Dry eye disease (DED) is arguably the most frequent ocular disease encountered in ophthalmic clinical practice. DED is frequently an underestimated condition causing a significant impact on visual function and quality of life. Many systemic autoimmune diseases (SAIDs) are related to moderate to severe DED. The main objective of this review is to enhance the awareness among ophthalmologists of the potential association of an underlying SAID in a high-risk patient with DED.
Methods
An exhaustive literature search was performed in the National Library of Medicine's Pubmed, Scopus, Web of Science, and Google Scholar databases for all English language articles published until November 2021. The main keywords included “dry eye disease” associated with autoimmune, connective tissue, endocrine, gastrointestinal, hematopoietic, vascular, and pulmonary diseases. Case reports, series, letters to the editor, reviews, and original articles were included.
Results
Although DED is frequently associated with SAIDs, its diagnosis is commonly delayed or missed, producing significant complications, including corneal ulceration, melting, scleritis, uveitis, and optic neuritis resulting in severe complications detrimental to visual function and quality of life. SAID should be suspected in a woman, 30 to 60 years old with a family history of autoimmunity, presenting with DED symptoms and extraocular manifestations including arthralgias, dry mouth, unexplained weight and hair loss, chronic fatigue, heat or cold intolerance, insomnia, and mood disorders.
Conclusions
Establishing the correct diagnosis and treatment of DED associated with SAIDs is crucial to avoid its significant burden and severe ocular complications.
BarabinoSAragonaPdi ZazzoA, et al.Updated definition and classification of dry eye disease: renewed proposals using the nominal group and Delphi techniques. Eur J Ophthalmol2021; 31: 42–48.
2.
CraigJPNicholsKKAkpekEK, et al.TFOS DEWS II definition and classification report. Ocul Surf2017; 15: 276–283.
PurnamawatiKOngJADeshpandeS, et al.The importance of Sex stratification in autoimmune disease biomarker research: a systematic review. Front Immunol2018; 9: 1208.
5.
AlhamadEHCalJGAlBoukaiAA, et al.Autoimmune symptoms in idiopathic pulmonary fibrosis: clinical significance. Clin Respir J2016; 10: 350–358.
6.
HenrichCFRamuluPYAkpekEK. Association of dry eye and inflammatory systemic diseases in a tertiary care-based sample. Cornea2014; 33: 819–825.
7.
UhligTKvienTKJensenJL, et al.Sicca symptoms, saliva and tear production, and disease variables in 636 patients with rheumatoid arthritis. Ann Rheum Dis1999; 58: 415–422.
MartinsTMiranda SipahiADos SantosFM, et al.Eye disorders in patients with celiac disease and inflammatory bowel disease: a study using clinical data warehouse. Eur J Ophthalmol2021. https://doi.org/10.1177/11206721211012849
10.
YuKBunyaVMaguireM, et al.Systemic conditions associated with severity of dry eye signs and symptoms in the dry eye assessment and management study. Ophthalmology2021; 128: 1384–1392.
11.
ManaviatMRRashidiMAfkhami-ArdekaniM, et al.Prevalence of dry eye syndrome and diabetic retinopathy in type 2 diabetic patients. BMC Ophthalmol2008; 8: 10. https://doi.org/10.1186/1471-2415-8-10
12.
KashkouliMBAlemzadehSAAghaeiH, et al.Subjective versus objective dry eye disease in patients with moderate-severe thyroid eye disease. Ocul Surf2018; 16: 458–462.
13.
MatossianCMcDonaldMDonaldsonKE, et al.dry eye disease: consideration for Women's Health. J Womens Health (Larchmt2019; 28: 502–514.
14.
SmithTJHegedusL. Graves’ disease. N Engl J Med2016; 375: 1552–1565.
15.
JonssonRBrokstadKAJonssonMV, et al.Current concepts on Sjogren's syndrome - classification criteria and biomarkers. Eur J Oral Sci2018; 126: 37–48.
