Improving polymerase chain reaction diagnostic rates for herpes simplex keratitis: results of a pilot study.

Background: Laboratory confirmation is crucial for diagnosis and management of herpes simplex virus (HSV) keratitis. However, the sensitivity of polymerase chain reaction (PCR) in keratitis is low (25%) compared with that of mucocutaneous disease (75%). We developed an educational intervention aimed at improving the diagnostic yield of PCR. Methods: The medical records of keratitis cases seen at the emergency department of a London tertiary ophthalmic referral hospital over two distinct periods, before and after an educational program on swab technique, were reviewed retrospectively. Results: A total of 252 HSV cases were included. Increases in the laboratory-confirmed diagnosis of HSV-1 were observed, in both first presentations (11.1%-57.7%) and recurrent cases (20%-57.6%). The rate of positive HSV-1 PCR in eyes with an epithelial defect increased from 19% pre-intervention to 62% post intervention. Notably, 3% were positive for varicella zoster virus DNA, and there was a single case of Acanthamoeba keratitis. Conclusion: Our results suggest that, with proper swabbing technique, PCR may be more sensitive than previously reported.

Incidence of Acanthamoeba Keratitis in the United Kingdom in 2015: A Prospective National Survey.

PURPOSE: The aims of this study were to quantify the incidence of Acanthamoeba keratitis (AK) in the United Kingdom and investigate risk factors and management parameters. METHODS: This was a prospective population-based study from January to December 2015 through the British Ophthalmic Surveillance Unit. Data were collected on demographics, clinical features, and management. Incidence rates were calculated from estimates of population and contact lens (CL) user numbers. Statistical analysis compared annualized incidences per million and altered risk ratios for AK with the England and Wales 24 months 1997/1998 to 1998/1999 study. RESULTS: The study identified 124 AK cases, an overall incidence of 2.35 per million. CL wearers accounted for 108 of 124 cases (87%), in whom the AK incidence was 26.94 per million. Herpes keratitis was initially misdiagnosed in 25 of 124 cases (20.2%). The highest incidence of AK was among planned replacement soft CL (PRSCL) wearers (50.65 per million), 7-fold greater than for daily disposable CL (DDSCL) users (7.24 per million). There was a significant increase in AK incidence ( P < 0.001) compared with both 1997/1998 [risk ratio 1.92, 95% confidence interval (CI) 1.38-2.66] and 1998/1999 (risk ratio 2.13, 95% CI 1.52-2.98) together with a higher incidence per million CL users of 26.94 versus 21.14 (1997/1998) and 17.53 (1998/1999). CONCLUSIONS: This study provides the first published data on the nationwide incidence of AK in the United Kingdom. The findings confirm an increasing incidence of AK, particularly among contact lens wearers since 1997/1998 to 1998/1999. PRSCLs were identified as a significant risk factor compared with DDSCLs. Misdiagnosis and treatment delays remain an ongoing problem for patients with AK.

Local Ugandan Production of Stable 0.2% Chlorhexidine Eye Drops.

Purpose: The purpose of this study was to develop a protocol to prepare buffered chlorhexidine (CHX) eye drops (0.2% w/v) in the United Kingdom that can be reproduced at a production facility in Uganda. Buffered CHX eye drops can prevent CHX degradation and improve ocular tolerability during the treatment of fungal keratitis. Methods: Buffered CHX eye drops in amber glass containers were prepared using sodium acetate buffer at pH 5.90 to 6.75. Two commercial CHX solutions and CHX in water were used as controls. Eye drops were stored at 40°C (70% humidity, 21 months) in the United Kingdom and at ambient temperature in Uganda (30 months). High-performance liquid chromatography was used to determine CHX stability over time, and pH was monitored. Sterility was achieved using an autoclave (121°C, 15 minutes) and water bath (100°C, 30 minutes). Results: The pH of acetate-buffered CHX eye drops did not change over 21 months at 40°C or at ambient temperature (30 months), whereas the pH of the unbuffered aqueous CHX displayed significant fluctuations, with an increase in acidity. The CHX concentration remained the same in both buffered and unbuffered eye-drop solutions. Eye drops sterilization was successful using an autoclave and a water bath. Conclusions: Stable, sterile, buffered CHX eye drops (pH 6.75) were successfully prepared first in the United Kingdom and then reproducibly in Uganda. This eye drops can be prepared in a hospital or pharmacy setting with limited resources, thus providing a cost-effective treatment for fungal keratitis. Translational Relevance: A protocol has been developed to prepare buffered CHX eye drops in low- and middle-income countries to treat fungal keratitis.

