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Aging Research https://doi.org/10.26599/AGR.2024.9340022
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Aging and dry eye disease

Show Author's Information Meiling Xie1,  Ruihan Yang1,  Jian Zhu2,  Jian Sima1( )
Laboratory of Aging Neuroscience and Neuropharmacology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China
Department of Psychology, Eastern Illinois University, Charleston, IL 61920, USA
Keywords:
aging, dry eye disease (DED), meibomian gland, lacrimal gland
Cite this article:
Xie M, Yang R, Zhu J, et al. Aging and dry eye disease. Aging Research, 2024, https://doi.org/10.26599/AGR.2024.9340022
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Abstract Full text About this article

Dry eye disease (DED) is an eye condition that primarily affects up to 30% of adults aged 50 years and older, impacting visual function and quality of life. The prevalence of the condition increases with age. Common symptoms of dry eye include dry eyes, redness, a sensation of having a foreign object in the eye, eye pain, sensitivity to light, increased eye discharge, eye itching, and visual fatigue. In this paper, we systematically review the primary pathological mechanisms of dry eye, the impact of aging on dry eye, and current strategies for clinical treatment.


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About this article

Aging and dry eye disease

Show Author's information Meiling Xie1, Ruihan Yang1, Jian Zhu2, Jian Sima1( )
Laboratory of Aging Neuroscience and Neuropharmacology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China
Department of Psychology, Eastern Illinois University, Charleston, IL 61920, USA

Abstract

Dry eye disease (DED) is an eye condition that primarily affects up to 30% of adults aged 50 years and older, impacting visual function and quality of life. The prevalence of the condition increases with age. Common symptoms of dry eye include dry eyes, redness, a sensation of having a foreign object in the eye, eye pain, sensitivity to light, increased eye discharge, eye itching, and visual fatigue. In this paper, we systematically review the primary pathological mechanisms of dry eye, the impact of aging on dry eye, and current strategies for clinical treatment.

Keywords: aging, dry eye disease (DED), meibomian gland, lacrimal gland

References(114)

[1]
Nelson, J. D., Helms, H., Fiscella, R., Southwell, Y., Hirsch, J. D. A new look at dry eye disease and its treatment. Advances in Therapy, 2000 , 17(2): 84–93. https://doi.org/10.1007/BF02854841
DOI
[2]

de Pinho Tavares, F., Fernandes, R. S., Bernardes, T. F., Bonfioli, A. A., Soares, E. J. C. Dry eye disease. Seminars in Ophthalmology, 2010, 25(3): 84–93. https://doi.org/10.3109/08820538.2010.488568.
DOI Google Scholar
[3]

Latkany, R., Miller, D., Zeev, M. S. B. Diagnosis of dry eye disease and emerging technologies. Clinical Ophthalmology, 2014, 8: 581. https://doi.org/10.2147/opth.s45444.
DOI Google Scholar
[4]

Rahman, M. Q., Chuah, K. S., MacDonald, E. C. A., Trusler, J. P. M., Ramaesh, K. The effect of pH, dilution, and temperature on the viscosity of ocular lubricants—Shift in rheological parameters and potential clinical significance. Eye, 2012, 26(12): 1579–1584. https://doi.org/10.1038/eye.2012.211.
DOI Google Scholar
[5]

Dana, R., Bradley, J. L., Guerin, A., Pivneva, I., Stillman, I. Ö., Evans, A. M., Schaumberg, D. A. Estimated prevalence and incidence of dry eye disease based on coding analysis of a large, all-age United States health care system. American Journal of Ophthalmology, 2019, 202: 47–54. https://doi.org/10.1016/j.ajo.2019.01.026.
DOI Google Scholar
[6]

Barabino, S., Labetoulle, M., Rolando, M., Messmer, E. M. Understanding symptoms and quality of life inPatients with dry eye syndrome. The Ocular Surface, 2016, 14(3): 365–376. https://doi.org/10.1016/j.jtos.2016.04.005.
DOI Google Scholar
[7]

Messmer, E. M. The pathophysiology, diagnosis, and treatment of dry eye disease. Deutsches Ärzteblatt International, 2015, 112(5): 71. https://doi.org/10.3238/arztebl.2015.0071.
DOI Google Scholar
[8]

McDonald, M., Patel, D. A., Keith, M. S., Snedecor, S. J. Economic and humanistic burden of dry eye disease in Europe, North America, and Asia: ASystematic literature review. The Ocular Surface, 2016, 14(2): 144–167. https://doi.org/10.1016/j.jtos.2015.11.002.
DOI Google Scholar
[9]

Wan, K. H., Chen, L. J., Young, A. L. Depression and anxiety in dry eye disease: A systematic review and meta-analysis. Eye, 2016, 30(12): 1558–1567. https://doi.org/10.1038/eye.2016.186.
DOI Google Scholar
[10]

Zheng, Y. J., Wu, X. H., Lin, X. M., Lin, H. T. The prevalence of depression and depressive symptoms among eye disease patients: A systematic review and meta-analysis. Scientific Reports, 2017, 7: 46453. https://doi.org/10.1038/srep46453.
DOI Google Scholar
[11]

