Trehalose-hyaluronate combination aids tear film after eyelid surgery

According to the study authors, a combination drop containing 3% trehalose and 0.15% sodium hyaluronate (SH) produced greater improvement in objective ocular surface metrics than SH monotherapy after eyelid surgery for ectropion, entropion, or eyelid reconstruction.¹ The retrospective comparative study, published in the International Journal of Ophthalmology, followed 114 patients for 3 months after surgery. Investigators reported superior outcomes with the combination drop on tear break-up time (TBUT), Oxford staining score, and meibomian gland loss (MGL), with the largest separation between groups seen in patients undergoing eyelid reconstruction.¹

Eyelid surgery is recognized as a contributor to postoperative ocular surface disruption through topical anesthetics, antiseptic exposure, and transient lagophthalmos.² SH drops are a standard postoperative supportive therapy in patients who have undergone oculoplastic surgery, and the study authors selected SH monotherapy as the comparator for this reason.¹ This analysis adds stratified subgroup data by surgical indication, an angle the authors describe as new for trehalose-based formulations in this population.¹

The single-center, retrospective study enrolled 114 patients treated between August 2021 and July 2024 for ectropion, entropion, or eyelid reconstruction.¹ Patients received either 0.15% SH alone (n = 57) or 3% trehalose plus 0.15% SH (n = 57), each dosed four times daily for three months.¹ Treatment allocation followed physician preference rather than randomization, and groups did not differ significantly in age, sex, or surgical indication.¹ Outcomes assessed at baseline and three months included TBUT, Ocular Surface Disease Index (OSDI), Oxford staining score, MGL by infrared meibography, and central corneal epithelial thickness (CCET) by anterior segment optical coherence tomography.¹

Subgroup results and safety considerations in trehalose-SH therapy

Both groups improved across all measured parameters, but between-group comparisons favored the trehalose-SH combination.¹ TBUT improved more with the combination drop, with a mean between-group difference of 0.77 seconds (95% CI, 0.12-1.42; P = .036).¹ Oxford staining score showed a mean difference of -0.39 (95% CI, -0.75 to -0.03; P = .036), and MGL showed a mean difference of -2.02% (95% CI, -3.78% to -0.26%; P = .025), each favoring trehalose-SH.¹ CCET improved more with the combination drop as well (P = .048).¹ OSDI improvement did not differ significantly between groups (P = .533), despite the objective measures favoring trehalose-SH.¹

Subgroup analysis showed the largest treatment difference in patients undergoing eyelid reconstruction (n = 34), where trehalose-SH outperformed SH alone across all five parameters, including OSDI (P = .043).¹ In the ectropion (n = 48) and entropion (n = 32) subgroups, trehalose-SH showed significant advantages on TBUT, Oxford score, and CCET, while OSDI and, in the entropion subgroup, MGL did not reach statistical significance.¹ No adverse events were reported with either formulation, and the study authors noted neither patients nor examiners were masked to treatment assignment.¹

Broader evidence on trehalose-containing drops has shown mixed results outside the surgical setting. A randomized trial comparing a hyaluronate-trehalose solution with hyaluronate alone reported superior OSDI improvement with the combination in patients with moderate to severe dry eye disease, while a separate short-term comparison found trehalose-hyaluronate drops did not significantly outperform other artificial tears on non-invasive tear break-up time.^3,4 The study authors suggested the more pronounced objective benefit seen in their surgical cohort may reflect the added oxidative and inflammatory burden of eyelid surgery itself.¹

The authors pointed to several limitations: retrospective, non-randomized design; a single masked grader for meibography, precluding assessment of inter-grader repeatability; unbalanced subgroup sizes; and a three-month follow-up window too short to capture longer-term ocular surface remodeling.¹ No a priori sample size calculation was performed, and the authors characterized the subgroup analyses as exploratory and potentially underpowered, particularly for OSDI.¹ They called for prospective studies with larger cohorts, extended follow-up, and assessment of patient-reported quality of life to confirm the role of trehalose-SH in postoperative oculoplastic care.¹

Frequently asked questions:

What did this study find about trehalose-sodium hyaluronate drops after eyelid surgery?
Patients using a combination of 3% trehalose and 0.15% sodium hyaluronate showed greater improvement in tear break-up time, corneal staining, and meibomian gland loss than patients using sodium hyaluronate alone over three months after eyelid surgery.

Which patients benefited most from the trehalose-containing drop?
Patients undergoing eyelid reconstruction showed the most consistent advantage with trehalose-sodium hyaluronate, with significant improvement across all five measured ocular surface parameters compared with sodium hyaluronate alone.

Did symptom scores improve along with objective findings?
OSDI scores improved similarly in both treatment groups, with no significant between-group difference, even though objective measures favored the trehalose-containing formulation.

References
1. Arslan N, Kakil ŞB, Çoban A. Improving the post-oculoplastic tear film: trehalose as a critical adjunct. Int J Ophthalmol. 2026;19(6):1158-1164. doi:10.18240/ijo.2026.06.17
2. Gomes JAP, Azar DT, Baudouin C, et al. TFOS DEWS II iatrogenic report. Ocul Surf. 2017;15(3):511-538.
3. Doan S, Bremond-Gignac D, Chiambaretta F. Comparison of the effect of a hyaluronate-trehalose solution to hyaluronate alone on Ocular Surface Disease Index in patients with moderate to severe dry eye disease. Curr Med Res Opin. 2018;34(8):1373-1376.
4. Maity M, Allay MB, Ali MH, et al. Effect of different artificial tears on tear film parameters in dry eye disease. Optom Vis Sci. 2025;102(1):37-43.