山东大学耳鼻喉眼学报 ›› 2022, Vol. 36 ›› Issue (5): 51-57.doi: 10.6040/j.issn.1673-3770.0.2021.303

• 论著 • 上一篇    

加速型角膜胶原交联术治疗真菌性角膜炎的临床研究

王旭,高芯,张玉光   

  1. 济南市第二人民医院 眼科, 山东 济南 250001
  • 发布日期:2022-09-20
  • 通讯作者: 张玉光. E-mail:wangxuzou@126.com

Clinical study of accelerated corneal collagen crosslinking in the treatment of fungal keratitis

WANG Xu, GAO Xin, ZHANG Yuguang   

  1. Department of Ophthalmology, Jinan Second People's Hospital, Jinan 250001, Shandong, China
  • Published:2022-09-20

摘要: 目的 评价角膜胶原交联术(CXL)治疗真菌性角膜炎的安全性和临床效果。 方法 对2017年1月-2019年12月期间济南市第二人民医院眼表疾病科确诊为“真菌性角膜炎”的患者92例(92眼),进行CXL治疗(观察组);同时回顾性分析2016年1月~2017年2月本院真菌性角膜炎单纯应用药物治疗的患者47例(47眼)的临床资料(对照组)。入组标准:病变深度<角膜厚度2/3;浅层的角膜溃疡,病变未累及的正常角膜厚度>400 μm;病变直径在3~6 mm范围、病变位置均偏离或少量影响瞳孔区;共聚焦显微镜可见真菌菌丝,真菌培养结果为镰刀菌。对两组治疗效果进行对比分析。 结果 观察组在术后2周开始,最佳矫正视力有显著改善,治疗效果优于对照组,差异有统计学意义(P<0.001);术后3个月最佳矫正视力较术前有显著提高,效果优于对照组,差异有统计学意义(P<0.001);观察组治疗2周后所有患眼的病变范围均保持稳定或缩小,术后3个月时,全部患眼病变区域均形成云翳,检查上皮愈合良好;观察组术后2周和术后1个月的真菌检出阳性率明显低于对照组,两组差异有统计学意义(P<0.001);随访期间,观察组所有患者均无真菌性疾病复发,且无并发症出现。 结论 针对范围较小、偏中心的真菌性角膜炎,CXL可以显著缩短病程,提高视力,是一种安全有效的治疗方法。

关键词: 角膜, 胶原交联术, 真菌, 角膜炎, 镰刀菌

Abstract: Objective To evaluate the safety and effectivity of corneal collagen cross-linking(CXL)in the treatment of fungal keratitis. Methods In the experimental group, 92 patients(92 eyes)with “fungal keratitis” were treated with CXL from January 2017 to December 2019, whereas in the control group, clinical data of 47 patients(47 eyes)(control group)with fungal keratitis whoreceiveddrug treatment alone in our hospital from January 2016 to February 2017 were retrospectively analyzed. The inclusion criteria were as follows: lesion depth <2/3 of the corneal thickness,superficial corneal ulcer with a normal corneal thickness >400 μm, lesiondiameter between 3-6 mm, deviation or slight affectation of the pupil area due to the location of the lesion,fungi hyphae on confocal microscopy,and positive Fusarium resultson fungal culture. Therapeutic effects were compared and analyzed between the two groups. Results At 2 weeks postoperatively, the best corrected visual acuity significantly improved in the experimental group, showing a better treatment effect than that in the control group(P<0.001). At 3 months postoperatively, the best corrected visual acuity significantly improved as compared to preoperative findings, with a better treatment effect in the experimental group than that in the control group(P<0.001). In the experimental group, the lesion scope of all eyes remained stable orreduced after 2 weeks of treatment. At 3 months postoperatively, clouds were observed in the lesion area of all eyes with good epithelial healing. The positive rate of fungi was significantly lower in the experimental group than in the control group(P<0.001)at 2 weeks and 1 month postoperatively. During follow-up, all patients in the test group had no fungal recurrences and complications. Conclusion CXL is a safe and effective treatment for fungal keratitis cases with a small range and partial center, as it can significantly shorten the disease course and improve vision.

