Browsing by Author "Cunha-Vaz, JG"
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- Alterations of retinal capillary blood flow in preclinical retinopathy in subjects with type 2 diabetes.Publication . Ludovico, J; Bernardes, RC; Pires, I; Figueira, J; Lobo, CL; Cunha-Vaz, JGBACKGROUND: To identify alterations of retinal capillary blood flow in the papillomacular area in preclinical diabetic retinopathy using the Heidelberg scanning laser Doppler flowmeter. METHODS: Ten eyes from ten patients with type 2 diabetes and no lesions visible on fundus photography (level 10 of Wisconsin grading) and ten eyes from ten healthy subjects of similar age range were examined with the HRF. Intravisit reproducibility of retinal capillary blood flow measurements was assessed in normal subjects and in type 2 diabetic patients, comparing different measurement areas and different analysis procedures: (a) 10x10 pixel box with original software, (b) 10x10 pixel box with SLDF software, and (c) whole-scan analysis with SLDF software (automatic full-field perfusion image analysis). RESULTS: Intravisit reproducibility for the whole-scan analysis in the papillomacular area was 3.52%, 4.81% and 4.60% for volume (VOL), flow (FLW) and velocity (VEL) respectively. Using this method, mean and SD values for retinal capillary blood-flow are 13.25+/-2.87, 214.58+/-55.30 and 0.74+/-0.17, for VOL, FLW and VEL for healthy eyes, comparing with 19.85+/-6.22, 360.87+/-158.70 and 1.20+/-0.48 in eyes with preclinical diabetic retinopathy (P<0.010, P<0.019 and P<0.015 respectively). CONCLUSIONS: The HRF shows acceptable reproducibility when using whole-scan analysis in the papillomacular area. Retinal capillary blood VOL, FLW and VEL were particularly increased in five of the ten diabetic eyes examined, with values over the mean + 2SD of the control population, suggesting that eyes showing increased retinal capillary blood flow may indicate risk of progression.
- Alterations of the blood-retinal barrier and retinal thickness in preclinical retinopathy in subjects with type 2 diabetesPublication . Lobo, CL; Bernardes, RC; Cunha-Vaz, JGOBJECTIVE: 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.
- Blood-retinal barrier permeability and its relation to progression of retinopathy in patients with type 2 diabetes. A four-year follow-up study.Publication . Cunha-Vaz, JG; Leite, E; Sousa, JC; Faria de Abreu, JRForty 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.
- Chorioretinal anastomosis and photodynamic therapy:a two-year follow-up studyPublication . Silva, RM; Figueira, J; Cachulo, ML; Duarte, L; Faria de Abreu, JR; Cunha-Vaz, JGBACKGROUND: 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.
- Diabetic macular edemaPublication . Cunha-Vaz, JGRetinal 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.
- Macular alterations after small-incision cataract surgeryPublication . Lobo, CL; Faria, PM; Soares, MA; Bernardes, RC; Cunha-Vaz, JGPURPOSE: To characterize macular edema that occurs after uneventful cataract surgery. SETTING: Centre of Ophthalmology, University Hospital, Institute of Biomedical Research on Light and Image, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. METHODS: Thirty-two eyes of 32 patients had uneventful phacoemulsification with implantation of a foldable intraocular lens. Postoperatively, patients were examined at 3, 6, 12, and 30 weeks. The examinations included retinal leakage analysis (Zeiss CSLO), optical coherence tomography (Humphrey Instruments), and retinal thickness analysis (Talia Technology, Ltd.). Results were compared with those in a control group comprising healthy subjects. RESULTS: Increases in retinal thickness (ie, over the mean +/- 2 SD in the control group) reached a maximum at 6 weeks in 13 of 32 eyes (41%), after which recovery was progressive. At 30 weeks, all eyes had good visual acuity, but 7 eyes (22%) still had macular edema. The edema was located primarily in the central macular region. Leaking sites involving the vascular areas of the macula, which indicated areas of abnormal blood-retinal barrier permeability, were a frequent finding. The number of sites remained relatively stable during the first 12 weeks (88%) and decreased to 68% at 30 weeks, indicating a trend toward recovery. CONCLUSION: Macular edema after cataract surgery occurred primarily in the central region of the macula and was associated with the presence of leaking sites, which were located predominantly in the vascular regions of the central macula.
