Electrophysiological assessment of visual function in newlydiagnosed IDDM patients

Summary Electrophysiological tests (electroretinogram, oscillatory potentials, visual evoked potentials, in the basal condition and after photostress) reveal an abnormal function of the visual system in insulin-dependent diabetic (IDDM) patients. The aim of our work was to assess whether electrophysiological abnormalities in visual function exist in newly-diagnosed diabetic patients free of any fluorangiographic signs of retinopathy. Ten control subjects (age 28.7 ± 2.44 years) and ten IDDM patients (age 25.2 ± 6.78 years; disease duration 5.3 ± 3.5 months) in stable metabolic control (HbA_{1 C} 7.5 ± 1.1 %) were evaluated. Flash-electroretinograms and oscillatory potentials were similar in both groups. Visual evoked potentials (VEP) recorded under basal conditions showed that P100 latency was significantly increased in the diabetic patients compared to control subjects (p < 0.01), while N75-P100 amplitude was similar in both groups. The recovery time of VEP after photostress was equivalent in diabetic patients and control subjects. The impaired basal VEPs suggest an early involvement of the nervous conduction in the optic nerve. However, the preserved flash-electroretinogram and the normal recovery time after photostress indicate that a short disease duration does not induce physiopathological changes in the outer retinal layers or in the macular function. [Diabetologia (1995) 38: 804–808] Received: 8 July 1994 and in revised form: 23 December 1994     

长期应用羟氯喹治疗风湿免疫病眼部安全性的前瞻性研究

目的 研究羟氯喹(HCQ)的眼部安全性. 方法 选择2005年8月至2007年6月正在服用HCQ的170例自身免疫病患者.每例患者均进行视力、眼压、眼底等常规眼部榆查,此外还进行了视野、视网膜电图(ERG)和眼电位图(EOG)检查.要求患者每6个月复诊1次.结果 170例风湿免疫病患者人均服用HCQ为16.1个月,服用时间最短为半个月,最长为48个月.服用HCQ的总剂量为6～584 g.用药过程中所有患者的视力、眼压、视野均正常.其中52例进行了ERG和EOG检查,ERG检杏均在正常范围内,且随用药时间延长差异无统计学意义,2例患者EOG检测光峰/暗谷比值(AMen比)低于正常,患者均无眼部不适,其中1例为高度近视,其他检企均正常. 结论 研究表明HCQ具有良好的眼部安全性,尚需要进一步扩大样本量并延长随访时间了解其长期用药的安全性.     

Correlation of electroretinography b-wave absolute latency,plasma levels of human basic fibroblast growth factor,vascular endothelial growth factor,soluble fatty acid synthase,and adrenomedullin in diabetic retinopathy

BackgroundWe investigated the b-wave latency of electroretinogram (ERG), human basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF), soluble fatty acid synthase (s-Fas), and adrenomedullin (ADM) in diabetic retinopathy.Patients and MethodsThirty control and 60 type II diabetic women (mean age 45±3.9 years, duration of diabetes 10.1±2.1 years) were investigated. Diabetics without complications (Group II) and with retinopathy (Group III) were diagnosed depending on clinical findings, abnormal fundus examination, and ERG. Plasma levels of b-FGF, VEGF, s-Fas, and ADM were measured.ResultsERG showed a significant increase of b-wave absolute latency, plasma b-FGF, VEGF, s-Fas, and ADM in diabetic retinopathy (P<.05). A positive correlation was found between b-wave latency and VEGF and s-Fas, and a negative correlation with b-FGF and ADM.ConclusionThis study elucidates the causative role of VEGF and s-Fas in diabetic retinopathy. VEGF may potently promote growth of endothelial cells and formation of new vessels implicated in proliferative retinopathy. s-Fas could be involved in advancement of apoptotic changes in retinopathy and high levels of b-FGF, and ADM may be compensatorily neuroprotective and vasculoprotective. The results showed that diabetic retinopathy is the result of multiple factors, so it is optimistic to believe that reversing VEGF or s-Fas will halt retinopathy, targeting multiple mechanisms simultaneously by administering combination treatments of VEGF antagonists; antiapoptotic drugs together with b-FGF and/or ADM may be prospective.     

