糖尿病性视网膜病变与其他眼底血管性疾病的玻璃体视网膜手术治疗研究

目的　探讨增生性糖尿病视网膜病变 (proliferative diabetic retinopathy,PDR)及眼底血管性疾病的玻璃体视网膜手术 (vitreous retinal surgery,VRS)效果。方法　统计 1999年 1月至 2 0 0 3年 7月我院 6 9例 (73只眼 ) PDR组和非 PDR组视网膜静脉阻塞 (retinal vein occlusion,RVO)及视网膜静脉周围炎 (retinal periphlebitis,又名 Eales病 ) VRS后的视力、视网膜复位情况及术后并发症 ,研究组分为 PDR组 30例 (33只眼 ) ,非 PDR组 39例 (40只眼 ) (包括 RVO2 6例 2 6只眼和 Eales病 13例 14只眼 )。手术方法主要包括玻璃体切除、膜剥离、过氟萘烷液体使用 ,眼内激光、气体或硅油填充。结果　 PDR组术后视网膜复位 31只眼 ,非 PDR组术后全部解剖复位 ,PDR组解剖复位率低于非 PDR组 ,但统计学差异无显著性 (P >0 .0 5 ) ;PDR组术后视力提高 11只眼 ,非 PDR组术后视力提高 31只眼 ,两组比较 ,差异有非常显著性 (χ2 =14 .4 37,P =0 .0 0 0 ) ;PDR组术后并发性白内障 14只眼 ,非 PDR组并发性白内障 2只眼 ,两组比较 ,差异有非常显著性 (χ2 =14 .798,P =0 .0 0 0 ) ;PDR组继发青光眼 5只眼 ,非 PDR组继发青光眼 1只眼 ,两组比较 ,差异有显著性 (χ2 =4 .0 15 ,P <0 .0 5 )。PDR组中术中高血压者发生缺血性     

瘦素在增殖性糖尿病性视网膜病变和增殖性玻璃体视网膜病变中的表达

目的 通过检测瘦素在增殖性糖尿病性视网膜病变（proliferative diabetic retinopathy,PDR）和增殖性玻璃体视网膜病变（proliferative vitreous retinopathy,PVR）中的表达,探讨瘦素在PDR、PVR发生、发展过程中可能的调节机制。方法 分别用免疫组织化学染色的方法和酶联免疫吸附实验检测30例PDR患者、20例PVR病变患者眼内视网膜前膜中瘦素的表达,以及患者的血清、眼前房水、玻璃体液中瘦素的浓度。用Chi－Square Tests统计学方法分析和比较PDR、PVR与对照组之间瘦素表达的差异。结果 免疫组织化学染色结果：30例PDR患者中,有18例患者眼内视网膜前膜的瘦素受体呈阳性表达,阳性率为60%,与对照组比较,差异有统计学意义;20例PVR患者中,有3例患者眼内视网膜前膜的瘦素受体呈阳性表达,其中2例为血管纤维性视网膜前膜,1例为细胞纤维性视网膜前膜,阳性率为15%,与对照组比较,差异无统计学意义。ELISA结果：检测30例PDR患者的血清、眼前房水、玻璃体液中瘦素的浓度,与对照组之间差异有统计学意义（P＜0.05）;检测20例PVR患者的血清、眼前房水、玻璃体液中瘦素的浓度,与对照组之间差异无统计学意义（P＞0.05）。结论 瘦素可能主要是通过促进新生血管的生成参与到增殖性糖尿病性视网膜病变的发生、发展中,与增殖性玻璃体视网膜病变的发生、发展无明显相关性。     

增生型糖尿病视网膜病变眼内液中血管内皮生长因子定量测定

目的：检测增生型糖尿病视网膜病变（PDR）患者房水和玻璃体中血管内皮生长因子（VEGF）水平。方法：应用酶联免疫吸附测定法（ELISA）。结果：房水VEGF含量,PDR患者（4例）较正常人升高,差异有显著性（P＜0.05）。玻璃体VEGF的含量,PDR患者（11例）较正常人（10例）升高,差异有显著性（P＜0.05）。结论：PDR患者房水和玻璃体中VEGF的含量升高,在PDR的病理过程中起一定的作用。     

