# Emerging Trends and Management for Sjogren Syndrome-Related Dry Eye Corneal Alterations
## 3. **Glandular Ocular Involvement: Dry Eye Disease (DED) or Keratoconjunctivitis Sicca (KCS)**
### Treatment Strategies  
In general, the optimal therapeutic approach to SS patients is still unknown, and although some treatments may improve symptoms and prevent complications, there is currently no cure for SS [3; 45; 46]. Several guidelines for the management of SS-related dry eye disease have been released in recent years [42; 43; 44; 55; 56]. The aim of the SS-related DED treatment should be to conserve, stimulate, and replace the tear secretion; to prevent or treat ocular surface inflammation and damage; to reduce eye symptoms; and to identify and grade the presence of an underlying systemic disease activity [42; 43; 44; 55; 56]. Furthermore, the paucity of RCTs supporting therapy recommendations in SS patients [57; 58] leads to an extremely heterogeneous approach. Treatments are chosen on an individual basis, depending on the presence and severity of the different clinical manifestations. SS-related DED therapeutic approach should be based on three cornerstones:  
* Comprehensive ophthalmological examination by a corneal specialist: it should be focused on the determination of the relative contribution of aqueous-deficient and evaporative dry eye and the severity level of the ocular surface damage and visual disturbance [55; 56];
* Multidisciplinary care team: The involvement of other specialists, such as odontostomologists, rheumatologists, and immunologists, is of fundamental importance in order to establish glandular and extragalundular systemic involvement and disease activity. The presence of severe vision-threatening ocular complications or systemic manifestation requires a prompt multidisciplinary approach and systemic immunosuppressive therapy prescribed by a rheumatologist/immunologist [42; 43; 44; 55; 56];
* Stepwise approach: the treatment should start with the patient's education about useful lifestyle modifications (Table 2) and with the prescription of artificial tear substitutes (eyedrops, gels, or ointments), which remain the first-line therapy in patients with DED of any cause [59] (Table 3). Other topical (Table 3), mechanical (Table 3), systemic, or surgical therapies should be recommended as second-line approaches depending on the ocular and systemic associated complications [42; 43; 44; 55; 56]. The treatment of the SS-related KCS is generally limited to topical or mechanical approaches (Table 3). In a subset of SS patients, DED is unresponsive to common treatment, resulting in severe clinical manifestations, including recurrent corneal infections and persistent corneal abrasion or scarring, which may require more complex treatments. Artificial tear drops, lubricating gels, and ointments [59] have traditionally been considered the first-line therapy in patients with DED of any cause [55; 56]. General rules for their use in DED patients include preferring viscous preparations that last longer and should be instilled less frequently, using artificial tears with lipid components in the presence of the MGD, and preferring preservative-free preparations to avoid local toxicity, which is of crucial importance in SS-related KCS patients that are more prone to developing ocular surface damage [55; 56; 59]. The most common preservative, benzalkonium chloride, has been indeed demonstrated to be toxic for the epithelium and the goblet cells and to cause tear film instability, ocular surface damage, epithelial apoptosis, conjunctival flogosis, and subconjunctival fibrosis [60]. Although several studies have demonstrated that tear substitutes may improve ocular symptoms and some ocular tests in DED patients [59], only a few studies have specifically included pSS patients [62]. Tear substitutes have varied formulations that differ in composition, viscosity, lipid content, and level of hydration. Moreover, the comparison of efficacy and safety of different artificial tear types has provided poor and inconclusive results, so none of the tear substitutes has been shown to be clearly superior in treating DED, specifically SS-related DED [61]. Autologous or homologous serum can be prepared as eyedrops.