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Image-guided evaluation and monitoring of treatment response in patients with dry eye disease

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Abstract

Background

Dry eye disease (DED) is one of the most common ocular disorders worldwide. The pathophysiological mechanisms involved in the development of DED are not well-understood, and thus treating DED has been a significant challenge for ophthalmologists. Most of the currently available diagnostic tests demonstrate low correlation to patient symptoms and have low reproducibility.

Methods

Recently, sophisticated in vivo imaging modalities have become available for patient care, namely, in vivo confocal microscopy (IVCM) and optical coherence tomography (OCT). These emerging modalities are powerful and non-invasive, allowing real-time visualization of cellular and anatomical structures of the cornea and ocular surface. Here we discuss how, by providing both qualitative and quantitative assessment, these techniques can be used to demonstrate early subclinical disease, grade layer-by-layer severity, and allow monitoring of disease severity by cellular alterations. Imaging-guided stratification of patients may also be possible in conjunction with clinical examination methods.

Conclusions

Visualization of subclinical changes and stratification of patients in vivo allows objective image-guided evaluation of tailored treatment response based on cellular morphological alterations specific to each patient. This image-guided approach to DED may ultimately improve patient outcomes and make it possible to study the efficacy of novel therapies in clinical trials.

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References

  1. (2007) The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 5:75–92

  2. Uchino M, Nishiwaki Y, Michikawa T, Shirakawa K, Kuwahara E, Yamada M, Dogru M, Schaumberg DA, Kawakita T, Takebayashi T, Tsubota K (2011) Prevalence and risk factors of dry eye disease in Japan: Koumi Study. Ophthalmology 118:2361–2367

    PubMed  Google Scholar 

  3. Han SB, Hyon JY, Woo SJ, Lee JJ, Kim TH, Kim KW (2011) Prevalence of dry eye disease in an elderly Korean population. Arch Ophthalmol 129:633–638

    PubMed  Google Scholar 

  4. Guo B, Lu P, Chen X, Zhang W, Chen R (2010) Prevalence of dry eye disease in Mongolians at high altitude in China: the Henan Eye Study. Ophthalmic Epidemiol 17:234–241

    PubMed  Google Scholar 

  5. Chia EM, Mitchell P, Rochtchina E, Lee AJ, Maroun R, Wang JJ (2003) Prevalence and associations of dry eye syndrome in an older population: the Blue Mountains Eye Study. Clin Exp Ophthalmol 31:229–232

    Google Scholar 

  6. McCarty CA, Bansal AK, Livingston PM, Stanislavsky YL, Taylor HR (1998) The epidemiology of dry eye in Melbourne, Australia. Ophthalmology 105:1114–1119

    CAS  PubMed  Google Scholar 

  7. Lin PY, Tsai SY, Cheng CY, Liu JH, Chou P, Hsu WM (2003) Prevalence of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study. Ophthalmology 110:1096–1101

    PubMed  Google Scholar 

  8. Lee AJ, Lee J, Saw SM, Gazzard G, Koh D, Widjaja D, Tan DT (2002) Prevalence and risk factors associated with dry eye symptoms: a population based study in Indonesia. Br J Ophthalmol 86:1347–1351

    Google Scholar 

  9. (2007) The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 5: 93–107

  10. Schaumberg DA, Dana R, Buring JE, Sullivan DA (2009) Prevalence of dry eye disease among US men: estimates from the Physicians’ Health Studies. Arch Ophthalmol 127:763–768

    PubMed Central  PubMed  Google Scholar 

  11. Schein OD, Munoz B, Tielsch JM, Bandeen-Roche K, West S (1997) Prevalence of dry eye among the elderly. Am J Ophthalmol 124:723–728

    CAS  PubMed  Google Scholar 

  12. Moss SE, Klein R, Klein BE (2000) Prevalence of and risk factors for dry eye syndrome. Arch Ophthalmol 118:1264–1268

    CAS  PubMed  Google Scholar 

  13. Schaumberg DA, Sullivan DA, Buring JE, Dana MR (2003) Prevalence of dry eye syndrome among US women. Am J Ophthalmol 136:318–326

    PubMed  Google Scholar 

  14. Galor A, Feuer W, Lee DJ, Florez H, Carter D, Pouyeh B, Prunty WJ, Perez VL (2011) Prevalence and risk factors of dry eye syndrome in a United States Veterans Affairs population. Am J Ophthalmol 152:377.e2–384.e2

    Google Scholar 

  15. Moschos MM, Chatziralli IP, Siasou G, Papazisis L (2012) Visual problems in young adults due to computer use. Klin Monatsbl Augenheilkd 229:379–381

    CAS  PubMed  Google Scholar 

  16. Thomson WD (1998) Eye problems and visual display terminals–the facts and the fallacies. Ophthalmic Physiol Opt 18:111–119

    Google Scholar 

  17. Uchino M, Schaumberg DA, Dogru M, Uchino Y, Fukagawa K, Shimmura S, Satoh T, Takebayashi T, Tsubota K (2008) Prevalence of dry eye disease among Japanese visual display terminal users. Ophthalmology 115:1982–1988

    PubMed  Google Scholar 

  18. Blehm C, Vishnu S, Khattak A, Mitra S, Yee RW (2005) Computer vision syndrome: a review. Surv Ophthalmol 50:253–262

    PubMed  Google Scholar 

  19. Tsubota K, Nakamori K (1993) Dry eyes and video display terminals. N Engl J Med 328:584

    CAS  PubMed  Google Scholar 

  20. Uchino M, Dogru M, Uchino Y, Fukagawa K, Shimmura S, Takebayashi T, Schaumberg DA, Tsubota K (2008) Japan Ministry of Health study on prevalence of dry eye disease among Japanese high school students. Am J Ophthalmol 146:925.e2–929.e2

    Google Scholar 

  21. Zhang Y, Chen H, Wu X (2012) Prevalence and risk factors associated with dry eye syndrome among senior high school students in a county of Shandong Province, China. Ophthalmic Epidemiol 19:226–230

    PubMed  Google Scholar 

  22. Pouyeh B, Viteri E, Feuer W, Lee DJ, Florez H, Fabian JA, Perez VL, Galor A (2012) Impact of ocular surface symptoms on quality of life in a United States Veterans Affairs population. Am J Ophthalmol 153:1061.e3–1066.e3

    Google Scholar 

  23. Li M, Gong L, Chapin WJ, Zhu M (2012) Assessment of vision-related quality of life in dry eye patients. Invest Ophthalmol Vis Sci 53:5722–5727

    PubMed  Google Scholar 

  24. Mertzanis P, Abetz L, Rajagopalan K, Espindle D, Chalmers R, Snyder C, Caffery B, Edrington T, Simpson T, Nelson JD, Begley C (2005) The relative burden of dry eye in patients’ lives: comparisons to a U.S. normative sample. Invest Ophthalmol Vis Sci 46:46–50

    PubMed  Google Scholar 

  25. Goto E, Yagi Y, Matsumoto Y, Tsubota K (2002) Impaired functional visual acuity of dry eye patients. Am J Ophthalmol 133:181–186

    PubMed  Google Scholar 

  26. Miljanovic B, Dana R, Sullivan DA, Schaumberg DA (2007) Impact of dry eye syndrome on vision-related quality of life. Am J Ophthalmol 143:409–415

    PubMed Central  PubMed  Google Scholar 

  27. Tong L, Waduthantri S, Wong TY, Saw SM, Wang JJ, Rosman M, Lamoureux E (2010) Impact of symptomatic dry eye on vision-related daily activities: the Singapore Malay Eye Study. Eye (Lond) 24:1486–1491

