Fungal keratitis

Sonal S TuliUniversity of Florida, Gainesville, FL, USA  Clinical question: What is the most appropriate management of fungal keratitis?Results: Traditionally, topical Natamycin is the most commonly used medication for filamentous fungi while Amphotericin B is most commonly used for yeast. Voriconazole is rapidly becoming the drug of choice for all fungal keratitis because of its wide spectrum of coverage and increased penetration into the cornea.Implementation: Repeated debridement of the ulcer is recommended for the penetration of topical medications. While small, peripheral ulcers may be treated in the community, larger or central ulcers, especially if associated with signs suggestive of anterior chamber penetration should be referred to a tertiary center. Prolonged therapy for approximately four weeks is usually necessary.Keywords: fungal keratitis, keratomycosis, antifungal medications, debridemen

Curvularia keratitis after laser in situ keratomileusis from a feline source

Fungal keratitis following laser in situ keratomileusis (LASIK) is extremely rare. Except in cases that follow trauma, the source of fungal organisms is unknown in published reports. We report a case of keratitis following LASIK that could be directly traced to a fungal skin infection of the patient's pet cat

Reduction in Severity of a Herpes Simplex Virus Type 1 Murine Infection by Treatment with a Ribozyme Targeting the UL20 Gene RNA▿

Hammerhead ribozymes were designed to target mRNA of several essential herpes simplex virus type 1 (HSV-1) genes. A ribozyme specific for the late gene UL20 was packaged in an adenovirus vector (Ad-UL20 Rz) and evaluated for its capacity to inhibit the viral replication of several HSV-1 strains, including that of the wild-type HSV-1 (17syn+ and KOS) and several acycloguanosine-resistant strains (PAAr5, tkLTRZ1, and ACGr4) in tissue culture. The Ad-UL20 Rz was also tested for its ability to block an HSV-1 infection, using the mouse footpad model. Mouse footpads were treated with either the Ad-UL20 Rz or an adenoviral vector expressing green fluorescent protein (Ad-GFP) and then infected immediately thereafter with 104 PFU of HSV-1 strain 17syn+. Ad-UL20 ribozyme treatment consistently led to a 90% rate of protection for mice from lethal HSV-1 infection, while the survival rate in the control groups was less than 45%. Consistent with this protective effect, treatment with the Ad-UL20 Rz reduced the viral DNA load in the feet, the dorsal root ganglia, and the spinal cord relative to that of the Ad-GFP-treated animals. This study suggests that ribozymes targeting essential genes of the late kinetic class may represent a new therapeutic strategy for inhibiting HSV infection

Overview of Corneal Transplantation for the Nonophthalmologist

Corneal transplant is a procedure that aims to replace dysfunctional corneal tissue with a transparent graft and is one of the most widely performed transplant surgeries, but its public and professional awareness is low outside of ophthalmology. Corneal tissue consists of 5 major layers that serve to maintain its structural integrity and refractive shape: the epithelium, Bowman’s layer, the stroma, Descemet’s membrane, and the endothelium. Failure or irreversible damage to any layer of the cornea may be an indication for corneal transplant, and variants of this procedure may be full thickness or selectively lamellar. Complications related to corneal transplantation may occur anywhere from during surgery to years afterward, including rejection, dehiscence, cataract, and glaucoma. Complications should be managed by an ophthalmologist, but other physicians should be aware of prophylactic medications. Topical immunosuppressants and steroids are effective for preventing and treating rejection episodes, whereas there is little evidence to support the use of systemic immunosuppression. Eye protection is recommended for any corneal transplant recipient. Physicians should counsel patients on corneal donation, especially if outside the United States, where donor tissue is in short supply

Connective tissue growth factor expression and action in human corneal fibroblast cultures and rat corneas after photorefractive keratectomy. Investigative Ophthalmology and Visual

