Efficacy of Riboflavin-Enhanced Hyaluronic Acid Eye Drops in Treating Dry Eye Disease

Modified Sodium Hyaluronate Conjugated to Riboflavin (HAr® 0.1%) as Lubricant Eyedrops in the Treatment of Dry Eye

The goal of this retrospective study is to evaluate the historical effectiveness of Riboflavin-Enhanced Hyaluronic Acid Eye Drops (HAr® 0.1%) in the treatment of Dry Eye Disease (DED) among patients. The product under investigation, Ribohyal®, had previously obtained certification and authorization from the relevant notified body for market sale (European patent n. 2228058)

The primary questions it aimed to address were:

• Did the use of Riboflavin-Enhanced Hyaluronic Acid Eye Drops result in a reduction of dry eye symptoms and an improvement in ocular comfort among patients with DED in a historical context?
• Was Riboflavin-Enhanced Hyaluronic Acid Eye Drops historically more effective in reducing photophobia and enhancing tear film stability when compared to standard treatment?

Participants in this retrospective analysis had historically:

• Used either Riboflavin-Enhanced Hyaluronic Acid Eye Drops or a standard hyaluronic acid eye drop, based on their assigned group.
• Historically reported their levels of ocular discomfort and photophobia at specified time points.
• Undergone historical clinical examinations to assess tear film stability and osmolarity.

Researchers conducted a retrospective analysis to compare the historical outcomes of the group using Riboflavin-Enhanced Hyaluronic Acid Eye Drops with the group using standard eye drops to determine if the former historically provided more significant improvements in dry eye symptoms and tear film stability.

Study Overview

• Status: Completed
• Conditions: Dry Eye Disease
• Intervention / Treatment: Drug: modified hyaluronic acid 0.1% covalently linked to Riboflavin; Drug: hyaluronic acid 0.1%

Detailed Description

In this retrospective study, the investigators have examined the historical therapeutic efficacy of Riboflavin-Enhanced Hyaluronic Acid Eye Drops (HAr® 0.1%) in the treatment of Dry Eye Disease (DED), adhering to good clinical practice principles.

Participants were historically divided into two groups:

• Group X: received Riboflavin-Enhanced Hyaluronic Acid Eye Drops (HAr® 0.1%) (Ribohyal Group).
• Group Y: received standard HA 0.1% eye drops (Control Group).

The historical outcome measures included the retrospective assessments of osmolarity, Tear Break-Up Time (TBUT), corneal staining, Schirmer test, tear meniscus measurement, and Non-invasive Break-Up Time (NIBUT). The Ocular Surface Disease Index (OSDI) score was historically recorded at various time points.

• Study Type: Observational
• Enrollment (Actual): 16

Contacts and Locations

Study Locations

• Italy
  • NAples, Italy, 80131
    • University of Naples Federico II

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

The study enrolled 16 consecutive patients with bilateral mild to severe Dry Eye Disease (DED) at the University of Naples Federico II, Italy. These participants were selected based on specific eligibility criteria, as outlined in other sections of the study. The selection aimed to ensure that the study population adequately represented individuals experiencing DED.

Description

Inclusion criteria for patient selection included a dry eye history of at least three months, OSDI score ≥ 23, and positivity in at least one eye for one or more of the following diagnostic criteria:

• Tear Break-Up Time (TBUT) < 7 seconds
• Schirmer test I at 5 minutes < 10 mm
• Corneal and/or conjunctival fluorescein staining
• Tear osmolarity > 308 mOsm/L or a difference of at least 8 mOsm/L between both eyes.

Exclusion Criteria:

• Age below 18 years
• Severe ocular surface affections
• Unilateral dry eye syndrome
• Refractive surgery performed within the last six months
• Eye surgery performed within the last three months
• Previous herpetic keratitis
• Signs of active corneal infection
• Systemic or topical steroid therapy within the last 30 days
• Topical therapy within the last 14 days
• Inability to understand the informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group X: Ribohyal Group; Composed of 16 eyes (right or left) assigned for the use of modified hyaluronic acid, HAr® 0.1%, covalently linked to Riboflavin	Drug: modified hyaluronic acid 0.1% covalently linked to Riboflavin; The patients used the eye drops no less than 3 times a day or no more than 6 times a day, according to their needs. They reported the instillation frequency (3/4 or 5/6 times per day) on the provided document
Group Y: (Control Group); Composed of 16 eyes (right or left) assigned for the use of HA 0.1% alone	Drug: hyaluronic acid 0.1%; The patients used the eye drops no less than 3 times a day or no more than 6 times a day, according to their needs. They reported the instillation frequency (3/4 or 5/6 times per day) on the provided document

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the efficacy and safety of a new 0.1% sodium hyaluronate-riboflavin-conjugated (HAr®) artificial tear in treating ocular discomfort and improving tear film stability in patients with dry eye disease.	Ocular discomfort reduction mesured by OSDI test.	From enrollment to the end of treatment at 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the reduction in Tear osmolarity	Tear osmolarity test. This measurement provides important information about tear composition.	From enrollment to the end of treatment at 8 weeks
Measure the stability of the tear film	Tear Break-Up Time (TBUT) test This measures the stability of the tear film.	From enrollment to the end of treatment at 8 weeks
Measure the tear production	Schirmer test I (without anesthetic) at 5 minutes. This measures tear production.	From enrollment to the end of treatment at 8 weeks
Evaluate corneal staining	Biomicroscopic observation with white light and cobalt blue light according to the Oxford scheme. It provides information on corneal health.	From enrollment to the end of treatment at 8 weeks

Collaborators and Investigators

• Sponsor: University of Naples

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2022
• Primary Completion (Actual): July 22, 2022
• Study Completion (Actual): October 10, 2022

Study Registration Dates

• First Submitted: October 12, 2023
• First Submitted That Met QC Criteria: November 2, 2023
• First Posted (Actual): November 8, 2023

Study Record Updates

• Last Update Posted (Actual): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: ocular surface; dry eye disease; ribohyal; tear check
• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Adjuvants, Immunologic; Vitamins; Vitamin B Complex; Viscosupplements; Hyaluronic Acid; Riboflavin
• Other Study ID Numbers: CIT_001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all collected IPD, available on 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