    CAS  Google Scholar 

  28. Le Q, Zhou X, Ge L, Wu L, Hong J, Xu J (2012) Impact of dry eye syndrome on vision-related quality of life in a non-clinic-based general population. BMC Ophthalmol 12:22

    PubMed Central  PubMed  Google Scholar 

  29. Schiffman RM, Walt JG, Jacobsen G, Doyle JJ, Lebovics G, Sumner W (2003) Utility assessment among patients with dry eye disease. Ophthalmology 110:1412–1419

    PubMed  Google Scholar 

  30. Buchholz P, Steeds CS, Stern LS, Wiederkehr DP, Doyle JJ, Katz LM, Figueiredo FC (2006) Utility assessment to measure the impact of dry eye disease. Ocul Surf 4:155–161

    PubMed  Google Scholar 

  31. Galor A, Zheng DD, Arheart KL, Lam BL, Perez VL, McCollister KE, Ocasio M, McClure LA, Lee DJ (2012) Dry eye medication use and expenditures: data from the medical expenditure panel survey 2001 to 2006. Cornea 31(12):1403–1407

    PubMed  Google Scholar 

  32. Reddy P, Grad O, Rajagopalan K (2004) The economic burden of dry eye: a conceptual framework and preliminary assessment. Cornea 23:751–761

    PubMed  Google Scholar 

  33. Rein DB, Zhang P, Wirth KE, Lee PP, Hoerger TJ, McCall N, Klein R, Tielsch JM, Vijan S, Saaddine J (2006) The economic burden of major adult visual disorders in the United States. Arch Ophthalmol 124:1754–1760

    PubMed  Google Scholar 

  34. Patel VD, Watanabe JH, Strauss JA, Dubey AT (2011) Work productivity loss in patients with dry eye disease: an online survey. Curr Med Res Opin 27:1041–1048

    CAS  PubMed  Google Scholar 

  35. Yu J, Asche CV, Fairchild CJ (2011) The economic burden of dry eye disease in the United States: a decision tree analysis. Cornea 30:379–387

    PubMed  Google Scholar 

  36. Akpek EK, Lindsley KB, Adyanthaya RS, Swamy R, Baer AN, McDonnell PJ (2011) Treatment of Sjogren’s syndrome-associated dry eye an evidence-based review. Ophthalmology 118:1242–1252

    PubMed  Google Scholar 

  37. Friedman NJ (2010) Impact of dry eye disease and treatment on quality of life. Curr Opin Ophthalmol 21:310–316

    PubMed  Google Scholar 

  38. Fiscella RG (2011) Understanding dry eye disease: a managed care perspective. Am J Manag Care 17(Suppl 16):S432–S439

    PubMed  Google Scholar 

  39. Luthe R (2010) Dry eye drug development: when will the floodgates open? Ophthalmol Manag

  40. Karpecki P (2013) Why dry eye trials often fail. Review Optom

  41. Caceres V (2011) Treating dry eye. ASCRS Eye World

  42. Epstein SP, Gadaria-Rathod N, Wei Y, Maguire MG, Asbell PA (2013) HLA-DR expression as a biomarker of inflammation for multicenter clinical trials of ocular surface disease. Exp Eye Res 111:95–104

    CAS  PubMed  Google Scholar 

  43. Gipson IK, Argueso P (2003) Role of mucins in the function of the corneal and conjunctival epithelia. Int Rev Cytol 231:1–49

    CAS  PubMed  Google Scholar 

  44. Spurr-Michaud S, Argueso P, Gipson I (2007) Assay of mucins in human tear fluid. Exp Eye Res 84:939–950

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Carraway KL, Perez A, Idris N, Jepson S, Arango M, Komatsu M, Haq B, Price-Schiavi SA, Zhang J, Carraway CA (2002) Muc4/sialomucin complex, the intramembrane ErbB2 ligand, in cancer and epithelia: to protect and to survive. Prog Nucleic Acid Res Mol Biol 71:149–185

    CAS  PubMed  Google Scholar 

  46. Gipson IK (2004) Distribution of mucins at the ocular surface. Exp Eye Res 78:379–388

    CAS  PubMed  Google Scholar 

  47. Hodges RR, Dartt DA (2013) Tear film mucins: Front line defenders of the ocular surface; comparison with airway and gastrointestinal tract mucins. Exp Eye Res 117:62–78

    CAS  PubMed  Google Scholar 

  48. Albertsmeyer AC, Kakkassery V, Spurr-Michaud S, Beeks O, Gipson IK (2010) Effect of pro-inflammatory mediators on membrane-associated mucins expressed by human ocular surface epithelial cells. Exp Eye Res 90:444–451

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Gipson IK, Hori Y, Argueso P (2004) Character of ocular surface mucins and their alteration in dry eye disease. Ocul Surf 2:131–148

    PubMed  Google Scholar 

  50. Dartt DA (2004) Interaction of EGF family growth factors and neurotransmitters in regulating lacrimal gland secretion. Exp Eye Res 78:337–345

    CAS  PubMed  Google Scholar 

  51. Knop E, Knop N, Millar T, Obata H, Sullivan DA (2011) The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci 52:1938–1978

    PubMed Central  PubMed  Google Scholar 

  52. Shimazaki J, Goto E, Ono M, Shimmura S, Tsubota K (1998) Meibomian gland dysfunction in patients with Sjogren syndrome. Ophthalmology 105:1485–1488

    CAS  PubMed  Google Scholar 

  53. Bron AJ, Yokoi N, Gafney E, Tiffany JM (2009) Predicted phenotypes of dry eye: proposed consequences of its natural history. Ocul Surf 7:78–92

    PubMed  Google Scholar 

  54. Mizuno Y, Yamada M, Miyake Y (2010) Association between clinical diagnostic tests and health-related quality of life surveys in patients with dry eye syndrome. Jpn J Ophthalmol 54:259–265

    PubMed  Google Scholar 

  55. Fuentes-Paez G, Herreras JM, Cordero Y, Almaraz A, Gonzalez MJ, Calonge M (2011) Lack of concordance between dry eye syndrome questionnaires and diagnostic tests. Arch Soc Esp Oftalmol 86:3–7

    CAS  PubMed  Google Scholar 

  56. Schein OD, Tielsch JM, Munoz B, Bandeen-Roche K, West S (1997) Relation between signs and symptoms of dry eye in the elderly. A population-based perspective. Ophthalmology 104:1395–1401

    CAS  PubMed  Google Scholar 

  57. Begley CG, Chalmers RL, Abetz L, Venkataraman K, Mertzanis P, Caffery BA, Snyder C, Edrington T, Nelson D, Simpson T (2003) The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity. Invest Ophthalmol Vis Sci 44:4753–4761

    PubMed  Google Scholar 

  58. Barboza MN, Barboza GN, de Melo GM, Sato E, Dantas MC, Dantas PE, Felberg S (2008) Correlation between signals and symptoms of dry eye in Sjogren’s syndrome patients. Arq Bras Oftalmol 71:547–552

    PubMed  Google Scholar 

  59. Nichols KK, Nichols JJ, Mitchell GL (2004) The lack of association between signs and symptoms in patients with dry eye disease. Cornea 23:762–770

    PubMed  Google Scholar 

  60. Blackie CA, Korb DR, Knop E, Bedi R, Knop N, Holland EJ (2010) Nonobvious obstructive meibomian gland dysfunction. Cornea 29:1333–1345

