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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-09-2017 | Cornea

Correlation between corneal innervation and inflammation evaluated with confocal microscopy and symptomatology in patients with dry eye syndromes: a preliminary study

Authors: Tudor C. Tepelus, Gloria B. Chiu, Jianyan Huang, Ping Huang, SriniVas R. Sadda, John Irvine, Olivia L. Lee

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 9/2017

Abstract

Purpose

To evaluate corneal innervation and inflammatory cell infiltration using in vivo confocal microscopy (IVCM) and to correlate these findings with subjective symptoms of dry eye, as measured by the Ocular Surface Disease Index (OSDI) in patients with non-Sjögren’s (NSDE) and Sjögren’s syndrome dry eyes (SSDE).

Methods

Central corneal images were prospectively captured from 10 age-matched healthy control eyes, 24 eyes with clinically diagnosed NSDE and 44 eyes with clinically diagnosed SSDE, using IVCM (HRT III RCM). Density, tortuosity and reflectivity of corneal nerves, presence of inflammatory dendritic cells (DCs) and OSDI scores were evaluated.

Results

Images obtained by IVCM from 78 eyes were analyzed. The density of nerve fibers was 1562 ± 996 μm/frame in the SSDE group, 2150 ± 1015 μm/frame in the NSDE group and 2725 ± 687 μm/frame in the control group (P < 0.05, ANOVA). In comparison to the control group, the density of nerve fibers was decreased in the SSDE (P < 0.001) and the NSDE groups (P = 0.06), with increased nerve tortuosity and decreased reflectivity in both groups (both P < 0.05). The density of DCs was 71.65 ± 72.54 cells/mm² in the SSDE group, 40.33 ± 31.63 cells/mm² in the NSDE group and 27.53 ± 5.58 cells/mm² in the control group (P < 0.05, ANOVA). In comparison to the control group, the density of DCs was increased in the SSDE (P < 0.001) and the NSDE groups (P = 0.07). Significant correlations were found between the nerve density and DC density (r = −0.57, P < 0.001), between the nerve density and OSDI scores (r = −0.91, P < 0.001) and between the nerve reflectivity and OSDI scores (r = −0.75, P < 0.001).

Conclusions

The corneas of eyes affected with NSDE and SSDE are characterized by alterations in corneal innervation and infiltration of inflammatory DCs. Corneal nerve density and reflectivity are correlated with severity of subjective dry eye symptoms, as measured by OSDI score.

Alhatem A, Cavalcanti B, Hamrah P (2012) In vivo confocal microscopy in dry eye disease and related conditions. Semin Ophthalmol 27:138–148. doi:10.3109/08820538.2012.711416 CrossRefPubMedPubMedCentral

Courtin R, Pereira B, Naughton G et al (2016) Prevalence of dry eye disease in visual display terminal workers: a systematic review and meta-analysis. BMJ Open 6:e009675. doi:10.1136/bmjopen-2015-009675 CrossRefPubMedPubMedCentral

Herrero-Vanrell R, Peral A (2007) International dry eye Workshop (DEWS). Update of the disease. Arch Soc Esp Oftalmol 82:733–734PubMed

Stern ME, Beuerman RW, Fox RI et al (1998) The pathology of dry eye: the interaction between the ocular surface and lacrimal glands. Cornea 17:584–589CrossRefPubMed

Stern ME, Gao J, Siemasko KF et al (2004) The role of the lacrimal functional unit in the pathophysiology of dry eye. Exp Eye Res 78:409–416CrossRefPubMed

Rolando M (2001) Sjogren’s syndrome as seen by an ophthalmologist. Scand J Rheumatol Suppl 115:23–27

Muller LJ, Pels L, Vrensen GF (1996) Ultrastructural organization of human corneal nerves. Invest Ophthalmol Vis Sci 37:476–488PubMed

Guthoff RF, Wienss H, Hahnel C, Wree A (2005) Epithelial innervation of human cornea: a three-dimensional study using confocal laser scanning fluorescence microscopy. Cornea 24:608–613CrossRefPubMed

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

10.