Management of Filamentous Fungal Keratitis: A Pragmatic Approach.

Filamentous fungal infections of the cornea known as filamentous fungal keratitis (FK) are challenging to treat. Topical natamycin 5% is usually first-line treatment following the results of several landmark clinical trials. However, even when treated intensively, infections may progress to corneal perforation. Current topical antifungals are not always effective and are often unavailable. Alternatives topical therapies to natamycin include voriconazole, chlorhexidine, amphotericin B and econazole. Surgical therapy, typically in the form of therapeutic penetrating keratoplasty, may be required for severe cases or following corneal perforation. Alternative treatment strategies such as intrastromal or intracameral injections of antifungals may be used. However, there is often no clear treatment strategy and the evidence to guide therapy is often lacking. This review describes the different treatment options and their evidence and provides a pragmatic approach to the management of fungal keratitis, particularly for clinicians working in tropical, low-resource settings where fungal keratitis is most prevalent.

Diagnosis of Fungal Keratitis in Low-Income Countries: Evaluation of Smear Microscopy, Culture, and In Vivo Confocal Microscopy in Nepal.

Clinically diagnosing fungal keratitis (FK) is challenging; diagnosis can be assisted by investigations including in vivo confocal microscopy (IVCM), smear microscopy, and culture. The aim of this study was to estimate the sensitivity in detecting fungal keratitis (FK) using IVCM, smear microscopy, and culture in a setting with a high prevalence of FK. In this cross-sectional study nested within a prospective cohort study, consecutive microbial keratitis (MK) patients attending a tertiary-referral eye hospital in south-eastern Nepal between June 2019 and November 2020 were recruited. IVCM and corneal scrapes for smear microscopy and culture were performed using a standardised protocol. Smear microscopy was performed using potassium hydroxide (KOH), Gram stain, and calcofluor white. The primary outcomes were sensitivities with 95% confidence intervals [95% CI] for IVCM, smear microscopy and culture, and for each different microscopy stain independently, to detect FK compared to a composite referent. We enrolled 642 patients with MK; 468/642 (72.9%) were filamentous FK, 32/642 (5.0%) were bacterial keratitis and 64/642 (10.0%) were mixed bacterial-filamentous FK, with one yeast infection (0.16%). No organism was identified in 77/642 (12.0%). Smear microscopy had the highest sensitivity (90.7% [87.9-93.1%]), followed by IVCM (89.8% [86.9-92.3%]) and culture (75.7% [71.8-79.3%]). Of the three smear microscopy stains, KOH had the highest sensitivity (85.3% [81.9-88.4%]), followed by Gram stain (83.2% [79.7-86.4%]) and calcofluor white (79.1% [75.4-82.5%]). Smear microscopy and IVCM were the most sensitive tools for identifying FK in our cohort. In low-resource settings we recommend clinicians perform corneal scrapes for microscopy using KOH and Gram staining. Culture remains an important tool to diagnose bacterial infection, identify causative fungi and enable antimicrobial susceptibility testing.

Delay in accessing definitive care for patients with microbial keratitis in Nepal.

