Skip to main content

Advertisement

Log in

Recent advances in the management of ocular complications of sjögren’s syndrome

  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Sjögren’s syndrome (SS) is an autoimmune disorder, the principal ocular manifestation of which is decreased tear production leading to chronic irritation and damage to the corneal and conjunctival epithelium. The most important advance in the treatment of ocular manifestations of SS is the introduction of topical anti-inflammatory agents such as cyclosporine A, which increases tear production and decreases symptoms without any significant side effect. Stimulators of tear secretion, both topical, such as diquafosol, and systemic, such as pilocarpine and cevimeline, are also effective, although they have been associated with frequent side effects. Topical use of autologous serum is another new and effective form of treatment, but problems in the preparations prevent their widespread use. Additionally, nonpharmacologic treatments, such as insertion of punctal plugs, are beneficial in the dry eye of SS, whereas several other modalities, such as anti-CD4 monoclonal antibody eye drops and gene transfer, are still in experimental phases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Kassan SS, Moutsopoulos HM: Clinical manifestations and early diagnosis of Sjogren syndrome. Arch Intern Med 2004, 164:1275–1284.

    Article  PubMed  Google Scholar 

  2. Rostron J, Rogers S, Longman L, et al.: Health-related quality of life in patients with primary Sjogren’s syndrome and xerostomia: a comparative study. Gerodontology 2002, 19:53–59.

    Article  PubMed  Google Scholar 

  3. Sutcliffe N, Stoll T, Pyke S, Isenberg DA: Functional disability and end organ damage in patients with systemic lupus erythematosus (SLE), SLE and Sjogren’s syndrome (SS), and primary SS. J Rheumatol 1998, 25:63–68.

    PubMed  CAS  Google Scholar 

  4. Reddy P, Rajagopalan K: The economic burden of dry eye. Cornea 2004, 23:751–761.

    Article  PubMed  Google Scholar 

  5. Moutsopoulos NM, Moutsopoulos HM: Therapy of Sjogren’s syndrome. Springer Semin Immunopathol 2001, 23:131–145.

    Article  PubMed  CAS  Google Scholar 

  6. Pflugfelder SC, Solomon A, Stern ME: The diagnosis and management of dry eye: a twenty-five-year review. Cornea 2000, 19:644–649.

    Article  PubMed  CAS  Google Scholar 

  7. Nelson JD: Much more than water. Br J Ophthalmol 1999, 83:384–385.

    PubMed  CAS  Google Scholar 

  8. Aragona P, Papa V, Micali A, et al.: Long-term treatment with sodium hyaluronate-containing artificial tears reduces ocular surface damage in patients with dry eye. Br J Ophthalmol 2002, 86:181–184.

    Article  PubMed  Google Scholar 

  9. Jumblatt JE, Jumblatt MM: Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjuctiva. Exp Eye Res 1998, 67:341–346.

    Article  PubMed  CAS  Google Scholar 

  10. Fujihara T, Murakami T, Fujita H, et al.: Improvement of corneal barrier function by the P2Y(2) agonist INS365 in a rat dry eye model. Invest Ophthalmol Vis Sci 2001, 42:96–100.

    PubMed  CAS  Google Scholar 

  11. Tauber J, Davitt WF, Bokosky JE, et al.: Double-masked, placebo-controlled safety and efficacy trial of diquafosol tetrasodium (INS365) ophthalmic solution for the treatment of dry eye. Cornea 2004, 23:784–792. A study involving more than 1000 patients that demonstrates the benefit of diquafosol in dry eye.

    Article  PubMed  CAS  Google Scholar 

  12. Yerxa BR, Mundasad M, Sylvester RN, et al.: Ocular safety of INS365 ophthalmic solution, a P2Y2 agonist, in patients with mild to moderate dry eye disease. Adv Exp Med Biol 2002, 506(Pt B):1251–1257.

    PubMed  CAS  Google Scholar 

  13. Rhodus NL: Oral pilocarpine HCl stimulates labial (minor) salivary gland flow in patients with Sjogren’s syndrome. Oral Dis 1997, 3:93–98.

    Article  PubMed  CAS  Google Scholar 

  14. Vivino FB, Al Hashimi I, Khan Z, et al.: Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjogren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group. Arch Intern Med 1999, 159:174–181. This is the largest of the studies demonstrating the benefit of pilocarpine tablets for sicca symptoms in SS.

    Article  PubMed  CAS  Google Scholar 

  15. Tsifetaki N, Kitsos G, Paschides CA, et al.: Oral pilocarpine for the treatment of ocular symptoms in patients with Sjogren’s syndrome: a randomised 12 week controlled study. Ann Rheum Dis 2003, 62:1204–1207.

