Research Article| Volume 3, ISSUE 2, 100270, June 2023

Age Associations with Dry Eye Clinical Signs and Symptoms in the Dry Eye Assessment and Management (DREAM) Study

Open AccessPublished:January 11, 2023DOI:


      To evaluate how increasing age is associated with dry eye disease (DED) signs and symptoms in the Dry Eye Assessment and Management (DREAM) study. This study was undertaken to better understand how DED signs and symptoms differ across decades of life with goals to help assess detection and treatment of DED.


      Secondary analysis of the DREAM study.


      One hundred twenty, 140, 185, and 90 participants aged < 50, 50 to 59, 60 to 69, and ≥ 70 years, respectively.


      We performed a secondary analysis of data from the DREAM study, a multicenter randomized clinical trial, to evaluate the effect of omega-3 fatty acid supplementation for the treatment of DED. At baseline, 6 months, and 12 months follow-up, participants underwent an assessment of DED symptoms and signs using Ocular Surface Disease Index, Brief Pain Inventory, tear break-up time (TBUT) (in seconds), Schirmer test with anesthesia (mm/5 minutes), conjunctival staining, corneal staining, meibomian gland dysfunction evaluation, and tear osmolarity (mOsm/l). Multivariable generalized linear regression models were used to compare DED symptoms and signs across the 4 age groups among all participants and by sex.

      Main Outcome Measures

      Scores of DED symptoms, individual signs, and composite scores of DED signs.


      Among 535 patients with DED, increasing age was significantly associated with worse TBUT (P = 0.01), corneal staining (P < 0.001), a composite severity score of DED signs (P = 0.007), and tear osmolarity (P = 0.001). Similar significant differences were found across 4 age groups of 334 women in TBUT, corneal staining score, composite severity score of DED signs, and tear osmolarity (all P < 0.05) but not in men.


      We found that corneal staining, TBUT, tear osmolarity, and a composite severity score of DED signs were significantly more severe with increasing age in women but not in men; worsening symptoms did not increase with increasing age.

      Financial Disclosure(s)

      The author(s) have no proprietary or commercial interest in any materials discussed in this article.


      Abbreviations and Acronyms:

