Cyclosporine and Intense Pulsed Light for Dry Eye in Contact Lens Users

Dry Eye Clinical Trial

— CycliP  

Official title:

Combination of 0.09% Cyclosporine and Intense Pulsed Light (IPL) Therapy for the Treatment of Dry Eye Disease in Symptomatic Contact Lens Wearers: a Sham-Controlled Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06392438
• Other study ID #: 2024-5200
• Status: Recruiting
• Phase: Phase 3
• Start date: April 25, 2024
• Est. completion date: September 2025

Study information

• Verified date: April 2024
• Source: Université de Sherbrooke
• Contact: Patrick Boissy, PhD
• Phone: 819-780-2220
• Email: patrick.boissy[@]usherbrooke.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study, two treatments typically used for dry eye disease will be tried for contact lens users to see if their symptoms when they use their contact lenses get better. Cyclosporine is a drop that is used for long-term management of the inflammation and Intense pulsed light (IPL) is a treatment done in a clinic to improve the health of the eyelid glands. The main question in this study is:

Does the combined treatment of cyclosporine and IPL improve the symptoms and the dry eye signs of contact lens wearers?

All the participants will receive the cyclosporine drops for 4 months twice a day. The research team will split the group of participants in two, half receiving the real IPL treatment and half receiving a sham IPL treatment during the last two months of the study. This will allow to compare the two groups to see how IPL helped. The dry eye tests will be done at the start of the study, after two months and after 4 months. The tests will include a dry eye symptoms questionnaire, measures on the tears, the structures of the front of the eye and the eyelids.

Description:

Dry eye disease is a complex and multifactorial pathology in which inflammation and changes to the tear film (instability and hyperosmolarity) play important roles. Dry eye disease is very common, with an estimated global prevalence of 11.59% although other analyses conclude to 50% of some populations suffering from dry eye. The condition has been traditionally classified in two subtypes: aqueous tear deficiency (secondary to a deficit of production by the lacrimal gland) and evaporative disease (secondary to a deficit of the lipid layer of the tear film), but when the condition progresses, almost all patients present characteristics of both subtypes. Meibomian gland dysfunction (MGD) is one of the conditions that is most frequently associated with dry eye disease and leads to evaporative dry eye and alterations of the ocular surface. The prevalence of MGD has been recently established between 21.2% and 29.5% in subjects of African and Caucasian race and higher among Arabs, Hispanics, and Asians. Many risk factors exist for dry eye disease and MGD, including age and usage of contact lens. Soft contact lenses (SCL) are used by hundreds of millions for visual correction. The wear of SCL, however, has the potential to create or worsen dry eye signs and symptoms. A comparative study has found that 39% of North-American wearers can be categorized as symptomatic of contact lens dry eye and the proportion of uncomfortable users increases with age. SCL wear can increase evaporative dry eye by weakening the lipid layer, which leads to decreased stability of the tear film and increased evaporation. It also contributes to aqueous dry eye etiology by reducing the tear volume. The wear of SCL has also been shown to have a damaging effect on meibomian glands and, in some cases, on the conjunctival goblet cells .

Arguments also support the role of SCL in the inflammation of the ocular surface, even in asymptomatic patients. Thus, dry eye disease associated with SCL wear is a complex condition that implies different mechanisms.

Cyclosporine A is a peptide produced by a fungus that has been used systemically for decades for its potent immunomodulatory effects. Usage for dry eye disease in a topical 0.05% oil-based formulation has been common since the early 2000s. On the ocular surface, cyclosporine acts by inhibiting calcineurin, which subsequently blocks the activation of T cells and prevents the release of cytokines, therefore reducing inflammation. It has been shown to increase tear volume, goblet cell density and to reduce surface staining as well as symptoms in dry eye patients. Divergent results have been observed on contact lens wearers, although one study has found an amplified effect on contact lens wearers symptomatic of dry eye when combining essential fatty acid supplements with topical cyclosporine. Despite having been shown useful in the management of dry eye disease, the oil-based formulation is considered having a low bioavailability. A new cyclosporine eyedrop has been approved in Canada and the USA in the recent past years and is based on nanomicelle technology with a concentration of 0.09%. This nano-micellar formulation could be more effective in delivering the cyclosporine to the tissues and have been shown to reduce ocular surface staining, to increase tear volume, and to be safe. Adverse events that are known to this product are mild, such as transient pain at instillation for about 23% of patients.