Background: The aim of this study was to describe the health-seeking journey for patients with microbial keratitis (MK) in Nepal and identify factors associated with delay. Methods: Prospective cohort study where MK patients attending a large, tertiary-referral eye hospital in south-eastern Nepal between June 2019 and November 2020 were recruited. We collected demographic details, clinical history, and examination findings. Care-seeking journey details were captured including places attended, number of journeys, time from symptom onset, and costs. We compared "direct" with "indirect" presenters, analyzing for predictors of delay. Results: We enrolled 643 patients with MK. The majority (96%) self-referred. "Direct" attenders accounted for only 23.6% (152/643) of patients, the majority of "indirect" patients initially presented to a pharmacy (255/491). Over half (328/643) of all cases presented after at least 7 days. The total cost of care increased with increasing numbers of facilities visited (p < 0.001). Those living furthest away were least likely to present directly (p < 0.001). Factors independently associated with delayed presentation included distance >50 km from the eye hospital [aOR 5.760 (95% CI 1.829-18.14, p = 0.003)], previous antifungal use [aOR 4.706 (95% CI 3.139-5.360)], and two or more previous journeys [aOR 1.442 (95% CI 1.111-3.255)]. Conclusions: Most patients visited at least one facility prior to our institution, with time to presentation and costs increasing with the number of prior journeys. Distance to the eye hospital is a significant barrier to prompt, direct presentation. Based on these findings, improving access to eye care services, strengthening referral networks and encouraging early appropriate treatment are recommended to reduce delay, ultimately improving clinical outcomes.

Assessing Virginia cooling centers as a heat mitigation strategy.

In the United States, heat kills more people on average than any other weather-related hazard, thus the mitigation of heat-related impacts remains a significant issue within emergency management and public health communities. Research indicates the use of community cooling centers as an effective way to reduce vulnerability and adverse heat impacts. Using the Commonwealth of Virginia as a study location, this research evaluates the placement of cooling centers and assesses emergency managers' understanding of heat-related issues. Surveying local emergency managers and aggregating media reports, a total of 256 cooling centers were identified across 39 localities. Vulnerable populations differed in their proximity to the identified cooling centers. While over 65 percent of Virginians live within a 15-minute drive of a cooling center, this favors wealthier community members; less than 7 percent of Virginia's population below poverty lives within this same 15-minute driveshed. Spatial variability exists with many communities not opening any cooling centers. Within city and county hazard plans, the inclusion of comprehensive heat-related hazard information remains low. The research suggests further cooperation across government and nongovernment agencies is needed to improve the resilience to heat-health concerns across Virginia.

Microbial Keratitis in Nepal: Predicting the Microbial Aetiology from Clinical Features.

Fungal corneal infection (keratitis) is a common clinical problem in South Asia. However, it is often challenging to distinguish this from other aetiologies, such as bacteria or acanthamoeba. In this prospective study, we investigated clinical and epidemiological features that can predict the microbial aetiology of microbial keratitis in Nepal. We recruited patients presenting with keratitis to a tertiary eye hospital in lowland eastern Nepal between June 2019 and November 2020. A structured assessment, including demographics, history, and clinical signs, was carried out. The aetiology was investigated with in vivo confocal microscopy and corneal scrape for microscopy and culture. A predictor score was developed using odds ratios calculated to predict aetiology from features. A fungal cause was identified in 482/642 (75.1%) of cases, which increased to 532/642 (82.9%) when including mixed infections. Unusually, dematiaceous fungi accounted for half of the culture-positive cases (50.6%). Serrated infiltrate margins, patent nasolacrimal duct, raised corneal slough, and organic trauma were independently associated with fungal keratitis (p < 0.01). These four features were combined in a predictor score. The probability of fungal keratitis was 30.1% if one feature was present, increasing to 96.3% if all four were present. Whilst microbiological diagnosis is the "gold standard" to determine the aetiology of an infection, certain clinical signs can help direct the clinician to find a presumptive infectious cause, allowing appropriate treatment to be started without delay. Additionally, this study identified dematiaceous fungi, specifically Curvularia spp., as the main causative agent for fungal keratitis in this region. This novel finding warrants further research to understand potential implications and any trends over time.

