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Dry eye syndrome (DES) is a multifactorial ocular disorder that affects millions of people worldwide. Among its various subtypes, immune-related dry eye syndrome stands out as an increasingly recognized entity. This condition involves a dysregulated immune response that leads to chronic inflammation of the ocular surface and tear film, resulting in discomfort, visual disturbances, and potential damage to the cornea. In this article, we delve into the pivotal role of inflammation in immune-related dry eye syndrome, exploring its underlying mechanisms and implications for diagnosis and treatment [1].

In recent years, with the aging of the population and the wide spread use of electronic terminal products, the dry eye prevalence rate increased significantly and the onset of the disease also shows a trend of getting younger. Among the patients with dry eye syndrome, some patients are complicated with the systemic immune system diseases. The dry eye symptoms and signs of such patients are often more serious, the treatment effect is poorer, and the prognosis is not ideal. There are clinical characteristics of immune-related dry eye. The aim of this study was to analyze and discuss the clinical characteristics of dry eye caused by immune-related diseases. The prevalence rates of primary Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) are the highest in systemic immune diseases [2].

Understanding Immune-Related Dry Eye Syndrome

Immune-related dry eye syndrome is characterized by an altered immune response that involves both innate and adaptive immunity. The ocular surface is equipped with a variety of immune cells, including neutrophils, dendritic cells, and lymphocytes, which serve as the first line of defense against pathogens. In this condition, these immune cells become dysregulated, leading to persistent inflammation.

Key Players in Inflammation

Cytokines and chemokines: Proinflammatory cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factoralpha (TNF-α), are significantly upregulated in immune-related dry eye [3]. These molecules play a crucial role in the recruitment and activation of immune cells, amplifying the inflammatory response.T Cells: CD4+ T cells, especially Th1 and Th17 subsets, are implicated in the pathogenesis of immune-related dry eye. These T cell subtypes release proinflammatory cytokines, which further perpetuate the immune response and tissue damage.

B cells: B cells contribute to inflammation by producing autoantibodies that target components of the lacrimal glands and the ocular surface, leading to reduced tear production and epithelial damage [4].

Matrix metalloproteinases (MMPs): Increased levels of MMPs are observed in immune-related dry eye. These enzymes degrade the extracellular matrix, promoting tissue remodeling and disrupting the epithelial barrier.

Mechanisms of Immune-Related Dry Eye Syndrome

The exact mechanisms triggering immune-related dry eye are not fully understood, but several factors have been implicated in its pathogenesis:

Autoimmunity: It is believed that immune-related dry eye may have an autoimmune component, where the body's immune system mistakenly targets and attacks healthy ocular tissues, leading to chronic inflammation.

Environmental triggers: Environmental factors, such as allergens and pollutants, can activate the immune system and exacerbate dry eye symptoms by inducing inflammation [5].

Dysfunctional lacrimal glands: Immune-related dry eye is associated with reduced tear production due to impaired function of the lacrimal glands, leading to insufficient lubrication of the ocular surface.

Neurogenic inflammation: Nerves play a crucial role in regulating tear production and ocular surface homeostasis. In immune-related dry eye, nerve dysfunction can contribute to inflammation and exacerbate the condition.

Clinical Implications

Diagnosing immune-related dry eye involves a comprehensive evaluation of clinical symptoms, ocular surface signs, and the measurement of inflammatory biomarkers. Tear film osmolarity, matrix metalloproteinase-9 (MMP-9) levels, and proinflammatory cytokine assays are some of the tests that can aid in identifying inflammation-driven dry eye [6].

Treatment Approaches

The management of immune-related dry eye syndrome revolves around suppressing inflammation and restoring ocular surface integrity. Some treatment options include:

Topical anti-inflammatory medications: Corticosteroids and cyclosporine eye drops can effectively reduce inflammation and alleviate symptoms.

Immunomodulatory therapies: Systemic immunosuppressive agents like methotrexate or biological therapies may be considered for severe cases with systemic involvement [7].

Environmental modifications: Avoiding triggers such as allergens and maintaining a humid environment can help manage symptoms.

Tear supplements: Artificial tears and ophthalmic lubricants can improve tear film stability and provide relief [8].

Discussion

The SS, SLE, and RA are all the autoimmune diseases with a higher incidence rate and often involve in the connective tissues of the skin, mucous membrane, glands, and so forth. Hence, the cornea, conjunctiva, and lacrimal gland tissues of the ocular surface have also become the immune attack positions, which lead to the damage of their structures and functions and cause the severe ocular surface problem, for example, dry eye. Compared with the simple dry eye, the immunerelated dry eye has also its special clinical manifestations in addition to the common features of the dry eye diseases. It was found in this study that the incidence rate of simple dry eye and immune-related dry eye in women was significantly higher than that in men, and this difference was more significant in the immune-related dry eye [9], which may be associated with such a fact that the incidence rate of dry eyes and immune diseases in women is significantly higher than that in men. Most of the patients with simple dry eye were middle-aged and elderly women. However, with the popularity of video terminal equipment such as computers and smart phones, the incidence rate of simple dry eye in men and youth crowds also appeared to rise year by year. Most of the patients with immune-related dry eye were middle-aged people and the youth, which are much younger than those with simple dry eye.

The comparison of ocular surface inflammatory reactions of the two groups also showed that the incidence rate of conjunctival congestion, conjunctival papillary, and follicular hyperplasia of the immune-related dry eye was significantly higher and conjunctival sac secretions was lesser, belonging to noninfectious inflammation. This showed that the ocular surface inflammatory reaction of this kind of patients was more serious than that of simple dry eye. In this study, we also found that corneal nerve fibers were less and the number of local lymphocytes was significantly increased in IRDE than those in SDE by confocal microscopy scan. This showed that immune reaction of autoimmune disease can promote and increase local lymphocyte inflammatory infiltration and reaction of ocular surface and would seriously damage the corneal nerve fibers. Because the patients with autoimmune diseases are in the state of unusual high immune response, the ocular surface inflammation reaction is serious, which increases the risk of producing the immune rejection after the corneal transplantation. For this reason, it must be very careful to conduct the corneal transplantation for the patients with autoimmune disease of serious dry eye, such as corneal dissolution and perforation [10]. Therefore, it is a better choice to adopt the conjunctival flap covering surgery plus tarsorrhapy for patients of this kind. The next step of our study will elevate inflammatory mediators of ocular surface and tear film between IRDE and SDE

Conclusion

Inflammation plays a central role in the development and progression of immune-related dry eye syndrome. Understanding the underlying mechanisms of inflammation in this condition is crucial for accurate diagnosis and the development of targeted therapeutic strategies. Further research in this area holds the potential to improve the quality of life for individuals affected by immune-related dry eye and enhance our overall understanding of ocular immune responses.

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