The role of in fl ammation and antiin fl ammation therapies in keratoconjunctivitis sicca

Purpose: To review and integrate recent advances in identifying the role of infl ammation in the pathogenesis of dry eye conditions and the biological rationale and practical clinical aspects of newer, antiinfl ammatory theories. Methods: A comprehensive literature survey. Results and conclusion: Keratoconjunctivitis Sicca (KCS) is a multifactorial and complex disorder in which ocular surface infl ammations play a central role. Identifi cation of specifi c CD4-T-Cell pathways and the recent recognition of targeting of alpha-fodrin suggest a case for novel new therapeutic aspects such as anti-CD4 monoclonal antibodies, systemic linoleic and gamma-linolenic acids, and omega-6 essential fatty acids. Replacement of tear volume with nonpreserved wetting agents and standard typical antiinfl ammatory corticosteroid and/or cyclosporine A continues to be central current conventional therapy for KCS.

[1]  G. Illei,et al.  Pathogenesis of Sjögren's syndrome , 2009, Current opinion in rheumatology.

[2]  K. Bjerrum,et al.  Keratoconjunctivitis sicca and primary Sjögren's syndrome in a Danish population aged 30-60 years. , 2009, Acta ophthalmologica Scandinavica.

[3]  K. Tsubota,et al.  Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft-versus-host disease , 2008, Bone Marrow Transplantation.

[4]  M. Irkec,et al.  Topical Cyclosporine A in the Treatment of Superior Limbic Keratoconjunctivitis: A Long-Term Follow-Up , 2008, Cornea.

[5]  B. Esmaeli,et al.  Orbital and adnexal sarcoidosis. , 2007, Archives of ophthalmology.

[6]  A. Tzioufas,et al.  Sjögren’s Syndrome—Study of Autoantigens and Autoantibodies , 2007, Clinical reviews in allergy & immunology.

[7]  C. Roberts,et al.  Comparison of Topical Cyclosporine, Punctal Occlusion, and a Combination for the Treatment of Dry Eye , 2007, Cornea.

[8]  J. Čejková,et al.  Nitric oxide synthase induction and cytotoxic nitrogen-related oxidant formation in conjunctival epithelium of dry eye (Sjögren's syndrome). , 2007, Nitric oxide : biology and chemistry.

[9]  K. Yoon,et al.  Comparison of autologous serum and umbilical cord serum eye drops for dry eye syndrome. , 2007, American journal of ophthalmology.

[10]  T. Matthias,et al.  Antibodies against Alpha‐Fodrin Are Associated with Sicca Syndrome in the General Population , 2007, Annals of the New York Academy of Sciences.

[11]  De-Quan Li,et al.  Strain-Related Cytokine Profiles on the Murine Ocular Surface in Response to Desiccating Stress , 2007, Cornea.

[12]  K. Tsubota,et al.  Involvement of oxidative stress on corneal epithelial alterations in a blink-suppressed dry eye. , 2007, Investigative ophthalmology & visual science.

[13]  Terry Kim,et al.  Recurrence after topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjögren's syndrome. , 2007, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[14]  L. Sobrin,et al.  Systemic Immunomodulatory Therapy in Severe Dry Eye Secondary to Inflammation , 2007, Ocular immunology and inflammation.

[15]  De-Quan Li,et al.  Corticosteroid and doxycycline suppress MMP-9 and inflammatory cytokine expression, MAPK activation in the corneal epithelium in experimental dry eye. , 2006, Experimental eye research.

[16]  R. Nussenblatt,et al.  Inhibition of Inflammatory Cytokine Production in Human Corneal Cells by Dexamethasone, but Not Cyclosporin , 2006, Cornea.

[17]  G. Mumcu,et al.  Comparative analysis of autoantibodies against a-fodrin in serum, tear fluid, and saliva from patients with Sjögren's syndrome. , 2006, The Journal of rheumatology.

[18]  D. Zoukhri.  Effect of inflammation on lacrimal gland function. , 2006, Experimental eye research.

[19]  K. Yoon,et al.  Application of Umbilical Cord Serum Eyedrops for the Treatment of Dry Eye Syndrome , 2006, Cornea.

[20]  Stephen Cohen,et al.  An Evaluation of the Efficacy of a Cyclosporine-Based Dry Eye Therapy When Used With Marketed Artificial Tears as Supportive Therapy in Dry Eye , 2006, Eye & contact lens.

[21]  C. Kublin,et al.  c‐Jun NH2‐terminal kinase mediates interleukin‐1β‐induced inhibition of lacrimal gland secretion , 2006, Journal of neurochemistry.

[22]  P. Aragona,et al.  Systemic omega-6 essential fatty acid treatment and pge1 tear content in Sjögren's syndrome patients. , 2005, Investigative ophthalmology & visual science.

[23]  De-Quan Li,et al.  Stress-activated protein kinase signaling pathways in dry eye and ocular surface disease. , 2005, The ocular surface.