Comparison of culture, confocal microscopy and PCR in routine hospital use for microbial keratitis diagnosis.

AIMS: To evaluate the sensitivity and specificity of polymerase chain reaction (PCR), in vivo confocal microscopy (IVCM) and culture for microbial keratitis (MK) diagnosis. METHODS: Retrospective review of PCR, IVCM and culture results for MK diagnosis at Moorfields Eye Hospital between August 2013 and December 2014. RESULTS: PCR results were available for 259 MK patients with concurrent culture for 203/259 and IVCM for 149/259. Sensitivities and specificities with 95% confidence intervals [95% CI] were calculated for Acanthamoeba keratitis (AK) and fungal keratitis (FK), by comparison with culture, for both IVCM and PCR. For AK, FK and bacterial keratitis (BK) sensitivities were calculated, for each diagnostic method, by comparison with a composite reference standard (a positive result for one or more of culture, PCR or IVCM having a specificity of 100% by definition). For the latter, sensitivities with [95% CI] were: for AK, IVCM 77.1% [62.7-88.0%], PCR 63.3% [48.3-76.6%], culture 35.6 [21.9-51.2]; for FK, IVCM 81.8% [48.2-97.7%], PCR 30.8% [9.09-61.4%], culture 41.7% [15.2-72.3%]; for BK, PCR 25.0% [14.7-37.9%], culture 95.6% [87.6-99.1%]. CONCLUSION: IVCM was the most sensitive technique for AK and FK diagnosis but culture remains our gold standard for BK. These findings reflect results to be expected from service providers to UK ophthalmology units and demonstrates the need at our centre for ongoing diagnostic result audit leading to the potential to improve PCR diagnosis. Both FK and AK are now common in the UK; ophthalmology units need to have all these techniques available to optimise their MK management.

The watery eye quality of life (WEQOL) questionnaire: a patient-reported outcome measure for surgically amenable epiphora.

OBJECTIVE OR PURPOSE: To develop and test a patient-reported outcome measure for assessing health-related quality of life (HRQOL) in surgically amenable epiphora. DESIGN: Questionnaire development and validation study. PARTICIPANTS: 201 patients with a cause of epiphora amenable to surgical intervention, recruited across three independent centres. METHODS, INTERVENTION OR TESTING: The watery eye quality of life (WEQOL) questionnaire was developed and refined according to defined psychometric standards. Both surgical and non-surgical participants completed WEQOL at baseline and follow-up (>3 months), along with the Lacrimal Symptom Questionnaire (Lac-Q), RAND Short Form Health Survey (SF-36) and Glasgow Benefit Inventory (GBI). Convergent validity of WEQOL was evaluated according to correlation (R > 0.40) with each of these additional tests. Responsiveness of WEQOL to intervention was evaluated according to patient-reported success. Test-retest reliability was assessed by the Bland-Altman method and intraclass correlation (ICC) in a subset of 64 participants at baseline. MAIN OUTCOME MEASURES: WEQOL construct validity, responsiveness and test-retest reliability. RESULTS: WEQOL was moderately correlated (R > 0.4) with the Lac-Q and several subscales of the SF-36 (physical role limitation, social, emotional role limitation and emotional well-being). A stronger correlation was found between the change in WEQOL at follow-up and GBI (R = 0.61). An appropriate graded response was found with a significant change in WEQOL score being observed in patients reporting successful (-28%, p < 0.0001) and partially successful surgery (-6%, p = 0.04), but not in those reporting unsuccessful surgery (+2%, p = 0.9). High test-retest reliability was observed (ICC = 0.93). CONCLUSIONS: The WEQOL questionnaire has been developed systematically according to modern psychometric standards and has been designed to evaluate the quality of life in patients with epiphora that is of a surgically amenable cause. In this study, it has demonstrated appropriate test-retest reliability, responsiveness and construct validity.