PURPOSE. Connective tissue growth factor (CTGF) has been linked to fibrosis in several tissues. In this study, the interactions between CTGF and transforming growth factor (TGF)-␤ were assessed in human corneal fibroblasts, and the levels and location of CTGF protein and mRNA were measured during healing of excimer laser ablation wounds in rat corneas. METHODS. Human corneal fibroblasts were incubated with TGF-␤1, -␤2, and -␤3 isoforms, and CTGF mRNA and protein were measured. CTGF was immunolocalized in the cultured fibroblasts by using a specific antibody. Regulation of collagen synthesis by TGF-␤ and CTGF was assessed in human corneal fibroblasts with a neutralizing antibody and an antisense oligonucleotide to CTGF. CTGF mRNA and protein were measured in rat corneas up to day 21 after excimer ablation of the cornea. CTGF protein was immunolocalized in rat corneas after photorefractive keratectomy (PRK), and the presence of CTGF mRNA and protein in ex vivo rat corneal scrapings was established. RESULTS. All three TGF-␤ isoforms stimulated expression of CTGF in human corneal fibroblasts, and CTGF was immunolocalized in the cells. Both TGF-␤ and CTGF increased collagen synthesis in corneal fibroblasts. Furthermore, CTGF antibody or antisense oligonucleotide blocked TGF-␤-stimulated collagen synthesis. CTGF protein and mRNA increased in rat corneas through day 21 after PRK. CTGF expression was also detected in ex vivo scrapings of rat corneas. CONCLUSIONS. These data demonstrate that CTGF is expressed by corneal cells after stimulation by TGF-␤, that CTGF expression increases significantly during corneal wound healing, and that CTGF mediates the effects of TGF-␤ induction of collagen synthesis by corneal fibroblasts. These data support the hypothesis that CTGF promotes corneal scar formation and imply that regulating CTGF synthesis and action may be an important goal for reducing corneal scarring. (Invest Ophthalmol Vis Sci. 2003;44:1879 -1887) DOI:10.1167/iovs.02-0860 C onnective tissue growth factor (CTGF) is a secreted, cysteine-rich monomer of approximately 38 kDa that was originally identified as a mitogen for fibroblast in conditioned media cultures from human umbilical vein endothelial cells. 8 Significant upregulation of CTGF was detected in human heart samples derived from patients with cardiac ischemia. Elevated CTGF protein and mRNA levels were found in sclerotic skin fibroblasts, 9 specimens of inflammatory bowel disease, 10 and retrocorneal membranes, 11 and overexpression of CTGF was linked to human renal fibrosis. 12 The transforming growth factor (TGF)-␤ system 13,14 has also been implicated in promoting scarring and fibrosis in numerous tissues, including lung, 15 kidney, The CTGF system has not been investigated in corneal wound healing. To help assess our hypothesis that CTGF regulates corneal scarring, we investigated the influence of TGF-␤ isoforms on expression of CTGF in human corneal fibroblasts and the role of CTGF in mediating the effects of TGF-␤ on CTGF levels and collagen synthesis by cultured human corneal fibroblasts. We measured the levels of CTGF protein and mRNA in rat corneas after PRK and localized CTGF in healing rat corneas

Infectious keratitis after LASIK

To report the clinical course, management, and outcomes of culture-proven infectious keratitis in 15 eyes of 13 subjects after LASIK. Retrospective, noncomparative, interventional case series. Fifteen eyes of 13 subjects who underwent LASIK and developed culture-positive keratitis. Infectious keratitis was encountered in the operative eyes between 1 day and 450 days. Cultures were obtained, and topical antibiotic therapy was administered in all cases. Some cases required flap lifting, irrigation, and soaking of the bed with antibiotics, flap amputation, or further surgical intervention. Time periods from onset to diagnosis, from clinical diagnosis to clinical resolution, final acuities, microbiologic profiles, and medical and surgical interventions were reviewed. Onset of symptoms of infection varied, depending on the infectious organism. Bacterial organisms tended to present earlier, whereas mycobacterial and fungal organisms had a later mean onset of presentation. Furthermore, the atypical organisms such as mycobacteria, fungus, and acanthamoeba also had a more delayed diagnosis, resulting in a prolonged disease course. Infectious keratitis after LASIK is a potentially vision-threatening complication. Onset of symptoms varies depending on causative agents. Furthermore, atypical organisms in the interface or beneath the flap can pose both diagnostic and therapeutic dilemmas. Location in the interface can make it more difficult to culture the organisms and prevent adequate penetration of topical antibiotics

Trends in Fungal Keratitis in the United States, 2001 to 2007

Fungal keratitis is a serious ocular infection that is considered to be rare among contact lens wearers. The recent Fusarium keratitis outbreak raised questions regarding the background rate of Fusarium-related keratitis and other fungal keratitis in this population. Retrospective, multicenter case series. Six hundred ninety-five cases of fungal keratitis cases who presented to 1 of 10 tertiary medical centers from 2001 to 2007. Ten tertiary care centers in the United States performed a retrospective review of culture-positive fungal keratitis cases at their centers between January 2001 and December 2007. Cases were identified using microbiology, pathology, and/or confocal microscopy records. Information was collected on contact lens status, method of diagnosis, and organism(s) identified. The quarterly number of cases by contact lens status was calculated and Poisson regression was used to evaluate presence of trends. The Johns Hopkins Medicine Institutional Review Board (IRB) and the IRBs at each participating center approved the research. Quarterly number of fungal keratitis cases and fungal species. We identified 695 fungal keratitis cases; 283 involved the use of contact lenses. The quarterly number of Fusarium cases increased among contact lens wearers (CLWs) during the period that ReNu with MoistureLoc (Bausch & Lomb, Rochester, NY) was on the market, but returned to prior levels after withdrawal of the product from the market. The quarterly frequency of other filamentous fungi cases showed a statistically significant increase among CLWs comparing October 2004 through June 2006 with July 2006 through December 2007 with January 2001 through September 2004 ( P<0.0001). The quarterly number of Fusarium fungal keratitis cases among CLWs returned to pre-Renu with Moistureloc levels after removal of the product from the market. However, the number of other filamentous fungal keratitis cases, although small, seems to have increased among refractive CLWs. Reasons for these apparent increases are unclear. Proprietary or commercial disclosure may be found after the references