Advances in Sjögren's Syndrome Dry Eye Diagnostics: Biomarkers and Biomolecules beyond Clinical Symptoms

Abstract

Sjögren's syndrome dry eye (SSDE) is a subset of Sjögren's syndrome marked by dry eye symptoms that is distinct from non-Sjögren's syndrome dry eye (NSSDE). As SSDE can lead to severe complications, its early detection is imperative. However, the differentiation between SSDE and NSSDE remains challenging due to overlapping clinical manifestations. This review endeavors to give a concise overview of the classification, pathophysiology, clinical features and presentation, ocular and systemic complications, clinical diagnosis, and management of SSDE. Despite advancements, limitations in current diagnostic methods underscore the need for novel diagnostic modalities. Thus, the current review examines various diagnostic biomarkers utilized for SSDE identification, encompassing serum, salivary, and tear analyses. Recent advancements in proteomic research and exosomal biomarkers offer promising diagnostic potential. Through a comprehensive literature review spanning from 2016 to 2023, we highlight molecular insights and advanced diagnostic modalities that have the potential to enhance our understanding and diagnosis of SSDE.

Keywords: Sjögren’s syndrome dry eye; diagnostic biomarkers; exosomal biomarkers; molecular diagnostics; ocular surface disease; ophthalmology; salivary analysis; serum analysis; tear analysis; tear proteomics.

Figure 1

Pathogenesis of primary Sjögren’s syndrome dry eye. Beginning with genetic predispositions and environmental triggers, it progresses through the development of autoimmunity, leading to the destruction of lacrimal glands and a subsequent aqueous tear deficiency. Ultimately, this results in the disruption of the entire functional lacrimal unit, initiating a self-perpetuating vicious cycle of dry eye disease.

Figure 2

Schematic representation of the tear film layers overlaying the cornea. The tear film is composed of three primary components: the outermost lipid layer, the central aqueous layer, and the innermost mucin layer. Although depicted as distinct layers, in reality, they are not sharply defined but rather merge and overlap into one another.

Figure 3

Diagnostic Scoring System of the 2016 ACR-EULAR Classification Criteria for primary Sjögren’s syndrome. The criteria emphasize the importance of labial salivary gland biopsies, autoantibody presence, and various ocular and salivary tests in the evaluation and diagnosis of primary Sjögren’s syndrome. Schirmer’s test, Ocular Staining Score and Saliva Flow Rate give a score of one each, and Anti-SSA/SSB and Biopsy of MSG give a score of 3 each.

Figure 4

In vivo confocal microscopy (IVCM) visualization of subbasal nerve network. This image demonstrates the capability of IVCM in detailing the intricate network of nerves situated between the epithelial layer and the anterior stromal layer of the cornea, offering a clear view of their distribution and morphology.