Efficacy and Safety of 20% and 100% Autologous Serum Eye Drops in Patients With Severe Dry Eye Disease (AST) (AST)

Efficacy and Safety of 20% and 100% Autologous Serum Eye Drops in Patients With Severe Dry Eye Disease: a Prospective, Blinded, Randomized, Crossover Study

A prospective, single-blinded, randomized, controlled crossover trial was conducted in patients with severe dry eye syndrome. Topical treatment with autologous serum eye drops (ASED) diluted at 20%, undiluted ASED and conventional preservative-free artificial tears (PFAT) were compared as a treatment for severe dry eye disease. The primary outcome measure was assessment of ocular symptoms using the Ocular Surface Disease Index (OSDI) questionnaire. Secondary outcomes were Schirmer 1 test, best-corrected visual acuity (BVCA), corneal fluorescein and conjunctival lissamine green staining using the Sjögren's International Collaborative Clinical Alliance Ocular Surface Staining (SICCA OSS) score, tear break up time (TBUT), conjunctival injection score (CIS) and Meibomian gland dysfunction (MGD) grading. Additionally, serum and tear cytokine analysis and microbiological cultures were performed.

Study Overview

• Status: Completed
• Conditions: Dry Eye Disease
• Intervention / Treatment: Drug: Preservative-free artificial tears; Drug: Autologous serum eyedrops 20%; Drug: Autologous serum eyedrops 100%

Detailed Description

This prospective, single-blinded, randomized, crossover clinical trial analyzed the difference in subjective symptoms and clinical signs between 20% and 100% autologous serum eye drops (ASED) versus preservative-free artificial tears (PFAT). After signing the informed consent form, each patient was randomized via RedCap. A 2-week washout was initiated prior to the baseline visit and the start of the first treatment. Patients were asked to discontinue current PFAT and/or ASED and replace them with the washout, in the form of preservative-free 3% trehalose and 0.15% hyaluronic acid (HA)-containing artificial tears. Concurrent use of necessary ocular anti-inflammatory therapy (cyclosporine, hydrocortisone) and moisturizing ocular ointment at night was allowed, provided it was maintained throughout the entire crossover study. Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment. The same preservative-free artificial tears containing 3% trehalose and 0.15% hyaluronic acid (HA) were used during the PFAT treatment as during the washout. The total study duration was 30 weeks (Figure 1). The examining ophthalmologist (DR) was blinded to the type of eyedrops given to each patient in the trial. The minimum dosage for the eye drops (AS and PFAT) was eight times a day. If necessary, hourly application was allowed. In that case, the patient was asked to continue hourly application for all three treatments.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • Ghent University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

The inclusion criteria for patients participating in this study are defined as follows: patients with severe Dry Eye Disease, including severe symptoms as evaluated with a standardized instrument (OSDI score > 33), associated with at least one of the following objective parameters:

A. Tear break-up time (tBUT) as a measure of tear film quality < 5 seconds B. Positive corneal and conjunctival staining quantified according to the SICCA OSS scale C. Schirmer 1 test score < 5 mm/5 min (without anesthesia)

Exclusion Criteria:

The exclusion criteria for patients participating in this study are defined as follows:

