感染性角膜炎相关角膜胶原交联在细菌性角膜炎中的临床研究进展

doi:10.3877/cma.j.issn.2095-2007.2026.03.010

多重耐药菌株感染角膜严重威胁视力。近年来，随着病原体的耐药性增强，即便细菌性角膜炎(BK)获得了及时诊治，仍可能出现角膜溶解和角膜穿孔等并发症。因此，寻找新的治疗手段应对日益严重的耐药菌株感染性角膜炎至关重要。角膜胶原交联(CXL)已广泛用于圆锥角膜及屈光术后角膜扩张等疾病治疗，现已作为多重耐药微生物所致感染性角膜炎的辅助治疗方式。为区分CXL在感染性角膜炎与角膜扩张疾病中的应用，感染性角膜炎相关CXL被特称为PACK-CXL。现有研究结果表明，PACK-CXL作为抗生素治疗的辅助手段，在BK中具有有效性。本文中笔者就PACK-CXL的治疗机制及其在BK中的临床应用进展进行综述。

关键词: 角膜炎, 感染性角膜炎相关角膜胶原交联, 交联, 治疗

Multidrug-resistant bacterial keratitis poses a serious threat to vision. In recent years, as pathogens have become increasingly resistant to antibiotics, complications such as corneal melting and perforation may still occur even when bacterial keratitis (BK) is diagnosed and treated promptly. Therefore, it is critical to explore new therapeutic approaches to combat the growing challenge of drug-resistant infectious keratitis. Corneal collagen cross-linking (CXL), originally established for the treatment of keratoconus and post-refractive ectasia, has now been introduced as an adjunctive modality for infectious keratitis caused by multidrug-resistant organisms. To distinguish its application in infectious keratitis from that in ectatic disorders, CXL used for infectious keratitis has been termed photoactivated chromophore for infectious keratitis-corneal cross-linking (PACK-CXL). Current evidence indicates that PACK-CXL, as an adjunct to antibiotic therapy, is effective in treating BK. The therapeutic mechanisms of PACK-CXL and its clinical application in BK was summarized in this paper.

Key words: Keratitis, Photoactivated chromophore for infectious keratitis-corneal cross-linking, Cross-linking, Treatment

表1 PACK-CXL联合抗生素治疗细菌性角膜炎的文献汇总

第一作者	研究类型	联合方案	主要协同机制	主要结果
Kling等^[32]	体外研究	高能量PACK-CXL＋喹诺酮类或糖肽类抗生素	破坏细菌生物膜，削弱耐药屏障	显示强效协同杀菌作用
Liu等^[33]	Meta分析	PACK-CXL＋规范抗生素治疗	提升抗菌效能，减轻组织破坏	治愈率87.2%，溃疡愈合周期缩短30%以上
Hafezi等^[24]	Ⅲ期随机对照试验	PACK-CXL＋一线抗菌药物	协同杀菌、抑制炎症、加固角膜	缩短愈合时间，减少角膜瘢痕
Olshaker等^[28]	前瞻性队列研究	加速高能量PACK-CXL＋广谱抗生素	强化杀菌，促进角膜上皮修复	加快愈合，降低角膜移植率
Aiello等^[34]	系统性综述	PACK-CXL＋常规抗菌药物	抑制炎症，加固基质，阻断损伤	对重症感染具有更高临床价值的综合干预效果

表1 PACK-CXL联合抗生素治疗细菌性角膜炎的文献汇总

第一作者	研究类型	联合方案	主要协同机制	主要结果
Kling等^[32]	体外研究	高能量PACK-CXL＋喹诺酮类或糖肽类抗生素	破坏细菌生物膜，削弱耐药屏障	显示强效协同杀菌作用
Liu等^[33]	Meta分析	PACK-CXL＋规范抗生素治疗	提升抗菌效能，减轻组织破坏	治愈率87.2%，溃疡愈合周期缩短30%以上
Hafezi等^[24]	Ⅲ期随机对照试验	PACK-CXL＋一线抗菌药物	协同杀菌、抑制炎症、加固角膜	缩短愈合时间，减少角膜瘢痕
Olshaker等^[28]	前瞻性队列研究	加速高能量PACK-CXL＋广谱抗生素	强化杀菌，促进角膜上皮修复	加快愈合，降低角膜移植率
Aiello等^[34]	系统性综述	PACK-CXL＋常规抗菌药物	抑制炎症，加固基质，阻断损伤	对重症感染具有更高临床价值的综合干预效果

