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Ocular Involvement

  • Stephen C. Pflugfelder
  • Karyn Siemasko
  • Michael E. Stern
Chapter

Abstract

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by diminished production and secretion of tears by the lacrimal glands and saliva by the salivary glands resulting in keratoconjunctivitis sicca and stomatitis sicca, respectively. The estimated prevalence of primary SS (pSS) in the USA is 1.3 million individuals and the prevalence is 10–20 greater in women [1–4].

Keywords

Ocular Surface Lacrimal Gland Meibomian Gland Sensory Nerve Ending Ocular Surface Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;58:15–25.PubMedCrossRefGoogle Scholar
  2. 2.
    Sullivan DA. Sex hormones and Sjogren’s syndrome. J Rheumatol Suppl. 1997;50:17–32.PubMedGoogle Scholar
  3. 3.
    Sullivan DA. Androgen deficiency & dry eye syndromes. Arch Soc Esp Oftalmol. 2004;79:49–50.PubMedCrossRefGoogle Scholar
  4. 4.
    Toda I, Sullivan BD, Wickham LA, Sullivan DA. Gender- and androgen-related influence on the expression of proto-oncogene and apoptotic factor mRNAs in lacrimal glands of autoimmune and non-autoimmune mice. J Steroid Biochem Mol Biol. 1999;71:49–61.PubMedCrossRefGoogle Scholar
  5. 5.
    Fox RI. Impact of systemic immune disease on the lacrimal functional unit. In: Pflugfelder SC, Stern ME, Beuerman R, editors. Dry eye and the ocular surface. New York: Marcel Dekker; 2004. p. 269–308.Google Scholar
  6. 6.
    Pflugfelder SC, Crouse CA, Monroy D, Yen M, Rowe M, Atherton S. Epstein-Barr virus and the lacrimal gland pathology of Sjogren’s syndrome. Am J Pathol. 1993;143:49–64.PubMedGoogle Scholar
  7. 7.
    Pflugfelder SC, Stern ME, Symposium Participants. Immunoregulation on the ocular surface: 2nd Cullen Symposium. Ocul Surf. 2009;7:67–77.PubMedGoogle Scholar
  8. 8.
    Fox RI, Michelson P. Approaches to the treatment of Sjogren’s syndrome. J Rheumatol Suppl. 2000;61:15–21.PubMedGoogle Scholar
  9. 9.
    Fox RI, Maruyama T. Pathogenesis and treatment of Sjogren’s syndrome. Curr Opin Rheumatol. 1997;9:393–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Stern ME, Beuerman RW, Fox RI, Gao J, Mircheff AK, Pflugfelder SC. The pathology of dry eye: the interaction between the ocular surface and lacrimal glands. Cornea. 1998;17:584–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Pflugfelder SC, Stern ME, Beuerman R. Dysfunction of the integrated functional unit – impact on tear film stability and composition. In: Pflugfelder SC, Stern ME, Beuerman R, editors. Dry eye and the ocular surface. New York: Marcel Dekker; 2004. p. 63–88.Google Scholar
  12. 12.
    Pflugfelder SC, Liu Z, Monroy D, Jones DT, Carvajal ME, Price-Schiavi S, et al. Detection of sialomucin complex (MUC4) in human ocular surface epithelium and tear fluid. Invest Ophthalmol Vis Sci. 2000;41:1316–26.PubMedGoogle Scholar
  13. 13.
    Stern ME, Beuerman R, Pflugfelder SC. The normal tear film and ocular surface. In: Pflugfelder SC, Stern ME, Beuerman R, editors. Dry eye and the ocular surface. New York: Marcel Dekker; 2004. p. 41–62.Google Scholar
  14. 14.
    Govindarajan B, Gipson IK. Membrane-tethered mucins have multiple functions on the ocular surface. Exp Eye Res. 2010;90:655–63.PubMedCrossRefGoogle Scholar
  15. 15.
    Inatomi T, Spurr-Michaud SJ, Tisdale AS, Zhan Q, Feldman ST, Gipson IK. Expression of secretory mucin genes by human conjunctival epithelia. Invest Ophthalmol Vis Sci. 1996;37:1684–92.PubMedGoogle Scholar
  16. 16.
    Jumblatt MM, McKenzie RW, Steele PS, Emberts CG, Jumblatt JE. MUC7 expression in the human lacrimal gland and conjunctiva. Cornea. 2003;22:41–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Watanabe H. Significance of mucin on the ocular surface. Cornea. 2002;21:S17–22.PubMedCrossRefGoogle Scholar