Abnormal retinal artery responses to stress in patients with type I diabetes

The brachial artery pressure and retinal artery pressure responses to a one-minute cold pressor test were evaluated simultaneously in 14 patients with type I diabetes mellitus (six with and eight without diabetic retinopathy) and 10 age-matched control subjects. Five patients with type I diabetes had autonomic neuropathy. Mean baseline brachial artery pressure and retinal artery pressure were similar in patients with type I diabetes and control subjects. After cold pressor testing, the brachial artery pressure increased significantly (p less than 0.01) compared with baseline values in both groups. Retinal mean arterial pressures increased significantly (p less than 0.001) after cold pressor testing compared with the baseline values only in patients with type I diabetes. Positive correlation was found between the brachial and retinal mean arterial pressures after cold pressor testing (r = 0.48; p less than 0.05) in the diabetic patients but not in the control subjects (r = 0.10; p = NS). No correlation was found between the retinal artery pressure and age of onset of diabetes, duration of diabetes, the presence or absence of diabetic retinopathy, and glycemic control. Four patients with autonomic neuropathy and low retinal artery pressures, which remained unchanged after cold pressor testing, had no diabetic retinopathy. The fifth patient with autonomic neuropathy and exaggerated systolic brachial artery pressure (175 mm Hg) and retinal artery pressure (more than 80 mm Hg) responses had severe background diabetic retinopathy. In conclusion, abnormal retinal artery responses to stress are present in patients with type I diabetes. This may be modified by the presence or absence of both autonomic neuropathy and hypertension. The biologic significance of these findings is yet to be determined.     

Presence and further development of retinal dysfunction after 3-year follow up in IDDM patients without angiographically documented vasculopathy

Summary Abnormalities in neuroretinal function may play a role in the development of diabetic retinopathy. The natural course of diabetic retinal dysfunction in a group of subjects with insulin-dependent diabetes mellitus and with no apparent microvascular alterations in the retina was followed-up with fluorescein angiography and a sensitive electrophysiological technique, i.e., steady-state focal electroretinogram at the macula, for 3 years. Before the beginning and throughout our study, strict glycaemic control was maintained by three or four daily insulin injections under careful monitoring. Analysis of macular electroretinogram provided information from different neural layers. At the first examination, functional activities of postreceptoral neurons were significantly decreased with respect to those of age-matched control subjects. Diabetic patients showed a functional loss of both ganglion cell (0.53±0.09 vs 0.42 ±0.11 V; t=5; p=0.0001) and preganglion cell (0.51±0.13 vs 0.42±0.14 V; t=2.8; p=0.007) layers. Diabetes did not alter photoreceptor activity. After 3 years, dysfunction was significantly greater in the preganglion cell layer (0.28±0.11 V; t=6.3; p=0.0001). Although in some patients further impairment of ganglion cell function was shown, no significant difference was found in 3 years. Photoreceptor function remained unaltered. No vascular abnormalities in the retina were noted after 3 years in this group of patients. Metabolic control was not correlated to functional changes. Our findings suggest that the middle retinal layer is the most sensitive physiological locus of progressive diabetes-induced dysfunction in the absence of angiographically documented abnormalities.Abbreviations IDDM insulin-dependent diabetes mellitus - ERG electroretinogram     

Fear of visual loss in patients with diabetes: results of the prevalence of diabetic eye disease in Tayside, Scotland (P-DETS) study.

