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Clinical & Experimental Ophthalmology Jul 2022Globally, infectious keratitis is the fifth leading cause of blindness. The main predisposing factors include contact lens wear, ocular injury and ocular surface... (Review)
Review
Globally, infectious keratitis is the fifth leading cause of blindness. The main predisposing factors include contact lens wear, ocular injury and ocular surface disease. Staphylococcus species, Pseudomonas aeruginosa, Fusarium species, Candida species and Acanthamoeba species are the most common causal organisms. Culture of corneal scrapes is the preferred initial test to identify the culprit organism. Polymerase chain reaction (PCR) tests and in vivo confocal microscopy can complement the diagnosis. Empiric therapy is typically commenced with fluoroquinolones, or fortified antibiotics for bacterial keratitis; topical natamycin for fungal keratitis; and polyhexamethylene biguanide or chlorhexidine for acanthamoeba keratitis. Herpes simplex keratitis is mainly diagnosed clinically; however, PCR can also be used to confirm the initial diagnosis and in atypical cases. Antivirals and topical corticosteroids are indicated depending on the corneal layer infected. Vision impairment, blindness and even loss of the eye can occur with a delay in diagnosis and inappropriate antimicrobial therapy.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Blindness; Corneal Ulcer; Eye Infections, Fungal; Humans
PubMed: 35610943
DOI: 10.1111/ceo.14113 -
Ophthalmology Nov 2017Infectious keratitis is a major global cause of visual impairment and blindness, often affecting marginalized populations. Proper diagnosis of the causative organism is... (Review)
Review
Infectious keratitis is a major global cause of visual impairment and blindness, often affecting marginalized populations. Proper diagnosis of the causative organism is critical, and although culture remains the prevailing diagnostic tool, newer techniques such as in vivo confocal microscopy are helpful for diagnosing fungus and Acanthamoeba. Next-generation sequencing holds the potential for early and accurate diagnosis even for organisms that are difficult to culture by conventional methods. Topical antibiotics remain the best treatment for bacterial keratitis, and a recent review found all commonly prescribed topical antibiotics to be equally effective. However, outcomes remain poor secondary to corneal melting, scarring, and perforation. Adjuvant therapies aimed at reducing the immune response associated with keratitis include topical corticosteroids. The large, randomized, controlled Steroids for Corneal Ulcers Trial found that although steroids provided no significant improvement overall, they did seem beneficial for ulcers that were central, deep or large, non-Nocardia, or classically invasive Pseudomonas aeruginosa; for patients with low baseline vision; and when started early after the initiation of antibiotics. Fungal ulcers often have worse clinical outcomes than bacterial ulcers, with no new treatments since the 1960s when topical natamycin was introduced. The randomized controlled Mycotic Ulcer Treatment Trial (MUTT) I showed a benefit of topical natamycin over topical voriconazole for fungal ulcers, particularly among those caused by Fusarium. MUTT II showed that oral voriconazole did not improve outcomes overall, although there may have been some effect among Fusarium ulcers. Given an increase in nonserious adverse events, the authors concluded that they could not recommend oral voriconazole. Viral keratitis differs from bacterial and fungal cases in that it is often recurrent and is common in developed countries. The Herpetic Eye Disease Study (HEDS) I showed a significant benefit of topical corticosteroids and oral acyclovir for stromal keratitis. HEDS II showed that oral acyclovir decreased the recurrence of any type of herpes simplex virus keratitis by approximately half. Future strategies to reduce the morbidity associated with infectious keratitis are likely to be multidimensional, with adjuvant therapies aimed at modifying the immune response to infection holding the greatest potential to improve clinical outcomes.
Topics: Anti-Bacterial Agents; Antifungal Agents; Antiviral Agents; Corneal Ulcer; Diagnostic Techniques, Ophthalmological; Eye Infections, Bacterial; Eye Infections, Fungal; Female; Glucocorticoids; Humans; Keratitis, Herpetic; Male; Randomized Controlled Trials as Topic; Visual Acuity
PubMed: 28942073
DOI: 10.1016/j.ophtha.2017.05.012 -
Parasite (Paris, France) 2015Free-living amoebae of the genus Acanthamoeba are causal agents of a severe sight-threatening infection of the cornea known as Acanthamoeba keratitis. Moreover, the... (Review)
Review
Free-living amoebae of the genus Acanthamoeba are causal agents of a severe sight-threatening infection of the cornea known as Acanthamoeba keratitis. Moreover, the number of reported cases worldwide is increasing year after year, mostly in contact lens wearers, although cases have also been reported in non-contact lens wearers. Interestingly, Acanthamoeba keratitis has remained significant, despite our advances in antimicrobial chemotherapy and supportive care. In part, this is due to an incomplete understanding of the pathogenesis and pathophysiology of the disease, diagnostic delays and problems associated with chemotherapeutic interventions. In view of the devastating nature of this disease, here we present our current understanding of Acanthamoeba keratitis and molecular mechanisms associated with the disease, as well as virulence traits of Acanthamoeba that may be potential targets for improved diagnosis, therapeutic interventions and/or for the development of preventative measures. Novel molecular approaches such as proteomics, RNAi and a consensus in the diagnostic approaches for a suspected case of Acanthamoeba keratitis are proposed and reviewed based on data which have been compiled after years of working on this amoebic organism using many different techniques and listening to many experts in this field at conferences, workshops and international meetings. Altogether, this review may serve as the milestone for developing an effective solution for the prevention, control and treatment of Acanthamoeba infections.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Adrenal Cortex Hormones; Amebicides; Animals; Biological Assay; Chlorhexidine; Corneal Transplantation; Cross-Linking Reagents; Diagnostic Techniques, Ophthalmological; Host-Parasite Interactions; Humans; Hydroxymercuribenzoates; Mice; Parasitology; Phagocytosis; Protozoan Proteins; Specimen Handling; Virulence
