This research investigates the associations between Dry Eye Disease (DED), pain perception, and mental health, focusing on how neuropathic pain influences treatment efficacy and patients’ quality of life.
Methods and Results
The study delves into the complexity of DED by assessing the correlation between ocular pain, depression, PTSD, and systemic pain conditions. It highlights the role of chronic neuropathic pain in DED and the nociceptive hypothesis, which suggests that psychological stress can exacerbate DED symptoms. Additionally, it explores diagnostic and management strategies for DED, emphasizing the importance of considering psychological aspects to improve patient care.
Conclusions
The intricate nature of DED, closely linked to mental health issues, requires a comprehensive diagnostic and therapeutic approach. Addressing neuropathic pain and psychological factors is crucial for effective DED management. Future efforts should focus on developing specific interventions targeting DED's physical and emotional impacts to enhance overall patient well-being.
The Epidemiology Subcommittee of the International Dry Eye WorkShop. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye Workshop (2007). Ocul Surf2007; 5: 93–107.
2.
KalangaraJPGalorALevittRC, et al.Burning eye syndrome: do neuropathic pain mechanisms underlie chronic dry eye?Pain Med2016; 17: 746–755.
3.
GalorAZlotcavitchLWalterSD, et al.Dry eye symptom severity and persistence are associated with symptoms of neuropathic pain. Br J Ophthalmol2015; 99: 665–668.
4.
GalorABatawiHFelixER, et al.Incomplete response to artificial tears is associated with features of neuropathic ocular pain. Br J Ophthalmol2016; 100: 745–749.
5.
McDonaldMPatelDAKeithMS,et al.Economic and humanistic burden of dry eye disease in Europe, North America, and Asia: a systematic literature review. Ocul Surf2016; 14: 144–167.
6.
UchinoMSchaumbergDA. Dry eye disease: impact on quality of life and vision. Curr Ophthalmol Rep2013; 1: 51–57.
7.
KastelanSBakijaIBogadiM, et al.Mental disorders as influencing factors for discordances in the signs and symptoms of dry eye disease. Psychiatr Danub2021; 33: 588–595.
8.
Schein ODB-RK, et al.Self-reported assessment of dry eye in a population-based setting. Invest Ophthalmol Vis Sci1997; 38: 2469–2475.
9.
NicholsKKNicholsJJ, et al.The lack of association between signs and symptoms in patients with dry eye disease. Cornea2004; 23: 762–770.
10.
GalorALevittRCFelixER,et al.Understanding the true burden of dry eye disease. Expert Rev Ophthalmol2015; 10: 403–405.
11.
PatelVDWatanabeJHStraussJA,et al.Work productivity loss in patients with dry eye disease: an online survey. Curr Med Res Opin2011; 27: 1041–1048.
12.
NaKSHanKParkYG, et al.Depression, stress, quality of life, and dry eye disease in Korean women: a population-based study. Cornea2015; 34: 733–738.
13.
CutrupiFDe LucaADi ZazzoA, et al.Real life impact of dry eye disease. Semin Ophthalmol2023; 38: 1–13.
14.
LempMAFoulksGN. Definition and classification of dry eye disease. Ocul Surf2007; 5: 75–92.
15.
KimKWHanSBHanER, et al.Association between depression and dry eye disease in an elderly population. Invest Ophthalmol Vis Sci2011; 52: 7954–7958.
16.
LabbéALiangQWangZ, et al.Dry eye disease, dry eye symptoms and depression: the Beijing eye study. Br J Ophthalmol2013; 97: 1399–1403.
17.
U.S. Department of Health and Human Services. Health-related quality of life and well-being. Washington, DC: U.S. Department of Health and Human Services, 2020. Updated October 8, 2020. https://www.healthypeople.gov/
18.
BuchholzPSteedsCSSternLS, et al.Utility assessment to measure the impact of dry eye disease. Ocul Surf2006; 4: 155–161.
19.
