# Emerging Trends and Management for Sjogren Syndrome-Related Dry Eye Corneal Alterations
## 4 Extragalundular Corneal Complications
### Therapeutic Interventions  
_A. General considerations:_ Severe ocular extragalundular manifestations, including persistent sterile corneal abrasion/scarring/ulceration/melting, PUK, necrotizing sclerockeratitis, and corneal/scleral perforation [2; 6; 7; 8; 9], require a complex approach integrating local treatments, prompt and aggressive systemic immunomodulatory therapy manages by the rheumatologist/immunologist, and sometimes surgical strategies [42; 43; 44]. Systemic medications include oral or intravenous corticosteroids [74], oral pilocarpine [93; 94], hydroxychloroquine [95; 96], and immunosuppressant agents [97; 98; 99; 100; 101; 102; 103] (Table 4). \begin{table}
\begin{tabular}{p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt}} \hline \hline
**Drug Class** **(Administration Route)** & **Active Component** & **Therapeutic Effects** & **Drawbacks and Side Effects** & **Efficacy in SS Pairs (Level of Evidence)** & **Guidelines Recommendations** [42; 43; 44; 45] \\ \hline \hline
**Systemic corticosteroids (oral/intravenous)** & Oral & & Hypertension, hyperglycemia, weight gain, lipid and intravenous methylpred-insolone & & First-line systemic approach in cases of pSS patients with severe ocular sight-threatening conditions, such as corneal melting, PUK, necrotizing scleritis, or vasculitisitis \\ \hline
**Parasym-pathomimetic** & (Cevimeline, not commercially available in Europe) & Parasympathomimetic ascertainic receptor & Nausea, excessive sweating, flushing, increased excorine gland secretion & High improvement of mouth dryness; salivvation, and urinary frequency & FDA-approved for managing motorate to severe; not recommended for dry eye \\ \hline
**Disease-modifying anti-rheumatic drugs (DMARDS)(oral)** & & & Nausea, diarrhea, fresh, hair changes, muscle weakness, anemia, and maculopathy & None in cases of non-SS DED [95] and SS-related DED [96] & First choice to treat fatigue and joint pain in SS patients in SS patients \\ \hline \hline \end{tabular}
\end{table} 
Table 4: Systemic approaches to the [PERSON]’s syndrome-related corneal manifestations. \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Drug Class** & **Active** & **Therapeutic Effects** & **Drawbacks and** & **Efficacy in SS** & **Guidelines Rec** & **Guidelines Rec** \\
**(Administration** & **Component** & **Therapeutic Effects** & **Side Effects** & **Patients (Level** & **ommendations** \\  & **Component** & **Therapeutic Effects** & **Side Effects** & **of Evidence)** & [42; 43; 55; 56] \\ \hline
**Systemic immuno-** & & & Gastrointestinal & Some evidence in & First choice to treat \\
**augents** & & & & intolerance, & preventing & joint disease in SS \\
**Antimetabolites** & & & & elevated liver & \\
**Antimetabolites** & & & enzymes, & complications & (after systemic CSs) \\
**Antimetabolites** & & & & stomatitis, dry eye, & and treating PUK & in sterile corneal \\
**Antimetabolites** & & & & etc. & \\
**Antimetabolites** & & & & & \\
**Antimetabolites** & & & synthesis/cell &  
Although not supported by strong scientific evidence [57; 58], the clinical guidelines suggest the systemic administration of CSs in pSS patients as a first-line systemic approach in cases of severe ocular sight-threatening conditions such as corneal melting, PUK, necrotizing scleritis, or vasculitisitis [42; 43; 44]. Systemic CSs can be administered orally (prednisolone 1 mg/kg/day till disease control, followed by tapering in steps of 10 mg every week, with a maintenance dose of 5-10 mg/day) or intravenously (methylprednisolone 1 gr/day for three consecutive days, followed by oral CSs).