    Article  PubMed  CAS  Google Scholar 

  16. Vivino FB: The treatment of Sjogren’s syndrome patients with pilocarpine-tablets. Scand J Rheumatol Suppl 2001, S115:1–9.

    Article  Google Scholar 

  17. Iwabuchi Y, Masuhara T: Sialogogic activities of SNI-2011 compared with those of pilocarpine and McN-A-343 in rat salivary glands: identification of a potential therapeutic agent for treatment of Sjorgen’s syndrome. Gen Pharmacol 1994, 25:123–129.

    PubMed  CAS  Google Scholar 

  18. Fife RS, Chase WF, Dore RK, et al.: Cevimeline for the treatment of xerostomia in patients with Sjogren syndrome: a randomized trial. Arch Intern Med 2002, 162:1293–1300.

    Article  PubMed  CAS  Google Scholar 

  19. Petrone D, Condemi JJ, Fife R, et al.: A double-blind, randomized, placebo-controlled study of cevimeline in Sjogren’s syndrome patients with xerostomia and keratoconjunctivitis sicca. Arthritis Rheum 2002, 46:748–754. This randomized, controlled study documents that cevimeline increases tear flow and improves symptoms in patients with SS.

    Article  PubMed  CAS  Google Scholar 

  20. Ono M, Takamura E, Shinozaki K, et al.: Therapeutic effect of cevimeline on dry eye in patients with Sjogren’s syndrome: a randomized, double-blind clinical study. Am J Ophthalmol 2004, 138:6–17.

    Article  PubMed  CAS  Google Scholar 

  21. Yannopoulos DI, Roncin S, Lamour A, et al.: Conjunctival epithelial cells from patients with Sjogren’s syndrome inappropriately express major histocompatibility complex molecules, La(SSB) antigen, and heat-shock proteins. J Clin Immunol 1992, 12:259–265.

    Article  PubMed  CAS  Google Scholar 

  22. Stern ME, Beuerman RW, Fox RI, et al.: The pathology of dry eye: the interaction between the ocular surface and lacrimal glands. Cornea 1998, 17:584–589.

    Article  PubMed  CAS  Google Scholar 

  23. Pflugfelder SC: Antiinflammatory therapy for dry eye. Am J Ophthalmol 2004, 137:337–342.

    Article  PubMed  Google Scholar 

  24. Marsh P, Pflugfelder SC: Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjogren syndrome. Ophthalmology 1999, 106:811–816.

    Article  PubMed  CAS  Google Scholar 

  25. Avunduk AM, Avunduk MC, Varnell ED, Kaufman HE: The comparison of efficacies of topical corticosteroids and nonsteroidal anti-inflammatory drops on dry eye patients: a clinical and immunocytochemical study. Am J Ophthalmol 2003, 136:593–602.

    Article  PubMed  CAS  Google Scholar 

  26. Avisar R, Robinson A, Appel I, et al.: Diclofenac sodium, 0.1% (Voltaren Ophtha), versus sodium chloride, 5%, in the treatment of filamentary keratitis. Cornea 2000, 19:145–147.

    Article  PubMed  CAS  Google Scholar 

  27. Drosos AA, Skopouli FN, Costopoulos JS, et al.: Cyclosporin A (CyA) in primary Sjogren’s syndrome: a double blind study. Ann Rheum Dis 1986, 45:732–735.

    PubMed  CAS  Google Scholar 

  28. Kaswan RL, Salisbury MA, Ward DA: Spontaneous canine keratoconjunctivitis sicca. A useful model for human keratoconjunctivitis sicca: treatment with cyclosporine eye drops. Arch Ophthalmol 1989, 107:1210–1216.

    PubMed  CAS  Google Scholar 

  29. 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.

    PubMed  CAS  Google Scholar 

  30. Power WJ, Mullaney P, Farrell M, Collum LM: Effect of topical cyclosporin A on conjunctival T cells in patients with secondary Sjogren’s syndrome. Cornea 1993, 12:507–511.

    Article  PubMed  CAS  Google Scholar 

  31. Kunert KS, Tisdale AS, Stern ME, et al.: Analysis of topical cyclosporine treatment of patients with dry eye syndrome: effect on conjunctival lymphocytes. Arch Ophthalmol 2000, 118:1489–1496.

    PubMed  CAS  Google Scholar 

  32. Phillips TE, McHugh J, Moore CP: Cyclosporine has a direct effect on the differentiation of a mucin-secreting cell line. J Cell Physiol 2000, 184:400–408.

    Article  PubMed  CAS  Google Scholar 

  33. Strong B, Farley W, Stern ME, Pflugfelder SC: Topical cyclosporine inhibits conjunctival epithelial apoptosis in experimental murine keratoconjunctivitis sicca. Cornea 2005, 24:80–85.