  18. 18.
    Komatsu M, Tatum L, Altman NH, Carothers Carraway CA, Carraway KL. Potentiation of metastasis by cell surface sialomucin complex (rat MUC4), a multifunctional anti-adhesive glycoprotein. Int J Cancer. 2000;87:480–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Guzman-Aranguez A, Argueso P. Structure and biological roles of mucin-type O-glycans at the ocular surface. Ocul Surf. 2010;8:8–17.PubMedGoogle Scholar
  20. 20.
    Rieger G. The importance of the precorneal tear film for the quality of optical imaging. Br J Ophthalmol. 1992;76:157–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Rolando M, Iester M, Macri A, Calabria G. Low spatial-contrast sensitivity in dry eyes. Cornea. 1998;17:376–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Chotikavanich S, de Paiva CS, de Li Q, Chen JJ, Bian F, Farley WJ, et al. Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome. Invest Ophthalmol Vis Sci. 2009;50:3203–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Goto T, Zheng Z, Okamoto S, Ohashi Y. Tear film stability analysis system: introducing a new application for videokeratography. Cornea. 2004;23:65–70.CrossRefGoogle Scholar
  24. 24.
    Jordan A, Baum J. Basic tear flow. Does it exist? Ophthalmology. 1980;87:920–30.PubMedGoogle Scholar
  25. 25.
    Dartt DA. Regulation of tear secretion. Adv Exp Med Biol. 1994;350:1–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Nakamura M, Tada Y, Akaishi T, Nakata K. M3 muscarinic receptor mediates regulation of protein secretion in rabbit lacrimal gland. Curr Eye Res. 1997;16:614–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Hodges RR, Zoukhri D, Sergheraert C, Zieske JD, Dartt DA. Identification of vasoactive intestinal peptide receptor subtypes in the lacrimal gland and their signal-transducing components. Invest Ophthalmol Vis Sci. 1997;38:610–9.PubMedGoogle Scholar
  28. 28.
    Hodges RR, Dicker DM, Rose PE, Dartt DA. Alpha 1-adrenergic and cholinergic agonists use separate signal transduction pathways in lacrimal gland. Am J Physiol. 1992;262:G1087–96.PubMedGoogle Scholar
  29. 29.
    Knop E, Knop N. A functional unit for ocular surface immune defense formed by the lacrimal gland, conjunctiva and lacrimal drainage system. Adv Exp Med Biol. 2002;506:835–44.PubMedCrossRefGoogle Scholar
  30. 30.
    Pflugfelder SC, De Paiva CS, Villarreal AL, Stern ME. Effects of sequential artificial tear and cyclosporine emulsion therapy on conjunctival goblet cell density and transforming growth factor-beta 2 production. Cornea. 2008;27:64–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Knop E, Knop N. Influence of the eye-associated lymphoid tissue (EALT) on inflammatory ocular surface disease. Ocul Surf. 2005;3(4 Suppl):S180–6.PubMedGoogle Scholar
  32. 32.
    Steven P, Gebert A. Conjunctiva-associated lymphoid tissue – current knowledge, animal models and experimental prospects. Ophthalmic Res. 2009;42:2–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Rosenthal P, Baran I, Jacobs DS. Corneal pain without stain. Is it real? Ocul Surf. 2009;7:28–40.PubMedGoogle Scholar
  34. 34.
    Pflugfelder SC, Farley W, Luo L, Zhuo Chen L, de Paiva CS, Olmos LC, et al. Matrix metalloproteinase-9 (MMP-9) knockout confers resistance to corneal epithelial barrier disruption in experimental dry eye. Am J Pathol. 2005;166:61–71.PubMedCrossRefGoogle Scholar
  35. 35.
    Hamrah P, Liu Y, Zhang Q, Dana MR. The corneal stroma is endowed with a significant number of resident dendritic cells. Invest Ophthalmol Vis Sci. 2003;44:581–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Hamrah P, Zhang Q, Liu Y, Dana MR. Novel characterization of MHC class II-negative population of resident corneal Langerhans cell-type dendritic cells. Invest Ophthalmol Vis Sci. 2002;43:639–46.PubMedGoogle Scholar
