# Advances in the Noninvasive Diagnosis of Dry Eye Disease
## 2 Noninvasive Text Break-Up Time  
Pre-corneal film stability plays a critical role in the homeostasis of the ocular surface, and it is an important parameter to be considered for DED diagnosis [4; 8]. In fact, the tear film is the first optical interface between the air and the ocular surface, and since there is a large difference in refractive index between the air and the tear, inhomogeneity in its structure has a major impact on the optical quality. In DED, there is a quantitative and/or qualitative tear deficiency that determines irregularities and/or the early break-up of the tear film [9; 10]. In clinical practice, the most frequently employed test for the measurement of tear film stability is the fluorescein tear film breakup time (BUT), which is the interval time between the eyelid opening after a complete blink and the first break in the tear film. Since BUT requires the use of fluorescein, whose quantity and concentration can also affect the final measurement, noninvasive BUT (NIBUT) has become widely used in both clinical practice and research settings. DEWS II indicated that a cutoff value of NIBUT \(\leq\) 10 s is an indicator for the diagnosis of DED, with a sensitivity of 82-84% and a \begin{table}
\begin{tabular}{c c c c c c} \hline \hline  & **IDRA** & **KERATOGRAPH** & **O.S.A.** & **LACRYDIAG** & **TEARCHECK** \\ \hline \multirow{3}{*}{N.I.B.U.T} & Automatic evaluation & Automatic evaluation & Automatic evaluation & Automatic evaluation & Automatic evaluation \\  & of tear film break-up & with infrared & of fear film & of fear film & of fear film \\  & time & illumination & break-up time & break-up time & break-up time \\ \hline \multirow{3}{*}{Meibography} & View of the presence & Morphological changes in & & & \\  & of abnormal gland & visible using the & View of the presence & Automatic detection & \\  & structures in a & Meibo-Scan and can be & of abnormal gland & of meibomian glands & View of the rate of \\  & high-resolution & discailled with the & Meibo-Scan and can be & structures in a & and automatic & gland loss in \% \\  & 3D image & JENVIS Melbo & high-resolution & calculation of the & \\  & 3D image & JENVIS Melbo & 3D image & percentage of loss & \\  & & Grading Scales & & & \\ \hline \multirow{3}{*}{Interferometry} & Automatic evaluation & The thickness of the lipid & & Qualitative and & \\  & of the lipid layer & layer is automatically & Manual evaluation of & of the lipid layer & \\  & of the lipid layer & assessed based on the & the lipid layer & Evaluation of lipid & Not available \\  & structure and color & & & layer thickness based & \\  & & & & on a grading scale & \\ \hline \multirow{3}{*}{Tear Meniscus} & Estimation of the tear & The height of the tear & Estimation of the tear & Measurement of tear & Calculate manually \\  & film quantity up to & meniscus can be precisely & finally with an & film quantity up to & meniscus & the height of the tear \\  & 5 values & integrated ruler & five values & height (mm) & meniscus \\ \hline \multirow{3}{*}{Bulbar Redness} & Comparison with all & The R-Scan automatically & Comparison with all & \\  & international grading & detects the blood vessels & international grading & Not available & Available \\ \cline{1-1}  & scales (efron, & evaluates the degree & scales (efron, cclru, & \\ \cline{1-1}  & cclru, jenvis) & of redness & jenvis) & \\ \hline \hline \end{tabular} NIBUT = noninvasive break up time, LACRYDIAG (Quantel Medical), IIDRA (Sbm Sistemi, Inc., Torino, Italy), OSA (Sbm Sistemi, Inc., Torino, Italy), KERATOGRAPH 5 M (Oculus Optikgerate GmbH, Wetzlar, Germany), TEARCECK (NewTech s.p.a., MI, Italy).  
\end{table} 
Table 1: Multi-imaging-integrated devices and features. specificity of 76-94% [4]. There are several commercially available NIBUT systems, based on topographic or videokeratopraphic methods, which analyze the inter-blink changes of reflected placido mites. A change in the edges of the mites reflects compromised tear film integrity. [PERSON] et al.