Gomes, J. A. P., Santo, R. M. The impact of dry eye disease treatment on patient satisfaction and quality of life: A review. The Ocular Surface, 2019, 17(1): 9–19. https://doi.org/10.1016/j.jtos.2018.11.003.
DOI Google Scholar
[12]

Craig, J. P., Nichols, K. K., Akpek, E. K., Caffery, B., Dua, H. S., Joo, C. K., Liu, Z. G., Nelson, J. D., Nichols, J. J., Tsubota, K. et al. TFOS DEWS II definition and classification report. The Ocular Surface, 2017, 15(3): 276–283. https://doi.org/10.1016/j.jtos.2017.05.008.
DOI Google Scholar
[13]

Tsubota, K., Yokoi, N., Shimazaki, J., Watanabe, H., Dogru, M., Yamada, M., Kinoshita, S., Kim, H. M., Tchah, H. W., Hyon, J. Y. et al. New perspectives on dry eye definition and diagnosis: A consensus report by the Asia dry eye society. The Ocular Surface, 2017, 15(1): 65–76. https://doi.org/10.1016/j.jtos.2016.09.003.
DOI Google Scholar
[14]

Den, S., Shimizu, K., Ikeda, T., Tsubota, K., Shimmura, S., Shimazaki, J. Association between meibomian gland changes and aging, sex, or tear function. Cornea, 2006, 25(6): 651–655. https://doi.org/10.1097/01.ico.0000227889.11500.6f.
DOI Google Scholar
[15]

Schaumberg, D. A., Nichols, J. J., Papas, E. B., Tong, L., Uchino, M., Nichols, K. K. The international workshop on meibomian gland dysfunction: Report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Investigative Opthalmology & Visual Science, 2011, 52(4): 1994. https://doi.org/10.1167/iovs.10-6997e.
DOI Google Scholar
[16]

Schaumberg, D. A. Hormone replacement therapy and dry eye syndrome. JAMA, 2001, 286(17): 2114. https://doi.org/10.1001/jama.286.17.2114.
DOI Google Scholar
[17]

Song, P. G., Xia, W., Wang, M. L., Chang, X. L., Wang, J. P., Jin, S., Wang, J. W., Wei, W., Rudan, I. Variations of dry eye disease prevalence by age, sex and geographic characteristics in China: A systematic review and meta-analysis. Journal of Global Health, 2018, 8(2): 020503. https://doi.org/10.7189/jogh.08.020503.
DOI Google Scholar
[18]

Gipson, I. K. Age-related changes and diseases of the ocular surface and cornea. Investigative Opthalmology & Visual Science, 2013, 54(14): ORSF48. https://doi.org/10.1167/iovs.13-12840.
DOI Google Scholar
[19]

Baudouin, C. The pathology of dry eye. Survey of Ophthalmology, 2001, 45: S211–S220. https://doi.org/10.1016/s0039-6257(00)00200-9.
DOI Google Scholar
[20]

Periman Laura, M., Perez Victor, L., Saban Daniel, R., Lin Meng, C., Piergiorgio, N. The immunological basis of dry eye disease and current topical treatment options. Journal of Ocular Pharmacology and Therapeutics: the Official Journal of the Association for Ocular Pharmacology and Therapeutics, 2020, 36(3): 137–146. https://doi.org/10.1089/jop.2019.0060.
DOI Google Scholar
[21]

Yu, L. F., Yu, C. J., Dong, H., Mu, Y. N., Zhang, R., Zhang, Q. S., Liang, W., Li, W. J., Wang, X., Zhang, L. J. Recent developments about the pathogenesis of dry eye disease: Based on immune inflammatory mechanisms. Frontiers in Pharmacology, 2021, 12: 732887. https://doi.org/10.3389/fphar.2021.732887.
DOI Google Scholar
[22]

Guzmán, M., Keitelman, I., Sabbione, F., Trevani, A. S., Giordano, M. N., Galletti, J. G. Desiccating stress-induced disruption of ocular surface immune tolerance drives dry eye disease. Clinical and Experimental Immunology, 2016, 184(2): 248–256. https://doi.org/10.1111/cei.12759.
DOI Google Scholar
[23]

Luo, L. H., Li, D. Q., Corrales, R. M., Pflugfelder, S. C. Hyperosmolar saline is a proinflammatory stress on the mouse ocular surface. Eye & Contact Lens: Science & Clinical Practice, 2005, 31(5): 186–193. https://doi.org/10.1097/01.icl.0000162759.79740.46.
DOI Google Scholar
[24]

Luo, L. H., Li, D. Q., Doshi, A., Farley, W., Corrales, R. M., Pflugfelder, S. C. Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface. Investigative Opthalmology & Visual Science, 2004, 45(12): 4293. https://doi.org/10.1167/iovs.03-1145.
DOI Google Scholar
[25]

Pelegrino, F. S. A., Pflugfelder, S. C., De Paiva, C. S. Low humidity environmental challenge causes barrier disruption and cornification of the mouse corneal epithelium via a c-Jun N-terminal kinase 2 (JNK2) pathway. Experimental Eye Research, 2012, 94(1): 150–156. https://doi.org/10.1016/j.exer.2011.11.022.
DOI Google Scholar
[26]

