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J G Cunha-Vaz

Publications and source records attributed to J G Cunha-Vaz.

At least 19 recordsLinked to original sources
PubMed2007

Chorioretinal anastomosis and photodynamic therapy: a two-year follow-up study.

BACKGROUND: To evaluate the two-year efficacy of photodynamic therapy with Visudyne (PDT) in neovascular age-related macular degeneration (AMD) eyes with chorioretinal anastomosis (CRA). METHODS: A non-randomized, institutional, prospective study, of 28 consecutive eyes of 23 patients, with CRA, treated with PDT. Masked best corrected visual acuity (VA) and angiographic features at baseline and during the period of two years were evaluated. RESULTS: Twenty eight eyes completed one year and 19 eyes completed two years of follow-up. The number of treatments was 3 in the first year, and 0.8 in the second year. A VA loss < 3 lines occurred in 53% of the eyes, at two years. Treated eyes lost 0.5 lines in the first year and 2.4 lines in the second (p < 0.01). Recurrence with additional significant VA loss occurred in four eyes (21%) during the second year. Fourteen eyes (74%) showed no fluorescein leakage at two years. CONCLUSION: AMD eyes with chorioretinal anastomosis can benefit from PDT with Verteporfin at two years. However, during the second year significant additional VA loss occurs mainly due to recurrence. New modalities of treatment are necessary to achieve VA improvement in CRA eyes.

Aged↗
PubMed2005

Polypoidal choroidal vasculopathy and photodynamic therapy with verteporfin.

BACKGROUND: We evaluated, in a nonrandomised, institutional, prospective study, the efficacy of photodynamic therapy (PDT) with verteporfin in age-related macular degeneration (AMD) eyes with polypoidal choroidal vasculopathy (PCV) and subfoveal exudation. METHODS: A prospective clinical and angiographic study was done in 40 consecutive eyes with PCV treated with PDT using masked best-corrected visual acuity (VA) and fluorescein and indocyanine green angiographic features at baseline and over 2 years. RESULTS: Twenty-one eyes completed 1-year follow-up and showed, after a mean 2.9 PDT sessions, VA improvement in 12 eyes, no change in five eyes, and VA decrease in four eyes. Leakage was absent at the retinal and choroidal level in 14 eyes at 1 year. Recurrence occurred in one eye during the first year. Six eyes completed 2 years of follow-up and showed, after a mean 4 PDT sessions, VA improvement in five eyes and VA decrease in one eye. Leakage was absent at the retinal and choroidal level in five eyes. Recurrence occurred in four of these six eyes during the second year of follow-up. No serious adverse events were observed during the 2 years of follow-up. CONCLUSIONS: PDT with verteporfin was shown to be safe and effective for treating AMD eyes with PCV with subfoveal involvement. VA improvement and absence of leakage were achieved, respectively, in 57.1% and 66.6% of the eyes at 1 year. Recurrences were more frequent during the second year of follow-up.

Aged↗
PubMed2004

Effects of neuropeptides on the sumatriptan-disturbed circulation in the optic nerve head of rabbits.

The purpose of this work was to study 'in vivo' the vascular responses of retinal vessels of New Zealand white rabbits to substance P (SP), neurokinin A (NKA), neurokinin B (NKB), senktide, capsaicin (CAPS), and calcitonin gene related peptide (CGRP) before and after selective antagonist administration. We examined the effects of these neuropeptides on the normal circulation in the optic nerve head of the rabbit. Drugs were injected via pars plana through a micropipette system. Ten minutes before perivascular injection of 10 nmol/l sumatriptan (to contract the vessel), a selective antagonist or its solvent was administered. Then, cumulative injection of the agonist was performed. The other eye was used as control. Direct measurement of retinal arteriole diameters was performed using digital angiography. The quantification of the relaxing effect is expressed as percentage related to the precontracted vascular diameter. Microinjection of SP (NK1 receptor agonist) up to 10 nmol/l induced a dose-dependent arteriolar dilating effect [E(max) (mean +/- SEM) 21.3 +/- 2.3%]. After the perivascular preinjection of 1 nmol/l L-668,169 or 1 nmol/l L-733,060 (NK1 receptor antagonists), the SP dose-response curve was shifted to the right. The same results were obtained with NKA (NK2 receptor agonist) which induced the most potent effect of all neuropeptides (E(max) 53.3+/-2.5%). The NK2 receptor antagonists L-659,877 and GR 159897 (1 nmol/l) strongly inhibited this arteriolar vasodilation. As for CGRP, doses up to 10 nmol/l induced a marked vasodilation (E(max) 41.1+/-0.4%) which decreased after microinjection of the selective antagonist CGRP8-37. The NK3 receptor agonists (senktide and NKB) showed a minor vasodilating effect (E(max) 5.1+/-1.2 and 8.0+/-0.9%, respectively). On the contrary, CAPS showed a marked dose-dependent vasodilating effect (E(max) 43.2+/-2.9%), antagonized by the tachykinin receptor antagonists and CGRP8-37. These results suggest, for the first time, the presence of NK1, NK2, and CGRP receptors on the retinal arteriolar wall of the rabbit.

