a Novel siRNA Eyedrops for DED Treatment

• Age ≥18 years at the time of consent.
• Provision of written informed consent.
• Male and female subjects of childbearing potential agree to use medically approved contraception during the trial and for 90 days after the trial ends.
• Subject-reported history of Dry Eye Disease (DED) in both eyes for at least 6 months prior to Visit 0.
• Subjects who have used artificial tears within 30 days prior to Visit 0 must discontinue their use for at least 72 hours before Visit 0.
• Tear film break-up time (TFBUT) ≤5 seconds at Visit 0.
• Ocular Surface Disease Index (OSDI) score ≥25 at Visit 0.
• Unanesthetized Schirmer's Test I ≤10 mm/5 minutes at Visit 0.
• Total corneal fluorescein staining (tCFS) score ≥2 (NEI scale, sum of 5 regions) at Visit 0.
• At least one eye (the same eye) must satisfy all criteria for TFBUT, Schirmer's Test, and tCFS at Visit 0.
• Ability and willingness to follow instructions, including participation in all trial assessments and visits.

Exclusion Criteria:

• History of ocular or periocular malignancies.
• DED secondary to scarring (e.g., radiation, chemical burns, Stevens-Johnson syndrome) or conjunctival goblet cell destruction.
• Active or anticipated ocular allergies during the trial.
• Ocular or systemic infections (bacterial, viral, or fungal), including fever, herpes simplex keratitis, or ongoing antibiotic therapy at Visit 0.
• History of glaucoma.
• History of immunodeficiency, HIV, hepatitis B/C, acute hepatitis A, or organ/bone marrow transplantation.
• Significant chronic disease interfering with study parameters (e.g., severe cardiopulmonary disease, uncontrolled hypertension, or diabetes), as determined by the investigator.
• Blood donation or significant blood loss (>400 mL) within 56 days prior to Visit 0.
• Active ocular rosacea, periocular acne, or pterygium.
• Eyelid anatomical abnormalities (e.g., lagophthalmos, entropion, or ectropion) or abnormal blinking.
• Clinically significant slit-lamp or fundus findings requiring treatment or potentially interfering with trial results.
• Intraocular or ocular laser surgery or meibomian gland procedures within 180 days prior to Visit 0, or planned during the trial.
• Punctal plug insertion or removal within the specified windows (60 days for surgical procedures and 180 days for dissolvable plugs), or planned insertion/removal or expected dissolution during the trial.
• Use of systemic immunomodulators, oral doxycycline, or tetracyclines within 90 days prior to Visit 0, or anticipated irregular use during the trial.
• Use of topical immunomodulators (e.g., cyclosporine A or tacrolimus) within 30 days prior to Visit 0.
• Use of medications known to induce dry eye (e.g., diuretics, antidepressants, or antihistamines) within 30 days prior to Visit 0, or anticipated irregular use.
• Active blepharitis or meibomian gland dysfunction (MGD) treated with eyelid scrubs, massage, systemic antibiotics, or similar treatments within 30 days prior to Visit 0, or anticipated irregular treatment.
• Use of ocular or systemic steroids or mast cell stabilizers within 30 days prior to Visit 0.
• Contact lens wear within 14 days prior to Visit 0 or planned use during the trial.
• Known hypersensitivity to the investigational drug, excipients, fluorescein, or trial-related substances.
• Pregnant, lactating, or planning pregnancy.
• Household members enrolled in this trial, or direct involvement of study staff or their relatives in trial management.
• Participation in other drug or device trials within 30 days or 5 half-lives (whichever is longer) prior to screening, or planned participation during this trial.
• Any condition that, in the judgment of the investigator or sponsor, may pose significant risk, confound study results, hinder participation, or compromise the subject's best interests.