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Dry Eye and Clinical Disease of Tear Film, Diagnosis and Management

US Ophthalmic Review, 2014;7(2):109–15 DOI:


Dry eye disease (DED) is a clinically significant multifactorial disorder of the ocular surface and tear film as it results in ocular discomfort and visual impairment and predisposes the cornea to infections. It is important for the quality of life and tends to be a chronic disease. It is also common, as the prevalence is estimated between 5 % to 30 % and this increases with age. Therefore, it is recognised as a growing public health problem that requires correct diagnosis and appropriate treatment. There are two main categories of DED: the deficiency of tear production (hyposecretive), which includes Sjögren syndrome, idiopathic or secondary to connective tissue diseases (e.g. rheumatoid arthritis), and non-Sjögren syndrome (e.g. age-related); and the tear evaporation category, where tears evaporate from the ocular surface too rapidly due to intrinsic causes (e.g. meibomian gland disease or eyelid aperture disorders) or extrinsic causes (e.g. vitamin A deficiency, contact lenses wear, ocular allergies). Management of the disease aims to enhance the corneal healing and reduce patient’s discomfort. This is based on improving the balance of tear production and evaporation by increasing the tear film volume (lubrication drops) and improving quality of tear film (ex omega-3 supplements, lid hygiene, tetracyclines), reducing the tear film evaporation (paraffin ointments, therapeutic contact lenses), reducing tear’s drainage (punctal plugs, cautery) and finally by settling down the ocular surface inflammation (steroids, cyclosporine, autologous serous), as appropriate. In this article we will review the clinical presentation, differential diagnosis and treatment options for DED.

Keywords: Dry eye disease, tear film, Sjögren, ocular inflammation.
Disclosure: Vasilis Achtsidis, Eleftheria Kozanidou, Panos Bournas, Nicholas Tentolouris and Panos G Theodossiadis have no conflicts of interest to declare. No funding was received in the publication of this article.
Received: February 27, 2014 Accepted: March 31, 2014
Correspondence: Vasilis Achtsidis, MD, FEBO, Consultant Ophthalmologist, Department of Ophthalmology, Worthing Hospital, Lyndhurst Road, Worthing, West Sussex BN11 2DH, UK. E:

There is now an increased recognition by clinicians that dry eye disease (DED) is a common disorder characterised by dryness and damage of the ocular surface. It affects quality of life, including aspects of physical, social and psychological functioning, because it induces ocular discomfort, burning sensation, light sensitivity, visual disturbances or even corneal erosions and infections. DED is also known as keratoconjunctivitis sicca, dry eye syndrome and dysfunctional tear syndrome.

DED prevalence has been reported to range from 5 % to 30 %, this being a likely result from differing study populations and DED definitions. In a large population study, Moss et al. reported the prevalence of dry eye to be 14.4 % in 3,722 subjects aged 48 to 91 years and noted that the prevalence of the condition doubled after the age of 59. As a consequence, DED prevalence is expected to increase in ageing populations, which will eventually make this health problem more prominent.1–4

In order to address the problem, the International Dry Eye Workshop (DEWS) defines dry eye as a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.3–5

Indeed, DEWS has recognised dry eye as a disturbance of the lacrimal functional unit, an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that innervate them.3,4 Dysfunction of any component of the lacrimal functional unit may lead to ocular surface disease, related to inflammation and increased tear film osmolarity.

This multifactorial aetiopathogenesis explains why the clinical diagnosis of dry eye remains a challenge, not only due to the wide spectrum of alterations of the ocular surface with different aetiology and pathophysiology,5 but also due to the lack of well standardised diagnostic tests,6 and the fact that corneal surface is sensitive to external stimuli and, while the most diagnostic tests are overly invasive, the non-invasive tests are still considered expensive for everyday practice. Therefore, a holistic approach and a careful examination of tear film, cornea, eyelids, anatomically and functionally, as well as a thorough clinical history is needed to diagnose DED.3,5–8

Early diagnosis of DED and identification of the underlying cause is essential not only for the management of the ocular surface disease, but also for the diagnosis and management of the systematic disease,which might be occult, and may serve as a common link between ophthalmologists and physicians.9,10

