镰孢菌属镰刀菌致与接触镜有关的真菌性角膜炎1例(英文)

目的:报道1例罕见的被确诊为由镰孢菌属镰刀菌引起的与接触镜有关的严重的真菌性角膜炎,该病例最后通过治疗性穿透性角膜移植术成功治疗。方法:病例报告。结果:一位39岁的马来西亚女士,私企职员,配戴长戴性软性接触镜18a。感右眼剧痛、眼红10d。眼部检查见多个长有伪足的圆形旁中心角膜溃疡,前房少许积脓,临床诊断为真菌性角膜炎。经重复角膜刮片检查真菌和细菌结果均阴性后给予局部广谱抗生素和抗真菌治疗,但患者右眼角膜炎病情进一步加重,又给予其他的局部和全身抗真菌药物治疗,患者右眼角膜溃疡进一步加深。最后,为保留眼球,限制感染,在发病1.5mo后,给予患者治疗性的穿透性角膜移植术。术后,角膜组织病理学检查和PCR检查证实为镰孢菌属镰刀菌感染所致。结论:这是1例罕见的由镰孢菌属镰刀菌感染引起的严重的与接触镜有关的真菌性角膜炎。这也说明了在真菌性角膜炎的治疗上存在挑战性。为控制真菌性角膜炎进一步发展,并保护眼球,治疗性的穿透性角膜移植术应该是最后的选择。     

主要致病真菌在角膜内生长方式的研究

目的 研究白色念珠菌、茄病镰刀菌、烟曲霉菌在角膜内的生长方式.方法 应用表层角膜植片术,在植床与植片间注射真菌菌液,建立浅层真菌性角膜感染的兔模型.28只健康成年家兔,分为白色念珠菌感染组、茄病镰刀菌感染组、烟曲霉菌感染组,每组随机取8只兔,并设立4只兔为对照组.进行组织病理学及透射电镜观察.结果 大体观察发现3种真菌感染的临床表现各有特点.组织病理学及透射电镜检测可见白色念珠菌垂直生长,茄病镰刀菌平行于角膜板层生长,烟曲霉菌斜行生长.结论 3种不同真菌在角膜内生长方式不同,可能存在不同的致病机制.     

环孢素A联合抗真菌药物体外抗茄病镰刀菌效果研究

目的：研究免疫抑制剂环孢素A联合使用抗真菌药物对镰刀菌体外抗真菌药物敏感性的影响。

方法：采用美国临床实验室标准化委员会(CLSI)M27-Ed4及M38-A3方法测定伏立康唑(voriconazole)、那他霉素(NAT)和两性霉素B(Amphotericin B)及氟康唑(FLU)对22株镰刀菌的最低抑菌浓度(MIC),棋盘法测定四种抗真菌药物单独及联合环孢素A使用抗真菌作用。

结果：那他霉素、伏立康唑、两性霉素B和氟康唑对镰刀菌(22株)MIC范围分别是2～8、1～8、1～8和8～512μg/mL。体外联合用药时,环孢素A与氟康唑对64%菌株(14/22)有协同效应,与两性霉素B对41%菌株(9/22)有协同效应,对所有菌株无拮抗效应。联合使用环孢素A后,镰刀菌对两性霉素B药物敏感性由4.5%提升至68.2%(P<0.001)。