      DED (dry eye disease), DREAM (Dry Eye Assessment and Management), MCS (mental component summary), MGD (meibomian gland dysfunction), OSDI (Ocular Surface Disease Index), TBUT (tear break-up time)
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        • Schiffman R.M.
        • Walt J.G.
        • Jacobsen G.
        • et al.
        Utility assessment among patients with dry eye disease.
        Ophthalmology. 2003; 110: 1412-1419
        • Uchino M.
        • Schaumberg D.A.
        Dry eye disease: impact on quality of life and vision.
        Curr Ophthalmol Rep. 2013; 1: 51-57
        • Schaumberg D.A.
        • Dana R.
        • Buring J.E.
        • Sullivan D.A.
        Prevalence of dry eye disease among US men: estimates from the Physicians’ Health Studies.
        Arch Ophthalmol. 2009; 127: 763-768
        • Schaumberg D.A.
        • Sullivan D.A.
        • Buring J.E.
        • Dana M.R.
        Prevalence of dry eye syndrome among US women.
        Am J Ophthalmol. 2003; 136: 318-326
        • de Paiva C.S.
        Effects of aging in dry eye.
        Int Ophthalmol Clin. 2017; 57: 47-64
        • Schein O.D.
        • Muñoz B.
        • Tielsch J.M.
        • et al.
        Prevalence of dry eye among the elderly.
        Am J Ophthalmol. 1997; 124: 723-728
        • Moss S.E.
        • Klein R.
        • Klein B.E.
        Incidence of dry eye in an older population.
        Arch Ophthalmol. 2004; 122: 369-373
        • Chia E.M.
        • Mitchell P.
        • Rochtchina E.
        • et al.
        Prevalence and associations of dry eye syndrome in an older population: the Blue Mountains Eye Study.
        Clin Exp Ophthalmol. 2003; 31: 229-232
        • Moss S.E.
        • Klein R.
        • Klein B.E.
        Prevalence of and risk factors for dry eye syndrome.
        Arch Ophthalmol. 2000; 118: 1264-1268
        • Paulsen A.J.
        • Cruickshanks K.J.
        • Fischer M.E.
        • et al.
        Dry eye in the beaver dam offspring study: prevalence, risk factors, and health-related quality of life.
        Am J Ophthalmol. 2014; 157: 799-806
        • McClellan A.J.
        • Volpe E.A.
        • Zhang X.
        • et al.
        Ocular surface disease and dacryoadenitis in aging C57BL/6 mice.
        Am J Pathol. 2014; 184: 631-643
        • Paschides C.A.
        • Petroutsos G.
        • Psilas K.
        Correlation of conjunctival impression cytology results with lacrimal function and age.
        Acta Ophthalmol (Copenh). 1991; 69: 422-425
        • Huang A.J.
        • Tseng S.C.
        • Kenyon K.R.
        Morphogenesis of rat conjunctival goblet cells.
        Invest Ophthalmol Vis Sci. 1988; 29: 969-975
        • Zhu W.
        • Hong J.
        • Zheng T.
        • et al.
        Age-related changes of human conjunctiva on in vivo confocal microscopy.
        Br J Ophthalmol. 2010; 94: 1448-1453
        • Vujković V.
        • Mikac G.
        • Kozomara R.
        Distribution and density of conjunctival goblet cells.
        Med Pregl. 2002; 55: 195-200
        • Wei A.
        • Hong J.
        • Sun X.
        • Xu J.
        Evaluation of age-related changes in human palpebral conjunctiva and meibomian glands by in vivo confocal microscopy.
        Cornea. 2011; 30: 1007-1012
        • Rocha E.M.
        • Alves M.
        • Rios J.D.
        • Dartt D.A.
        The aging lacrimal gland: changes in structure and function.
        Ocul Surf. 2008; 6: 162-174
        • Ríos J.D.
        • Horikawa Y.
        • Chen L.L.
        • et al.
        Age-dependent alterations in mouse exorbital lacrimal gland structure, innervation and secretory response.
        Exp Eye Res. 2005; 80: 477-491
        • Coursey T.G.
        • Bian F.
        • Zaheer M.
        • et al.
        Age-related spontaneous lacrimal keratoconjunctivitis is accompanied by dysfunctional T regulatory cells.
        Mucosal Immunol. 2017; 10: 743-756
        • Alghamdi Y.A.
        • Mercado C.
        • McClellan A.L.
        • et al.
        Epidemiology of meibomian gland dysfunction in an elderly population.
        Cornea. 2016; 35: 731-735
        • Galor A.
        • Feuer W.
        • Lee D.J.
        • et al.
        Prevalence and risk factors of dry eye syndrome in a United States Veterans Affairs population.
        Am J Ophthalmol. 2011; 152: 377-384.e2
        • Volpe E.A.
        • Henriksson J.T.
        • Wang C.
        • et al.
        Interferon-gamma deficiency protects against aging-related goblet cell loss.
        Oncotarget. 2016; 7: 64605-64614
        • You I.C.
        • Bian F.
        • Volpe E.A.
        • et al.
        Age-related conjunctival disease in the C57BL/6.NOD-Aec1Aec2 mouse model of Sjögren syndrome develops independent of lacrimal dysfunction.
        Invest Ophthalmol Vis Sci. 2015; 56: 2224-2233
        • Yamaguchi M.
        • Kutsuna M.
        • Uno T.
        • et al.
        Marx line: fluorescein staining line on the inner lid as indicator of meibomian gland function.
        Am J Ophthalmol. 2006; 141: 669-675
        • Boren E.
        • Gershwin M.E.
        Inflamm-aging: autoimmunity, and the immune-risk phenotype.
        Autoimmun Rev. 2004; 3: 401-406
        • Butcher S.K.
        • Lord J.M.
        Stress responses and innate immunity: aging as a contributory factor.
        Aging Cell. 2004; 3: 151-160
        • Canaday D.H.
        • Parker K.E.
        • Aung H.
        • et al.
        Age-dependent changes in the expression of regulatory cell surface ligands in activated human T-cells.
        BMC Immunol. 2013; 14: 45
        • Capri M.
        • Monti D.
        • Salvioli S.
        • et al.
        Complexity of anti-immunosenescence strategies in humans.
        Artif Organs. 2006; 30: 730-742
        • Ozdemir M.
