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      Long-term Rebamipide and Diquafosol in Two Cases of Immune-Mediated Dry Eye

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          Abstract

          Supplemental digital content is available in the text.

          ABSTRACT

          Purpose

          Two new drugs with mucin-inducing and secretion-promotive effects, rebamipide and diquafosol, were recently approved as topical dry-eye treatments. We report two cases in which the long-term use of mucin-inducing eye drops improved chronic ocular graft-versus-host disease (cGVHD)–related dry eye and ocular cicatricial pemphigoid (OCP)-like disease.

          Case Reports

          Case 1. A 61-year-old woman had cGVHD-related dry eye that resisted traditional medications. Next, we use topical diquafosol in addition to conventional treatments. The patient used diquafosol for 6 months without experiencing any side effects. The symptoms, including dry-eye sensation, ocular pain, foreign body sensation, and photophobia, as well as ocular surface findings including fluorescein and rose bengal scores and tear break-up time (TBUT), partly improved. To further improve the clinical signs and symptoms and decrease chronic inflammation, rebamipide was added to diquafosol. The symptoms, TBUT, and fluorescein and rose bengal scores markedly improved after long-term dual treatment without any side effects for 6 months. Case 2. A 77-year-old woman had OCP-like disease with dry eye. The patient did not improve using the currently available conventional treatments. Next, we use topical rebamipide in addition to conventional treatments. Symptoms including asthenopia, dry-eye sensation, ocular pain, and dull sensation, as well as fluorescein and rose bengal scores and TBUT, partly improved. Specifically, functional visual acuity was markedly improved after commencement of rebamipide. To further improve the clinical signs and symptoms and increase tear film stability and tear film volume, diquafosol was added to rebamipide. The combination of diquafosol and rebamipide worked for the patient. Improvements were seen in several symptoms, fluorescein and rose bengal scores, Schirmer test value, and TBUT without any side effects for 12 months.

          Conclusions

          Long-term treatment with topical rebamipide and diquafosol can improve dry eye in patients with cGVHD or OCP-like disease.

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          Most cited references34

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          Distribution of mucins at the ocular surface.

          Ilene K. Gipson (2004)
          Mucins are vital for maintenance of a healthy, wet ocular surface. Once only thought to be secreted by goblet cells, mucins are now also known to be of the membrane-associated type. Stratified ocular surface epithelia express at their apical-tear fluid surface a repertoire of membrane-associated mucins including MUC1, MUC4, MUC16. These mucins are concentrated on the tips of the microplicae, forming a dense glycocalyx at the epithelial tear film interface. A major mucin of the secretory class is the goblet-cell-derived gel-forming mucin MUC5AC. A small soluble mucin, MUC7, is expressed by the lacrimal gland acini. Our hypothesis of the role/distribution of the secreted and membrane-associated mucins at the ocular surface is that the secreted mucins are soluble in the tear fluid, and are moved about and shunted to the nasolacrimal duct and by the eyelids during blinking. Thus, in the tears, the secreted mucins act as clean-up/debris removing multimeric networks that at the same time, through their hydrophilic nature, hold fluids in place and harbor defense molecules secreted by the lacrimal gland. Membrane-associated mucins, on the other hand, form a dense barrier in the glycocalyx at the epithelial tear film interface. This barrier prevents pathogen penetrance and is a lubricating surface that allows lid epithelia to glide over the corneal epithelia without adherence. The secreted mucins move easily over the glycocalyx mucins because both have anionic character that creates repulsive forces between them. Little is known regarding regulation of expression and glycosylation of mucins by ocular surface epithelia. Since ocular surface drying diseases alter both goblet cell and mucin production, and production and glycosylation of membrane-associated mucins, studies of mucin gene regulation and glycosylation may yield treatment modalities for these diseases.
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            International Chronic Ocular Graft-vs-Host-Disease (GVHD) Consensus Group: Proposed Diagnostic Criteria for Chronic GVHD (Part I)

            Yoko Ogawa, Stella Kim, Reza Dana … (2013)
            The International Chronic Ocular GVHD Consensus Group held 4 working meetings to define new diagnostic metrics for chronic ocular graft-versus-host disease (GVHD). After considering the factors currently used to diagnose chronic ocular GVHD, the Consensus Group identified 4 subjective and objective variables to measure in patients following allogeneic hematopoietic stem cell transplantation (HSCT): OSDI, Schirmer's score without anesthesia, corneal staining, and conjunctival injection. Each variable was scored 0–2 or 0–3, with a maximum composite score of 11. Consideration was also given to the presence or the absence of systemic GVHD. On the basis of their composite score and the presence or absence of systemic GVHD, patients were assigned to one of three diagnostic categories: NO, PROBABLE, or DEFINITE ocular GVHD. New diagnostic criteria for chronic ocular GVHD are presented by the Consensus Group. Validation studies are needed to identify the best combination of the proposed metrics to maximize diagnostic sensitivity and specificity.
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              The effect of autologous serum eyedrops in the treatment of severe dry eye disease: a prospective randomized case-control study.

              Takashi Kojima, Reiko Ishida, Murat Dogru … (2005)
              To evaluate the effectiveness of the autologous serum eyedrops in the treatment of severe dry eye patients.
              Article 0 comments Cited 53 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Optom Vis Sci
                Journal ID (iso-abbrev): Optom Vis Sci
                Journal ID (publisher-id): OPX
                Title: Optometry and Vision Science
                Publisher: Lippincott Williams & Wilkins
                ISSN (Print): 1040-5488
                ISSN (Electronic): 1538-9235
                Publication date (Print): April 2015
                Publication date (Electronic): 27 March 2015
                Volume: 92
                Issue: 4 Suppl
                Pages: S25-S32
                Affiliations
                [1]*MD
                [2] †PhD
                Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan (all authors).
                Author notes
                Yoko Ogawa Department of Ophthalmology Keio University School of Medicine 35, Shinanomachi, Shinjuku-ku Tokyo, 160-8582 Japan e-mail: yoko@ 123456z7.keio.jp
                Article
                Publisher ID: OPX14129 Accession ID: 00007
                DOI: 10.1097/OPX.0000000000000523
                PMC ID: 4376271
                PubMed ID: 25785527
                SO-VID: 6fbae5ac-3331-4623-b883-38f7c0adde22
                Copyright © Copyright © 2015 American Academy of Optometry
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

                History
                Date received : 17 March 2014
                Date accepted : 22 January 2014
                Categories
                Subject: Clinical Cases
                Custom metadata
                OPEN-ACCESS TRUE
                SDC T
                STATUS ONLINE-ONLY

                Keywords: dry eye,rebamipide,diquafosol,eye drops,mucin,chronic graft-versus-host disease,ocular cicatricial pemphigoid
                Data availability:
                Keywords: dry eye, rebamipide, diquafosol, eye drops, mucin, chronic graft-versus-host disease, ocular cicatricial pemphigoid

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