KalangaraJPGalorALevittRC, et al.Characteristics of ocular pain complaints in patients with idiopathic dry eye symptoms. Eye Contact Lens2017; 43: 192–198.
20.
GalorAFelixERFeuerW, et al.Dry eye symptoms align more closely to non-ocular conditions than to tear film parameters. Br J Ophthalmol2015; 99: 1126–1129.
21.
AlvesMFonsecaECAlvesMF, et al.Determinants of ocular pain severity in patients with dry eye disease. Am J Ophthalmol2017; 179: 198–204.
22.
ErbCHornAGunthnerA, et al.Psychosomatic aspects of patients with primary keratoconjunctivitis sicca. Klin Monbl Augenheilkd1996; 208: 96–99.
23.
GalorASeidenBEParkJJ, et al.The association of dry eye symptom severity and comorbid insomnia in US veterans. Eye Contact Lens2017; 43: 355–361.
24.
GalorALevittRCMcManusKT, et al.Assessment of somatosensory function in patients with idiopathic dry eye symptoms. JAMA Ophthalmol2016; 134: 1290–1298.
25.
VehofJKozarevaDHysiPG, et al.Relationship between dry eye symptoms and pain sensitivity. JAMA Ophthalmol2013; 131: 1304–1308.
26.
GoyalSHamrahP. Understanding neuropathic corneal pain–gaps and current therapeutic approaches. Semin Ophthalmol2016; 31: 59–70.
JensenTS. An improved understanding of neuropathic pain. Eur J Pain2002; 6: 3–11.
29.
GalorALevittRCFelixER, et al.Neuropathic ocular pain: an important yet underevaluated feature of dry eye. Eye (Lond)2015; 29: 301–312.
30.
MansourARFarmerMABalikiMN, et al.Chronic pain: the role of learning and brain plasticity. Restor Neurol Neurosci2014; 32: 129–139.
31.
CostiganMScholzJWoolfCJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci2009; 32: 1–32.
32.
Di ZazzoACoassinMSuricoPL,et al.Age-related ocular surface failure: a narrative review. Exp Eye Res2022; 205: 108527.
33.
MomiSKFabianeSMLachanceG, et al.Neuropathic pain as part of chronic widespread pain: environmental and genetic influences. Pain2015; 156: 2100–2106.
34.
YunusMB. Central sensitivity syndromes: a new paradigm and group nosology for fibromyalgia and overlapping conditions, and the related issue of disease versus illness. Semin Arthritis Rheum2008; 37: 339–352.
35.
AaronLABurkeMMBuchwaldD. Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch Intern Med2000; 160: 221–227.
36.
YunusMB. Editorial review: an update on central sensitivity syndromes and the issues of nosology and psychobiology. Curr Rheumatol Rev2015; 11: 70–85.
37.
FinanPHSmithMT. The comorbidity of insomnia, chronic pain, and depression: dopamine as a putative mechanism. Sleep Med Rev2013; 17: 173–183.
38.
GalorAFeuerWLeeDJ, et al.Depression, post-traumatic stress disorder, and dry eye syndrome: a study utilizing the national United States veterans affairs administrative database. Am J Ophthalmol2012; 154: 340–346.e2.
39.
BalikiMNPetreBTorbeyS, et al.Corticostriatal functional connectivity predicts transition to chronic back pain. Nat Neurosci2012; 15: 1117–1119.
40.
LeknesSLeeMBernaC, et al.Relief as a reward: hedonic and neural responses to safety from pain. PLoS One2011; 6: e17870.
41.
SeymourBDawNDRoiserJP, et al.Serotonin selectively modulates reward value in human decision-making. J Neurosci2012; 32: 5833–5842.
42.
AblerBWalterHErkS, et al.Prediction error as a linear function of reward probability is coded in human nucleus accumbens. Neuroimage2006; 31: 790–795.
43.
