Korean J Ophthalmol.  2007 Dec;21(4):189-194. 10.3341/kjo.2007.21.4.189.

Short Term Effects of Topical Cyclosporine and Viscoelastic on the Ocular Surfaces in Patients with Dry Eye

Affiliations
  • 1Department of Ophthalmology, Konkuk University Hospital, Seoul, Korea.
  • 2Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea. kmk9@snu.ac.kr
  • 3Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute, Seoul, Korea.
  • 4Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea.

Abstract

PURPOSE: To compare the short term effects of topical 0.05% cyclosporine (CsA) and a mixture of 0.08% chondroitin sulfate and 0.06% sodium hyaluronate (CS-HA) on dry eye ocular surfaces. METHODS: 36 patients with moderate to severe dry eye (5 mm/5 min or less with Schirmer's test or tear break up time (BUT) less than 6 seconds), were treated with topical application of CS-HA on one eye and CsA on the other 4 times a day for 6-8 weeks. BUT, Schirmer's test without anesthesia, and conjunctival impression cytology (CIC; goblet cell density, nucleus to cytoplasmic ratio, and epithelial cell morphology) were evaluated and compared between eyes before and after treatment (repeated measurement of ANOVA). RESULTS: After treatment, BUT and tear wettings were significantly prolonged in each group. Topical CsA treated eyes had greater increase in BUT (p=0.026); there was no significant difference in tear wetting (p=0.132). While the 3 parameters of CIC improved in both groups, goblet cell density was significantly higher in eyes treated with CsA (p=0.033). CONCLUSIONS: While both CS-HA and 0.05% CsA eyedrops improve ocular surfaces, topical CsA may have a better effect on enhancing tear film stability and goblet cell density.

Keyword

Dry eye; Topical cyclosporine; Topical viscoelastic

MeSH Terms

Adjuvants, Immunologic/administration & dosage
Administration, Topical
Cell Count
Chondroitin Sulfates/*administration & dosage
Conjunctiva/drug effects/pathology
Cyclosporine/*administration & dosage
Drug Administration Schedule
Drug Combinations
Drug Therapy, Combination
Dry Eye Syndromes/*drug therapy/metabolism/pathology
Epithelium/drug effects/pathology
Female
Follow-Up Studies
Goblet Cells/drug effects/pathology
Humans
Hyaluronic Acid/*administration & dosage
Immunosuppressive Agents/*administration & dosage
Male
Middle Aged
Ophthalmic Solutions/administration & dosage
Tears/drug effects/metabolism
Time Factors
Treatment Outcome

Figure

  • Fig. 1 Comparing tear film BUT between eyes before and after topical application of topical 0.077% chondroitin sulfate with 0.06% hyaluronate (on right eyes) and 0.05% cyclosporine (on left eyes). Before treatment, there was no significant difference between eyes. After applications, tear film BUT increased significantly in both eyes but was more profound in left eyes.

  • Fig. 2 Comparing aqueous tear production (Schirmer's test) between eyes before and after topical application of 0.077% chondroitin sulfate with 0.06% hyaluronate (on right eyes) and 0.05% cyclosporine (on left eyes). After treatment with the assigned eyedrop, aqueous production increased significantly in both eyes. The amount of increase in both eyes was similar.

  • Fig. 3 Before treatment with topical eyedrops, goblet cell densities (GCD) were similar between eyes. After assigned treatments (topical chondroitin sulfate with sodium hyaluronate (CS-HA) for right eyes and topical cyclosporine (CsA) for left eyes), there was a significant GCD increase in both eyes. However, GCD increase was greater in left eyes.

  • Fig. 4 Before topical eyedrops, nucleus to cytoplasmic ratios (NCR) of conjunctival impression cytology were similar between the two groups. After assigned treatments (topical chondroitin sulfate with sodium hyaluronate (CS-HA) for right eyes and topical cyclosporine (CsA) for left eyes), there was significant NCR improvement in both eyes. There was no significant differences among treatment groups.

