Abstract: Objective: To evaluate the efficacy and safety of a comprehensive treatment regimen based on intrastromal voriconazole injection in the treatment of deep stromal fungal keratitis in which the lesion has infiltrated more than half of the corneal stroma. Methods: This was a retrospective study. Sixty-two patients (62 eyes) with deep stromal fungal keratitis who underwent intrastromal voriconazole injection were selected at the Eye Hospital, Wenzhou Medical University from March 2013 to July 2017. Age, the diameter of the ulcer, cure rate, recurrence rate, complications, etc., were measured. All the patients were followed up for at least 6 months. Sixty-two patients were divided into an effective group (EGII) and an ineffective group (IGII) based on the effect of the pure intrastromal voriconazole injection. The data were analyzed by an independent samples t-test and Chi-square test. Results: The 62 patients had ulcer diameters ranging from 2.8 to 11.0 (5.5±2.1)mm. The time from onset to treatment for the 62 patients ranged from 2 days to 2 years (44.2±98.6)days. Six patients sought treatment more than half a year after onset, and the remaining 56 patients had an onset time of 21.2±13.6 days. All patients were followed up for 6 to 36 (10.5±7.5)months. Forty-two patients (42 eyes) were cured by pure intrastromal voriconazole injection, 1 patient (1 eye) underwent a corneal transplant to improve vision after intrastromal voriconazole injection was effective; 19 patients (19 eyes) underwent conjunctival flap coverage after the injection failed. Combined with conjunctival flap coverage, 11 eyes were cured, 8 eyes required corneal transplants, and 2 patients relapsed after corneal transplants. The cure rate of the comprehensive treatment regimen was 85.5%, and the recurrence rate was 3.2%. The EGII group had a smaller ulcer diameter than the IGII group, and the difference between the two groups was statistically significant (t=-2.199, P=0.032). There were no complications during or after the operation. Conclusions: Intrastromal voriconazole injection has a safe and beneficial effect on deep stromal fungal keratitis that does not respond to conventional drugs. For eyes with a wide range of lesions, the effect of pure intrastromal voriconazole injection was not good, but the cure rate can be improved when treatment is combined with conjunctival flap coverage.
吴思腾1 赵泽林1 潘瑜2 陈蔚1. 深基质真菌性角膜炎综合治疗方案的疗效评估[J]. 中华眼视光学与视觉科学杂志, 2020, 22(10): 750-755.
Siteng Wu1,Zelin Zhao1,Yu Pan2,Wei Chen1. The Effect of a Comprehensive Treatment Regimen for Deep Stromal Fungal Keratitis. Chinese Journal of Optometry Ophthalmology and Visual science, 2020, 22(10): 750-755. DOI: 10.3760/cma.j.cn115909-20191218-00332
Kaur IP, Rana C, Singh H. Development of effective ocularpreparations of antifungal agents. J Ocul Pharmacol Ther, 2008, 24(5): 481-493. DOI: 10.1089/jop.2008.0031.
[4]
O'Day DM, Head WS, Robinson RD, et al. Corneal penetration of topical amphotericin B and natamycin. Curr Eye Res, 1986, 5(11): 877-882. DOI: 10.3109/02713688609029240.
[5]
Austin A, Lietman T, Rose-Nussbaumer J. Update on the management of infectious keratitis. Ophthalmology, 2017, 124(11): 1678-1689. DOI: 10.1016/j.ophtha.2017.05.012.
[6]
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 Clin Microbiol, 2003, 41(8): 3623-3626. DOI: 10.1128/jcm.41.8.3623-3626.2003.
Prakash G, Sharma N, Goel M, et al. Evaluation of intrastromal injection of voriconazole as a therapeutic adjunctive for the management of deep recalcitrant fungal keratitis. Am J Ophthalmol, 2008, 146(1): 56-59. DOI: 10.1016/ j.ajo.2008.02.023.
[9]
Sharma N, Chacko J, Velpandian T, et al. Comparative evaluation of topical versus intrastromal voriconazole as an adjunct to natamycin in recalcitrant fungal keratitis. Ophthalmology, 2013, 120(4): 677-681. DOI: 10.1016/ j.ophtha.2012.09.023.
[10]
Kalaiselvi G, Narayana S, Krishnan T, et al. Intrastromal voriconazole for deep recalcitrant fungal keratitis: A case series. Br J Ophthalmol, 2015, 99(2): 195-198. DOI: 10.1136/ bjophthalmol-2014-305412.
[11]
Sharma N, Agarwal P, Sinha R, et al. Evaluation of intrastromal voriconazole injection in recalcitrant deep fungal keratitis: Case series. Br J Ophthalmol, 2011, 95(12): 1735-1737. DOI: 10.1136/bjo.2010.192815.
[12]
Siatiri H, Daneshgar F, Siatiri N, et al. The effects of intrastromal voriconazole injection and topical voriconazole in the treatment of recalcitrant Fusarium keratitis. Cornea, 2011, 30(8): 872-875. DOI: 10.1097/ICO.0b013e3182100993.
Neoh CF, Leung L, Vajpayee RB, et al. Treatment of Alternaria keratitis with intrastromal and topical caspofungin in combination with intrastromal, topical, and oral voriconazole. Ann Pharmacother, 2011, 45(5): e24. DOI: 10.1345/aph.1P586.
[15]
Tanure MA, Cohen EJ, Sudesh S, et al. Spectrum of fungal keratitis at Wills Eye Hospital, Philadelphia, Pennsylvania. Cornea, 2000, 19(3): 307-312. DOI: 10.1097/00003226- 200005000-00010.
Gugnani HC, Talwar RS, Njoku-Obi AN, et al. Mycotic keratitis in Nigeria. A study of 21 cases. Br J Ophthalmol, 1976, 60(9): 607-613. DOI: 10.1136/bjo.60.9.607.
Niki M, Eguchi H, Hayashi Y, et al. Ineffectiveness of intrastromal v-oriconazole for filamentous fungal keratitis. Clin Ophthalmol, 2014, 8(8): 1075-1079. DOI: 10.2147/OPTH. S63516.
[23]
Shen YC, Wang MY, Wang CY, et al. Pharmacokinetics of intracameral voriconazole injection. Antimicrob Agents Chemother, 2009, 53(5): 2156-2157. DOI: 10.1128/AAC.01125- 08.
[24]
Tu EY. Alternaria keratitis: Clinical presentation and resolution withtopical fluconazole or intrastromal voriconazole and topical caspofungin. Cornea, 2009, 28(1): 116-119. DOI: 10.1097/ ICO.0b013e31818225f8.
Ti SE, Scott JA, Janardhanan P, et al. Therapeutic keratoplasty for advanced suppurative keratitisl. Am J Ophthalmol, 2007, 143(5): 755-762. DOI: 10.1016/j.ajo.2007.01.015.
Xie L, Hu J, Shi W. Treatment failure after lamellar keratoplasty for fungal keratitis. Ophthalmology, 2008, 115(1): 33-36. DOI: 10.1016/j.ophtha.2007.03.072.