Sjogren’s Syndrome: An Ocular Overview

Sarah Coates

Introduction

Sjogren’s syndrome (SS) is a chronic systemic autoimmune disorder which predominantly affects the salivary and lacrimal glands (exocrine glands) resulting in presentation of dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia), collectively known as sicca symptoms (1, 2). Although ren SS primarily affects glands, in some cases there is extra-glandular involvement indicating an autoimmune response can occur in other organs and tissues. SS is categorised into primary, when symptoms occur in isolation, or secondary, when symptoms occur in conjunction with another autoimmune disorder such as rheumatoid arthritis or systemic lupus erythematosus (2, 3).

Pathophysiology and Aetiology

A Swedish ophthalmologist named Henrik Sjogren, was the first person to discover a link between keratoconjunctivitis sicca, xerostomia and polyarthritis, hence the syndrome is named after him (4).

It is thought that both environmental factors and genetic predisposition are attributed to its presentation. Viral infections, including hepatitis C and Epstein-Barr virus are thought to be connected to the development of SS (5, 6). A genetic link between alleles within major histocompatibility complex class II, HLA-DR and HLA-DQ, and SS has been found, however further research is required to confirm this (7). A high prevalence of anti-Ro/SSA and anti-La/SSB has been noted in individual’s with SS (8).

Multiple research studies into the underlying pathophysiology of SS suggests that epithelial cells within the exocrine glands become dysregulated and undergo destruction secondary to infiltration of abnormal B cell and T cell lymphocytes in response to environmental and genetic factors, but requires further research (1, 2, 9, 10, 11).

Ocular Manifestations

The most common ocular manifestation in SS is keratoconjunctivitis sicca (12, 13). Individuals present with a variety of symptoms ranging from mild to severe, including, burning or sore eyes, grittiness, a foreign-body sensation, excessive blinking, eye pain, inability to cry and blurred vision (14, 15).

Ocular surface involvement can lead to chronic conjunctivitis, non-healing corneal ulcers and sterile keratolysis. Studies have shown that sight threatening conditions, such as scleritis, uveitis, retinal vasculitis, optic neuropathy and corneal perforation can occur in SS (16). Further research is required to determine if corneal and conjunctival involvement is linked to the inflammatory process in meibomian or lacrimal glands or if there is direct autoimmune activity.

Ophthalmic Investigations

There are three tests utilised in SS to assess the level of eye dryness, including Schirmer test, tear break-up time and ocular surface staining.

Schirmer test involves placing sterile filter paper over the margin of each lower eyelid and holding it there for 5 minutes with the eyes closed. This measures reflex tear production and if wetting is ≤5mm, this signifies a deficiency in aqueous tear production (17, 18).

Tear break-up time is measured by administering fluorescein staining to the tear film and recording the time in seconds for a disruption in the tear film to present. The tear film is visualised under slit-lamp magnification with the cobalt-blue light and a tear break-up time for ≤10 seconds is reduced and shows an abnormal tear film (19).

Ocular surface staining investigates damage to corneal and conjunctival epithelial cells. Rose Bengal staining can be used, however has been reported as painful in dry eyes, therefore it is being replaced by fluorescein which stains the cornea and lissamine green which stains the conjunctiva. Rose Bengal dye is introduced into the inferior fornix of an anesthetised eye and the patient advised to blink twice (20, 21). A score of ≥4 using the Bijsterveld scoring method supports a diagnosis of SS (22). Fluorescein staining is viewed under slit lamp magnification with the cobalt-blue light for approximately 4 minutes. Lissamine green dye, is administered to an unanaesthetised eye, excess wiped away and observed immediately under slit lamp magnification. The Sjögren’s International Collaborative Clinical Alliance (SICCA) scoring method is utilised for fluorescein/lissamine green staining and a score of ≥5 implies a diagnosis of SS (21).

The American College of Rheumatology (ACR) and the European League Again Rheumatism (EULAR) formulated a diagnostic classification criterion to aid in diagnosis of SS (23).

Ocular Management

The aim of treatment is to maintain a stable tear film. There are multiple treatment options available to preserve, alter and/or substitute the inadequate secretion of tears. The first step in managing SS is educating your patient about their condition, modifying their environment such as reducing screen time, reviewing their existing medication to causative medications, advising warm compresses for lid hygiene and oral essential fatty acids which have been shown to reduce ocular surface dryness (24).

Preservative-free ocular drops, gels or ointments can be used to replace the deficient tear film (24, 2). A randomised control study found that autologous serum eyedrops are beneficial in severe dry eyes as they have been shown to reduce ocular surface staining and improve tear film stability (25). Studies have shown that topical corticosteroids, due to their anti-inflammatory properties, have been found to improve subjective and objective ocular signs and symptoms, however they do not increase tear production (26). Ciclosporin drops may also be beneficial as they act as an anti-inflammatory and increase tear production (2).