Animals↗
PubMed2001

One-year follow-up of blood-retinal barrier and retinal thickness alterations in patients with type 2 diabetes mellitus and mild nonproliferative retinopathy.

OBJECTIVE: To examine the 1-year alterations of the blood-retinal barrier and changes in retinal thickness occurring in the macular region in patients with type 2 diabetes mellitus and mild nonproliferative retinopathy. METHODS: We classified 12 eyes of 12 patients with type 2 diabetes mellitus and mild nonproliferative retinopathy by 7-field stereoscopic fundus photography, levels 20 and 35 of Wisconsin grading, and examined them 3 times, at 6-month intervals, by fluorescein angiography, retinal leakage analyzer (RLA) (modified confocal scanning laser ophthalmoscope), and retinal thickness analyzer. The maps of retinal leakage and retinal thickness were aligned and integrated into one image. Data from the group of individuals with diabetes were compared with those from a healthy control population (n = 14; mean age, 48 years; age range, 42-55 years) to establish reference maps for the RLA and the retinal thickness analyzer. RESULTS: Areas of abnormally increased fluorescein sodium leakage and increased thickness were detected in all eyes examined at baseline. The sites of increased fluorescein leakage reached values as high as 483% above normal, but in 10 of the total 36 examinations performed, fluorescein leakage returned to normal levels. A statistically significant correlation was found between changes in hemoglobin A(1c) values and variations in percentage of abnormal fluorescein leakage between the 6- and 12-month examinations (P<.001). When comparing the RLA-leaking sites among the 3 examinations, a good correlation was seen among the location of these sites of maximum leakage, but there was a clear fluctuation in the percentage of increases. A correlation was noted between the location of the RLA-leaking sites and the location of areas of increased retinal thickness in subsequent examinations, either 6 or 12 months later. Microaneurysms showed relatively little leakage and leaked progressively less in successive examinations. CONCLUSIONS: The dominant alteration in the retina of patients with type 2 diabetes mellitus and mild nonproliferative retinopathy is the presence of RLA-leaking sites, indicating spotty retinal vascular damage characterized by alteration of the blood-retinal barrier. This damage appears to be reversible and directly associated with variations in glycemic metabolic control. Retinal edema appears to develop mainly as a result of retinal vascular leakage.

Adult↗
PubMed2000

Alterations of the blood-retinal barrier and retinal thickness in preclinical retinopathy in subjects with type 2 diabetes.

