| ObjectiveTo determine the clinical characteristics and pathogens of severe fungal corneal ulcer in the tropical areas of China,and to investigate the therapeutic effects of drugs and surgical interventions on severe fungal corneal ulcer.Materials and Methods1.Cases with severe fungal corneal ulcer presenting to Hainan Eye Hospital from 2014 to October 2019 were enrolled,and their clinical characteristics,pathogenic fungi,diagnosis and treatment were collected and analyzed.2.Since Fusarium solani is the most common pathogenic fungus for severe fungal corneal ulcer in tropical areas of China.In this study,twenty-four strains of fusarium solani isolated from corneas of patients with severe fungal corneal ulcer were adopted.The minimum inhibitory concentration(MIC)of fluconazole,natamycin,amphotericin B,voriconazole and cyclosporine A on fusarium solani were detected by CLSI M27-A3 microdilution method.The in vitro antifungal effects of cyclosporine A combined with fluconazole,natamycin,amphotericin B or voriconazole respectively were evaluated by checkerboard microdilution method.3.Forty-nine patients diagnosed with severe fungal corneal ulcer but did not respond to anti-fungal drugs were randomly divided into 4 groups: Control group(14 patients),corneal collagen crosslinking(CXL)group(12 patients),Conjunctival Flap Covering(CFC)group(12patients),CFC Combined with CXL(CFC+CXL)Group(11 patients).All groups of patients received anti-fungal drug treatment.And corresponding surgical procedures were adopted in each group except for the Control Group.Slit lamp examination and microscopy,corneal sodium fluorescein staining,intraocular pressure,best corrected vision acuity,in vivo confocal microscopy and anterior segment optical coherence tomography(AS-OCT)were accessed before surgery and postoperatively after the first week,first month of surgery.The therapeutic effects of treatment strategies in four groups were compared.Result1.In the study,there were 456 patients identified with severe fungal corneal ulcer,most of which were male farmers aged at 50-60 years with the popular onset period from January to March.The hyphae positivity rate by in vivo confocal microscopy was the highest,followed by corneal fungal culture,and corneal fungal smear was the lowest.Fusarium solani(80 cases,44.69%,)was found as the most common pathogenic fungi,followed by non-sporing fungi(35 cases,19.55%)and aspergillus(14 cases,7.82%).Among them,fusarium solani strain was most sensitive to voriconazole(50%)but resistant to fluconazole(100%).Corneal infections could be suppressed simply by anti-fungal drugs treatment among 198 patients.A total of258 patients underwent surgical treatment,of which the overall effective rate of penetrating keratoplasty,lamellar keratoplasty and conjunctival flap covering surgery was 92.73%(51/55),100%(4/4)and 76.77%(152/198),respectively.All patients with eviseration and orbital implant procedures were well healed.2.In vitro drug sensitivity test found that the MIC of cyclosporine A,fluconazole,voriconazole,natamycin and amphotericin B against fusarium solani was 32?512 ?g/m L,8 ? 512 ?g/m L,1 ? 8 ? g/m L,2 ? 8 ? g/m L and 1 ? 4 ? g/m L,respectively.Cyclosporine A combined with voriconazole treatment exerted antagonistic effects on 12.5% of the strains(n=24).Whereas cyclosporine A combined and natamycin treatment did not shown additional relevance.Cyclosporine A combined with fluconazole therapy exhibited slight synergistic effect(FICI=0.5)on 87.5% of the strains(n=24),while cyclosporine had a synergistic effect with amphotericin B on 33.3% of the strains(n=24).3.The overall severity score of ulcer lesion in CXL group at one month after surgery was significantly lower than that before surgery,compared with the control group.The neovascularization of CXL group one month after surgery was obviously promoted than that before surgery,but not significantly different from the control group.Visual acuity of CXL group did not significantly improve within one month after surgery,and no significantly difference was found compared with control group.In terms of perforation,there was no statistically significant difference in perforation rate and perforation timing between CXL group and control group.The infiltration depth and density of hyphal in CXL patients at one month after surgery significantly decreased compared with that before surgery.Postoperative dissolution and perforation of conjunctival flaps occurred in 4 patients from CFC group and 3patients from CFC+CXL Group after surgery.There was no significant difference in length of hospital stay between the two groups.In addition,the therapeutic effects were not significantly different among the four groups.Conclusion1.In this study,the top three pathogenic fungi causing severe fungal corneal ulcer in tropical areas of China were fusarium solani(44.69%),non-sporing fungus(19.55%)and aspergillus(7.82%),among which the high incidence of non-sporing fungus infection was related to the tropical climate in Hainan.2.The in vitro drug sensitivity test on Fusarium Solani suggested that cyclosporine A exerted low sensitivity when applied alone,while combined with voriconazole or natamycin respectively did not improve the sensitivity neither.But the combination of cyclosporine A and amphotericin B or fluconazole respectively partially improved the sensitivity to fusarium solani.3.For patients with severe fungal corneal ulcer but do not respond to drug treatment,keratoplasty is proved to be the safest and most effective therapeutic strategy.4.While it might not significantly reduce the occurrence of ulcer perforation. |
PDF Full Text Request