  1. Friedman NJ, Impact of dry eye disease and treatment on quality of life, Curr Opin Ophthalmol, 2010;21:310–16.
  2. Pflugfelder SC, Prevalence, burden, and pharmacoeconomics of dry eye disease, Am J Manag Care, 2008;14(Suppl. 3):S102–6.
  3. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007), Ocul Surf, 2007;5:75.
  4. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007), Ocul Surf, 2007;5:93.
  5. Savini G, Prabhawasat P, Kojima T, et al., The challenge of dry eye diagnosis, Clin Ophthalmol, 2008;2:31–55.
  6. Foulks GN, Challenges and pitfalls in clinical trials of treatments fo dry eye, Ocul Surf, 2003;1:20–30.
  7. Yokoi N, Komuro A, Non-invasive methods of assessing the tear film, Experiment Eye Res, 2004;78:399–407.
  8. Labbé A, Brignole-Baudouin F, Baudouin C, Ocular surface investigations in dry eye, J Fr Ophtalmol, 2007;30:76–97.
  9. Achtsidis V, Tentolouris N, Theodoropoulou S, et al., Dry eye in Graves’ ophthalmopathy: correlation with corneal hypoesthesia, Eur J Ophthalmol, 2013;23:473–9.
  10. Gupta A, Sadeghi PB, Akpek EK, Occult thyroid eye disease in patients presenting with dry eye symptoms, Am J Ophthalmol, 2009;147:919–23.
  11. Behrens A, Doyle JJ, Stern L, et al., Dysfunctional tear syndrome: a Delphi approach to treatment recommendations, Cornea, 2006;25:900–7.
  12. Moss SE, Klein R, Klein BE, Prevalence of and risk factors for dry eye syndrome, Arch Ophthalmol, 2000;118:1264–8.
  13. Latkany R, Dry eyes: etiology and management, Curr Opin Ophthalmol, 2008;19:287.
  14. Belmonte C, Acosta MC, Gallar J, Neural basis of sensation in intact and injured corneas, Exp Eye Res, 2004;78:513.
  15. Zhang M, Chen J, Luo L, et al., Altered corneal nerves in aqueous tear deficiency viewed by in vivo confocal microscopy, Cornea, 2005;24:818–24.
  16. Fox RI, Stern M, Michelson P, Update in Sjögren syndrome, Curr Opin Rheumatol, 2000;12:391–8.
  17. Ramos-Casals M, Tzioufas AG, Font J, Primary Sjögren’s syndrome: new clinical and therapeutic concepts, Ann Rheum Dis, 2005;64:347.
  18. Gilbard JP, Gray KL, Rossi SR, A proposed mechanism for increased tear-film osmolarity in contact lens wearers, Am J Ophthalmol, 1986;102:505.
  19. Ramos-Remus C, Suarez-Almazor M, Russell AS, Low tear production in patients with diabetes mellitus is not due to Sjogren’s syndrome, Clin Exp Rheumatol, 1994;12:375–80.
  20. Kaiserman I, Kaiserman N, Nakar S, Vinker S, Dry eye in diabetic patients, Am J Ophthalmol, 2005;139:498–503.
  21. Lemp MA, Crews LA, Bron AJ, et al., Distribution of aqueousdeficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study, Cornea, 2012;31:472–8.
  22. Johnson ME, Murphy PJ, The effect of instilled fluorescein solution volume on the values and repeatability of TBUT measurements, Cornea, 2005;24:811–7.
  23. Bandeen-Roche K, Munoz B, Tielsch JM, et al., Self-reported assessment of dry eye in a population-based setting, Invest Ophthalmol Vis Sci, 1997;38:2469–75. 24. Schiffman RM, Christianson MD, Jacobsen G, et al., Reliability and validity of the Ocular Surface Disease Index, Arch Ophthalmol, 2000;118:615–21.
  24. Foulks GN, Bron AJ, Meibomian Gland Dysfunction: a clinical scheme for description, diagnosis, classification, and grading, Ocul Surf, 2003;1:107–26.
  25. Nepp J, Abela C, Polzer I, et al., Is there a correlation between the severity of diabetic retinopathy and keratoconjunctivitis sicca?, Cornea, 2000;19:487–91.
  26. Kam KY, Cole CJ, Bunce C, et al., The lateral tarsal strip in ectropion surgery: is it effective when performed in isolation?, Eye (Lond), 2012;26:827–32.
  27. Berry-Brincat A, Burns J, Sampath R, Inverting sutures for tarsal ectropion (the leicester modified suture technique), Ophthal Plast Reconstr Surg, 2013;29:400–2.
  28. Lemp M, Sullivan B, Crews L, Biomarkers In dry eye disease, European Ophthalmic Review, 2012;6:157–63.
  29. Yokoi N, Komuro A, Maruyama K,et al., New instruments for dry eye diagnosis, Semin Ophthalmol, 2005;20:63–70.
  30. Khanal S, Millar TJ, Barriers to clinical uptake of tear osmolarity measurements, Br J Ophthalmol, 2012;96:341–4.
  31. Preferred Practice Pattern Guidelines: Dry Eye Syndrome – Limited Revision, American Academy of Ophthalmology, San Francisco, CA, US, 2011.
