Ocular involvement in sporotrichosis: report of two cases in children

Abstract Sporotrichosis is a subcutaneous mycosis that affects humans and animals, with a typically subacute or chronic evolution, caused by Sporothrix spp., a dimorphic fungus. Although the cutaneous form is the most frequent presentation, the ocular involvement has been more frequently diagnosed in endemic areas, affecting mainly children and the elderly. Approximately 80% of affected patients have the lymphocutaneous form, while only 2.3% have conjunctival lesions, with 0.7% showing primary ocular involvement. We describe two cases of sporotrichosis with ocular involvement in children through inoculation by felines, with a good response to antifungal treatment.

The clinical features and prognostic analysis of visual function damage caused by fungal sphenoid sinusitis / 中华眼底病杂志

Objective:To observe the clinical characteristics of patients with visual impairment caused by fungal sphenoid sinusitis and analyze the influencing factors related to visual prognosis.Methods:A retrospective clinical study. From January 2006 to December 2020, 44 patients (55 eyes) with visual impairment caused by fungal sphenoid sinusitis confirmed by imaging and pathological examination in the Department of Ophthalmology of Beijing Tongren Hospital were included in the study. Patients was first diagnosed in the Department of Ophthalmology due to monocular or binocular vision loss, or binocular diplopia, limited eye movement and ptosis. All patients underwent visual acuity examination and fundus color photography. CT examination of paranasal sinus or orbit was performed in 37 cases; magnetic resonance imaging (MRI) of paranasal sinus, brain or orbit was performed in 34 cases. All patients underwent endoscopic sinus opening combined with intrasinus lesion clearance; 14 cases were treated with antifungal drugs after operation. The average follow-up time was 59.61±37.70 months. Comparison of clinical characteristics between invasive and non-invasive fungal sphenoid sinusitis were by χ 2 test or Fisher exact test. The influencing factors with P<0.2 in univariate analysis were selected for multivariate regression analysis. Results:Among the 44 patients, there were 19 males and 25 females; the ratio of male to female was 1:1.3; the average age of visual symptoms was 61.48 ± 12.17 years; 23 cases (52.3%, 23/44) suffered from immune dysfunction, including 21 cases of diabetes mellitus. The visual acuity decreased in 33 cases (44 eyes) (75.0%, 33/44). There were 15 cases of binocular diplopia with eye movement disorder (34.0%, 15/44), including 6 cases with visual impairment. The visual acuity of the affected eye was no light perception-0.8. There were 35 cases with headache (79.5%, 35/44). Nasal symptoms were found in 14 cases (31.8%, 14/44). There were 40 and 4 cases of Aspergillus and Mucor infection in sphenoid sinus, respectively. Among the 37 cases who underwent CT examination of paranasal sinus or orbit, there were soft tissue filling in the sinus cavity, including 19 cases of high-density calcification in the sinus cavity (51.4%, 19/37); bone defect of sinus wall were in 24 cases (64.9%, 24/37). There were 26 cases (70.3%, 26/37) of sinus wall osteosclerosis. MRI of paranasal sinus, brain or orbit was performed in 34 cases. T1WI of sphenoid sinus lesions showed low signal, high signal and equal signal in 14, 10 and 9 cases, respectively; T2WI showed high signal, low signal and equal signal in 13, 16 and 2 cases respectively. After enhancement, the lesions were strengthened in 11 cases, no obvious enhancement in 23 cases, and the surrounding mucosa was thickened and strengthened. The lesions involved the orbital apex and cavernous sinus in 18 and 16 cases, respectively; orbital apex and cavernous sinus were involved in 12 cases. Six months after operation, visual acuity was significantly improved in 27 eyes (65.9%, 27/41); visual acuity did not improve in 14 eyes (34.1%, 14/41). Multivariate regression analysis showed that the change of sinus wall osteosclerosis was associated with higher visual acuity improvement rate (odds ratio= 0.089, 95% confidence interval 0.015-0.529, P=0.008). Conclusions:Fungal sphenoid sinusitis related visual impairment is relatively common in elderly female patients with low immune function; monocular vision loss with persistent headache is the most common clinical symptom; imaging findings of sphenoid sinus lesions are an important basis for diagnosis. Sphenoid sinus opening combined with sinus lesion clearance is an effective treatment. After operation, the visual acuity of most patients can be improved. The prognosis of visual acuity was relatively good in patients with hyperplasia and sclerosis of sphenoid sinus wall bone.

Fungal keratitis management in a referral cornea center in Brazil / Manejo de ceratites fúngicas em centro de referência no Brasil

Abstract Purpose: To report etiological diagnosis, predisposing risk factors, therapeutic strategies and visual outcome of patients treated at the Department of Ophthalmology of Federal University of São Paulo. Methods: This is a retrospective, descriptive, and observational study from medical and laboratory records of the Department of Ophthalmology of Federal University of São Paulo, including all patients with culture proven fungal keratitis in 5 years, from October 2012 through October 2017. Results: There were 2260 fungi microbiologic test requests. Of these, 140 samples had positive cultures for fungi and sixty-six patients were followed at our clinic. Forty-five patients (68.2%) were men, and the mean age was 48.06 (±17.39) years. Fusarium spp. was the most frequently isolated fungus (32 cases; 48.5%), followed by Candida parapsilosis (12 cases; 18.2%). Thirty-four patients (51.5%) underwent intracameral injection of amphotericin B (5 µg per 0.1 ml). In 11 patients (32.3%), infection was eradicated after intracameral amphotericin B associated to topical antifungal treatment and, in 23 patients (67.7%), therapeutic keratoplasty was needed. No complication related to intracameral amphotericin B injection was observed in this series. Forty-three patients (65.1%) ended up with therapeutic keratoplasty. Three patients (4.5%) evolved to evisceration or enucleation. At the last follow-up visit, 53 patients (80.3%) had visual acuity worse than 20/200. Conclusion: Despite current antifungals drugs and distinct administration strategies, fungal keratitis remains challenging. Delayed antifungal therapy may explain poor clinical outcomes. Intracameral amphotericin B associated to topical antfungal treatment seems to be a safe and helpful alternative for non-responsive fungal keratitis. But it is important to formulate other treatment strategies, hence to improve patients' outcomes, since most patients ended-up with significant visual impairment even after current treatment.

