Seeking Solutions for DME Patients Who Respond Poorly to Anti-VEGF Agents

October 5, 2016

No difference in the superficial capillary plexuses was found in cases of diabetic macular edema that responded well to anti-vascular endothelial growth factor as opposed to those that didn't, but poor responders had more damage and microaneurysms in the deep capillary plexus.

Many cases of diabetic macular edema (DME) are resistant to intravitreal injection with anti-vascular endothelial growth factor (anti-VEGF) agents, which is the primary treatment for the condition. Such resistance suggests that chronic inflammation, which responds well to corticosteroids, plays a role in the pathogenesis of DME in these cases. Moreover, because anti-VEGF agents are relatively expensive when compared with corticosteroids, identifying baseline factors that predict a lack of response to anti-VEGF agents is the key to successful and economical treatment of DME.

Because diabetic vascular changes such as hyperpermeable retina capillaries and microaneurysms occur primarily in the deep retinal layer, the structural integrity of the deep capillary plexus (DCP) may reflect the pathogenesis of DME and its response to treatment.

To determine the association between the structural integrity of the deep and superficial capillary plexuses and response to anti-VEGF treatment, a team of South Korean investigators did a retrospective, case-control study based on optical coherence tomography angiography (OCTA), which reveals blood flow in the deep retinal capillary layer more precisely than fluorescein angiography and OCT.

Cases included 51 DME eyes with a poor response to anti-VEGF agents, defined as a reduction of <50 μm or an increase in central retinal thickness after 3 consecutive anti-VEGF injections. Controls included 32 age-matched DME eyes with a good response, defined as a reduction of >50 μm in central retinal thickness after 3 consecutive anti-VEGF injections. The third group included 20 fellow eyes without DME of patients with an eye in the case or the control group.

The team evaluated study eyes by using OCTA and spectral-domain (SD) OCT and comparing the images that resulted from the use of each technique. They measured vascular density and the foveal avascular zone (FAZ) and counted the number of microaneurysms in each capillary layer.

They found that eyes with DME had a lower vascular density and a larger FAZ in the DCP and more microaneurysms in both layers. Although they found no statistically significant difference between good and poor responders in the integrity of the SCP, poor responders had more damage and microaneurysms in the DCP and a larger FAZ.

They also checked the integrity of the outer plexiform layer (OPL), where the DCP is located. They found multiple instances of OPL disruption, which allows communication between nuclear layers via intraretinal cyst, in 47 of 51 poor responders (92%) but only 1 of 32 good responders (3%). OPL disruption persisted even after edema improved, so the damage appeared permanent.

They also found that the location of the disrupted synaptic portion of the OPL shown by SD-OCT exactly corresponded to the area of the DCP in which blood flow was absent as shown by OCTA.

They concluded that, unlike good responders, poor responders showed substantial damage to the integrity of the DCP, and the extent of DCP loss and corresponding OPL disruption could be useful predictors of response to anti-VEGF treatment.

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