What is causing the corneal ulcer? Management strategies for unresponsive corneal ulceration.

Infectious keratitis represents a significant cause of ocular morbidity in the United States. The work-up and treatment of presumed infectious keratitis (PIK) has changed in the past two decades. The development of newer topical antibiotics has enabled broad-spectrum antibiotic coverage with good tissue penetration. The majority of PIK cases respond well to this strategy. The small numbers of cases that do not respond to the treatment are the cases that offer a diagnostic and therapeutic challenge. This review will describe different algorithms that can be followed for the successful management of patients with difficult or progressive PIK. These algorithms are based on scientific work and on our empirical clinical experience. The review will also present three different clinical cases of PIK that were managed according to the algorithms presented in this review.

Topical interferon alpha 2b eye-drops for treatment of ocular surface squamous neoplasia: a dose comparison study.

BACKGROUND/AIMS To compare the effectiveness and side-effect profile of two doses of interferon alpha2b (IFNalpha2b) eye-drops (1 million international units (IU)/ml versus 3 million IU/ml) in the treatment of ocular surface squamous neoplasia (OSSN). METHODS Retrospective case series. RESULTS Thirty-five eyes were identified over an 11-year period (1996-2007). Twenty-one eyes (19 patients) with conjunctival intraepithelial neoplasia (CIN) were treated with 1 million IU/ml of topical IFN-alpha2b; 12 eyes (nine patients) with CIN were treated with 3 million IU/ml. Two patients with squamous cell carcinoma (SCC) were treated with topical interferon, one with 1 million IU/ml and one with 3 million IU/ml. Baseline demographic information was not statistically different between the two groups. In patients with CIN, topical therapy eliminated disease in 81% of eyes in the 1 million IU/ml group versus 92%, in the 3 million IU/ml group, p=0.41. The median time to OSSN resolution was 2.8 months in the 1 million IU/ml group and 1.9 months in the 3 million IU/ml group, p=0.55. Neither eye with SCC responded to interferon therapy. Topical therapy was well tolerated. After a median follow-up of 24 months, three recurrences were seen in eyes successfully treated with topical therapy. CONCLUSION In our study, there were no significant differences between the 1 million IU/ml group and the 3 million IU/ml group for the treatment of CIN.

Molecular identification of t4 and t5 genotypes in isolates from acanthamoeba keratitis patients.

Acanthamoeba keratitis (AK) is a rare but sight-threatening ocular infection. Outbreaks have been associated with contaminated water and contact lens wear. The epidemiology and pathology may be associated with unique genotypes. We determined the Rns genotype for 37 clinical isolates from 23 patients presenting at the University of Miami Bascom Palmer Eye Institute with confirmed AK infections in 2006 to 2008. The genus-specific ASA.S1 amplicon allowed for rapid genotyping of the nonaxenic cultures. Of the 37 isolates, 36 were of the T4 genotype. Within this group, 13 unique diagnostic fragment 3 sequences were identified, 3 of which were not in GenBank. The 37th isolate was a T5, the first in the United States and second worldwide to be found in AK. For five patients with isolates from the cornea and contact lens/case, identical sequences within each patient cluster were observed, confirming the link between contact lens contamination and AK infection. Genotyping is an important tool in the epidemiological study of AK. In this study, it allowed for the detection of new strains and provided an etiological link between source and infection. Additionally, it can allow for accurate categorizing of physiological differences, such as strain virulence, between isolates and clades.

Pseudomonas aeruginosa in vitro corneal isolate sensitivity to ofloxacin, ciprofloxacin, and trovafloxacin: a comparative study.

PURPOSE: To compare sensitivity of Pseudomonas aeruginosa corneal isolates to ofloxacin, ciprofloxacin, and trovafloxacin. METHODS: Sensitivities of P. aeruginosa corneal isolates to each antibiotic from the periods 1985 to 1987 (n = 32) and 1995 to 1999 (n = 85) were evaluated in vitro with E tests (AB Biodisk; Remel, Lenexa, Kansas). RESULTS: Overall, the percent of P. aeruginosa corneal isolates sensitive in vitro to ofloxacin (106/117, 90.6%) was significantly less than to ciprofloxacin (113/117, 96.6%, P =.016) and trovafloxacin (113/117, 96.6%, P =.016). We observed trends of decreasing sensitivity to ciprofloxacin and trovafloxacin, which were not statistically significant. Sensitivity to ofloxacin remained unchanged; however, sensitivity to ofloxacin was always less than sensitivity to ciprofloxacin and trovafloxacin. CONCLUSION: Although in vitro susceptibilities may not correlate with in vivo efficacy, our data suggest that ciprofloxacin and trovafloxacin are superior to ofloxacin in the treatment of P. aeruginosa keratitis.