AIMS: To describe the relationship between fear of visual loss and dependent variables (visual acuity, retinopathy treatment, severity of retinopathy) in community-based diabetic patients. METHODS: Subjects were identified from the Diabetes Audit and Research in Tayside, Scotland (DARTS) diabetes register. From a total of 4825 individuals known to have diabetes and who were resident in Dundee and Perth (population 216 204; diabetes prevalence 2.23%), 586 persons with diabetes were randomly selected. Participants completed a self-administered questionnaire in Likert grade format which incorporated two items addressing presence and intensity of fear of visual loss. RESULTS: Questionnaires were returned by 61.4% of the cohort. Fear of visual loss was 'often in mind' for 37% of respondents, and that fear was intense for 47.4%. Analysis by diabetes type revealed differences in reported fear of Type 1 and Type 2 patients in relation to disease and treatment variables. Linear regression highlighted the complexity of the issue with retinal status, acuity and treatment only partly explaining reported patient concern (r(2) range: 0.051-0.125 for presence of fear; 0.026-0.04 for intensity of fear, depending on diabetes type). CONCLUSIONS: Fear of visual loss is preoccupying and intense for a substantial proportion of the diabetic population. Reasons for this are multiple and complex. Objective measures of visual impairment and retinal status are inadequate predictors of fear. Carers and researchers need to be mindful of this when approaching patients with diabetes.     

Brainstem auditory and visual evoked potentials in Type 1 (insulin-dependent) diabetic patients

Summary Brainstem auditory evoked potentials and pattern shift visual evoked potentials were measured in 34 Type 1 (insulin-dependent) diabetic patients with long-standing disease and in 43 control subjects. Thirty-two percent of diabetic patients had abnormal brainstem auditory evoked potentials and 15% had abnormal visual evoked potentials. These abnormalities were not related to duration of diabetes, diabetic control or individual diabetic complications (retinopathy, nephropathy, peripheral or autonomic neuropathy). The aetiology of the abnormalities must remain a subject for speculation. The findings of this study are consistent with a central diabetic neuropathy involving the brainstem in long-standing diabetic patients.     

Factors predicting lower extremity amputations in patients with type 1 or type 2 diabetes mellitus: a population-based 7-year follow-up study

Objectives. The aim of the study was to find factors predicting lower extremity amputation in patients with type 1 or type 2 diabetes mellitus through a 7-year follow-up period. Design. Follow-up study. Subjects. Altogether 733 diabetic patients, aged 10–79 years, were drawn from the national drug reimbursement register. Methods. At baseline, the patients underwent a podiatric, circulatory and neurophysiological examination. Seven years later a follow-up study was performed based on clinical and register data. Patient data for those who died during the follow-up were collected from hospital records and death certificates. All amputations were recorded. The patients with amputation were compared with the other patients and also, in a case-control manner, by taking three nonamputated patients matched by sex, type of diabetes, and age for each patient with amputation. Results. The number of amputations was 25 in the sample. Compared with all patients without amputation, patients with amputation differed in altogether 24 variables concerning diabetes and its complications. Compared with the matched nonamputated patients, the amputated patients had longer duration of diabetes, lower ankle/brachial pressure index (ABI), more often history of retinopathy, nephropathy, and hypertension, more often visual handicap, elevated serum creatinine level, abnormal neurophysiological indices and electrophysiological findings. In the logistic regression analysis, vibration perception threshold, low ABI, history of retinopathy, visual handicap, and male sex were independently associated with lower extremity amputation. Conclusions. Lower extremity amputations were strongly associated with retinopathy, nephropathy, and neuropathy. The presence of any of these complications should lead to intensified actions in order to prevent amputations. As far as arterial circulation is concerned, claudication or absent peripheral pulses were not good predictors of amputation, whereas low ABI, despite its known weaknesses, was a reliable indicator of future amputation.     

