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

NCT ID: NCT05653921

Last Updated: 2026-01-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

SUSPENDED

Total Enrollment

438 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-12-16

Study Completion Date

2026-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Dry Eye Syndromes Corneal Disease

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Dry Eye Disease Group

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.

In vivo confocal microscopy (IVCM)

Intervention Type OTHER

In vivo confocal microscopy (IVCM) allows for visualization of the corneal structures at the cellular level, allowing for assessment of corneal nerves. With a magnification of 800 times, it makes it possible to detect and quantify changes in the epithelial layers and sub-basal nerve plexus.

Neuropathic Corneal Pain Group

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.

In vivo confocal microscopy (IVCM)

Intervention Type OTHER

In vivo confocal microscopy (IVCM) allows for visualization of the corneal structures at the cellular level, allowing for assessment of corneal nerves. With a magnification of 800 times, it makes it possible to detect and quantify changes in the epithelial layers and sub-basal nerve plexus.

Control Group

No symptoms of ocular surface discomfort or dry eye disease.

In vivo confocal microscopy (IVCM)

Intervention Type OTHER

In vivo confocal microscopy (IVCM) allows for visualization of the corneal structures at the cellular level, allowing for assessment of corneal nerves. With a magnification of 800 times, it makes it possible to detect and quantify changes in the epithelial layers and sub-basal nerve plexus.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

In vivo confocal microscopy (IVCM)

In vivo confocal microscopy (IVCM) allows for visualization of the corneal structures at the cellular level, allowing for assessment of corneal nerves. With a magnification of 800 times, it makes it possible to detect and quantify changes in the epithelial layers and sub-basal nerve plexus.

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Tufts Medical Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Pedram Hamrah, MD

Role: PRINCIPAL_INVESTIGATOR

Tufts Medical Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Scheie Eye Institute, University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Fry HJ. Overuse syndrome, alias tenosynovitis/tendinitis: the terminological hoax. Plast Reconstr Surg. 1986 Sep;78(3):414-7. doi: 10.1097/00006534-198609000-00025. No abstract available.

Reference Type BACKGROUND
PMID: 3737766 (View on PubMed)

Nichols KK, Nichols JJ, Mitchell GL. The lack of association between signs and symptoms in patients with dry eye disease. Cornea. 2004 Nov;23(8):762-70. doi: 10.1097/01.ico.0000133997.07144.9e.

Reference Type BACKGROUND
PMID: 15502475 (View on PubMed)

Iuganov EM, Krylov IuV, Kuznetsov VS. [Use of psychophysiological indices in the practice of audiological studies]. Izv Akad Nauk SSSR Biol. 1971 Jul-Aug;4:587-95. No abstract available. Russian.

Reference Type BACKGROUND
PMID: 5121784 (View on PubMed)

Sullivan BD, Crews LA, Messmer EM, Foulks GN, Nichols KK, Baenninger P, Geerling G, Figueiredo F, Lemp MA. Correlations between commonly used objective signs and symptoms for the diagnosis of dry eye disease: clinical implications. Acta Ophthalmol. 2014 Mar;92(2):161-6. doi: 10.1111/aos.12012. Epub 2012 Dec 28.

Reference Type BACKGROUND
PMID: 23279964 (View on PubMed)

Nichols KK, Bacharach J, Holland E, Kislan T, Shettle L, Lunacsek O, Lennert B, Burk C, Patel V. Impact of Dry Eye Disease on Work Productivity, and Patients' Satisfaction With Over-the-Counter Dry Eye Treatments. Invest Ophthalmol Vis Sci. 2016 Jun 1;57(7):2975-82. doi: 10.1167/iovs.16-19419.

Reference Type BACKGROUND
PMID: 27273596 (View on PubMed)

Fovaeus M, Andersson KE, Hedlund H. Calcium channel blockade and contractile responses in the isolated human vas deferens. J Urol. 1987 Sep;138(3):654-8. doi: 10.1016/s0022-5347(17)43292-7.

Reference Type BACKGROUND
PMID: 2442424 (View on PubMed)

Classification of Chronic Pain, Part III: Pain Terms, A Current List with Definitions and Notes on Usage. Second ed. Seattle: IASP Press; 1994

Reference Type BACKGROUND

Dieckmann G, Koseoglu N, Moein HR, Kataguiri P, Hamrah P. Epidemiological factors of neuropathic corneal pain. IASP: The 18th World Congress on Pain; 2018; Boston, MA.

Reference Type BACKGROUND

Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, Liu Z, Nelson JD, Nichols JJ, Tsubota K, Stapleton F. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017 Jul;15(3):276-283. doi: 10.1016/j.jtos.2017.05.008. Epub 2017 Jul 20.

Reference Type BACKGROUND
PMID: 28736335 (View on PubMed)

Yu J, Asche CV, Fairchild CJ. The economic burden of dry eye disease in the United States: a decision tree analysis. Cornea. 2011 Apr;30(4):379-87. doi: 10.1097/ICO.0b013e3181f7f363.

Reference Type BACKGROUND
PMID: 21045640 (View on PubMed)

Lopez MJ, Jamali A, Dieckmann G, et al. Corneal Pain Has a Negative Impact on the Quality of Life of Patients with Neuropathic Corneal Pain. Investigative ophthalmology & visual science. 2018;59(9):138-138

Reference Type BACKGROUND

Lopez MJ, Abbouda A, Pondelis N, et al. The Ocular Pain Assessment Survey and In Vivo Confocal Microscopy as Valuable Tools in the Diagnosis and Management of Patients with Corneal Neuropathic Pain. Investigative ophthalmology & visual science. 2017;58(8):1013-1013.

Reference Type BACKGROUND

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

4R33NS113341-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00003018

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Immune Indicators of Uveitis
NCT00089739 COMPLETED
Intravitreal Celecoxib for Chronic Uveitis
NCT02131012 TERMINATED PHASE1
Analysis of Eye Tissue
NCT00001224 COMPLETED