Ebstein anomaly associated with retinal venular dilatation, migraine, and visual snow syndrome: a case report.

BACKGROUND: To present a case with Ebstein anomaly, a rare congenital heart disorder, with ophthalmological and neurophthalmological signs and symptoms. To date, retinal venous dilatation and visual snow syndrome have not been previously been published in this anomaly. CASE PRESENTATION: A 10-year-old white girl was diagnosed with Ebstein anomaly. From age 12, she regularly suffered from migraines with auras and photophobia. At age 16 she started to see short-term bouts of white snow, that after a year were present all day. At age 20, she was found to have a decreased retinal arteriovenous ratio. CONCLUSIONS: Retinal arterial tortuosity and venular dilatation are common in congenital heart disease but have not been described in Ebstein anomaly, nor has the visual snow syndrome.

Factors associated with serum/plasma concentrations of vitamins A, C, E and carotenoids in older people throughout Europe: the EUREYE study.

PURPOSE: To report on plasma/serum levels of antioxidant vitamin and carotenoids in older adults resident in multiple countries in Europe and examine relationships with potential modifiers. METHODS: Population-based cross-sectional European Eye Study in 7 centres from northern to southern Europe. In total, 4,133 participants aged 65 years or over, collected by random sampling, were recruited. Questionnaires relating to diet, lifestyle and medical history were administered. Non-fasting blood samples were analysed in a single laboratory for vitamins A, C and E and a panel of carotenoids. Associations were analysed by bootstrapped multivariable regression analysis. RESULTS: Centre and season influenced the serum and plasma concentrations of all antioxidant vitamins and carotenoids. Gender, BMI, smoking, age, education, alcohol consumption and supplement use were also significantly associated with some, but not all, of the antioxidant vitamins and carotenoids examined. The proportion of variance explained ranged from 4.8 % for retinol to 25.2 % for zeaxanthin. CONCLUSIONS: In older people, antioxidant vitamin and carotenoid status varies by centre and season, but is also associated with other behavioural and lifestyle variables. Studies aiming to demonstrate an association between antioxidant vitamins and carotenoid status and chronic disease risk should consider these potential confounders.

Mutations in ABCC6 cause pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a heritable disorder of the connective tissue. PXE patients frequently experience visual field loss and skin lesions, and occasionally cardiovascular complications. Histopathological findings reveal calcification of the elastic fibres and abnormalities of the collagen fibrils. Most PXE patients are sporadic, but autosomal recessive and dominant inheritance are also observed. We previously localized the PXE gene to chromosome 16p13.1 (refs 8,9) and constructed a physical map. Here we describe homozygosity mapping in five PXE families and the detection of deletions or mutations in ABCC6 (formerly MRP6) associated with all genetic forms of PXE in seven patients or families.

Elusive drusen and changing terminology of AMD.

The first descriptions of ageing macula disorder (AMD), be it under other names, appeared in 1855 and 1868. The earliest accounts of AMD linked the presence of drusen with visual loss. It took a century before these connections between drusen and AMD were generally accepted by medical science and in clinical articles. The first signs of AMD appear in the region of the choriocapillaris, Bruch's membrane and the retinal pigment epithelium. The pathogenesis of drusen and of AMD is still uncertain. This is reflected in the wide variation in nomenclature of both, since the first publications.

Cigarette smoking and age-related macular degeneration in the EUREYE Study.

OBJECTIVE: To examine the association between cigarette smoking and age-related maculopathy (ARM) including age-related macular degeneration (AMD) in the European population. DESIGN: Cross-sectional study. PARTICIPANTS: Four thousand seven hundred fifty randomly sampled > or =65-year-olds from 7 study centers across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain). METHODS: Participants underwent an eye examination and digital retinal photography. The images were graded at a single center. Smoking history was ascertained by a structured questionnaire administered by trained fieldworkers. Multinomial and binary logistic regressions were used to examine the association between smoking history and ARM grade and type of AMD, taking account of potential confounders and the multicenter study design. MAIN OUTCOME MEASURES: Photographic images were graded according to the International Classification System for ARM and stratified using the Rotterdam staging system into 5 exclusive stages (ARM 0-3 and ARM 4, also known as AMD). Age-related macular degeneration also was classified as neovascular AMD or geographic atrophy (GA). RESULTS: One hundred fifty-eight cases were categorized as AMD (109 neovascular AMD and 49 GA); 2260 had no signs of ARM (ARM 0). Current smokers had increased odds of neovascular AMD (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.4-4.8) or GA (OR, 4.8; 95% CI, 2.1-11.1), whereas for ex-smokers the odds were around 1.7. Compared with people with unilateral AMD, those with bilateral AMD were more likely to have a history of heavy smoking in the previous 25 years (OR, 5.1; 95% CI, 1.3-20.0). The attributable fraction for AMD due to smoking was 27% (95% CI, 19%-33%). There was no consistent association with ARM grades 1 to 3 and smoking. CONCLUSIONS: These findings highlight the need for increasing public awareness of the risks associated with smoking and the benefit of quitting smoking. Patients with unilateral disease who are current smokers should be advised of the risk of second-eye disease.

Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa.

OBJECTIVE: To identify mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. METHODS: Mutation analysis was carried out in a group of 35 unrelated patients with juvenile autosomal recessive retinitis pigmentosa (ARRP), Leber's congenital amaurosis (LCA), or juvenile isolated retinitis pigmentosa (IRP), by denaturing high performance liquid chromatography followed by direct sequencing. RESULTS: All three groups of patients showed typical combinations of eye signs associated with retinitis pigmentosa: pale optic discs, narrow arterioles, pigmentary changes, and nystagmus. Mutations were found in 34% of PATIENTS: in CRB1 (11%), GUCY2D (11%), RPE65 (6%), and RPGRIP1 (6%). Nine mutations are reported, including a new combination of two mutations in CRB1, and new mutations in GUCY2D and RPGRIP1. The new GUCY2D mutation (c.3283delC, p.Pro1069ArgfsX37) is the first pathological sequence change reported in the intracellular C-terminal domain of GUCY2D, and did not lead to the commonly associated LCA, but to a juvenile retinitis pigmentosa phenotype. The polymorphic nature of three previously described (pathological) sequence changes in AIPL1, CRB1, and RPGRIP1 was established. Seven new polymorphic changes, useful for further association studies, were found. CONCLUSIONS: New and previously described sequence changes were detected in retinitis pigmentosa in CRB1, GUCY2D, and RPGRIP1; and in LCA patients in CRB1, GUCY2D, and RPE65. These data, combined with previous reports, suggest that LCA and juvenile ARRP are closely related and belong to a continuous spectrum of juvenile retinitis pigmentosa.

Total hip replacement with a superolateral bone graft for osteoarthritis secondary to dysplasia: a long-term follow-up.

We evaluated the long-term results of 116 total hip replacements with a superolateral shelfplasty in 102 patients with osteoarthritis secondary to developmental dysplasia of the hip. After a mean follow-up of 19.5 years (11.5 to 26.0), 14 acetabular components (12%) had been revised. The cumulative survival at 20 years was 78%, with revision for loosening of the acetabular component as the end-point. All grafts were well integrated and showed remodelling. In six grafts some resorption had occurred under the heads of the screws where the graft was not supporting the socket. Apart from these 14 revisions, seven acetabular components had possible radiological signs of loosening at a mean follow-up of 14.5 years, one had signs of probable loosening, and five had signs of definite loosening. These results indicate that this technique of bone grafting for acetabular reconstruction in hip dysplasia is a durable solution for cemented acetabular components.

Retinopathy, glucose, and insulin in an elderly population. The Rotterdam Study.

We studied the association between retinopathy and glucose metabolism in a population-based study of elderly men and women. Glucose metabolism was assessed by serum fructosamine and a nonfasting oral glucose tolerance test, and retinopathy was evaluated by fundus photography. Retinopathy was present in 296 of 6,191 subjects examined (4.8%; 120 men and 176 women). Serum glucose and fructosamine levels were higher in subjects with retinopathy compared with those without (8.4 vs. 6.8 mmol/l and 329.8 vs. 308.5 mumol/l, respectively, P < 0.001). Two-hour postload insulin levels and insulin resistance, assessed by the ratio of postload insulin over postload glucose level, did not differ between the two groups. These associations were similar in men and women and in subjects with and without diabetes and did not change after adjustment for body mass index or systolic blood pressure. Within the group of subjects who had retinopathy, serum glucose was significantly associated with the number of hemorrhages. These findings suggest that the presence and severity of retinopathy are associated with higher serum glucose levels, both in subjects with and without diabetes.

Low diastolic blood pressure and atherosclerosis in elderly subjects. The Rotterdam study.