Key words: Corneal, Collagen crosslinking, Fungus, Keratitis, Fusarium

中图分类号: 

  • R779.6
[1] Ng JK, Fraunfelder FW, Winthrop KL. Review and update on the epidemiology,clinical presentation,diagnosis, and treatment of fungal keratitis[J]. Curr Fungal Infect Rep, 2013, 7(4): 293-300. doi:10.1007/s12281-013-0163-9.
[2] 谢立信. 我国角膜基础和临床研究的现状及发展[J]. 中华眼科杂志, 2010, 46(10): 883-887. doi:10.3760/cma.j.issn.0412-4081.2010.10.003. XIE Lixin. Advancesin basic and clinical cornealresearch[J]. Chinese Journal of Ophthalmology, 2010, 46(10): 883-887. doi:10.3760/cma.j.issn.0412-4081.2010.10.003.
[3] Hu LT, du ZD, Zhao GQ, et al. Role of TREM-1 in response to Aspergillus fumigatus infection in corneal epithelial cells[J]. Int Immunopharmacol, 2014, 23(1): 288-293. doi:10.1016/j.intimp.2014.09.011.
[4] 蔡志刚,夏泽梅. 穿透性角膜移植术治疗真菌性角膜炎的临床观察[J]. 临床和实验医学杂志, 2012, 11(10): 767-768. CAIZhigang, XIAZemei. Clinical study on effect of penetrating keratoplasty in treatment of fungal keratitis[J]. Journal of Clinicaland Experimental Medicine, 2012, 11(10): 767-768.
[5] 史伟云,谢立信. 关注我国首个生物工程角膜的临床应用[J]. 中华眼科杂志, 2016, 52(3): 161-163. doi:10.3760/cma.j.issn.0412-4081.2016.03.001. SHI Weiyun, XIE Lixin. Focus on the clinical application of the first artificial bioengineered cornea in China[J]. Chinese Journal of Ophthalmology, 2016, 52(3): 161-163. doi:10.3760/cma.j.issn.0412-4081.2016.03.001.
[6] 谢立信,晋秀明,李绍伟,等. 穿透性角膜移植治疗真菌性角膜溃疡穿孔的疗效评价[J]. 中国实用眼科杂志,2002, 20(6): 453-455. doi:10.3760/cma.j.issn.1006-4443.2002.06.019. XIE Lixin, JIN Xiuming, LI Shaowei, et al. Thetherapeutic effects of penetrating keratoplasty onperforatedfungalkeratitiswith corneal perforation[J]. Chinese Journal of Practical Opht, 2002, 20(6): 453-455. doi:10.3760/cma.j.issn.1006-4443.2002.06.019.
[7] Schnitzler E, Sporl E, Seiler T. Crosslinking of the corneal collagen by UV-radiation with riboflavin for the mode of treatment melting ulcera of the cornea, first results of four patients[J]. Klinische Monatsblatter Fur Augenheilkunde, 2000, 217(3): 190-193.
[8] 丁刚,高芯,位宁,等. 硝酸银涂布治疗真菌性角膜炎的经验[J]. 中华眼外伤职业眼病杂志, 2020, 42(8): 624-627. doi:10.3760/cma.j.cn116022-20191210-00406. DING Gang, GAO Xin, WEI Ning, et al. Experience of local infriction of silver nitrate for the treatment of fungal keratitis[J]. Chinese Journal of Ocular Trauma and Occupational Eye Disease, 2020, 42(8): 624-627. doi:10.3760/cma.j.cn116022-20191210-00406.
[9] Thomas PA, Kaliamurthy J. Mycotic keratitis: epidemiology, diagnosis and management[J]. Clin Microbiol Infect, 2013, 19(3): 210-220. doi:10.1111/1469-0691.12126.
[10] 陈蔚,张京娜,孙莉,等. 光学全厚板层角膜移植术治疗真菌性角膜炎的初步探讨[J]. 眼视光学杂志, 2009, 11(4): 285-289. doi:10.3760/cma.j.issn.1674-845X.2009.04.013. CHEN Wei, ZHANG Jingna, SUN Li, et al. Preliminary investigation of optical full-thickness lamellar keratoplasty for fungal keratitis[J]. Chinese Journal of Optometry Ophthalmology and Visual Science, 2009, 11(4): 285-289. doi:10.3760/cma.j.issn.1674-845X.2009.04.013.
[11] Tsugita A, Okada Y, Uehara K. Photosensitized inactivation of ribonucleic acids in the presence of riboflavin[J]. Biochim Biophys Acta, 1965, 103(2): 360-363. doi:10.1016/0005-2787(65)90182-6.