- Medical treatment of retinopathy of type-2 diabetesPublication . Cunha-Vaz, JGThe medical treatment of retinopathy in type-2 diabetes should be considered as a major component in the overall management of diabetic retinal disease. It is clear that specific and timely interventions, such as glycemic and blood pressure control, are the basis for good management of diabetic retinopathy. The American Diabetes Association has developed specific recommendations concerning diabetic retinopathy for the primary care physician and diabetologist. The ophthalmologist must be aware of these recommendations and establish efficient communication channels with the colleagues who follow their patients and the progression of diabetes closely. The challenge for the ophthalmologist is to make sure that, when signs of retinopathy are detected, information regarding the status of the retina, prognostic factors and the rate of progression must be given to the primary care physician and diabetologist. Under these circumstances, excellent glycemic control, aggressive management of blood pressure and normalization of lipids are all needed, and the goals to be achieved must be shared between the ophthalmologist and the primary care physician or diabetologist. Appropriate medical management of diabetic retinopathy is fundamental to reduce the risk of blindness. This goal can only be achieved if the ophthalmologist is fully aware of the role of medical management and establishes an efficient flow of communication with the primary care physician or diabetologist, particularly for the diabetic patients whose eyes show signs of risk for rapid progression of their retinopathy.
- Microperfusion studies on the permeability of retinal vessels. A new model demonstrating organic anion transport and a reabsorptive fluid fluxPublication . Murta, JN; Cunha-Vaz, JG; Sabo, CA; Jones, CW; Laski, MEWe developed an experimental model to study the permeability of individual retinal vessels in vitro using microperfusion techniques adapted from kidney tubule studies. The retinal vessels were isolated by freehand dissection and mounted on a microperfusion apparatus. When inulin was perfused luminally, it was diluted to 80.2 +/- 2.3% of its initial concentration. However, no radioactive leak into the bath side was observed, suggesting that the dilution was due to fluid flux from bath to lumen. The dilution of fluorescein (81.9 +/- 3.8%) was in the same range as that of inulin, the reference marker. The extremely low lumen-to-bath fluorescein flux, 0.5 +/- 0.9 X 10(-12) mol/min/mm, increased by 68% when probenecid was added to the perfusate and by 210% when probenecid was placed in the bath. The effect was concentration-dependent. When placed in the bath, fluorescein moved rapidly across the retinal vessel walls, accumulating in the lumen to concentrations 40 times higher than in the bath. This movement from bath to lumen, which was much higher (13.6 +/- 0.3 X 10(-12) mol/min/mm) than the lumen-to-bath fluorescein flux for the same fluorescein concentration, decreased by adding probenecid to the bath. The kinetics of this unidirectional movement of fluorescein were consistent with a saturable active transport process. The fluid flux from bath to lumen across the retinal vessels, which was 6.3 +/- 1.0 nl/min/mm for perfusion rates of 6.6 +/- 0.2 nl/min, was temperature-dependent and was coupled to the fluorescein transport. Fluorescein stimulated the fluid flux by 17% when added to the perfusate and by 60% when added to the bath, and this effect could be reversed by probenecid. Our results showed an active transport of fluorescein in the rabbit retinal vessels coupled with net fluid flux from outside the vessels into the lumen.
- A moment at the Institute of OphthalmologyPublication . Cunha-Vaz, JG
- Nonproliferative retinopathy in diabetes type 2. Initial stages and characterization of phenotypes.Publication . Cunha-Vaz, JG; Bernardes, RCThis review addresses the initial stages of nonproliferative diabetic retinopathy in diabetes type 2. The natural history of the initial lesions occurring in the diabetic retina has particular relevance for our understanding and management of diabetic retinal disease, one of the major causes of vision loss in the western world. Diabetic retinal lesions are still reversible at this stage opening entirely new opportunities for effective intervention. Four main alterations characterize these early stages of diabetic retinopathy: microaneurysms/hemorrhages, alteration of the blood-retinal barrier, capillary closure and alterations in the neuronal and glial cells of the retina. These alterations may be monitored by red-dot counting on eye fundus images and by fluorescein leakage and retinal thickness measurements. A combination of these methods through multimodal macula mapping has contributed by identifying three different phenotypes of diabetic retinopathy. They show different types and rates of progression which suggest the involvement of different susceptibility genes. The identification of different phenotypes opens the door for genotype characterization, different management strategies targeted treatments.