Permeability of the blood-ocular barrier in adolescent and adult diabetic patients.

The permeability of the blood-ocular barrier was examined by fluorophotometry in adolescent and adult diabetic patients before the onset of retinopathy. The adolescent group consisted of 52 eyes of 52 insulin dependent diabetic patients aged 11 to 19 years and a control group of 10 eyes of 10 normal adolescents. The adult group consisted of 74 eyes of 74 non-insulin dependent diabetics and a control group of 30 eyes of 30 normal adults. The increase in lens autofluorescence in the adolescent diabetic patients compared with the controls was striking and showed a significant positive correlation (r = 0.79, p < 0.0001) with the duration of diabetes. Anterior chamber (AQ) values, an index of the permeability of the blood-aqueous barrier (BAB), increased in the adolescent diabetic patients compared with the controls and showed a significant positive correlation with glycosylated haemoglobin levels. No significant differences from the controls were observed regarding the permeability of the blood-retinal barrier (BRB). In the adult group there was no significant difference in either the permeability of the BRB or the AQ values between the diabetic and the control groups. Our results suggest that adolescent diabetic patients differ from adults in that BAB permeability is increased before the onset of retinopathy, suggesting that this is the cause of the striking increase in lens autofluorescence.     

Blood-retinal and blood-aqueous barrier permeability,lens autofluorescence and transmission in insulin-dependent diabetic youngsters

The permeability of the blood aqueous and blood retinal barrier, the lens transmission, and the lens autofluorescence were measured by fluorophotometry in 7 diabetic youngsters treated by conventional therapy (mean age, 10.9 ± 4.4 years), 9 diabetic youngsters treated by continuous s.c. insulin infusion (mean age, 12.3 ± 5.0 years), and 13 healthy controls (mean age, 12.4 ± 5.1 years). The mean permeability value for the blood retinal barrier of the diabetic juveniles did not differ significantly from that of the controls (P > 0.4), and no correlation with metabolic control (HbAl_c) or duration of diabetes was found (P > 0.1). No differences in lens transmission larger than 4% were found. The mean value of lens autofluorescence corrected for normal age-dependency was found to correlate with the metabolic control: an increase of mean HbAl_c by 1% resulted in an extra increase of autofluorescence by 11% (P = 0.002). This result suggests that good metabolic control can suppress excess lens autofluorescence, a precursor of cataract.Supported by the Diabetes Fonds Nederland, the Stichting Blindenpenning, the Stichting Vrienden van het Oogziekenhuis, and the Stichting Blindenhulp     

Clinical and metabolic factors associated with the blood retinal barrier permeability in insulin dependent diabetes mellitus without retinopathy

The authors assessed a study pointing out the relationship between the permeability of Blood Retinal Barrier (BRB), using vitreous fluorophotometry, and several risk clinical and laboratory data in Insulin Dependent Diabetes Mellitus (IDDM). Eighty eyes of 40 IDDM patients were evaluated. Their mean age was 14.8 ± 3.2 years. Twenty healthy volunteers served as control group (mean age 15.3 ± 3.2 years). Preexisting diabetic retinopathy was dismissed after funduscopy and fluorescein angiography. The studied risk factors were: age, duration of diabetes, HLA antigens, blood pressure, cholesterol and triglycerides levels, glycosylated hemoglobin, insulin dose/kg body weight and fructosamine. Vitreous and lens fluorophotometry was performed in both groups (VPRt). The mean VPRt in IDDM patients was 3.56 ± 1.47 × 10–6 min^–1. In healthy subjects it was 2.53 ± 0.55 × 10–6 min^–1, establishing a significant difference (p < 0.01). We found a statistically significant correlation between VPRt and duration of diabetes, insulin dose/kg body weight and HbAlc. No correlation was found between VPRt and the rest of parameters. We conclude that vitreous fluorophotometry is a valid method to measure BRB; and the three factors mentioned above are related to the BRB permeability.Abbreviations BRB blood retinal barrier - DR diabetic retinopathy - VF vitreous fluorophotometry     

