OBJECTIVE: To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK) treatment.
METHODS: Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895).
METHODS: One hundred thirty-five patients treated at 6 European centers.
METHODS: Principal inclusion criteria were 12 years of age or older and in vivo confocal microscopy with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis who were using topical steroids and antiviral and antifungal drugs before randomization. Principal exclusion criteria were concurrent herpes or fungal keratitis and use of antiamebic therapy (AAT). Patients were randomized 1:1 using a computer-generated block size of 4. This was a superiority trial having a predefined noninferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20-percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (MCR; without surgery or change of AAT) within 12 months, cure defined by clinical criteria 90 days after discontinuing anti-inflammatory agents and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes.
METHODS: The main outcome measure was MCR within 12 months, with secondary outcomes including best-corrected visual acuity and treatment failure rates. Safety outcomes included adverse event rates.
RESULTS: One hundred thirty-five participants were randomized, providing 127 in the full-analysis subset (61 receiving PHMB 0.02%+ propamidine and 66 receiving PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR within 12 months was 86.6% (unadjusted, 88.5%) for PHMB 0.02%+ propamidine and 86.7% (unadjusted, 84.9%) for PHMB 0.08%; the noninferiority requirement for PHMB 0.08% was met (adjusted difference, 0.1 percentage points; lower one-sided 95% confidence limit, -8.3 percentage points). Secondary outcomes were similar for both treatments and were not analyzed statistically: median best-corrected visual acuity of 20/20 and an overall treatment failure rate of 17 of 127 patients (13.4%), of whom 8 of 127 patients (6.3%) required therapeutic keratoplasty. No serious drug-related adverse events occurred.
CONCLUSIONS: PHMB 0.08% monotherapy may be as effective (or at worse only 8 percentage points less effective) as dual therapy with PHMB 0.02%+ propamidine (a widely used therapy) with medical cure rates of more than 86%, when used with the trial treatment delivery protocol in populations with AK with similar disease severity.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Acanthamoeba keratitis (AK) is an eye disease often occurring in contact lens wearers. AK treatment is prolonged and requires multiple drugs, which can lead to adverse effects. Our study aimed to compare the in vitro activities and safety of Miltefosine with that of conventional antimicrobial agents used to treat AK. Acanthamoeba castellanii genotype T4 was obtained from a patient with keratitis and subjected to in vitro susceptibility testing with various antimicrobial agents, including Chlorhexidine (CHX), Pentamidine isethionate (PI)Polyhexamethylene biguanide (PHMB), and Miltefosine to assess their efficacy against Acanthamoeba trophozoites and cyst. The cytotoxicity of the agents was evaluated in Vero cells, and their selectivity indexes (SI) were calculated. Chlorhexidine exhibited the highest amoebicidal activity with the highest selectivity index against the trophozoite and cyst, ranging from 1.17 to 8.35. The selectivity index of PHMB is slightly comparable to Chlorhexidine, exhibiting significant anti-Acanthamoeba activity. On the other hand, Pentamidine isethionate and Miltefosine displayed low SI among the compounds. Pentamidine isethionate was effective at high concentrations, which was toxic. Miltefosine exhibited the lowest cytotoxicity; nevertheless, due to the lowest anti-Acanthamoeba activity presented a low selectivity against the parasite. Further studies on more clinical samples and prolonged incubation time should be done to investigate the effectiveness and toxicity of drugs in both in vitro and in vivo conditions.

OBJECTIVE: The aim of this study was to analyze real-world practice patterns and graft survival after corneal transplantation for infectious keratitis in the Netherlands.
METHODS: All consecutive keratoplasties for infectious keratitis registered in the Netherlands Organ Transplant Registry were included. Graft survival was analyzed using Kaplan-Meier survival curves with Cox regression to compare the 3 most common pathogens with subgroup analysis for type and reason of transplantation, sex, and graft size. Multivariable analysis was performed using the same explanatory factors.
RESULTS: Between 2007 and 2017, 1111 keratoplasties for infectious keratitis were registered in the Netherlands Organ Transplant Registry. The most common pathogens were viruses (n = 437), bacteria (n = 271), and Acanthamoeba (n = 121). Human leukocyte antigen (HLA) matching did not provide a significant survival benefit, whereas emergency procedures showed worse graft survival [hazard ratio (HR) = 0.40, P = 0.120; HR = 2.73, P < 0.001, respectively]. Graft size >8.5 mm was significantly worse than graft size 8.5 mm (HR = 2.062, P = 0.010). In therapeutic keratoplasty, graft survival was significantly worse for Acanthamoeba than viral keratitis (HR = 2.36, P = 0.008). In the multivariable model, adjusting for graft size, type, and reason for transplantation, viral and bacterial keratitis did not differ significantly in graft survival, and Acanthamoeba showed a significantly worse prognosis (vs. viral keratitis, HR = 2.30, P < 0.001; bacterial keratitis, HR = 2.65, P < 0.001).
CONCLUSIONS: Viral keratitis was the most common indication for transplantation, followed by bacterial and Acanthamoeba keratitis. HLA matching did not offer protection over elective non-HLA-matched procedures, whereas emergency procedures and grafts sized >8.5 mm showed poor survival. In optical keratoplasty, survival is high for all pathogens, whereas in therapeutic keratoplasty Acanthamoeba shows poor outcome.