BACKGROUND: A low diastolic blood pressure has been associated with increased cardiovascular risk. The following proposed mechanisms underlie this phenomenon: a low diastolic pressure that compromises coronary blood flow, a low diastolic pressure that is due to deteriorating health, and a low diastolic pressure that is a consequence of stiffening of the large arteries. Atherosclerosis may be the link between stiffening of the arteries, a low diastolic pressure, and an increased cardiovascular risk. OBJECTIVE: To study whether a low diastolic blood pressure in older subjects is a reflection of atherosclerosis. METHODS: The Rotterdam (the Netherlands) Study is a population-based follow-up study of 7983 subjects (age, > or = 55 years) who are living in the suburb of Ommoord of Rotterdam. Baseline measurements included ultrasonographic evaluation of the carotid arteries, measurement of blood pressure, and determination of other cardiovascular risk factors. The main cross-sectional analyses were performed among 930 subjects who currently were not using blood pressure-lowering drugs. RESULTS: A J-shaped association of the intima-media thickness of the common carotid artery with diastolic blood pressure was found with a nadir from 60 to 69 mm Hg. The intima-media thickness was increased in subjects with a diastolic pressure that was less than 60 mm Hg compared with that in subjects with a diastolic pressure that was between 60 and 69 mm Hg (a difference of 0.033 mm [95% confidence limits; 0.001, 0.065]). Beyond a diastolic pressure of 70 mm Hg, a gradual increase in the intima-media thickness was observed. The association was most pronounced among subjects with relatively high pulse pressures. CONCLUSIONS: Results of the present study indicate the existence of a J-shaped association between carotid atherosclerosis and diastolic pressure. These findings support the hypothesis that in elderly subjects, a low diastolic pressure may be a reflection of widespread atherosclerosis.

Renin, prorenin, and immunoreactive renin in vitreous fluid from eyes with and without diabetic retinopathy.

Renin, prorenin, and immunoreactive renin were present in vitreous and subretinal fluid of eyes from subjects with and without diabetic retinopathy. Renin substrate, albumin, transferrin, and immunoglobin G were also found in these ocular fluids. In many samples renin levels were close to the detection limit of the assay. The levels of renin substrate, albumin, transferrin, and immunoglobulin G varied widely among ocular fluid samples, but in each individual sample the levels were, relative to each other, similar to those in plasma. In contrast, the prorenin level in ocular fluid was up to 100 times higher than expected on the basis of the plasma protein content of ocular fluid. Moreover, there was little difference in prorenin concentrations between samples with low and high plasma protein contents. Prorenin, relative to albumin and other plasma proteins, was higher in vitreous fluid from eyes with proliferative diabetic retinopathy complicated by traction retinal detachment than in eyes of nondiabetic subjects with spontaneous retinal detachment. It appears that prorenin (and possibly renin) in ocular fluid is controlled by an active and specific process, possibly local synthesis within the eye. In view of the vascular actions of angiotensin II, an intraocular renin-angiotensin system may play a role in diabetic retinopathy.

Cardiovascular determinants of carotid artery disease. The Rotterdam Elderly Study.

The objective of the present study was to assess the prevalence of moderate and severe stenosis of the right carotid artery in the elderly and its associations with smoking, blood pressure, serum lipid levels, and hemostatic factors. The Rotterdam Elderly Study is a recently started single-center prospective follow-up study of a cohort of 11,854 elderly people aged 55 years or more. In 1990, 954 participants of the Rotterdam Elderly Study underwent ultrasonic duplex examination of the right internal carotid artery. A reduction of the lumen diameter of 16-49% was found in 29 people (3.0%). Severe stenosis (50% or more) was observed in 13 people (1.4%). With differences in age, sex, and body mass index taken into account, subjects with moderate-to-severe carotid artery disease had, compared with participants without stenosis, lower mean high density lipoprotein cholesterol levels (mean difference, 0.10 mmol/l; 95% confidence interval, 0, 0.20) and higher mean fibrinogen levels (difference, 0.24 g/l; 0.04, 0.45). Among them were more people with hypertension (mean difference, 16%) and more current smokers (mean difference, 13%). Factor VIIc and factor VIIIc activity was higher in subjects with carotid artery disease, without, however, reaching statistical significance (mean difference, 0.06 IU/ml [-0.01, 0.12] and 0.21 IU/ml [-0.05, 0.47], respectively). Our data suggest that hypertension, smoking, and reduced serum high density lipoprotein cholesterol levels, combined with unfavorable increases in hemostatic factors, may be related to carotid artery disease in the elderly.

