Key messages

• No direct evidence that compares aflibercept versus dexamethasone in diabetic macular edema was found.
• We are uncertain whether aflibercept compared to dexamethasone improves visual acuity or reduces adverse events as the certainty of the evidence has been assessed as very low.

What is the evidence.
See evidence matrix in Epistemonikos later

No evidence that compares the interventions directly in the population of interest was found, so systematic reviews that provide an estimate of the effect indirectly using network meta-analysis were selected.

We found two systematic reviews [1], [2], which included four primary studies [3], [4], [5], [6], all randomized trials.

This summary is based on the latter, since they evaluate the intervention in the population of interest, but against a different comparison.

What types of patients were included*

All trials included patients with the diagnosis of diabetic macular edema.

None of the reviews reported if all the included patients had central involvement.

What types of interventions were included*

Two trials evaluated aflibercept [5], [6]: one compared it against other medications [4] and the other trial compared it against placebo [6].

Two trials evaluated dexamethasone [3], [5]: one evaluated the addition of dexamethasone to laser treatment [3] and the other compared it against another drug [5].

What types of outcomes 
were measured

To whom this evidence does and does not apply

• The evidence presented applies to patients with diagnosis of diabetic macular edema, regardless of the stage, central involvement and previously used treatments.

• The outcomes included in this summary of the evidence are those considered critical for decision-making in the opinion of the authors and generally coincide with those reported by the identified systematic reviews, since they have clinical repercussions on the patient, both favorable, as is the gain in visual acuity, and unfavorable, referring to the complications during therapy.

• Both treatments are widely used, however, there are no studies that directly compare both drugs.
• Indirect evidence facing both treatments shows a possible benefit of the use of aflibercept in improving visual acuity and reducing complications, but the uncertainty associated with these results is very high.
• Therefore, it is not possible to make an adequate balance between risks and benefits between the evaluated interventions.

• The systematic reviews presented did not analyze the cost-effectiveness of the aforementioned treatments.
• Although an aflibercept injection is considered to be less expensive than the dexamethasone implant, the price of both treatments would be similar considering the total number of injections used.
• In the absence of a proven benefit, it is not possible to establish whether the use of aflibercept compared with dexamethasone is a cost-effective intervention.

• In clinical practice, the most widely used treatment worldwide by specialists are anti-VEGF drugs, among which aflibercept stands out due to its long half-life. On the other hand, patients in general do not have preferences for one treatment over another.
• Faced with the available evidence, it is likely that this same trend will continue, although the decision making will ultimately depend on the clinical history, characteristics and individualized preferences of the patients.

Differences between this summary and other sources

• The conclusions of this summary are in agreement with those of one systematic review [1], which states that although aflibercept would be superior to dexamethasone in terms of visual acuity gain and safety, there is not enough evidence to conclude it with certainty, requiring new and better studies.
• The second systematic review [2] concludes that aflibercept is superior to dexamethasone in gaining visual acuity. However, these differences may be due to the fact that this review does not take into consideration the certainty of the evidence.
• The American Academy of Ophthalmology [7] and the Sociedad Española de Retina y Vítreo [8] suggests anti-vascular endothelial growth factor drugs as the first line for this condition, without a clear preference for one medication over another.

• It is very probable that the information presented in this summary of the evidence will change in the future, because of the very low certainty of the available evidence.
• We did not identify ongoing trials in the International Clinical Trials Registry Platform of the World Health Organization that answer the question investigated.
• There is one systematic review in progress [9] registered in PROSPERO that compares anti vascular endothelial growth factor drugs versus dexamethasone, so that it could eventually include some direct analysis between aflibercept and dexamethasone.