OBJECTIVE: To identify alterations of the blood-retinal barrier by mapping retinal fluorescein leakage into the vitreous and changes in retinal thickness occurring in the macular region in preclinical diabetic retinopathy. METHODS: Ten eyes from 10 patients with type 2 diabetes and no lesions visible on fundus photography (level 10 of Wisconsin grading) were examined with the retinal leakage analyzer (RLA) (Confocal Scanning Laser Ophthalmoscope [modified]; Carl Zeiss Inc, Thornwood, NY) and the retinal thickness analyzer (RTA) (Talia Technology, Mevaseret Zion, Israel). The maps of retinal leakage and retinal thickness were aligned and integrated in the same image to correlate leakage with thickness. Data from the group of individuals with diabetes were compared with those of a healthy control population (N = 14; mean age, 48 years; range, 42-55 years) and used to establish reference maps for the RLA and RTA. RESULTS: Areas of abnormally increased fluorescein leakage were detected in 9 of 10 eyes examined. The increased leakage in 6 (67%) of 9 eyes reached values higher than 40% more than the mean +2 SD RLA control value. Areas of abnormally increased thickness were found in 7 of 10 eyes examined. For the most part, the increases in retinal thickness were not severe (ie, <15% increase in 5 eyes and an 18% increase in 1 eye). The eyes with the most extensive leakage (cases 1, 3, and 9) showed relatively good coincidence between the location of the areas of increased leakage and the location of the areas of increased thickness. In 4 eyes (cases 2, 5, 7, and 8), no such correlation was apparent. The 3 remaining eyes showed little coincidence between these locations. Characteristically, the latter 3 eyes had areas of abnormally increased thickness that were much larger than the areas of increased fluorescein leakage, which were relatively moderate or absent of any leakage. CONCLUSIONS: Localized sites of increased fluorescein leakage and zones of increased retinal thickness were found in most eyes in a series of 10 eyes in the preretinopathy stage from 10 patients with type 2 diabetes. Increases in retinal thickness may be observed that do not coincide with sites of retinal leakage. Two types of increased retinal thickness may, therefore, be present in the preretinopathy stage of diabetic retinopathy, one directly associated with an alteration of the blood-retinal barrier, and another occurring without apparent breakdown of blood-retinal barrier.

Adult↗
PubMed2000

Nitric oxide synthase activity in retinas from non-insulin-dependent diabetic Goto-Kakizaki rats: correlation with blood-retinal barrier permeability.

The aim of this work was to examine whether the non-insulin-dependent diabetic Goto-Kakizaki (GK) rats develop retinal changes with similar characteristics to those observed in insulin-dependent diabetic rats in what concerns blood-retinal barrier (BRB) permeability, nitric oxide (NO) production, and retinal IL-1beta level. BRB permeability was evaluated by vitreous fluorophotometry. NO synthase (NOS) activity was assessed by the production of l-[(3)H]-citrulline and retinal IL-1beta level was determined by ELISA. The expression of the inducible isoform of NOS (iNOS) protein was evaluated by Western blot analysis and immunohistochemistry. The in vivo studies indicated that in GK rats the BRB permeability to fluorescein was increased (787.81 +/- 68 min(-1)) in comparison to that in normal Wistar rats (646.6 +/- 55 min(-1)). The ex vivo studies showed that in retinas from GK rats the NOS activity was higher (207 +/- 28.9 pmol l-[(3)H]-citrulline/mg protein/30 min) than that in normal Wistar rats (125 +/- 32.3 pmol l-[(3)H]-citrulline/mg protein/30 min). These results were correlated with an increase in the protein level of iNOS in the retinas of GK rats, which was confirmed not only by the study of the iNOS protein expression but also by the use of NOS activity inhibitors. Indeed, the data about the effect of specific inhibitors on the NOS activity revealed that in retinas from GK rats the most effective inhibitor was aminoguanidine, which predominantly inhibits the iNOS isoform whereas in retinas from normal Wistar rats it was N(G) nitro l-arginine that predominantly inhibits the constitutive isoforms of NOS. In summary, in retinas from GK rats there is an increased production of NO which may contribute to the BRB breakdown.

Animals↗
PubMed2000

Effect of cyclosporin-A on the blood--retinal barrier permeability in streptozotocin-induced diabetes.

