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BMC Ophthalmology
Published in: BMC Ophthalmology 1/2017

Open Access 01-12-2017 | Research article

Association of ARMS2 genotype with response to anti-vascular endothelial growth factor treatment in polypoidal choroidal vasculopathy

Authors: Un Chul Park, Joo Young Shin, Hum Chung, Hyeong Gon Yu

Published in: BMC Ophthalmology | Issue 1/2017

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Abstract

Background

To investigate whether genetic risk variants for age-related macular degeneration (AMD) are associated with response to intravitreal anti-vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV) patients.

Methods

This prospective cohort study included 95 treatment-naïve patients that underwent anti-VEGF treatment for PCV for 12 months. Patients were genotyped for 10 single nucleotide polymorphisms in eight AMD-relevant genes. Genotypic association with visual and anatomic outcome measures at 12 months after initial treatment, including mean change in best-corrected visual acuity (BCVA) and total foveal thickness, visual gain of ≥ 15 letters, dry status on optical coherence tomography (OCT), pigment epithelial detachment (PED) regression on OCT, polyp regression on indocyanine green angiography, and injection numbers, were investigated using regression models with adjustment for non-genetic covariates under additive genetic model.

Results

In 81 patients who completed 12-month anti-VEGF monotherapy without photodynamic therapy, significant pharmacogenetic association was found between ARMS2 rs10490924 and PED regression on OCT. Proportions of PED regression were 26.4% for TT, 45.7% for TG, and 63.6% for GG genotype, showing additive effect of G allele for higher chance of PED regression (OR, 2.96; 95% CI, 1.38–6.36; corrected P = 0.043). For entire 95 patients, no significant association was found between candidate polymorphisms and receiving photodynamic therapy within 12 months.