结论：镰刀菌在体外对那他霉素敏感,对伏立康唑部分敏感。与环孢素A联合应用时,可与氟康唑及两性霉素B产生协同效应,并显著提高镰刀菌对两性霉素B药物敏感性。     

与隐形眼镜相关的感染性角膜炎-埃及5年流行病学研究

目的：研究埃及Tanta大学医院与隐形眼镜相关的感染性角膜炎患者的不同流行病学特点,评估这类疾病各方面的特点,以提高患者对这类疾病的认识,找出可行的解决方案。

方法：选取我院2009-01/2013-12期间在眼科门诊就诊的所有角膜炎患者仔细检查,并对所有与隐形眼镜相关的感染性角膜炎患者进一步检查和调查。

结果：本研究期间,总共108 496位有不同主诉的患者中,1463例(1.3%)患有不同形式的角膜炎,其中151例(0.1%)为隐形眼镜相关感染性角膜炎。结果发现患有隐形眼镜相关感染性角膜炎常见的年龄群<30岁,大多数是学生(64%),家庭人数多且较为拥挤,农村居民高于城市居民,患者采用户外水源及污水处理不卫生。从病史分析发现：隐形眼镜相关感染性角膜炎通常为彻夜使用,储存或者配戴不卫生,或者隐形眼镜来源不安全,例如化妆品商店和理发店。结膜囊微生物培养结果提示阳性率92%,阴性率8%。大多数培养阳性的病例是由细菌和真菌混合感染引起,共53例(38.1%),单纯细菌感染43例(30.9%),真菌31例( 22.3%),阿米巴12例(8.6%)。

结论：与隐形眼镜相关的感染性角膜炎常见于学生群体,与农村生活、户外供水、不卫生的污水处理等危险因素有关。彻夜配戴、储存或配戴不卫生及隐形眼镜来源不安全都可增加隐形眼镜相关感染性角膜炎的发病率。     

Time-dependent matrix metalloproteinases and tissue inhibitor of metalloproteinases expression change in fusarium solani keratitis

AIM: To investigate matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) expression during the progress of fusarium solani (F.solani) keratitis in a rat model. METHODS: A rat model of F.solani keratitis was produced using corneal scarification and a hand-made contact lens. MMPs and TIMPs expressiond were explored in this rat model of F.solani keratitis using real-time polymerase chain reaction (PCR) and DIF. GM6001 (400 μmol/mL) was used to treat infected corneas. The keratitis duration, amount and area of corneal neovascularization (CNV) were evaluated. RESULTS: MMP-3 expression was 66.3 times higher in infected corneas compared to normal corneas. MMP-8, -9, and -13 expressions were significantly upregulated in the mid-period of the infection, with infected-to-normal ratios of 4.03, 39.86, and 5.94, respectively. MMP-2 and -7 expressions increased in the late period, with the infected-to-normal ratios of 5.94 and 16.22, respectively. TIMP-1 expression was upregulated in the early period, and it was 43.17 times higher in infected compared to normal corneas, but TIMP-2, -3, and -4 expressions were mildly downregulated or unchanged. The results of DIF were consistent with the result of real-time PCR. GM6001, a MMPs inhibitor, decreased the duration of F.solani infection and the amount and area of CNV. CONCLUSION: MMPs and TIMPs contributed into the progress of F.solani keratitis.     

Clinical profile and treatment outcomes of Fusarium keratitis

Purpose:To determine the seasonality, clinical profile, and treatment outcome of Fusarium keratitis.Methods:A retrospective medical chart review of 97 patients with culture-proven Fusarium keratitis at a tertiary eye care institution from January 2018 to December 2019.Results:The median (SD) age at enrollment was 44.6 (16) years; 75 (79.8%) of them were male. Presence of infiltrate less than 4 mm² at baseline indicated 4.4 times the odds of achieving final BCVA more than 20/60 (95% CI: 1.4–13.3; P = 0.008). The absence of surgical management indicated 8.1 times the odds of achieving final BCVA of more than 20/60 (95% CI: 0.9–71.5; P = 0.06). The visual acuity at presentation, duration between symptoms and presentation, history of ocular trauma, previous use of topical medications, and presence of hypopyon were not identified as significant predictors of final BCVA in the multivariable regression analysis.Conclusion:Smaller infiltrate size and absence of surgical management are the significant predictors of good visual outcome. Visual outcome of Fusarium keratitis is poor, and a significant number of patients did not respond to anti-fungal therapy and had to undergo surgeries. To the best of our knowledge, this is the largest case series on Fusarium keratitis to date.     

