라니비주맙으로 치료한 결절맥락막혈관병증 환자에서 안구 내 사이토카인 변화
Intraocular Cytokine Changes in Patients with Polypoidal Choroidal Vasculopathy Treated with Ranibizumab
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목적: 결절맥락막혈관병증 환자에서 라니비주맙 주사 후 안구 내 사이토카인의 변화를 알아보고자 하였다. 대상과 방법: 결절맥락막혈관병증 환자를 라니비주맙으로 4주 간격 3회 주사 시행 후 24주까지 전향적 다기관 연구를 진행하였다. 4주마다 최대교정시력, 세극등검사, 안저촬영, 빛간섭단층촬영을 시행하였으며, 주사 전, 주사 후 8주째, 재발 시점 또는 20주째에 방수를 채취하여 사이토카인의 변화를 조사하였다. 사이토카인 농도와 시력 변화, 중심황반두께, 중심맥락막두께, 이상혈관 면적, 결절 폐쇄 여부 사이의 상관관계를 분석하였다. 결과: 총 25안이 연구에 포함되었다. 평균 나이는 70.3 ± 6.1세였다. 치료 전에 비해 치료 후 8주에는 VEGF가 유의한 감소를 보였으나, 재발 시에는 IFN-γ, TIMP-2, MCP-2만이 유의하게 감소하였다. 치료 전 ENA-78, IL-17, Leptin, TGB-β1 농도가 높을수록 재발까지 시간이 길었으며, 중심황반두께는 FGF-4, IL-10 농도가 높을수록 두꺼웠다. 중심맥락막두께는 bFGF 농도가 낮거나, IFN-γ 농도가 높을수록 두꺼웠다. 결절이 폐쇄된 2안은 치료 전에 비해 MCP-3, Tie-2의 농도가 유의하게 감소하였다. 결론: 결절맥락막혈관병증에서 라니비주맙 주사 후 안구 내 VEGF 농도가 감소되고, 질환이 호전되었으나, 재발 시에는 VEGF가 아닌 IFN-γ, TIMP-2, MCP-2 등 다양한 사이토카인들의 변화와 관련이 있었다. 향후 결절맥락막망병증에서 혈관신생과 관련된 다양한 사이토카인에 대한 연구가 필요하다.
Abstract
Purpose: To investigate the changes in intraocular cytokines after ranibizumab treatment in patients with polypoidal choroidal vasculopathy (PCV). Methods: This multicenter, prospective study enrolled patients with PCV treated with three monthly ranibizumab followed by a pro re nata regimen for 24 weeks. Best corrected visual acuity, slit lamp examination, fundus photography, and optical coherence tomography were performed every 4 weeks. Aqueous humor was collected to measure intraocular cytokines at baseline, week 8, and the time of recurrence or week 20. The association of changes in intraocular cytokines with visual acuity, central macular thickness, central choroidal thickness, area of abnormal vessels, and polyp closure was assessed. Results: This study included 25 eyes. The mean patient age was 70.3 ± 6.1 years. The vascular endothelial growth factor (VEGF) concentration decreased at week 8, but only interferon (IFN)-γ, tissue inhibitors of matrix metalloproteinases (TIMP)-2, and monocyte chemoattractant protein (MCP)-2 decreased at the time of recurrence. The recurrence interval was positively associated with the baseline epithelial-neutrophil activating peptide (ENA)-78, interleukin (IL)-17, leptin, and transforming growth factor-β1, and baseline central macular thickness was positively correlated with the baseline fibroblast growth factor-4 and IL-10. Thick central choroidal thickness was associated with a low basic fibroblast growth factor and high IFN-γ at baseline. The MCP-3 and Tie-2 levels decreased in two eyes with polyp closure. Conclusions: Ranibizumab significantly reduced intraocular VEGF concentrations and consequently improved PCV. However, the cytokines IFN-γ, TIMP-2, and MCP-2, rather than VEGF, were associated with PCV recurrence. Further studies of intraocular cytokines involved in neovascularization in PCV are needed.
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