Toll样受体4及相关炎性细胞因子在糖尿病大鼠视网膜中的表达

目的 观察糖尿病大鼠视网膜中Toll受体4（TLR4）、炎性细胞因子的表达水平以及视网膜中白细胞聚集与视网膜通透性改变。方法 Brown Norway大鼠120只,剔除自然死亡14只,随机分为实验组和对照组,每组均为53只大鼠。实验组大鼠腹腔注射链脲佐菌素建立糖尿病模型;对照组大鼠腹腔注射等体积柠檬酸-柠檬酸钠缓冲液。建模后4周行定量聚合酶链反应、蛋白质免疫印迹法检测,观察大鼠视网膜中TLR4的基因及蛋白表达,酶联免疫吸附试验测定大鼠视网膜匀浆上清液中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β(IL-1β)、单核细胞趋化蛋白-1（MCP-1）等炎性细胞水平;吖啶橙眼底血管造影观察视网膜中白细胞密度;伊凡思蓝（EB）检测视网膜通透性。结果 对照组、实验组大鼠视网膜TLR4 mRNA、蛋白表达量比较,差异均有统计学意义（F=1.606、0.789,P＜0.05）;视网膜匀浆上清液中MCP-1、IL-1β、TNF-α表达量比较,差异均有统计学意义（F=24.622、5.758、4.829,P＜0.05）。实验组、对照组大鼠视网膜中白细胞密度分别为（6.2±0.5）×10^-5、(2.2 ±0.3）×10^-5个细胞 /像素2,实验组大鼠视网膜中白细胞密度较对照组显著增加,差异有统计学意义（F=2.025,P＜0.05）。实验组、对照组大鼠视网膜EB渗漏量分别为（23.41±4.47）、（13.22±3.59） ng/mg,实验组大鼠视网膜EB渗漏量较对照组增加,差异有统计学意义（F=21.08,P＜0.05）。结论 糖尿病大鼠视网膜中TLR4及炎性细胞因子表达均显著提高;视网膜中白细胞密度和视网膜渗漏量增加。     

Protective effect of captopril on the blood-retina barrier in normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy

The effect of 18 months' inhibition of angiotensin-converting enzyme by captopril on the leakage of fluorescein through the blood-retina barrier was examined in a prospective, randomized control study of 20 normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy. After 18 months, 15 patients remained in the study. Fluorescein leakage remained nearly unchanged in the captopril-treated group, being 4.1 ± 4.1 (mean ± SD) × 10^–7 cm/s at baseline and 4.2±4.1 × 10^–7 cm/s after 18 months' treatment. The permeability increased significantly (P<0.01) from 3.3±2.2 × 10^–7 cm/s to 5.6±3.5 × 10^–7 cm/s at 18 months in the control group. Arterial blood pressure was nearly constant in both groups throughout the study. The results indicate that angiotensin-converting enzyme inhibition with captopril can arrest or delay a progressive breakdown of the blood-retina barrier in normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy.The authors have no commercial or proprietory interest in the drugs or instruments used in this study     

Evaluation of diabetic retinopathy by fluorophotometry

Background: Fluorophotometric variables (permeability of the blood-retinal barrier (BRB) and blood-aqueous barrier (BAB), corneal autofluorescence, and lenticular light transmittance) are reported to correlate with the severity of diabetic retinopathy. This preliminary multicenter study was performed to measure these variables simultaneously in patients with type 2 diabetes mellitus and to assess which of these variables could be of help in evaluating diabetic retinopathy. Methods: Eighty-two patients with type 2 diabetes and diabetic retinopathy were recruited in seven European university clinics. Each patient was investigated three times, at intervals of about one year. The investigations included fluorophotometric determination of corneal autofluorescence, lenticular light transmittance, and permeability of the BRB and BAB. Retinopathy was classified into four grades, using a simplified evaluation system based on the Modified Airlie House retinopathy classification and applied to color fundus slides of standard fields 1 and 2. Results: Multiregression analyses revealed that only corneal autofluorescence and BRB permeability were correlated with the severity of diabetic retinopathy (P < 0.05). Corneal autofluorescence and BRB permeability as single variables were found to be indicative of severe nonproliferative retinopathy and proliferative retinopathy (sensitivity 100% and 86%, respectively, and specificity 65% and 85%, respectively). Combination of both variables increased specificity to 92%. Conclusions: This preliminary multicenter study shows that fluorophotometric variables can be measured simultaneously and reliably in patients with diabetes and that corneal autofluorescence and BRB permeability (individually or in combination) could be of help in detecting severe non-proliferative retinopathy and proliferative retinopathy. This revised version was published online in July 2006 with corrections to the Cover Date.     

