Angiographic biomarkers are significant predictors of treatment response to intravitreal aflibercept in diabetic macular edema

Abstract

This prospective single-center study aims to identify biomarkers that predict improvement in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at 6 months, in 76 eyes with diabetic macular edema (DME) treated monthly with intravitreal aflibercept. At baseline, all patients underwent standardized imaging with color photography, optical coherence tomography (OCT), fluorescein angiography (FA) and OCT angiography (OCTA). Glycosylated hemoglobin, renal function, dyslipidemia, hypertension, cardiovascular disease and smoking were recorded. Retinal images were graded in a masked fashion. Baseline imaging, systemic and demographic variables were investigated to detect associations to BCVA and CRT change post aflibercept. Predictors of BCVA improvement included greater macular vessel density quantified using OCTA (p = 0.001) and low-density lipoprotein (LDL) ≥ 2.6 mmol/L (p = 0.017). Lower macular vessel density eyes showed a significant reduction in CRT but no BCVA improvement. Predictors of CRT reduction included peripheral non-perfusion seen on ultrawide-field FA (p = 0.005) and LDL ≥ 2.6 mmol/L (p < 0.001). Retinal angiographic biomarkers derived from OCTA and ultrawide-field FA may help predict functional and anatomic response to anti-vascular endothelial growth factor (VEGF) therapy in patients with DME. Elevated LDL is associated with treatment response in DME. These results may be used to better-select patients who will benefit from intravitreal aflibercept for treatment of DME.

Aflibercept Off-Target Effects in Diabetic Macular Edema: An In Silico Modeling Approach

“…However, some patients have been reported to present persistent DME after IAI treatment [74,86]. While recent prospective and real-world studies have been undertaken to identify disease markers and factors related to reduced response [87,88], the proposed models herein could be enhanced in the future to address the molecular reasons behind non-responsiveness in some DME patients. Similarly, these models could serve as the foundation for more complex QSP models, which would allow comparing different dosing schemes in mechanistical terms [89].…”

Current understanding of subclinical diabetic retinopathy informed by histology and high‐resolution in vivo imaging

“…In the setting of DR, OCTA has demonstrated utility by visualising morphological changes in the macula and also as tool to identify biomarkers for disease progression and treatment response. [160][161][162] Pertinent to DR, features implying capillary drop out, such as enlargement of the foveal avascular zone (FAZ) and reductions in capillary density are seen in subclinical disease. [162][163][164][165] Several papers only document significant capillary density reductions in the deep capillary plexus, however these results must be interpreted in the context of OCTAs limitations.…”

Linking Vascular Structure and Function: Image-Based Virtual Populations of the Retina

“…Vascular morphology has been established as a biomarker for the development, progression, and prognosis of several retinal diseases, 29 , 30 including diabetic retinopathy 31 , 32 and age-related macular degeneration. 6 , 33 Changes in these metrics may indicate impairment to retinal or macular blood flow, which could contribute to development of the disease.…”