PagnoniGZinkCFMontaguePR,et al.Activity in human ventral striatum locked to errors of reward prediction. Nat Neurosci2002; 5: 97–98.
44.
NicolaSMYunIAWakabayashiKT,et al.Firing of nucleus accumbens neurons during the consummatory phase of a discriminative stimulus task depends on previous reward predictive cues. J Neurophysiol2004; 91: 1866–1882.
45.
HartASRutledgeRBGlimcherPW,et al.Phasic dopamine release in the rat nucleus accumbens symmetrically encodes a reward prediction error term. J Neurosci2014; 34: 698–704.
46.
LöfflerMLevineSMUsaiK, et al.Corticostriatal circuits in the transition to chronic back pain: the predictive role of reward learning. Cell Rep Med2022; 3: 100677.
47.
AaronLAArguellesLMAshtonS, et al.Health and functional status of twins with chronic regional and widespread pain. J Rheumatol2002; 29: 2426–2434.
AaronLAHerrellRAshtonS, et al.Comorbid clinical conditions in chronic fatigue: a co-twin control study. J Gen Intern Med2001; 16: 24–31.
50.
StapletonFAlvesMBunyaVY, et al.TFOS DEWS II epidemiology report. Ocul Surf2017; 15: 334–365.
51.
BronAJde PaivaCSChauhanSK, et al.TFOS DEWS II pathophysiology report. Ocul Surf2017; 15: 438–510.
52.
BelmonteCNicholsJJCoxSM, et al.TFOS DEWS II pain and sensation report. Ocul Surf2017; 15: 404–437.
53.
MrugaczMOstrowskaLBrylA, et al.Pro-inflammatory cytokines associated with clinical severity of dry eye disease of patients with depression. Adv Med Sci2017; 62: 338–344.
54.
SullivanDARochaEMAragonaP, et al.TFOS DEWS II sex, gender, and hormones report. Ocul Surf2017; 15: 284–333.
55.
WangMTMVidal-RohrMMuntzA, et al.Systemic risk factors of dry eye disease subtypes: a New Zealand cross-sectional study. Ocul Surf2020; 18: 374–380.
56.
BourcierTAcostaMCBorderieV, et al.Decreased corneal sensitivity in patients with dry eye. Invest Ophthalmol Vis Sci2005; 46: 2341–2345.
57.
OngESFelixERLevittRC, et al.Epidemiology of discordance between symptoms and signs of dry eye. Br J Ophthalmol2018; 102: 674–679.
58.
GalorACovingtonDLevittAE, et al.Neuropathic ocular pain due to dry eye is associated with multiple comorbid chronic pain syndromes. J Pain2015; 17: 310–318.
59.
Lund HåheimLNafstadPOlsenI, et al.C-reactive protein variations for different chronic somatic disorders. Scand J Public Health2009; 37: 640–646.
60.
ChungSDLiuHTLinH, et al.Elevation of serum c-reactive protein in patients with OAB and IC/BPS implies chronic inflammation in the urinary bladder. Neurourol Urodyn2011; 30: 417–420.
61.
HashimotoK. Brain-derived neurotrophic factor (BDNF) and its precursor proBDNF as diagnostic biomarkers for major depressive disorder and bipolar disorder. Eur Arch Psychiatry Clin Neurosci2014; 264: 1–2. (Note: The issue number might need to be verified as “1–2” suggests a range that is unusual for journal formatting.).
62.
FauchaisALBoumedieneALalloueF, et al.Brain-derived neurotrophic factor and nerve growth factor correlate with T-cell activation in primary Sjogren’s syndrome. Scand J Rheumatol2009; 38: 50–57.
BelmonteCAracilAAcostaMC, et al.Nerves and sensations from the eye surface. Ocul Surf2004; 2: 248–253.
65.
GalorAFeuerWLeeDJ, et al.Ocular surface parameters in older male veterans. Invest Ophthalmol Vis Sci2013; 54: 1426–1433.
66.
