Advances in the treatment of ocular dryness associated with Sjögren׳s syndrome
Introduction
SS is a common autoimmune rheumatic condition, associated with localised symptoms of ocular and mouth dryness as a consequence of decreased lacrimal and salivary secretion due to the lymphocyte infiltration of the exocrine glands [1], [2]. The incidence of pSS varies among different populations and depends on the classification criteria used for diagnosis [3], [4]. A recent meta-analysis showed an incidence of 6.92 (95% CI: 4.98–8.86) per 100,000 person-years and overall prevalence of 60.82 (95% CI: 43.69–77.94) cases per 100,000 [5].
The pathogenesis of dry eye symptoms associated with SS remains uncertain [6], [7]; lacrimal gland infiltration with B and T lymphocytes and epithelial cells activation driven by cytotoxic T cells, together with increased apoptosis, and expression of Ro and La antibodies on the surface of apoptotic cells are considered to be the main pathogenic events associated with glandular destruction in SS [8]. More recently, it was found that abnormal apoptosis, cytokine and toll-like receptor (TLR) activation and perivascular lymphocytic infiltration are present in the glandular tissue even before the onset of clinical symptoms associated with SS [9]. In contrast, the systemic features of SS seem to be more associated with B-cell activation, autoantibody production and polyclonal hypergammaglobulinaemia, which is likely to be linked to the increased risk of lymphoma observed in these patients [10].
Despite the recent efforts of ophthalmologists to define and classify the dry eye disease [11], very few publications have critically reviewed the evidence for treatment recommendations [12].
The ocular dryness is always associated with a localised inflammatory process and damage of the ocular surface, which is common to all underlying conditions [13]. Although often labelled as a benign feature of SS, the eye dryness can lead to decreased quality of life and potentially severe complications [14]. A recent study found no correlation between the perceived sicca symptoms and the tear secretion in pSS patients, despite good correlation with age and disease activity [15]. The incidence of dry eye is increased in the older population [16] and also after cataract and refractive surgery [17]. Symptoms of ocular dryness are reported with different frequency by patients with rheumatic conditions [18], [19].
Section snippets
Methods
We search PubMed (MEDLINE) and EMBASE electronic data bases from January 1994 to September 2014, aiming to identify reports about different therapies for dry ocular symptoms associated with SS, using the following MeSH terms: Sjogren׳s syndrome treatment, dry eye treatment, sicca syndrome and keratoconjunctivitis sicca treatment. Using all these terms combined, we identified 458 articles. Only the articles in English, reporting on data about the effectiveness of treatment in SS were included in
A proposed algorithm
Based on the available evidence from the literature data and the current recommendations for the management of dry eye symptoms [60], we propose a following algorithm (Fig.) of ocular dryness treatment in patients with SS.
Conclusions
Despite being one of the central symptoms of SS, associated with significant impact of the quality of life of these patients, the ocular dryness is usually managed with tear substitution or topical anti-inflammatory/immunomodulatory medication. There is no good evidence for the efficacy of conventional DMARDs in improving lacrimal gland secretion in SS patients, apart from methotrexate, which only improved the subjective symptoms of ocular dryness in a small study and hydroxychloroquine, which
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