Redefining the human corneal immune compartment using dynamic intravital imaging.

The healthy human cornea is a uniquely transparent sensory tissue where immune responses are tightly controlled to preserve vision. The cornea contains immune cells that are widely presumed to be intraepithelial dendritic cells (DCs). Corneal immune cells have diverse cellular morphologies and morphological alterations are used as a marker of inflammation and injury. Based on our imaging of corneal T cells in mice, we hypothesized that many human corneal immune cells commonly defined as DCs are intraepithelial lymphocytes (IELs). To investigate this, we developed functional in vivo confocal microscopy (Fun-IVCM) to investigate cell dynamics in the human corneal epithelium and stroma. We show that many immune cells resident in the healthy human cornea are T cells. These corneal IELs are characterized by rapid, persistent motility and interact with corneal DCs and sensory nerves. Imaging deeper into the corneal stroma, we show that crawling macrophages and rare motile T cells patrol the tissue. Furthermore, we identify altered immune cell behaviors in response to short-term contact lens wear (acute inflammatory stimulus), as well as in individuals with allergy (chronic inflammatory stimulus) that was modulated by therapeutic intervention. These findings redefine current understanding of immune cell subsets in the human cornea and reveal how resident corneal immune cells respond and adapt to chronic and acute stimuli.

Acanthamoeba Keratitis Risk Factors for Daily Wear Contact Lens Users: A Case-Control Study.

PURPOSE: 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. DESIGN: Case-control study. PARTICIPANTS: 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. METHODS: Analysis of a self-administered questionnaire. MAIN OUTCOME MEASURES: Independent risk factors and population attributable risk percentage (PAR%) for AK. RESULTS: 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. CONCLUSIONS: 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.

Human tear metabolites associated with nucleoside-signalling pathways in bacterial keratitis.

OBJECTIVE: The study aimed to profile and quantify tear metabolites associated with bacterial keratitis using both untargeted and targeted metabolomic platforms. METHODS: Untargeted metabolomic analysis using liquid-chromatography-Q Exactive-HF mass-spectrometry explored tear metabolites significantly associated with bacterial keratitis (n = 6) compared to healthy participants (n = 6). Differential statistics and principal component analysis determined meaningful metabolite differences between cases and controls. Purines and nucleosides were further quantified and compared between 15 cases and 15 controls in the targeted metabolomic platform using TSQ quantum access triple quadrupole mass spectrometry. Compound quantification was done by plotting the calibration curves and the difference in the compound levels was evaluated using the Wilcoxon rank-sum test. RESULTS: In the untargeted analysis, 49 tear metabolites (27 upregulated and 22 downregulated) were differentially expressed between cases and controls. The untargeted analysis indicated that the purine metabolism pathway was the most affected by bacterial keratitis. Metabolite quantification in the targeted analysis further confirmed the upregulation of xanthine (P = 0.02) and downregulation of adenine (P < 0.0001), adenosine (P < 0.0001) and cytidine (P < 0.0001) in the tears of participants with bacterial keratitis compared to that of healthy participants. CONCLUSIONS: Bacterial keratitis significantly changes the tear metabolite profile, including five major compound classes such as indoles, amino acids, nucleosides, carbohydrates, and steroids. This study also indicates that tear fluids can be used to map the metabolic pathways and uncover metabolic markers associated with bacterial keratitis. Conceivably, the inhibition of nucleoside synthesis may contribute to the pathophysiology of bacterial keratitis because nucleosides are required for maintaining cellular energy homeostasis and immune adaptability.

Assessment of genotypes, endosymbionts and clinical characteristics of Acanthamoeba recovered from ocular infection.

