Prospective Study to Validate the Imaging Biomarker for NCP (R33)

Recruiting

• Conditions: Dry Eye Syndromes; Corneal Disease
• Interventions: Other: In vivo confocal microscopy (IVCM)

• Registration Number: NCT05653921
• Lead Sponsor: Tufts Medical Center

Brief Summary

The aim of this study is establish the reliability and clinical utility of microneuromas as identified via in vivo confocal microscopy as the diagnostic biomarker for NCP.

Detailed Description

Dry Eye Disease (DED) is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities.

Neuropathic corneal pain (NCP), an ocular and severe type of neuropathic pain describes patients with symptoms of ocular discomfort out of proportion with clinical signs. The lack of clinical signs observed by standard ophthalmic examination has resulted in underdiagnosis of NCP or misdiagnosis as dry eye disease. Thus, having a biomarker for NCP is critical to identify and treat these patients. No biomarker or clinical signs exists to identify NCP patients.

Investigating corneal neurosensory abnormalities could help to diagnose NCP and potentially differentiate these patients from those with DED. In vivo confocal microscopy (IVCM) allows for real-time optical biopsies at a quasi-histological level, allowing for assessment of corneal nerves. IVCM non-invasive diagnostic imaging across NCP, DED, and healthy individuals will be analyzed to validate corneal microneuromas as a biomarker for NCP.

Study Timeline

• Study First Submitted: 2022-09-06
• Study First Submitted QC: 2022-12-08
• Study Start: 2022-12-16
• Study First Posted: 2022-12-16
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-18
• Last Update Posted: 2025-04-23
• Primary Completion: 2025-05-31
• Study Completion: 2025-07-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 438

Inclusion Criteria

All Subjects:

1. 18 years of age or older
2. Ability to consent
3. Best corrected visual acuity of 20/40 or better in each eye

Dry Eye Disease Group:

1. Chief complaint is ocular surface discomfort or dry eye disease, but subject reports no ocular pain on OPAS questionnaire

2. Symptoms lasting at least 3 months

3. Presence of at least two of the following within the same eye:

   1. Anesthetized Schirmer score =/< 10mm
   2. Corneal staining of >3/15 based on NEI scale
   3. Tear break up time < 10 seconds

Neuropathic Corneal Pain Group:

1. Chief complain is ocular surface discomfort or dry eye disease

2. Symptoms lasting at least 3 months

3. All of the following in both eyes:

   1. Corneal staining of less than or equal to 3/15 based on NEI scale
   2. Tear break up time =/> 10 seconds

4. Must have at least 25% peripheral pain

5. Subject reported discomfort prior to drop response testing of at least 3 out of 10

Control Group:

1. No symptoms of ocular surface discomfort or dry eye disease

2. All of the following in both eyes

   1. Anesthetized Schirmer score > 10 mm
   2. Corneal staining of less than or equal to 3/15 based on NEI scale
   3. Tear break up time > 10 seconds

3. The same sex and within 5 years of age of a patient within the NCP group.

Exclusion Criteria

1. Pregnant or nursing
2. Irregular corneal disease
3. Ocular surgery in the past 3 months
4. Ocular infection in the past 3 months
5. Active ocular allergies
6. Participation in a study that could potentially impact the IVCM in the opinion of the investigator
7. Current use of corneal nerve regeneration therapy that has been on-going for 3 months or more.
8. For NCP group only, patients for whom their pain and symptoms can be attributed to other causes in the opinion of the investigator

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Neuropathic Corneal Pain Group	In vivo confocal microscopy (IVCM)	Symptoms of ocular surface discomfort or pain for at least 3 months, that are reported to have a significant impact on quality of life and ability to perform daily activities.
Dry Eye Disease Group	In vivo confocal microscopy (IVCM)	Symptoms of ocular surface discomfort or dry eye disease for at least 3 months, supported by clinical exam findings. Reported quality of life is not effected by ocular pain.
Control Group	In vivo confocal microscopy (IVCM)	No symptoms of ocular surface discomfort or dry eye disease.

Primary Outcome Measures

Name	Time	Method
Presence of microneuromas as assessed by in vivo confocal microscopy (IVCM).	Day 1	The obtained sequence of IVCM imaging scans of both eyes will be evaluated for findings of microneuromas; defined as either observed presence or absence of microneuroma

Secondary Outcome Measures

Name	Time	Method
Ocular Pain Assessment Survey (OPAS) questionnaire results correlation to microneuromas; OPAS reported quality of life score compared across the 3 cohorts.	Day 1	Ocular Pain Assessment Survey (OPAS) questionnaire: 27-item quantitative questionnaire designed to provide an assessment of the symptoms and quality of life effect of ocular pain. The 27 items of the OPAS questionnaire are graded on a scale of 0 to 10, or 10 to 100, where 0 indicates none and 10 or 100 indicate maximum. Higher scores indicate greater impact of ocular pain on quality of life dimensions.
Establish the reference interval for the microneuroma biomarker	Day 1	Quantification of microneuromas as assessed by IVCM in each cohort (Normal vs. NCP vs. DED)
Hyperosmolar functional nerve tests in correlation to microneuromas; hyperosmolar functional nerve tests results compared cross cohorts	Day 1	Using the Pain Visual Analogue Scale (VAS), Symptoms of ocular comfort and dryness at the time in question will be graded for each eye verbally on a scale of 0-10, where 0=excellent comfort, no dryness and 10=extremely uncomfortable, extremely dry. A single drop of hypertonic sodium chloride solution (Muro 128®, 5%) at room temperature will be instilled into each eye. After 20 seconds, participants will be asked to grade their ocular comfort and dryness symptoms as described in the VAS procedure again allowing assessment of changes in sensation due to the hyperosmolar drop and activation of the polymodal nociceptors
Intra-subject repeatability; Presence of the microneuroma biomarker in the same participant at 2 weeks	From Day 1 to 2 weeks	Confirmation of presence of microneuroma on IVCM at 2 weeks in participants with IVCM finding of microneruoma at Visit 1
Test the utility of already configured AI software to diagnose NCP patients	Day 1 to 2 weeks	categorical variables of NCP and DED as diagnosed by the AI system and the classification of subjects into the NCP and DED groups based on inclusion criteria set by the study

Trial Locations

Locations (2)

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Scheie Eye Institute, University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States