Contact lens-related microbial keratitis: how have epidemiology and genetics helped us with pathogenesis and prophylaxis

Contact lens wear is a common predisposing factor in microbial keratitis and is one of the two preventable risk factors for corneal infection in a working age population. Our understanding of the prevention and prophylaxis of contact lens-related corneal infection is informed by recent epidemiological studies describing the incidence of and risk factors for the disease, the effect of causative organism on disease severity, and an appreciation of individual immune profiles in susceptibility to and severity of the disease. Although contemporary contact lenses have not reduced the overall incidence of keratitis, a reduction in morbidity may be achievable through recognition of appropriate risk factors in severe disease, including avoiding delays in presenting for appropriate treatment, and attention to storage case hygiene practise. Severe keratitis is most commonly associated with an environmental causative organism, and daily disposable lenses are associated with less severe disease. Pseudomonas aeruginosa remains the commonest cause of contact lens-related corneal infection probably because of its unique virulence characteristics and ability to survive in the contact lens/storage case/ocular environment. In two recent outbreaks of contact lens-related infections, there has been a strong association demonstrated with particular contact lens solutions. Since the recall of these specific contact lens solutions, the rate of Acanthamoeba keratitis has remained above the expected baseline, indicating unidentified risk factors that may include environmental exposures. Individual differences in susceptibility to microbial keratitis may be partly explained by differences in single-nucleotide polymorphisms in certain cytokine genes, particularly those with a proven protective role in corneal infection.     

Acanthamoeba keratitis: A masquerade of presentation in six cases

Acanthamoeba keratitis is an uncommon but devastating complication of contact lens wear causing significant ocular morbidity. Six consecutive cases occurring in Western Australia in an 18-month period are reported. In all cases either poor contact lens hygiene or an association with swimming pools and contact lens use is a feature.
There is invariably a delay in making the diagnosis, with the appearance frequently mistaken for herpes simplex keratitis. In all cases corneal biopsy was required to confirm the diagnosis. Of the six patients, four responded to medical therapy alone, one required a corneal graft and one required enucleation.
We suggest that earlier rather than later corneal biopsy is important in unresponsive cases of culture-negative keratitis, especially in contact lens wearers. We would agree that the treatment of choice is intensive topical propamidine and neosporin. Prevention by strict adherence to contact lens care and hygiene is urged.     

Non-ulcerative fungal keratitis diagnosed by posterior lamellar biopsy*

We report a case of Fusarium solani keratitis which highlights the difficulties often associated with management of fungal corneal infections. This case demonstrates several unusual and interesting features: the occurrence of deep fungal pathology after superficial injury, the difficulties encountered in attempting to isolate and identify the causative organism, and the protracted course taken by an organism often noted to be rapidly destructive. These features necessitated an individual approach to therapy, employing unconventional medical and surgical techniques to achieve a satisfactory outcome     

Medical treatment for combined Fusarium and Acanthamoeba keratitis

Purpose: Acanthamoeba and fungal keratitis are rare ocular infections. We report cases of combined Fusarium and Acanthamoeba keratitis and the clinical course of medical treatment. Methods: We reviewed the medical records of patients treated for culture‐proven Acanthamoeba keratitis at a referral centre, during 2001?2006. Results: Eleven consecutive patients were treated for culture‐proven Acanthamoeba keratitis during the 5 years, two of whom had combined fungal infections. A 29‐year‐old man presented with ground‐glass corneal oedema and epitheliopathy caused by contact lens use. The other patient, a 7‐year‐old girl, had eye trauma that led to a feathery corneal infiltrate. Both cases were treated with topical 0.02% polyhexamethylene biguanide (PHMB), 0.1% propamidine, 1% clotrimazole and 5% natamycin. Therapeutic keratoplasty was not required in either case. Conclusions: Timely identification of the pathogen, with repeated culture and smear if necessary, as well as adequate dosage to prevent recurrence is highly recommended in order to preclude the need for therapeutic penetrating keratoplasty.     

