Risk Factors of Microbial Keratitis in Uganda: A Case Control Study

ABSTRACT

Purpose

Microbial keratitis (MK), is a frequent cause of sight loss worldwide, particularly in low and middle-income countries. This study aimed to investigate the risk factors of MK in Uganda.     

Decision-making in the Management of Microbial Keratitis

The successful management of suppurative microbial keratitis requires five steps: (1) make the clinical diagnosis, (2) perform the proper laboratory procedures, (3) initiate antimicrobial therapy, (4) modify the initial therapy, and (5) terminate therapy. The most helpful guidelines to decision-making in these steps are: (1) the clinical impression, (2) severity of keratitis, (3) results of laboratory studies, (4) disease potential of the responsible organism, and (5) effectiveness and toxicity of various antimicrobial agents. Selection of initial antibiotics ideally should be directed by interpretation of the corneal smears. The preferred initial antibiotic for keratitis caused by a Gram-positive coccus is cefazolin; for a Gram-negative rod, gentamicin; and for a filamentous fungi or yeast, natamycin. Broad, antibacterial therapy should be reserved for suspected bacterial keratitis with negative smears or for severe infections with antecedent treatment. Miconazole may be an effective, alternate agent in fungal keratitis. The safety and efficacy of cortico-steroids in microbial keratitis have not been established.     

Current State of In Vivo Confocal Microscopy in Management of Microbial Keratitis

Purpose: The purpose of this study was to review the current literature on in vivo confocal microscopy of the cornea and to discuss the current clinical indications for its use in microbial keratitis.

Methods: Review of select recent literature on in vivo confocal microscopy and atypical microbial keratitis.

Results: Delayed diagnosis of Acanthamoeba and fungal keratitis is typical, resulting in significant vision loss. This is partially due to the low sensitivity and time delay of corneal cultures. In the hands of an experienced viewer, the confocal microscope has been found to have a sensitivity of up to 90% in the diagnosis of Acanthamoeba keratitis and close to 80% for fungal keratitis.

Conclusion: In vivo confocal microscopy is emerging as a tool for rapid diagnoses in severe infectious keratitis with high sensitivity. In addition, it can be used to monitor treatment response, allowing guidance to clinicians for medical or surgical management.     

Evaluation of Intracameral Amphotericin B in the Management of Fungal Keratitis: Randomized Controlled Trial

Purpose: To evaluate the efficacy and safety of intracameral amphotericin B (ICAMB) in the management of fungal keratitis.

Methods: In total, 45 eyes with smear-confirmed fungal keratitis with hypopyon were randomized into three treatment groups: Group I (topical antifungal treatment?+?oral antifungal); Group II (topical antifungal treatment?+?ICAMB?+?oral antifungal); and Group III (topical antifungal treatment?+?drainage of hypopyon?+?ICAMB?+?oral antifungal). The main outcome measures were treatment success rate, time to heal, visual acuity gain, and presence of complications.

Results: There were no differences in the treatment success rates (p?=?0.66), time to healing (p?=?0.18), or mean final visual acuity (logMAR) (p?=?0.8) between the three groups. The major complication observed was increased incidence of cataract in group III (40%), though it was statistically insignificant.

Conclusions: ICAMB does not offer any benefit over topical antifungal therapy when performed alone or associated with drainage of hypopyon.     

