法瑞西单抗治疗难治性湿性年龄相关性黄斑变性的疗效研究

doi:10.3969/j.issn.1003-9198.2025.07.006

摘要/Abstract

摘要： 目的评估玻璃体腔内注射法瑞西单抗治疗难治性湿性年龄相关性黄斑变性(nAMD)的效果。方法选取既往多次行抗血管内皮生长因子(VEGF)治疗效果不佳的20例难治性nAMD病人,于2024年4月27日至5月31日于南京中医药大学附属医院眼科进行玻璃体腔内注射法瑞西单抗治疗1次,分别在治疗前(T1),治疗后1周(T2)、1个月(T3)、2个月(T4)、3个月(T5)时评估最佳矫正视力(BCVA)、黄斑视网膜厚度(内界膜到Bruch膜)(MRT)、中心视网膜厚度(CST)、脉络膜厚度(CCT)、视网膜外层厚度(外丛状层到Bruch膜)、色素上皮脱离(PED)最高点高度及面积、新生血管面积(NA)。结果共20例病人(20只眼)接受了治疗。与治疗前相比,治疗后1周BCVA、NA较治疗前改善,差异有统计学意义;治疗后1个月,BCVA、NA和PED高度较治疗前改善,差异有统计学意义;治疗后2个月,BCVA、CST、MRT、PED高度、NA均较治疗前改善,差异有统计学意义;治疗后3个月,BCVA、CST、PED高度、PED面积与治疗前比较,差异有统计学意义(P＜0.05)。治疗后1周、1个月时,CCT与PED面积、PED高度均呈正相关(P＜0.05)。结论玻璃体腔内注射法瑞西单抗可以有效改善难治性nAMD病人的BCVA,降低CST、PED高度,缩小PED面积。

关键词: 法瑞西单抗, 玻璃体腔内注射, 年龄相关性黄斑变性, 色素上皮脱离, 难治性, 治疗效果

Abstract: Objective To evaluate the efficacy of intravitreal injection of faricimab in the patients with refractory neovascular age-related macular degeneration (nAMD). Methods A total of twenty patients with refractory nAMD who had poor responses to previous multiple antivascular endothelial growth factor(VEGF)treatments were enrolled. They received a single intravitreal injection of faricimab in the Ophthalmologic Department of Affiliated Hospital of Nanjing University of Chinese Medicine from April 27 to May 31, 2024. Best corrected vision acuity (BCVA), macular retinal thickness (MRT) which meant the inner limiting membrane to Bruch membrane, central retinal thickness (CST),central choroid thickness (CCT), outer retinal thickness (the outer plexiform layer to Bruch membrane), maximal pigment epithelial detachment (PED) height and area, and neovascularization area (NA) were evaluated before treatment(T1) and 1 week(T2), 1 month(T3), 2 months(T4), and 3 months(T5) after treatment. Results The study included 20 patients (20 eyes). Compared with those before treatment, BCVA and NA were significantly improved 1 week after treatment. BCVA, PED height and NA were significantly improved 1 month after treatment. BCVA, CST, MRT, PED height and NA were significantly improved 2 months after treatment. BCVA, CST, PED height and PED area were significantly improved 3 months after treatment. Additionally, 1 week and 1 month after treatment, CCT showed a positive correlation with PED height and PED area. Conclusions Intravitreal injection of faricimab can effectively improve BCVA, reduce CST and PED height, and decrease PED area in the patients with refractory nAMD.

Key words: faricimab, intravitreal injection, age-related macular degeneration, pigment epithelial detachment, refractory, treatment efficacy

中图分类号:

R774.5

方祎鸣, 施炜, 周欣, 赵春林, 张思雅, 王菁, 孙化萍, 裴昱, 陈茜, 潘莉, 金青子, 陶康, 林琳. 法瑞西单抗治疗难治性湿性年龄相关性黄斑变性的疗效研究[J]. 实用老年医学, 2025, 39(7): 674-680.