Acanthamoeba keratitis cluster: an increase in Acanthamoeba keratitis in Australia

Background:  This study was undertaken in response to an increase in the number of patients treated for Acanthamoeba keratitis at a tertiary referral hospital in Brisbane, Australia. Incidence and patient characteristics were investigated over a 4-year period.
Methods:  A retrospective consecutive case series study was performed on patients with Acanthamoeba keratitis presenting to the Princess Alexandra Hospital between January 2003 and March 2007.
Results:  Nine cases of Acanthamoeba keratitis were identified over 12 months from March 2006 to March 2007 compared with four cases over the previous 37 months from January 2003 to February 2006. This was an increase from 0.07 cases per 1000 outpatient visits to 0.42 per 1000 ( P  = 0.003). Of the 13 cases, 11 patients used soft contact lenses of which two used monthly extended overnight wear silicone hydrogel lenses. Of the five patients who specified the type of contact lens solution they had used, three reported using AMO Complete Moistureplus Multipurpose solution, one reported using the AMO Complete Comfortplus Multipurpose solution and one was unsure which type of AMO Complete solution they were using.
Conclusions:  There has been a significant increase in incidence of cases of Acanthamoeba keratitis presenting to our institution. The type of contact lens solution and the use of silicon hydrogel lenses combined with extended overnight wear may play a role; however, the significance is unclear given the small numbers for analysis. Further study of incidence and patient characteristics is warranted to identify risk factors and causes for the rising incidence.     

Antifungal efficacy of natamycin in experimental fusarium solani keratitis

AIM: To evaluate the efficacy of topical administration Natamycin, which is produced by China, in an experimental rabbit model of Fusarium solani keratitis, to provide experimental basis for the application of clinical safety. METHODS: Fusarium solani was induced in the right eye of 30 New Zealand rabbits. Forty-eight hours after inoculation, the animals were divided into 3 different treatment groups, 10 rabbit eyes of each group: Group 1 (Natamycin) treated with topical Natamycin, group 2 (Natacyn) treated with topical Natacyn, group 3 (control) treated with topical saline solution. The eyes of each group was examined clinically with slit lamp using ulcer scoring system on day 4, 10, 15, and 21 for status of healing, corneal vascularisation, iritis, hypopyon and macular nebula. The findings were recorded on day 10 and day 21. RESULTS: Ulcer score on day 10, day 15, day 21: The score of Natamycin group are 1.45±0.16, 1.08±0.11, 0.70±0.40. The score of Natacyn group are 1.35±0.12, 1.10±0.12, 0.65±0.35. the score of control group are 1.30±0.08, 3.63±0.28, 3.80±0.16. Natamycin group and Natacyn group were different from control group (P<0.01). There is no difference between Natamycin group and Natacyn group. Status of healing on day 10 and day 21: The cure rate of the Natamycin group is 90% on day 10, and 100% on day 21. The cure rate of the Natacyn group is 80% on day 10, and 100% on day 21.Natamycin group and Natacyn group were different from control group (P<0.01) There is no difference between Natamycin group and Natacyn group. Corneal vascularisation, iritis, hypopyon and macular nebula on day 10 and day 21: in Natamycin group, the number of the eyes which have Corner vascularisation, iritis, hypopyon and macular nebula are 2,0,0,2. In Natacyn group, the number of the eyes which have Corner vascularisation, iritis, hypopyon and macular nebula are 1,0,0,2. In control group, the number of the eyes which have Corner vascularisation, iritis, hypopyon and macular nebula are 9,9,8,9.Natamycin group and Natacyn group were different from control group (P<0.01). There is no difference between Natamycin group and Natacyn group. CONCLUSION: Natamycin was found to be effective in fungal keratitis, similar to Natacyn, and it can stop the corner vascularisation, iritis, hypopyon and macular nebula to happen. Natamyin manufactured in China is effective against fungal keratitis, with esay availability and low toxicity in its use.     