INTRODUCTION: Acanthamoeba is an emerging pathogen, infamous for its resilience against antiprotozoal compounds, disinfectants and harsh environments. It is known to cause keratitis, a sight-threatening, painful and difficult to treat corneal infection which is often reported among contact lens wearers and patients with ocular trauma. Acanthamoeba comprises over 24 species and currently 23 genotypes (T1-T23) have been identified. AIMS: This retrospective study was designed to examine the Acanthamoeba species and genotypes recovered from patients with Acanthamoeba keratitis (AK), determine the presence of endosymbionts in ocular isolates of Acanthamoeba and review the clinical presentations. METHODOLOGY: Thirteen culture-confirmed AK patients treated in a tertiary eye care facility in Hyderabad, India from February to October 2020 were included in this study. The clinical manifestations, medications and visual outcomes of all patients were obtained from medical records. The Acanthamoeba isolates were identified by sequencing the ribosomal nuclear subunit (rns) gene. Acanthamoeba isolates were assessed for the presence of bacterial or fungal endosymbionts using molecular assays, PCR and fluorescence in situ hybridization (FISH). RESULTS: The mean age of the patients was 33 years (SD ± 17.4; 95% CI 22.5 to 43.5 years). Six (46.2%) cases had AK associated risk factors; four patients had ocular trauma and two were contact lens wearers. A. culbertsoni (6/13, 46.2%) was the most common species, followed by A. polyphaga and A. triangularis. Most of the isolates (12/13) belonged to genotype T4 and one was a T12; three sub-clusters T4A, T4B, and T4F were identified within the T4 genotype. There was no significant association between Acanthamoeba types and clinical outcomes. Eight (61.5%) isolates harboured intracellular bacteria and one contained Malassezia restricta. The presence of intracellular microbes was associated with a higher proportion of stromal infiltrates (88.9%, 8/9), epithelial defect (55.6%, 5/9) and hypopyon (55.6%, 5/9) compared to 50% (2/4), 25% (1/4) and 25% (1/4) AK cases without intracellular microbes, respectively. CONCLUSIONS: Genotype T4 was the predominant isolate in southern India. This is the second report of T12 genotype identified from AK patient in India, which is rarely reported worldwide. The majority of the Acanthamoeba clinical isolates in this study harboured intracellular microbes, which may impact clinical characteristics of AK.

Diagnostic accuracy of AS-OCT vs gonioscopy for detecting angle closure: a systematic review and meta-analysis.

PURPOSE: This study aims to review the literature that compares the accuracy of Anterior Segment-Optical Coherence Tomography (AS-OCT) against gonioscopy in detecting eyes with angle closure. It is currently unclear how AS-OCT fits into clinical practice for detecting angle closure. This is a systematic review and meta-analysis. METHODS: A literature search was performed on Medline, Embase, Scopus and the Cochrane Central Register of Controlled Trials to identify studies that investigated the diagnostic accuracy of AS-OCT in detecting eyes with angle closure as diagnosed by gonioscopy. Eligible studies included in the analysis met stringent inclusion criteria determining the sensitivity and specificity of AS-OCT. RESULTS: The initial search identified 727 studies, of which 23 were included in the final analysis. We found substantial variation in the parameters being studied and methodologies. The sensitivity of AS-OCT ranged from 46 to 100% (median 87%). Twenty-one studies identified parameters that showed sensitivity above 80%. The specificity ranged from 55.3 to 100% (median 84%). CONCLUSION: AS-OCT demonstrates good sensitivity for detecting angle closure. It may provide an avenue to address high rates of undiagnosed angle closure, such as found in developing Asian countries. However, AS-OCT is not yet able to replace gonioscopy. Clinicians should consider whether the diagnostic accuracy of AS-OCT is acceptable for their specific clinical use before adopting it. More studies are needed to determine the utility of AS-OCT, including longitudinal studies to determine the significance of eyes classified to have closed angles by AS-OCT but open on gonioscopy.

Epidemiology, Microbiology, and Genetics of Contact Lens-Related and Non-Contact Lens-Related Infectious Keratitis.

ABSTRACT: Infectious keratitis is a rare but severe condition associated with a range of ocular and systemic predisposing conditions, including ocular trauma, prior surgery, surface disease, and contact lens (CL) wear. This review explores the epidemiology of infectious keratitis, specifically the differences in disease incidence and risk factors, causative organism profile and virulence characteristics and host microbiome, genetics, gene expression, proteomics, and metabolomic characteristics in CL-related and non-CL-related diseases. Differences exist in the epidemiology, demographics, causative organisms, and their virulence characteristics in CL-related and non-CL-related diseases, and there is less evidence to support differences between these groups of individuals in the ocular surface microbiome, genetics, and pathways of disease. Genetic variations, however, in the host immune profile are implicated in both the onset and severity of infectious keratitis in CL and non-CL wearers. As technologies in metabolomics, proteomics, and genomics improved to be better able to process small-volume samples from the ocular surface, there will be improved understanding of the interplay between the CL, ocular surface, host immune profile, and the microbial environment. This may result in a more personalized approach in the management of disease to reduce disease severity.