A. Inability to complete the study protocol, including study-specific procedures.

B. Inability to understand the Dutch-language ICF and/or unwillingness or inability to provide signed informed consent.

C. History of non-compliance with the proposed therapy D. Presence of known severe anemia based on medical history E. Hypersensitivity to the proposed treatment F. Pregnancy G. Age <18 years H. In the opinion of the investigator, the subject is not suitable for participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1: T1-T2-T3; After a washout of 2 weeks, study participants in this arm first received 8 weeks of preservative-free artificial tears (PFAT) (T1). After 8 weeks of treatment, the first treatment effect was evaluated during a scheduled study visit. Patients were then instructed to start a new washout of 2 weeks to immediately follow with the next treatment. The second treatment is this arm was autologous serum eye drops (ASED) at a concentration of 20% (T2). After 8 weeks of treatment, the second treatment effect was evaluated during a scheduled study visit. Patients were then instructed to start a new washout of 2 weeks to immediately follow with the next treatment. The third treatment is this arm was autologous serum eye drops (ASED) at a concentration of 100% (T3). After 8 weeks of treatment, the third treatment effect was evaluated during a scheduled study visit.	Drug: Preservative-free artificial tears; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: PFAT; Drug: Autologous serum eyedrops 20%; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: ASED 20%; Drug: Autologous serum eyedrops 100%; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: ASED 100%
Experimental: Sequence 2: T1-T3-T2; After a washout of 2 weeks, study participants in this arm first received 8 weeks of preservative-free artificial tears (PFAT) (T1). After 8 weeks of treatment, the first treatment effect was evaluated during a scheduled study visit. Patients were then instructed to start a new washout of 2 weeks to immediately follow with the next treatment. The second treatment is this arm was autologous serum eye drops (ASED) at a concentration of 100% (T3). After 8 weeks of treatment, the second treatment effect was evaluated during a scheduled study visit. Patients were then instructed to start a new washout of 2 weeks to immediately follow with the next treatment. The third treatment is this arm was autologous serum eye drops (ASED) at a concentration of 20% (T2). After 8 weeks of treatment, the third treatment effect was evaluated during a scheduled study visit.	Drug: Preservative-free artificial tears; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: PFAT; Drug: Autologous serum eyedrops 20%; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: ASED 20%; Drug: Autologous serum eyedrops 100%; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: ASED 100%
Experimental: Sequence 3: T2-T3-T1; After a washout of 2 weeks, study participants in this arm first received 8 weeks of autologous serum eye drops (ASED) at a concentration of 20% (T2). After 8 weeks of treatment, the first treatment effect was evaluated during a scheduled study visit. Patients were then instructed to start a new washout of 2 weeks to immediately follow with the next treatment. The second treatment is this arm was autologous serum eye drops (ASED) at a concentration of 100% (T3). After 8 weeks of treatment, the second treatment effect was evaluated during a scheduled study visit. Patients were then instructed to start a new washout of 2 weeks to immediately follow with the next treatment. The third treatment is this arm was preservative-free artificial tears (PFAT) (T1). After 8 weeks of treatment, the third treatment effect was evaluated during a scheduled study visit.	Drug: Preservative-free artificial tears; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: PFAT; Drug: Autologous serum eyedrops 20%; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: ASED 20%; Drug: Autologous serum eyedrops 100%; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: ASED 100%
Experimental: Sequence 4: T2-T1-T3; After a washout of 2 weeks, study participants in this arm first received 8 weeks of autologous serum eye drops (ASED) at a concentration of 20% (T2). After 8 weeks of treatment, the first treatment effect was evaluated during a scheduled study visit. Patients were then instructed to start a new washout of 2 weeks to immediately follow with the next treatment. The second treatment is this arm was preservative-free artificial tears (PFAT) (T1). After 8 weeks of treatment, the second treatment effect was evaluated during a scheduled study visit. Patients were then instructed to start a new washout of 2 weeks to immediately follow with the next treatment. The third treatment is this arm was autologous serum eye drops (ASED) at a concentration of 100% (T3). After 8 weeks of treatment, the third treatment effect was evaluated during a scheduled study visit.	Drug: Preservative-free artificial tears; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: PFAT; Drug: Autologous serum eyedrops 20%; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: ASED 20%; Drug: Autologous serum eyedrops 100%; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: ASED 100%
Experimental: Sequence 5: T3-T1-T2; After a washout of 2 weeks, study participants in this arm first received 8 weeks of autologous serum eye drops (ASED) at a concentration of 100% (T3). After 8 weeks of treatment, the first treatment effect was evaluated during a scheduled study visit. Patients were then instructed to start a new washout of 2 weeks to immediately follow with the next treatment. The second treatment is this arm was preservative-free artificial tears (PFAT) (T1). After 8 weeks of treatment, the second treatment effect was evaluated during a scheduled study visit. Patients were then instructed to start a new washout of 2 weeks to immediately follow with the next treatment. The third treatment is this arm was autologous serum eye drops (ASED) at a concentration of 20% (T2). After 8 weeks of treatment, the third treatment effect was evaluated during a scheduled study visit.	Drug: Preservative-free artificial tears; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: PFAT; Drug: Autologous serum eyedrops 20%; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: ASED 20%; Drug: Autologous serum eyedrops 100%; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: ASED 100%
Experimental: Sequence 6: T3-T2-T1; After a washout of 2 weeks, study participants in this arm first received 8 weeks of autologous serum eye drops (ASED) at a concentration of 100% (T3). After 8 weeks of treatment, the first treatment effect was evaluated during a scheduled study visit. Patients were then instructed to start a new washout of 2 weeks to immediately follow with the next treatment. The second treatment is this arm was autologous serum eye drops (ASED) at a concentration of 20% (T2). After 8 weeks of treatment, the second treatment effect was evaluated during a scheduled study visit. Patients were then instructed to start a new washout of 2 weeks to immediately follow with the next treatment. The third treatment is this arm was preservative-free artificial tears (PFAT) (T1). After 8 weeks of treatment, the third treatment effect was evaluated during a scheduled study visit.	Drug: Preservative-free artificial tears; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: PFAT; Drug: Autologous serum eyedrops 20%; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: ASED 20%; Drug: Autologous serum eyedrops 100%; Each patient received three 8-week treatments in a randomized sequence, being PFAT, AS 20% and AS 100%. After 8 weeks of treatment, the treatment effect was evaluated during a scheduled study visit. The patient was then instructed to start a new washout of 2 weeks to immediately follow with the next treatment.; Other Names: ASED 100%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in participant-reported severity and/or frequency of dry eye-related symptoms based on a validated patient symptom questionnaire (Ocular Surface Disease Index questionnaire, OSDI)	OSDI	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in ocular staining with fluorescein and lissamine green according to the Sjögren's International Collaborative Clinical Alliance Ocular Staining Score (SICCA OSS)	SICCA OSS	8 weeks
Change from baseline in Schirmer 1 tear production test (mm)	Schirmer 1 test	8 weeks
Change from baseline in best-corrected visual acuity (BCVA, Snellen)	BCVA	8 weeks
Change from baseline in tear film break-up time at the slit lamp (tBUT, sec)	tBUT	8 weeks
Change from baseline in non-invasive break-up-time (NiBUT) using anterior segment ocular coherence tomography (OCT) (sec)	NiBUT	8 weeks
Change from baseline in conjunctival injection score (CIS)	CIS	8 weeks
Change from baseline in Meibomian Gland Dysfunction (MGD) grade	MGD	8 weeks

