Clinical Efficacy of Amniotic Membrane Extract Eye Drops in Dry Eye Treatment

This prospective longitudinal study aims at evaluating the clinical efficacy of human amniotic fluid extract eye drops in the treatment of dry eye disease. 25 patients who are diagnosed with dry eye disease as defined by our criteria will be recruited from the cornea and dry eye clinic at Stein Eye Institute, UCLA. Pre-treatment baseline evaluations, 6 weeks, 12 weeks, and 24 weeks post treatment assessments will be performed by the principle investigator and co-investigator. All tests are considered non-invasive and are within the standard of practice in the evaluation for dry eye disease: (1) Ocular Surface Disease Index Questionnaire (OSDI); (2) Non-contact Tear Break-up Time (NITBUT); (3) Shirmer's test without anesthesia; (4) Ocular Surface Staining with Fluorescein and Lissamine green. Result of each test will be compared and analyzed to provide evidence of treatment efficacy. Treatment will be initiated for 12 weeks at a self-administered dose of one drop in both eyes two times per day. A follow-up of the study will be observed at the 24th week from the first day of treatment. All side effects and adverse events will be carefully observed and documented. Patients will be able to discontinue using the medication if they are not tolerating any side effects.

Study Overview

• Status: Withdrawn
• Conditions: Dry Eyes Chronic
• Intervention / Treatment: Biological: RegenerEyes

• Study Type: Interventional
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults (18 years or older)

• Presence of dry eye disease as defined as:

  1. Ocular Suface Disease Index (OSDI) score >13 AND EITHER i: Non-contact tear break-up time (NITBUT) < 10 seconds OR ii: Ocular Surface Staining (OSS) score > 1 in either eye

Exclusion Criteria:

1. Systemic diseases or comorbidities that may cause severe or secondary dry eye:

   1. Previous diagnosis of lymphoma, hepatitis C, HIV/AIDS, sarcoidosis, or amyloidosis that involves lacrimal glands
   2. Previous diagnosis of graft versus host disease (e.g., after bone marrow transplantation treatment for cancer) or cicatrizing conjunctivitis (e.g., Steven Johnson Syndrome, mucous membrane pemphigoid, trachoma)
   3. Anatomical or neurological lid closure problems (e.g., Bell's palsy, cicatricial ectropion, Alzheimer's disease, Parkinson's disease) 4
   4. Any history of chemotherapy, head or neck radiation treatment, or radioactive iodine treatment within 1 year prior to enrollment
   5. High dose oral or systemic steroids (equivalent to or greater than 5 mg prednisone) or immunosuppressive medication within 30 days prior to enrollment. Patients who are on stable dosing are eligible.
   6. Frequent or recent change in systemic medication regimen (e.g., diuretics, beta blockers, immunosuppressive medications, antidepressants that are known to interfere with dry eye) within 3 months prior to enrollment that may influence the ocular surface.

2. Other ocular surface diseases or surgical history that may cause severe or secondary dry eye:

   1. History of corneal dystrophy that in the opinion of the investigator is significantly affecting the ocular surface (e.g., significant anterior basement membrane dystrophy, Fuch's dystrophy with significant corneal edema and bullae, neurotrophic keratoconjunctivitis or corneal/conjunctival scarring including herpes simplex virus [HSV] or varicella zoster virus [VZV] keratitis)
   2. Any history of surgery for glaucoma (e.g., trabeculectomy, tube shunt)
   3. Corneal refractive surgery (e.g., laser in-situ keratomileusis [LASIK], photorefractive keratectomy [PRK], Intacs) within 6 months prior to enrollment
   4. Cataract, eyelid surgery, or retinal surgery (in operating room) within 6 months prior to enrollment

3. Use of treatments that may interfere with the ocular surface and/or treatment efficacy:

   1. Any in-office dry eye procedures (e.g., Intense Pulsed Light [IPL], LipiFlow®, nasolacrimal duct probing) within 30 days prior to enrollment
   2. Use of anti-glaucoma drops, topical antihistamines drops, or topical steroid drops within 7 days prior to enrollment
   3. Use of contact lenses. Patients willing to discontinue usage for 48 hours prior to each study visit will be eligible.
   4. Use of scleral lens, such as the prosthetic replacement of the ocular surface ecosystem (PROSE) lens
   5. Current use of topical lifitegrast (Xiidra®), topical cyclosporine (Restasis®), topical tacrolimus, or topical pimecrolimus. Patients willing to discontinue their due to insufficient benefit will be eligible.

4. Other important exclusion criteria:

   1. Current smoker (within 1 year prior to enrollment).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Study group; Treatment group to receive study drops (RegenerEyes) twice daily for 12 weeks	Biological: RegenerEyes; Biologic eye drop

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ocular Surface Disease Index	Symptom Questionnaire	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ocular Surface Staining Score		12 weeks
Schirmer Score	Schirmer score after 5 minutes with anesthesia	12 weeks
Non-contact Tear Break-up Time		12 weeks

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Investigators: Principal Investigator: Saba Al-Hashimi, M.D, University of California, Los Angeles

Publications and helpful links

General Publications

• O'Neil EC, Henderson M, Massaro-Giordano M, Bunya VY. Advances in dry eye disease treatment. Curr Opin Ophthalmol. 2019 May;30(3):166-178. doi: 10.1097/ICU.0000000000000569.
• Murri MS, Moshirfar M, Birdsong OC, Ronquillo YC, Ding Y, Hoopes PC. Amniotic membrane extract and eye drops: a review of literature and clinical application. Clin Ophthalmol. 2018 Jun 18;12:1105-1112. doi: 10.2147/OPTH.S165553. eCollection 2018.
• Quinto GG, Camacho W, Castro-Combs J, Li L, Martins SA, Wittmann P, Campos M, Behrens A. Effects of topical human amniotic fluid and human serum in a mouse model of keratoconjunctivitis sicca. Cornea. 2012 Apr;31(4):424-30. doi: 10.1097/ICO.0b013e31823f0a64.
• Yeu E, Goldberg DF, Mah FS, Beckman KA, Luchs JI, Solomon JD, White DE, Gupta PK. Safety and efficacy of amniotic cytokine extract in the treatment of dry eye disease. Clin Ophthalmol. 2019 May 27;13:887-894. doi: 10.2147/OPTH.S203510. eCollection 2019.
• Chen M, Chang CK, Lin SY, Chen M. A Pilot Study of the Short Term Effectiveness and Safety of Amniotic Fluid in Severe Dry Eye Disease. Med Hypothesis Discov Innov Ophthalmol. 2019 Summer;8(2):81-84.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 1, 2022
• Primary Completion (ANTICIPATED): April 1, 2022
• Study Completion (ANTICIPATED): May 1, 2022

Study Registration Dates

• First Submitted: December 14, 2021
• First Submitted That Met QC Criteria: December 14, 2021
• First Posted (ACTUAL): December 27, 2021

Study Record Updates

• Last Update Posted (ACTUAL): November 10, 2022
• Last Update Submitted That Met QC Criteria: November 7, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca
• Other Study ID Numbers: 21-001915

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No