Choroidal characteristics to predict the therapeutic response of anti-vascular endothelial growth factor drugs in polypoidal choroidal vasculopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Zhao Yue , Jiang Qin ,  Yao Jin

Nanjing Medical University Eye Hospital, Nanjing 210029, China;

Corresponding?author：

Yao Jin, Email: dryaojin@126.com

Keywords：

Choroid/physiopathology; Choroidal neovascularization/drug therapy; Angiogenesis inhibitors/therapeutic use; Forecasting

DOI：

10.3760/cma.j.cn511434-20200503-00192

Video：

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Objective To observe the changes in choroidal characteristics of polypoid choroidal vascular disease (PCV) eyes after intravitreal injection of anti-VEGF drugs, and to preliminarily evaluate its predictive effect on the response of PCV anti-VEGF drugs.Methods A retrospective clinical study. From January 2015 to May 2020, 63 eyes (63 PCV patients) diagnosed in NanJing Medical University Eye Hospital were included in the study. There were 39 eyes (39 males) and 24 eyes (24 females); all were monocular, with the average age of 62.53±6.05 years old. All eyes were treated with intravitreal injection of ranibizumab, and those with poor response after treatment were treated with photodynamic therapy (PDT) combined with anti-VEGF drugs. Among the 63 eyes, 38 eyes did not respond or responded poorly after treatment, and 25 eyes responded well. Based on response results, patients were divided into the poor response group and the good response group. The confocal laser synchronous angiography system (HRA+OCT) enhanced depth scanning technology of Herdelberg (Germany) was used to measure the foveal choroid thickness (SFCT) and the choroidal large vessel thickness (LCVT). The choroidal hyperpermeability (CVH) was judged based on the ICGA inspection results. CVH: In the middle and late stages (10-15 min after indocyanine green injection), the choroid of the posterior pole can be seen with multifocal strong fluorescence with blurred edges. The SFCT and LVCT changes of the two groups of eyes before treatment and 6 months after treatment in the good response group, and 6 months after the treatment of the poor response group combined with PDT were observed. SFCT and LCVT were compared with t test before and after treatment.Results Before treatment, of the 63 eyes, 38 eyes (60.3%) with CVH manifestations, of which 5 eyes (20.0%, 5/25) and 33 eyes (86.8%, 33/ 38). The SFCT and LCVT of the good response group and the poor response group were 244.16±23.74, 152.76±22.70 μm and 367.34±35.21, 271.84±35.42 μm, respectively. The comparison of SFCT and LVCT between the two groups of eyes before treatment showed statistically significant differences (t=7.24, 6.87; P=0.01, 0.01). Six months after treatment, the SFCT and LVCT of the eyes in the good response group were 241.04±32.56 and 150.44±23.45 μm, respectively; compared with those before treatment, the difference was not statistically significant (t=5.35, 8.64; P=0.08, 0.07). Six months after the poor response group combined with PDT treatment, SFCT and LCVT were 311.63±25.36 and 220.11±41.30 μm respectively; compared with those before treatment, the difference was statistically significant (t=6.84, 9.23; P=0.02, 0.01). After treatment, the CVH manifestations of all the eyes did not change significantly, but the eyes of the poor response group were treated with PDT, and the multifocal strong fluorescence was significantly weakened.Conclusions PCV thick choroid is mostly caused by abnormal thickening of choroidal large vessels. Eyes with thick choroid and CVH have poor response to anti-VEGF drug therapy alone, and combined PDT therapy may be more suitable for this type of patients.