    Article  PubMed  Google Scholar 

  34. Gunduz K, Ozdemir O: Topical cyclosporin treatment of keratoconjunctivitis sicca in secondary Sjogren’s syndrome. Acta Ophthalmol (Copenh) 1994, 72:438–442.

    Article  CAS  Google Scholar 

  35. Stevenson D, Tauber J, Reis BL: Efficacy and safety of cyclosporin A ophthalmic emulsion in the treatment of moderate-to-severe dry eye disease: a dose-ranging, randomized trial. The Cyclosporin A Phase 2 Study Group. Ophthalmology 2000, 107:967–974.

    Article  PubMed  CAS  Google Scholar 

  36. 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. CsA Phase 3 Study Group. Ophthalmology 2000, 107:631–639. A large study presenting high-quality evidence in support of the benefit of cyclosporine ophthalmic emulsion.

    Article  PubMed  CAS  Google Scholar 

  37. Small DS, Acheampong A, Reis B, et al.: Blood concentrations of cyclosporin A during long-term treatment with cyclosporin A ophthalmic emulsions in patients with moderate to severe dry eye disease. J Ocul Pharmacol Ther 2002, 18:411–418.

    Article  PubMed  CAS  Google Scholar 

  38. Noble BA, Loh RS, MacLennan S, et al.: Comparison of autologous serum eye drops with conventional therapy in a randomised controlled crossover trial for ocular surface disease. Br J Ophthalmol 2004, 88:647–652. This randomized, controlled study established that autologous serum drops are at least as effective as conventional therapy for dry eye.

    Article  PubMed  CAS  Google Scholar 

  39. Tsubota K, Goto E, Fujita H, et al.: Treatment of dry eye by autologous serum application in Sjogren’s syndrome. Br J Ophthalmol 1999, 83:390–395.

    Article  PubMed  CAS  Google Scholar 

  40. O’Brien PD, Collum LM: Dry eye: diagnosis and current treatment strategies. Curr Allergy Asthma Rep 2004, 4:314–319.

    Article  PubMed  Google Scholar 

  41. Shimmura S, Ueno R, Matsumoto Y, et al.: Albumin as a tear supplement in the treatment of severe dry eye. Br J Ophthalmol 2003, 87:1279–1283.

    Article  PubMed  CAS  Google Scholar 

  42. Khurshudian AV: A pilot study to test the efficacy of oral administration of interferon-alpha lozenges to patients with Sjogren’s syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003, 95:38–44.

    Article  PubMed  Google Scholar 

  43. Tai MC, Cosar CB, Cohen EJ, et al.: The clinical efficacy of silicone punctal plug therapy. Cornea 2002, 21:135–139.

    Article  PubMed  Google Scholar 

  44. Sakamoto A, Kitagawa K, Tatami A: Efficacy and retention rate of two types of silicone punctal plugs in patients with and without Sjogren syndrome. Cornea 2004, 23:249–254.

    Article  PubMed  Google Scholar 

  45. Murube J, Murube E, ChenZhuo L, Rivas L: Subcutaneous abdominal artificial tears pump-reservoir for severe dry eye. Orbit 2003, 22:29–40.

    Article  PubMed  Google Scholar 

  46. Hayashi Y, Ishimaru N, Arakaki R, et al.: Effective treatment of a mouse model of Sjogren’s syndrome with eyedrop administration of anti-CD4 monoclonal antibody. Arthritis Rheum 2004, 50:2903–2910. Interesting and carefully conducted study showing the efficacy of a new form of treatment in an animal model of SS.

    Article  PubMed  CAS  Google Scholar 

  47. Nakamura S, Shibuya M, Saito Y, et al.: Protective effect of D-beta-hydroxybutyrate on corneal epithelia in dry eye conditions through suppression of apoptosis. Invest Ophthalmol Vis Sci 2003, 44:4682–4688.

    Article  PubMed  Google Scholar 

  48. Fleck M, Zhang HG, Kern ER, et al.: Treatment of chronic sialadenitis in a murine model of Sjogren’s syndrome by local fasL gene transfer. Arthritis Rheum 2001, 44:964–973.

    Article  PubMed  CAS  Google Scholar 

  49. Guerrissi JO, Belmonte J: Surgical treatment of dry eye syndrome: conjunctival graft of the minor salivary gland. J Craniofac Surg 2004, 15:6–10.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Samarkos, M., Moutsopoulos, H.M. Recent advances in the management of ocular complications of sjögren’s syndrome. Curr Allergy Asthma Rep 5, 327–332 (2005). https://doi.org/10.1007/s11882-005-0077-x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-005-0077-x

Keywords

Navigation