Chi, W., Hua, X., Chen, X., Bian, F., Yuan, X. Y., Zhang, L. L., Wang, X. R., Chen, D., Deng, R. Z., Li, Z. J. et al. Mitochondrial DNA oxidation induces imbalanced activity of NLRP3/NLRP6 inflammasomes by activation of caspase-8 and BRCC36 in dry eye. Journal of Autoimmunity, 2017, 80: 65–76. https://doi.org/10.1016/j.jaut.2017.02.006.
DOI Google Scholar
[27]

Niu, L. L., Zhang, S. J., Wu, J. H., Chen, L., Wang, Y. Upregulation of NLRP3 inflammasome in the tears and ocular surface of dry eye patients. PLoS One, 2015, 10(5): e0126277. https://doi.org/10.1371/journal.pone.0126277.
DOI Google Scholar
[28]

Zheng, Q. X., Ren, Y. P., Reinach, P. S., She, Y. J., Xiao, B., Hua, S. S., Qu, J., Chen, W. Reactive oxygen species activated NLRP3 inflammasomes prime environment-induced murine dry eye. Experimental Eye Research, 2014, 125: 1–8. https://doi.org/10.1016/j.exer.2014.05.001.
DOI Google Scholar
[29]

Zheng, Q. X., Ren, Y. P., Reinach, P. S., Xiao, B., Lu, H. H., Zhu, Y. R., Qu, J., Chen, W. Reactive oxygen species activated NLRP3 inflammasomes initiate inflammation in hyperosmolarity stressed human corneal epithelial cells and environment-induced dry eye patients. Experimental Eye Research, 2015, 134: 133–140. https://doi.org/10.1016/j.exer.2015.02.013.
DOI Google Scholar
[30]

Bron, A. J., de Paiva, C. S., Chauhan, S. K., Bonini, S., Bonini, S., Gabison, E. E., Jain, S., Knop, E., Markoulli, M., Ogawa, Y. et al. TFOS DEWS II pathophysiology report. Ocul Surf, 2017, 15(3): 438–510. https://doi.org/10.1016/j.jtos.2017.05.011.
DOI Google Scholar
[31]

Baudouin, C., Aragona, P., Messmer, E. M., Tomlinson, A., Calonge, M., Boboridis, K. G., Akova, Y. A., Geerling, G., Labetoulle, M., Rolando, M. Role of hyperosmolarity in the pathogenesis and management of dry eye disease: Proceedings of the OCEAN group meeting. The Ocular Surface, 2013, 11(4): 246–258. https://doi.org/10.1016/j.jtos.2013.07.003.
DOI Google Scholar
[32]

Yazici, A., Sari, E. S., Sahin, G., Kilic, A., Cakmak, H., Ayar, O., Ermis, S. S. Change in tear film characteristics in visual display terminal users. European Journal of Ophthalmology, 2015, 25(2): 85–89. https://doi.org/10.5301/ejo.5000525.
DOI Google Scholar
[33]

Chhadva, P., Goldhardt, R., Galor, A. Meibomian gland disease: The role of gland dysfunction in dry eye disease. Ophthalmology, 2017, 124(11S): S20–S26. https://doi.org/10.1016/j.ophtha.2017.05.031.
DOI Google Scholar
[34]

Baudouin, C., Messmer, E. M., Aragona, P., Geerling, G., Akova, Y. A., Benítez-del-Castillo, J., Boboridis, K. G., Merayo-Lloves, J., Rolando, M., Labetoulle, M. Revisiting the vicious circle of dry eye disease: A focus on the pathophysiology of meibomian gland dysfunction. British Journal of Ophthalmology, 2016, 100(3): 300–306. https://doi.org/10.1136/bjophthalmol-2015-307415.
DOI Google Scholar
[35]

Hykin, P. G., Bron, A. J. Age-related morphological changes in lid margin and meibomian gland anatomy. Cornea, 1992, 11(4): 334–342. https://doi.org/10.1097/00003226-199207000-00012.
DOI Google Scholar
[36]

Norn, M. Expressibility of meibomian secretion. Relation to age, lipid precorneal film, scales, foam, hair and pigmentation. Acta Ophthalmologica, 1987, 65(2): 137–142. https://doi.org/10.1111/j.1755-3768.1987.tb06991.x.
DOI Google Scholar
[37]

Arita, R., Itoh, K., Inoue, K., Amano, S. Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population. Ophthalmology, 2008, 115(5): 911–915. https://doi.org/10.1016/j.ophtha.2007.06.031.
DOI Google Scholar
[38]
Obata, H. Anatomy and histopathology of human meibomian gland. Cornea, 2002 , 21(Supplement 2): S70–S74. https://doi.org/10.1097/01.ico.0000263122.45898.09
DOI
[39]

Nien, C. J., Paugh, J. R., Massei, S., Wahlert, A. J., Kao, W. W., Jester, J. V. Age-related changes in the meibomian gland. Experimental Eye Research, 2009, 89(6): 1021–1027. https://doi.org/10.1016/j.exer.2009.08.013.
DOI Google Scholar
[40]

