Evidence Of Retinopathy Research Articles

Diabetes Can Alter the Interpretation of Visual Dysfunction in Ocular Hypertension

The authors examined the influences of diabetes on the results of visual function testing in patients with ocular hypertension (OHT). Color vision (desaturated D-15), contrast sensitivity together with both transient and steady-state pattern electroretinogram (PERG) findings from patients with documented OHT were examined in a historic cohort study. All patients were examined at least four times (mean, 7.8 examinations) during a follow-up period that ranged from 1.5 to 4 years. Only individuals who maintained normal visual fields throughout the follow-up period were included in this analysis. The sample included 158 patients with OHT. Of these patients, 32 were African-American and 23 had a history of noninsulin-dependent diabetes with no evidence of retinopathy (by ophthalmoscopy). Normative data were obtained from a control group that included 65 white subjects with normal vision who did not have diabetes and who were similar in age to the patients in the OHT group. Color vision, contrast sensitivity, and PERG results were reduced significantly in patients with diabetes and OHT relative to control subjects. Patients with OHT who did not have diabetes did not have similar abnormalities. Color vision and PERG results also were reduced significantly in patients with diabetes and OHT relative to those with OHT who did not have diabetes. Only the steady-state PERG was reduced in African-American patients with OHT (relative to both control subjects and white patients with OHT). Patients with diabetes and OHT have significantly greater color vision, contrast sensitivity and PERG abnormalities than patients with OHT without diabetes. Race factors do not play a major role in these differences. Screening for diabetes is recommended before drawing conclusions from the results of these types of functional tests in patients with OHT.

Retinopathy of prematurity in a Danish county. Trends over the 12-year period 1982-93.

An analysis of the ophthalmic recordings from the pre-term infants born 1991-93 considered at risk of developing retinopathy of prematurity is added to three previous 3-year clinical surveys from the same Danish county. Out of the 203 subjects of the recent study 34 showed evidence of retinopathy of prematurity. In 27 the maximum retinopathy of prematurity stage was 1 or 2 prior to regression. Out of the seven subjects with stage 3, one progressed to bilateral blindness in spite of the cryotherapy given in this single case. Comparing with the four retinopathy of prematurity-blind born 1982-84, the trend over the 12 years appears to be towards a better overall ophthalmic outcome. Along with an increasing number of survivors of the low GA/BW groups, the retinopathy of prematurity percentage has shown a decline, and apparently with less serious sequelae. Together with other Danish experience, eventually the present data may lead to lower screening limits for retinopathy of prematurity regarding GA/BW. Prior to this, however, there should be support from the case data currently collected in the compulsory Danish register of visually impaired children. Hence our present basic recommendation is that gestational ages up to (and including) 31 full weeks qualify for serial eye examination.

Clinical characteristics and follow‐up of subjects with non‐insulin‐dependent diabetes mellitus diagnosed by screening

AbstractThere is increasing evidence for the need to screen for non‐insulindependent diabetes mellitus (NIDDM). However, little is known about the clinical characteristics of subjects with NIDDM diagnosed by screening. We present data from 109 subjects with NIDDM diagnosed by such means. The majority (59%) were male, 59% were obese and 25% had a previous history of hypertension. At diagnosis mean fasting glucose concentration was 10.8mmol/l and mean cholesterol concentration was 6.7mmol/l with only 14% of subjects having a cholesterol concentration less than 5.2mmol/l. Forty eight per cent of subjects had a systolic blood pressure greater than 160mmHg and 68% of subjects had a diastolic blood pressure in excess of 90mmHg.Eighty two subjects underwent a review for the presence of complications; 8% had evidence of retinopathy, 15% of neuropathy and 2% of foot ulceration. Twelve weeks after diagnosis there was a significant fall in fasting glucose concentration (p<0.001), systolic blood pressure (p<0.02), and diastolic blood pressure (p<0.009). There was a mean weight loss of 3.0kg (p<0.0001).Screening for NIDDM identifies a group of subjects with significant cardiovascular risk factors and substantial numbers with retinopathy and neuropathy. The latter need regular medical review and hence the earlier they are detected the better. Early follow‐up suggests that simple dietary advice and diabetes education in subjects whose diabetes is identified in such a fashion is very effective both in terms of improved glycaemic control and weight reduction.

