Blood retinal and blood aqueous barriers in diabetics by fluorophotometry

The permeability of the blood retinal barrier (P_BRB) and the diffusion coefficient into the anterior chamber (k_d) in 20 insulin dependent (ID) and in 11 non-insulin dependent (NID) diabetics with various degrees of retinopathy were determined by fluorophotometry with a 25% accuracy. The difference of P_BRB and the k_d values between the NID and the ID patients was not significant (p > 0.05 and p > 0.22).The mean P_BRB and the mean k_d values differed significantly from those of a healthy population (p < 0.0013 and p = 0.025). A significant correlation was established between P_BRB and diabetes duration (r = 0.55; p < 0.01) but not between P_BRB or k_d values and metabolic control (HbA1) (p > 0.5) or creatinine clearance (p > 0.5). The time integrals of unbound plasma fluorescein in the diabetics between the time of injection and 1 hour later were comparable with those of healthy controls.The difference between the mean P_BRB value of diabetics with advanced retinopathy and that of a healthy population was significant (p < 0.003) but the difference for the mean values of diabetics with no or minimal background retinopathy was not (p > 0.2), indicating that P_BRB values do not increase to an abnormal level while signs of diabetic retinopathy are absent on fluorescein angiography.     

Grading of diabetic retinopathy from non-stereoscopic color fundus photographs--relationship to fluorescein angiography findings and three-year prognosis

PURPOSE: To evaluate the grading of diabetic retinopathy from non-stereoscopic color fundus photographs, we examined the relation of the photos to fluorescein angiography findings and to the three-year prognosis. METHODS: Fifty diabetic patients(70 eyes) who had severe non-proliferative diabetic retinopathy or early proliferative retinopathy without photocoagulation treatment were graded regarding 11 items of four-field fundus photographs using a 50-degree mydriatic camera. Fluorescein angiography was performed and the relation of the images to the grades of diabetic retinopathy were analyzed. In 51 eyes, the relation between the grading and the progression and treatment of diabetic retinopathy were evaluated. RESULTS: The grading of microaneurysms and retinal hemorrhages (p < 0.001), soft exudates (p = 0.01), intraretinal microvascular abnormalities (p < 0.001), arteriolar white threads (p = 0.003), venous loops (p = 0.01), and new vessels (p < 0.001) was significantly related to the nonperfused areas on fluorescein angiograms. The grading of diabetic retinopathy was also significantly related to the threeyear prognosis. CONCLUSION: These results indicated that the grading of diabetic retinopathy from fundus photographs may have a potential advantage over conventional classifications of diabetic retinopathy.     

Effects of aldose reductase inhibition with tolrestat on diabetic retinopathy in a six months double blind trial

To study the effects of the new aldose reductase inhibitor tolrestat on diabetic retinopathy, 31 diabetic patients with various degrees of retinopathy were randomly assigned to either tolrestat (200 mg once daily) or placebo treatment for six months. Separate morphological features of diabetic retinopathy were assessed by fundus photography and fluorescein angiography before and at the end of the study. The results showed some amelioration of clinical signs of diabetic retinopathy during aldose reductase treatment. Hard exudates, intraretinal hemorrhages and focal fluorescein leakage increased on average in the placebo and decreased in the tolrestat group. The difference was statistically significant for focal fluorescein leakage only. The permeability of the blood retinal barrier was determined by vitreous fluorophotometry before and at the end of the study. No change in permeability values was found.     

Peripheral Vessel Leakage (PVL): A New Angiographic Finding in Diabetic Retinopathy Identified with Ultra Wide-Field Fluorescein Angiography

Purpose: To characterize the relationship between peripheral vessel leakage and other angiographic features of diabetic retinopathy.

Design: Retrospective, consecutive case series.

Methods: Consecutive ultra wide-field angiographs obtained at a single institution for diabetic retinopathy were graded for angiographic characteristics including macular edema, retinal neovascularization, retinal vascular perfusion abnormalities, and retinal vascular staining and leakage.

Results: Angiographic characteristics of 264 eyes of 143 patients were evaluated. Findings included focal and diffuse angiographic macular edema (150/264, 57%), neovascularization (107/264, 41%), late peripheral vascular leakage (PVL) (107/264, 41%), and peripheral non-perfusion (142/264, 54%). Amongst all subjects untreated peripheral non-perfusion was associated with anterior neovascularization (78% vs. 48%, p?=?0.0001, Fisher exact test) and posterior neovascularization (78% vs. 43%, p?<?0.0001), but not with macular edema (p?=?0.71). PVL was associated with peripheral non-perfusion (78% vs. 38%, p?<?0.0001) and posterior neovascularization (53% vs. 35%, p?=?0.01), but not with macular edema (p?=?0.449). However, focal macular edema was strongly associated with PVL (33% vs. 13%, p?=?0.008) in eyes without peripheral non-perfusion. Amongst untreated eyes with non-proliferative retinopathy and macular edema, there was a trend for association between macular edema and peripheral non-perfusion (p?=?0.065).