Nishida T (2005) Neurotrophic mediators and corneal wound healing. Ocul Surf 3:194–202CrossRefPubMed

11.

Cruzat A, Witkin D, Baniasadi N et al (2011) Inflammation and the nervous system: the connection in the cornea in patients with infectious keratitis. Invest Ophthalmol Vis Sci 52:5136–5143. doi:10.1167/iovs.10-7048 CrossRefPubMedPubMedCentral

12.

Lin H, Li W, Dong N, et al. (2010) Changes in corneal epithelial layer inflammatory cells in aqueous tear-deficient dry eye. Invest Ophthalmol Vis Sci 51:122–128. doi:10.1167/iovs.09-3629

13.

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. doi:10.1007/s00417-004-1075-8 CrossRefPubMed

14.

Cruzat A, Pavan-Langston D, Hamrah P (2010) In vivo confocal microscopy of corneal nerves: analysis and clinical correlation. Semin Ophthalmol 25:171–177. doi:10.3109/08820538.2010.518133 CrossRefPubMedPubMedCentral

15.

Patel DV, McGhee CN (2009) In vivo confocal microscopy of human corneal nerves in health, in ocular and systemic disease, and following corneal surgery: a review. Br J Ophthalmol 93:853–860. doi:10.1136/bjo.2008.150615 CrossRefPubMed

16.

Vitali C, Bootsma H, Bowman SJ et al (2013) Classification criteria for Sjogren’s syndrome: we actually need to definitively resolve the long debate on the issue. Ann Rheum Dis 72:476–478. doi:10.1136/annrheumdis-2012-202565 CrossRefPubMed

17.

Meijering E, Jacob M, Sarria JC et al (2004) Design and validation of a tool for neurite tracing and analysis in fluorescence microscopy images. Cytom A 58:167–176. doi:10.1002/cyto.a.20022 CrossRef

18.

Schiffman RM, Christianson MD, Jacobsen G et al (2000) Reliability and validity of the ocular surface disease Index. Arch Ophthalmol 118:615–621. doi:10.1001/archopht.118.5.615 CrossRefPubMed

19.

Authors N (2007) Research in dry eye: report of the research Subcommittee of the International dry eye WorkShop (2007). Ocul Surf 5:179–193. doi:10.1016/S1542-0124(12)70086-1 CrossRef

20.

García-Carrasco M, Fuentes-Alexandro S, Escárcega RO et al (2006) Pathophysiology of Sjogren’s syndrome. Arch Med Res 37:921–932. doi:10.1016/j.arcmed.2006.08.002 CrossRefPubMed

21.

Authors N (2007) The epidemiology of dry eye disease: report of the epidemiology Subcommittee of the International dry eye WorkShop (2007). Ocul Surf 5:93–107. doi:10.1016/S1542-0124(12)70082-4 CrossRef

22.

Niederer RL, Perumal D, Sherwin T, McGhee CN (2007) Age-related differences in the normal human cornea: a laser scanning in vivo confocal microscopy study. Br J Ophthalmol 91:1165–1169. doi:10.1136/bjo.2006.112656 CrossRefPubMedPubMedCentral

23.

Hamrah P, Cruzat A, Dastjerdi MH et al (2010) Corneal sensation and subbasal nerve alterations in patients with herpes simplex keratitis: an in vivo confocal microscopy study. Ophthalmology 117:1930–1936. doi:10.1016/j.ophtha.2010.07.010 CrossRefPubMedPubMedCentral

24.

Malik RA, Kallinikos P, Abbott CA et al (2003) Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients. Diabetologia 46:683–688. doi:10.1007/s00125-003-1086-8 CrossRefPubMed

25.

Rosenberg ME, Tervo TM, Immonen IJ et al (2000) Corneal structure and sensitivity in type 1 diabetes mellitus. Invest Ophthalmol Vis Sci 41:2915–2921PubMed

26.

Kallinikos P, Berhanu M, O’Donnell C et al (2004) Corneal nerve tortuosity in diabetic patients with neuropathy. Invest Ophthalmol Vis Sci 45:418–422CrossRefPubMed

27.

