Choroidal Vascular Remodeling and Retinal Response After Aflibercept Loading in Diabetic Macular Edema

To investigate choroidal changes after aflibercept treatment for diabetic macular edema (DME) and to assess their association with treatment response.

A retrospective interventional cohort study.

Thirty eyes from 30 patients who were injection-naïve for DME and received initial 5 monthly loading injections of aflibercept.

Choroidal and retinal changes after loading injections were analyzed using spectral-domain OCT with enhanced depth imaging (EDI-SD-OCT) and ultra-widefield indocyanine green angiography (UWF-ICGA). The correlation between choroidal and retinal changes, along with factors associated with a good treatment response, was investigated.

Changes in subfoveal choroidal thickness (sfCT), total choroidal area (TA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI) measured by EDI-SD-OCT; choroidal vascular density (CVD) and choroidal fractal dimension (CFD) of macula and widefield assessed by UWF-ICGA; as well as treatment response, including central retinal thickness (CRT) and inflammatory hyperreflective foci (HRF) evaluated through EDI-SD-OCT.

Aflibercept induced a significant reduction in sfCT, TA, LA, and SA (all P < 0.001), accompanied by an increase in CVI (P=0.005) on EDI-SD-OCT. On UWF-ICGA, CVD showed no significant change in either macular or widefield (P = 0.127 and 0.517, respectively), while CFD significantly decreased in both fields (P = 0.033 and 0.040, respectively). Decrease in TA, especially SA, and consequent CVI increase were significant factors associated with CRT reduction (P = 0.017, 0.004, and 0.044) and good treatment response in univariate analysis (P = 0.049, 0.026, and 0.047); however, only the reduction in inflammatory HRF maintained significance in multivariable analysis (P = 0.021 and 0.045). The reduction in inflammatory HRF was significantly associated with the decrease in TA, LA, and SA in univariate analysis (P = 0.001, 0.003, and 0.002), whereas only the decrease in sfCT remained significant in multivariable analysis (P = 0.027).

Aflibercept treatment induces stromal-dominant choroidal thinning with a consequent increase in CVI. This choroidal remodeling may be associated with the anatomical resolution of DME through mechanisms involving reduction of inflammatory HRF.

The authors have no proprietary or commercial interest in any materials discussed in this article.