Outcomes of amoebic, fungal, and bacterial keratitis: A retrospective cohort study.

BACKGROUND: Acanthamoeba keratitis is challenging to treat and thought to result in poor outcomes, but very few comparative studies exist to assess whether ulcers caused by Acanthamoeba are worse than those caused by bacteria or fungus. METHODS: In a retrospective cohort study, all cases of smear- or culture-proven Acanthamoeba keratitis diagnosed from January 2006 to June 2011 at an eye hospital in South India were identified from the microbiology database. Random samples of the same number of cases of bacterial and fungal keratitis, matched by year, were identified from the same database in order to compare outcomes between the three types of organism. The main outcomes were the time until the following events: re-epithelialization, discontinuation of antimicrobials, perforation/keratoplasty, elevated intraocular pressure, and new cataract. RESULTS: The median time until re-epithelialization was 113 days for Acanthamoeba keratitis, 30 days for fungal keratitis, and 25 days for bacterial keratitis, and the median time until discontinuation of antimicrobial therapy was 100 days for Acanthamoeba keratitis, 49 days for fungal keratitis, and 40 days for bacterial keratitis. Compared to the other two organisms, Acanthamoeba ulcers took significantly longer to re-epithelialize (adjusted HR 0.4, 95% CI 0.3 to 0.6 relative to bacterial ulcers and HR 0.3, 95% CI 0.2 to 0.5 relative to fungal ulcers; overall p<0.001) and had significantly longer courses of antimicrobials (adjusted HR 0.3, 95% CI 0.2 to 0.6 relative to bacterial ulcers and HR 0.5, 95%CI 0.3 to 0.8 relative to fungal ulcers; overall p<0.001). No statistically significant difference was observed between the three organisms for the other time-to-event outcomes. CONCLUSIONS: Acanthamoeba keratitis was more difficult to treat and had worse clinical outcomes than bacterial or fungal ulcers, highlighting the lack of adequate treatment regimens for this infection.

Visual Impairment in Fungal Versus Bacterial Corneal Ulcers 4 Years After Successful Antimicrobial Treatment.

PURPOSE: To compare longitudinal outcomes of visual acuity after fungal corneal ulcers with those of bacterial ulcers. DESIGN: Prospective cohort study. METHODS: This study was conducted in a tertiary eye hospital in South India. The population consisted of 100 of 152 individuals whose fungal or bacterial keratitis had been diagnosed 4 years prior and had been enrolled in 1 of 2 concurrent randomized trials. Causative organisms of infectious keratitis were either bacterial or fungal. Presenting visual acuity consisted of best spectacle corrected visual acuity (BSCVA) and hard contact lens-corrected visual acuity (CLVA). RESULTS: Fifty study participants with prior fungal keratitis and 50 with prior bacterial keratitis were enrolled. Four years after treatment for keratitis, participants' presenting vision in the better eye was worse than 20/60 for 12 individuals (24.0%) in the fungal group and 10 individuals (20.0%) in the bacterial group. Median BSCVA in the affected eye at the 4-year visit in the fungal group was similar to that in the bacterial group (Snellen equivalent, 20/32 for each), although vision worse than 20/400 was more common in the fungal ulcer group after spectacle correction (odds ratio [OR] 4.19; 95% confidence interval [CI], 1.11-15.8) and contact lens correction (OR, 5.74; 95% CI, 1.37-24.1). CONCLUSIONS: In this South Indian population with a previous episode of fungal or bacterial keratitis, correctable bilateral visual impairment was common. Although long-term visual outcomes were, on average, similar between fungal and bacterial ulcers, fungal ulcers were more likely to produce severe visual impairment.

Ocular manifestations of isolated corneal bee sting injury, management strategies, and clinical outcomes.

