Abstract
Purpose
To evaluate the symptoms and signs of ocular surface disease (OSD) and tear-film matrix metalloproteinase-9 (MMP-9) overexpression using point-of-care testing (InflammaDry test) in patients with primary open-angle glaucoma (POAG).
Methods
This prospective, case-control study included 67 patients diagnosed with POAG and 47 healthy control subjects. The OSD assessment included Schirmer-I test, the Oxford corneal stain scale, tear breakup time (TBUT), and the five-item dry eye questionnaire (DEQ-5). Measurement of extracellular MMP-9 level was performed using the InflammaDry test. The OSD parameters and MMP-9 expression levels were compared between the POAG group and the control group. Additional subgroup analysis in POAG group was performed according to number of topical glaucoma medications (Bottle 1, 2, or 3 medications).
Results
There were significant differences between the control and POAG groups for all OSD parameters. MMP-9 overexpression was observed in 71.6% of POAG group, whereas only 31.9% of control group showed MMP-9 overexpression. The subgroup analysis revealed that DEQ-5, Oxford stain score, Schirmer-I, and MMP-9 overexpression demonstrated no significant difference among the three groups. Abnormal TBUT (≤5 s) was observed in 37.5%, 59.1%, and 76.2% for each subgroup according to number of bottles (1, 2, and 3), and strong MMP-9 overexpression were also detected in 25.0%, 40.9%, and 61.9%, respectively (P = 0.032, P = 0.043).
Conclusions
The use of preservative-containing medications may affect the ocular surface in patients with POAG. Graded measurement of tear-film MMP-9 could provide more information on OSD and might be a more useful marker for inflammation than then conventional results obtained by using an MMP-9 kit.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
European Glaucoma Society Terminology and Guidelines for Glaucoma, 4th edition—Chapter 2. Classification and terminology supported by the EGS foundation: part 1: foreword; introduction; glossary; Chapter 2 classification and terminology. Br J Ophthalmol. 2017;101:73–127. PMID: 28424171.
Cvenkel B, Stunf S, Srebotnik Kirbis I, Strojan Flezar M. Symptoms and signs of ocular surface disease related to topical medication in patients with glaucoma. Clin Ophthalmol. 2015;9:625–31.
Steven DW, Alaghband P, Lim KS. Preservatives in glaucoma medication. Br J Ophthalmol. 2018;102:1497–503.
Lucca JA, Nunez JN, Farris RL. A comparison of diagnostic tests for keratoconjunctivitis sicca: lactoplate, Schirmer, and tear osmolarity. CLAO J. 1990;16:109–12.
Sambursky R, Davitt WF 3rd, Friedberg M, Tauber S. Prospective, multicenter, clinical evaluation of point-of-care matrix metalloproteinase-9 test for confirming dry eye disease. Cornea. 2014;33:812–8.
Nichols KK, Mitchell GL, Zadnik K. The repeatability of clinical measurements of dry eye. Cornea. 2004;23:272–85.
Sambursky R, Davitt WF 3rd, Latkany R, Tauber S, Starr C, Friedberg M, 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.
Chan TC, Ye C, Chan KP, Chu KO, Jhanji V. Evaluation of point-of-care test for elevated tear matrix metalloproteinase 9 in post-LASIK dry eyes. Br J Ophthalmol. 2016;100:1188–91.
Chotikavanich S, de Paiva CS, Li de Q, Chen JJ, Bian F, Farley WJ, et al. Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome. Investig Ophthalmol Vis Sci. 2009;50:3203–9.
Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008;17:350–5.
Lee SM, Lee JE, Kim SI, Jung JH, Shin J. Effect of topical glaucoma medication on tear lipid layer thickness in patients with unilateral glaucoma. Indian J Ophthalmol. 2019;67:1297–302.
Batra R, Tailor R, Mohamed S. Ocular surface disease exacerbated glaucoma: optimizing the ocular surface improves intraocular pressure control. J Glaucoma. 2014;23:56–60.
Pflugfelder SC, Baudouin C. Challenges in the clinical measurement of ocular surface disease in glaucoma patients. Clin Ophthalmol. 2011;5:1575–83.
Yang WJ, Yang YN, Cao J, Man ZH, Yuan J, Xiao X, et al. Risk factors for dry eye syndrome: a retrospective case-control study. Optom Vis Sci. 2015;92:e199–205.