  32. Sullivan BD, Crews LA, Messmer EM, et al., Correlations between commonly used objective signs and symptoms for the diagnosis of dry eye disease: clinical implications, Acta Ophthalmol, 2014;92:161–6.
  33. Sambursky R, Davitt WF, Latkany R, et al., Sensitivity and specificity of a point-of-care matrix metalloproteinase 9 immunoassay for diagnosing inflammation related to dry eye, JAMA Ophthalmol, 2013;131:24–8.
  34. Mavragani CP, Skopouli FN, Moutsopoulos HM, Increased prevalence of antibodies to thyroid peroxidise in dry eyes and mouth syndrome or sicca asthenia polyalgia syndrome, J Rheumatol, 2009;36:1626–30.
  35. Abusharha AA, Pearce EI, The effect of low humidity on the human tear film, Cornea, 2013;32:429–34.
  36. Alex A, Edwards A, Hays JD, et al., Factors predicting the ocular surface response to desiccating environmental stress, Invest Ophthalmol Vis Sci, 2013 7;54:3325–32.
  37. Baudouin C, Cochener B, Pisella PJ, et al., Randomized, phase III study comparing osmoprotective carboxymethylcellulose with sodium hyaluronate in dry eye disease, Eur J Ophthalmol, 2012;22:751–61.
  38. Luchs J, Efficacy of topical azithromycin ophthalmic solution 1 % in the treatment of posterior blepharitis, Adv Ther, 2008;25:858.
  39. Torkildsen GL, Cockrum P, Meier E, et al., Evaluation of clinical efficacy and safety of tobramycin/dexamethasone ophthalmic suspension 0.3%/0.05% compared to azithromycin ophthalmic solution 1% in the treatment of moderate to severe acute blepharitis/blepharoconjunctivitis. Curr Med Res Opin, 2011;27:171.
  40. Frucht-Pery J, Sagi E, Hemo I, Ever-Hadani P ,Efficacy of doxycycline and tetracycline in ocular rosacea, Am J Ophthalmol, 1993;15;116:88–92.
  41. Iovieno A, Lambiase A, Micera A, et al., In vivo characterization of doxycycline effects on tear metalloproteinases in patients with chronic blepharitis, Eur J Ophthalmol, 2009;19:708.
  42. Lee JH, Min K, Kim SK, et al., Inflammatory cytokine and osmolarity changes in the tears of dry eye patients treated with topical 1% methylprednisolone, Yonsei Med J, 2014;55:203–8.
  43. Byun YJ, Kim TI, Kwon SM, Efficacy of combined 0.05 % cyclosporine and 1 % methylprednisolone treatment for chronic dry eye, Cornea, 2012;31:509–13.
  44. Kymionis GD, Bouzoukis DI, Diakonis VF, et al., Treatment of chronic dry eye: focus on cyclosporine, Clin Ophthalmol, 2008;2:829–36.
  45. Cho YK, Huang W, Kim GY, Lim BS, Comparison of autologous seroum eye drops with different dilutents, Curr Eye Res, 2013;38:9–17.
  46. Urzua CA, Vasquez DH, Huidobro A, et al., Randomized double-blind clinical trial of autologous seroum versus artificial tears in dry eye syndrome, Curr Eye Res, 2012;37:684–8. 48. Ervin AM, Wojciechowski R, Schein O, Punctal occlusion for dry eye syndrome, Cochrane Database Syst Rev, 2010;CD006775.
  47. Ohba E, Dogru M, Hosaka E, et al., Surgical punctal occlusion with a high heat-energy releasing cautery device for severe dry eye with recurrent punctal plug extrusion, Am J Ophthalmol, 2011;151:483–7.
  48. Oleñik A, Effectiveness and tolerability of dietary supplementation with a combination of omega-3 polyunsaturated fatty acids and antioxidants in the treatment of dry eye symptoms: results of a prospective study, Clin Ophthalmol, 2014;8:169–76.
  49. Rand AL, Asbell PA, Nutritional supplements for dry eye syndrome, Curr Opin Ophthalmol, 2011;22:279–82.
  50. Simopoulos AP, The importance of the ratio of omega-6/ omega-3 essential fatty acids, Biomed Pharmacother, 2002;56:365–79.
  51. Rashid S, Jin Y, Ecoiffier T, et al., Topical omega-3 and omega-6 fatty acids for treatment of dry eye, Arch Ophthalmol, 2008;126:219–25.
  52. Roncone M, Bartlett H, Eperjesi F, Essential fatty acids for dry eye: A review, Cont Lens Anterior Eye, 2010;33:49–54.
  53. Grey F, Carley F, Biswas S, Scleral contact lens management of bilateral exposure and neurotrophic keratopathy, Cont Lens Anterior Eye, 2012;35:288–91.
  54. Albietz J, Sanfilippo P, Troutbeck R, Lenton LM, Management of filamentary keratitis associated with aqueous-deficient dry eye, Optom Vis Sci, 2003;80:420–30.
  55. McMonnies CW, Incomplete blinking: exposure keratopathy, lid wiper epitheliopathy, dry eye, refractive surgery, and dry contact lenses, Cont Lens Anterior Eye, 2007;30:37–51.
Keywords: Dry eye disease, tear film, Sjögren, ocular inflammation.