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Biomedical subjects

J Cunha-Vaz

Publications and source records attributed to J Cunha-Vaz.

17 recordsLinked to original sources

[The European Vision Institute. Opening up new frontiers?].

The European Vision Institute EEIG (EVI) creates a new legal entity based on Community law to facilitate and encourage cross-border co-operation in vision research. Its major objectives are to conduct and support research, training, health information dissemination and other programmes with respect to blinding eye diseases, visual disorders, mechanisms of visual function, preservation of sight and the special health problems and requirements of the blind and visually disabled. EVI aims to foster centres in the EU in capacity building for innovative projects, to increase the flexibility, attractiveness and competitiveness of research careers, especially for young researchers. In addition, EVI will serve to co-ordinate activities with patient organisations and to build a pan-European platform for clinical trials.

Academies and Institutes↗

Effects of ibopamine eye drops on intraocular pressure and aqueous humor flow in healthy volunteers and patients with open-angle glaucoma.

PURPOSE: On the basis of intraocular pressure measurements and fluorophotometry we assessed the effects of 2% ibopamine eye drops on aqueous humor production in normal and glaucomatous eyes. METHODS: Thirty subjects (15 healthy volunteers and 15 open-angle glaucoma patients with ocular hypertension) were included in a placebo-controlled study with random assignment of treatment from masked containers. All subjects underwent ophthalmologic examinations and intraocular pressure (IOP) measurements. Fluorophotometry was done in both eyes at baseline (without treatment) and during treatment. Each subject was treated with 1 drop of 2% ibopamine in one eye and 1 drop of placebo in the fellow eye 30 minutes before fluorophotometric scans and every hour after the first instillation (for a total of 4 times). Safety was evaluated by recording adverse events and ocular symptoms and signs. Aqueous humor flow data were analyzed using the paired t-test, comparing ibopamine and placebo-treated eyes. RESULTS: No changes in IOP were detected in normal eyes, whereas glaucomatous eyes showed a mean increase of 4 mmHg (95% CI 3.46-4.51) from baseline. The difference in IOP between healthy eyes and those with glaucoma was significant (p < 0.0001). In normal eyes and patients with glaucoma ibopamine led to a significant increase in aqueous humor flow compared with placebo-treated eyes (p < 0.01). The safety profile of ibopamine was very good. CONCLUSIONS: The results seem to confirm that ibopamine increases aqueous humor production in normal and glaucomatous eyes, raising IOP only in eyes with glaucoma.

Adult↗

Comparison of topical travoprost eye drops given once daily and timolol 0.5% given twice daily in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: This 9-month study compared the intraocular pressure (IOP)-lowering efficacy and safety of once-daily travoprost ophthalmic solutions (0.0015% and 0.004%) with twice-daily timolol 0.5%. PATIENTS AND METHODS: This study was conducted using a double-masked, randomized, parallel-group design; adult patients with open-angle glaucoma or ocular hypertension (IOP between 24 and 36 mm Hg, inclusive at 9 am and between 21 and 36 mm Hg, inclusive, at 11 am and 4 pm on two eligibility visits after an appropriate washout of previous treatments). In both eyes, the travoprost vehicle (placebo) was instilled at 9 am and travoprost (0.0015% or 0.004%) was instilled at 9 pm, or timolol 0.5% was instilled at both times. The primary efficacy variable was mean IOP measured at 9 am, 11 am, and 4 pm at baseline and follow-up visits. RESULTS: Five hundred seventy-three patients were randomized to the study treatments. Mean IOP, which was combined across study visits, was lower with travoprost 0.004% than with timolol 0.5% at 9 am (P = 0.0246), 11 am (P = 0.0039), and 4 pm (P = 0.0004). Intraocular pressure was lower with travoprost 0.004% than with travoprost 0.0015% at 11 am (P = 0.0314), the time of peak drug activity. Mean IOP was consistently lower with travoprost 0.0015% than with timolol 0.5%. Mean IOP reductions from baseline were significantly (P less than equal 0.0001) greater with travoprost 0.004% (8.0-8.9 mm Hg) than with timolol 0.5% (6.3-7.9 mm Hg). The most frequent related adverse events were hyperemia, pruritus, discomfort, pain, and iris pigmentation changes. The local tolerance was better in the timolol group compared with patients receiving travoprost. There were no serious unexpected treatment-related adverse events in any group. CONCLUSIONS: Travoprost 0.004% reduced diurnal mean intraocular pressure significantly more than timolol 0.5%. Both concentrations of travoprost were well tolerated and safe for use in patients with open-angle glaucoma or ocular hypertension.