  37. 37.
    Hamrah P, Huq SO, Liu Y, Zhang Q, Dana MR. Corneal immunity is mediated by heterogeneous population of antigen-presenting cells. J Leukoc Biol. 2003;74:172–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Hamrah P, Liu Y, Zhang Q, Dana MR. Alterations in corneal stromal dendritic cell phenotype and distribution in inflammation. Arch Ophthalmol. 2003;121:1132–40.PubMedCrossRefGoogle Scholar
  39. 39.
    McCulley JP, Shine WE. The lipid layer of tears: dependent on meibomian gland function. Exp Eye Res. 2004;78:361–5.PubMedCrossRefGoogle Scholar
  40. 40.
    Beuerman R, Stern ME, Mircheff A, Pflugfelder SC. The lacrimal functional unit. In: Pflugfelder SC, Stern ME, Beuerman R, editors. Dry eye and the ocular surface. New York: Marcel Dekker; 2004. p. 11–40.Google Scholar
  41. 41.
    Szliter EA, Lighvani S, Barrett RP, Hazlett LD. Vasoactive intestinal peptide balances pro- and anti-inflammatory cytokines in the Pseudomonas aeruginosa-infected cornea and protects against corneal perforation. J Immunol. 2007;178:1105–14.PubMedGoogle Scholar
  42. 42.
    Robinson CP, Brayer J, Yamachika S, Esch TR, Peck AB, Stewart CA, et al. Transfer of human serum IgG to nonobese diabetic Igmu null mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjögren’s syndrome. Proc Natl Acad Sci USA. 1998;95:7538–43.PubMedCrossRefGoogle Scholar
  43. 43.
    Benítez-Del-Castillo JM, Acosta MC, Wassfi MA, Díaz-Valle D, Gegúndez JA, Fernandez C, et al. Relationship between corneal innervation with confocal microscopy and corneal sensitivity with non-contact esthesiometry in patients with dry eye. Invest Ophthalmol Vis Sci. 2007;48(1):173–81.PubMedCrossRefGoogle Scholar
  44. 44.
    Tuominen IS, Konttinen YT, Vesaluoma MH, Moilanen JA, Helintö M, Tervo TM. Corneal morphology and innervation in primary Sjögren’s syndrome. Invest Ophthalmol Vis Sci. 2003;44:2545–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Zoukhri D, Hodges RR, Byon D, Kublin CL. Role of proinflammatory cytokines in the impaired lacrimation associated with autoimmune xerophthalmia. Invest Ophthalmol Vis Sci. 2002;43:1429–36.PubMedGoogle Scholar
  46. 46.
    Kong L, Robinson CP, Peck AB, Vela-Roch N, Sakata KM, Dang H, et al. Inappropriate apoptosis of salivary and lacrimal gland epithelium of immunodeficient NOD-scid mice. Clin Exp Rheumatol. 1998;16:675–81.PubMedGoogle Scholar
  47. 47.
    Cha S, Brayer J, Gao J, Brown V, Killedar S, Yasunari U, et al. A dual role for interferon-gamma in the pathogenesis of Sjogrens syndrome-like autoimmune exocrinopathy in the nonobese diabetic mouse. Scand J Immunol. 2004;60:552–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Kimura-Shimmyo A, Kashiwamura S, Ueda H, Ikeda T, Kanno S, Akira S, et al. Cytokine-induced injury of the lacrimal and salivary glands. J Immunother. 2002;25 Suppl 1:S42–51.PubMedCrossRefGoogle Scholar
  49. 49.
    Lam H, Bleiden L, de Paiva CS, Farley W, Stern ME, Pflugfelder SC. Tear cytokine profiles in dysfunctional tear syndrome. Am J Ophthalmol. 2009;147:198–205.PubMedCrossRefGoogle Scholar
  50. 50.
    De Paiva CS, Villarreal AL, Corrales RM, Rahman HT, Chang VY, Farley WJ, et al. Dry eye-induced conjunctival epithelial squamous metaplasia is modulated by interferon-gamma. Invest Ophthalmol Vis Sci. 2007;48:2553–60.PubMedCrossRefGoogle Scholar
  51. 51.
    Pflugfelder SC, Tseng SCG, Yoshino K, Monroy D, Felix C, Reis B. Correlation of goblet cell density and mucosal epithelial mucin expression with rose bengal staining in patients with ocular irritation. Ophthalmology. 1997;104:223–35.PubMedGoogle Scholar
  52. 52.
    Chen Z, Tong L, Li Z, Yoon KC, Qi H, Farley W, et al. Hyperosmolarity-induced cornification of human corneal epithelial cells is regulated by JNK MAPK. Invest Ophthalmol Vis Sci. 2008;49:539–49.PubMedCrossRefGoogle Scholar
