重视真菌性角膜炎个性化手术治疗的研究

doi:10.3877/cma.j.issn.2095-2007.2018.01.001

真菌性角膜炎是由致病真菌感染引起的致盲率极高的一种角膜病变。真菌性角膜炎在我国发病率较高，临床上以农民、工人等弱势群体更为多见。由于就诊条件相对较差，导致病情延误，且因缺乏特异性的抗真菌药物，真菌性角膜炎的致盲率呈现出逐年上升趋势。故患者在临床确诊为真菌性角膜炎后，医师应及时给予药物治疗。若药物治疗无效时，应根据角膜炎病灶的位置、大小、深度、病情进展情况、真菌菌种培养结果及患者经济情况等多方面因素综合考虑，及时制定个体化的手术治疗方案，以达到最佳的预后效果。

关键词: 角膜疾病, 眼内感染, 真菌性, 角膜炎, 治疗

Fungal keratitis is a kind of keratopathy with high blindness caused by pathogenic fungi infection. The incidence of fungal keratitis in China is high, and more disadvantaged groups, such as farmers and workers, are more common in our country. The blindness rate of fungal keratitis is increasing year by year due to the relatively poor visiting condition and the delayed condition. The patients in the clinical diagnosis of fungal keratitis, should be given prompt medical treatment, if drug therapy, should be based on the location of the lesion, keratitis size, depth and the progress of the disease, fungal culture factors and the economic situation of patients considering surgical treatment timely, individualized, to to achieve the best prognosis.

Key words: Corneal disease, Intraocular infection, Fungal, Keratitis, Treatment

图1 真菌性角膜溃疡患者行前房注药术前后不同时间点裂隙灯显微镜检查的对比图像　A图为前房注药术前裂隙灯显微镜检查图；B　图为前房注药术后一周时裂隙灯显微镜检查图；C　图为前房注药术后1个月时裂隙灯显微镜检查图；D　图为前房注药术后3个月时裂隙灯显微镜检查图

图2 真菌性角膜溃疡患者行板层角膜移植术前后裂隙灯显微镜检查的对比图像　经共聚焦显微镜检查可见患眼真菌菌丝呈水平方向生长，故选择板层角膜移植术，A图为板层角膜移植术前裂隙灯显微镜检查图；B　图为板层角膜移植术后1个月时裂隙灯显微镜检查图

图3 真菌性角膜溃疡伴前房积脓患者穿透性角膜移植术前后不同时间点裂隙灯显微镜检查的对比图像经共聚焦显微镜检查可见患眼真菌菌丝呈垂直方向生长，故选择穿透性角膜移植术。A图为穿透性角膜移植术前裂隙灯显微镜检查图；B　图为穿透性角膜移植术后一周时裂隙灯显微镜检查图；C　图为穿透性角膜移植术后1个月时裂隙灯显微镜检查图；D　图为穿透性角膜移植术后6个月时裂隙灯显微镜检查图

图4 真菌性角膜溃疡伴前房积脓并行穿透性角膜移植术后真菌复发患者行眼球前段重建术前后裂隙灯显微镜检查的对比图像　A图为穿透性角膜移植术前裂隙灯显微镜检查图；B　图为穿透性角膜移植术后真菌复发裂隙灯显微镜检查图；C　图为眼球前段重建术后裂隙灯显微镜检查图，　达到了保住眼球的效果

图5 重症真菌性角膜溃疡患者自体结膜瓣遮盖术后行穿透性角膜移植术前后不同时间点裂隙灯显微镜检查的对比图像　A图为自体结膜瓣遮盖术后裂隙灯显微镜检查图；B　图为自体结膜瓣遮盖术后3个月时裂隙灯显微镜检查图，　此时结膜瓣稳定，但未行穿透性角膜移植术；C图为穿透性角膜移植术后1周时裂隙灯显微镜检查图；D　图为穿透性角膜移植术后3个月时裂隙灯显微镜检查图，　未发生排斥反应

