Low-Level Light Therapy for Dry Eye Disease in Thyroid Eye Disease: A Randomized, Double-Masked, Sham-Controlled Trial
11 affiliations
- 1Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
- 2Ophthalmology Clinic, Cai Ferate Clinical Hospital, 700506 Iasi, Romania
- 3Laboratory of Immunology, St. Spiridon County Clinical Hospital, 700111 Iasi, Romania
- 4Advanced Research and Development Center for Experimental Medicine “Prof. Ostin C. Mungiu”—CEMEX, Grigore T. Popa University of Medicine and Pharmacy Iasi, 700259 Iasi, Romania
- 5Eye Clinic, Department of Surgical Sciences, University of Cagliari, 09124 Cagliari, Italy
- 6Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- 7Optissima, Barbu Văcărescu 102, 020283 Bucharest, Romania
- 8Faculty of Physics, Alexandru Ioan Cuza University, 700506 Iasi, Romania
- 9Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy
- 10Eye Clinic, Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, 80131 Naples, Italy
- 11Ophthalmologic Unit, Salerno University Hospital, 84131 Salerno, Italy
Abstract
Dry eye disease (DED) affects the majority of patients with thyroid eye disease (TED) and frequently persists despite maximal conservative therapy. Low-level light therapy (LLLT), or photobiomodulation, is a non-invasive treatment with anti-inflammatory and pro-reparative properties whose value in autoimmune, chronically driven ocular surface disease is unknown. In this prospective, randomized, double-masked, sham-controlled trial, eyes of patients with TED-associated DED that remained symptomatic despite intensive preservative-free lubrication, bedtime ophthalmic ointment and daily periocular hygiene were allocated 2:1 to periocular LLLT (630 nm LED mask, 15 min per session, applied over closed eyelids) or to sham treatment (identical procedure with light emission reduced to <30% of therapeutic output). Background ocular surface therapy was maintained unchanged in both arms. Assessments were performed at baseline (T0), weekly during treatment (T1–T3) and at one month (T4) and two months (T5) after the last session. The primary outcome was the Ocular Surface Disease Index (OSDI); secondary outcomes were non-invasive break-up time (NIBUT), fluorescein break-up time (FBUT), Schirmer I test, tear osmolarity, upper- and lower-eyelid meibography, corneal fluorescein staining and lipid-layer grade. The primary OSDI assessment was the change from baseline to T3, the end-of-treatment visit. Additional follow-up assessments were performed at T4 and T5. Forty-six eyes of 46 patients were analyzed (30 LLLT, 16 sham); baseline disease was active in 14/30 (46.7%) and 6/16 (37.5%) eyes, respectively. At T3, adjusted OSDI was lower with LLLT than with sham (between-group difference −7.49 points; 95% CI −11.66 to −3.32; p < 0.001). The difference persisted at T4 and T5 (−11.97 and −16.86 points, respectively; both Holm-adjusted p < 0.001). Tear osmolarity was lower with LLLT at T4 (−10.91 mOsm/L; 95% CI −18.96 to −2.87; p = 0.009) and T5 (−13.81 mOsm/L; 95% CI −22.55 to −5.06; p = 0.004). No multiplicity-adjusted between-group differences were demonstrated for NIBUT, FBUT, Schirmer I test or meibography. The adjusted probability of corneal staining was numerically lower with LLLT (T4: 15.7% vs. 34.7%; risk difference −19.0 percentage points; p = 0.100). In exploratory analyses, the treatment-by-visit-by-activity interaction was significant (p = 0.0159), with OSDI differences of −21.45 and −25.90 points in active disease versus −5.50 and −10.09 points in inactive disease at T4 and T5. CAS and OSDI were positively correlated at baseline (Spearman ρ = 0.547; Holm-adjusted p < 0.001) and at T5 (Spearman ρ = 0.428; Holm-adjusted p = 0.003). No treatment-related adverse events occurred. In conclusion, in TED-associated DED refractory to maximal conservative therapy, LLLT produced a significant and progressively increasing reduction in symptom burden together with an objective reduction in tear hyperosmolarity. Effects on break-up time, aqueous secretion, gland morphology, and lipid layer grade were not demonstrable within two months. The pattern and pace of response differ from those observed with the same technology after cataract surgery and are consistent with a chronic, systemically driven disease in which the ocular surface insult is continuously renewed.