Effects of hyperglycaemia on visual evoked potentials in insulin-dependent diabetic patients

Multimodality evoked potentials frequently reveal subclinical involvement of the central nervous system in patients with insulin-dependent diabetes mellitus. We devised this study to evaluate the possible effects of acute hyperglycaemia on visual evoked potential (VEP) parameters in type 1 diabetic patients. A hyperglycaemic clamp (250 mg/dl for 180 min) was performed in ten patients. Monocular pattern reversal VEPs (check size 15, contrast 50%) were recorded before, and every 30 min after the start of the clamp. Basal VEP latencies and amplitudes were normal bilaterally in nine patients. No significant changes in pattern reversal and flash VEP parameters were observed after the induction or during the clamp period. None of the neurophysiological parameters evaluated during the test was related to the duration of the disease, the basal VEP latency or amplitude or the presence of retinopathy. Our data suggest that the neurophysiological abnormalities detected in insulin-dependent diabetic patients are due to structural involvement of the central nervous pathways and not to functional damage induced by acute short-term hyperglycaemia.     

The effect of puberty on the development of early diabetic microvascular disease in insulin-dependent diabetes

We studied the prevalence of early diabetic retinopathy and nephropathy in 21 prepubertal and 55 late-pubertal subjects with insulin-dependent diabetes (IDD). All subjects had IDD of 5-7 years duration at the time of evaluation. The prevalence of early diabetic retinopathy was significantly greater in the late-pubertal subjects than prepubertal subjects (33% vs. 9.5%, P = 0.05), despite similar glycosylated hemoglobin values between the two groups (11.7 +/- 2.7% vs. 10.1 +/- 1.6%) at the time of evaluation. Nephropathy was infrequent in late-pubertal subjects (9%), and absent in the prepubertal subjects. We hypothesize that puberty plays an important role in the development of microvascular complications of IDD, and that increases in growth factors, sex hormones and deterioration in glycemic control at the time of puberty may each enhance the development of diabetic microvascular disease.     

A behavioral screen for isolating zebrafish mutants with visual system defects.

Optokinetic and phototactic behaviors of zebrafish larvae were examined for their usefulness in screening for recessive defects in the visual system. The optokinetic response can be reliably and rapidly detected in 5-day larvae, whereas the phototactic response of larvae is variable and not robust enough to be useful for screening. We therefore measured optokinetic responses of mutagenized larvae as a genetic screen for visual system defects. Third-generation larvae, representing 266 mutagenized genomes, were examined for abnormal optokinetic responses. Eighteen optokinetic-defective mutants were identified and two mutants that did not show obvious morphological defects, no optokinetic response a (noa) and partial optokinetic response a (poa), were studied further. We recorded the electroretinogram (ERG) to determine whether these two mutations affect the retina. The b-wave of noa larvae was grossly abnormal, being delayed in onset and significantly reduced in amplitude. In contrast, the ERG waveform of poa larvae was normal, although the b-wave was reduced in amplitude in bright light. Histologically, the retinas of noa and poa larvae appeared normal. We conclude that noa larvae have a functional defect in the outer retina, whereas the outer retina of poa larvae is likely to be normal.     

Early selective neuroretinal disorder in prepubertal type 1 (insulin-dependent) diabetic children without microvascular abnormalities

The duration of diabetes before puberty is not considered relevant to the future development of complications. To evaluate the effects of diabetes on the neural retina, we analysed macular function by steady-state focal electroretinography in 20 prepubescent diabetic children without vascular retinopathy and in 39 sex- and age-matched normal children. The mean (±SD) response related to retinal cellular elements between the photoreceptors and ganglion cells was significantly lower in diabetic children than in the control group (0.38±0.12 vs. 0.51±0.13 V; unpairedt-test=3;P=0.005). Similarly, ganglion cell function showed a significant impairment in diabetic children with respect to the control group (0.4±0.13 vs. 0.53±0.09 V; unpairedt-test=5.4;P=0.0001), whereas the photoreceptors appeared unaffected. Metabolic control and disease duration were not correlated with functional deficits. Our results suggest that before puberty, early diabetes may have a selective effect on the neural retina prior to the appearance of microvascular changes. A focal electroretinogram could identify diabetic children with neurosensory disorders who may have a higher risk of developing microvascular retinopathy.     