PDR及孔源性视网膜脱离玻璃体中PEDF的定量分析

目的定量测定色素上皮细胞衍生因子（PEDF）在增生型糖尿病视网膜病变（PDR）及孔源性视网膜脱离（RRD）患者玻璃体中的质量浓度，探讨其在PDR及RRD发病机制中的作用。方法采用双抗体夹心酶联免疫吸附测定法定量检测56例PDR、11例RRD及9例对照组患者玻璃体中PEDF的质量浓度。结果PDR组、RRD组、对照组玻璃体中PEDF质量浓度分别为1．071、1.83、1.53μg／mL，PDR组玻璃体中PEDF质量浓度小于对照组（P〈0．05）及RRD组（P〈0．05）。RRD组玻璃体中PEDF质量浓度大于正常对照组（P〈0.05）。PDR组中Ⅳ期、Ⅴ期、Ⅵ期玻璃体中PEDF质量浓度分别为1．21、1．14、0．81μg／mL。Ⅵ期患者玻璃体中PEDF质量浓度小于Ⅳ期（P〈0.05）及Ⅴ期（P〈0．05）。结论PDR患者玻璃体中PEDF降低，随PDR患者眼底病变的加重，PEDF逐渐降低，PEDF降低与视网膜新生血管的形成有关，其在PDR中起着重要作用。RRD患者PEDF升高，PEDF可能在视网膜脱离的病变过程中起着神经营养作用。     

血管生成素样蛋白4(ANGPTL4)在增生型糖尿病视网膜病变患者血清和玻璃体中的表达

目的 定量检测增生型糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)患者血清和玻璃体内血管生成素样蛋白4(ANGPTL4)的表达,并探索ANGPTL4在PDR中的作用.方法 收集需经睫状体平坦部20G标准三通道玻璃体切割术的患者共69例69眼,其中,PDR组49例49眼,对照组(非糖尿病性全层黄斑裂孔或黄斑裂孔性视网膜脱离患者)20例20眼.酶联免疫吸附试验定量检测两组患者血清及玻璃体标本中ANGPTL4表达水平.使用SPSS 17.0统计学软件对数据进行统计学分析.结果 PDR组患者血清中ANGPTL4的表达水平(30.761±2.996)ng · mL-较对照组患者(35.912±1.763)ng·mL-低,差异有统计学意义(t=-8.851,P=0.000);玻璃体ANGPTL4的表达水平(14.723±1.324)ng·mL-1较对照组患者(7.892±0.812)ng·mL-1高,差异有统计学意义(t =24.642,P=0.000).两组患者血清中ANGPTL4表达水平均高于其玻璃体,且PDR组患者血清与玻璃体中ANGPTL4变化呈正相关关系(r=0.884,P=0.000);对照组患者血清与玻璃体中ANGPTL4变化亦呈正相关关系(r=0.881,P=0.000).PDR组患者血清及玻璃体中ANGPTL4表达水平均与甘油三酯呈正相关,与高密度脂蛋白呈负相关关系(均为P＜0.05),而与其他临床指标无明显相关关系.术前玻璃体内注射雷珠单抗与不注射PDR患者血清及玻璃体中ANGPTL4表达水平,差异均无统计学意义(均为P＜0.05).结论 PDR患者血清中ANGPTL4表达水平低于非糖尿病患者,其可能在糖尿病患者糖脂代谢的病理生理过程中发挥了一定的作用;PDR患者玻璃体中ANGPTL4表达水平高于非糖尿病患者,其可能参与了PDR的发生发展过程,针对PDR患者玻璃体中ANGPTL4的高表达进行干预可能为未来PDR患者的治疗提供新的思路.     

