Microaneurysms Research Articles

Diagnosis and treatment of eye diseases associated with HIV infection and AIDS

To investigate the manifestations and treatment principles of ocular diseases associated with human immunodeficiency virus infection (HIV) and acquired immunodeficiency syndrome (AIDS). It was a retrospective case series. One hundred and ten patients were recruited. Two hundred and twenty eyes underwent ophthalmologic examination that included vision acuity, anterior segment and fundus examinations with papillary dilation and fundus fluorescein angiography. CD(4)(+)T-lymphocyte was counted in peripheral blood of 110 patients. Intravitreal injection of ganciclovir 400 microg was performed in 4 eyes (2 patients) with cytomegalovirus (CMV) retinitis associated with AIDS. All statistical analyses were performed using SPSS 13.0 software. The association between the age, duration of HIV infection and HIV/AIDS related ocular manifestations was analyzed by Pearson Correlation Analysis. The association between the gender and HIV/AIDS related ocular manifestations was analyzed by Pearson Chi-Square test. For comparison of the CD(4)(+)T cells counts of the patients with normal fundus, HIV retinopathy, CMV retinitis, Kruskal-Wallis Test for Several Independent Samples was used. Baseline visual acuity: no light perception (NLP) 5 eyes; light perception (LP) to 0.04, 10 eyes; 0.05 to 0.2, 14 eyes; 0.3 to 0.7, 62 eyes and >/= 0.8, 129 eyes. Small grayish keratin precipitates or pigment keratin precipitates were present in 25 eyes, 22 eyes had positive aqueous flare, 4 eyes had posterior synechia of the iris, 28 eyes had cataract. HIV retinopathy was present in 34 eyes. Cotton-wool spots, retinal hemorrhages, and retinal microaneurysms were found in eyes with HIV retinopathy. CMV retinitis was present in 32 eyes. The fundus manifestations of CMV retinitis included retinal vasculitis; dense, full-thickness, yellow-white lesions along vascular distribution with irregular granules at the border, and hemorrhage on the retinal surface in 26 eyes. Late stage retinopathy was demonstrated in 3 eyes characterized as atrophic retina, sclerotic and attenuated vessels, and optic nerve atrophy. Retinal detachment was found in 3 eyes. The median of CD(4)(+)T-lymphocyte counts of the patients with normal fundus was 100.0/mm(3). The median of CD(4)(+)T-lymphocyte counts of the patients with HIV retinopathy was 41.0/mm(3). The median of CD(4)(+)T-lymphocyte counts of the patients with CMV retinitis was 18.0/mm(3). The difference of CD(4)(+)T-lymphocyte counts between patients with normal fundus and HIV retinopathy was statistically significant (chi(2) = 4.848, P = 0.028). The difference of CD(4)(+)T-lymphocyte counts between patients with normal fundus and CMV retinitis was statistically significant (chi(2) = 15.696, P = 0.000). The difference of CD(4)(+)T-lymphocyte counts between patients with CMV retinitis and HIV retinopathy was statistically significant (chi(2) = 4.860, P = 0.027). Four eyes (2 patients) with CMV retinitis underwent intravitreal injection of ganciclovir 400 microg. After intravitreal injection of ganciclovir, visual acuity was improved and fundus lesions disappeared in 4 eyes. HIV retinopathy is a common intraocular complication in HIV-infected patients. CMV retinitis is the severest intraocular complication in patients with AIDS. Highly active anti-retroviral therapy allows immune reconstitution. Intravitreal injection of ganciclovir can effectively control CMV retinitis and save the vision.

Semi‐automated assessment of microaneurysm formation rate from color fundus photographs in patients with mild NPDR

Abstract Purpose To assess the reliability of microaneurysm (MA) formation rate, computed from color fundus photographs, in type‐2 diabetic patients with mild NPDR. Methods In a 2‐years observational and prospective study of 400 type‐2 diabetic patients with mild NPDR, MA formation rate (MAFR) was computed using a new method (MA‐Tracker). This method allows graders to earmark MAs location on color fundus photographs. By using image co‐registration, it became possible to track previously identified MAs and to identify newly earmarked ones. The reliability of the procedure, assessed using 3 independent graders and a total of 235 color fundus photographs from a previous dataset, demonstrated a very good agreement between graders for the number of MAs (ICC=0.964) and for the MAFR (ICC=0.981). Results Sixty‐three of the 400 patients/eyes that completed the baseline and the 6‐month visits had MAFR computed using the MA‐Tracker. While the number of MAs earmarked at baseline (mean±SD: 2.0±2.5 MAs) and at 6‐months (2.7±3.7 MAs) showed no statistically significant increase (P=0.105), the MAFR, on the other hand, showed a high MA turnover (mean±SD: 2.7±3.7 new MAs for this 6‐months period of follow‐up). Conclusion Microaneurysm formation rate obtained from color fundus photographs using the MA‐Tracker show a very good reliability between graders making it a new tool with potential to be used as a biomarker of DR progression.