Resumo Objetivo: Descrever diagnósticos etiológicos, fatores de risco, estratégias terapêuticas e resultados visuais de pacientes com ceratite fúngica tratados no Departamento de Oftalmologia da Universidade Federal de São Paulo. Métodos: Trata-se de um estudo retrospectivo, descritivo e observacional, a partir da análise de prontuários médicos e laboratoriais do Departamento de Oftalmologia da Universidade Federal de São Paulo, incluindo todos os pacientes com ceratite fúngica comprovada por cultura no período de outubro de 2012 a outubro de 2017. Resultados: Foram realizadas 2260 solicitações de testes microbiológicos. Destas, 140 amostras apresentaram culturas positivas para fungos, e 66 pacientes foram acompanhados em nosso serviço. Quarenta e cinco pacientes (68,2%) eram do sexo masculino, e a média de idade foi de 48,06 (± 17,39) anos. Fusarium spp. foi o fungo mais freqüentemente isolado (32 casos; 48,5%), seguido por Candida parapsilosis (12 casos; 18,2%). Trinta e quatro pacientes (51,5%) foram submetidos à injeção intracameral de anfotericina B (5 µg por 0,1 ml). Destes, 11 pacientes (32,3%) tiveram a infecção erradicada. Nos outros 23 pacientes (67,7%), o transplante terapêutico foi necessário. Nenhuma complicação relacionada à injeção intracameral de anfotericina B foi observada neste estudo. No total, 43 pacientes (65,1%) evoluíram para transplante terapêutico, e 3 pacientes (4,5%) foram submetidos à evisceração ou enucleação. Cinquenta e três pacientes (80,3%) apresentaram acuidade visual final pior que 20/200. Conclusões: Apesar dos diversos medicamentos antifúngicos atuais e vias de administração, o tratamento das ceratites fúngicas permanece desafiador. O atraso no início do tratamento adequado pode justificar o desfecho clínico desfavorável de grande parte dos pacientes. A injeção intracameral de anfotericina B mostrou-se uma alternativa terapêutica segura para ceratites fúngicas refratárias. Mas outras estratégias de tratamento devem ser formuladas, visando melhorar os resultados visuais dos pacientes.

Endoftalmite fúngica bilateral endógena / Bilateral endogenous fungal endophthalmitis

Resumo É apresentado o caso de uma paciente do sexo feminino, 77 anos, internada por pielonefrite e tratada com antibóticos de amplo espectro, tendo desenvolvido endoftalmite endógena bilateral presumida por Candida. Foi submetida à vitrectomia via pars plana e injeção intravítrea de anfotericina B, além de voriconazol oral. São abordados, ainda, os aspectos clínicos da endoftalmite endógena por meio de revisão da literatura.

Abstract A 77 year-old female patient suffering from pyelonephritis developed bilateral endogenous endophthalmitis presumed by Candida after have been treated with global spectrum antibiotics. Early vitrectomy and intravitreal amphotericin B injection were performed, in addition to oral voriconazole. Clinical aspects of endogenous endophthalmitis are also pointed out by a literature review.

Post-laser in situ keratomileusis interface Arthrographis kalrae keratitis / Interface de pós-laser ceratomileuse in situ Arthographis Kalrae ceratite

ABSTRACT We describe a case of keratomycosis caused by Arthographis kalrae after excimer laser keratomileusis. A 38-year-old female developed stromal keratitis eight weeks after refractive surgery. She developed severe corneal stromal infiltration and mild anterior segment inflammation, which could not be treated with topical voriconazole 1%, but topical natamycin 5% ameliorated her condition. A reactivation of keratomycosis symptoms was observed; therefore, longer treatment was administered to the patient. It has been reported that A. kalrae keratomycosis is associated with exposure to soil and contact lens usage. However, the patient, who lived in a rural location, was neither involved in gardening activities nor had a history of wearing contact lenses. This is the first case of post-refractive A. kalrae keratomycosis.

RESUMO Descrevemos um caso de ceratomicose por Arthographis kalrae após ceratomileusis por excimer laser. Uma mulher de 38 anos desenvolveu ceratite estromal oito semanas após a cirurgia refrativa. Ela desenvolveu infiltração estromal grave da córnea e uma leve inflamação do segmento anterior, que não pode ser tratada com voriconazol tópico a 1%, mas a natamicina tópica a 5% melhorou sua condição. Uma reativação dos síntomas de ceratomicose foi observada; portanto, tratamento mais prolongado foi administrado a paciente. Tem sido relatado que a ceratomicose por A. kalrae está associada à exposição ao solo e ao uso de lentes de contato. No entanto, a paciente, que vivía em um local rural, não estava envolvida em atividades de jardinagem e nem tinha histórico de uso de lentes de contato. Este é o primeiro caso de ceratomicose pós-refrativa por A. kalrae.

