Study identifies key biomarkers for aflibercept response in diabetic macular edema

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Brazilian researchers headed up by Marcussi Palata Rezende, MD, and colleagues used swept-source optical coherence tomography (SS-OCT) and OCT-angiography (SS-OCTA) to investigate the effect of a loading dose of aflibercept (Eylea, Regeneron Pharmaceuticals) on diabetic macular edema (DME) in treatment-naive patients and determine if there were biomarkers to signal treatment responders and non-responders. Rezende is from the Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil.

The investigators observed improvement in the evaluated biomarkers, ie, the best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), avascular area of the superficial plexus (AASP), avascular area of the deep plexus (AADP), and vessel density (VD, but those pretreatment biomarkers did not predict a treatment response between the responsive and resistant patients.¹

However, the CCT was identified as a valuable parameter, in that patients with CCTs that fell within normal limits had significantly greater reductions in CCT, AADP, VD, BCVA, and AASP, indicating a better response to treatment than those with extremely low or high choroidal thicknesses.

“Different parameters obtained by these advanced technologies have been investigated as potential biomarkers for DME, including CMT, choroidal vascularity index (CVI), CCT, foveal avascular zone (FAZ), VD, deep capillary plexus (DCP), superficial capillary plexus (SCP), and others. These metrics provide valuable information on the structural and microvascular alterations associated with DME, allowing a more personalized approach for its detection, prognosis, and therapeutic response. Furthermore, the integration of multiple biomarkers can improve the understanding of DME pathophysiology and guide more effective therapeutic strategies, thus making quantitative analysis (via OCT and OCTA) an essential tool in clinical practice and research on diabetic retinopathy.²

Study methodology and results

In the study under discussion, the investigators explained both that they evaluated the several previously mentioned biomarkers provided by SS-OCT and SS-OCTA and that this prospective, noncomparative, interventional case series study was the first to adopt a stratified approach to choroidal thickness to identify which subgroups of patients showed the greatest response to treatment with aflibercept. “This provides new perspectives on the impact of antiangiogenic therapy on the choroidal microenvironment as well as a dichotomous analysis of these biomarkers,” they said.

The 3 objectives of the study were to evaluate the best-corrected visual acuity BCVA, CMT, CCT, AASP, AADP, and VD, before and after the loading dose; determine the response to treatment of those biomarkers provided by SS-OCT and SS-OCTA, which is determined by stratifying the choroidal thickness; and perform a dichotomous analysis of the pretreatment biomarkers between the group of patients who were responsive or resistant to treatment with the loading dose of aflibercept.

A secondary objective was an assessment of whether the posttreatment biomarkers also showed any statistically significant differences.

The study included 28 eyes of 25 patients.

Rezende and colleagues reported significant improvements were observed in the BCVA (0.7250 ± 0.23 to 0.3957 ± 0.21; p < 0.000), CMT µm (339.04 ± 66.19 to 265.21 ± 55.75; p < 0.000), CCT µm (221.71 ± 69.69 to 209.07 ± 70.92; p < 0.000), VD (17.90 ± 7.82 to 15.35 ± 5.80; p < 0.038), AASP µm² (235,374 ± 91,299 to 157,326 ± 77,815; p < 0.000) and AADP µm² (996,335 ± 1,000,047 to 362,161 ± 277,225; p < 0.000).

The dichotomous analysis found that 15 patients (53.57%) were responders (53.57%), and 13 patients (46.43%) were refractory to treatment.

No significant differences were seen between any of the pretreatment biomarkers evaluated.

Regarding the choroidal thickness, the eyes were divided into four groups of seven eyes each: the CCTs in each group were as follows: group 1, 71 to 180 µm; group 2, 181 to 210 µm, group 3, 211 to 270 µm; and group 4, 271 to 360 µm.

“In group 3, we found the lowest p value (P = 0.004) among the four groups of the CCT subdivision, indicating that group 3 had a greater statistically significant reduction in the CCT among the four groups after treatment,” they reported.

There were also more significant reductions in the AADP and CD in group 3 than in the other groups after the treatment. In group 2, the BCVA and AASP had the greatest statistically significant reductions after the treatment.

The key takeaways from the study were as follows:

• The BCVA, CMT, CCT, AASP, AADP, and VD decreased significantly after treatment with a loading dose of aflibercept.
• The dichotomous analysis performed using SS-OCT and SS-OCTA did not identify any pretreatment biomarkers that could predict a response to aflibercept.
• The subdivision of the CCT was proven to be an important biomarker for assessing the response to aflibercept in treatment-naïve patients with DME. Patients with CCTs that fell within normal limits (groups 2 and 3) had significantly greater reductions in CCT, AADP, VD, BCVA, and AASP, indicating a better response to treatment than those with extreme choroidal thicknesses (groups 1 and 4, thinner and thicker, respectively).

“Notably, our study is unique in that it evaluated the response of biomarkers provided by SS-OCT and SS-OCTA to treatment on the basis of the subdivision of choroidal thickness. These findings contribute to a better understanding of the relationships between choroidal characteristics and DME treatment outcomes. Overall, our study provides valuable insights into the role of choroidal thickness in predicting treatment response and highlights the potential utility of assessing choroidal thickness as an objective parameter in DME treatment,” the investigators concluded.

References

1. Rezende MP, Faria FA, Beraldo DP, et al. Prospective and dichotomous study of biomarkers with swept-source OCT and OCT-angiography in naive patients with diabetic macular edema. Int J Retin Vitr. 2025;11;51. https://doi.org/10.1186/s40942-025-00672-7

2. Suciu CI, Suciu VI, Nicoara SD. Optical coherence tomography (angiography) biomarkers in the assessment and monitoring of diabetic macular edema. J Diabetes Res. 2020;31(2020):6655021. https://doi.org/10.1155/2020/6655021.