Abstract
The recently developed confocal cornea microscopy offers the opportunity to examine pathologies of the cornea and to gain insight into the activity of innate immunity. We aimed to investigate the corneal epithelial and Langerhans cell (LC) densities along with dry eye parameters in primary open-angle glaucoma (POAG) subjects, treated with either of two commercially available travoprost 0.004 % topical medications containing different preservatives. (1: benzalkonium chloride 0.015 % (TravBAK) and 2: polyquaternium-1 (PQ) 0.001 % (TravPQ). Consecutive case series of nineteen POAG patients on TravBAK (mean age: 64.8 ± 13.6 years), nineteen POAG patients on TravPQ (mean age: 66.8 ± 11.3 years) and nineteen age-matched healthy control subjects (63.8 ± 8.2 years). Ocular surface disease index (OSDI), lid parallel conjunctival folds (LIPCOF), Schirmer test (ST) and tear break up time (TBUT) were assessed, and then corneal epithelial and LC densities were investigated with confocal microscopy. Tear production was significantly reduced in both glaucoma patient groups compared to healthy individuals (p < 0.05). TBUT was significantly reduced and epithelial cell densities were significantly greater in patients treated with TravBAK compared to healthy individuals (p < 0.05 for all). LC densities were greater in both glaucoma groups compared to control subjects (p < 0.05 for all). Travoprost therapy may compromise ocular surface. The limited alertness of the corneal immune system found in patients with TravPQ can be considered as indicators of a less disturbed ocular surface and better controlled corneal homeostasis.
Similar content being viewed by others
References
Martone G, Frezzotti P, Tosi GM, Traversi C, Mittica V, Malandrini A, Pichierri P, Balestrazzi A, Motolese PA, Motolese I, Motolese E (2009) An in vivo confocal microscopy analysis of effects of topical antiglaucoma therapy with preservative on corneal innervation and morphology. Am J Ophthalmol 147:725–735
Epstein SP, Chen D, Asbell PA (2009) Evaluation of biomarkers of inflammation in response to benzalkonium chloride on corneal and conjunctival epithelial cells. J Ocul Pharmacol and Ther 25:415–424
Noecker RJ, Herrygers LA, Anwaruddin R (2004) Corneal and conjunctival changes caused by commonly used glaucoma medications. Cornea 23:490–496
Whitson JT, Petroll WM (2012) Corneal epithelial cell viability following exposure to ophthalmic solutions containing preservatives and/or antihypertensive agents. Adv Ther 29:874–888
Horsley MB, Kahook MY (2009) Effects of prostaglandin analog therapy on the ocular surface of glaucoma patients. Clin Ophthalmol 3:291–295
Labbé A, Pauly A, Liang H, Brignole-Baudouin F, Martin C, Warnet JM, Baudouin C (2006) Comparison of toxicological profiles of benzalkonium chloride and polyquaternium-1: an experimental study. J Ocul Pharmacol 22:267–278
Aptel F, Cucherat M, Denis P (2008) Efficacy and tolerability of prostaglandin analogs: a meta-analysis of randomized controlled clinical trials. J Glaucoma 17:667–673
Hamrah P, Huq SO, Liu Y, Zhang Q, Dana MR (2003) Corneal immunity is mediated by heterogeneous population of antigen-presenting cells. J Leuk Biol 74:172–178
Hazlett LD, McClellan SM, Hume EB, Dajcs JJ, O’Callaghan RJ (1999) Willcox, M.D. Extended wear contact lens wear usage induces Langerhans cell migration into cornea. Exp Eye Res 69:575–577
Zhivov A, Stave J, Vollmar B, Guthoff R (2007) In vivo confocal microscopic evaluation of Langerhans cell density and distribution in the corneal epithelium of healthy volunteers and contact lens wearers. Cornea 26:47–54
Marsovszky L, Resch MD, Németh J, Toldi G, Medgyesi E, Kovács L, Balog A (2013) In vivo confocal microscopic evaluation of corneal Langerhans cell density, and distribution and evaluation of dry eye in rheumatoid arthritis. Innate Immun 19:348–354
Pult H, Purslow C, Murphy PJ (2011) The relationship between clinical signs and dry eye symptoms. Eye 25:502–510