A case of recurrent keratitis caused by Paecilomyces lilacinus and treated by voriconazole / Uso do voriconazol na ceratite recorrente causada por fungo Paecilomyces lilacinus

ABSTRACT - We describe here a case of a 21-year-old woman who presented with low visual acuity, pain, and hyperemia in the left eye for 45 days. Her eye had extensive corneal infiltrate, with melting and a central perforation that was glued with cyanoacrylate, but with Seidel (+). She underwent tectonic corneal transplantation, and anterior chamber lavage with subconjunctival infiltration with voriconazole, as well as intracameral injections of amphotericin B. Laboratory tests revealed Paecilomyces lilacinus as the infectious agent. The patient was then maintained with oral voriconazole and eye drops for three months, after which the infection was considered cured. However, in the sixth postoperative month she presented with endothelial rejection, and two weeks later signs of recurrence of the fungal infection. She was treated with two further washes of the anterior chamber and subconjunctival injection of voriconazole, followed by intravenous voriconazole that was replaced with drops after ten days. The infection initially worsened, but then regressed, and at last follow-up, the patient was still infection-free.

RESUMO - Descrevemos aqui um caso de uma mulher de 21 anos que apresentou baixa acuidade visual, dor e hiperemia no olho esquerdo por 45 dias. O olho apresentava infiltrado corneano extenso, com fusão e perfuração central colada com cianoacrilato, mas com Seidel (+). Ela foi submetida a transplante de córnea tectônica e lavagem de câmara anterior com infiltração subconjuntival com voriconazol, além de injeções intracamerais de anfoterecina B. Testes laboratoriais revelaram Paecilomyces lilacinus como agente infeccioso. A paciente foi então mantida com voriconazol oral e colírio por período de três meses, após o qual a infecção foi considerada curada. No entanto, no sexto mês de pós-operatório, ela apresentou rejeição endotelial e, duas semanas após, sinais de recidiva de infecção fúngica. Ela foi tratada com mais duas lavagens de câmara anterior e injeção subconjuntival de voriconazol, seguida por voriconazol intravenoso que foi substituído por gotas após 10 dias. A infecção piorou inicialmente, mas depois regrediu e, no último seguimento, o paciente ainda estava livre de infecção.

Correlation between pathogenic species and clinical findings, disease severity, and visual outcome in patients with fungal keratitis / Correlação entre espécies patogênicas e achados clínicos, gravidade da doença e desfecho visual em pacientes com ceratite fúngica

ABSTRACT Purpose: To determine whether a correlation exists between pathogenic species and clinical findings, disease severity, and visual outcome in patients with keratitis and fungal growth in microbiological culture. Methods: A retrospective study of patients with fungal growth in the microbiological culture of corneal scrapings. Patients were treated at an ophthalmologic reference center in Southeastern Brazil from January 1992 to October 2015. Results: Medical records of 181 patients (131 males and 50 females) with a mean age of 47 ± 18 years were analyzed. The three most common etiologies were Fusarium sp. (38.7%), Aspergillus sp. (15%), and Candida sp. (13.2%). Among these, Fusarium sp. was the most frequent in patients aged £50 years (p=0.002) and in those with a recent history of a foreign body and/or ocular trauma (p=0.01). Candida sp. was the most frequent etiology in patients aged >50 years (p=0.002), in those with postoperative ocular surgery (p=0.002); in those with a previous ocular pathology (p=0.0007); and in immunodepressed patients (p=0.0004). Conclusion: Fusarium sp. was predominant in patients aged £50 years and those with a recent history of foreign body and/or ocular trauma, whereas Candida sp. was predominant in older adults, in those with a postoperative ocular surgery, in those with a previous ocular pathology, and in immunodepressed patients.

RESUMO Objetivo: Determinar se existe uma correlação entre espécies patogênicas e achados clínicos, gravidade da doença e resultado visual em pacientes com ceratite e crescimento de fungos em cultura microbiológica. Métodos: Estudo retrospectivo de pacientes com crescimento de fungos na cultura microbiológica de raspado de córnea. Os pacientes foram tratados em um centro de referência oftalmológica no Sudeste do Brasil de janeiro de 1992 a outubro de 2015. Resultados: Foram analisados registros médicos de 181 pacientes (131 homens e 50 mulheres) com idade média de 47 ± 18 anos. As três etiologias mais comuns foram Fusarium sp. (38,7%), Aspergillus sp. (15%) e Candida sp. (13,2%). Entre estas, Fusarium sp. foi a mais frequente em pacientes com idade £50 anos (p=0,002) e naqueles com história recente de corpo estranho e/ou trauma ocular (p=0,01). Candida sp. foi a etiologia mais frequente em pacientes com idade >50 anos (p=0,002), naqueles com cirurgia ocular pós-operatória (p=0,002); naqueles com patologia ocular prévia (p=0,0007); e em pacientes imunodeprimidos (p=0,0004). Conclusão: Fusarium sp. foi predominante em pacientes com idade £50 anos e naqueles com história recente de corpo estranho e/ou trauma ocular; enquanto Candida sp. foi predominante em adultos mais velhos, naqueles com cirurgia ocular pós-operatória, naqueles com patologia ocular prévia e em pacientes imunodeprimidos.