  • Fig. 5 Before treatments, epithelial morphologies (ECM) of conjunctival epithelium in conjunctival impression cytology were similar between eyes. While there was significant ECM improvement in both eyes after treatments (topical chondroitin sulfate with sodium hyaluronate (CS-HA) for right eyes and topical cyclosporine (CsA) for left eyes), the degree of change in both eyes was similar.


Cited by  1 articles

Effect of 0.1% Sodium Hyaluronate and 0.05% Cyclosporine on Tear Film Parameters after Cataract Surgery
Won Choi, Kyung-Chul Yoon
J Korean Ophthalmol Soc. 2011;52(7):800-806.    doi: 10.3341/jkos.2011.52.7.800.


Reference

1. Baudouin C. The pathology of dry eye. Surv Ophthalmol. 2001; 45:S211–S220. PMID: 11587145.
Article
2. Lemp MA. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. CLAO J. 1995; 21:221–232. PMID: 8565190.
3. Yeh S, Song XJ, Farley W, et al. Apoptosis of ocular surface cells in experimentally induced dry eye. Invest Ophthalmol Vis Sci. 2003; 44:124–129. PMID: 12506064.
Article
4. Kunert KS, Tisdale AS, Gipson IK. Goblet cell numbers and epithelial proliferation in the conjunctiva of patients with dry eye syndrome treated with cyclosporine. Arch Ophthalmol. 2002; 120:330–337. PMID: 11879137.
Article
5. Turner K, Pflugfelder SC, Ji Z, et al. Interleukin-6 levels in the conjunctival epithelium of patients with dry eye disease treated with cyclosporine ophthalmic emulsion. Cornea. 2000; 19:492–496. PMID: 10928765.
Article
6. 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. PMID: 9052626.
Article
7. Baudouin C, Brignole F, Becquet F, et al. Flow cytometry in impression cytology specimens: a new method for evaluation of conjunctival inflammation. Invest Ophthalmol Vis Sci. 1997; 8:1458–1464. PMID: 9191610.
8. Brignole F, Pisella PJ, Dupas B, et al. Efficacy and safety of 0.18% sodium hyaluronate in patients with moderate dry eye syndrome and superficial keratitis. Graefes Arch Clin Exp Ophthalmol. 2005; 243:531–538. PMID: 15965673.
Article
9. Sall K, Stevenson OD, Mundorf TK, Reis BL. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. Ophthalmology. 2000; 107:631–639. PMID: 10768324.
10. Tatlipinar S, Akpek EK. Topical ciclosporin in the treatment of ocular surface disorders. Br J Ophthalmol. 2005; 89:1363–1367. PMID: 16170133.
Article
11. Papa V, Aragona P, Russo S, et al. Comparison of hypotonic and isotonic solutions containing sodium hyaluronate on the symptomatic treatment of dry eye patients. Ophthalmologica. 2001; 215:124–127. PMID: 11244343.
Article
12. Nepp J, Schauersberger J, Schild G, et al. The clinical use of viscoelastic artificial tears and sodium chloride in dry-eye syndrome. Biomaterials. 2001; 22:3305–3310. PMID: 11700802.
Article
13. Campo GM, Avenoso A, Campo S, et al. Efficacy of treatment with glycosaminoglycans on experimental collagen-induced arthritis in rats. Arthritis Res Ther. 2003; 5:R122–R131. PMID: 12723984.
14. Hamano H, Hori M, Hamano T, et al. A new method for measuring tears. CLAO J. 1983; 9:281–289. PMID: 6413088.
15. Toda I, Tsubota K. Practical double vital staining for ocular surface evaluation. Cornea. 1993; 12:366–367. PMID: 7687944.
Article
16. Saini JS, Rajwanshi A, Dhar S. Clinicopathological correlation of hard contact lens related changes in tarsal conjunctiva by impression cytology. Acta Ophthalmol(Copenh). 1990; 68:65–70. PMID: 2336936.
Article
17. Kinoshita S, Kiorpes TC, Friend J, Thoft RA. Goblet cell density in ocular surface disease. A better indicator than tear mucin. Arch Ophthalmol. 1983; 101:1284–1287. PMID: 6882259.