Proliferative and inflammatory factors in the vitreous of patients with proliferative diabetic retinopathy

Purpose:

The purpose was to measure the concentrations of various cytokines and growth factors (including vascular endothelial growth factor [VEGF] and pigment epithelium-derived factor [PEDF]) in the vitreous of patients with proliferative diabetic retinopathy (PDR) and to investigate interaction between inflammatory and proliferative factors in the genesis of PDR.

Materials and Methods:

Vitreous samples from 32 eyes with PDR and 25 eyes without diabetes mellitus and signs of DR (control) were collected. Vitreous concentrations of VEGF, PEDF, monocyte chemotactic protein-1 (MCP-1), interleukin-4 (IL-4), IL-6, IL-8, IL-10, IL-17A, and secretory immunoglobulin A (sIgA) were simultaneously measured using enzyme-linked immunoassay.

Results:

Vitreous levels of VEGF, PEDF, IL-17A, IL-6, IL-8, IL-4, and sIgA were significantly (Π < 0.05) higher in eyes with PDR compared to control. The concentration of VEGF was more than 17-times higher than in control, and the concentration of PEDF was not changed oppositely and was also higher (1.45-times) compared to control, that may indicate disturbances of compensatory mechanisms in angiogenesis regulation in PDR. Significant (P < 0.05) positive correlations were observed between vitreous concentrations of VEGF and IL-17A (r = 0.45), VEGF and IL-8 (r = 0.48), VEGF and IL-4 (r = 0.51), PEDF and IL-17A (r = 0.48), PEDF and IL-8 (r = 0.59), MCP-1 and PEDF (r = 0.72), MCP-1 and IL-8 (r = 0.45), IL-4 and IL-17A (r = 0.65), IL-4 and IL-8 (r = 0.71), IL-8 and IL-17A (r = 0.59).

Conclusions:

Significantly raised levels of inflammatory and proliferative factors and numerous positive correlations between them may demonstrate a significant role of activation of vascular proliferation and local inflammation in the pathogenesis of PDR.     

Osteopontin expression in vitreous and proliferative retinal membranes of patients with proliferative vitreous retinopathy

AIM: To analyze osteopontin (OPN) expression in vitreous and proliferative retinal membranes of patients with proliferative vitreous retinopathy (PVR). METHODS: A total of 54 vitreous fluid samples were obtained between 2009 and 2010, which contained 45 with PVR (group A) and 9 without PVR (group B). Enzyme-linked immunosorbent assay was applied to quantify the OPN concentrations in vitreous fluid. Four samples of proliferative retinal membrane were also obtained at the time of vitrectomy, and their contents of OPN were measured by Real-time RT-PCR. RESULTS: The OPN levels in the vitreous fluid were 778.48±62.06ng/mL in group A and 452.99±32.52ng/mL in group B. The vitreous OPN levels in group A were significantly higher than those in group B and to rise by time in the early stages of PVR. The average OPN levels in the proliferative retinal membranes (F=0.14) were also higher than those in the retinal pigment cells (F=0) using Real-time RT-PCR. CONCLUSION: The high vitreous and proliferative retinal membrane OPN levels in PVR suggest that OPN might promote the development of PVR. The vitreous OPN concentrations are rising by the time in the early phases of PVR.     

增生型糖尿病视网膜病变的玻璃体手术治疗

目的 回顾性分析玻璃体切割术治疗增生型糖尿病视网膜病变(PDR)的疗效。方法 对18例(22眼)PDR患者行常规平部三通道玻璃体切割术，并根据病情分别联合晶状体摘出或超声乳化、剥膜、视网膜复位、眼内光凝、硅油填充、巩膜环扎等附加术式。结果 随访4—22个月，术后矫正视力改善16眼(72．7％)，脱盲率59．1％，脱残率9．1％，解剖复位率86．3％；牵拉性视网膜脱离未累及黄斑但已引起黄斑变形的患眼其术后视力改善好于已累及黄斑的。结论 玻璃体切割术仍是治疗PDR的有效手段，牵拉性视网膜脱离威胁到黄斑或导致黄斑变形时早期手术疗效更好。     

