Diabetic retinopathy: different risk factors for exudates and haemorrhages

The retinae of 137 patients were examined ophthalmologically and for visual acuity at diagnosis of noninsulin dependent diabetes and again in 1982 and 1983, approximately 7 and 8 years later, when colour photographs were also taken. In 1983, 46% were without detectable retinopathy, 32% had haemorrhages (including microaneurysms) only, 4% exudates alone and 18% both lesions. Those with haemorrhages were more hyperglycaemic than those without retinopathy and those with exudates only. Indeed, those with exudates alone had lower mean glucose levels than those without retinopathy (p<0.05). Patients with exudates (± haemorrhages) had a lower percentage of the fatty acids of plasma cholesterol esters as linoleate than those without (p<0.05) but this did not hold for those developing haemorrhages. Different risk factors appear to operate in different features of diabetic retinophathy. In some respects exudate formation may be more akin to macro than to micro angiopathy.     

增殖性糖尿病视网膜病变多次手术临床分析

目的：探讨增殖性糖尿病视网膜病变玻璃体切割术后多次手术的原因及处理。方法：回顾性分析3a来因增殖性糖尿病视网膜病变行玻璃体切割术后需要再次手术的患者。结果：患者189眼术后需要再次进行手术的为24例26眼（占总观察眼数13.8%）。分别是：玻璃体再积血3眼,前房积血1眼,视网膜脱离11眼（占总观察眼数5.8%,占再手术眼42.3%,其中3眼合并新生血管性青光眼）,白内障6眼（占总观察眼数3.2%）,单纯硅油取出5眼。189眼中有6眼发生了新生血管性青光眼（3.2%）,6眼均为玻璃体晶状体联合手术或玻璃体切割术后又摘除白内障病例。2次手术19眼,3次或以上手术7眼（其中5眼合并视网膜脱离）。结论：发生视网膜脱离是糖尿病视网膜病变玻璃体切割术后需要多次手术的主要原因;也占据需要3次或以上手术的主要部分。新生血管性青光眼的发生值得重视,出现视网膜脱离时要提高警惕,需要摘除晶状体时必须慎重。     

多药耐药蛋白1和多药耐药相关蛋白5、7在糖尿病小鼠视网膜中表达的变化

目的 观察多药耐药蛋白1(muhidrug resistance 1,MDR1)、多药耐药相关蛋白(multidrug resistance-associated protein,MRP)5和MRP7在不同时期糖尿病小鼠视网膜中的表达变化.方法 通过腹腔注射链脲佐菌素诱导C57 BL/6小鼠建立糖尿病模型,伊文思蓝灌注检测血-视网膜内屏障变化.分别于糖尿病造模成功后的4周、12周和24周取小鼠视网膜,进行实时定量-PCR、免疫荧光、Western blotting等实验,检测各组小鼠视网膜中MDR1、MRP5和MRP7的表达变化.结果 伊文思蓝灌注结果显示在糖尿病12周就出现视网膜渗漏;实时定量-PCR结果发现与对照组相比,随糖尿病进展,MDR1、MRP5和MRP7在4周、12周和24周的表达均呈下降趋势(MDR1:P4周=0.028,P12周=0.003,P24周＜0.001;MRP5:P4周=0.045,P12周=0.009,P24周＜0.001;MRPy7:P4周=0.019,P12周＜0.001,P24周 =0.001),在糖尿病不同时期其变化也呈下降趋势(均为P＜0.05);免疫荧光观察到MDR1、MRP5和MRP7的荧光强度随糖尿病发展逐渐减弱;Western blotting检测可见在4周、12周、24周糖尿病小鼠视网膜中MDR1、MRP5和MRP7的表达均呈下降趋势.结论 在DR早期血-视网膜内屏障会受到破坏,视网膜中外排转运蛋白的表达也会受糖尿病的影响导致不同程度的下降.     

OCTA在糖尿病视网膜病变中的临床应用现状

糖尿病视网膜病变是糖尿病引起的微血管病变中最常见的疾病,晚期对视力危害极大,如不及时治疗,可致盲。糖尿病视网膜病变以往诊治、随访主要依据荧光素眼底血管造影,因其操作有创、容易发生过敏不良反应等副作用在临床应用中有一定的局限性。近年兴起的光学相干断层扫描血管成像无创、快速、眼底血管成像分辨率高,它不仅可以分层显示视网膜脉络膜血管网信息,而且能定量分析黄斑区血流变化情况,并且首次实现在活体上对视盘、黄斑区的血流分析达到组织解剖水平,应用前景广阔,越来越受眼科医生的青睐。本文就OCTA在糖尿病视网膜病变中的临床应用现状进行简要综述。     

In diabetic retinopathy, foveal thickness of 300 μm seems to correlate with functionally significant loss of vision

