Acute effects of insulin on aqueous humor flow in patients with type 1 diabetes

PURPOSE: Previous studies reported reduced aqueous humor flow through the anterior segment of the eye in patients with type 1 diabetes. This study investigates whether reduced flow is the result of the diabetic state or of alterations in glucose or insulin concentrations. METHODS: A cross-sectional study, involving patients with type 1 diabetes and healthy controls, measured aqueous flow at different insulin concentrations. Eleven patients with type 1 diabetes (hemoglobin A1C = 7.0 +/- 0.3% [mean +/- SEM], normal < 6.5) with no microvascular complications and 17 controls were prospectively studied. Controls were studied fasting and during a hyperinsulinemic-euglycemic clamp (insulin 2 mU/kg per minute). Patients with type 1 diabetes were similarly studied during two euglycemic clamp procedures (insulin 0.5 and 2.0 mU/kg per minute). Aqueous flow was measured by fluorophotometry. Pulsatile ocular blood flow and intraocular pressure were measured with a Langham flow probe. RESULTS: Control subjects had no change in aqueous flow during fasting and hyperinsulinemic conditions (3.0 +/- 0.1 vs 2.8 +/- 0.1 microl per minute). In the patients with type 1 diabetes, aqueous flow was not decreased with hyperinsulinemia, compared with the low insulin state (P =.7). Compared with control subjects, patients with type 1 diabetes had lower aqueous flow during hyperinsulinemia (2.4 +/- 0.1 microl per minute, P =.03) and at lower insulin conditions (2.6 +/- 0.1 microl per minute, P <.05). No differences in intraocular pressure or pulsatile ocular blood flow were noted between groups or between insulin states within groups. CONCLUSIONS: Aqueous flow is decreased in patients with type 1 diabetes under euglycemic conditions of high and relatively low insulin concentrations, despite the absence of microvascular complications.     

Effects of intensive control of blood glucose and blood pressure on microvascular complications in patients with type II diabetes mellitus

AIM:To evaluate the effects of intensive control of blood glucose and blood pressure on microvascular complications in patients with type II diabetes by comparing the therapeutic effects of intensive and standard treatment in patients with type II diabetes.METHODS: A total of 107 patients with type II diabetes were randomly assigned into intensive and standard treatment groups. Patients in the intensive treatment group received preterax (perindopril/ indapamide) to control blood pressure, and gliclazide (diamicron) MR to control blood glucose. Patients in the standard treatment group received routine medications or placebo. Urinary microalbumin (UMA), urinary creatinine (UCR), the UMA/UCR ratio, and visual acuity were monitored according to the study design of the ADVANCE trial. Direct ophthalmoscopy and seven-field stereoscopic retinal photography were used to examine the fundi at baseline, and repeated after 5 years of treatment.RESULTS: The characteristics of patients in both groups were well balanced at baseline. After 5 years of treatment, visual acuity was found to be decreased in the standard group (P=0.04), but remained stable in the intensive group. The severity of diabetic retinopathy had not progressed in patients in the intensive group, but had deteriorated in the standard group (P=0.0006). The UMA/UCR ratio was not obviously changed in patients in the intensive group, whereas it was significantly increased in the standard group (P=0.00).CONCLUSION: Intensive control of blood glucose and blood pressure can decrease the incidence or slow the progression of microvascular complications in patients with type II diabetes, and maintain stable vision.     

强化降糖和降压对2型糖尿病患者微血管病变的影响

目的 观察强化降糖和降压对2型糖尿患者底微血管病变的影响.方法 将入选的107例2型糖尿病患者随机分入强化组和标准组,强化组给予低剂量培哚普利-蚓哒帕胺联合降压和以格利齐特缓释片为基础的强化降糖治疗,标准组接受常规治疗或安慰剂治疗.定期检查患者尿微量白蛋白、尿肌苷水平,并通过直接眼底镜检查眼底和眼底七个视野彩色立体照相,比较5年后患者尿微量白蛋白/尿肌苷指数(UMA/UCR)、视力及眼底变化情况.结果 强化组基线与5年UMA/UCR比较无差异,而标准组则有上升(P=0.00).两组患者基线时视力分布无统计学差异;治疗5年后强化组视力保持稳定,而标准组视力有所下降(P=0.04).基线时两组眼底糖尿病病变无差异,治疗5年后强化组眼底病变无发展趋势,而标准组糖尿病视网膜病变有所加重(P=0.0006),并有1例患者新发生视网膜静脉分支阻塞.结论 强化降糖和降压治疗能有效控制糖尿病患者微血管病变的发展,并能保持糖尿病患者视力稳定.     

