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

Dry Eye Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05131152
• Other study ID #: 2021KYPJ186
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2021
• Est. completion date: May 2024

Study information

• Verified date: February 2022
• Source: Zhongshan Ophthalmic Center, Sun Yat-sen University
• Contact: Yuqing Deng, MD
• Phone: 18120557291
• Email: 15927646647[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: May 2024
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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).

Related Conditions & MeSH terms

• Dry Eye
• Dry Eye Syndromes
• Keratoconjunctivitis Sicca

Intervention

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

Locations

Country	Name	City	State
China	Zhongshan Ophthalmic Center, Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Zhongshan Ophthalmic Center, Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Conjunctival microvascular blood flow		12 weeks after commencement of treatment-16 weeks after commencement of treatment
Other	Df (vascular complexity index)		12 weeks after commencement of treatment-16 weeks after commencement of treatment
Other	D0 (vascular density index)		12 weeks after commencement of treatment-16 weeks after commencement of treatment
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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