图6 真菌性角膜溃疡穿孔患者自体结膜瓣遮盖术前后裂隙灯显微镜检查的对比图像　A图为自体结膜瓣遮盖术前裂隙灯显微镜检查图；B　图为自体结膜瓣遮盖术后裂隙灯显微镜检查图，　患者术后裸眼视力达到0.4

图7 真菌性角膜溃疡患者紫外光核黄素角膜胶原交联术前后裂隙灯显微镜和共聚焦显微镜检查的对比图像　1A、2A、3A图分别为为紫外光核黄素角膜胶原交联术前、术后1周及术后1个月时的裂隙灯显微镜检查图；1B　图为紫外光核黄素角膜胶原交联术前共聚焦显微镜检查图，　图中可见大量菌丝，2B图为紫外光核黄素角膜胶原交联术后1周时共聚焦显微镜检查图，　图中可见溃疡逐渐修复，菌丝逐渐减少，3B图为紫外光核黄素角膜胶原交联术后1个月时共聚焦显微镜检查图，　图中可见角膜溃疡基本愈合，共聚焦显微镜未见菌丝，仅见纤维瘢痕增生

图8 真菌性角膜溃疡患者紫外光核黄素角膜胶原交联术前后不同时间点裂隙灯显微镜检查的对比图像A图为紫外光核黄素角膜胶原交联术前裂隙灯显微镜检查图；B　图为紫外光核黄素角膜胶原交联术后1周时裂隙灯显微镜检查图；C　图为紫外光核黄素角膜胶原交联术后1个月时裂隙灯显微镜检查图；D　图为紫外光核黄素角膜胶原交联术后3个月时裂隙灯显微镜检查图；E　图为紫外光核黄素角膜胶原交联术后6个月时裂隙灯显微镜检查图；F　图为紫外光核黄素角膜胶原交联术后1年时裂隙灯显微镜检查图；G　图为紫外光核黄素角膜胶原交联术后2年时裂隙灯显微镜检查图；H　图为紫外光核黄素角膜胶原交联术后3年时裂隙灯显微镜检查图