Gas-permeable scleral contact lenses can be utilised as they aid with healing of corneal epithelial defect, reduce discomfort and reduce light sensitivity in patients with severe dry eyes (27). Punctal occlusion using plugs or cauterisation can be implemented to block the drainage of tears, preserving the tear film (28).

A tarsorrhaphy is a temporary surgical option whereby lid margins are sutured together to allow healing of persistent corneal epithelial defects secondary to dry eyes and has a reported 80%-100% success rate for complete healing due to various factors (29, 30).

Conclusion

SS is a chronic systemic autoimmune disorder mainly affecting the lacrimal and salivary glands, however, can present with extra-glandular manifestations. Research has shown that environmental factors and genetic predisposition are attributed to the presentation of SS. The main features of SS are keratoconjunctivitis sicca and xerostomia. Ocular manifestations can vary from mild to sight threatening. The 3 main tests to assess the tear film and test for dry eyes are the Schirmer test, ocular surface staining and tear break-up time. Although there is no cure for SS, conservative, medical and surgical treatment options are available to improve quality of life

References

  1. Brito-Zerón,P. Baldini,C. Bootsma,H. Bowman,S.J. Jonsson,R. Mariette,X. Sivils,K. Theander,E. Tzioufas,A. Ramos-Casals,M. (2016). Sjögren syndrome. Nat Rev Dis Primers. 7;2:16047. doi: 10.1038/nrdp.2016.47. PMID: 27383445.
  2. Carsons,S.E. Patel,B.C. (2022). Sjogren Syndrome. Treasure Island (FL): StatPearls. PMID: 28613703.
  3. Fox ,R. Howell,F. Bone,R. Michelson,P. (1984). Primary Sjögren syndrome: clinical and immunopathologic features. Semin Arthritis Rheum. 14:77–105.
  4. Carsons,S. (2006). Sjögren’s syndrome. In: Firestein GS, Budd RC, Harris ED, McInnes IB, Ruddy S, Sergent JS, editors. Kelley’s textbook of rheumatology. 8. Philadelphia: W.B. Saunders. 
  5. Pflugfelder,S,C. Crouse,C.A, Monroy,D. Yen,M. Rowe,M. Atherton,S.S. (1993). Epstein-Barr virus and the lacrimal gland pathology of Sjogren’s syndrome. Am J Pathol.  143:49–64
  6. Ramos-Casals,M. Loustaud-Ratti,V. De Vita,S. Zeher,M. Bosch,J.A. Toussirot,E. (2005). Sjögren syndrome associated with hepatitis C virus: a multicenter analysis of 137 cases. Medicine. 84:81–9
  7. Nair,J,J, Singh,T.P. (2017). Sjogren’s syndrome: Review of the aetiology, Pathophysiology & Potential therapeutic interventions. J Clin Exp Dent. 9(4):e584-e589. doi: 10.4317/jced.53605. PMID: 28469828; PMCID: PMC5410683.
  8. Hernandez-Molina,G. Avila-Casado,C. Cardenas-Velazquez,F. Hernandez-Hernandez,C. Calderillo,M.L. Marroquin,V. Soto-Abraham,V. Recillas-Gispert,C. Sanchez-Guerrero,J. (2010). Similarities and Differences Between Primary and Secondary Sjögren’s Syndrome. The Journal of Rheumatology. 37 (4) 800-808; DOI: 10.3899/jrheum.090866 
  9. Kroese,F.G.M.Haacke,E.A. Bombardieri,M. (2018). The role of salivary gland histopathology in primary Sjögren’s syndrome: promises and pitfalls. Clin Exp Rheumatol. 36 Suppl 112(3):222-233. PMID: 30156550.
  10. Tzioufas,A.G. Goules,A.V. (2018). Limited efficacy of targeted treatments in Sjögren’s syndrome: why? Clin Exp Rheumatol. 36 Suppl 112(3):27-28. PMID: 29998826.
  11. Voulgarelis,M. Tzioufas,A.G. (2010). Pathogenetic mechanisms in the initiation and perpetuation of Sjögren’s syndrome. Nat Rev Rheumatol. 6(9):529-37. doi: 10.1038/nrrheum.2010.118. PMID: 20683439.
  12. Lim,R. Gunasekeran,D. Kam,J. Thong,B. Agrawal,R.V. (2016). Ocular Involvement In Sjogren’s syndrome – The Singapore Sjogren’s Syndrome Study. Investigative Ophthalmology & Visual Science. Vol.57, 3879.