Topical Chlorhexidine 0.2% versus Topical Natamycin 5% for the Treatment of Fungal Keratitis in Nepal: A Randomized Controlled Noninferiority Trial.

PURPOSE: To investigate if topical chlorhexidine 0.2%, which is low cost and easy to formulate, is noninferior to topical natamycin 5% for the treatment of filamentous fungal keratitis. DESIGN: Randomized controlled, single-masked, noninferiority clinical trial. PARTICIPANTS: Adults attending a tertiary-level ophthalmic hospital in Nepal with filamentous fungal infection confirmed on smear or confocal microscopy. METHODS: Participants were randomly allocated to receive topical chlorhexidine 0.2% or topical natamycin 5%. Primary analysis (intention-to-treat) was by linear regression, using baseline logarithm of the minimum angle of resolution (logMAR) best spectacle-corrected visual acuity (BSCVA) and treatment arm as prespecified covariates. Mixed fungal-bacterial infections were excluded from the primary analysis but included in secondary analyses and secondary safety-related outcomes. The noninferiority margin was 0.15 logMAR. This trial was registered with ISRCTN, number ISRCTN14332621. MAIN OUTCOME MEASURES: The primary outcome measure was BSCVA at 3 months. Secondary outcome measures included perforation or therapeutic penetrating keratoplasty by 90 days. RESULTS: Between June 3, 2019, and November 9, 2020, 354 eligible participants were enrolled and randomly assigned: 178 to chlorhexidine and 176 to natamycin. Primary outcome data were available for 153 and 151 of the chlorhexidine and natamycin groups, respectively. Of these, mixed bacterial-fungal infections were found in 20 cases (12/153 chlorhexidine, 8/151 natamycin) and excluded from the primary analysis. Therefore, 284 patients were assessed for the primary outcome (141 chlorhexidine, 143 natamycin). We did not find evidence to suggest chlorhexidine was noninferior to natamycin and in fact found strong evidence to suggest that natamycin-treated participants had significantly better 3-month BSCVA than chlorhexidine-treated participants, after adjusting for baseline BSCVA (regression coefficient, -0.30; 95% confidence interval [CI], -0.42 to -0.18; P < 0.001). There were more perforations and emergency corneal grafts in the chlorhexidine arm (24/175, 13.7%) than in the natamycin arm (10/173, 5.8%; P = 0.018, mixed infections included), whereas natamycin-treated cases were less likely to perforate or require an emergency corneal graft, after adjusting for baseline ulcer depth (odds ratio, 0.34; 95% CI, 0.15-0.79; P = 0.013). CONCLUSIONS: Treatment with natamycin is associated with significantly better visual acuity, with fewer adverse events, compared with treatment with chlorhexidine. Natamycin remains the preferred first-line monotherapy treatment for filamentous fungal keratitis.

Chlorhexidine gluconate 0.2% as a treatment for recalcitrant fungal keratitis in Uganda: a pilot study.

OBJECTIVE: Fungal keratitis is a major ophthalmic public health problem, particularly in low-income and middle-income countries. The options for treating fungal keratitis are limited. Our study aimed to describe the outcomes of using chlorhexidine 0.2% eye-drops as additional treatment in the management of patients with recalcitrant fungal keratitis. METHODS: This study was nested within a large cohort study of people presenting with microbial keratitis in Uganda. We enrolled patients with recalcitrant fungal keratitis not improving with topical natamycin 5% and commenced chlorhexidine 0.2%. Follow-up was scheduled for 3 months and 1 year. The main outcome measures were healing, visual acuity and scar size at final follow-up. RESULTS: Thirteen patients were followed in this substudy. The patients were aged 27-73 years (median 43 years). Filamentous fungi were identified by microscopy of corneal scrape samples in all cases. Isolated organisms included Aspergillus spp, Fusarium spp, Candida spp, Bipolaris spp and Acremoninum spp. At the final follow-up, nine patients (75%) had healed; three had vision of better than 6/18. Three patients lost their eyes due to infection. In the remaining nine cases, corneal scarring was variable ranging from 4.6 to 9.4 mm (median 6.6 mm, IQR 5.9-8.0 mm); of these five had dense scars, three had moderate scars and one had a mild scar. None of the patients demonstrated signs of chlorhexidine toxicity during the follow-up. CONCLUSION: Chlorhexidine 0.2% was found to be a useful sequential adjunctive topical antifungal in cases of fungal keratitis not responding to natamycin 5%, which warrants further evaluation.