PURPOSE: The purpose of this study is to describe the presenting features, management strategies, and clinical outcome following bee sting injury to the cornea. METHODS: Retrospective case series involving 11 eyes of 11 patients with corneal bee sting injuries who presented over a period of 2 years. Nine of these 11 eyes had the presence of intact bee stinger in the cornea, which was removed immediately under an operating microscope and sent for microbiological and histopathological evaluation. The patients were managed as per the individual treatment protocol of the respective treating physicians. RESULTS: Six eyes (54.5%) had a good clinical outcome (best-corrected visual acuity [BCVA] >20/40) with medical therapy alone with no need for surgical intervention. Five eyes (45.5%) had a poor clinical outcome (BCVA <20/40) with medical therapy and required surgery; of which three required a combined penetrating keratoplasty with cataract surgery, while one required isolated cataract surgery and one underwent penetrating keratoplasty. Glaucoma was present in 3/5 eyes undergoing surgery, one of which required a trabeculectomy. Five of the six eyes who had a good clinical outcome with medical therapy alone had been treated with concomitant oral steroids, along with topical antibiotic-steroid combination therapy. CONCLUSION: Oral corticosteroid supplementation to the topical steroid antibiotic treatment in patients with corneal bee sting injury where corneal involvement and anterior reaction is severe at presentation or inflammation not ameliorating with topical steroids alone prevents serious vision-threatening complications such as corneal decompensation, cataract, and glaucoma.

Trends in antibiotic resistance in bacterial keratitis isolates from South India.

AIMS: To report trends in antibiotic resistance in cases of bacterial keratitis from a large eye hospital in South India. METHODS: In this retrospective cross-sectional study, the microbiology laboratory records of patients with infectious keratitis diagnosed at an eye hospital in South India from 2002 to 2013 were reviewed to determine the proportion with antibiotic non-susceptibility. RESULTS: 3685 bacterial isolates had susceptibility testing performed over the 12-year period. The two most common organisms with resistance were Streptococcus pneumoniae (n=1204) and Pseudomonas aeruginosa (n=894). Antibiotic non-susceptibility was generally uncommon for these two organisms and no significant trends were detected over the course of the study. In contrast, Staphylococcus aureus (N=211) isolates demonstrated a significant increase in fluoroquinolone non-susceptibility over the 12-year study period. This coincided with a significant increase in methicillin-resistant S. aureus (MRSA) during the study period, though the increase in fluoroquinolone resistance was likewise seen in methicillin-sensitive S. aureus (MSSA). For example, ofloxacin resistance in MSSA increased from 11.1% in 2002 to 66.7% in 2013 (p=0.002). No trends were apparent for the aminoglycosides, cefazolin or vancomycin, for which in vitro non-susceptibility generally appeared to be low. CONCLUSION: Resistance to antibiotics was generally stable for infectious keratitis isolates from a large eye hospital in South India, except for S. aureus, which experienced a significant increase in fluoroquinolone resistance from 2002 to 2013. Fluoroquinolone antibiotics currently have poor in vitro activity against both MRSA and MSSA in South India and are therefore not the ideal therapy for Staphylococcal corneal ulcers.

Risk factors for low vision related functioning in the Mycotic Ulcer Treatment Trial: a randomised trial comparing natamycin with voriconazole.

BACKGROUND/AIMS: The Mycotic Ulcer Treatment Trial I (MUTT I) was a double-masked, multicentre, randomised controlled trial, which found that topical natamycin is superior to voriconazole for the treatment of filamentous fungal corneal ulcers. In this study, we determine risk factors for low vision-related quality of life in patients with fungal keratitis. METHODS: The Indian visual function questionnaire (IND-VFQ) was administered to MUTT I study participants at 3 months. Associations between patient and ulcer characteristics and IND-VFQ subscale score were assessed using generalised estimating equations. RESULTS: 323 patients were enrolled in the trial, and 292 (90.4%) completed the IND-VFQ at 3 months. Out of a total possible score of 100, the average VFQ score for all participants was 81.3 (range 0-100, SD 23.6). After correcting for treatment arm, each logMAR line of worse baseline visual acuity in the affected eye resulted in an average 1.2 points decrease on VFQ at 3 months (95% CI -1.8 to 0.6, p<0.001). Those who required therapeutic penetrating keratoplasty had an average of 25.2 points decrease on VFQ after correcting for treatment arm (95% CI -31.8 to -18.5, p<0.001). Study participants who were unemployed had on average 28.5 points decrease on VFQ (95% CI -46.9 to -10.2, p=0.002) after correcting for treatment arm. CONCLUSIONS: Monocular vision loss from corneal opacity due to fungal keratitis reduced vision-related quality of life. Given the relatively high worldwide burden of corneal opacity, improving treatment outcomes of corneal infections should be a public health priority. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov Identifier: NCT00996736.

Inter-grader Agreement of the Ocular Staining Score in the Sjögren's International Clinical Collaborative Alliance (SICCA) Registry.