Conclusions

In PCV patients, ARMS2 rs10490924 showed association with anatomic therapeutic response to anti-VEGF, suggesting pharmacogenetic relationship.
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Literature
1.
Honda S, Matsumiya W, Negi A. Polypoidal choroidal vasculopathy: clinical features and genetic predisposition. Ophthalmologica Journal international d’ophtalmologie International journal of ophthalmology Zeitschrift fur Augenheilkunde. 2014;231(2):59–74.CrossRefPubMed
2.
Laude A, Cackett PD, Vithana EN, Yeo IY, Wong D, Koh AH, Wong TY, Aung T. Polypoidal choroidal vasculopathy and neovascular age-related macular degeneration: same or different disease? Prog Retin Eye Res. 2010;29(1):19–29.CrossRefPubMed
3.
Nakashizuka H, Mitsumata M, Okisaka S, Shimada H, Kawamura A, Mori R, Yuzawa M. Clinicopathologic findings in polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci. 2008;49(11):4729–37.CrossRefPubMed
4.
Uyama M, Wada M, Nagai Y, Matsubara T, Matsunaga H, Fukushima I, Takahashi K, Matsumura M. Polypoidal choroidal vasculopathy: natural history. Am J Ophthalmol. 2002;133(5):639–48.CrossRefPubMed
5.
Matsumiya W, Honda S, Kusuhara S, Tsukahara Y, Negi A. Effectiveness of intravitreal ranibizumab in exudative age-related macular degeneration (AMD): comparison between typical neovascular AMD and polypoidal choroidal vasculopathy over a 1 year follow-up. BMC Ophthalmol. 2013;13:10.CrossRefPubMedPubMedCentral
6.
Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1419–31.CrossRefPubMed
7.
Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1432–44.CrossRefPubMed
8.
Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, Brown DM, Chong V, Nguyen QD, Ho AC, Ogura Y, Simader C, Jaffe GJ, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014;121(1):193–201.CrossRefPubMed
9.
Cho HJ, Koh KM, Kim HS, Lee TG, Kim CG, Kim JW. Anti-vascular endothelial growth factor monotherapy in the treatment of submacular hemorrhage secondary to polypoidal choroidal vasculopathy. Am J Ophthalmol. 2013;156(3):524–31. e521CrossRefPubMed
10.
Hikichi T, Higuchi M, Matsushita T, Kosaka S, Matsushita R, Takami K, Ohtsuka H, Kitamei H, Shioya S. Results of 2 years of treatment with as-needed ranibizumab reinjection for polypoidal choroidal vasculopathy. Br J Ophthalmol. 2013;97(5):617–21.CrossRefPubMedPubMedCentral
11.
Hikichi T, Ohtsuka H, Higuchi M, Matsushita T, Ariga H, Kosaka S, Matsushita R, Takami K. Improvement of angiographic findings of polypoidal choroidal vasculopathy after intravitreal injection of ranibizumab monthly for 3 months. Am J Ophthalmol. 2010;150(5):674–82. e671CrossRefPubMed
12.
Kokame GT, Yeung L, Teramoto K, Lai JC, Wee R. Polypoidal choroidal vasculopathy exudation and hemorrhage: results of monthly ranibizumab therapy at one year. Ophthalmologica Journal international d’ophtalmologie International journal of ophthalmology Zeitschrift fur Augenheilkunde. 2014;231(2):94–102.CrossRefPubMed
13.
Koh A, Lee WK, Chen LJ, Chen SJ, Hashad Y, Kim H, Lai TY, Pilz S, Ruamviboonsuk P, Tokaji E, et al. EVEREST study: efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Retina (Philadelphia, Pa). 2012;32(8):1453–64.CrossRef
14.
Oishi A, Kojima H, Mandai M, Honda S, Matsuoka T, Oh H, Kita M, Nagai T, Fujihara M, Bessho N, et al. Comparison of the effect of ranibizumab and verteporfin for polypoidal choroidal vasculopathy: 12-month LAPTOP study results. Am J Ophthalmol. 2013;156(4):644–51.CrossRefPubMed
15.
Imamura Y, Engelbert M, Iida T, Freund KB, Yannuzzi LA. Polypoidal choroidal vasculopathy: a review. Surv Ophthalmol. 2010;55(6):501–15.CrossRefPubMed
16.
Hagstrom SA, Ying GS, Pauer GJ, Sturgill-Short GM, Huang J, Callanan DG, Kim IK, Klein ML, Maguire MG, Martin DF. Pharmacogenetics for genes associated with age-related macular degeneration in the comparison of AMD treatments trials (CATT). Ophthalmology. 2013;120(3):593–9.CrossRefPubMedPubMedCentral
17.
Lotery AJ, Gibson J, Cree AJ, Downes SM, Harding SP, Rogers CA, Reeves BC, Ennis S, Chakravarthy U. Pharmacogenetic associations with vascular endothelial growth factor inhibition in participants with neovascular age-related macular degeneration in the IVAN study. Ophthalmology. 2013;120(12):2637–43.CrossRefPubMed
18.
Park UC, Shin JY, McCarthy LC, Kim SJ, Park JH, Chung H, HG Y. Pharmacogenetic associations with long-term response to anti-vascular endothelial growth factor treatment in neovascular AMD patients. Mol Vis. 2014;20:1680–94.PubMedPubMedCentral
19.
Park UC, Shin JY, Kim SJ, Shin ES, Lee JE, McCarthy LC, Newcombe PJ, Xu CF, Chung H, Yu HG. Genetic factors associated with response to intravitreal ranibizumab in Korean patients with neovascular age-related macular degeneration. Retina (Philadelphia, Pa). 2014;34(2):288–97.CrossRef
20.
Hata M, Tsujikawa A, Miyake M, Yamashiro K, Ooto S, Oishi A, Nakanishi H, Takahashi A, Yoshimura N. Two-year visual outcome of ranibizumab in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Graefe’s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2015;253(2):221–7.CrossRefPubMed
21.
