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

Tufts University

Status: Suspended

Conditions: Corneal Disease; Dry Eye Syndromes

Treatments: Other: In vivo confocal microscopy (IVCM)

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT05653921

4R33NS113341-02 (U.S. NIH Grant/Contract)

STUDY00003018

Details and patient eligibility

About

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.

Full 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.

Enrollment: 438 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

438 participants in 3 patient groups

Dry Eye Disease Group

Description:

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.

Treatment:

Other: In vivo confocal microscopy (IVCM)

Neuropathic Corneal Pain Group

Description:

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.

Treatment:

Other: In vivo confocal microscopy (IVCM)

Control Group

Description:

No symptoms of ocular surface discomfort or dry eye disease.

Treatment:

Other: In vivo confocal microscopy (IVCM)