Evaluation of agent and host factors in progression of mycotic keratitis: A histologic and microbiologic study of 167 corneal buttons

Abstract

PurposeTo evaluate the host and agent factors in the progression of mycotic keratitis through the microbiologic evaluation and histologic study of human corneal buttons obtained at the time of therapeutic keratoplasty. DesignRetrospective noncomparative consecutive case series. MaterialsOne hundred sixty-seven corneal buttons from 148 patients of microbiologically diagnosed and treated cases of mycotic keratitis who underwent therapeutic keratoplasty between January 1995 and May 1998. MethodsTherapeutic penetrating keratoplasty, review of microbiologic results, histopathologic and microbiologic evaluation of the corneal buttons of mycotic keratitis Main outcome measuresHistologic evaluation of the buttons for morphologic changes, degree and distribution of inflammatory cells, presence or absence of fungal filaments, and their degree and distribution within the corneal buttons. ResultsThe diagnosis of fungal infection was made on corneal scrapings in 36 cases; whereas in 131 (78%), the fungus was grown in cultures and identified as Aspergillus in 55 (42%), Fusarium in 42 (32%), unidentified hyaline fungi in 22 (17%), dematiaceous (unidentified) in 4 (3%), and others in 8 (6%). The mean interval between diagnosis and keratoplasty was 19 (±40) days. From the keratoplasty specimen, the fungus was identified at histologic examination in 127 of 167 (76%) buttons and grown by culture techniques in 76 of 115 (66%) buttons. The fungal species identified in the corneal button were Fusarium in 30 (39%); Aspergillus in 25 (33%); unidentified hyaline in 19 (25%), and others in 2 (3%). Fungus-positive corneal buttons had early surgery (mean, 15 days) compared with fungus-negative (39 days) corneal buttons (P = 0.0005), with 93% fungus positivity in the buttons removed within 2 weeks and 42% after 2 months. In the fungus-positive buttons, there was an inverse correlation between the degree, distribution of inflammatory cells, and fungal filaments (r = −0.255, P = 0.024; r = −0.199, P = 0.027), respectively. The factors necessitating an early keratoplasty were heavy fungal load, deeper penetration of fungus, and possibly insufficient inflammation to combat infection. A granulomatous reaction was noted in the posterior stroma and around the fragmented Descemet’s membrane in 23 buttons (13.8%), independent of fungal species. Inflammation was unaffected by elimination of fungus and increasing interval between diagnosis and treatment. ConclusionsRapid progression of mycotic keratitis in the early phases is by agent factors such as heavy load and deeper penetration of the fungus, insufficient inflammatory response, and possibly relative ineffectiveness of antifungal agents. Progression in the later phase of mycotic keratitis need not necessarily be agent mediated; it could be either host-modulated, species-related, or drug resistance, thereby suggesting that ideal treatment regimens should include sensitivity-based antifungal therapy aided by in vivo monitoring of fungal filaments.