Effect of Low-Level Light Therapy on Ocular Surface Parameters in Patients With Graves Disease

NCT07332988 | Enrolling By Invitation DMC

• 1 other identifier: 598/20.05.2025
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, interventional, randomized, controlled, double-blind clinical study evaluates the effect of Low-Level Light Therapy (LLLT) delivered by a polychromatic periocular mask (Eye-light®️) versus a sham device in adults with dry eye disease (DED) associated with Graves' ophthalmopathy, refractory to conventional topical treatment. The LLLT protocol applies photobiomodulation to eyelid and periocular tissues to support meibomian gland function and reduce tear inflammatory biomarkers. The primary endpoint is the change in tear film stability measured by Non-Invasive Tear Break-Up Time (NIBUT) and Fluorescein Tear Break-Up Time (FBUT). Secondary outcomes include symptom scores (OSDI), Schirmer I test, tear osmolarity, ocular surface staining scales, automated conjunctival hyperemia, blink analysis, meibomian gland morphology (meibography/meiboscale), tear inflammatory biomarkers, and safety/tolerability.

Conditions

Graves Ophthalmopathy; Dry Eye Disease (DED)

Keywords

DED associated with Graves Ophtalmopaty; DED; Graves; Ophtalmopaty; LLLT; Photobiomodulation

Outcome Measures

Primary Outcomes (1)

• Changes in tear film stability (NIBUT and FBUT) from baseline during the treatment and in the follow-up period in patients with Graves' ophthalmopathy who undergo low-level light therapy (LLLT)

  Noninvasive Tear Break-Up Time (NIBUT) is an eye test measuring the stability of the tear film without using dye (fluorescein), making it more accurate than standard tests. It determines how long the tear film stays intact before breaking, with results typically indicating dry eye if the time is under 10 seconds. Fluorescein Breakup Time (FBUT) is a diagnostic test measuring the time (in seconds) between the last blink and the appearance of the first dry spot or break in the tear film. Both of these measurements were assessed objectively on average of three repeats in order to obtain the average value using the DEA 520 Dry Eye Analyzer; Moptim / Shenzhen Certainn Technology Co., Ltd., China. The primary outcome is the change in the tear film stability from baseline to 3 months after the final treatment, comparing the LLLT group to the sham group.

  Before first mask session, and weekly before each treatment to the final treatment, at 1 month, 2 months and 3 months follow ups after the final treatment.

Secondary Outcomes (12)

• Ocular Surface Disease Index (OSDI)

  Before first mask session, and weekly before each treatment to the final treatment, at 1 month, 2 months and 3 months follow ups after the final treatment.

• Schirmer I Test

  Before first mask session, and weekly before each treatment to the final treatment, at 1 month, 2 months and 3 months follow ups after the final treatment.

• Tear osmolarity

  Before first mask session, at 1 month and 3 months follow ups after the final treatment.

• Tear meniscus height

  Before first mask session, and weekly before each treatment to the final treatment, at 1 month, 2 months and 3 months follow ups after the final treatment.

• Meibography graded with the meiboscale for upper and lower eyelids

  Before first mask session, and weekly before each treatment to the final treatment, at 1 month, 2 months and 3 months follow ups after the final treatment.

Study Arms (2)

LLLT Group

EXPERIMENTAL

A total of 20 patients will be enrolled and treated as per the classical protocol for dry eye treatment (4 sessions at weekly intervals and 3 monthly follow ups).The treatment was delivered through a wearable mask emitting polychromatic red and near-infrared light, targeting the eyelids and meibomian glands. Ocular surface assessments were performed at baseline (before the first treatment), once a week (before each treatment) for 4 weeks, and later on at one month, 2 months and 3 months follow ups to evaluate the effects of LLLT on tear film quality, inflammation, and meibomian gland function.

Device: Low Light Level therapy

Sham Group

SHAM COMPARATOR

A total of 10 patients will be enrolled and treated as per the classical protocol for dry eye treatment (4 sessions at weekly intervals and 3 monthly follow ups). The procedure mimicked the experience of the active LLLT intervention, using the same mask device without activation of the therapeutic light emission. The ocular surface assessments were conducted at the same time points as the active treatment group-baseline, every week for the first month, at 1 month, 2 months and 3 months follow ups to evaluate tear film function, ocular surface condition, and meibomian gland performance.

Device: Sham (No Treatment)

Interventions

Sham (No Treatment) DEVICE

The sham group had undergone a similar procedure using the Eye-light® device (Espansione Group, Italy), as the one described above but in this case the device emits only 30% of the treatment power. Patients had a similar visual and sensory experience of the treatment but without actual biologic effects. Each treatment session lasted a total of 15 minutes. It is non-pharmacological, non-contact, and well-tolerated. The light is delivered through closed eyelids, ensuring safety and comfort. This approach allowed for masking of participants and investigators to minimise bias, while ensuring that patients in the control group received no active therapeutic exposure.

Sham Group

Low Light Level therapy DEVICE

The intervention consists of non-invasive periocular photobiomodulation using the Eye-light® device (Espansione Group, Italy), which delivers low-level polychromatic red and near-infrared light through a specially designed mask. The LLLT mask consisted of light emitting diodes (LEDs) with red light, 633 nm wavelengths. The treatment is designed to improve tear film stability, stimulate meibomian gland activity, reduce ocular surface inflammation. This protocol targets cellular mitochondrial activity to enhance tissue repair and anti-inflammatory effects. Each treatment session lasted a total of 15 minutes. It is non-pharmacological, non-contact, and well-tolerated. The light is delivered through closed eyelids, ensuring safety and comfort, and the device used is CE-marked for ophthalmic applications.

LLLT Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with dry eye disease, particularly associated with Graves' ophthalmopathy.
• Refractory to conventional dry eye treatments (e.g., artificial tears, cyclosporine, corticosteroid eye drops).
• Adult patients (over 18 years old).

You may not qualify if:

• Pregnant or breastfeeding.
• Uncontrolled systemic diseases (other than Graves' disease).
• Use of general corticosteroids in the last 6 months.
• Ocular or orbital surgery in the last 6 months.
• Use of contact lenses within the last week.
• Active ocular infection or allergy.

Sponsors & Collaborators

• Grigore T. Popa University of Medicine and Pharmacy: lead

Study Sites (1)

University of Medicine and Pharmacy "Grigore T. Popa"

Iași, Iaşi, 700115, Romania

Location

MeSH Terms

Conditions

Dry Eye Syndromes; Graves Ophthalmopathy

Interventions

Low-Level Light Therapy

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Laser Therapy; Therapeutics; Phototherapy

Study Officials

• Mihaela Madalina Timofte Zorila

  University of Medicine "Gr. T. Popa", Iasi, Romania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a randomized, controlled, single-masked, parallel-group trial. Eligible participants diagnosed with Graves' disease are randomly assigned in a 2:1 ratio to receive either low-level light therapy (LLLT) or a sham treatment. Interventions are scheduled once per week over a 4-week period. Clinical outcomes are assessed at baseline, after each treatment session, and at 4, 8, 12 and 16 weeks. Participants remain in their assigned group for the duration of the study, with no crossover between groups.

Study Record Dates

• First Submitted: December 30, 2025
• First Posted: January 12, 2026
• Study Start: August 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: January 12, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR

Locations

RO (1)