    PubMed  Google Scholar 

  61. Nelson JD, Shimazaki J, Benitez-del-Castillo JM, Craig JP, McCulley JP, Den S, Foulks GN (2011) The international workshop on meibomian gland dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci 52:1930–1937

    PubMed Central  PubMed  Google Scholar 

  62. Cuevas M, Gonzalez-Garcia MJ, Castellanos E, Quispaya R, Parra Pde L, Fernandez I, Calonge M (2012) Correlations among symptoms, signs, and clinical tests in evaporative-type dry eye disease caused by Meibomian gland dysfunction (MGD). Curr Eye Res 37:855–863

    PubMed  Google Scholar 

  63. Viso E, Rodriguez-Ares MT, Abelenda D, Oubina B, Gude F (2012) Prevalence of asymptomatic and symptomatic meibomian gland dysfunction in the general population of Spain. Invest Ophthalmol Vis Sci 53:2601–2606

    PubMed  Google Scholar 

  64. Adatia FA, Michaeli-Cohen A, Naor J, Caffery B, Bookman A, Slomovic A (2004) Correlation between corneal sensitivity, subjective dry eye symptoms and corneal staining in Sjogren’s syndrome. Can J Ophthalmol 39:767–771

    PubMed  Google Scholar 

  65. (2007) Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 5: 108–152

  66. Nichols KK, Zadnik K (2002) The repeatability of diagnostic tests and surveys in dry eye. Adv Exp Med Biol 506:1171–1175

    PubMed  Google Scholar 

  67. Nichols KK, Mitchell GL, Zadnik K (2004) The repeatability of clinical measurements of dry eye. Cornea 23:272–285

    PubMed  Google Scholar 

  68. Johnson ME, Murphy PJ (2005) The agreement and repeatability of tear meniscus height measurement methods. Optom Vis Sci 82:1030–1037

    PubMed  Google Scholar 

  69. Lemp MA, Bron AJ, Baudouin C, Benitez Del Castillo JM, Geffen D, Tauber J, Foulks GN, Pepose JS, Sullivan BD (2011) Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol 151:792.e1–798.e1

    Google Scholar 

  70. Sullivan BD, Whitmer D, Nichols KK, Tomlinson A, Foulks GN, Geerling G, Pepose JS, Kosheleff V, Porreco A, Lemp MA (2010) An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci 51:6125–6130

    PubMed  Google Scholar 

  71. Tomlinson A, Khanal S, Ramaesh K, Diaper C, McFadyen A (2006) Tear film osmolarity: determination of a referent for dry eye diagnosis. Invest Ophthalmol Vis Sci 47:4309–4315

    PubMed  Google Scholar 

  72. Versura P, Profazio V, Campos EC (2010) Performance of tear osmolarity compared to previous diagnostic tests for dry eye diseases. Curr Eye Res 35:553–564

    CAS  PubMed  Google Scholar 

  73. Amparo F, Jin Y, Hamrah P, Schaumberg DA, Dana R (2014) What is the value of incorporating tear osmolarity measurement in assessing patient response to therapy in dry eye disease? Am J Ophthalmol 157:69.e2–77.e2

    Google Scholar 

  74. Kerimoglu H, Ozturk B, Gunduz K, Bozkurt B, Kamis U, Okka M (2010) Effect of altered eating habits and periods during Ramadan fasting on intraocular pressure, tear secretion, corneal and anterior chamber parameters. Eye (Lond) 24:97–100

    CAS  Google Scholar 

  75. Carney LG, Hill RM (1976) Human tear pH. Diurnal variations. Arch Ophthalmol 94:821–824

    CAS  PubMed  Google Scholar 

  76. Patel S, Bevan R, Farrell JC (1988) Diurnal variation in precorneal tear film stability. Am J Optom Physiol Opt 65:151–154

    CAS  PubMed  Google Scholar 

  77. Cedarstaff TH, Tomlinson A (1983) Human tear volume, quality and evaporation: a comparison of Schirmer, tear break-up time and resistance hygrometry techniques. Ophthalmic Physiol Opt 3:239–245

    CAS  PubMed  Google Scholar 

  78. (2007) Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 5: 163–178

  79. Siak JJ, Tong L, Wong WL, Cajucom-Uy H, Rosman M, Saw SM, Wong TY (2012) Prevalence and risk factors of Meibomian gland dysfunction: the Singapore Malay Eye Study. Cornea 31(11):1223–1228

    Google Scholar 

  80. Schaumberg DA, Nichols JJ, Papas EB, Tong L, Uchino M, Nichols KK (2011) The international workshop on meibomian gland dysfunction: report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Invest Ophthalmol Vis Sci 52:1994–2005

    PubMed Central  PubMed  Google Scholar 

  81. Foulks GN, Borchman D (2010) Meibomian gland dysfunction: the past, present, and future. Eye Contact Lens 36:249–253

    PubMed  Google Scholar 

  82. Hom MM, Martinson JR, Knapp LL, Paugh JR (1990) Prevalence of Meibomian gland dysfunction. Optom Vis Sci 67:710–712

    CAS  PubMed  Google Scholar 

  83. Nichols KK, Foulks GN, Bron AJ, Glasgow BJ, Dogru M, Tsubota K, Lemp MA, Sullivan DA (2011) The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci 52:1922–1929

    PubMed Central  PubMed  Google Scholar 

  84. Sullivan DA, Sullivan BD, Evans JE, Schirra F, Yamagami H, Liu M, Richards SM, Suzuki T, Schaumberg DA, Sullivan RM, Dana MR (2002) Androgen deficiency, Meibomian gland dysfunction, and evaporative dry eye. Ann N Y Acad Sci 966:211–222

    CAS  PubMed  Google Scholar 

  85. Sullivan DA, Schaumberg DA, Suzuki T, Schirra F, Liu M, Richards S, Sullivan RM, Dana MR, Sullivan BD (2002) Sex steroids, meibomian gland dysfunction and evaporative dry eye in Sjogren’s syndrome. Lupus 11:667

    CAS  PubMed  Google Scholar 

  86. Dougherty JM, McCulley JP (1984) Comparative bacteriology of chronic blepharitis. Br J Ophthalmol 68:524–528

    CAS  PubMed Central  PubMed  Google Scholar 

  87. Dougherty JM, McCulley JP (1986) Bacterial lipases and chronic blepharitis. Invest Ophthalmol Vis Sci 27:486–491

    CAS  PubMed  Google Scholar 

  88. McCulley JP, Dougherty JM (1986) Bacterial aspects of chronic blepharitis. Trans Ophthalmol Soc U K 105(Pt 3):314–318

    PubMed  Google Scholar 

  89. Lee HJ, Chang C (2003) Recent advances in androgen receptor action. Cell Mol Life Sci 60:1613–1622

    CAS  PubMed  Google Scholar 

  90. Sullivan DA, Sullivan BD, Ullman MD, Rocha EM, Krenzer KL, Cermak JM, Toda I, Doane MG, Evans JE, Wickham LA (2000) Androgen influence on the meibomian gland. Invest Ophthalmol Vis Sci 41:3732–3742

    CAS  PubMed  Google Scholar 

  91. Sullivan BD, Evans JE, Cermak JM, Krenzer KL, Dana MR, Sullivan DA (2002) Complete androgen insensitivity syndrome: effect on human meibomian gland secretions. Arch Ophthalmol 120:1689–1699

