Achieving diagnostic excellence for infectious keratitis: A future roadmap

Ting, Darren Shu Jeng; Chodosh, James; Mehta, Jodhbir S.

doi:10.3389/fmicb.2022.1020198

Cited by 7 publications

(7 citation statements)

References 29 publications

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“…In the future, multiplex PCR or metagenomic next generation sequencing may also further improve the diagnosis of IK, though its routine use in clinic is currently limited by the cost and the availability of technical expertise and resources. [47][48][49][50][51] In conclusion, this study demonstrated good diagnostic performance of all three different microbiological diagnostic modalities, namely direct culture, indirect culture and PCR. We also highlight the potential adjuvant role of 16S rRNA PCR for bacterial keratitis, particularly in culture-negative and less severe IK cases.…”

Section: Discussionsupporting

confidence: 54%

“…In the future, multiplex PCR or metagenomic next generation sequencing may also further improve the diagnosis of IK, though its routine use in clinic is currently limited by the cost and the availability of technical expertise and resources. 44–48 However, it has also been reported that by adopting an intensive antibiotic treatment regime for sight threatening IK, the clinical outcome of culture positive and culture negative cases was not significantly different. 4,49 Our study observed a moderate diagnostic yield in both culture and PCR methods (ranged 40-50%), which might be related to the inclusion of less severe infection cases (∼60% of the cases have an infiltrate size of <3mm).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Microbiological Culture Versus 16S/18S Ribosomal RNA PCR-Sanger Sequencing for Infectious Keratitis: A Three-Arm, Diagnostic Cross-Sectional Study

Hammoudeh,

Suresh,

Ong

et al. 2023

Preprint

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Purpose: To compare the diagnostic performance of microbiological culture and 16S/18S polymerase chain reaction (PCR) for infectious keratitis (IK). Methods: This was a monocentric, three-arm, diagnostic comparative study. We included 81 patients (86 episodes of IK) who presented with presumed bacterial/fungal keratitis to the Queens Medical Centre, Nottingham, UK, between June 2021 and September 2022. All patients underwent simultaneous microbiological culture (either direct culture, indirect culture, or both) and 16S (pan-bacterial)/18S (pan-fungal) ribosomal RNA (rRNA) PCR-Sanger sequencing. Main outcome measures included diagnostic yield, performance, and inter-test agreement. Results: All organisms identified were of bacterial origin. Diagnostic yields were similar among direct culture (52.3%), indirect culture (50.8%), and PCR (43.1%; p=0.13, Cochran Q test). The addition of PCR enabled a positive diagnostic yield in 3 (9.7%) direct culture-negative cases. Based on composite reference standard, direct culture had the highest sensitivity (87.5%; 95% CI, 72.4-95.3%), followed by indirect culture (85.4%; 95% CI, 71.6-93.5%) and PCR (73.5%; 95% CI, 59.0-84.6%), with 100% specificity noted in all three tests. Pairwise comparisons showed substantial agreement among the three tests (percent agreement=81.8-86.2%, Cohen k=0.67-0.72). Clinico-microbiological correlation demonstrated higher culture-PCR concordance in cases with worse presenting visual acuity and greater severity of infection. Conclusion: This study highlights a similar diagnostic performance of direct culture, indirect culture and 16S rRNA PCR for bacterial keratitis, with substantial inter-test concordance. PCR serves as a useful diagnostic adjuvant to culture, particularly in culture-negative cases or those with lesser disease severity (where culture-PCR concordance is lower).

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Section: Discussionsupporting

confidence: 54%

“…In the future, multiplex PCR or metagenomic next generation sequencing may also further improve the diagnosis of IK, though its routine use in clinic is currently limited by the cost and the availability of technical expertise and resources. 44–48 However, it has also been reported that by adopting an intensive antibiotic treatment regime for sight threatening IK, the clinical outcome of culture positive and culture negative cases was not significantly different. 4,49 Our study observed a moderate diagnostic yield in both culture and PCR methods (ranged 40-50%), which might be related to the inclusion of less severe infection cases (∼60% of the cases have an infiltrate size of <3mm).…”

Section: Discussionmentioning

confidence: 99%

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Microbiological Culture Versus 16S/18S Ribosomal RNA PCR-Sanger Sequencing for Infectious Keratitis: A Three-Arm, Diagnostic Cross-Sectional Study

Hammoudeh,

Suresh,

Ong

et al. 2023

Preprint

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“…20 These results show that the culture-exclusive model is particularly useful to clinicians given the limitations of corneal cultures including low culture yield and long turnaround. 21 By categorizing patients as high risk without the need for positive cultures, clinicians can start treatment with more aggressive management and refer patients to a corneal specialist earlier in hopes of preventing the need for emergency surgery.…”

Section: Discussionmentioning

confidence: 99%

Validation of the C-DU(KE) Calculator as a Predictor of Outcomes in Patients Enrolled in Steroids for Corneal Ulcer and Mycotic Ulcer Treatment Trials

