Because of the chronic nature of these particular types of immune mediated dry-eye diseases, long-term safety is clearly needed.6 In our cases, long-term efficacy in addition to other currently available therapy was observed at least for 10 months during single or dual treatment using these medications, although future work with a larger sample size is necessary to confirm this.
There are no particular side effects in the two patients. Although we have been treating cGVHD- or OCP-related dry-eye patients using currently available treatments,27,28 specific therapies have yet to be developed for these diseases. Therapeutic interventions for these specific types of dry-eye diseases are limited at present because adding several treatments to basic therapies depends on the signs and symptoms in each case and the severity of the disease.
The dry-eye cases in this study may be considered mild to moderate according to the 2007 Report of the International Dry Eye WorkShop1; that is, the goblet cells of the conjunctiva might not be severely damaged as we have previously reported.18,29 In both cases, the mucin-related drugs may contribute to the improvement by increasing the mucin from goblet cells or secretory vesicles of the cornea and conjunctival epithelia.2,3,30 In addition, the diquafosol eye drops probably increased water secretion,8 whereas rebamipide eye drops had anti-inflammatory effects11,12 on these types of immune-mediated dry eye.31
In the two specific types of dry-eye disease in this case report, the long-term use of a combination of diquafosol and rebamipide eye drops improved the signs and symptoms of the two dry-eye patients. The conditions of their eyes were stabilized by the treatment, and they did not experience any disabling side effects.
Based on these findings and previous reports, we hypothesized the following mechanism of improvement of dry-eye disease in two cases. Regeneration of barrier function in ocular surface epithelium, increased mucin production, and increased lubrication for palpebral friction in conjunctival fibrosis by rebamipide and diquafosol are among the underlying mechanisms of ocular surface improvement caused by the synergic effect of both eye drops. Washing out inflammatory cytokines in tear fluid by both medications might be one of the mechanisms for the improvement of signs and symptoms of the specific type of dry-eye disease. Increased tear volume by diquafosol and anti-inflammatory effects such as inhibition of cytokine production and infiltration of inflammatory cells by rebamipide can result in an improvement of this type of dry-eye condition. Taking these mechanisms of action together, the dual treatment can be useful in treating these types of immune-mediated dry-eye disease.
This work was supported by the Japanese Ministry of Education, Science, Sports and Culture (no. 23592590 and no. 26462668).
The authors declare that there is no conflict to disclose.
This work was presented at the 37th Japan Cornea Society, Japan Cornea Conference 2013 in Wakayama, Japan.
Received March 17, 2014; accepted January 22, 2015.
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