Simo R.,Autonomous University of Barcelona |
Ballarini S.,Vifor Pharma |
Cunha-Vaz J.,University of Coimbra |
Cunha-Vaz J.,AIBILI Association for Innovation and Biomedical Research on Light and Image |
And 5 more authors.
Current Medicinal Chemistry | Year: 2015
The rapid escalation in the global prevalence diabetes, with more than 30% being afflicted with diabetic retinopathy (DR), means it is likely that associated vision-threatening conditions will also rise substantially. This means that new therapeutic approaches need to be found that go beyond the current standards of diabetic care, and which are effective in the early stages of the disease. In recent decades several new pharmacological agents have been investigated for their effectiveness in preventing the appearance and progression of DR or in reversing DR; some with limited success while others appear promising. This up-to-date critical review of non-traditional systemic treatments for DR is based on the published evidence in MEDLINE spanning 1980-December 2014. It discusses a number of therapeutic options, paying particular attention to the mechanisms of action and the clinical evidence for the use of renin-angiotensin system blockade, fenofibrate and calcium dobesilate monohydrate in DR. © 2015 Bentham Science Publishers.
PubMed | AIBILI Association for Innovation and Biomedical Research on Light and Image, PortugalbUniversity of Coimbra and University of Coimbra
Type: Journal Article | Journal: Journal of biomedical optics | Year: 2013
The automatic segmentation of the retinal vascular network from ocular fundus images has been performed by several research groups. Although different approaches have been proposed for traditional imaging modalities, only a few have addressed this problem for optical coherence tomography (OCT). Furthermore, these approaches were focused on the optic nerve head region. Compared to color fundus photography and fluorescein angiography, two-dimensional ocular fundus reference images computed from three-dimensional OCT data present additional problems related to system lateral resolution, image contrast, and noise. Specifically, the combination of system lateral resolution and vessel diameter in the macular region renders the process particularly complex, which might partly explain the focus on the optic disc region. In this report, we describe a set of features computed from standard OCT data of the human macula that are used by a supervised-learning process (support vector machines) to automatically segment the vascular network. For a set of macular OCT scans of healthy subjects and diabetic patients, the proposed method achieves 98% accuracy, 99% specificity, and 83% sensitivity. This method was also tested on OCT data of the optic nerve head region achieving similar results.
Leal S.,University of Coimbra |
Leal S.,AIBILI Association for Innovation and Biomedical Research on Light and Image |
Silva R.,University of Coimbra |
Silva R.,AIBILI Association for Innovation and Biomedical Research on Light and Image |
And 10 more authors.
Retina | Year: 2010
Purpose: The purpose of this study was to evaluate the efficacy of verteporfin photodynamic therapy on the treatment of polypoidal choroidal vasculopathy. Methods: A prospective, nonrandomized institutional study was conducted involving 42 eyes of 38 patients with newly diagnosed symptomatic polypoidal choroidal vasculopathy treated exclusively with photodynamic therapy. Twenty-seven eyes completed 3 years of follow-up. Subjects were observed every 3 months with evaluation of best-corrected visual acuity (BCVA), retinography, and fluorescein and indocyanine green angiography. Treatment was given whenever the patient exhibited subfoveal exudation on fluorescein angiography. Results: Mean BCVA was 0.91 ± 0.33 logarithm of the minimum angle of resolution on the initial visit and 0.93 ± 0.39 on the 36-month visit. Patients were submitted to an average of 3.19 treatment sessions. On the final evaluation at 36 months, 14.8% of the treated eyes improved their BCVA by at least 0.3 logarithm of the minimum angle of resolution, 74.1% had no significant loss of BCVA, and 25.9% lost ≥ 0.3 logarithm of the minimum angle of resolution. Recurrences were frequent (59.3% of the eyes at 3 years of follow-up), responded well to retreatment, and were not associated with additional BCVA loss. Conclusion: Photodynamic therapy remains a good option for management of polypoidal choroidal vasculopathy. After 3 years, approximately three fourths of the treated eyes had no significant loss of vision, and 14.8% showed significant improvement in visual acuity. Copyright © by Ophthalmic Communications Society, Inc.