Leber miliary aneurysms and multiple sclerosis

To describe a patient with Leber miliary aneurysms who fulfilled the criteria for clinically definite multiple sclerosis (MS) in remission. Case report. We performed a complete ophthalmologic examination in a 45-year-old woman who was referred to our department for retinal vascular abnormalities in her left eye. Twenty-eight years previously,the patient had been diagnosed with MS. Following a complete ophthalmologic examination,the patient was diagnosed with Leber miliary aneurysms and coincident MS in remission. To our knowledge, there are no previous reports describing association between Leber miliary aneurysms and MS. Leber miliary aneurysms have been found in association with multiple ocular and systemic syndromes. In this report, we suggest another possible systemic association (MS) with Leber miliary aneurysms.

AUTOMATIC DETECTION OF MICROANEURYSMS IN COLOR FUNDUS IMAGES USING A LOCAL RADON TRANSFORM METHOD

Introduction: Diabetic retinopathy (DR) is one of the most serious and most frequent eye diseases in the world and the most common cause of blindness in adults between 20 and 60 years of age. Following 15 years of diabetes, about 2% of the diabetic patients are blind and 10% suffer from vision impairment due to DR complications. This paper addresses the automatic detection of microaneurysms (MA) in color fundus images, which plays a key role in computer-assisted early diagnosis of diabetic retinopathy. Materials and Methods: The algorithm can be divided into three main steps. The purpose of the first step or pre-processing is background normalization and contrast enhancement of the images. The second step aims to detect candidates, i.e., all patterns possibly corresponding to MA, which is achieved using a local radon transform, Then, features are extracted, which are used in the last step to automatically classify the candidates into real MA or other objects using the SVM method. A database of 100 annotated images was used to test the algorithm. The algorithm was compared to manually obtained gradings of these images. Results: The sensitivity of diagnosis for DR was 100%, with specificity of 90% and the sensitivity of precise MA localization was 97%, at an average number of 5 false positives per image. Discussion and Conclusion: Sensitivity and specificity of this algorithm make it one of the best methods in this field. Using the local radon transform in this algorithm eliminates the noise sensitivity for MA detection in retinal image analysis.

Microaneurysm number and distribution in the macula of Chinese type 2 diabetics with early diabetic retinopathy: a population-based study in Kinmen, Taiwan

To explore the number and distribution of microaneurysms (MA) in the macula of type 2 diabetics in Kinmen, Taiwan and associated risks for early diabetic retinopathy (DR). A baseline mass screening extracts 971 type 2 diabetics between 1991 and 1993 and follow-up eye screening at 1999 was then done. Number of MA was counted and associated systemic factors collected from a centered 45 degrees color fundus photograph of dilated eyes of type 2 diabetics (Topcon-NW5). Thirty-three (6.2%, n = 527) had MA retinopathy. Those with one eye involved (n = 26) had two mean MA; those with bilateral involvement (n = 7) had four mean per eye. Most MA were located temporally (mean MA = 0.79), then superiorly (mean = 0.58), inferiorly (mean = 0.46) and nasal (mean = 0.28). MA occurred at the 6,000-microm outermost ring (mean = 1.51), then the 3,000-microm ring (mean = 0.35), the 1,500-microm ring (mean = 0.26) and center 500 microm circle (mean = 0.01). After adjusting for confounding factors, early DR with MA was associated with longer duration of type 2 diabetes [odds ratios (OR) = 1.10, 95% confidence interval (CI) 1.00-1.21], higher glycosylated hemoglobin (OR = 1.36, 95%CI 1.11-1.66) and wider waist circumference (OR = 1.04, 95%CI 1.01-1.07). Our photograph grading system suggests that MA number and distribution at the macula may reflect severity of early DR and is a valid tool for predicting the progression of DR. Identifying those factors associated with MA only DR is important in developing prevention strategies for this early microvascular complication of type 2 diabetes.