Purpose To study the relationship between foveal thickness assessed by optical coherence tomography (OCT) and foveal function measured with multi focal electroretinography (mfERG) in patients with non-proliferative diabetic retinopathy, and with no previous laser treatment. Methods Twenty-six eyes from 18 diabetic patients (13 men), aged 59 years, (range 28–79 years), diabetes duration 15 years, (range 2–27 years), with a macular thickness between 200 and 600 μm were evaluated by mfERG, visual acuity (ETDRS score) and OCT. Mean amplitudes and implicit times of the mfERG responses were analyzed within the four innermost (14 degrees) of the six concentric rings. For comparison with the results from the OCT (diameter of measured area = 6 mm) we analyzed the summed response from the first and second ring (central zone), corresponding to the central area of the OCT. The third(zone 2) and fourth (zone 3)of the four innermost of the six concentric rings measured by the mfERG corresponding to the second and third area of OCT. Results An increased macular thickness in the central area of the OCT correlated to reduced amplitudes (r = −0.541; P = 0.004) and prolonged implicit times (r = 0.548; P = 0.004) in the central zone of the mfERG, and inversely correlated with visual acuity, −0.49; P = 0.045. Retinal thickness in the second area was correlated to prolonged implicit times in the second mfERG zone (r = −0.416; P = 0.034). No correlations were found for the third area of the OCT. When macular thickness exceeded 300 μm the decrease of amplitudes and prolonged implicit times, measured by mfERG, seemed to be more pronounced. Conclusion In conclusion increased macular thickness is correlated with reduced amplitudes and prolonged implicit times on the mf ERG and worse visual acuity.     

Functional and morphological changes in diabetic macular edema over the course of anti‐vascular endothelial growth factor treatment

Purpose:  To evaluate macular morphology and function in diabetic macular edema (DME) over the course of intravitreal anti‐vascular endothelial growth factor (VEGF) treatment with Ranibizumab. Methods:  A consecutive series of 39 study eyes with centre‐involving DME were included in this study. In all subjects, best‐corrected visual acuity (BCVA) according ETDRS protocol, fluorescein angiography (FA), microperimetric macular sensitivity (MP) and Spectral Domain optical coherence tomography (SD‐OCT) cross‐sectional scans were obtained before treatment and after 3 monthly applied intravitreal Ranibizumab injections. Six different morphological qualities [IS/OS layer integrity, outer nuclear layer (ONL) cysts, ONL cyst size, inner nuclear layer (INL) cysts, blocking phenomenon and subretinal fluid] were graded of each cross‐sectional OCT scan before and over the course of treatment by two experienced graders. Correlation analyses between functional and morphological parameters were obtained. Results:  Mean BCVA increased from 26 ± 14 to 33 ± 13 letters after 3 consecutive monthly applied Ranibizumab injections (p < 0.001). Central retinal thickness (CRT) decreased from 504 ± 144 to 387 ± 122 μm (p < 0.001). Over the course of treatment, IS/OS continuity improved (index: 0.56 ± 0.52 to 0.43 ± 0.49, Z = ?1.415, p = 0.157), ONL cyst prevalence and size decreased significantly (index: 0.61 ± 0.44 to 0.56 ± 0.35, Z = ?3.41, p = 0.001 and 1.75 ± 0.88 to 1.17 ± 1.05, Z = ?4.02, p < 0.001), INL cyst prevalence decreased (index: 0.35 ± 0.52 to 0.28 ± 0.52, Z = ?1.60, p = 0.109), blocking phenomenon did not change significantly (index: 00.12 ± 0.16 to 0.13 ± 0.15, Z = ?0.45, p = 0.656) and subretinal fluid almost disappeared (index: 0.10 ± 0.24 vs. 0.00 ± 0.01, Z = ?2.56, p = 0.011). Correlation analyses revealed highest significant correlations between ONL cyst prevalence and their size and CRT as well as BCVA and MP before treatment and over the course of treatment. Conclusions:  ONL cysts and their size as morphological parameters correlate with retinal function measured with BCVA and microperimetry before and over the course of anti‐VEGF therapy with Ranibizumab in patients with DME.     

糖尿病大鼠早期视网膜神经节细胞凋亡机制的探讨

目的：探讨糖尿病大鼠模型早期视网膜神经节细胞(retinal ganglion cells,RGCs)凋亡的机制。

方法：SD大鼠60只,随机分为对照组(CON)及糖尿病组(DM),糖尿病组一次性腹腔注射1% STZ诱发糖尿病鼠模型,两组于第4,8,12wk分别行HE、透射电镜及TUNEL法检测RGCs的凋亡情况,并应用激光共聚焦显微镜检测RGCs内钙离子浓度的变化。

结果：糖尿病组第8wk开始出现RGCs数量减少、细胞排列紊乱的病理改变,第12wk更为明显。糖尿病组透射电镜下可见第4wk时RGCs出现线粒体肿胀; 第8wk时RGCs内肿胀的线粒体更为明显、数目增多,染色质边集于核膜周边,部分细胞体积缩小、细胞器减少; 第12wk时出现RGCs体积变小,甚至出现细胞核断裂。TUNEL阳性RGCs最早于糖尿病组第4wk时出现,随病程延长凋亡的阳性细胞逐渐增多,凋亡指数与同期对照组相比,差异有统计学意义(P<0.01)。糖尿病组第8,12wk时RGCs内钙离子浓度明显高于同期对照组,差异显著(P<0.01); 糖尿病组第8wk与第12wk比较,升高差异亦有统计学意义(P<0.05)。