PubMed: 25687209
DOI: 10.1051/parasite/2015010 -
Eye (London, England) Apr 2021Corneal opacity is the 5th leading cause of blindness and visual impairment globally, affecting ~6 million of the world population. In addition, it is responsible for... (Review)
Review
Corneal opacity is the 5th leading cause of blindness and visual impairment globally, affecting ~6 million of the world population. In addition, it is responsible for 1.5-2.0 million new cases of monocular blindness per year, highlighting an ongoing uncurbed burden on human health. Among all aetiologies such as infection, trauma, inflammation, degeneration and nutritional deficiency, infectious keratitis (IK) represents the leading cause of corneal blindness in both developed and developing countries, with an estimated incidence ranging from 2.5 to 799 per 100,000 population-year. IK can be caused by a wide range of microorganisms, including bacteria, fungi, virus, parasites and polymicrobial infection. Subject to the geographical and temporal variations, bacteria and fungi have been shown to be the most common causative microorganisms for corneal infection. Although viral and Acanthamoeba keratitis are less common, they represent important causes for corneal blindness in the developed countries. Contact lens wear, trauma, ocular surface diseases, lid diseases, and post-ocular surgery have been shown to be the major risk factors for IK. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though its effectiveness is being challenged by the emergence of antimicrobial resistance, including multidrug resistance, in some parts of the world. In this review, we aim to provide an updated review on IK, encompassing the epidemiology, causative microorganisms, major risk factors and the impact of antimicrobial resistance.
Topics: Acanthamoeba Keratitis; Anti-Bacterial Agents; Cornea; Drug Resistance, Bacterial; Humans; Risk Factors
PubMed: 33414529
DOI: 10.1038/s41433-020-01339-3 -
Pathogens (Basel, Switzerland) May 2022is a free-living amoeba genus able to cause severe infections, such as Granulomatous amoebic encephalitis (GAE), epithelial disorders and a sight-threatening disease...
is a free-living amoeba genus able to cause severe infections, such as Granulomatous amoebic encephalitis (GAE), epithelial disorders and a sight-threatening disease called keratitis (AK) [...].
PubMed: 35631129
DOI: 10.3390/pathogens11050609 -
Pathogens (Basel, Switzerland) Mar 2021keratitis is an unusual corneal infection that is recently increasing in frequency and is often contracted by contact lens wearers, someone who experienced recent eye... (Review)
Review
keratitis is an unusual corneal infection that is recently increasing in frequency and is often contracted by contact lens wearers, someone who experienced recent eye trauma, or someone exposed to contaminated waters. survive in air, soil, dust, and water. Therefore, eye trauma and poor contact lens hygiene practices lead to the entrapment of debris and thus infection. keratitis results in severe eye pain, inflammation, and defects of the epithelium and stroma that can potentially result in vision loss if not diagnosed early and treated promptly. The disease can be diagnosed using corneal scrape/biopsy, polymerase chain reactions, impression cytology, or in vivo confocal microscopy. Once diagnosed, it is usually treated with an antimicrobial combination therapy of biguanide and aromatic diadine eye drops for several months. Advanced stages of the disease result in vision loss and the need for corneal transplants. Avoiding the risk factors and diagnosing the disease early are the most effective ways to combat keratitis.
PubMed: 33801905
DOI: 10.3390/pathogens10030323 -
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 -
Experimental Eye Research Jan 2021Acanthamoeba keratitis (AK) is a rare protozoal infection of the cornea. At least eight species of Acanthamoeba are known to cause this sight-threatening disease of the... (Review)
Review
Acanthamoeba keratitis (AK) is a rare protozoal infection of the cornea. At least eight species of Acanthamoeba are known to cause this sight-threatening disease of the ocular surface. Acanthamoeba spp. exist in a wide array of niches ranging from thermal springs to under ice and every conceivable habitat in between. Contact lens wear is the leading risk factor for AK and is practiced by over 30 million individuals in the United States, yet the incidence of AK is less than 33 cases per one million contact lens wearers. Serological studies have reported that 90%-100% of individuals with no history of AK possess antibodies specific for Acanthamoeba antigens indicating that exposure to this organism is commonplace, yet disease is remarkably rare. Animal studies have shed light on the pathobiology and immunobiology of AK and indicate that a constellation of factors including the ocular surface microbiome and the microbiome of Acanthamoeba itself contribute to the pathogenesis of AK. Interesting, secretory antibodies produced by the adaptive immune response can prevent the initiation of corneal infection, but once Acanthamoeba trophozoites breach the corneal epithelium the adaptive immune system is helpless in altering the course of AK. It has been almost 50 years since AK was first described, yet many questions remain unanswered about this curious and enigmatic disease of the ocular surface.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Animals; Antibodies, Protozoan; Contact Lenses; Cornea; Eye Infections, Parasitic; Humans; Risk Factors
PubMed: 33221372
DOI: 10.1016/j.exer.2020.108365