Risk markers for progression of mild nonproliferative retinopathy to clinically significant macular edema in type 2 diabetic patients

Abstract Purpose To determine risk markers for the development of clinically significant macular edema (CSME) needing photocoagulation treatment in type 2 diabetic patients with mild nonproliferative retinopathy (NPDR), during a 7‐year period. Methods Fifty‐one type 2 diabetic patients with mild NPDR, followed‐up for 2 years as controls of diabetic retinopathy clinical trials, were selected. Patients underwent ophthalmological examinations every 6 months, including stereoscopic color fundus photography, fluorescein angiography and vitreous fluorophotometry, and were metabolically controlled. These patients were thereafter followed‐up for the next 5 years by conventional general and ophthalmological care. Results At the end of the 7‐year follow‐up period, 8 patients developed CSME, needing photocoagulation treatment. These patients presented a higher microaneurysm (MA) formation rate at the first year of follow‐up (p<0.001), a higher blood‐retinal barrier (BRB) permeability value (p=0.042), an abnormal foveal avascular zone (FAZ) contour on fluorescein angiography (p=0.009) and a higher HbA1C level at baseline (p=0.001). Conclusion Microaneurysm formation rate higher or equal to 3 MA/year, BRB permeability values over or equal to 4.0 nm.s‐1, evidence of abnormalities in the FAZ, and hemoglobin A1C levels at baseline, are risk markers for progression of NPDR to CSME in patients with type 2 diabetes.

Fibrinoid necrosis of small brain arteries and arterioles and miliary aneurysms as causes of hypertensive hemorrhage: a critical reappraisal

Cerebral hemorrhage in hypertensive patients is still an important source of morbidity and death. Understanding its underlying pathological basis is essential for the development of fact-based attempts to prevent the hemorrhage. Fibrinoid necrosis and miliary aneurysms are associated with and are the probable underlying causative lesions. Unfortunately much misunderstanding and confusion surrounds understanding of both lesions. This review clarifies several points. These include the following: the nature of fibrinoid necrosis and the susceptibility of small brain arteries and arterioles to this lesion even in the so-called benign hypertension; the relationship of fibrinoid necrosis to lipohyalinosis and the reasons for preferring the term fibrinoid; the existence of miliary aneurysms; the distinction between these aneurysms and pseudo-aneurysms or fibrin globes; the importance of, and basis for, recognizing healed miliary aneurysms; the relationship of fibrinoid necrosis to these aneurysms.

Follow-up and management of Coats disease diagnosed in childhood

To investigate retrospectively the clinical manifestation and the final visual prognosis through a long-term fellow-up study. It was retrospective case series study. Twenty four patients (26 eyes) were diagnosed with Coats disease from 1962 through 2006 at the Department of Ophthalmology, Peking Union Medical Hospital, Chinese Academy of Medical Sciences. Age, visual acuity, time of initial visit, method of treatment and the condition of eye fundus for each patient were documented. The time of follow-up ranged from 1-44 years, averaged 5 years. Age of the patients at initial visit ranged between 1 to 18 years old, 7 years on average. Eighteen patients (75%) were male and 6 were female (25%). Twenty two cases were unilateral and only 2 female patients were bilateral. In 26 eyes, 7 eyes exhibited capillary irregular dilatation, miliary aneurysms and nonperfusion area on fluorescein angiography located at peripheral fundus; 15 eyes were complicated with exudative retinal detachment. Four eyes reached end stage with no light perception or only finger count. Laser photocoagulation was performed in 21 eyes. In 10 eyes, retinal exudates and hemorrhages were absorbed with improvement of visual acuity. Ten eyes with extensive retinal detachment including macula underwent closed vitrectomy, the best visual acuity was 0.1 after surgery. The onset of Coats disease is in early young childhood. Abnormal vascular lesions and military aneurysms appeared at peripheral fundus with early retinal exudation involving the macula. Early treatment with laser coagulation could obtain good visual prognosis. The supplement treatment is required for new lesions occurring during the long- term follow-up period.

Aneurisma miliar de Leber associado à síndrome de tração vítreomacular: relato de caso

Retinal telangiectasias are idiopathic vascular abnormalities of the retina characterized by irregular dilatation of the retinal vessels, intraretinal and subretinal exudation. The aim of this article is to describe the uncommon association of Leber's miliary aneurysms and vitreomacular traction syndrome in a female patient. The diagnosis was established with angiofluoresceinography and optic coherence tomography. The patient was treated with focal photocoagulation with argon green laser directed to the perimacular aneurysms and pars plana posterior vitrectomy. The visual acuity showed great improvement after a four-month follow-up. The present report supports the importance of optic coherence tomography in cases where the vitreoretinal interface must be evaluated, including vascular pathologies, which allowed us to offer a better treatment to this patient.