Increased melatonin levels in aqueous humor of patients with proliferative retinopathy in type 2 diabetes mellitus

AIM: To report the association between melatonin levels in aqueous humor and serum, and diabetic retinopathy (DR) grade in type 2 diabetic patients. METHODS: Aqueous humor and plasma samples from 26 patients with DR (in nonproliferative and proliferative stages) and 14 control subjects were collected during cataract surgery after 6 p.m. Melatonin concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Melatonin levels were significantly higher in the aqueous humor of patients with proliferative diabetic retinopathy (PDR) [18.57±2.67 pg/mL (range 15.20-23.06) vs 13.63±2.71 pg/mL (range 10.20-20.20), P=0.0001], but not in those with nonproliferative retinopathy (NPDR) [13.79±2.56 pg/mL (range 9.80-20.10) vs 13.63±2.71 pg/mL (range 10.20-20.20), P=0.961] compared to controls. There was decrement in the plasma melatonin level of patients with PDR, but no significant differences between the plasma melatonin levels of the study groups [5.37±1.74 pg/mL (range 2.85-8.65) vs 6.11±1.90 pg/mL (range 3.13-9.41), P=0.293], or between control and DR groups [NPDR 6.11±1.90 pg/mL (range 3.13-9.41) vs control 6.15±1.91 pg/mL (range 2.18-9.86); PDR (5.37±1.74 pg/mL (range 2.85-8.65) vs control 6.15±1.91 pg/mL (range 2.18-9.86), P=0.808, P=0.264]. CONCLUSION: Elevated melatonin levels in aqueous humor in PDR may indicate the level to be associated with DR severity.     

Intraocular pressure and aqueous flow are decreased by cholera toxin

Delivery of 2.1 microgram of cholera toxin, a specific, irreversible activator of adenylate cyclase, via the blood lowers IOP from 17.4 to 11.2 mm Hg in 81/2 hr. decreases net aqueous flow by about 50% in 8 hr, and doubles blood flow to the anterior uvea at 8 to 13 hr. Intravitreal injection of 0.26 microgram of cholera toxin lowered IOP from 15.0 to 9.6 mm Hg, but heat-inactivated toxin had no effect on IOP. The toxin activates adenylate cyclase from ciliary processes 2.2-fold and stimulates cyclic AMP production by ciliary processes 7.4 times. Absence of aqueous flare, normal protein concentrations in the aqueous, and histologic examination all confirmed the functional and structural integrity of the blood-aqueous barrier after cholera toxin infusion. The data point to an important role for ciliary process adenylate cyclase in regulation of aqueous flow and maintenance of IOP.     

Endothelial function and aqueous humor flow rate in patients with Fuchs' dystrophy

Using a two-dimensional scanning fluorophotometer, we studied 50 subjects with symmetric ocular involvement of Fuchs' dystrophy without epithelial edema. Twenty-six subjects with confluent or nearly confluent cornea gutata with increased corneal thickness and 24 subjects with mild to moderate cornea guttata with normal corneal thickness were compared to normal control subjects. There were no statistically significant differences in endothelial permeability between the three groups. Corneal thickness was significantly increased in the subjects with confluent to nearly confluent guttae, however. These results suggest that endothelial pump function may be affected in subjects with advanced cornea guttata with stromal edema.     

Prostaglandin F2 alpha-1-isopropylester lowers intraocular pressure without decreasing aqueous humor flow

Using fluorophotometry, we performed a randomized, dose-response study of the effects of a prostaglandin derivative on aqueous humor flow. Prostaglandin F2 alpha 1-isopropylester, 0.224 micrograms, 0.448 micrograms, and 1.120 micrograms, in saline with polysorbate 80 was instilled into one eye of 20 subjects in three separate dose studies. Polysorbate 80 in saline was instilled in the fellow eye as a control. The drug had no measurable effect on aqueous humor flow or corneal endothelial permeability. Intraocular pressure measured eight hours after administration of the highest dose, 1.120 micrograms, was 20% lower in the treated eye as compared to the fellow eye (P less than .001).     

Intraocular pressure during vitrectomy in diabetic patients

23 eyes underwent vitrectomy for diabetic proliferative retinopathy complications: vitreous hemorrhage with or without tractional retinal detachment. After 6 months of follow-up, 64% of eyes had final visual acuities of 1/40 or better. Preoperative iris neovascularization and preoperative detachment of the macula have a worse prognosis. Decrease of peroperative complications is allowed by checking of intraocular pressure during vitrectomy.     