High plasma prorenin in diabetes mellitus and its correlation with some complications.

Plasma prorenin is abnormally high, whereas renin is normal or even low, in many patients with long-standing diabetes mellitus complicated by microvascular disease. Nephropathy or autonomic neuropathy has been put forward as a cause. We found that in 223 consecutive diabetics prorenin correlated positively with serum creatinine, the presence of macroalbuminuria (greater than 250 mg/L), and the presence of diabetic retinopathy, particularly the proliferative type. This correlation did not depend on the presence of neuropathy or whether the patient was receiving insulin. It was also independent of sex, age, duration of diabetes, blood pressure, and blood levels of glucose and hemoglobin-A1c. The association between elevated prorenin and retinopathy remained significant after adjustment for creatinine and the presence of macroalbuminuria. Of the whole group of diabetics 94 consecutive patients were assessed for the presence of microalbuminuria (30-300 mg/24 h). Independently of the presence of micro- or macroalbuminuria, the mean level of prorenin was not above normal in the patients without retinopathy and was 2-3 times normal in those with proliferative retinopathy. Thus, retinopathy appears to be a more important determinant of abnormally high prorenin than nephropathy. In addition, the renal vein to artery ratio of prorenin in 7 diabetics with both advanced nephropathy and proliferative retinopathy was not elevated, despite the high peripheral venous prorenin level and the impaired renal perfusion. Thus, the abnormally high prorenin level in these patients could not be explained by abnormal secretion by the kidneys. Finally, prorenin was not high in 16 nondiabetics with loss of sympathetic activity due to chronic autonomic neuropathy, which indicates that in the absence of diabetes, this type of autonomic failure is not sufficient to cause the high prorenin levels seen in diabetics. Our findings are evidence that abnormally high plasma prorenin levels in diabetics are not an immediate consequence of altered glucose metabolism. This abnormality is related to the development of microvascular disease in the eye and kidney and is at least in part due to decreased clearance of prorenin from the circulation, increased production from extrarenal sources, or both.

The association of dietary fat and fiber with coagulation factor VII in the elderly: the Rotterdam Study.

Considerable evidence suggests that a high concentration of coagulation factor VII is a risk factor for ischemic heart disease. Factor VII is known to be influenced by dietary fat and probably by dietary fiber in young and middle-aged people. There are no data available in elderly people and the effects of different types of fat are unclear. This study examines the relation of factor VII activity (factor VIIc) with dietary fat and fiber in The Rotterdam Study. The Rotterdam Study is a population-based study among 7983 men and women aged > or = 55 y. Factor VIIc was measured in 3007 subjects (1730 women and 1277 men aged 67.3 +/- 7.8 and 66.3 +/- 7.0 y, respectively). Measurements included cardiovascular risk factors and habitual diet was assessed by a semiquantitative food-frequency questionnaire. Associations that were significant or nearly significant differed for some nutrients between men and women. Total fat intake showed a direct association with factor VIIc only in women (beta = 0.1%/g; 95% CI: 0.01, 0.20). Saturated fat intake was associated with factor VIIc in women (beta = 0.18%/g; 95% CI: 0.001, 0.36) and in men (beta = 0.11%/g; 95% CI: -0.06, 0.27). Monounsaturated fat was positively related to factor VIIc in women (beta = 0.17%/g; 95% CI: -0.05, 0.39) and polyunsaturated fat was inversely associated with factor VIIc in men (beta = -0.15%/g; 95% CI: -0.33, 0.03). Fiber intake was inversely associated with factor VIIc in both men (beta = -0.31%/g; 95% CI: -0.57, -0.06) and women (beta = -0.36%/g; 95% CI: -0.63, -0.09). No associations were found for energy intake. In elderly persons, factor VIIc is associated with fat and fiber intake. This suggests that factor VIIc is influenced by nutritional factors, even in old age.

Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study.