Genetic risk factors in diabetic retinopathy

Diabetic retinopathy is the leading cause of blindness in adults aged 30 to 65 years. However, 20% of the diabetic population does not develop significant retinopathy. To examine the influence of immune-related genetic factors on the development of diabetic retinopathy, we studied immunoglobulin allotypes in 102 subjects aged 8 to 20 years, who had had Type 1 (insulin-dependent) diabetes mellitus for 4.5 to 11 years (mean 7.3 years). HLA had been previously typed on 59 of these subjects. Retinopathy was assessed by expert review of retinal photographs. Among the 44 patients who had evidence of retinopathy, 33(75%) were G2m(23+), while among the 58 patients without retinopathy but with similar duration of disease, only 28(48%) were G2m(23+) (p = 0.006). The HLA-DR types of patients with and without retinopathy were not significantly different. We conclude that there is significant evidence of an association between G2m(23) at the locus encoding IgG2 subclass heavy chains and susceptibility to the development of diabetic retinopathy early in the clinical course of the disease. Our findings provide important independent confirmation of a previous report of association between Gm allotypes and predisposition to diabetic retinopathy. We are unable to determine if the Gm effect on development of retinopathy is due to the G2m(23) allotype itself, or due to genes that are closely linked to, and in linkage disequilibrium with, the locus encoding the G2m(23) allotype.

Von Willebrand factor and early diabetic retinopathy: no evidence for a relationship in patients with type 1 (insulin-dependent) diabetes mellitus and normal urinary albumin excretion.

High plasma levels of von Willebrand factor, an indicator of endothelial cell dysfunction, have been reported in both diabetic retinopathy and nephropathy. It is unclear, however, whether von Willebrand factor is related to diabetic retinopathy in the absence of diabetic nephropathy. The relationship between retinal status and plasma von Willebrand factor concentration was investigated in a cohort of 17 patients with Type 1 (insulin-dependent) diabetes mellitus who were followed-up for a median of 42 months. The patients were examined three times. They were selected for having had normal urinary albumin excretion and no evidence of retinopathy (on fundoscopy) at the first and second examination. They were then divided into two groups, according to absence (Group A; n = 9) or presence (Group B; n = 8) of retinopathy on fundoscopy or fluorescein angiography at the third examination. Urinary albumin excretion remained normal in all patients. Plasma von Willebrand factor levels were similar in both groups: (median) 128 vs 123%, 164 vs 132% and 159 vs 130% (first, second and third examination, respectively). Median changes in plasma von Willebrand factor were also similar: +7 vs +9% and +5 vs +1% (first-second and second-third examination). Patients in whom the plasma von Willebrand factor concentration increased had higher systolic blood pressure at the third examination (150 +/- 30 vs 130 +/- 12 mmHg, p = 0.02) when compared to those in whom plasma von Willebrand factor did not increase, but were of similar age and had similar diabetes duration, retinal status, diastolic blood pressure, glycated haemoglobin and serum cholesterol concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhancement of Spontaneous Fibrinolytic Activity in Diabetic Retinopathy

The fibrinolytic system was studied in 96 patients with type I diabetes mellitus. Patients were grouped according to their degree of retinopathy; 38 patients with no evidence of retinopathy, 28 patients with background retinopathy and 30 patients with proliferative retinopathy. Thirty healthy individuals served as controls. The basal fibrinolytic activity as measured by clot lysis time and t-PA activity was increased in diabetic patients. This was associated with low levels of plasminogen activator inhibitor. Increased levels of D-dimer in diabetic patients further indicate enhanced in vivo fibrinolysis. The increase in fibrinolytic activity was highest in diabetics without retinopathy, and decreased with increasing retinopathy. Endothelial release of t-PA after venous occlusion was not different between controls and all diabetic groups. These findings suggest that in type I diabetics the fibrinolytic system is in an activated state. With worsening of retinopathy this increase in fibrinolytic activity diminishes.

Retinal changes and alterations in blood pressure and albumin excretion rate (AER) during exercise in type 1 diabetes

The association of retinal changes with exercise microalbuminuria and with changes in systolic and diastolic blood pressure (BP) were evaluated in 162 young subjects with insulin-dependent (type 1) diabetes mellitus. Higher systolic and diastolic BPs at rest or after 10 or 20 min of exercise were significantly associated with more severe retinal changes in the subjects with diabetes compared to controls (P less than 0.02; global ANOVA). The mean (+/- SEM) exercise albumin excretion rate (AER) was 17.6 +/- 3.1 if there was no evidence of retinopathy compared to 81.5 +/- 23.5 when only microaneurysms were detected and 467.1 +/- 133.3 when more severe retinopathy was present. The percentage of subjects with abnormal AERs for these three retinal groups was 13, 30 and 60, respectively. (P less than 0.0001, chi-square test). It is clear that retinal changes relate to early renal changes, as monitored by exercise AERs and changes in resting and exercise BPs. It is concluded that the renal and retinal microvascular changes occur concurrently in young subjects with type 1 diabetes.

