# Emerging Trends and Management for Sjogren Syndrome-Related Dry Eye Corneal Alterations
## 3. **Glandular Ocular Involvement: Dry Eye Disease (DED) or Keratoconjunctivitis Sicca (KCS)**
### Clinical Characteristics  
Clinical signs of DED or KCS are present in almost all SS patients [6; 7; 17]. SS-related DED is characterized by moderate-to-severe eye dryness, ocular surface fluorosis and damage of various degrees of severity, neurotrophic features, and increased ocular surface susceptibility to infections [6; 7; 17]. Eye dryness represents the first and most common sign and symptom of pSS, objectively present in 97-100% of cases and reported by 80-92% of pSS patients [6; 7; 12; 17]. SS-related DED may have a wide clinical spectrum, ranging from mild eye dryness and clear ocular surface to severe dry eye with filamentary keratitis. Typical SS-related DED clinical signs at the slit lamp include lacimal meniscus height reduction; conjunctival and perihepatic hyperemia; punctate superficial keratopathy, mild in 100% of cases and moderate-to-severe in more than 50% of cases; recurrent epithelial erosions/scarring (20%); nonhealing corneal ulcers (1-2% of cases); xerophthalmia (20-35% of cases); filamentary keratitis characterized by debris of damaged epithelium and mucous filaments, present in 20-35% of cases; corneal or conjunctival keratinization (1-2% of cases) [6; 7; 12; 17]; seborrheic anterior plehbaritis (20% of cases); or posterior blebaritis or MGD (45-60% of cases) [12; 29]. Real cicatrizing conjunctivitis is infrequently associated with SS [6; 7; 12] and most frequently found in Graft versus host disease or Stevens-Johnson syndrome, so its presence therefore requires investigations to exclude other causes of severe dry eye [16]. The clinical severity of the KCS, as evaluated using the Schirmer's test and the ocular surface staining score, is significantly linked to visual performance [12] and, in pSS (not in sSS patients), appears associated with the systemic disease activity as evaluated using the serum anti-La/SSB and anti-Ro/SSA antibodies and tear IL-17 levels [36]. Characteristic SS-related DED symptoms include eye dryness, discomfort, irritation or pain, photosensitivity, reduced or increased tearing, itching, burning, soreness, grittiness, scratchiness, foreign body sensation, blurred vision, decreased visual acuity, significant vision fluctuation with transient improvement after blinking or artificial tears instillation, blinking, and eye fatigue [6; 7; 17]. Clinical symptoms of SS-related DED are generally worsened by heat, wind, dust, smoke, air dryness, and activities related to a low blinking rate, such as reading, using a computer, driving, or watching television [6; 7; 17]. SS-related DED symptoms typically progressively increase in duration and intensity and, in late stages, may become severe pain and chronic visual impairment that significantly reduce the quality of life of SS patients [6; 7; 17; 37]. Eye dryness has been demonstrated to be the single most disturbing symptom in pSS. Together with chronic fatigue, it has the greatest impact on pSS patients' quality of life. Patients perceive it as more burdensome than other systemic manifestations of the disease, and it is the most complained-about symptom when pSS patients require a medical check-up [37]. As compared to non-SS DED, SS-related DED is characterized by several hallmarks, including the following:  
* More severe eye dryness developing at a younger age and progressing more severely and rapidly [38]. It has been estimated that 70-85% of SS patients show a Schirmer's test \(\leq 5\) mm/5 min, indicating a severe eye dryness degree [12];
* More complex eye dryness (aqueous deficient + evaporative): Although SS-related DED is classified as a form of ADDE [23], an associated damage of conjunctival goblet cells and Meibomian glands may be present in 45-60% of cases [12; 29].