Archives: Projects/Publication

Nonproliferative retinopathy in diabetes type 2. Initial stages and characterization of phenotypes.

Cunha-Vaz J., Bernardes R.

This 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.

Progress in Retinal and Eye Research. 2005; 24:355-377.

2005
http://rihuc.huc.min-saude.pt/bitstream/10400.4/660/1/Nonproliferative%20retinopathy%20in%20diabetes%20type.pdf

Multimodal Functional and Morphological Nonrigid Image Registration.

Bernardes R., Baptista P., Dias J., Cunha-Vaz J.

The aim of this work is to present the registration of two different and complementary imaging modalities of the human eye fundus. One is a widely used modality consisting of a color photograph of the human retina and the other consists of a functional imaging modality that assesses, in vivo, the human blood-retinal barrier function. The need for the nonrigid registration of these two modalities is demonstrated and is due to the acquisition mode of the functional modality. The two modalities here with registered are from two different devices, have different resolutions and different fields-of-view, i.e., the smaller is only a subset of the larger one. In this paper, all these problems were addressed and a solution proposed.

IEEE International Conference on Image Processing ICIP-05, pages 1133–1136, September 11-14, 2005.

2005
http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?arnumber=1529955

Distortion free registration between multifocal ERG and retinal leakage analyzer.

Bernardes R., Ferreira J., Baptista P., Sebastião A., Dias J., Cunha-Vaz J.

The aim of the present work is the registration of two functional imaging modalities while simultaneously correcting for the intrinsic distortions present on both. Two recently introduced imaging modalities are used in this work, one that measures the retina response to blue light stimuli and another that measures the blood-retinal barrier function. A deformable registration procedure was developed, comprising a model for saccadic eye movements which allows for an important reduction in the number of parameters which need to be estimated. Finally, simultaneous correction for the intrinsic distortions was achieved through resorting to an additional imaging modality, thus resulting in practice in the registration of three different modalities, the former two of the functional type and the latter of the morphological type.

IFMBE Proceedings, Vol. 11. Prague: IFMBE, 2005. ISSN 1727-1983. – Proceedings of the 3rd European Medical & Biological Engineering Conference – EMBEC´05. Prague, Czech Republic, November 20-25, 2005, pages 1868-1 to 1868-6.

2005

Earmarking retinal changes in a sequence of digital color fundus photographs.

Ferreira J., Bernardes R., Baptista P., Cunha-Vaz J.

This paper presents a novel approach for earmarking retinal changes in a sequence of digital color fundus photographs, using Principal Component Analysis (PCA) and a temporal color-coded scheme so as to improve the representation of the global effect of these changes — its aim is to assist graders in detecting alterations on digital color photographic follow-up time-sequences of the human retina. The color-coded scheme was developed so that: the earliest earmarking color of areas which have been detected in multiple instances in the followup timeline is kept; areas which have suffered changes but have returned to their original appearance are earmarked with a specific color-code. The composite image formed by the projection of the color-code image onto the baseline image used as reference then guides the grader’s attention to changes detected on the fundus photographs.

IFMBE Proceedings, Vol. 11. Prague: IFMBE, 2005. ISSN 1727-1983. – Proceedings of the 3rd European Medical & Biological Engineering Conference – EMBEC´05. Prague, Czech Republic, 20-25.11.2005. ID of full-paper followed by page – from 1924-1 to 1924-6.

2005

Multimodal Macula Mapping: study for rigid, perspective and deformable image registration.

Baptista P., Bernardes R., Ferreira J., Dias J., Cunha-Vaz J.

In this work, thirteen image-pairs, composed of a color fundus photograph and a scanning laser ophthalmoscope fluorescein angiography (SLO.FA), were registered by rigid, non-rigid and deformable image registration procedures to assess the need for deformable image registration methods when using SLO.FA modalities. Each registration was quantitatively assessed by three different metrics that showed improved performance of the deformable approach. Moreover, the computed deformation grids demonstrated the infeasibility of global transformation approaches to deal with saccadics, as expected. Also, in the registration of medical images, some knowledge of the acquisition mode and its particularities was shown necessary to successfully achieve good registration results with a reduced search space for the parameters involved.

