Level Of Retinopathy Research Articles

Ischemic ophthalmoplegia in diabetic mellitus

Purpose : To analyze the natural course of ischemic diabetic palsies of the 3 rd , 4 th , and 6 th cranial nerves and their correlations with the status of diabetic control and retinopathy. Materials and methods : Twenty-nine patients with diabetic ophthalmoplegia, treated in Kaohsiung Medical University Hospital during the period 1996-1999, were included in the study. Data on clinical characteristics of the patients were obtained by chart review and the natural course of the cranial nerve palsies was analyzed. Laboratory studies, neuroimaging, and fundus studies were also performed. Results : Thirty-six episodes of ischemic ophthalmoplegia were recorded in 29 patients. Seventeen episodes of ophthalmoplgia occurred in patients with poor diabetic status. Third cranial nerve involvement occurred in 21 episodes, six of which (28.6%) had pupil involvement. Four patients had 4 th cranial nerve palsy and 11 episodes in nine patients involved 6 th cranial nerve palsy. Four patients had recurrent or alternate cranial nerve involvement, and three had simultaneous multiple cranial nerve involvement.The mean duration of paralysis was 2.8 ± 1.5 months with a significant difference ( p = 0.009) between the complete and incomplete palsy groups. Most of the cases had either no diabetic retinopathy ( No-DR )(55.2%) or only background diabetic retinopathy ( BDR )(34.5%). Except for average age, no significant difference was found between No-DR , BDR , and proliferative diabetic retinopathy ( PDR ) groups with respect to the duration of the palsies and fasting blood sugar levels. Age was significantly higher in the less severe diabetic retinopathy group (especially in the No-DR group). Conclusion : Cranial neuropathy with ophthalmoplegia is benign and self-limited. The oculomotor nerve was the most frequently involved in our group. Recovery time was dependent on ophthalmoplegia severity.The status of diabetic retinopathy and blood sugar level was not significantly related to the prognosis. Older diabetics (age > 63 years) had less severe retinopathy during attacks of ophthalmoplegia (p < 0.05). There might also be other risk factors, such as arteriosclerosis, inflammation, or anatomic variation, intervening in the pathogenesis of diabetic ophthalmoplegia.

Photodynamic therapy with verteporfin for choroidal neovascularization in patients with diabetic retinopathy

PURPOSE: To report the use of photodynamic therapy (PDT) with verteporfin in three patients with choroidal neovascularization (CNV) from age-related macular degeneration and underlying diabetic retinopathy. The level of diabetic retinopathy would have excluded these patients from participation in previously reported randomized clinical trials evaluating PDT with verteporfin due to a theoretic concern of damage to the overlying retinal vasculature. DESIGN: Retrospective interventional case series. METHODS: Three patients from a referral practice with at least severe nonproliferative diabetic retinopathy and a history of clinically significant macular edema developed loss of vision from concurrent choroidal neovascularization evaluated with fundus photography and fluorescein angiography before and after PDT with verteporfin to identify adverse retinal vascular events. RESULTS: Four eyes in three patients had PDT using verteporfin. Three eyes received two treatments. With short follow-up, visual acuity remained stable in two eyes, improved from 20/400 to 20/320 in one eye, and decreased from 20/200 to 20/400 in one eye. Fluorescein angiograms at intervals from 2 weeks to 3 months after PDT showed no damage to the retinal vasculature or progression of the diabetic retinopathy, but did show a decreased area of fluorescein leakage from CNV. One eye that had new subretinal hemorrhage following treatment appeared to show new vasculopathy on initial evaluation of the post-treatment angiogram. Retrospective review suggested that the subretinal hemorrhage provided increased contrast to more easily visualize vasculopathy that was present before the PDT. CONCLUSIONS: Three patients with diabetic retinopathy undergoing a total of seven PDT treatments with verteporfin in four eyes had no new retinal vascular abnormalities develop. No other atypical responses of CNV to PDT were noted except new subretinal hemorrhage, providing increased contrast of the overlying vasculature, which gave the false impression of the development of new vasculopathy in one eye. Patients with diabetic retinopathy who have concurrent CNV for which PDT with verteporfin is recommended should be cautioned regarding the theoretical concerns of harming the retinal vasculature. Periodic surveillance for such concerns seems warranted until more experience is obtained.