Spectrum of fungal keratitis change in South China / 中华实验眼科杂志

Background Fungal keratitis has a high incidence in China and its clinical treatment is very difficult,and its etiology diagnosis and appraisal is the premise to improve the prognosis of disease.With the changes of regional environment and climate in recent years,whether the spectrum of fungal keratitis change in South China is remarkable.Objective The purpose of this study was to investigate recent pathogenic distribution of fungal keratitis in South China area.Methods The consecutive fungal culture resuhs of 3 350 purulent keratitis at Zhongshan Ophthalmic Center from January 2009 to December 2014 were retrospectively reviewed.The positive rate of fungal culture,genus or species distribution,seasonal distribution and different term distribution were analyzed.Results The culture-positive rate was 31.34％ in this study (1 050/3 350),and the average culture-positive number was 175 strains per year.In the positive fungus,the highest positive rate was Fusarium SP (32.10％,337/1 050),and followed by Aspergillus SP (25.71％,270/1 050),Heminthosporium SP (14.29 ％,150/1 050) and Mucor SP (9.14％,96/1 050).The fungal culture-positive rate was 36.05％ (367/1 018) in 2009 to 2010,32.45％ (324/1 014) in 2011 to 2012,and 26.86％ (354/1 318) in 2013 to 2014,respectively,with a significant difference among the three periods (x2 =22.37,P＜0.01),showing a decreasing tendency of incidence.Two hundreds and sixtyone strains were isolated from January to March (31.15 ％,261/838),182 strains from April to June (25.53 ％,182/713),237 strains from July to September (30.00％,237/790),370 strains from October to December (36.67％,370/1 009),showing a statistically significant difference among them (x2 =25.19,P ＜ 0.01).The number of infectious strains was most during October to December and fewest during April to June.Conclusions The leading pathogenic fungi of fungal keratitis is Fusarium SP and followed by Aspergillus SP,Helminthosporium SP,Mucor SP in turn.Fungal keratitis is usually prevalent from October to December,and its incidence is still rising in Chinese mainland recently.However,the increasing tendency in South China has been prevented in recent six years.

Analysis of causative genus of keratomycosis and antifungal susceptibility in tropical area of China / 中华实验眼科杂志

Background Hainan Island is a tropical and subtropical area in China,with a suitable climate for fungal growth and breeding.Keratomycosis occurred frequently in this area.It is essential to analyze the causative genus and investigate the sensitive drugs prior to the clinical treatment of fungal keratitis.Objective This study attempted to analyze the fungal population of fungal corneal ulcer patients in Hainan Island of China and examine the susceptibility of antifungal drugs.Methods A series cases observational study was carried out.One hundred and seventy-four eyes of 174 fungal corneal ulcer patients were enrolled in Hainan Eye Hospital from February 2014 to May 2016 based on the diagnosis criteria in Ophthalmology.The specimens at corneal lesions were collected under the aseptic conditions,and fungus was examined by KOH based smear.Mycological culture was performed with potatodextrose agar and Sabourand's agar.The 82 cultured causative strains were identified to characterize the spectrum of the species associated with keratitis infections in Hainan Province.Susceptibilities of these causative strains to ten antifungals were determined in vitro by slip diffusion method.Results By smear microscopy,fungal hyphae and spores were found in 34 specimens of 126 patients,with the positive rate 27.0％.In 174 specimens of fungal culture,82 strains of fungi were found,with the positive rate 47.1％,and typing results revealed that the isolates were distributed among species in the fusarium (47.5％),non-spore fungus (12.2％),aspergillus (9.8％) and phoma (9.8％).Nystatin was proved to be the most effective drug to 77 strains of antifungal drug susceptibility,followed by amphotericin B and terbinafine,with the susceptibility of 88.3 ％,72.7 ％,and 71.4％,respectively.Conclusions Fusarium species,non-spore fungus,aspergillus,and phoma are common pathogenic fungi of keratomycosis around Hainan Island in China,and nystatin,amphotericin B and terbinafine are efficient in the treatment of the fungal corneal ulcer.

Fonsecaea pedrosoi as a rare cause of acute conjunctival ulceration / Fonsecaea pedrosoi como agente raramente associado à úlcera conjuntival aguda

ABSTRACT Conjunctival ulceration accompanied with secretion and pain was observed in a 30-year-old male, 3 days after a perforating corneal trauma. Cultures of conjunctival ulcer samples grew Fonsecaea pedrosoi, a major causative agent of chromoblastomycosis that is typically transmitted during trauma. The conjunctival ulcer was successfully treated with amphotericin B, itraconazole, and fluconazole. This case report summarizes the diagnosis and treatment of a conjunctival ulcer due to F. pedrosoi, which is a rare complication of contaminated ocular trauma. To the best of our knowledge, this is the first reported case of F. pedrosoi causing acute conjunctival ulceration in the literature.

RESUMO O quadro clínico de uma úlcera conjuntival acompanhada de secreção e dor foi observado em homem de 30 anos de idade, 3 dias após um trauma perfurante da córnea. As culturas de uma amostra retirada da úlcera conjuntival foi positiva para Fonsecaea pedrosoi, uma cromoblastomicose, geralmente transmitido após traumatismos. O caso foi tratado com sucesso com a anfotericina B, itraconazol e fluconazol. Este relato de caso reporta o diagnóstico e tratamento de uma úlcera conjuntival causada por F. pedrosoi, que raramente é visto nos olhos expostos a traumatismos contaminados. Até onde sabemos, este é o primeiro caso relatado na literatura de F. pedrosoi causando úlcera conjuntival aguda.

Disseminated cutaneous sporotrichosis associated with ocular lesion in an immunocompetent patient

Abstract: A 59-year-old female patient, previously healthy, immunocompetent, presented left bulbar conjunctiva lesions and nodular-ulcerated lesions on the arms and cervical region, besides left cervical and retroauricular lymphadenopathy. She had previous contact with domestic cats that excoriated her face. The diagnosis was conclusive of disseminated sporotrichosis through clinical and epidemiological history and cultures of skin and ocular secretions. It evolved with good response to oral antifungal therapy.