Administration, Topical↗

What works? Success stories in Type 2 diabetes mellitus.

The increasing prevalence of Type 2 diabetes mellitus has made diabetes a major public health problem worldwide. Healthcare systems are faced with the major challenge of developing innovative approaches to improving the prevention of diabetes and associated complications, particularly in populations undergoing rapid cultural development. Examples of community-based primary prevention projects in two Native communities in Canada that have high incidences of diabetes are reviewed. These projects are notable for the active participation of the communities, the collaborative relationship that was established between the communities and the researchers, and the way that traditional native culture and beliefs were incorporated into the intervention design. This phenomenon has impacted on the success of the projects and has enhanced their long-term sustainability.

Canada↗

Progression of retinopathy and alteration of the blood-retinal barrier in patients with type 2 diabetes: a 7-year prospective follow-up study.

BACKGROUND: The study was carried out to evaluate the correlation between blood-retinal barrier (BRB) permeability and the progression of diabetic retinopathy (DR), defined by development of "need for photocoagulation", over a 7-year period by means of vitreous fluorometry (VF). METHODS: Forty type 2 diabetic patients with minimal or no retinopathy, aged 40-65 years (mean 53.9 + 7.3 years), were followed up prospectively for 7 years. Investigations including standard ophthalmological examination, fundus photography, fluorescein angiography and VF were performed at entry and 1, 4, 5 and 7 years later. Only one eye per patient was included in the study. Need for photocoagulation was based on Early Treatment Diabetic Retinopathy Study protocols and decided by the attending ophthalmologist. RESULTS: After 7 years of follow-up a total of 22 of the 40 eyes had received photocoagulation. The eyes that needed photocoagulation were those that had higher VF values at the entry of the study and showed higher rates of deterioration (initial values 5.1 + 1.9 vs 2.8 + 1.5 x 10(-6) min-1, P < 0.001; annual increase in leakage for the first year, 1.5 + 0.8 vs 0.5 + 1.0 x 10(-6) min-1, P < 0.001,). The eyes that did not need photocoagulation during the 7 years of follow-up showed stable VF readings (-0.1 + 1.2 x 10(-6) min-1, difference between initial values and 7 years later). CONCLUSIONS: Abnormally high VF values and their rapid increase over time are good indicators of progression and worsening of the retinopathy in diabetes type 2.

Adult↗

Nitric oxide synthase activity and L-arginine metabolism in the retinas from streptozotocin-induced diabetic rats.

1. Nitric oxide synthase (NOS) activity was studied in the retinas from normal rats and in the retinas from two groups of streptozotocin-induced (8 days and 4 months) diabetic rats. In each animal group, the NOS activity was correlated to the concentration of amino acids related to L-arginine metabolism and to L-arginine uptake. 2. Retinas from both groups of streptozotocin-induced diabetes (8 days and 4 months) showed an increased NOS activity compared with the NOS activity in retinas from normal rats. In retinas lysate from normal rats, the NOS activity was most potently inhibited by NO-Arg (1 mM), whereas, in both groups of streptozotocin-induced diabetes, the NOS activity was most potently inhibited by the NOS inhibitor aminoguanidine (0.5 mM). 3. The basal levels of the amino acids related to L-arginine metabolism-namely, L-arginine, L-citrulline, L-ornithine and L-glutamine-in retinas from both groups of rats with streptozotocin-induced diabetes were decreased compared with the amino acid levels in retinas from normal rats. 4. The uptake of L-[3H]arginine in retinas from both groups of rats with streptozotocin-induced diabetes was increased compared with the uptake of of L-[3H]arginine in retinas from normal rats.