Role of neuropathy and plasma nitric oxide in recurrent neuropathic and neuroischemic diabetic foot ulcers.

Various factors are associated with foot ulceration, including delayed reporting of ulcers, poor glycemic control, and severity of neuropathy. Several studies have looked at the role of nitric oxide in wound healing. However, no studies have examined its role in the occurrence and recurrence of diabetic foot ulceration. In a cross-sectional study we examined the role of neuropathy, retinopathy, nephropathy, and plasma nitric oxide (estimated from plasma nitrite and nitrate) levels in diabetic patients with recurrent and non-recurrent neuropathic and neuroischemic foot ulcers. Patients with recurrent foot ulcers had higher vibration perception threshold values compared to patients with non-recurrent foot ulcers (47.4 +/- 5.7 volts versus 39.5 +/- 10.3 volts respectively, P < 0.05). In addition, subjects with recurrent foot ulcers had significantly higher plasma nitric oxide compared to subjects with non-recurrent foot ulcers (46.9 +/- 6.3 microm/L versus 30.2 +/- 2.4 microm/L respectively, P < 0.01). Multivariate logistic regression analysis adjusted for age, sex, hemoglobin A1c, presence of retinopathy and nephropathy, vibration perception threshold, plasma creatinine, and total nitric oxide, indicated that only vibration perception threshold was independently associated with the presence of an ulcer [odds ratio: 1.26 (1.10-1.46); P <0.001)] and the recurrence of foot ulcers [odds ratio: 1.13 (1.01-1.27); P =0.04)]. This study has shown that although plasma nitric oxide is higher in patients with recurrent neuropathic and neuroischemic foot ulcers, severity of neuropathy was the most important factor associated with the development and recurrence of foot ulcers in diabetic patients.

Cisapride improves gallbladder emptying in patients with type 2 diabetes mellitus.

Gallbladder motor function is impaired in many patients with diabetes, and may be related to cholinergic nerve damage. Cisapride is a prokinetic drug of the gastrointestinal tract and acts by releasing acetylcholine from cholinergic nerve endings. The aim of this study was to determine the effect of cisapride on gallbladder emptying in patients with type 2 diabetes mellitus (DM). Gallbladder emptying and tests for autonomic neuropathy (AN) were performed in 27 patients with type 2 DM and in 10 healthy subjects. Gallbladder emptying was studied by using real-time ultrasonography after an overnight fast, and after the subjects received a breakfast that contained 2500 J. Gallbladder emptying was repeated after the treatment with cisapride (10 mg t.i.d.) for 1 week in all subjects. Abnormal gallbladder emptying was present in 14 (51.9%) patients. The residual gallbladder volume (mean +/- SEM) was higher (9.3 +/- 1.0 vs 4.6 +/- 0.6; P = 0.002), and ejection fraction was lower (57.4 +/- 4.0 vs 74.2 +/- 2.4; P = 0.015) in diabetic patients than it was in healthy subjects. Cisapride produced a reduction in fasting and residual volumes (24.6 +/- 2.4 vs 20.0 +/- 1.4; P = 0.034 and 9.3 +/- 1.0 vs 5.9 +/- 1.1; P = 0.00003, respectively), and an improvement in ejection fraction (57.4 +/- 4.0 vs 72.6 +/- 3.8; P = 0.000007). The improvement in gallbladder emptying after cisapride therapy was confined to the patients with AN (n = 13) (57.3 +/- 5.4 vs 80.4 +/- 2.9; P = 0.0017), suggesting denervation supersensitivity with an upregulation of cholinergic receptors. There was no significant change in the ejection fraction in patients without AN (57.5 +/- 6.1 vs 65.4 +/- 6.5; P = NS). Sex, duration of diabetes, peripheral neuropathy, diabetic retinopathy and serum cholesterol level did not influence gallbladder emptying. Impaired gallbladder emptying is common in patients with type 2 DM. Cisapride significantly improves gallbladder emptying in patients with autonomic neuropathy.

Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy.

Clinical studies have shown a relationship between diabetic retinopathy and vascular endothelial growth factor (VEGF) levels in ocular fluid. Advanced glycation end products (AGEs) have been implicated in diabetes complications, including diabetic retinopathy. Nepsilon-(carboxymethyl) lysine (CML) is a glycoxidation product that may be a marker of oxidative stress. In this study, we used enzyme-linked immunosorbent assays to determine the levels of VEGF, non-CML AGE and CML in the aqueous humor and serum of 82 Japanese patients with type 2 diabetes and 60 non-diabetic subjects. VEGF, non-CML AGE, and CML concentrations in aqueous humor and serum were then compared with the severity of diabetic retinopathy. Immunohistochemical detection analysis of non-CML AGE and CML was also performed using retinal tissues from patients with progressive diabetic retinopathy. Aqueous levels of VEGF, non-CML AGE and CML increased along with the progression of diabetic retinopathy compared to age-matched controls. After coagulation therapy, the VEGF, non-CML AGE, and CML levels were significantly reduced. Immunostaining showed diffuse co-localization of non-CML AGE and CML around microvessels and in the glial cells of proliferative membranes from patients with progressive diabetic retinopathy. These findings suggest that glycation and glycoxidation reactions (or oxidation, as revealed by CML) may contribute to both the onset and progression of diabetic retinopathy.

How many steps of progression of diabetic retinopathy are meaningful? The Wisconsin epidemiologic study of diabetic retinopathy.

To determine whether a 1-step or more or 2-step or more progression on the Early Treatment Diabetic Retinopathy Study retinopathy severity scale over a 4-year period is meaningful in predicting the subsequent incidence of proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME) over the following 6 years. Population-based study of diabetic persons with 10 years of follow-up. Eleven-county area in southern Wisconsin. There were 1025 persons with diabetes who had fundus photographs at baseline and at 4- and 10-year follow-up examinations. Incidence of PDR or CSME between the 4- and 10-year follow-up examinations as determined by masked grading of color stereoscopic fundus photographs of 7 standard fields. In a univariate analysis, those with 1 or more steps of progression (n = 551) over the first 4 years of the study were significantly (P<.0001) more likely to develop PDR over the next 6 years than those with no progression (n = 474) (26% vs 4%) (relative risk, 5.85; 95% confidence interval, 4.05-8.47). Similarly, those with 2 or more (n = 364) (33%) or 3 or more (n = 231) (41%) steps of progression over the first 4 years of the study were significantly (P<.0001) more likely to develop PDR over the next 6 years than those with lesser progression (n = 661 [7%] and n = 794 [9%], respectively) (relative risk, 5.10; 95% confidence interval, 3.83-6.80; and relative risk, 4.61; 95% confidence interval, 3.57-5.99, respectively). Similar associations were apparent at every level of retinopathy, duration of diabetes, and glycosylated hemoglobin, and by type of diabetes at baseline. There were also associations between retinopathy progression and incidence of CSME. It seems that 1 or more or 2 or more steps of progression of retinopathy over a 4-year period strongly predict the development of PDR over the next 6 years. Therefore, using these end points of progression would result in the need for fewer subjects or shorter follow-up in some clinical trials.

Stereo nonmydriatic digital-video color retinal imaging compared with Early Treatment Diabetic Retinopathy Study seven standard field 35-mm stereo color photos for determining level of diabetic retinopathy11The Joslin Vision Network Research Team consists of Rita Botti; Dahlia K. Bursell, Richard M. Calderon, OD; W. Kelley Gardner, BS; Richard Jackson, MD; Paula Katalinic, B. Optom.; Vincent O’Brien, BS; Philip M. Silver, OD;