Spatial frequency-selective losses with pattern electroretinogram in Type 1 (insulin-dependent) diabetic patients without retinopathy

Summary Neurosensory abnormalities have been implicated in the first stages of diabetic retinopathy. The activity of retinal ganglion cells in 24 Type 1 (insulin-dependent) diabetic patients with short disease duration without retinopathy on fluorescein angiography was investigated by using a pattern electroretinogram in response to sinusoidal gratings of different spatial frequencies (0.6, 1.0, 1.4, 2.2, 4.8 cycles/deg), counterphase modulated at 8 Hz. The pattern electroretinogram reflects, at least in part, the activity of subsets of generators (i. e., ganglion cells) which show spatial selectivity. Mean pattern electroretinogram amplitude was significantly reduced in patients at lower and intermediate, but not at higher spatial frequencies compared with 40 agematched control subjects. At 1.4 cycles/deg the pattern electroretinogram amplitude was significantly correlated (r=0.59) with age at onset (p=0.002) and duration of disease (p=0.002). Our results suggest that in Type 1 diabetic patients without retinopathy, there is an early sensory deficit of specific inner retina neurons which respond preferentially to gratings of medium and large size.     

Biomarkers of Diabetic Retinopathy

Diabetic retinopathy (DR), a leading cause of acquired vision loss, is a microvascular complication of diabetes. While traditional risk factors for diabetic retinopathy including longer duration of diabetes, poor blood glucose control, and dyslipidemia are helpful in stratifying patient’s risk for developing retinopathy, many patients without these traditional risk factors develop DR; furthermore, there are persons with long diabetes duration who do not develop DR. Thus, identifying biomarkers to predict DR or to determine therapeutic response is important. A biomarker can be defined as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Incorporation of biomarkers into risk stratification of persons with diabetes would likely aid in early diagnosis and guide treatment methods for those with DR or with worsening DR. Systemic biomarkers of DR include serum measures including genomic, proteomic, and metabolomics biomarkers. Ocular biomarkers including tears and vitreous and retinal vascular structural changes have also been studied extensively to prognosticate the risk of DR development. The current studies on biomarkers are limited by the need for larger sample sizes, cross-validation in different populations and ethnic groups, and time-efficient and cost-effective analytical techniques. Future research is important to explore novel DR biomarkers that are non-invasive, rapid, economical, and accurate to help reduce the incidence and progression of DR in people with diabetes.     

Diabetic retinopathy in chronic pancreatitis

Using fluorescein angiography, we studied the prevalence and characteristics of diabetic retinopathy in 40 patients with chronic pancreatitis complicated by diabetes and in 40 type 1 diabetics with comparable duration of diabetes. Retinopathy was found in 19 pancreatitis patients (47.5%) and in 20 type 1 diabetic patients (50%); it was background, minimal, or mild to moderate, without impairment of visual function, in all 19 pancreatitis patients and in 17 of the 20 type 1 diabetics. In the remaining three idiopathic diabetics, retinopathy was background of severe degree in two and proliferative, with impairment of vision, in one. No differences between patients with and without retinopathy were observed in fasting blood glucose, glycosylated hemoglobin, serum cholesterol, or triglyceride levels. The only significant difference (p less than 0.001) was the greater duration of diabetes in patients with retinopathy when compared with those without it (10.8 +/- 5.7 vs. 5.2 +/- 3.9 yr in pancreatitis patients; 11.2 +/- 5.0 vs. 5.1 +/- 3.5 yr in type 1 diabetics; mean +/- SD). Contrary to what is generally believed, the results indicate that the risk of retinopathy and the characteristics of this complication in patients with chronic pancreatitis and secondary diabetes are similar to those in patients with idiopathic diabetes.     