[1]	谢立信. 真菌性角膜炎[J]. 中国眼耳鼻喉科杂志，2005，39(4):638-640.
[2]	钟文贤，谢立信. 真菌性角膜炎发病机制的研究进展[J]. 中华眼科杂志，2007，43(4):381-384.
[3]	李娜，赵桂秋. 真菌性角膜炎免疫机制研究进展[J]. 中华眼科杂志，2011，47(4):378-381.
[4]	王丽娅，许中中，张俊杰，等. 局部应用伏立康唑治疗真菌性角膜炎的临床观察[J]. 中华眼科杂志，2016，52(9):657-662.
[5]	王巧萍，汤学荣. 伊曲康唑联合氟康唑治疗真菌性角膜溃疡[J]. 中华眼视光学与视觉科学杂志，2002，4(1):74.
[6]	Jeng BH. Challenges in the Management of Fungal Keratitis[J]. Jama Ophthalmol, 2017, 135(6):525-526.
[7]	Schein OD. Evidence－Based Treatment of Fungal Keratitis[J]. Jama Ophthalmol, 2016, 134(12):1372-1373.
[8]	Prajna NV, Krishnan T, Rajaraman R, et al. Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial Ⅱ (MUTT Ⅱ): A Randomized Clinical Trial[J]. Jama Ophthalmol, 2016, 134(12):1365-1372.
[9]	Florcruz NV, IP Jr. Medical interventions for fungal keratitis[J]. Cochrane Database Syst Rev, 2012, 130(1):CD004241.
[10]	史伟云，王婷. 我国真菌性角膜炎诊断和治疗中的几个问题[J]. 中华眼科杂志，2013，49(1):2-5.
[11]	何彦，潘志强. 真菌性角膜炎的诊治进展[J]. 中华眼科杂志，2009，45(9):860-864.
[12]	Diekema DJ, Messer SA, Hollis RJ, et al. Activities of Caspofungin, Itraconazole, Posaconazole, Ravuconazole, Voriconazole, and Amphotericin B against 448 Recent Clinical Isolates of Filamentous Fungi[J]. Journal of Clinical Microbiology, 2003, 41(8):3623-3626.
[13]	Espinel－Ingroff A. Comparison of In vitro activities of the new triazole SCH56592 and the echinocandins MK－0991 (L－743，872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeasts[J]. Journal of Clinical Microbiology, 1998, 36(10):2950-2956.
[14]	Pfaller MA, Messer SA, Hollis RJ, et al. Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp. and other filamentous fungi: report from SENTRY Antimicrobial Surveillance Pr[J]. Antimicrobial Agents & Chemotherapy, 2002, 46(4):1032-1037.
[15]	Misra R, Malik A, Singhal S. Comparison of the activities of amphotericin B, itraconazole, and voriconazole against clinical and environmental isolates of Aspergillus species.[J]. Indian Journal of Pathology & Microbiology, 1900, 54(1):112-116.
[16]	李连洲. 角膜病灶刮片检查在角膜炎中的应用评价[J]. 中外医学研究，2013，11(32):53-54.
[17]	谢立信，李绍伟，史伟云. 共焦显微镜在真菌性角膜炎临床诊断中的应用[J]. 中华眼科杂志，1999，35(1):7-9.
[18]	史伟云，牛晓光，王富华，等. 真菌性角膜炎药物治疗后转归的共焦显微镜观察[J]. 中华眼科杂志，2005，41(7):614-619.
[19]	Chidambaram JD, Prajna NV, Larke N, et al. In vivo confocal microscopy appearance of Fusarium and Aspergillus species in fungal keratitis[J]. Br J Ophthalmol, 2017, 101(8):1119-1123.
[20]	Ledbetter EC, Norman ML, Starr JK. In vivo confocal microscopy for the detection of canine fungal keratitis and monitoring of therapeutic response[J]. Veterinary Ophthalmology, 2015, 19(3):220-229.
[21]	董晓光，谢立信. 穿透性角膜移植治疗真菌性角膜溃疡的评价[J]. 中华眼科杂志，1999，35(5):386-387.
[22]	胡建章，谢立信. 真菌性角膜炎板层角膜移植术后复发的临床研究[J]. 中华眼科杂志，2008，44(2):111-115.
[23]	史伟云，李绍伟，谢立信. 板层角膜移植术治疗真菌性角膜炎的临床疗效分析[J]. 中华眼科杂志，2002，38(6):347-350.
[24]	陆勤康，童奇湖，赖晓明，等. 深板层角膜移植术与穿透性角膜移植术治疗真菌性角膜溃疡的视功能疗效观察[J]. 中华眼科杂志，2011，47(5):423-426.
[25]	Alshehri JM, Caballerolima D, Hillarby MC, et al. Evaluation of Corneal Cross－Linking for Treatment of Fungal Keratitis: Using Confocal Laser Scanning Microscopy on an Ex Vivo Human Corneal Model[J]. Invest Ophthalmol Vis Sci, 2016, 57(14):6367-6373.
[26]	Garg P, Roy A, Roy S. Update on fungal keratitis[J]. Current Opinion in Ophthalmology, 2016, 27(4):333-339.
[27]	Uddaraju M, Mascarenhas J, Das MR, et al. Corneal cross－linking as an adjuvant therapy in the management of recalcitrant deep stromal fungal keratitis: a randomized trial[J]. Am J Ophthalmol, 2015, 160(1):131-134.
[28]	王殿强，董燕玲，赵靖，等. 改良角膜溃疡清创术联合抗真菌药物治疗真菌性角膜溃疡[J]. 眼科，2010，19(3):166-170.
