This is a Single Center, Open-label Prospective Study to Evaluate the Effect of Xiidra® (Lifitegrast Ophthalmic Solution 5.0%) on Tear Film Biomarkers in Dry Eye

Single-Center, Open-Label Trial to Evaluate the Effect of Lifitegrast Ophthalmic Solution 5.0% on Tear Film Biomarkers in Dry Eye Disease

This is a single-center prospective open-label, clinical trial to explore proteomic expression of tear fluid biomarkers in patients with dry eye treated with Lifitegrast.

Approximately 30 subjects with dry eye disease (DED) will receive Xiidra®, while 6 non DED subjects will serve as a non treatment group. The study will evaluate changes in tear fluid biomarker expression using mass spectrometry-based proteomic analysis.

Inclusion Criteria: DED Subjects receiving Xiidra®

1. At least 18 years of age or older at time of screening
2. Ability to understand and provide informed consent
3. Subject reported 6-month history of DED in both eyes
4. No use of ophthalmic drops other than lifitegrast within 2 hours of tear fluid collection to minimize interference with baseline biomarker levels
5. Willingness to comply with follow-up schedule and required visits
6. Corneal fluorescein staining score of inferior 1/3rd of cornea ≥ 2
7. EDS ≥40 (0-100-point VAS, both eyes) at Day 0
8. Schirmer ≥ 5 and ≤ 10 (without anesthesia)
9. Best corrected visual acuity (BCVA) of 0.7 logMAR of better (logMAR <0.7; Snellen equivalent score

Exclusion Criteria: DED Subjects receiving Xiidra®

1. Have a known hypersensitivity or contraindication to the product or their components.

2. Active ocular infection within the last 30 days.

3. Any ocular surgical procedure within the last 6 months.

4. Any subject who has previously tried and failed a course of lifitegrast.

5. Unwilling to discontinue contact lens use for the duration of the study.

6. Any female of childbearing potential (FOCBP) who is unwilling to agree to: a) Have a urine pregnancy testing performed at Baseline (Day 0) b) Use at least 1 medically acceptable form of birth control for at least 14 days prior to the first dose of study drug, throughout the study duration, and for 1 month after the last dose of investigational drug. NOTE: FOCBP include all females who have experienced menarche and have not experienced menopause (as defined by amenorrhea for greater than 12 consecutive months) or have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) NOTE: Acceptable forms of birth control include:

   • Mechanical (spermicide in conjunction with a barrier such as a diaphragm or condom)
   • Hormonal contraceptive (oral, injectable, implantable, or transdermal)
   • Intrauterine device, or
   • Surgical sterilization of male partner at least 3 months prior to the first dose of investigational drug NOTE: For non-sexually active female subjects, abstinence may be regarded as an adequate method of birth control when this is in line with the preferred and usual lifestyle of the subject; however, if the subject becomes sexually active during the trial, she must agree to use adequate birth control as defined above for the remainder of the trial.

7. Any male who is unwilling to agree to use at least 1 medically acceptable form of birth control with female partner (FOCBP) who also is not using an acceptable form of birth control (as described above). NOTE: Acceptable forms of birth control include: • True abstinence (when this is in line with the preferred and usual lifestyle of the subject), or • Vasectomy at least 3 months prior to the first dose of study drug. Without a vasectomy, must use condoms with spermicidal foam, gel, film, cream, suppository at least 14 days prior to the first dose of investigational drug and throughout the study duration, and for 1 month after the last dose of the investigational drug.

8. Pregnancy or lactation

9. Current or past treatment with prescription drops for dry eye within the last six weeks.

10. Any ocular condition that, in the opinion of the investigator, could affect study parameters including, but not limited to, lid margin disorders (e.g. Blepharitis, staphylococcal, demodex etc.)

11. Any known history of immunodeficiency disorder, human immunodeficiency virus, hepatitis B or C, evidence of acute active hepatitis A (antihepatitis A virus immunoglobulin M), or organ or bone marrow transplant.

12. Any known history of alcohol and/or drug abuse within 12 months prior to the screening visit that, in the opinion of the investigator, may have interfered with study compliance, outcome measures, safety parameters, and/or the general medical condition of the subject.

Inclusion Criteria: (Non-DED) subjects not receiving Xiidra® (non-treatment arm)

1. At least 18 years of age or older at time of screening
2. Ability to understand and provide informed consent
3. No use of ophthalmic drops within 2 hours of tear fluid collection to minimize interference with baseline biomarker levels
4. Willingness to comply with follow-up schedule and required visits
5. No subject reported history of DED
6. Schirmer ≥ 10 (without anesthesia)
7. Best corrected visual acuity (BCVA) of 0.7 logMAR of better (logMAR <0.7; Snellen equivalent score of 20/100 or better) in each eye at the screening visit (Day 0).

Exclusion Criteria: (Non-DED) subjects not receiving Xiidra® (non-treatment arm)

1. Active ocular infection within the last 30 days

2. Any ocular surgical procedure within the last 6 months

3. Unwilling to discontinue contact lens use for the duration of the study

4. Pregnancy or lactation

5. Any female of childbearing potential (FOCBP) who is unwilling to agree to: a) Have a urine pregnancy testing performed at Baseline (Day 0) b) Use at least 1 medically acceptable form of birth control for at least 14 days prior to the first dose of study drug, throughout the study duration, and for 1 month after the last dose of investigational drug. NOTE: FOCBP include all females who have experienced menarche and have not experienced menopause (as defined by amenorrhea for greater than 12 consecutive months) or have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) NOTE: Acceptable forms of birth control include:

   • Mechanical (spermicide in conjunction with a barrier such as a diaphragm or condom)
   • Hormonal contraceptive (oral, injectable, implantable, or transdermal)
   • Intrauterine device, or
   • Surgical sterilization of male partner at least 3 months prior to the first dose of investigational drug NOTE: For non-sexually active female subjects, abstinence may be regarded as an adequate method of birth control when this is in line with the preferred and usual lifestyle of the subject; however, if the subject becomes sexually active during the trial, she must agree to use adequate birth control as defined above for the remainder of the trial.

6. Any male who is unwilling to agree to use at least 1 medically acceptable form of birth control with female partner (FOCBP) who also is not using an acceptable form of birth control (as described above). NOTE: Acceptable forms of birth control include: True abstinence (when this is in line with the preferred and usual lifestyle of the subject), or Vasectomy at least 3 months prior to the first dose of study drug. Without a vasectomy, must use condoms with spermicidal foam, gel, film, cream, suppository at least 14 days prior to the first dose of investigational drug and throughout the study duration, and for 1 month after the last dose of the investigational drug.

7. History of DED diagnosis

8. Any ocular condition that, in the opinion of the investigator, could affect study parameters including, but not limited to, lid margin disorders (eg. Blepharitis, staphylococcal, demodex etc.)

9. Any known history of immunodeficiency disorder, human immunodeficiency virus, hepatitis B or C, evidence of acute active hepatitis A (antihepatitis A virus immunoglobulin M), or organ or bone marrow transplant.

10. Any known history of alcohol and/or drug abuse within 12 months prior to the screening visit that, in the opinion of the investigator, may have interfered with study compliance, outcome measures, safety parameters, and/or the general medical condition of the subject.

11. Any subject that has punctal occlusion such as permanent/semi-permanent punctal plugs, temporary plugs, punctal cauterization