Archives: Projects/Publication

Alterations of retinal capillary blood flow in preclinical retinopathy in subjects with type 2 diabetes.

Ludovico J., Bernardes R., Pires I., Figueira J., Lobo C., Cunha-Vaz J.

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) 10×10 pixel box with original software, (b) 10×10 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.

Graefes Arch. Clin. Exp. Ophthalmol. 2003; 41:181-186.

2003

Measurement and mapping of retinal leakage and retinal thickness surrogate – outcomes for the initial stages of diabetic retinopathy.

Cunha-Vaz J

Current Medical Chemistry. 2002; 2: 91-108.

2002

Retinal Thickness in Eyes With Mild Nonproliferative Retinopathy in Patients With Type 2 Diabetes Mellitus: Comparison of Measurements Obtained by Retinal Thickness Analysis and Optical Coherence Tomography.

Pires I., Bernardes R., Lobo C., Soares M., Cunha-Vaz J.

Objective: To compare measurements of retinal thickness in eyes with mild nonproliferative retinopathy in patients with type 2 diabetes mellitus using 2 different techniques: the retinal thickness analyzer (RTA) and optical coherence tomography (OCT).

Methods: Twenty-eight eyes from 28 patients with type 2 diabetes mellitus and mild nonproliferative retinopathy were classified according to the Wisconsin grading system by 7-field stereoscopic fundus photography. Ten eyes were classified as level 10 (absence of visible lesions) and 18 as level 20 or 35 (minimal retinopathy). All eyes were examined by the RTA and OCT. Healthy populations were used to establish reference maps for the RTA (n=14; mean age, 48 years; age range, 42-55 years) and OCT (n=10; mean age, 56 years; age range, 43-68 years). Reference maps were computed using the means + 2 SDs of the values obtained for each location. Increases in thickness were computed as a percentage of increase over these reference maps.

Results: The RTA detected increases in thickness in 1 or more locations in 24 of the 28 diabetic eyes examined, whereas OCT detected increases in only 3 eyes. The percentages of increase detected by the RTA ranged from 0.3% to 73.5%, whereas OCT detected percentages of increase of 0.3% to 4.8%.

Conclusion: Optical coherence tomography is less sensitive than the RTA in detecting localized increases in retinal thickness in the initial stages of diabetic retinal disease.

Arch. Ophthalmol. 2002; 120: 1301-1306.

2002
http://archopht.ama-assn.org/cgi/reprint/120/10/1301?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&author1=Bernardes%2C+R&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&fdate=1/1/2002&tdate=12

Multimodal Macula Mapping: A new approach to study diseases of the Macula.

Bernardes R., Lobo C., Cunha-Vaz J.

Multimodal macula mapping is presented as a combination of a variety of diagnostic tools and techniques to examine the macular region in order to obtain information on its structure and function in a clinical environment. Foundations of macular mapping are reviewed and discussed. New methodologies for multimodal macula mapping based on a combination of scanning laser angiography, retinal leakage analysis, retinal thickness analysis, and visual field testing are presented, demonstrating the potential of macula mapping. Other available detection devices are briefly reviewed considering their potential to be included and utilized in future developments of multimodal macula mapping. Multimodal macula mapping appears to offer unique perspectives and insights that are expected to contribute to improved diagnosis and better understanding of macular diseases.

Surv. Ophthalmol. 2002, 47:580-589.

2002
http://www.surveyophthalmol.com/article/S0039-6257%2802%2900355-7/abstract

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

Lobo C., Bernardes R., Faria de Abreu J., Cunha-Vaz J.

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 A1c 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 maximumleakage, 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.

Arch. Ophthalmol. 2001; 119: 1469-1474.

2001
http://cat.inist.fr/?aModele=afficheN&cpsidt=14102170

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

Lobo C., Bernardes R., Cunha-Vaz J.

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.

Arch. Ophthalmol. 2000; 118: 1364-1369.

2000
http://archopht.ama-assn.org/cgi/content/abstract/118/10/1364?ck=nck