 49例。治疗眼接受PRP后部分患者出现SNP神经纤维变细,伴有不同程度的涡状区神经结构缺失的神经损伤表现;各观察时间点NFL值总体比较差异有统计学意义（F=8.039,P=0.004）,且PRP治疗 前NFL值[（15.5±3.7）mm/mm2]与第2次光凝后1周[（15.0±3.5）mm/mm2]、第3次光凝后1周[（13.4± 4.3）mm/mm2]和第4次光凝后1周[（13.5±4.1）mm/mm2]比较差异均有统计学意义（均P<0.05）。同 时,治疗眼LC密度增加,并以涡状区为中心聚集,成熟LC浸润区伴有SNP神经结构的缺失;各观 察时间点LC密度总体比较差异有统计学意义（F=12.350,P<0.001）,且PRP治疗前LC密度[（40± 54）cells/mm2]与第3次光凝后1周[（79±91）cells/mm2]、第4次光凝后1周[（98±126）cells/mm2]以 及PRP完成后1个月[（87±102）cells/mm2]比较差异均具有统计学意义（均P<0.05）;相关分析显示治 疗眼第4次激光后1周LC密度与其基线水平呈正相关（r=0.674,P<0.001）;且重复测量的NFL值与 LC密度呈负相关（P-=-0.041）。结论：PRP多次光凝可以导致LC密度增加;成熟LC可以导致SNP神经结构破坏。     

Long-Term Survival Rates of Patients Undergoing Vitrectomy for Proliferative Diabetic Retinopathy

Purpose: Reported 5-year survival rates in patients undergoing vitreous surgery for proliferative diabetic retinopathy (PDR) range from 68–95%. Studies relating survival rates to medical baseline characteristics predate the millennium. This study aimed to update data on life expectancy of patients undergoing vitrectomy for PDR and identify baseline factors which may influence survival.

Methods: A retrospective cohort study of consecutive patients who underwent their first pars-plana vitrectomy for PDR between April 2004 and May 2005 was performed. Survival status on 1 May 2012 was the primary endpoint. The Kaplan-Meier life table method was used to determine survival rates. Univariate and multiple variable Cox proportional hazards regressions were used to identify risk factors for mortality.

Results: A total of 148 patients were included in the study, with a mean age of 54 years (range 20–80 years) at time of surgery. The 3-, 5- and 7-year survival rates were 94%, 86% and 77%, respectively (95% confidence interval, CI, 88–97%, 79–91% and 68–84%, respectively). Renal failure was the most common cause of death. The presence of limb ulcers at baseline was the most important prognostic indicator for mortality, with a hazard ratio of 3.13 (95% CI 1.46–6.71, p = 0.003) and a survival rate at 5 years reduced to 79%.

Conclusion: The 5-year survival rate remains comparable to those reported 20 years ago despite a lowering in threshold for vitrectomy and increased health awareness. Limb ulcers are strongly associated with increasing mortality. Clinicians should remain mindful of the systemic associations of diabetes particularly in advanced retinal disease.