BACKGROUND: Our previous results showed that in retinas from streptozotocin (STZ)-induced diabetic rats there is an increased level of interleukin-1beta (IL-1beta). This cytokine may be involved in the expression of the inducible isoform of the nitric oxide synthase (iNOS), with consequent synthesis of large amounts of NO and blood-retinal barrier (BRB) breakdown. AIMS: The aim of this work was to examine whether the administration of cyclosporin-A (Cs-A) to STZ-induced diabetic rats inhibits the synthesis of IL-1beta and the expression of the inducible proteins, iNOS and cyclo-oxygenase-2 (COX-2) in retinal cells, and whether the activity of these proteins contribute to BRB breakdown. METHODS: The level of IL-1beta was evaluated by ELISA and the NO production by L-[3H]-citrulline formation. Expression of iNOS and COX-2 proteins was determined by two methods, western blot and immunohistochemistry. The permeability of the BRB was assessed by quantification of the vitreous protein. RESULTS AND DISCUSSION: Our results indicated that the levels of IL-1beta and NO in retinas from Cs-A-treated diabetic rats are significantly reduced, as compared to that in non-treated diabetic rats. The treatment of diabetic rats with Cs-A also significantly inhibited the expression of the inducible proteins, iNOS and COX-2. The evaluation of the vitreous protein content revealed that Cs-A also reduces the BRB permeability. Taken together, these results suggest that the increased production of the inflammatory mediators, IL-1beta and NO, in diabetes may affect the BRB permeability and therefore contribute to the development of diabetic retinopathy.

Animals↗
PubMed2000

Diabetic retinopathy: surrogate outcomes for drug development for diabetic retinopathy.

Diabetic retinopathy remains the most frequent cause of new cases of blindness among adults aged 20-74 years. A number of large clinical trials have validated treatment methods now considered standard. However, the disease continues to progress in approximately 50% of the eyes treated by photocoagulation. Other forms of therapy targeted at the earliest stages of retinal disease are needed. The difficulties in defining and accepting surrogate outcomes appropriate to evaluate the earlier stages of retinopathy are discussed. Special attention is given to trial design and the most likely possibilities for surrogate outcomes: mean difference on the Early Treatment Diabetic Retinopathy Study retinopathy scale of at least 2 steps per eye, reduction in macular thickening and reduction in fluorescein leakage.

Diabetic Retinopathy↗
PubMed1999

Mapping retinal fluorescein leakage with confocal scanning laser fluorometry of the human vitreous.

OBJECTIVE: To demonstrate an objective, quantitative, and sensitive method of mapping retinal fluorescein leakage into the vitreous while simultaneously imaging the retina. METHODS: A prototype Zeiss confocal scanning laser ophthalmoscope was modified to obtain fluorometric measurements from 18 optical planes across the retina and cortical vitreous, separated from each other by 150 microm, and parallel to the retinal surface. After intravenous administration of fluorescein, an axial graphic of equivalent fluorescein concentration in the vitreous may be obtained from any region of interest. After correcting for fluorescence levels in the retina and choroid and plasma levels of free fluorescein, permeability values of the blood-retinal barrier to fluorescein were obtained from 1512 regions measuring 75 x 75 microm, from a total 3150 x 2700-microm area of the fundus, generating a detailed map of retinal fluorescein leakage. The method was assessed in vitro and in 7 healthy subjects who underwent scans during separate visits. Depth resolution and influence of chorioretinal fluorescence were further tested in 2 patients with multiple drusen and in 2 eyes after vitrectomy. Fourteen eyes from 7 patients with diabetes and nonproliferative retinopathy were also examined. Lateral resolution was tested in 3 diabetic eyes that underwent focal photocoagulation. Four eyes from 2 patients with diabetes and minimal retinopathy were examined at 3-month intervals. All eyes examined had less than 2 diopters of astigmatism. RESULTS: Characteristics of the modified confocal scanning laser fluorometer included a lower limit of detection equal to 0.40 Eq ng/mL and depth precision of +/-15 microm. Values for the blood-retinal barrier permeability index in healthy subjects, measured 30 minutes after a single intravenous pulse of fluorescein (14 mg/kg), ranged from 1.3 +/- 0.4 x 10(-6) cm/s over the foveal avascular zone to 2.2 +/- 0.6 x 10(-6) cm/s over vessels in the retina. Diabetic eyes with retinopathy showed higher values, ranging from 1.4 to 15.0 x 10(-6) cm/s. Vitrectomized eyes and eyes with multiple drusen showed the validity of the correction algorithm demonstrating that measurements of fluorescence in the vitreous are not influenced by the chorioretinal fluorescence level. Argon laser photocoagulation burns placed in the diabetic retina demonstrated a lateral resolution on the order of 75 to 100 microm. Intravisit and intervisit reproducibility was +/-10.2% and +/-13%, respectively. CONCLUSIONS: This new method measures localized alterations of the blood-retinal barrier and allows for direct correlation with retinal anatomy. Its most interesting feature is the ability to map retinal fluorescein leakage while simultaneously imaging the retina. This capability is expected to improve our understanding and management of retinal disease.