[1]	Marrie A, Abdullatif AM, Gamal-El-Dine S, et al. Corneal cross-linking guards against infectious keratitis: an experimental model [J]. Int Ophthalmol, 2023, 43(4): 1241-1248.
[2]	Diacou R, Singh RB, Romanowski EG, et al. Moxifloxacin-resistant and moxifloxacin-susceptible Staphylococcus aureus keratitis: outcomes from a 10-year retrospective study [J]. Ocul Surf, 2025, 38(c): 97-103.
[3]	中国医师协会眼科医师分会眼感染学组. 中国细菌性角膜炎诊断与治疗专家共识(2025年) [J]. 中华眼科杂志，2025，61(11)：854-860.
[4]	Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue [J]. Exp Eye Res, 1998, 66(1): 97-103.
[5]	Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus [J]. Am J Ophthalmol, 2003, 135(5): 620-627.
[6]	Budhiraja G. Evolution of corneal collagen cross-linking [J]. Delhi J Ophthalmol, 2023, 33(2): 143-148.
[7]	Schnitzler E, Spörl E, Seiler T. Irradiation of cornea with ultraviolet light and riboflavin administration as a new treatment for erosive corneal processes, preliminary results in four patients [J]. Klin Monatsbl Augenheilkd, 2000, 217(3): 190-193.
[8]	Iseli HP, Thiel MA, Hafezi F, et al. Ultraviolet a/riboflavin corneal cross-linking for infectious keratitis associated with corneal melts [J]. Cornea, 2008, 27(5): 590-594.
[9]	Makdoumi K, Mortensen J, Sorkhabi O, et al. UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study [J]. Graefes Arch Clin Exp Ophthalmol, 2012, 250(1): 95-102.
[10]	Hafezi F, Randleman JB. PACK-CXL: defining CXL for infectious keratitis [J]. J Refract Surg, 2014, 30(7): 438-439.
[11]	Al-Mahrouqi H, Cheung IMY, Angelo L, et al. Therapeutic non-ectasia applications of cornea cross-linking [J]. Clin Exp Optom, 2023, 106(6): 580-590.
[12]	甘敏，林莉，张晓慧. 角膜交联术治疗感染性角膜炎的研究进展 [J]. 临床医学进展，2025，15(8)：236-243.
[13]	何缘圆，李彦玉，尹云弟，等. 光照与核黄素浓度对核黄素光动力灭活病原体效果的研究 [J]. 安徽医科大学学报，2023，58(6)：959-962.
[14]	Farhadi F, Salehi-Pourmehr H, Arasteh A, et al. Corneal cross-linking for infectious keratitis of various causes: an umbrella review [J]. BMC Ophthalmol, 2025, 25(1): 238.
[15]	孙明甡，张丰菊. 紫外线a-核黄素角巩膜胶原交联术的研究进展 [J]. 中华眼科杂志，2018，54(12)：948-953.
[16]	Sharma A, Sharma R, Chander J, et al. In vitro antimicrobial efficacy of riboflavin, ultraviolet-A radiation, and combined riboflavin/ultraviolet-a radiation on ocular pathogens [J]. Taiwan J Ophthalmol, 2023, 13(1): 21-27.
[17]	Osipyan G, Khraistin H, Jourieh M. Collagen cross-linking beyond corneal ectasia: a comprehensive review [J]. Indian J Ophthalmol, 2024, 72(S2): S191-S202.
[18]	Menzel-Severing J, Streit T, Schmiedel J, et al. Hyperbaric oxygenation increases available oxygen and resistance to enzymatic digestion in accelerated corneal collagen crosslinking [J]. Transl Vis Sci Technol, 2025, 14(4): 13.
[19]	Tawfeek MMM, Ahmed H, Bor'i A, et al. Repeated sessions of PACK-CXL WA for the treatment of resistant bacterial keratitis: a retrospective study [J]. BMC Ophthalmol, 2023, 23(1): 333.
[20]	Davis SA, Bovelle R, Han G, et al. Corneal collagen cross-linking for bacterial infectious keratitis [J]. Cochrane Database Syst Rev, 2020, 6(6): Cd013001.
[21]	王旭，高芯，张玉光. 角膜胶原交联术治疗有严重感染的暴露性角膜炎 [J]. 中华眼外伤职业眼病杂志，2020，42(7)：536-540.
[22]	Shetty R, Nagaraja H, Jayadev C, et al. Collagen crosslinking in the management of advanced non-resolving microbial keratitis [J]. Br J Ophthalmol, 2014, 98(8): 1033-1035.
[23]	Bamdad S, Malekhosseini H, Khosravi A. Ultraviolet A/riboflavin collagen cross-linking for treatment of moderate bacterial corneal ulcers [J]. Cornea, 2015, 34(4): 402-406.
[24]	Hafezi F, Hosny M, Shetty R, et al. Pack-cxl vs. Antimicrobial therapy for bacterial, fungal, and mixed infectious keratitis: a prospective randomized phase 3 trial [J]. Eye Vis (Lond), 2022, 9(1): 1-11.
[25]	Papaioannou L, Miligkos M, Papathanassiou M. Corneal collagen cross-linking for infectious keratitis: a systematic review and meta-analysis [J]. Cornea, 2016, 35(1): 62-71.
[26]	贾桂祯，程梦雅，王林农. 角膜胶原交联术治疗角膜病的新进展 [J]. 中华实验眼科杂志，2020，38(3)：245-249.
[27]	Saini S, Singh S, Dwivedi K, et al. Photo-activated chromophore for infectious keratitis cross-linking and its efficacy as a treatment modality in managing microbial keratitis [J]. Indian J Ophthalmol, 2022, 70(5): 1571-1577.