Animals↗

Blood-retinal barrier permeability and its relation to progression of retinopathy in patients with type 2 diabetes. A four-year follow-up study.

Forty patients with late-onset diabetes (age at diagnosis 30 years or more) and minimal retinopathy as found by fundus photography were followed prospectively by repeated examination (baseline, 1 year, and 4 years). The study shows that early retinopathy changes are not permanent or invariably progressive. In the 1st year of follow-up microaneurysms worsened in 25%, improved in 10%, and remained stabilized in 65%. Vitreous fluorometry was able to detect an overall increase of 0.84 +/- 1.06 x 10(-6) min-1 in blood-retinal barrier (BRB) penetration ratios. After 4 years, 16 of the 40 patients had undergone photocoagulation (focal photo-coagulation in 11 and pan retinal photocoagulation in 5). The eyes that needed photocoagulation were the eyes that had higher fluorometry penetration ratios at the patient's entry into the study and showed a higher rate of deterioration during the 1st year of the study (5.54 +/- 1.97 vs 3.11 +/- 1.22 x 10(-6) min-1, P < 0.001, initial values; 1.52 +/- 0.76 vs 0.45 +/- 0.99 x 10(-6) min-1, P < 0.001, annual increase in leakage). The eyes that did not need photocoagulation, 24 out of 40, showed stable fluorometry readings within the 4-year period of follow-up (+0.02 +/- 0.98 10(-6) min-1). Abnormally high vitreous fluorometry values and their rapid increase over time appear to be good indicators of rapid progression and worsening of the retinopathy.

Adult↗

[Follow-up of early diabetic maculopathy by angiography and fluorophotometry].

We evaluated prospectively for 12 months 22 patients with late-onset diabetes mellitus and minimal retinopathy by fluorescein angiography and fluorophotometry. The study showed that early retinopathy changes were not permanent or invariably progressive, but may regress. Microaneurysm gradings worsened in 24%, improved in 14% and remained stabilized in 62%. Capillary closure worsened in 33%, improved in 10% and remained stabilized in 57%. The evolution of early diabetic maculopathy is slow and irregular, and this study has shown that vitreous fluorophotometry must be included when short follow-up periods of up to 12 months are considered. Finally, eyes with higher fluorophotometry values at entry showed significantly more deterioration during the 12-months follow-up period (p less than 0.05).

Diabetes Mellitus, Type 2↗

Vitreous fluorophotometry in patients with hypertension.

Vitreous fluorophotometry performed on 22 patients with moderate to severe hypertension showed that patients with active retinopathy, as manifested by retinal hemorrhages, cotton-wool spots, retinal exudates and edema, or disc edema, generally had elevated values (20/28 eyes). Control of the BP resulted in a decrease in the values toward the normal range. Patients with only arteriolar sclerosis, even some with particularly high BP, generally had normal fluorophotometric values (14/16 eyes). The two exceptions showed minimal elevations. Vitreous fluorophotometry is a useful tool to quantitate the blood-retinal barrier in patients with moderate to severe hypertension and may be a sensitive indicator of treatment efficacy.

Adult↗

Vitreous fluorophotometry in patients with retinitis pigmentosa.

Fifteen patients with various genetic types of retinitis pigmentosa and three carriers of the X-linked recessive type were examined with vitreous fluorophotometry. All patients with retinitis pigmentosa showed abnormally high concentrations of fluorescein within the vitreous that reflected an abnormality of the blood-retinal barrier. The amount of fluorescein within the vitreous correlated with the extent of photoreceptor and retinal pigment epithelial disease, as well as with the presence of leakage from retinal capillaries. Vitreous fluorophotometric measurements can show breakdown of the blood-retinal barrier in patients with retinitis pigmentosa who have no ophthalmoscopically apparent abnormalities and only minor changes on the electroretinogram (ERG). Furthermore, a breakdown of the blood-retinal barrier can be apparent in carrier of the X-linked recessive from of retinitis pigmentosa, even though the findings from a fundus examination and ERG recordings are normal.