Epidemiologia de ceratites fúngicas tratadas com ceratoplastia penetrante através de achados histopatológicos / Epidemiology of fungal keratitis treated with penetrating keratoplasty by means of histopathologic findings

RESUMO Objetivo: Estudar, através do exame histopatológico, a epidemiologia de ceratites fúngicas tratadas com ceratoplastia penetrante terapêutica, enfatizando a presença de cirurgia ocular prévia. Métodos: Inicialmente, o estudo foi observacional e transversal de botões corneanos provenientes de ceratoplastia penetrante no período de 2006-2015 enviados para exame histopatológico ao banco de olhos do Hospital Geral de Fortaleza. Os tecidos foram corados com Hematoxilina-eosina, PAS ou Grocott, e examinados com microscópio óptico. Foram selecionados casos com diagnóstico histopatológico de ceratite fúngica. Após a selecão, realizamos revisão de prontuários buscando idade e sexo do paciente, data(s) do(s) transplante(s) por ceratite fúngica, diagnóstico clínico précirúrgico, presença/tipo de cirurgias anteriores e/ou posteriores. Incluímos 62 botões corneanos de 55 pacientes. Resultados: A maioria dos pacientes era do sexo masculino. Apenas 7 (11,29%) casos tiveram recidiva da infecção tratada cirurgicamente. 10 (16,13%) casos possuíam cirurgia ocular prévia a ceratite fúngica tratada por transplante. Nenhum caso teve ceratite fúngica como diagnóstico clínico pré-cirúrgico. A principal forma de fungo no exame histopatológico foi forma leveduriforme isolada, seguida pela leveduriforme associada à filamentosa. O aspecto predominante da membrana de Descemet foi livre de fungos. Conclusão: Demonstramos o potencial curativo das ceratites fúngicas quando tratadas com ceratoplastia penetrante terapêutica e uma possível associação do fator cirurgia ocular prévia ao desenvolvimento dessas infecções. Características do exame histopatológico foram abordadas diferente de outros estudos que, em sua maioria, citam apenas o exame microbiológico. A dificuldade no diagnóstico clínico précirúrgico foi ressaltada, o que pode ter contribuído com a evolução dos casos estudados para tratamento cirúrgico.

ABSTRACT Objective: To study, by means of histopathological examination, the epidemiology of fungal keratitis treated with penetrating keratoplasty therapy, emphasizing the presence of previous ocular surgery. Methods: Initially, we made an observational and cross-sectional study of corneal buttons from penetrating keratoplasty in the 2006-2015 period sent for histopathological examination at the Hospital Geral de Fortaleza Eye Bank.Tissues were stained with hematoxylin-eosin, PAS or Grocott, and examined with an optical microscope. We selected the cases with histopathological diagnosis of fungal keratitis. After the selection, we carried out a review of records seeking for age and sex of patients, date(s) of the graft(s) made to treat fungal keratitis, preoperative clinical diagnosis, presence/type of earlier and/or subsequent surgeries.We included 62 corneal buttons from 55 patients. Results: Most patients were male. Only 7 (11.29%) cases had recurrence of the surgically treated infection. 10 (16.13%) cases had eye surgery prior to fungal keratitis treated by transplant. No cases had fungal keratitis as preoperative clinical diagnosis.The main form of fungus in histopathological examination was isolated yeast form, followed by the yeast form associated with the filamentous form.The predominant aspect of Descemet's membrane was free of fungus. Conclusion: We demonstrated the healing potential of fungal keratitis when treated with penetrating therapeutic keratoplasty and the possible association of previous eye surgery factor for the development of these infections. Characteristics of histopathological examination have been approached differently from other studies that mostly specify only the microbiological examination. The difficulty in preoperative clinical diagnosis was highlighted, which may have contributed to the evolution of the cases studied for surgical treatment.

Correlação clínico-patológica em ceratites fúngicas e uma possível evidência de infecção oportunista: relato de dois casos / Clinicopathological correlation in fungal keratitis and a possible evidence of opportunistic infection: a report of two cases

RESUMO Os autores relatam dois casos de ceratite fúngica, que apresentam em comum no exame histopatológico: a ausência de epitélio, sem ulceração e a integridade da camada de Bowman com a presença de formas fúngicas no seu interior. São sugeridos prováveis mecanismos de recidiva das ceratites fúngicas, ressaltando uma possível "via externa não usual", por meio da penetração do fungo através da camada de Bowman íntegra. A existência desta infecção oportunista não está relatada na literatura oftalmológica e são necessárias mais evidências para que seja considerada como tal.

ABSTRACT The authors describe two cases of fungal keratitis which, upon histopathological examination, are found to have in common the absence of epithelium, without ulceration and the lack of integrity of the Bowman's layer with the presence of fungal forms in their interior. Through them the authors suggest probable mechanisms of recurrence of fungal keratitis, highlighting the possible existence of an "unusual external route" that would occur by the fungus penetration through the full Bowman layer. Although these findings appear not yet reported or recovered in the ophthalmic literature, the authors suggest that they could be possible opportunistic infection signals which, however, require more evidence to be considered as such.