Intense pulsed light (IPL) is a therapeutic process that has been used for many years in dermatology and esthetics. The noncoherent pulses of light produce photo-biochemical effects and, in the treatment of dry eye disease, the application on the skin around the orbit to produces these effects on the meibomian glands and their surrounding tissue. The mechanisms by which IPL improves signs and symptoms of dry eye are not fully understood, but the melting of the meibum, the clogging of telangiectatic inflammatory vessels, the reduction of epithelial turnover, the improvement in the collagen synthesis, a mitochondrial activity enhancement (photo modulation), and the destruction of parasitic and bacterial species are the main theoretical explanations. IPL has been shown to be an effective therapeutic option to manage MGD.

Dozens of studies have shown that IPL reduces dry eye symptoms, increases tear break-up time, improves the secreting function of the glands as well as the quality of the meibum and reduces corneal staining. IPL is often combined with meibomian gland expression to maximize the therapeutic effects; however, controlled studies have shown that IPL is largely responsible of these effects and that it is the core mechanism of this combination. Two studies have observed the effect of IPL on SCL users, with the conclusion that it is an effective treatment for this population. IPL is considered to be a safe treatment.

Since SCL have been linked to both aqueous and evaporative etiologies or dry eye, this research project aims to study the effect of combining these two treatments to target the entirety of the tear film, believed to be essential to comfortable SCL wear. This study will be a randomized clinical trial that contains two interventions: the 0.09% cyclosporine eyedrops (Cequa) and IPL treatment. The main objective of this study is to establish if the treatment of contact lens related dry eyes by the combination of 0.09% cyclosporine for 16 weeks and a standard IPL treatment (3 sessions) is more effective in relieving dry eye symptoms when compared to 0.09% cyclosporine for 16 weeks with a sham IPL treatment (3 sessions). The secondary objectives are to compare the effects of each treatment combination (0.09% cyclosporine+IPL vs 0.09% cyclosporine+sham) on signs of dry eye, to explore the effects of cyclosporine 0.09% drops alone on contact lens wearers and to assess the security profile of these interventions on SCL wearers.

Based on prior data from the f-CLDEQ-8 validation study, a major study on the cyclosporine nanomicelle formulation and the first clinical trial on IPL for contact lens wearers, a sample size of 44 participants (22/group) was calculated to be necessary to detect a significant difference between the groups. 44 participants will thus be recruited from a primary care optometric clinic and nearby clinics. Participation to the study will require 5 visits from the participants. The first visit will be a collection of data and the dispensing of the 0.09% cyclosporine drops. 8 weeks later, the participants will present for their 2nd visit, during which data will be collected once again and participants will be randomized to either the treatment or the sham group and will receive their first treatment (IPL or sham accordingly to the assignation). The 2 following visits, 3 weeks apart, will be for the 2 last IPL/sham treatments. A final visit will be for data collection 2 weeks after the last IPL/sham treatment. Participants will take 0.09% cyclosporine for the whole 16 weeks.

A bilateral t-test for independent samples will be used to compare the difference in change on the f-CLDEQ-8 between groups on the 16 weeks interval. Concerning the dry eye signs, statistical treatment will be made to account for inter-eye correlation. Continuous variables will be analyzed using a multi-level model to assess the difference in change between groups on the 16 weeks interval. Discrete variable will be analyzed using a general linear model (GLM) for the same comparison. Data will be handled in an intent-to-treat way.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Soft silicone-hydrogel contact lens wearers

• Monthly, 2-weeks, opr daily replacement schedule of contact lens

• Minimum wear of contact lens for 1 day/week and 4 hours consecutive

• f-CLDEQ-8 score = 12

Exclusion Criteria:

• Past usage of cyclosporine 0.09% (Cequa)

• Use of another ophthalmic cyclosporine drop in the past 6 months

• Known intolerance to cyclosporine

• Pregnancy or breastfeeding (or planned pregnancy in the duration study)

• History of ocular herpes simplex infection

• Active ocular infectious condition

• Usage of photosensitizing medication

• Epilepsy

• History of skin cancer in the IPL treatment zone

• Tattoo/pigmented lesion/keloid scars in the IPL treatment zone

• Refractive surgery in the past 12 months

• In-clinic thermal pulsation eyelid treatment in the past 12 months

• Usage of glaucoma drops

• Regular continuous wear of contact lenses (including sleep)

• Excessive movement or decentration of the contact lenses (assessed at first visit)

• Giant papillary conjunctivitis

Related Conditions & MeSH terms

• Contact Lens Complication
• Dry Eye
• Dry Eye Syndromes
• Keratoconjunctivitis Sicca

Intervention

Drug:
• CycloSPORINE Ophthalmic
Unidose of Cequa provided without charge to the participant. 1 drop in each eye morning and evening.