PURPOSE: To determine the intra-observer and inter-observer reliability of a novel ocular staining score among trained ophthalmologists. DESIGN: Reliability analysis within a prospective, observational, multicenter cohort study. METHODS: Those enrolled in the National Institutes of Health-funded Sjögren's International Collaborative Clinical Alliance (SICCA) who presented for follow-up at the University of California San Francisco, Aravind Eye Hospital, Johns Hopkins University, and the University of Pennsylvania were included. Study participants were graded using the ocular staining score by at least 2 masked SICCA-trained ophthalmologists. The primary outcome for this study was the intraclass correlation coefficient (ICC) for the total ocular staining score. ICCs were also calculated for tear break-up time (TBUT) and conjunctival and corneal staining. RESULTS: Total ocular staining score had an ICC of 0.91 for the right eye (95% confidence interval [CI] 0.85-0.96) and 0.90 for the left eye (95% CI 0.83-0.97). Corneal staining (right eye 0.86, 95% CI 0.76-0.93, left eye 0.90, 95% CI 0.81-0.95) and conjunctival staining (right eye 0.87, 95% CI 0.80-0.93, left eye 0.85, 95% CI 0.75-0.93) demonstrated excellent agreement. The ICC for TBUT was slightly lower (right eye 0.77, 95% CI 0.64-0.89; left eye 0.81, 95% CI 0.68-0.90). CONCLUSIONS: Previous studies have shown that the ocular staining score is correlated with other diagnostic components of Sjögren syndrome. In this study, we demonstrate high reliability in grading among trained ophthalmologists, completing the validation of this test.

In vivo Confocal Microscopic Analysis of Limbal Stroma in Patients With Limbal Stem Cell Deficiency.

PURPOSE: Using in vivo confocal microscopy, we established that unique hyperreflective structures in the anterior limbal stroma of healthy individuals represent the limbal stromal niche. The aim of this study was to characterize the limbal stromal microarchitecture in patients with limbal stem cell deficiency (LSCD). METHODS: After obtaining informed consent, 10 patients with LSCD and 3 with macular corneal dystrophy were recruited. In vivo confocal imaging of the limbus and cornea of the affected and normal eyes was performed using an HRT III laser scanning microscope, beyond the epithelium deep into the stroma. RESULTS: In the case of LSCD, the limbal epithelium was replaced by conjunctival epithelium. A large number of inflammatory and dendritic cells were identified along with blood vessels from the epithelium to deep stromal layers. The unique hyperreflective niche structures were replaced by homogenously bright fibrous structures in all eyes with total LSCD. In patients with partial LSCD, even the clinically defined normal limbus had fibrotic stroma. In a patient with focal LSCD, only the affected limbal stroma remained fibrotic, whereas the adjacent clinically normal limbus had the unique hyperreflective structures. Although the opaque corneal stroma appeared bright because of proteoglycan deposition, it was possible to identify the normal limbal epithelial and stromal architecture in macular corneal dystrophy. CONCLUSIONS: In the case of LSCD, the limbal stromal niche was replaced by bright fibrotic structures indicating persistence of damage several months after injury. Further studies are required to characterize the sequential events occurring in the anterior limbal stroma after injury using this noninvasive method.

Corneal Cross-linking as an Adjuvant Therapy in the Management of Recalcitrant Deep Stromal Fungal Keratitis: A Randomized Trial.

PURPOSE: To assess the efficacy of corneal cross-linking (CXL) as an adjuvant to appropriate antifungal therapy in nonresolving deep stromal fungal keratitis. DESIGN: Randomized clinical trial. METHODS: Eyes with culture-positive deep stromal fungal keratitis not responding to appropriate medical therapy for a period of 2 weeks were randomized to receive either adjuvant CXL or no additional treatment. Antifungal medical therapy was continued in both groups. The prespecified primary outcome was treatment failure at 6 weeks after enrollment, defined as perforation and/or increase in ulcer size by ≥2 mm. RESULTS: The trial was stopped before full enrollment because of a marked difference in the rate of perforation between the 2 groups. Of the 13 cases enrolled in the study, 6 were randomized to the CXL group and 7 to the non-CXL group. Five eyes in the CXL group and 3 eyes in the non-CXL group experienced treatment failure by 6 weeks (P = .56). In a secondary analysis, the CXL group experienced more perforations than the non-CXL group (4 vs 0, respectively; P = .02). CONCLUSION: CXL used as adjuvant therapy for recalcitrant deep stromal fungal keratitis did not improve outcomes.