Adult↗
PubMed1999

L-arginine transport in retinas from streptozotocin diabetic rats: correlation with the level of IL-1 beta and NO synthase activity.

Several evidences suggest that the pro-inflammatory cytokines IL-1 beta and the radical NO are implicated as effectors molecules in the pancreatic beta-cells dysfunction; an event preceding the pathogenesis of diabetes. IL-1 beta induces the expression of the inducible isoform of NO synthase (iNOS), which use L-arginine as substrate to overproduce NO. However, it is not known whether these events may participate in the development of diabetic retinopathy, which is the main cause of blindness. In this work, we found an increased level of IL-1 beta in retinas from streptozotocin-induced (STZ) diabetic rats. We also observed that the activity of the NO synthase (NOS) and the L-arginine uptake are enhanced in retinas from STZ-induced diabetic rats as compared to retinas from control rats. We found that the uptake of L-arginine in retinas from control and diabetic rats occurs through a transporter resembling the Y + system, i.e. it is saturable, not affected over the pH range 6.5 to 7.4, and is independent of the extracellular Na+. Nevertheless, the L-arginine transport in retinas from diabetic rats occurs through a carrier with lower affinity (K(m) = 25 microM) and higher capacity (Vmax = 295 +/- 22.4 pmol L-arginine/mg protein) than in retinas from control rats (K(m) = 5 microM and Vmax = 158 +/- 12.8 pmol L-arginine/mg protein) which is correlated with the increased NOS activity and consequent depletion of the intracellular pool of L-arginine.

Animals↗
PubMed1999

Novel imaging techniques for diabetic macular edema.

Retinal edema should be defined as any increase of water of the retinal tissue resulting in an increase in its volume. It may be of cytotoxic or vasogenic origin. Development of vasogenic macular edema is dependent on a series of factors such as blood pressure, blood-retinal barrier permeability, retinal cell damage, retinal tissue osmotic pressure and retinal tissue compliance. Objective measurements of retinal thickness are now possible using the Retinal Thickness Analyser. Localised measurements of blood-retinal barrier permeability may also be obtained using the Retinal Leakage Analyser, a modified confocal scanning laser fluorometer, while obtaining simultaneously angiographic images of the choroid and retina. These new imaging techniques show that cytotoxic and vasogenic retinal edema may occur independently in the early stages of diabetic retinopathy. These findings offer new perspectives for designing novel therapeutic strategies.

Diabetic Retinopathy↗
PubMed1997

The blood-ocular barriers: past, present, and future.

The blood-ocular barriers system is formed by two main barriers: the blood-aqueous barrier and the blood-retinal barrier. They combine to maintain the eye as a privileged site and are essential for normal visual function. After reviewing where the blood-aqueous barrier and blood-retinal barrier are located and the main transport mechanisms involved in the regulation of the microenvironment of ocular tissues, special attention is given to the clinical significance of breakdown of the blood-retinal barrier. New perspectives on the clinical significance of breakdown of the blood-retinal barrier are offered by the demonstration of a specific alteration of the glucose transport in diabetes, by the development of a new diagnostic instrumentation, and by the utilization of the blood-retinal barrier for new strategies for drug delivery to the retina. New diagnostic instrumentation includes the topographic imaging vitreous fluorometer, which simultaneously measures the localized blood-retinal barrier and images the retinal region, and the retinal thickness analyzer for mapping retinal edema. Drug delivery to the retina may be improved by modification of blood-retinal barrier permeability, chemical modification of the drug for better blood-retinal barrier penetration, and liposome encapsulation or coupling of the drug to specific vectors.

Blood-Aqueous Barrier↗
PubMed1996

Prevalence and surgical complications of pseudoexfoliation syndrome in Portuguese patients with senile cataract.

