Glaucoma is one of the leading causes of irreversible but preventable blindness in working age populations.Color fundus photography (CFP) is the most cost-effective imaging modality to screen for retinal disorders.However, its application to glaucoma has been limited to the computation of a few related biomarkers such as the vertical cup-to-disc ratio. Deep learning approaches, although widely applied for medical image analysis, have not been extensively used for glaucoma assessment due to the limited size of the available data sets. Furthermore, the lack of a standardize benchmark strategy makes difficult to compare existing methods in a uniform way. In order to overcome these issues we set up the Retinal Fundus Glaucoma Challenge, REFUGE (https://refuge.grand-challenge.org), held in conjunction with MICCAI 2018. The challenge consisted * Corresponding authors: Yanwu Xu (ywxu@ieee.org) and Xiulan Zhang (

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ABSTRACT.Purpose: Elevated intra-ocular pressure (IOP) has been identified as a major risk factor for glaucoma. Additionally, extensive literature depicts a vascular dysfunction to exist in these patients. However, a large ocular blood floworiented trial to integrate these findings in the clinical setting is lacking. This study would likely help to identify which of these vascular data can be used as a clinical tool for screening and disease stratification. Method: Prospective, cross-sectional, case-control hospital-based study.Patients with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), ocular hypertension (OHT), glaucoma suspects and healthy volunteers were recruited. In addition to a comprehensive ophthalmological examination, a vascular-oriented questionnaire was completed and ocular blood flow assessment (colour Doppler imaging of retrobulbar vessels, retinal oximetry, dynamic contour tonometry, optical coherent tomography enhanced-depth imaging of the choroid) were performed. Statistical analysis was based on multiple imputation to account for missingness. Results: A total of 614 subjects (291 males) were recruited between March and December 2013 (POAG: 214, NTG: 192; OHT: 27; glaucoma suspect: 41; healthy controls: 140). Glaucoma groups (NTG and POAG) were age and gender matched with the control group (p > 0.05). Glaucoma groups were paired in terms of functional and structural parameters (p > 0.08). Mean ocular perfusion pressure was higher in the glaucoma groups than in controls (p < 0.001). Glaucoma groups had lower retrobulbar velocities, higher retinal venous saturation and choroidal thickness asymmetries when compared to the healthy group, in line with the current literature. Conclusions: The Leuven Eye Study stands as one of the largest clinical trials on ocular blood flow in glaucoma. The creation of this vast database may help integrate the vascular aspects of glaucoma into the clinical practice of glaucoma.

Introduction: Ocular manifestations in several neurological pathologies accentuate the strong relationship between the eye and the brain. Retinal alterations in particular can serve as surrogates for cerebral changes. Offering a "window to the brain," the transparent eye enables non-invasive imaging of these changes in retinal structure and vasculature. Fractal dimension (FD) reflects the overall complexity of the retinal vasculature. Changes in FD could reflect subtle changes in the cerebral vasculature that correspond to preclinical stages of neurodegenerative diseases. In this review, the potential of this retinal vessel metric to serve as a biomarker in neurodegeneration and stroke will be explored.Methods: A literature search was conducted, following the PRISMA Statement 2009 criteria, in four large bibliographic databases (Pubmed, Embase, Web Of Science and Cochrane Library) up to 12 October 2019. Articles have been included based upon their relevance. Wherever possible, level of evidence (LOE) has been assessed by means of the Oxford Centre for Evidence-based Medicine Level of Evidence classification.Results: Twenty-one studies were included for qualitative synthesis. We performed a narrative synthesis and produced summary tables of findings of included papers because methodological heterogeneity precluded a meta-analysis. A significant association was found between decreased FD and neurodegenerative disease, mainly addressing cognitive impairment (CI) and dementia. In acute, subacute as well as chronic settings, decreased FD seems to be associated with stroke. Differences in FD between subtypes of ischemic stroke remain unclear. Conclusions:This review provides a summary of the scientific literature regarding the association between retinal FD and neurodegenerative disease and stroke. Central pathology is associated with a decreased FD, as a measure of microvascular network complexity. As retinal FD reflects the global integrity of the cerebral microvasculature, it is an attractive parameter to explore. Despite obvious concerns, mainly due to a lack of methodological standardization, retinal FD Lemmens et al.Retinal Fractals: Neurodegeneration and Stroke remains a promising non-invasive and low-cost diagnostic biomarker for neurodegenerative and cerebrovascular disease. Before FD can be implemented in clinic as a diagnostic biomarker, the research community should strive for uniformization and standardization.

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Glaucoma is the leading cause of irreversible but preventable blindness in the world. Its major treatable risk factor is the intra-ocular pressure, although other biomarkers are being explored to improve the understanding of the pathophysiology of the disease. It has been recently observed that glaucoma induces changes in the ocular hemodynamics. However, its effects on the functional behavior of the retinal arterioles have not been studied yet. In this paper we propose a first approach for characterizing those changes using computational hemodynamics. The retinal blood flow is simulated using a 0D model for a steady, incompressible non Newtonian fluid in rigid domains. The simulation is performed on patient-specific arterial trees extracted from fundus images. We also propose a novel feature representation technique to comprise the outcomes of the simulation stage into a fixed length feature vector that can be used for classification studies. Our experiments on a new database of fundus images show that our approach is able to capture representative changes in the hemodynamics of glaucomatous patients. Code and data are publicly available in https://ignaciorlando.github.io.

Retinal toxicity/biocompatibility of medical devices in direct contact with the retina is an important subject for clinicians and scientists. As these effects are not very frequent, there is also a relative lack of information for many clinicians. The past has taught us multiple times that there is a significant safety problem associated with severe loss of vision in affected patients. In this review, we want to classify medical products that are used in the back of the eye, describe recent examples of toxicity, critically reflect on the regulations that exist and suggest improvements that can be done to ensure patient safety without hindering innovation. Methods: Critical review of the recent papers and personal experience of the authors in this issue. Medical devices used in the back of the eye and recent examples of toxicity are described, regulations that exist are critically reflected and improvements suggested that can ensure patient safety without hindering innovation. Results: There is clear evidence of toxicity after intraocular surgery in any category. Some cytotoxic indirect methods have failed in detecting this toxicity. Some ISO rules do not seem appropriate. Postmarketing safety is missing. There is little data on this issue. Conclusions: The absence of a clear regulation of the production, purification and evaluation of the toxic effects of the medical devices supposes the possibility that products are not sufficiently safe to obtain the CE mark.