# AS-OCT and Ocular Hygrometer as Innovative Tools in Dry Eye Disease Diagnosis
## 2 Current Methods of Diagnosis
Although the Schirmer test is one of the most widely used tools in diagnosing DED, the protracted nature of the test, the irritating and invasive sensations experienced by the patients and its unreliable and largely irreproducible features may lead to a high risk of underdiagnosis [17; 33]. TBUT is one of the most common tests for measuring tear film stability. TBUT is evaluated during a slit lamp examination with blue light and after fluorescein staining. TBUT measures the amount of time it takes for the first break in the tear film to appear after a blink while the patient refrains from blinking. The test result is suggestive of dry eye disease when it is less than 10 s [34]. Once the instability of the tear film has been confirmed, the physician has the task of further investigating the causes and looking for the presence of superficial irregularities or diseases of the eyelid margin. Although this test is cheap, quick to perform and uses readily available supplies, it is inaccurate, operator dependent and not reproducible [17; 21; 35; 36]. The tear film osmolarity reflects the balance between tear production, evaporation, drainage and absorption [37]. The measurement of these variables can identify the cause of DED due to the associated derangement in the normal physiological parameters [38]. For a more accurate diagnosis, it is necessary to evaluate the average tear film osmolarity as a single osmolarity reading could be normal even in patients with DED [38]. Moreover, the variability of tear film osmolarity has been shown to correlate directly with DED severity [39]. An osmolarity value greater than 308 mOsm/L is generally indicative of dry eye disease [39]. However, this technological investigation methodology is costly and time-consuming and, at the same time, is unable to accurately differentiate between dry eye disease patients and controls. Another way to assess dryness is by analyzing tear protein patterns. Quantitatively, dry eye disease patients typically have a lower protein content than healthy controls [40]. Qualitatively, however, tear samples from dry eye disease patients contain fewer protective proteins and more proinflammatory markers, such as matrix metalloproteinase 9, interleukin-1 Ra and interleukin-8 [41]. In addition, elevated cytokine levels of interleukin-17, interleukin-6 and tumor necrosis factor-alpha have been found in patients with both dry eye disease and [PERSON] syndrome compared to patients with dry eye disease without [PERSON] syndrome and controls [42]. Furthermore, dry eye disease biomarkers can also be analyzed on conjunctival cell samples, which are obtained quickly and painlessly by impression cytology. However, further studies are needed to elucidate its sensitivity and specificity in the differential diagnosis of various diseases involving the ocular surface. The study of biomarkers may lead to developments in drugs that can help to treat dry eye disease. However, although promising, its use is limited in current clinical practice due to high costs and the absence of insurance reimbursement. Non-contact infrared meibography, based on transillumination with infrared photography, provides the two-dimensional shape of the meibomian glands (MGs) [43]. Healthy meibum is showed as a bright area due to its autofluorescence while dark areas in the MGs indicate an altered meibum condition, which is determined as MG dropout [43; 44]. In order to evaluate MG dropout, the MGF Workshop recommend the Gestalt grading scale and the meiboscale among the various grading scales proposed [43]. Continuous grading scales have also recently been developed using semiautomated software, which in an automatic way of estimating the ratio of the MG loss area to the total eyelid area [45]. Both the severity of MGD and the percentage of MG dropout showed a positive correlation with the TBUT, dry eye disease symptom score and corneal stain score [44; 45]. MG dropout measured using infrared meibography has proven to be useful for differential diagnosis between MGD and aqueous deficiency DED [46].