To evaluate the ability to determine clinical levels of diabetic retinopathy, timing of next appropriate retinal evaluation, and necessity of referral to ophthalmology specialists using stereoscopic nonmydriatic digital-video color retinal images as compared with Early Treatment Diabetic Retinopathy Study (ETDRS) seven standard field 35-mm stereoscopic color fundus photographs. Prospective, clinic-based, comparative instrument validation study. Fifty-four patients (108 eyes) with type 1 or type 2 diabetes mellitus selected after chart review from a single center to include the full spectrum of diabetic retinopathy. Nonsimultaneous 45 degrees -field stereoscopic digital-video color images (JVN images) were obtained from three fields with the Joslin Vision Network (JVN) system before pupil dilation. Following pupil dilation, ETDRS seven standard field 35-mm stereoscopic color 30 degrees fundus photographs (ETDRS photos) were obtained. Joslin Vision Network images and ETDRS photos were graded on a lesion-by-lesion basis by two independent, masked readers to assess ETDRS clinical level of diabetic retinopathy. An independent ophthalmology retina specialist adjudicated interreader disagreements in a masked fashion. Determination of ETDRS clinical level of diabetic retinopathy, timing of next ophthalmic evaluation of diabetic retinopathy, and need for prompt referral to ophthalmology specialist. There was substantial agreement (kappa = 0.65) between the clinical level of diabetic retinopathy assessed from the undilated JVN images and the dilated ETDRS photos. Agreement was excellent (kappa = 0.87) for suggested referral to ophthalmology specialists for eye examinations. Comparison of individual lesions between the JVN images and the ETDRS photos and for interreader comparisons were comparable to the prior ETDRS study. Undilated digital-video images using the JVN system were comparable photographs for the determination of diabetic retinopathy level. The results validate the agreement between nonmydriatic JVN images and dilated ETDRS photographs and suggest that this digital technique may be an effective telemedicine tool for remotely determining the level of diabetic retinopathy, suggesting timing of next retinal evaluation and identifying the need for prompt referral to ophthalmology specialists. Thus, the JVN system would be an appropriate tool for facilitating increased access of diabetic patients into recommended eye evaluations, but should not be construed as a paradigm that would replace the need for comprehensive eye examinations.

Trends in the pathophysiological characteristics of malignant hypertension.

The aim of the present study is to investigate the pathophysiological characteristics of a number of recent cases of malignant hypertension (MHT) and to compare them to the characteristics of earlier cases. Patients with MHT (age 25-76, mean 44+/-2 years) who were admitted to our hospital from 1984-1999 were retrospectively studied. All of the patients had either grade III or IV retinopathy and diastolic blood pressure levels higher than 120 mmHg. The observations in this study were compared to previously reported findings regarding 59 MHT patients who were admitted from 1971-1983. Of the 37 recent MHT patients, 20 had essential hypertension (EHT) as the underlying disease, 13 had chronic glomerulonephritis (CGN), and the remaining 4 presented with other diseases including pyelonephritis and renovascular hypertension. A positive family history of hypertension was more prevalent in the EHT patients than in other patients, and persistent proteinuria, microhematuria, and anemia were more prevalent in the CGN patients. These characteristics were similar between the recent and previous cases. Within 4 weeks after admission, hemodialysis was initiated in 3 of the 13 patients (23%) with CGN and 2 of the 20 (10%) patients with EHT. The prevalence of renal death at 1 year after admission was 30%, which was lower than the prevalence in the previous cases (42%). Grade IV retinopathy was seen in 45% of the patients admitted from 1984-1999, significantly less than in the patients admitted from 1971-1983 (66%, p<0.05). In addition, left ventricular hypertrophy was less frequently observed on electrocardiogram in the recent cases (67%) than in the previous cases (88%, p<0.05). Our results suggest that the recent cases of MHT demonstrate less severe organ damage.

Tele-ophthalmology via stereoscopic digital imaging: a pilot project.

Diabetic eye disease is present in remote communities across Canada. A pilot study was designed to assess the feasibility of stereoscopic digital imaging to identify levels of diabetic retinopathy via teleophthalmology. Diabetic patients were assessed for diabetic retinopathy by seven field stereoscopic digital imaging through a dilated pupil. Images were transferred by satellite to a tertiary eye center for review by a retinal specialist. Images were viewed stereoscopically on a video monitor, with grading of all images using a modified Early Treatment Diabetic Retinopathy Study (ETDRS) classification. Patients found to have treatable diabetic retinopathy were transferred to a tertiary eye center for assessment and treatment by a retinal specialist. One hundred patients (199 eyes) had stereoscopic digital imaging of the retina. Microaneurysms were identified in 70 eyes, hard exudates in 31 eyes. Two eyes were identified with neovascularization of the disc (NVD) and 15 eyes with clinically significant macular edema (CSME). All eyes identified by stereoscopic digital imaging with treatable disease were confirmed by clinical examination with contact lens biomicroscopy. Stereoscopic digital imaging of the retina enables the identification of diabetic retinopathy. Further research is needed to delineate the sensitivity and specificity of stereoscopic digital imaging when compared to slide film and clinical examination.

Retinal blood flow changes in diabetic retinopathy measured with the Heidelberg scanning laser Doppler flowmeter

Investigation of retinal blood flow in patients with and without diabetic retinopathy (DR). Retinal blood flow is measured with the non-invasive Heidelberg Retinal Flowmeter (HRF). The clinical suitability of the HRF in patients with diabetes mellitus is investigated, and measured blood flow is compared with blood flow in a group of non-diabetic persons. Cross-sectional study of retinal capillary perfusion in eighty diabetic patients and forty-nine control persons, non-invasively measured with the Heidelberg scanning laser Doppler flowmeter. In the control group, HRF measurements could be performed in all subjects. In the diabetes group some patients had media opacities or were not able to maintain stable fixation. Therefore HRF measurement was only possible in 79%, 75% and 60% of the subjects for the nasal, papillo-macular and foveal areas respectively. Retinal blood flow as measured in the perifoveal and nasal areas was associated with the level of diabetic retinopathy. In patients with proliferative DR (levels 4 and 5) the blood flow was reduced, in comparison with that of the patients with exudative or non-proliferative DR (levels 1 and 2) and preproliferative DR (level 3). Blood flow was not correlated with age, systemic blood pressure, intra-ocular pressure and perfusion pressure in either group. A significant negative correlation with the actual blood glucose level was found in the perifoveal area (R = -0.585, P = 0.0001). The HRF offers an interesting non-invasive method for measurement of retinal blood flow. In this cross-sectional study variations in retinal blood flow could be detected in various stages of DR in relation to clinically visible funduscopic changes.

Microvascular complications of diabetes: the role of angiotensin converting enzyme inhibitors Proceedings of a Round Table Meeting, June 1999, San Diego, USA

Microvascular complications of diabetes: the role of angiotensin converting enzyme inhibitors Proceedings of a Round Table Meeting, June 1999, San Diego, USA

Maculopathy in patients with diabetes mellitus type 1 and type 2: associations with risk factors

AIMTo examine possible relation between diabetic maculopathy and various risk factors for diabetic complications in patients with diabetes mellitus type 1 and type 2.METHODSCross sectional study of two cohorts of...

A comparison between one- and two-field 60° fundus photography when screening for diabetic retinopathy

To compare the severity level of diabetic retinopathy obtained when assessed from two versus only one 60 degrees photographic field using colour transparencies and red-free, black-and-white photographs. To compare the areal coverage of these two photographic strategies to that of seven-field 30 degrees photography. Two ophthalmologists graded photographs of 74 eyes of 74 type I and II diabetes patients. Inter-method agreement was expressed in percentages and using kappa statistics and scatter-diagrams. The comparison of the approximate photographic areal coverage was done from diagrams using planimetry. The severity level of retinopathy when judged from two photographic fields was more severe in 13.5% (Grader 1) and in 16.2% (Grader 2) from colour transparencies and in 13.5% (Grader 1) and in 14.9% (Grader 2) from red-free black-and-white prints, as compared to assessments from only one field. Kappa values (0.84-0.86) for inter-method agreement for five pooled retinopathy levels revealed good agreement. Neither grader missed retinopathy requiring clinical assessment or treatment (levels > or = 47) when minimal retinopathy (levels 14-20) was detected using only one 60 degrees colour slide or red-free photograph. A second optic disc-centred field provided valuable additional information when more severe retinopathy lesions (levels > or = 30) were detected in the macula-centred field. One macula-centred 60 degrees photograph covered 60% and two 60 degrees photographs 80% of the area covered by seven-field 30 degrees photography. Two-field 60 degrees photography covers areas left outside seven-field 30 degrees photography. We propose the use of one macula-centred 60 degrees photograph when screening for the first lesions of diabetic retinopathy. After they have been found two-field 60 degrees photography is recommended.