The effects of an aldose reductase inhibitor on the progression of diabetic retinopathy

The polyol pathway has long been associated with diabetic retinopathy. Glucose is converted to sorbitol with the aid of the enzyme aldose reductase. Aldose reductase inhibitors can prevent changes induced by diabetes. A total of 30 patients with minimal background retinopathy were randomly divided into a ponalrestat-taking group and a placebo-taking group. All were followed for 6 months and twenty-three were followed for 12 months. The baseline microaneurysm count was 2.6 ± 1.9 (mean ± SD) for the ponalrestat group and 3.5 ± 2.9 for the placebo group. At 6 months the counts were 3.1 ± 3.5 and 2.9 ± 3.6 and after 12 months 3.0 ± 4.1 and 2.9 ± 3.4. There is no statistically significant difference between the groups at 0, 6 or 12 months of study. The change in retinopathy severity level did not significantly differ between the two groups at either 6 or 12 months. Ponalrestat adminstration at a dosage of 600 mg daily for 12 months has no significant effect on the course of minimal retinopathy in diabetic patients.     

Treatment of early diabetic retinopathy with cyclandelate.

In order to assess the effect of cyclandelate on the abnormal permeability of the blood-retinal barrier which occurs in diabetic patients before any other lesions are apparent in the retina a well-controlled, double blind, and paired trial was carried out in 22 patients. The treatments were randomised. The permeability of the blood-retinal barrier was assessed by vitreous fluorophotometry. Each patient was examined before being involved in the trial and then another 3 times with 1 month's interval. The total duration of treatment was 3 months. The results showed that the breakdown of the blood-retinal barrier as evidenced by the degree of abnormal fluorescein penetration into the vitreous suffered a significant decrease in the diabetic patients treated with cyclandelate when compared to the patients submitted to placebo administration, and this effect is particularly apparent in the third month of treatment.     

The effect of intravitreal triamcinolone on diabetic macular oedema

Background Diabetic macular oedema is a frequent cause of visual loss in patients with diabetic retinopathy. The purpose of this study was to assess the efficacy of intravitreal triamcinolone acetonide in reducing diabetic macular oedema and improving visual acuity.Methods In this prospective study 12 eyes of 12 patients with diabetic macular oedema unresponsive to prior laser treatment received an intravitreal injection of 4 mg triamcinolone acetonide. Examinations were performed 1 day preoperatively and at 1 week and 1, 3, 6, and 9 months after surgery and included slit-lamp examination, measurement of IOP, assessment of distance as well as reading visual acuity and assessment of macular thickness using optical coherence tomography (OCT).Results Mean age of the patients (mean±SD) was 66.6±8.6 years. Mean best-corrected visual acuity (BCVA) for distance (LogMAR using ETDRS charts) improved from 1.0±0.4 preoperatively to 0.9±0.4 (p=0.01) 1 week and to 0.9±0.4 (p=0.02) 1 month postoperatively. Mean BCVA for reading vision (LogRAD using Radner Reading Charts) improved from 1.1±0.4 preoperatively to 0.9±0.4 (p=0.002) 1 month postoperatively. Mean macular thickness decreased from 450±190 (m) preoperatively to 305±153 (p=0.02) 1 month postoperatively. No significant improvement in VA and no significant reduction of macular thickness could be observed 3, 6, and 9 months postoperatively. Mean intraocular pressure significantly increased from 14.7±2.7 mmHg preoperatively to 16.9±3.0 mmHg at 1 month (p=0.02).Conclusion A single intravitreal injection of triamcinolone acetonide led to a significant improvement in mean VA in patients with diabetic macular oedema. However, the significant effect was not permanent and persisted for only 1 month.The study was carried out at the Medical University of Vienna, Department of Ophthalmology, Austria. The authors have no proprietary or financial interest in any product mentioned in this article and received no financial support for this study.     

Intraocular barrier permeability in spontaneously diabetic Chinese hamster]

Fluorophotometry was performed with normal and spontaneously diabetic Chinese hamsters (CHAD) in order to investigate differences in blood-ocular barrier permeability and lens autofluorescence. Blood-aqueous barrier permeability was evaluated by the fluorescence value in the anterior chamber which was corrected using both autofluorescence value and the concentration of fluorescein in the plasma. The results showed that the diabetic group had significantly higher values than the normal group (p less than 0.01). Blood-retinal barrier permeability was evaluated in the vitreous by the same method. There was no significant difference between the two groups. Lens autofluorescence values were also significantly higher for the diabetic group compared with the normal group (p less than 0.001). In these spontaneously diabetic Chinese hamsters, the permeability function of the blood-retinal barrier seemed to be maintained its normal level, while both the blood-aqueous barrier and lens were damaged by deleterious effects of diabetes.     

