The Correlation between Tear Matrix Metalloproteinase-9 Concentration and Clinical Findings in Dry Eye Disease

Hae Rang Kim; Hyo Kyung Lee

doi:10.3341/jkos.2019.60.12.1140

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Kim and Lee: The Correlation between Tear Matrix Metalloproteinase-9 Concentration and Clinical Findings in Dry Eye Disease

Original Article

Journal of the Korean Ophthalmological Society 2019; 60(12): 1140-1147.

Published online: 17 December 2019

DOI: https://doi.org/10.3341/jkos.2019.60.12.1140

The Correlation between Tear Matrix Metalloproteinase-9 Concentration and Clinical Findings in Dry Eye Disease

Hae Rang Kim, MD, Hyo Kyung Lee, MD

Department of Ophthalmology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.

Address reprint requests to Hyo Kyung Lee, MD. Department of Ophthalmology, Haeundae Paik Hospital, #875 Haeundae-ro, Haeundae-gu, Busan 48108, Korea. Tel: 82-51-797-2311, Fax: 82-51-797-2314, qthoi85@hanmail.net

Received 22 May 2019 Revised 4 July 2019 Accepted 6 December 2019

The Korean Ophthalmological Society

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To investigate the correlation between the matrix metalloproteinase-9 (MMP-9) concentration, and subjective symptoms and objective signs in dry eye patients.

Methods

We retrospectively reviewed the medical records of 134 eyes of 67 patients who were diagnosed with dry eye disease. The results of tear MMP-9, which were conducted at a care testing facility, were defined as negative (N), equivocal (E), weak positive (W), positive (P) or strong positive (S). Using three methods with different classification ranges, MMP-9 results were classified into a negative group or positive group. The objective signs of dry eye disease, including tear break-up time (TBUT), tear volume measured by Schirmer's test, degree of corneal erosion estimated by the Oxford stain score (OSS), and ocular surface disease index (OSDI) as the subjective symptom, were recorded. The differences of indices were compared between the negative and positive groups.

Results

There was no significant difference of the TBUT, Schirmer's test, or OSS between the MMP-9 negative and positive groups. Also, the percentage of females was significantly higher in the negative group compared with the positive group regardless of the classification methods (all, p < 0.05). When the MMP-9N alone was classified as a negative group, the OSDI score was significantly higher in the positive group when compared to that of the negative group (p = 0.009).

Conclusions

The measurement of MMP-9 in patients with dry eye disease may be helpful in predicting subjective symptoms of dry eye disease.

Keywords: Dry eye disease, Matrix metalloproteinase 9, Ocular surface disease index, Tear matrix metalloproteinase-9

Figures and Tables

Figure 1

Classification of matrix metalloproteinase-9 (MMP-9) test results. Distinct blue line in the result zone guarantees both the accuracy of test procedures and the validity of test results. Absence of red line is defined as ‘Negative (N)’ and marked red line parallel to blue line is defined as ‘Strong positive (S)’, with in-between subdivisions proportionally to the clarity of the red line. The red line gradually becomes more prominent from the left to the right configurations.

Figure 2

Categorization of the patients based on the results of matrix metalloproteinase-9 (MMP-9). (A) Result of MMP-9 negative was identified as negative group and the result of MMP-9 equivocal, weak positive, positive, and strong positive were categorized as positive group. (B) Result of MMP-9 negative and equivocal were categorized as negative group and the result of MMP-9 weak positive, positive, and strong positive were categorized as positive group. (C) Result of MMP-9 negative, equivocal, and weak positive were categorized as negative group while the other results of MMP-9 were categorized as positive group.

Figure 3

The difference of ocular surface disease index (OSDI) between the groups. (A) OSDI scores when result of matrix metalloproteinase-9 (MMP-9) negative was identified as negative. Note the significant difference of the average of OSDI scores between the negative (N) and positive (EWPS) (^*p < 0.05). No significant difference of OSDI score was found when result of MMP-9 negative and equivocal were assumed as negative (B) nor result of MMP-9 negative, equivocal, and weak positive were assumed as negative (C).

Table 1

Baseline characteristics

Values are presented as mean ± standard deviation unless otherwise indicated.

BCVA = best corrected visual acuity; logMAR = logarithm of minimal angle of resolution; TBUT = tear breakup time; OSS = oxford stain score; OSDI = ocular surface disease index.

Table 2

Comparison of the demographics and test results between MMP-9 negative group and MMP-9 positive group when assuming result of MMP-9 negative as negative group

Values are presented as mean ± standard deviation unless otherwise indicated.

MMP = matrix metalloproteinase; BCVA = best corrected visual acuity; logMAR = logarithm of minimal angle of resolution; TBUT = tear breakup time; OSS = Oxford stain score; OSDI = Ocular surface disease index.

^*The comparison was performed by using Student t-test; ^†the comparison was performed by using Pearson's chi-squared test; ‡the comparison was performed by division based on the subjects, not by eyes. If MMP-9 results in both eyes are not identical, more severe MMP-9 results are selected for the analysis. Eight patients are included in the negative group (N) and 59 patients are included in the positive group (EWPS).