[24]  De-Quan Li,et al.  Matrix metalloproteinases in corneal inflammation. , 2005, The ocular surface.

[25]  D. Tilch,et al.  [Diagnostics of Sjögren's syndrome by means of anti-alpha-fodrin antibody]. , 2005, Klinische Monatsblatter fur Augenheilkunde.

[26]  S. Tatlıpınar,et al.  Topical Cyclosporin in the Treatment of Ocular Surface Disorders: An Evidence–based Update , 2005 .

[27]  C. Kublin,et al.  Age-dependent alterations in mouse exorbital lacrimal gland structure, innervation and secretory response. , 2005, Experimental eye research.

[28]  De-Quan Li,et al.  Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface. , 2004, Investigative ophthalmology & visual science.

[29]  G. Geerling,et al.  Autologous serum eye drops for ocular surface disorders , 2004, British Journal of Ophthalmology.

[30]  H. Shiota,et al.  Effective treatment of a mouse model of Sjögren's syndrome with eyedrop administration of anti-CD4 monoclonal antibody. , 2004, Arthritis and rheumatism.

[31]  I. Gipson,et al.  Character of ocular surface mucins and their alteration in dry eye disease. , 2004, The ocular surface.

[32]  E. Kansu.  The pathophysiology of chronic graft-versus-host disease , 2004, International journal of hematology.

[33]  H. Direskeneli,et al.  Anti-Ro/SSA and anti-La/SSB autoantibodies in the tear fluid of patients with Sjögren’s syndrome , 2004, British Journal of Ophthalmology.

[34]  S. Pflugfelder.  Antiinflammatory therapy for dry eye. , 2004, American journal of ophthalmology.

[35]  P. Brandt,et al.  Down regulation of interleukin-1β-induced nitric oxide production in lacrimal gland acinar cells by sex steroids , 2004, Current eye research.

[36]  M. Kuwana,et al.  Dry Eye as a Major Complication Associated with Chronic Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation , 2003, Cornea.

[37]  J. Buring,et al.  Prevalence of dry eye syndrome among US women. , 2003, American journal of ophthalmology.

[38]  James P McCulley,et al.  Meibomian gland function and the tear lipid layer. , 2003, The ocular surface.

[39]  Ronald Klein,et al.  Incidence of dry eye in an older population. , 2003, Archives of ophthalmology.

[40]  K. Tsubota,et al.  Autologous serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease , 2003, Bone Marrow Transplantation.

[41]  G. Ravera,et al.  Systemic Linoleic and &ggr;-Linolenic Acid Therapy in Dry Eye Syndrome With an Inflammatory Component , 2003, Cornea.

[42]  C. Agostini,et al.  T-lymphocytes and cytokines in sarcoidosis , 2002, Current opinion in pulmonary medicine.

[43]  D. Thompson,et al.  Conjunctival T-cell subpopulations in Sjögren's and non-Sjögren's patients with dry eye. , 2002, Investigative ophthalmology & visual science.

[44]  R. Jonsson,et al.  Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group , 2002, Annals of the rheumatic diseases.

[45]  W. Feuer,et al.  The effect of punctal occlusion on tear production, tear clearance, and ocular surface sensation in normal subjects. , 2001, American journal of ophthalmology.

[46]  C. Baudouin.  The pathology of dry eye. , 2001, Survey of ophthalmology.

[47]  A. Berra,et al.  Muscarinic acetylcholine receptor antibodies as a new marker of dry eye Sjögren syndrome. , 2001, Investigative ophthalmology & visual science.

[48]  Shigeo Koyasu,et al.  Two distinct action mechanisms of immunophilin–ligand complexes for the blockade of T‐cell activation , 2000, EMBO reports.

[49]  I. Gipson,et al.  Analysis of topical cyclosporine treatment of patients with dry eye syndrome: effect on conjunctival lymphocytes. , 2000, Archives of ophthalmology.

[50]  R. Klein,et al.  Prevalence of and risk factors for dry eye syndrome. , 2000, Archives of ophthalmology.

[51]  Ji,et al.  Doxycycline inhibition of interleukin-1 in the corneal epithelium , 2000, American journal of ophthalmology.

[52]  W. Feuer,et al.  Interleukin-6 Levels in the Conjunctival Epithelium of Patients with Dry Eye Disease Treated with Cyclosporine Ophthalmic Emulsion , 2000, Cornea.

[53]  M. Rischmueller,et al.  Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjögren's syndrome. , 2000, Arthritis and rheumatism.

[54]  S. Matsuda,et al.  Mechanisms of action of cyclosporine. , 2000, Immunopharmacology.

[55]  B. Reis,et al.  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. , 2000, Ophthalmology.

[56]  B. Reis,et al.  Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease1 , 2000 .

[57]  T. Fujihara,et al.  Cyclosporin A increases tear fluid secretion via release of sensory neurotransmitters and muscarinic pathway in mice. , 1999, Experimental eye research.

