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Laura Kowalczuk, Ali Dirani, Alexandre Matet, Alejandra Daruich, Aude Ambresin, Irmela Mantel, Natacha Turck, Francine F Behar-Cohen; Biological rationale for the clinical effect of aflibercept in patients with idiopathic macular telangiectasia type 1. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Ocular diseases associated with increased Placental Growth Factor (PlGF) could benefit from aflibercept which neutralizes both Vascular Endothelial Growth Factor (VEGF-A) and PlGF. In this retrospective observational clinical study, we evaluated the effect of intravitreal aflibercept in patients presenting macular edema (ME) associated with idiopathic macular telangiectasia (MT) type 1 and measured angiogenic factors levels in aqueous humors.
Seven subjects with ME due to MT type 1, responding incompletely to standard anti-VEGF agents and/or laser therapy, and 8 control subjects, undergoing cataract surgery and having no history of diabetes or retinal disease, were included. Best-corrected visual acuity (BCVA), central macular thickness (CMT), macular volume (MV) and the area of cystic spaces quantified on optical coherence tomography (OCT) B-scan were assessed at 4 time points: at presentation, before and one month after the first aflibercept injection, and one month after the last injection. Aqueous humor was sampled before cataract surgery in controls and before aflibercept injection in MT type 1 patients. VEGF-A, C, D, PlGF, soluble VEGF receptor 1 (sFlt-1), Tie-2 and basic Fibroblast Growth Factor were quantified using a multi-array immunoassay. The nonparametric Mann-Whitney U-test was used to compare data.
Before aflibercept injection, patients with MT type 1 have higher aqueous levels of PlGF (P=0.006), but no difference in VEGF-A levels (P=0.17), as compared to sex and age-matched controls. The comparison of the angiogenic factors profiles also revealed significantly higher levels of sFlt-1 (P=0.004), Tie-2 (P=0.006), VEGF-C (P=0.029) and VEGF-D (P=0.029). After aflibercept therapy, BCVA improved significantly (74.4 vs 69.7 ETDRS letters prior to aflibercept initiation, P=0.043), CMT and MV were also significantly reduced (P=0.028, P=0.018 respectively). Importantly, aflibercept induced a significantly higher reduction in intraretinal cysts (P=0.016) than other anti-VEGF agents (P=0.15 as compared to presentation).
The combination of biological and clinical evidence strongly suggests that PlGF is involved in the pathogenesis of MT type 1. The efficacy of its neutralization should be evaluated in larger cohorts of patients presenting with non-proliferative vascular retinal diseases.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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