# Discovery of the Biomarker Signature for Neuropathic Corneal Pain

> **NIH NIH R33** · TUFTS MEDICAL CENTER · 2022 · $750,704

## Abstract

PROJECT ABSTRACT
Neuropathic corneal pain (NCP) is an ocular type of neuropathic pain. It causes patients to have severe
discomfort and a severely compromised quality of life (QoL). The lack of signs observed by standard
examination has resulted in misdiagnosis as dry eye disease (DED) resulting in an inefficient use of
healthcare funds. The identification of a diagnostic biomarker for NCP and development of a detection
method would allow adequate and timely treatment, improve patients’ QoL, and decrease the health care
system’s financial burden. An optical biopsy can be performed using laser in vivo confocal microscopy
(IVCM), which allows for visualization of subbasal corneal nerves at a quasi-histological level. Preliminary
data has shown that IVCM identified microneuromas (a bulb at the end of a severed nerve caused by build-up
of molecular constituents) are present in NCP, but not DED, patients. We propose to validate microneuromas
as a novel biomarker for NCP. In Aim 1 we will use our database of over 2,000 DED/NCP subjects and over
500,000 IVCM images to confirm that the presence of microneuromas is an appropriate biomarker for NCP by
comparing the sensitivity and specificity of identification of NCP patients via microneuromas to other IVCM
parameters. Three observers will each grade images twice for this confirmed biomarker to assess inter- and
intra-observer precision, and descriptive statistics of the IVCM datasets will allow for determination of the
minimum number of images necessary for high precision of microneuroma detection. Aim 2 will provide
biological validation of microneuromas. Both the intensity of ocular pain and the compromise to QoL caused
by ocular pain as assessed by the Ocular Pain Assessment Survey (OPAS) will be compared between those
with microneuromas and those without. Further, the change in ocular pain/discomfort in response to
instillation of hyperosmolar saline into the eyes will be compared between those with microneuromas and
those without. In Aim 3 we will develop a validated artificial intelligence (AI) program for automated
identification of microneuromas to allow rapid and wide-scale adoption by clinicians. Accuracy of the program
will be determined by evaluating the agreement of the AI program’s assessment of IVCM images with the
assessment of 2 observers. A similar assessment of accuracy will be assessed using images obtained from
an independent site so that inter-site precision can be evaluated. The AI program will also be assessed for its
specificity and sensitivity in NCP identification. Aim 4 will establish the clinical utility of microneuromas
observed by IVCM as a biomarker for NCP in a prospective, multi-center study. The biomarker’s precision,
reference intervals, and harmonization of performance between sites as well as the sensitivity and specificity
of NCP diagnosis will be determined using this prospective cohort. Next, the microneuroma findings will be
correlated with the OPAS and hyperosmol...

## Key facts

- **NIH application ID:** 10617101
- **Project number:** 4R33NS113341-02
- **Recipient organization:** TUFTS MEDICAL CENTER
- **Principal Investigator:** Pedram Hamrah
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $750,704
- **Award type:** 4N
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10617101

## Citation

> US National Institutes of Health, RePORTER application 10617101, Discovery of the Biomarker Signature for Neuropathic Corneal Pain (4R33NS113341-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10617101. Licensed CC0.

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