Biomarkers for macular disease

Ongoing research is helping to identify and validate a wide range of traditional and novel biomarkers that can prove useful in monitoring disease activity and response to treatment in diabetic macular oedema (DME), according to Anat Loewenstein MD. “Biomarkers can help us to answer some fundamental questions relating to our treatment strategies. It can shed light on why a patient responds to one specific steroid or anti-VEGF agent and not another and what the level of response might be,” she told delegates attending the European Society of Ophthalmology (SOE) meeting in Nice, France. Dr Loewenstein defined a biologic biomarker as a characteristic that is objectively measured and evaluated as an indicator of normal biological occurrence, pathologic processes or pharmacological response to a therapeutic intervention. She noted that there are multiple assessments possible with current biomarkers, many of which lack validation in controlled trials. She cited functional tests such as ETDRS, microperimetry and contrast sensitivity, biological samples of aqueous or vitreous to target specific cytokines or molecules such as VEGF or imaging tests such as optical coherence tomography (OCT), fundus photography and fundus autofluorescence. Focusing on the biomarkers that may have the greatest utility in tracking DME, Dr Loewenstein cited baseline visual acuity, lens status, as well as a variety of specific OCT biomarkers as potentially valuable. The value of baseline visual acuity as a biomarker has been shown over the years in landmark studies such as Protocol I and II and others, she said. “We learnt from Protocol I, for instance, that baseline visual acuity was a valuable prognostic predictive biomarker not to treat with laser photocoagulation too quickly. It was actually shown to do more harm than good for those patients with better visual acuity at baseline,” she said. LENS STATUS Lens status has also proven a useful biomarker in some recent studies, with pseudophakic eyes tending to respond better to triamcinolone in Protocol I, for instance, and also in the BEVORDEX trial where phakic eyes responded less well to both triamcinolone and bevacizumab, she said. In terms of OCT, Dr Loewenstein said that her colleagues at Tel Aviv University had recently identified some interesting biomarker candidates for DME treated by intravitreal dexamethasone (DEX) implant. Among eyes with DME, those with submacular fluid, no hyper-reflective foci and a continuous inner segment-outer segment layer responded better to DEX implants than those without these features. Two other biomarkers of interest as possible predictors of functional or anatomical improvement in anti-VEGF treatments include the disorganisation of retinal inner layers (DRIL) and the height of intraretinal cystoid fluid at baseline, concluded Dr Loewenstein. Anat Loewenstein: anatl@tlvmc.gov.il

Tags: macular disease