Advantages of Lissamine Green Vital Staining as an Endpoint in Dry Eye Clinical Trials.

Purpose: The absence of a standardized diagnostic method for clinical signs of Dry Eye Disease (DED) complicates clinical trials for future treatments. This paper evaluated Lissamine Green (LG) conjunctival staining as a valid, stable and modifiable endpoint for both clinical practice and clinical trials.

Methods: Screening and pre-randomization data from two identically designed clinical trials for DED resulted in a pooled dataset of 494 subjects.

A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1).

Purpose: Dry eye disease (DED) symptoms can negatively impact quality of life (QoL). AR-15512, a transient receptor potential melastatin 8 (TRPM8) agonist, was evaluated as a potential therapy for DED.

Methods: In a Phase 2b study, patients with DED were randomized 1:1:1 to 0.

TNF-α inhibitor tanfanercept (HBM9036) improves signs and symptoms of dry eye in a phase 2 trial in the controlled adverse environment in China.

Purpose: This study evaluated the clinical safety and efficacy of tanfanercept (HBM9036) ophthalmic solution as a novel treatment for dry eye disease (DED) in a controlled adverse environment (CAE) study conducted in China.

Methods: In a single-center, double-masked, randomized, placebo-controlled study, 100 patients received 0.25% tanfanercept, or placebo, twice daily for eight weeks.

A Water-free 0.1% Cyclosporine A Solution for Treatment of Dry Eye Disease: Results of the Randomized Phase 2B/3 ESSENCE Study.

Purpose: To assess the efficacy, safety, and tolerability of a topical water-free cyclosporine A formulation (CyclASol 0.1% ophthalmic solution) in comparison with vehicle for the treatment of dry eye disease (DED).

Methods: Three hundred twenty-eight patients were enrolled in this prospective, 12-week, multicenter, randomized, double-masked, confirmatory, vehicle-controlled clinical study.

Symptom improvement in dry eye subjects following intranasal tear neurostimulation: Results of two studies utilizing a controlled adverse environment.

Purpose: To evaluate the safety and effectiveness of the intranasal tear neurostimulator (ITN) in improving dry eye symptoms assessed in a controlled adverse environment (CAE®).

Methods: Study 1: Multicenter, subject-masked, randomized-sequence, crossover design. Single intranasal (active) and extranasal (control) ITN administration during CAE exposure.

A Clinical Phase II Study to Assess Efficacy, Safety, and Tolerability of Waterfree Cyclosporine Formulation for Treatment of Dry Eye Disease.

Purpose: To compare the efficacy, safety, and tolerability of waterfree cyclosporine formulation (CyclASol) at 2 concentrations (0.1% and 0.05% of cyclosporine [CsA]) to vehicle when applied twice daily for 16 weeks in patients with dry eye disease (DED).

Characterization of tear production in subjects with dry eye disease during intranasal tear neurostimulation: Results from two pivotal clinical trials.

Purpose: The intranasal tear neurostimulator (ITN) activates the nasolacrimal pathway, which is involved with basal and bolus tear secretion. These studies characterized the acute and long-term effectiveness of the ITN in stimulating tear production in subjects with dry eye disease (DED).

Methods: Study 1: Randomized, double-masked, dual-controlled, 1-day crossover.

RGN-259 (thymosin β4) improves clinically important dry eye efficacies in comparison with prescription drugs in a dry eye model.

This study evaluated the clinical activity of RGN-259 (thymosin β4) in comparison with cyclosporine A (CsA), diquafosol (DQS), and lifitegrast (LFA) in a murine model of dry eye. The model was NOD.B10-H2 mice in a 30-40% humidified environment together with daily scopolamine hydrobromide injections for 10 days.

Blink: Characteristics, Controls, and Relation to Dry Eyes.

Blink is a complex phenomenon that is profoundly affected by diverse endogenous and exogenous stimuli. It has been studied in the context of cognition, emotional, and psychological states, as an indicator of fatigue and sleepiness, particularly in the automobile and transportation industry, in visual tasking, and finally, as it relates to tear film stability and ocular surface health. The fact that it is highly variable and has input from so many sources makes it very difficult to study.

