QST for Corneal Nerve Function

Dry Eye Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05758753
• Other study ID #: STUDY00002510
• Status: Enrolling by invitation
• Phase: N/A
• Start date: May 16, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: January 2024
• Source: Tufts Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 108
• Est. completion date: June 30, 2025
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Corneal Disease
• Corneal Diseases
• Dry Eye Disease
• Dry Eye Syndromes
• Eye Diseases
• Keratitis
• Neuropathy
• Neurotrophic Keratitis

Intervention

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.

Locations

Country	Name	City	State
United States	Tufts Medical Center	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Tufts Medical Center	Dompé Farmaceutici S.p.A

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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