Keratoconjunctivitis Sicca in Sjögren Disease: Diagnostic Challenges and Therapeutic Advances

Keratoconjunctivitis sicca (KCS), also commonly known as dry eye disease (DED), is one of the most prevalent and crippling features of Sjögren disease (SD), a chronic systemic autoimmune disorder featuring lymphocytic infiltration and progressive impairment of exocrine glands. KCS affects up to 95% of patients with SD and is often the earliest and most persistent manifestation, significantly compromising visual function, ocular comfort, and overall quality of life. Beyond the ocular surface, KCS mirrors a wider spectrum of immune dysregulation and epithelial damage characteristic of the disease, making it a valuable window into the underlying systemic pathology. The pathophysiology of KCS in SD is complex and multifactorial, involving an interplay between autoimmune-mediated lacrimal gland dysfunction, neuroimmune interactions, ocular surface inflammation, and epithelial instability. Tear film instability and epithelial injury result from the aberrant activation of innate and adaptive immunity, involving T and B lymphocytes, pro-inflammatory cytokines, and type I interferon pathways. Despite the clinical significance of KCS, its diagnosis remains challenging, with frequent discrepancies between subjective symptoms and objective findings. Traditional diagnostic tools often lack sensitivity and specificity, prompting the development of novel imaging techniques, tear film biomarkers, and standardized scoring systems. Concurrently, therapeutic strategies have evolved from palliative approaches to immunomodulatory and regenerative treatments, aiming to restore immune homeostasis and epithelial integrity. This review provides a comprehensive update on the pathogenesis, diagnostic landscape, and emerging treatments of KCS in the context of SD.