Procedure:
• Intense Pulsed Light
Appropriate eye patches and IPL gel will be applied. 15 triggers per passage will be applied from the right temple to the left temple (7 shots from the right temple to the right nose wing, 1 on the nose bridge and 7 shots from the left nose wing to the left temple). 2 passage/session will be applied.
• Sham Intense Pulse Light
Appropriate eye patches and IPL gel will be applied. 15 triggers per passage will be applied with the plastic blocker mounted on the IPL prism from the right temple to the left temple (7 shots from the right temple to the right nose wing, 1 on the nose bridge and 7 shots from the left nose wing to the left temple). 2 passage/session will be applied.

Locations

Country	Name	City	State
Canada	Opto-Réseau Sherbrooke Est	Sherbrooke	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Université de Sherbrooke

Country where clinical trial is conducted

Canada, 

References & Publications (62)

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Xue AL, Wang MTM, Ormonde SE, Craig JP. Randomised double-masked placebo-controlled trial of the cumulative treatment efficacy profile of intense pulsed light therapy for meibomian gland dysfunction. Ocul Surf. 2020 Apr;18(2):286-297. doi: 10.1016/j.jtos.2020.01.003. Epub 2020 Jan 30. — View Citation

Yan S, Wu Y. Efficacy and safety of Intense pulsed light therapy for dry eye caused by meibomian gland dysfunction: a randomised trial. Ann Palliat Med. 2021 Jul;10(7):7857-7865. doi: 10.21037/apm-21-1303. — View Citation

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* Note: There are 62 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Contact lens dry eye symptoms	f-CLDEQ-8 questionnaire (French version of the Contact Lens Dry Eye Questionnaire - 8). Scores possible are from 1 to 37; higher score means more symptoms and worse dry eye	Measured at each visit (Baseline, week 8, week 11, week 14 and week 16)
Secondary	Global rating scale of change	Rating 0-100 of perceived comfort during contact lens wear in the past days; question sent by platform of ecological momentary assessment REDCap	Tuesday and Saturday of every week for 16 consecutive weeks (while participating in the study)
Secondary	Average number of hours spent wearing contact lenses	Question sent by platform of ecological momentary assessment REDCap	Tuesday and Saturday of every week for 16 consecutive weeks (while participating in the study))
Secondary	Artificial tear usage while wearing contact lenses	Question sent by platform of ecological momentary assessment REDCap	Tuesday and Saturday of every week for 16 consecutive weeks (while participating in the study)
Secondary	Non-invasive tear break-up time over contact lenses (pre-lens tear film)	Measured with the TFSQ NIBUT of the Medmont corneal topographer	Baseline, week 8, and week 16
Secondary	Non-invasive tear break-up time (natural tear film)	Measured with the TFSQ NIBUT of the Medmont E300 corneal topographer	Baseline, week 8, and week 16
Secondary	Tear break-up time	Average of 3 readings with fluorescein and observation through a slit lamp using cobalt and yellow filter	Baseline, week 8, and week 16
Secondary	Corneal staining score	Pictures of the cornea taken through an anterior segment imagery system (mounted on slit lamp) after fluorescein instillation. Pictures analyzed by automated AOS system, which counts the exact number of corneal punctate lesions	Baseline, week 8, and week 16
Secondary	Conjunctival staining score	Pictures of the nasal and temporal conjunctiva taken through an anterior segment imagery system (mounted on slit lamp) after lissamine green instillation. Pictures analyzed by masked experienced rater and graded using Efron grading scale (grade 0 to 4, a higher score meaning worse condition)	Baseline, week 8, and week 16
Secondary	Tear meniscus height (with contact lens in place)	Measured at the inferior meniscus with the Myah (Topcon) automated function before contact lens removal	Baseline, week 8, and week 16
Secondary	Tear osmolarity (with contact lens in place)	Measured on inferior palpebral conjunctiva with the iPen (i-Med) before contact lens removal	Baseline, week 8, and week 16
Secondary	Meibomian gland atrophy	Meibography scans performed on all 4 eyelids with the Lipiscan (Johnson & Johnson) and sent to masked experienced rater for rating using the Meiboscore (Pult)	Baseline and week 16
Secondary	Adverse effects	Measured with home questionnaire containing 16 questions on adverse effects from both interventions	Week 8, week 11, week 14, and week 16
Secondary	Distance visual acuity	Variable measured for safety assessment. Snellen chart used with current correction (contact lens or glasses)	Measured at each visit (Baseline, week 8, week 11, week 14 and week 16)
Secondary	Intraocular pressure	Variable measured for safety assessment. Non-contact airpuff tonometer (Nidek RKT-7700)	Measured at each visit (Baseline, week 8, week 11, week 14 and week 16)