In vivo confocal microscopic analysis of normal human anterior limbal stroma.

PURPOSE: To characterize the microarchitecture of anterior limbal stroma in healthy individuals using in vivo confocal microscopy (IVCM) and to correlate it with mesenchymal stem cells (MSCs), a component of the limbal niche. METHODS: The corneal side of the superior limbus was scanned in 30 eyes of 17 normal subjects beyond the basal epithelium, deep into the stroma using an HRT III laser scanning microscope. The IVCM findings were correlated with the immunohistochemical features of MSCs in the anterior limbal stroma. RESULTS: Clusters of hyperreflective structures were observed in the anterior limbal stroma, subjacent to the basal epithelium (depth, 50.2 ± 8.7 µm to 98 ± 12.8 µm), but not in the corneal stroma. The structures showed unique morphology compared with epithelial cells, keratocytes, neurons, and dendritic cells. In parallel, confocal analysis of immunostained sections showed clusters of cells, double positive for MSC-specific markers (CD90 and CD105) in the anterior limbal stroma at a depth of 55.3 ± 12.7 µm to 72 ± 37.6 µm. The organization and distribution of the MSC clusters locates them within the hyperreflective region in the anterior limbal stroma. CONCLUSIONS: The hyperreflective structures, demonstrated for the first time in the human anterior limbal stroma, probably represent an important component of the limbal niche. Our approach of in vivo imaging may pave the way for assessing the limbal stromal health.

Vision-Related Quality-of-Life Outcomes in the Mycotic Ulcer Treatment Trial I: A Randomized Clinical Trial.

IMPORTANCE: Given the limitations in health care resources, quality-of-life measures for interventions have gained importance. OBJECTIVE: To determine whether vision-related quality-of-life outcomes were different between the natamycin and voriconazole treatment arms in the Mycotic Ulcer Treatment Trial I, as measured by an Indian Vision Function Questionnaire. DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis (performed October 11-25, 2014) of a double-masked, multicenter, randomized, active comparator-controlled, clinical trial at multiple locations of the Aravind Eye Care System in South India that enrolled patients with culture- or smear-positive filamentous fungal corneal ulcers who had a baseline visual acuity of 20/40 to 20/400 (logMAR of 0.3-1.3). INTERVENTIONS: Study participants were randomly assigned to topical voriconazole, 1%, or topical natamycin, 5%. MAIN OUTCOMES AND MEASURES: Subscale score on the Indian Vision Function Questionnaire from each of the 4 subscales (mobility, activity limitation, psychosocial impact, and visual function) at 3 months. RESULTS: A total of 323 patients were enrolled in the trial, and 292 (90.4%) completed the Indian Vision Function Questionnaire at 3 months. The majority of study participants had subscale scores consistent with excellent function. After adjusting for baseline visual acuity and organism, we found that study participants in the natamycin-treated group scored, on average, 4.3 points (95% CI, 0.1-8.5) higher than study participants in the voriconazole-treated group (P = .046). In subgroup analyses looking at ulcers caused by Fusarium species and adjusting for baseline best spectacle-corrected visual acuity, the natamycin-treated group scored 8.4 points (95% CI, 1.9-14.9) higher than the voriconazole-treated group (P = .01). Differences in quality of life were not detected for patients with Aspergillus or other non-Fusarium species as the causative organism (1.5 points [95% CI, -3.9 to 6.9]; P = .52). CONCLUSIONS AND RELEVANCE: We found evidence of improvement in vision-related quality of life among patients with fungal ulcers who were randomly assigned to natamycin compared with those randomly assigned to voriconazole, and especially among patients with Fusarium species as the causative organism. Incorporation of quality-of-life measures in clinical trials is important to fully evaluate the effect of the studied interventions. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00996736.

Trends in bacterial and fungal keratitis in South India, 2002-2012.

