Symptom Response in Normal and Dry Eye Patients Secondary to Application of a Menthol-Containing Eyedrop (Rohto® Hydra)

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to analyze the sensation to eye drops containing menthol in people with healthy eyes and in people with dry eyes. This study also examines the temperature of your eye using an Infrared Camera.

Detailed Description
-----------------
Dry eye disease (DED) has been defined as a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface1. An estimated 25 million Americans are reported to have dry eye disease (DED)2, which is a number that will only increase with the U.S. aging population3. The only treatment currently available in the U.S. targets inflammation on the ocular surface. Because dry eye is a complicated disease that encompasses many conditions of the eye, diversified ways to treating the disease are necessary. Some recent studies suggests that some Dry Eye symptoms are caused by corneal cold thermoreceptors (such as TRPM8) chronically firing at below-normal thresholds. It thus logically follows that dry eye patients could be distinguished from normal patients by possessing higher symptom responses secondary to topical application of menthol, a potent agonist of TRPM8. If dry eye patients indeed have lower threshold firing of TRPM8, agonizing TRPM8 with menthol will elicit a more severe symptom response, given equal concentrations across populations. To fully elucidate this relationship between TRPM8 agonists, sensation, and tear film cooling, two dry eye populations will be tested - one population which has exhibited symptom response to a previous dry eye agent, and one population with no symptom response to the same agent.

Official Title
-----------------
An Open-Label, Single-Center Study to Evaluate Symptom Response and Tear Film Cooling Dynamics of Normal and Dry Eye Patients Secondary to Application of a Menthol-Containing Eyedrop (Rohto® Hydra)

Conditions
-----------------
Dry Eye

Intervention / Treatment
-----------------
* Drug: Rohto (r) Hydra
* Drug: Systane (r) Ultra


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Be male or female of any race, at least 18 years of age at Visit 1. Have provided verbal and written informed consent. Have a best corrected visual acuity of +0.70 logMAR or better in both eyes at Visit 1, as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. Qualify for exactly one of the three cohorts. Exclusion Criteria: Have any contraindications to the use of Systane® Ultra, or Rohto® Hyrda, or its components (including Menthol). Have a known allergy to the study medications or their components. Have any clinically significant slit lamp findings at Visit 1, including active blepharitis, meibomian gland dysfunction (MGD), lid margin inflammation or ocular allergies that requires therapeutic treatment and/or, in the opinion of the investigator, may interfere with the study parameters. Be diagnosed with an ongoing ocular infection (bacterial, viral or fungal), or active ocular inflammation (e.g., follicular conjunctivitis) at Visit 1. Have a history of laser in situ keratomileusis (LASIK) surgery in either eye. Have had any ocular surgical procedure within 12 months prior to Visit 1. Have used contact lenses within 30 days prior to Visit 1 and for the duration of the study. Have used any topical ocular prescription (including medications for glaucoma) or over-the-counter (OTC) solutions, artificial tear substitutes, gels or scrubs within 24 hours prior to Visit 1 and for the duration of the study, except for the study drops. Have an uncontrolled systemic disease. Be a woman who is pregnant, nursing an infant, or planning a pregnancy. Have a condition or is in a situation that, in the opinion of the investigator, may put the patient at significant risk, may confound the study results, or may interfere significantly with the patients' participation in the study. Be currently enrolled in an investigational drug or device study or have used an investigational drug or device within 30 days prior to Visit 1. Currently have any punctal occlusions in either eye.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rohto (r) Hydra<br>Menthol containing over the counter eyedrop | Drug: Rohto (r) Hydra<br>* Rohto (r) Hydra; Over the counter Eyedrop, 1 gtt OU single-masked in-office dose<br>* Other names: Rohto Hydra;Drug: Systane (r) Ultra<br>* Systane (r) Ultra; Over the counter Eyedrop, 1 gtt OU single-masked in-office dose<br>* Other names: Systane Ultra;|
| Placebo Comparator: Systane (r) Ultra<br>Non-Menthol containing over the counter eyedrop | Drug: Rohto (r) Hydra<br>* Rohto (r) Hydra; Over the counter Eyedrop, 1 gtt OU single-masked in-office dose<br>* Other names: Rohto Hydra;Drug: Systane (r) Ultra<br>* Systane (r) Ultra; Over the counter Eyedrop, 1 gtt OU single-masked in-office dose<br>* Other names: Systane Ultra;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of the Cooling Scale For Rohto (r) Hydra | Participants completed the cooling scale after receiving 1 dose of Rohto (r) Hydra at 6 time points (0, 0.5, 1, 2, 3, and 4 minutes post-treatment), and the scores were summed across these time points. The cooling scale was on a scale of 0 to 10, where 0=not cool and 10=very cool. The summed total was on a scale of 0= not cool and 60=very cool. | 4 Minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of the Cooling Scale For Systane (r) Ultra | Participants completed the cooling scale after receiving 1 dose of Systane (r) Ultra at 6 time points (0, 0.5, 1, 2, 3, and 4 minutes post-treatment), and the scores were summed across these time points. The cooling scale was on a scale of 0 to 10, where 0=not cool and 10=very cool. The summed total was on a scale of 0= not cool and 60=very cool. | 4 minutes |