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Ophthalmology Mar 2024To 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)... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
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.
DESIGN
Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895).
PARTICIPANTS
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.
MAIN OUTCOME MEASURES
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.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Acanthamoeba Keratitis; Benzamidines; Biguanides; Orphan Drug Production; Prospective Studies
PubMed: 37802392
DOI: 10.1016/j.ophtha.2023.09.031 -
Diagnostics (Basel, Switzerland) Aug 2023keratitis (AK) is a painful and sight-threatening parasitic corneal infection. In recent years, the incidence of AK has increased. Timely and accurate diagnosis is... (Review)
Review
keratitis (AK) is a painful and sight-threatening parasitic corneal infection. In recent years, the incidence of AK has increased. Timely and accurate diagnosis is crucial during the management of AK, as delayed diagnosis often results in poor clinical outcomes. Currently, AK diagnosis is primarily achieved through a combination of clinical suspicion, microbiological investigations and corneal imaging. Historically, corneal scraping for microbiological culture has been considered to be the gold standard. Despite its technical ease, accessibility and cost-effectiveness, the long diagnostic turnaround time and variably low sensitivity of microbiological culture limit its use as a sole diagnostic test for AK in clinical practice. In this review, we aim to provide a comprehensive overview of the diagnostic modalities that are currently used to diagnose AK, including microscopy with staining, culture, corneal biopsy, in vivo confocal microscopy, polymerase chain reaction and anterior segment optical coherence tomography. We also highlight emerging techniques, such as next-generation sequencing and artificial intelligence-assisted models, which have the potential to transform the diagnostic landscape of AK.
PubMed: 37627913
DOI: 10.3390/diagnostics13162655 -
Indian Journal of Ophthalmology Apr 2024This is a comprehensive review after a thorough literature search in PubMed-indexed journals, incorporating current information on the pathophysiology, clinical... (Review)
Review
This is a comprehensive review after a thorough literature search in PubMed-indexed journals, incorporating current information on the pathophysiology, clinical features, diagnosis, medical and surgical therapy, as well as outcomes of Acanthamoeba keratitis (AK). AK is a significant cause of ocular morbidity, and early diagnosis with timely institution of appropriate therapy is the key to obtaining good outcomes. The varied presentations result in frequent misdiagnosis, and co-infections can increase the morbidity of the disease. The first line of therapy continues to be biguanides and diamidines, with surgery as a last resort.
Topics: Humans; Acanthamoeba Keratitis; Pentamidine; Biguanides
PubMed: 38454853
DOI: 10.4103/IJO.IJO_2627_23 -
Biology Dec 2023Keratitis (AK) is a severe corneal infection caused by the species of protozoa, potentially leading to permanent vision loss. AK requires prompt diagnosis and... (Review)
Review
Keratitis (AK) is a severe corneal infection caused by the species of protozoa, potentially leading to permanent vision loss. AK requires prompt diagnosis and treatment to mitigate vision impairment. Diagnosing AK is challenging due to overlapping symptoms with other corneal infections, and treatment is made complicated by the organism's dual forms and increasing virulence, and delayed diagnosis. In this review, new approaches in AK diagnostics and treatment within the last 5 years are discussed. The English-language literature on PubMed was reviewed using the search terms " keratitis" and "diagnosis" or "treatment" and focused on studies published between 2018 and 2023. Two hundred sixty-five publications were initially identified, of which eighty-seven met inclusion and exclusion criteria. This review highlights the findings of these studies. Notably, advances in PCR-based diagnostics may be clinically implemented in the near future, while antibody-based and machine-learning approaches hold promise for the future. Single-drug topical therapy (0.08% PHMB) may improve drug access and efficacy, while oral medication (i.e., miltefosine) may offer a treatment option for patients with recalcitrant disease.
