Intense pulsed light (IPL) has been reported to improve signs and symptoms of dry eye (DE). Additionally, meibomian gland secretion of lipids has been observed to improve through the use of IPL. Diquafosol ophthalmic solution (DQS) stimulates P2Y2 receptors on the ocular surface, which enhances mucin secretion from goblet cells. Therefore, tear film stability and hydration of the ocular surface can be achieved independent from lacrimal glands function. The purpose of this prospective study was to evaluate and compare the effects of IPL (IPL group), DQS (DQS group) and IPL in combination with DQS (IPL+ group) in participants with persistent DE. Tear film lipid layer (TFLL), non-invasive breakup time (NITBUT), tear meniscus height (TMH), corneoconjunctival staining score (CS), meibum gland (MG) function, conjunctival hyperemia (RS score), ocular surface disease index (OSDI) will be assessed and compared at baseline, day-14, and day-28.

Evaporative dry eye (EDE) has been reported to be the most prevalent form of dry eye disease (DED), which is primarily caused by meibomian gland hypofunction or meibomian gland dysfunction (MGD). MGD is defined as ''a chronic, diffuse anomaly of the meibomian glands, often characterized by terminal duct blockage and/or qualitative/quantitative alterations in glandular secretion'' by the International Workshop on MGD.These glands are modified sebaceous glands that release meibum directly onto the ocular surface. Signs and symptoms of EDE and MGD can be addressed by improving the quality and quantity of meibum secretion.

Intense pulsed light (IPL) is widely used to treat dermatological conditions, and its noncoherent polychromatic light source with wide wavelength range of 500-1200 nm has been reported to stimulate facial sebaceous glands. The photothermal effect of IPL is postulated to relieve inflammation by removing aberrant surface microvasculature and enhances meibomian gland function. Furthermore, an increase in fibroblast proliferation, collagen formation and local blood flow has been associated with the application of IPL on the skin. Several studies have documented the benefits of IPL in alleviating signs and symptoms of DED on the periocular skin.

Diquafosol ophthalmic solution (DQS) is a dinucleotide polyphosphate which a purinoceptor agonist, when administered to the ocular surface, it binds to P2Y2 receptors and stimulates mucin and tear secretion. The corneal epithelium, conjunctival epithelium, lacrimal gland ductal epithelium, meibomian gland sebaceous cells, and meibomian gland ductal cells all express the P2Y2 receptor. Subsequently, enhanced secretion of mucin and tear secretion due to DQS ophthalmic solution leads to stabilization of the tear film, minimizes tear evaporation, and reduces mechanical friction thereby protecting the corneal epithelium.

The purpose of this study is to assess the management of DE by combining IPL and DQS eye drops.

Inclusion Criteria:

• Age ≥18 years
• Consenting participants
• Able and willing to comply with the treatment/follow-up schedule
• Bilateral signs and symptoms of dry eye disease: (i) Ocular Surface Disease Index (OSDI) questionnaire ≥13, (ii) Non-invasive tear break-up (NITBUT) ≤ 5 seconds, (iii) conjunctival staining score (CS) ≥3 points. The presence of two or more criteria was used to establish a positive DE diagnosis based on the 2016 Asia Dry Eye Society criteria

Exclusion Criteria:

• A recent history (past 30 days) of topical ophthalmic medication use, including antibiotics, steroids, non-steroidal anti-inflammatory drugs, or required the chronic use of topical ophthalmic medications.
• Eyelids or intraocular tumors.
• Active allergy or infection, or inflammatory disease may prevent the subjects from completing the study at the ocular surface.
• Any structural changes in the lacrimal passage
• Glaucoma
• Diabetes or other systemic, dermatologic, or neurologic diseases that affect the health of the ocular surface.
• Use of any systemic anti-inflammatory drugs or medication that may interfere with tear production, such as antianxiety, anti-depressive, and antihistamine medications, within three months.
• Pregnancy or breastfeeding
• Contact lenses wearers.

The study's findings will be shared regardless of the effect's direction. All possible beneficiaries of the research, including patients, carers, family, doctors, advisory boards, and medical boards, will receive trial data. Publications in high impact, open-access medical journals and talks at national and international medical conferences will serve this purpose.

The Steering Committee will write and submit the report for publication at the end of the study

Use in clinical studies

Masked examiner for all clinical assessments will not involved in the data collection or group allocation procedure for this research. The investigator will not be aware of the three groups.