Effect of Water Exposure on Contact Lens Storage Case Contamination in Soft Lens Wearers.

SIGNIFICANCE: Water exposure during contact lens wear can transfer pathogenic microorganisms to the eye, causing ocular complications. This study determined that water exposure is prevalent among lens wearers and is independently associated with higher case contamination. Contact lens compliance education to minimize water exposure should be reenforced by contact lens organizations and practitioners. PURPOSE: Given the increasing association between water exposure and contact lens disease, this study aimed to explore the effect of water exposure and storage case contamination in soft contact lens users. METHODS: A total of 165 daily soft lens wearers completed a self-administered questionnaire on contact lens hygiene. Lens cases were collected, and microbial analysis was conducted using an adenosine triphosphate assay (for overall microbial bioburden) and limulus amebocyte lysate assay (for endotoxin levels). The lens hygiene (excellent, >35; moderate, 28 to 35; poor, <28) and water contact (≤1, good; >1, poor) scores measured the compliance and water exposure during lens wear, respectively. Multiple regression determined the association between water behaviors and case contamination. RESULTS: The average (standard deviation) age of participants was 28 (13.5) years (18 to 78 years), and 65% were female. The average overall microbial bioburden of storage cases was 3.10 (0.98) log colony-forming unit/mL (1.09 to 5.94 log colony-forming unit/mL). Forty-five percent of participants reported showering, 49.7% reported swimming while wearing lenses (65.4% of whom swam without goggles), 27.8% used wet hands to handle lenses, and 17.5% used tap water to rinse storage cases. Showering with lenses significantly increased the risk of higher storage case bioburden (P = .001), whereas using wet hands (P = .01) doubled the risk of higher case endotoxin levels (odds ratio, 2.41; confidence interval 1.19 to 4.86). CONCLUSIONS: Water contact behavior while wearing lenses is prevalent among soft lens wearers and is associated with higher case contamination. Practitioners may improve contact lens education to reduce water exposure and case contamination to reduce the risk of lens-related adverse events.

American Academy of Optometry Microbial Keratitis Think Tank.

SIGNIFICANCE: Think Tank 2019 affirmed that the rate of infection associated with contact lenses has not changed in several decades. Also, there is a trend toward more serious infections associated with Acanthamoeba and fungi. The growing use of contact lenses in children demands our attention with surveillance and case-control studies. PURPOSE: The American Academy of Optometry (AAO) gathered researchers and key opinion leaders from around the world to discuss contact lens-associated microbial keratitis at the 2019 AAO Annual Meeting. METHODS: Experts presented within four sessions. Session 1 covered the epidemiology of microbial keratitis, pathogenesis of Pseudomonas aeruginosa, and the role of lens care systems and storage cases in corneal disease. Session 2 covered nonbacterial forms of keratitis in contact lens wearers. Session 3 covered future needs, challenges, and research questions in relation to microbial keratitis in youth and myopia control, microbiome, antimicrobial surfaces, and genetic susceptibility. Session 4 covered compliance and communication imperatives. RESULTS: The absolute rate of microbial keratitis has remained very consistent for three decades despite new technologies, and extended wear significantly increases the risk. Improved oxygen delivery afforded by silicone hydrogel lenses has not impacted the rates, and although the introduction of daily disposable lenses has minimized the risk of severe disease, there is no consistent evidence that they have altered the overall rate of microbial keratitis. Overnight orthokeratology lenses may increase the risk of microbial keratitis, especially secondary to Acanthamoeba, in children. Compliance remains a concern and a significant risk factor for disease. New insights into host microbiome and genetic susceptibility may uncover new theories. More studies such as case-control designs suited for rare diseases and registries are needed. CONCLUSIONS: The first annual AAO Think Tank acknowledged that the risk of microbial keratitis has not decreased over decades, despite innovation. Important questions and research directions remain.

The risk of vision loss in contact lens wear and following LASIK.