Endophthalmitis after keratoprosthesis: incidence, bacterial causes, and risk factors.

OBJECTIVES: To determine the rate of endophthalmitis in a group of patients with keratoprostheses and to analyze possible risk factors. METHODS: A total of 108 patient eyes, operated on between 1990 and 2000 with double-plated keratoprostheses, were analyzed with regard to the surface flora, the incidence and cause of bacterial endophthalmitis or sterile vitreitis, the keratoprosthesis design, prophylactic antibiotics, concomitant immunosuppression, and preoperative diagnosis. RESULTS: Surveillance cultures were obtained from 30 uninfected eyes. The flora was similar to that reported in the normal population and did not vary significantly with time. Thirteen cases of bacterial endophthalmitis occurred 2 to 46 months postoperatively in the patient population that had been followed up for 2 months to 17 years (average, 3 years 4 months). The incidence was 39% in 13 patients with Stevens-Johnson syndrome, 19% in 27 patients with ocular cicatricial pemphigoid, and 7% in 28 patients with ocular burns. Only 1 of the other 40 cases (consisting mostly of repeated graft failures in noncicatrizing conditions) developed endophthalmitis; this patient had a filtering bleb. All endophthalmitis pathogens were gram positive: Streptococcus pneumoniae, 23%; other streptococci, 39%; Staphylococcus aureus, 23%; and Staphylococcus epidermidis, 15%. CONCLUSIONS: The most important risk factor for endophthalmitis after these keratoprostheses was found to be preoperative diagnosis. The rate of infection was very high in Stevens-Johnson syndrome and ocular cicatricial pemphigoid, moderate in chemical burns, and low in noncicatrizing corneal disease.

Recurrent fungal keratitis and endophthalmitis.

PURPOSE: To report a case of recurrent fungal sclerokeratitis and endophthalmitis with a very successful outcome due to aggressive combined surgical and medical therapy. To discuss the management of this potentially devastating infection. METHODS: A 65-year-old man presented with 6 months of left eye redness and irritation after injury from organic matter propelled from an airboat. Initially, he had been treated with foreign body removal, antibiotics, and steroids. He was diagnosed with reactive sclerokeratitis at presentation and was treated with steroids. However, when he did not improve, cultures were obtained and Acremonium species filamentous fungi was identified. Despite treatment with appropriate topical and systemic antifungals, his fungal sclerokeratitis progressed to endophthalmitis. Two therapeutic penetrating keratoplasties (PKs) with iridectomy and intraocular amphotericin B were necessary to eradicate the fungal infection. RESULTS: Visual acuity was restored to 20/25-3 with correction 9 months after initial presentation. There was no recurrence of fungal infection after the second therapeutic PK. CONCLUSION: The possible reasons for recurrence of fungal infection are discussed. The role of timely and aggressive medical and surgical intervention for fungal sclerokeratitis and endophthalmitis in restoring excellent vision is emphasized.

Shifting trends in bacterial keratitis in south Florida and emerging resistance to fluoroquinolones.

