Meibomian gland dysfunction (MGD) is a common ocular surface condition that affects the meibomian glands (MGs). MGs are modified sebaceous glands located within the tarsal plate of the eyelids. They belong to the category of holocrine glands, an often forgotten subset of exocrine glands (1), similar to the more familiar lacrimal and salivary glands. MGs produce meibum which contributes to the lipid layer of the human tear film (2, 3). The lipid layer plays a vital role in reducing evaporation of the tears, enhancing tear film stability, and maintaining the integrity of the ocular surface (4, 5). In MGD, there is an alteration in the quantity or quality of lipids produced, leading to symptoms of dryness, irritation, redness, and blurred vision, significantly impacting the comfort and quality of life of affected individuals (2, 6). MGD is highly prevalent and is considered the leading cause of evaporative dry eye disease (7). Recently, there has been increasing evidence highlighting the co-occurrence of MGD among Sjögren's Disease (SjD) (8–11), challenging the long-established belief that SjD dry eye disease is exclusively due to aqueous deficiency (11–20).

SjD, formerly known as Sjögren's Syndrome (SS), is a chronic autoimmune disease which primarily affects the exocrine glands, most notably the lacrimal and salivary glands (21, 22). Historically, SjD has been classified into “primary” and “secondary” disease based on the absence or presence, respectively, of other autoimmune conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. However, in 2022, the Sjögren's Foundation recommended migrating away from this nomenclature, noting that there is no significant difference between the phenotype of “primary” and “secondary” SjD (23). SjD is marked by the infiltration of T cells and B cells into the exocrine glands, along with the presence of autoantibodies, including anti-Ro/SSA and anti-La/SSB (24). SjD is well-known for its hallmark symptoms of dry eyes and dry mouth, resulting from lacrimal and salivary gland dysfunction, respectively (25). Inflammation induced by the infiltrating immune cells disrupts the lacrimal and salivary gland epithelia, leading to diminished tear and saliva production (26). Beyond these primary target organs, SjD may also affect other exocrine glands, including the MGs (27). While the role of lacrimal gland dysfunction in SjD dry eye has been extensively studied, the involvement of MGs is gaining increased attention as an important yet underexplored component of the disease. Emerging evidence suggests that MGD is prevalent among SjD patients and may also contribute to the severity of dry eye symptoms (8, 28). Considering these current findings, it is important to understand MGD in SjD. This report discusses the manifestations of MGD among SjD patients, explores possible pathophysiological mechanisms, and reviews current management options.

SjD is widely known for its effect on the lacrimal glands, leading to aqueous tear deficiency and, ultimately, dry eye disease. This pathophysiological feature has been extensively studied and has shaped the clinical approach to managing SjD dry eye (29). Recently, attention has shifted toward a more combined disease mechanism, emphasizing the role of the meibomian glands in SjD dry eye. As shown in Table 1, studies have increasingly reported MGD as a frequent occurrence in SjD, underscoring its significance in the pathophysiology of the disease. Several studies have demonstrated evidence of MG structural loss in SjD. In an initial study by Shimazaki et al. (10), the meibomian glands of SjD patients were found to be mostly atrophied, showing clear signs of structural damage to the MGs. When compared to age- and sex-matched aqueous-deficient dry eye patients without SjD, SjD patients exhibited higher rates of meibomian gland dropout (57.9 vs. 18.7%, p = 0.017) as measured by meibography. Additionally, the authors assessed meibomian gland obstruction by applying digital pressure to the upper eyelid, and the ease at which meibum was expressed was evaluated as follows: grade 0 = clear meibum is easily expressed; grade 1= cloudy meibum is expressed with mild pressure; grade 2 = cloudy meibum is expressed with more than moderate pressure; and grade 3 = meibum cannot be expressed even with hard pressure. It was observed that the incidence of glandular obstruction (grade 3) was significantly higher in SjD patients compared to the dry eye cohorts (38.9 vs. 11.1%, p = 0.028). Similarly, Wang et al. (12) observed greater areas of meibomian gland atrophy in both eyes of SjD patients compared to patients with MGD not associated with SjD. This suggests that the damage to the meibomian glands is more extensive and widespread in SjD, potentially due to the underlying autoimmune destruction present in SjD.

In addition to MG structural impairment, there have been other reports evidencing functional impairment, such as diminished lipid layer thickness (LLT) and rapid tear evaporation rates among SjD patients (20, 30, 31). Menzies and associates recruited 11 SjD patients and 10 age- and sex-matched normal controls. They measured LLT using a Keeler Tearscope Plus (Keeler, Windsor, UK) and assessed tear film stability by measuring the non-invasive tear break-up time (NITBUT). SjD patients had significantly thinner LLTs and more rapid NITBUTs compared to the normal controls. Also, there was a positive correlation between LLT and NITBUT in SjD (R = 0.54, calculated R² = 0.291, p < 0.05), but not in normal controls. A potential limitation of this study is that it only included normal controls and not patients with non-SjD MGD. Despite this shortcoming, the results from this study shed light on the impairment of MGs in SjD. In another study, Hwang et al. compared the meibography parameters with LLT in 30 SjD dry eye patients and 30 non-SjD dry eye patients using the LipiView II interferometer (Johnson & Johnson Inc., New Brunswick, NJ). Meibomian gland dropout was significantly greater in SjD, and the average LLT was significantly lower, compared to the non-SjD dry eye patients.