    CAS  PubMed  Google Scholar 

  92. Sullivan BD, Evans JE, Dana MR, Sullivan DA (2002) Impact of androgen deficiency on the lipid profiles in human meibomian gland secretions. Adv Exp Med Biol 506:449–458

    CAS  PubMed  Google Scholar 

  93. Foulks GN, Bron AJ (2003) Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification, and grading. Ocul Surf 1:107–126

    PubMed  Google Scholar 

  94. Tomlinson A, Bron AJ, Korb DR, Amano S, Paugh JR, Pearce EI, Yee R, Yokoi N, Arita R, Dogru M (2011) The international workshop on meibomian gland dysfunction: report of the diagnosis subcommittee. Invest Ophthalmol Vis Sci 52:2006–2049

    PubMed Central  PubMed  Google Scholar 

  95. Golebiowski B, Chim K, So J, Jalbert I (2012) Lid margins: sensitivity, staining, meibomian gland dysfunction, and symptoms. Optom Vis Sci 89:e1443–e1449

    Google Scholar 

  96. Powell DR, Nichols JJ, Nichols KK (2012) Inter-examiner reliability in meibomian gland dysfunction assessment. Invest Ophthalmol Vis Sci 53:3120–3125

    PubMed Central  PubMed  Google Scholar 

  97. Nichols JJ, Berntsen DA, Mitchell GL, Nichols KK (2005) An assessment of grading scales for meibography images. Cornea 24:382–388

    PubMed  Google Scholar 

  98. Pult H, Riede-Pult B (2013) Comparison of subjective grading and objective assessment in meibography. Contact Lens Anterior Eye J Br Contact Lens Assoc 36:22–27

    Google Scholar 

  99. Koh YW, Celik T, Lee HK, Petznick A, Tong L (2012) Detection of meibomian glands and classification of meibography images. J Biomed Opt 17:086008

    PubMed  Google Scholar 

  100. Hwang HS, Shin JG, Lee BH, Eom TJ, Joo CK (2013) In vivo 3D meibography of the human eyelid using real time imaging fourier-domain OCT. PloS One 8:e67143

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Goto E, Shimazaki J, Monden Y, Takano Y, Yagi Y, Shimmura S, Tsubota K (2002) Low-concentration homogenized castor oil eye drops for noninflamed obstructive meibomian gland dysfunction. Ophthalmology 109:2030–2035

    PubMed  Google Scholar 

  102. Korb DR, Henriquez AS (1980) Meibomian gland dysfunction and contact lens intolerance. J Am Optom Assoc 51:243–251

    CAS  PubMed  Google Scholar 

  103. Dougherty JM, Osgood JK, McCulley JP (1991) The role of wax and sterol ester fatty acids in chronic blepharitis. Invest Ophthalmol Vis Sci 32:1932–1937

    CAS  PubMed  Google Scholar 

  104. Shine WE, McCulley JP (1993) Role of wax ester fatty alcohols in chronic blepharitis. Invest Ophthalmol Vis Sci 34:3515–3521

    CAS  PubMed  Google Scholar 

  105. McCulley JP, Shine WE (2004) The lipid layer of tears: dependent on meibomian gland function. Exp Eye Res 78:361–365

    CAS  PubMed  Google Scholar 

  106. Suzuki T, Sano Y, Sasaki O, Kinoshita S (2002) Ocular surface inflammation induced by Propionibacterium acnes. Cornea 21:812–817

    PubMed  Google Scholar 

  107. Freedberg IM, Tomic-Canic M, Komine M, Blumenberg M (2001) Keratins and the keratinocyte activation cycle. J Invest Dermatol 116:633–640

    CAS  PubMed  Google Scholar 

  108. Mathers WD (1993) Ocular evaporation in meibomian gland dysfunction and dry eye. Ophthalmology 100:347–351

    CAS  PubMed  Google Scholar 

  109. Mathers WD, Lane JA (1998) Meibomian gland lipids, evaporation, and tear film stability. Adv Exp Med Biol 438:349–360

    CAS  PubMed  Google Scholar 

  110. Shimazaki J, Sakata M, Tsubota K (1995) Ocular surface changes and discomfort in patients with meibomian gland dysfunction. Arch Ophthalmol 113:1266–1270

    CAS  PubMed  Google Scholar 

  111. Lee SH, Tseng SC (1997) Rose bengal staining and cytologic characteristics associated with lipid tear deficiency. Am J Ophthalmol 124:736–750

    CAS  PubMed  Google Scholar 

  112. Yokoi N, Mossa F, Tiffany JM, Bron AJ (1999) Assessment of meibomian gland function in dry eye using meibometry. Arch Ophthalmol 117:723–729

    CAS  PubMed  Google Scholar 

  113. Goto E, Monden Y, Takano Y, Mori A, Shimmura S, Shimazaki J, Tsubota K (2002) Treatment of non-inflamed obstructive meibomian gland dysfunction by an infrared warm compression device. Br J Ophthalmol 86:1403–1407

    CAS  PubMed Central  PubMed  Google Scholar 

  114. Matsumoto Y, Dogru M, Goto E, Ishida R, Kojima T, Onguchi T, Yagi Y, Shimazaki J, Tsubota K (2006) Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction. Cornea 25:644–650

    PubMed  Google Scholar 

  115. Matsumoto Y, Sato EA, Ibrahim OM, Dogru M, Tsubota K (2008) The application of in vivo laser confocal microscopy to the diagnosis and evaluation of meibomian gland dysfunction. Mol Vis 14:1263–1271

    CAS  PubMed Central  PubMed  Google Scholar 

  116. Arita R, Itoh K, Maeda S, Maeda K, Furuta A, Fukuoka S, Tomidokoro A, Amano S (2009) Proposed diagnostic criteria for obstructive meibomian gland dysfunction. Ophthalmology 116:2058.e1–2063.e1

    Google Scholar 

  117. Romero JM, Biser SA, Perry HD, Levinson DH, Doshi SJ, Terraciano A, Donnenfeld ED (2004) Conservative treatment of meibomian gland dysfunction. Eye Contact Lens 30:14–19

    PubMed  Google Scholar 

  118. Prabhasawat P, Tesavibul N, Mahawong W (2012) A randomized double-masked study of 0.05% cyclosporine ophthalmic emulsion in the treatment of meibomian gland dysfunction. Cornea 31:1386–1393

    PubMed  Google Scholar 

  119. Goto E, Endo K, Suzuki A, Fujikura Y, Tsubota K (2002) Improvement of tear stability following warm compression in patients with meibomian gland dysfunction. Adv Exp Med Biol 506:1149–1152

    PubMed  Google Scholar 

  120. Olson MC, Korb DR, Greiner JV (2003) Increase in tear film lipid layer thickness following treatment with warm compresses in patients with meibomian gland dysfunction. Eye Contact lens 29:96–99

    PubMed  Google Scholar 

  121. Lane SS, DuBiner HB, Epstein RJ, Ernest PH, Greiner JV, Hardten DR, Holland EJ, Lemp MA, McDonald JE 2nd, Silbert DI, Blackie CA, Stevens CA, Bedi R (2012) A new system, the LipiFlow, for the treatment of meibomian gland dysfunction. Cornea 31:396–404

    PubMed  Google Scholar 

  122. Greiner JV (2013) Long-term (12-month) improvement in meibomian gland function and reduced dry eye symptoms with a single thermal pulsation treatment. Clin Exp Ophthalmol 41:524–530

    Google Scholar 

  123. Greiner JV (2012) A single LipiFlow(R) Thermal Pulsation System treatment improves meibomian gland function and reduces dry eye symptoms for 9 months. Curr Eye Res 37:272–278