  53. 53.
    De Paiva CS, Pflugfelder SC. Corneal epitheliopathy of dry eye induces hyperesthesia to mechanical air jet stimulation. Am J Ophthalmol. 2003;2004(137):109–15.Google Scholar
  54. 54.
    Vitali C, Bombardieri S, Moutsopoulos HM, Balestrieri G, Bencivelli W, Bernstein RM, et al. Preliminary criteria for the classification of Sjögren’s syndrome. Results of a prospective concerted action supported by the European Community. Arthritis Rheum. 1993;36:340–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Pflugfelder SC, Tseng SC, Sanabria O, Kell H, Garcia CG, Felix C, et al. Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorders known to cause ocular irritation. Cornea. 1998;17:38–56.PubMedCrossRefGoogle Scholar
  56. 56.
    Nemeth J, Erdelyi B, Csakany B, Gaspar P, Soumelidis A, Kahlesz F, et al. High-speed videotopographic measurement of tear film build-up time. Invest Ophthalmol Vis Sci. 2002;43:1783–90.PubMedGoogle Scholar
  57. 57.
    Lemp MA, Dohlman CH, Kuwabara T, Holly FJ, Carroll JM. Dry eye secondary to mucus deficiency. Trans Am Acad Ophthalmol Otolaryngol. 1971;75:1223–7.PubMedGoogle Scholar
  58. 58.
    McCulley JOP, Sciallis GF. Meibomian keratoconjunctivitis. Am J Ophthalmol. 1877;84:788–93.Google Scholar
  59. 59.
    Zengin N, Tol H, Gunduz K, Okudan S, Balevi S, Endogru H. Meibomian gland dysfunction and tear film abnormalities in rosacea. Cornea. 1995;14:144–6.PubMedCrossRefGoogle Scholar
  60. 60.
    de Paiva CS, Lindsey JL, Pflugfelder SC. Assessing the severity of keratitis sicca with videokeratoscopic indices. Ophthalmology. 2003;110:1102–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Schirmer O. Studien zur Physiologie und Pathologie der Tranenabsonderung and Tranenabfuhr. Graefes Arch Clin Exp Ophthalmol. 1903;56:197.Google Scholar
  62. 62.
    Farris RL, Gilbard JP, Stuchell RN, Mandel ID. Diagnostic tests in keratoconjunctivitis sicca. CLAO J. 1983;9:23–8.PubMedGoogle Scholar
  63. 63.
    Tsubota K. The importance of the Schirmer test with nasal stimulation. Am J Ophthalmol. 1991;111:106.PubMedGoogle Scholar
  64. 64.
    van Bijsterveld OP. Diagnostic tests in sicca syndrome. Arch Ophthalmol. 1969;82:10–4.PubMedGoogle Scholar
  65. 65.
    Nelson JD. Diagnosis of keratoconjunctivitis sicca. Int Ophthalmol Clin. 1994;34:37–56.PubMedCrossRefGoogle Scholar
  66. 66.
    Behrens A, Doyle JJ, Stern L, Chuck RS, McDonnell PJ, Azar DT, et al. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea. 2006;25:900–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Pflugfelder S. Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop. Ocul Surf. 2007;5:163–78.Google Scholar
  68. 68.
    Petrone D, Condemi JJ, Fife R, Gluck O, Cohen S, Dalgin P. Double-blind randomized ­placebo-controlled study of cevimeline in Sjögren’s syndrome patients with xerostomia and keratoconjunctivitis sicca. Arthritis Rheum. 2002;46:748–54.PubMedCrossRefGoogle Scholar
  69. 69.
    Stason WB, Razavi M, Jacobs DS, Shepard DS, Suaya JA, Johns L, et al. Clinical benefits of the Boston Ocular Surface Prosthesis. Am J Ophthalmol. 2010;149:54–61.PubMedCrossRefGoogle Scholar
  70. 70.
    Rosenthal P, Croteau A. Fluid-ventilated, gas-permeable scleral contact lens is an effective option for managing severe ocular surface disease and many corneal disorders that would otherwise require penetrating keratoplasty. Eye Contact Lens. 2005;31:130–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2011

Authors and Affiliations

  • Stephen C. Pflugfelder
    • 1
  • Karyn Siemasko
    • 2
  • Michael E. Stern
    • 1
  1. 1.Department of Ophthalmology¸ Ocular Surface Center, Cullen Eye InstituteBaylor College of MedicineHoustonUSA
  2. 2.Biological SciencesAllergan, IncIrvineUSA

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