VEGF,IL-6,leptin水平测定在2型糖尿病患者房水中的临床意义

目的:检测2型糖尿病患者眼房水中血管内皮生长因子(vascular endothelial growth factor,VEGF)、白细胞介素-6(interleukin-6,IL-6)和瘦素(leptin)的含量,并探讨其临床意义。方法:对70例70眼2型糖尿病患者房水中VEGF和IL-6的含量采用双抗体夹心酶联免疫吸附法检测,leptin含量采用放射免疫法检测。根据散瞳眼底检查和眼底荧光素血管造影检查,将实验组分为:无糖尿病性视网膜病变组22例22眼、单纯型糖尿病性视网膜病变组28例28眼、增生型糖尿病性视网膜病变组20例20眼,对照组为健康的老年性白内障患者20例20眼。结果:3组房水VEGF的含量分别为(250.32±26.77),(300.11±58.89),(496.23±91.06)ng/L,IL-6含量分别为(162.81±33.92),(256.76±64.15),(391.27±90.46)ng/L,leptin含量分别为(69.80±21.37),(155.08±32.76),(230.27±56.92)ng/L,对照组房水VEGF含量为(144.69±26.55)ng/L、IL-6含量为(86.71±22.69)ng/L,leptin含量为(43.62±20.02)ng/L,对照组与实验组比较差异均有统计学意义(F=118.62,P<0.01;F=110.53,P<0.01;F=101.22,P<0.01)。对照组、NDR,BDR与PDR组房水VEGF,IL-6,leptin含量有依次增加的趋势。房水中VEGF与IL-6,leptin含量有相关性(r=0.995,P<0.01;r=0.776,P<0.01);房水中VEGF,IL-6,leptin含量与糖尿病患者的病程及糖尿病性视网膜病变的严重程度有相关性(r=0.722,P<0.01;r=0.716,P<0.01)(r=0.869,P<0.01;r=0.865,P<0.01)(r=0.776,P<0.01;r=0.765,P<0.01)。结论:VEGF,IL-6,leptin在糖尿病性视网膜病变的形成过程中有重要作用,且VEGF与IL-6,VEGF与leptin之间有相关性。     

病毒性前葡萄膜炎患者房水病毒类型检测分析

目的 分析临床诊断为病毒感染性前葡萄膜炎患者的房水病毒检测结果.设计回顾性病例系列.研究对象临床诊断为病毒感染性前葡萄膜炎患者25例(25眼).方法 记录患者全身病毒感染病史,对患者进行血清免疫学检查(HLA-B27、RF等)、常规眼科检查(包括视力、眼压、裂隙灯、间接检眼镜检查等),通过前房穿刺获取房水,应用RT-P...     

Effects of ibopamine eye drops on intraocular pressure and aqueous humor flow in healthy volunteers and patients with open-angle glaucoma

PURPOSE: On the basis of intraocular pressure measurements and fluorophotometry we assessed the effects of 2% ibopamine eye drops on aqueous humor production in normal and glaucomatous eyes. METHODS: Thirty subjects (15 healthy volunteers and 15 open-angle glaucoma patients with ocular hypertension) were included in a placebo-controlled study with random assignment of treatment from masked containers. All subjects underwent ophthalmologic examinations and intraocular pressure (IOP) measurements. Fluorophotometry was done in both eyes at baseline (without treatment) and during treatment. Each subject was treated with 1 drop of 2% ibopamine in one eye and 1 drop of placebo in the fellow eye 30 minutes before fluorophotometric scans and every hour after the first instillation (for a total of 4 times). Safety was evaluated by recording adverse events and ocular symptoms and signs. Aqueous humor flow data were analyzed using the paired t-test, comparing ibopamine and placebo-treated eyes. RESULTS: No changes in IOP were detected in normal eyes, whereas glaucomatous eyes showed a mean increase of 4 mmHg (95% CI 3.46-4.51) from baseline. The difference in IOP between healthy eyes and those with glaucoma was significant (p < 0.0001). In normal eyes and patients with glaucoma ibopamine led to a significant increase in aqueous humor flow compared with placebo-treated eyes (p < 0.01). The safety profile of ibopamine was very good. CONCLUSIONS: The results seem to confirm that ibopamine increases aqueous humor production in normal and glaucomatous eyes, raising IOP only in eyes with glaucoma.     