OngESAlghamdiYALevittRC, et al.Longitudinal examination of frequency of and risk factors for severe dry eye symptoms in US veterans. JAMA Ophthalmol2017; 135: 116–123.
67.
GorenMBGorenSB. Diagnostic tests in patients with symptoms of keratoconjunctivitis sicca. Am J Ophthalmol1988; 106: 570–574.
68.
ScheinODTielschJMMuñozB, et al.Relation between signs and symptoms of dry eye in the elderly. A population-based perspective. Ophthalmology1997; 104: 1395–1401.
69.
JaeschkeRSingerJGuyattGH. Measurement of health status. Ascertaining the minimal clinically important difference. Control Clin Trials1989; 10: 407–415.
70.
McCormickJDWernerBCShimerAL. Patient-reported outcome measures in spine surgery. J Am Acad Orthop Surg2013; 21: 99–107.
71.
SchwartzCEAyandehAFinkelsteinJA. When patients and surgeons disagree about surgical outcome: investigating patient factors and chart note communication. Health Qual Life Outcomes2015; 13: 161.
72.
RoitbergBZThaciBAuffingerB, et al.Comparison between patient and surgeon perception of degenerative spine disease outcomes: a prospective blinded database study. Acta Neurochir (Wien2013; 155: 757–764.
73.
BroadbentEWilkesCKoschwanezH, et al.A systematic review and meta-analysis of the brief illness perception questionnaire. Psychol Health2015; 30: 1361–1385.
74.
LeventhalHDiefenbachMLeventhalEA. Illness cognition: using common-sense to understand treatment adherence and affect-cognition interactions. Cognit Ther Res1992; 16: 143–163.
75.
QaziYHurwitzSKhanS, et al.Validity and reliability of a novel ocular pain assessment survey (OPAS) in quantifying and monitoring corneal and ocular surface pain. Ophthalmology2016; 123: 1458–1468.
76.
BouhassiraDAttalNFermanianJ, et al.Development and validation of the neuropathic pain symptom inventory. Pain2004; 108: 248–257.
77.
JensenMPGammaitoniAROlaleyeDO, et al.The pain quality assessment scale: assessment of pain quality in carpal tunnel syndrome. J Pain2006; 7: 823–832.
78.
TonookaKYukiKKouyamaK, et al.Dry eye disease is associated with deterioration of mental health in male Japanese university staff. Tohoku J Exp Med2014; 233: 215–220.
79.
LiMGongLChapinWJ,et al.Assessment of vision-related quality of life in dry eye patients. Invest Ophthalmol Vis Sci2012; 53: 5722–5727.
80.
AsieduKDzasimatuSKKyeiS. Impact of dry eye on psychosomatic symptoms and quality of life in a healthy youthful clinical sample. Eye Contact Lens2018; 44: S404–S409.
81.
SayeghRRYuYFarrarJT, et al.Ocular discomfort and quality of life among patients in the dry eye assessment and management study. Cornea2021; 40: 869–876.
82.
AsmundsonGJAbramowitzJSRichterAA,et al.Health anxiety: current perspectives and future directions. Curr Psychiatry Rep2010; 12: 306–312.
83.
TothMJokić-BegićN. Psychological contribution to understanding the nature of dry eye disease: a cross-sectional study of anxiety sensitivity and dry eyes. Health Psychol Behav Med2020 May 28; 8: 202–219.
84.
Bourgault-FagnouMDHadjistavropoulosHD. Understanding health anxiety among community dwelling seniors with varying degrees of frailty. Aging Ment Health2009; 13: 226–237.
85.
BarabinoSLabetoulleMRolandoM,et al.Understanding symptoms and quality of life in patients with dry eye syndrome. Ocul Surf2016; 14: 365–376.
86.
FriedmanNJ. Impact of dry eye disease and treatment on quality of life. Curr Opin Ophthalmol2010; 21: 310–316.
87.
LiMGongLSunX,et al.Anxiety and depression in patients with dry eye syndrome. Curr Eye Res2011; 36: 1–7.
