CNV
玻璃体腔注射血管内皮生长因子(vascular endothelial growth factor, VEGF)抑制剂是目前CNV的主要治疗方法。[29]Schmidt-Erfurth U, Chong V, Loewenstein A, et al. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). Br J Ophthalmol. 2014;98:1144-1167.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145443/http://www.ncbi.nlm.nih.gov/pubmed/25136079?tool=bestpractice.com雷珠单抗[30]Solomon SD, Lindsley K, Vedula SS, et al. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2014;(8):CD005139.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005139.pub3/abstracthttp://www.ncbi.nlm.nih.gov/pubmed/25170575?tool=bestpractice.com[31]Boyer DS, Heier JS, Brown DM, et al. A Phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology. 2009;116:1731-1739.http://www.ncbi.nlm.nih.gov/pubmed/19643495?tool=bestpractice.com和阿柏西普[32]Heier JS, Boyer D, Nguyen QD, et al. The 1-year results of CLEAR-IT 2, a phase 2 study of vascular endothelial growth factor trap-eye dosed as-needed after 12-week fixed dosing. Ophthalmology. 2011;118:1700.http://www.ncbi.nlm.nih.gov/pubmed/21640258?tool=bestpractice.com[33]National Institute for Health and Care Excellence. Aflibercept solution for injection for treating wet age‑related macular degeneration. July 2013. http://www.nice.org.uk (last accessed 26 September 2017).http://www.nice.org.uk/guidance/TA294[34]Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014;121:193-201.http://www.aaojournal.org/article/S0161-6420(13)00729-X/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/24084500?tool=bestpractice.com是目前批准的治疗方法。雷珠单抗和阿柏西普具有相似的效力。[35]Sarwar S, Clearfield E, Soliman MK, et al. Aflibercept for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2016;(2):CD011346.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011346.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26857947?tool=bestpractice.com贝伐珠单抗没有得到批准,但近期头对头研究表明其有效性与雷珠单抗类似。[36]Martin DF, Maguire MG, Fine SL, et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology. 2012;119:1388-1398.http://www.ncbi.nlm.nih.gov/pubmed/22555112?tool=bestpractice.com[37]Chakravarthy U, Harding SP, Rogers CA, et al. Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN randomized trial. Ophthalmology. 2012;119:1399-1411.[38]Chakravarthy U, Harding SP, Rogers CA, et al; IVAN study investigators. Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial. Lancet. 2013;382:1258-1267.http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61501-9/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/23870813?tool=bestpractice.com此外,贝伐珠单抗已被证明具有高性价比,而雷珠单抗则不是。[39]Chakravarthy U, Harding SP, Rogers CA, et al. A randomised controlled trial to assess the clinical effectiveness and cost-effectiveness of alternative treatments to inhibit VEGF in age-related choroidal neovascularisation (IVAN). Health Technol Assess. 2015;19:1-298.http://www.journalslibrary.nihr.ac.uk/hta/volume-19/issue-78#table-of-contentshttp://www.ncbi.nlm.nih.gov/pubmed/26445075?tool=bestpractice.com曾有因为贝伐珠单抗在分装过程中缺乏足够的无菌技术保证,在注射后引起眼内炎的报道。[40]U.S. Food and Drug Administration. FDA alerts health care professionals of infection risk from repackaged Avastin intravitreal injections. August 2011. http://www.fda.gov (last accessed 26 September 2017).http://www.fda.gov/Drugs/Drugsafety/ucm270296.htm一项纳入比较贝伐珠单抗和雷珠单抗的随机对照试验的系统评价未发现两种药物之间的差异。[41]Moja L, Lucenteforte E, Kwag KH, et al. Systemic safety of bevacizumab versus ranibizumab for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2014;(9):CD011230.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011230.pub2/abstracthttp://www.ncbi.nlm.nih.gov/pubmed/25220133?tool=bestpractice.com另外一种VEGF抑制剂——哌加他尼,由于其效果不如以上药物,目前已基本停用。
