Abstract
HRT3 in vivo confocal microscopy (IVCM) images may indicate clinical outcome, but few studies have analysed this in fungal keratitis (FK). Adults with FK (diameter ≥3 mm) presenting to Aravind Eye Hospital, India from 2012-3 were enrolled prospectively. IVCM was performed at baseline, days 7, 14 and 21 post-enrolment (+/− 3 days where possible). Specific morphologies were identified in IVCM images by a grader masked to microbiology and clinical outcome (defined as good: healed/improving, or poor: enlarged ulcer, perforation or transplant/glue). Associations with final visit outcome assessed using logistic regression. 143 FK participants were enrolled; 87 had good outcome, 56 had poor outcome. Poor outcomes were associated with stellate interconnected cellular processes with no visible nuclei (OR 2.28, 95% CI: 1.03–5.06, p = 0.043) in baseline IVCM images, and fungal filaments (OR 6.48, 95% CI:2.50–16.78, p < 0.001) or honeycomb distribution of inflammatory cells (OR 5.24, 95% CI: 1.44–19.06, p = 0.012) in final visit images. Fungal filaments (OR 3.61, 95% CI:1.64–7.95, p = 0.001), stromal dendritiform cells (OR 2.88, 95% CI:1.17–7.11, p = 0.022), or stellate cellular processes with no visible nuclei (OR 2.09, 95% CI:1.14–3.82, p = 0.017) were associated with poor outcome if not in baseline but present in final visit images. IVCM can reveal morphological changes associated with clinical outcome.
Highlights
After initiation of antimicrobial therapy for microbial keratitis (MK), it may be difficult to assess therapeutic response of some ulcers based upon clinical appearances alone[1]
One-hundred and eighty-two participants with fungal keratitis (FK) were initially enrolled into the study (FK diagnosed as follows: 143 culture-positive, 30 culture-negative/light microscopy positive, and 9 microbiologically-negative/In vivo confocal microscopy (IVCM)-positive for fungi.) 39 patients were excluded from the study due to the following reasons: 7 lost to follow-up after the first visit; inability to perform IVCM at the final visit in 32
After being seen in the cornea clinic, the 143 final study participants were commenced on the following intensive antifungal eyedrops: 5% natamycin alone in 93, 5% natamycin and 1% voriconazole in 46, topical 1% itraconazole eyedrops in one, initial antibiotic in one until fungal culture results noted at first follow-up visit natamycin started; fortified cefazolin, levofloxacin and polymyxin B ointment in one patient whose ulcer had resolved by the time fungal results were available
Summary
After initiation of antimicrobial therapy for microbial keratitis (MK), it may be difficult to assess therapeutic response of some ulcers based upon clinical appearances alone[1]. Shi et al used the confoscan IVCM to monitor 121 FK patients during antifungal therapy, and observed that fungal hyphae disappeared over time in parallel with reduction in the inflammatory cell infiltrate, no quantitative data were presented on the association of specific IVCM cellular changes with clinical outcome[5]. In this study we quantitatively assessed serial HRT3 IVCM images from a prospective cohort of severe bacterial and fungal keratitis patients in South India for morphological features that were associated with healing or worsening clinical outcome. We chose to focus on moderate-to-severe keratitis in this study since these ulcers often present with an atypical clinical appearance and may be difficult to manage during their clinical course[7], we felt these ulcers would benefit the most from investigation of the cellular response with the use of IVCM
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