Making the diagnosis of Sjögren’s syndrome in patients with dry eye

Abstract

Sjögren’s syndrome (SS) is a chronic and progressive systemic autoimmune disease that often presents initially with symptoms of dry eye and dry mouth. Symptoms are often nonspecific and develop gradually, making diagnosis difficult. Patients with dry eye complaints warrant a step-wise evaluation for possible SS. Initial evaluation requires establishment of a dry eye diagnosis using a combination of patient questionnaires and objective ocular tests, including inflammatory biomarker testing. Additional work-up using the Schirmer test and tear film break-up time can differentiate between aqueous-deficient dry eye (ADDE) and evaporative dry eye. The presence of ADDE should trigger further work-up to differentiate between SS-ADDE and non-SS-ADDE. There are numerous non-ocular manifestations of SS, and monitoring for SS-related comorbid findings can aid in diagnosis, ideally in collaboration with a rheumatologist. The clinical work-up of SS can involve a variety of tests, including tear function tests, serological tests for autoantibody biomarkers, minor salivary gland and lacrimal gland biopsies. Examination of classic SS biomarkers (SS-A/Ro, SS-B/La, antinuclear antibody, and rheumatoid factor) is a convenient and non-invasive way of evaluating patients for the presence of SS, even years prior to confirmed diagnosis, although not all SS patients will test positive, particularly those with early disease. Recently, newer biomarkers have been identified, including autoantibodies to salivary gland protein-1, parotid secretory protein, and carbonic anhydrase VI, and may allow for earlier diagnosis of SS. A diagnostic test kit is commercially available (Sjö®), incorporating these new biomarkers along with the classic autoantibodies. This advanced test has been shown to identify SS patients who previously tested negative against traditional biomarkers only. All patients with clinically significant ADDE should be considered for serological assessment for SS, given the availability of new serological diagnostic tests and the potentially serious consequences of missing the diagnosis.

Efficacy and safety of retinol palmitate ophthalmic solution in the treatment of dry eye: a Japanese Phase II clinical trial

“…Schirmer’s test I is commonly used to diagnose dry eye, but because it is performed without anesthesia, it evaluates not only the amount of tear storage and basal secretion but also reflective secretion. This evaluation method is more pertinent in Sjögren’s syndrome and other conditions in which the lacrimal gland is damaged and tear secretion is decreased 17. As described earlier, we concluded that VApal mainly acted on the corneal and conjunctival epithelial layer of the ocular surface, not on the lacrimal glands or via a mechanism that increased tear production.…”

The Potential Role for Early Biomarker Testing as Part of a Modern, Multidisciplinary Approach to Sjögren’s Syndrome Diagnosis

“…Tear function tests [40,41] are used to distinguish between ADDE and EDE, as mentioned above. Schirmer's test and tear meniscus assessment (tear lake) may help identify ADDE and distinguish it from EDE; the details of the differential diagnosis of dry eye have been reviewed in greater detail elsewhere [42,43]. The tear function index (TFI) and vital dye stains (Rose Bengal; lissamine green) are also used.…”

“…The patient was presumed to have early SS and referred back to a rheumatologist for further care. He was treated with oral hydroxychloroquine therapy and later treated Table 3 Traditional and novel biomarkers included in the Sjö diagnostic test; adapted with permission from Beckman et al [42] Diagnostic characteristics Traditional biomarkers [7] Anti-SS-A/Ro, anti-SS-B/La Not specific for SS; occurs in other autoimmune disorders, particularly SLE Antinuclear antibody (ANA) Titer C1:40 present in about two-thirds of SS patients [35] Rheumatoid factor (RF) Found in many rheumatic conditions but is not unique to SS…”

Immunological impression cytology of the conjunctival epithelium in patients with thyroid orbitopathy-related dry eye

“…Aqueous tear production was quantified by measuring the amount of wetting. Less than 5 mm of wetting is highly suggestive of aqueous tear deficiency, while 5-10 mm is equivocal (Hikichi et al, 1995;Shrestha et al, 2011;Beckman et al, 2015;Courtin et al, 2016).…”

“…The timing of the appearance of the first randomly distributed dry spot of tear film is the tear BUT. A BUT of less than 10 s is considered abnormal (Brasche et al, 2001;Beckman et al, 2015;Courtin et al, 2016).…”