这些药物的最佳给药方案目前仍有争议。在临床上较为常用的方案包括负荷剂量(通常为3次),之后根据病情需要安排治疗。一些研究使用了“治疗和延长”的给药方案,因此与每月随访注射相比,能够减少患者随访和治疗次数,降低每年的直接医疗费用。[42]Gupta OP, Shienbaum G, Patel AH, et al. A treat and extend regimen using ranibizumab for neovascular age-related macular degeneration clinical and economic impact. Ophthalmology. 2010;117:2134-2140.http://www.ncbi.nlm.nih.gov/pubmed/20591490?tool=bestpractice.com可以作为每月治疗的一种替代方案。
对年龄相关性黄斑变性治疗试验比较 (Comparison of Age-related Macular Degeneration Treatments Trials, CATT) 研究的长期随访比较了雷珠单抗和贝伐珠单抗,结果发现尽管治疗还在持续,但最初 2 年获得的视力改善未能在 5 年时继续保持。然而,仍存在一个长期重要益处,50% 的眼睛获得 20/40 或更好的视力。[43]Maguire MG, Martin DF, Ying GS, et al.; Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group. Five-year outcomes with anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration: the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2016;123:1751-1761.http://www.aaojournal.org/article/S0161-6420(16)30092-6/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/27156698?tool=bestpractice.com
使用维替泊芬进行的光动力治疗可以用于治疗中心凹外CNV。但对于中心凹下的CNV来说,其效果不如VEGF抑制剂。[44]Bressler NM; Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials-TAP report 2. Arch Ophthalmol. 2001;119:198-207.http://www.ncbi.nlm.nih.gov/pubmed/11176980?tool=bestpractice.com[45]Verteporfin In Photodynamic Therapy Study Group. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization - verteporfin in photodynamic therapy report 2. Am J Ophthalmol. 2001;131:541-560.http://www.ncbi.nlm.nih.gov/pubmed/11336929?tool=bestpractice.com[46]Barbazetto I, Burdan A, Bressler NM, et al. Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin: fluorescein angiographic guidelines for evaluation and treatment - TAP and VIP report No. 2. Arch Ophthalmol. 2003;121:1253-1268.http://www.ncbi.nlm.nih.gov/pubmed/12963608?tool=bestpractice.com[47]Blinder KJ, Bradley S, Bressler NM, et al. Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report no. 1. Am J Ophthalmol. 2003;136:407-418.http://www.ncbi.nlm.nih.gov/pubmed/12967792?tool=bestpractice.com[48]Brown DM, Michels M, Kaiser PK, et al. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study. Ophthalmology. 2009;116:57-65.e5.http://www.ncbi.nlm.nih.gov/pubmed/19118696?tool=bestpractice.com
玻璃体腔注射VEGF抑制剂和光动力治疗的联合疗法也得到了研究,但仍无充分证据表明优于单纯抗VEGF治疗。[49]Kaiser PK, Boyer DS, Cruess AF, et al; DENALI Study Group. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration: twelve-month results of the DENALI study. Ophthalmology. 2012;119:1001-1010.http://www.ncbi.nlm.nih.gov/pubmed/22444829?tool=bestpractice.com[50]Larsen M, Schmidt-Erfurth U, Lanzetta P, et al; MONT BLANC Study Group. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration: twelve-month MONT BLANC study results. Ophthalmology. 2012;119:992-1000.http://www.ncbi.nlm.nih.gov/pubmed/22424834?tool=bestpractice.com
由于热激光光凝治疗的破坏性作用,热激光光凝治疗已不再用于中心凹下CNV,但对于中心凹外CNV仍然可以考虑使用。[51]Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy. Five-year results from randomized clinical trials. Arch Ophthalmol. 1991;109:1109-1114.http://www.ncbi.nlm.nih.gov/pubmed/1714270?tool=bestpractice.com[52]Macular Photocoagulation Study Group. Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year results from randomized clinical trials. Arch Ophthalmol.1994;112:500-509.http://www.ncbi.nlm.nih.gov/pubmed/7512336?tool=bestpractice.com