Clinical trial NCT05429229: Effect of Topical Antioxidants in Dry Eye Disease and Diabetic Retinopathy
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Dry Eye Syndromes
Diabetic Retinopathy
Oxidative Stress
Tear Film Deficiency
Keywords: Dry Eye Disease
Oxidative Stress biomarkers
Inflammatory biomarkers
Tear film
Eye drops
Diabetic Retinopathy
Lead sponsor: University of Guadalajara
Sponsor class: OTHER
Collaborators: name: Hospital Civil de Guadalajara
First posted: 2022-06-23
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Clinical trial phase 2 A.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in levels of tumor necrosis factor alpha (TNF-a) in tear film at 30 days.
timeFrame: 30 days
measure: Change from baseline in levels of interleukin 8 (IL-8)
timeFrame: 30 days
measure: Change from baseline in levels of interleukin 6 (IL-6)
timeFrame: 30 days
measure: Change from baseline in levels of interleukin 10 (IL-10)
timeFrame: 30 days
measure: Changes from baseline in total antioxidant capacity in the tear film at 30 days.
timeFrame: 30 days
measure: Change from baseline in lipoperoxides levels in tear film at 30 days.
timeFrame: 30 days
Secondary outcomes:
measure: Change from baseline in the pattern of ocular surface staining with fluorescein sodium according to Oxford Scheme at 30 days.
timeFrame: 30 days
measure: Change from baseline in the pattern of ocular surface staining with lissamine green according to Oxford Scheme at 30 days.
timeFrame: 30 days
measure: Change from baseline in the tear break-up time (TBUT) in seconds at 30 days.
timeFrame: 30 days
measure: Change from baseline in tear film osmolarity at 30 days.
timeFrame: 30 days
measure: Change from baseline in tear secretion in mm with Schirmer I test at 30 days.
timeFrame: 30 days
Other outcomes:
measure: Change from baseline severity of dry eye symptoms according the punctuation in Ocular Surface Disease Index (OSDI) at 30 days
timeFrame: 30 days.
Locations:
city: Guadalajara
country: Mexico
facility: Institute of Experimental and Clinical Therapeutics,
state: Jalisco
Study officials:
affiliation: University of Guadalajara
name: Adolfo D Rodriguez-Carrizalez, M.D/PhD
role: STUDY_DIRECTOR
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