Use of the Controlled Adverse Environment (CAE) in Clinical Research: A Review.

The many internal and external factors that contribute to the pathophysiology of dry eye disease (DED) create a difficult milieu for its study and complicate its clinical diagnosis and treatment. The controlled adverse environment (CAE) model has been developed to minimize the variability that arises from exogenous factors and to exacerbate the signs and symptoms of DED by stressing the ocular surface in a safe, standardized, controlled, and reproducible manner. By integrating sensitive, specific, and clinically relevant endpoints, the CAE has proven to be a unique and adaptable model for both identifying study-specific patient populations with modifiable signs and symptoms, and for tailoring the evaluation of interventions in clinical research studies.

Dynamic Sensitivity of Corneal TRPM8 Receptors to Menthol Instillation in Dry Eye Versus Normal Subjects.

Purpose: To assess the sensitivity of corneal cold receptors to a known transient receptor potential melastatin 8 (TRPM8) agonist, menthol, in dry eye and normals, and to determine whether factors such as disease duration or age affect responses.

Methods: Dry eye disease (DED) (N = 33) and normal (N = 15) subjects were randomly assigned to receive Rohto Hydra (0.01% menthol) or Systane Ultra treatments (OU) in a prospective, double-blind, crossover study.

Diurnal Tracking of Blink and Relationship to Signs and Symptoms of Dry Eye.

Purpose: To assess diurnal changes in the signs and symptoms of dry eyes and their relationship to diurnal interblink interval (IBI) in normal subjects and in subjects with dry eye.

Methods: Blink data were collected from 9:00 AM to 8:00 PM during 2 days of normal activity using an electrocardiogram monitoring device. All subjects recorded ocular discomfort (0-5 scale) and primary activity hourly each day in a diary.

The IMPACT study: a prospective evaluation of the effects of cyclosporine ophthalmic emulsion 0.05% on ocular surface staining and visual performance in patients with dry eye.

Objective: The aim of this study was to evaluate the effects of cyclosporine ophthalmic emulsion 0.05% on ocular surface staining and visual performance in patients with dry eye.

Methods: This was a single-center, 6-month, open-label, Phase IV study.

Optimizing Reading Tests for Dry Eye Disease.

Purpose: The aim of this study was to evaluate the visual function information obtained from multiple reading tests in a dry eye population.

Methods: In this case-control, single-center clinical research center-based study, 15 subjects with dry eye (mean age 65 years) and 10 normal subjects (mean age 40 years) were included. The Standardized Mini-Mental Examination was given to assure that subjects had normal cognitive function.

Automated Grading System for Evaluation of Superficial Punctate Keratitis Associated With Dry Eye.

Purpose: To develop an automated method of grading fluorescein staining that accurately reproduces the clinical grading system currently in use.

Methods: From the slit lamp photograph of the fluorescein-stained cornea, the region of interest was selected and punctate dot number calculated using software developed with the OpenCV computer vision library. Images (n = 229) were then divided into six incremental severity categories based on computed scores.

Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE™) model.

Background: The purpose of this study was to evaluate the safety and efficacy of thymosin beta 4 ophthalmic solution (RGN-259; Tβ4) in subjects with moderate to severe dry eye using the CAE™ model.

Methods: This single-center, prospective, double-masked, placebo-controlled Phase II study randomized 72 qualifying subjects 1:1 to receive either 0.1% Tβ4 or placebo treatment for a total of 28 days.

Blink patterns and lid-contact times in dry-eye and normal subjects.

Purpose: To classify blinks in dry eye and normal subjects into six subtypes, and to define the blink rate and duration within each type of blink, as well as the total lid-contact time/minute.

Materials And Methods: This was a single-centered, prospective, double-blind study of eleven dry-eye and ten normal subjects. Predefined subjects watched a video while blinks were recorded for 10 minutes.

Safety and efficacy of MIM-D3 ophthalmic solutions in a randomized, placebo-controlled Phase 2 clinical trial in patients with dry eye.

