Treatment strategies for refractory diabetic macular edema: switching anti-VEGF treatments, adopting corticosteroid-based treatments, and combination therapy

ABSTRACT

Introduction: The pathophysiology of diabetic macular edema (DME) is complex, involving vascular endothelial growth factor (VEGF) and other inflammatory mediators. DME is currently treated first-line with intravitreal anti-VEGF treatments, though some cases are refractory to multiple anti-VEGF treatments.

Areas covered: This article examines the evolution of treatment practices for DME, with discussion of the recent studies that guide treatment for refractory cases of DME. A literature search was performed using the following terms: anti-VEGF, DME, aflibercept, bevacizumab, ranibizumab, refractory macular edema, and VEGF.

Expert opinion: Focal extrafoveal DME may be treated first-line with laser. In patients with center-involving DME and only mild vision loss, consider starting treatment with bevacizumab, especially when cost is an issue, whereas aflibercept may be considered more strongly in patients with moderate visual loss or worse. There are no standard protocols that define ‘treatment failure,’ but several studies have reported that switching from bevacizumab to either ranibizumab or aflibercept will result in further reduction of CSFT and improvement in BCVA. Further study with prospective randomized trials is warranted to validate these findings. Switching to intravitreal corticosteroids may be of particular benefit to pseudophakic patients. Anti-VEGF combination with sustained-release corticosteroids also appears promising for refractory DME.

KEYWORDS:

• Aflibercept
• Avastin
• bevacizumab
• dexamethasone
• diabetic macular edema
• DME
• Eylea
• fluocinolone acetonide
• Iluvien
• ranibizumab
• Lucentis
• Ozurdex
• VEGF

Article Highlights

• The complex pathophysiology of DME involves upregulation of VEGF and other inflammatory mediators.

• Anti-VEGF agents are first-line treatment for center-involved DME. Bevacizumab is a cost-effective and widely used anti-VEGF treatment, though aflibercept is the most effective option in patients with BCVA worse than 20/40 using ETDRS protocol eye charts.

• Some cases of DME are refractory to multiple bevacizumab treatments, and small studies report that switching to ranibizumab or aflibercept results in additional improvement in BCVA and macular thickness

• Future research will focus on efficacy of combined anti-VEGF and sustained-release corticosteroids to control refractory DME

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.