16.
GarciaDMReis de OliveiraFModuloCM, et al.Is sjogren's syndrome dry eye similar to dry eye caused by other etiologies? Discriminating different diseases by dry eye tests. PLoS One2018; 13: e0208420.
17.
Le GoffMCornecDJousse-JoulinS, et al.Comparison of 2002 AECG and 2016 ACR/EULAR classification criteria and added value of salivary gland ultrasonography in a patient cohort with suspected primary sjogren's syndrome. Arthritis Res Ther2017; 19: 269.
18.
WolffsohnJSAritaRChalmersR, et al.TFOS DEWS II diagnostic methodology report. Ocul Surf2017; 15: 539–574.
19.
WhitcherJPShiboskiCHShiboskiSC, et al.A simplified quantitative method for assessing keratoconjunctivitis sicca from the sjogren's syndrome international registry. Am J Ophthalmol2010; 149: 405–415.
20.
NicholsKKFoulksGNBronAJ, et al.The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci2011; 52: 1922–1929.
21.
Ruiz-LozanoREHernandez-CamarenaJCGarza-GarzaLA, et al.Isotretinoin and the eye: a review for the dermatologistDermatol Ther2020; 33: e14029.
22.
PflugfelderSCTsengSCSanabriaO, et al.Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorders known to cause ocular irritation. Cornea1998; 17: 38–56.
23.
SenchynaMWaxMB. Quantitative assessment of tear production: a review of methods and utility in dry eye drug discovery. J Ocul Biol Dis Infor2008; 1: 1–6.
24.
BegleyCCafferyBChalmersR, et al.Review and analysis of grading scales for ocular surface staining. Ocul Surf2019; 17: 208–220.
25.
MathersWDShieldsWJSachdevMS, et al.Meibomian gland morphology and tear osmolarity: changes with Accutane therapy. Cornea1991; 10: 286–290.
26.
Rodriguez-GarciaAMacias-RodriguezYGonzalez-GonzalezJM. Efficacy and safety of 0.1% lodoxamide for the long-term treatment of superior limbic keratoconjunctivitis. Int Ophthalmol2018; 38: 1243–1249.
27.
YamaguchiMSakaneYKamaoT, et al.Noninvasive dry eye assessment using high-technology ophthalmic examination devices. Cornea2016; 35: S38–S48.
28.
TianLQuJHZhangXY, et al.Repeatability and reproducibility of noninvasive Keratograph 5M measurements in patients with dry eye disease. J Ophthalmol2016; 2016: 8013621.
29.
KamaoTYamaguchiMKawasakiS, et al.Screening for dry eye with newly developed ocular surface thermographer. Am J Ophthalmol2011; 151: 782–791.
30.
SchmidlDSchlatterAChuaJ, et al.Novel approaches for imaging-based diagnosis of ocular surface disease. Diagnostics (Basel2020; 10: 589.
31.
StegmannHAranha Dos SantosVMessnerA, et al.Automatic assessment of tear film and tear meniscus parameters in healthy subjects using ultrahigh-resolution optical coherence tomography. Biomed Opt Express2019; 10: 2744–2756.
32.
SchmidlDWitkowskaKJKayaS, et al.The association between subjective and objective parameters for the assessment of dry-eye syndrome. Invest Ophthalmol Vis Sci2015; 56: 1467–1472.
33.
ChenQZhangXCuiL, et al.Upper and lower tear menisci in Sjogren's syndrome dry eye. Invest Ophthalmol Vis Sci2011; 52: 9373–9378.
34.
Altan-YayciogluRSizmazSCananH, et al.Optical coherence tomography for measuring the tear film meniscus: correlation with schirmer test and tear-film breakup time. Curr Eye Res2013; 38: 736–742.
35.
LempMABronAJBaudouinC, et al.Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol2011; 151: 792–798.
36.
JacobiCJacobiAKruseFE, et al.Tear film osmolarity measurements in dry eye disease using electrical impedance technology. Cornea2011; 30: 1289–1292.