PubMed: 38132315
DOI: 10.3390/biology12121489 -
Survey of Ophthalmology 2023During infectious keratitis, the production of collagenolytic and inflammatory substances, along with increased corneal matrix metalloproteinase (MMP) activity, induces... (Review)
Review
During infectious keratitis, the production of collagenolytic and inflammatory substances, along with increased corneal matrix metalloproteinase (MMP) activity, induces the degradation of corneal collagen and may cause postkeratitis complications, such as opacity, thinning, and corneal perforation. MMPs, especially MMP-2 and MMP-9, are overexpressed in infectious keratitis and sustained over time by inflammatory and nonmicrobial mechanisms. The high MMP levels are correlated with excessive corneal destruction in bacterial, herpetic, fungal, and acanthamoeba infections. Nonspecific treatments, such as tetracyclines, particularly doxycycline, or corticosteroids, are used as adjuvants to antimicrobials to alleviate the disproportionate degradation and inflammation of the corneal layers caused by corneal MMPs and decrease the recruitment and infiltration of inflammatory cells. Treatments showing inhibition of specific MMPs (Galardin, ZHAWOC7726), interfering with pro-MMP activation (EDTA, ascorbic acid), or showing anticytokine effect (epigallocatechin-2-gallate, TRAM-34) have been reported. Other treatments show a direct action over corneal collagen structure such as corneal cross-linking or have been associated with reduction of MMP levels such as amniotic membrane grafting. Although the use of these drugs has been shown in studies to be effective in controlling inflammation, especially in experimental ones, robust studies are still needed based on randomized and randomized clinical trials to demonstrate their potential effect as adjuvants in the management of infectious keratitis.
Topics: Humans; Corneal Ulcer; Keratitis; Cornea; Inflammation; Collagen
PubMed: 37352980
DOI: 10.1016/j.survophthal.2023.06.007 -
Current Research in Parasitology &... 2023This report explores the molecular profiling of spp. from individuals in the UK suffering from a debilitating, sight-threatening disease of the cornea known as...
This report explores the molecular profiling of spp. from individuals in the UK suffering from a debilitating, sight-threatening disease of the cornea known as keratitis (AK). Seventy ocular samples from individuals undergoing investigations for AK were sent to the Scottish Microbiology Reference Laboratories (SMiRL), Glasgow during 2017-2019, and subjected to DNA extraction followed by in-depth molecular typing using a nested PCR/bi-directional sequencing approach. Of the 70 samples tested, 40 were PCR-positive. Of these, 32 were successfully sequenced and assigned to two of 23 existing genotypes termed T1 to T23. Molecular profiling of the 32 samples highlighted two genotypes, namely T3 ( = 3) and T4 ( = 29). For those 29 samples identified as the T4 genotype, a sub-genotype (T4A-T4H) was recorded: T4A ( = 18); T4B ( = 5); T4C ( = 1); T4E ( = 4); and T4F ( = 1). This study highlights that the T4 genotype and T4A subtype are the predominant molecular variants to cause ocular disease in the UK. Gaining in-depth information on the molecular profiling of spp. is essential to increase our understanding of the source(s) of infection, transmission pathways, and potential associations with clinical outcomes for this rare, yet potentially debilitating ocular disease.
PubMed: 37680763
DOI: 10.1016/j.crpvbd.2023.100141 -
Pathogens (Basel, Switzerland) Feb 2024keratitis (AK) is a severe, rare protozoal infection of the cornea. can survive in diverse habitats and at extreme temperatures. AK is mostly seen in contact lens... (Review)
Review
keratitis (AK) is a severe, rare protozoal infection of the cornea. can survive in diverse habitats and at extreme temperatures. AK is mostly seen in contact lens wearers whose lenses have become contaminated or who have a history of water exposure, and in those without contact lens wear who have experienced recent eye trauma involving contaminated soil or water. Infection usually results in severe eye pain, photophobia, inflammation, and corneal epithelial defects. The pathophysiology of this infection is multifactorial, including the production of cytotoxic proteases by that degrades the corneal epithelial basement membrane and induces the death of ocular surface cells, resulting in degradation of the collagen-rich corneal stroma. AK can be prevented by avoiding risk factors, which includes avoiding water contact, such as swimming or showering in contact lenses, and wearing protective goggles when working on the land. AK is mostly treated with an antimicrobial therapy of biguanides alone or in combination with diaminidines, although the commercial availability of these medicines is variable. Other than anti-amoeba therapies, targeting host immune pathways in disease may lead to the development of vaccines or antibody therapeutics which could transform the management of AK.
PubMed: 38392880
DOI: 10.3390/pathogens13020142