# Emerging Trends and Management for Sjogren Syndrome-Related Dry Eye Corneal Alterations
## 3. **Glandular Ocular Involvement: Dry Eye Disease (DED) or Keratoconjunctivitis Sicca (KCS)**
### Histology, Biochemistry, Anatomy, and Physiology
#### 3.1.1 Salivary and Lachrymal Glands  
Histological studies have shown salivary and lacrimal gland infiltration by T and B lymphocytes, which represents the histological hallmark of the pSS [24; 25] and one of the most important diagnostic features [18]. Considering this, in pSS patients, lacrimal gland damage has been demonstrated to develop earlier than that of the salivary glands [24], and eye dryness may represent the earlier phase of the disease. Ectopic lymphoid germinal  
\begin{table}
\begin{tabular}{c c c} \hline
**Tissue/Organ** & **Diagnostic Method** & **Findings** \\ \hline
**Meibomian glands** & **Slit lamp, keratography [29]** & Anterior plepharitis \\ \hline
**Conjunctiva** & **In vivo confocal scanning** & **Conjunctival epithelial cells decreased density and morphological** \\  & **laser microscopy, impression cytology [30; 31]** & **alterations, with microcystic degeneration** \\ \hline
**Conjunctiva** & **Significant reduction in goblet cell density and decreased tear film mucous layer (zerophthalmia);** \\ \hline
**Conjunctiva** & **Infiltration of lymphocytes CD4+ T helper cells (Th1 and Th17), CD8+ T cytotoxic cells, B lymphocytes, plasma cells, macrophages, fibroblasts, and dendritic and mast cells; reduced levels of T regulatory cells** \\ \hline
**Conjunctival** & **Presence of autoantibodies, including anti-Ro/SSA, anti-La/SSB, ANA, and rheumatoid factor** \\ \hline
**Conjunctival** & **Increased levels of proinflammatory cytokine (e.g., IL-1, IL-6, and IFN-\(\gamma\))** \\ \hline
**Conjunctival** & **Over-expression of human leukocytes antigen (HLA)-DR and HLA-DQ and CD40 antigens on both lymphocytes and conjunctival epithelial cells** \\ \hline
**Conjunctival** & **Over-expression of antigen intercellular adhesion molecule (ICAM)-1, which may induce apoptosis of the epithelial cells** \\ \hline
**Conjunctival** & **Conjunctival epithelial squamous metaplasia or keratinization (rare)** \\ \hline
**Conjunctival** & **Cicatrizing conjunctivitis (rare)** \\ \hline
**Convena** & **In vivo confocal scanning** & **M morphological alteration of all epithelial layers** \\ \hline
**Convena** & **Increased cell density of superficial epithelium and outer and inner layers of the wing cells** \\ \hline
**Conjunctival** & **Reduced or increased basal epithelial cell density** \\ \hline
**Conjunctival** & **Squamous metaplasia or keratinization of the superficial epithelium (rare)** \\ \hline
**Convena** & **Decreased or increased stromal keratocyte density** \\ \hline
**Convena** & **Increased stromal dendritic cell density and activation** \\ \hline
**Convena** & **Increased Bowman’s and stromal collagen degradation and stromal thinning** \\ \hline
**Convena** & **Sub-basal nerve plexus morphological abnormalities (increased nerve reflectivity, width, and tortuosity)** \\ \hline
**Convena** & **Sub-basal nerve plexus reduced density and length** \\ \hline
**Ocular Response Analyzer** [35]** & **Reduced corneal stiffness** \\ \hline \end{tabular}
\end{table}
Table 1: _Cont._center-like structures containing recirculating autoreactive B cells are present in the salivary glands of 25% of pSS patients and have been associated with an increased risk of B-cell lymphoma development [26].