Cerebral white matter lesions are a common finding on MRI in elderly persons. We studied the prevalence of white matter lesions and their relation with classic cardiovascular risk factors, thrombogenic factors, and cognitive function in an age- and gender-stratified random sample from the general population that consisted of 111 subjects 65 to 84 years of age. Overall, 27% of subjects had white matter lesions. The prevalence and severity of lesions increased with age. A history of stroke or myocardial infarction, factor VIIc activity, and fibrinogen level were each significantly and independently associated with the presence of white matter lesions. Significant relations with blood pressure level, hypertension, and plasma cholesterol were present only for subjects aged 65 to 74 years. White matter lesions tended to be associated with lower scores on tests of cognitive function and were significantly associated with subjective mental decline. This study suggests that classic cardiovascular risk factors, as well as thrombogenic factors, are associated with white matter lesions in subjects over 65 years of age in the general population, and that these lesions may be related to cognitive function.

Dietary electrolyte intake and blood pressure in older subjects: the Rotterdam Study.

OBJECTIVE: To examine the relation between dietary electrolyte intake and blood pressure in older people. METHODS: The study included 3239 participants of the Rotterdam Study (41% of the total cohort) who were aged over 55 years and had not been prescribed antihypertensive drugs. Their dietary intake was assessed by a semiquantitative food frequency questionnaire. The association of energy-adjusted intakes of potassium, magnesium and calcium with blood pressure was studied in a linear regression model with adjustment for age, sex, body mass index and alcohol intake. RESULTS: An increase in potassium intake of 1 g/day was associated with a 0.9 mmHg lower systolic and a 0.8 mmHg lower diastolic blood pressure. An increase in magnesium intake of 100 mg was associated with a 1.2 mmHg lower systolic and a 1.1 mmHg lower diastolic blood pressure. Calcium intake was not independently related to blood pressure, except for a subgroup of 1360 hypertensive subjects in which a significant inverse association with diastolic blood pressure was observed. CONCLUSIONS: Our findings support the view that an increase in the intake of foods rich in potassium and magnesium could lower blood pressure at older age.

Insulin, hypertension and antihypertensive drugs in elderly patients: the Rotterdam Study.

OBJECTIVE: To investigate the association between insulin, hypertension and antihypertensive drug use in elderly patients. DESIGN AND METHODS: Blood pressure, use of antihypertensive drugs and glucose metabolism were examined in 5453 men and women (mean age 68.8 years). This was part of the baseline examination of the Rotterdam Study, a population-based study of chronic diseases in elderly patients. Serum insulin was measured 2 h after an oral glucose load. RESULTS: Patients with hypertension had a significantly higher mean post-load insulin level than those without: 71.3 mU/l versus 59.3 mU/l (P < 0.001, adjusted for age). Systolic blood pressure increased by 0.25 mmHg per 10 mU/l insulin (95% confidence interval 0.15-0.35, adjusted for age, sex and antihypertensive drugs), whereas the increase in diastolic blood was 0.07 mmHg per 10 mU/l (0.01-0.13). Whereas insulin resistance was higher in patients with hypertension, the increase in insulin resistance with age was much more apparent in normotensive patients, resulting in similar insulin levels at high ages. Those using antihypertensive drugs, however, had higher insulin levels at all ages. CONCLUSION: The results of this study show that hyperinsulinemia is associated with raised blood pressure in elderly people, and suggest that the age-associated increase in insulin resistance is diminished in patients with raised blood pressure. The use of antihypertensive drugs, however, appears to be accompanied by an independent additional increase in insulin resistance at all ages.

Intraocular light scattering in age-related cataracts.

Intraocular light scattering was studied in 34 controls and 65 patients with cortical, nuclear, or posterior subcapsular cataracts by measuring forward scatter and backscatter. Forward scatter was measured by the psychophysical direct compensation method. Backscatter was determined with the Lens Opacity Meter of Interzeag. Contrast sensitivity loss caused by forward scatter was assessed with a glare tester (Vistech MCT 8000). Mean forward scatter was in the upper range for subcapsular cataracts compared to nuclear and cortical cataracts. Experimental results of the glare test (the contrast loss) deviated systematically from expected results based on measured forward scatter. Mean backscatter was largest for nuclear, intermediate for posterior subcapsular, and almost zero for cortical cataracts. Thus, each cataract has a characteristic mean ratio between forward scatter and backscatter. However, this ratio varied considerably among individuals, especially for cortical and posterior subcapsular cataracts. As a rule, forward scatter cannot be derived from backscatter (or the slit-lamp image).

Risk of acute angle-closure glaucoma after diagnostic mydriasis in nonselected subjects: the Rotterdam Study.