Knowledge and awareness-based survey of COVID-19 within the eye care profession in Nepal: Misinformation is hiding the truth.

BACKGROUND: Nepal was under a severe lockdown for several months in 2020 due to the COVID-19 pandemic. There were concerns regarding misinformation circulating on social media. This study aimed to analyse the knowledge and awareness of COVID-19 amongst eye care professionals in Nepal during the first wave of the pandemic. METHODOLOGY: We invited 600 participants from 12 ophthalmic centres across Nepal to complete a qualitative, anonymous online survey. Altogether, 25 questions (both open and closed-ended) were used. An overall performance score was calculated from the average of the 12 "Knowledge" questions for all the participants. RESULTS: Of the 600 eye care professionals invited, 310 (51%) participated in the survey. The symptoms of COVID-19 were known to 94%, whilst only 49% of the participants were aware how the disease was transmitted, with 54% aware that anyone can be infected with SARS-CoV-2. Almost 98% of participants recognized the World Health Organization's (WHO) awareness message, but surprisingly, 41% of participants felt that consumption of hot drinks helps to destroy the virus, in contradiction to WHO information. Importantly, 95% of the participants were aware of personal protective equipment (PPE) and what the acronym stands for. Social distancing was felt to be key to limiting the disease spread; whilst 41% disagreed that PPE should be mandatory for eye care practitioners. The mean overall "Knowledge" performance score was 69.65% (SD ± 22.81). CONCLUSION: There is still considerable scope to improve the knowledge of COVID-19 amongst ophthalmic professionals in Nepal. Opinion is also split on measures to prevent transmission, with misinformation potentially fuelling confusion. It is recommended to follow WHO and national guidelines, whilst seeking published scientific evidence behind any unofficial statements, to accurately inform one's clinical practice.

Mycotic Keratitis-A Global Threat from the Filamentous Fungi.

Mycotic or fungal keratitis (FK) is a sight-threatening disease, caused by infection of the cornea by filamentous fungi or yeasts. In tropical, low and middle-income countries, it accounts for the majority of cases of microbial keratitis (MK). Filamentous fungi, in particular Fusarium spp., the aspergilli and dematiaceous fungi, are responsible for the greatest burden of disease. The predominant risk factor for filamentous fungal keratitis is trauma, typically with organic, plant-based material. In developed countries, contact lens wear and related products are frequently implicated as risk factors, and have been linked to global outbreaks of Fusarium keratitis in the recent past. In 2020, the incidence of FK was estimated to be over 1 million cases per year, and there is significant geographical variation; accounting for less than 1% of cases of MK in some European countries to over 80% in parts of south and south-east Asia. The proportion of MK cases is inversely correlated to distance from the equator and there is emerging evidence that the incidence of FK may be increasing. Diagnosing FK is challenging; accurate diagnosis relies on reliable microscopy and culture, aided by adjunctive tools such as in vivo confocal microscopy or PCR. Unfortunately, these facilities are infrequently available in areas most in need. Current topical antifungals are not very effective; infections can progress despite prompt treatment. Antifungal drops are often unavailable. When available, natamycin is usually first-line treatment. However, infections may progress to perforation in ~25% of cases. Future work needs to be directed at addressing these challenges and unmet needs. This review discusses the epidemiology, clinical features, diagnosis, management and aetiology of FK.