Conclusion: Untreated peripheral non-perfusion and late peripheral vascular leakage detected using ultra wide-field FA are associated with neovascularization in diabetic retinopathy. PVL may be associated with focal diabetic macular leakage in this cohort.     

Retinal blood flow in diabetic children and adolescents

A total of 209 diabetic children and adolescents aged 6–17 years (mean, 12.6 ± 2.3 years) were examined by ophthalmoscopy, video fluorescein angiography and hemoglobin (HbA1c) tests. Microaneurysms were found in 26% of the children (ophthalmoscopy, 11%; angiography, 23%). The prevalence of retinopathy was 16% in patients aged 6–10 years, 27% in those aged 11–13 years and 36% in those aged 14–17 years. Only five diabetics aged 11–17 years showed lesions other than microaneurysms (hard exudates, intraretinal hemorrhages or retinal capillar leakage). Retinal blood flow was quantified using video fluorescein angiography. The arm-retina time (ART) and the arteriovenous passage time (AVP) as parameters of the retinal microcirculation were obtained using an image analysing system. The mean value for ART was 9.7±2.5 s and that for AVP was 1.43±0.52 s. AVP was significantly shorter in diabetic children and adolescents with good glycemic control (HbAlc, <7%; AVP, 1.35±0.44 s) than in those with bad glycemic control (HbA1c, 9 % ; AVP, 1.65 ±0.51 s).Supported by Deutsche Forschungsgemeinschaft grant 152/25-1. We are most grateful to Dr. Bürger-Büsing (University of Schad), President of the Child and Adolescent Diabetic's Association, for his assistance Offprint requests: B. Bertram     

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.     

数码眼底照相对住院糖尿病患者筛查DR并早期干预的应用价值

目的：探讨数码眼底照相机对住院糖尿病患者筛查糖尿病视网膜病变(DR)并早期干预的临床价值。

方法：选取2015-01/2016-12在我院内分泌科住院的糖尿病患者130例260眼,进行数码眼底照相检查和FFA检查。

结果：数码眼底照相中NPDR 82眼,PDR 28眼。荧光眼底血管造影检查中,NPDR 89眼,PDR 29眼。与FFA检查的金标准结果比较,免散瞳数码眼底照相筛查DR的Kappa值为0.87(>0.61)。两种方法对不同病程分期DR的检出结果无差异(P>0.05)。病程>10a的糖尿病患者,DR的阳性率明显增高(P<0.05)。

结论：数码眼底照相对住院糖尿病患者行常规视网膜检查,是早期发现DR的有效方法,进行早期干预对降低DR的致盲率具有重要意义。     

Red blood cell membrane mechanical fluctuations in non-proliferative and proliferate diabetic retinopathy

Purpose To study whether cell membrane mechanical fluctuation (CMF) of red blood cells (RBCs) are attenuated in non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR).Patients and methods Point dark-field microscopy-based recordings of local membrane displacements (frequency 0.3–25 Hz) were compared between type 2 diabetes patients with mild-to-moderate and severe NPDR and type 2 diabetes patients with PDR. The matched control group, corresponding to each stage of diabetic retinopathy, was based on non-diabetic patients who were evaluated in our clinic due to cataract.Results The average mean values of the maximal CMF amplitude did not differ between RBCs of NPDR patients (n=20) and controls (n=20) (19.5±1.5% and 19.6±1.7%, respectively). A statistically significant decrease in CMF amplitudes was observed in patients with PDR compared with patients with a non-proliferative disease (NPDR –20%, PDR –90%).Conclusion This new rheological characteristic demonstrates differences in the mechanical properties of RBCs in different stages of diabetic retinopathy. The significant reduction in CMF in patients with PDR may shed more light on the possible mechanism modulating retinal ischemia and leading to angiogenesis in these patients. Larger-scale studies are needed to evaluate these findings and the possible correlation between significantly lower CMF values and the progression of diabetic retinopathy.     