Santos-Carvalho A.,University of Coimbra |
Santos-Carvalho A.,Institute Educacao e Cidadania |
Ambrosio A.F.,University of Coimbra |
Ambrosio A.F.,AIBILI Association for Innovation and Biomedical Research on Light and Image |
Cavadas C.,University of Coimbra
Progress in Retinal and Eye Research | Year: 2015
The retina is a highly complex structure where several types of cells communicate through countless different molecules to codify visual information. Each type of cells plays unique roles in the retina, presenting a singular expression of neurotransmitters. Some neurotransmitter systems in the retina are well understood, while others need to be better explored to unravel the intricate signaling system involved. Neuropeptide Y (NPY), a 36 amino acid peptide, is one of the most common peptide neurotransmitter in the CNS and a highly conserved peptide among species. We review the localization of NPY and NPY receptors (mainly NPY Y1, Y2, Y4 and Y5) in retinal cells. Common features of the expression of NPY and NPY receptors in mammalian and non-mammalian species indicate universal roles of this system in the retina. In the present review, we highlight the putative roles of NPY receptor activation in the retina, discussing, in particular, their involvement in retinal development, neurotransmitter release modulation, neuroprotection, microglia and Muller cells function, retinal pigmented epithelium changes, retinal endothelial physiology and proliferation of retinal progenitor cells. Further studies are needed to confirm that targeting the NPY system might be a potential therapeutic strategy for retinal degenerative diseases. © 2015 Elsevier Ltd.
Oliveira C.M.,Critical Health SA |
Cristovao L.M.,University of Coimbra |
Ribeiro M.L.,AIBILI Association for Innovation and Biomedical Research on Light and Image |
Abreu J.R.F.,AIBILI Association for Innovation and Biomedical Research on Light and Image
Ophthalmologica | Year: 2011
Aim: To assess a two-step automated system (RetmarkerSR) that analyzes retinal photographs to detect diabetic retinopathy for the purpose of reducing the burden of manual grading. Methods: Anonymous images from 5,386 patients screened in 2007 were obtained from a nonmydriatic diabetic retinopathy screening program in Portugal and graded by an experienced ophthalmologist. RetmarkerSR earmarked microaneurysms, generating two outputs: 'disease' or 'no disease'. A second-step analysis, based on coregistration, combining two visits, was subsequently performed in 289 patients who underwent repeated examinations in 2008. The study was extended by analyzing all referrals considered urgent by the ophthalmologist from 2001 to 2007. Results were compared with those obtained by manual grading. Results: The RetmarkerSR classified in a first-step analysis 2,560 patients (47.5%) as having 'no disease' and 2,826 patients (52.5%) as having 'disease', thus requiring manual grading. RetmarkerSR detected all eyes considered urgent referrals. The two-step analysis further reduced the number of false-positive results by 26.3%, indicating an overall sensitivity of 95.8% and a specificity of 63.2%. Conclusion: Automated grading of diabetic retinopathy may safely reduce the burden of grading patients in diabetic retinopathy screening programs. The novel two-step automated analysis system offers improved sensitivity and specificity over published automated analysis systems. © 2011 S. Karger AG, Basel.
Coutinho A.M.,University of Coimbra |
Silva R.M.,University of Coimbra |
Silva R.M.,AIBILI Association for Innovation and Biomedical Research on Light and Image |
Nunes S.G.,AIBILI Association for Innovation and Biomedical Research on Light and Image |
And 5 more authors.
