# Optimizing methotrexate use for the management of chronic pediatric non-infectious uveitis

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $591,273

## Abstract

PROJECT SUMMARY
Pediatric chronic non-infectious uveitis (NIU) is an inflammatory ocular disease that has a substantial risk for
sight-threatening complications. Methotrexate (MTX) is the preferred first line systemic treatment for all subtypes
of NIU given its overall safety and affordability. However, MTX failure is as high as 50%. Biologic drugs are
reserved for those who fail MTX. The long delays waiting for therapeutic effect leads to prolonged glucocorticoid
use and continued accrual of ocular damage. As MTX may not be the appropriate first line treatment for all
subtypes of NIU, identifying predictors of MTX responsiveness will allow expeditious initiation of biologic
therapies. Our long-term goal is to prevent sight-threatening damage in children with NIU by initiating early
effective treatment that controls inflammation quickly.
This investigation is a longitudinal translational study that is a collaborative effort consisting of experts in
rheumatology, ophthalmology, ocular imaging, immunology and biostatistics. The objectives of this study are: 1)
To identify baseline demographic, clinical, laboratory, and imaging features in children with NIU that correlate
with response to MTX; 2) To assess the value of adding quantitative imaging modalities to monitor response to
MTX in children with NIU; and 3) To discover gene expression signatures that predict response and non-
response to MTX in children with NIU. A total of 120 children who are starting MTX for NIU will be enrolled in all
aims and followed prospectively at 3 and 6 months. Children will undergo serial clinical ophthalmic examinations
and imaging by anterior segment optical coherence tomography (AS-OCT), ultrawide field fluorescein
angiography (UWFFA), and OCT to assess MTX response. Aim 1 will identify the combination of variables at
baseline that predict a patient’s risk of response by 6 months. Aim 2 will assess the use of quantitative imaging
to evaluate and monitor MTX response over 6 months. These modalities will also be compared to the clinical
examination. In Aim 3, 20 pediatric non-uveitic controls will also be included. This aim is designed to discover
gene expression signatures that are associated with clinical and imaging based MTX response and non-
response. The success of this study will 1) optimize treatment of children with NIU by allowing earlier initiation
of biologics in those unlikely to respond to MTX, 2) demonstrate the clinical usefulness of quantitative imaging
in therapeutic decision-making, and 3) eventually shift the current treatment standard of NIU leading to improved
ocular health of children.

## Key facts

- **NIH application ID:** 10795976
- **Project number:** 5R01EY034565-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Sheila Therese Angeles-Han
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $591,273
- **Award type:** 5
- **Project period:** 2023-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795976

## Citation

> US National Institutes of Health, RePORTER application 10795976, Optimizing methotrexate use for the management of chronic pediatric non-infectious uveitis (5R01EY034565-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10795976. Licensed CC0.

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