Research Update

Patients with persistent Diabetes-related Macular Edema experience beneficial outcomes even on eight week treatment interval.

Diabetes Mellitus is a chronic disease caused by excessive glucose levels in the bloodstream, and develops when the body fails to produce insulin (Type-I Diabetes), or because the body has become resistant to insulin (Type-2 Diabetes). According to the International Diabetes Federation, 463 million people live with Diabetes worldwide, all of whom are at an increased risk of developing one of a broad spectrum of Diabetes-related Eye Diseases (DEDs), including Diabetes-related Retinopathy and Diabetes-related Macular Edema1.

Non-proliferative Diabetes-related Retinopathy develops when high blood-glucose levels cause blockages to form in the retina’s blood-vessels, which may begin to leak. If undiagnosed and left untreated, a more advanced and severe form of Diabetes-related Retinopathy, called proliferative Diabetes-related Retinopathy ensues. In this stage, a substance responsible for regulating blood-vessel growth, called Vascular Endothelial Growth Factor (VEGF) becomes overactive, and leads to the excessive growth of blood-vessels to compensate for this blood leakage. As these blood-vessels are immature, they are much weaker and prone to bursting.

Diabetes-related Macular Edema is defined as retinal thickening within two disc diameters (disc diameters refers to the size of the optic nerve head) of the central retina and occurs when blood accumulates outside the vessels in the central region of the retina called the macula to cause a decline in central visual acuity.

Research presented at the virtual Association for Research in Vision and Ophthalmology conference in May describes how treating with the anti-VEGF therapy, aflibercept can achieve visual improvements in people living with persistent DME, who were previously treated with bevacizumab or ranibizumab anti-VEGF therapy2.

This study included 16 patients (20 eyes) receiving aflibercept injections over a 24 month period. Changes to macula thickness and best corrected visual acuity; the greatest improvements that can be achieved to visual performance as measured on a Snellen eye chart, were the primary outcome measures used to assess physical features of the visual system and visual capacity, following treatment intervention. Capillary perfusion density; the amount of blood-supply to the retina, and the foveal avascular zone; the region within the macula which has no blood-vessels present and helps to maximise visual quality, were also analysed using an imaging technique called optical coherence tomography (OCT) angiography.

Patients received a fixed dose regimen of aflibercept once every four weeks until DME swelling resolved, in which case they were transferred to a dosing interval of one anti-VEGF injection every eight weeks. On average, patients received 15.2 aflibercept injections over the 24 month period.

Following the 24 month treatment duration, statistically significant improvements were recorded with respect to both reductions in macula thickness (P < 0.001) and best corrected visual acuity (P < 0.042), meaning these changes are not as a result of chance. On average, patients who received aflibercept treatment could identify 5.5 extra letters on the Snellen eye chart, compared to baseline levels prior to receiving aflibercept.

The foveal avascular zone also experienced a statistically significant increase in size, when comparing measurements taken prior to treatment administration and at 24 month period. Additionally, Brittney Statler, MD, presenter of this research remarked that “Less superficial foveal and parafoveal capillary perfusion density loss were correlated with better final best corrected visual acuity”. These findings are consistent with 6 and 12 month interim finding reports, are statistically significant, and thus are not as a result of chance2,3.

Overall, this research indicates that improvements to visual acuity can be achieved with aflibercept anti-VEGF therapy and sustained through a longer dosing interval of eight weeks, as indicated over a two year  treatment period. Additionally, this evidence is strongly supportive of beginning anti-VEGF treatment earlier to achieve greatest improvements to visual acuity. Less frequent treatment intervals will also reduce the burden on patients to attend regular appointments and will make a positive contribution to their overall lifestyle.



1. International Diabetes Federation. Available at Accessed May 2020.

2. Statler B. Foveal capillary perfusion density decreases in diabetics with DME treated on a fixed regimen of intravitreal aflibercept injections over 24 months. Presented at: Association for Research in Vision and Ophthalmology annual meeting; May 6, 2020 (virtual meeting).

3. Babiuch, A.S., Conti, T.F., Conti, F.F., Silva, F.Q., Rachitskaya, A., Yuan, A. and Singh, R.P., 2019. Diabetic macular edema treated with intravitreal aflibercept injection after treatment with other anti-VEGF agents (SWAP-TWO study): 6-month interim analysis. International journal of retina and vitreous, 5(1), p.17.

4. Golshani, C., Conti, T.F., Conti, F.F., Silva, F.Q., Rachitskaya, A., Yuan, A., Schachat, A., Kaiser, P.K., Singh, R.P. and Babiuch, A., 2019. Diabetic Macular Edema Treated With Intravitreal Aflibercept Injection After Treatment With Other Anti-VEGF Agents (SWAP-TWO Study)—12-Month Analysis. Journal of VitreoRetinal Diseases, p.2474126420916074.

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