OBJECTIVE: To study the distribution, current trends, and patterns of resistance to antimicrobial agents of bacterial keratitis isolates in South Florida. DESIGN: Retrospective, observational, case series. PARTICIPANTS: The microbiology records of all patients with bacterial keratitis seeking treatment at the Bascom Palmer Eye Institute from January 1, 1990 through December 31, 1998 were reviewed. MAIN OUTCOME MEASURES: In vitro laboratory minimum inhibitory concentration testing of the corneal isolates to the fluoroquinolones (ofloxacin and ciprofloxacin) and to the aminoglycosides (tobramycin and gentamicin) was performed using the Vitek (Automatic Microbial System Biomerieux Vitek, Inc., Hazelwood, Missouri) method. RESULTS: During this 9-year period, 2920 consecutive corneal cultures were obtained, and a pathogen was recovered in 1468 cultures (50%). The number of corneal ulcers scraped, positive cultures, recovered bacterial isolates, and ratio of gram-positive to gram-negative isolates per year remained approximately equal throughout the study period. Staphylococcus aureus and Pseudomonas aeruginosa represented 19.4% and 25.7%, respectively, of the total bacterial isolates during this period. However, we documented a gradual increase in the number of S. aureus keratitis isolates (29% of gram-positive organisms in 1990 versus 48% in 1998, P = 0.01) coupled with a decrease in the number of P. aeruginosa isolates (54% of gram-negative organisms in 1990 versus 46% in 1998). A decrease in the incidence of contact lens-associated keratitis and P. aeruginosa isolates in this group of patients was documented. Serratia marcescens and P. aeruginosa were most commonly isolated in contact lens-associated keratitis (18% each). There was increasing laboratory resistance of S. aureus keratitis isolates to the fluoroquinolones (11% in 1990 to 28% in 1998), but resistance patterns to the aminoglycosides remained unchanged. There was a three-fold increase in the percentage of resistant S. aureus isolates to fluoroquinolones between 1990 and 1994 and between 1995 and 1998. Both fluoroquinolones and aminoglycosides exhibited low in vitro effectiveness against P. aeruginosa throughout the study period. CONCLUSIONS: The increased recovery of S. aureus keratitis isolates and decreased laboratory effectiveness against fluoroquinolones to these pathogens present an important therapeutic challenge.

Capnocytophaga keratitis.

PURPOSE: To review the clinical course, treatment, and visual outcomes of keratitis caused by the gram negative rod CAPNOCYTOPHAGA: DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Ten patients with culture-proven unilateral CAPNOCYTOPHAGA: keratitis examined at the Bascom Palmer Eye Institute between January 1, 1989, and December 31, 1998. INTERVENTION: All patients underwent standard diagnostic microbiologic evaluation, and topical antimicrobial therapy was instituted. A penetrating keratoplasty or enucleation was performed in some patients. MAIN OUTCOME MEASURES: The changes in visual acuity and clinical response to antimicrobial therapy. RESULTS: Predisposing factors were present in all patients. Cultures identified CAPNOCYTOPHAGA: species at a mean of 7.5 days. Initial topical treatment consisted of an aminoglycoside and vancomycin in four patients, a quinolone or aminoglycoside alone in two patients each, and ofloxacin with vancomycin or tobramycin with ceftazidime in one patient each. After the microbiologic identification of CAPNOCYTOPHAGA:, treatment in four patients was changed to intensive, topical clindamycin. Five of the 10 eyes were medically cured (3 of these eyes underwent penetrating keratoplasty for corneal scarring), and 5 eyes required enucleation. The indications for enucleation included persistent infection with development of endophthalmitis or blind, painful eye. Five of the 10 eyes achieved 20/80 or better final visual acuity. Four of these five eyes were treated with topical clindamycin. CONCLUSIONS: Important factors in achieving a good visual outcome in CAPNOCYTOPHAGA: keratitis include early microbiologic identification and intensive therapy with topical clindamycin. CAPNOCYTOPHAGA: should be included in the differential diagnosis of bacterial keratitis in patients with suggestive predisposing factors or with protracted keratitis unresponsive to treatment.

Corneal biopsy in the management of progressive microbial keratitis.

PURPOSE: To study the indications and role of diagnostic corneal biopsy in the management of patients with progressive microbial keratitis. METHODS: The records of 33 consecutive patients who underwent a diagnostic corneal biopsy from January 1, 1986, to December 31, 1998, were reviewed. The indication for corneal biopsy was progressive infectious keratitis despite intensive broad-spectrum topical antimicrobial therapy, or progressive stromal infiltration inaccessible to corneal scrapings. Microbiologic evaluation of all corneal biopsies was performed, and 11 of the 33 biopsies were also examined histopathologically. RESULTS: A microorganism was isolated from 27 (82%) of the 33 corneal biopsies. Of the six patients with a negative biopsy, a penetrating keratoplasty was performed in five patients and the pathogen was identified by examination of the corneal button. In one patient no microorganism was identified; however, the infection resolved with topical antimicrobial therapy. The most common risk factor for keratitis was foreign body exposure or corneal abrasion (14 patients). A solid stromal infiltrate was the most common pattern of corneal involvement. Corneal biopsy revealed previously unidentified microorganisms that led to a change in antimicrobial therapy in 24 (89%) of the 27 patients and confirmed prior culture results in the remaining 3 patients. Microbiologic evaluation of the corneal biopsy was more sensitive than histopathologic examination. Acanthamoeba was the most commonly isolated pathogen (five cases), followed by Propionibacterium acnes and Fusarium (four cases each). Gram-positive organisms were isolated in 16 patients. Only five of the 27 patients with a positive corneal biopsy required a penetrating keratoplasty, in contrast to five of the six patients with a negative corneal biopsy (P =.005). During the 13-year period of the study, only three corneal biopsies were performed in the last 6 years. CONCLUSIONS: Microbiologic evaluation of a diagnostic corneal biopsy contributed significantly to the diagnosis, treatment, and outcome of patients with progressive infectious keratitis.