Calvillo MP, McLaren JW, Hodge DO, Bourne WM (2004) Corneal reinnervation after LASIK: prospective 3-year longitudinal study. Invest Ophthalmol Vis Sci 45:3991–3996. doi:10.1167/iovs.04-0561 CrossRefPubMed

28.

Erie JC, McLaren JW, Hodge DO, Bourne WM (2005) Recovery of corneal subbasal nerve density after PRK and LASIK. Am J Ophthalmol 140:1059–1064. doi:10.1016/j.ajo.2005.07.027 CrossRefPubMed

29.

Villani E, Galimberti D, Viola F et al (2008) Corneal involvement in rheumatoid arthritis: an in vivo confocal study. Invest Ophthalmol Vis Sci 49:560–564. doi:10.1167/iovs.07-0893 CrossRefPubMed

30.

Benitez-Del-Castillo JM, Acosta MC, Wassfi MA et al (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. doi:10.1167/iovs.06-0127 CrossRefPubMed

31.

Hosal BM, Ornek N, Zilelioglu G, Elhan AH (2005) Morphology of corneal nerves and corneal sensation in dry eye: a preliminary study. Eye 19:1276–1279. doi:10.1038/sj.eye.6701760 CrossRefPubMed

32.

Tuominen IS, Konttinen YT, Vesaluoma MH et al (2003) Corneal innervation and morphology in primary Sjogren’s syndrome. Invest Ophthalmol Vis Sci 44:2545–2549CrossRefPubMed

33.

Zhang M, Chen J, Luo L et al (2005) Altered corneal nerves in aqueous tear deficiency viewed by in vivo confocal microscopy. Cornea 24:818–824CrossRefPubMed

34.

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 43:639–646PubMed

35.

Nakamura T, Ishikawa F, Sonoda KH et al (2005) Characterization and distribution of bone marrow-derived cells in mouse cornea. Invest Ophthalmol Vis Sci 46:497–503. doi:10.1167/iovs.04-1154 CrossRefPubMed

36.

Mastropasqua L, Nubile M, Lanzini M et al (2006) Epithelial dendritic cell distribution in normal and inflamed human cornea: in vivo confocal microscopy study. Am J Ophthalmol 142:736–744. doi:10.1016/j.ajo.2006.06.057 CrossRefPubMed

37.

Labbe A, Gheck L, Iordanidou V et al (2010) An in vivo confocal microscopy and impression cytology evaluation of pterygium activity. Cornea 29:392–399. doi:10.1097/ICO.0b013e3181bd44ce CrossRefPubMed

38.

Wang Y, Zhao F, Zhu W et al (2010) In vivo confocal microscopic evaluation of morphologic changes and dendritic cell distribution in pterygium. Am J Ophthalmol 150:650–655 e1. doi:10.1016/j.ajo.2010.05.025 CrossRefPubMed

39.

Tuisku IS, Konttinen YT, Konttinen LM, Tervo TM (2008) Alterations in corneal sensitivity and nerve morphology in patients with primary Sjögren’s syndrome. Exp Eye Res 86:879–885. doi:10.1016/j.exer.2008.03.002 CrossRefPubMed

40.

Comstock TL, Decory HH (2012) Advances in corticosteroid therapy for ocular inflammation: Loteprednol etabonate. Int J Inflam. doi:10.1155/2012/789623 PubMedPubMedCentral

41.

Villani E, Garoli E, Termine V et al (2015) Corneal confocal microscopy in dry eye treated with corticosteroids. Optom Vis Sci 92:e290–e295. doi:10.1097/OPX.0000000000000600 CrossRefPubMed

Title: Correlation between corneal innervation and inflammation evaluated with confocal microscopy and symptomatology in patients with dry eye syndromes: a preliminary study
Authors: Tudor C. Tepelus
Gloria B. Chiu
Jianyan Huang
Ping Huang
SriniVas R. Sadda
John Irvine
Olivia L. Lee
Publication date: 01-09-2017
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 9/2017
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-017-3680-3

At a glance: The STEP trials

Springer Medicine

Correlation between corneal innervation and inflammation evaluated with confocal microscopy and symptomatology in patients with dry eye syndromes: a preliminary study

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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