*Current Diagnostic Tests for Dry Eye Disease in Sjögren's Syndrome DOI: http://dx.doi.org/10.5772/intechopen.103671*

the height and curvature of the tear meniscus are used to determine the presence or absence of dry eye [65]. The normal height of the tear meniscus is 0.2–0.5 mm; but in patients with dry eye, it is usually less than 0.2 mm [69, 70]. The evaluation of the tear meniscus should be carried out without having instilled artificial tears or other types of drops; since it can be higher and therefore unreliable; although measurement of the tear meniscus is a good parameter for determining tear production, a low tear lake alone does not necessarily indicate dry eye and should be used as an adjunct to other dry eye tests [69]. The tear meniscus can be reliably assessed using a slit lamp that is capable of micrometer measurements, or it can be done by taking a photograph of the tear meniscus after instilling a small amount of fluorescein. Tear meniscus height (THM) is a noninvasive test for tear quantification and is used as a reliable and repeatable adjunct to the diagnosis of DED [71]. Placido's advanced topography, the keratograph 5M (K5M; Oculus Optikgerate GmbH, Wetzlar, Germany), has additional imaging modalities designed to measure TMH [72, 73]. TMH can also be measured using a corneal adapter, in optical coherence tomography, RTVue-100 FD-OCT system (Optovue, Fremont, AC); reliably and noninvasively. Studies comparing these technologies found that although the tear meniscus height measurements measured with keratography are lower than those taken with OCT, they are closely correlated with each other; therefore, either method could be useful to assess the height of the tear meniscus more objectively [74]. Lacrimal meniscus height (TMH) is an important test because it shows a positive correlation with the value of the Schirmer test [75, 76]. Lacrimal point occlusion in patients with dry eye has been shown to induce increases in the volumes of the upper and lower tear meniscus, but no change in lacrimal menisci of control eyes; this may indicate the presence of a self-regulatory mechanism in the lacrimal system that maintains balance in tear volume (**Figure 7**) [77].

**Figure 7.** *Tear meniscus height.*

## *2.5.9 Meibography*

The meibomian glands are highly specialized sebaceous glands that secrete a lipid compound that is responsible for tear stability. Meibomian gland disease (MGD) is defined as a chronic and diffuse abnormality of the meibomian glands (MG), commonly characterized by terminal duct obstruction and qualitative/quantitative changes in glandular secretion [78]. The prevalence of MGD in published studies ranges from 20% to 70%, depending on diagnostic criteria for evaluating MGD and geographic differences [79, 80]. MGD is considered the main cause of evaporative dry eye [81, 82].

The pathophysiology of MGD is complex and involves several mechanisms and risk factors, including primary obstructive keratinization of the MG orifices, inflammation of the eyelids, abnormal MG secretion, and changes in the microbial flora of the ocular surface or Demodex infestation [24].

Among the main mechanisms of pathophysiology of MGD in patients with SS, the following have been proposed. Women with pSS have been shown to have androgen deficiency similar to that of patients with SLE and RA [83]; in these patients there is a significant decrease in serum levels of androgen precursors (DHEA [dehydroepiandrosterone] and DHEA sulfate), which are the main substrate for androgen synthesis in peripheral tissues. Androgen deficiency in humans has been found to be associated with an increase in eyelid keratinization and the number of occluded and metaplastic orifices of MGs; reduction in the quality of meibum; altered lipid patterns of the meibum; a decrease in the breakup time of the tear film; increased corneal staining with consequent increase in DED symptoms. It has been proposed that the beneficial effect of androgens stimulates the function of this glandular tissue, increasing its lipogenesis and suppressing its keratinization, this may explain why androgen therapy relieves signs and symptoms of DGM and DED in humans [24].

Additionally, it has been proposed that androgen deficiency can lead to a decrease in the influence of insulin-like growth factor 1 (IGF-1) on the meibomian glands. These androgens increase IGF-1 production, positively regulate IGF-1 receptor expression, modulate IGF-1 signaling, and stimulate human meibomian gland epithelial cell function [84]. On the other hand, there is an accumulation of lymphocytes in the conjunctiva of patients with SS and leads to signs of tarsal and periglandular inflammation. Such conjunctival inflammation can create a toxic environment, leading to the release of proinflammatory cytokines that affect the terminal duct of the meibomian gland [85]; as evidence of this, both SSp and SSs subjects and MGD patients showed occluded metaplastic orifices of the MG, as well as decreased quality of the secretions of these glands. These signs are characteristic of obstructive MGD (hyperkeratinization of the terminal duct epithelium, reduced quality of the meibum, and posterior obstruction) [24]. It has been hypothesized that some symptoms in pSS patients, such as sleep disturbances, depressed mood, and fatigue, may also lead to GDM due to decreased blinking, as the above symptoms are already the result of a lower secretion of dopamine, positively with the frequency of blinking. In patients with SS, the lacrimal glands are severely damaged early in the disease; however, the meibomian glands in patients with SSp will undergo further deterioration when the clinical history of dry eye is more than 3 years [85].

Another mechanism contributing to MGD in SS may be that lymphocytic infiltration adjacent to the tarsal conjunctiva in SS could trigger gland destruction.