IFMBE Proceedings, Vol. 11. Prague: IFMBE, 2005. ISSN 1727-1983. – Proceedings of the 3rd European Medical & Biological Engineering Conference – EMBEC´05. Prague, Czech Republic, 20-25.11.2005. ID of full-paper followed by page – from 1867-1 to 1867-6.

2005

Three-year Follow-up Study of Blood-Retinal Barrier and Retinal Thickness Alterations in Patients with Type 2 Diabetes Mellitus and Mild Nonproliferative Diabetic Retinopathy.

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

Purpose: To examine the 3-year alterations of the blood-retinal barrier and changes in retinal thickness occurring in the macular region in 14 eyes of 14 patients with type 2 diabetes mellitus (DM) and mild nonproliferative diabetic retinopathy.

Methods: We classified 14 eyes of 14 patients with type 2 DM and mild nonproliferative diabetic retinopathy, as having disease levels 20 (microaneurysms only) or 35 (microaneurysm plus retinal hemorrhage[s] and/or hard exudates) of Wisconsin Card-Sorting Test grading, by using 7-field stereoscopic fundus photographs. We examined them 7 times at 6-month intervals, using fundus photography, fluorescein sodium angiography, the retinal leakage analyzer (RLA)-modified confocal scanning laser ophthalmoscope, and the retinal thickness analyzer. The retinal leakage and retinal thickness maps were aligned and integrated into 1 image. Data from the group of individuals with type 2 DM were compared with those of a healthy control population (n = 14; mean age, 48 years; age range, 42-55 years) to establish reference maps for the RLA and retinal thickness analyzers.

Results: Areas of abnormally increased fluorescein leakage were detected in all eyes examined at baseline. The sites of increased fluorescein leakage reached values as high as 483% above normal levels, but in 20 of the total 95 examinations performed, fluorescein leakage returned to normal levels. Every eye that showed reversal to normal levels of fluorescein leakage showed stabilization or a decrease in glycosylated hemoglobin A(1c) values at the same visit. When comparing the RLA-leaking sites among the 7 examinations, they remained, in general, in the same locations, but there was a clear fluctuation in the percentage of increases. No clear correlation was observed among the location of areas of increased retinal thickness and RLA-leaking sites, the number of microaneurysms, or the glycosylated hemoglobin A(1c) values. Microaneurysms on fundus photographs showed different cumulative incidences throughout the follow-up period in the different eyes. Associations between these different abnormalities suggest specific patterns of evolution of type 2 DM-related retinal disease.

Conclusions: The dominant alteration in the retina of patients with type 2 DM and mild nonproliferative retinopathy is the presence of RLA-leaking sites. This damage seems to be reversible and directly associated with variations in glycemic metabolic control. Together with the intensity and persistence of RLA-leaking sites, the rates of microaneurysm accumulation and alterations of the foveal avascular zone may characterize different genetically based phenotypes of diabetic retinopathy.

Arch. Ophthalmol. 2004; 122:211-217.

2004
http://www.ncbi.nlm.nih.gov/pubmed/14769598

Macular alterations after small incision cataract surgery.

Lobo C., Faria P., Soares M., Bernardes R., Cunha-Vaz J.

Purpose: 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.

J. Cataract Refract. Surg. 2004; 30:752-760.

2004
https://estudogeral.sib.uc.pt/dspace/bitstream/10316/4789/1/filec8f25efa8d4c466193440dc56773c881.pdf

Multimodal Macula Mapping: Characterization of Phenotypes of Diabetic Retinopathy.

Cunha-Vaz J., Bernardes R.

Proceedings of the 5th International Symposium on Ocular Pharmacology and Therapeutics ISOPT. 2004; 15-19.

2004

Mapping Clinically Significant Diabetic Macular Edema. Comparison Between Stereofundus Photography, RTA and OCT.

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

Proceedings of the 5th International Symposium on Ocular Pharmacology and Therapeutics ISOPT. 2004; 197-200.

2004

The blood-retinal barriers system. Basic concepts and clinical evaluation.

Cunha-Vaz, J.

Experimental Eye Research 78 (2004) 715-721.

2004

Interpretation of Objectively Acquired Retinal Thickness Values.

Bernardes R., Cunha-Vaz J.

Arch. Ophthalmol. 2003; 121(9):1344-1345.

2003