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Prognostic phenotypic and genotypic factors associated with photodynamic therapy response in patients with age-related macular degeneration.

ABSTRACT: 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.

SUBMITTER: Tsuchihashi T

PROVIDER: S-EPMC4266424 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Prognostic phenotypic and genotypic factors associated with photodynamic therapy response in patients with age-related macular degeneration.

Tsuchihashi Takashi T Mori Keisuke K Horie-Inoue Kuniko K Okazaki Yasushi Y Awata Takuya T Inoue Satoshi S Yoneya Shin S

Clinical ophthalmology (Auckland, N.Z.) 20141205

<h4>Background</h4>This study aimed to demonstrate the phenotypic and genotypic factors associated with photodynamic therapy (PDT) for age-related macular degeneration (AMD).<h4>Methods</h4>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, tw ...[more]

PMID: 25525324

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Project description:PurposePhotodynamic therapy (PDT) using verteporfin was the first pharmacologic therapy for neovascular age-related macular degeneration and changed the treatment paradigm for a major, blinding disease. The experimental work in the nonhuman primate was essential in developing treatment parameters for verteporfin PDT that could successfully occlude choroidal neovascularization with limited injury to the neural retina. Early in the preclinical primate studies, we hypothesized that higher irradiances could be used for ocular PDT than had been used in dermatology and other applications, which typically utilized an irradiance of 150 to 200 mW/cm(2). We set out to test the feasibility of irradiances up to 1800 mW/cm(2).MethodsPDT was applied to normal monkey eyes using verteporfin/benzoporphyrin derivative (BPD) (2 mg/kg) mixed with low-density lipoprotein in DMSO, and 692-nm light, with a spot size 1250mum, fluence approximately 50 J/cm(2), and irradiance varying from 150 (treatment time, 6 minutes) to 1800 mW/cm(2) (treatment time, 30 seconds). Photocoagulation lesions were applied using 514-nm and 692-nm laser light without drug, with irradiance of 18,750 to 200,000 mW/cm(2) and spot size of 500 mum. Treatment effect was evaluated by fundus photography, angiography, and light and electron microscopy with collagen denaturation as a marker of thermal injury.ResultsVerteporfin/BPD PDT at irradiances of 150 to 1800 mW/cm(2) showed no collagen denaturation in contrast to photocoagulation lesions without dye (irradiance 10-fold and higher).ConclusionsVerteporfin PDT could safely be performed at higher irradiances, permitting a clinically practical therapy. Ultimately, clinical trials demonstrated that verteporfin PDT could limit moderate vision loss in neovascular age-related macular degeneration. Although anti-VEGF therapy has replaced PDT as a first-line therapy, PDT may still have a role, perhaps in combination therapies. Further investigations to optimize drug delivery and to better understand the molecular mechanisms of PDT effects in both choroidal neovascularization and retina will improve its application in macular diseases.

Dataset Information

Prognostic phenotypic and genotypic factors associated with photodynamic therapy response in patients with age-related macular degeneration.

Publications

Prognostic phenotypic and genotypic factors associated with photodynamic therapy response in patients with age-related macular degeneration.

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