Comparison of Efficacy Between 100% Platelet-rich Plasma and 100% Serum Eye Drops in Dry Eye Disease

Study Overview
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Brief Summary
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Dry eye disease (DED) is a common eye problem, affecting 5% to 50% of the world population. Although the disease is not fatal, it substantially reduces quality of life and creates a high economic burden as high as over 50 billion from a societal perspective. Several biological tear substitutes (e.g., autologous serum (AS), autologous platelet rich plasma (APRP), and autologous platelet lysate (APL)) could effectively improve dry eyes, especially in patients with moderate to severe DED.. However, evidence on their comparative efficacy is controversial. The objective of the study is to compare the efficacy of 100% APRP with 100% AS eye drops in patients with moderate to severe DED.

Detailed Description
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The study is a single-center, double-blinded randomized, parallel, non-inferiority trial. Patients will be recruited from out-patient clinic, Department of Ophthalmology, Ramathibodi Hospital, Bangkok and will be randomized to receive either 100% APRP or 100% AS eye drops (1:1 ratio) for 4 weeks. The primary outcomes include ocular surface disease index (OSDI) and ocular surface staining evaluated using the Oxford scale. Secondary outcomes are fluorescein break-up time (FBUT), Schirmer's I test (ST I), meibomian gland parameters and adverse events.

Official Title
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Comparison of Treatment Efficacy Between 100% Platelet-rich Plasma and 100% Serum Eye Drops in Moderate to Severe Dry Eye Disease: A Randomized Controlled Trial Protocol

Conditions
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Dry Eye Disease

Intervention / Treatment
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* Drug: 100% Autologous platelet rich plasma
* Drug: 100% Autologous serum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 to less than 75 years. Have OSDI scores ≥ 23 or Oxford staining grade ≥ 2. Do not have following conditions: Uncontrolled systemic diseases, active infection, advanced cancer. Pregnant and nursing women. • Have not recently used the following medications/interventions/surgery: Anticoagulants or anti-platelets. Topical undiluted blood products within 3 months. Punctal plug or contact lenses. Ocular surgery within 6 months. Do not have active ocular infection/inflammation, abnormal eyelid function or severe meibomian gland dysfunction (MGD stage 4). Have no contraindication for blood donations: Positive human immunodeficiency virus, hepatitis B or C, or syphilis. Anemia (Hb < 11 g/dL) or platelet concentration < 150,000/ml. Being able to stop current dry eye treatment for 48 hours before staring trial intervention Willing to comply with the 4-week study protocol and provide informed consent. Exclusion Criteria: • None

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomly allocated to receive either 100% APRP or 100% AS (the same treatment for both eyes).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100% APRP<br>Patients will be instructed to apply every 2 hours (8 times/day). The currently used bottle will be required to store at 4 C for 24 hours, and the remaining bottles at -20 C in a freezer until day of use. | Drug: 100% Autologous platelet rich plasma<br>* Patients' blood (36 ml per tube) will be collected in three 50-ml sterile centrifuge tubes containing 4 ml of 3.2% buffered citrate acid for anticoagulation. Tubes will be centrifuged at 350 g for 10 minutes at 20 C. The two upper layers of the centrifuged blood, the plasma and the superficial buffy coat, will be separated in a sterile manner under a laminar air flow hood. A 1.5 ml aliquot of both final blood products will be transferred into identical opaque eye drop bottles, labelled name, hospital number, dated and sealed.<br>* Other names: APRP;|
| Active Comparator: 100% AS<br>Patients will be instructed to apply every 2 hours (8 times/day). The currently used bottle will be required to store at 4 C for 24 hours, and the remaining bottles at -20 C in a freezer until day of use. | Drug: 100% Autologous serum<br>* Patients' blood (36 ml per tube) will be collected in three 50-ml sterile centrifuge tubes. The tubes will be left standing in an upright position for 1-2 hours to enable blood clot formation at room temperature (18-25 C). The tubes will be centrifuged at 3000 g for 30 minutes at 20 C. The supernatant serum will be aseptically transferred into a sterile syringe to enable filtration through a 0.2 µm pore size membrane filter under a laminar air flow hood. A 1.5 ml aliquot of both final blood products will be transferred into identical opaque eye drop bottles, labelled name, hospital number, dated and sealed.<br>* Other names: AS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular surface score index (OSDI) | The OSDI is a patient-reported outcome (PRO) questionnaire which was designed by Allergan, Inc. to assess range of ocular symptoms related to chronic dry eye disease and reflect patient's ability of function. It comprised 12 questions which are divided into 3 subscales including ocular symptoms (5 questions), vision-related function (4 questions), and environmental triggers (3 questions). Each of question is rated from 0 to 4 indicating none of the time, some of the time, half of the time, most of the time and all of the time, respectively. The average OSDI is transformed into a score ranged from 0 to 100, with a higher score indicating more severity of dry eye disease. The OSDI is classified as normal (0-12 points), mild (13-22 points), moderate (23-32 points) and severe (33-100). | 4 weeks | 
| Ocular surface staining (OSS) | To assess total ocular surface staining, the cornea and conjunctival staining are graded by using Oxford scale guidelines (range grade 0 to 5). The higher score refers to higher severity of dry eye. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluorescein break up time (FBUT) | The break up time (seconds) will be measured after fluorescein staining by using a stopwatch starting from the time of complete eye lid opening to the time of the first tear break up appear. The average values of 3 times of FBUT will be used. The reference value for DED diagnosis is used ranged from a cut-off time of less than 10 seconds for dry eye and less than 5 seconds for severe dry eye. | 4 weeks | 
| Schirmer's test (ST) | The Schirmer test (ST) was performed using commercially available prepackaged sterile paper strips without anesthesia. The rounded bulb end of the strip was folded and placed in the lateral canthus away from the cornea and left in place for 5 minutes after which the wet strip length was recorded in mm. Tear deficiency is defined if ST is less than 5 mm wetting of the paper after 5 minutes. | 4 weeks | 
| Meibum quality and expressibility. | Meibum quality is assessed by applying the pressure on each of 8 glands of the central third of the lower lid on a scale of 0 to 3 for each gland: 0, clear; 1, cloudy; 2, cloudy with debris (granular); and 3, thick, like toothpaste (total score range, 0-24). Higher score indicates the higher severity of meibomian gland dysfunction. Expressibility is assessed on a scale of 0 to 3 in five glands in the lower or upper lid, according to the number of glands expressible: 0, all glands; 1, three to four glands; 2, one to two glands; and 3, no glands. Higher score indicates the higher severity of meibomian gland dysfunction. | 4 weeks | 
| Number of patients with ocular adverse events | All ocular adverse events will be recorded throughout the study. | 4 weeks |