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Dimitri Roels, MD, Department of Ophthalmology, Ghent University Hospital Belgium

Publications and helpful links

General Publications

• Tananuvat N, Daniell M, Sullivan LJ, Yi Q, McKelvie P, McCarty DJ, Taylor HR. Controlled study of the use of autologous serum in dry eye patients. Cornea. 2001 Nov;20(8):802-6. doi: 10.1097/00003226-200111000-00005.
• Kojima T, Ishida R, Dogru M, Goto E, Matsumoto Y, Kaido M, Tsubota K. The effect of autologous serum eyedrops in the treatment of severe dry eye disease: a prospective randomized case-control study. Am J Ophthalmol. 2005 Feb;139(2):242-6. doi: 10.1016/j.ajo.2004.08.040.
• Urzua CA, Vasquez DH, Huidobro A, Hernandez H, Alfaro J. Randomized double-blind clinical trial of autologous serum versus artificial tears in dry eye syndrome. Curr Eye Res. 2012 Aug;37(8):684-8. doi: 10.3109/02713683.2012.674609. Epub 2012 Jun 6.
• Celebi AR, Ulusoy C, Mirza GE. The efficacy of autologous serum eye drops for severe dry eye syndrome: a randomized double-blind crossover study. Graefes Arch Clin Exp Ophthalmol. 2014 Apr;252(4):619-26. doi: 10.1007/s00417-014-2599-1. Epub 2014 Feb 25.
• Noble BA, Loh RS, MacLennan S, Pesudovs K, Reynolds A, Bridges LR, Burr J, Stewart O, Quereshi S. Comparison of autologous serum eye drops with conventional therapy in a randomised controlled crossover trial for ocular surface disease. Br J Ophthalmol. 2004 May;88(5):647-52. doi: 10.1136/bjo.2003.026211.
• Bachtalia K, Plakitsi A, Voudouri A, Terzidou C, Dalianis G, Kopsinis G, Palioura S. The Effect of Autologous Serum Tears 50% on the Ocular Surface of Patients With Severe Dry Eye Disease due to Sjogren Syndrome: A Prospective, Double-Blind, Randomized, Controlled, Contralateral Eye Study. Cornea. 2025 Jan 14;44(7):856-865. doi: 10.1097/ICO.0000000000003795.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2021
• Primary Completion (Actual): November 14, 2024
• Study Completion (Actual): December 30, 2025

Study Registration Dates

• First Submitted: March 9, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Systemic Sclerosis; Graft-versus-Host Disease; Artificial Tears; Sjögren's Syndrome; Dry eye disease; Autologous Serum; Tear Cytokines
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Skin Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Lacrimal Apparatus Diseases; Skin and Connective Tissue Diseases; Sjogren's Syndrome; Dry Eye Syndromes; Scleroderma, Systemic; Graft vs Host Disease
• Other Study ID Numbers: BC-10591; B6702021001102 (Registry Identifier: Belgian Unique Notification Number)

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
• product manufactured in and exported from the U.S.: No