Amadori albumin in type 1 diabetic patients: correlation with markers of endothelial function, association with diabetic nephropathy, and localization in retinal capillaries.

Nonenzymatic glycation is increased in diabetes. Most studies so far have focused on the role of advanced glycation end products (AGEs) in vascular complications, whereas the role of early glycation Amadori-modified proteins, which is the predominant form of glycated proteins, has not been systemically investigated in humans. We developed an antiserum against glycated human serum albumin (HSA) and used this to study the role of early glycation products in vascular complications in type 1 diabetic patients. Amadori albumin was determined to be the recognition epitope of the antiserum. The antibody recognized a specific glucose adduct and a conformational component specific for human albumin in Amadori albumin, with no recognition of AGEs. Plasma Amadori albumin levels were significantly higher in type 1 diabetic patients (n = 55) than in healthy control subjects (n = 60) (39.2+/-9.9 vs. 20.9+/-4.0 U/ml, P < 0.0005). Amadori albumin correlated with levels of plasma markers of endothelial function von Willebrand factor (r = 0.29, P < 0.05) and vascular cell adhesion molecule-1 (r = 0.41, P < 0.005), but not soluble E-selectin. In addition, Amadori albumin immunoreactivity was detected in the capillaries of retinas of diabetic patients. Plasma levels of Amadori albumin were determined in a second group of type 1 diabetic patients with long-standing diabetes with (n = 199) or without (n = 192) diabetic nephropathy. Patients with nephropathy had higher Amadori albumin levels than did those without it (50.9+/-9.5 vs. 45.1+/-6.3 U/ml, P < 0.0005). Age-, sex-, and diabetes duration-adjusted analyses showed that nephropathy was significantly associated with Amadori albumin with an odds ratio (OR [95% CI]) of 1.11 [1.08-1.15] per U/ml increase. After additional adjustment for levels of creatinine, glycated hemoglobin, cholesterol, triglycerides, blood pressure, preexistent retinopathy, and cardiovascular disease, Amadori albumin continued to be significantly associated with nephropathy (OR 1.06 [1.01-1.11]) per U/ml increase. Our results are consistent with a proposed pathophysiological role of Amadori albumin in microvascular complications of type 1 diabetic patients.

Entoptic Foveal Avascular Zone Measurement and Diabetic Retinopathy

Entoptic visualization of the foveal avascular zone (FAZ) provides a noninvasive method for measurement of the FAZ. To determine if repeatability of measurement with this technique is good enough to monitor changes in diabetic retinopathy, we quantify (1) the repeatability of entoptic FAZ measurement in healthy subjects and (2) the relationship between measured FAZ diameter and the severity of retinopathy. (1) To determine FAZ measurement repeatability, 10 healthy adults entoptically measured their FAZ diameters in 11 separate testing sessions. (2) In a separate experiment, 53 patients with varying levels of diabetic retinopathy and 21 control subjects used a vascular entoptoscope to measure their FAZ diameters. The disease-related increase in FAZ diameter is large (approximately 400 microm) compared to the repeatability of the entoptic measurement within a subject (SD approximately 35 microm). Entoptic measurements have the repeatability necessary to reliably monitor increases in FAZ diameter of the magnitude of those induced by diabetes.

