Effect of Topical Antioxidants in Dry Eye Disease and Diabetic Retinopathy

June 23, 2022 updated by: Adolfo Daniel Rodriguez-Carrizalez

Effect of Combined Antioxidant Therapy in Eye Drops on Inflammatory and Oxidative Stress Biomarkers in Tear Film in Patients With Diabetic Retinopathy and Dry Eye Syndrome

The main objective of our study is to evaluate the effect of eye drops with antioxidants on mild to moderate dry eye symptoms in patients with diabetic retinopathy, evaluating the levels of inflammatory cytokines and oxidative stress in the tear film.

The researchers intend to include 78 patients, divided into three intervention groups, who will be randomly assigned an eye drop with antioxidants, where the patient must apply one drop in each eye for 1 month.

In the study, the characteristics of the surface of the eye will be evaluated and tear samples will be taken from each eye, before and after the intervention with the eye drops. Subsequently, the clinical and sample results will be evaluated to compare the effects between them.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Dry eye syndrome is a multifactorial disease where tear film homeostasis is lost, accompanied by ocular symptoms such as burning, blurred vision, foreign body sensation, ocular redness, itching, in which tear film instability and hyperosmolarity, causing inflammation of the ocular surface, endothelial damage and neurosensory alterations.

Worldwide, in patients with diabetic retinopathy it has a prevalence of 54%, however in Mexico, only a prevalence of 41% has been described in the diabetic population, without having reports of prevalence in patients with diabetic retinopathy.

The state of chronic hyperglycemia in diabetes mellitus causes neuropathic corneal damage and dysfunction of the meibomian glands, this promotes a decrease in tear production, establishing dysfunction of the tear film and a state of hyperosmolarity in it, the latter induces activation of inflammatory mediators and release of proinflammatory cytokines that generate more damage to the corneal surface, entering a vicious cycle of tear film instability.

Likewise, the preexisting state of oxidative stress in patients with diabetic retinopathy, where there is an imbalance between the production and degradation of reactive oxygen species, contributes to the induction of changes in the corneal surface and tear film dysfunction.

Dry eye treatment is focused on the characteristics of the tear film and the characteristics of the ocular surface, with the aim of controlling and improving symptoms, with the use of different formulations and tolerability profiles. However, these are not adequate to reduce the effect of the inflammatory state and oxidative stress present in the tear film and the ocular surface, causing the patient's visual quality to worsen.

The researchers intend to assess whether antioxidant therapy in eye drops influences levels of oxidative stress and inflammatory markers in the tear film.

Study Type

Interventional

Enrollment (Anticipated)

78

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Adolfo D Rodríguez-Carrizalez, M.D./PhD
  • Phone Number: +52 33 10585200
  • Email: leinadkit@hotmail.com

Study Contact Backup

Study Locations

  • Mexico
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44340
        • Recruiting
        • Institute of Experimental and Clinical Therapeutics,
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Cecilia Olvera-Montaño, MD
        • Sub-Investigator:
          • Ana K López-Contreras, PBCh
        • Sub-Investigator:
          • Diana E Arévalo-Simental, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with type 2 diabetes, with presence of diabetic retinopathy in any of its stages without data on severity
  • Patients who voluntarily give their informed consent.
  • Patients who meet an Ocular Surface Disease Index (OSDI) score between 13-32 points (mild to moderate severity)
  • Patients who meet one or more of the following:
  • Tear film breakup time equal to or less than 10 seconds
  • Corneal fluorescein staining with more than 5 sites
  • Conjunctival staining with more than 9 sites.
  • Non-smokers or history of inactive smoking > 6 months
  • Metabolic criteria:
  • Glycated hemoglobin equal to or less than 9%
  • LDL less than or equal to 100 mg/dl
  • Triglycerides less than or equal to 180 mg/dl
  • Blood pressure less than or equal to 140/80 mm Hg

Exclusion Criteria:

  • Patients with autoimmune diseases and/or Sjögren's disease
  • Patients with neurodegenerative processes and/or cancer
  • Present aggregate ophthalmological diagnosis of:
  • Glaucoma
  • Allergic, viral or bacterial conjunctivitis.
  • Demodex
  • Eye parasitic infections.
  • Unresolved eye trauma
  • Scarring diseases of the ocular surface
  • Corneal or conjunctival ulcers.
  • Filamentous keratitis, neurotrophic
  • Bullous keratopathy
  • Patients taking any of the following medications:
  • Osmotic diuretics
  • Alpha agonists
  • NSAIDs, cannabinoids or opioids
  • Benzodiazepines, selective serotonin reputate inhibitors, monoamine oxidate inhibitors
  • nonlepromatous, antimalarials (Chloroquine / Hydroxychloroquine)
  • Corticosteroids