    PubMed  Google Scholar 

  124. Friedland BR, Fleming CP, Blackie CA, Korb DR (2011) A novel thermodynamic treatment for meibomian gland dysfunction. Curr Eye Res 36:79–87

    PubMed  Google Scholar 

  125. Korb DR, Blackie CA (2010) Restoration of meibomian gland functionality with novel thermodynamic treatment device—a case report. Cornea 29:930–933

    PubMed  Google Scholar 

  126. Korb DR, Blackie CA (2013) Case report: a successful lipiflow treatment of a single case of Meibomian gland dysfunction and dropout. Eye Contact Lens 39(3):e1–e3

    PubMed  Google Scholar 

  127. Guillon M, Maissa C, Wong S (2012) Eyelid margin modification associated with eyelid hygiene in anterior blepharitis and meibomian gland dysfunction. Eye Contact Lens 38:319–325

    PubMed  Google Scholar 

  128. Guillon M, Maissa C, Wong S (2012) Symptomatic relief associated with eyelid hygiene in anterior blepharitis and MGD. Eye Contact Lens 38:306–312

    PubMed  Google Scholar 

  129. Sanchez J, Somolinos AL, Almodovar PI, Webster G, Bradshaw M, Powala C (2005) A randomized, double-blind, placebo-controlled trial of the combined effect of doxycycline hyclate 20-mg tablets and metronidazole 0.75% topical lotion in the treatment of rosacea. J Am Acad Dermatol 53:791–797

    PubMed  Google Scholar 

  130. Frucht-Pery J, Sagi E, Hemo I, Ever-Hadani P (1993) Efficacy of doxycycline and tetracycline in ocular rosacea. Am J Ophthalmol 116:88–92

    CAS  PubMed  Google Scholar 

  131. Yoo SE, Lee DC, Chang MH (2005) The effect of low-dose doxycycline therapy in chronic meibomian gland dysfunction. Korean J Ophthalmol 19:258–263

    PubMed  Google Scholar 

  132. Theobald K, Bradshaw M, Leyden J (2007) Anti-inflammatory dose doxycycline (40 mg controlled-release) confers maximum anti-inflammatory efficacy in rosacea. Skinmed 6:221–226

    PubMed  Google Scholar 

  133. Del Rosso JQ, Webster GF, Jackson M, Rendon M, Rich P, Torok H, Bradshaw M (2007) Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea. J Am Acad Dermatol 56:791–802

    PubMed  Google Scholar 

  134. Lee H, Min K, Kim EK, Kim TI (2012) Minocycline controls clinical outcomes and inflammatory cytokines in moderate and severe Meibomian gland dysfunction. Am J Ophthalmol 154(6):949.e1–957.e1

    Google Scholar 

  135. Foulks GN, Borchman D, Yappert M, Kakar S (2013) Topical azithromycin and oral doxycycline therapy of meibomian gland dysfunction: a comparative clinical and spectroscopic pilot study. Cornea 32(1):44–53

    Google Scholar 

  136. Dougherty JM, McCulley JP, Silvany RE, Meyer DR (1991) The role of tetracycline in chronic blepharitis. Inhibition of lipase production in staphylococci. Invest Ophthalmol Vis Sci 32:2970–2975

    CAS  PubMed  Google Scholar 

  137. Duerden JM, Tiffany JM (1990) Lipid synthesis in vitro by rabbit Meibomian gland tissue and its inhibition by tetracycline. Biochim Biophys Acta 1042:13–18

    CAS  PubMed  Google Scholar 

  138. Shine WE, McCulley JP, Pandya AG (2003) Minocycline effect on meibomian gland lipids in meibomianitis patients. Exp Eye Res 76:417–420

    CAS  PubMed  Google Scholar 

  139. Souchier M, Joffre C, Gregoire S, Bretillon L, Muselier A, Acar N, Beynat J, Bron A, D’Athis P, Creuzot-Garcher C (2008) Changes in meibomian fatty acids and clinical signs in patients with meibomian gland dysfunction after minocycline treatment. Br J Ophthalmol 92:819–822

    CAS  PubMed  Google Scholar 

  140. Nelson M, Hillen W, Greenwald RA (eds) (2001) Tetracyclines in biology, chemistry and medicine. Springer, Germany, 336 p

    Google Scholar 

  141. Yamaryo T, Oishi K, Yoshimine H, Tsuchihashi Y, Matsushima K, Nagatake T (2003) Fourteen-member macrolides promote the phosphatidylserine receptor-dependent phagocytosis of apoptotic neutrophils by alveolar macrophages. Antimicrob Agents Chemother 47:48–53

    CAS  PubMed Central  PubMed  Google Scholar 

  142. Sanz MJ, Nabah YN, Cerda-Nicolas M, O’Connor JE, Issekutz AC, Cortijo J, Morcillo EJ (2005) Erythromycin exerts in vivo anti-inflammatory activity downregulating cell adhesion molecule expression. Br J Pharmacol 144:190–201

    CAS  PubMed Central  PubMed  Google Scholar 

  143. Xu G, Fujita J, Negayama K, Yuube K, Hojo S, Yamaji Y, Kawanishi K, Takahara J (1996) Effect of macrolide antibiotics on macrophage functions. Microbiol Immunol 40:473–479

    CAS  PubMed  Google Scholar 

  144. Bouwman JJ, Visseren FL, Bouter PK, Diepersloot RJ (2004) Azithromycin inhibits interleukin-6 but not fibrinogen production in hepatocytes infected with cytomegalovirus and chlamydia pneumoniae. J Lab Clin Med 144:18–26

    CAS  PubMed  Google Scholar 

  145. Foulks GN, Borchman D, Yappert M, Kim SH, McKay JW (2010) Topical azithromycin therapy for meibomian gland dysfunction: clinical response and lipid alterations. Cornea 29:781–788

    PubMed Central  PubMed  Google Scholar 

  146. Luchs J (2010) Azithromycin in DuraSite for the treatment of blepharitis. Clin Ophthalmol 4:681–688

    PubMed Central  PubMed  Google Scholar 

  147. Akyol-Salman I, Azizi S, Mumcu UY, Ates O, Baykal O (2011) Comparison of the efficacy of topical N-acetyl-cysteine and a topical steroid-antibiotic combination therapy in the treatment of meibomian gland dysfunction. J Ocul Pharmacol Ther 28:49–52

    PubMed  Google Scholar 

  148. Matsumoto Y, Shigeno Y, Sato EA, Ibrahim OM, Saiki M, Negishi K, Ogawa Y, Dogru M, Tsubota K (2009) The evaluation of the treatment response in obstructive meibomian gland disease by in vivo laser confocal microscopy. Graefes Arch Clin Exp Ophthalmol 247:821–829

    PubMed  Google Scholar 

  149. Lindsley K, Matsumura S, Hatef E, Akpek EK (2012) Interventions for chronic blepharitis. Cochrane Database Syst Rev 5, CD005556

    PubMed  Google Scholar 

  150. Hamrah P, Qazi Y, Blackie CA, Korb DR (2012) Subclinical inflammation may explain the persistence of refractory dry eye symptoms after apparently successful treatment for meibomian gland dysfunction. ARVO Meeting Abstracts 53(6):594

    Google Scholar 

  151. Villani E, Ceresara G, Beretta S, Magnani F, Viola F, Ratiglia R (2011) In vivo confocal microscopy of meibomian glands in contact lens wearers. Invest Ophthalmol Vis Sci 52:5215–5219