Design and Baseline Characteristics for the Aminoguanidine Clinical Trial in Overt Type 2 Diabetic Nephropathy (ACTION II)

Advanced glycosylation endproduct (AGE) formation has been implicated in the development and progression of nephropathy in type 2 diabetes mellitus. In diabetic animals, aminoguanidine inhibits AGE-mediated cross-linking of proteins in vascular and renal tissue and slows the progression of renal disease. ACTION II is a randomized, double-blind, placebo-controlled trial comparing two dose levels of aminoguanidine with placebo on the progression of nephropathy in 599 type 2 diabetic patients with renal disease from 84 centers in the United States and Canada. The primary endpoint is time to doubling of serum creatinine concentration. Secondary endpoints include the effect of aminoguanidine on time to all-cause mortality, end-stage renal disease (ESRD), cardiovascular morbidity and mortality, rate of change in indices of renal function (iothalamate, Cockcroft and Gault [C&G] calculated creatinine and measured creatinine clearances), proteinuria, retinopathy, circulating and urinary AGE levels, and estimation of the relationship between plasma aminoguanidine concentrations and primary and secondary efficacy endpoints and adverse events. Progression of macrovascular disease was monitored and fundus photography performed. Type 2 diabetic patients aged 30 to 70 years were eligible for the trial if their blood pressure was ⩽180 mm Hg systolic and ⩽120 mm Hg diastolic, serum creatinine concentration ⩾1.0 mg/dL (in women) or ⩾1.2 mg/dL (in men), C&G clearance ⩾40 mL/min, and proteinuria ⩾500 mg/d with diabetic retinopathy or diabetic nephropathy on renal biopsy. Recruitment began in July 1995 and terminated in December 1996. The trial randomized a total of 599 subjects. At baseline, the mean (standard deviation [SD]) age was 58 (7.7) years, diabetes duration 16.5 (7.5) years, body mass index 32 kg/m 2 (10–90% range 26–42), arterial blood pressure 105 (12) mm Hg, C-peptide concentration 2.55 (1.71) ng/mL, serum glucose concentration 201 (89) mg/dL, hemoglobin A1c 8.7% (1.6), serum creatinine concentration 1.6 (0.5) mg/dL, iothalamate clearance 52 (25) mL/min/1.73 m 2, proteinuria 4.1 (4.2) g/d, triglycerides 259 (214) mg/dL, and LDL cholesterol 144 (40) mg/dL. Patients are 72% male, 68% white, 16% black, and 16% Asian American and Native American. At baseline, 76% were receiving concomitant angiotensin-converting enzyme (ACE) inhibitors and 43% lipid-lowering agents. Follow-up in ACTION II was scheduled to continue through December 1998, so that follow-up was to be 2 years after the date of randomization of the final enrolled patient. The trial in fact ended in March 1998. This trial will contribute to our understanding of the natural history of type 2 diabetes mellitus–associated nephropathy and determine whether aminoguanidine will slow the progression of established diabetic renal disease. Control Clin Trials 1999; 20:493–510

Progression to proliferative retinopathy and macular oedema requiring treatment. Assessment of the alternative classification of the Wisconsin Study

To study the ability of the alternative classification of the Wisconsin Study to predict progression to retinopathy requiring laser treatment in patients with diabetes. A total of 1585 diabetic patients were included in the study. Of them, 294 (19%) were diagnosed with diabetes before and 1291 (81%) after age 30 years. Retinopathy was diagnosed on fundus photographs using a modification of the Wisconsin scale, and graded into 6 levels according to the worse eye. The first visit during the study period was used to represent baseline examination. The time points for detection of proliferative retinopathy (PDR) and clinically significant macular oedema (CSME) were recorded during a mean follow-up time of 2.9 years. Progression to PDR and/or CSME was significantly related to increasing severity of retinopathy at baseline (p<0.001; test for trend). Fifty per cent of patients with severe non-proliferative retinopathy (NPDR) (level 51) at entry progressed within one year to PDR and/or CSME; the 3-year risk for such progression in patients with mild (level 31) and moderate NPDR (level 41) was 25 and 60%, respectively. The incidence of progression to PDR and to CSME was 0.95 and 2.3/100 person-years, respectively. Progression to PDR and/or CSME was furthermore associated with a higher level of glycosylated haemoglobin, longer duration of the diabetes and use of antihypertensive treatment. Increasing severity of retinopathy as recorded by this modification of the alternative classification of the Wisconsin Study was significantly associated with increased risk of progression to retinopathy requiring treatment.