Perception and Challenges of Preventive Measures of COVID-19 Among Nepalese Frontline Health Professionals: An Unexplored Realism.

Background: A new coronavirus causes COVID-19, a developing respiratory illness. Unfortunately, there is little information assessing healthcare workers' understanding of technology and preventative strategies during the Nepalese epidemic. Researchers from other subspecialties uncovered some mythical thoughts. As a result, we decided to put it to the test with healthcare personnel on the front lines. The research also looked at the problems experienced by frontline health care personnel (HCP) because of the COVID-19 strategic shift in work policy. Methods: Nepalese healthcare workers participated in web-based cross-sectional research. A pre-tested, structured questionnaire utilizing a Google form was used to get self-informed, digitally typed consent, and examine critical perspectives and problems with current technology and COVID-19 prevention efforts. Results: In total, 243 participants with mean age of 29.66 ± 7.61 years agreed to participate and were doctors (n = 27), health assistants (n = 2), medical intern doctors (n = 1), paramedical (n = 139), pharmacy (n = 1), and paramedical interns (n = 73) in this study. The calculated mean percentage score of knowledge on instruments and tools was 73.64 (SD ± 10.43) %, and perception on COVID-19 transmission and control was 70.06 (SD ± 18.30) %. At various levels, frontline health workers faced significant challenges, including the adoption of digital health technology. Conclusion: Frontline HCPs are anticipated to have updated knowledge from what the study has outlined. It is recommended to follow national guidelines. Policies should be put in place so that every frontline worker can demonstrate high standards in prevention, control, and equipment use that do not create misinformation among HCPs. Throughout, support for digital health materials and disease control methods for HCPs is essential.

Topical chlorhexidine 0.2% versus topical natamycin 5% for fungal keratitis in Nepal: rationale and design of a randomised controlled non-inferiority trial.

INTRODUCTION: Fungal infections of the cornea, fungal keratitis (FK), are challenging to treat. Current topical antifungals are not always effective and are often unavailable, particularly in low-income and middle-income countries where most cases occur. Topical natamycin 5% is usually first-line treatment, however, even when treated intensively, infections may progress to perforation of the eye in around a quarter of cases. Alternative antifungal medications are needed to treat this blinding disease.Chlorhexidine is an antiseptic agent with antibacterial and antifungal properties. Previous pilot studies suggest that topical chlorhexidine 0.2% compares favourably with topical natamycin. Full-scale randomised controlled trials (RCTs) of topical chlorhexidine 0.2% are warranted to answer this question definitively. METHODS AND ANALYSIS: We will test the hypothesis that topical chlorhexidine 0.2% is non-inferior to topical natamycin 5% in a two-arm, single-masked RCT. Participants are adults with FK presenting to a tertiary ophthalmic hospital in Nepal. Baseline assessment includes history, examination, photography, in vivo confocal microscopy and cornea scrapes for microbiology. Participants will be randomised to alternative topical antifungal treatments (topical chlorhexidine 0.2% and topical natamycin 5%; 1:1 ratio, 2-6 random block size). Patients are reviewed at day 2, day 7 (with reculture), day 14, day 21, month 2 and month 3. The primary outcome is the best spectacle corrected visual acuity (BSCVA) at 3 months. Primary analysis (intention to treat) will be by linear regression, with treatment arm and baseline BSCVA prespecified covariates. Secondary outcomes include epithelial healing time, scar/infiltrate size, ulcer depth, hypopyon size, perforation and/or therapeutic penetrating keratoplasty (corneal transplant), positive reculture rate (day 7) and quality of life (EuroQol-5 dimensions, WHO/PBD-VF20, WHOQOL-BREF). ETHICS AND DISSEMINATION: The Nepal Health Research Council, the Nepal Department of Drug Administration and the London School of Hygiene and Tropical Medicine ethics committee have approved the trial. The results will be presented at local and international meetings and submitted to peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: ISRCTN14332621; pre-results.

