Korean J Ophthalmol.  2019 Feb;33(1):26-35. 10.3341/kjo.2018.0065.

Association between Three Heavy Metals and Dry Eye Disease in Korean Adults: Results of the Korean National Health and Nutrition Examination Survey

• Jung SJ
• Lee SH

• KMID: 2434302
• DOI: http://doi.org/10.3341/kjo.2018.0065

Abstract

PURPOSE
To investigate the associations between blood heavy metal concentrations and dry eye disease using a Korean population-based survey.
METHODS
This study included 23,376 participants >40 years of age who participated in the Korean National Health and Nutrition Examination Survey from 2010 to 2012. Blood concentrations of lead, cadmium, and mercury were measured in all participants. The associations between blood heavy metal concentrations and dry eye disease were assessed using multivariate logistic regression analyses.
RESULTS
After adjusting for potential confounders, including age, sex, lifestyle behaviors and sociodemographic factors, the analyses revealed an increased odds ratio (OR) for dry eye disease with higher blood mercury concentrations (tertile 2: OR, 1.22; 95% confidence interval [CI], 0.91 to 1.64; tertile 3: OR, 1.39; 95% CI, 1.02 to 1.89; p = 0.039). The prevalence of dry eye disease was not associated with blood lead (tertile 2: OR, 1.15; 95% CI, 0.87 to 1.51; tertile 3: OR, 0.83; 95% CI, 0.59 to 1.16; p = 0.283) or cadmium (tertile 2: OR, 1.05; 95% CI, 0.77 to 1.44; tertile 3: OR, 1.15; 95% CI, 0.84 to 1.58; p = 0.389) concentrations. There were no significant associations between any of the three heavy metals and dry eye disease in males after adjusting for potential confounding factors, but blood mercury concentrations in females were associated with dry eye disease (tertile 2: OR, 1.18; 95% CI, 0.83 to 1.69; tertile 3: OR, 1.58; 95% CI, 1.12 to 2.24; p = 0.009).
CONCLUSIONS
Mercury concentrations in blood were associated with dry eye disease. Our results suggested that controlling environmental exposure to mercury may be necessary to reduce the incidence of dry eye disease.

Keyword

Dry eye syndromes; Heavy metals; Mercury; Republic of Korea

MeSH Terms

Adult*
Cadmium
Dry Eye Syndromes
Environmental Exposure
Eye Diseases*
Female
Humans
Incidence
Life Style
Logistic Models
Male
Metals, Heavy*
Nutrition Surveys*
Odds Ratio
Prevalence
Republic of Korea
Cadmium
Metals, Heavy

Reference

1. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017; 15:276–283.

2. Fergusson JE. The heavy elements: chemistry, environmental impact, and health effects. Oxford: Pergamon Press;1990. p. 614.

3. He ZL, Yang XE, Stoffella PJ. Trace elements in agroecosystems and impacts on the environment. J Trace Elem Med Biol. 2005; 19:125–140.

4. Bradl H. Heavy metals in the environment: origin, interaction and remediation. Amsterdam: Elsevier Academic Press;2005. p. 1–25.

5. Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy metal toxicity and the environment. In : Luch A, editor. Molecular, clinical and environmental toxicology. . Basel: Springer;2012. p. 133–164.

6. Lee SH, Kang EM, Kim GA, et al. Three toxic heavy metals in open-angle glaucoma with low-teen and high-teen intraocular pressure: a cross-sectional study from South Korea. PLoS One. 2016; 11:e0164983.

7. Chung SH, Myong JP. Are higher blood mercury levels associated with dry eye symptoms in adult Koreans? A population-based cross-sectional study. BMJ Open. 2016; 6:e010985.

8. Kweon S, Kim Y, Jang MJ, et al. Data resource profile: the Korea National Health and Nutrition Examination Survey (KNHANES). Int J Epidemiol. 2014; 43:69–77.

9. Yoon KC, Mun GH, Kim SD, et al. Prevalence of eye diseases in South Korea: data from the Korea National Health and Nutrition Examination Survey 2008-2009. Korean J Ophthalmol. 2011; 25:421–433.

10. Bhan A, Sarkar NN. Mercury in the environment: effect on health and reproduction. Rev Environ Health. 2005; 20:39–56.

11. Warfvinge K, Bruun A. Mercury distribution in the squirrel monkey retina after in Utero exposure to mercury vapor. Environ Res. 2000; 83:102–109.