    PubMed  Google Scholar 

  152. Villani E, Beretta S, De Capitani M, Galimberti D, Viola F, Ratiglia R (2010) In vivo confocal microscopy of meibomian glands in Sjogren’s syndrome. Invest Ophthalmol Vis Sci 52:933–939

    Google Scholar 

  153. Ibrahim OM, Matsumoto Y, Dogru M, Adan ES, Wakamatsu TH, Shimazaki J, Fujishima H, Tsubota K (2012) In vivo confocal microscopy evaluation of meibomian gland dysfunction in atopic-keratoconjunctivitis patients. Ophthalmology 119:1961–1968

    PubMed  Google Scholar 

  154. Wei A, Hong J, Sun X, Xu J (2011) Evaluation of age-related changes in human palpebral conjunctiva and meibomian glands by in vivo confocal microscopy. Cornea 30:1007–1012

    PubMed  Google Scholar 

  155. Kobayashi A, Yoshita T, Sugiyama K (2005) In vivo findings of the bulbar/palpebral conjunctiva and presumed meibomian glands by laser scanning confocal microscopy. Cornea 24:985–988

    PubMed  Google Scholar 

  156. Cavanagh HD, Jester JV, Essepian J, Shields W, Lemp MA (1990) Confocal microscopy of the living eye. CLAO J 16:65–73

    CAS  PubMed  Google Scholar 

  157. Bohnke M, Masters BR (1999) Confocal microscopy of the cornea. Prog Retin Eye Res 18:553–628

    CAS  PubMed  Google Scholar 

  158. Efron N, Al-Dossari M, Pritchard N (2009) In vivo confocal microscopy of the palpebral conjunctiva and tarsal plate. Optom Vis Sci 86:E1303–E1308

    PubMed  Google Scholar 

  159. Muller LJ, Marfurt CF, Kruse F, Tervo TM (2003) Corneal nerves: structure, contents and function. Exp Eye Res 76:521–542

    CAS  PubMed  Google Scholar 

  160. Grupcheva CN, Wong T, Riley AF, McGhee CN (2002) Assessing the sub-basal nerve plexus of the living healthy human cornea by in vivo confocal microscopy. Clin Exp Ophthalmol 30:187–190

    Google Scholar 

  161. Oliveira-Soto L, Efron N (2001) Morphology of corneal nerves using confocal microscopy. Cornea 20:374–384

    CAS  PubMed  Google Scholar 

  162. Marfurt CF, Cox J, Deek S, Dvorscak L (2010) Anatomy of the human corneal innervation. Exp Eye Res 90:478–492

    CAS  PubMed  Google Scholar 

  163. Tuominen IS, Konttinen YT, Vesaluoma MH, Moilanen JA, Helinto M, Tervo TM (2003) Corneal innervation and morphology in primary Sjogren’s syndrome. Invest Ophthalmol Vis Sci 44:2545–2549

    PubMed  Google Scholar 

  164. Villani E, Galimberti D, Viola F, Mapelli C, Ratiglia R (2007) The cornea in Sjogren’s syndrome: an in vivo confocal study. Invest Ophthalmol Vis Sci 48:2017–2022

    PubMed  Google Scholar 

  165. Erdelyi B, Kraak R, Zhivov A, Guthoff R, Nemeth J (2007) In vivo confocal laser scanning microscopy of the cornea in dry eye. Graefes Arch Clin Exp Ophthalmol 245:39–44

    PubMed  Google Scholar 

  166. Zhang X, Chen Q, Chen W, Cui L, Ma H, Lu F (2011) Tear dynamics and corneal confocal microscopy of subjects with mild self-reported office dry eye. Ophthalmology 118:902–907

    PubMed  Google Scholar 

  167. Benitez del Castillo JM, Wasfy MA, Fernandez C, Garcia-Sanchez J (2004) An in vivo confocal masked study on corneal epithelium and subbasal nerves in patients with dry eye. Invest Ophthalmol Vis Sci 45:3030–3035

    PubMed  Google Scholar 

  168. Vera LS, Gueudry J, Delcampe A, Roujeau JC, Brasseur G, Muraine M (2009) In vivo confocal microscopic evaluation of corneal changes in chronic Stevens–Johnson syndrome and toxic epidermal necrolysis. Cornea 28:401–407

    PubMed  Google Scholar 

  169. Hamrah P, Zhang Q, Liu Y, Dana MR (2002) Novel characterization of MHC class II-negative population of resident corneal Langerhans cell-type dendritic cells. Invest Ophthalmol Vis Sci 43:639–646

    PubMed  Google Scholar 

  170. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252

    CAS  PubMed  Google Scholar 

  171. Tuisku IS, Konttinen YT, Konttinen LM, Tervo TM (2008) Alterations in corneal sensitivity and nerve morphology in patients with primary Sjogren’s syndrome. Exp Eye Res 86:879–885

    CAS  PubMed  Google Scholar 

  172. Zhivov A, Stave J, Vollmar B, Guthoff R (2005) In vivo confocal microscopic evaluation of Langerhans cell density and distribution in the normal human corneal epithelium. Graefes Arch Clin Exp Ophthalmol 243:1056–1061

    PubMed  Google Scholar 

  173. Lin H, Li W, Dong N, Chen W, Liu J, Chen L, Yuan H, Geng Z, Liu Z (2010) Changes in corneal epithelial layer inflammatory cells in aqueous tear-deficient dry eye. Invest Ophthalmol Vis Sci 51:122–128

    PubMed  Google Scholar 

  174. Cruzat A, Witkin D, Baniasadi N, Zheng L, Ciolino JB, Jurkunas UV, Chodosh J, Pavan-Langston D, Dana R, Hamrah P (2011) Inflammation and the nervous system: the connection in the cornea in patients with infectious keratitis. Invest Ophthalmol Vis Sci 52:5136–5143

    CAS  PubMed Central  PubMed  Google Scholar 

  175. Benitez-Del-Castillo JM, Acosta MC, Wassfi MA, Diaz-Valle D, Gegundez JA, Fernandez C, Garcia-Sanchez J (2007) Relation between corneal innervation with confocal microscopy and corneal sensitivity with noncontact esthesiometry in patients with dry eye. Invest Ophthalmol Vis Sci 48:173–181

    PubMed  Google Scholar 

  176. Zhang M, Chen J, Luo L, Xiao Q, Sun M, Liu Z (2005) Altered corneal nerves in aqueous tear deficiency viewed by in vivo confocal microscopy. Cornea 24:818–824

    PubMed  Google Scholar 

  177. Labbe A, Alalwani H, Van Went C, Brasnu E, Georgescu D, Baudouin C (2012) The relationship between subbasal nerve morphology and corneal sensation in ocular surface disease. Invest Ophthalmol Vis Sci 53:4926–4931

    PubMed  Google Scholar 

  178. Bourcier T, Acosta MC, Borderie V, Borras F, Gallar J, Bury T, Laroche L, Belmonte C (2005) Decreased corneal sensitivity in patients with dry eye. Invest Ophthalmol Vis Sci 46:2341–2345

    PubMed  Google Scholar 

  179. Xu KP, Yagi Y, Tsubota K (1996) Decrease in corneal sensitivity and change in tear function in dry eye. Cornea 15:235–239

    CAS  PubMed  Google Scholar 

  180. Hosal BM, Ornek N, Zilelioglu G, Elhan AH (2005) Morphology of corneal nerves and corneal sensation in dry eye: a preliminary study. Eye (Lond) 19:1276–1279

