Dexamethasone for Macular Edema Unresponsive to Anti-VEGF

Laird Harrison

October 09, 2020

When diabetic macular edema does not improve with anti-vascular endothelial growth-factor (VEGF) therapy, a quick and complete switch to dexamethasone might help, results from a pair of new studies suggest.

The findings could provide guidance for clinicians searching for the right protocol to switch a patient from one class of drug to another.

"It appears that the more you wait, the worse results you get," said Jose Ruiz Medrano, MD, PhD, from the Autonomous University of Madrid.

The best way to make the switch between the therapies was examined in two separate studies, presented at the virtual European Society of Retina Specialists 2020 Congress by Ruiz and by Gökhan Demir, MD, from the Fatih Sultan Mehmet Education and Research Hospital in Istanbul.

Diabetic macular edema is a complex disease, and both anti-VEGF drugs and steroids are considered first-line treatments. But recent surveys showed that more than 95% of Spanish ophthalmologists begin treatment with anti-VEGF therapy and reserve dexamethasone for recalcitrant cases, Ruiz said.

A 2018 analysis of data from the Diabetic Retinopathy Clinical Research Network database showed that 40% of eyes treated with ranibizumab had persistent edema after 2 years, said Ruiz, so the need for a plan B is strong.

Yet he and his colleagues found conflicting advice about how long to wait for a response from anti-VEGF therapy before switching to dexamethasone.

To clarify the issue, they looked at two groups of patients who had inadequate responses after three anti-VEGF injections. The patients met at least one of the following conditions: a nonimproving best-corrected visual acuity (BCVA), a central retinal thickness reduction of less than 20%, an edema relapse despite monthly intravitreal monthly injections, worsening edema with stable BCVA, or worsening edema and worsening BCVA.

There was a 169.1% (95% CI, 100.1 - 323.2) improvement in the 32 eyes that received only a loading dose of three injections of aflibercept before switching to a dexamethasone intravitreal implant (Ozurdex), whereas there was a 63.8% (95% CI, 20.0 - 107.7) improvement in the 76 eyes switched after more than three injections. The difference was statistically significant (P = .0118). In all eyes, a 20% reduction in central retinal thickness was achieved.

In the retrospective analysis conducted by Demir and his colleagues, none of the eyes assessed had achieved anatomic improvement with ranibizumab. A dexamethasone intravitreal implant was added to ongoing ranibizumab therapy in 30 of the eyes, and ranibizumab was replaced with dexamethasone in the other 34 eyes.

Three months after the initiation of dexamethasone, neither group experienced much change in BCVA or central retinal thickness. But after 6 months, average BCVA and central retinal thickness improved in both groups. At 9 and 12 months, those measures began to decline in the combination group, while the improvements were retained in the switch group.

The mean number of injections administered was 2.33 (range, 2 - 3) in the switch group and 5.65 (range, 5 - 7) in the combination group.

"It seems more reasonable to use [dexamethasone] as a switch therapy than an adjuvant therapy," Demir concluded.

And a sooner switch could stop the progression of chronic alterations in the retina. "Once the vascular network is really lost, functional vision is harder to get back," Ruiz told Medscape Medical News.

His group is now working on a cost–benefit analysis of the timing of a switch to dexamethasone. "Ozurdex is more expensive, but you treat patients less," he explained.

Ruiz said he sometimes combines the two drugs in patients who have already been switched to dexamethasone but aren't showing adequate improvement. "I think most of us do that more or less with refractory cases," he said.

Ruiz and Demir have disclosed no relevant financial relationships.

European Society of Retina Specialists (EURETINA) 2020: Abstracts 9419 and 9364. Presented October 2, 2020.

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