Effects of travoprost on aqueous humor dynamics in patients with elevated intraocular pressure

PURPOSE: To determine the mechanism by which travoprost 0.004% reduces intraocular pressure (IOP) in patients with ocular hypertension or primary open angle glaucoma. DESIGN: This is a randomized, double-masked, placebo-controlled, single center study of 26 patients scheduled for 3 visits (baseline, day 15, and days 17 to 18) following screening. METHODS: After appropriate washout of all ocular medications, baseline IOPs were taken and travoprost 0.004% was administered once-daily in the evening for 17 consecutive doses to 1 eye and its vehicle to the fellow eye in a randomized, masked fashion. On day 15, beginning 12 hours after the 14th consecutive dose, IOP was measured by pneumatonometry, aqueous flow and outflow facility by fluorophotometry, and episcleral venous pressure by venomanometry. Uveoscleral outflow was determined by mathematical calculation. Two days later, the last drop of drug/vehicle was given at 2000 hours. Fluorophotometry and tonometry measurements were repeated between 2200 and 0600 hours. Treated eyes were compared with contralateral control eyes or baseline measurements, and daytime measurements were compared with nighttime measurements using paired t tests. RESULTS: Travoprost-treated eyes showed a significant (P<0.001) decrease in daytime IOP compared with baseline (26%) or to vehicle-treated eyes (22%), and an increase in daytime outflow facility (P=0.001; 64%). The increase in uveoscleral outflow was not statistically significant. At night, the IOPs of travoprost-treated eyes remained 21% to 24% below baseline daytime values. Seated and supine IOPs in control eyes were significantly (P<0.04) lower at 2200 hours than 1700 hours (P<0.04). Supine IOPs were higher than seated IOPs in both control and treated eyes (P<0.001). Aqueous flow was significantly (P<0.001) reduced at night in both travoprost (30%) and vehicle-treated (25%) eyes when compared with daytime values. No other comparisons were statistically significant. CONCLUSIONS: Travoprost seems to lower IOP by increasing trabecular outflow facility. An effect on uveoscleral outflow cannot be ruled out.     

2型糖尿病合并皮质性白内障患者房水中Txnip、Trx的定量检测及相关性分析

目的 探讨2型糖尿病合并皮质性白内障的患者房水中硫氧还蛋白(thioredoxin,Trx)、硫氧还蛋白互作蛋白(thioredoxin interacting protein,Txnip)的含量以及与皮质性白内障程度的相关性.方法 采用酶联免疫吸附实验(ELISA法)测定60例(60眼)明确诊断2型糖尿病合并皮质性白内障患者的房水中Trx及Txnip的含量,其中按照患者糖化血红蛋白(hemoglobin A1c,HbA1c)值将患者分组:A组(对照组,20例)HbA1c＜ 5.5％;B组(20例)5.5％≤HbA1c＜ 6.5％和C组(20例)HbA1c≥6.5％.结果 与A组相比,B组患者房水中Txnip浓度增高,而C组浓度最高,差异均有统计学意义(均为P＜0.05);与A组相比,B组TⅨ的浓度升高,而C组Trx的浓度最低,差异均有统计学意义(均为P＜0.05).A组中Trx与Txnip的浓度呈正相关(r=0.810,P=0.000);在C组中,Trx与Txnip的浓度呈负相关(r=-0.809,P=0.000),与白内障程度呈负相关(r=-0.727,P=0.001),其余均不相关(均为P＞0.05).Logistic回归分析显示,Txnip和HbA1c是白内障发病的危险因素.结论 Trx、Txnip可能参与了糖尿病患者中白内障的发生发展.     

Latrunculins' effects on intraocular pressure, aqueous humor flow, and corneal endothelium