Retina | Year: 2011
Purpose: To evaluate the long-term safety and efficacy of photodynamic therapy in the treatment of choroidal neovascularization associated with pathologic myopia. Methods: Five-year retrospective study of 43 consecutive eyes of 36 patients with juxtafoveal or subfoveal choroidal neovascularization and pathologic myopia treated with photodynamic therapy. Results: Mean best-corrected visual acuity changed from 20/125 +1 letter (0.78 logarithm of the minimum angle of resolution) at baseline to 20/100 (0.70 logarithm of the minimum angle of resolution) at 5 years (P = 0.122). Final best-corrected visual acuity improved in 53.5% of the eyes, remained stable in 11.6%, and decreased in 34.9%. A visual acuity gain of ≥3 lines occurred in 32.6% of the eyes, and a visual acuity decrease of ≥3 lines was registered in 20.9% of the cases at 5 years. Only patient's age and initial visual acuity showed to have a significant predictive value for the final visual acuity outcome (P = 0.024 and P = 0.002, respectively). Conclusion: Photodynamic therapy with verteporfin may increase the chance of stabilizing and improving vision in patients with choroidal neovascularization from pathologic myopia at 5 years. Better results were found in younger patients (<55 years). Copyright © 2011 Lippincott Williams &Wilkins.
Ribeiro L.,AIBILI Association for Innovation and Biomedical Research on Light and Image |
Cunha-Vaz J.,AIBILI Association for Innovation and Biomedical Research on Light and Image |
Cunha-Vaz J.,University of Coimbra
Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry | Year: 2013
Diabetic retinopathy remains the most frequent cause of new cases of blindness among adults aged 20-74 years. A number of large trials have validated that laser photocoagulation is a useful treatment but the disease continues to progress in approximately 50% of eyes treated by photocoagulation. Current treatment of diabetic retinopathy is only available for advanced stages of the disease and is given independently of the diabetes disease status itself and metabolic status. Other forms of therapy targeted at the earliest stages of retinal disease are needed. Proposals for defining and accepting surrogate outcomes that appropriately evaluate the earlier stages of the retinopathy are presented in this review. The most likely candidates for surrogate outcomes are: mean difference in ETDRS retinopa-thy scale, 2 steps per eye, microaneurysm turnover and reduction in macular thickening. © 2013 Bentham Science Publishers.
Santos-Carvalho A.,University of Coimbra |
Elvas F.,University of Coimbra |
Elvas F.,AIBILI Association for Innovation and Biomedical Research on Light and Image |
Alvaro A.R.,Royal University |
And 2 more authors.
Cell Death and Disease | Year: 2013
It has been claimed that glutamate excitotoxicity might have a role in the pathogenesis of several retinal degenerative diseases, including glaucoma and diabetic retinopathy. Neuropeptide Y (NPY) has neuroprotective properties against excitotoxicity in the hippocampus, through the activation of Y 1, Y2 and/or Y5 receptors. The principal objective of this study is to investigate the potential protective role of NPY against glutamate-induced toxicity in rat retinal cells (in vitro and in an animal model), unraveling the NPY receptors and intracellular mechanisms involved. Rat retinal neural cell cultures were prepared from newborn Wistar rats (P3-P5) and exposed to glutamate (500 lM) for 24 h. Necrotic cell death was evaluated by propidium iodide (PI) assay and apoptotic cell death using TUNEL and caspase-3 assays. The cell types present in culture were identified by immunocytochemistry. The involvement of NPY receptors was assessed using selective agonists and antagonists. Pre-treatment of cells with NPY (100 nM) inhibited both necrotic cell death (PI-positive cells) and apoptotic cell death (TUNEL-positive cells and caspase 3-positive cells) triggered by glutamate, with the neurons being the cells most strongly affected. The activation of NPY Y2, Y4 and Y5 receptors inhibited necrotic cell death, while apoptotic cell death was only prevented by the activation of NPY Y5 receptor. Moreover, NPY neuroprotective effect was mediated by the activation of PKA and p38K. In the animal model, NPY (2.35 nmol) was intravitreally injected 2 h before glutamate (500 nmol) injection into the vitreous. The protective role of NPY was assessed 24 h after glutamate (or saline) injection by TUNEL assay and Brn3a (marker of ganglion cells) immunohistochemistry. NPY inhibited the increase in the number of TUNEL-positive cells and the decrease in the number of Brn3a-positive cells induced by glutamate. In conclusion, NPY and NPY receptors can be considered potential targets to treat retinal degenerative diseases, such as glaucoma and diabetic retinopathy. © 2013 Macmillan Publishers Limited. All rights reserved.
