Stephen Tuft1, Catey Bunce2, Surjo De3, John Thomas4. 1. Moorfields Eye Hospital, 162 City Road, London, EC1V 2PD, UK. Stephen.tuft@nhs.net. 2. The Royal Marsden Hospital, 203 Fulham Rd, Chelsea, London, SW3 6JJ, UK. 3. Department of Clinical Microbiology, University College London Hospitals, 235 Euston Rd, London, NW1 2BU, UK. 4. Micropathology Limited, Venture Centre, Sir William Lyons Road, Coventry, CV4 7EZ, UK.
Abstract
PURPOSE: The true disease status of a population with suspected microbial keratitis (MK) cannot be verified. There is not an accurate (gold) reference standard to confirm infection and inter-test comparisons of sensitivity and specificity therefore lead to bias with questionable estimates of test utility. We present an alternative method to report results. METHODS: We used a decision to treat as the definition for MK. We retrospectively compared the results of corneal culture and polymerase chain reaction (PCR) as these are objective tests available for the three principal groups of pathogens. We then estimated the potential contribution of positive results, either alone or in combination, to support the working diagnosis. RESULTS: We included 2021 (77.4%) eyes with suspected bacterial keratitis, 365 (14.0%) with suspected acanthamoeba keratitis, and 226 (8.6%) with suspected fungal keratitis, all treated between July 2013 and December 2019. In these groups, there were 51.6% positive culture and 6.5% positive PCR results for bacteria, 19.0% and 40.5% for acanthamoeba, and 28.3% and 15.0% for fungi. Between groups the differences in the proportions of positive results from culture and PCR was statistically significant (P < 0.001). The added benefit of PCR to the result of culture in identifying a potential pathogen was 1.4% for bacteria (P = 0.6292), 24.4% for acanthamoeba (P = 0.0001), and 5.8% for fungi (P = 0.3853). CONCLUSIONS: For suspected MK a comparison of the test positivity rate is an easily comprehensible outcome measure of test utility.
PURPOSE: The true disease status of a population with suspected microbial keratitis (MK) cannot be verified. There is not an accurate (gold) reference standard to confirm infection and inter-test comparisons of sensitivity and specificity therefore lead to bias with questionable estimates of test utility. We present an alternative method to report results. METHODS: We used a decision to treat as the definition for MK. We retrospectively compared the results of corneal culture and polymerase chain reaction (PCR) as these are objective tests available for the three principal groups of pathogens. We then estimated the potential contribution of positive results, either alone or in combination, to support the working diagnosis. RESULTS: We included 2021 (77.4%) eyes with suspected bacterial keratitis, 365 (14.0%) with suspected acanthamoeba keratitis, and 226 (8.6%) with suspected fungal keratitis, all treated between July 2013 and December 2019. In these groups, there were 51.6% positive culture and 6.5% positive PCR results for bacteria, 19.0% and 40.5% for acanthamoeba, and 28.3% and 15.0% for fungi. Between groups the differences in the proportions of positive results from culture and PCR was statistically significant (P < 0.001). The added benefit of PCR to the result of culture in identifying a potential pathogen was 1.4% for bacteria (P = 0.6292), 24.4% for acanthamoeba (P = 0.0001), and 5.8% for fungi (P = 0.3853). CONCLUSIONS: For suspected MK a comparison of the test positivity rate is an easily comprehensible outcome measure of test utility.
Authors: Jeena Mascarenhas; Prajna Lalitha; N Venkatesh Prajna; Muthiah Srinivasan; Manoranjan Das; Sean S D'Silva; Catherine E Oldenburg; Durga S Borkar; Elizabeth J Esterberg; Thomas M Lietman; Jeremy D Keenan Journal: Am J Ophthalmol Date: 2013-11-05 Impact factor: 5.258
Authors: Alejandro Lichtinger; Sonia N Yeung; Peter Kim; Maoz D Amiran; Alfonso Iovieno; Uri Elbaz; Judy Y F Ku; Rachel Wolff; David S Rootman; Allan R Slomovic Journal: Ophthalmology Date: 2012-05-23 Impact factor: 12.079
Authors: Lottie Brown; Astrid K Leck; Michael Gichangi; Matthew J Burton; David W Denning Journal: Lancet Infect Dis Date: 2020-10-22 Impact factor: 25.071
Authors: A K Leck; P A Thomas; M Hagan; J Kaliamurthy; E Ackuaku; M John; M J Newman; F S Codjoe; J A Opintan; C M Kalavathy; V Essuman; C A N Jesudasan; G J Johnson Journal: Br J Ophthalmol Date: 2002-11 Impact factor: 4.638
Authors: Daniel Sand; Rosemary She; Ira A Shulman; David S Chen; Mathew Schur; Hugo Y Hsu Journal: Ophthalmology Date: 2015-01-15 Impact factor: 12.079
Authors: Stephen Kaye; Stephen Tuft; Timothy Neal; Derek Tole; John Leeming; Francisco Figueiredo; Malcolm Armstrong; Peter McDonnell; Andrew Tullo; Christopher Parry Journal: Invest Ophthalmol Vis Sci Date: 2009-08-13 Impact factor: 4.799
Authors: Hugo Y Hsu; Benjamin Ernst; Eric J Schmidt; Rohit Parihar; Chelsea Horwood; Sean L Edelstein Journal: Am J Ophthalmol Date: 2018-10-09 Impact factor: 5.258