PURPOSE: To compare the risk of vision loss following contemporary laser-assisted in situ keratomileusis (LASIK) with different types and modality of use of contact lenses. METHODS: Data from a previously published study were used to derive the incidence of vision loss (≥ 2 line loss of best corrected spectacle acuity) following microbial keratitis for different contact lens types and wearing modality, stratified by duration of lens wear. A literature search on vision loss following LASIK was performed between 2003 and 2019. The prevalence of vision loss at six months post-surgery was captured from clinical trials published after 2003. A proportion meta-analysis was applied to derive the prevalence of vision loss following LASIK. A least-squares fitting of cumulative vision loss (P, /10 000 wearers) over time (t, years) using an exponential model estimated the years of contact lens wear to which the risk of vision loss with LASIK was equivalent. RESULTS: Vision loss following LASIK occurred in 66 (95% confidence interval [CI] 34-108) per 10 000 wearers. As a conservative estimate based on the lower confidence interval of the estimated equivalent years of contact lens wear, daily wear contact lenses and extended overnight silicone wear hydrogel contact lens need to be worn for 103 (95% [CI] 103-391) and 25 (95% [CI] 25-79) years respectively, to equal the rate of vision loss equivalent to a one-off LASIK procedure. CONCLUSIONS: The risk of vision loss to the individual is low with either contact lens wear or refractive surgery. Contact lens wear does not pose a higher risk of vision loss than LASIK surgery for the most common wear modalities.

Are cataract surgery referrals to public hospitals in Australia poorly targeted?

IMPORTANCE: Referral letters constitute the first step on the pathway to cataract surgery; however, little is known on how effective referral letters are in providing adequate information to triage patients and inform surgical prioritization. BACKGROUND: Benchmarking exercises are important to document referral processes and to identify areas where improvements can be made. DESIGN: Cross-sectional study with longitudinal follow-up conducted at two metropolitan public hospitals in New South Wales, Australia. PARTICIPANTS: A total of 400 sequential cataract referral letters. METHODS: An audit of cataract referral letters was performed and content benchmarked against international prioritization tools. Medical records were reviewed 1 year following referral. MAIN OUTCOME MEASURES: Referral quality and waiting times. RESULTS: Two-thirds of patients referred for cataract surgery were yet to have their initial hospital appointment in the year following referral (65%, 245/376). One half of referrals seen in clinic (49%, 64/113) were not listed for cataract surgery. Multivariate analysis revealed referral letter content was not indicative of surgical booking, with the major predictors being hospital-recorded visual acuity and grading of cataract (P < 0.0001). Referral content lacked sufficient detail to apply prioritization tools developed in other settings. CONCLUSION AND RELEVANCE: This audit highlights a disconnect between referral letter content and hospital assessment of patients. Current referrals to public hospitals are poorly targeted, with high numbers of referred patients not proceeding to surgery. Patients commonly waited over 1 year to have their ophthalmic assessment at these public hospital eye clinics, revealing lengthy 'wait-for-waits' as a barrier to care. Standardized referral templates may facilitate improvement of referral pathways and shorten waiting times.

Oxidative stress and reactive oxygen species: a review of their role in ocular disease.

For many years, oxidative stress arising from the ubiquitous production of reactive oxygen species (ROS) has been implicated in the pathogenesis of various eye diseases. While emerging research has provided some evidence of the important physiological role of ROS in normal cell function, disease may arise where the concentration of ROS exceeds and overwhelms the body's natural defence against them. Additionally, ROS may induce genomic aberrations which affect cellular homoeostasis and may result in disease. This literature review examines the current evidence for the role of oxidative stress in important ocular diseases with a view to identifying potential therapeutic targets for future study. The need is particularly pressing in developing treatments for conditions which remain notoriously difficult to treat, including glaucoma, diabetic retinopathy and age-related macular degeneration.

The Impact of Topical Corticosteroids Used in Conjunction with Antiamoebic Therapy on the Outcome of Acanthamoeba Keratitis.