Arboleda

Prajna

Lalitha

et al. 2023

Cornea

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The aim of this study was to validate the C-DU(KE) calculator as a predictor of treatment outcomes on a data set derived from patients with culture-positive ulcers.Methods: C-DU(KE) criteria were compiled from a data set consisting of 1063 cases of infectious keratitis from the Steroids for Corneal Ulcer Trial (SCUT) and Mycotic Ulcer Treatment Trial (MUTT) studies. These criteria include corticosteroid use after symptoms, visual acuity, ulcer area, fungal etiology, and elapsed time to organism-sensitive therapy. Univariate analysis was performed followed by multivariable logistic regressions on cultureexclusive and culture-inclusive models to assess for associations between the variables and outcome. The predictive probability of treatment failure, defined as the need for surgical intervention, was calculated for each study participant. Discrimination was assessed using the area under the curve for each model.Results: Overall, 17.9% of SCUT/MUTT participants required surgical intervention. Univariate analysis showed that decreased visual acuity, larger ulcer area, and fungal etiology had a significant association with failed medical management. The other 2 criteria did not. In the culture-exclusive model, 2 of 3 criteria, decreased vision [odds ratio (OR) = 3.13, P , 0.001] and increased ulcer area (OR = 1.03, P , 0.001), affected outcomes. In the culture-inclusive model, 3 of 5 criteria, decreased vision (OR = 4.9, P , 0.001), ulcer area (OR = 1.02, P , 0.001), and fungal etiology (OR = 9.8, P , 0.001), affected results. The area under the curves were 0.784 for the culture-exclusive model and 0.846 for the culture-inclusive model which were comparable to the original study. Conclusions:The C-DU(KE) calculator is generalizable to a study population from large international studies primarily taking place in India. These results support its use as a risk stratification tool assisting ophthalmologists in patient management.

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“…In current clinical practice, IK is usually diagnosed on clinical grounds with support from additional tests, including microbiological investigations (eg, smear microscopy, culture and sensitivity testing, and PCR) and/or corneal imaging (eg, in vivo confocal microscopy (IVCM)) 15–17. However, these approaches have multiple challenges, including the need for clinical expertise and equipment, low microbiological culture yield, long turnaround time, poorly differentiated clinical features and polymicrobial infections 7 15 18–20. Moreover, access to such microbiological and imaging investigations is not available in many ophthalmic units in LMICs, leading to a reliance of empirical treatment.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic performance of deep learning in infectious keratitis: a systematic review and meta-analysis protocol

et al. 2023

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IntroductionInfectious keratitis (IK) represents the fifth-leading cause of blindness worldwide. A delay in diagnosis is often a major factor in progression to irreversible visual impairment and/or blindness from IK. The diagnostic challenge is further compounded by low microbiological culture yield, long turnaround time, poorly differentiated clinical features and polymicrobial infections. In recent years, deep learning (DL), a subfield of artificial intelligence, has rapidly emerged as a promising tool in assisting automated medical diagnosis, clinical triage and decision-making, and improving workflow efficiency in healthcare services. Recent studies have demonstrated the potential of using DL in assisting the diagnosis of IK, though the accuracy remains to be elucidated. This systematic review and meta-analysis aims to critically examine and compare the performance of various DL models with clinical experts and/or microbiological results (the current ‘gold standard’) in diagnosing IK, with an aim to inform practice on the clinical applicability and deployment of DL-assisted diagnostic models.Methods and analysisThis review will consider studies that included application of any DL models to diagnose patients with suspected IK, encompassing bacterial, fungal, protozoal and/or viral origins. We will search various electronic databases, including EMBASE and MEDLINE, and trial registries. There will be no restriction to the language and publication date. Two independent reviewers will assess the titles, abstracts and full-text articles. Extracted data will include details of each primary studies, including title, year of publication, authors, types of DL models used, populations, sample size, decision threshold and diagnostic performance. We will perform meta-analyses for the included primary studies when there are sufficient similarities in outcome reporting.Ethics and disseminationNo ethical approval is required for this systematic review. We plan to disseminate our findings via presentation/publication in a peer-reviewed journal.PROSPERO registration numberCRD42022348596.

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Achieving diagnostic excellence for infectious keratitis: A future roadmap

Cited by 7 publications

References 29 publications

Microbiological Culture Versus 16S/18S Ribosomal RNA PCR-Sanger Sequencing for Infectious Keratitis: A Three-Arm, Diagnostic Cross-Sectional Study

Microbiological Culture Versus 16S/18S Ribosomal RNA PCR-Sanger Sequencing for Infectious Keratitis: A Three-Arm, Diagnostic Cross-Sectional Study

Validation of the C-DU(KE) Calculator as a Predictor of Outcomes in Patients Enrolled in Steroids for Corneal Ulcer and Mycotic Ulcer Treatment Trials

Diagnostic performance of deep learning in infectious keratitis: a systematic review and meta-analysis protocol

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