Another key characteristic of the manifestation of MGD in SjD is its progressive nature. In a retrospective cross-sectional study, Noh and colleagues analyzed MG images from 108 female SjD patients to explore the correlation between the duration of SjD diagnosis and meibomian gland atrophy. The authors defined the duration of SjD diagnosis to be the interval from the time SjD was confirmed by a rheumatologist to the time meibomian gland imaging was conducted. According to the study, there was a strong positive correlation between SjD duration and MG atrophy (r = 0.766, calculated R² = 0.587 p < 0.001). Even after controlling for age, the association remained significant (r = 0.559, calculated R² = 0.312, p < 0.001). This finding highlights that MG atrophy in SjD is independently linked to disease progression, not just aging. Thus, MGs in SjD patients atrophy over time, with longer disease duration leading to more severe gland dropout. This relationship raises an important pathophysiological question: are the meibomian glands directly attacked by the immune system in SjD, or does their degeneration result from inflammatory spillover of the ocular surface caused by lacrimal gland dysfunction? To date, this question has not been thoroughly investigated, creating a significant gap in our understanding of how MGD develops in SjD. In the following section, three potential mechanisms linking MGD to SjD are explored.

MGD is a common clinical feature of SjD leading to tear instability and evaporative dry eye. The mechanisms behind MGD in SjD are still not fully understood. However, some researchers propose that MGD associated with SjD might be linked to inflammation, hormonal influences, and neurological mechanisms.

It is well-documented that MGD plays a significant role in the severe dry eye symptoms experienced by patients with SjD (28). This may partly explain why conventional treatments often fail to provide relief for all SjD patients with dry eye. While current research identifies MGD as a major factor in SjD-related dry eye, there is limited information on targeted treatments in this patient population. In this section, we will explore some remedies supported by studies that have been shown to effectively improve MGD in SjD patients, prioritizing those that have been evaluated as first-line or standalone treatments.

While current literature supports the presence of MGD in SjD, there are some limitations that should be acknowledged. Many cited studies relied on relatively small sample sizes which could reduce the statistical power and increase the risk of sampling bias (10, 11, 20, 30, 31, 51, 85). This limitation is of great importance especially in a heterogeneous condition like SjD, where disease presentation, severity, and systemic involvement can vary widely. Furthermore, the majority of the studies were observational and cross-sectional in nature (9–12, 16, 20, 30, 31, 33, 51, 85, 86). While they effectively demonstrated that SjD is associated with increased meibomian gland dropout, thinner lipid layer thickness, and more unstable tear films, the underlying mechanisms behind such features could not be assessed due to the study design. Another common shortcoming is the lack of an appropriate “disease control” group, specifically, those who have MGD but do not have SjD (9–11, 16, 20, 30, 31, 85). Without an appropriate disease control group, it is difficult to determine whether the observed MG features are specific to SjD or a reflection of the generic MGD pathology. These methodological constraints highlight the need for larger, prospective, controlled studies to better understand the relationship between MGD and SjD and to guide development of targeted management strategies.

The traditional belief that lacrimal gland dysfunction is the primary driver of dry eye disease in SjD has been challenged by recent literature. Instead, MGD has been identified as a frequent occurrence among SjD patients and is reported to contribute to severe dry eye symptoms. Despite the high prevalence of MGD in SjD, surprisingly little research has been conducted to explore its underlying pathophysiology. While some hypotheses have been proposed—such as the roles of inflammation, hormonal imbalances, and neurological mechanisms—these speculations are still in the early stages of being investigated and/or validated. As a result, the mechanism behind MGD in SjD remains poorly understood, creating a significant gap in the development of targeted therapies to alleviate MGD-related signs and symptoms in this patient population.

Emerging research suggests potential promise in treatments such as VTP, IPL, and punctal plugs. However, the specific mechanisms by which these therapies might improve MGD in SjD remain unclear. Given these uncertainties, there is an urgent need for research focused on uncovering the underlying cause of MGD in SjD. We propose that future studies should prioritize investigating specific immune pathways that may contribute to MGD pathology, particularly since SjD is an autoimmune condition. Additionally, larger-scale clinical trials are needed to compare the effectiveness of existing MGD therapies in SjD, including VTP and IPL but also other off-label dry eye medications, warm compresses, lid hygiene, doxycycline, etc. By addressing these research gaps, we can move closer to developing more effective treatments to address an often-overlooked aspect of SjD dry eye.