In this study, the TF test was investigated for its capacity to distinguish between normal and early photokeratitis status in a mouse UVB-induced model. With photokeratitis, although both the Masmali and the SK criteria could distinguish the damage from the blank groups after 4 days, the SK criteria could decern the damage group on day 3. This capacity of earlier detection would render the SK criteria more helpful than the Masmali grading if the TF test is used in the clinical settings. This advantage of the SK criteria is likely due to that the subtler changes can be reflected. However, this advantage cannot be generalized that TF can show early changes than those reflected by TBUT and TV, simply because the latter two measurements were conducted at a later time in our experimental design.
To further verify the TF test as a reliable method for early photokeratitis diagnosis, we correlated the TF results with other commonly used clinical ocular surface parameters. The TF test showed strong correlations with TV, TBUT, and cornea staining, indicating that the TF test may provide a general view of all the three indicators under the photokeratitis status. Besides, the TF test correlation with TBUT was stronger than with TV, suggesting that the TF test can reflect more about tear quality than quantity. The insight of this finding would be a potential use of TF to reflect the important component within the tear. For example, cornea damage may be due to loss of lactoferrin, which is a significant component of the tear film and plays an important role in maintaining ocular surface health.
26 Reduced lactoferrin levels in the tears may contribute to tear film instability and may alter the TF formation. Another potential use of TF may be to correlate with cornea staining for confirmation of ocular surface status, particularly at early stages when the staining remains not evident. In the present study, our data showed a very strong positive correlation between lissamine green staining and TF grading, supporting the use of TF for the evaluation of corneal epithelial injuries. However, to bring the TF test into clinical settings, human clinical trials are mandatory to confirm its applicability as an earlier indicator for photokeratitis.
Differential diagnosis among ocular surface diseases is critical for clinical management. For example, early photokeratitis and dry eye share some common symptoms such as tearing, itchy sensation, and ocular surface redness and swelling. In addition, allergic conjunctivitis shares similar symptoms at the early stage,
27 which is a challenge for differential diagnosis. Incorrect management for these diseases, for example, between dry eye and allergic conjunctivitis at early stages, may lead to worsen the pathogenetic aftermath.
28 Nevertheless, the commonly used assessments, such as TBUT and Schirmer's test, have been shown only weakly correlated with signs and symptoms.
16,17 Other assessments, such as in vivo confocal microscopy (IVCM) and osmolarity test,
29 demand substantial time, expensive instruments, or personnel skills for completion. Therefore, a quick, easy to perform, reproducible, and cost-effective measurement for early and preferentially differential diagnosis would be more acceptable in clinical settings. We hypothesize that different ocular surface disorders may have their characteristic tear composition, and therefore may display differential TF results. In this regard, the TF test may offer another option for ocular surface diagnosis.
In conclusion, the present study has demonstrated the use of the TF test for early diagnosis of photokeratitis, particularly by using the SK grading criteria. Furthermore, because the TF test can generally reflect the results of TV, TBUT, and cornea staining, and can be easily performed, it may be used as a primary test for mass screening of ocular surface diseases.