Related
- Effects of a Saccharomyces uvarum Cell-Based Preparation on Gut Microbial Ecology and Metabolic Activity in Adults Without Diagnosed Gastrointestinal Disease: A Randomized Placebo-Controlled Crossover Pilot Study
- Ferroptosis and the Thyroid: Emerging Links Between Iron Homeostasis, Oxidative Stress, and Thyroid Disease
- Sialic Acids: From Biosynthesis and Molecular Recognition to Disease and Therapy
- Systemic Inflammatory Markers, Thyroid Autoimmunity, and Neuroretinal Structure in Graves’ Disease: A Comparative OCT Study According to Ophthalmopathy Status
- From patient cells to patient therapy: Twenty years of iPSC-based translation in neurodegenerative disease
BibTeX
@article{timoftezorila2026lowlevel,
title = {{Low-Level Light Therapy for Dry Eye Disease in Thyroid Eye Disease: A Randomized, Double-Masked, Sham-Controlled Trial}},
author = {Mihaela-Madalina Timofte-Zorila and Alin Constantin Pînzariu and Mariana Pavel-Tanasa and Giuseppe Giannaccare and Sinziana Istrate and Nicoleta Vlas and Diana Alecu and Tudor-Stefan Rotaru and Radu Tanasa and Filippo Lixi and Mario Troisi and Cristina Preda and Daniel Constantin Branisteanu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219802},
url = {https://www.mdpi.com/1422-0067/27/21/9802},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Low-Level Light Therapy for Dry Eye Disease in Thyroid Eye Disease: A Randomized, Double-Masked, Sham-Controlled Trial
AU - Mihaela-Madalina Timofte-Zorila
AU - Alin Constantin Pînzariu
AU - Mariana Pavel-Tanasa
AU - Giuseppe Giannaccare
AU - Sinziana Istrate
AU - Nicoleta Vlas
AU - Diana Alecu
AU - Tudor-Stefan Rotaru
AU - Radu Tanasa
AU - Filippo Lixi
AU - Mario Troisi
AU - Cristina Preda
AU - Daniel Constantin Branisteanu
PY - 2026
DA - 2026/10/31
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219802
UR - https://www.mdpi.com/1422-0067/27/21/9802
AB - Dry eye disease (DED) affects the majority of patients with thyroid eye disease (TED) and frequently persists despite maximal conservative therapy. Low-level light therapy (LLLT), or photobiomodulation, is a non-invasive treatment with anti-inflammatory and pro-reparative properties whose value in autoimmune, chronically driven ocular surface disease is unknown. In this prospective, randomized, double-masked, sham-controlled trial, eyes of patients with TED-associated DED that remained symptomatic despite intensive preservative-free lubrication, bedtime ophthalmic ointment and daily periocular hygiene were allocated 2:1 to periocular LLLT (630 nm LED mask, 15 min per session, applied over closed eyelids) or to sham treatment (identical procedure with light emission reduced to <30% of therapeutic output). Background ocular surface therapy was maintained unchanged in both arms. Assessments were performed at baseline (T0), weekly during treatment (T1–T3) and at one month (T4) and two months (T5) after the last session. The primary outcome was the Ocular Surface Disease Index (OSDI); secondary outcomes were non-invasive break-up time (NIBUT), fluorescein break-up time (FBUT), Schirmer I test, tear osmolarity, upper- and lower-eyelid meibography, corneal fluorescein staining and lipid-layer grade. The primary OSDI assessment was the change from baseline to T3, the end-of-treatment visit. Additional follow-up assessments were performed at T4 and T5. Forty-six eyes of 46 patients were analyzed (30 LLLT, 16 sham); baseline disease was active in 14/30 (46.7%) and 6/16 (37.5%) eyes, respectively. At T3, adjusted OSDI was lower with LLLT than with sham (between-group difference −7.49 points; 95% CI −11.66 to −3.32; p < 0.001). The difference persisted at T4 and T5 (−11.97 and −16.86 points, respectively; both Holm-adjusted p < 0.001). Tear osmolarity was lower with LLLT at T4 (−10.91 mOsm/L; 95% CI −18.96 to −2.87; p = 0.009) and T5 (−13.81 mOsm/L; 95% CI −22.55 to −5.06; p = 0.004). No multiplicity-adjusted between-group differences were demonstrated for NIBUT, FBUT, Schirmer I test or meibography. The adjusted probability of corneal staining was numerically lower with LLLT (T4: 15.7% vs. 34.7%; risk difference −19.0 percentage points; p = 0.100). In exploratory analyses, the treatment-by-visit-by-activity interaction was significant (p = 0.0159), with OSDI differences of −21.45 and −25.90 points in active disease versus −5.50 and −10.09 points in inactive disease at T4 and T5. CAS and OSDI were positively correlated at baseline (Spearman ρ = 0.547; Holm-adjusted p < 0.001) and at T5 (Spearman ρ = 0.428; Holm-adjusted p = 0.003). No treatment-related adverse events occurred. In conclusion, in TED-associated DED refractory to maximal conservative therapy, LLLT produced a significant and progressively increasing reduction in symptom burden together with an objective reduction in tear hyperosmolarity. Effects on break-up time, aqueous secretion, gland morphology, and lipid layer grade were not demonstrable within two months. The pattern and pace of response differ from those observed with the same technology after cataract surgery and are consistent with a chronic, systemically driven disease in which the ocular surface insult is continuously renewed.
SN - 1422-0067
ER -