    CAS  Google Scholar 

  181. De Paiva CS, Pflugfelder SC (2004) Corneal epitheliopathy of dry eye induces hyperesthesia to mechanical air jet stimulation. Am J Ophthalmol 137:109–115

    PubMed  Google Scholar 

  182. Stevenson W, Chauhan SK, Dana R (2012) Dry eye disease: an immune-mediated ocular surface disorder. Arch Ophthalmol 130:90–100

    CAS  PubMed Central  PubMed  Google Scholar 

  183. Zheng X, de Paiva CS, Li DQ, Farley WJ, Pflugfelder SC (2010) Desiccating stress promotion of Th17 differentiation by ocular surface tissues through a dendritic cell-mediated pathway. Invest Ophthalmol Vis Sci 51:3083–3091

    PubMed Central  PubMed  Google Scholar 

  184. Li S, Sack R, Vijmasi T, Sathe S, Beaton A, Quigley D, Gallup M, McNamara NA (2008) Antibody protein array analysis of the tear film cytokines. Optom Vis Sci 85:653–660

    PubMed Central  PubMed  Google Scholar 

  185. Solomon A, Dursun D, Liu Z, Xie Y, Macri A, Pflugfelder SC (2001) Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease. Invest Ophthalmol Vis Sci 42:2283–2292

    CAS  PubMed  Google Scholar 

  186. Katsifis GE, Rekka S, Moutsopoulos NM, Pillemer S, Wahl SM (2009) Systemic and local interleukin-17 and linked cytokines associated with Sjogren’s syndrome immunopathogenesis. Am J Pathol 175:1167–1177

    CAS  PubMed Central  PubMed  Google Scholar 

  187. Kang MH, Kim MK, Lee HJ, Lee HI, Wee WR, Lee JH (2011) Interleukin-17 in various ocular surface inflammatory diseases. J Korean Med Sci 26:938–944

    CAS  PubMed Central  PubMed  Google Scholar 

  188. Massingale ML, Li X, Vallabhajosyula M, Chen D, Wei Y, Asbell PA (2009) Analysis of inflammatory cytokines in the tears of dry eye patients. Cornea 28:1023–1027

    PubMed  Google Scholar 

  189. Pflugfelder SC, de Paiva CS, Li DQ, Stern ME (2008) Epithelial-immune cell interaction in dry eye. Cornea 27(Suppl 1):S9–S11

    PubMed  Google Scholar 

  190. Garcia-Hirschfeld J, Lopez-Briones LG, Belmonte C (1994) Neurotrophic influences on corneal epithelial cells. Exp Eye Res 59:597–605

    CAS  PubMed  Google Scholar 

  191. Beuerman RW, Schimmelpfennig B (1980) Sensory denervation of the rabbit cornea affects epithelial properties. Exp Neurol 69:196–201

    CAS  PubMed  Google Scholar 

  192. Beuerman RW, Stern ME (2005) Neurogenic inflammation: a first line of defense for the ocular surface. Ocul Surf 3:S203–S206

    PubMed  Google Scholar 

  193. Belmonte C, Acosta MC, Gallar J (2004) Neural basis of sensation in intact and injured corneas. Exp Eye Res 78:513–525

    CAS  PubMed  Google Scholar 

  194. Avetisov SE, Borodina NV, Safonova TN, Fedorov AA, Lutsevich EE, Matevosova EA, Malozhen SA (2009) Potentialities of confocal microscopy in the evaluation of the cornea in the dry eye syndrome. Vestn Oftalmol 125:52–54

    CAS  PubMed  Google Scholar 

  195. Labbe A, Liang Q, Wang Z, Zhang Y, Xu L, Baudouin C, Sun X (2013) Corneal nerve structure and function in patients with non-sjogren dry eye: clinical correlations. Invest Ophthalmol Vis Sci 54:5144–5150

    PubMed  Google Scholar 

  196. Ibrahim OM, Matsumoto Y, Dogru M, Adan ES, Wakamatsu TH, Goto T, Negishi K, Tsubota K (2010) The efficacy, sensitivity, and specificity of in vivo laser confocal microscopy in the diagnosis of meibomian gland dysfunction. Ophthalmology 117:665–672

    PubMed  Google Scholar 

  197. Qazi Y, Cavalcanti B, Cruzat A, Cheng S, Williams C, Trinidad M, Witkin D, Blackie CA, Korb DR, Hamrah P (2012) Immune response in meibomian gland dysfunction (MGD) and the effect of anti-inflammatory therapy: an in vivo confocal microscopy (IVCM) study. ARVO Meeting Abstracts 53

  198. Qazi Y, Cavalcanti BC, Cruzat A, Trinidad M, Williams C, Blackie CA, Korb DR, Hamrah P (2012) Symptomatic, clinical and imaging response following anti-inflammatory therapy for Meibomian Gland Dysfunction (MGD); Chicago. pp. page 186

  199. Maskin SL (2010) Intraductal meibomian gland probing relieves symptoms of obstructive meibomian gland dysfunction. Cornea 29:1145–1152

    Google Scholar 

  200. Wladis EJ (2012) Intraductal meibomian gland probing in the management of ocular rosacea. Ophthal Plast Reconstr Surg 28(6):416–418

    Google Scholar 

  201. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA et al (1991) Optical coherence tomography. Science 254:1178–1181

    CAS  PubMed  Google Scholar 

  202. Zhou Y, Tian L, Wang N, Dougherty PJ (2011) Anterior segment optical coherence tomography measurement of LASIK flaps: femtosecond laser vs microkeratome. J Refract Surg 27:408–416

    PubMed  Google Scholar 

  203. Werner L, Michelson J, Ollerton A, Leishman L, Bodnar Z (2012) Anterior segment optical coherence tomography in the assessment of postoperative intraocular lens optic changes. J Cataract Refract Surg 38:1077–1085

    PubMed  Google Scholar 

  204. Zhang XX, Zhong XW, Wu JS, Wang Z, Yu KM, Liu Q, Yang B (2012) Corneal flap morphological analysis using anterior segment optical coherence tomography in laser in situ keratomileusis with femtosecond lasers versus mechanical microkeratome. Int J Ophthalmol 5:69–73

    PubMed Central  PubMed  Google Scholar 

  205. Shabana N, Aquino MC, See J, Ce Z, Tan AM, Nolan WP, Hitchings R, Young SM, Loon SC, Sng CC, Wong W, Chew PT (2012) Quantitative evaluation of anterior chamber parameters using anterior segment optical coherence tomography in primary angle closure mechanisms. Clin Exp Ophthalmol 40:792–801

    Google Scholar 

  206. Sayegh RR, Pineda R 2nd (2012) Practical applications of anterior segment optical coherence tomography imaging following corneal surgery. Semin Ophthalmol 27:125–132

    PubMed  Google Scholar 

  207. Salim S (2012) The role of anterior segment optical coherence tomography in glaucoma. J Ophthalmol 2012:476801

    PubMed Central  PubMed  Google Scholar 

  208. Majander AS, Lindahl PM, Vasara LK, Krootila K (2012) Anterior segment optical coherence tomography in congenital corneal opacities. Ophthalmology 119:2450–2457

    PubMed  Google Scholar 

  209. Jhanji V, Constantinou M, Beltz J, Vajpayee RB (2011) Evaluation of posterior wound profile after penetrating keratoplasty using anterior segment optical coherence tomography. Cornea 30:277–280