PURPOSE: To report the prevalence of narrow anterior chamber angles on slit-lamp examination and the incidence of acute angle-closure glaucoma (AACG) after diagnostic mydriasis in nonselected white subjects aged 55 years and over. METHODS: Of all subjects in the population-based Rotterdam Study (n = 7983), 6760 participated in the ophthalmologic examination and received both tropicamide 0.5% and phenylephrine 5% eye drops for diagnostic mydriasis. No exclusion criteria (e.g., level of intraocular pressure, presence of narrow anterior chamber angles, history of or treatment for glaucoma) were used. After the ophthalmologic examination, all participants received thymoxamine 0.5% drops in both eyes and were warned about the symptoms of AACG. RESULTS: The prevalence of narrow angles was 2.2% and was twice as high in women. In two subjects (0.03%), an attack of AACG developed in one eye after diagnostic mydriasis. After medical therapy, peripheral iridotomies were made with a Nd:YAG laser, and both eyes healed without loss of visual acuity or visual field. CONCLUSIONS: In nonselected white subjects of 55 years of age or older, the 2% prevalence of narrow anterior chamber angles is similar to that in a mixed black and white population in the United States. According to our protocol, 3 in 10,000 subjects are likely to develop AACG after diagnostic mydriasis followed by miotic drops.

Analysis of carbohydrate structures in basal laminar deposit in aging human maculae.

PURPOSE: To analyze carbohydrate structures in basal laminar deposit (BLD), an extracellular material that accumulates between the retinal pigment epithelium (RPE) and Bruch's membrane. BLD has been shown to correlate positively with visual loss in age-related macular degeneration. METHODS: Thirteen postmortem human maculae with BLD were histochemically examined by light microscopy using the monoclonal antibody HNK-1 and seven lectins; canavalia ensiformis (ConA), soybean agglutinin (SBA), wheat germ agglutinin (WGA), dolichos bifloris (DBA), ulex europaeus (UEA-I), ricinius communis agglutinin I (RCA-I), and peanut agglutinin (PNA). Three maculae were stained with polyclonal antibodies against laminin and collagen type IV. RESULTS: BLD was exclusively stained by DBA and SBA, whereas Con A, WGA, UEA-I, RCA-I, and HNK-1 stained various other structures in the human macula as well. The main part of the BLD adjacent to Bruch's membrane stained with these lectins and the monoclonal antibody HNK-1, whereas only a small part of the BLD adjoining the RPE stained with antibodies against laminin and collagen type IV. Drusen stained neither with any lectin nor with any antibody. CONCLUSIONS: DBA and SBA, which bind specifically to an alpha-D-GalNAc moiety, are specific markers for the light-microscopic detection of BLD in human macular tissue. Furthermore, the authors conclude that BLD contains several carbohydrate structures other than the carbohydrate moieties on laminin and collagen type IV. If drusen contain carbohydrate structures, these must be different from those in BLD.

Angiotensin levels in the eye.

PURPOSE: Ocular tissues contain renin and ocular fluids contain prorenin in amounts that are too high to be explained by admixture with blood or diffusion from blood. It was the purpose of the present study to obtain further evidence for the presence of a local renin-angiotensin system (RAS) in the eye. METHODS: The authors measured the concentrations of angiotensins I and II (ANG I and II) in vitreous fluid and ocular tissues of anesthetized pigs and in human aqueous, vitreous, and subretinal fluid obtained during eye surgery. RESULTS: In tissues obtained from normal porcine eyes (anterior uveal tract, neural retina, retinal pigment epithelium + choroid), ANG I and II were 5- to 100-fold higher than could be accounted for by contamination with blood. ANG I and II in ocular tissues are therefore unlikely to be derived from the circulation. In porcine vitreous fluid, ANG I and II were close to the limit of detection. In addition, during a 2-hour infusion of 125I-ANG I in the rabbit, 125I-ANG I in vitreous fluid reached a level only 1% of the level in arterial plasma. Thus, in the presence of an intact blood-retinal barrier, little or no ANG I or II enters the vitreous compartment. In human ocular fluids obtained from diseased eyes, ANG I and II levels were readily measurable and correlated linearly with the level of serum albumin, indicating that after partial breakdown of the BRB, diffusion of ANG I and II from the circulation into the eye may occur. CONCLUSION: Results indicate that both ANG I and II are generated locally in ocular tissues with little leakage into ocular fluids. These findings, together with previously published data on renin and prorenin, show a high degree of compartmentalization of the RAS in the eye and are in agreement with similar findings in other tissues, where there is evidence for the existence of a local RAS.