FernandezCAGalorAArheartKL, et al.Dry eye syndrome, posttraumatic stress disorder, and depression in an older male veteran population. Invest Ophthalmol Vis Sci2013; 54: 3666–3672.
90.
VriezekolkJEGeenenRHartkampA, et al.Psychological and somatic predictors of perceived and measured ocular dryness of patients with primary Sjogren's syndrome. J Rheumatol2005; 32: 2351–2355.
91.
KimKWHanJWChoHJ, et al.Association between comorbid depression and osteoarthritis symptom severity in patients with knee osteoarthritis. J Bone Joint Surg Am2011; 93: 556–563.
92.
AnYKimH. Sleep disorders, mental health, and dry eye disease in South Korea. Sci Rep2022; 12: 1–11.
93.
WuMLiuXHanJ, et al.Association between sleep quality, mood status, and ocular surface characteristics in patients with dry eye disease. Cornea2019; 38: 311–317.
94.
KaiserTJanssenBSchraderS,et al.Depressive symptoms, resilience, and personality traits in dry eye disease. Graefes Arch Clin Exp Ophthalmol2019; 257: 591–599.
95.
VehofJSmitt-KammingaNSNibourgSA,et al.Predictors of discordance between symptoms and signs in dry eye disease. Ophthalmology2017; 124: 280–286.
96.
ApkarianAV. Pain perception in relation to emotional learning. Curr Opin Neurobiol2008; 18: 464–468.
97.
WangMTMMuntzAWolffsohnJS,et al.Association between dry eye disease, self-perceived health status, and self-reported psychological stress burden. Clin Exp Optom2021; 104: 835–840.
98.
ZhengYWuXLinX,et al.The prevalence of depression and depressive symptoms among eye disease patients: a systematic review and meta-analysis. Sci Rep2017; 7: 46453. Published 2017 Apr 12.
99.
YilmazUGoklerMEUnsalA. Dry eye disease and depression-anxiety-stress: a hospital-based case-control study in Turkey. Pakistan J Med Sci2015; 31: 626–631.
100.
FeltonBJRevensonTA. Age differences in coping with chronic illness. Psychol Aging1987; 2: 164–170.
101.
WestbrookMTVineyLL. Age and sex differences in patients’ reactions to illness. J Health Soc Behav1983; 24: 313–324.
102.
MertzanisPAbetzLRajagopalanK, et al.The relative burden of dry eye in patients’ lives: comparisons to a U.S. Normative sample. Invest Ophthalmol Vis Sci2005; 46: 46–50.
103.
LeQZhouXGeL, et al.Impact of dry eye syndrome on vision-related quality of life in a non-clinic-based general population. BMC Ophthalmol2012; 12: 22. Published 2012 Jul 16.
104.
LiMGongLSunX,et al.Assessment of vision-related quality of life in dry eye patients. Invest Ophthalmol Vis Sci2012; 53: 5722–5727.
105.
SakaneYYamaguchiMYokoiN,et al.Development and validation of the dry eye-related quality-of-life score questionnaire. JAMA Ophthalmol2013; 131: 1331–1338.
106.
KheirkhahACrnejARenA, et al.Patients’ perceived treatment effectiveness in dry eye disease. Cornea2017; 36: 893–897.
107.
WeatherbyTJMRamanVRVAgiusM. Depression and dry eye disease: a need for an interdisciplinary approach?Psychiatr Danub2019; 31: 619–621.
108.
FillingimRBKingCDRibeiro-DasilvaMC, et al.Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain2009; 10: 447–485.
109.
VehofJSniederHJansoniusN,et al.Prevalence and risk factors of dry eye in 79,866 participants of the population-based lifelines cohort study in The Netherlands. Ocul Surf2021; 19: 83–93.
110.