37.
ChanCCBorovikAHofmannI, et al.Validity and reliability of a novel handheld osmolarity system for measurement of a national institute of standards traceable solution. Cornea2018; 37: 1169–1174.
38.
SzalaiEBertaASzekaneczZ, et al.Evaluation of tear osmolarity in non-sjogren and sjogren syndrome dry eye patients with the TearLab system. Cornea2012; 31: 867–871.
39.
FoulksGNPflugfelderSC. New testing options for diagnosing and grading dry eye disease. Am J Ophthalmol2014; 157: 1122–1129.
40.
Biomarkers Definitions WorkingG. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther2001; 69: 89–95.
41.
TamhaneMCabrera-GhayouriSAbelianG, et al.Review of biomarkers in ocular matrices: challenges and opportunities. Pharm Res2019; 36: 40.
42.
SamburskyRDavittWF3rdFriedbergM, et al.Prospective, multicenter, clinical evaluation of point-of-care matrix metalloproteinase-9 test for confirming dry eye disease. Cornea2014; 33: 812–818.
43.
LamHBleidenLde PaivaCS, et al.Tear cytokine profiles in dysfunctional tear syndrome. Am J Ophthalmol2009; 147: 198–205.
44.
ChotikavanichSde PaivaCSLi deQ, et al.Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome. Invest Ophthalmol Vis Sci2009; 50: 3203–3209.
45.
AqrawiLAGaltungHKVestadB, et al.Identification of potential saliva and tear biomarkers in primary sjogren's syndrome, utilising the extraction of extracellular vesicles and proteomics analysis. Arthritis Res Ther2017; 19: 14.
46.
YoonKCParkCSYouIC, et al.Expression of CXCL9, −10, −11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome. Invest Ophthalmol Vis Sci2010; 51: 643–650.
47.
ArguesoPBalaramMSpurr-MichaudS, et al.Decreased levels of the goblet cell mucin MUC5AC in tears of patients with sjogren syndrome. Invest Ophthalmol Vis Sci2002; 43: 1004–1011.
48.
AkpekEKWuHYKarakusS, et al.Differential diagnosis of sjogren versus Non-sjogren dry eye through tear film biomarkers. Cornea2020; 39: 991–997.
49.
DeutschOKriefGKonttinenYT, et al.Identification of sjogren's syndrome oral fluid biomarker candidates following high-abundance protein depletion. Rheumatology (Oxford2015; 54: 884–890.
50.
DelaleuNMydelPKweeI, et al.High fidelity between saliva proteomics and the biologic state of salivary glands defines biomarker signatures for primary sjogren's syndrome. Arthritis Rheumatol2015; 67: 1084–1095.
51.
KramerJMKlimatchevaERothsteinTL. CXCL13 Is elevated in sjogren's syndrome in mice and humans and is implicated in disease pathogenesis. J Leukoc Biol2013; 94: 1079–1089.
52.
Hamm-AlvarezSFJangaSREdmanMC, et al.Tear cathepsin S as a candidate biomarker for sjogren's syndrome. Arthritis Rheumatol2014; 66: 1872–1881.
53.
ByunYSLeeHJShinS, et al.Tear ATG5 as a potential novel biomarker in the diagnosis of sjogren syndrome. Diagnostics (Basel2021; 11: 71.
54.
AqrawiLAGaltungHKGuerreiroEM, et al.Proteomic and histopathological characterisation of sicca subjects and primary sjogren's syndrome patients reveals promising tear, saliva and extracellular vesicle disease biomarkers. Arthritis Res Ther2019; 21: 181.
55.
HaganS. Biomarkers of ocular surface disease using impression cytology. Biomark Med2017; 11: 1135–1147.
56.
McNamaraNAGallupMPorcoTC. Establishing PAX6 as a biomarker to detect early loss of ocular phenotype in human patients with sjogren's syndrome. Invest Ophthalmol Vis Sci2014; 55: 7079–7084.
