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.

Development and Validation of a Digital (Peek) Near Visual Acuity Test for Clinical Practice, Community-Based Survey, and Research.

Purpose: Unaddressed near vision impairment (NVI) affects more than 500 million people. Testing near vision is necessary to identify those in need of services. To make such testing readily accessible, we have developed and validated a new smartphone-based near visual acuity (NVA) test: Peek Near Vision (PeekNV). Methods: Two forms of the PeekNV test were developed: (1) quantitative measurement of NVA, and (2) binary screening test for presence or absence of NVI. The validity study was carried out with 483 participants in Sagarmatha Choudhary Eye Hospital, Lahan, Nepal, using a conventional Tumbling "E" Near Point Vision Chart as the reference standard. Bland-Altman limits of agreement (LoA) were used to evaluate test agreement and test-retest repeatability. NVI screening was assessed using Cohen's kappa coefficient, sensitivity, and specificity. Results: The mean difference between PeekNV and chart NVA results was 0.008 logMAR units (95% confidence interval [CI], -0.005 to 0.021) in right eye data, and the 95% LoA between PeekNV and chart testing were within 0.235 and -0.218 logMAR. As a NVI screening tool, the overall agreement between tests was 92.9% (κ = 0.85). The positive predictive value of PeekNV was 93.2% (95% CI, 89.6% to 96.9%), and the negative predictive value 92.7% (95% CI, 88.9% to 96.4%). PeekNV had a faster NVI screening time (11.6 seconds; 95% CI, 10.5 to 12.6) than the chart (14.9 seconds; 95% CI, 13.5 to 16.2; P < 0.001). Conclusions: The PeekNV smartphone-based test produces rapid NVA test results, comparable to those of an accepted NV test. Translational Relevance: PeekNV is a validated, reliable option for NV testing for use with smartphones or digital devices.

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.

Surveillance Surveys for Reemergent Trachoma in Formerly Endemic Districts in Nepal From 2 to 10 Years After Mass Drug Administration Cessation.

Importance: To verify districts for elimination of blinding trachoma, the World Health Organization requires a population-based surveillance survey for follicular trachoma (TF) and trachomatous trichiasis (TT) 2 years after mass drug administration (MDA) activities have ceased. However, it is unknown if 2 years provides enough time to discover reemergence. Objective: To determine the prevalence of trachoma from surveys among 4 districts in Nepal (Dailekh, Dang, Surkhet, and Kanchanpur) that had surveillance intervals of 2, 4, 8, and 10 years, respectively, after cessation of MDA. Design, Setting, and Participants: Cross-sectional surveys were carried out in 2015 and 2016. Data analyses were done from March to September 2016. Among 20 clusters randomly selected from each district, 15 were randomly selected for infection and antibody testing: TF and TT were assessed, conjunctival swabs were tested for chlamydial infection, and blood spots were collected on filter paper to test for antibodies to Chlamydia trachomatis pgp3 using a multiplex bead assay. The study setting was 4 districts previously endemic for trachoma in Nepal. Participants were randomly selected and included 50 children aged 1 to 9 years and 100 adolescents and adults 15 years and older from each of the 20 clusters; this investigation reports on the children. Main Outcomes and Measures: Length of time since the last round of MDA and the prevalence of TF among children aged 1 to 9 years and the prevalence of TT among adolescents and adults 15 years and older. Results: Of 3024 children surveyed in the clusters, 48.0% (n = 1452) were female. The mean (SD) age of the children was 5.4 (2.6) years. Eleven cases of TF were found, with a TF prevalence less than 1% in all 4 districts. Three cases of infection were found. Seropositivity for pgp3 antibody varied from 1.4% (95% CI, 0.7-2.6) in the district with a 10-year surveillance interval to 2.5% (95% CI, 1.3-4.5) in the district with a 4-year surveillance interval. Seropositivity increased slightly with age in only one district. The TT prevalence was less than 1 case per 1000 among the total population in all 4 districts after accounting for cases known to the health system and cases with no scarred conjunctiva. Conclusions and Relevance: This study found no evidence of reemergence of trachoma up to 10 years after cessation of MDA in 4 districts in children in Nepal. The recommendation for a surveillance survey at 2 years, as proposed by the World Health Organization, is supported by these data. Determining if individuals with TT had scarring or are known to the health system was critical for meeting elimination criteria of blinding trachoma.

The World Health Organization Recommendations for Trachoma Surveillance, Experience in Nepal and Added Benefit of Testing for Antibodies to Chlamydia trachomatis pgp3 Protein: NESTS Study.

BACKGROUND: The World Health Organization (WHO) now requires a second surveillance survey for trachoma after an impact assessment has found follicular trachoma (TF) <5% to determine if re-emergence has occurred. Using new WHO guidelines, we undertook surveillance surveys, and determined the prevalence of infection and antibody positivity, in two districts in Nepal. METHODS: 20 clusters were randomly selected within each district, 15 were randomly selected for antibody testing. In each cluster, we randomly selected 50 children ages 1-9 years and 100 adults ≥15 years. TF and trachomatous trichiasis (TT) were evaluated. Conjunctival swabs to test for chlamydial infection using GenXpert platform were obtained, and dried blood spots were collected to test for antibodies to Chlamydia Trachomatis pgp3 using the Luminex platform. FINDINGS: 3 cases of TF were found in the two districts, and one case of infection. Pgp3 antibody positivity was 2·4% (95% confidence interval: 1·4%, 3·7%), and did not increase with age (P = 0.24). No clustering of antibody positivity within communities was found. TT prevalence was <1/1,000 population. INTERPRETATION: The surveillance surveys, as proposed by WHO, showed no evidence for re-emergence of trachoma in two districts of Nepal. The low level and no significant increase by age in seroprevalence of antibodies to C trachomatis pgp3 antigen deserve further investigation as a marker of interruption of transmission.

Fiberoptic-guided Fogarty catheter placement using the same diaphragm of an adapter within the single-lumen tube in children.

IMPLICATIONS: We describe successful placement of a Fogarty catheter for one-lung ventilation through a single-lumen tube using a single diaphragm of an adapter for both the fiberoptic bronchoscope and the Fogarty catheter.