Adolescent↗

Kinetic vitreous fluorophotometry in experimental diabetes.

Kinetic vitreous fluorophotometry was used to measure dynamic alterations in blood-retinal barrier function. Normal hooded rats were compared with diabetic animals before and after insulin treatment. Rats with streptozocin-induced diabetes demonstrated significantly longer (P less than .001) half-periods of fluorescein loss from the vitreous when compared with controls, and insulin treatment significantly reduced (P less than .001) the mean half-period toward control values without normalization of serum glucose. These results suggest that kinetic vitreous fluorophotometry is a good indicator of blood-retinal barrier function and that sufficient amounts of insulin may be more important than normal blood glucose levels in recovery of altered barrier function in diabetes.

Animals↗

Early breakdown of the blood-retinal barrier in diabetes.

The blood-retinal barrier plays an important part in the processes of retinal pathophysiology. A new clinical method for the study of the blood-retinal barrier by vitreous fluorophotometry appears to satisfy the necessary requirements in that it is quantitative and shows good reproducibility and high sensitivity. The application of this method to a series of diabetic patients with apparently "normal" fundi revealed the presence of a significant breakdown of the blood-retinal barrier in the early stages of retinal involvement in diabetes. The extent of the breakdown can be measured allowing for comparative and evolutionary evaluations. The disturbance of the blood-retinal barrier, as evidence by vitreous fluorophotometry, appears before microaneurysms or capillary closure can be demonstrated by fluorescein angiography.

Adolescent↗

The blood-ocular barriers.

The introduction of the concept of blood-ocular barriers in the ophthalmic literature is briefly reviewed. Two main blood-ocular barriers are proposed: the blood-aqueous barrier and the blood-retinal barrier. The blood-aqueous barrier is formed by an epithelial barrier located in the nonpigmented layer of the ciliary epithelium and in the posterior iridial epithelium, and by the endothelium of the iridial vessels. Both these layers have tight junctions of the "leaky" type. The pereability of the blood-aqueous barrier shows a significant degree of pressure-dependent diffusion associated with transport activity, resembling the standing gradient osmotic flow model. The blood-retinal barrier is located at two levels, forming an outer barrier in the retinal pigment epithelium and an inner barrier in the endothelial membrane of the retinal vessels. Both these membranes have tight junctions of the "nonleaky" type. The permeability of the blood-retinal barrier resembles cellular permeability in general, diffusion being directly related to the predominant roles of lipid solubility and transport mechanisms. Finally, the clinical significance of the blood-ocular barrier is analyzed. The metabolism of cornea and lens and the regulation of intraocular fluids are directly influenced by the blood-aqueous barrier. Similarly, an alteration of the blood-retinal barrier appears to play an important role in the development of vascular retinopathies, pigment epitheliopathies, and retinal edema.

Animals↗

Diabetic macular edema.

Retinal edema is defined as any increase of water in retinal tissue resulting in an increase in its volume. This increase may be initially intracellular or extracellular. In the first case, there is cytotoxic edema. In the second, vasogenic edema, directly associated with an alteration of the blood-retinal barrier (BRB). Retinal thickness can now be measured, using the retinal thickness analyser (RTA). Similarly, local breakdown of the BRB can now be mapped using the retinal leakage analyser (RLA). The application of these methods to diabetic macular edema has shown that both types of retinal retinopathy edema occur in the initial stages of diabetic retinal disease. These observations suggest a role for neuroprotective and vasoprotective agents in the management of diabetic retinal disease.

Diabetic Retinopathy↗