57.
PawlowskiPMysliwiecJMrugaczM, et al.Elevated percentage of HLA-DR( + ) and ICAM-1( + ) conjunctival epithelial cells in active Graves’ orbitopathy. Graefes Arch Clin Exp Ophthalmol2014; 252: 641–645.
58.
HsuSLLeePYChangCH, et al.Immunological impression cytology of the conjunctival epithelium in patients with thyroid orbitopathy-related dry eye. Genet Mol Res2016; 15: 10–4238.
59.
BruscoliniALambiaseASegattoM, et al.Evaluation of IL8 pathway on the ocular surface: new insights in patients with ocular mucous membrane pemphigoid. Acta Ophthalmol2020; 98: e173–e177.
60.
MaslinskaMManczakMKwiatkowskaB, et al.Iga immunoglobulin isotype of rheumatoid factor in primary sjogren's syndrome. Rheumatol Int2021; 41: 643–649.
61.
SolomonDHKavanaughAJSchurPH, et al.Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing. Arthritis Rheum2002; 47: 434–444.
62.
JohnJABasheerAGovindarajanD, et al.Diagnostic accuracy of anti-thyroid antibodies in hashimoto’s thyroiditis. J Evid Based Med Healthc2018; 5: 1045–1047.
63.
GilmourJBrownleeYFosterP, et al.The quantitative measurement of autoantibodies to thyroglobulin and thyroid peroxidase by automated microparticle based immunoassays in hashimoto's disease, Graves’ disease and a follow-up study on postpartum thyroid disease. Clin Lab2000; 46: 57–61.
64.
VillaltaDOrunesuETozzoliR, et al.Analytical and diagnostic accuracy of "second generation" assays for thyrotrophin receptor antibodies with radioactive and chemiluminescent tracers. J Clin Pathol2004; 57: 378–382.
65.
ShamsianAAGhazviniKSokhtanlooM, et al.Which quantitative method in determination of the thyroid hormone levels is more consistent with the clinical symptoms of the thyroid disorders?Comp Clin Path2016; 25: 101–106.
66.
BasSPernegerTVSeitzM, et al.Diagnostic tests for rheumatoid arthritis: comparison of anti-cyclic citrullinated peptide antibodies, anti-keratin antibodies and IgM rheumatoid factors. Rheumatology (Oxford2002; 41: 809–814.
67.
SotoMEHernandez-BecerrilNPerez-ChineyAC, et al.Predictive value of antinuclear antibodies in autoimmune diseases classified by clinical criteria: analytical study in a specialized health institute, one year follow-up. Results Immunol2015; 5: 13–22.
68.
SlaterCADavisRBShmerlingRH. Antinuclear antibody testing. A study of clinical utility. Arch Intern Med1996; 156: 1421–1425.
69.
QuCZhangJZhangX, et al.Value of combined detection of anti-nuclear antibody, anti-double-stranded DNA antibody and C3, C4 complements in the clinical diagnosis of systemic lupus erythematosus. Exp Ther Med2019; 17: 1390–1394.
70.
Spencer-GreenGAlterDWelchHG. Test performance in systemic sclerosis: anti-centromere and anti-Scl-70 antibodies. Am J Med1997; 103: 242–248.
71.
KavanaughATomarRReveilleJ, et al.Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. American college of pathologists. Arch Pathol Lab Med2000; 124: 71–81.
72.
WuRShovmanOZhangY, et al.Increased prevalence of anti-third generation cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis and CREST syndrome. Clin Rev Allergy Immunol2007; 32: 47–56.
73.
AwadAMStevensonM. Isolated central nervous system vasculitis associated with antiribonuclear protein antibody. Case Rep Neurol Med2011; 2011: 495201.
74.
Benito-GarciaESchurPHLahitaR, et al.Guidelines for immunologic laboratory testing in the rheumatic diseases: anti-Sm and anti-RNP antibody tests. Arthritis Rheum2004; 51: 1030–1044.