[12] Martins SA, Combs JC, Noguera G, et al. Antimicrobialefficacy of riboflavin/UVA combination(365 nm)in vitro for bacterial and fungal isolates: apotential new treatment for infectious keratitis[J]. Invest Ophthalmol Vis Sci, 2008, 49(8): 3402-3408. doi:10.1167/iovs.07-1592.
[13] Özdemir HB, Kalkancı A, Bilgihan K, et al. Comparison of corneal collagen cross-linking(PACK-CXL)and voriconazole treatments in experimental fungal keratitis[J]. Acta Ophthalmol, 2019, 97(1): e91-e96. doi:10.1111/aos.13829.
[14] 潘士印,安娜,肖湘华,等. 角膜胶原交联方法联合那他霉素抗真菌效果研究[J]. 国际眼科杂志, 2019, 19(1): 14-20. doi:10.3980/j.issn.1672-5123.2019.1.03. PAN Shiyin, AN Na, XIAO Xianghua, et al. Antifungaleffectofcombinedapplication of corneal collagen cross-linkingand natamycin[J]. International Eye Science, 2019, 19(1): 14-20. doi:10.3980/j.issn.1672-5123.2019.1.03.
[15] 朱子芊. 角膜胶原交联治疗真菌性角膜炎的实验性研究[D]. 郑州: 郑州大学, 2018. ZHU Ziqian. Antimicrobialefficacyof corneal cross-linkingin vitro andin vivo for Fusarium solani: a potential new treatment for fungal keratitis[D]. Zhengzhou: Zhengzhou University, 2018.
[16] Ashar JN, Vadavalli PK. Long-term results of riboflavin ultraviolet A cornealcollagen cross-linking for Keratoconus in Italy: the Siena eye cross study. Am J Ophthalmol, 2010, 150(4):588[J]. doi:10.1016/j.ajo.2010.06.032.
[17] Al-Sabai N, Koppen C, Tassignon MJ. UVA/riboflavin crosslinking as treatment for corneal melting[J]. Bull Soc Belge Ophtalmol, 2010(315): 13-17.
[18] Spoerl E, Mrochen M, Sliney D, et al. Safety of UVA-riboflavin cross-linking of the cornea[J]. Cornea, 2007, 26(4): 385-389. doi:10.1097/ICO.0b013e3180334f78.
[19] 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. doi:10.1016/s0002-9394(02)02220-1.
[20] 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. doi:10.3760/cma.j.cn116022-20191228-00452. WANG Xu, GAO Xin, ZHANG Yuguang. Collagen cross-linking for the treatment of exposure keratitis with severe infection[J]. Chinese Journal of Ocular Trauma and Occupational Eye Disease, 2020, 42(7): 536-540. doi:10.3760/cma.j.cn116022-20191228-00452.
[21] Goodrich RP. The use of riboflavin for the inactivation of pathogens in blood products[J]. Vox Sang, 2000, 78(Suppl 2): 211-215.
[22] Khandelwal SS, Randleman JB. Current and future applications of corneal cross-linking[J]. Curr Opin Ophthalmol, 2015, 26(3): 206-213. doi:10.1097/ICU.0000000000000146.
[23] Gopinathan U, Ramakrishna T, Willcox M, et al. Enzymatic, clinical and histologic evaluation of corneal tissues in experimental fungal keratitis in rabbits[J]. Exp Eye Res, 2001, 72(4): 433-442. doi:10.1006/exer.2000.0971.
[24] MacFie A, Hagan E, Zhitkovich A. Mechanism of DNA-protein cross-linking by chromium[J]. Chem Res Toxicol, 2010, 23(2): 341-347. doi:10.1021/tx9003402.
[25] Bilgihan K, Kalkanci A, Ozdemir HB, et al. Evaluation of antifungal efficacy of 0.1% and 0.25% riboflavin with UVA: acomparative in vitrostudy[J]. Curr Eye Res, 2016, 41(8): 1050-1056. doi:10.3109/02713683.2015.1088956.
[26] Wei AJ, Wang KD, Wang Y, et al. Evaluation of corneal cross-linking as adjuvant therapy for the management of fungal keratitis[J]. Albrecht Von Graefes Arch Fur Klinische Und Exp Ophthalmol, 2019, 257(7): 1443-1452. doi:10.1007/s00417-019-04314-1.
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