FANG Yiming, SHI Wei, ZHOU Xin, ZHAO Chunlin, ZHANG Siya, WANG Jing, SUN Huaping, PEI Yu, CHEN Xi, PAN Li, JIN Qingzi, TAO Kang, LIN Lin. Efficacy of faricimab in the treatment of refractory neovascular age-related macular degeneration[J]. Practical Geriatrics, 2025, 39(7): 674-680.

参考文献

[1] NITA M, GRZYBOWSKI A. Antioxidative role of heterophagy, autophagy, and mitophagy in the retina and their association with the age-related macular degeneration (AMD) etiopathogenesis[J]. Antioxidants: Basel, 2023, 12(7): 1368.
[2] 陈彬彬, 楼丽霞, 叶娟. 中国眼病疾病负担现状及三十年变化趋势[J]. 浙江大学学报(医学版), 2021, 50(4): 420-428.
[3] AMINI M A, KARBASI A, VAHABIRAD M, et al. Mechanistic insight into age-related macular degeneration (AMD): anatomy, epidemiology, genetics, pathogenesis, prevention, implications, and treatment strategies to pace AMD management[J]. Chonnam Med J, 2023, 59(3): 143-159.
[4] Five-year follow-up of fellow eyes of patients with age-related macular degeneration and unilateral extrafoveal choroidal neovascularization. Macular Photocoagulation Study Group[J]. Arch Ophthalmol, 1993, 111(9): 1189-1199.
[5] AMOAKU W M, CHAKRAVARTHY U, GALE R, et al. Defining response to anti-VEGF therapies in neovascular AMD[J]. Eye: Lond, 2015, 29(6): 721-731.
[6] SHIRLEY M. Faricimab: first approval[J]. Drugs, 2022, 82(7): 825-830.
[7] PENHA F M, MASUD M, KHANANI Z A, et al. Review of real-world evidence of dual inhibition of VEGF-A and ANG-2 with faricimab in NAMD and DME[J]. Int J Retina Vitreous, 2024, 10(1): 5.
[8] LI P, FAN H. Pericyte loss in diseases[J]. Cells, 2023, 12(15): 1931.
[9] TRIMM E, RED-HORSE K. Vascular endothelial cell development and diversity[J]. Nat Rev Cardiol, 2023, 20(3): 197-210.
[10] NGUYEN Q D, HEIER J S, DO D V, et al. The Tie2 signaling pathway in retinal vascular diseases: a novel therapeutic target in the eye[J]. Int J Retina Vitreous, 2020, 6: 48.
[11] LIBERSKI S, WICHROWSKA M, KOCIE, CKI J. Aflibercept versus faricimab in the treatment of neovascular age-related macular degeneration and diabetic macular edema: a review[J]. Int J Mol Sci, 2022, 23(16): 9424.
[12] INOUE M, ARAKAWA A, YAMANE S, et al. Variable response of vascularized pigment epithelial detachments to ranibizumab based on lesion subtypes, including polypoidal choroidal vasculopathy[J]. Retina, 2013, 33(5): 990-997.
[13] SHEN Y, XU M, REN L, et al. A novel retinoic acid drug, EYE-502, inhibits choroidal neovascularization by targeting endothelial cells and pericytes[J]. Sci Rep, 2023, 13(1): 10439.
[14] HUANG H. Pericyte-endothelial interactions in the retinal microvasculature[J]. Int J Mol Sci, 2020, 21(19): 7413.
[15] KHAN M, AZIZ A A, SHAFI N A, et al. Targeting angiopoietin in retinal vascular diseases: a literature review and summary of clinical trials involving faricimab[J]. Cells, 2020, 9(8): 1869.
[16] NICOLÒ M, FERRO DESIDERI L, VAGGE A, et al. Faricimab: an investigational agent targeting the Tie-2/angiopoietin pathway and VEGF-A for the treatment of retinal diseases[J]. Expert OpinInvestig Drugs, 2021, 30(3): 193-200.