[29]	张自平. 碘伏烧灼联合氟康唑那他霉素治疗真菌性角膜溃疡[J]. 黑龙江医药，2009，22(6):871-872.
[30]	Kamoshita M, Matsumoto Y, Nishimura K, et al. Wickerhamomyces anomalus, fungal keratitis responds to topical treatment with antifungal micafungin[J]. J Infect Chemother, 2015, 21(2):141-143.
[31]	Hu J, Zhang J, Li Y, et al. A Combination of Intrastromal and Intracameral Injections of Amphotericin B in the Treatment of Severe Fungal Keratitis[J]. J Ophthalmol, 2016, 2016(4):3436415.
[32]	Kalaiselvi G, Narayana S, Krishnan T, et al. Intrastromal voriconazole for deep recalcitrant fungal keratitis: a case series[J]. Br J Ophthalmol, 2015, 99(2):195-198.
[33]	Sharma N, Chacko J, Velpandian T, et al. Comparative Evaluation of Topical versus Intrastromal Voriconazole as an Adjunct to Natamycin in Recalcitrant Fungal Keratitis[J]. Ophthalmology, 2013, 120(4):677-681.
[34]	Sharma N, Agarwal P, Sinha R, et al. Evaluation of intrastromal voriconazole injection in recalcitrant deep fungal keratitis: case series[J]. Br J Ophthalmol, 2011, 95(12):1735-1737.
[35]	Haddad RS, El－Mollayess GM. Combination of Intracameral and Intrastromal Voriconazole in the Treatment of Recalcitrant Acremonium Fungal Keratitis[J]. Middle East African Journal of Ophthalmology, 2012, 19(2):265-268.
[36]	Sharma N, Sankaran P, Agarwal T, et al. Evaluation of Intracameral Amphotericin B in the Management of Fungal Keratitis: Randomized Controlled Trial[J]. Ocular Immunology & Inflammation, 2015, 24(5):493-497.
[37]	Shen YC, Wang CY, Tsai HY, et al. Intracameral voriconazole injection in the treatment of fungal endophthalmitis resulting from keratitis[J]. Am J Ophthalmol, 2010, 149(6):916-921.
[38]	Yoon KC, Jeong IY, Im SK, et al. Therapeutic effect of intracameral amphotericin B injection in the treatment of fungal keratitis[J]. Cornea, 2007, 26(7):814-818.
[39]	鹿秀海，高彦，张莉，等. 真菌性角膜炎334例的病原学分析[J]. 中华眼科杂志，2013，49(1):12-15.
[40]	国洪昌，刘勇，曲红. 桥式结膜瓣遮盖治疗真菌性角膜炎的临床观察[J]. 中国实用眼科杂志，2008，26(3):276-277.
[41]	刘顺慧，王军. 清创术加结膜瓣遮盖治疗真菌性角膜溃疡[J]. 中华眼外伤职业眼病杂志，2014，36(6):452-454.
[42]	张进. 病灶清创及结膜瓣遮盖术治疗真菌性角膜溃疡[J]. 中华眼外伤职业眼病杂志，2015，37(8):627-629.
[43]	吴护平，罗顺荣，董诺，等. 角膜胶原交联联合药物治疗感染性角膜疾病的临床研究[J]. 中华眼科杂志，2013，49(10):890-895.
[44]	郝兆芹，宋金鑫，吴洁，等. 角膜交联对真菌性角膜溃疡的治疗作用[J]. 中华实验眼科杂志，2014，32(9):802-806.
[45]	Spoerl E, Wollensak G, Seiler T. Increased resistance of crosslinked cornea against enzymatic digestion[J]. Current Eye Research, 2004, 29(1):35-40.
[46]	马小倩，刘苏冰，聂晓丽，等. 紫外光－核黄素胶原交联疗法治疗真菌性角膜溃疡临床观察[J]. 眼科新进展，2015，35(10):965-967.
[47]	Makdoumi K, Mortensen J, Crafoord S. Infectious Keratitis Treated With Corneal Crosslinking[J]. Cornea, 2010, 29(12):1353-1358.
[48]	Morn H, Malmsjö M, Mortensen J, et al. Riboflavin and ultraviolet a collagen crosslinking of the cornea for the treatment of keratitis[J]. Cornea, 2010, 29(1):102-107.
[49]	余继锋，黄一飞. 角膜交联疗法治疗角膜疾病的研究进展[J]. 中华眼科杂志，2010 ，46(5):472-475.
[50]	Vajpayee RB, Shafi SN, Maharana PK, et al. Evaluation of corneal collagen cross－linking as an additional therapy in mycotic keratitis[J]. Clinical & Experimental Ophthalmology, 2015, 43(2):103-107.
[51]	Martins SA, Combs JC, Noguera G, et al. Antimicrobial efficacy of riboflavin/UVA combination (365 nm) in vitro for bacterial and fungal isolates: a potential new treatment for infectious keratitis[J]. Invest Ophthalmol Vis Sci, 2008, 49(8):3402-3408.
[52]	Gupta A, Fontana J, Crowe C, et al. Emergence of Multidrug－Resistant Salmonella enterica Serotype Newport Infections Resistant to Expanded－Spectrum Cephalosporins in the United States[J]. Journal of Infectious Diseases, 2003, 188(11):1707-1716.