Effect of morphological abnormalities on blood retinal barrier permeability in diabetic retinopathy

The morphological base for the impaired function of the blood retinal barrier was studied in 50 eyes of 10 insulin dependent and 21 non-insulin dependent patients with various levels of diabetic retinopathy. The permeability of the blood retinal barrier (P_BRB) was determined by vitreous fluorophotometry with correction for autofluorescence, lenstransmission and non-protein bound plasma fluorescein concentration. Morphological abnormalities of diabetic retinopathy assessed by fundus photography and fluorescein angiography were individually scored on a decimal scale and related to the P_BRB by multiple regression analysis. The P_brb was not correlated to morphological abnormalities of non-proliferative retinopathy [(1) microaneurysms, (2) hard exudates, (3) soft exudates, (4) intraretinal hemorrhages, (5) fluorescein leakage, and (6) capillary closure, p > 0.3]. The P_BRB was correlated to morphological abnormalities of (pre)proliferative retinopathy [(1) intraretinal microvascular abnormalities (S_irma) and (2) new vessels (S_neo): p_brb = A – B.S_IRMA – C.S_neo with P_BRB in nm/sec, A = 1.5 ± 0.5, B = 0.9 ± 0.2 and C = 1.7 ± 0.4, R² = 0.65, p < 0.0001]. It can be concluded that the increased blood retinal barrier permeability in diabetic patients is mainly due to (pre)proliferative abnormalities and not to non-proliferative abnormalities.     

Posterior sub-Tenon injection of triamcinolone acetonide as pretreatment for focal laser photocoagulation in diabetic macular edema patients

Purpose  To determine whether a posterior sub-Tenon injection of triamcinolone acetonide (TA) before focal photocoagulation is safe and effective in patients with diabetic macular edema. Methods  Sixteen eyes of 11 diabetic patients with unresolved diffuse macular edema were treated with a 20-mg sub-Tenon injection of TA 1 to 2 months before focal photocoagulation. Focal photocoagulation was applied only to microaneurysms, and grid laser photocoagulation was not performed. The main outcome measures used were visual acuity (VA), central macular thickness (CMT) determined by optical coherence tomography (OCT), and the fluorescein angiographic appearance of the retina. Patients were followed for at least 6 months. Results  One month after the sub-Tenon injection of TA, the macular edema was resolved with a significant reduction of the CMT on OCT. VA improved slightly. Subsequent focal photocoagulation of the microaneurysms maintained the significant reduction of CMT for up to 6 months. A significant improvement of VA was observed in 37.5% patients at 6 months, and there was no decrease in VA in any of the patients. Conclusions  A 20-mg sub-Tenon TA injection prior to focal laser photocoagulation is a safe and beneficial treatment in patients with diabetic macular edema. An erratum to this article can be found at     

Blood-retinal barriers in juvenile diabetics in relation to early clinical manifestations,HLA-DR types,and metabolic control

Eighty-seven diabetics 8.5–26 years old (mean ± SD 15.3 ± 3.9) and 32 healthy non-diabetic controls 8–27 years old (13.9 ± 4.3) were included in the study. They had had the disease for 2 months to 19 years (5.8–4.0 years). Seventy-two of the diabetic patients were HLA-DR type, 13 patients had DR 3 alone, 25 DR4, 33 DR 3,4 and 1 patient was neither DR 3 nor 4. The mean fluorescein concentration in the vitreous body 3.5–7 mm from the retinal surface at 60 min after intravenous administration of fluorescein was 15.5 ± 11.9 ng/ml in the diabetics and 7.2 ± 3.7 ng/ml in the non-diabetic controls (P < 0.001). The diabetics still in partial remission had an almost normal blood-retinal barrier (BRB; 7.9 ± 4.8 ng/ml) while about 55% of the diabetics beyond remission had impaired barrier function. Abnormal leakage was found in some patients who had had diabetes for less than 2 years and also before the onset of puberty. The incidence of abnormal leakage increased with increasing age and duration. There was a positive correlation between fluorescein leakage and the blood glucose level at the onset of diabetes (P < 0.01). There was no statistically significant relationship between specific HLA-DR types and abnormal leakage. A defect BRB was significantly correlated with poor short-term metabolic controls, expressed as glucosuria index during the last week before examination with vitreous fluorophotometry. Prospective studies will show whether abnormal BRB gradually leads to irreversible retinopathy.     