Zhivov A, Stave J, Vollmar B, Guthoff R (2005) In vivo confocal microscopic evaluation of Langerhans cells density and distribution in the normal corneal epithelium. Graefe’s Arch Clin Exp Ophthalmol 243:1056–1061
Marsovszky L, Németh J, Resch MD, Toldi G, Legány N, Kovács L, Balog A (2013) Corneal Langerhans cell and dry eye examinations in ankylosing spondylitis. Innate Immun Aug 19
Baratz KH, Nau CB, Winter EJ, McLaren JW, Hodge DO, Herman DC, Bourne WM (2006) Effects of glaucoma medications on corneal endothelium, keratocytes, and subbasal nerves among participants in the Ocular Hypertension Treatment Study. Cornea 25:1046–1052
Ammar DA, Kahook MY (2011) Effects of benzalkonium chloride- or polyquad-preserved fixed combination glaucoma medications on human trabecular meshwork cells. Mol Vision 17:1806–1813
Guenoun JM, Baudouin C, Rat P, Pauly A, Warnet JM, Brignole-Baudouin F (2005) In vitro comparison of cytoprotective and antioxidative effects of latanoprost, travoprost, and bimatoprost on conjuctiva-derived epithelial cells. Inv Ophth Vis Sci 46:4594–4599
Villani E, Beretta S, De Capitani M, Galimberti D, Viola F, Ratiglia R (2011) In vivo confocal microscopy of meibomian glands in Sjögren’s syndrome. Invest Ophthalmol Vis Sci 52:933–939
Pisella PJ, Pouliquen P, Baudouin C (2002) Prevalence of ocular symptoms and signs with preserved and preservative-free glaucoma medications. Br J Ophthalmol 86:418–423
Zhivov A, Kraak R, Bergter H, Kundf G, Beck R, Guthoff RF (2010) Influence of benzalkonium chloride on Langerhans cells in corneal epithelium and development of dry eye in healthy volunteers. Curr Eye Res 35:762–769
Gery I, Davies P, Derr J, Krett N, Barranger JA (1981) Relationship between production and release of lymphocyte-activating factor (interleukin-1) by murine macrophages: 1. Effects of various agents. Cell Immunol 64:293–303
Niederkorn JY, Peeler JS, Mellon J (1989) Phagocytosis of particulate antigens by corneal epithelial cells stimulate interleukin-1 secretion and migration of Langerhans cells into the central cornea. Reg Immunol 2:83–90
Dekaris I, Zhu SN, Dana MR (1999) TNF-alpha regulates corneal Langerhans cell migration. J Immunol 162:4235–4239
Hattori T, Chauhan SK, Lee H, Ueno H, Dana MR (2011) Characterization of Langerin-Expressing Dendritic Cell Subsets in the Normal Cornea. Invest Ophthalmol Vis Sci 52:4598–4604
Zhivov A, Stachs O, Kraak R, Stave J, Guthoff RF (2006) In vivo confocal microscopy of the ocular surface. Ocul Surf 4:81–93
Liang H, Brignole-Baudouin F, Riancho L, Baudouin C (2012) Reduced in vivo ocular surface toxicity with polyquad-preserved travoprost versus benzalkonium-preserved travoprost or latanoprost ophthalmic solutions. Ophthalmic Res 48:89–101
Paimela T, Ryhänen T, Kauppinen A, Marttila L, Salminen A, Kaarniranta K (2012) The preservative polyquaternium-1 increases cytoxicity and NFkappaB linked inflammation in human corneal epithelial cells. Mol Vis 18:1189–1196
Ranno S, Fogagnolo P, Rossetti L, Orzalesi N, Nucci P (2011) Changes in corneal parameters at confocal microscopy in treated glaucoma patients. Clin Ophthalmol 5:1037–1042
Acknowledgement
We would like to express our gratitude to Shikha Sud (specialist optometrist at Nottingham University, Dept. of Ophthalmology) for her valuable contribution in proofreading of the manuscript.
Conflict of Interest
None of the authors have financial, proprietary or other interest in any of the materials and instruments applied in the study. No financial support was received in this study.
Author information
Authors and Affiliations
Corresponding author
Additional information
There was no proprietary interest involved in this study.
Rights and permissions
About this article
Cite this article
Marsovszky, L., Resch, M.D., Visontai, Z. et al. Confocal Microscopy of Epithelial and Langerhans Cells of the Cornea in Patients Using Travoprost Drops Containing Two Different Preservatives. Pathol. Oncol. Res. 20, 741–746 (2014). https://doi.org/10.1007/s12253-014-9755-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12253-014-9755-0