MorthenMKMagnoMSUtheimTP, et al.The physical and mental burden of dry eye disease: a large population-based study investigating the relationship with health-related quality of life and its determinants. Ocul Surf2021; 21: 107–117.
111.
FinkPØrnbølEChristensenKS. The outcome of health anxiety in primary care. A two-year follow-up study on health care costs and self-rated health. PLoS ONE2010; 5: e9873.
112.
LeventhalHPhillipsLABurnsE. The common-sense model of self-regulation (CSM): a dynamic framework for understanding illness self-management. J Behav Med2016; 39: 935–946.
113.
WenWWuYChenY, et al.Dry eye disease in patients with depressive and anxiety disorders in Shanghai. Cornea2012; 31: 686–692.
114.
BarbasioCVagelliRMarengoD, et al.Illness perception in systemic lupus erythematosus patients: the roles of alexithymia and depression. Compr Psychiatry2015; 63: 88–95.
115.
KnowlesSSwanLSalzbergM, et al.Exploring the relationships between health status, illness perceptions, coping strategies and psychological morbidity in a chronic kidney disease cohort. Am J Med Sci2014; 348: 271–276.
116.
JuergensMCSeekatzBMoosdorfRG, et al.Illness beliefs before cardiac surgery predict disability, quality of life, and depression 3 months later. J Psychosom Res2010; 68: 553–560.
117.
CherringtonCCMoserDKLennieTA,et al.Illness representation after acute myocardial infarction: impact on in-hospital recovery. Am J Crit Care2004; 13: 136–145.
118.
FurzeGLewinRJMurbergT, et al.Does it matter what patients think? The relationship between changes in patients’ beliefs about angina and their psychological and functional status. J Psychosom Res2005; 59: 323–329.
119.
LiyueHChiangPPCSungSC,et al.Dry eye-related visual blurring and irritative symptoms and their association with depression and anxiety in eye clinic patients. Curr Eye Res2016; 41: 590–599.
120.
SzakátsISebestyénMNémethJ, et al.The role of health anxiety and depressive symptoms in dry eye disease. Curr Eye Res2016; 41: 1044–1049.
121.
LiangCYCheangWMWangCY, et al.The association of dry eye syndrome and psychiatric disorders: a nationwide population-based cohort study. BMC Ophthalmol2020; 20: 123.
122.
UmSBYeomHKimNH, et al.Association between dry eye symptoms and suicidal ideation in a Korean adult population. PLoS One2018; 13: e0199131.
123.
BernertRAJoinerTE. Sleep disturbances and suicide risk: a review of the literature. Neuropsychiatr Dis Treat2007; 3: 735–743.
124.
ConnerKR. Meta-analysis of sleep disturbance and suicidal thoughts and behaviors. J Clin Psychiatry2012; 73: e1160–e1167.
125.
FoulksGNForstotSLDonshikPC, et al.Clinical guidelines for management of dry eye associated with Sjögren syndrome. Ocul Surf2015; 13: 118–132.
126.
MossSEKleinRKleinBE. Prevalence of and risk factors for dry eye syndrome. Arch Ophthalmol2000; 118: 1264–1268.
127.
KoçerEKoçerAÖzsütçüM, et al.Dry eye related to commonly used new antidepressants. J Clin Psychopharmacol2015; 35: 411–413.
128.
WanKHChenLJYoungAL. Depression and anxiety in dry eye disease: a systematic review and meta-analysis. Eye2016; 30: 1558–1567.
129.
TiskaogluNSYazıcıAKarlıdereT, et al.Dry eye disease in patients with newly diagnosed depressive disorder. Curr Eye Res2017; 42: 672–676.
130.
KnopEKnopNMillarT, et al.The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci2011; 52: 1938–1978.
131.
ImadaTNakamuraSHisamuraR, et al.Serotonin hormonally regulates lacrimal gland secretory function via the serotonin type 3a receptor. Sci Rep2017; 7: 7.
132.
YeoSTongL. Coping with dry eyes: a qualitative approach. BMC Ophthalmol2018; 18: 8.