Prognosis of clinical treatment for fungal keratitis and its influence factors / 中华实验眼科杂志

Background Fungal keratitis has poor prognosis and high blinding rate,so it is vital to identify the risk factors that affect the treating outcome and prognosis of fungal keratitis.Objective This study was to evaluate the clinical outcome of fungal keratitis and identify the affecting factors.Methods This was a series cases-observational study.A total of 267 eyes of 267 patients with fungal keratitis were included in Henan Eye Institute during January 2013 to January 2014.Eye examinations were performed including slit-lamp microscope examination,corneal smears,confocal microscopy,fungal culture and identification.Combined anti-fungal drugs were topically used in all eyes for the initial treatment then the treating regimen were selected based on the susceptibility testing.corneal lesion resection combined with conjunctival flap transplantation,lamellar corneal transplantation or penetrating corneal transplantation was performed respectively on the patients with poor curative effect after drug treatment.The clinical prognosis of the patients was graded and the affecting factors for clinical outcome were evaluated.This study protocol complied with Helsinki Declaration and was approved by Ethic Committee of Henan Eye Hospital.Written informed consent was obtained from patients or guardians.Results One hundred and eighty-five eyes were cured by anti-fungal eye drops with the effective rate of 69.29％,and the inflammation was controlled in 60 eyes who received combination procedure of anti-fungal drugs with different surgeries,while 22 eyes lost visual function because of refractory glaucoma and final evisceration.The total clinical effective rate was 91.76％.Aspergillus and Fusarium spp.appeared to be the most common pathogenic fungi by drug sensitivity test.The keratitis caused by Aspergillus had lowest cure rate among different fungi (x2 =11.350,P =0.002) and the most poor clinical prognosis (H=31.285,P =0.013).The medication curative rate was 71.8％ in the patients with positive culture outcome,which was higher than 62.5％ in the patients with negative culture outcome (x2=8.75,P＜0.01).A significant difference was found in the medication curative rate and prognosis between the patients with ≥ 2 kinds of sensitive anti-fungal drugs and the patients with ＜2 kinds of sensitive anti-fungal drugs (77.5％ versus 52.3％,x2 =9.63,P＜0.01;H=24.281,P =0.021).Size of infiltration area,with or without hypopyon,number of sensitive drugs,and pathogenic fungi were significantly correlated with clinical outcome (all at P ＜ 0.05).Conclusions In vitro susceptibility testing can guide clinical drug treatment of fungal keratitis.Infiltration area ＞ 16 mm2,hypopyon ＞2 mm,resistance to those drugs in vitro and infection of Fusarium.spp or Aspergillus.spp are predictors of a poor outcome.

The features of in vivo laser confocal microscope images of frequent fungal keratitis / 中华实验眼科杂志

Background Fungal keratitis is one of primary infectious ocular diseases in China.Conventional diagnostic method is fungal cultivation.In vivo laser confocal microscope is a noninvasive examination of ocular surface.However,the study on features of in vivo laser confocal microscope images of frequent fungal keratitis is still not thorough.Objective This study was to analyze laser confocal microscope imaging features of four typical fungal keratitis.Methods The clinical data of 65 eyes from 65 patients with fungal keratitis were retrospectively analyzed.The patients were initially diagnosed in Nanjing General Hospital of Nanjing Military Command PLA from January 2007 to November 2011, and laser confocal microscope examination of ocular surface and fungal cultivation were performed.The characteristics of laser confocal microscope images were investigated,including shape and type of hypha,distribution of spores and the relationship of hypha with lesion.The differentiation between fungal hypha and other corneal tissues was summarized.Results Fungal cultivation showed that among the 65 patients,Fusarium,Aspergillus,Candida and Alternaria were common pathogenic fungus with the infected proportion 63.0％ , 16.9％,3.0％ and 4.6％ ,respectively, and 12.5％ patients were infected by other fungus.In the images of laser confocal microscope,hyphae of Fusarium presented the branch-like high reflective structure in the corneal superficial stromal layer and thinning line shape in the deep stromal layer.Few inflammatory cells were found.The peudohyphae and spores from Candida were seen in corneal superficial and mid stroma layers, with few inflammatory cells and many proliferating stromal fibers in the lesions.The hyphae of Aspergillus presented worm-like, showing the thinner and shorter shapes in comparison with those of Candida.The hyphae of Alternaria were long,straight and thick in shape,and spherical chlamydospores were found on the hyphal tip.The hyphae, subepithelial plexus, dendritic cells, fibrosis of the cornea all showed high reflection under the laser confocal microscope, but evidently differences appeared in shape,distribution and course in corneas.Conclusions Hyphae are the main basis to diagnose fungal keratitis and differentiate fungi.As a non-invasive examination method,laser confocal microscope can provide useful information for the early diagnosis and treatment of fungal keratitis in vivo.

Distribuição das ceratites infecciosas em hospital terciário no Brasil / Distribution of infectious keratitis in a tertiary hospital in Brazil

OBJETIVO: Investigar sazonalidade de ceratities infecciosas em serviço terciário no Brasil. MÉTODOS: Estudo retrospectivo de dados coletados do Laboratório de Microbiologia Ocular do Departamento de Oftalmologia da Universidade Federal de São Paulo de 2005 a 2009. Foram definidas como ceratites infecciosas aquelas com cultura positiva para o agente. Dados foram distribuídos de acordo com os meses do ano e modelos de regressão linear com variáveis "dummy" foram utilizados para testar sazonalidade. RESULTADOS: Foram diagnosticados 1.468 casos de ceratite infecciosa durante o período do estudo. Bactérias foram responsáveis por 80,3% dos casos seguidas por fungos (7%), Acanthamoeba (6%) e casos mistos (6,7%). Testes estatísticos não mostraram sazonalidade para bactérias (p=0,064), fungos (p=0,379), Acanthamoeba (p=0,062) ou casos mistos (p=0,441). CONCLUSÃO: Não foi observada sazonalidade nas ceratites infecciosas em nossa amostra.

