<i>Acanthamoeba</i> keratitis: confirmation of the UK outbreak and a prospective case-control study identifying contributing risk factors

Carnt, Nicole; Hoffman, Jeremy; Verma, Seema; Hau, Scott; Radford, Cherry; Minassian, Darwin; Dart, John

doi:10.1136/bjophthalmol-2018-312544

Cited by 140 publications

(127 citation statements)

References 27 publications

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“…430 cases seen at Moorfields in the study recruitment period . 18 Supplementary Table 1 summarises the demographic data of patients at the initiation of AAT. No patients were included who had concurrent fungal or herpes keratitis although over 44% of patients were treated with anti-viral and steroid therapy before the diagnosis of AK due to misdiagnosis or delayed diagnosis of AK.…”

Section: Resultsmentioning

confidence: 99%

“…However, it is not possible in a retrospective study like this, even with these detailed data regarding the onset of severe inflammatory complications developing after the start of AAT, to distinguish whether these are definitively related to the inefficacy or side effects of the initial baseline AAT, or to some other currently unidentified cause. This question will be best answered in a prospective randomised controlled trial of PHMB monotherapy versus combined AAT therapy, such as the one that is currently in progress 18 . Supplementary Appendix Table 2 Comparison of medical cure rates within 12 months of initiating Acanthamoeba keratitis treatment for 227 patients using mutually exclusive anti-amoebic therapies (AAT).…”

Section: Discussionmentioning

confidence: 99%

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Acanthamoeba keratitis therapy: time to cure and visual outcome analysis for different antiamoebic therapies in 227 cases

Papa¹,

Rama

Radford

et al. 2019

Br J Ophthalmol

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AimsTo test the hypothesis that Acanthamoeba keratitis (AK) outcomes differ for different topical antiamoebic therapies (AAT) and to provide the detailed patient outcome data.MethodsA retrospective cohort study of 227 patients developing AK between 25 July 1991 and 10 August 2012. Inclusion criteria required a complete record of AAT treatment for both the primary outcome of a medical cure rate at 12 months and the secondary outcome of Snellen visual acuity ≤6/24 and/or surgical intervention. Analysis used multivariable regression to control for differences in baseline disease characteristics for both primary and secondary outcomes with unadjusted analyses for other outcomes. Subjects were categorised for analysis both by the AAT used at baseline and also by mutually exclusive AAT (patients exposed to all the drugs in each group, and no others, for some period). AAT categories were PHMB monotherapy, PHMB+diamidine, PHMB+chlorhexidine+diamidine, diamidine monotherapy and other AAT.ResultsAnalysis by baseline AAT showed no notable difference between treatments for both a medical cure at 12 months in 60.79% (138/227) or for a poor outcome in 49.34% (112/227). When AATs were analysed by mutually exclusive groups, PHMB monotherapy provided the best outcomes. These findings are subject to bias requiring careful interpretation. Overall cure rates for the 214 subjects with resolved outcomes were 94.27% (214/227), median time to cure 5 months (IQR 3.25–9.00 months) and range 1–26.24 months.ConclusionPHMB 0.02% monotherapy for the initial treatment of AK is as effective as biguanide+diamidine combination therapy. Chlorhexidine monotherapy was too infrequent for comparison. The outcome data are the most detailed available.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Acanthamoeba keratitis therapy: time to cure and visual outcome analysis for different antiamoebic therapies in 227 cases

Papa¹,

Rama

Radford

et al. 2019

Br J Ophthalmol

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“…However, even with a DD modality it is important to reinforce water avoidance and a "no-water" campaign has been launched to try to address this issue [73]. Therefore compliant wear with DD contact lenses should reduce the prevalence of serious corneal infection [67,74,75], although there is currently no evidence in the literature to support this supposition.…”

Section: Compliance With Contact Lens Replacement and Contact Lens Camentioning

confidence: 99%

Silicone hydrogel daily disposable benefits: The evidence

Sulley¹,

Dumbleton

2020

Contact Lens and Anterior Eye

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Daily disposable (DD) contact lenses first came to the market approximately 25 years ago and eye care professionals (ECPs) started prescribing silicone hydrogel (SiH) contact lenses, primarily for extended or continuous wear, approximately 20 years ago. It has now been over ten years since SiH DD contact lenses have been available, and while SiH materials are routinely prescribed by ECPs for reusable daily wear, hydrogel materials are still frequently selected for the DD modality of contact lens wear. This article reviews the evidence to support the benefits of both a DD modality and SiH materials and how patients' needs may be met with SiH DD contact lenses, with respect to clinical performance, health outcomes, satisfaction, compliance and convenience. Factors which may enable or constrain ECPs from prescribing SiH DD contact lenses, as opposed to hydrogel DD and reusable contact lenses, for more of their patients are discussed with the objective of providing ECPs with a greater understanding of the advantages that can be afforded by prescribing SiH DD contact lenses to both their new and existing contact lens wearers.