412例真菌性角膜炎的回顾性分析

目的：对真菌性角膜炎患者的流行病学特征、实验室检查方法和结果及治疗效果进行分析,为真菌 性角膜炎诊治提供依据。方法： 回顾性系列病例研究。对2012年1月至2017年12月在冀中能源邢 台矿业集团总医院诊治的412例（412眼）真菌性角膜炎的流行病学特点、临床体征、病原学诊断方式、 结果及治疗效果采用Kruskal-Wallis H检验等统计学方法进行分析。结果：9-12月份是真菌性角膜 炎高发期,占全年患者总数的61.2%（252/412）。患病人群以农民为主,占59.5%（245/412）,植物性 外伤为首要病因者185例（44.9%）,其次为非植物性外伤86例（20.9%）。男女比例为1.82∶1。年龄 14～81（45.6±14.3）岁,41～60岁患者占53.9%（222/412）。真菌培养阳性率为88.8%（366/412）,高 于氢氧化钾湿片法[77.2%（318/412）],2种检测方式比较差异有统计学意义（χ2 =31.14,P<0.001）。 前几位的致病菌依次是镰刀菌属167例（40.5%）,链格孢菌属75例（18.2%）,曲霉菌属62例（15.0%）, 青霉菌属28例（6.9%）。真菌性角膜炎所致典型临床体征中以菌丝苔被最为常见（366例,88.8%）, 其次为伪足（224例,54.4%）、前房积脓（111例,26.9%）。镰刀菌属、链格孢菌属、曲霉菌属及青 霉菌属所致真菌性角膜炎的病情分级和预后水平比较差异均有统计学意义（Hc=40.676,P< 0.001; Hc=40.109,P<0.001）,显示镰刀菌属和曲霉菌属的病情分级重于链格孢菌属和青霉菌属,预后水平 也差于链格孢菌属和青霉菌属。结论：真菌性角膜炎患者呈逐年增多趋势;氢氧化钾湿片法和真菌 培养都是有效的诊断方法,镰刀菌属和曲霉菌属所致的真菌性角膜炎较链格孢菌和青霉菌引起的真 菌性角膜炎病情相对较重,且预后较差。     

福州地区真菌性角膜炎的流行病学特征

目的 分析真菌性角膜炎患者的病因和流行病学特征。方法 对2000年1月至2005年12月在我院确诊为真菌性角膜炎的354例患者进行回顾性分析,研究其人口特征、发病诱因、诊疗情况和病原学特征等。结果 354例真菌性角膜炎中,218例（占61.6%）的患者为男性,31～50岁是发病集中年龄,152例（占42.8%）患者的职业是农民,92例（占26.0%）患者由植物性外伤引起,秋季是高发季节,就诊史明确的患者中261例（占73.6%）在1周内就诊于各级医疗机构,而接受抗真菌治疗的仅为23.4%。分离到的真菌中镰刀菌属有163例（占66.3%）,其次为曲霉菌属,有32例（占13.1%）。结论 真菌性角膜炎是严重的致盲性眼病,高发于以农业生产为主的中、青年男性农民;其致病真菌以镰刀菌属和曲霉菌属为主。应改善农业生产条件,提高对该病的认识和诊断水平。     

糖皮质激素对真菌性角膜炎预后的影响

探讨在确诊为真菌性角膜炎之前使用糖皮质激素对真菌性角膜炎患者的视力预后及治疗方式的影响。方法：回顾性病例对照研究。收集2014年12月至2015年12月于山东省眼科医院确诊的真菌性角膜炎患者211例（211眼），其中36例（36眼）在确诊为真菌性角膜炎之前的治疗中有明确使用过糖皮质激素的患者作为激素组，175例（175眼）在治疗过程中从未使用过激素者作为对照组。采集患者的人口学信息、临床检查结果、抗真菌药物治疗后的病情变化、治疗方案和治愈后2个月的最佳矫正视力（BCVA）。采用独立样本t检验与卡方检验对数据进行统计分析。结果：2组患者人口学特征对比差异无统计学意义。激素组发病时间为（14.5±10.1）d，明显短于对照组[（20.6±22.5）d]，差异有统计学意义（t=2.657，P=0.008）。激素组病灶大小为（6.3±2.4）mm，明显大于对照组[（4.8±2.1）mm]，差异有统计学意义（t=3.683，P<0.001）。激素组角膜刮片阳性率为97.2%，对照组阳性率为90.6%，差异无统计学意义（χ2 =1.633，P=0.201）。激素组有1例（2.8%）为药物治愈，明显低于对照组[34例（19.4%）]，差异有统计学意义（χ2 =5.983，P=0.014）；激素组中行穿透性角膜移植术的患者22例（61.1%），明显高于对照组[55例（31.4%）]，差异有统计学意义（χ2 =11.351，P=0.001）。激素组中（BCVA）低于 0.3的患者32例（88.9%），明显高于对照组[110例（62.8%）]，差异有统计学意义（χ2 =9.194，P=0.002）。结论：真菌性角膜炎使用糖皮质激素后病损范围增大，抗真菌药物治愈率低，穿透性角膜移植手术率高，预后不佳。     