Three-dimensional analysis of pathological characteristics of a microaneurysm

The etiology of Charcot-Bouchard microaneurysms (MAs), especially before rupture, has been unclear. A surgical specimen of an MA was removed from an acute intracerebral hemorrhage in a 69-year-old man. The MA was fixed with formalin and embedded in paraffin, and serial sections were cut and stained by the Azan and Elastica van Gieson methods and immunohistochemically. Three-dimensional reconstructive analysis was performed. The MA presented as local enlargement of an artery with a maximal diameter of 840 microm, but was not ruptured. The wall of the MA consisted of thickened, fine collagen fibrils, which were found to be similar to adventitia immunohistochemically, but with no internal elastic lamina or medial smooth muscle layer. The lumen was empty, with no mural thrombi, but the inner wall endothelial cells had expanded from the normal and/or residual arterial wall, which suggested that the MA had been present for a long period of time. Because the bare wall of the MA consisted of thickened collagen fibrils, the MA was not ruptured, but the possibility of rupture in the future was deemed high, with the risk of intracerebral hemorrhage.

Spontaneous Separation of Thick Epiretinal Membrane After Photocoagulation for Leber's Multiple Miliary Aneurysms

Spontaneous Separation of Thick Epiretinal Membrane After Photocoagulation for Leber's Multiple Miliary Aneurysms

Automated microaneurysm detection using local contrast normalization and local vessel detection

Screening programs using retinal photography for the detection of diabetic eye disease are being introduced in the UK and elsewhere. Automatic grading of the images is being considered by health boards so that the human grading task is reduced. Microaneurysms (MAs) are the earliest sign of this disease and so are very important for classifying whether images show signs of retinopathy. This paper describes automatic methods for MA detection and shows how image contrast normalization can improve the ability to distinguish between MAs and other dots that occur on the retina. Various methods for contrast normalization are compared. Best results were obtained with a method that uses the watershed transform to derive a region that contains no vessels or other lesions. Dots within vessels are handled successfully using a local vessel detection technique. Results are presented for detection of individual MAs and for detection of images containing MAs. Images containing MAs are detected with sensitivity 85.4% and specificity 83.1%.

Lacunar Infarct

The term lacuna, or cerebral infarct, refers to a well-defined, subcortical ischemic lesion at the level of a single perforating artery, determined by primary disease of the latter. The radiological image is that of a small, deep infarct. Arteries undergoing these alterations are deep or perforating arteries with a diameter ranging between 100 and 400 μm, numbering 6–12, that generally originate at right angles directly from the main arteries. The concept of lacunar syndrome was introduced in clinical practice to describe those clinical pictures that generally, although not always, have a cerebral infarct of lacunar type as the underlying mechanism. Classic clinical syndromes induced by lacunar infarcts are, in decreasing order of frequency, pure motor stroke, pure sensory stroke, sensorimotor stroke, ataxic hemiparesis, and dysarthria with motor disability of one hand, as well as a number of rare or incomplete syndromes. Small lacunar infarct that will then degenerate into a lacuna is caused by a reduction of blood flow to a perforating artery. In turn, this is the result of various arterial disorders, the most frequent of which include microatheroma, lipohyalinosis, fibrinoid necrosis, and Charcot-Bouchard aneurysm. Other forms of arteriopathy that can affect small vessels include amyloid angiopathy, and cerebral autosomic dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Hemodynamic disorders also can be a cause of the disease. Diagnosis is made with 1,5 Tesla MRI and prognosis is generally good.

Distal Lenticulostriate Artery Aneurysm Rupture Presenting as Intraparenchymal Hemorrhage: Case Report

Aneurysms involving the distal lenticulostriate artery branches are a rare cause of spontaneous intracerebral hemorrhage. We report a case of ruptured lenticulostriate aneurysm in an otherwise healthy patient and review the literature on this topic. Computed tomography showed a right basal ganglia hemorrhage in a 44-year-old Native American woman with acute left hemiparesis. Cerebral angiography showed a 2-mm aneurysm in a distal lenticulostriate artery branch. A pterional craniotomy was performed on a delayed basis using computed tomographic angiography and frameless stereotactic guidance. The basal ganglia hematoma was evacuated, and the aneurysm was identified and clipped using microsurgical technique. Because the base of the aneurysm involved a portion of the parent vessel wall, it was wrapped with cotton and reinforced with cyanoacrylate glue. The patient did well after surgery and was discharged to home with outpatient rehabilitation on the third postoperative day. Although intraparenchymal hemorrhages are fairly common, the underlying vascular abnormality is rarely identified. Most are related to hypertensive vascular degeneration, rupture of a Charcot-Bouchard aneurysm, or both. When intracerebral hemorrhage occurs in young patients, however, aggressive investigation is warranted to rule out a structural vascular abnormality.

