DME progression

Predictors identified for progression in diabetic retinopathy help guide who needs treatment most

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José Cunha-Vaz MD, PhD
The identification of diabetic retinopathy (DR) phenotypes characterised by different dominant retinal alterations and different rates of progression to clinically significant macular oedema (CSME) paves the way for more personalised management of diabetic retinopathy, according to José Cunha-Vaz MD, PhD. “If the patients with the greatest risk of progression and with the greatest potential to benefit from treatment can be identified, fewer patients will need to be followed closely to prevent vision loss from proliferative DR and diabetic macular oedema,” he told delegates attending the 17th EURETINA Congress in Barcelona. Prof Cunha-Vaz, Emeritus Professor of Ophthalmology of the University of Coimbra, Portugal, said that DR is currently classified according to the ETDRS scale. “This is the best and most recognised scale for classification of DR, and whatever new developments we have in this field we still have to refer to this gold standard. However, it does have some limitations – macular oedema can occur at any level and it is not included in the scale, so something more precise is needed to help us manage our DR patients,” he said. Risk algorithms based on diabetic disease are helpful, but they don’t address the full picture, said Prof Cunha-Vaz, as there are different risks for vision loss in different patients with similar metabolic control and duration of disease. “We have all seen diabetic patients with excellent metabolic control who follow their physicians' instructions carefully and they may still develop CSME and potentially proliferative DR, whereas other patients who are less careful never go on to develop any macular vision-threatening problem. We definitely need more natural history studies to try to identify some of the possible causes,” he said. Much of Prof Cunha-Vaz’s research in recent years has focused on trying to answer the question of why different patients with the same metabolic control and disease duration progress differently. Using non-invasive colour fundus photography and optical coherence tomography over repeated examinations yields a lot of valuable information, such as micro-aneurysm (MA) turnover, blood-retinal barrier (BRB) alteration and neuronal and glial damage, he said. An initial prospective two-year study of 410 DR eyes confirmed clinical observations that micro-aneurysm turnover and central retinal thickness measurements were different in patients with comparable ETDRS levels, disease durations and metabolic controls. Three different DR phenotypes with different risks for CSME were thereby identified: type A, ‘slow progression’, with absence or low levels of leakage and MA turnover; type B, ‘leaky’, with increased retinal thickness on OCT; and type C, ‘ischaemic’, with increased MA turnover and active remodelling of the retinal circulation. POOLED ANALYSIS These results were further refined in a recent pooled analysis of four independent longitudinal DR studies involving a total of 882 patients with non-proliferative diabetic retinopathy (NPDR). “It is important to bear in mind that this pooled analysis was based on four different studies involving mild NPDR eyes but having the same inclusion criteria, using the same methodology, and having the image analysis performed by the same reading centre,” said Prof Cunha-Vaz. Of the 882 eyes/patients that completed the studies, 103 developed CSME – 14 from phenotype A (14 of 466: 3.0%), 48 from phenotype B (48 of 164: 18.6%) and 41 from phenotype C (41 of 252: 16.3%). The patients from phenotypes B and C showed much higher risks for macular oedema development compared with phenotype A characterised by low MA turnover and no signs of increased RT, said Prof Cunha-Vaz. “This is of great relevance as phenotype A, representing approximately 50% of the mild NPDR patient population, shows a negative predictive value of 97% for the development of macular oedema,” he said. This observation has important implications for the management of DR, added Prof Cunha-Vaz, as it suggests that a large proportion of eyes presenting initial stages of retinal vascular disease will progress very slowly, and those eyes are not likely to develop macular oedema for a period of at least two years. He said that this subtype of NPDR should, therefore, be excluded from clinical trials evaluating new therapies for DR because of its slow rate of progression. José Cunha-Vaz: cunhavaz@aibili.pt
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