PURPOSE: To determine the prevalence and surgical complications of pseudoexfoliation syndrome (PES) in a Portuguese population of patients with senile cataract. SETTING: Department of Ophthalmology, Coimbra University Hospitals, Coimbra, Portugal. METHODS: In a prospective study, 183 consecutive patients with senile cataract referred to the Implant and Refractive Surgery Section of the Department of Ophthalmology were examined for PES. To determine the occurrence of intraoperative and postoperative complication of extracapsular extraction with posterior chamber intraocular lens implantation in patients with PES, two groups of similar age were compared: one with PES (n = 31) and a control group without PES (n = 31). RESULTS: The prevalence of PES in the 183 Portuguese patients with senile cataract was 23.5%. There was statistically significant difference between the two groups in the presence of phacodonesis (P < .05), insufficient intraoperative mydriasis (P < .001), need to perform sphincterotomies to facilitate nucleus expression (P < .01), and formation of pupillary fibrin membranes in the postoperative period (P < .01). These complication were more frequent in the PES group. Zonular breaks also occurred more often in patients with PES, although this was not statistically significant. CONCLUSIONS: Pseudoexfoliation syndrome was a common condition in patients with senile cataract having surgery in Portugal. Inadequate mydriasis was the major intraoperative difficulty; a pupil enlargement procedure should be performed in these cases. In the first days postoperatively, therapy with topical, subconjunctival, and systemic corticosteroids is recommended to reduce the inflammatory reaction in the anterior chamber.

Aged↗
PubMed1995

Blood-retina barrier in acute retinal branch vein occlusion.

BACKGROUND: Extensive clinical studies on retinal branch vein occlusion have not yet been able to clarify its pathogenesis. A study designed to look at the associated blood-retina barrier changes may contribute to a better understanding of the different forms of evolution of this pathology. METHODS: A prospective study was done in seven patients with recent large temporal branch vein occlusion. Vitreous fluorophotometry, fluorescein angiography and retinal colour photography were performed within the 1st week after the onset of symptoms, 1 week later, and at 12 and 24 weeks. RESULTS: A more marked blood-retina barrier breakdown was found at 1, 2, 12 and 24 weeks in the eyes that later developed extensive capillary nonperfusion. CONCLUSIONS: Our results suggest that the breakdown of the blood-retina barrier may play an important role in the subsequent development of retinal nonperfusion in eyes with large branch vein occlusion. We postulate that the eyes that will present later extensive capillary nonperfusion develop, from the initial stages of the disease, a progressive "ischaemic capillaropathy" characterized by blood-retina barrier breakdown. Retinal pigment epithelium degeneration and arterial lumen narrowing, secondary to the vein obstruction, may help to increase and perpetuate the blood-retina barrier breakdown during the first 6 months after the occlusion.

Acute Disease↗
PubMed1994

The blood-retinal barrier in diabetes during puberty.

OBJECTIVE: To assess the alteration of the blood-retinal barrier in patients with type I diabetes during puberty. DESIGN: A 7-year prospective study evaluated retinal changes occurring in diabetic children during puberty. Patients between the ages of 10 and 20 years underwent annual ophthalmologic examinations that included fluorescein angiography and vitreous fluorophotometry. SETTING: Clinical research facility. PATIENTS: Fifty-seven diabetic children met preset eligibility criteria. During the study, 241 ophthalmologic examinations were scheduled and 210 (87.1%) were performed. MAIN OUTCOME MEASURE: Vitreous fluorophotometry penetration ratio (VFPR) was used to indicate blood-retinal barrier permeability. RESULTS: No sign of retinopathy was detected before puberty (age 13 years for boys and 11 or 12 years for girls). The prevalence of retinopathy in the 4 years immediately after puberty was 6%. In the next 4 years, the prevalence was 29.6% (P = .0003). When all VFPRs were correlated with age, and data for male and female patients were analyzed separately, we found that the lowest VFPRs occurred at the expected time of puberty. When patients were paired by gender and duration of diabetes, there was a significant difference between VFPR values before and after puberty (P = .03). Also, a progressive deterioration of the blood-retinal barrier became apparent when only VFPR values after puberty were considered. CONCLUSIONS: These results support the view that the blood-retinal barrier remains stable until puberty, achieving a maximum of efficiency and protection. A progressive decline then begins, suggesting that this period of growth is associated with factors that, under the influence of diabetes, contribute to the progressive damage of the blood-retinal barrier.

Adolescent↗