Citation： Zhao Yue, Jiang Qin, Yao Jin. Choroidal characteristics to predict the therapeutic response of anti-vascular endothelial growth factor drugs in polypoidal choroidal vasculopathy. Chinese Journal of Ocular Fundus Diseases, 2020, 36(10): 754-758. doi: 10.3760/cma.j.cn511434-20200503-00192 Copy

1.	Yannuzzi LA, Sorenson J, Spaide RF, et al. Idiopathic polypoidal choroidal vasculopathy (IPCV)[J]. Retina, 2013, 32 Suppl 1: S1-8.
2.	Koh A, Lee WK, Chen LJ, 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[J]. Retina, 2012, 32(8): 1453-1464. DOI: 10.1097/IAE.0b013e31824f91e8.
3.	Gomi F, Oshima Y, Mori R, et al. Initial versus delayed photodynamic therapy in combination with ranibizumab for treatment of polypoidal choroidal vasculopathy: the Fujisan study[J]. Retina, 2015, 35(8): 1569-1576. DOI: 10.1097/IAE.0000000000000526.
4.	Yannuzzi LA, Wong DW, Sforzolini BS, et al. Polypoidal choroidal vasculopathy and neovascularized age-related macular degeneration[J]. Arch Ophthalmol, 1999, 117: 1503-1510. DOI: 10.1001/archopht.117.11.1503.
5.	Guyer DR, Yannuzzi LA, Slankter JS, et al. Digital indocyanine green videoangiography of central serous chorioretinopathy[J]. Arch Ophthalmol, 1994, 112(8): 1057-1062. DOI: 10.1001/archopht.1994.01090200063023.
6.	Spaide RF, Hall L, Haas A, et al. Indocyanine green videoangiography of older patients with central serous chorioretinopathy[J]. Retina, 1996, 16(3): 203-213. DOI: 10.1097/00006982-199616030-00004.
7.	馬楠, 陳有信, 鞏迪, 等. 息肉樣脈絡膜血管病變吲哚青綠血管造影與光相干斷層掃描血管成像圖像特征對比觀察[J]. 中華眼底病雜志, 2015, 31(5): 421-424. DOI: 10.3760/cma.j.issn.1005-1015.2015.05.003.Ma N, Chen YX, Gong D, et al. Comparative observation of indocyanine green angiography and optical coherence tomography angiography in polypoidal choroidal vasculopathy[J]. Chin J Ocul Fundus Dis, 2015, 31(5): 421-424. DOI: 10.3760/cma.j.issn.1005-1015.2015.05.003.
8.	Koizumi H, Yamagishi T, Yamazaki T, et al. Subfoveal choroidal thickness in typical age-related macular degeneration and polypoidal choroidal vasculopathy[J]. Graefe’s Arch Clin Exp Ophthalmol, 2011, 249(8): 1123-1128. DOI: 10.1007/s00417-011-1620-1.
9.	Chung SE, Kang SW, Lee JH, et al. Choroidal thickness in polypoidal choroidal vasculopathy and exudative age-related macular degeneration[J]. Ophthalmology, 2010, 118(5): 840-845. DOI: 10.1016/j.ophtha.2010.09.012.
10.	Kim SW, Oh J, Kwon SS, et al. Comparison of choroidal thickness among patients with healthy eyes, early age-related macular degeneration, central serous chorioretinopathy and polypoidal vasculopathy[J]. Retina, 2011, 31(9): 1904-1911. DOI: 10.1097/IAE.0b013e31821801c5.
11.	Spaide RF, Yannuzzi LA, Slakter JS, et al. Indocyanine green videoangiography of idiopathic polypoidal choroidal vasculopathy[J]. Retina, 1995, l5(2): 100-110. DOI: 10.1097/00006982-199616030-00004.
12.	Maruko I, Iida T, Oyamada H, et al. Choroidal thickness changes after intravitreal ranibizumab and photodynamic therapy in recurrent polypoidal choroidal vasculopathy[J]. Am J Ophthalmol, 2013, 156(3): 548-556. DOI: 10.1016/j.ajo.2013.03.041.
