The core mechanism of dry eye is the tear film instability. Tear film-oriented diagnosis (TFOD) is a concept to clarify the cause of tear film instability by tear film, and tear film-oriented treatment (TFOT) is a concept to treat dry eye disease by replacing the lacking components of the tear film layer based on the TFOD. In TFOD, the fluorescein breakup pattern of the tear film is important, and the subtype of dry eye can be judged to some extent from the breakup patterns. Current noninvasive devices related to the dynamic analysis of the tear film and visual acuity enabled the diagnosis of dry eye, subtype analysis, and the extent of severity. In Asian countries, secretagogues represent the main treatment in TFOT. Since meibomian gland dysfunction is a factor that greatly affects the tear breakup time, its treatment is also essential in the dry eye treatment strategy. A newly discovered dry eye subtype is the short breakup time-type (BUT) of dry eye. The only abnormal finding in this disease is the short BUT, suggesting a relationship with ocular neuropathic pain and eye strain. Recently, data from many studies have accumulated which show that dry eye is a life-style disease. In addition to the treatment of dry eyes, it is becoming possible to prevent the onset by intervening with the daily habits, diet, exercise and sleep, etc. It has been pointed out that oxidative stress is also involved in the pathology of dry eye, and intervention is being carried out by improving diet and taking supplements. Future research will be needed to link clinical findings to the molecular biological findings in the tear film.

Conventional treatment of dry eye mainly consists of the use of preservative-free artificial eye drops and punctal occlusion. None of the commercially available artificial tear preparations include essential tear components such as epidermal growth factor, hepatocyte growth factor, fibronectin, neurotrophic growth factor, and vitamin A-all of which have been shown to play important roles in the maintenance of a healthy ocular surface epithelial milieu. We reported previously that autologous serum (AS) eye drops contain these essential factors and that AS eye drops are beneficial in the treatment of ocular surface diseases such as persistent epithelial defects, superior limbic keratoconjunctivitis, keratoconjunctivitis sicca, and neurotrophic keratopathy. However, there is some controversy regarding the efficacy of AS treatment. We demonstrated that this modality is more effective than artificial tears in a randomized control study. In in vivo and in vitro experiments, AS eye drops showed marked suppression of apoptosis in the conjunctival and corneal epithelium. Albumin, the major protein in serum, improved ocular surface damage in vivo and rescued apoptosis after serum deprivation in vitro. The biological background of AS eye drops and previous clinical studies of these medications for the treatment of dry eye are discussed.

Contact lens wearers complain of various types of contact lens discomfort (CLD), which may result in the discontinuation of contact lenses. CLD is often associated with dry eye disease. A contact lens divides the tear film into two layers: the pre- and post-lens tear film. This change leads to instability of the pre-lens tear film, thinning of pre- and post-lens tear film thickness, and increased friction between the contact lens and the ocular surface. The Japanese Dry Eye Society recommends the diagnosis of tear film abnormality first (tear film-oriented diagnosis [TFOD]) and the treatment of dry eye disease based on TFOD (tear film-oriented therapy [TFOT]). These concepts can be applied for contact lens–associated dry eye disease (CLADE). Noninvasive tear film breakup time, tear volume evaluation, vital staining, and assessment of Meibomian glands are performed to evaluate the tear film. On vital staining analysis of CLADE, lid wiper epitheliopathy and conjunctival edge staining are major findings. In TFOT of CLADE, secretagogues of water or mucins, such as diquafosol and rebamipide, have been first used in Japan. Material, design, wettability, and friction coefficient of the contact lens could affect CLADE. Changes of contact lens may be an option in TFOD. However, the effects of contact lens properties on the tear film and ocular surface are still unclear. Further controlled studies are needed in the future.

Hyaluronic acid (HA) ophthalmic solution is widely used in dry eye treatment worldwide. However, there are no reports comparing the dry eye treatment effects of high molecular weight HA with low molecular weight HA. Sixty eight-week-old C57BL/6 mice were assigned to the following 6 groups and exposed to environmental dry eye stress (EDES) that mimics office work environment: (1) 0.1% low molecular weight HA (LMWHA) eye drops, (2) 0.3% LMWHA eye drops, (3) 3% diquafosol sodium (DQ) eye drops, (4) 0.15% high molecular weight HA (HMWHA) eye drops, (5) no treatment with exposure to EDES (EDES+/Treatment−), and (6) no treatment without exposure to EDES (EDES−/Treatment−). After EDES, the HMWHA group had significantly longer break-up time (BUT) than the 0.1%, 0.3% LMWHA groups and the DQ group. After EDES, the HMWHA group had significantly lower lissamine green staining scores than the LMWHA and DQ groups. Subepithelial presumed dendritic cell density in the HMWHA group was significantly lower than the EDES+/Treatment− group. After EDES exposure, Conjunctival Muc5AC mRNA expression in the HMWHA group was significantly higher than the 0.1 and 0.3% LMWHA groups. Ophthalmic HMWHA solution may have a better dry eye treatment effect than LMWHA or DQ solution, owing to its anti-inflammatory effect.