OBJECTIVE: To assess the trends in microbiological organisms identified from corneal scrapings from patients with infectious keratitis at a tertiary care medical centre in South India. METHODS: We reviewed the records of the microbiology laboratory at Aravind Eye Hospital in Madurai, India, from 2002 until 2012. We identified the microbiological causes of all corneal ulcers from the culture and smear results, and assessed for trends in bacterial and fungal keratitis over time. RESULTS: Of 23 897 corneal patients with ulcer with a corneal smear from 2002 to 2012 a fungal organism was identified in 34.3%, a bacterial organism in 24.7% and no organism in 38.3%. During this period, the annual number of keratitis cases due to bacteria decreased from 677 to 412, and the annual number due to fungus increased from 609 to 863. In analyses accounting for the total number of outpatients seen each year, the decline in number of smears positive for bacteria was statistically significant (p<0.001) but the increase in the number positive for fungus was not (p=0.73). The relative frequency of individual bacterial or fungal organisms remained relatively stable over this time. CONCLUSIONS: At a tertiary eye care centre in South India, there has been a reduction in the numbers of smear-positive bacterial keratitis over the past 11 years. This decline likely reflects economic development in India and increased access to antibiotics.

Microsporidial stromal keratitis masquerading as acute graft rejection.

PURPOSE: To describe the clinical features, disease course, management, and visual outcome of stromal microsporidial keratitis involving the corneal graft in an immunocompetent patient. METHODS: Case report. RESULTS: We report the case of a 21-year-old immunocompetent woman, who underwent penetrating keratoplasty for advanced keratoconus in her right eye and presented with features of acute graft rejection after 15 months. Standard treatment using topical and systemic steroids failed to reverse the graft rejection. A regraft was performed in that eye. Histopathology of the donor corneal button revealed microsporidiosis involving the deep stroma. CONCLUSIONS: Microsporidiosis is rarely encountered in a corneal graft and masquerades as acute graft rejection. Histopathology could help in making a final diagnosis.

Early addition of topical corticosteroids in the treatment of bacterial keratitis.

IMPORTANCE: Scarring from bacterial keratitis remains a leading cause of visual loss. OBJECTIVE: To determine whether topical corticosteroids are beneficial as an adjunctive therapy for bacterial keratitis if given early in the course of infection. DESIGN, SETTING, AND PARTICIPANTS: The Steroids for Corneal Ulcers Trial (SCUT) was a randomized, double-masked, placebo-controlled trial that overall found no effect of adding topical corticosteroids to topical moxifloxacin hydrochloride in bacterial keratitis. Here, we assess the timing of administration of corticosteroids in a subgroup analysis of the SCUT. We define earlier administration of corticosteroids (vs placebo) as addition after 2 to 3 days of topical antibiotics and later as addition after 4 or more days of topical antibiotics. MAIN OUTCOMES AND MEASURES: We assess the effect of topical corticosteroids (vs placebo) on 3-month best spectacle-corrected visual acuity in patients who received corticosteroids or placebo earlier vs later. Further analyses were performed for subgroups of patients with non-Nocardia keratitis and those with no topical antibiotic use before enrollment. RESULTS: Patients treated with topical corticosteroids as adjunctive therapy within 2 to 3 days of antibiotic therapy had approximately 1-line better visual acuity at 3 months than did those given placebo (-0.11 logMAR; 95% CI, -0.20 to -0.02 logMAR; P = .01). In patients who had 4 or more days of antibiotic therapy before corticosteroid treatment, the effect was not significant; patients given corticosteroids had 1-line worse visual acuity at 3 months compared with those in the placebo group (0.10 logMAR; 95% CI, -0.02 to 0.23 logMAR; P = .14). Patients with non-Nocardia keratitis and those having no topical antibiotic use before the SCUT enrollment showed significant improvement in best spectacle-corrected visual acuity at 3 months if corticosteroids were administered earlier rather than later. CONCLUSIONS AND RELEVANCE: There may be a benefit with adjunctive topical corticosteroids if application occurs earlier in the course of bacterial corneal ulcers.

Visual outcomes in treated bacterial keratitis: four years of prospective follow-up.