Comparison of venous filling times and SLO findings at each quadrant region in diabetic retinopathy.

Our purpose is to evaluate the correlation of retinal venous filling time (VFT), which reflects the peripheral retinal microcirculation in diabetic retinopathy, with fluorescein angiography (FAG) findings such as microaneurysm (MA), non-perfusion area (NP), neovascularization (NV) and relative retinal venous diameter (RRVD), and further, to evaluate the correlation between arteriovenous passage time (AVPT) and these factors. Partial F-test (multiple regression analysis) was performed on patients (32 eyes of diabetic retinopathy) who underwent video FAG, using scanning laser ophthalmoscope. In the four quadrants, VFT was compared with each MA, NP, and NV at each vascular arch at a distance of one disc diameter distant from the optic disc. VFT was significantly correlated to RRVD, NP, and NV at each quadrant (r > 0.7). However, AVPT was not significantly correlated to any of the factors studied. Delayed VFT was associated with the hemodynamic change of the peripheral retinal microcirculation at each quadrant in diabetic retinopathy. VFT can be used as an index to indicate the peripheral microcirculation of the retina.

A comparison of digital nonmydriatic fundus imaging with standard 35-millimeter slides for diabetic retinopathy

Purpose The purpose of this study was to compare nonmydriatic digital images with 35-mm slide images for the detection of diabetic retinal findings. Study design Comparative, observational case series. Participants Forty patients with diabetes. Methods Diabetic patients underwent digital (nonmydriatic fundus camera attached to a digital back) and standard dilated 35-mm retinal photography of three areas: posterior pole, nasal retina, and temporal retina. The images were reviewed by a single masked grader for the presence or absence of specific retinal findings. Primary outcome measures Presence or absence of neovascularization of the disc (NVD), neovascularization elsewhere (NVE), venous beading (VB), nerve fiber layer (NFL) hemorrhage, dot–blot hemorrhage, microaneurysm (MA), clinically significant macular edema, cotton wool spot, intraretinal microvascular anomaly (IRMA), hard exudate (HE), and retinal pigment epithelial (RPE) pigmentary changes. Results Forty eyes of 22 patients underwent both imaging procedures. The agreement between image type was highest for IRMA (97.5%) and VB (95%) and lowest for RPE pigmentary changes (65%) and MA (62.5%). Sensitivity ranged from 25% (NVD) to 100% (VB). Specificity ranged from 90% (RPE pigmentary changes) to 100% (NVD, NVE, VB, NFL hemorrhage, HE). Positive predictive value ranged from 50% (IRMA) to 100% (NVD, NVE, HE, NFL, VB). Negative predictive value ranged from 48% (MA) to 100% (IRMA). Conclusions Nonmydriatic digital fundus imaging for detection of diabetic retionopathy has a low sensitivity rate and a high specificity rate and is less clinically useful than standard dilated 35-mm fundus slide images.

Retinal arteriovenous shunt at the arteriovenous crossing

Objective The purpose of the study was to demonstrate that the arteriovenous shunt at the arteriovenous crossing could occur in major retinal vascular diseases other than Takayasu disease. Design Clinical review of consecutive case series. Participants The authors studied 1885 eyes with retinal vascular diseases such as diabetic retinopathy, branch retinal vein occlusion, central retinal vein occlusion, central retinal artery occlusion, Leber’s miliary aneurysms, Eales disease, Behçet disease, and systemic lupus erythematosus retinopathy. Intervention Fluorescein fundus angiography using a wide-field fundus camera (60 degrees) was performed. Main outcome measures Dye transit from artery to vein through sequential angiography. Results The arteriovenous shunt at the arteriovenous crossing was found in 8 eyes with proliferative diabetic retinopathy, 27 eyes with branch retinal vein occlusion in the chronic stage, 2 eyes with central retinal vein occlusion, 2 eyes with central retinal artery occlusion, and 2 eyes with miliary aneurysms. The arteriovenous shunt was formed by a direct inflow from artery to vein, showing vasodilatation and hyperpermeability, followed by obliteration peripheral to the shunts. The pattern of initial inflow was classified into axial flow and laminar flow, and the inflow became wider and more rapid in the advanced stage. Conclusions These findings indicate that the arteriovenous shunt at the arteriovenous crossing is not a unique phenomenon in Takayasu disease but rather is a basic pattern of retinal vascular reaction pathologic states.