Residual B-cell function in insulin-dependent (type I) diabetics with and without retinopathy

Summary In order to evaluate if residual B-cell function is a protecting factor against the development of diabetic retinopathy in type I diabetics we measured C-peptide levels before and after glucagon stimulation (1 mg i.v.) in 74 type I diabetics. In all patients retinopathy was assessed by fluorescein angiography and retinal lesions were classified as: grade 0, normal; grade 1, background retinopathy; grade 2, proliferative retinopathy. We then correlated the degree of retinopathy to sex, age, duration of diabetes, smoking, percentage of ideal body weight, systolic and diastolic blood pressure, serum cholesterol, triglycerides, creatinine and C-peptide by means of multiple linear regression analysis. Twenty-three out of 74 type I diabetics had retinopathy. In all 7 subjects with proliferative retinopathy duration of diabetes exceeded 10 years. There was significant correlation between retinopathy and duration of diabetes (r=0.373, p<0.001). No correlation was found between retinopathy and all the other variables, in particular between retinopathy and basal C-peptide or C-peptide increment (Δ). An inverse correlation was found between the increment of C-peptide and duration of diabetes (r=−0.404, p<0.01). Our data show that residual B-cell function cannot be considered a protecting factor against the development of diabetic retinopathy.     

Preliminary Study on Electrophysiological Changes After Cellular Autograft in Age-Related Macular Degeneration

Evolving atrophic macular degeneration represents at least 80% of all macular degenerations and is currently without a standardized care. Autologous fat transplantation efficacy was demonstrated by several studies, as these cells are able to produce growth factors. The aim of the work was to demonstrate possible therapeutic effect of the joined suprachoroidal graft of adipocytes, adipose-derived stem cells (ADSCs) in stromal vascular fractions (SVFs) of adipose tissue, and platelet-rich plasma (PRP).Twelve eyes in 12 dry age-related macular degeneration (AMD) patients, aged 71.25 (SD ± 6.8) between 62 and 80 years, were analyzed. A complete ocular evaluation was performed using best corrected visual acuity (BCVA), retinographic analysis, spectral-domain optical coherence tomography, microperimetry, computerized visual field, and standard electroretinogram (ERG). Each eye received a cell in graft between choroid and sclera of mature fat cells and ADSCs in SVF enriched with PRP by means of the variant second Limoli (Limoli retinal restoration technique [LRRT]). In order to test if the differences pre- and post-treatment were significant, the Wilcoxon signed-rank test has been performed.Adverse effects were not reported in the patients. After surgery with LRRT, the most significant increase in the ERG values was recorded by scotopic rod-ERG (answer coming from the rods), from 41.26 to 60.83 μV with an average increase of 47.44% highly significant (P < 0.05). Moderately significant was the one recorded by scotopic maximal ERG (answer coming from the rods and cones), from 112.22 to 129.68 μV with an average increase of 15.56% (P < 0.1).Cell-mediated therapy based on growth factors used appears interesting because it can improve the retinal functionality responses in the short term. The ERG could, therefore, be used to monitor the effect of cell-mediated regenerative therapies.     

TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells

The ON pathway of the visual system, which detects increases in light intensity, is established at the first retinal synapse between photoreceptors and ON-bipolar cells. Photoreceptors hyperpolarize in response to light and reduce the rate of glutamate release, which in turn causes the depolarization of ON-bipolar cells. This ON-bipolar cell response is mediated by the metabotropic glutamate receptor, mGluR6, which controls the activity of a depolarizing current. Despite intensive research over the past two decades, the molecular identity of the channel that generates this depolarizing current has remained elusive. Here, we present evidence indicating that TRPM1 is necessary for the depolarizing light response of ON-bipolar cells, and further that TRPM1 is a component of the channel that generates this light response. Gene expression profiling revealed that TRPM1 is highly enriched in ON-bipolar cells. In situ hybridization experiments confirmed that TRPM1 mRNA is found in cells of the retinal inner nuclear layer, and immunofluorescent confocal microscopy showed that TRPM1 is localized in the dendrites of ON-bipolar cells in both mouse and macaque retina. The electroretinogram (ERG) of TRPM1-deficient (TRPM1^−/−) mice had a normal a-wave, but no b-wave, indicating a loss of bipolar cell response. Finally, whole-cell patch-clamp recording from ON-bipolar cells in mouse retinal slices demonstrated that genetic deletion of TRPM1 abolished chemically simulated light responses from rod bipolar cells and dramatically altered the responses of cone ON-bipolar cells. Identification of TRPM1 as a mGluR6-coupled cation channel reveals a key step in vision, expands the role of the TRP channel family in sensory perception, and presents insights into the evolution of vertebrate vision.     