PURPOSE: To examine the impact of topical corticosteroid use after the start of antiamoebic therapy (AAT) on the outcomes of Acanthamoeba keratitis (AK) therapy. DESIGN: Cohort study. PARTICIPANTS: A total of 196 patients diagnosed with AK at Moorfields Eye Hospital, London, between January 1991 and April 2012. In 13 patients with bilateral AK, 1 eye was randomly excluded from analysis. METHODS: Patient demographics and clinical examination findings were collected both at the start of AAT and subsequently at the time that topical corticosteroid therapy was initiated. Preliminary a priori investigations were used to identify effect modifiers/confounders and extreme associations requiring consideration in multivariate regression modeling. A multivariable logistic model, optimized for assessment of corticosteroid use after the start of AAT, was used to estimate the odds ratios (ORs) of a suboptimal outcome. MAIN OUTCOME MEASURES: Suboptimal outcome was defined as final visual acuity ≤20/80, corneal perforation, or the need for keratoplasty. RESULTS: In multivariable analysis, restricted to 129 eyes (1 eye per patient) free of scleritis and hypopyon at the start of AAT, topical corticosteroids were not associated with worse outcomes (OR, 1.08; 95% confidence interval [CI], 0.39-3.03), even when corticosteroids had been used before the start of AAT. Risk factors significantly associated with worse outcomes were topical corticosteroid use before the start of AAT (OR, 3.85; 95% CI, 1.35-11.03), a corneal ring infiltrate (together with at least 1 other feature of AK) present at the start of AAT (OR, 5.89; 95% CI, 1.17-29.67), and age ≥33 years at the start of AAT (OR, 4.02; 95% CI, 1.46-11.06). CONCLUSIONS: Many corneal specialists currently are uncertain about the risk benefit associated with the use of topical corticosteroids for the management of inflammatory complications of AK. The evidence from this study gives clinicians and patients reassurance that the potential benefits of topical corticosteroid therapy, for treating pain and discomfort, are not associated with worse outcomes when initiated after starting modern AAT. Other potential benefits, in terms of resolution of inflammatory complications, will not be demonstrated without a carefully designed randomized clinical trial.

Prospective Study of the Diagnostic Accuracy of the In Vivo Laser Scanning Confocal Microscope for Severe Microbial Keratitis.

PURPOSE: To determine the diagnostic accuracy of in vivo confocal microscopy (IVCM) for moderate to severe microbial keratitis (MK). DESIGN: Double-masked prospective cohort study. PARTICIPANTS: Consecutive patients presenting to Aravind Eye Hospital, Madurai, India, between February 2012 and February 2013 with MK (diameter ≥3 mm, excluding descemetocele, perforation, or herpetic keratitis). METHODS: Following examination, the corneal ulcer was scanned by IVCM (HRT3/RCM, Heidelberg Engineering, Heidelberg, Germany). Images were graded for the presence or absence of fungal hyphae or Acanthamoeba cysts by the confocal microscopist who performed the scan (masked to microbial diagnosis) and 4 other experienced confocal graders (masked to clinical features and microbiology). The regrading of the shuffled image set was performed by 3 graders, 3 weeks later. Corneal-scrape samples were collected for microscopy and culture. MAIN OUTCOME MEASURES: The main outcome measures were sensitivity, specificity, and positive and negative predictive values of IVCM compared with those of a reference standard of positive culture or light microscopy. Sensitivities and specificities for multiple graders were pooled and 95% confidence intervals calculated using a bivariate random-effects regression model. RESULTS: The study enrolled 239 patients with MK. Fungal infection was detected in 176 (74%) and Acanthamoeba in 17 (7%) by microbiological methods. IVCM had an overall pooled (5 graders) sensitivity of 85.7% (95% confidence interval [CI]: 82.2%-88.6%) and pooled specificity of 81.4% (95% CI: 76.0%-85.9%) for fungal filament detection. For Acanthamoeba, the pooled sensitivity was 88.2% (95% CI: 76.2%-94.6%) and pooled specificity was 98.2% (95% CI: 94.9%-99.3%). Intergrader agreement was good: κ was 0.88 for definite fungus; κ was 0.72 for definite Acanthamoeba. Intragrader repeatability was high for both definite fungus (κ: 0.88-0.95) and definite Acanthamoeba classification (κ: 0.63-0.90). IVCM images from 11 patients were considered by all 5 graders to have a specific organism present (10 fungus, 1 Acanthamoeba) but had negative results via culture and light microscopy. CONCLUSIONS: Laser scanning IVCM performed with experienced confocal graders has high sensitivity, specificity, and test reproducibility for detecting fungal filaments and Acanthamoeba cysts in moderate to large corneal ulcers in India. This imaging modality was particularly useful for detecting organisms in deep ulcers in which culture and light microscopy results were negative.

Strategies for the prevention of contact lens-related Acanthamoeba keratitis: a review.

