Blood-retinal barrier plays crucial role

[caption id="attachment_5235" align="alignnone" width="750"] EURETINA General Secretary Anat Loewenstein, presents Prof Cunha-Vaz with his certificate for the EURETINA lecture on the blood-retinal barrier[/caption] The blood-retinal barrier (BRB) plays a crucial role in the regulation of the micro-environment of the retina, with breakdown of the BRB directly implicated in the development of a range of retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD), according to José Cunha-Vaz MD, PhD. “There is a lot at stake in this issue as diabetic retinopathy  is the leading cause of blindness in the working age population, and AMD is the leading cause of blindness among individuals older than 50 years of age,” said Prof Cunha-Vaz in his EURETINA Medal Lecture at the 16th EURETINA Congress in Copenhagen, Denmark. Prof Cunha-Vaz noted that recent progress in the treatment of retinal diseases using intravitreal administration of anti-VEGF drugs or steroids has completely changed the perspective of successful vision recovery. “These agents work by stabilising the blood-retinal barrierand correcting abnormal permeability in disease,” he said. In a broad overview of current knowledge , Prof Cunha-Vaz, Emeritus Professor of Ophthalmology of the University of Coimbra, Portugal, said that the blood-retinal barrier plays a fundamental role in the micro-environment of the retina. “The blood-retinal barrier is involved in the regulation of the retinal cell environment. The blood-retinal barrier is particularly tight and restrictive and is a physiological barrier that regulates ion, protein and water flux into and out of the retina,” he said. He noted that the blood-retinal barrier consists of inner and outer components, with the inner blood-retinal barrier being formed of tight junctions between retinal capillary endothelial cells and the outer blood-retinal barrier of tight junctions between retinal pigment epithelial cells. Alterations of the blood-retinal barrier play a crucial role in the development of retinal diseases, said Prof Cunha-Vaz. “One of the nonspecific and ubiquitous signs of ocular disease is macular oedema, and this is a fundamental result of alterations in the blood-retinal barrier. It is an accumulation of fluid in the retina involving the macular region and often the central fovea with major vision consequences,” he said. Furthermore, the two most frequent and relevant retinal diseases, diabetic retinopathy and age-related macular degeneration , are directly associated with alterations of the blood-retinal barrier, he said. CLINICAL EVALUATION Diabetic retinopathy is initiated by an alteration of the inner blood-retinal barrier and neovascular age-related macular degeneration  is a result of an alteration of the outer blood-retinal barrier. Treatment of retinal diseases must also deal with the blood-retinal barrier, either by using its specific transport mechanisms or by circumventing it through intravitreal injections. Clinical evaluation of the blood-retinal barrier has evolved greatly over the past few decades, said Prof Cunha-Vaz, moving from earlier invasive techniques such as fluorescein angiography, vitreous fluorophotometry and retinal leakage analysis to more recent non-invasive methods such as optical coherence tomography-leakage (OCT-L) measurement and quantification of extracellular space of the retina. An important breakthrough came with the finding that optical coherence tomography-leakage can successfully measure retinal optical reflectivity ratios, said Prof Cunha-Vaz. “With this technique it is possible to reliably locate and quantify increases in the retinal extracellular space. Our studies have shown that the changes in the retinal extracellular space correlate well with the occurrence and degree of retinal oedema. Furthermore, optical coherence tomography-leakage is able to identify the location of the increases of retinal extracellular space in the different layers of the retina,” he added. Combining optical coherence tomography-leakage with optical coherence tomography micro-angiography (AngioPlex, Zeiss OCTA) allows for quantification of changes in the retinal extracellular fluid and non-invasive identification of sites of alteration of the blood-retinal barrier . Importantly for clinical use, it also enables evaluation of the status of the blood-retinal barrier in individual patients and their response to treatments, said Prof Cunha-Vaz. Prof Cunha-Vaz said that non-invasive monitoring of the blood-retinal barrier by optical coherence tomography-leakage  enables improved understanding of the role of the blood-retinal barrier in retinal disease, is useful in the testing and validation of new treatments, and contributes to the personalised management of retinal disease. José Cunha-Vaz: cunhavaz@aibili.pt

Tags: anti-VEGF drugs, retina