Hashemi, H., Khabazkhoob, M., Kheirkhah, A., Emamian, M. H., Mehravaran, S., Shariati, M., Fotouhi, A. Prevalence of dry eye syndrome in an adult population. Clinical & Experimental Ophthalmology, 2014, 42(3): 242–248. https://doi.org/10.1111/ceo.12183.
DOI Google Scholar
[41]

Schaumberg, D. A., Sullivan, D. A., Buring, J. E., Dana, M. R. Prevalence of dry eye syndrome among US women. American Journal of Ophthalmology, 2003, 136(2): 318–326. https://doi.org/10.1016/s0002-9394(03)00218-6.
DOI Google Scholar
[42]

Schaumberg, D. A. Prevalence of dry eye disease among US men. Archives of Ophthalmology, 2009, 127(6): 763. https://doi.org/10.1001/archophthalmol.2009.103.
DOI Google Scholar
[43]

Chia, E. M., Mitchell, P., Rochtchina, E., Lee, A. J., Maroun, R., Wang, J. J. Prevalence and associations of dry eye syndrome in an older population: The Blue Mountains Eye Study. Clinical & Experimental Ophthalmology, 2003, 31(3): 229–232. https://doi.org/10.1046/j.1442-9071.2003.00634.x.
DOI Google Scholar
[44]

Luderschmidt, C., Eiermann, W., Jawny, J. Steroid hormone receptors and their relevance for sebum production in the sebaceous gland ear model of the Syrian hamster. Archives of Dermatological Research, 1983, 275(3): 175–180. https://doi.org/10.1007/BF00510049.
DOI Google Scholar
[45]

Rocha, E. M. Identification of androgen receptor protein and 5alpha-reductase mRNA in human ocular tissues. British Journal of Ophthalmology, 2000, 84(1): 76–84. https://doi.org/10.1136/bjo.84.1.76.
DOI Google Scholar
[46]

Krenzer, K. L., Reza Dana, M., Ullman, M. D., Cermak, J. M., Tolls, D. B., Evans, J. E., Sullivan, D. A. Effect of androgen deficiency on the human meibomian gland and ocular Surface1. The Journal of Clinical Endocrinology & Metabolism, 2000, 85(12): 4874–4882. https://doi.org/10.1210/jcem.85.12.7072.
DOI Google Scholar
[47]

Schirra, F., Richards, S. M., Sullivan, D. A. Androgen influence on cholesterogenic enzyme mRNA levels in the mouse meibomian gland. Current Eye Research, 2007, 32(5): 393–398. https://doi.org/10.1080/02713680701316674.
DOI Google Scholar
[48]
Rosignoli, C., Nicolas, J. C., Jomard, A., Michel, S. Involvement of the SREBP pathway in the mode of action of androgens in sebaceous glands in vivo. Experimental Dermatology, 2003 , 12(4): 480–489. https://doi.org/10.1034/j.1600-0625.2003.00014.x
DOI
[49]

Miyazaki, M., Man, W. C., Ntambi, J. M. Targeted disruption of stearoyl-CoA Desaturase1 gene in mice causes atrophy of sebaceous and meibomian glands and depletion of wax esters in the eyelid. The Journal of Nutrition, 2001, 131(9): 2260–2268. https://doi.org/10.1093/jn/131.9.2260.
DOI Google Scholar
[50]

Feldman, H. A., Longcope, C., Derby, C. A., Johannes, C. B., Araujo, A. B., Coviello, A. D., Bremner, W. J., McKinlay, J. B. Age trends in the level of serum testosterone and other hormones in middle-aged men: Longitudinal results from the Massachusetts male aging study. The Journal of Clinical Endocrinology & Metabolism, 2002, 87(2): 589–598. https://doi.org/10.1210/jcem.87.2.8201.
DOI Google Scholar
[51]

Morley, J. E., Kaiser, F. E., Perry, H. M. III, Patrick, P., Morley, P. M. K., Stauber, P. M., Vellas, B., Baumgartner, R. N., Garry, P. J. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism, 1997, 46(4): 410–413. https://doi.org/10.1016/s0026-0495(97)90057-3.
DOI Google Scholar
[52]

McKay, T. B., Priyadarsini, S., Karamichos, D. Sex hormones, growth hormone, and the cornea. Cells, 2022, 11(2): 224. https://doi.org/10.3390/cells11020224.
DOI Google Scholar
[53]

Erdem, U., Ozdegirmenci, O., Sobaci, E., Sobaci, G., Göktolga, U., Dagli, S. Dry eye in post-menopausal women using hormone replacement therapy. Maturitas, 2007, 56(3): 257–262. https://doi.org/10.1016/j.maturitas.2006.08.007.
DOI Google Scholar
[54]

Suzuki, T., Schirra, F., Richards, S. M., Jensen, R. V., Sullivan, D. A. Estrogen and progesterone control of gene expression in the mouse meibomian gland. Investigative Opthalmology & Visual Science, 2008, 49(5): 1797. https://doi.org/10.1167/iovs.07-1458.
DOI Google Scholar
[55]