Lacunar Infarction in Patients With Hypertensive Intracerebral Hemorrhage

Of 300 patients with computerized tomographic (CT) evidence of acute hypertensive intracerebral hemorrhage, high-resolution CT scans showed cerebral lacunar infarction (lacunes) in only nine cases (3%). The lacunes were seen in putaminal (six cases), thalamic (one case), and occipital (two cases) hematomas. All patients with lacunes and intracerebral hemorrhage had had systemic arterial hypertension for 7 to 14 years, cardiographic evidence of ventricular hypertrophy, chest radiographic evidence of cardiomegaly, and funduscopic evidence of retinopathy. The intracerebral hemorrhages were small, with maximal diameters of the hematomas 9 to 18 mm. All patients had good clinical outcome. In a 3-year follow-up, three patients had symptomatic lacunar infarcts but none had recurrent hemorrhage, whereas six patients had myocardial infarction or congestive heart failure.

Treatment of Diabetic Retinopathy

Diabetic retinopathy has been and probably remains one of the four major causes of blindness in the United States.1,2 The risk of retinopathy is directly related to the degree and duration of hyperglycemia.3 After diabetes mellitus has been present for 20 years, almost all persons in whom the onset of diabetes occurred before the age of 30 years have some evidence of retinopathy, and about half have proliferative retinopathy. Persons who are 30 years of age or older when diabetes develops are at lower risk for retinopathy, but in this group retinopathy may be the first sign of diabetes. . . .

Retinopathy of prematurity in extremely low birthweight infants.

From 1977 to 1982, 108 infants weighing less than 1000 g at birth were examined in a nursery for premature babies for evidence of retinopathy of prematurity (ROP). Of these 108 infants, 88 were subjected to follow-up examinations for periods of 10 months to six years. ROP had been observed in 53% (47/88) of these children; it had been severe in 31% (27/88). Subsequently, 19% (17/88) of these children developed retrolental fibroplasia (RLF); all of these had had severe ROP, except one, in whom it is presumed to have been missed. The RLF was severe in only one eye of one child. Each of these infants had received only 25 mg of vitamin E by mouth. The writers consider that the case for the administration of large doses of vitamin E in the prevention of RLF is still not proven and conclude that, if vitamin E does have a protective effect, then a dose of 25 mg is sufficient.

VITREOUS FLUOROPHOTOMETRY IN CHILDREN WITH TYPE I DIABETES MELLITUS

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

Secondary prevention in diabetes mellitus

THE PAPER by Bennett and Knowler is concerned in the main with primary prevention of diabetes. The comments in this discussion will reflect another traditional public health concern, that is, the role of secondary prevention in this disease. Is there a need for screening or examining in a systematic fashion those persons known to have diabetes to determine whether more preventive or therapeutic efforts would benefit this high risk population? I will limit my discussion of this question to the eye and visual function in diabetic persons. Diabetes is a major cause of blindness in the United States and has been estimated to account for 5000 new cases each year [l]. The adverse effects of diabetes on the visual system may occur through several different pathways. Retinopathy is the pathologic process which is most commonly thought to occur in eyes of diabetic persons. In 1979-1980 the Wisconsin Epidemiologic Study of Diabetic Retinopathy was undertaken. That study was designed to determine the prevalence and severity of retinopathy in diabetic persons who received primary medical care in an eleven county area (Health Service Area 1) in southern Wisconsin [2]. All persons whose age at onset of diabetes was less than 30 years and who were taking insulin were examined; these persons have been referred to as the “younger onset” group. A stratified sample of persons who were diagnosed after 30 years of age was also examined; these persons have been referred as the “older onset” group. The population has been described in detail in other reports [3-51. Rates of legal blindness, that is, visual acuity of 20/200 or worse in the better eye may be compared with rates reported from the Framingham Eye Study, and from the Health and Nutrition Examination survey. Rates of legal blindness increased with increasing age in all groups. The rates in the diabetic persons were much higher at each age. In the younger onset persons, the overall rate of legal blindness was 3.6%; about 86% of the cases were attributable to diabetic retinopathy. In the older onset persons, the rate of blindness was 1.6x, and 33% of the cases were caused by diabetic retinopathy [6]. Davidson has cited rates of complications in diabetic patients. Rates of retinopathy, proteinuria, neovascularization, azotemia, blindness, and atherosclerosis all increased in frequency as the number of years of diabetes increased. Retinopathy occurred relatively early in the disease, and was the most frequent of these complications. More than 70% of patients had evidence of retinopathy after 25 years of the disease [7]. There are other recent sources of data that have been used to estimate the rates and severity of retinopathy in diabetic persons. Frank er al. [S] and Palmberg et al. [9] described the experience from their clinic practices in which they examined insulin dependent diabetic patients. Frank et al. reported no cases of retinopathy in 60 patients who had had diabetes for &4 years; Palmberg et al. found no cases in 80 patients who had &3 years of disease, but found 21% when he saw the same group again at 4-5 years. In the Wisconsin population, Klein et al. reported that in younger onset persons with from 0 to 4 years of diabetes, 13.6% had retinopathy [4].