13.	Maruko I, Iida T, Sugano Y, et al. Subfoveal choroidal thickness after treatment of central serous chorioretinopathy[J]. Ophthalmology, 2010, 1179(9): 1792-1799. DOI: 10.1016/j.ophtha.2010.01.023.
14.	Ting DS, Ng WY, Ng SR, et al. Choroidal thickness changes in age-related macular degeneration and polypoidal choroidal vasculopathy: a 12-month prospective study[J]. Am J Ophthalmol, 2016, 164: 128-136. DOI: 10.1016/j.ajo.2015.12.024.
15.	Alshareef RA, Khuthaila MK, Januwada M, et al. Choroidal vascular analysis in myopic eyes: evidence of foveal medium vessel layer thinning[J/OL]. Int J Retina Vitreous, 2017, 3: 28[2017-05-26]. https://pubmed.ncbi.nlm.nih.gov/28560051/. DOI: 10.1186/s40942-017-0081-z.
16.	Tong JP, Chan WM, Liu DT, et al. Aqueous humor levels of vascular endothelial growth factor and pigment epithelium-derived factor in polypoidal choroidal vasculopathy and choroidal neovascularization[J]. Am J Ophthalmol, 2006, 141(3): 456-462. DOI: 10.1016/j.ajo.2005.10.012.
17.	Matsuoka M, Ogata N, Otsuji T, et al. Expression of pigment epithelium derived factor and vascular endothelial growth factor in choroidal neovascular membranes and polypoidal choroidal vasculopathy[J]. Br J Ophthalmol, 2004, 88(6): 809-815. DOI: 10.1136/bjo.2003.032466.
18.	Lee WK, Baek J, Dansingani KK, et al. Choroidal morphology in eyes with polypoidal choroidal vasculopathy and normal or subnormal subfoveal choroidal thickness[J]. Retina, 2016, 368(Suppl 1): S73-82. DOI: 10.1097/IAE.0000000000001346.
19.	何呂福, 王曉華, 溫旭. 脈絡膜厚度研究進展[J]. 中華實驗眼科雜志, 2017, 35(10): 949-954. DOI: 10.3760/cma.j.issn.2095-0160.2017.10.021.He LF, Wang XH, Wen X. Review on progress of choroidal thickness[J]. Chin J Exp Ophthalmol, 2017, 35(10): 949-954. DOI: 10.3760/cma.j.issn.2095-0160.2017.10.021.
20.	Kawamura A, Yuzawa M, Mori R, et al. Indocyanine green angiographic and optical coherence tomographic findings support classification of polypoidal choroidal vasculopathy into two types[J]. Acta Ophthalmol, 2013, 91(6): 474-481. DOI: 10.1111/aos.12110.
21.	Warrow DJ, Hoang QV, Freund KB. Pachychoroid pigment epitheliopathy[J]. Retina, 2013, 33(8): 1659-1672. DOI: 10.1097/IAE.0b013e3182953df4.
22.	Moussa M, Sabry D, Soliman W. Macular choroidal thickness in normal Egyptians measured by swept source optical coherence tomography[J]. BMC Ophthalmol, 2016, 16: 138. DOI: 10.1186/s12886-016-0314-1.
23.	Tan CS, Lim LW, Ngo WK, et al. Everest report 5: clinical outcomes and treatment response of polypoidal choroidal vasculopathy subtypes in a multicenter, randomized controlled trial[J]. Invest Ophthalmol Vis Sci, 2018, 59(2): 889-896. DOI: 10.1167/iovs.17-22683.
24.	Koh AH, Chen LJ, Chen SJ, et al. Polypoidal choroidal vasculopathy: evidence-based guidelines for clinical diagnosis and treatment[J]. Retina, 2013, 33(4): 686-716. DOI: 10.1097/IAE.0b013e3182852446.
25.	Koizumi H, Kano M, Yamamoto A, et al. Short-term changes in choroidal thickness after aflibercept therapy for neovascular age-related macular degeneration[J]. Am J Ophthalmol, 2015, 159(4): 627-633. DOI: 10.1016/j.ajo.2016.04.026.