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Q10 coenzyme, vitamin E and cross-linked hyaluronic acid
This arm will administer eye drops with a combination of cross-linked hyaluronic acid, Q10 coenzyme and vitamin E, it will consist of 26 patients with diabetic retinopathy and mild to moderate dry eye syndrome. One drop will be instilled in each eye every 4 hours for a month.
Drug: VisuXL®
It consists of a preservative-free eye drop composed of 100 mg cross-linked hyaluronic acid, 100 mg coenzyme Q10, 500 mg vitamin E TPGS (D-alpha-tocopheryl polyethylene glycol succinate), one drop is applied in each eye every 4 hours for a month.
Other Names:
  • VisuXL tear drop
Active Comparator: Sodium hyaluronate
This arm will administer eye drops with sodium hyaluronate, it will consist of 26 patients with diabetic retinopathy and mild to moderate dry eye syndrome. One drop will be instilled in each eye every 4 hours for a month.
Drug: Lagricel PF®
It consists of a preservative-free eye drop composed of sodium hyaluronate 0.4%, one drop is applied in each eye every 4 hours for a month.
Other Names:
  • Lagricel preservative free
Active Comparator: Sodium hyaluronate and chondroitin sulfate
This arm will administer eye drops with a combination of sodium hyaluronate and chondroitin sulfate, it will consist of 26 patients with diabetic retinopathy and mild to moderate dry eye syndrome. One drop will be instilled in each eye every 4 hours for a month.
Drug: Humylub PF®
It consists of eye drops without preservatives composed of 0.1% sodium hyaluronate and 0.18% chondroitin sulfate, one drop is applied to each eye every 4 hours for a month.
Other Names:
  • Humylub preservative free

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in levels of tumor necrosis factor alpha (TNF-a) in tear film at 30 days.
Time Frame: 30 days
Tears will be collected with Drummond glass® micro capillary tubes without stimulation of tear secretion and placed in an eppendorf tube at -80 celsius degrees. The cytokine concentration will be determined with multiplex bead immunoassays technique and reported in picogram per milliliter units (pg/mL)
30 days
Change from baseline in levels of interleukin 8 (IL-8)
Time Frame: 30 days
Tears will be collected with Drummond glass® micro capillary tubes without stimulation of tear secretion and placed in an eppendorf tube at -80 celsius degrees. The cytokine concentration will be determined with multiplex bead immunoassays technique and reported in picogram per milliliter units (pg/mL)
30 days
Change from baseline in levels of interleukin 6 (IL-6)
Time Frame: 30 days
Tears will be collected with Drummond glass® micro capillary tubes without stimulation of tear secretion and placed in an eppendorf tube at -80 celsius degrees. The cytokine concentration will be determined with multiplex bead immunoassays technique and reported in pg/mL.
30 days
Change from baseline in levels of interleukin 10 (IL-10)
Time Frame: 30 days
Tears will be collected with Drummond glass® micro capillary tubes without stimulation of tear secretion and placed in an eppendorf tube at -80 celsius degrees. The cytokine concentration will be determined with multiplex bead immunoassays technique and reported in picogram per milliliter units (pg/mL)
30 days
Changes from baseline in total antioxidant capacity in the tear film at 30 days.
Time Frame: 30 days
Tears will be collected with Drummond glass® micro capillary tubes without stimulation of tear secretion and placed in an eppendorf tube at -80 celsius degrees. Total antioxidant capacity concentration will be determined with colorimetric assay technique and reported in units called Trolox equivalents (TE), nmol/sample.
30 days
Change from baseline in lipoperoxides levels in tear film at 30 days.
Time Frame: 30 days
Tears will be collected with Drummond glass® micro capillary tubes without stimulation of tear secretion and placed in an eppendorf tube at -80 celsius degrees. Lipoperoxides concentration will be determined with colorimetric assay technique and reported in nmol/mL.
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in the pattern of ocular surface staining with fluorescein sodium according to Oxford Scheme at 30 days.
Time Frame: 30 days
Ocular surface staining with fluorescein sodium dye it will be assessed during slit lamp examination and it will be measure on a scale from 0 to 5 according to the Oxford scheme, with 5 being the most severe staining.
30 days
Change from baseline in the pattern of ocular surface staining with lissamine green according to Oxford Scheme at 30 days.
Time Frame: 30 days
Ocular surface staining with lissamine green dye it will be assessed during slit lamp examination and it will be measure on a scale from 0 to 5 according to the Oxford scheme, with 5 being the most severe staining.
30 days
Change from baseline in the tear break-up time (TBUT) in seconds at 30 days.
Time Frame: 30 days
It will be measured the time interval in seconds between a complete blink and the first appearance of a dry spot in the tear film after fluorescein sodium administration during slit-lamp examination, considering less than 10 seconds as abnormal.
30 days
Change from baseline in tear film osmolarity at 30 days.
Time Frame: 30 days
It will be measured collecting a tear sample in each eye with TearLab® Test reporting osmolarity in milliosmol per liter (mOsm/L)
30 days
Change from baseline in tear secretion in mm with Schirmer I test at 30 days.
Time Frame: 30 days
Tear secretion will be assessed with a graduated test strip placed on the lower eyelid margin without anesthesia, after five minutes, the strip is removed and the amount of wetting is measured in mm, less than 10 mm is considered abnormal.
30 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline severity of dry eye symptoms according the punctuation in Ocular Surface Disease Index (OSDI) at 30 days
Time Frame: 30 days.
OSDI is a questionnaire that will be assessed on a scale of 0 to 100 to measure dry eye disease severity (normal, mild to moderate and severe) and effect on vission-related function.
30 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Adolfo Daniel Rodriguez-Carrizalez

Collaborators

Hospital Civil de Guadalajara

Investigators

  • Study Director: Adolfo D Rodriguez-Carrizalez, M.D/PhD, University of Guadalajara

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2021

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

January 31, 2024

Study Registration Dates

First Submitted

May 30, 2022

First Submitted That Met QC Criteria

June 17, 2022

First Posted (Actual)

June 23, 2022

Study Record Updates

Last Update Posted (Actual)

June 29, 2022

Last Update Submitted That Met QC Criteria

June 23, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OSRD-20200831-1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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