Schäfer, G., Krause, W. The effect of estradiol on the sebaceous gland of the hamster ear and its antagonism by tamoxifen. Archives of Dermatological Research, 1985, 277(3): 230–234. https://doi.org/10.1007/BF00404322.
DOI Google Scholar
[56]

Sriprasert, I., Warren, D. W., Mircheff, A. K., Stanczyk, F. Z. Dry eye in postmenopausal women: A hormonal disorder. Menopause, 2016, 23(3): 343–351. https://doi.org/10.1097/GME.00000000 00000530.
DOI Google Scholar
[57]

Jester, J. V., Parfitt, G. J., Brown, D. J. Meibomian gland dysfunction: Hyperkeratinization or atrophy. BMC Ophthalmology, 2015, 15(1): 156. https://doi.org/10.1186/s12886-015-0132-x.
DOI Google Scholar
[58]

Ibrahim, O. M. A., Dogru, M., Matsumoto, Y., Igarashi, A., Kojima, T., Wakamatsu, T. H., Inaba, T., Shimizu, T., Shimazaki, J., Tsubota, K. Oxidative stress induced age dependent meibomian gland dysfunction in Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice. PLoS One, 2014, 9(7): e99328. https://doi.org/10.1371/journal.pone.0099328.
DOI Google Scholar
[59]

Galor, A., Moein, H. R., Lee, C., Rodriguez, A., Felix, E. R., Sarantopoulos, K. D., Levitt, R. C. Neuropathic pain and dry eye. The Ocular Surface, 2018, 16(1): 31–44. https://doi.org/10.1016/j.jtos.2017.10.001.
DOI Google Scholar
[60]

Guzmán, M., Miglio, M., Keitelman, I., Shiromizu, C. M., Sabbione, F., Fuentes, F., Trevani, A. S., Giordano, M. N., Galletti, J. G. Transient tear hyperosmolarity disrupts the neuroimmune homeostasis of the ocular surface and facilitates dry eye onset. Immunology, 2020, 161(2): 148–161. https://doi.org/10.1111/imm.13243.
DOI Google Scholar
[61]

De Silva, M. E. H., Hill, L. J., Downie, L. E., Chinnery, H. R. The effects of aging on corneal and ocular surface homeostasis in mice. Investigative Opthalmology & Visual Science, 2019, 60(7): 2705. https://doi.org/10.1167/iovs.19-26631.
DOI Google Scholar
[62]

Messmer, E. M. Pathophysiology of dry eye disease and novel therapeutic targets. Experimental Eye Research, 2022, 217: 108944. https://doi.org/10.1016/j.exer.2022.108944.
DOI Google Scholar
[63]

Alcalde, I., Íñigo-Portugués, A., González-González, O., Almaraz, L., Artime, E., Morenilla-Palao, C., Gallar, J., Viana, F., Merayo-Lloves, J., Belmonte, C. Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice. Journal of Comparative Neurology, 2018, 526(11): 1859–1874. https://doi.org/10.1002/cne.24454.
DOI Google Scholar
[64]
Schaumberg, D. A., Sullivan, D. A., Dana, M. R. Epidemiology of dry eye syndrome. In: Advances in Experimental Medicine and Biology. Boston: Springer US, 2002 : 989–998. https://doi.org/10.1007/978-1-4615-0717-8_140
DOI
[65]

de Souza, R. G., Yu, Z. Y., Hernandez, H., Trujillo-Vargas, C. M., Lee, A., Mauk, K. E., Cai, J. Y., Alves, M. R., de Paiva, C. S. Modulation of oxidative stress and inflammation in the aged lacrimal gland. The American Journal of Pathology, 2021, 191(2): 294–308. https://doi.org/10.1016/j.ajpath.2020.10.013.
DOI Google Scholar
[66]

Ríos, J. D., Horikawa, Y., Chen, L. L., Kublin, C. L., Hodges, R. R., Dartt, D. A., Zoukhri, D. Age-dependent alterations in mouse exorbital lacrimal gland structure, innervation and secretory response. Experimental Eye Research, 2005, 80(4): 477–491. https://doi.org/10.1016/j.exer.2004.10.012.
DOI Google Scholar
[67]

Sohal, R. S., Marzabadi, M. R., Galaris, D., Brunk, U. T. Effect of ambient oxygen concentration on lipofuscin accumulation in cultured rat heart myocytes—a novel in vitro model of lipofuscinogenesis. Free Radical Biology and Medicine, 1989, 6(1): 23–30. https://doi.org/10.1016/0891-5849(89)90155-x.
DOI Google Scholar
[68]

Terman, A., Brunk, U. T. Ceroid/lipofuscin formation in cultured human fibroblasts: The role of oxidative stress and lysosomal proteolysis. Mechanisms of Ageing and Development, 1998, 104(3): 277–291. https://doi.org/10.1016/s0047-6374(98)00073-6.
DOI Google Scholar
[69]

Draper, C. E., Adeghate, E. A., Singh, J., Pallot, D. J. Evidence to suggest morphological and physiological alterations of lacrimal gland acini with ageing. Experimental Eye Research, 1999, 68(3): 265–276. https://doi.org/10.1006/exer.1998.0605.
DOI Google Scholar
[70]