Microbial keratitis in West Anatolia,Turkey: a retrospective review

Purpose To analyze the clinical and microbiological characteristics of microbial keratitis in West Anatolia, Turkey during a 16-year period. Methods This is a retrospective study in which medical records were reviewed for all eyes with clinically diagnosed microbial keratitis presenting at the Izmir Ataturk Training and Research Hospital from January 1990 to December 2005. Risk factors, microbial isolations and clinical features were analyzed. Results Microbial keratitis was diagnosed for 620 eyes in 620 patients (250 women and 370 men; mean age: 54.13 years ± 20.06). Pathogens from cultures were identified for 225 eyes (36.2%) and included Gram-negative (8.9%) and Gram-positive micro-organisms (68.8%) and fungi (22.3%). Staphylococcus epidermidis was the most commonly isolated micro-organism (26.6%), followed by S. aureus (24.4%), Streptococci pneumoniae (15.5%), fungi (22.3%), Pseudomonas species (6.6%), Enterobacter (2.2%) and Corynebacterium (2.2%). Ocular trauma was the most common predisposing factor (26.6%). Mean duration from onset of symptoms to diagnosis was 11.68 ± 11.29 days. Conclusion Staphylococci are the most commonly isolated microbial agents in cases of infectious keratitis in West Anatolia, Turkey. These findings will provide valuable background information and facilitate successful treatment in this region, and they will be useful as reference data for the particular population in this region as a basis for empirical antibiotic therapy.     

Geographic Disparities in the Etiology of Bacterial and Fungal Keratitis in the United States of America

ABSTRACT

Infectious keratitis is a serious cause of vision loss. Proper treatment of infectious keratitis requires antimicrobials that target the organism responsible for a patient’s ulcer. The frequency of infection by a given organism varies by location. We examined the literature to determine geographic disparities in the etiology of bacterial and fungal keratitis in the United States of America. Bacterial keratitis makes up a greater proportion of cases in northern locations, and fungal keratitis increases in prevalence in southern locations. Gram-negative organisms make up a greater proportion of bacterial keratitis in southern locations when compared to northern locations.     

Role of IL-36γ/IL-36R Signaling in Corneal Innate Defense Against Candida albicans Keratitis

PurposeInterleukin (IL)-36 cytokines have been shown to play either beneficial or detrimental roles in the infection of mucosal tissues in a pathogen-dependent manner, but their involvement in fungal keratitis remains elusive. We herein investigated their expression and function in mediating corneal innate immunity against Candida albicans infection.MethodsGene expression in mouse corneas with or without C. albicans infection was determined by regular RT- and real-time (q)-PCR, Western blot analysis, ELISA or proteome profile assay. The severity of C. albicans keratitis was assessed using clinical scoring, bacterial counting, and myeloperoxidase (MPO) activity as an indicator of neutrophil infiltration. IL36R knockout mice and IL-33-specific siRNA were used to assess the involvement IL-33 signaling in C. albicans–infected corneas. B6 CD11c–DTR mice and clodronate liposomes were used to define the involvement of dendritic cells (DCs) and macrophages in IL-36R signaling and C. albicans keratitis, respectively.ResultsIL-36γ were up-regulated in C57BL6 mouse corneas in response to C. albicans infection. IL-36 receptor-deficient mice display increased severity of keratitis, with a higher fungal load, MPO, and IL-1β levels, and lower soluble sIL-1Ra and calprotectin levels. Exogenous IL-36γ prevented fungal keratitis pathogenesis with lower fungal load and MPO activity, higher expression of sIL-1Ra and calprotectin, and lower expression of IL-1β, at mRNA or protein levels. Protein array analysis revealed that the expression of IL-33 and REG3G were related to IL-36/IL36R signaling, and siRNA downregulation of IL-33 increased the severity of C. albicans keratitis. Depletion of dendritic cells or macrophages resulted in severe C. albicans keratitis and yet exhibited minimal effects on exogenous IL-36γ-induced protection against C. albicans infection in B6 mouse corneas.ConclusionsIL-36/IL36R signaling plays a protective role in fungal keratitis by promoting AMP expression and by suppressing fungal infection–induced expression of proinflammatory cytokines in a dendritic cell- and macrophage-independent manner.     

