Predictive value of VEGF A and VEGFR2 polymorphisms in the response to intravitreal ranibizumab treatment for wet AMD

• Published in: Graefe's archive for clinical and experimental ophthalmology 2014-03, Vol.252 (3), p.469-475
• Main Authors: Cruz-Gonzalez, Fernando, Cabrillo-Estévez, Lucía, López-Valverde, Gloria, Cieza-Borrella, Clara, Hernández-Galilea, Emiliano, González-Sarmiento, Rogelio
• Format: Article
• Language: English
• Subjects: Aged; Angiogenesis Inhibitors - therapeutic use; Antibodies, Monoclonal, Humanized - therapeutic use; Cohort Studies; Female; Fluorescein Angiography; Genetics; Genotype; Humans; Intravitreal Injections; Male; Medicine; Medicine & Public Health; Ophthalmology; Polymorphism, Single Nucleotide; Prospective Studies; Ranibizumab; Tomography, Optical Coherence; Treatment Outcome; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor Receptor-2 - genetics; Visual Acuity - physiology; Wet Macular Degeneration - drug therapy; Wet Macular Degeneration - genetics; Wet Macular Degeneration - physiopathology
• ISSN: 0721-832X; 1435-702X
• DOI: 10.1007/s00417-014-2585-7

Background To determine whether gene polymorphisms of the vascular endothelial growth factor A (VEGF A) and its receptor (VEGFR) influence the response to a variable-dosing treatment regimen with ranibizumab for age-related macular degeneration. Methods This prospective cohort study included 94 patients (94 eyes) with exudative age-related macular degeneration (AMD) treated with ranibizumab. Patients underwent a 1-year treatment as in the Study of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (SUSTAIN). Injections were administered monthly during 3 months to all the patients diagnosed of neovascular AMD; reinjections were made when a patient lost 5 letters on the Early Treatment Diabetic Retinopathy Study chart or gained 100 μm in central subfield retinal thickness measured by OCT. Genotypes (VEGF A (rs 699947, rs833061) and VEGFR (rs 2071559)) were analyzed using TaqMan probes. Best-corrected visual acuity (BCVA), subjective improvement, and macular thickness measured with OCT values were compared with VEGF A and VEGFR genotypes. Multiple regression analysis was used to assess the statistical significance. Results We found statistically significant differences in allelic distribution of VEGF A rs833061 polymorphism in relation with the response to intravitreal ranibizumab regarding to visual acuity improvement [ p  = 0,.34; OR: 1.619 (1.098–2.386)]. Patients carrying “protector” genotype CC had higher probability of best corrected visual acuity improvement. When we analyzed VEGF A rs699947 polymorphism we found that patients expressing AA genotype had a higher chance of increasing their best corrected visual acuity [ p :0,022; OR 1,532 (1,015–2,313)]. We did not find statistically significant differences reagarding VEGFR rs2071559 polymorphism and treatment response. Conclusions Polymorphisms of VEGF A seem to influence the different response to antiangiogenic treatment in patients with AMD in our population, although further investigation is needed to know the mechanisms of this relationship.