[28]	Olshaker H, Achiron A, Chorny A, et al. Accelerated high fluence photoactivated chromophore for infectious keratitis-corneal cross-linking (PACK-CXL) at the slit lamp: a pilot study [J]. Front Pharmacol, 2023, 14: 1229095.
[29]	Achiron A, Elhaddad O, Regev T, et al. Pack cross-linking as adjuvant therapy improves clinical outcomes in culture-confirmed bacterial keratitis [J]. Cornea, 2022, 41(9): 1069-1073.
[30]	Hafezi F, Richoz O, Torres-Netto E, et al. Corneal cross-linking at the slit lamp [J]. J Refract Surg, 2021, 37(2): 78-82.
[31]	Bor′i A, El-Haig WM. Combined photoactivated chromophore for infectious keratitis-corneal collagen cross-linking (PACK-CXL) and therapeutic penetrating keratoplasty for resistant bacterial keratitis [J]. Clin Ophthalmol, 2022, 16: 273-279.
[32]	Kling S, Hufschmid FS, Torres-Netto EA, et al. High fluence increases the antibacterial efficacy of pack cross-linking [J]. Cornea, 2020, 39(8): 1020-1026.
[33]	Liu S, Fang S, Zhang L. Photoactivated chromophore-corneal cross-linking accelerates corneal healing in fungal keratitis: an updated meta-analysis [J]. Syst Rev, 2023, 12(1): 208.
[34]	Aiello F. Cornea on fire: PACK-CXL in the treatment of infectious keratitis [J]. Acta Ophthalmol, 2024, 102(S279): 1-10.
[35]	Barac IR, Artamonov AR, Baltä G, et al. Photoactivated chromophore corneal collagen cross-linking for infectious keratitis (PACK-CXL)——a comprehensive review of diagnostic and prognostic factors involved in therapeutic indications and contraindications [J]. J Pers Med, 2022, 12(11): 1907.
[36]	Antonopoulou NI, Spyropoulou MS, Papadakos SP, et al. Bridging gaps in corneal ulcer management: can photoactivated chromophore for infectious keratitis-corneal collagen cross-linking delay or replace therapeutic keratoplasty? [J]. World J Transplant, 2026, 16(1): 1-8.
[37]	Kowalska ME, Pot SA, Hartnack S. Photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL)——a scoping review based on preclinical studies [J]. Transl Vis Sci Technol, 2024, 13(7): 14.
[38]	Lu NJ, Koliwer-Brandl H, Hillen M, et al. High-fluence accelerated PACK-CXL for bacterial keratitis using riboflavin/uv-a or rose bengal/green in the ex vivo porcine cornea [J]. Transl Vis Sci Technol, 2023, 12(9): 14.
[39]	Marasini S, Zhang AC, Dean SJ, et al. Safety and efficacy of uv application for superficial infections in humans: a systematic review and meta-analysis [J]. Ocul Surf, 2021, 21: 331-344.
[40]	Knyazer B, Krakauer Y, Tailakh MA, et al. Accelerated corneal cross-linking as an adjunct therapy in the management of presumed bacterial keratitis: a cohort study [J]. J Refract Surg, 2020, 36(4): 258-264.
[41]	Kowalska M, Mischi E, Stoma S, et al. How modifications of corneal cross-linking protocols influence corneal resistance to enzymatic digestion and treatment depth [J]. Transl Vis Sci Technol, 2023, 12(5): 18.
[42]	严梦迪，黄锦海，王勤美，等. 角膜胶原交联中核黄素浓度检测方法的研究进展 [J]. 中华眼视光学与视觉科学杂志，2021，23(8)：636-640.
[43]	Knyazer B, Krakauer Y, Baumfeld Y, et al. Accelerated corneal cross-linking with photoactivated chromophore for moderate therapy-resistant infectious keratitis [J]. Cornea, 2018, 37(4): 528-531.
[44]	Lu NJ, Koliwer-Brandl H, Gilardoni F, et al. The antibacterial efficacy of high-fluence pack cross-linking can be accelerated [J]. Transl Vis Sci Technol, 2023, 12(2): 12.
[45]	Sepulveda-Beltran PA, Levine H, Altamirano DS, et al. Rose bengal photodynamic antimicrobial therapy: a review of the intermediate-term clinical and surgical outcomes [J]. Am J Ophthalmol, 2022, 243: 125-134.
[46]	Fiegler-Rudol J, Kapłon K, Kotucha K, et al. Hypocrellin-mediated pdt: a systematic review of its efficacy, applications, and outcomes [J]. Int J Mol Sci, 2025, 26(9): 4038.
[47]	Abdel-Radi M, Abdelmohsen N, Abdelmotaal H, et al. The effect of accelerated pulsed high-fluence corneal cross-linking on corneal endothelium; a prospective specular microscopy study [J]. BMC Ophthalmol, 2023, 23(1): 163.
[48]	Ehlers N, Hjortdal J, Nielsen K, et al. Riboflavin-UVA treatment in the management of edema and nonhealing ulcers of the cornea [J]. J Refract Surg, 2009, 25(9): S803-S806.
[49]	Yagci A, Palamar M, Polat Hilmioglu S, et al. Cross-linking treatment and corneal transplant in refractory acremonium keratitis: case report [J]. Exp Clin Transplant, 2016, 14(5): 580-583.