This study was designed to establish risk factors for the development of Acanthamoeba keratitis (AK) for daily disposable (DD) contact lens (CL) users compared with daily wear (DW) reusable lens users and for risks unique to DD users. This is important because, in many major economies, CL use is the principal cause of microbial keratitis, of which AK accounts for approximately 50% of cases with sight loss. Determining these AK risks informs practitioner advice and consumer behavior.
Case-control study.
Cases and controls were recruited from an Accident and Emergency Department serving South-East England. Cases were new CL users with AK recruited retrospectively from January 2011 to February 2013 and prospectively thereafter until August 2014. Controls were recruited prospectively from February 2014 to June 2015.
Analysis of a self-administered questionnaire.
Independent risk factors and population attributable risk percentage (PAR%) for AK.
A total of 83 AK cases and 122 controls were recruited; DD use was reported by 20 (24%) cases and 66 (54%) controls. In multivariable analyses adjusted for potential confounders, the odds of AK was higher for DW reusable soft lenses (odds ratio [OR], 3.84; 95% confidence interval [CI], 1.75-8.43) and rigid lenses (OR, 4.56; 95% CI, 1.03-20.19) than for DD lenses. Within the DD-using subset, AK was associated with the following modifiable risk factors: less frequent professional follow-up visits (OR, 10.12; 95% CI, 5.01-20.46); showering in lenses (OR, 3.29, 95% CI, 1.17-9.23); lens reuse (OR, 5.41; 95% CI, 1.55-18.89); and overnight wear (OR, 3.93; 95% CI, 1.15-13.46). The PAR% estimated that 30% to 62% of cases could be prevented by switching from reusable soft lens to DD lens use.
Acanthamoeba keratitis risks are increased > threefold in DW reusable lens users versus DD lens use. Acanthamoeba keratitis risks for DD lens users can be minimized by adherence to safe use guidelines (no reuse, overnight wear, or contamination by water). Safe CL use can be improved by increasing the prominence of risk avoidance information from manufacturers and regulators. Because AK accounts for half of severe keratitis in CL users, these measures can be expected to have public health benefits.

Acanthamoeba keratitis (AK) is a vision-threatening disease, usually associated with contact lens (CL) wear. As overnight orthokeratology (OOK) is increasingly used to control myopia, we have found incidence of OOK-associated AK is increasing. This study aimed to investigate the clinical presentation and visual outcomes of OOK-associated AK.
Demographic characteristics, clinical features, and treatment outcomes were collected by reviewing the medical charts of CL-associated AK patients (n = 35) diagnosed at Taipei Veterans General Hospital from 2001 to 2016. Cases were OOK-associated AK patients (n = 13), and controls were all other CL-associated AK patients (n = 22). Student t tests and chi-square tests were used to compare cases and controls. Linear regression analyses were used to identify factors associated with the final visual outcome in CL-associated AK.
OOK-associated AK accounted for half of all CL-associated AK after 2010. OOK-associated AK patients and other CL-associated patients had similar best-corrected logarithm of the minimum angle of resolution visual acuity (BCLVA) before treatment (1.10 ± 0.75 vs 1.13 ± 0.76, p = 0.893), but OOK-associated AK patients were younger (17.15 ± 3.21 vs 26.36 ± 12.81 years, p = 0.004), had less severe disease (ring infiltration, 0% vs 31.82%, p = 0.023), and had better post-treatment BCLVA (0.06 ± 0.15 vs 0.51 ± 0.95, p = 0.041). Multiple linear regression analysis showed that better BCLVA after treatment in CL-associated AK was associated with initial presentation without ring infiltration (p = 0.002) but not with OOK use itself (p = 0.793). Twenty-six of 35 CL-associated AK patients had final BCLVA equal to or better than 0.10 (Snellen visual acuity of 6/7.5). All 13 OOK-associated AK cases were treated with chlorhexidine 0.02% ± voriconazole 1% ± oral voriconazole, and 12 of these patients had final BCLVA equal to or better than 0.10.
Most CL-associated AK patients had satisfactory visual outcomes. Half of AK at our hospital is OOK-associated since 2010. Early diagnosis and correct treatment may be the reason why OOK-associated AK patients had better vision prognosis.