Borchman, D., Ramasubramanian, A., Foulks, G. N. Human meibum cholesteryl and wax ester variability with age, sex, and meibomian gland dysfunction. Investigative Opthalmology & Visual Science, 2019, 60(6): 2286. https://doi.org/10.1167/iovs.19-26812.
DOI Google Scholar
[71]

Yoon, C. H., Ryu, J. S., Hwang, H. S., Kim, M. K. Comparative analysis of age-related changes in lacrimal glands and meibomian glands of a C57BL/6 male mouse model. International Journal of Molecular Sciences, 2020, 21(11): 4169. https://doi.org/10.3390/ijms21114169.
DOI Google Scholar
[72]

Nien, C. J. Effects of age and dysfunction on human meibomian glands. Archives of Ophthalmology, 2011, 129(4): 462. https://doi.org/10.1001/archophthalmol.2011.69.
DOI Google Scholar
[73]

Kitazawa, K., Inomata, T., Shih, K., Hughes, J. W B., Bozza, N., Tomioka, Y., Numa, K., Yokoi, N., Campisi, J., Dana, R. et al. Impact of aging on the pathophysiology of dry eye disease: A systematic review and meta-analysis. The Ocular Surface, 2022, 25: 108–118. https://doi.org/10.1016/j.jtos.2022.06.004.
DOI Google Scholar
[74]

Wei, A. J., Hong, J. X., Sun, X. H., Xu, J. J. Evaluation of age-related changes in human palpebral conjunctiva and meibomian glands by in vivo confocal microscopy. Cornea, 2011, 30(9): 1007–1012. https://doi.org/10.1097/ico.0b013e31820ca468.
DOI Google Scholar
[75]

Abdel-Khalek, L. M., Williamson, J., Lee, W. R. Morphological changes in the human conjunctival epithelium. I. in the normal elderly population. British Journal of Ophthalmology, 1978, 62(11): 792–799. https://doi.org/10.1136/bjo.62.11.792.
DOI Google Scholar
[76]

Vujkovic, V., Mikac, G., Kozomara, R. Distribution and density of conjunctival goblet cells. Medicinski Pregled, 2002, 55(5-6): 195–200. https://doi.org/10.2298/mpns0206195v.
DOI Google Scholar
[77]

Jung, Y. H., Ryu, J. S., Yoon, C. H., Kim, M. K. Age-dependent distinct distributions of dendritic cells in autoimmune dry eye murine model. Cells, 2021, 10(8): 1857. https://doi.org/10.3390/cells10081857.
DOI Google Scholar
[78]

Bian, F., Xiao, Y. Y., Barbosa, F. L., de Souza, R. G., Hernandez, H., Yu, Z. Y., Pflugfelder, S. C., de Paiva, C. S. Age-associated antigen-presenting cell alterations promote dry-eye inducing Th1 cells. Mucosal Immunology, 2019, 12(4): 897–908. https://doi.org/10.1038/s41385-018-0127-z.
DOI Google Scholar
[79]

Di Pascuale, M. A. Clinical characteristics of conjunctivochalasis with or without aqueous tear deficiency. British Journal of Ophthalmology, 2004, 88(3): 388–392. https://doi.org/10.1136/bjo.2003.025460.
DOI Google Scholar
[80]

Le, Q. H., Cui, X. H., Xiang, J., Ge, L., Gong, L., Xu, J. J. Impact of conjunctivochalasis on visual quality of life: A community population survey. PLoS One, 2014, 9(10): e110821. https://doi.org/10.1371/journal.pone.0110821.
DOI Google Scholar
[81]

Karger, R., White, W., Park, W., Rosales, A., McLaren, J., Olson, E., Woog, J. Prevalence of floppy eyelid syndrome in obstructive sleep apnea–hypopnea syndrome. Ophthalmology, 2006, 113(9): 1669–1674. https://doi.org/10.1016/j.ophtha.2006.02.053.
DOI Google Scholar
[82]

Pawelec, G. Age and immunity: What is “immunosenescence”. Experimental Gerontology, 2018, 105: 4–9. https://doi.org/10.1016/j.exger.2017.10.024.
DOI Google Scholar
[83]

Kemeny-Beke, A., Szodoray, P. Ocular manifestations of rheumatic diseases. International Ophthalmology, 2020, 40(2): 503–510. https://doi.org/10.1007/s10792-019-01183-9.
DOI Google Scholar
[84]

Yu, K., Bunya, V., Maguire, M., Asbell, P., Ying, G. S. Systemic conditions associated with severity of dry eye signs and symptoms in the dry eye assessment and management study. Ophthalmology, 2021, 128(10): 1384–1392. https://doi.org/10.1016/j.ophtha.2021.03.030.
DOI Google Scholar
[85]

Kuklinski, E., Asbell, P. A. Sjogren’s syndrome from the perspective of ophthalmology. Clinical Immunology, 2017, 182: 55–61. https://doi.org/10.1016/j.clim.2017.04.017.
DOI Google Scholar
[86]

Vehof, J., Utheim, T. P., Bootsma, H., Hammond, C. J. Advances, limitations and future perspectives in the diagnosis and management of dry eye in Sjögren’s syndrome. Clinical and Experimental Rheumatology, 2020, 38(4): 301–309.
Google Scholar
[87]