Effects of methylprednisolone and cyclosporine A on fungal growth in vitro.

PURPOSE: The management of corneal transplants after mycotic keratitis often poses a therapeutic dilemma. Clinicians are hesitant to use topical steroids because of their potential enhancement of fungal growth. This study seeks to evaluate the in vitro effects of methylprednisolone and cyclosporine A on the growth of various molds that often are responsible for keratomycoses. METHODS: Fusarium oxysporum, Fusarium solani, and Aspergillus fumigatus were grown in the presence of varying concentrations of methylprednisolone, cyclosporine A, and vehicle controls. Fungal growth was evaluated in a masked fashion based on the number of colonies and their morphologies. RESULTS: All tested concentrations of cyclosporine A (1%, 2%, 4%) had a statistically significant suppressive effect on the growth of F. oxysporum (p<0.001) and F. solani (p<0.001) compared with methylprednisolone and vehicle control solutions. A dose-dependent decrease in the number of colonies grown also was noted for F. oxysporum (p<0.001) and F. solani (p<0.001). In the case of A. fumigatus, cyclosporine A significantly decreased the colony size (p<0.015) in a dose-dependent fashion. CONCLUSIONS: Cyclosporine A appears to have an inhibitory effect on fungal growth in vitro. Cyclosporine A may be an important alternative to topical steroids for management of corneal transplants after mycotic keratitis.

Nontuberculous mycobacterial keratitis in south Florida.

OBJECTIVE: This study aimed to review the clinical features, therapeutic response, and histopathology of cases of nontuberculous mycobacterial keratitis at the Bascom Palmer Eye Institute. DESIGN AND PARTICIPANTS: Retrospective review of medical records, clinical photographs, histopathology, and microbiology of 24 cases of nontuberculous acid-fast keratitis over the past 15 years. RESULTS: Causal organisms included Mycobacterium chelonae (16), M. fortuitum (3), M. avium-intracellulare (2), M. nonchromogenicum (1), M. triviale (1), and M. asiaticum (1). Clinically, the keratitis had a superficial location except in those patients with a history of surgery. Amikacin was the most commonly used antibiotic (63%). Three patients were treated with Clarithromycin. In one patient, it was stopped because of toxicity; the other two had resolution of their infiltrates. Fifty-five percent did not respond to topical antimicrobial therapy. The organisms as a group were sensitive to amikacin and Clarithromycin and resistant to the fluoroquinolones. Sixty-four percent of the group that failed to respond to medical treatment were treated with steroids after the diagnosis was known, in comparison to 44% of the group treated successfully with medications. The histopathology of the patients treated with steroids showed minimal inflammation despite a large number of organisms, in contrast to the dense infiltrates seen in the specimens from patients not treated with topical steroids. CONCLUSION: Nontuberculous mycobacterial keratitis is a chronic insidious infection that is often unresponsive to medical therapy. The authors recommend that steroids be withheld. Based on the authors' experience of three patients, topical Clarithromycin may hold promise as a therapeutic agent. Lamellar keratectomy or penetrating keratoplasty should be considered in those patients who do not respond to medical therapy or those who have recurrent exacerbations on attempted weaning of topical antibiotic therapy.

Results of large penetrating keratoplasty in microbial keratitis.