[17] TAKAHASHI K, CHEUNG C M G, IIDA T, et al. Efficacy, durability, and safety of faricimab in patients from Asian countries with neovascular age-related macular degeneration: 1-year subgroup analysis of the TENAYA and LUCERNE trials[J]. Graefes Arch Clin Exp Ophthalmol, 2023, 261(11): 3125-3137.
[18] ALDHANHANI A A, AZZAM O A, ALALI S H, et al. Switch to faricimab after initial treatment with aflibercept in eyes with neovascular age-related macular degeneration[J]. Int Ophthalmol, 2024, 44(1): 369.
[19] NG B, KOLLI H, AJITH KUMAR N, et al. Real-world data on faricimab switching in treatment-refractory neovascular age-related macular degeneration[J]. Life: Basel, 2024, 14(2): 193.
[20] CHEUNG C M G, LIM J I, PRIGLINGER S, et al. Anatomic outcomes with faricimab vs aflibercept in head-to-head dosing phase of the TENAYA/LUCERNE trials in neovascular age-related macular degeneration[J]. Ophthalmology, 2025, 132(5): 519-526.
[21] KIM J H, KIM J Y, LEE D W, et al. Fibrovascular pigment epithelial detachment in eyes with subretinal hemorrhage secondary to neovascular AMD or PCV: a morphologic predictor associated with poor treatment outcomes[J]. Sci Rep, 2020, 10(1): 14943.
[22] PEPPLE K, MRUTHYUNJAYA P. Retinal pigment epithelial detachments in age-related macular degeneration: classification and therapeutic options[J]. Semin Ophthalmol, 2011, 26(3): 198-208.
[23] KARAMPELAS M, MALAMOS P, PETROU P, et al. Retinal pigment epithelial detachment in age-related macular degeneration[J]. Ophthalmol Ther, 2020, 9(4): 739-756.
[24] SHIJO T, SAKURADA Y, TANAKA K, et al. Incidence and risk of advanced age-related macular degeneration in eyes with drusenoid pigment epithelial detachment[J]. Sci Rep, 2022, 12(1): 4715.
[25] MINNELLA A M, CENTINI C, GAMBINI G, et al. Choroidal thickness changes after intravitreal aflibercept injections in treatment-Naïve neovascular AMD[J]. Adv Ther, 2022, 39(7): 3248-3261.
[26] ARNOULD L, GUENANCIA C, BINQUET C, et al. Retinal vascular network: changes with aging and systemic vascular disease (cardiac and cerebral)[J]. J Fr Ophtalmol, 2022, 45(1): 104-118.
[27] PRZEZAK A, BIELKA W, PAWLIK A. Hypertension and type 2 diabetes-the novel treatment possibilities[J]. Int J Mol Sci, 2022, 23(12): 6500.
[28] HYMAN L, SCHACHAT A P, HE Q, et al. Hypertension, cardiovascular disease, and age-related macular degeneration. Age-Related Macular Degeneration Risk Factors Study Group[J]. Arch Ophthalmol, 2000, 118(3): 351-358.
[29] KAŠTELAN S, OREŠKOVIĆ I, BIŠĆAN F, et al. Inflammatory and angiogenic biomarkers in diabetic retinopathy[J]. Biochem Med: Zagreb, 2020, 30(3): 030502.
[30] REDDY S K, DEVI V, SEETHARAMAN A T M, et al. Cell and molecular targeted therapies for diabetic retinopathy[J]. Front Endocrinol: Lausanne, 2024, 15: 1416668.
[31] HIRSCHI K K, D’AMORE P A. Pericytes in the microvasculature[J]. Cardiovasc Res, 1996, 32(4): 687-698.
[32] FERRO DESIDERI L, TRAVERSO C E, NICOLÒ M, et al. Faricimab for the treatment of diabetic macular edema and neovascular age-related macular degeneration[J]. Pharmaceutics, 2023, 15(5): 1413.
[33] PANOS G D, LAKSHMANAN A, DADOUKIS P, et al. Faricimab: transforming the future of macular diseases treatment-a comprehensive review of clinical studies[J]. Drug Des Devel Ther, 2023, 17: 2861-2873.