Influence of mitochondrial haplogroups in response to ranibizumab teraphy in neovascular age-related macular degeneration

Purpose To analyze the results after one year with intravitreal ranibizumab therapy in neovascular Aged‐related macular degeneration (nAMD) patients according to the mitochondrial‐DNA haplogroup (mt‐DNA Hg) Methods Ninety‐eight eyes corresponding to 91 Caucasian patients with nAMD were treated with an initial series of 3 monthly loading intravitreal ranibizumbab injections 0.5 mg in 0.05 ml followed by a flexible pro re nata (PRN). Patients were classified into four groups according to their mtDNA genetic background determined by PCR (Hg H‐ m.7028C>T; Hg HV‐ m.14766T>C; Hg JT‐ m.421 6T>C; and Hg U‐ m.12308A>G). Statistical tests (chi‐square, Kolmogorov–Smirnov, paired and unpaired t test, ANOVA, Mann–Whitney U , Kruskal–Wallis H , Wilcoxon and Friedman tests). A p value < 0.05 was considered to be statistically significant. Results Gender, age and risk factors were equally distributed among the four groups. There were no significant differences between groups in baseline best corrected visual acuity (BCVA), central foveal thickness (CFT) and neovascular lesion type. After three loading dose, BCVA and CFT was significantly higher in all Hg without differences between them. Eighteen patients were not included at 12 months because of exclusion criteria. After receiving in average 6.7 ± 1.7 inyections of ranibizumab at 12 month, BCVA and CFT remained stable in haplogroups HV and U without significant worsening; however, haplogroup JT showed lower BCVA and higher CFT values than baseline (p = 1.00). In fact, CFT values were significantly different between groups (p = 0.004, Kruskal–Wallis H test) at 12 month. In particular, haplogroups JT and U were significantly different between them (p = 0.010, multiple comparison tests). Conclusions mtDNA genetic background showed different response to intravitreal ranibizumab therapy at 12 month. It could be a potencial biomarker to predict the response to intravitreal ranibizumab therapy in nAMD patients.