VITREOUS FLUOROPHOTOMETRY IN CHILDREN WITH TYPE I DIABETES MELLITUS

A clinical, biochemical and ocular study was carried out on 17 children with type I diabetes mellitus. Eight had no clinical or angiographic evidence of retinopathy (Stage 0), seven had stage 1, one had stage 2 background retinopathy (Malone's classification) and one had intraretinal microvascular abnormalities. The vitreous fluorescein concentration 3 to 5 mm in front of the macula in those without retinopathy varied from low to abnormally high, while the concentrations in those with retinopathy were above normal. There was no correlation between haemoglobin A₁ estimations taken at the time of the study and the vitreous fluorophotometry readings. This variation in fluorophotometry values obtained in diabetics with stage 0 disease differs from the findings in previous reports and may be of prognostic value in determining those patients at risk of developing retinopathy, and may be an indication for improving diabetic control.     

虹膜荧光血管造影联合眼底荧光血管造影在全视网膜激光光凝术后糖尿病视网膜病变患者中的应用研究

目的　探讨虹膜荧光血管造影（ｉｒｉｓｆｌｕｏｒｅｓｃｅｉｎａｎｇｉｏｇｒａｐｈｙ,ＩＦＡ）联合眼底荧光血管造影（ｆｕｎｄｕｓｆｌｕｏｒｅｓｃｅｉｎａｎｇｉｏｇｒａｐｈｙ,ＦＦＡ）检查在全视网膜激光光凝术后（ｐａｎｒｅｔｉｎａｌｐｈｏ-ｔｏｃｏａｇｕｌａｔｉｏｎ,ＰＲＰ）增生型糖尿病视网膜病变患者中的临床应用。方法　对ＰＲＰ术后的６５例１２３眼增生型糖尿病视网膜病变患者均行视力、眼压、裂隙灯、ＩＦＡ联合ＦＦＡ检查。采用非参数检验法对比分析裂隙灯和ＩＦＡ检测虹膜新生血管灵敏性的差异。结果　ＦＦＡ显示１２３眼中,２１眼视网膜无灌注区,３９眼视网膜新生血管,１２眼玻璃体积血和３２眼黄斑水肿。ＩＦＡ显示１２３眼中,９７眼无糖尿病虹膜病变,１３眼非增生型虹膜病变,１１眼增生型虹膜病变,２眼新生血管性青光眼。所有非增生型虹膜病变眼不能被裂隙灯发现,能被ＩＦＡ检测。ＩＦＡ检查发现虹膜新生血管眼（１１眼）比裂隙灯检查（５眼）更灵敏（Ｐ＝０．０３）。结论　ＩＦＡ联合ＦＦＡ检查能及早发现ＰＲＰ术后的增生型糖尿病视网膜病变合并糖尿病虹膜病变患者,为及时治疗提供帮助。     

眼底荧光血管造影在糖尿病视网膜病变中的应用价值及特征分析

目的：研究并探讨眼底荧光血管造影(FFA)在糖尿病视网膜病变(DR)诊疗中的应用价值。

方法：选择2014-01/2018-02期间在我院住院且疑似发生视网膜病变的糖尿病患者130例,所有患者均接受眼底照相和FFA检查。以临床确诊结果为参照,计算眼底照相和FFA检查对DR的诊断灵敏度、特异度、准确性,并比较二者对不同程度DR的诊断符合率,分析DR的FFA检查特征,采用Kappa一致性检验对两种诊断方法与临床确诊结果之间的一致性进行分析。

结果：FFA检查对DR的诊断灵敏度、特异度、准确性分别为96.8%、97.1%、96.9%,均高于眼底照相(P<0.05)。FFA检查对DR轻度、中度、重度的诊断符合率分别为97.1%、97.0%、96.4%,均高于眼底照相,但差异均无统计学意义(P>0.05)。经Kappa一致性检验分析,FFA检查诊断结果与临床确诊结果之间的一致性良好,而眼底照相与临床确诊结果之间的一致性仅为中等。FFA检查结果显示,DR多发生于鼻侧象限,在距视盘中周部分布较多,可见视网膜内微循环异常,视网膜微血管瘤、出血点、静脉串珠、视网膜毛细血管无灌注区的数量和分布位置各有不同; 部分患者在出现视网膜微血管瘤、出血点之前,出现黄斑中心凹厚度增加、局灶性棉绒斑、局灶性视网膜毛细血管无灌注区等表现。

结论：FFA检查对DR的诊断灵敏度、特异度、准确性高,与临床确诊结果之间的一致性较强,对于眼底照相检查中的疑似病变诊断准确。     

三种不同造影方式在糖尿病性视网膜病变诊断中的应用对比

目的：比较分析虹膜荧光血管造影(iris fluorescein angiography,IFA)联合眼底荧光血管造影(fundus fluorescein angiography,FFA)、吲哚菁绿血管造影(indocyanine green angiogrsphy,ICGA)和FFA在早期糖尿病性视网膜病变(diabetic retinitis,DR)中的诊断价值。