1g/L氟米龙滴眼液联合软性角膜接触镜治疗丝状角膜炎

目的：探讨1g/L氟米龙滴眼液联合软性角膜接触镜治疗丝状角膜炎的疗效。

方法：确诊丝状角膜炎患者30例45眼,随机分为治疗组16例23眼、对照组14例22眼。治疗组取出丝状物后配戴软性角膜接触镜,点糖皮质激素眼液(1g/L氟米龙滴眼液)和人工泪液(玻璃酸钠眼液); 对照组取出丝状物后仅使用人工泪液(玻璃酸钠眼液)点眼。随访3mo,比较两组疗效。

结果：治疗组患者临床治疗总有效率22眼(96%),明显高于对照组17眼(77%),差异有统计学意义(P=0.046),且发现未对眼压有明显影响。

结论：1g/L氟米龙联合软性角膜接触镜治疗丝状角膜炎有较好疗效。     

Rethinking contact lens associated keratitis

This review presents a critical analysis of the literature relating to the use of binomial and polynomial classification schemes for categorising corneal infiltrative events (CIEs) associated with contact lens wear and the epidemiology of such events. The results of the Manchester Keratitis Study—a 12‐month, prospective, hospital‐based epidemiological study of contact lens wearers suffering from CIEs—are used as a tool to challenge and test traditional thinking in relation to contact lens associated keratitis. An innovative aspect of this study is the use of a novel clinical severity matrix to systematically score the severity of CIEs based on 10 key signs and symptoms. The ambiguities inherent in using binomial classification schemes (such as, microbial versus sterile, ulcerative versus non‐ulcerative et cetera) are highlighted. The failure of a polynomial scheme—due to extensive classification overlap between proposed sub‐types of CIEs—is demonstrated using a Venn diagram. A cartographic analysis reveals that infiltrates tend to occur in the superior cornea of patients wearing extended wear silicone hydrogel lenses, in the central cornea of patients wearing daily wear hydrogel daily disposable lenses and in the peripheral cornea of patients wearing daily wear hydrogel (excluding daily disposable) lenses. Infiltrates that occur more towards the limbus are less severe. The incidence of CIEs is higher when contact lenses are worn overnight. Logistic analysis reveals that the risk of developing a severe CIE is five times greater with conventional hydrogel extended wear versus silicone hydrogel extended wear. The male gender, smoking, a healthy eye and body, and the late Winter months are associated with an increased risk of developing CIEs. The rate of significant visual loss as a result of developing a CIE is low. Two key conclusions are drawn from this work, which represent a radical rethinking of this potentially sight‐threatening condition.

• 1 CIEs should be considered as a continuous spectrum of ocular disease.
• 2 If a contact lens wearer presents with a sore eye that is becoming progressively worse and a CIE is observed in that eye, lens wear should be suspended and anti‐microbial therapy initiated immediately.

     

角膜溃疡清创术联合抗真菌药物治疗真菌性角膜炎

目的:总结角膜溃疡清创术联合抗真菌药物治疗真菌性角膜炎的效果。方法:收集2010-09/2011-09在我院就诊的真菌性角膜炎患者30例,对患者进行常规角膜刮片检查,并对全部患者施行角膜溃疡清创术,根据角膜炎的严重程度联合给予氟康唑或那他霉素眼水点眼治疗,清创术治疗无效者采用自体结膜覆盖术及板层角膜移植术治疗,随访观察治疗效果。结果:角膜刮片阳性结果 27例,阳性率90%,2例于外院行共聚焦显微镜检查菌丝阳性;1例为明确植物外伤史的8岁儿童,不能配合真菌检查。轻度角膜炎6例,施行角膜溃疡清创术联合氟康唑眼水点眼治疗全部痊愈,病程2～3wk;中度度角膜炎17例,行角膜溃疡清创术联合那他霉素眼水点眼治疗痊愈12例,病程4～8wk;重度角膜炎7例,行角膜溃疡清创术联合那他霉素眼水点眼治疗痊愈3例,病程8～10wk。角膜溃疡清创术联合抗真菌药物治疗真菌性角膜炎有效率70%。结论:角膜溃疡清创术联合抗真菌药物治疗真菌性角膜炎操作简单,是一种经济、有效、可行的治疗方式。     

Clinical and microbial spectrum of fungal keratitis in Singapore: a 5-year retrospective study