[58]  S. Pflugfelder,et al.  Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjögren syndrome. , 1999, Ophthalmology.

[59]  I. Gipson,et al.  Alteration of mucin in human conjunctival epithelia in dry eye. , 1998, Investigative ophthalmology & visual science.

[60]  R. Beuerman,et al.  The pathology of dry eye: the interaction between the ocular surface and lacrimal glands. , 1998, Cornea.

[61]  J. Gao,et al.  The role of apoptosis in the pathogenesis of canine keratoconjunctivitis sicca: the effect of topical Cyclosporin A therapy. , 1998, Cornea.

[62]  J. McCulley,et al.  Keratoconjunctivitis sicca associated with meibomian secretion polar lipid abnormality. , 1998, Archives of ophthalmology.

[63]  H. Taylor,et al.  The epidemiology of dry eye in Melbourne, Australia , 1998 .

[64]  Jaipaul Singh,et al.  Age-related changes in morphology and secretory responses of male rat lacrimal gland. , 1998, Journal of the autonomic nervous system.

[65]  B. Munoz,et al.  Prevalence of dry eye among the elderly. , 1997, American journal of ophthalmology.

[66]  C. Foster,et al.  Ocular rosacea: patient characteristics and follow-up. , 1997, Ophthalmology.

[67]  R. Plevin,et al.  Stress-activated protein kinases: activation, regulation and function. , 1997, Cellular signalling.

[68]  M. Lemp.  Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. , 1995, The CLAO journal : official publication of the Contact Lens Association of Ophthalmologists, Inc.

[69]  K. Gündüz,et al.  Topical cyclosporin treatment of keratoconjunctivitis sicca in secondary Sjögren's syndrome , 1994, Acta ophthalmologica.

[70]  J. Ferrara,et al.  Cytokine dysregulation and acute graft-versus-host disease. , 1992, Blood.

[71]  J. Greiner,et al.  Effects of eye rubbing on the conjunctiva as a model of ocular inflammation. , 1985, American journal of ophthalmology.

[72]  D. Coster,et al.  PROLONGED SURVIVAL OF CORNEAL ALLOGRAFTS IN RABBITS TREATED WITH CYCLOSPORIN A , 1979, The Lancet.

[73]  E. Cadman,et al.  Sjögren's Syndrome , 1953, Medicine illustrated.

[74]  E. Miyazaki,et al.  Circulating IL-12 p40 is increased in the patients with sarcoidosis, correlation with clinical markers. , 2007, Internal medicine.

[75]  X. Li,et al.  The epitope study of alpha-fodrin autoantibody in primary Sjögren's syndrome. , 2007, Clinical and experimental immunology.

[76]  K. Tsubota,et al.  Autologous serum eye drops for dry eye after LASIK. , 2006, Journal of refractive surgery.

[77]  T. Hattori,et al.  Elevated serum levels of CXCL9/monokine induced by interferon-gamma and CXCL10/interferon-gamma-inducible protein-10 in ocular sarcoidosis. , 2006, Investigative ophthalmology & visual science.

[78]  De-Quan Li,et al.  JNK and ERK MAP kinases mediate induction of IL-1beta, TNF-alpha and IL-8 following hyperosmolar stress in human limbal epithelial cells. , 2006, Experimental eye research.

[79]  M. Gershwin,et al.  T cell immunity and graft-versus-host disease (GVHD). , 2006, Autoimmunity reviews.

[80]  H. Dai,et al.  Production of soluble tumor necrosis factor receptors and tumor necrosis factor-alpha by alveolar macrophages in sarcoidosis and extrinsic allergic alveolitis. , 2005, Chest.

[81]  C. Creuzot-Garcher,et al.  [Treating severe dry eye syndromes with autologous serum]. , 2004, Journal francais d'ophtalmologie.

[82]  I. Gipson,et al.  Role of mucins in the function of the corneal and conjunctival epithelia. , 2003, International review of cytology.

[83]  A. Solomon,et al.  Dry eye and delayed tear clearance: "a call to arms.". , 2002, Advances in experimental medicine and biology.

[84]  A. Heiligenhaus,et al.  [Tear-film deficiencies in patients with sarcoidosis; clinical study of 56 patients]. , 2002, Klinische Monatsblatter fur Augenheilkunde.

[85]  K. Tsubota,et al.  A significant role of stromal fibroblasts in rapidly progressive dry eye in patients with chronic GVHD. , 2001, Investigative ophthalmology & visual science.

[86]  A. Di Iorio,et al.  Dry eye in allergic conjunctivitis: role of inflammatory infiltrate. , 1999, International journal of immunopathology and pharmacology.

[87]  J. P. Gilbard.  Dry eye, blepharitis and chronic eye irritation: divide and conquer. , 1999, Journal of ophthalmic nursing & technology.

[88]  E. Borda,et al.  Autoantibodies against lacrimal gland M3 muscarinic acetylcholine receptors in patients with primary Sjögren's syndrome. , 1998, Investigative ophthalmology & visual science.