PURPOSE: To determine the effects of latrunculin (LAT)-A or -B on intraocular pressure (IOP), aqueous humor flow (AHF), anterior chamber (AC) protein concentration ([protein]AC), corneal endothelial permeability and morphology, and corneal thickness in living cynomolgus monkeys. METHODS: Topical LAT-A or LAT-B was administered to one eye, and vehicle to the other. IOP was measured by Goldmann tonometry, AHF and corneal endothelium transfer coefficient (ka) by fluorophotometry, [protein]Ac by Lowry assay, corneal endothelial cell morphology by specular microphotography, and corneal thickness by ultrasound pachymetry. RESULTS: LAT-A began to lower IOP at 6 hours and maximally reduced IOP by 4.6 mm Hg at 9 hours. LAT-B lowered IOP within 1 hour and maximally reduced IOP by 3.1 mm Hg at 6 hours. LAT-A increased AHF by 87% for 3 hours and increased ka by 94% over 6 hours; LAT-B increased ka by 39% over 6 hours without affecting AHF. LAT-A increased IV fluorescein entry into the cornea approximately 10 fold, but did not affect IV fluorescein entry into the AC. LAT-A increased [protein]AC by 25% at 2 hours but not 5.5 hours. LAT-B variably and insignificantly increased [protein]AC: at 1 hour but not at 6.5 hours. LAT-A induced extensive corneal endothelial pseudoguttata within 1 hour, with normal cell counts by 7 days. LAT-B increased central corneal thickness maximally by 47 microm at 3.5 hours. CONCLUSIONS: LAT-A and -B significantly reduced IOP and were consistent in their facility-increasing effect, indicating that pharmacologic disorganization of the actin cytoskeleton in the trabecular meshwork by latrunculins may be a useful antiglaucoma strategy. However, effects on corneal endothelium or ciliary epithelium are a potential safety issue.     

Intraocular lenses in patients with diabetes mellitus

Presented are personal experiences concerning the application of artificial intraocular lenses in patients with diabetes and cataract. Operated were patients aged 50-76 years in whom implantation of an artificial lens of Alcon or Cilco was performed either to the anterior or posterior chamber. During the qualification for surgery eliminated were patients with proliferating retinopathy, with rubeosis iridis (with or without secondary glaucoma) and with juvenile diabetes. In 16 patients the obtained visual acuity was 0.8-1.0, in one female patient 0.5; in the remaining 2 persons the visual acuity amounted 0.2 and 0.3. These patients exhibited a simple exudative retinopathy with a macular oedema and after surgery they were subjected to a laser therapy. Observation of our material showed that qualifying diabetic patients for cataract extraction and taking into consideration the over mentioned contraindications one can obtain good results similar as in other patients with cataract.     

HMGB-1在DR患者房水及血浆中水平变化分析

目的:观察糖尿病性视网膜病变(diabetic retinopathy,DR)患者房水和血浆中高迁移率族蛋白-1(high-mobility groupbox-1,HMGB-1)的变化及其临床意义。方法:以西安交通大学第一附属医院眼科2010-08/12住院糖尿病(diabets mellitus,DM)患者为研究对象,按有无DR分为糖尿病无视网膜病变(non-diabetic retinopathy,NDR)组及DR组。DR组按病程分为单纯性糖尿病性视网膜病变(background diabetic retinopathy,BDR)组及增殖性糖尿病性视网膜病变(proliferative diabetic retinopathy,PDR)组。设正常对照组,对研究对象分别收集房水和血浆标本,共收集房水28例,血浆40例,均采用双抗体夹心ABC-ELISA法进行人HMGB-1定量ELISA测定。结果:DM患者房水中的HMGB-1浓度明显高于对照组(P<0.05),DM患者按DR病程分组时,HMGB-1浓度未见明显差异(P>0.05)。DM患者血浆中HMGB-1浓度与对照组比较未见明显差异(P>0.05)。结论:HMGB-1在DR的发生中可能起到重要作用,但与DR的病理进程无明显关系。     

2型糖尿病患者白内障术后黄斑水肿与房水中TGF-β2、FGF及 MCP-1的研究

目的：探讨房水中转化生长因子-β2（TGF-β2）、成纤维细胞生长因子（FGF）及单核细胞趋化因子1（ MCP-1）水平与2型糖尿病患者白内障术后黄斑水肿的联系。方法选取在我院接受手术治疗的85例白内障合并2型糖尿病患者,将术后出现黄斑水肿的39例列为观察组,未出现黄斑水肿的46例作为对照组。对比两组研究对象视网膜厚度;分析两组研究对象房水中细胞因子（ TGF-β2、FGF及MCP-1）水平;分析观察组患者TGF-β2、FGF及MCP-1与视网膜厚度的关系。结果观察组研究对象黄斑区全层视网膜各部位厚度中中心凹、鼻内侧、颞内侧及平均厚度水平显著高于对照组;观察组研究对象TGF-β2、FGF及MCP-1水平明显高于对照组;观察组患者房水中TGF-β2、FGF及MCP-1与视网膜平均厚度值呈正相关。结论房水中TGF-β2、FGF及MCP-1与2型糖尿病患者术后黄斑水肿关系紧密,可作为评价其相关的特异性指标,为临床上预防及减轻黄斑水肿的发生提供有关依据。