18. Barber LD, Pflugfelder SC, Tauber J, Foulks GN. Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years. Ophthalmology. 2005; 112:1790–1794. PMID: 16102833.
Article
19. Strong B, Farley W, Stern ME, Pflugfelder SC. Topical cyclosporine inhibits conjunctival epithelial apoptosis in experimental murine keratoconjunctivitis sicca. Cornea. 2005; 24:80–85. PMID: 15604871.
Article
20. Moore CP, McHugh JB, Thorne JG, Phillips TE. Effect of cyclosporine on conjunctival mucin in a canine keratoconjunctivitis sicca model. Invest Ophthalmol Vis Sci. 2001; 42:653–659. PMID: 11222523.
21. el Tayar N, Mark AE, Vallat P, et al. Solvent-dependent conformation and hydrogen-bonding capacity of cyclosporin A: evidence from partition coefficients and molecular dynamics simulations. J Med Chem. 1993; 36:3757–3764. PMID: 8254605.
Article
22. Mithani SD, Bakatselou V, TenHoor CN, Dressman JB. Estimation of the increase in solubility of drugs as a function of bile salt concentration. Pharm Res. 1996; 13:163–167. PMID: 8668668.
23. Kuwano M, Ibuki H, Morikawa N, et al. Cyclosporine A formulation affects its ocular distribution in rabbits. Pharm Res. 2002; 19:108–111. PMID: 11837694.
24. Limberg MB, McCaa C, Kissling GE, Kaufman HE. Topical application of hyaluronic acid and chondroitin sulfate in the treatment of dry eyes. Am J Ophthalmol. 1987; 103:194–197. PMID: 3101502.
Article
25. Shimmura S, Ono M, Shinozaki K, et al. Sodium hyaluronate eyedrops in the treatment of dry eyes. Br J Ophthalmol. 1995; 79:1007–1011. PMID: 8534643.
Article
26. Fukuda K, Miyamoto Y, Miyara Y. Hyaluronic acid in tear fluid and its synthesis by corneal epithelial cells. Asia-pacific J Ophthalmo. 1998; 40:62–65.
27. Inoue M, Katakami C. The effect of hyaluronic acid on corneal epithelial cell proliferation. Invest Ophthalmol Vis Sci. 1993; 34:2313–2315. PMID: 8505213.
28. Nishida T, Nakamura M, Mishima H, Otori T. Hyaluronan stimulates corneal epithelial migration. Exp Eye Res. 1991; 53:753–758. PMID: 1783012.
Article
29. Lerner LE, Schawrtz DM, Hwang DG, et al. Hyaluronan and CD44 in the human cornea and limbal conjunctiva. Exp Eye Res. 1998; 67:481–484. PMID: 9820796.
Article
30. Entwistle J, Hall CL, Turley EA. HA receptors: signalling to the cytoskeleton. J Cell Biochem. 1996; 61:569–577. PMID: 8806080.
31. Rosales C, O'Brien V, Kornberg L, Juliano R. Signal transduction by cell adhesion receptors. Biochem Biophys Acta. 1995; 1242:77–98. PMID: 7542926.
Article
32. Miyazaki T, Miyauchi S, Nakamura T, et al. The effect of sodium hyaluronate on the growth of rabbit corneal epithelial cells in vitro. J Ocul Pharmacol Ther. 1996; 12:409–415. PMID: 8951677.
33. Nakamura M, Hikida M, Nakano T, et al. Characterization of water retentive properties of hyaluronan. Cornea. 1993; 12:433–436. PMID: 8306665.
Article
34. Nelson JD, Farris RL. Sodium hyaluronate and polyvinyl alcohol artificial tear preparations. A comparison in patients with keratoconjunctivitis sicca. Arch Ophthalmol. 1988; 106:484–487. PMID: 2451494.
35. Stadler J, Stefanovic-Racic M, Billiar TR, et al. Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide. J Immunol. 1991; 147:3915–3920. PMID: 1658153.
36. Solomon A, Dursun D, Liu Z, et al. 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. PMID: 11527941.
37. Luo L, Li DQ, Doshi A, et al. Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface. Invest Ophthalmol Vis Sci. 2004; 45:4293–4301. PMID: 15557435.
Article
Full Text Links
  • KJO
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr