Improving Outcomes Assessment for Microbial Keratitis

NIH RePORTER · NIH · K23 · $224,134 · view on reporter.nih.gov ↗

Abstract

ABSTRACT The overarching research goal of this K23 Mentored Career Development Award is to improve outcomes assessment for microbial keratitis (MK), or infectious corneal ulceration. MK affects 2 million people per year and causes significant harm to vision and quality of life. Meaningful measurement of MK for clinical and research purposes remains challenging. Traditional clinical assessments of MK severity and response to treatment are subjective and imprecise, making it difficult to compare efficacy of treatments in clinical research studies due to low reproducibility and increased sample size requirements. Prior MK clinical trials have used outcome metrics such as best spectacle-corrected visual acuity which are not disease-specific and may fail to capture key information about corneal damage caused by MK. These measurement limitations reduce the quality and impact of MK research. To date, most large-scale prospective randomized trials in MK have failed to demonstrate clinically meaningful or statistically significant differences in treatment response between groups. Single-center MK studies can also lack applicability to other healthcare settings due to differences in patient characteristics and microbial distributions across populations. Developing more objective, reproducible, clinically relevant, and generalizable outcome metrics and predictors for MK would enhance the clinical relevance and statistical power of future multicenter MK studies. New imaging modalities such as Scheimpflug tomography and anterior segment optical coherence tomography (ASOCT) can provide objective, precise, reproducible, and clinically relevant assessments of corneal structure, but these modalities have not been critically evaluated for MK clinical care or research using prospective studies. This application proposes to conduct a prospective cohort study of MK patients at Johns Hopkins. We will collect detailed clinical and microbiologic data and perform serial multimodal imaging using slit lamp photography, Scheimpflug tomography, and ASOCT over 6 months. Aim 1 will compare the reproducibility and concordance of ultrasound pachymetry, Scheimpflug tomography, and ASOCT for objective quantification of corneal thinning in MK. Aim 2 will evaluate Scheimpflug densitometry as a means of objectively quantifying longitudinal changes in corneal scar density in MK. Aim 3 will assess whether certain early anatomic or clinical features can improve prediction of subsequent visual outcomes in MK and whether these predictors are applicable across different MK populations and infection subgroups, indicating the suitability of these novel outcome metrics for use in collaborative multicenter clinical trials. This proposal will provide the candidate with the advanced training and research experience needed to become an expert in clinical trials methodology and an independently funded clinician-scientist in the field of cornea and external diseases. The candidate proposes a compre...

Key facts

NIH application ID
10818549
Project number
5K23EY032988-03
Recipient
JOHNS HOPKINS UNIVERSITY
Principal Investigator
Nakul Shekhawat
Activity code
K23
Funding institute
NIH
Fiscal year
2024
Award amount
$224,134
Award type
5
Project period
2022-06-01 → 2027-03-31