    PubMed  Google Scholar 

  210. Aptel F, Beccat S, Fortoul V, Denis P (2011) Biometric analysis of pigment dispersion syndrome using anterior segment optical coherence tomography. Ophthalmology 118:1563–1570

    PubMed  Google Scholar 

  211. Gumus K, Crockett CH, Pflugfelder SC (2010) Anterior segment optical coherence tomography: a diagnostic instrument for conjunctivochalasis. Am J Ophthalmol 150:798–806

    PubMed Central  PubMed  Google Scholar 

  212. Ibrahim OM, Dogru M, Takano Y, Satake Y, Wakamatsu TH, Fukagawa K, Tsubota K, Fujishima H (2010) Application of visante optical coherence tomography tear meniscus height measurement in the diagnosis of dry eye disease. Ophthalmology 117:1923–1929

    PubMed  Google Scholar 

  213. Lim LS, Aung HT, Aung T, Tan DT (2008) Corneal imaging with anterior segment optical coherence tomography for lamellar keratoplasty procedures. Am J Ophthalmol 145:81–90

    PubMed  Google Scholar 

  214. Sarunic MV, Asrani S, Izatt JA (2008) Imaging the ocular anterior segment with real-time, full-range Fourier-domain optical coherence tomography. Arch Ophthalmol 126:537–542

    PubMed Central  PubMed  Google Scholar 

  215. Asrani S, Sarunic M, Santiago C, Izatt J (2008) Detailed visualization of the anterior segment using fourier-domain optical coherence tomography. Arch Ophthalmol 126:765–771

    PubMed Central  PubMed  Google Scholar 

  216. Radhakrishnan S, Rollins AM, Roth JE, Yazdanfar S, Westphal V, Bardenstein DS, Izatt JA (2001) Real-time optical coherence tomography of the anterior segment at 1310 nm. Arch Ophthalmol 119:1179–1185

    CAS  PubMed  Google Scholar 

  217. Gora M, Karnowski K, Szkulmowski M, Kaluzny BJ, Huber R, Kowalczyk A, Wojtkowski M (2009) Ultra high-speed swept source OCT imaging of the anterior segment of human eye at 200 kHz with adjustable imaging range. Opt Express 17:14880–14894

    CAS  PubMed  Google Scholar 

  218. Jungwirth J, Baumann B, Pircher M, Gotzinger E, Hitzenberger CK (2009) Extended in vivo anterior eye-segment imaging with full-range complex spectral domain optical coherence tomography. J Biomed Opt 14:050501

    PubMed Central  PubMed  Google Scholar 

  219. Hutchings N, Simpson TL, Hyun C, Moayed AA, Hariri S, Sorbara L, Bizheva K (2010) Swelling of the human cornea revealed by high-speed, ultrahigh-resolution optical coherence tomography. Invest Ophthalmol Vis Sci 51:4579–4584

    PubMed  Google Scholar 

  220. Bizheva K, Lee P, Sorbara L, Hutchings N, Simpson T (2010) In vivo volumetric imaging of the human upper eyelid with ultrahigh-resolution optical coherence tomography. J Biomed Opt 15:040508

    PubMed  Google Scholar 

  221. Qiu X, Gong L, Lu Y, Jin H, Robitaille M (2012) The diagnostic significance of Fourier-domain optical coherence tomography in Sjogren syndrome, aqueous tear deficiency and lipid tear deficiency patients. Acta Ophthalmol 90:e359–e366

    PubMed  Google Scholar 

  222. Qiu X, Gong L, Sun X, Jin H (2010) Age-related variations of human tear meniscus and diagnosis of dry eye with Fourier-domain anterior segment optical coherence tomography. Cornea 30:543–549

    Google Scholar 

  223. Nguyen P, Huang D, Li Y, Sadda SR, Ramos S, Pappuru RR, Yiu SC (2012) Correlation between optical coherence tomography-derived assessments of lower tear meniscus parameters and clinical features of dry eye disease. Cornea 31:680–685

    PubMed Central  PubMed  Google Scholar 

  224. Ibrahim OM, Dogru M, Kojima T, Matsumoto Y, Wakamatsu TH, Tsubota K, Fujishima H (2012) OCT assessment of tear meniscus after punctal occlusion in dry eye disease. Optom Vis Sci 89:E770–E776

    PubMed  Google Scholar 

  225. Altan-Yaycioglu R, Sizmaz S, Canan H, Coban-Karatas M (2013) Optical coherence tomography for measuring the tear film meniscus: correlation with Schirmer test and tear-film breakup time. Curr Eye Res 38:736–742

    PubMed  Google Scholar 

  226. Werkmeister RM, Alex A, Kaya S, Unterhuber A, Hofer B, Riedl J, Bronhagl M, Vietauer M, Schmidl D, Schmoll T, Garhofer G, Drexler W, Leitgeb RA, Groeschl M, Schmetterer L (2013) Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography. Invest Ophthalmol Vis Sci 54:5578–5583

    PubMed  Google Scholar 

  227. Chen Q, Zhang X, Cui L, Huang Q, Chen W, Ma H, Lu F (2011) Upper and lower tear menisci in Sjogren’s syndrome dry eye. Invest Ophthalmol Vis Sci 52:9373–9378

    PubMed  Google Scholar 

  228. Veres A, Tapaszto B, Kosina-Hagyo K, Somfai GM, Nemeth J (2011) Imaging lid-parallel conjunctival folds with OCT and comparing its grading with the slit lamp classification in dry eye patients and normal subjects. Invest Ophthalmol Vis Sci 52:2945–2951

    PubMed  Google Scholar 

  229. Tapaszto B, Veres A, Kosina-Hagyo K, Somfai GM, Nemeth J (2011) OCT Imaging of lid-parallel conjunctival folds in soft contact lens wearers. Optom Vis Sci 88:1206–1213

    PubMed  Google Scholar 

  230. Zeiss C (2009) Visante Omni — a new dimension in anterior segment evaluation (Carl Zeiss Meditech Inc.)

  231. Dartt D, Bex P, D’Amore P, Dana R, Mcloon L, Niederkorn J (2011) Ocular periphery and disorders. Academic Press, Oxford, UK

    Google Scholar 

  232. Bioptigen (2013) Envisu C-Class System Comparison. Bioptigen Inc.

  233. Li Y, Tang M, Zhang X, Salaroli CH, Ramos JL, Huang D (2010) Pachymetric mapping with Fourier-domain optical coherence tomography. J Cataract Refract Surg 36:826–831

    PubMed Central  PubMed  Google Scholar 

  234. Optovue (2008–2013) RTVue: power for your practice

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Acknowledgments

We would like to thank our sponsors for their generous support through grants from the National Institute of Health (NIH K08-EY020575 to PH), Research to Prevent Blindness Career Development Award (PH) and Falk Medical Research Foundation (PH).

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None for all authors.

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Authors and Affiliations

  1. Ocular Surface Imaging Center, Cornea Service, Cornea & Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, and Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, MA, 02114, USA

    Yureeda Qazi, Shruti Aggarwal & Pedram Hamrah

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  1. Yureeda Qazi
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  2. Shruti Aggarwal
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  3. Pedram Hamrah
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Correspondence to Pedram Hamrah.

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Yureeda Qazi and Shruti Aggarwal contributed equally to this work.

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Qazi, Y., Aggarwal, S. & Hamrah, P. Image-guided evaluation and monitoring of treatment response in patients with dry eye disease. Graefes Arch Clin Exp Ophthalmol 252, 857–872 (2014). https://doi.org/10.1007/s00417-014-2618-2

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