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

Validation of the Postnatal Growth and Retinopathy of Prematurity (G-ROP) screening criteria

Background: Retinopathy of prematurity (ROP) is a leading cause of irreversible blindness in infants. The Postnatal Growth and ROP (G-ROP) study proposed new screening criteria for ROP. This study aimed to validate the G-ROP screening criteria in a group of Iranian premature infants who were treated in the neonatal intensive care unit (NICU) for at least 40 days. Methods: In this retrospective study, we extracted the data pertaining to infants admitted to the NICU from January 2020 to December 2021. We screened all the included infants for ROP based on the Iranian national screening criteria. We applied the G-ROP criteria to our study population, and if no criterion was met, the infant was exempted from ROP screening. We determined the sensitivity and specificity of the G-ROP guidelines for ROP detection, along with its capacity for predicting the requirement for ROP treatment. Moreover, we compared the G-ROP guidelines with the Iranian and North American guidelines for ROP screening. Results: A total of 166 premature infants with complete datasets were included: 130 had ROP, of whom 61 were treated. There were 109 female infants (65.7%). The mean (standard deviation [SD]) birth weight and gestational age were 1080 (256) g and 28.28 (1.97) weeks, respectively. Applying the G-ROP criteria, 127 of 130 infants with ROP were identified (sensitivity, 97.69%; 95% confidence interval [CI], 95.11% – 100%), and of 36 infants without ROP, three were correctly excluded (specificity, 8.33%; 95% CI, 0% – 17.36%). The G-ROP criteria did not fail to identify infants who required treatment for ROP (sensitivity, 100%; 95% CI, 98.29 – 100) and had a specificity of 8.69% (95% CI, 2.04% – 15.34%). Although the Iranian and North American criteria had 100% sensitivity for infants with any stage of ROP, they could not detect infants without ROP (0% specificity). Conclusions: The G-ROP screening criteria had a sensitivity of 100% in identifying infants requiring treatment for ROP in our high-risk group; however, specificity was not sufficiently high. Further studies with larger numbers of referred infants could confirm a decrease in the burden of retinal examinations using these criteria

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

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

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

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