Background: The epidemiology of fungal keratitis varies geographically, but commonly occurs in warm, tropical climates. To determine the microbial and clinical characteristics of this disease in Singapore, we conducted a5-year hospital-based retrospective study. Methods: A retrospective reviewo f culture-positive fungal keratitis at the Singapore National Eye Center and Singapore General Hospital, from January 1991 to December 1995. Results: Twenty-nine consecutive cases of culture-positive fungal keratitis were seen over the study period. The mean age of the cases was 41 years and 23 were males. Amongst the varied occupations, 9 were construction workers. The most common cultured organisms were Fusarium sp. (52%) and Aspergillus flavus (17%). More than half had a history of ocular trauma prior to the development of keratitis, while a quarter had antecedent topical corticosteroid therapy. In contrast, only 2 patients were contact-lens wearers. Despite medical therapy, 10 patients eventually required therapeutic penetrating keratoplasties; of these, 6 were caused by Fusarium species. Conclusion: Fusarium is the commonest cultured organism in fungal keratitis in Singapore and is associated with significant ocular morbidity. This revised version was published online in August 2006 with corrections to the Cover Date.     

Hydrogel dressings on neurotrophic keratitis in an experimental animal model

AIM: To investigate the therapeutic effects of hydrogel dressings on neurotrophic keratitis in rats. METHODS: Male Wistar rats, aged 42–56d, were randomly divided into control, experimental, and treatment groups, each consisting of five rats. The experimental and treatment groups underwent neurotrophic keratitis modeling in both eyes. After successful modeling, biomedical hydrogels formed with polyvinyl alcohol and polyvinyl pyrrolidone were used in treatment group for 7d. Ocular irritation response and keratitis index scores, Schirmer’s test, tear film break-up time (BUT), sodium fluorescein staining, and hematoxylin and eosin (HE) staining were used to evaluate the effectiveness of the treatment. RESULTS: The neurotrophic keratitis model was successfully established in rats with severe ophthalmic nerve injury, characterized by keratitis, ocular irritation, reduced tear secretion measured by decreased BUT and Schirmer test values, corneal epithelial loss, and disorganized collagen fibers in the stromal layer. Following treatment with hydrogel dressings, significant improvements were observed in keratitis scores and ocular irritation symptoms in model eyes. Although the recovery of tear secretion, as measured by the Schirmer’s test, did not show statistical differences, BUT was significantly prolonged. Fluorescein staining confirmed a reduction in the extent of corneal epithelial loss after treatment. HE staining revealed the restoration of the structural disorder in both the epithelial and stromal layers to a certain extent. CONCLUSION: Hydrogel dressing reduces ocular surface irritation, improves tear film stability, and promotes the repair and restoration of damaged epithelial cells by maintaining a moist and clean environment on the ocular surface in the rat model.     

Photo-activated chromophore for infectious keratitis cross-linking and its efficacy as a treatment modality in managing microbial keratitis

Purpose:To assess Photo Activated Chromophore for Infective Keratitis-Cross Linking (PACK-CXL) and its efficacy as a treatment modality in managing microbial keratitis.Methods:Single Centre prospective interventional study in infectious keratitis. A total of eleven patients were taken who had corneal thickness (CT) more than 400µm. PACK-CXL was performed according to Dresden’s protocol. The response was assessed by slit lamp examination, BCVA and AS-OCT at the time of complete healing.Results:The mean visual acuity at presentation was 1.207logMAR (0.3-3) which improved to mean value of 0.53logMAR (0.3-1). Mean time taken for complete epithelization was 17.45 days (14- 30 days) and that for complete healing was 33.72 days (21- 60 days). Mean CT at the baseline was 650.5± 108µm which reduced on consecutive follow up visits. There was reduction in the symptoms in nine patients except in two. One case reported increase in symptoms with worsening increase in endoexudates and hypopyon, and the other developed drug toxicity due to topical medications.Conclusion:Patients who underwent PACK-CXL showed good and early healing, good remodelling of cornea and improved visual acuity. The recalcitrant cases became responders to the same medications after PACK-CXL. Thus, PACK-CXL works well for both fungal and bacterial keratitis.