PURPOSE: To investigate the seasonality of infectious keratitis in a tertiary hospital in Brazil. METHODS: Charts from the Ocular Microbiology Laboratory of the Department of Ophthalmology of the Federal University of Sao Paulo were reviewed from 2005 to 2009. Infectious keratitis were defined as those with positive culture. Data were distributed monthly and linear regressions with seasonal dummy models were used to test for seasonal trends. RESULTS: Total of 1,468 cases of keratitis was diagnosed during the study period. Bacterial keratitis were reponsible for 80.3% of all cases, followed by fungal (7%), and Acanthamoeba (6%); 6.7% were mixed cases. Statistical tests showed that there were no seasonal trends for bacteria (p=0.064), fungi (p=0.379), Acanthamoeba (p=0.062) or mixed infections (p=0.441). Conclusions: No seasonal trends for infectious keratitis were observed in our sample.

Queratitis fúngica: revisión actual sobre diagnóstico y tratamiento / Fungal keratitis: review of diagnosis and treament

La queratitis fúngica es una infección característica de zonas tropicales, asociada a trauma vegetal. Existen dudas respecto al método diagnóstico óptimo y la efectividad de los tratamientos disponibles. ¿Cuál es el manejo más apropiado en queratitis fúngica? y ¿Cuál es la mejor forma de establecer el diagnóstico? El cultivo para hongos es el gold standard diagnóstico de elementos fúngicos. Respecto al tratamiento, natamicina y anfotericina B fueron los más utilizados y no demostraron efectividad en estudios prospectivos. Voriconazol demostró efectividad en múltiples infecciones fúngicas. Pudiera ser la droga de elección en condiciones óptimas, dado su mejor penetración intraocular. Se ha reconocido su elevado costo dificultando su aplicación generalizada. Esta revisión entrega recomendaciones para el manejo y establece la necesidad de realizar estudios que evalúen la costo-efectividad de voriconazol para la queratitis fúngica.

Fungal keratitis is a characteristic infection upon tropical zones, associated with vegetal trauma. Doubt exists about the best diagnostic test and the effectiveness of available treatment. Which is the best diagnostic method for fungal keratitis? And, which is the best management? Fungal culture remains as diagnostic gold standard of fungal elements. As of treatment, natamycin and amphotericin B are the most popular drugs for fungal keratitis and they have not shown effectiveness in randomized controlled trials or systematic reviews. Voriconazole showed effectiveness and security in multiple fungal infections. It may be the drug of choice in optimal conditions, because of its better ocular penetration and wider coverage. However, its high price difficult general application. This review establishes management recommendations and the need to perform studies that address cost-effectiveness analysis of voriconazole for fungal keratitis.

The diagnosis and monitor for fungal keratitis by detection of (1,3-) β-D-glucan in tears / 中华实验眼科杂志

Background The diagnosis and treatment of fungal keratitis are knotty.There is no quantitative method to identify the disease and judge the therapeutic effect of the antifungal agent.Studies have determined that serum (1,3-) β-D-glucan level can sensitively and specifically reflect the state of systemic mycotic-causing diseases.However,whether (1,3-) β-D-glucan level in tear can monitor and diagnose mycotic keratitis is unclear.Objective Purpose of this study was to investigate the change of tear (1,3-) β-D-glucan level following the administration of antifungal drug in fungal keratitis patients,and evaluate the diagnosis and monitor value of (1,3-) β-D-glucan in tears for fungal keratitis.Methods Sixty patients who were diagnosed as fungal keratitis by fungal culture were analyzed in Affiliated Hospital of Qingdao University Medical College from July 2010 to May 2012.The patients received the topical administration of antifungal drug for 28 days.Thirty healthy volunteers without eye disease served as normal controls.The tear of 50 μl was collected from each subject for the detection of (1,3)-β-D-glucan before the therapy,7,14,28 days after therapy and 7 days,14 days after the drugs were stopped,respectively.The dynamic changes of (1,3-) β-D-glucan levels in tears were evaluated and compared with the manifestation of the lesions under the laser scanning confocal microscope.The patients without hyphal by the laser scanning confocal microscopy and tear (1,3-)β-D-glucan level less than 20 ng/L were subsequently treated for another 7 days,and the following-up duration was 2 months.The informed consent was obtained before any medical examination was performed from each subject.Results (1,3-)β-D-glucan level in tears (Log value) was (6.37 ±0.48)ng/L in the patient group,and was significantly higher than (2.00±0.31) ng/L in the normal control group (t =2.89,P＜0.01).The lesion was smaller with the gradually clear border,and the number of mycelia was decreased under the laser scanning confocal microscope 7 days after treatment.(1,3-) β-D-glucan level in tears was gradually declined in a time-dependent manner after treatment.The (1,3)-β-D-glucan level in tears (Log) was (5.19 ± 0.42),(4.16 ± 0.33),(2.99 ±0.42),(2.91 ±0.39),(2.80±0.40) ng/L 7,14,28 days after treatment,and 7 days,14 days after the drugs were stopped,respectively,with a statistically significant difference in comparison with (6.37±0.48)ng/L before treatment (P＜0.01).(1,3)-β-D-gluean level in tears remained a lower level till the end of follow-up,and no recurrence of lesion was found in the patient group.Conclusions Detecting (1,3)-β-D-glucan level in tears is of good diagnosis and monitor value in the evaluation of fungal keratitis.