133.
ZhangYGanMHeY, et al.Anxiety disorders and gut dysbiosis in primary Sjögren’s syndrome-mediated dry eye patients. Int J Gen Med2023; 16: 1735–1746.
134.
HeQChenZXieC, et al.Relationship between dry eye disease and emotional disorder: the mediating effect of health anxiety. Front Public Health2022; 10: 771554.
135.
PetrieKJCameronLDEllisCJ, et al.Changing illness perceptions after myocardial infarction: an early intervention randomized controlled trial. Psychosom Med2002; 64: 580–586.
136.
BroadbentEEllisCJThomasJ, et al.Further development of an illness perception intervention for myocardial infarction patients: a randomized controlled trial. J Psychosom Res2009; 67: 17–23.
137.
KawashimaMSanoKTakechiS,et al.Impact of lifestyle intervention on dry eye disease in office workers: a randomized controlled trial. J Occup Health2018; 60: 281–288.
138.
KawashimaMUchinoMYokoiN, et al.The association between dry eye disease and physical activity as well as sedentary behavior: results from the Osaka study. J Ophthalmol2014; 2014: 943786.
139.
WolffsohnJSAritaRChalmersR, et al.TFOS DEWS II diagnostic methodology report. Ocul Surf2017; 15: 539–574.
140.
CraigJPNicholsKKAkpekEK, et al.TFOS DEWS II definition and classification report. Ocul Surf2017; 15: 276–283.
141.
PultHRiede-PultBHMurphyPJ. The relation between blinking and conjunctival folds and dry eye symptoms. Optom Vis Sci2013; 90: 1034–1039.
142.
CollinsMHeronHLarsenR,et al.Blinking patterns in soft contact lens wearers can be altered with training. Am J Optom Physiol Opt1987; 64: 100–103.
143.
MurakamiDBlackieCAKorbDR. Blinking exercises can be used to decrease partial blinking and improve gland function and symptoms in patients with evaporative dry eye. Denver: American Academy of Optometry, 2014.
144.
AsbellPAMaguireMGPistilliM, et al.n-3 fatty acid supplementation for the treatment of dry eye disease. N Engl J Med2018; 378: 1681–1690.
145.
OzenSOzerMAAkdemirMO. Vitamin B12 deficiency evaluation and treatment in severe dry eye disease with neuropathic ocular pain. Graefes Arch Clin Exp Ophthalmol2017; 255: 1173–1177.
MoriAShimazakiJShimmuraS, et al.Disposable eyelid-warming device for the treatment of meibomian gland dysfunction. Jpn J Ophthalmol2003; 47: 578–586.
148.
OtaKNizyoSYamadaS, et al.Influences of warm compression to eye area on physiological index and pleasant sensation and profile of mood states. Health Sciences Research2019; 10: 43–50.
149.
AbramsonDITuckSJrLeeSW, et al.Comparison of wet and dry heat in raising temperature of tissues. Arch Phys Med Rehabil1967; 48: 654–661.
150.
IgakiMHigashiTHamamotoS, et al.A study of the behavior and mechanism of thermal conduction in the skin under moist and dry heat conditions. Skin Res Technol2014; 20: 43–49.
151.
NagashimaYOdaHIgakiM, et al.Application of heat- and steam-generating sheets to the lumbar or abdominal region affects autonomic nerve activity. Auton Neurosci2006; 126-127: 68–71.
152.
KatoK. Effects of the application of a hot compress to the posterior region of the neck on physiological indices, subjective sleep, and feelings of pleasure among inpatients. Japanese J Nurs Art Sci 2012; 10: 10–18.
153.
HashimotoK. BDNF And proBDNF as biomarkers for bipolar disorder. Br J Psychiatry2014; 205: 410.
154.
MurphyHDickensCCreedF, et al.Depression, illness perception and coping in rheumatoid arthritis. J Psychosom Res1999; 46: 155–164.
