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

NCT05653921 | Suspended

• 2 other identifiers: STUDY000030184R33NS113341-02
• Study Type: observational
• Target: 438
• Locations: 1 country
• Sites: 2

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.

Conditions

Dry Eye Syndromes; Corneal Disease

Outcome Measures

Primary Outcomes (1)

• Presence of microneuromas as assessed by in vivo confocal microscopy (IVCM).

  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

  Day 1

Secondary Outcomes (5)

• Intra-subject repeatability; Presence of the microneuroma biomarker in the same participant at 2 weeks

  From Day 1 to 2 weeks

• Establish the reference interval for the microneuroma biomarker

  Day 1

• Ocular Pain Assessment Survey (OPAS) questionnaire results correlation to microneuromas; OPAS reported quality of life score compared across the 3 cohorts.

  Day 1

• Hyperosmolar functional nerve tests in correlation to microneuromas; hyperosmolar functional nerve tests results compared cross cohorts

  Day 1

• Test the utility of already configured AI software to diagnose NCP patients

  Day 1 to 2 weeks

Study Arms (3)

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.

Other: In vivo confocal microscopy (IVCM)

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.

Other: In vivo confocal microscopy (IVCM)

Control Group

No symptoms of ocular surface discomfort or dry eye disease.

Other: In vivo confocal microscopy (IVCM)

Interventions

In vivo confocal microscopy (IVCM) 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; Dry Eye Disease Group; Neuropathic Corneal Pain Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

We will not be limiting the inclusion of the NCP or DED groups for this study. We will be recruiting from two Cornea Clinics in diverse large cities of Boston and Philadelphia. Thus, the sample collected from this group is expected to be representative of the population for each of these groups. We will be limiting inclusion of the control group to those age and sex matched controls as described above. This will allow for the conclusions drawn from this study to be more applicable in clinical practice. Without an age and sex matched control group, one could attribute differences in IVCM to these two variables instead of the disease(s).

You may qualify if:

• All Subjects:
• years of age or older
• Ability to consent
• Best corrected visual acuity of 20/40 or better in each eye
• Dry Eye Disease Group:
• Chief complaint is ocular surface discomfort or dry eye disease, but subject reports no ocular pain on OPAS questionnaire
• Symptoms lasting at least 3 months
• Presence of at least two of the following within the same eye:
• Anesthetized Schirmer score =/\< 10mm
• Corneal staining of \>3/15 based on NEI scale
• Tear break up time \< 10 seconds
• Neuropathic Corneal Pain Group:
• Chief complain is ocular surface discomfort or dry eye disease
• Symptoms lasting at least 3 months
• All of the following in both eyes:

You may not qualify if:

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

Sponsors & Collaborators

• Tufts Medical Center: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (2)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Scheie Eye Institute, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (12)

• Bujang MA, Adnan TH. Requirements for Minimum Sample Size for Sensitivity and Specificity Analysis. J Clin Diagn Res. 2016 Oct;10(10):YE01-YE06. doi: 10.7860/JCDR/2016/18129.8744. Epub 2016 Oct 1.

  PMID: 27891446 BACKGROUND

• Ferrari G, Nallasamy N, Downs H, Dana R, Oaklander AL. Corneal innervation as a window to peripheral neuropathies. Exp Eye Res. 2013 Aug;113:148-50. doi: 10.1016/j.exer.2013.05.016. Epub 2013 Jun 14.

  PMID: 23769950 BACKGROUND

• 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.

  PMID: 15502475 BACKGROUND

• 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.

  PMID: 23279964 BACKGROUND

• 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.

  PMID: 27273596 BACKGROUND

• Devigili G, Tugnoli V, Penza P, Camozzi F, Lombardi R, Melli G, Broglio L, Granieri E, Lauria G. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain. 2008 Jul;131(Pt 7):1912-25. doi: 10.1093/brain/awn093. Epub 2008 Jun 4.

  PMID: 18524793 BACKGROUND

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

  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.

  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.

  PMID: 28736335 BACKGROUND

• 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.

  PMID: 21045640 BACKGROUND

• 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

  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.

  BACKGROUND

MeSH Terms

Conditions

Dry Eye Syndromes; Corneal Diseases

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases

Study Officials

• Pedram Hamrah, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2022
• First Posted: December 16, 2022
• Study Start: December 16, 2022
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)