1. Yannuzzi LA, Sorenson J, Spaide RF, et al. Idiopathic polypoidal choroidal vasculopathy (IPCV)[J]. Retina, 2013, 32 Suppl 1: S1-8.
2. Koh A, Lee WK, Chen LJ, 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[J]. Retina, 2012, 32(8): 1453-1464. DOI: 10.1097/IAE.0b013e31824f91e8.
3. Gomi F, Oshima Y, Mori R, et al. Initial versus delayed photodynamic therapy in combination with ranibizumab for treatment of polypoidal choroidal vasculopathy: the Fujisan study[J]. Retina, 2015, 35(8): 1569-1576. DOI: 10.1097/IAE.0000000000000526.
4. Yannuzzi LA, Wong DW, Sforzolini BS, et al. Polypoidal choroidal vasculopathy and neovascularized age-related macular degeneration[J]. Arch Ophthalmol, 1999, 117: 1503-1510. DOI: 10.1001/archopht.117.11.1503.
5. Guyer DR, Yannuzzi LA, Slankter JS, et al. Digital indocyanine green videoangiography of central serous chorioretinopathy[J]. Arch Ophthalmol, 1994, 112(8): 1057-1062. DOI: 10.1001/archopht.1994.01090200063023.
6. Spaide RF, Hall L, Haas A, et al. Indocyanine green videoangiography of older patients with central serous chorioretinopathy[J]. Retina, 1996, 16(3): 203-213. DOI: 10.1097/00006982-199616030-00004.
7. 馬楠, 陳有信, 鞏迪, 等. 息肉樣脈絡膜血管病變吲哚青綠血管造影與光相干斷層掃描血管成像圖像特征對比觀察[J]. 中華眼底病雜志, 2015, 31(5): 421-424. DOI: 10.3760/cma.j.issn.1005-1015.2015.05.003.Ma N, Chen YX, Gong D, et al. Comparative observation of indocyanine green angiography and optical coherence tomography angiography in polypoidal choroidal vasculopathy[J]. Chin J Ocul Fundus Dis, 2015, 31(5): 421-424. DOI: 10.3760/cma.j.issn.1005-1015.2015.05.003.
8. Koizumi H, Yamagishi T, Yamazaki T, et al. Subfoveal choroidal thickness in typical age-related macular degeneration and polypoidal choroidal vasculopathy[J]. Graefe’s Arch Clin Exp Ophthalmol, 2011, 249(8): 1123-1128. DOI: 10.1007/s00417-011-1620-1.
9. Chung SE, Kang SW, Lee JH, et al. Choroidal thickness in polypoidal choroidal vasculopathy and exudative age-related macular degeneration[J]. Ophthalmology, 2010, 118(5): 840-845. DOI: 10.1016/j.ophtha.2010.09.012.
10. Kim SW, Oh J, Kwon SS, et al. Comparison of choroidal thickness among patients with healthy eyes, early age-related macular degeneration, central serous chorioretinopathy and polypoidal vasculopathy[J]. Retina, 2011, 31(9): 1904-1911. DOI: 10.1097/IAE.0b013e31821801c5.
11. Spaide RF, Yannuzzi LA, Slakter JS, et al. Indocyanine green videoangiography of idiopathic polypoidal choroidal vasculopathy[J]. Retina, 1995, l5(2): 100-110. DOI: 10.1097/00006982-199616030-00004.
12. Maruko I, Iida T, Oyamada H, et al. Choroidal thickness changes after intravitreal ranibizumab and photodynamic therapy in recurrent polypoidal choroidal vasculopathy[J]. Am J Ophthalmol, 2013, 156(3): 548-556. DOI: 10.1016/j.ajo.2013.03.041.
13. Maruko I, Iida T, Sugano Y, et al. Subfoveal choroidal thickness after treatment of central serous chorioretinopathy[J]. Ophthalmology, 2010, 1179(9): 1792-1799. DOI: 10.1016/j.ophtha.2010.01.023.
