Key messages

• We are uncertain whether aflibercept compared to dexamethasone leads to a greater level of improvement in visual acuity, because the certainty of the evidence has been assessed as very low.
• We are uncertain whether aflibercept compared to dexamethasone is safer, either due to adverse events or loss of visual acuity, because the certainty of the evidence has been assessed as very low.

What is the evidence.
See evidence matrix  in Epistemonikos later

We found two systematic reviews [1], [2] that included four primary studies [3], [4], [7], [9], reported in eight references [3], [4], [5], [6 ], [7], [8], [9], [10]. All corresponded to randomized trials.

What types of patients were included*

All selected trials included patients with a diagnosis of macular edema secondary to occlusion of the central vein of the retina. One trial [4] also considered patients with occlusion of branches of the central vein of the retina, but these were analyzed separately, so they are not part of the results of this summary. Two trials [7], [9] specified that patients should not have been older than 9 months since the diagnosis of the mentioned condition.

What types of interventions were included*

Two trials [7], [9] evaluated injections of aflibercept compared to placebo. Another trial [4] considered a dexamethasone implant against placebo. The fourth trial compared dexamethasone versus ranibizumab [3].

What types of outcomes 
were measured

• Visual acuity measured as proportion of patients who gained 3 lines or more on the Early Treatment Diabetic Retinopathy Study scale at 6 and 12 months, and as an average change of the best corrected visual acuity in 6 months using the same scale. 
• Proportion of patients who lost 3 lines or more on the Early Treatment Diabetic Retinopathy Study scale at 6 months.
• Adverse events in each treatment.

To whom this evidence does and does not apply

• This evidence applies to patients diagnosed with macular edema secondary to occlusion of the central vein of the retina.

• The selected outcomes are the most relevant for decision-making according to the opinion of experts in the subject, since they are those that directly affect the patient's quality of life, either due to the improvement in their visual acuity or to the avoidance of complications during treatment.

• Both treatments, aflibercept and dexamethasone, have proven effectiveness regarding the gain of visual acuity in patients with macular edema secondary to occlusion of the central vein of the retina, however there are no direct comparisons.
• Regarding safety, there is also no direct evidence comparing both treatments.
• Therefore, the certainty of the evidence is very low, so it is not adequate to estimate the balance between risks and benefits of one treatment over another.

• Systematic reviews did not evaluate the economic impact of each treatment. The individual cost of each aflibercept injection is less expensive than dexamethasone implant, but since the injection must be repeated several times unlike the corticosteroid implant that lasts approximately six months, the direct costs of anti-VEGF drugs could end up being higher than that of corticosteroids.
• Considering the very low certainty of the evidence, it is not possible to make an adequate balance between benefits and costs.

• The most used treatment worldwide for this condition by ophthalmologists experts in the field, is the injection of anti-VEGF drugs, and within these, lately there is a tendency to use aflibercept for its longer half-life, although there is no proven evidence of superiority with respect to dexamethasone, which is another common therapy with proven efficacy.
• Additionally, patients might also be in favor of anti-VEGF medications, since they are associated with lower incidence of undesirable outcomes such as cataract or increased intraocular pressure, which might frequently lead to loss of visual acuity.
• With the evidence presented, it is unlikely to expect a modification in current behaviors, since according to expert’s opinion, anti-VEGF would have better clinical outcomes.

Differences between this summary and other sources

• The conclusions of this summary coincide with those of one of the systematic reviews identified [1], since it establishes there is no clear superiority of one treatment over the other, considering the very low certainty of the evidence. However, the second review [2] concluded that aflibercept would be superior and safer than dexamethasone as a treatment of macular edema secondary to occlusion of the central vein of the retina. These conclusions could be explained in part because this review did not conduct an analysis of the certainty of the evidence, but simply limited its conclusions to the results of the statistical analysis.
• The guideline of The Royal College of Ophthalmologists of the United Kingdom [11] concluded, like this summary, that aflibercept or other anti-VEGF would not be superior to dexamethasone. In contrast, the guideline of the American Academy of Ophthalmology of the United States [12] recommends anti-VEGF drugs over corticosteroids, with no clear superiority of aflibercept or another specific one.

• It is very likely that the information provided in this summary will change with future research, because the certainty of the available evidence is very low.
• We searched PROSPERO database and the International Clinical Trials Registry Platform of the World Health Organization, without finding ongoing reviews or trials that answer the question of interest.