        • Temizdemir H.
        Age- and gender-related tear function changes in normal population.
        Eye (Lond). 2010; 24: 79-83
        • Maïssa C.
        • Guillon M.
        Tear film dynamics and lipid layer characteristics--effect of age and gender.
        Cont Lens Anterior Eye. 2010; 33: 176-182
        • Obata H.
        • Yamamoto S.
        • Horiuchi H.
        • Machinami R.
        Histopathologic study of human lacrimal gland. Statistical analysis with special reference to aging.
        Ophthalmology. 1995; 102: 678-686
        • Obata H.
        Anatomy and histopathology of the human lacrimal gland.
        Cornea. 2006; 25: S82-S89
        • Zhao M.
        • Yu Y.
        • Roy N.S.
        • et al.
        Sex-related differences and hormonal effects in the Dry Eye Assessment and Management (DREAM) study.
        Br J Ophthalmol. Published online December 8, 2022;
        • Asbell P.A.
        • Maguire M.G.
        • et al.
        • Dry Eye Assessment and Management Study Research Group
        n-3 Fatty acid supplementation for the treatment of dry eye disease.
        N Engl J Med. 2018; 378: 1681-1690
        • Pistilli M.
        • Peskin E.
        • Brader H.
        • et al.
        Evaluation of a modification of the brief pain inventory (BODI) as a measure of severity of dry eye disease.
        Invest Ophthalmol Vis Sci. 2013; 54: 4359
        • Jenkinson C.
        The SF-36 physical and mental health summary measures: an example of how to interpret scores.
        J Health Serv Res Policy. 1998; 3: 92-96
        • Yu K.
        • Bunya V.
        • Maguire M.
        • et al.
        Systemic conditions associated with severity of dry eye signs and symptoms in the Dry Eye Assessment and Management study.
        Ophthalmology. 2021; 128: 1384-1392
        • Zhou Y.
        • Murrough J.
        • Yu Y.
        • et al.
        Association between depression and severity of dry eye symptoms, signs, and inflammatory markers in the DREAM study.
        JAMA Ophthalmol. 2022; 140: 392-399
        • Sullivan B.D.
        • Whitmer D.
        • Nichols K.K.
        • et al.
        An objective approach to dry eye disease severity.
        Invest Ophthalmol Vis Sci. 2010; 51: 6125-6130
        • Ong E.S.
        • Felix E.R.
        • Levitt R.C.
        • et al.
        Epidemiology of discordance between symptoms and signs of dry eye.
        Br J Ophthalmol. 2018; 102: 674-679
        • Lemp M.A.
        • Bron A.J.
        • Baudouin C.
        • et al.
        Tear osmolarity in the diagnosis and management of dry eye disease.
        Am J Ophthalmol. 2011; 151: 792-798.e1
        • Hashemi H.
        • Khabazkhoob M.
        • Kheirkhah A.
        • et al.
        Prevalence of dry eye syndrome in an adult population.
        Clin Exp Ophthalmol. 2014; 42: 242-248
        • Tellefsen Nøland S.
        • Badian R.A.
        • Utheim T.P.
        • et al.
        Sex and age differences in symptoms and signs of dry eye disease in a Norwegian cohort of patients.
        Ocul Surf. 2021; 19: 68-73
        • Badian R.A.
        • Utheim T.P.
        • Chen X.
        • et al.
        Meibomian gland dysfunction is highly prevalent among first-time visitors at a Norwegian dry eye specialist clinic.
        Sci Rep. 2021; 1123412
        • Viso E.
        • Rodríguez-Ares M.T.
        • Abelenda D.
        • et al.
        Prevalence of asymptomatic and symptomatic meibomian gland dysfunction in the general population of Spain.
        Invest Ophthalmol Vis Sci. 2012; 53: 2601-2606
        • Dogru M.
        • Kojima T.
        • Simsek C.
        • Tsubota K.
        Potential role of oxidative stress in ocular surface inflammation and dry eye disease.
        Invest Ophthalmol Vis Sci. 2018; 59: DES163-DES168
        • Junqueira V.B.
        • Barros S.B.
        • Chan S.S.
        • et al.
        Aging and oxidative stress.
        Mol Aspects Med. 2004; 25: 5-16
        • Augustin A.J.
        • 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
        • Grossweiner L.I.
        Photochemistry of proteins: a review.
        Curr Eye Res. 1984; 3: 137-144
        • Tseng S.C.
        Staging of conjunctival squamous metaplasia by impression cytology.
        Ophthalmology. 1985; 92: 728-733
        • Lemp M.A.
        Recent developments in dry eye management.
        Ophthalmology. 1987; 94: 1299-1304
        • Lemp M.A.
        • Gold J.B.
        • Wong S.
        • et al.
        An in vivo study of corneal surface morphologic features in patients with keratoconjunctivitis sicca.
        Am J Ophthalmol. 1984; 98: 426-428
        • Seen S.
        • Tong L.
        Dry eye disease and oxidative stress.
        Acta Ophthalmol. 2018; 96: e412-e420
        • Uchino Y.
        • Kawakita T.
        • Ishii T.
        • et al.
        A new mouse model of dry eye disease: oxidative stress affects functional decline in the lacrimal gland.
        Cornea. 2012; 31: S63-S67
        • Uchino Y.
        • Kawakita T.
        • Miyazawa M.
        • et al.
        Oxidative stress induced inflammation initiates functional decline of tear production.
        PLOS ONE. 2012; 7e45805
        • Auw-Haedrich C.
        • Feltgen N.
        Estrogen receptor expression in meibomian glands and its correlation with age and dry-eye parameters.
        Graefes Arch Clin Exp Ophthalmol. 2003; 241: 705-709
        • Lekhanont K.
        • Rojanaporn D.
        • Chuck R.S.
        • Vongthongsri A.
        Prevalence of dry eye in Bangkok, Thailand.
        Cornea. 2006; 25: 1162-1167
        • Bourcier T.
        • Acosta M.C.
        • Borderie V.
        • et al.
        Decreased corneal sensitivity in patients with dry eye.
        Invest Ophthalmol Vis Sci. 2005; 46: 2341-2345