14. Ting DS, Ng WY, Ng SR, et al. Choroidal thickness changes in age-related macular degeneration and polypoidal choroidal vasculopathy: a 12-month prospective study[J]. Am J Ophthalmol, 2016, 164: 128-136. DOI: 10.1016/j.ajo.2015.12.024.
15. Alshareef RA, Khuthaila MK, Januwada M, et al. Choroidal vascular analysis in myopic eyes: evidence of foveal medium vessel layer thinning[J/OL]. Int J Retina Vitreous, 2017, 3: 28[2017-05-26]. https://pubmed.ncbi.nlm.nih.gov/28560051/. DOI: 10.1186/s40942-017-0081-z.
16. Tong JP, Chan WM, Liu DT, et al. Aqueous humor levels of vascular endothelial growth factor and pigment epithelium-derived factor in polypoidal choroidal vasculopathy and choroidal neovascularization[J]. Am J Ophthalmol, 2006, 141(3): 456-462. DOI: 10.1016/j.ajo.2005.10.012.
17. Matsuoka M, Ogata N, Otsuji T, et al. Expression of pigment epithelium derived factor and vascular endothelial growth factor in choroidal neovascular membranes and polypoidal choroidal vasculopathy[J]. Br J Ophthalmol, 2004, 88(6): 809-815. DOI: 10.1136/bjo.2003.032466.
18. Lee WK, Baek J, Dansingani KK, et al. Choroidal morphology in eyes with polypoidal choroidal vasculopathy and normal or subnormal subfoveal choroidal thickness[J]. Retina, 2016, 368(Suppl 1): S73-82. DOI: 10.1097/IAE.0000000000001346.
19. 何呂福, 王曉華, 溫旭. 脈絡膜厚度研究進展[J]. 中華實驗眼科雜志, 2017, 35(10): 949-954. DOI: 10.3760/cma.j.issn.2095-0160.2017.10.021.He LF, Wang XH, Wen X. Review on progress of choroidal thickness[J]. Chin J Exp Ophthalmol, 2017, 35(10): 949-954. DOI: 10.3760/cma.j.issn.2095-0160.2017.10.021.
20. Kawamura A, Yuzawa M, Mori R, et al. Indocyanine green angiographic and optical coherence tomographic findings support classification of polypoidal choroidal vasculopathy into two types[J]. Acta Ophthalmol, 2013, 91(6): 474-481. DOI: 10.1111/aos.12110.
21. Warrow DJ, Hoang QV, Freund KB. Pachychoroid pigment epitheliopathy[J]. Retina, 2013, 33(8): 1659-1672. DOI: 10.1097/IAE.0b013e3182953df4.
22. Moussa M, Sabry D, Soliman W. Macular choroidal thickness in normal Egyptians measured by swept source optical coherence tomography[J]. BMC Ophthalmol, 2016, 16: 138. DOI: 10.1186/s12886-016-0314-1.
23. Tan CS, Lim LW, Ngo WK, et al. Everest report 5: clinical outcomes and treatment response of polypoidal choroidal vasculopathy subtypes in a multicenter, randomized controlled trial[J]. Invest Ophthalmol Vis Sci, 2018, 59(2): 889-896. DOI: 10.1167/iovs.17-22683.
24. Koh AH, Chen LJ, Chen SJ, et al. Polypoidal choroidal vasculopathy: evidence-based guidelines for clinical diagnosis and treatment[J]. Retina, 2013, 33(4): 686-716. DOI: 10.1097/IAE.0b013e3182852446.
25. Koizumi H, Kano M, Yamamoto A, et al. Short-term changes in choroidal thickness after aflibercept therapy for neovascular age-related macular degeneration[J]. Am J Ophthalmol, 2015, 159(4): 627-633. DOI: 10.1016/j.ajo.2016.04.026.

Chinese Journal of Ocular Fundus Diseases

Choroidal characteristics to predict the therapeutic response of anti-vascular endothelial growth factor drugs in polypoidal choroidal vasculopathy

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