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“…In immunosuppressed patients, Acanthamoebae may cause encephalitis (6). Acanthamoeba is an emerging pathogen, because 80 to 90% of infections are associated with growing contact lens use (7–9). Water for hand washing is often scarce in places where Acanthamoeba is endemic (e.g.…”

Section: Introductionmentioning

confidence: 99%

Three stages in the development of the cyst wall of the eye pathogen Acanthamoeba castellanii

Magistrado-Coxen

Aqeel

Lopez

et al. 2019

Preprint

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9When deprived of nutrients, trophozoites of the eye pathogen Acanthamoeba castellanii make 10 a cyst wall, which contains cellulose and has two layers connected by cone-shaped ostioles. 11 We recently showed chitin is also present and identified three sets of lectins, which localize to 12 the ectocyst layer (Jonah lectin) or the endocyst layer and ostioles (Luke and Leo lectins). To 13 Acanthamoeba was used to discover and characterize roles of actin and associated proteins in 54 the cytoskeleton, phagocytosis, and cell motility (16). Whole genome sequences of A. 55 castellanii identified >500 genes derived from bacteria by HGT, which is the greatest number 56 of any eukaryote described to date (17). A mannose-binding protein on the surface of 57 trophozoites, secreted proteases, and pore-forming peptides each appear to contribute to 58 contact-mediated cytolysis of corneal epithelial cells by Acanthamoebae (18)(19)(20). 59 The Acanthamoeba cyst wall, which forms when trophozoites are starved, is an 60 important virulence factor, because it makes cysts resistant to surface disinfectants, sterilizing 61 agents in contact lens solutions, and antibiotics applied to the eye (21, 22). Fifty years ago, 62 the cyst wall was shown to contain cellulose and have two microfibril-dense layers (outer 63 ectocyst and an inner endocyst), as well as conical structures (ostioles) that connect the layers 64 (23, 24). During excystation, the trophozoites escape through one of the ostioles, which were 65 not counted (25). Although the electron micrographs were beautiful, none of the cyst wall 66 proteins were identified, and there was minimal information as to how the two layers and 67 ostioles are formed. Further, monoclonal antibodies, potentially useful as diagnostic reagents, 68 were made to trophozoites but not to cysts (26, 27). 69To better understand its structure, we recently identified chitin and three sets of 70 cellulose-and chitin-binding lectins in the cyst wall of A. castellanii Neff, which is the best 71 studied strain of the protist (28). These lectins are present in 12 copies (Luke), 5 copies 72 (Jonah), or 14 copies (Leo) in the cyst wall, which make them by far the most abundant 73 proteins. These lectins contain carbohydrate-binding modules that were shown to bind 74 cellulose in Dictyostelium and plants (CBM49s of Luke lectins), were previously identified in 75 bacteria but were uncharacterized (choice of anchor A (CAA) domains of Jonah lectins), or are 76 unique to Acanthamoebae (8-Cys domains of Leo lectins) (Fig. 1) (29-31). A representative 77 Jonah lectin is present in the ectocyst layer, while representative Luke and Leo lectins are 78 present in the endocyst layer and ostioles. 79 Here we used structured illumination microscopy (SIM), probes for glycopolymers, and 80 green fluorescent protein (GFP) tags for cyst wall lectins to determine the sequence of events 81 (stages) involved in the formation of the A. castellanii cyst wall during encystation (32). To 82 characterize their carbohydrate-bi...

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Acanthamoeba keratitis: confirmation of the UK outbreak and a prospective case-control study identifying contributing risk factors

Cited by 140 publications

References 27 publications

Acanthamoeba keratitis therapy: time to cure and visual outcome analysis for different antiamoebic therapies in 227 cases

Acanthamoeba keratitis therapy: time to cure and visual outcome analysis for different antiamoebic therapies in 227 cases

Silicone hydrogel daily disposable benefits: The evidence

Three stages in the development of the cyst wall of the eye pathogen Acanthamoeba castellanii

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