The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol. 2000;130:429–40. PMID: 11024415.
Sihota R, Angmo D, Ramaswamy D, Dada T. Simplifying “target” intraocular pressure for different stages of primary open-angle glaucoma and primary angle-closure glaucoma. Indian J Ophthalmol. 2018;66:495–505.
Chalmers RL, Begley CG, Caffery B. Validation of the 5-item dry eye questionnaire (DEQ-5): discrimination across self-assessed severity and aqueous tear deficient dry eye diagnoses. Contact Lens Anterior Eye. 2010;33:55–60.
Wolffsohn JS, Arita R, Chalmers R, Djalilian A, Dogru M, Dumbleton K, et al. TFOS DEWS II Diagnostic Methodology report. Ocul Surf. 2017;15:539–74.
Camp A, Wellik SR, Tzu JH, Feuer W, Arheart KL, Sastry A, et al. Dry eye specific quality of life in veterans using glaucoma drops. Contact Lens Anterior Eye. 2015;38:220–5.
Fernandez CA, Galor A, Arheart KL, Musselman DL, Venincasa VD, Florez HJ, et al. Dry eye syndrome, posttraumatic stress disorder, and depression in an older male veteran population. Investig Ophthalmol Vis Sci. 2013;54:3666–72.
Lanza NL, McClellan AL, Batawi H, Felix ER, Sarantopoulos KD, Levitt RC, et al. Dry eye profiles in patients with a positive elevated surface matrix metalloproteinase 9 point-of-care test versus negative patients. Ocul Surf. 2016;14:216–23.
Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop. Ocul Surf. 2007;5:108–52. PMID: 17508118.
Han SB, Hyon JY, Woo SJ, Lee JJ, Kim TH, Kim KW. Prevalence of dry eye disease in an elderly Korean population. Arch Ophthalmol. 2011;129:633–8.
Perez-Bartolome F, Martinez-de-la-Casa JM, Arriola-Villalobos P, Fernandez-Perez C, Polo V, Garcia-Feijoo J. Ocular surface disease in patients under topical treatment for glaucoma. Eur J Ophthalmol. 2017;27:694–704.
Zaleska-Zmijewska A, Strzemecka E, Wawrzyniak ZM, Szaflik JP. Extracellular MMP-9-based assessment of ocular surface inflammation in patients with primary open-angle glaucoma. J Ophthalmol. 2019;2019:1240537.
Behzadian MA, Wang XL, Windsor LJ, Ghaly N, Caldwell RB. TGF-beta increases retinal endothelial cell permeability by increasing MMP-9: possible role of glial cells in endothelial barrier function. Investig Ophthalmol Vis Sci. 2001;42:853–9.
Afonso AA, Sobrin L, Monroy DC, Selzer M, Lokeshwar B, Pflugfelder SC. Tear fluid gelatinase B activity correlates with IL-1alpha concentration and fluorescein clearance in ocular rosacea. Investig Ophthalmol Vis Sci. 1999;40:2506–12.
Broadway DC, Grierson I, O’Brien C, Hitchings RA. Adverse effects of topical antiglaucoma medication. I. The conjunctival cell profile. Arch Ophthalmol. 1994;112:1437–45.
Liang H, Pauly A, Riancho L, Baudouin C, Brignole-Baudouin F. Toxicological evaluation of preservative-containing and preservative-free topical prostaglandin analogues on a three-dimensional-reconstituted corneal epithelium system. Br J Ophthalmol. 2011;95:869–75.
Amparo F, Jin Y, Hamrah P, Schaumberg DA, Dana R. What is the value of incorporating tear osmolarity measurement in assessing patient response to therapy in dry eye disease? Am J Ophthalmol. 2014;157:69–77.e62.
Garcia-Feijoo J, Sampaolesi JR. A multicenter evaluation of ocular surface disease prevalence in patients with glaucoma. Clin Ophthalmol. 2012;6:441–6.
Funding
Supported by a VHS Medical Center research grant, Republic of Korea (Grant number: VHSMC 18016). The funding organization had no role in the design or conduct of this research.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kim, D.W., Seo, J.H. & Lim, SH. Evaluation of ocular surface disease in elderly patients with glaucoma: expression of matrix metalloproteinase-9 in tears. Eye 35, 892–900 (2021). https://doi.org/10.1038/s41433-020-0993-y
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41433-020-0993-y