PURPOSE: We described the change in visual acuity experienced by eyes successfully treated for bacterial keratitis. METHODS: This was a prospective cohort study of a subset of study participants who had previously enrolled in the Steroids for Corneal Ulcers Trial (SCUT). All study participants had been diagnosed with culture-proven bacterial keratitis before enrollment in SCUT and subsequently were randomized to adjunctive topical corticosteroids or placebo. During SCUT, we monitored study participants at enrollment, 3 weeks, 3 months, and 12 months. We invited a subset to complete a comprehensive eye examination approximately 4 years after enrollment in SCUT. Certified refractionists assessed best spectacle-corrected visual acuity (BSCVA) using the same protocol at each study visit. RESULTS: We examined 50 SCUT participants at 4 years after enrollment. Among those in this cohort, mean logMAR BSCVA at enrollment was 0.85 (Snellen equivalent, 20/160; 95% confidence interval [CI], 0.71-0.99). On average, visual acuity improved by 2.9 logMAR lines from enrollment to 3 weeks (P < 0.001), 1.2 lines from 3 weeks to 3 months (P = 0.002), and 0.8 lines from 3 to 12 months (P = 0.01). The BSCVA did not change significantly between 12 months and 4 years (0.04-line improvement, P = 0.88). After controlling for visual acuity at enrollment, BSCVA was not significantly different between the corticosteroid and placebo groups at 4 years (P = 0.53). CONCLUSIONS: Cases of bacterial keratitis may continue to demonstrate improvements in visual acuity up to 12 months following diagnosis, but further improvements are unlikely. These findings may guide the appropriate timing of surgical intervention in these patients. (ClinicalTrials.gov number, NCT00324168.).

The steroids for corneal ulcers trial (SCUT): secondary 12-month clinical outcomes of a randomized controlled trial.

PURPOSE: To determine whether topical corticosteroids as adjunctive therapy for bacterial keratitis improves long-term clinical outcomes. DESIGN: Randomized, placebo-controlled, double-masked clinical trial. METHODS: This multicenter trial compared 1.0% prednisolone sodium phosphate to placebo in the treatment of bacterial keratitis among 500 patients with culture-positive ulcers receiving 48 hours of moxifloxacin before randomization. The primary endpoint was 3 months from enrollment, and 399 patients were evaluated at 12 months. The outcomes examined were best spectacle-corrected visual acuity (BSCVA) and scar size at 12 months. Based on previous results, regression models with adjustments for baseline status and/or causative organism were used for analysis. RESULTS: No significant differences in clinical outcomes by treatment group were seen with the prespecified regression models (BSCVA: -0.04 logMAR, 95% CI, -0.12 to 0.05, P = .39; scar size: 0.03 mm, 95% CI, -0.12 to 0.18, P = .69). A regression model including a Nocardia-treatment arm interaction found corticosteroid use associated with a mean 1-line improvement in BSCVA at 12 months among patients with non-Nocardia ulcers (-0.10 logMAR, 95% CI, -0.19 to -0.02, P = .02). No significant difference was observed in 12-month BSCVA for Nocardia ulcers (0.18 logMAR, 95% CI, -0.04 to 0.41, P = .16). Corticosteroids were associated with larger mean scar size at 12 months among Nocardia ulcers (0.47 mm, 95% CI, 0.06-0.88, P = .02) and no significant difference was identified by treatment for scar size for non-Nocardia ulcers (-0.06 mm, 95% CI, -0.21 to 0.10, P = .46). CONCLUSIONS: Adjunctive topical corticosteroid therapy may be associated with improved long-term clinical outcomes in bacterial corneal ulcers not caused by Nocardia species.

Acanthamoeba, fungal, and bacterial keratitis: a comparison of risk factors and clinical features.

PURPOSE: To determine risk factors and clinical signs that may differentiate between bacterial, fungal, and acanthamoeba keratitis among patients presenting with presumed infectious keratitis. DESIGN: Hospital-based cross-sectional study. METHODS: We examined the medical records of 115 patients with laboratory-proven bacterial keratitis, 115 patients with laboratory-proven fungal keratitis, and 115 patients with laboratory-proven acanthamoeba keratitis seen at Aravind Eye Hospital, Madurai, India, from 2006-2011. Risk factors and clinical features of the 3 organisms were compared using multinomial logistic regression. RESULTS: Of 95 patients with bacterial keratitis, 103 patients with fungal keratitis, and 93 patients with acanthamoeba keratitis who had medical records available for review, 287 (99%) did not wear contact lenses. Differentiating features were more common for acanthamoeba keratitis than for bacterial or fungal keratitis. Compared to patients with bacterial or fungal keratitis, patients with acanthamoeba keratitis were more likely to be younger and to have a longer duration of symptoms, and to have a ring infiltrate or disease confined to the epithelium. CONCLUSIONS: Risk factors and clinical examination findings can be useful for differentiating acanthamoeba keratitis from bacterial and fungal keratitis.