Lens fluorescence in relation to nephropathy in insulin-dependent diabetes mellitus

The relationship between diabetic nephropathy and blue-green lens fluorescence, lens transmittance, and other lens fluorometry parameters was studied in patients with long-term insulin-dependent diabetes mellitus. The findings in 10 patients who presented with diabetic nephropathy were compared with those of 11 patients of comparable age and duration of diabetes but without nephropathy. Diabetic nephropathy was associated with increased lens fluorescence (P=0.04) and decreased lens transmittance (P=0.045). We propose that lens changes may be responsible for various psychophysical abnormalities in diabetic patients and that our results explain the correlation of these abnormalities with the degree of microangiopathy.All legal requirements governing consent were met for this study. The authors have no proprietary or financial interest in the Fluorotron or in Coherent, Inc. Offprint requests to: M. Larsen     

Evaluation of the blood–aqueous barrier by laser flare cell photometry following retinal cryocoagulation

Purpose To evaluate the influence of peripheral 360° retinal cryocoagulation on the blood–aqueous barrier of patients with retinal vascular disorders.Methods The aqueous of 50 eyes of 50 patients with diabetic retinopathy or central vein occlusion was measured by laser flare photometry (FC-2000, Kowa) before peripheral 360° retinal cryocoagulation and 1 day, 1 week, and 1 month thereafter.Results Mean aqueous flare values before treatment were 15.7 (±8.2) photon counts/ms; mean cell count was 9.8 (±14.8) cells/0.5 mm³. One day after retinal cryocoagulation flare values had increased statistically significantly to a mean of 39.2 (±85.8) photon counts/ms, while the increase in mean cell number to 15.0 (±37.2) cells/0.5 mm³ did not reach statistical significance. One week following treatment, mean flare values had dropped to 30.9 (±49.6) photon counts/ms and were no longer significantly elevated compared with baseline, while the mean cell count of 11.1 (±27.0) cells/0.5 mm³ was now statistically significantly elevated compared with baseline. One month after treatment the flare values had decreased to a mean of 19.7 (±12.0) photon counts/ms, and mean cell count had decreased to 8.1 (±10.4) cells/0.5 mm³; at this point neither parameter showed a statistically significant difference from baseline values.Conclusion Peripheral 360° retinocryocoagulation does not lead to permanent disturbance of the blood–aqueous barrier.     

Blood-aqueous barrier permeability determination in HLA B27-positive acute anterior uveitis patients

The blood-aqueous barrier (BAB) permeability was studied by fluorophotometry in 17 healthy control subjects and in 27 eyes from 27 patients with HLA-B27-positive acute anterior uveitis (HLA-B27 AAU). Twenty of these patients had an associated spondyloarthropathy. BAB permeability was studied during the ocular inflammatory crisis and in the disease-free periods in the same patients. Anterior chamber fluorophotometric scans were performed before and 30 minutes after the intravenous injection of 14 mg/kg of sodium fluorescein. The diffusion coefficient (Kd) was obtained from the ratio between the fluorescein concentration in the anterior chamber and the NPBF. Data were analyzed using the Student's t test and analysis of variance. A statistically significant difference (P < 0.001) was found between the Kd of active HLA-B27 AAU (61.4±16.8×10^–4 min^–1) and the Kd of inactive HLA-B27 AAU (4.8±1.6×10^–4 min^–1). No statistically significant differences were found between the Kd of inactive HLA-B27 AAU and the Kd of the control subjects (4.3±1.0×10^–4min^–1). We also failed to detect significant differences between patients with and without spondyloarthropathy either during the acute attack or during the disease-free period. On the basis of these results we conclude that the permeability of the BAB remains intact in inactive HLA-B27-positive AAU. The parallel fluorophotometric behaviour of HLA-B27-positive AAU with spondyloarthropathy and without spondyloarthropathy suggests that both share a common pathogenetic mechanism.Presented in part at the ARVO meeting, Sarasota, USA, May 1993.     

玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab辅助微创玻璃体视网膜手术治疗严重增生型糖尿病视网膜病变的临床观察

目的 观察玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab（IVR）辅助微创玻璃体视网膜手术（VRS）治疗严重增生型糖尿病视网膜病变（PDR）的临床效果。方法 回顾性非随机临床对照研究。临床确诊为严重PDR的60例患者70只眼纳入研究。依据手术前是否行IVR治疗将患者分为IVR组和对照组。IVR组31例35只眼,对照组29例35只眼。IVR组于手术前3～4 d玻璃体腔注射10 mg/ml的ranibizumab 0.05 ml（含ranibizumab 0.5 mg）,然后行23G微创VRS。对照组直接行23G微创VRS。手术后随访3~12个月,平均随访时间（4.5±1.8）个月。对比分析两组患者最小分辨角对数（logMAR）最佳矫正视力（BCVA）、眼压、黄斑中心凹视网膜厚度（CRT）和视网膜复位及手术后并发症的发生情况。结果 IVR组患者均未发生与注射及药物相关的局部及全身不良反应。手术后1周,1、3个月,IVR组玻璃体积血（VH）发生率分别为8.6%、0.0%、0.0%,对照组VH发生率分别为28.6%、17.1%、8.6%。两组手术后各时间点VH发生率比较,手术后1周及1个月之间差异有统计学意义（χ²=4.63、4.56,P＜0.05）,手术后3个月之间差异无统计学意义（χ²=0.24,P＞0.05）。IVR组、对照组手术后平均logMAR BCVA分别为0.81±0.40、1.05±0.42,均较手术前提高。IVR组、对照组手术前后平均logMAR BCVA比较,差异有统计学意义（t=12.78、4.39,P＜0.05）。IVR组手术后平均logMAR BCVA较对照组提高,两组手术后平均logMAR BCVA比较,差异有统计学意义（t=-2.36,P＜0.05）。IVR组、对照组手术后平均CRT分别为（297.6±79.8）、（347.6±85.0） μm,两组平均CRT比较,差异有统计学意义（t=-2.53,P＜0.05）。IVR组、对照组手术后视网膜复位率分别为97.1%、94.3%,两组视网膜复位率比较,差异无统计学意义（χ²=0.35,P＞0.05）。IVR组、对照组一过性高眼压发生率分别为14.3%、34.3%,两组间一过性高眼压发生率比较,差异有统计学意义（χ²=4.79,P＜0.05）。IVR组、对照组视网膜前膜、新生血管性青光眼等并发症发生情况比较,差异也无统计学意义（χ²=0.97、0.51,P＞0.05）。结论 IVR辅助23G微创VRS治疗严重PDR能提高患者视力,降低手术后VH发生率,减小CRT。     

Effect of cyclospasmol on early diabetic retinopathy

A randomized, double-blind, placebo controlled study to investigate the long-term effect of Cyclospasmol^R (cyclandelate) on the abnormal permeability of the blood-retinal barrier was performed in 26 patients with insulin-dependent diabetes mellitus for at least 1 year and minimal retinopathy. Cyclospasmol 400 mg or placebo capsules were taken 4 times daily for 12 months by equal numbers in both groups.Each patient underwent a routine ophthalmoscopic examination, retinal fluorescein angiography and quantitative vitreous fluorophotometry to assess the permeability of the blood-retinal barrier just before the trial and following 6 and 12 months of therapy. Laboratory tests for determining blood and urine glucose levels and blood HbA₁-levels were also carried out at these assessments.Statistically significant changes in diabetic control, in HbA₁-levels or in the frequency of retinal microaneurysms could not be shown in either treatment group during the trial, nor were there any significant differences in these parameters between the two groups. Analysis of fluorophotometric data on fluorescein penetration into the left posterior vitreous demonstrated significant reductions in this parameter during the trial compared to the pretreatment level in Cyclospasmol treated diabetics. These changes in the pretreatment level after 6 and 12 months also differed significantly between the two groups.However, this statistically significant beneficial reduction in fluorescein penetration into the left posterior vitreous did not occur in the right eye in the Cyclospasmol group.In placebo treated patients a consistently deleterious trend for this parameter was observed for both eyes during the one year study. The consistently beneficial trend in the right eye following Cyclospasmol and the consistently deleterious trend in both eyes following placebo with regard to the abnormal permeability of the blood-retinal barrier of diabetics with minimal retinopathy could probably be explained by the small number of patients in both groups. No side-effects were reported.     