[53]	Khan YA, Kashiwabuchi RT, Martins SA, et al. Riboflavin and ultraviolet light a therapy as an adjuvant treatment for medically refractive Acanthamoeba keratitis: report of 3 cases[J]. Ophthalmology, 2011, 118(2):324-331.
[54]	Dever LL, Smith SM, Dejesus D, et al. Treatment of vancomycin－resistant Enterococcus faecium infections with an investigational streptogramin antibiotic (quinupristin/dalfopristin): a report of fifteen cases[J]. Microbial Drug Resistance, 1996, 2(4):407-413.
[55]	Matsumura SO, Louie L, Louie M, et al. Synergy testing of vancomycin－resistant Enterococcus faecium against quinupristin－dalfopristin in combination with other antimicrobial agents[J]. Antimicrobial Agents & Chemotherapy, 1999, 43(11):2776-2779.
[56]	Cupo－Abbott J, Holtom P, Rho JP. Focus on quinupristin/dalfopristin: An investigational streptogramin antibiotic for the treatment of multidrug－resistant gram－positive infections[J]. Formulary, 1998, 33(9):841-857.
[57]	Moellering RC, Linden PK, Reinhardt J, et al. The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin－resistant Enterococcus faecium. Synercid Emergency－Use Study Group[J]. J Antimicrob Chemother, 1999, 44(2):251-261.
[58]	Mcneil SA, Clark NM, Chandrasekar PH, et al. Successful Treatment of Vancomycin－Resistant Enterococcus faecium Bacteremia with Linezolid after Failure of Treatment with Synercid (Quinupristin/Dalfopristin)[J]. Clinical Infectious Diseases, 2000, 30(2):403-404.
[59]	Aeschlimann JR, Rybak MJ. Pharmacodynamic Analysis of the Activity of Quinupristin－Dalfopristin against Vancomycin－Resistant Enterococcus faecium with Differing MBCs via Time－Kill－Curve and Postantibiotic Effect Methods[J]. Antimicrobial Agents & Chemotherapy, 1998, 42(9):2188-2192.
[60]	Allen GP, Cha R, Rybak MJ. In Vitro Activities of Quinupristin－Dalfopristin and Cefepime, Alone and in Combination with Various Antimicrobials, against Multidrug－Resistant Staphylococci and Enterococci in an In Vitro Pharmacodynamic Model[J]. Antimicrobial Agents & Chemotherapy, 2002, 46(8):2606-2612.
[61]	Pavie J, Lefort A, Zarrouk V, et al. Efficacies of Quinupristin－Dalfopristin Combined with Vancomycin In Vitro and in Experimental Endocarditis Due to Methicillin－Resistant Staphylococcus aureus in Relation to Cross－Resistance to Macrolides, Lincosamides, and Streptogramin B－ Type Antibiotics[J]. Antimicrobial Agents & Chemotherapy, 2002, 46(9):3061-3064.
[62]	Nailor MD, Sobel JD. Antibiotics for gram－positive bacterial infection: vancomycin, teicoplanin, quinupristin/dalfopristin, oxazolidinones, daptomycin, telavancin, and ceftaroline[J]. Medical Clinics of North America, 2011, 95(4):723-742.
[63]	Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter－related infection: 2009 update by the infectious diseases society of America[J]. Chinese Journal of Infection & Chemotherapy, 2009, 49(1):1-45.
[64]	Lucet JC, Chevret S, Durandzaleski I, et al. Prevalence and risk factors for carriage of methicillin－resistant Staphylococcus aureus at admission to the intensive care unit: results of a multicenter study[J]. Archives of Internal Medicine, 2003, 163(2):181-188.
[65]	Caron F, Carbon C, Gutmann L. Triple－Combination Penicillin－Vancomycin－Gentamicin for Experimental Endocarditis Caused by a Moderately Penicillin－ and Highly Glycopeptide－Resistant Isolate of Enterococcus faecium[J]. Journal of Infectious Diseases, 1991, 168(3):888-893.