结论：糖尿病早期出现了视网膜神经节细胞的凋亡,其机制可能与细胞内钙离子浓度升高有关。     

糖尿病早期NOS亚型的蛋白表达及其在血流变化中作用的实验研究

目的探讨在糖尿病早期,3种亚型一氧化氮合酶(NOS)在大鼠视网膜不同组织细胞中蛋白表达的变化,及其与视网膜血流变化的关系。方法将Wistar大鼠随机分成正常对照组与链脲佐菌素(STZ)腹腔注射诱导的糖尿病组各10只,采用彩色多谱勒对大鼠视网膜中央动脉(CRA)进行血流参数的测量,运用免疫组织化学技术观察视网膜eNOS、iNOS、nNOS蛋白表达的变化。结果8wk糖尿病大鼠视网膜尚未出现病变,但血流参数已显著异常,表现为糖尿病组大鼠CRA的血流速度较对照组显著降低(P<0.05),而阻力指数则显著增高(P<0.05),搏动指数高于对照组,但尚未有显著意义。3种亚型NOS在糖尿病与正常对照组视网膜中表达部位一致;但与正常对照组比较,iNOS免疫反应的强度在糖尿病大鼠视网膜中的内核层显著增强,而eNOS与nNOS的免疫反应强度则未见显著变化。结论在糖尿病早期,大鼠视网膜已开始出现血流灌注不良,此时NOS亚型中iNOS在视网膜中的表达上调可能与之相关。     

Vitronectin and proliferative intraocular disorders. II. Expression of cell surface receptors for fibronectin and vitronectin in periretinal membranes

Several cell types participate in the formation of vitreoretinal traction membranes in proliferative intraocular disorders. The communication between these cells involves hormones, growth factors, and the interaction with extracellular matrix molecules. We have previously demonstrated a partial colocalisation of two potent mediators of cell attachment, fibronectin and vitronectin, in periretinal membranes from patients with proliferative vitreoretinopathy (PVR). We found a similar pattern of vitronectin and fibronectin deposition in proliferative diabetic retinopathy (PDR) (n = 6). Now we show the expression of the corresponding cell surface receptors, integrins, for fibronectin and vitronectin by proliferating cells in 22 periretinal membranes, including traumatic (n = 8) and idiopathic (n = 8) PVR as well as PDR membranes (n = 6). Integrins are membrane receptors for extracellular matrix macromolecules which are involved in such basic biological phenomena as embryogenesis and metastasis. Future studies on the pathogenesis of vitreoretinal proliferation will have to focus on the initiation, maintenance, and regulation of this intercellular communication network involving attachment proteins and integrins.     

海德堡视网膜断层扫描监测糖尿病黄斑水肿的可行性及其临床意义

目的：探讨海德堡视网膜断层扫描（HRT）监测糖尿病性黄斑水肿（DME）的可行性及其临床意义。方法：采用HRTⅡ对经裂隙灯显微镜加三面镜检查、荧光素眼底血管造影（FFA）检查确诊的DME、糖尿病无黄斑水肿（NDME）患者和无糖尿病正常对照者共77例120只眼进行黄斑中心凹水肿指数（e值）测定。其中，DME组23例40只眼，男性13例23只眼，女性10例17只眼，年龄44～68岁，平均年龄（55．17±8．26）岁；NDME组32例40只眼，男性18例22只眼，女性14例18只眼，年龄44～68岁，平均年龄（55．17±6．5）岁；正常对照组22例40只眼，男性10例19只眼，女性12例21只眼，年龄42～65岁，平均年龄（53．32±6．04）岁。3组间性别、年龄差异均无统计学意义（P〉O．05）。根据FFA检查黄斑区可疑渗漏或渗漏面积〈25％、渗漏面积在25％～66％、渗漏面积〉66％将DME分为3级。40只DME眼中FFA1、2、3级分别为9、10、21只眼。观察分析DME患眼e值与FFA渗漏面积和视力的关系以及受检组之间不同黄斑直径与e值的相互关系。结果：黄斑直径为1、2、3mm的e值行方差分析，组间差异有统计学意义（P〈0．05）。两两比较，正常对照组与NDME组e值差异无统计学意义（P〉0．05），正常对照组、NDME组分别与DME组比较，e值差异均有统计学意义（P〈O．05）。DME组视力的对数与e值存在相关性（P〈0．05）。DME组FFA1、2、3级之间的e值行方差分析，两两比较，三者之间总体有差异。FFA1级与3级、2级与3级黄斑渗漏面积差异有统计学意义（P〈0．05），1级与2级之间差异无统计学意义（P〉0．05），结果与黄斑区测定的直径大小无关。结论：HRTⅡ黄斑模块中的e值能够量化测量和客观评价DME程度。