PURPOSE: Acanthamoeba keratitis is a severe, often sight threatening, corneal infection which in Western countries is predominantly seen in daily wear of contact lenses. This review aims to summarise the pathobiology and epidemiology of contact lens-related Acanthamoeba keratitis, and to present strategies for prevention, particularly with respect to modifiable risk factors in contact lens wear. RECENT FINDINGS: The virulence of Acanthamoeba and resistance to treatment in keratitis appears to be linked with the production of a low molecular weight protease MIP133 by the organism, in response to binding to corneal epithelial cells through a mannose binding protein, and to the ability of the organism to convert from the trophozoite to the resistant cyst form. Recent epidemiological studies in contact lens relate disease have confirmed the link between solution topping up and Acanthamoeba keratitis and have reinforced the importance of avoidance of tap water, either as part of the care for the contact lens or storage case, handling lenses with wet hands or showering while wearing lenses. In the most recent analysis from the USA, there were no strong effects for solution type, water source or water disinfection process. Wearer age, lens wear time and history to appear to be linked with Acanthamoeba keratitis. Daily disposable contact lens use would be expected to reduce the prevalence of Acanthamoeba disease although this is unproven. SUMMARY: While Acanthamoeba keratitis remains challenging to diagnose and manage, strategies to limit the disease severity in contact lens wearers should include attention to recently identified risk factors, particularly those related to water contact. Public health awareness measures, the use of daily disposable contact lenses, a better understanding of the contribution of the host immunity and the development of standardised methods for culture of amoeba and testing of contact lens care systems against Acanthamoeba in the licensing process may be of value. Alternative treatments for the future may include those which target the mannose binding protein or the genes which control conversion to the cyst form.

Therapeutic and optical keratoplasty in the management of Acanthamoeba keratitis: risk factors, outcomes, and summary of the literature.

OBJECTIVE: To report the risk factors for and outcomes of therapeutic and optical keratoplasty in the management of Acanthamoeba keratitis (AK). DESIGN: Retrospective case series. PARTICIPANTS: A total of 50 eyes of 196 patients with retrievable medical records, diagnosed with AK at Moorfields Eye Hospital, London, underwent keratoplasty between January 1991 and April 2012. METHODS: Patient demographics, initial clinical examination findings, and management details were collected. The ophthalmic characteristics of patients who underwent keratoplasty for AK were compared with those who did not. Patients undergoing therapeutic keratoplasty were compared with those undergoing optical keratoplasty for baseline characteristics, management details, and visual outcomes. A multivariate logistic model was used to derive the odds ratios of a poor visual outcome in all keratoplasty patients. MAIN OUTCOME MEASURES: Poor visual outcome was defined as final visual acuity of 20/200 or worse. Secondary outcomes of interest included number of clinic visits and the need for additional intraocular surgery. RESULTS: Of the 196 AK patients, a total of 50 patients (25.5%) underwent penetrating or anterior lamellar keratoplasty, 10 of whom (20%) underwent repeat procedures. Of these 50 patients, 26 (52%) had therapeutic keratoplasty, predominantly for corneal perforation. The remaining 24 patients (48%) underwent optical keratoplasty for visual rehabilitation. Thirty-seven (80.4%) patients in the keratoplasty group initially were misdiagnosed as having herpes simplex keratitis versus 59 (41.8%) patients who did not require a keratoplasty (P < 0.001). Final visual outcomes were significantly better in the optical group compared with the therapeutic group, with 13 (54.2%) achieving visual acuity of 20/30 or better versus 7 (26.9%), respectively. On multivariate analysis, beginning therapy at a hospital other than Moorfields and undergoing a therapeutic, rather than an optical, keratoplasty were associated significantly with a poor visual outcome from keratoplasty. CONCLUSIONS: The prognosis of keratoplasty differs markedly when performed for therapeutic purposes compared with visual rehabilitation. Where possible, keratoplasty should be delayed until such time as the eye is uninflamed and medically cured of Acanthamoeba.

The impact of topical corticosteroid use before diagnosis on the outcome of Acanthamoeba keratitis.