Diabetic retinopathy. The primary care physician's role in evaluation and management.

The primary care physician should educate all diabetics regarding the roles of diet, exercise, and insulin therapy in controlling the course of their disease, as well as the potential complications, including retinopathy. In type I diabetes, blood glucose levels should be controlled as rigidly as possible with multiple insulin injections and self-monitoring of glucose level. Hypertension should be aggressively treated in all diabetics. Yearly eye examination in patients with type I diabetes is important, and ophthalmologic referral should be considered after the disease has been present for five to ten years, with the first evidence of retinopathy, at puberty, during pregnancy, or if ocular symptoms occur. In patients with type II diabetes an ophthalmologist should make an evaluation as soon as the blood glucose level is controlled. Through use of these steps, the risk of blindness in diabetics will be minimized.

Prevalence of retinopathy in a diabetic clinic.

In a prospective study lasting 14 months an attempt was made to measure the visual acuity and examine the fundi, after mydriasis, of all patients attending the diabetic clinic of a district general hospital. Of 704 patients, 160 (22.7%) had some evidence of retinopathy, and 52 (7.4%) of these were already attending an ophthalmologist. A further 18 (2.6%) were known to have retinopathy and were being followed up in the diabetic clinic. Ninety (12.8%) new patients with diabetic retinopathy were discovered. Most had minimal changes, but 30 (4.3%) were considered to have changes severe enough to be referred to an ophthalmologist. Twenty-two (2.1%) underwent, or were awaiting, photocoagulation, and half of these had had no visual symptoms when first seen. Although some of these patients were already being treated or observed for retinopathy, it is encouraging that relatively few new patients needing treatment for retinopathy were discovered. If retinopathy could be detected early enough physicians might be able to deal with it and so ease pressure on ophthalmological services.

Retinopathy in Pima Indians. Relationships to glucose level, duration of diabetes, age at diagnosis of diabetes, and age at examination in a population with a high prevalence of diabetes mellitus.

The occurrence of retinopathy and its relationship to diabetes in 1,640 Pima Indians age 15 and over has been determined. Eighteen per cent of those with two-hour postload plasma glucose levels of equal to or greater than 200 mg./dl. had some evidence of retinopathy. Of those with retinopathy and diabetes, 7 per cent were found to have proliferative or neovascular changes, the remainder having microaneurysms and/or exudates. The frequency of retinopathy increased from 3 per cent among newly diagnosed diabetics to 47 per cent among those with diabetes of 10 or more years duration. No relationship was found with sex, age at diagnosis of diabetes, or age at time of examination when duration of diabetes was taken into account. The occurrence of retinopathy was confined largely to those who fell into the second or hyperglycemic component of the frequency distribution of plasma glucose levels in the population, indicating the significance of the bimodal glucose tolerance frequency distribution.

The diagnosis of retinopathy by fluorescein angiography in latent diabetes.

Four cases of diabetes are reported in which there was no ophthalmoscopic evidence of retinopathy and diabetes remained obscure until fluorescein angiography disclosed signs of retinopathy and multiple microaneurysms. The diagnosis of latent diabetes was made in three of these patients whose fasting blood sugar was normal but the glucose tolerance test was abnormal; in the fourth patient, whose fasting blood sugar and glucose tolerance test were abnormal, the diagnosis of manifest diabetes was made.

