Prognostic phenotypic and genotypic factors associated with photodynamic therapy response in patients with age-related macular degeneration
Authors Tsuchihashi T, Mori K, Horie-Inoue K, Okazaki Y, Awata T, Inoue S, Yoneya S
Received 17 July 2014
Accepted for publication 23 September 2014
Published 5 December 2014 Volume 2014:8 Pages 2471—2478
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Scott Fraser
Takashi Tsuchihashi,1 Keisuke Mori,1 Kuniko Horie-Inoue,2 Yasushi Okazaki,3 Takuya Awata,4,5 Satoshi Inoue,2 Shin Yoneya1
1Department of Ophthalmology, 2Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Division of Translational Research, Research Center for Genomic Medicine, 4Division of Endocrinology and Diabetes, Department of Medicine, 5Division of RI Laboratory, Biomedical Research Center, Saitama Medical University, Iruma, Saitama, Japan
Background: This study aimed to demonstrate the phenotypic and genotypic factors associated with photodynamic therapy (PDT) for age-related macular degeneration (AMD).
Methods: The study included 149 patients with exudative AMD treated by PDT. Eight phenotypic factors and ten genotypic factors for three single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996) in the complement factor H (CFH) gene, rs 11200638-SNP in the high temperature requirement A-1 (HTRA1) gene, two SNPs (rs699947, rs2010963) in the vascular endothelial growth factor (VEGF) gene, and four SNPs (rs12948385, rs12150053, rs9913583, rs1136287) in the pigment epithelium-derived factor (PEDF) gene were evaluated.
Results: A significant association with best-corrected visual acuity change was demonstrated in the greatest linear dimension, presence or absence of pigment epithelial detachment, and HTRA1-rs11200638 genotype statistically (P=3.67×10-4, 1.95×10-2, 1.24×10-3, respectively). Best-corrected visual acuity in patients with AA genotype of HTRA1-rs11200638 significantly decreased compared with that in patients with GG genotype (P=1.33×10-3). Logistic regression analyses demonstrated HTRA1-rs11200638 genotype was most strongly associated with best-corrected visual acuity outcome from baseline at 12 months after photodynamic therapy (P=4.60×10-3; odds ratio 2.363; 95% confidence interval 1.303–4.285).
Conclusion: The HTRA1-rs11200638 variant showed the most significant association. Therefore, this variant may be used as a prognostic factor to estimate the PDT response with significant predictive power.
Keywords: age-related macular degeneration, photodynamic therapy, phenotypic and genotypic factors, high temperature requirement A-1, greatest linear dimension, pigment epithelial detachment
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