康柏西普治疗增殖性糖尿病视网膜病变患者玻璃体切除术后迟发性玻璃体出血

目的：观察玻璃体腔注射康柏西普治疗增殖性糖尿病视网膜病变(PDR)患者玻璃体切除术后迟发性玻璃体出血(POVCH)的效果。

方法：回顾性分析。纳入PDR患者玻璃体术后发生POVCH患者56例57眼,其中康柏西普组28眼行玻璃体腔内注射0.05mL康柏西普,对照组29眼不进行玻璃体腔内注射康柏西普,观察或使用口服药物治疗。记录患者玻璃体切除前后、玻璃体腔注药前后、POVCH后1mo时及随访结束时最佳矫正视力(BCVA)、玻璃体积血分级、眼压、眼底情况及再次手术(玻璃体腔灌术)情况。并观察POVCH发生时患者血糖、血压及心理等全身情况。

结果：POVCH后1mo时,康柏西普组的BCVA优于对照组(1.26±0.13 vs 1.76±0.20; P=0.04),POVCH发生时及随访结束时两组BCVA无统计学差异(P=0.08,0.24)。玻璃体积血混浊改善程度：康柏西普组显效13眼,有效9眼,无效6眼; 对照组显效11眼,有效3眼,无效15眼,差异有统计学意义(P=0.03)。康柏西普组POVCH眼再次手术率低于对照组(21% vs 51%, P=0.045)。康柏西普组平均玻璃体注药次数为2.24±1.16(1～5)次。随访12～24(平均16.47±3.34)mo。POVCH发生的28眼中,发现眼底纤维血管膜11眼(19%),视网膜新生血管11眼(19%),新生血管性青光眼10眼(18%),虹膜新生血管4眼(7%)。POVCH出血吸收后补充视网膜光凝44眼(77%)。POVCH发生时患者血糖和(或)糖化血红蛋白高、血压异常者43例(75%),情绪激动或劳累者6例(11%)。

结论：玻璃体腔内注射康柏西普可促进PDR患者POVCH积血吸收,提高视力,降低再次玻璃体切除手术的几率,同时也应注意严格控制PDR患者的血糖、血压、精神心理等全身因素。     

RBP4在增生期糖尿病性视网膜病变患者玻璃体中的表达及临床意义

目的：探讨RBP4在增生期糖尿病性视网膜病变(proliferative diabetic retinopathy, PDR)炎症反应中的作用。

方法：收集2017-02/07在武汉大学人民医院眼科中心就诊患者65例66眼玻璃体标本, 其中PDR组23例,非增生期糖尿病性视网膜病变(nonproliferative diabetic retinopathy, NPDR)组16例,非糖尿病患者26 例作为对照组。各组患者人口基线特征相匹配,PDR组及NPDR组患者糖尿病病程、血糖水平及糖化血红蛋白水平差异均有统计学意义(P<0.05)。ELISA检测各组玻璃体标本中视黄醇结合蛋白4(RBP4)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的浓度。应用单因素方差分析比较并分析各组玻璃体中RBP4、IL-6、TNF-α的浓度。采用Pearson相关分析法分析RBP4与IL-6的相关性。

结果：RBP4在PDR组、NPDR组、对照组中浓度分别为13.68±2.66、11.03±1.12、10.45±1.17μg/mL。IL-6在PDR组、NPDR组、对照组中浓度分别为56.0±10.27、20.92±5.77、10.26±1.91pg/mL。PDR组中RBP4、IL-6浓度明显高于对照组及NPDR组,3组间总体差异有统计学意义(F=12.135、161.167,P<0.01),NPDR组玻璃体中RBP4浓度与对照组RBP4浓度差异无统计学意义(P>0.05)。NPDR组玻璃体中IL-6浓度较对照组显著升高,差异具有统计学意义(P<0.05)。玻璃体中RBP4浓度与IL-6浓度成明显正相关(r=0.606,P=0.001)。