  13. Roszkowska,A.M. Oliverio,G.W. Aragona,E. Inferrera,L. Severo,A.A. Alessandrello,F. Spinella,R. Postorino,EI. Aragona,P. (2021). Ophthalmologic Manifestations of Primary Sjögren’s Syndrome. Genes (Basel). 12(3):365. doi: 10.3390/genes12030365. PMID: 33806489; PMCID: PMC7998625.
  14. Mohamed,H.B. Abd El-Hamid,B.N. Fathalla,D. Fouad,E.A. (2022). Current trends in pharmaceutical treatment of dry eye disease: A review. European Journal of Pharmaceutical Sciences. Volume 175. Available at: https://www.sciencedirect.com/science/article/pii/S0928098722000914?via%3Dihub
  15. Stefanski,A.L. Tomiak,C. Pleyer,U. Dietrich,T. Burmester,G.R. Dörner,T. (2017). The Diagnosis and Treatment of Sjögren’s Syndrome. Dtsch Arztebl Int. 114(20):354-361. doi: 10.3238/arztebl.2017.0354. PMID: 28610655; PMCID: PMC5471601.
  16. Akpek,E.K. Mathews,P. Hahn,S. Hessen,M. Kim,J. Grader-Beck,T. Birnbaum,J, Baer,A.N. (2015). Ocular and systemic morbidity in a longitudinal cohort of Sjögren’s syndrome. Ophthalmology. 122(1):56-61. doi: 10.1016/j.ophtha.2014.07.026. PMID: 25178806.
  17. Alfonso,A.A. Monroy,D. Stern,M.E. et al. (1999). Correlation of tear fluorescein clearance and Schirmer test scores with ocular irritation symptoms. Ophthalmology. 106:803.
  18. Vitali,C. Bombardieri,S. Jonsson,R. et al. (2002). Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by America-Suropean Consensus Group. Ann Rheum Dis. 61:554.
  19. Nichols,K.K. Foulks,G.N. Bron,A.J. et al. (2011). The international workshop on meibomian gland dysfunction: executive summart. Invest Ophthalmol Vis Sci. 52:1922.
  20. Bron,A.J. Evans,V.E. Smith,J.A. (2003). Grading of corneal and conjunctival staining in the context of other
  21. Whitcher,J.P. Shiboski,C.H. Shiboski,S.C. et al. (2010). A simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjogren’s Syndome International Registry. Am J Ophthalmol. 149:405.
  22. Van Bijsterveld,O.P. (1969). Diagnostic tests in the Sicca syndrome. Arch Ophthalmol. 82:10
  23. Shiboski,C.H. Shiboski,S.C. Seror,R. Criswell,L.A. Labetoulle,M. Lietman,T.M. Rasmussen,A. Scofield,H. Vitali,C. Bowman,S.J. Mariette,X; International Sjögren’s Syndrome Criteria Working Group. (2016). American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren’s Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts. Arthritis Rheumatol. 69(1):35-45. doi: 10.1002/art.39859. PMID: 27785888; PMCID: PMC5650478.
  24. Golden,M.I. Meyer,J.J. Patel,B.C. (2022). Dry Eye Syndrome. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470411/
  25. Kojima,T. Ishida,R. Dogru,M. Goto,E. Matsumoto,Y. Kaido,M. Tsubota,K. (2005). The effect of autologous serum eyedrops in the treatment of severe dry eye disease: A prospective randomized case-control study. American Journal of Ophthalmology. Volume 139. Issue 2. P242-246. DOI:https://doi.org/10.1016/j.ajo.2004.08.040
  26. Hyon,J.Y. Lee,Y.J. Yun,P.Y. (2007). Management of ocular surface inflammation in Sjögren syndrome. Cornea. 26(9 Suppl 1):S13-5. doi: 10.1097/ICO.0b013e31812f6782. PMID: 17881909.
  27. Romero-Rangel,T. Stavrou,P. Cotter,J. Rosenthal,P. Baltatzis,S. Foster,C.S. (2000). Gas-permeable scleral contact lens therapy in ocular surface disease. Am J Ophthalmol. 130(1):25-32. doi: 10.1016/s0002-9394(00)00378-0. PMID: 11004256.
  28. Ervin,A.M. Law,A. Pucker,A.D. (2017). Punctal occlusion for dry eye syndrome. Cochrane Database Syst Rev. 6(6):CD006775. doi: 10.1002/14651858.CD006775.pub3. PMID: 28649802; PMCID: PMC5568656.
  29. Acharya,M, Gour,A. Dave,A. (2020). Commentary: Tarsorrhaphy: A stitch in time. Indian J Ophthalmol. 68(1):33-34. doi: 10.4103/ijo.IJO_1824_19. PMID: 31856461; PMCID: PMC6951190.
  30. Hamill,M.B. (1997). Corneal injury. In: Krachmer JH, Mannis MJ, Holland EJ, editors. Cornea. Vol. 2. St. Louis: Mosby. pp. 1403–22.

Leave a Reply