PubMed | Carl Zeiss GmbH and AIBILI Association for Innovation and Biomedical Research on Light and Image
Type: Journal Article | Journal: The British journal of ophthalmology | Year: 2016
To analyse and compare the classification of eyes with diabetic retinopathy using fluorescein angiography (FA) and optical coherence tomography angiography (OCTA) performed either with AngioPlex or AngioVue.This was an observational cross-sectional study of 50 eyes from 26 diabetic subjects. Two independent graders classified the FA angiograms, to assess the presence and severity of several characteristics according to the ETDRS Report 11, and a similar evaluation was performed for each 33 mm OCTA image from the superficial retinal layer and for the full retina slab.Percentages of non-gradable images for the outline of foveal avascular zone (FAZ) in the central subfield (CSF) were 29.0% for FA, 12.0% for AngioVue and 3.0% for AngioPlex. For capillary loss, percentages of non-gradable images in the CSF were 25.0% for FA, 11% for AngioVue and 0.0% for AngioPlex. For the inner ring (IR), percentages of non-gradable images were 12.5% for FA, 11.5% for AngioVue and 0.5% for AngioPlex. Agreement between graders was substantial for outline of FAZ. For capillary loss, the agreement was fair for the CSF, and moderate for the IR.The OCTA allows better discrimination of the CSF and parafoveal macular microvasculature than FA, especially for FAZ disruption and capillary dropout, without the need of an intravenous injection of fluorescein. In addition, FA had also a higher number of non-gradable images. The OCTA can replace with advantage the FA, as a non-invasive and more sensitive procedure for detailed morphological evaluation of central macular vascular changes.NCT02391558, Pre-results.
PubMed | University Hospitals Leuven, AIBILI Association for Innovation and Biomedical Research on Light and Image, Glaucoma Research Unit, Imperial College London and 3 more.
Type: Journal Article | Journal: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie | Year: 2016
The aim of this study was to investigate the efficacy and safety of Bimatoprost Unit Dose Preservative Free (BUDPF) and Latanoprost Unit Dose Preservative Free (LUDPF).A prospective, randomized, investigator-masked, cross-over comparison was used. Inclusion criteria were ocular hypertension (OHT) or open-angle glaucoma (OAG) with a maximum intraocular pressure (IOP) of 21mmHg on a preserved prostaglandin monotherapy. After 6weeks washout, patients were randomized to BUDPF or LUDPF for 3months and then switched to the other treatment for 3months. IOP curves were performed at baseline and after each treatment period. Statistical analysis was performed in a R programming environment. Linear mixed modeling was used to account for repeated measures on the same subject and clustering of observations from the same center. Safety outcomes included visual acuity, adverse events, slit-lamp biomicroscopy, ocular tolerability, and optic nerve assessment.Analysis at 6months (primary outcome) showed a 1.60.5-mmHg difference in IOP values between LUDPF and BUDPF (p<0.01). A mean intra-subject IOP difference of 0.90.2mmHg (LUDPF - BUDPF) was observed (p<0.01).. Significant differences in IOP were observed for both drugs at 3 and at 6months compared to baseline: -4,00.5mmHg for both BUDPF and LUDPF at 3months (p<0.01 for both drugs; p=0.32 between the two drugs); -5.20.5 and -3.40.5mmHg for BUDPF and LUDPF, respectively (both p<0.01), at 6months. Both drugs were tolerated well, the only statistically significant difference being lower hyperemia scores for LUDPF (albeit low for both drugs).This study demonstrates a superior efficacy of BUDPF over LUDPF in lowering IOP. The results are consistent both in the parallel comparison between the two treatment groups at 6months as well as in the intra-subject pressure comparison.