Prajna 2010.
| Methods | Parallel group randomised controlled trial (multicentre) 1 eye per patient, only 1 eye enrolled in trial Date conducted: November 2007 to May 2008 |
|
| Participants | Setting: corneal clinics in Madurai and Pondicherry, India Participants: 120 (79 male, 41 female) average age 47 years Inclusion criteria: presence of a corneal ulcer, smear positive for filamentous fungi on potassium hydroxide wet mount, Giemsa or Gram stain, able to understand the purpose of the study and consent Exclusion criteria: overlying epithelial defect, impending perforation, evidence of acanthamoeba, evidence of herpetic keratitis, corneal scar, < 16 years, bilateral ulcers, previous penetrating keratoplasty, pregnancy, outside 200 km radius of hospital, best spectacle‐corrected visual acuity worse than 6/60 in the fellow eye, no light perception in the affected eye, not willing to return for follow‐up visits |
|
| Interventions |
The interventions were applied every hour while awake for 1 week, and then every 2 hours while awake until 3 weeks after enrolment. Further continuation was at the discretion of the physician. Patients were also randomly allocated to repeat scraping of the cornea. |
|
| Outcomes |
Follow‐up: 3 months |
|
| Notes | Funding: That Man May See and the South Asia Research Fund; core grant EY02162 from the National Eye Institute (Department of Ophthalmology at University of California, San Francisco); grant K23EY017897 from the National Eye Institute (Dr Acharya); a Research to Prevent Blindness Career Development Award (Drs Acharya and Lietman); grant U10‐EY015114 from the National Eye Institute (Dr Lietman); That Man May See Foundation at University of California, San Francisco (Dr Porco); Alcon Inc; and Pfizer Inc. Conflict of interest: reported "none". Role of the Sponsors: "Alcon Inc. donated natamycin and Pfizer Inc. donated voriconazole for the study. The sponsors did not have a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript." | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | “This study was a randomized, double‐masked, clinical trial of patients with fungal corneal ulcers.” Page 673 "Patients were block randomized in groups of 4 (using the statistical package R; http: //www.r‐project.org) by T.P." Page 673 |
| Allocation concealment (selection bias) | Low risk | "Double‐masking of treatment assignment was achieved by dispensing the medications in identical opaque bottles and by having the ward nurses wipe any white residue from the patient’s eye prior to study assessment. In addition, patients were no longer receiving treatment at 3 months, the time that the primary outcome of final visual acuity was measured.Only the biostatisticians responsible for the randomization coding and the study pharmacist were unmasked." Page 673 |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | "Double‐masking of treatment assignment was achieved by dispensing the medications in identical opaque bottles and by having the ward nurses wipe any white residue from the patient’s eye prior to study assessment. In addition, patients were no longer receiving treatment at 3 months, the time that the primary outcome of final visual acuity was measured.Only the biostatisticians responsible for the randomization coding and the study pharmacist were unmasked." Page 673 |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | "Double‐masking of treatment assignment was achieved by dispensing the medications in identical opaque bottles and by having the ward nurses wipe any white residue from the patient’s eye prior to study assessment. In addition, patients were no longer receiving treatment at 3 months, the time that the primary outcome of final visual acuity was measured.Only the biostatisticians responsible for the randomization coding and the study pharmacist were unmasked." Page 673 |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | "Efficacy endpoints were analyzed on an intent‐to‐treat basis for all randomized patients enrolled in the study. The primary analysis included the actual 3‐month data when available and last observation carried forward for missing values." Page 674 "Sensitivity analyses were also performed in which we separately (1) assigned surgical patients the value 1.7 instead of 1.9, (2) assigned patients with perforation (but no surgery) the value 1.7 or 1.9 (instead of using last observation carried forward), (3) analyzed only patients with complete follow‐up, or (4) used multiple imputation (recursive random partitioning‐based hot deck method)" Page 674 11/120 lost to follow‐up but evenly distributed across study groups 2/2/4/3 |
| Selective reporting (reporting bias) | Low risk | "The primary efficacy endpoint was BSCVA at 3 months in the study eye, using a linear regression model with 3‐month logMAR BSCVA as the outcome variable and treatment arm (voriconazole vs natamycin) and enrollment logMAR BSCVA and scraping (yes or no) as covariates." Page 674 "Other prespecified endpoints included BSCVA at 3 weeks, adjusting for enrollment BSCVA, and infiltrate/scar size at 3 weeks and 3 months, adjusting for enrollment infiltrate/scar size." Page 674 |