# 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
Guidelines suggest its use in cases of severe DED [63], although a Cochrane review investigating the use of autologous serum in the dry eye found inconsistency in the benefits for both symptoms and objective measures [64]. Several small studies [65; 66] have demonstrated its efficacy in helping the management of glandular and extragalandular corneal manifestations in SS patients. \begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline \hline
**Therapeutic Option** & **Active Components** & **Therapeutic Effects** & **Drawbacks and Side Effects** & **Efficacy in Side Effects** & **Guidelines Recommendation in (Level of Evidence)** & **Guidelines Recommendation in SS-Related DED** \\ \hline  & & & Increased risk of infections and & & & \\
**Temporary or** & **Tear delux** & **reduction, tear** & **accumulation of** & **Controversial: high [62] or inflammatory cytokines on the ocular surface & **High [62] or moderate-to-severe DED** \\ \hline  & & **Ocular surface protection from eyelironment, permanentence of artificial tears or drugs on the ocular surface, ocular surface, desiccation reduction, corneal healing promotion, and discomfort relieve & **Controversial: high [62] or moderate-to-severe DED** \\ \hline \hline \end{tabular}
\end{table} 
Table 3: _Cont._Non-steroidal anti-inflammatory drugs (NSAIDs) eyedrops have been demonstrated to reduce ocular discomfort and dry eye signs in SS patients [67] but may also decrease corneal sensitivity and delay epithelium healing [68]. Moreover, some cases of corneal melting/perforations have been associated with the use of topical NSAIDs [68] and also in SS patients [69; 70]. For these reasons, NSAID eye drops should be used with caution or are better avoided in SS patients [42; 43; 44; 55; 56];  
Although a 2022 Cochrane review of the outcomes of topical corticosteroids in DED patients showed small to moderate degrees of DED symptom relief and poor evidence of DED signs reduction [71], CS eyedrops have demonstrated their efficacy in reducing ocular surface inflammation and improving symptoms and some objective parameters in SS-related DED in two RCTs [72; 73]. They may have many side effects, including glaucoma, cataracts, herpes simplex virus reactivation [74], epithelial healing delay, and collagen production downregulation, with increased risk of corneal and scleral perforation [69]. Topical CSs should be considered with caution, and guidelines suggest CSs short-term or pulse topical therapy (two to four weeks) in patients who do not respond to other therapies [42; 43; 44; 55; 56]. Cyclosporine A is an immunosuppressive agent [75]. Its topical use has been approved for the treatment of moderate-to-severe DED and also in SS patients [55; 56; 75] based on RCTs [76]. However, a Cochrane systematic review published in 2019 reported that its efficacy in DED patients may not be better than placebo or artificial tears [77]. Small studies have demonstrated that its use in SS patients may increase the total tear production, the number of conjunctival goblet cells, and the corneal sub-basal nerve density [78]. Lifitegrast is an integrin antagonist that inhibits activation and migration of the antigen-presenting cells and the CD4+ T cells and downregulates the intracellular adhesion molecule-1 (ICAM-1) [79]. It has been shown to improve both signs and symptoms of DED in large RCTs [79], and its ophthalmic formulation was approved in 2016 for the treatment of DED-related ocular surface inflammation by the U.S. Food and Drug Administration (FDA) [79]. Although no specific data about pSS patients are currently available, topical lifitegrast has been shown to improve clinical signs of KCS in pSS animal models [80]. The presence of persistent anterior blepharitis or Meibomian gland dysfunction requires appropriate therapy with eyelid cleaning, warm compresses, and topical and oral antibiotics.