So far there is no proof Xiidra or Lifitegrast improves meibomian gland function.
A drug rep told me there was, but I have not seen anything published.
References:
1.
Although many subjects with DED have mixed components of both lid margin disease and aqueous-deficient DED, the role of lifitegrast in managing the inflammatory component of predominately meibomian gland disease has not yet been evaluated.
2.
Expert Opinion on Pharmacotherapy
Volume 18, 2017 – Issue 14
Lifitegrast ophthalmic solution 5.0% is the first pharmacological medication to be approved by the FDA for the treatment of DED since 2003, when CsA 0.05% was approved for the indication of increasing tear production in DED patients. The approval of CsA 0.05% was based on significant improvements in Schirmer wetting in clinical trials; CsA 0.05% is not indicated for the treatment of the symptoms of DED. Results from clinical trials [35,36], and clinical experience post approval, have shown that marked improvement with CsA 0.05% generally takes at least 3 months. In contrast, significant symptom improvements occurred with lifitegrast in three of four 12-week trials (phase 2, OPUS-2, and OPUS-3) by 6 weeks and as early as 2 weeks in two trials (OPUS-2 and OPUS-3).
CsA inhibits the protein phosphatase, calcineurin, which results in inhibition of IL-2 production and inhibition of T-cell activation [37]. However, CsA does not inhibit activated T cells [38,39], so there is a delay for activated T cells to undergo apoptosis and for new unstimulated T cells to form. Estimates for the median life span of human T cells are reported as up to 164 days for CD4+ and 157 days for CD8+ memory T cells [40]. In contrast to CsA, lifitegrast is expected to act on all circulating T cells because it blocks a specific pathway (LFA-1/ICAM-1) in the DED inflammatory process, which has a role in T-cell activation and the migration/recruitment of activated T cells to ocular surface tissues [19].
Current limitations of the clinical data are a lack of head-to-head comparisons between lifitegrast and CsA, limited published data on the real-world use of lifitegrast and on the predictors of the response to treatment with lifitegrast. In addition, given the heterogeneous nature of DED, it is not clear whether everyone with the symptoms of the condition would benefit from an agent that inhibits ocular surface inflammation. Further studies are also needed to investigate whether lifitegrast could be used in a combination pharmacotherapy approach utilizing medications with different mechanisms of action that reduce inflammation (e.g. lifitegrast, corticosteroids, CsA) and improve tear function/protection of the ocular surface (e.g. artificial tear substitutes, mucin and tear secretagogues). In particular, whether the combination of lifitegrast with topical CsA has synergistic/additive effects, as has been observed for CsA 0.05% plus loteprednol [41], would be of interest. It would also be interesting to determine whether the incidence of dysgeusia (unpleasant taste/change in taste sensation), which has been observed in lifitegrast trials, could be reduced with punctal plugs. Other future research could also provide information on whether lifitegrast can penetrate other parts of the eye (e.g. the meibomian glands and lacrimal glands), which would be useful in understanding whether lifitegrast has a particular role in treating evaporative DED caused by meibomian gland dysfunction.
LFA-1/ICAM-1 Interaction as a Therapeutic Target in Dry Eye Disease.
Abstract
1. CD4+ T cells have been shown to be present in lacrimal gland biopsy tissue from patients with Sjögren’s syndrome (SS)6 and in conjunctival biopsy samples from patients with DED.7 A reduction in activated lymphocytes in the conjunctiva of patients with SS has also been seen with DED treatment.8 TH1 cells are well recognized to secrete the proinflammatory cytokines TNF-α, interferon-γ (IFN-γ), and IL-2, which activate macrophages,9,10 and in the case of IFN-γ, cause goblet cell dysfunction and death.11–14 TH17 cells secrete the cytokine IL-17, which stimulates the production of other proinflammatory molecules, recruits neutrophils, and has been shown to promote corneal epithelial barrier disruption.15,16 Evidence supporting a fundamental role of dendritic cells in DED is provided by a study demonstrating accumulation of mature CD11c+ cells (dendritic cells) in the draining cervical lymph nodes within 24 h of desiccating stress-induced DED in mice, and correlation with the formation of autoreactive CD4+ T cells.17 Furthermore, this study provided evidence that resident APCs in the ocular surface tissue are required for secondary activation of CD4+ T cells in the ocular surface, with local depletion of dendritic cells inhibiting the ability of activated CD4+ T cells to accumulate in ocular surface tissues.17
2. efferent arm of the DED immunoinflammatory pathway, naive T cells are primed in the lymph nodes through interaction with dendritic cells and differentiate to TH1 and TH17 effector cells.3,4,36 These activated CD4+ effector T cells migrate from the lymph nodes to the ocular surface and lacrimal glands, where they exert inflammatory effects. LFA-1 and ICAM-1 may have roles at each step in this pathway, including T cell activation in the lymph node, T cell migration, and potentially secondary activation of T cells at the ocular surface.
3. authors further investigated the effects of ICAM-1 and LFA-1 inhibition in these mice and found that intraperitoneal administration of monoclonal antibodies targeting ICAM-1 and LFA-1 resulted in a reduction in the number of inflammatory infiltrates in the lacrimal glands.55 Notably, the greatest inhibition of cellular infiltration in the conjunctiva was achieved with the administration of a combination of monoclonal antibodies against ICAM-1 and LFA-1, rather than the use of either anti-ICAM-1 or anti-LFA-1 antibody alone. Taken together, these results suggest a potential role of LFA-1/ICAM-1 in the recruitment and retention of LFA-1-expressing T cells to the epithelial cells of the conjunctiva, where they could induce damage via proinflammatory cytokine release.