方法：选择2015-08/2016-08期间我院收治的DR患者70例136眼,全部患者分别接受ICGA、FFA、IFA+FFA检查,分析三种造影方式的检出结果。

结果：FFA检出病变120眼(88.2%),ICGA检出病变124眼(91.2%),IFA+FFA检出病变130眼(95.6%),三种检查方法病变检出率比较,差异无统计学意义(P>0.05); FFA检出48眼出现新生血管,18眼玻璃体积血,38眼黄斑水肿,16眼无灌注区; ICGA检出49眼新生血管,38眼黄斑水肿,17眼玻璃体积血,20眼无灌注区; IFA+FFA检出17眼增殖性糖尿病性虹膜病变(DI),22眼非增殖性DI,5眼NVG,92眼无DI。

结论：在DR诊断中,IFA+FFA、FFA、ICGA均具有不错的诊断价值,但IFA+FFA可及时发现合并的糖尿病虹膜病变,为及时治疗提供帮助。     

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     

Local retinal sensitivity in relation to specific retinopathy lesions in diabetic macular oedema

Purpose: To study microperimetric macular sensitivity in diabetic macular oedema (DMO) in relation to lesion characteristics obtained by optical coherence tomography (OCT), colour fundus photography, and fluorescein angiography (FA). Methods: The study comprised 20 eyes in 15 patients with nonproliferative diabetic retinopathy and recently diagnosed untreated DMO. Investigations included microperimetry, fluorescein angiography, colour fundus photography, and OCT. All measures and gradings were made for each of the nine fields of an early treatment diabetic retinopathy study macula template. Statistical analysis was made using Spearman’s nonparametric test including field and mean values within fields. Comparisons were made within the study population and with a normative microperimetry database. Results: Subnormal microperimetric sensitivity was associated with cystoid macular oedema, both in foveal petaloid (r = ?0.50, p = 0.02) and extrafoveal honeycomb patterns (r = ?0.8, p < 0.0001) and with outer nuclear layer cysts (r = ?0. 5, p = 0.024), inner nuclear layer cysts (r = ?0.31, p = 0.03), and hard exudate (r = ?0.38, p = 0.0026). There was no detectable effect of focal noncystoid oedema (r = ?0.16, p = 0. 48), diffuse noncystoid oedema (r = ?0.14, p = 0.55), capillary nonperfusion (r = ?0.33, p = 0.15), intraretinal haemorrhage (r = ?0.15, p = 0.53), or serous retinal detachment (r = ?0.11, p = 0.63). Foveal thickening was associated with locally reduced sensitivity (r = ?0.54, p = 0.01). Foveal sensitivity was positively correlated to the visual acuity, with a correlation of 0.44 and a borderline significance (p = 0.0509). Conclusions: Macular hard exudates and cystoid oedema were associated with locally reduced sensitivity. Thus, the lesions associated with reduced sensitivity for a white‐on‐white stimulus were such lesions that cause light to be blocked or scattered before it reaches the photoreceptors, suggesting that optical effects are a major cause of sensitivity loss.     

Does microaneurysm count reflect severity of early diabetic retinopathy?

In a group of 55 insulin-dependent diabetic patients with early diabetic retinopathy, microaneurysm counts from fluorescein angiograms were related to the level and severity of retinopathy derived by grading eight standard stereo color photographs as used in the Early Treatment of Retinopathy Study (ETDRS). All patients were studied at 0, 8, and 24 months. Significant correlations were present between both "definite" and "possible" microaneurysm count and retinopathy level of the eye studied and the mean retinopathy level of the two eyes, at all three time intervals, (P less than 0.05-less than 0.001). Similarly, there were significant correlations between microaneurysm counts and severity of the following lesions: microaneurysms and haemorrhages, cotton-wool spots (P less than 0.05-less than 0.001); to a lesser degree, severity of hard exudates (P less than 0.1-less than 0.001) and intraretinal microvascular abnormalities (P not significant-less than 0.001). There was no correlation between microaneurysm count and venous abnormalities (as at no time were there more than 11 eyes with any venous abnormality). We conclude that microaneurysm counts from fluorescein angiograms accurately reflect the severity of important signs in early diabetic retinopathy.     