Plasma levels of endothelin-1 in diabetic retinopathy in pregnancy.

Raised circulating levels of the potent vasoconstrictor endothelin-1 (ET-1) have been demonstrated in diabetes and pregnancy-induced hypertension. Pregnant women with diabetic retinopathy are known to be at a higher risk of developing pregnancy-induced hypertension than those without retinopathy. To examine the association between ET-1, pregnancy, diabetes and diabetic retinopathy, circulating ET-1 levels were measured in each trimester in a cohort of women with and without diabetes during pregnancy. A cohort of women with diabetes (n = 13) and normal controls (n = 8) were followed throughout pregnancy. Detailed clinical and fundoscopic examinations were carried out according to ETDRS protocols. Plasma ET-1 levels were measured in each trimester using a sensitive radioimmunoassay. Those with diabetes were further divided into those with retinopathy (n = 7) and those without (n = 6). Plasma levels of ET-1 increased progressively during normal pregnancy and peaked in the third trimester. Women with diabetes had significantly higher levels of plasma ET-1 (14.0 vs 4.6 pg/ml in the first trimester, 14.0 vs 4.8 pg/ml in the second trimester and 15.8 vs 7.2 pg/ml in the third trimester) compared with those without diabetes. These were no significant differences in plasma ET-1 levels between women with diabetes who had pre-existing diabetic retinopathy and those without. This study has shown that ET-1 levels rise during normal pregnancy, and are higher in women with diabetes, which may reflect pre-existing endothelial damage. Although no association could be demonstrated between diabetic retinopathy and serum ET-1 levels, this may reflect the small sample size in this study.

Is the risk of diabetic retinopathy greater in non-Hispanic blacks and Mexican Americans than in non-Hispanic whites with type 2 diabetes? A U.S. population study.

To compare the risk for diabetic retinopathy in non-Hispanic white, non-Hispanic black, and Mexican-American adults with type 2 diabetes in the U.S. population. Representative population-based samples of people aged > or = 40 years in each of the three racial/ethnic groups were studied in the 1988-1994. Third National Health and Nutrition Examination Survey (NHANES III). Diagnosed diabetes was ascertained by medical history interview, and undiagnosed diabetes by measurement of fasting plasma glucose. A fundus photograph of a single eye was taken with a nonmydriatic camera, and a standardized protocol was used to grade diabetic retinopathy. Information on risk factors for retinopathy was obtained by interview and standard laboratory procedures. Prevalence of any lesions of diabetic retinopathy in people with diagnosed diabetes was 46% higher in non-Hispanic blacks and 84% higher in Mexican Americans, compared with non-Hispanic whites. Blacks and Mexican Americans also had higher rates of moderate and severe retinopathy and higher levels of many putative risk factors for retinopathy. Blacks had lower retinopathy prevalence among those with undiagnosed diabetes. In logistic regression, retinopathy in people with diagnosed diabetes was associated only with measures of diabetes severity (duration of diabetes, HbA1c, level, treatment with insulin and oral agents) and systolic blood pressure. After adjustment for these factors, the risk of retinopathy in Mexican Americans was twice that of non-Hispanic whites, but non-Hispanic blacks were not at higher risk for retinopathy. These risks were similar when people with undiagnosed diabetes were included in the logistic regression models. The prevalence and severity of diabetic retinopathy is greater in non-Hispanic blacks and Mexican Americans with type 2 diabetes in the U.S. population than in non-Hispanic whites. For blacks, this can be attributed to their higher levels of risk factors for retinopathy, but the excess risk in Mexican Americans is unexplained.

Simple, low-cost, portable corneal fluorometer for detection of the level of diabetic retinopathy

A simple, low-cost, portable instrument for measurement of the autofluorescence of the human cornea is presented. Corneal autofluorescence has proved to be strongly correlated with the grade of retinopathy in diabetic patients. It is therefore a reliable parameter for detection of different levels of diabetic retinopathy, thus permitting timely intervention by ophthalmologists. The instrument contains custom optics and electronics and exhibits excellent linearity and repeatability both in vitro and in vivo. Preliminary tests on volunteers show promise for its use in clinical practice.