Disorders of the blood-aqueous barrier after phacoemulsification in diabetic patients

PURPOSE: To evaluate the function of the blood-aqueous barrier after phacoemulsification with implantation of a foldable intraocular lens (IOL) in diabetic patients. METHODS: All patients were enrolled from those scheduled for phacoemulsification with intraocular lens implantation in Zhongshan Ophthalmic Center Guangzhou from March 2002 to June 2002. The classification on diabetic retinopathy (DR) was based on the fundus examination after cataract surgery. The blood-aqueous barrier function was examined using the laser flare cell meter (Kowa FC-2000) preoperatively and on postoperative days 1, 7, 30, and 90 by an independent examiner who was masked to the DR classification. Patients were operated by one experienced surgeon as per standard clinical protocol and were provided the same postoperative medical care. A linear regression and Wilcoxon test were used for the analysis. RESULTS: A total of 112 patients were divided into three groups: patients without diabetic mellitus as normal control (n=56), diabetic patients without diabetic retinopathy (n=2), with nonproliferation diabetic retinopathy (NPDR) (n=37), and diabetic patients with proliferation diabetic retinopathy (PDR) (n=17). All patients were examined and successfully followed up for 3 months after cataract surgery. Aqueous flare mean photon counts in PDR, NPDR, and control eyes were 8.94+/-0.57, 7.03+/-0.27, and 6.94+/-0.34 before surgery and increased to 32.42+/-0.67, 26.07+/-0.83, 26.27+/-1.37 on the first day after surgery (P<0.05), then decreased to 19.86+/-0.78, 14.08+/-0.54 and 13.96+/-1.05 at 7 days after surgery (P<0.05), 13.24+/-0.29, 9.86+/-0.33, and 9.07+/-0.43 at 30 days after surgery (P<0.05); eventually, the counting decreased to 11.25+/-0.31, 7.24+/-0.67, and 7.16+/-0.27 at 90 days after surgery (P<0.05). Linear regression model suggested that other potential variables, such as age, sex, eye (left/right), phaco time, phaco energy, and hypertension were not related to the outcome. For patients without diabetes mellitus and diabetic patients with NPDR, highly statistically significant differences (P<0.05) were found between preoperative flare value and those measured on days 1, 7, and 30 after surgery, but no statistically significant differences (P>0.05) were found between the preoperative flare value and those measured on postoperative days 90. However, patients with PDR still had a higher flare value even on postoperative day 90. The patients with intraoperative iris prolapse had a higher flare value between days 1 and 7 postoperatively. CONCLUSION: Phacoemulsification with a foldable intraocular lens implantation affects the blood-aqueous barrier more severely in diabetic patients with PDR than patients with NPDR and nondiabetic patients.     

Permeability of the blood-retinal barrier in healthy humans

Background: The aim of the study was to compare the inward permeability of the blood-retinal barrier in healthy subjects from six European cities. Methods: Seventy-two healthy subjects (age 20–70 years) were selected. At 30 min and 60 min after fluorescein injection, fluorescein mass in vitreous was calculated from the concentrations measured along the optical axis of the eye. Non-protein-bound fluorescein (NPBF) concentrations were measured in plasma prepared from blood samples taken 7, 15 and 55 min after injection. Blood-retinal barrier permeability (P_BRB) was calculated from the vitreous fluorescein mass and the time integral of NPBF and was corrected for the autofluorescence of ocular tissue and for lenticular light transmittance. Results: Mean PBRB values±SD (nm-^–1) were 2.07±0.54 (Coimbra), 2.01±0.43 (Frankfurt), 2.24±0.50 (Ghent), 2.37±0.56 (Herlev), 1.89±0.44 (Leiden) and 1.74±0.38 (Porto). Differences between centers were not significant (P>0.35). Measurements were reproducible and independent of the time after fluorescein injection (P>0.50). A PBRB higher than 3.16 nm·s^–1 or a value which had increased by 32% was considered abnormal (P<0.05). Conclusion: P_BRB values were similar in all centers. The results demonstrate that this is a highly sensitive and reliable method for measuring the permeability of the blood-retinal barrier.