Reversed flow through the Ophthalmic Artery as a cause of Rubeosis Iridis

Case 1—A 58-year-old white man was first seen two months prior to admission with a one-week his­ tory of tearing in the left eye. Two days after the onset of symptoms, the eye became red and painful. The pain and tearing subsided spontaneously in two days but the redness continued. Examination one week after the beginning of symptoms revealed a normal right eye with visual acuity correctable to 20/20. The left eye was correctable to 20/50. There was a 2-freticulate injection of the conjunctiva, the cornea was steamy, and the anterior chamber was of average depth. The pupil was reactive but the iris stroma was covered with small, newly formed blood vessels. The left lens was clear and the optic nerve re­ vealed a slight pallor. A small flame-shaped hemor­ rhage was present at 2 o'clock on the disk border. There was no other evidence of retinopathy. Gonioscopy revealed intermittent trabecular synechiae with 4 + neovascularization of the angle. By applanation tonotnetry the intraocular pres­ sure measured 12 mm Hg in the right eye and 18 mm Hg in the left eye. The right coefficient of out­ flow was not determined because of poor fixation. The left coefficient of outflow was 0.04 mmVmin/mm Hg. The central visual fields were normal to 2/1000 white. The left eye was treated with topical dexamethasone and remained comfortable. The central visual acuity ranged between 20/50 and 20/100 and the intraocular pressure varied between 18 and 28 mm Hg, as determined by applanation tonometry. The clinical impression at that time was that this represented an occlusion of the long posterior cili­ ary arteries and an impending central retinal artery

Isolated Macular Infarction in Sickle Cell (Ss) Disease

A 10-year-old black girl complained of a painless decrease of vision in her left eye over a twoto three-week period. She had become icteric about the time that the vision decreased. Sickle cell disease was diagnosed when this patient was four years of age; thus it was probable that she was having a sickle cell crisis. Hemoglobin electrophoresis at San Francisco Children's Hospital when she was four years of age showed 99% Hb S, and 1% Hb A, therefore, the patient is homozygous S, (sickle cell SS disease). Past eye history included a strabismus operation on the right eye at the age of nine years for a right esotropia present since the age of three or four years. She had never been hospitalized for sickle cell crises. Best corrected vision prior to the present illness was RE: 20/60, LE: 20/20. Her present vision was RE: 20/60, LE: 20/100. There was a variable left esotropia of 1 to about 40 prism diopters. The bulbar conjunctiva appeared icteric, and the conjunctival vessels exhibited sludging and commas. The retina of the left eye revealed an atrophie, beaten silver appearance in the macular area, and the blood vessels appeared ophthalmoscopically normal without significant tortuosity. There was no other evidence of retinopathy, except for some slight distortion of the foveal light reflex in the right macula. The periphery of both retinas was checked with the indirect ophthalmoscope and showed no abnormality. The child was not coopera­ tive enough for a formal tangent screen examina­ tion, but she described a central scotoma.

Changes in serum proteins and protein-bound carbohydrates in diabetes mellitus.

Studies of serum proteins and protein-bound carbohydrates were carried out on twenty-one diabetics without proteinuria and twenty controls. The diabetics had depression of serum total protein and albumin levels, and elevation of levels of all four types of protein-bound carbohydrate. The degree of elevation was greatest for fucose and least for sialic acid. When the diabetic group was divided into patients with and without evidence of retinopathy or neuropathy, the only significant difference found was an increase of alpha 2-globulin in diabetics with these sequelae. Alpha 2-globulin levels were found to be correlated with both fasting plasma glucose and duration of diabetes. Alpha 2-macroglobulin levels were elevated equally in diabetics with and without sequelae, and appeared related to atherosclerosis rather than to diabetes mellitus. Although disorders other than diabetes increase the magnitude of protein-bound carbohydrate elevation seen, their presence or absence has little influence on the fucose-dominated pattern of elevation found.

The rarity of hypertensive retinopathy in the African

Fifty patients with severe hypertension were selected for study over a two-year-period. Of these, fifteen had detectable retinal vascular changes which, however, were minimal in nine. Papilloedema occurred in only one patient. No particular age group appeared unduly susceptible to retinal vascular damage. In none of five pregnant patients with moderately severe hypertension was there evidence of retinopathy. In two patients retinal changes diminished considerably following hypotensive therapy, and have remained so for two years. A total of seven patients died, five from renal failure. Data from other areas of Africa and from Europe are presented and attention is drawn to the comparative rarity of severe hypertensive retinopathy in the indigenous African.