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Early switch to steroids recommended in case of poor response to anti-VEGF
Research on biomarkers of response to therapy is gathering increasing interest.
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Being able to predict as early as possible if a patient’s response to treatment is going to be good, and switching to an alternative treatment in case the answer is no, is crucial in order to preserve vision and optimize care.
“Basically we have very good results with all treatment regimens, and now we are beginning to discover some biomarkers that show us that one patient might better respond to one agent than the other. We need a lot more data, but what comes out loud and clear is that if a patient does not respond to a specific therapy, then we definitely need to start thinking about switching him or her to another treatment,” Anat Loewenstein, MD, told Ocular Surgery News.
With diabetic macular edema, a favorable response to therapy depends on many factors, she said. First, the initial visual acuity: Patients with a good visual acuity have fewer chances to improve vision because of the ceiling effect.
“We also know that patients with low baseline visual acuity respond less well to laser therapy. Even if you consider laser, it should be deferred, as it was shown in a sub-analysis of [the DRCR.net] Protocol I,” Loewenstein said.
Although most patients respond well to anti-VEGFs, in 40% of the cases after three injections they have less than five letters of improvement. It has been widely shown that in such cases, even if the anti-VEGF treatment is repeated at short, regular intervals, as it was in Protocol I, the five-letter threshold is never overcome.
“You have to take care and watch your patients, and if the response is not good enough, you may need to switch the therapy,” Loewenstein said.
Phenotypes and other factors
Studies are also looking into potential correlations between specific phenotypes and the better response to one agent over another. Among them, the BEVORDEX trial and a study by Jay Chhablani in India showed that patients with hard exudates intraretinally respond well to steroids. Another study by the International Retina Group, recently accepted for publication in Ophthalmology, showed that patients with subretinal fluid may respond better to steroids, which should therefore be considered as first-line therapy in these cases.
“Another important factor is chronicity. If the patient has chronic disease and a history of several treatment attempts, the chances to improve vision are much lower,” Loewenstein said.
Chronic disease is often correlated with disorganization of the retinal inner layers (DRIL), which is strongly associated with low visual acuity improvement. If after treatment DRIL decreases, the chances for visual acuity improvement tend to increase, she explained.
Loewenstein said it is important to look at the data and characteristics of each patient individually. She also recommended making sure that patients come for frequent monitoring, particularly if they are treated with anti-VEGFs. All studies have shown that frequent monitoring and frequent treatments are necessary with these drugs to achieve the good results that have been seen in trials.
“It is also important to consider comorbidities because even though we don’t have any clear data, anti-VEGFs can aggravate cardiovascular disease. We should remember that in most trials candidates were excluded if they had had a cardiovascular event 3 to 6 months before the treatment, and in most trials 50% of the patients never had had any cardiovascular event. This is something to keep in mind if we treat a patient with a recent myocardial infarction or a stroke, which is not so rare in real life,” she said.
OCT biomarkers
“When we start treating a patient, we normally start with whatever is generally accepted as first-line therapy, and along that path we use a certain number of injections. When we see a patient with diabetes, in most cases we start now with an anti-VEGF, and very often it takes quite a while before we start considering alternatives,” Marc de Smet, MD, told OSN.
Studies have shown that approximately half of patients do well with anti-VEGF injections. They show a quick response and improvement in vision, and the treatment eventually leads to reduction of the edema. However, the other half of patients do not respond quite so well.
“After the second to fourth injection, you can already know that they won’t improve much more if you stay on that path. At that point, you should not hesitate to switch to another treatment. According to studies, an early decision to switch to an effective treatment increases the chances that vision will improve because persistence of edema reduces the potential for vision recovery,” de Smet said.
Biomarkers of response to therapy are an important area of research. Biomarkers might spare a lot of the time and resources that are today spent pursuing results that will never be accomplished in that 40% to 50% of patients who are eventually classified as nonresponders.
OCT is an important ally in the investigation of biomarkers, de Smet said.
“OCT looks at the various layers and how they are organized. If there is DRIL, for example, and this improves from one visit to the next, then you can expect that 4 months later the patient will have an improvement in vision. In a similar way, if you look at the outer segment by OCT angiography and there is a lot of disruption in the deeper layers of the capillary network, you know that these patients are not likely to improve. If they show little response after one or two injections, they may in fact do better with the use of Ozurdex (dexamethasone intravitreal implant, Allergan),” de Smet said. – by Michela Cimberle
- For more information:
- Marc de Smet, MD, PhD, can be reached at MIOS, Av. du Léman 32, Lausanne 1005, Switzerland; email: doctors@retina-uveitis.eu.
- Anat Loewenstein, MD, can be reached at Tel Aviv Sourasky Medical Center, Department of Ophthalmology, 6 Weizmann St., Tel Aviv, Israel 64239; email: anatlow@tasmc.health.gov.il.
Disclosures: De Smet reports he is a consultant to Allergan, Alcon, Novartis, Santen and Sanofi. Loewenstein reports she is a consultant to Allergan, Bayer, Notal Vision, Novartis and ForSight Labs.