Collagen Cross-Linking in the Management of Microbial Keratitis

Increasing resistance to antimicrobial agents has contributed to an elevated risk of complications of infectious keratitis. Corneal collagen cross-linking (CXL) has been widely adopted for the management of keratoconus and post-refractive surgery corneal ectasia. It has recently been introduced as an option for treating keratitis due to multidrug resistant organisms. The purpose of this review is to discuss the rationale, safety, and evidence for CXL in infectious keratitis and its possible effect on ocular surface inflammation. Published data show that CXL is effective and safe as an adjunct to antibiotic treatment in selected cases of bacterial keratitis. The benefit of CXL probably varies according to the etiology of the infection.     

河南地区真菌性角膜炎病因学及流行病学分析

目的调查报告真菌性角膜炎病人的流行病学特征及易患因素。方法对确诊为真菌性角膜炎的1074例病人进行回顾性分析,评估流行病学特征及患病的危险因素。结果真菌性角膜炎的发病呈上升趋势,635例(59.1%)的患者为男性,21-60岁是发病集中年龄,911例(85%)患者的职业是农民,448例(41.7%)患者有明确的外伤史,就诊史明确的患者中731例(97%)在一周内就诊于各级医疗机构而被诊断为真菌性角膜炎的仅为22%。结论真菌性角膜炎是严重的致盲性眼病,其发病率呈上升趋势。应提高对该病的认识和诊断水平,对具有患病危险因素的患者应进行积极的抗真菌治疗。     

福建地区真菌性角膜炎的流行病学研究

目的:研究福建地区真菌性角膜炎的流行病学特征。方法:回顾性分析2006-07/2008-07住院确诊的真菌性角膜炎患者176例176眼,分析其发病高峰、人群特征、发病诱因、病原学特征。结果:每年10～12月份发病率最高,农村居民106例(60.2%),男女患病率比为1.5∶1,41～60岁为发病集中年龄,仅70例(39.8%)有明确外伤史,菌属鉴定结果:前两位病原菌为镰刀菌属(60.4%)和曲霉菌属(25.4%)。结论:福建地区真菌性角膜炎在10～12月份为高发季节,多发于中老年的农村居民,多数无明显诱因发病,致病菌属以镰刀菌属和曲霉菌属为主。     

Collagen Cross-Linking for the Treatment of Fungal Keratitis

Objective: To evaluate whether corneal collagen cross-linking improves the outcome of fungal keratitis. Methods: This was a retrospective clinical study. Patients (n=82) with fungal infected eyes were treated at Affiliated Xiamen Eye Center of Xiamen University, from November 2011 to December 2017. Corneal cross-linking was performed using the standard protocol after a multi-antifungal drug treatment failed to resolve the infection in patients. Main outcome measures: Clinical symptoms and corneal healing were examined using a slit lamp biomicroscope and an in vivo laser confocal microscope. Visual acuity improvement was also evaluated. Results: After 6 months to 3 years of follow-up, corneal scars eventually developed in 71 of 82 eyes. In 52 of 82 eyes, visual acuity improved. However, corneal melting was exacerbated and uncontrolled in 8 patients who immediately underwent corneal transplant surgery. In one patient, self-conjunctival transplantation was performed, and two others received a therapeutic corneal transplant due to recurrent inflammation and melting. Conclusions: Our results demonstrate that corneal collagen cross-linking is an effective procedure to manage patients afflicted with fungal keratitis.     

角膜胶原交联治疗真菌性角膜溃疡的临床疗效

目的：探讨角膜胶原交联术在治疗真菌性角膜溃疡的可行性及临床疗效。方法：回顾性系列病例研究。收集2011年11月至2017年12月于厦门大学附属厦门眼科中心住院治疗的真菌性角膜溃疡患者82例（82眼）,在联合用药无效或效果不佳的情况下行角膜胶原交联术。术后观察指标包括患者的主观症状、角膜溃疡愈合情况、视力恢复情况,共聚焦显微镜检查角膜溃疡情况。结果：所有患者术后观察时间为6个月至3年,角膜溃疡逐渐愈合形成不同程度瘢痕71例（愈合率87%）,其中视力提高且不需要再次手术患者52例;病情仍然进一步加重,急性期行角膜移植手术患者8例,急性期行自体结膜瓣遮盖术患者1例;溃疡稳定但再次复发加重并行角膜移植术患者2例。结论：角膜胶原交联术是真菌性角膜溃疡新的治疗方法,且其联合药物治疗真菌性角膜溃疡简单、安全、有效。     