Mavragani, C. P., Moutsopoulos, H. M. Sjögren syndrome. CMAJ, 2014, 186(15): E579–E586. https://doi.org/10.1503/cmaj.122037.
DOI Google Scholar
[88]

De Freitas, G. R., Ferraz, G. A. M., Gehlen, M., Skare, T. L. Dry eyes in patients with diabetes mellitus. Primary Care Diabetes, 2021, 15(1): 184–186. https://doi.org/10.1016/j.pcd.2020.01.011.
DOI Google Scholar
[89]

Su, Y. C., Hung, J. H., Chang, K. C., Sun, C. C., Huang, Y. H., Lee, C. N., Hung, M. J., Lai, C. C., Shao, S. C., Lai, E. C. C. Comparison of sodium-glucose cotransporter 2 inhibitors vs glucagonlike peptide-1 receptor agonists and incidence of dry eye disease in patients with type 2 diabetes in Taiwan. JAMA Network Open, 2022, 5(9): e2232584. https://doi.org/10.1001/jamanetworkopen.2022.32584.
DOI Google Scholar
[90]

Dias, A. C., Batista, T. M., Roma, L. P., Módulo, C. M., Malki, L. T., Dias, L. C., Alves, M., Reinach, P. S., Carneiro, E. M., Rocha, E. M. Insulin replacement restores the vesicular secretory apparatus in the diabetic rat lacrimal gland. Arquivos Brasileiros De Oftalmologia, 2015, 78(3): 158. https://doi.org/10.5935/0004-2749.20150041.
DOI Google Scholar
[91]

Wu, K. J., Joffre, C., Li, X. D., MacVeigh-Aloni, M., Hom, M., Hwang, J., Ding, C. Q., Gregoire, S., Bretillon, L., Zhong, J. F. et al. Altered expression of genes functioning in lipid homeostasis is associated with lipid deposition in NOD mouse lacrimal gland. Experimental Eye Research, 2009, 89(3): 319–332. https://doi.org/10.1016/j.exer.2009.03.020.
DOI Google Scholar
[92]

Foulks, G. N. Pharmacological management of dry eye in the elderly patient. Drugs & Aging, 2008, 25(2): 105–118. https://doi.org/10.2165/00002512-200825020-00003.
DOI Google Scholar
[93]

Ezuddin, N. S., Alawa, K. A., Galor, A. Therapeutic strategies to treat dry eye in an aging population. Drugs & Aging, 2015, 32(7): 505–513. https://doi.org/10.1007/s40266-015-0277-6.
DOI Google Scholar
[94]
Oleñik, A., Jiménez-Alfaro, Alejandre, Mahillo-Fernández. A randomized, double-masked study to evaluate the effect of omega-3 fatty acids supplementation in meibomian gland dysfunction. Clinical Interventions in Aging, 2013 : 1133. https://doi.org/10.2147/cia.s48955
DOI
[95]
Brignole-Baudouin, F., Baudouin, C., Aragona, P., Rolando, M., Labetoulle, M., Pisella, P. J., Barabino, S., Siou-Mermet, R., Creuzot-Garcher, C. A multicentre, double-masked, randomized, controlled trial assessing the effect of oral supplementation of omega-3 and omega-6 fatty acids on a conjunctival inflammatory marker in dry eye patients. Acta Ophthalmologica, 2011 , 89(7): e591–e597. https://doi.org/10.1111/j.1755-3768.2011.02196.x
DOI
[96]

Wei, Y., Troger, A., Spahiu, V., Perekhvatova, N., Skulachev, M., Petrov, A., Chernyak, B., Asbell, P. The role of SKQ1 (visomitin) in inflammation and wound healing of the ocular surface. Ophthalmology and Therapy, 2019, 8(1): 63–73. https://doi.org/10.1007/s40123-018-0158-2.
DOI Google Scholar
[97]

Baiula, M., Spampinato, S. Experimental pharmacotherapy for dry eye disease: A review. Journal of Experimental Pharmacology, 2021, 13: 345–358. https://doi.org/10.2147/jep.s237487.
DOI Google Scholar
[98]

Zernii, E. Y., Gancharova, O. S., Baksheeva, V. E., Golovastova, M. O., Kabanova, E. I., Savchenko, M. S., Tiulina, V. V., Sotnikova, L. F., Zamyatnin, A. A., Philippov, P. P. et al. Mitochondria-targeted antioxidant SkQ1 prevents anesthesia-induced dry eye syndrome. Oxidative Medicine and Cellular Longevity, 2017, 2017: 9281519. https://doi.org/10.1155/2017/9281519.
DOI Google Scholar
[99]

Papageorgiou, P., Clayton, W., Norwood, S., Chopra, S., Rustin, M. Treatment of rosacea with intense pulsed light: Significant improvement and long-lasting results. British Journal of Dermatology, 2008, 159(3): 628–632. https://doi.org/10.1111/j.1365-2133.2008.08702.x.
DOI Google Scholar
[100]

Arita, R., Fukuoka, S. Non-pharmaceutical treatment options for meibomian gland dysfunction. Clinical and Experimental Optometry, 2020, 103(6): 742–755. https://doi.org/10.1111/cxo.13035.
DOI Google Scholar
[101]

