Rebamipide Versus Diquafosol and Cyclosporine for Perioperative Dry Eye in Cataract Surgery

Rebamipide Versus Diquafosol-Cyclosporine for Perioperative Dry Eye Disease in Cataract Surgery: A Randomized Trial

The goal of this clinical trial is to compare the efficacy of 2% rebamipide monotherapy versus a combination therapy of 3% diquafosol and 0.05% cyclosporine for the management of dry eye disease in patients undergoing cataract surgery. It will also evaluate the safety and ocular surface stability effects of these treatments during the perioperative period.

The main questions it aims to answer are:

Does rebamipide monotherapy maintain tear film breakup time (TBUT) and prevent corneal damage as effectively as the combination therapy after surgery? How do patient symptoms (OSDI scores) and inflammation markers (MMP-9) change with each treatment?

Researchers will compare the rebamipide group to the diquafosol-cyclosporine combination group to evaluate their effects on perioperative dry eye management.

Participants will:

Use the assigned study eye drops starting 1 month before their cataract surgery and continuing for 3 months after surgery.

Visit the clinic for eye examinations at baseline, the day of surgery, and at 1 week, 1 month, and 3 months postoperatively.

Undergo tests including tear film breakup time measurement, corneal staining, Schirmer's test, and tear MMP-9 level assessments.

Study Overview

• Status: Completed
• Conditions: Cataract; Dry Eye Disease (DED)
• Intervention / Treatment: Drug: Rebamipide 2% ophthalmic solution; Drug: Diquafosol 3% ophthalmic solution; Drug: Cyclosporine 0.05% ophthalmic solution

Detailed Description

Dry eye disease (DED) is common in patients undergoing cataract surgery and may worsen during the perioperative period, leading to ocular discomfort and delayed visual recovery. Pharmacologic treatments targeting tear film instability and ocular surface inflammation are therefore important in perioperative management.

This prospective, randomized, parallel-group clinical trial compared two perioperative treatment strategies for DED in patients scheduled for cataract surgery. Eligible participants with pre-existing dry eye disease were randomized in a 1:1 ratio to receive either topical rebamipide 2% monotherapy or combination therapy with topical diquafosol 3% and cyclosporine 0.05%. Study medications were initiated 1 month prior to surgery and continued for 3 months postoperatively.

The primary outcome measure was the change in tear film breakup time (TBUT) during the early postoperative period. Secondary outcome measures included changes in corneal staining graded by the Oxford scale, patient-reported symptoms assessed by the Ocular Surface Disease Index (OSDI), tear secretion measured by Schirmer's test, and ocular surface inflammation evaluated using a tear matrix metalloproteinase-9 (MMP-9) point-of-care immunoassay.

Clinical assessments were performed at baseline, on the day of surgery, and at postoperative week 1, month 1, and month 3. Safety was evaluated by monitoring intraoperative and postoperative adverse events throughout the study period.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 4

Contacts and Locations

Study Locations

• South Korea
  • Seoul
    • Seoul, Seoul, South Korea
      • Samsung Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults scheduled for cataract surgery

• Presence of dry eye disease, defined as an Ocular Surface Disease Index (OSDI) score ≥12 and at least one of the following:

  • Tear film breakup time (TBUT) ≤7 seconds
  • Oxford corneal staining grade ≥1
  • Schirmer's test value ≤10 mm/5 min
• Ability and willingness to comply with the study protocol and follow-up schedule
• Provision of written informed consent

Exclusion Criteria:

• Presence of ocular surface or ocular conditions that could affect dry eye status (e.g., active keratitis or ocular infection)
• Use of topical intraocular pressure-lowering medications
• History of ocular surgery other than cataract surgery in the study eye
• Any systemic or ocular condition judged by the investigator to interfere with study participation or outcome assessment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group R; Participants receive topical rebamipide 2% ophthalmic solution four times daily, initiated 1 month before cataract surgery and continued for 3 months postoperatively.	Drug: Rebamipide 2% ophthalmic solution; Topical administration, four times daily
Active Comparator: Group DC; Participants receive topical diquafosol 3% ophthalmic solution four times daily in combination with cyclosporine 0.05% ophthalmic solution twice daily, initiated 1 month before cataract surgery and continued for 3 months postoperatively.	Drug: Diquafosol 3% ophthalmic solution; Topical administration, four times daily; Drug: Cyclosporine 0.05% ophthalmic solution; Topical administration, two times daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Tear Film Breakup Time (TBUT)	Change in tear film breakup time (TBUT) from baseline and during the early postoperative period following cataract surgery, comparing rebamipide monotherapy with diquafosol-cyclosporine combination therapy.	From baseline to postoperative week 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Ocular Surface Disease Index (OSDI) Score	Change in patient-reported ocular symptoms assessed using the Ocular Surface Disease Index (OSDI) questionnaire, comparing rebamipide monotherapy with diquafosol-cyclosporine combination therapy.	From baseline to 1 and 3 months postoperatively
Change in Corneal Staining Grade (Oxford Scale)	Change in corneal epithelial staining graded using the Oxford grading scale following fluorescein staining, comparing ocular surface stability between treatment groups.	From baseline to postoperative week 1, and to 1 and 3 months postoperatively
Change in Schirmer's Test Value	Change in tear secretion measured by Schirmer's test without anesthesia, comparing tear production between rebamipide monotherapy and diquafosol-cyclosporine combination therapy.	From baseline to 1 and 3 months postoperatively
Change in Tear Matrix Metalloproteinase-9 (MMP-9) Level	Change in tear matrix metalloproteinase-9 (MMP-9) levels assessed using a point-of-care immunoassay (InflammaDry), comparing ocular surface inflammation between treatment groups.	From baseline to 1 and 3 months postoperatively

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Actual): May 1, 2025
• Study Completion (Actual): May 1, 2025

Study Registration Dates

• First Submitted: February 2, 2026
• First Submitted That Met QC Criteria: February 2, 2026
• First Posted (Actual): February 9, 2026

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Lens Diseases; Cataract; Dry Eye Syndromes; Pharmaceutical Solutions; Peptides; Amino Acids, Peptides, and Proteins; Pharmaceutical Preparations; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Polycyclic Compounds; Solutions; Specialty Uses of Chemicals; Macrocyclic Compounds; Peptides, Cyclic; Cyclosporins; Cyclosporine; Ophthalmic Solutions; rebamipide; diquafosol
• Other Study ID Numbers: NRF-2021R1C1C1007795

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The detailed study protocol and the data that support the findings of this study are available from the corresponding author upon reasonable request.

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