Yamashiro K, Tomita K, Tsujikawa A, Nakata I, Akagi-Kurashige Y, Miyake M, Ooto S, Tamura H, Yoshimura N. Factors associated with the response of age-related macular degeneration to intravitreal ranibizumab treatment. Am J Ophthalmol. 2012;154(1):125–36.CrossRefPubMed
22.
Kim SJ, Yu HG. Efficacy of combined photodynamic therapy and intravitreal bevacizumab injection versus photodynamic therapy alone in polypoidal choroidal vasculopathy. Retina (Philadelphia, Pa). 2011;31(9):1827–34.CrossRef
23.
Tsujikawa A, Sasahara M, Otani A, Gotoh N, Kameda T, Iwama D, Yodoi Y, Tamura H, Mandai M, Yoshimura N. Pigment epithelial detachment in polypoidal choroidal vasculopathy. Am J Ophthalmol. 2007;143(1):102–11.CrossRefPubMed
24.
Ma L, Li Z, Liu K, Rong SS, Brelen ME, Young AL, Kumaramanickavel G, Pang CP, Chen H, Chen LJ. Association of Genetic Variants with Polypoidal choroidal vasculopathy: a systematic review and updated meta-analysis. Ophthalmology. 2015;122(9):1854–65.CrossRefPubMed
25.
Yanagisawa S, Kondo N, Miki A, Matsumiya W, Kusuhara S, Tsukahara Y, Honda S, Negi A. Difference between age-related macular degeneration and polypoidal choroidal vasculopathy in the hereditary contribution of the A69S variant of the age-related maculopathy susceptibility 2 gene (ARMS2). Mol Vis. 2011;17:3574–82.PubMedPubMedCentral
26.
Liang XY, Lai TY, Liu DT, Fan AH, Chen LJ, Tam PO, Chiang SW, Ng TK, Lam DS, Pang CP. Differentiation of exudative age-related macular degeneration and polypoidal choroidal vasculopathy in the ARMS2/HTRA1 locus. Invest Ophthalmol Vis Sci. 2012;53(6):3175–82.CrossRefPubMed
27.
Chen H, Liu K, Chen LJ, Hou P, Chen W, Pang CP. Genetic associations in polypoidal choroidal vasculopathy: a systematic review and meta-analysis. Mol Vis. 2012;18:816–29.PubMedPubMedCentral
28.
Zhang X, Li M, Wen F, Zuo C, Chen H, Wu K, Zeng R. Different impact of high-density lipoprotein-related genetic variants on polypoidal choroidal vasculopathy and neovascular age-related macular degeneration in a Chinese Han population. Exp Eye Res. 2013;108:16–22.CrossRefPubMed
29.
Zhang X, Wen F, Zuo C, Li M, Chen H, Wu K. Association of genetic variation on chromosome 9p21 with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011;52(11):8063–7.CrossRefPubMed
30.
Sakurada Y, Kubota T, Imasawa M, Mabuchi F, Tanabe N, Iijima H. Association of LOC387715 A69S genotype with visual prognosis after photodynamic therapy for polypoidal choroidal vasculopathy. Retina (Philadelphia, Pa). 2010;30(10):1616–21.CrossRef
31.
Nakata I, Yamashiro K, Yamada R, Gotoh N, Nakanishi H, Hayashi H, Tsujikawa A, Otani A, Ooto S, Tamura H, et al. Genetic variants in pigment epithelium-derived factor influence response of polypoidal choroidal vasculopathy to photodynamic therapy. Ophthalmology. 2011;118(7):1408–15.PubMed
32.
Honda S, Bessho H, Kondo N, Kusuhara S, Tsukahara Y, Negi A. Positive association of CD36 gene variants with the visual outcome of photodynamic therapy in polypoidal choroidal vasculopathy. Mol Vis. 2012;18:2796–804.PubMedPubMedCentral
33.
Hata M, Tsujikawa A, Miyake M, Yamashiro K, Ooto S, Oishi A, Nakata I, Takahashi A, Yoshimura N. Two-year visual outcome of polypoidal choroidal vasculopathy treated with photodynamic therapy combined with intravitreal injections of ranibizumab. Graefes Arch Clin Exp Ophthalmol. 2015;253(2):189–97.CrossRefPubMed
34.
Fritsche LG, Loenhardt T, Janssen A, Fisher SA, Rivera A, Keilhauer CN, Weber BH. Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA. Nat Genet. 2008;40(7):892–6.CrossRefPubMed
35.
Sakurada Y, Kubota T, Imasawa M, Mabuchi F, Tateno Y, Tanabe N, Iijima H. Role of complement factor H I62V and age-related maculopathy susceptibility 2 A69S variants in the clinical expression of polypoidal choroidal vasculopathy. Ophthalmology. 2011;118(7):1402–7.PubMed
36.
De Salvo G, Vaz-Pereira S, Keane PA, Tufail A, Liew G. Sensitivity and specificity of spectral-domain optical coherence tomography in detecting idiopathic polypoidal choroidal vasculopathy. Am J Ophthalmol. 2014;158(6):1228–38. e1221CrossRefPubMed
37.
Chevreaud O, Oubraham H, Cohen SY, Jung C, Blanco-Garavito R, Gherdaoui F, Souied EH. Ranibizumab for vascularized pigment epithelial detachment: 1-year anatomic and functional results. Graefes Arch Clin Exp Ophthalmol. 2017;255(4):743–51.CrossRefPubMed
38.
Cheng Y, Shi X, JF Q, Zhao MW, Li XX. Comparison of the 1-year outcomes of Conbercept therapy between two different angiographic subtypes of Polypoidal choroidal vasculopathy. Chin Med J. 2016;129(21):2610–6.CrossRefPubMedPubMedCentral
39.
Cho HJ, Kim KM, Kim HS, Lee DW, Kim CG, Kim JW. Response of pigment epithelial detachment to anti-vascular endothelial growth factor treatment in age-related macular degeneration. Am J Ophthalmol. 2016;166:112–9.CrossRefPubMed
Metadata
Title
Association of ARMS2 genotype with response to anti-vascular endothelial growth factor treatment in polypoidal choroidal vasculopathy
Authors
Un Chul Park
Joo Young Shin
Hum Chung
Hyeong Gon Yu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Ophthalmology / Issue 1/2017
Electronic ISSN: 1471-2415
DOI
https://doi.org/10.1186/s12886-017-0631-z

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