Giannaccare, G., Taroni, L., Senni, C., Scorcia, V. Intense pulsed light therapy in the treatment of meibomian gland dysfunction: Current perspectives. Clinical Optometry, 2019, 11: 113–126. https://doi.org/10.2147/opto.s217639.
DOI Google Scholar
[102]

Dartt, D. A. Neural regulation of lacrimal gland secretory processes: Relevance in dry eye diseases. Progress in Retinal and Eye Research, 2009, 28(3): 155–177. https://doi.org/10.1016/j.preteyeres.2009.04.003.
DOI Google Scholar
[103]

Brinton, M., Chung, J. L., Kossler, A., Kook, K. H., Loudin, J., Franke, M., Palanker, D. Electronic enhancement of tear secretion. Journal of Neural Engineering, 2016, 13(1): 016006. https://doi.org/10.1088/1741-2560/13/1/016006.
DOI Google Scholar
[104]

Mason, L., Jafri, S., Dortonne, I., Sheppard, J. D. Jr. Emerging therapies for dry eye disease. Expert Opinion on Emerging Drugs, 2021, 26(4): 401–413. https://doi.org/10.1080/14728214.2021.2011858.
DOI Google Scholar
[105]

Ansari, Z., Singh, R., Alabiad, C., Galor, A. Prevalence, risk factors, and morbidity of eye lid laxity in a veteran population. Cornea, 2015, 34(1): 32–36. https://doi.org/10.1097/ico.0000000000000286.
DOI Google Scholar
[106]

Mastrota, K. M. Impact of floppy eyelid syndrome in ocular surface and dry eye disease. Optometry and Vision Science, 2008, 85(9): 814–816. https://doi.org/10.1097/opx.0b013e3181852777.
DOI Google Scholar
[107]

Ezra, D. G., Beaconsfield, M., Sira, M., Bunce, C., Shah-Desai, S., Verity, D. H., Uddin, J., Collin, R. Long-term outcomes of surgical approaches to the treatment of floppy eyelid syndrome. Ophthalmology, 2010, 117(4): 839–846. https://doi.org/10.1016/j.ophtha.2009.09.009.
DOI Google Scholar
[108]

Chhadva, P., Alexander, A., McClellan, A. L., McManus, K. T., Seiden, B., Galor, A. The impact of conjunctivochalasis on dry eye symptoms and signs. Investigative Opthalmology & Visual Science, 2015, 56(5): 2867. https://doi.org/10.1167/iovs.14-16337.
DOI Google Scholar
[109]

Singh, V. K., Sharma, P., Vaksh, U. K. S., Chandra, R. Current approaches for the regeneration and reconstruction of ocular surface in dry eye. Frontiers in Medicine, 2022, 9: 885780. https://doi.org/10.3389/fmed.2022.885780.
DOI Google Scholar
[110]

Pflugfelder Stephen, C., Michael, S., Steven, Z., Amir, S. LFA-1/ICAM-1 interaction as a therapeutic target in dry eye disease. Journal of Ocular Pharmacology and Therapeutics: the Official Journal of the Association for Ocular Pharmacology and Therapeutics, 2017, 33(1): 5–12. https://doi.org/10.1089/jop.2016.0105.
DOI Google Scholar
[111]

Kawashima, M., Ozawa, Y., Shinmura, K., Inaba, T., Nakamura, S., Kawakita, T., Watanabe, M., Tsubota, K. Calorie restriction (CR) and CR mimetics for the prevention and treatment of age-related eye disorders. Experimental Gerontology, 2013, 48(10): 1096–1100. https://doi.org/10.1016/j.exger.2013.04.002.
DOI Google Scholar
[112]

Uchino, M., Yokoi, N., Uchino, Y., Dogru, M., Kawashima, M., Komuro, A., Sonomura, Y., Kato, H., Kinoshita, S., Schaumberg, D. A. et al. Prevalence of dry eye disease and its risk factors in visual display terminal users: The Osaka study. American Journal of Ophthalmology, 2013, 156(4): 759–766.e1. https://doi.org/10.1016/j.ajo.2013.05.040.
DOI Google Scholar
[113]

Kawashima, M., Uchino, M., Yokoi, N., Dogru, M., Uchino, Y., Komuro, A., Sonomura, Y., Kato, H., Kinoshita, S., Tsubota, K. Decreased tear volume in patients with metabolic syndrome: the Osaka study. The British journal of ophthalmology, 2014, 98(3): 418. https://doi.org/10.1136/bjophthalmol-2013-303953.
DOI Google Scholar
[114]

Mehdi, M. M., Solanki, P., Singh, P. Oxidative stress, antioxidants, hormesis and calorie restriction: The Current perspective in the biology of aging. Archives of Gerontology and Geriatrics, 2021, 95: 104413. https://doi.org/10.1016/j.archger.2021.104413.
DOI Google Scholar
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Received: 22 January 2024
Revised: 24 February 2024
Accepted: 29 February 2024
Published: 07 April 2024

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© The Author(s) 2024. Aging Research published by Tsinghua University Press.

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