QST for Corneal Nerve Function

The Efficacy of Quantitative Sensory Test (QST) in Assessing Corneal Nerve Functions in Patients With Ocular Surface Diseases

This study is designed to learn more about the impact different types of stimuli, such as heat, cold and vibration, can have on ocular pain response. This is called quantitative sensory testing (QST). Most procedures being performed in this study, except the QST, are standard of care which means they are performed during the participant's routine eye examination.

Study Overview

• Status: Suspended
• Conditions: Neurotrophic Keratitis; Neuropathy; Dry Eye Disease; Corneal Disease
• Intervention / Treatment: Device: Quantitative Sensory Test

Detailed Description

Quantitative Sensory Test (QST) is a non-invasive neurophysiological method that refers to a group of procedures that assess the perceptual responses to systematically applied and quantifiable sensory stimuli for the purpose of characterizing somatosensory function or dysfunction.

In this study, we propose to evaluate corneal nerve functions in patients with corneal nerve abnormalities by QST and correlate the nerve functions with symptoms, clinical signs and nerve morphology detected by In-Vivo Confocal Microscopy (IVCM). Identification of corneal nerve functions and correlations with other findings may help us to understand underlying pathological mechanisms of the disease and may guide us toward new treatment targets.

We hypothesize that, QST may provide us detailed information about corneal nerve function alterations and may correlate with morphological nerve changes detected by IVCM.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Group 1: Stage I Neurotrophic Keratopathy (NK)

1. Clinical findings of Stage I NK
2. Decreased nerve density by IVCM
3. Decreased corneal sensation

Group 2: Stage II NK

1. Clinical findings of Stage II NK
2. Decreased nerve density by IVCM
3. Decreased corneal sensation

Group 3: Dry Eye Disease (DED)

1. Symptoms of DED at least 3 months
2. Presence of at least one of the following DED signs; tear film break-up time lower than 7, ocular surface staining more than +1 based on NIH scale
3. Normal or mildly effected corneal sensation

Group 4: Healthy Individuals

1. Absence of any ocular surface symptoms
2. Absence of ocular surface findings
3. Transparent and clear cornea
4. Normal corneal sensation

Group 5: NCP

1. Presence of neuropathic symptoms AND
2. Symptoms out of proportion to clinical findings AND
3. Nerve abnormalities detected by in vivo confocal microscopy

Exclusion Criteria:

1. History of diabetes
2. History of ocular surgery, corneal infection, or corneal injury within the last 3 months
3. Systemic regular anti-inflammatory and/or steroid and/or immune-modulatory therapy in the last 3 months
4. Active ocular allergies
5. Any major psychiatric illness including bipolar, psychosis, obsessive-compulsive disorder and major depression
6. Pregnancy
7. History of surgery within the last 3 months
8. History of , sarcoidosis, GVHD or collagen vascular disease
9. Allergic to benzalkonium chloride "BAK" (an eye-drop preservative)
10. Concurrent enrollment in other studies that in the opinion of the investigator will interfere with the results of this study
11. Non-English speakers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage I Neurotrophic Keratopathy; Clinical findings of corneal hyperplasia and irregularity, scattered small facets of dried epithelium, decreased nerve density as assessed by in vivo confocal microscopy (IVCM), and decreased corneal sensation.	Device: Quantitative Sensory Test; Quantitative Sensory Test (Medoc Ltd, Israel), QST is a non-invasive neurophysiological method that refers to a group of procedures that assess the perceptual responses to systematically applied and quantifiable sensory stimuli (modalities including heat, cold and vibration) for the purpose of characterizing somatosensory function or dysfunction. For this test, subjects will be seated comfortably on a chair in a quiet room, or laying supine in a horizontal examination chair, with ambient temperature of 24-25◦ C. Medial upper eyelid; just below the supraorbital notch, nasolacrimal sac area; 4-5 mm medial to nasal cantus, and non-dominant forearm will be used as test sites. Patients will be instructed in detail of the nature of the test and the need to react attentively and promptly to change in temperatures.
Experimental: Stage II Neurotrophic Keratopathy; Clinical findings of corneal epithelial defect with smooth and rolled edges, decreased nerve density as assessed by in vivo confocal microscopy (IVCM), and decreased corneal sensation.	Device: Quantitative Sensory Test; Quantitative Sensory Test (Medoc Ltd, Israel), QST is a non-invasive neurophysiological method that refers to a group of procedures that assess the perceptual responses to systematically applied and quantifiable sensory stimuli (modalities including heat, cold and vibration) for the purpose of characterizing somatosensory function or dysfunction. For this test, subjects will be seated comfortably on a chair in a quiet room, or laying supine in a horizontal examination chair, with ambient temperature of 24-25◦ C. Medial upper eyelid; just below the supraorbital notch, nasolacrimal sac area; 4-5 mm medial to nasal cantus, and non-dominant forearm will be used as test sites. Patients will be instructed in detail of the nature of the test and the need to react attentively and promptly to change in temperatures.
Experimental: Dry Eye Disease; Symptoms of dry eye disease for at least 3 months, supported by clinical finding of decreased tear film break-up time or ocular surface staining. Normal corneal sensation.	Device: Quantitative Sensory Test; Quantitative Sensory Test (Medoc Ltd, Israel), QST is a non-invasive neurophysiological method that refers to a group of procedures that assess the perceptual responses to systematically applied and quantifiable sensory stimuli (modalities including heat, cold and vibration) for the purpose of characterizing somatosensory function or dysfunction. For this test, subjects will be seated comfortably on a chair in a quiet room, or laying supine in a horizontal examination chair, with ambient temperature of 24-25◦ C. Medial upper eyelid; just below the supraorbital notch, nasolacrimal sac area; 4-5 mm medial to nasal cantus, and non-dominant forearm will be used as test sites. Patients will be instructed in detail of the nature of the test and the need to react attentively and promptly to change in temperatures.
Experimental: Healthy Individuals; Absence of any ocular symptoms, absence of surface findings (including corneal or conjunctival staining, corneal scar or surgical wound), and normal corneal sensation.	Device: Quantitative Sensory Test; Quantitative Sensory Test (Medoc Ltd, Israel), QST is a non-invasive neurophysiological method that refers to a group of procedures that assess the perceptual responses to systematically applied and quantifiable sensory stimuli (modalities including heat, cold and vibration) for the purpose of characterizing somatosensory function or dysfunction. For this test, subjects will be seated comfortably on a chair in a quiet room, or laying supine in a horizontal examination chair, with ambient temperature of 24-25◦ C. Medial upper eyelid; just below the supraorbital notch, nasolacrimal sac area; 4-5 mm medial to nasal cantus, and non-dominant forearm will be used as test sites. Patients will be instructed in detail of the nature of the test and the need to react attentively and promptly to change in temperatures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thermal stimulus response to QST on site of trigeminal nerve first branch, as assessed by cold detection threshold (CDT) and hot detection threshold (HDT)	Cold and heat sensation thresholds will be evaluated by placing a 16 mm x 16 mm probe over the skin on the site to be tested, and an average of 3 reading while be taken for each stimuli. Participants will receive successive ramps of gradually decreasing or increasing temperature, starting from a resting neutral temperature of 32°C. Participants will be instructed to press a response button when a thermal sensation (either cold or warm) is perceived.	From visit 1 up to 4 weeks
Mechanical stimulus response to QST on site of trigeminal nerve first branch, as assessed by vibration detection threshold (VDT)	Vibration sensation threshold will be evaluated by placing a 16 mm x 16 mm probe over the skin on the site to be tested, and an average of 3 reading while be taken. Participants will receive successive ramps of gradually decreasing or increasing vibration, starting from. Participants will be instructed to press a response button when a mechanical sensation is perceived.	From visit 1 up to 4 weeks
Differences in thermal stimulus pain threshold across the 4 study arms	Cold pain threshold (CPT) and heat pain threshold (HPT) will be measured by asking participants to press a response button when they first feel a pain or discomfort from probe on QST testing	From visit 1 up to 4 weeks
Differences in mechanical stimulus pain threshold across the 4 study arms	Vibration pain threshold (VPT) will be measured by asking participants to press a response button when they first feel a pain or discomfort from vibration probe on QST testing	From visit 1 up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To correlate the QST responses with morphological changes of corneal nerves detected by IVCM	In vivo confocal microscopy (IVCM) imaging will be performed to observe for any morphological nerve changes; such as decreased nerve density, nerve tortuosity presence of microneuromas.	From visit 1 up to 4 weeks
To correlate symptom severity as assessed by the Ocular Surface Disease Index (OSDI), to stimulus response across the 4 interventional arms.	Ocular Surface Disease Index (OSDI) questionnaire A 12-item questionnaire designed to provide a rapid assessment of the symptoms of ocular irritation consistent with dry eye disease and their impact on vision-related functioning. The 12 items of the OSDI questionnaire are graded on a scale of 0 to 4, where 0 indicates none of the time; 1, some of the time; 2, half of the time; 3, most of the time; and 4, all of the time. The total OSDI score is then calculated on the basis of the following formula: OSDI= [(sum of scores for all questions answered) x 100]/[(total number of questions answered) x 4]. Higher OSDI scores represent greater severity of symptoms.	From visit 1 up to 4 weeks
To compare QST response differences between trigeminal nerve first branch and forearm in patients.	Measurement of stimuli detection thresholds, pain thresholds and pain ranges for different stimuli (cold, heat and vibration) type in study groups at 3 different periocular sites (just below supraorbital notch, lateral canthus, inferior orbital bone; 1 cm lateral of medial canthus) and non-dominant hand hypothenar eminence (as a reference site)	From visit 1 up to 4 weeks

Collaborators and Investigators

• Sponsor: Tufts Medical Center
• Collaborators: Dompé Farmaceutici S.p.A
• Investigators: Principal Investigator: Pedram Hamrah, MD, Tufts Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2023
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: September 6, 2022
• First Submitted That Met QC Criteria: February 24, 2023
• First Posted (Actual): March 7, 2023

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Quantitative Sensory Test
• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Dry Eye Syndromes; Corneal Diseases
• Other Study ID Numbers: STUDY00002510

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No