Table 3

Comparison of the demographics and test results between MMP-9 negative group and MMP-9 positive group when assuming result of MMP-9 negative and equivocal as negative group

Values are presented as mean ± standard deviation unless otherwise indicated.

^*The comparison was performed by using Student t-test; ^†the comparison was performed by using Pearson's chi-squared test; ^‡the comparison was performed by division based on the subjects, not by eyes. If MMP-9 results in both eyes are not identical, more severe MMP-9 results are selected for the analysis. Twenty six patients are included in the negative group (NE) and 41 patients are included in the positive group (WPS).

Table 4

Comparison of the demographics and test results between MMP-9 negative group and MMP-9 positive group when assuming result of MMP-9 negative, equivocal and weak positive as negative group

Values are presented as mean ± standard deviation unless otherwise indicated.

^*The comparison was performed by using student t-test; ^†the comparison was performed by using Pearson's chi-squared test; ^‡the comparison was performed by division based on the subjects, not by eyes. If MMP-9 results in both eyes are not identical, more severe MMP-9 results are selected for the analysis. Thirty three patients are included in the negative group (NEW) and 34 patients are included in the positive group (PS).

Notes

^{Conflicts of Interest} The authors have no conflicts to disclose.

References

1. Lemp MA. Report of the national eye institute/industry workshop on clinical trials in dry eyes. CLAO J. 1995; 21:221–232.

2. 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; 5:75–92.

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

4. Uchino M, Dogru M, Yagi Y, et al. The features of dry eye disease in a Japanese elderly population. Optom Vis Sci. 2006; 83:797–802.

5. Ahn JM, Lee SH, Rim TH, et al. Prevalence of and risk factors associated with dry eye: the Korea National Health and Nutrition Examination Survey 2010-2011. Am J Ophthalmol. 2014; 158:1205–1214.

6. Roh HC, Lee JK, Kim M, et al. Systemic comorbidities of dry eye syndrome: the Korean National Health and Nutrition Examination Survey V, 2010 to 2012. Cornea. 2016; 35:187–192.

7. Bron AJ. Diagnosis of dry eye. Surv Ophthalmol. 2001; 45 Suppl 2:S221–S226.

8. Mishima S, Kubota Z, Farris RL. The tear flow dynamics in normal and in keratoconjunctivitis sicca cases. Excerpta Medica Int Congr Ser. 1970; 222:1801–1805.

9. Baudouin C, Aragona P, Van Setten G, et al. Diagnosing the severity of dry eye: a clear and practical algorithm. Br J Ophthalmol. 2014; 98:1168–1176.

10. Messmer EM, von Lindenfels V, Garbe A, Kampik A. Matrix metalloproteinase 9 testing in dry eye disease using a commercially available point-of-care immunoassay. Ophthalmology. 2016; 123:2300–2308.

11. Lanza NL, Valenzuela F, Perez VL, Galor A. The matrix metalloproteinase 9 point-of-care test in dry eye. Ocul Surf. 2016; 14:189–195.

12. Lanza NL, McClellan AL, Batawi H, 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; 14:216–223.

13. Seo MH, Shin JY, Lee DH, Kim JH. Objective parameters associated with subjective symptom severity in dry eye syndrome patients. J Korean Ophthalmol Soc. 2017; 58:259–267.

14. Sambursky R, Davitt WF 3rd, 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; 131:24–28.

15. Pflugfelder SC, de Paiva CS. The pathophysiology of dry eye disease: what we know and future directions for research. Ophthalmology. 2017; 124:S4–S13.

16. 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; 33:812–818.

17. Bron AJ, Evans VE, Smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea. 2003; 22:640–650.

18. Miller KL, Walt JG, Mink DR, et al. Minimal clinically important difference for the ocular surface disease index. Arch Ophthalmol. 2010; 128:94–101.

19. Kaufman HE. The practical detection of mmp-9 diagnoses ocular surface disease and may help prevent its complications. Cornea. 2013; 32:211–216.

20. Park JY, Kim BG, Kim JS, Hwang JH. Matrix metalloproteinase 9 point-of-care immunoassay result predicts response to topical cyclosporine treatment in dry eye disease. Transl Vis Sci Technol. 2018; 7:31.

21. Kolaczkowska E, Arnold B, Opdenakker G. Gelatinase B/MMP-9 as an inflammatory marker enzyme in mouse zymosan peritonitis: comparison of phase-specific and cell-specific production by mast cells, macrophages and neutrophils. Immunobiology. 2008; 213:109–124.

22. Chotikavanich S, de Paiva CS, Li de Q, et al. Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome. Invest Ophthalmol Vis Sci. 2009; 50:3203–3209.

23. Starr CE, Gupta PK, Farid M, et al. An algorithm for the preoperative diagnosis and treatment of ocular surface disorders. J Cataract Refract Surg. 2019; 45:669–684.

24. Schargus M, Ivanova S, Kakkassery V, et al. Correlation of tear film osmolarity and 2 different MMP-9 tests with common dry eye tests in a cohort of non-dry eye patients. Cornea. 2015; 34:739–744.

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