OBJECTIVE: To examine the impact of topical corticosteroid use before the diagnosis of Acanthamoeba keratitis (AK) on final visual outcomes and to determine the prognostic factors predicting poorer outcomes. DESIGN: Cohort study. PARTICIPANTS: A total of 209 eyes of 196 patients with retrievable medical records, diagnosed with AK at Moorfields Eye Hospital, London, between January 1991 and April 2012. One eye was randomly excluded from analysis in the 13 cases of bilateral AK. METHODS: Patient demographic, initial clinical examination findings, and management details were collected. The outcomes of patients treated with topical corticosteroids before diagnosis of AK were compared with those not treated with topical corticosteroids before diagnosis. A multivariable logistic model, optimized for prior corticosteroid use, was used to derive the odds ratios (ORs) of a suboptimal visual outcome. MAIN OUTCOME MEASURES: Suboptimal visual outcome was defined as final visual acuity (VA) ≤ 20/80, corneal perforation, or need for keratoplasty. RESULTS: Acanthamoeba keratitis was diagnosed on microbiological culture in 94 eyes (48.0%), on histopathologic examination in 27 eyes (13.8%), on confocal microscopy in 38 eyes (19.4%), and on the basis of a typical clinical course and response to treatment in 37 eyes (18.9%). Final VA and prior corticosteroid use data were available for 174 eyes (88.8%). In multivariable analysis, corticosteroid use before diagnosis was associated with suboptimal visual outcome (OR, 3.90; 95% confidence interval [CI], 1.78-8.55), as were disease stage 3 at presentation (OR, 5.62; 95% CI, 1.59-19.80) and older age (60+ years) at diagnosis (OR, 8.97; 95% CI, 2.13-37.79). CONCLUSIONS: Corticosteroid use before diagnosis of AK is highly predictive of a poorer visual outcome. This is largely due to the initial misdiagnosis of AK as herpetic keratitis. It is important to include AK in the differential diagnosis of keratitis in all contact lens users with keratitis, particularly before making a diagnosis of herpes keratitis and before the use of topical corticosteroids in the therapy of any indolent keratitis.

Acanthamoeba sclerokeratitis: epidemiology, clinical features, and treatment outcomes.

PURPOSE: To describe the epidemiology, clinical features, and treatment outcomes of Acanthamoeba sclerokeratitis (ASK). DESIGN: Retrospective case series. PARTICIPANTS: All cases of both Acanthamoeba keratitis (AK) and ASK identified between January 1, 2000, and January 8, 2011, at Moorfields Eye Hospital. METHODS: Acanthamoeba keratitis was defined as the presence of AK with concurrent ipsilateral scleral inflammation. Topical steroids and oral nonsteroidal anti-inflammatory drugs (NSAIDs) were used as the first line of treatment. In unresponsive cases, oral NSAIDs were replaced by oral prednisolone with cyclosporine, azathioprine, or mycophenolate as steroid-sparing agents. Cyclosporine was combined with azathioprine or mycophenolate in cases unresponsive to only 1 of these drugs alone. MAIN OUTCOME MEASURES: Epidemiology, clinical phenotype, response to therapy, resolution of inflammation, visual outcome, corneal transplantation, and enucleation rate. RESULTS: From a series of 178 patients with AK, 36 eyes of 33 patients (18.5%) developed ASK. A total of 25 of 33 patients (76%) with ASK were tertiary referrals. The incidence of the disease in greater London was 0.13 per million, and the incidence in this population of patients with AK was 33 of 178 (18.5%). Mild scleritis/limbitis responsive to topical steroids and oral NSAIDs was present in 11 of 36 eyes (31%), and moderate/severe scleritis, requiring systemic immunosuppressive therapy, was present in 25 eyes (69%). Before the initiation of ASK treatment, 2 of 36 eyes (6%) had corrected distance visual acuity (CDVA) ≥ 20/40. The length of ASK treatment was 15.3 ± 20.7 months. The follow-up after discontinuation of scleritis treatment was 27.2 ± 31.8 months. An improvement in visual acuity was recorded in 23 of 36 eyes (64%). At the final visit, 13 of 36 eyes (36%) had CDVA ≥ 20/40. Control of scleral inflammation and pain was achieved in all but 2 eyes (2 enucleations). Cataract developed in 10 of 36 eyes (28%), and 14 of 36 eyes (39%) developed a persistent epithelial defect. Keratoplasty was performed in 21 of 36 eyes (58%), 9 therapeutic/tectonic and 12 for visual rehabilitation. Six eyes had more than 1 keratoplasty. The mild scleritis group had better outcomes in terms of visual improvement and need for keratoplasty. CONCLUSIONS: Acanthamoeba sclerokeratitis is associated with poor clinical outcomes. Management of ASK with anti-inflammatory/immunosuppressive treatment is usually effective in reducing both scleral inflammation and symptoms and possibly reduces the number of enucleations.