Extensive corneal disease secondary to microbial keratitis can result in frank or impending corneal perforation requiring a large penetrating keratoplasty. In an 8-year period, 26 penetrating keratoplasties with recipient beds of > or = 9.5 mm were performed on 22 eyes: 11 for bacterial keratitis, 10 for fungal keratitis, and one for a mixed bacterial and fungal keratitis. The graft failed in 18 of 19 eyes (94.7%), with a median time to failure of 12.9 weeks in bacterial keratitis and 4.0 weeks in fungal keratitis. After large keratoplasty, 17 of 20 eyes (85.0%) maintained the structural integrity of the globe. The remainder became phthisical or required enucleation. With preservation of the structural integrity of the globe, a subsequent smaller optical penetrating keratoplasty is an option in some of these eyes.

Endophthalmitis associated with microbial keratitis.

PURPOSE: The purpose of the study is to investigate possible risk factors, organisms cultured, and visual acuity outcomes of endophthalmitis associated with microbial keratitis. METHODS: Records were reviewed of all patients with both positive corneal and positive intraocular cultures at the Bascom Palmer Eye Institute between January 1, 1990, and March 31, 1995. RESULTS: Thirteen (92.9%) of 14 patients identified had documented keratitis before the diagnosis of endophthalmitis was made. Thirteen (92.9%) patients recently had used 1% prednisolone acetate eye drops, 2 (14.3%) received oral prednisone, and 5 (35.7%) were being treated for systemic conditions associated with relative immune dysfunction. Eight (57.1%) patients had a history of ocular surgery, and seven (50.0%) had wound abnormalities. Eight (57.1%) patients lacked an intact posterior capsule, four (28.6%) had a corneal perforation, and three (21.4%) had a history of dry eye. Gram-negative organisms (7), Staphylococcus aureus (3), streptococcal species (2), and fungi (4) were the most frequently isolated organisms. Coagulase-negative staphylococci were not isolated. Six (42.9%) patients achieved a post-treatment visual acuity of 20/200 or better. Three (21.4%) patients underwent enucleation or evisceration. Although not statistically significant, there was an association between appropriate initial antibiotic therapy and improved visual outcomes. CONCLUSION: Patients in whom endophthalmitis associated with microbial keratitis develops have a frequent history of corticosteroid use, systemic conditions associated with relative immune dysfunction, lack of an intact posterior capsule, dry eye, wound abnormalities, and/or corneal perforation. In general, agents cultured consisted of organisms less frequently reported to be the causative agents in series of postoperative and post-traumatic endophthalmitis. Post-treatment visual outcomes generally were poor.

Infection after radial keratotomy.

PURPOSE/METHODS: Eight years after eight-incision radial keratotomy, a corneal ulcer developed around the inferotemporal incision in an otherwise healthy 39-year-old man. There was no history of corneal trauma or contact lens wear. RESULTS/CONCLUSIONS: Both Fusarium and Acanthamoeba organisms were eventually isolated from the ulcer. A therapeutic keratoplasty was performed. Inferotemporal incisions may be predisposed to epithelial breakdown and infection many years after radial keratotomy.

The changing spectrum of fungal keratitis in south Florida.

PURPOSE: To review the clinical experience with fungal keratitis in south Florida over a 10-year period. METHODS: One hundred twenty-five cases of fungal keratitis were identified in the microbiology laboratory records between January 1982 and January 1992. The medical record of each patient was reviewed. RESULTS: The most commonly associated risk factor was trauma (44%). Fungal keratitis developed in five patients using extended wear contact lenses and one patient wearing a therapeutic bandage contact lens. Clinical features included irregular, feathery margins (62%), a dry, rough texture (47%), and satellite lesions (41%). An initial positive culture was obtained in 90% of patients, with a majority of cultures becoming positive within 48 hours. The Fusarium sp accounted for 62% of the isolates, with Fusarium oxysporum being the most commonly isolated organism. New fungal isolates include Candida parapsilosis, Aspergillus terreus, Candida tropicalis, and Trichosporon beigellii. Natamycin 5% suspension was the initial antifungal agent used for 91% of the patients, with an average duration of treatment of 38 days. Twenty-five patients were treated with oral ketoconazole for a median duration of 2 weeks, in addition to topical antifungal therapy. Thirty-four patients (27%) required a penetrating keratoplasty. Six patients had recurrence of fungal keratitis after penetrating keratoplasty. CONCLUSIONS: Trauma, including contact lens wear, is the most commonly associated risk factor. The fungal organisms can be readily identified in culture. F. oxysporum is the most common organism, with new isolates identified. The mainstay of therapy is topical natamycin with the increasing use of imidazoles.