Dataset Information

Meibomian gland dysfunction is suppressed via selective inhibition of immune responses by topical LFA-1/ICAM antagonism with lifitegrast in the allergic eye disease (AED) model.

ABSTRACT:

Purpose

The etiology of meibomian gland dysfunction (MGD) is incompletely understood, despite being a common ophthalmic condition and an area of unmet medical need. It is characterized by an insufficiency in glandular provision of specialized lipids (meibum) to the tear film and is a major cause of dry eye. Work in the allergic eye disease (AED) mouse model has revealed an immunopathogenic role in MGD causation, now raising interest in the applicability of immunomodulatory therapies. As such, we herein ask whether inhibition of lymphocyte function associated antigen (LFA)-1/intracellular adhesion molecules (ICAM)-1 signaling via topical lifitegrast administration has a therapeutic effect on MGD in AED mice.

Methods

Mice were induced with AED by i.p. injection of ovalbumin (OVA) mixed with alum and pertussis toxin, followed 2 weeks later by once daily topical OVA challenges for 7 days. Mice were treated topically with 5% lifitegrast ophthalmic solution or vehicle (PBS) 30 min prior to challenge. We developed a clinical ranking method to assess MGD severity, and also scored clinical allergy. Conjunctivae and draining lymph nodes were collected for flow cytometry.

Results

Topical lifitegrast significantly inhibited clinical MGD severity, which was associated with diminished pathogenic T_H17 cell and neutrophil numbers in the conjunctiva. No significant change in conjunctival T_H2 cells or eosinophils, and only marginal differences in ocular allergy were observed.

Conclusions

In AED mice, lifitegrast inhibited MGD severity marked by a reduction in select immune populations in the conjunctiva. Our findings warrant future examination of lifitegrast in the treatment of patients with forms of MGD.

SUBMITTER: Singh PP

PROVIDER: S-EPMC8606044 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTo investigate the comparative efficacy of intense pulsed light (IPL) therapy alone with that of IPL plus meibomian gland expression (MGX) for meibomian gland dysfunction (MGD).MethodsThis is a prospective randomized crossover clinical trial. Sixty patients were enrolled and randomly assigned to two groups. All of patients underwent four treatment sessions in total, which were two weeks apart. Group 1 underwent two sessions of IPL therapy with MGX, as well as two sessions of IPL alone. Group 2 received two sessions of IPL therapy alone, and two sessions of IPL therapy with MGX. The following parameters were measured at baseline (BL), 2 weeks after the second treatment session (FU1), and 2 weeks after the fourth treatment session (FU2): tearfilm break-up time (BUT), Oxford grade for corneal staining, meibomian gland expressibility (MGE), meibum quality (MQ), and ocular surface disease index (OSDI). The separate effect of MGX on improvement of MGD parameters was evaluated using generalized estimating equation (GEE).ResultsThe mean age of the participants was 57.52 ± 10.50 years. The BUT, Oxford grade, MGE, MQ, and OSDI of both groups improved significantly (from baseline) by the end of four treatment sessions (FU2 compared to BL; all p-values <0.05). The MGE and MQ significantly improved after the first and second treatment sessions (FU1 compare to BL; all p-values < 0.001). However, the improvement was not statistically significant after the third and fourth treatment sessions (FU2 compared to FU1; p-value of 0.388 for MGE and 0.645 for MQ in group 1, 0.333 for MGE and 0.333 for MQ in group 2). The IPL plus MGX therapy produced greater improvements in the BUT scores than did IPL therapy alone (p = 0.003 by GEE). In contrast, the Oxford grade, MGE, MQ, and OSDI were not influenced by the addition of MGX to IPL (p = 0.642, 0.663, 0.731, and 0.840, respectively by GEE).ConclusionIPL therapy effectively improves the subjective symptoms and objective ocular findings of MGD. MGX enhanced the improvement of BUT driven by IPL therapy. The meibomian gland function (MGE and MQ) recovers faster in response to IPL therapy than did the other parameters.