QST for Corneal Nerve Function

Not Applicable

• Conditions: Neurotrophic Keratitis; Dry Eye Disease; Corneal Disease; Neuropathy
• Interventions: Device: Quantitative Sensory Test

• Registration Number: NCT05758753
• Lead Sponsor: Tufts Medical Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2022-09-06
• Study First Submitted QC: 2023-02-24
• Study First Posted: 2023-03-07
• Study Start: 2023-05-16
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-13
• Last Update Posted: 2025-01-15
• Primary Completion: 2025-10-31
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 108

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Stage I Neurotrophic Keratopathy	Quantitative Sensory Test	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.
Stage II Neurotrophic Keratopathy	Quantitative Sensory Test	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.
Dry Eye Disease	Quantitative Sensory Test	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.
Healthy Individuals	Quantitative Sensory Test	Absence of any ocular symptoms, absence of surface findings (including corneal or conjunctival staining, corneal scar or surgical wound), and normal corneal sensation.

Primary Outcome Measures

Name	Time	Method
Thermal stimulus response to QST on site of trigeminal nerve first branch, as assessed by cold detection threshold (CDT) and hot detection threshold (HDT)	From visit 1 up to 4 weeks	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.
Differences in mechanical stimulus pain threshold across the 4 study arms	From visit 1 up to 4 weeks	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
Mechanical stimulus response to QST on site of trigeminal nerve first branch, as assessed by vibration detection threshold (VDT)	From visit 1 up to 4 weeks	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.
Differences in thermal stimulus pain threshold across the 4 study arms	From visit 1 up to 4 weeks	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

Secondary Outcome Measures

Name	Time	Method
To compare QST response differences between trigeminal nerve first branch and forearm in patients.	From visit 1 up to 4 weeks	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)
To correlate the QST responses with morphological changes of corneal nerves detected by IVCM	From visit 1 up to 4 weeks	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.
To correlate symptom severity as assessed by the Ocular Surface Disease Index (OSDI), to stimulus response across the 4 interventional arms.	From visit 1 up to 4 weeks	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.

Trial Locations

Locations (1)

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States