Cardiovascular disease, mortality, and retinal microvascular characteristics in type 1 diabetes: Wisconsin epidemiologic study of diabetic retinopathy

BACKGROUND: Diabetic retinopathy and proteinuria, manifestations of microvascular abnormalities, occur early in the course of diabetes mellitus; in contrast, macrovascular cardiovascular complications usually occur later. Retinal vessel characteristics may be informative about risk of cardiovascular disease in persons with diabetes. We evaluated this in a longitudinal cohort study of persons with type 1 diabetes. METHODS: The population consisted of persons with type 1 diabetes who were receiving care in 11 counties in Wisconsin. Subjects (n = 996) were examined at baseline (1980-1982), and 4, 10, 14, and 20 years later. Evaluations included medical history and measurements of height, weight, blood pressure, and glycosylated hemoglobin. Fundus photographs were graded for diabetic retinopathy at baseline, and the same photographs were graded later for the diameters of retinal blood vessels. At each examination, a history of cardiovascular disease events since the last examination (and prior to baseline) was obtained. Mortality was monitored yearly. RESULTS: The 20-year age-adjusted cumulative incidences were 18.1% for angina, 14.8% for myocardial infarction, and 5.9% for stroke. Severity of diabetic retinopathy was associated with angina and stroke. Arteriovenous ratio was associated with myocardial infarction. Of 273 deaths, 176 involved heart disease. The severity of retinopathy and arteriovenous ratio was associated with heart disease mortality. Nephropathy was more informative about the cardiovascular end points than were the blood vessel characteristics. CONCLUSIONS: Incidences of cardiovascular disease, including mortality, were common in people with type 1 diabetes during a 20-year interval. Retinal vascular characteristics were associated with these end points, but this association was confounded by nephropathy.     

Screening for diabetic retinopathy: the utility of nonmydriatic retinal photography in Egyptian adults

Although regular screening for diabetic retinopathy with ophthalmoscopy or retinal photography is widely recommended in the United States and Europe, few reports of its use in developing countries are available. We compared the performance of screening by retinal photography with that of indirect ophthalmoscopy by using data from a population-based survey of diabetes and its complications in Egypt. During that project, 427 persons with diabetes underwent an eye examination and fundus photography with a non-mydriatic camera through a dilated pupil. Data from the examinations of the right eye of each patient are presented. Ninety-two (22 %) of the 427 retinal photographs were ungradable; in 58 eyes (63 %), this was due to media opacity (42 eyes with cataract, 3 with corneal opacity, and 13 with both). Agreement between retinal photography and indirect ophthalmoscopy was poor (kappa = 0.33; 95 % CI = 0.27–0.39) and primarily due to the large number of eyes (n = 79) with ungradable photographs that could be graded by ophthalmoscopy. None of these eyes was judged by ophthalmoscopy to have sight-threatening retinopathy. Fifty-four photographs were diagnosed with greater retinopathy than found on ophthalmoscopy. Retinal photography with the nonmydriatic camera through a dilated pupil is a useful method to screen for diabetic retinopathy in most adults in Egypt. However, such screening strategies have limited use in older persons and in persons with corneal disease or cataract. © 1998 John Wiley & Sons, Ltd.