An Overview of the Dry Eye Disease in Sjögren’s Syndrome Using Our Current Molecular Understanding

Abstract

Sjögren’s syndrome is a chronic and insidious auto-immune disease characterized by lymphocyte infiltration of exocrine glands. The patients typically present with ocular surface diseases related to dry eye and other systemic manifestations. However, due to the high prevalence of dry eye disease and the lack of objective and clinically reliable diagnostic tools, discriminating Sjögren’s syndrome dry eye (SSDE) from non-Sjögren’s syndrome dry eye (NSSDE) remains a challenge for clinicians. Diagnosing SS is important to improve the quality of life of patients through timely referral for systemic workups, as SS is associated with serious systemic complications such as lymphoma and other autoimmune diseases. The purpose of this article is to describe the current molecular understanding of Sjögren’s syndrome and its implications for novel diagnostic modalities on the horizon. A literature review of the pre-clinical and clinical studies published between 2016 and 2022 was conducted. The SSDE pathophysiology and immunology pathways have become better understood in recent years. Novel diagnostic modalities, such as tear and saliva proteomics as well as exosomal biomarkers, provide hope on the horizon.

Discovery and Verification of Sjögren’s Syndrome Protein Biomarkers in Tears by Targeted LC-MRM

“…5 Sjogren's syndrome is a chronic and systemic inflammatory autoimmune disorder causing inflammation and destruction of the lacrimal and salivary glands. 5,9,10 The main manifestation of SS is severe dry eyes and mouth resulting from lymphocyte infiltration and inflammation. 9,11 Other mucosal tissues, including the nose, larynx, gastrointestinal tract, and vagina, are also affected in some cases.…”

“…5,9,10 The main manifestation of SS is severe dry eyes and mouth resulting from lymphocyte infiltration and inflammation. 9,11 Other mucosal tissues, including the nose, larynx, gastrointestinal tract, and vagina, are also affected in some cases.…”

“…13−15 An estimated 10% of DED patients have Sjogren's syndrome, with a majority not having a confirmed diagnosis. 9 SS diagnosis is based on ACR/EULAR classification criteria, 16 involving a multistep process, including the evaluation for ocular and oral dryness, detection of specific antibodies and glandular biopsy. This process requires several medical specialists, including a rheumatologist, ophthalmolo- gist, otorhinolaryngologist, and/or dentist.…”

Unveiling the Power of Gabapentin-Loaded Nanoceria with Multiple Therapeutic Capabilities for the Treatment of Dry Eye Disease

“…Clinically, DE is categorized into two types: aqueous-deficient DE, which is characterized by reduced lacrimal secretion, and evaporative DE, which is associated with excessive tear evaporation . In the Western world, Sjögren’s syndrome (also referred to as canonical aqueous-deficient DE) exemplifies this disorder with its characteristic lacrimal gland defects. , Although some medications such as lactoferrin can significantly alleviate the symptoms of aqueous-deficient DE, the condition tends to worsen again after cessation of the treatment. − Therefore, existing treatments lack the ability to deliver a comprehensive cure, underscoring the need for innovative and effective solutions.…”

A Pilot Study of a Panel of Ocular Inflammation Biomarkers in Patients with Primary Sjögren’s Syndrome

“…The chronic ocular surface inflammation provoked by SS is due to direct damage of the corneal epithelium, whereas the associated dry eye disease (DED) is due to the functional impairment and destruction of the lacrimal glands. Aqueous tear deficiency causes tear film hyperosmolarity, which in turn activates epithelial inflammatory cascades [ 7 ]. The DED secondary to SS is less symptomatic but shows more severe medical signs and more blurred vision than the non-SS DED [ 8 ].…”