结论：RBP4可能参与糖尿病性视网膜病变增生期的炎症反应过程,为疾病的诊断与治疗提供新的思路。     

合并玻璃体积血的糖尿病视网膜病变患者的手术治疗分析

目的: 探讨合并玻璃体积血的增殖性糖尿病视网膜病变(proliferativediabeticretinopathy,PDR)的手术干预时机。方法: 采用回顾性的研究方法对128例177眼合并玻璃体积血的PDR患者的手术疗效进行对比观察。PDR患者依据疾病进程分为Ⅳ级组、Ⅴ级组以及Ⅵ级组。采用玻璃体切除术以及眼内视网膜激光对各组患者进行治疗,观察并比较三组患者手术并发症、前房炎症反应、术后1wk眼压以及术后6mo视力恢复情况。结果: 与术前相比,所有患者视力均恢复,但三组中以Ⅳ组视力恢复最为显著(P<0.05);三组患者手术相关并发症发生率、前房炎症以及术后平均眼压,均未发现统计学差异(P>0.05)。结论: 在Ⅳ级时对PDR患者进行手术干预可在不增加手术风险的同时显著提高疗效。     

Increased glutamate levels in the vitreous of patients with retinal detachment

Experimental models have implicated glutamate in the irreversible damage to retinal cells following retinal detachment. In this retrospective study we investigated a possible role for glutamate and other amino acid neurotransmitters during clinical rhegmatogenous retinal detachment (RRD). Undiluted vitreous samples were obtained from 176 patients undergoing pars plana vitrectomy. The study group consisted of 114 patients (114 eyes) with a rhegmatogenous retinal detachment. Controls included 52 eyes with an idiopathic macular hole or idiopathic epiretinal membrane and 10 eyes with a traction retinal detachment due to proliferative diabetic retinopathy. Vitreous concentrations of glutamate, gamma-aminobutyric acid (GABA), taurine, glycine, and aspartate were determined by high-pressure liquid chromatography (HPLC). Multivariate analysis was used to examine a possible association between amino acid neurotransmitter levels and several clinical variables including visual acuity. The mean vitreous concentration of glutamate in eyes with a rhegmatogenous retinal detachment (16.6 +/- 5.6 microM) was significantly higher as compared to the controls (13.1 +/- 5.2 microM) (P = 0.001). Taurine levels were also increased in RRD, whereas no significant difference could be observed in glycine, aspartate and GABA levels when comparing RRD with controls. A correlation was found between increased vitreous glutamate and a lower pre-operative visual acuity. No association was, however, observed between post-operative visual acuity and the level of any of the five amino acid neurotransmitters. RRD was associated with a significantly increased vitreous glutamate concentration. Using visual acuity as a functional parameter in this study, we could not demonstrate a correlation between vitreous glutamate, or any of the other tested amino acid neurotransmitters and visual outcome.     

增生性糖尿病视网膜病变和增生性玻璃体视网膜病变患者玻璃体中TGF-β2的表达及意义

Objective To observe the expression of transforming growth factor-β2 （TGF-β2） in the vitreous body of patients with proliferative vitreoretinal diseases; to investigate the role of TGF-β2 in the pathogenesis of proliferative vitreoretinal diseases. Methods In an experimental study, vitreous specimens were obtained during vitrectomy from 61 patients （61 eyes） with proliferative vitreoretinal diseases. The vitreous specimens were obtained from 37 eyes with proliferative diabetic retinopathy （PDR） and 24 eyes with proliferative vitreoretinopathy （PVR）. Eight vitreous fluid samples were obtained from a normal control group. The concentrations of TGF-β2 in the vitreous body were detected by enzyme-linked immunosorbent assay （ELISA）. Results The concentrations of TGF-β2 in the vitreous bodies of eyes with PDR, PVR and the normal controls were 22.71±2.32 ng/ml, 21.28±1.7）ng/ml, and 19.00±0.62 ng/ml, respectively. Intravitreous concentrations of TGF-β2 were higher in patients with PDR and PVR than in the control group. The difference was statistically significant（F=7.756, P<0.01）. The concentration of TGF-β2 in the vitreous body from eyes of PDR patients was clearly higher than concentrations in PVR patients. The difference was statistically significant （P<0.05）. The concentrations of TGF-β2 in the vitreous body were higher in level Ⅵ of the PDR group in comparison to level Ⅴ of the PDR group. The difference was statistically significant （P<0.01）. The concentrations of TGF-β2 in the vitreous body were higher in the D class of the PVR group in comparison to the C class. The difference was statistically significant （P<0.01）. The concentrations of TGF-β2 in the vitreous bodies were positively correlated with the duration of the diseases： the correlation for the PDR group was r=0.705 （P<0.01） and the correlation for the PVR group was r=0.934（P<0.01）. Conclusion TGF-β2 may play an important role in the pathogenesis and development of proliferative vitreoretinal diseases.     

