1 Conjunctival Goblet cell Density Following Sequential Therapy
1 Conjunctival Goblet cell Density Following Sequential Therapy With Artificial Tear and Cyclosporine 0. 05% Frank A. Bucci, Jr, MD 1; Stephen C. Pflugfelder, MD 2; Solherny Pangelinan, MD 2 1 Bucci Laser Vision Institute, Wilkes-Barre, PA; 2 Ocular Surface Center, Baylor College of Medicine, Houston, TX
2 INTRODUCTION • Inflammation plays a major role in the development of dry eye disease 1, 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 MUC 5 AC, 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: Systane® or REFRESH Liquigel®b Washouta -2 0 Cyclosporine 0. 05% BID 3 6 Weeks Evaluation of goblet cell density in inferior bulbar conjunctiva Determination of growth factors and cytokine levels in tear a. Patients received non-preserved artificial tear REFRESH PLUS®. b. Patients were randomized to receive either of the artificial tears QID. 9
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-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 Mean Number of Goblet Cells Per Field Conjunctival Goblet Cell Density 53. 8* 18. 3 Week 0 (Baseline) 20. 8 Week 3 Week 9 (Artificial tear) (Cyclosporine 0. 05%) *P <. 001 compared to weeks 0 and 3
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.
REFERENCES 1. Wilson SE. Inflammation: a unifying theory for the origin of dry eye syndrome. Manag Care 2003; 12: 14 -19. 2. 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. 3. Solomon A, Dursun D, Liu Z, Xie Y, Macri A, Pflugfelder SC. Pro- and antiinflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dryeye disease. Invest Ophthalmol Vis Sci 2001; 42: 2283 -2292. 4. Zhao H, Jumblatt JE, Wood TO, Jumblatt MM. Quantification of MUC 5 AC protein in human tears. Cornea 2001; 20: 873 -877. 5. 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. 6. Argueso P, Balaram M, Spurr-Michaud S, et al. Decreased levels of the goblet cell mucin MUC 5 AC in tears of patients with Sjogren syndrome. Invest Ophthalmol Vis Sci. 2002; 43: 1004– 1011. 7. Sall K, Stevenson OD, Mundorf TK, Reis BL, and the Cs. A 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. 8. Tseng SC. Staging of conjunctival squamous metaplasia by impression cytology. Ophthalmology. 1985; 92: 728– 733. 9
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