Purpose: To evaluate the safety and efficacy of ophthalmic MIM-D3, a tyrosine kinase TrkA receptor agonist, in patients with dry eye.

Design: A prospective, two-center, randomized, double-masked, placebo-controlled Phase 2 study.

Methods: A total of 150 dry eye patients were randomized 1:1:1 to study medication (1% MIM-D3, 5% MIM-D3, or placebo) and dosed twice daily (BID) for 28 days.

Automated grading system for evaluation of ocular redness associated with dry eye.

Background: We have observed that dry eye redness is characterized by a prominence of fine horizontal conjunctival vessels in the exposed ocular surface of the interpalpebral fissure, and have incorporated this feature into the grading of redness in clinical studies of dry eye.

Aim: To develop an automated method of grading dry eye-associated ocular redness in order to expand on the clinical grading system currently used.

Methods: Ninety nine images from 26 dry eye subjects were evaluated by five graders using a 0-4 (in 0.

Investigation of extended blinks and interblink intervals in subjects with and without dry eye.

Background: The purpose of this study was to investigate the occurrence and duration of extended blinks ≥ 70 msec and their associated interblink intervals in normal subjects and in subjects with mild to moderate dry eye.

Methods: This single-center, prospective, double-blind study included 11 subjects with dry eye and eight subjects with normal eyes. Extended blinks were defined as lid closure in at least two successive video frames (≥70 msec).

Exacerbation of signs and symptoms of allergic conjunctivitis by a controlled adverse environment challenge in subjects with a history of dry eye and ocular allergy.

Background: The goal of this study was to assess the effect of a controlled adverse environment (CAE) challenge on subjects with both allergic conjunctivitis and dry eye.

Methods: Thirty-three subjects were screened and 17 completed this institutional review board-approved study. Subjects underwent baseline ocular assessments and conjunctival allergen challenge (CAC) on days 0 and 3.

Thymosin β4: a potential novel dry eye therapy.

The purpose of this manuscript is to review the clinical entity of dry eye syndrome (DES) and to provide a scientific basis and rationale for the usage of thymosin beta 4 (Tβ4) as a novel therapy for DES. DES is a common disorder affecting an estimated 25-30 million people in the United States alone and is characterized by inflammation of the ocular surface. Consequently, patients can suffer from burning, irritation, severe discomfort, foreign body sensation, and blurry and decreased vision.

A phase 2 randomized, double-masked, placebo-controlled study of a novel integrin antagonist (SAR 1118) for the treatment of dry eye.

Purpose: To investigate the efficacy and safety of an investigational integrin antagonist (SAR 1118) ophthalmic solution compared to placebo (vehicle) in subjects with dry eye disease.

Design: Multicenter, prospective, double-masked, placebo-controlled trial.

Methods: A total of 230 dry eye subjects selected with use of a controlled adverse environment were randomized 1:1:1:1 to receive SAR 1118 (0.

Ocular iontophoresis of EGP-437 (dexamethasone phosphate) in dry eye patients: results of a randomized clinical trial.

Purpose: To assess safety and efficacy of EGP-437 (dexamethasone phosphate 40 mg/mL [DP]) in dry eye patients.

Methods: The study employed a prospective, single-center, double-masked design utilizing a Controlled Adverse Environment (CAE). Patients (n = 103) with confirmed signs and symptoms of dry eye syndrome were randomized into 1 of 3 iontophoresis treatment groups: 7.

Diurnal variation of visual function and the signs and symptoms of dry eye.

Purpose: Subjects with dry eye often complain of disturbances in visual function and worsening of symptoms in the evening. To clinically substantiate these reports of diurnal variations, the present study tested subjects with dry eye on a series of visual function and ocular physiology measures.

Methods: Twenty-one subjects with dry eye were enrolled and underwent ophthalmic examinations, including best spectacle-corrected visual acuity, visual function decay as measured by the interblink interval visual acuity decay test without ocular anesthetic, reading rate test, slit-lamp biomicroscopy, and tear film breakup time.