Microvascular and Inflammatory Responses of 0.05 Cyclosporine Eye Drop (II) in Treatment of Dry Eye

Microvascular and Inflammatory Responses of 0.05 Cyclosporine Eye Drop (II) in Treatment of Mild to Moderate Dry Eye

To explore the law of changes in ocular surface inflammation when 0.05% cyclosporine eye drops (II) is used to treat dry eye, 50 cases of mild to moderate dry eyes were included. The expectation is finding out whether cyclosporine has a regulatory effect on conjunctival microvascular parameters and other inflammation indicators after cyclosporine eye drops treat dry eye, and analyze the value of conjunctival microvascular indicators in dry eye immunosuppressive therapy.

Study Overview

• Status: Recruiting
• Conditions: Dry Eye
• Intervention / Treatment: Drug: Cyclosporine; Device: oculus keratograph, in vivo laser confocal microscopy, Functional slit lamp biomicroscopy

Detailed Description

Dry eye is a common ocular surface disease that affects people's visual function and quality of life. In recent years, with the changes of lifestyles, the prevalence of dry eye is gradually increased. According to the consensus definition of Chinese dry eye experts in 2020, dry eye is a chronic ocular surface disease caused by multiple factors, while inflammation is emphasized as an important role in the occurrence and development of dry eye. Therefore, in addition to use artificial tears to alleviate the symptoms of dry eye, it is clinically recommended to combine low-concentration ocular surface hormones or immunosuppressant for anti-inflammatory therapy. As an immunosuppressant, cyclosporine can inhibit the infiltration of CD4+ T cells on the ocular surface, inhibit the apoptosis of conjunctival goblet and lacrimal gland acinar cells, and effectively alleviate ocular surface inflammation. In addition, cyclosporine can inhibit the calcineurin pathway by forming an intracellular complex with cyclophilin, promote the production of tears, and increase the density of goblet cells. Cyclosporine has an impact on many molecules in the immune pathway of dry eye.

However, how to use and adjust immunosuppressant according to the ocular surface inflammation still depends on the subjective experience of doctors, and there is no uniform standard. Therefore, finding biological reference indicators for ocular surface inflammation is the key to promoting the standardization and precision of anti-inflammatory drugs. The stimulation of inflammation factors can lead to the expansion of the capillary network, thus, the function of ocular surface capillaries can be used as an important indicator of ocular surface inflammation. Now, the intelligent analysis technology based on ocular surface micro vessels owned by my research team can clearly obtain blood flow imagines and topographic maps of blood vessel distribution in conjunctival micro vessels, and quantify the changes in microvascular shape, density and complexity, which is a kind of non-contact and convenient evaluation method. In our previous studies, it was confirmed that the treatment of moderate to severe dry eye with low concentrations of ocular surface hormones can cause changes of ocular surface microvascular parameters. Investigators hope to further observe the temporal and spatial changes of ocular surface microvascular function during the treatment of dry eye with cyclosporine, and correlation with inflammatory cells, inflammatory factors and neuroinflammation, explore the effect of the drug on dry eye related inflammation target issues and the guiding value of conjunctival microvascular indicators in dry eye immunosuppressive therapy, in order to change the previous dry eye anti-inflammatory treatment and the mode of medication based on the doctor's personal experience.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yuqing Deng, MD; Phone Number: 18120557291; Email: 15927646647@163.com
• Study Contact Backup: Name: Jin Yuan, PHD

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Zhongshan Ophthalmic Center, Sun Yat-sen University
      • Contact: Yuqing Deng, MD; Phone Number: 18120557291; Email: 15927646647@163.com
      • Contact: Jin Yuan, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-65 years old;
• meet the 2-3 grade dry eye diagnosis: 1) At least one eye has one or more ocular discomfort symptoms and OSDI score ≥23; 2) At least one eye meets one of the following two: 2 mm/5min≤Schirmer I test (no anesthesia) <10 mm/5min; BUT≤10s. 3) Corneal spotting but no extensive erosion.

Exclusion Criteria:

• Contact lens wearers;
• Allergies to the study drug;
• Active eye infections; history of serious systemic diseases;
• Pregnancy or breastfeeding;
• Receiving or starting other treatments that may interfere with the interpretation of the results;
• Participating any other clinical trials within 3 months;
• Previous eye surgery, including laser treatment and refractive surgery;
• Need or have undergone punctal embolization or nasolacrimal duct obstruction;
• KCS secondary to the destruction of conjunctival goblet cells (such as vitamin A deficiency) ;
• Scar formation (such as cicatricial pemphigus, alkali burn, trachoma or radiation).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cyclosporine group; Mild DE patients: topical usage of 0.05% cyclosporine Eye Drops BID + 0.1% Sodium Hyaluronate Eye Drops QID, both use for 16 weeks. Moderate DE patients: topical usage of 0.05% cyclosporine Eye Drops BID +0.1% Sodium Hyaluronate Eye Drops QID, both use for 16 weeks, and 0.02% Fluoromethalone Eye Drops BID for 4 weeks.	Drug: Cyclosporine; 0.05% cyclosporine Eye Drops; Sodium Hyaluronate Eye Drops, 0.02% Fluoromethalone Eye Drops.; Device: oculus keratograph, in vivo laser confocal microscopy, Functional slit lamp biomicroscopy; oculus keratograph, in vivo laser confocal microscopy, Functional slit lamp biomicroscopy
Experimental: control group; Mild DE patients: 0.1% Sodium Hyaluronate Eye Drops QID for 16 weeks Moderate DE patients: 0.02% Fluoromethalone Eye Drops BID for 4 weeks +0.1% Sodium Hyaluronate Eye Drops QID for 16 weeks.	Device: oculus keratograph, in vivo laser confocal microscopy, Functional slit lamp biomicroscopy; oculus keratograph, in vivo laser confocal microscopy, Functional slit lamp biomicroscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conjunctival microvascular blood flow velocity	Achieved by Functional slit lamp Biomicroscopy: a traditional slit lamp (HAAG-STREIT SWISS MADE 900.7.2.34925) with a digital. camera (Canon 60D. Canon Inc, Melville, NY) and a custom software.	12 weeks after commencement of treatment-16 weeks after commencement of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tear collection and analysis	After communicating with the patient, 5 μL of tear fluid was collected with a 5 μL capillary tear collector at the medial and lateral canthus (collected three times per eye and mixed the tears from the left and right eyes into one centrifuge tube). The sample was transferred into Centrifuge tubes and stored at -80 °C until further analysis. Cytokine concentrations were measured using microsphere-based immunoassay analysis.	12 weeks after commencement of treatment-16 weeks after commencement of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conjunctival microvascular blood flow		12 weeks after commencement of treatment-16 weeks after commencement of treatment
Df (vascular complexity index)		12 weeks after commencement of treatment-16 weeks after commencement of treatment
D0 (vascular density index)		12 weeks after commencement of treatment-16 weeks after commencement of treatment
Conjunctival microvascular diameter	Acheived by a traditional slit lamp (HAAG-STREIT SWISS MADE 900.7.2.34925) with a digital camera (Canon 60D. Canon Inc, Melville, NY) and a custom software.	12 weeks after commencement of treatment-16 weeks after commencement of treatment
The hyperemia index	The hyperemia index (HI) was measured by determining the percentage of conjunctival microvascular area in the conjunctiva automatically. The subjects were required to keep their eyes open and focus on the illuminated ring in front. Three consecutive readings were recorded, and the median was used. All data were recorded and analyzed with TF-scan software in the system of Keratograph 5M (Oculus, Wetzlar, Germany).	12 weeks after commencement of treatment-16 weeks after commencement of treatment
Ocular Surface Disease Index (OSDI)	The dry eye diagnosis flowchart begins with history-taking, risk factors are questioned in suspicious cases, and a screening test such as the Ocular Surface Disease Index (OSDI) Questionnaire is applied.	12 weeks after commencement of treatment-16 weeks after commencement of treatment
Non-invasive tear-film break-up time	Non-invasived tear-film break-up time is measured by tear film pattern of Keratograph 5M (Oculus, Wetzlar, Germany) with a scale of seconds. Higher values represent a better outcome.	12 weeks after commencement of treatment-16 weeks after commencement of treatment
Schirmer I test	The tear production was measured with Schirmer strips without anaesthesia 15 minutes after corneal staining.	12 weeks after commencement of treatment-16 weeks after commencement of treatment
Corneal Fluorescein Staining	Fluorescein was administered into the conjunctival sac under a cobalt blue light from the slit lamp. Corneal epithelial cell disruption was measured via corneal staining (National Eye Institute (NEI) scale (0-3 scale for each area of 5 areas, total score 15). Higher values represent a worse outcome.	12 weeks after commencement of treatment-16 weeks after commencement of treatment
Infrared imaging of meibomian gland	Infrared photography of the upper meibomian glands were measured and imaged by tear film and meibography pattern of Keratograph 5M (Oculus, Wetzlar, Germany).	12 weeks after commencement of treatment-16 weeks after commencement of treatment
In Vivo Confocal imaging	IVCM image acquisition for all DE patients was completed using the in vivo corneal confocal microscopy (Heidelberg Engineering GmbH, 101 Heidelberg, Germany).	12 weeks after commencement of treatment-16 weeks after commencement of treatment

Collaborators and Investigators

• Sponsor: Zhongshan Ophthalmic Center, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: November 10, 2021
• First Submitted That Met QC Criteria: November 10, 2021
• First Posted (Actual): November 23, 2021

Study Record Updates

• Last Update Posted (Actual): February 11, 2022
• Last Update Submitted That Met QC Criteria: February 9, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: inflammation; dry eye; conjunctival micro-circulation
• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 2021KYPJ186

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No