Back to resultsProspective Study to Validate the Imaging Biomarker for NCP (R33)
Primary Purpose
Dry Eye Syndromes, Corneal Disease
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
In vivo confocal microscopy (IVCM)
Sponsored by
About this trial
This is an interventional diagnostic trial for Dry Eye Syndromes
Eligibility Criteria
Inclusion Criteria: All Subjects: 18 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: Corneal staining of less than or equal to 3/15 based on NEI scale Tear break up time =/> 10 seconds Must have at least 25% peripheral pain Subject reported discomfort prior to drop response testing of at least 3 out of 10 Control Group: No symptoms of ocular surface discomfort or dry eye disease All of the following in both eyes Anesthetized Schirmer score > 10 mm Corneal staining of less than or equal to 3/15 based on NEI scale Tear break up time > 10 seconds The same sex and within 5 years of age of a patient within the NCP group. Exclusion Criteria: 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
Sites / Locations
- Tufts Medical CenterRecruiting
- Scheie Eye Institute, University of PennsylvaniaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Other
Other
Other
Arm Label
Dry Eye Disease Group
Neuropathic Corneal Pain Group
Control Group
Arm 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.
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.
No symptoms of ocular surface discomfort or dry eye disease.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Intra-subject repeatability; Presence of the microneuroma biomarker in the same participant at 2 weeks
Confirmation of presence of microneuroma on IVCM at 2 weeks in participants with IVCM finding of microneruoma at Visit 1
Establish the reference interval for the microneuroma biomarker
Quantification of microneuromas as assessed by IVCM in each cohort (Normal vs. NCP vs. DED)
Ocular Pain Assessment Survey (OPAS) questionnaire results correlation to microneuromas; OPAS reported quality of life score compared across the 3 cohorts.
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.
Hyperosmolar functional nerve tests in correlation to microneuromas; hyperosmolar functional nerve tests results compared cross cohorts
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
Test the utility of already configured AI software to diagnose NCP patients
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
Full Information
NCT ID
NCT05653921
First Posted
September 6, 2022
Last Updated
August 9, 2023
Sponsor
Tufts Medical Center
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
1. Study Identification
Unique Protocol Identification Number
NCT05653921
Brief Title
Prospective Study to Validate the Imaging Biomarker for NCP (R33)
Official Title
Prospective Study to Validate the Imaging Biomarker for Neuropathic Corneal Pain.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 16, 2022 (Actual)
Primary Completion Date
May 31, 2024 (Anticipated)
Study Completion Date
July 14, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tufts Medical Center
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye Syndromes, Corneal Disease
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
438 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dry Eye Disease Group
Arm Type
Other
Arm 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.
Arm Title
Neuropathic Corneal Pain Group
Arm Type
Other
Arm 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.
Arm Title
Control Group
Arm Type
Other
Arm Description
No symptoms of ocular surface discomfort or dry eye disease.
Intervention Type
Other
Intervention Name(s)
In vivo confocal microscopy (IVCM)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Presence of microneuromas as assessed by in vivo confocal microscopy (IVCM).
Description
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
Time Frame
Day 1
Secondary Outcome Measure Information:
Title
Intra-subject repeatability; Presence of the microneuroma biomarker in the same participant at 2 weeks
Description
Confirmation of presence of microneuroma on IVCM at 2 weeks in participants with IVCM finding of microneruoma at Visit 1
Time Frame
From Day 1 to 2 weeks
Title
Establish the reference interval for the microneuroma biomarker
Description
Quantification of microneuromas as assessed by IVCM in each cohort (Normal vs. NCP vs. DED)
Time Frame
Day 1
Title
Ocular Pain Assessment Survey (OPAS) questionnaire results correlation to microneuromas; OPAS reported quality of life score compared across the 3 cohorts.
Description
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.
Time Frame
Day 1
Title
Hyperosmolar functional nerve tests in correlation to microneuromas; hyperosmolar functional nerve tests results compared cross cohorts
Description
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
Time Frame
Day 1
Title
Test the utility of already configured AI software to diagnose NCP patients
Description
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
Time Frame
Day 1 to 2 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
All Subjects:
18 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:
Corneal staining of less than or equal to 3/15 based on NEI scale
Tear break up time =/> 10 seconds
Must have at least 25% peripheral pain
Subject reported discomfort prior to drop response testing of at least 3 out of 10
Control Group:
No symptoms of ocular surface discomfort or dry eye disease
All of the following in both eyes
Anesthetized Schirmer score > 10 mm
Corneal staining of less than or equal to 3/15 based on NEI scale
Tear break up time > 10 seconds
The same sex and within 5 years of age of a patient within the NCP group.
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nancy Gee, MPH
Phone
617-636-5489
Email
ngee@tuftsmedicalcenter.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pedram Hamrah, MD
Organizational Affiliation
Tufts Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nancy Gee, MPH
Phone
617-636-5489
Email
ngee@tuftsmedicalcenter.org
First Name & Middle Initial & Last Name & Degree
Pedram Hamrah, MD
Facility Name
Scheie Eye Institute, University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giacomina Massaro-Giordano, MD
First Name & Middle Initial & Last Name & Degree
Giacomina Massaro-Giordano, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
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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.
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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.
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Classification of Chronic Pain, Part III: Pain Terms, A Current List with Definitions and Notes on Usage. Second ed. Seattle: IASP Press; 1994
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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.
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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.
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Prospective Study to Validate the Imaging Biomarker for NCP (R33)
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