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EURETINA lecture highlights critical role of blood-retinal barrier in retinal disease

Dermot McGrath

Posted: Friday, September 9, 2016

Prof Jose Cunha-Vaz

Prof Jose Cunha-Vaz

Alterations of the blood-retinal barrier (BRB) play a crucial role in the development of retinal diseases such as diabetic retinopathy and wet age-related macular degeneration (AMD), said Prof Jose Cunha-Vaz in his EURETINA Lecture as part of yesterday’s official opening ceremony at the 16th EURETINA Congress in Copenhagen.

“There is a lot at stake here 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,” he said.

Prof Cunha-Vaz said 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 BRB and correcting abnormal permeability in disease,” he said.
In a broad overview of current knowledge pertaining to the BRB, Prof Cunha-Vaz, Emeritus Professor of Ophthalmology of the University of Coimbra, Portugal, told delegates that the BRB plays a fundamental role in the microenvironment of the retina.

PHYSIOLOGICAL BARRIER

The BRB 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 BRB consists of inner and outer components, with the inner BRB being formed of tight junctions between retinal capillary endothelial cells and the outer BRB of tight junctions between retinal pigment epithelial cells.

Alterations of the BRB play a crucial role in the development of retinal diseases. The two most frequent and relevant retinal diseases, diabetic retinopathy and AMD, are directly associated with alterations of the BRB, he said.

Diabetic retinopathy is initiated by an alteration of the inner BRB and neovascular AMD is a result of an alteration of the outer BRB. Treatment of retinal diseases must also deal with the BRB, either by using its specific transport mechanisms or by circumventing it through intravitreal injections.

Clinical evaluation of the BRB 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 OCT-L 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. The changes in the retinal extracellular space correlate well with the occurrence and degree of retinal oedema. Furthermore, OCT-L is able to identify the location of the increases of retinal extracellular space in the different layers of the retina,” he said.

OCT-L as performed with Angioplex (Zeiss OCTA) allows for quantification of changes in the retinal extracellular fluid and non-invasive identification of sites of alteration of the BRB. Importantly for clinical use, it also enables the status of the BRB in individual patients and their response to treatments, said Prof Cunha-Vaz.

Summing up, Prof Cunha-Vaz said that non-invasive monitoring of the BRB by OCT-L has resulted in an improved understanding of the role of the BRB in retinal disease in the individual patient, the testing and validation of new treatments and personalised management of retinal disease.