The Expression Levels of Diadenosine Polyphosphates and Mucin in Mechanical Stress-related Ocular Surface Disorders

Ocular surface disorders are diseases involving the most outer surface of the eyeball - the transparent layers that forms the front of the eye, including cornea and conjunctiva. One of the most common ocular surface disorders is dry eye disease (DED) which has a great impact on patients' quality of life. In addition, ocular graft-versus-host disease (GVHD) and superior limbic keratoconjunctivitis (SLK) are also ocular surface disorders affecting patients' quality of life significantly.

1. Great impact of ocular surface disorders on quality of life 1.1. Impact of dry eye disease Dry eye disease (DED) is a common ocular surface disorder. Vision-related quality of life in dry eye patients is impaired and is correlated with anxiety and depression.1 Patients with DED are often evaluated by a symptom scale called ocular surface disorder index (OSDI). The OSDI is a valid and reliable scale for diagnosis and measurement of the severity of DED or other ocular surface disorder. It is also a convenient option for clinical use as a result of its shorter completion time.

1.2. Impact of GVHD GVHD caused by alloreactive donor T cells is an important cause of nonrelapse mortality and morbidity after allogeneic hematopoietic cell transplantation (HCT). Ocular GVHD reportedly occurs in more than 50% of allogeneic HCT recipients with chronic GVHD. It can affect all parts of the eye, but the ocular surface is the most common level of involvement. Yoshi et al suggested strong correlations of serial changes in the NIH eye score, the OSDI, and the Lee eye subscale. Given that the OSDI consists of 12 items instead of the 3 for the Lee eye subscale, they found little basis for recommending the OSDI to measure change in the activity of ocular GVHD. Therefore, the Lee eye subscale might be a good choice for determining the impact of ocular GVHD on quality of life.

1.3. Impact of SLK SLK is an ocular surface disorder characterized by unilateral or bilateral redundancy of the superior bulbar conjunctiva with inflammation of the superior tarsal and bulbar conjunctiva. There are many patients suffering by the symptoms of SLK because of its unclear etiology and no standard treatment. In addition, SLK is not easy to make a definite diagnosis, the impact of SLK on quality of life could be underestimated. 2. Mechanical stress from eyelid blinking may be an aggravating or contributing factor of ocular GVHD and SLK 2.1. The symptoms of ocular GVHD relieved by bandage soft contact lens (BSCL) application via the isolation from mechanical stress (eyelid blinking) and ocular surface The standard treatment of ocular GVHD is still not in consensus. Because of the immune reaction participating in the pathogenesis of ocular GVHD, some topical immunosuppressants, such as cyclosporine A (CsA) and tacrolimus, are applied on the patients with ocular GVHD. Allogeneic serum eye drops and autologous plasma rich in platelet-derived growth factor (PDGF) eye drops were also reported to be effective in chronic ocular GVHD patients. For medication refractory cases, punctal plugs, scleral lens, and bandage soft contact lens (BSCL) could be applied as alternative treatments for ocular GVHD patient. According to previous report, BSCL is a safe and effective treatment option that improves manifestations of ocular GVHD. BSCL can act as a barrier to further epithelial disruption and corneal nerve stimulation by the shearing force of the upper lid during the blink.

2.2. Mechanical stress plays a role in the pathogenesis of SLK Mechanical stimulation may contribute to the pathogenesis of SLK. We speculated that this kind of physical trauma not only results in the keratinization of conjunctival epithelium, but also induced inflammatory cells and mediators, such as mast cells and cytokines, respectively. Three out of 8 SLK patients benefitted from large diameter contact lens application. Conjunctival resection with Tenon's capsule excision was also reported as a beneficial treatment for medication refractory SLK patients. 3. The expression of diadenosine polyphosphates and mucin may alter the clinical presentation or diagnosis of ocular surface disorders 3.1. Dinucleoside polyphosphates in ocular surface disorder Diadenosine polyphosphates are a family of dinucleotides, consisting of two adenosine nucleosides joined by a phosphate chain whose length can vary from 2 to 7 phosphates. They are released from nerve terminals to the extracellular milieu where they can exert actions by interacting with purinergic receptors.