12. Bridges CC, Battle JR, Zalups RK. Transport of thiol-conjugates of inorganic mercury in human retinal pigment epithelial cells. Toxicol Appl Pharmacol. 2007; 221:251–260.

13. Tanan CL, Ventura DF, de Souza JM, et al. Effects of mercury intoxication on the response of horizontal cells of the retina of thraira fish (Hoplias malabaricus). Braz J Med Biol Res. 2006; 39:987–995.

14. Cavalleri A, Belotti L, Gobba F, et al. Colour vision loss in workers exposed to elemental mercury vapour. Toxicol Lett. 1995; 77:351–356.

15. Sabelaish S, Hilmi G. Ocular manifestations of mercury poisoning. Bull World Health Organ. 1976; 53:suppl. 83–86.

16. Botelho SY, Hisada M, Fuenmayor N. Functional innervation of the lacrimal gland in the cat. Origin of secretomotor fibers in the lacrimal nerve. Arch Ophthalmol. 1966; 76:581–588.

17. Sibony PA, Walcott B, McKeon C, Jakobiec FA. Vasoactive intestinal polypeptide and the innervation of the human lacrimal gland. Arch Ophthalmol. 1988; 106:1085–1088.

18. Dartt DA. Neural regulation of lacrimal gland secretory processes: relevance in dry eye diseases. Prog Retin Eye Res. 2009; 28:155–177.

19. Milioni AL, Nagy BV, Moura AL, et al. Neurotoxic impact of mercury on the central nervous system evaluated by neuropsychological tests and on the autonomic nervous system evaluated by dynamic pupillometry. Neurotoxicology. 2017; 59:263–269.

20. Augustin AJ, Spitznas M, Kaviani N, et al. Oxidative reactions in the tear fluid of patients suffering from dry eyes. Graefes Arch Clin Exp Ophthalmol. 1995; 233:694–698.

21. Nabi S. Mercury as a source of reactive oxygen species. In : Nabi S, editor. Toxic effects of mercury. [place unknown]: Springer;2014. p. 95–99.

22. Hessen M, Akpek EK. Dry eye: an inflammatory ocular disease. J Ophthalmic Vis Res. 2014; 9:240–250.

23. Fortes MB, Diment BC, Di Felice U, et al. Tear fluid osmolarity as a potential marker of hydration status. Med Sci Sports Exerc. 2011; 43:1590–1597.

24. Walsh NP, Fortes MB, Esmaeelpour M. Influence of modest changes in whole-body hydration on tear fluid osmolarity: important considerations for dry eye disease detection. Cornea. 2011; 30:1517.

25. Walsh NP, Fortes MB, Raymond-Barker P, et al. Is wholebody hydration an important consideration in dry eye? Invest Ophthalmol Vis Sci. 2012; 53:6622–6627.

26. 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.

27. Research in dry eye: report of the Research Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007; 5:179–193.

28. Brake J, Hester PY, Thaxton P, et al. Effect of mercury toxiocity on serum osmolality, plasma sodium and potassium, and serum proteins in the chicken. Arch Environ Contam Toxicol. 1980; 9:431–436.

29. Erie JC, Butz JA, Good JA, et al. Heavy metal concentrations in human eyes. Am J Ophthalmol. 2005; 139:888–893.

30. Bhattacharyya MH, Wilson AK, Rajan SS, Jonah M. Biochemical pathways in cadmium toxicity. In : Zalup RK, Koropatnick J, editors. Molecular biology and toxicology of metals. London: Taylor & Francis;2000. p. 1–74.

31. Beatty S, Koh H, Phil M, et al. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 2000; 45:115–134.

32. Hahn P, Milam AH, Dunaief JL. Maculas affected by age-related macular degeneration contain increased chelatable iron in the retinal pigment epithelium and Bruch's membrane. Arch Ophthalmol. 2003; 121:1099–1105.

33. Tsubota K, Kawashima M, Inaba T, et al. The antiaging approach for the treatment of dry eye. Cornea. 2012; 31:Suppl 1. S3–S8.

34. Hirayama K, Yasutake A. Sex and age differences in mercury distribution and excretion in methylmercury-administered mice. J Toxicol Environ Health. 1986; 18:49–60.

35. Thomas DJ, Fisher HL, Sumler MR, et al. Sexual differences in the distribution and retention of organic and inorganic mercury in methyl mercury-treated rats. Environ Res. 1986; 41:219–234.

36. Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II epidemiology report. Ocul Surf. 2017; 15:334–365.