532nm眼底激光联合和血明目片治疗重度NPDR的疗效

目的：观察532 nm眼底激光联合和血明目片治疗患有重度非增殖性糖尿病视网膜病变( non proliferative diabetic retinopathy, NPDR)患者的疗效。方法：纳入经门诊确诊为重度NPDR患者120例226眼,采用随机数字表分为治疗组和对照组。治疗组采取全视网膜光凝术联合口服和血明目片3mo,而对照组只行全视网膜激光光凝治疗。分别观察光凝术后的1、2、3 mo时两组患者视功能、眼底视网膜出血、渗出、水肿等情况,同时记录两组患者光凝术后3 mo眼底荧光血管造影情况。结果：两组患者在光凝治疗术后1、2 mo时,治疗组患者患眼视功能恢复情况显著优于对照组,差异具有统计学意义(P<0.05)。光凝术后3mo时,治疗组与对照组患眼视功能指标之间却无显著性区别,但与对照组相比,治疗组患者在眼底渗出、视网膜出血以及水肿消退方面具有显著性优势,差异具有统计学意义(P<0.05)。结论：对重度NPDR患者采用激光联合和血明目片进行治疗,可有效地缩短患眼视功能指标恢复速度,并可以促进视网膜出血及渗出的吸收速度,减少激光继发再损伤有一定的作用。     

The correlation between optical coherence tomographic features and severity of retinopathy,macular thickness and visual acuity in diabetic macular edema

Purpose To investigate the correlation between the features of optical coherence tomography (OCT) and the severity of concurrent retinopathy, central macular thickness (CMT), and best-corrected visual acuity in clinically significant diabetic macular edema.Methods In a prospective study, OCT was performed in 55 eyes of 55 patients with clinically significant diabetic macular edema, in 58 eyes of 30 patients with diabetes without retinopathy, and in 40 eyes of 21 healthy control subjects. The OCT features were categorized into: type 1, sponge-like retinal swelling; type 2, cystoid macular edema; type 3, serous retinal detachment; and type 4, vitreofoveal traction.Results The CMT in eyes with diabetic macular edema was significantly higher than in eyes of healthy controls or in eyes of diabetic patients without retinopathy (P < 0.001). Visual acuity correlated with CMT in diabetic macular edema (r = 0.558, P < 0.001). The prevalence of OCT type 1 was significantly higher in eyes with mild-to-moderate non-proliferative retinopathy (NPDR) than in eyes with severe NPDR to proliferative retinopathy (PDR) (P = 0.0069). The prevalence of OCT types 3 and 4 was significantly higher in eyes with severe NPDR to PDR than in eyes with mild-to-moderate NPDR (P = 0.0056). OCT type 1 showed the least CMT (P < 0.001) and the best visual acuity (P = 0.002).Conclusions There was a significant correlation between OCT patterns of clinically significant diabetic macular edema and severity of retinopathy, CMT, and visual acuity.     

Retinopathy in monkeys with spontaneous type 2 diabetes

PURPOSE: Type 2 diabetes occurs spontaneously in rhesus monkeys and shows an extraordinary similarity to human diabetes in clinical features and relative time course. The purpose of this study was to investigate clinically and histopathologically the ocular changes in these monkeys. METHODS: Ophthalmoscopic examinations were performed on aged normal and diabetic monkeys. Retinas from 16 diabetic monkeys and 6 nondiabetic monkeys were incubated postmortem for adenosine diphosphatase (ADPase) activity (labels viable retinal blood vessels) and flat-embedded in JB-4. Tissue sections were cut through areas of interest. RESULTS: Cotton-wool spots, intraretinal hemorrhages, and hard exudates in the macula were observed by ophthalmoscopy in some diabetic monkeys. Dot/blot hemorrhages, cotton-wool spots, and small nonperfused areas were the earliest histologically documented changes in the retinas. Large nonperfused areas extending from optic disc to midfovea were observed in four diabetic monkeys. Formation of small intraretinal microvascular abnormalities (IRMAs) and microaneurysms were associated with the areas of nonperfusion. There were apparent fluid-filled spaces in the outer plexiform layer in three of these maculas, suggesting macular edema. There was a significant correlation between the occurrence of retinopathy and hypertension (P = 0.037 for systolic pressure; P = 0.019 for diastolic pressure). In elastase-digested retinas, the ratio of pericytes to endothelial cells was 0.66:1 in diabetic and 0.64:1 in nondiabetic (P = 0.75) retinas. CONCLUSIONS: This is the first detailed analysis of retinopathy in a colony of spontaneous type 2 diabetic monkeys. Monkeys with type 2 diabetes have many of the angiopathic changes associated with human diabetic retinopathy. Hypertension correlates with the severity of the diabetic retinopathy.     

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.