Objective To explore the optimal treatment for non-tuberculous mycobacterial keratitis (NTMK).Methods Experimental stndy.Fifty-one New Zealand white rabbits were inoculated with nontuberculous mycobacteria (NTM) to establish the animal model of NTMK.Eyes with NTMK were randomly divided into 7 groups and topically treated with amikacin (2.5％) (B),gatifloxacin (3％) (C),azithromycin (1％) (D),amikacin(2.5％) plus gatifloxacin(3％) (E),amikacin (2.5％) plus gatifloxacin (3％) combined with debridement (F),early lamellar keratoplasty (G) and balanced salt water (as a control) (A).All the drugs were administered 8 times per day within initial 7 days followed by 4 times per day after 1 week.The clinical manifestations of each rabbit were observed and recorded every week.The score of clinical manifestations before and after treatment does not meet the normal distribution,so it was presented by the median ± quantile interval and compared with rank sum test and SNK test.Fisher exact test was used to compare differences in the distribution of presenting the healing rate of keratitis.Results After 1 week treatment,six eyes were cured in group G,and none were cured in other groups,the scores of clinical manifestations of group B,C,D,E,F and G were 6 ± 4,8 ± 2,6 ± 4,8 ± 3,7 ± 4,3 ± 1,they were higher than that of group A (q =20.36,11.43,19.21,16.93,18.64,37.50,P ＜ 0.05).Atter 2 weeks,the scores of group B,C,E,F and G were higher than that of group A(q =23.50,16.71,15.21,12.43,30.87,P ＜ 0.05),and the healing rate of group G was higher than that of group A.After 3 weeks,the score of clinical manifestations of group B,D,F and G was higher than that of group A,and the healing rate of group F and G was higher than that of group A.After 4 weeks,the inflammation of group F and G were healed,and a little inflammation remained in the eye of group A.The score of clinical manifestations of group D,E,F and G was higher than that of group A.None was detected in the bacterial culture after 4 weeks.In histopathological examination,there were integrated and proliferated corneal epithelium,fibroblast cells proliferation in the eyes of experimental groups was found,while corneal cells edema,stroma degeneration and necrosis with lymphocytes and plasma cells in the ulcerated lesion in the corneal stromal of group A.Conclusions Amikacin,gatifloxacin or azithromycin is effective in arresting NTM,while antibiotic combined with debridement is more effective and early lamellar keratoplasty is the most rapid and thorough treatment of NTMK.%目的 探讨兔非结核分枝杆菌性角膜炎(NTMK)的最佳治疗方法.方法 实验研究.建立兔NTMK模型,51只兔(51只眼)抽签法随机分为7组,分别使用阿米卡星(B组)、加替沙星(C组)、阿奇霉素(D组)、阿米卡星联合加替沙星(E组)、药物(阿米卡星+加替沙星)联合清创(F组)及早期深板层角膜移植(G组)进行治疗,生理盐水(A组)作对照；观察治疗前后角膜浸润等变化,并对治疗4周后的角膜病灶进行细菌培养.各治疗组治疗前后的临床表现综合评分结果不符合正态分布,采用中位数±四分位数间距表示,秩和检验进行统计学分析,组间两两比较采用SNK法.角膜炎愈合率的两两比较采用Fisher精确概率法.结果 治疗后1周,G组有6例愈合,而其他各组无1例愈合,B、C、D、E、F、G组临床表现综合评分分别为6±4,8±2,6±4,8±3,7±4,3±1,与对照组11.86 ±3.24比较,差异均有统计学意义(q=20.36,11.43,19.21,16.93,18.64,37.50;均P＜ 0.05).治疗后2周,B、C、E、F、G组评分分别为2±6,4±6,5±8,4±4,0±1,与对照组相比差异均有统计学意义(q =23.50,16.71,15.21,12.43,30.87;均P＜0.05),且仅G组愈合率(7/9)高于对照组(P =0.003).治疗后3周,B、D、F、G组临床症状改善且仅F组及G组愈合率高于对照组.治疗后4周,F、G组的病灶全部愈合,而对照组大部分兔角膜仍留有轻度的炎症反应.治疗后4周,各组角膜细菌培养均为阴性；组织病理学观察大部分角膜组织HE染色可见角膜上皮完整、局限性增生,基质层纤维增厚,局部可见小血管组织；部分角膜组织(主要是A组)HE染色可见角膜组织细胞反应性水肿,基质变性坏死溃疡形成、病灶可见淋巴细胞、浆细胞浸润,并见新生血管形成及纤维组织增生.结论 阿米卡星、加替沙星、阿奇霉素均能控制NTMK,而药物联合清创术相对单纯药物治疗NTMK更为有效.
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