[1]	衣晓丽, 胡沙沙, 张彦. HER-2低表达对乳腺癌新辅助治疗疗效及预后的影响[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 340-346.
[2]	谭巧, 苏小涵, 侯令密, 黎君彦, 邓世山. 乳腺髓样癌的诊治进展[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 366-368.
[3]	杨小菁, 姜瑞瑞, 石玉香, 王静静, 李长天. 乳腺孤立性纤维性肿瘤一例[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 375-377.
[4]	王宏宇. 固定与活动平台假体在全膝关节置换术中的应用价值[J]. 中华关节外科杂志(电子版), 2023, 17(06): 871-876.
[5]	李善武, 叶永杰, 王兵, 王子呓, 银毅, 孙官军, 张大刚. 胫骨高位截骨与单髁置换的早期疗效比较[J]. 中华关节外科杂志(电子版), 2023, 17(06): 882-888.
[6]	彭旭, 邵永孚, 李铎, 邹瑞, 邢贞明. 结肠肝曲癌的诊断和外科治疗[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 108-110.
[7]	马伟强, 马斌林, 吴中语, 张莹. microRNA在三阴性乳腺癌进展中发挥的作用[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 111-114.
[8]	陈垚, 徐伯群, 高志慧. 改良式中间上入路根治术治疗甲状腺癌的有效性安全性研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 619-622.
[9]	邱朋, 邓正栋, 王剑明. 肝内胆管结石微创治疗策略[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 591-596.
[10]	杜锡林, 谭凯, 贺小军, 白亮亮, 赵瑶瑶. 肝细胞癌转化治疗方式[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 597-601.
[11]	钟广俊, 刘春华, 朱万森, 徐晓雷, 王兆军. MRI联合不同扫描序列在胃癌术前分期诊断及化疗效果和预后的评估[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 378-382.
[12]	陆志峰, 周佳佳, 梁舒. 虚拟现实技术在治疗弱视中的临床应用研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(08): 891-895.
[13]	李田, 徐洪, 刘和亮. 尘肺病的相关研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(08): 900-905.
[14]	岳瑞雪, 孔令欣, 郝鑫, 杨进强, 韩猛, 崔国忠, 王建军, 张志生, 孔凡庭, 张维, 何文博, 李现桥, 周新平, 徐东宏, 胡崇珠. 乳腺癌HER2蛋白表达水平预测新辅助治疗疗效的真实世界研究[J]. 中华临床医师杂志(电子版), 2023, 17(07): 765-770.
[15]	符梅沙, 周玉华, 李慧, 薛春颜. 淋巴细胞免疫治疗对复发性流产患者外周血T淋巴细胞亚群分布与PD1/PD-L1表达的影响及意义[J]. 中华临床医师杂志(电子版), 2023, 17(06): 726-730.

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

Pay attention to Study on individualized surgical treatment of fungal keratitis

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

Pay attention to Study on individualized surgical treatment of fungal keratitis