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Conjunctival Goblet cell Density Following Sequential Therapy With Artificial Tear and Cyclosporine 0.05% PowerPoint Presentation
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Conjunctival Goblet cell Density Following Sequential Therapy With Artificial Tear and Cyclosporine 0.05%

Conjunctival Goblet cell Density Following Sequential Therapy With Artificial Tear and Cyclosporine 0.05%

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Conjunctival Goblet cell Density Following Sequential Therapy With Artificial Tear and Cyclosporine 0.05%

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  1. Conjunctival Goblet cell Density Following Sequential Therapy With Artificial Tear and Cyclosporine 0.05% Frank A. Bucci, Jr, MD1; Stephen C. Pflugfelder, MD2; Solherny Pangelinan, MD2 1Bucci Laser Vision Institute, Wilkes-Barre, PA; 2Ocular Surface Center, Baylor College of Medicine, Houston, TX

  2. INTRODUCTION • Inflammation plays a major role in the development of dry eye disease1, which is characterized by abnormal tear film composition.2-4 • Goblet cell are important for normal composition of tear film and may serve as an indicator of ocular surface health. • Goblet cells secrete the soluble mucin MUC5AC, which increases the viscosity and resistance of the tear film against thinning and breakup during the blink cycle.5 • The number of conjunctival goblet cells is decreased in dry eye patients.6 • Soluble mucin concentration is also reduced by 60% in the tear film. • Cyclosporine 0.05% was demonstrated to significantly improve tear production and alleviate disease symptoms in dry eye patients.7 • The aim of this study was to evaluate conjunctival goblet cell density and the levels of tear growth factor and cytokines following sequential therapy with artificial tears and cyclosporine 0.05% in patients with dry eye disease.

  3. METHODS • Multicenter, randomized, prospective trial • Enrolled dry eye patients with • Ocular Surface Disease Index (OSDI) score ≥ 25 • Tear fluorescein break-up time ≤ 8 seconds. • Study treatments: Washouta Systane® or REFRESH Liquigel®b Cyclosporine 0.05% BID -2 0 3 6 9 Weeks Evaluation of goblet cell density in inferior bulbar conjunctiva Determination of growth factors and cytokine levels in tear aPatients received non-preserved artificial tear REFRESH PLUS®. bPatients were randomized to receive either of the artificial tears QID.

  4. METHODS • Impression cytology • Cytology samples were taken from the inferior bulbar conjunctiva using a nitrocellulose membrane. • Membranes were stained with a modified periodic acid–Schiff (PAS) Papanicolaou stain.8 • Goblet cells were counted in 5 (400 x 400 mm) representative microscopic fields in each membrane. • Tear Immunoassays • Epidermal growth factor (EGF) and a panel of 8 inflammatory cytokines/chemokines (IL-1 , IL-1 , IL-2, IL-6, IL-8, IL-12, IL-13, and RANTES) were measured on a Luminex multiplex system using Upstate Biotechnology Beadlyte reagents.

  5. RESULTS Patient Disposition • A total of 19 patients were enrolled • 16 patients completed the study • 9 patients had inadequate samples • 7 patients were included in the analyses

  6. Conjunctival Goblet Cell Density 53.8* *P < .001 compared to weeks 0 and 3 Mean Number of Goblet Cells Per Field 20.8 18.3 Week 0 (Baseline) Week 3 (Artificial tear) Week 9 (Cyclosporine 0.05%)

  7. Tear EGF and Cytokine Levels • An increase in the level of tear IL-13 was noted after the treatment with cyclosporine 0.05% at week 9. This difference, however, did not reach statistical significance. • The levels of tear EGF and other cytokines were not changed after the treatment with artificial tears or cyclosporine 0.05%.

  8. CONCLUSIONS • Cyclosporine 0.05%, but not artificial tears, increased goblet cell density in conjunctiva of dry eye patients. • These findings suggest that chronic dry eye patients may benefit more from cyclosporine 0.05% therapy than artificial tears.

  9. REFERENCES • Wilson SE. Inflammation: a unifying theory for the origin of dry eye syndrome. Manag Care 2003;12:14-19. • Ogasawara K, Mitsubayashi K, Tsuru T, Karube I. Electrical conductivity of tear fluid in healthy persons and keratoconjunctivitis sicca patients measured by a flexible conductimetric sensor. Graefes Arch Clin Exp Ophthalmol 1996;234:542-546. • Solomon A, Dursun D, Liu Z, Xie Y, Macri A, Pflugfelder SC. Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease. Invest Ophthalmol Vis Sci 2001;42:2283-2292. • Zhao H, Jumblatt JE, Wood TO, Jumblatt MM. Quantification of MUC5AC protein in human tears. Cornea 2001;20:873-877. • Pflugfelder SC, Tseng SC, Yoshino K, et al. Correlation of goblet cell density and mucosal epithelial membrane mucin expression with rose bengal staining in patients with ocular irritation. Ophthalmology. 1997;104:223–235. • Argueso P, Balaram M, Spurr-Michaud S, et al. Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjogren syndrome. Invest Ophthalmol Vis Sci. 2002;43:1004–1011. • Sall K, Stevenson OD, Mundorf TK, Reis BL, and the CsA Phase 3 Study Group. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease [published correction appears in Ophthalmology. 2000;107:1220]. Ophthalmology. 2000;107:631-639. • Tseng SC. Staging of conjunctival squamous metaplasia by impression cytology. Ophthalmology. 1985;92:728–733.