The effect of pregnancy on mild diabetic retinopathy

To study microaneurysm (MA) formation and disappearance rates during pregnancy and postpartum in diabetic women with mild diabetic retinopathy. Red-free photographs were taken at the 12th, 24th and 32nd-36th weeks of pregnancy and 3 and 6 months postpartum from 21 type 1 diabetics with mild diabetic retinopathy. In a subset of 13 patients follow-up was continued until 1 year after pregnancy. Fundus photographs were analysed using a computer-assisted fundus lesion localization system. In the whole material the total MA count was 3.1 +/- 3.6 (mean +/- SD) at the 12th week, 3.4 +/- 3.1 at the 24th week, 4.1 +/- 4.9 at the 32nd-36th week, 5.4 +/- 6.2 at 3 months postpartum and 5.2 +/- 5.8 at 6 months postpartum. We found that MA count increased during pregnancy, but it was highest 3 months postpartum. Both the rate of MA formation and the rate of MA disappearance increased during pregnancy, with the disappearance rate exceeding the formation rate 6 months postpartum. In patients having mean HbA1c levels below the median value of 6.38 mmol/l there was a flare-up of MAs during pregnancy, levelling by 3 months postpartum. Patients with a higher than the median (0.76 mmol/l) decrease in HbA1c level compared to pre-pregnancy HbA1c also developed more MAs during the course of pregnancy. These data suggest that there is continuous turnover of MAs during pregnancy. MA count increases during pregnancy but the MA count was highest 3 months postpartum, after which the formation rate started to decline. Temporary aggravation of mild retinopathy occurs in diabetic patients after normalization of blood glucose levels.

A Review of the Short-Term Benefits of Antihypertensive Treatment With Emphasis on Stroke

Hypertension is the major underlying risk factor for stroke, and the risk of stroke increases proportionally to the rise in blood pressure. In the elderly, systolic hypertension increases the risk of stroke. Stroke in hypertensive patients may be due to Charcot-Bouchard aneurysm, to atherosclerosis of the extracranial and major cerebral arteries, or to embolism as a result of cardiac disease. Reduction of blood pressure greatly reduces the risk of stroke in severe, mild-to-moderate, and isolated systolic hypertension. The reduction in stroke risk occurs up to a year after the onset of treatment and appears to persist thereafter. The use of dihydropyridine calcium antagonists may confer further benefits in addition to those related to blood pressure reduction as these agents block the influx of calcium into ischemic brain cells, thereby limiting the extent of the infarction. However, although these effects have been impressive in experimental models, there is as yet no convincing evidence of this effect in clinical studies.

Effect of Aspirin Alone and Aspirin Plus Dipyridamole in Early Diabetic Retinopathy: A Multicenter Randomized Controlled Clinical Trial

In a double-blind randomized controlled clinical trial conducted in two French and two United Kingdom centers, the effect of antiplatelet agents, i.e., aspirin alone (330 mg 3 times daily) or in combination with dipyridamole (75 mg 3 times daily), was tested versus placebo in 475 patients with early diabetic retinopathy. The assessment of retinopathy was based on change in the number of microaneurysms (MAs) present in the macular field, as seen on fluorescein angiograms, over 3 yr. Forty-one patients did not complete the study. At least three readable initial and yearly angiograms were available on 420 patients (266 treated with insulin and 154 not treated); the results reported are based on these patients. The mean yearly increase in definite MAs was similar in insulin-treated and non-insulin-treated diabetic patients. There was no significant difference between the aspirin-alone group (0.69 ± 5.1 mean ± SD, n = 145) and the aspirin-plus-dipyridamole group (0.34 ± 3.0, n = 142). In the placebo group the mean yearly increase (1.44 ± 4.5, n = 133) was significantly higher than in the treated group (P = .02,1-tailed t test). There was a clear relationship between the deterioration in ophthalmological signs and the increase in mean yearly MAs (clinically stable, 0.38 ± 3.96, n = 293; deteriorating, 1.79 ±4.89, n = 127; P = .002, 2-tailed f test). We conclude that aspirin alone and in conjunction with dipyridamole significantly slows the progression of MA evolution in early diabetic retinopathy.