华南地区某眼科医院的感染性角膜炎病原菌谱特征

目的 探讨华南地区某眼科医院感染性角膜炎的病原菌谱及其特点。方法 回顾性系列病例研究。选择2013年7月1日至2017年12月31日在中山大学中山眼科中心进行角膜取材和微生物检测的角膜感染患者3 914例。表面麻醉后刮取病灶边缘的病灶组织,进行细菌、真菌培养及鉴定。培养结果阳性的细菌采用生化比色或质谱进行种属鉴定;真菌依据形态学进行种属鉴定。各季节菌谱阳性率差异比较采用卡方检验。结果 感染性角膜炎患者中,男2 468例（63.1%）,女1 446例（36.9%）,年龄（49.5±16.8）岁。病原菌培养阳性的患者共1 673例（42.7%）,其中单纯细菌749例（44.8%）,单纯真菌849例（50.7%）,混合感染75例（4.5%）。最常见的细菌是葡萄球菌属（20.1%）,其次是假单胞菌属（7.5%）;最常见的真菌是镰刀菌属（25.5%）,其次是曲霉菌属（10.3%）。细菌的阳性率在5-8月明显高于1-2月和9-12月（P<0.05）,真菌的阳性率在5-6月明显低于1-2月和9-12月（P<0.05）。结论 在华南地区一所三甲眼科医院的感染性角膜炎中,真菌感染略高于细菌感染,且细菌和真菌感染存在季节性差异。     

Infectious keratitis in Vietnam: etiology, organisms, and management at Vietnam National Eye Hospital

AIM:To report the etiologies,risk factors,treatments,and outcomes of infectious keratitis(IK)at a major Vietnamese eye hospital.METHODS:This is a retrospective review of all cases of IK at Vietnam National Eye Hospital(VNEH)in Hanoi,Vietnam.Medical histories,demographics,clinical features,microbiological results,and treatment outcomes were reviewed.RESULTS:IK was diagnosed in 1974 eyes of 1952 patients,with ocular trauma being the greatest risk factor for IK(34.2%),frequently resulting from an agriculturerelated injur y(53.3%).The mean duration between symptom onset and presentation to VNEH was 19.3±14.4 d,and 98.7%of patients had been treated with topical antibiotic and/or antifungal agents prior to evaluation at VNEH.Based on smear results of 1706 samples,the most common organisms identified were bacteria(n=1107,64.9%)and fungi(n=1092,64.0%),with identification of both bacteria and fungi in 614(36.0%)eyes.Fifty-five of 374 bacterial cultures(14.7%)and 426 of 838 fungal cultures(50.8%)were positive,with the most commonly cultured pathogens being Pseudomonas aeruginosa,Streptococcus pneumonia,Fusarium spp.,and Aspergillus spp.Corneal perforation and descemetocele developed in 391(19.8%)and 93(4.7%)eyes,respectively.Medical treatment was successful in resolving IK in 50.4%eyes,while 337(17.1%)eyes underwent penetrating or anterior lamellar keratoplasty.Evisceration was performed in 7.1%of eyes,most commonly in the setting of fungal keratitis.CONCLUSION:Ocular trauma is a major risk factor for IK in Vietnam,which is diagnosed in almost 400 patients each year at VNEH.Given this,and as approximately one quarter of the eyes that develop IK require corneal transplantation or evisceration,greater emphasis should be placed on the development of prevention and treatment programs for IK in Vietnam.     

Resistant Microbial Keratitis in South Nile Delta,Egypt: Influence of Regional Risk Factors

Purpose: This study was conducted in an attempt to identify the regional, geographic, climatic, socioeconomic, and other risk factors for microbial keratitis in south Nile Delta, Egypt. Methods: This is a prospective cross-sectional study that was carried out on 340 eyes of 340 patients with microbial keratitis attending at the outpatient clinic of Ophthalmology Department of Menoufia University Hospital during a period of three years between March 2010 and March 2013. Results: Epidemiological factors, lines of management, and follow-up results were recorded and statistically analyzed and there were regional variations in the prevalence, risk factors, and outcome in resistant corneal ulcers. Conclusion: Higher incidence of affections and complications has appeared in farmers, rural area residents, and illiterates which are considered the main predisposing factors for ulcer resistance. According to culture results, bacterial organisms (especially Staphylococcus aureus) were the main cause of resistant corneal ulcers.