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.
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.
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.
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.

The true disease status of a population with suspected microbial keratitis (MK) cannot be verified. There is not an accurate (gold) reference standard to confirm infection and inter-test comparisons of sensitivity and specificity therefore lead to bias with questionable estimates of test utility. We present an alternative method to report results.
We used a decision to treat as the definition for MK. We retrospectively compared the results of corneal culture and polymerase chain reaction (PCR) as these are objective tests available for the three principal groups of pathogens. We then estimated the potential contribution of positive results, either alone or in combination, to support the working diagnosis.
We included 2021 (77.4%) eyes with suspected bacterial keratitis, 365 (14.0%) with suspected acanthamoeba keratitis, and 226 (8.6%) with suspected fungal keratitis, all treated between July 2013 and December 2019. In these groups, there were 51.6% positive culture and 6.5% positive PCR results for bacteria, 19.0% and 40.5% for acanthamoeba, and 28.3% and 15.0% for fungi. Between groups the differences in the proportions of positive results from culture and PCR was statistically significant (P < 0.001). The added benefit of PCR to the result of culture in identifying a potential pathogen was 1.4% for bacteria (P = 0.6292), 24.4% for acanthamoeba (P = 0.0001), and 5.8% for fungi (P = 0.3853).
For suspected MK a comparison of the test positivity rate is an easily comprehensible outcome measure of test utility.

OBJECTIVE: The purpose of this study is to compare the predisposing factors, clinical findings, treatment results, and prognosis for polymicrobial keratitis.
METHODS: In this retrospective comparative case study, we identified the cases of polymicrobial keratitis from the microbiological records (n = 649) at Balcalı Hospital, Çukurova University (Adana, Turkey; October 2010-2018). We included all the cases of infectious keratitis with two different types of microbial agents and grouped them as follows: group 1 (n = 25), bacterium-fungus coexistence; group 2 (n = 12), herpes simplex virus (HSV) or Acanthamoeba with bacterial infection; and group 3 (n = 7), HSV or Acanthamoeba with fungal infection. We compared the clinical and microbiological characteristics, and treatment outcomes among the groups.
RESULTS: In our study, we found that 44 infectious keratitis cases (6.7%) were of polymicrobial nature. The mean follow-up period was 11.4 ± 17.8 months. In total, 17 different bacteria along with 3 different fungi, HSV, and Acanthamoeba were isolated. The most common bacterium was Staphylococcus epidermidis (25%). Most of the fungal pathogens were filamentous. Patients with initial treatment failure and requiring surgical intervention had larger infiltrates (p = 0.023, p = 0.003, respectively) than other patients. Older age was associated with delayed recovery and poor visual prognosis.
CONCLUSIONS: Bacterial-fungus coexistence is the most common combination among patients, but other combinations should also be considered for suspected polymicrobial etiology. The corneal infiltrate size may be an important indicator of the course of disease and response to treatment. A closer and longer follow-up period should be planned for older patients.

暂无摘要。

To investigate the relationship between Acanthamoeba cysts and inflammatory cells in Acanthamoeba keratitis (AK) by in vivo confocal microscopy (IVCM).
A case-control study included 30 patients with AK and 20 normal controls. The severity of the AK was divided into mild, moderate, and severe. The central cornea and four standard quadrants of the peripheral cornea were imaged by IVCM. The cyst infiltration and dendritic cell (DC) density and maturity (size, length, field, and number of dendrites) were quantified. The relationship between clinical severity, cyst density, and DC alterations was characterized by Spearman correlation analysis.
The maximum cyst density in the mild, moderate, and severe groups was 31.3 cysts/mm2 (17.2-32.8), 62.5 cysts/mm2 (59.3-103.1), and 162.5 cysts/mm2 (65.6-215.6), respectively. Compared to normal participants, a significant increase in the mean corneal DC density was detected in patients with AK (290.2 ± 97.0 vs. 25.3 ± 8.3 cells/mm2; P < 0.001). Patients with AK presented an increase in median DC size (178.3 vs. 63.6 µm2/cell, P < 0.001), median DC field (518.1 vs. 256.6 µm2/cell, P = 0.008), and median DC dendrite length (42.3 vs. 14.7 µm/cell, P < 0.001). Increased AK severity was correlated with an increase in cyst density, DC size, and dendrite length (all P < 0.05). An increase in cyst density was significantly correlated with an increase in DC density (β = 0.484, P = 0.026) and DC size (β = 0.557, P = 0.009).
Cyst density and depth of infiltration as well as maturity of the surrounding DC increased significantly with the severity of AK.
Quantitative analysis of cyst density and DC maturity may provide a new method of evaluating the severity of AK.