Etiological identification of 50 isolates from fungal corneal ulceration by semi-nested PCR amplification of ITS2 region / 中华检验医学杂志

Objective To identify the pathogens of 50 cases of fungal corneal ulceration by using semi-nested PCR amplification of ITS2 region.Methods Fifty isolates of fungal corneal ulceration and 3standard fungal strains cultures were collected and their DNAs were extracted.Their ITS2 regions were amplified by semi-nested PCR and sequenced.The results were compared with the nucleotide sequences in the NCBI GenBank.The pathogens of the fungi were identified and their distribution were analysed.Results The sequences results of the 3 standard fungal strains were consistent with the information in the GenBank.The pathological microorganisms of 50 cases of fungal corneal ulceration were:24 Fusarium (48％),including 17 Fusarium solani,6 Fusarium oxysporum and 1 Fusarium verticillioide; 10 Aspergillius (20％),including 5 Aspergillius flavus,3 Aspergillius sydowii and 2 Aspergillius nidulans; 6 Penicillium (12％),including 2 Penicillium citreo-viride,2 Penicillium multicolor and 2 Penicillium oxalicum ;5 Candida (10％),including 3 Candida albicans and 2 Candida parapsilosis; 3 Cladosporium (6％),including 2 Cladosporium herbarum and 1 case of Cladosporium cladosporioides ; 1 case of Neurospora crassa (2％) ;1 Alternaria alternata(2％).Conclusion Semi-nested PCR amplification of ITS2 region was proved to be a fast,simple and accurate method to identify pathogens of fungal corneal ulceration,and may be useful for personalized treatment and epidemiological investigation of local fungi.

Epidemiology and medical prediction of microbial keratitis in southeast Brazil / Epidemiologia e previsibilidade no diagnóstico clínico de ceratite microbiana no sudeste do Brasil

PURPOSE: The goals of the study were the following: 1) to show the epidemiology of microbial keratitis (MK) in the southeast Brazil, 2) to compare the epidemiological differences between fungal (FK) and bacterial keratitis (BK), and 3) to evaluate the frequency which ophthalmologists accurately differentiate bacterial keratitis from fungal keratitis based on clinical diagnosis. METHODS: A retrospective chart analysis of all clinically diagnosed microbial keratitis patients presenting between October, 2003 and September, 2006 was performed. Demographic features, ocular and laboratory findings, and information regarding the risk factors and clinical evolution were recorded. RESULTS: Among 118 consecutive patients with a clinical diagnosis of microbial keratitis, the positive culture rate was 61 percent. The predominant bacterial and fungal pathogens isolated were S. epidermidis and Fusarium spp. Prior corneal injury was more frequent among fungal keratitis than bacterial keratitis cases (p<0.0001). Coexisting systemic diseases, ocular diseases, and previous ocular surgery were more frequent among BK cases (p=0.001; p=0.001; p=0.004; respectively). The following clinical findings were more frequent in bacterial keratitis: hypopion, corneal peripheral superficial vascularisation, and ulceration area >20 mm² (p<0.05). The diagnosis was predicted correctly in 81.6 percent of bacterial keratitis cases and in 48.1 percent of fungal keratitis cases. CONCLUSION: Medical judgment of microbial keratitis agent is possible based on clinical and epidemiological data, but it is more difficult for fungal infection. Thus, such data cannot be the only basis for the diagnosis of suspected microbial keratitis, but oriented clinical suspicion based on these data may be beneficial for guiding antimicrobial treatment and earlier therapy.

OBJETIVO: Os objetivos deste estudo foram os seguintes: 1) mostrar epidemiologia da ceratite microbiana (CM) no sudeste do Brasil, 2) para comparar as diferenças epidemiológicas entre ceratites fúngicas (CF) e bacterianas (CB) e 3) avaliar a frequência com que os oftalmologistas distinguem com precisão ceratite fúngica de ceratite bacteriana baseado no diagnóstico clínico. MÉTODOS: Uma análise retrospectiva de todas as ceratites microbianas diagnosticadas clinicamente apresentando entre outubro de 2003 e setembro de 2006 foi realizada. As características demográficas, relativas ocular e de laboratório, e informações aos fatores de risco e evolução clínica foram registrados. RESULTADOS: Dentre 118 pacientes consecutivos com diagnóstico clínico de ceratite microbiana, a taxa de cultura positiva foi de 61 por cento. Os patógenos predominantes de bactérias e fungos isolados foram S. epidermidis e Fusarium spp. O trauma de córnea foi mais frequente entre os casos de ceratite fúngica do que ceratite bacteriana (p<0,0001). A coexistência de doenças sistêmicas, doenças oculares e cirurgia ocular prévia foram mais frequentes entre os casos de ceratite bacteriana (p=0,001, p=0,001, p=0,004, respectivamente). Os seguintes achados clínicos foram mais frequentes em ceratite bacteriana: hipópio, vascularização periférica da córnea superficial e área de ulceração >20 mm² (p<0,05). O diagnóstico foi corretamente estimado em 81,6 por cento dos casos de CB e em 48,1 por cento dos casos de CF. CONCLUSÃO: A presunção clínica do agente da ceratite microbiana é possível baseada em dados clínicos e epidemiológicos, mas é mais difícil para infecção fúngica. Assim, esses dados não podem ser a única base para o diagnóstico de suspeita de ceratite microbiana, mas a suspeita clínica orientada com base nesses dados pode ser benéfica para orientar o tratamento antimicrobiano e terapia precoce.