增殖性糖尿病视网膜病变玻璃体视网膜手术后玻璃体出血的临床观察

目的：探讨增殖性糖尿病视网膜病变（proliferative diabetic retinopathy,PDR)玻璃体视网膜手术严重玻璃体出血的原因，并发症及处理方法。方法：对我院1997年1月至2001年3月住院行玻璃体视网膜手术治疗PDR的182例（198只眼）患者中术后发生严重玻璃体出血的16例（17只眼）患者进行回顾性分析。结果：术后玻璃体出血中52.9%出现于术后第一天，出血原因包括纤维血管膜残端出血，视网膜新生血管膜渗血，视网膜切开，视网膜裂孔，前玻璃体纤维血管增殖等；出血并发症包括继发性青光眼，增殖膜形成等。结论：PDR玻璃体切割术后玻璃体出血为术后常见的并发症；对于出血量大、难于吸收及出现并发症的病例，积极治疗可改善视力预力预后。     

活性维生素D治疗非增殖型糖尿病视网膜病变的疗效

目的:探讨活性维生素D(骨化三醇)治疗非增殖型糖尿病视网膜病变的临床疗效。方法:选取本院眼科门诊及内分泌科病房诊断明确的2型糖尿病视网膜病变患者96例,患者按随机数字表法随机均分为对照组(C组)和观察组(T组)各48例,C组给予二甲双胍降糖治疗,T组患者在对照组的基础上给予骨化三醇0.25μg/d治疗。另选取本院体检中心健康体检者20例作为正常组(N组),观察各组患者治疗前后血清钙、磷、25-(OH)D3、1,25-(OH)2D3及甲状旁腺激素(PTH)水平,并观察两组患者治疗后眼底病变减轻的有效率。结果:与N组相比,C组、T组患者治疗前均存在血清25-(OH)D3和1,25-(OH)2D3水平低下,甲状旁腺素上升;给予骨化三醇治疗后,T组患者维生素D及甲状旁腺素水平有改善,同时视力及眼底出血渗出均改善,有效率明显高于C组,两组比较差异均有统计学意义(P<0.05)。以上三组患者治疗前后血清钙、磷水平差异无统计学意义。结论:DR患者存在血清维生素D代谢紊乱,给予维生素D治疗可以改善其代谢紊乱,同时可以明显改善患者视力及眼底病变。     

玻璃体切除术治疗增殖型糖尿病性视网膜病变

目的 回顾性分析玻璃体切除治疗增殖型糖尿病性视网膜病谱（ｐｒｏｌｉｆｅｒａｔｉｖｅ ｄｉａｂｅｔｉｃ ｒｅｔｉｎｏｐａｔｈｙ,ＰＤＲ）的疗效。方法 对３４例（４０眼０ＰＤＲ患者（ＩＶ期１０眼,Ｖ期１４眼,ＶＩ期１６眼）行常规扁平部三切口闭合式玻璃体切除术,同时根据病情分别行晶状体超声粉碎晶状体切除、视网膜复位、眼内激光、硅油注入等。结果 随访３～３６ｍｏ（平均１８．５ｍｏ）,术后脱盲率４７．５０％