Assault-related severe ocular chemical injury at a London ophthalmic referral hospital: a 3-year retrospective observational study.

OBJECTIVES: To understand the incidence, causes, management and outcomes of intentional (assault) and unintentional severe ocular chemical injuries (SOCI) at an urban tertiary referral centre in the UK. DESIGN: Retrospective observational study. SETTING: A London tertiary referral ophthalmic centre, Moorfields Eye Hospital. PARTICIPANTS: All cases of SOCI presenting between 1 September 2011 and 31 August 2014 were identified. The definition of SOCI was grade 3 or 4 on the Hughes-Roper-Hall classification system. We identified 25 cases (6 in 2011-2012, 8 in 2012-2013, 11 in 2013-2014). Median age was 31.1 years. 23 cases (92%) were male. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of cases of SOCI caused by assault, per year. Secondary outcome measures included the number of cases of SOCI, injury characteristics and mechanism, initial and long-term management, visual outcome and the need for surgical intervention. RESULTS: Between 2011 and 2012, 3/6 cases were due to assault (50%); between 2012 and 2013, 7/8 were due to assault (87.5%); and between 2013 and 2014, 6/11 were due to assault (54.4%). Assault was responsible for 16/25 (64%) cases overall, while 8/25 (32%) cases were work related. The causative agent was known to be alkali in 16/25 (64%), while 10/25 (40%) did not complete the follow-up. The mean number of clock hours of limbal ischaemia was 5.24 (SD 2.97). 17/25 (68%) were Hughes-Roper-Hall grade 3. Surgical intervention occurred in 1/25. The final best-corrected visual acuity was 6/12 or worse in 11/25 (44%) and was counting fingers or worse in 4/25 (16%). CONCLUSIONS: Previous studies found that SOCI had a low incidence and that work-related injuries were the most common cause. Our study demonstrates an increasing incidence of SOCI, which may be accounted for by a rise in assault using corrosive substances. A high number of patients did not attend regularly for follow-up and visual outcomes from these injuries are poor.

In vivo confocal microscopy and trachomatous conjunctival scarring: Predictors for clinical progression.

IMPORTANCE: In vivo confocal microscopy (IVCM) provides high-resolution images of the ocular surface and has been validated in trachomatous conjunctival scarring. BACKGROUND: This study used IVCM to identify parameters associated with clinical scarring progression. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 800 participants in Northern Tanzania with trachomatous scarring. METHODS: Participants underwent clinical examination, photography and IVCM at baseline and 24-months. Clinical progression of scarring was defined by comparing baseline and 24-month photographs. Masked grading of IVCM images was used to identify scarring at both time points. Multivariable logistic regression was used to assess factors associated with clinical progression. MAIN OUTCOME MEASURES: Risk factors associated with clinical scarring progression. RESULTS: Clinical and IVCM assessment of 800 participants were performed at baseline, with 617 (77.1%) seen at 24-months. Of these, 438 of 617 (71.0%) had gradable IVCM images at both time points and 342 of 438 (78.1%) of these could be graded as showing definite clinical progression or no progression on image comparison. Clinical progression was found to occur in 79 of 342 (23.1%). After adjusting for age and sex, clinical scarring progression was strongly associated with a high IVCM connective tissue organization score at both baseline (odds ratio [OR] = 1.84 for each increase in scarring category; P = .002) and 24-months (OR = 1.60; P = .02). Dendritiform cells present at 24-months were strongly associated with clinical scarring progression after adjustment (OR = 2.62; P = .03). CONCLUSIONS AND RELEVANCE: Quantitative IVCM parameters, including connective tissue organization score and the presence of dendritiform cells, are associated with disease progression and may be useful markers in trachoma and other conjunctival fibrotic diseases.