[1]	王鑫, 阎龙, 戴朝六. 人工智能化与个体化在肝癌微创外科的应用[J/OL]. 中华普外科手术学杂志(电子版), 2026, 20(04): 315-318.
[2]	吴禹锟, 项方政, 郑伏甫. 上尿路尿路上皮癌保肾策略新进展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2026, 20(04): 367-372.
[3]	郭任博, 邹本奎, 边家盛. 转移性激素敏感性前列腺癌治疗决策及展望[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2026, 20(04): 373-382.
[4]	杨龙雨禾, 王跃强, 卫娜, 杨剑兵, 招云亮, 马真, 田雨, 白蕾. 输尿管狭窄腔内治疗的研究进展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2026, 20(04): 463-467.
[5]	王杰艳, 胡博文, 曾小兰, 孙邓南, 梁辉. 电生理技术在泌尿外科中的应用和研究进展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2026, 20(04): 474-479.
[6]	张俊峰, 牛越, 陈鹏. 局部进展期肾细胞癌新辅助和辅助治疗策略的现实挑战与未来发展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2026, 20(03): 248-254.
[7]	陈海珊, 李琨. 前列腺癌接受雄激素剥夺治疗患者及其配偶二元应对与心理困扰的主客体效应分析[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2026, 20(03): 323-329.
[8]	曾桂能, 杨鹏辉, 刘荣. 表达IL-21的重组溶瘤流感病毒在胰腺癌中的抗肿瘤及免疫激活作用研究[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(03): 129-139.
[9]	黄霞, 张和平, 何永成. 机器学习驱动的IgA肾病精准治疗：疗效评估、预后预测及临床转化[J/OL]. 中华肾病研究电子杂志, 2026, 15(03): 166-169.
[10]	洪士皓, 杨昕. 个性化骨科手术中3D打印技术的临床应用与展望[J/OL]. 中华临床医师杂志(电子版), 2026, 20(04): 249-255.
[11]	席雅楠, 姚国栋, 郭秀珍, 高斌礼, 赵渊, 李婷, 钟李岩, 李梦倩. IDEAS模式对机器人辅助结直肠癌根治术患者康复结局的影响[J/OL]. 中华临床医师杂志(电子版), 2026, 20(04): 285-291.
[12]	齐洪武, 徐泽雨. 脑脓肿的临床诊治进展[J/OL]. 中华临床医师杂志(电子版), 2026, 20(04): 327-331.
[13]	中国卒中学会遗传学分会. 肯尼迪病诊断和管理中国专家共识2025[J/OL]. 中华脑血管病杂志(电子版), 2026, 20(03): 240-249.
[14]	辛伽伦, 卑红喆, 何佳, 鞠东升, 孙太欣, 马熙岳, 陈佳佳, 李振波, 王伟, 郭强, 张恒, 王杰, 姚力. 前循环急性大血管闭塞性轻型脑卒中患者行血管内治疗的临床疗效[J/OL]. 中华脑血管病杂志(电子版), 2026, 20(03): 280-286.
[15]	徐林, 简讯, 刘道权, 易东, 鄢华. 人工智能在心脑血管内介入诊疗中的应用进展——从单一影像模式到多模态影像融合[J/OL]. 中华脑血管病杂志(电子版), 2026, 20(03): 334-341.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Clinical research progress of the bacterial keratitis with photoactivated chromophore for infectious keratitis-corneal cross-linking

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Clinical research progress of the bacterial keratitis with photoactivated chromophore for infectious keratitis-corneal cross-linking