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Disease and treatment

People with a diabetes complication may require fewer treatments

New Danish research shows that the number of times people with diabetic macular oedema need therapy may be halved simply by combining two approved therapies.

By combining laser therapy with injecting vascular endothelial growth factor inhibitor (anti-VEGF) into the vitreous (the white of the eye) of people with diabetic macular oedema, ophthalmologists can halve the expected number of injections in the first 12 months of therapy – benefitting those with the condition and society.

New Danish research integrated anti-VEGF therapy with a stabilizing type of laser therapy to sustain the good results.

The results pave the way for new trials in which the researchers will test the combination therapy on more people with diabetic macular oedema to validate the results.

“People with diabetes already have many tasks, including visits to hospital departments of nephrology and endocrinology and appointments with podiatrists. Reducing the number of times they need anti-VEGF therapy would be financially sensible and would benefit many people,” explains the researcher behind the new study, Søren Leer Blindbæk, PhD student, Department of Ophthalmology, Odense University Hospital, Denmark.

Søren Leer Blindbæk’s supervisors are Jakob Grauslund, Professor, Department of Ophthalmology, Odense University Hospital and Tunde Peto, Clinical Professor, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, United Kingdom.

Optimal therapy is expensive and risky

About 3% of the people with diabetes develop diabetic macular oedema, a complication of diabetes.

It specifically affects the tiny area in the centre of the retina called the macula, which fills up with fluid.

People with this condition experience blurred vision, and many also find that straight lines, such as door frames or flagpoles, become distorted.

Fortunately, ophthalmologists can offer people with diabetic macular oedema two really good types of therapy.

Laser therapy is a standard procedure. A doctor attempts to stabilize the person’s vision to prevent it from deteriorating further. Sometimes people’s vision can be improved modestly.

About a decade ago, anti-VEGF therapy was introduced, in which ophthalmologists inject anti-VEGF directly into the vitreous, which helps to reduce fluid retention.

“People have benefitted enormously from anti-VEGF therapy because it works really well. Unfortunately, they need 8–10 injections in the first year alone, and each injection poses a slight risk of serious eye infection. This is also expensive and costs DKK 8000 per session,” says Søren Leer Blindbæk.

Different therapies, same results

Researchers and ophthalmologists had already thought of combining the two therapies by first mitigating the negative effects of diabetic macular oedema with anti-VEGF therapy and then using laser therapy to stabilize the improved vision.

Unfortunately, major trials in the United States have not had the anticipated positive results and have been inconclusive.

However, in the past 2 years, a new navigated laser has been developed that can very accurately target the damaged areas of the retina and thus theoretically enhance the effect of laser therapy on diabetic macular oedema.

Small studies in Germany and others indicated that integrating anti-VEGF therapy and navigated laser therapy can benefit people with diabetic macular oedema more than anti-VEGF followed by traditional manual laser therapy.

Søren Leer Blindbæk investigated this by initially giving two groups anti-VEGF therapy and then giving the first group traditional manual laser therapy and the second group navigated laser therapy.

“Finding that navigated laser therapy was significantly better than manual laser therapy in stabilizing the positive effect of anti-VEGF on people’s eyesight would have been great. Unfortunately, our results did not confirm this and showed no difference between the two types of therapy,” says Søren Leer Blindbæk.

Halving the need for anti-VEGF therapy

The story could have ended here – but it did not.

Although the groups did not differ in outcome, the researchers found something interesting that could benefit many people with diabetic macular oedema.

For both therapeutic strategies, the number of anti-VEGF injections needed in the first year of treatment declined from 8–10 to 4–5.

According to Søren Leer Blindbæk, the reason is probably that intensive anti-VEGF therapy before laser therapy made both types of laser therapy more effective.

“If you wanted to hit the bottom layer of the retina with a laser and there was fluid on top, it would be like shooting a laser through a waterbed, which could make the therapy more imprecise and difficult to assess as you proceed. However, if you could remove the liquid with intensive anti-VEGF therapy over 3–4 months, you might reap the full benefit from the laser, which would then reduce the need for additional anti-VEGF therapy,” explains Søren Leer Blindbæk.

Larger trial involving people with diabetic macular oedema

Søren Leer Blindbæk is encouraged by the new results, and he hopes to be able to test this on more people with diabetic macular oedema.

“The exciting thing is that we are only using approved therapies that ophthalmologists are using today. So we would really be encouraged if we can achieve the same good results and yet halve the need for expensive anti-VEGF therapy in the future simply by changing the therapeutic strategy,” says Søren Leer Blindbæk.

Aflibercept and navigated versus conventional laser in diabetic macular oedema: a 12-month randomized clinical trial.” has been published in Acta Ophthalmologica. The Danish Diabetes Academy and the Novo Nordisk Foundation have supported Søren Leer Blindbæk’s research.

Søren Leer Blindbæk
MSc
Diabetic macular oedema is a leading cause of visual impairment in the working aged population in developed countries. It was established by the Early Treatment Diabetic Retinopathy Study that focal/grid laser photocoagulation reduces the risk of visual loss in patients with centre‐involving DME but with a small likelihood of visual improvement. Currently, vascular endothelial growth factor inhibitors are the established first line of treatment and have consistently demonstrated efficacy in DME treatment. However, a high number of injections are needed to sustain visual improvement. Whereas the efficacy of focal/grid laser photocoagulation is modest in regard to visual improvement, its protracted effect is a desired shortcoming of current anti‐VEGF agents. Hence, combination therapy could be attractive to relieve the burden of repetitive intravitreal injections. However, most attempts with combination therapy for DME have so far not been able to reduce the need of intravitreal therapy. Modern navigated laser photocoagulation systems benefit from technical advantages of integrated software which allows for capture and/or import and overlay of, for example fundus fluorescein angiography images and optical coherence tomography thickness maps. In a 12‐month prospective randomized clinical trial of patients with centre‐involving DME, we aimed to compare the percentage of eyes that needed additional aflibercept injections after laser at month 12 (primary outcome) and the mean number of injections and mean change in visual acuity and central retinal thickness (CRT) between baseline and month 12 (secondary outcomes) in treatment arms of intravitreal aflibercept and navigated laser vs intravitreal aflibercept and conventional laser. Aflibercept was chosen over ranibizumab as aflibercept is often the drug of choice in clinical practice and due to the 1‐year results reported from the DRCR.net protocol T trial.