75.
TheanderEJonssonRSjostromB, et al.Prediction of sjogren's syndrome years before diagnosis and identification of patients with early onset and severe disease course by autoantibody profiling. Arthritis Rheumatol2015; 67: 2427–2436.
76.
ShenLMalyavanthamKSureshL, et al.Early detection of sjögren’s syndrome; sensitivity and specificity of the Sjö® diagnostic testInvest Ophthalmol Visual Sci2016; 57: 5681–5681.
77.
ShenLSureshLLindemannM, et al.Novel autoantibodies in sjogren's syndrome. Clin Immunol2012; 145: 251–255.
78.
BunyaVYMassaro-GiordanoMVivinoFB, et al.Prevalence of novel candidate sjogren syndrome autoantibodies in the penn sjogren's international collaborative clinical alliance cohort. Cornea2019; 38: 1500–1505.
79.
OhJYKimMKChoiHJ, et al.Investigating the relationship between serum interleukin-17 levels and systemic immune-mediated disease in patients with dry eye syndrome. Korean J Ophthalmol2011; 25: 73–76.
80.
MatheisNGrusFHBreitenfeldM, et al.Proteomics differentiate between thyroid-associated orbitopathy and dry eye syndrome. Invest Ophthalmol Vis Sci2015; 56: 2649–2656.
81.
OrmerodLDFongLPFosterCS. Corneal infection in mucosal scarring disorders and sjogren's syndrome. Am J Ophthalmol1988; 105: 512–518.
82.
BjordalONorheimKBRodahlE, et al.Primary sjogren's syndrome and the eye. Surv Ophthalmol2020; 65: 119–132.
83.
PapagiannuliERhodesBWallaceGR, et al.Systemic lupus erythematosus: an update for ophthalmologists. Surv Ophthalmol2016; 61: 65–82.
84.
Kemeny-BekeASzodorayP. Ocular manifestations of rheumatic diseases. Int Ophthalmol2020; 40: 503–510.
85.
Ong ToneSElbazUSilvermanE, et al.Evaluation of dry eye disease in children with systemic lupus erythematosus and healthy controls. Cornea2019; 38: 581–586.
86.
ShoughySSTabbaraKF. Ocular findings in systemic lupus erythematosus. Saudi J Ophthalmol2016; 30: 117–121.
87.
ReschMDMarsovszkyLNemethJ, et al.Dry eye and corneal langerhans cells in systemic lupus erythematosus. J Ophthalmol2015; 2015: 543835.
88.
MondinoBJ. Inflammatory diseases of the peripheral cornea. Ophthalmology1988; 95: 463–472.
89.
LiuYChenSSunY, et al.Clinical characteristics of immune thrombocytopenia associated with autoimmune disease: a retrospective study. Medicine (Baltimore2016; 95: e5565.
90.
ZhuFXHuangJYYeZ, et al.Risk of systemic lupus erythematosus in patients with idiopathic thrombocytopenic purpura: a population-based cohort study. Ann Rheum Dis2020; 79: 793–799.
CerveraRPietteJCFontJ, et al.Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum2002; 46: 1019–1027.
93.
UsubaFSLopesJBFullerR, et al.Sjogren's syndrome: an underdiagnosed condition in mixed connective tissue disease. Clinics (Sao Paulo2014; 69: 158–162.
94.
Ruiz-LozanoREHernandez-CamarenaJCLoya-GarciaD, et al.The molecular basis of neurotrophic keratopathy: diagnostic and therapeutic implications. A review. Ocul Surf2021; 19: 224–240.
ZhangXZhaoLDengS, et al.Dry eye syndrome in patients with diabetes Mellitus: prevalence, etiology, and clinical characteristics. J Ophthalmol2016; 2016: 8201053.
97.
WangSJiaYLiT, et al.Dry eye disease Is more prevalent in children with diabetes than in those without diabetes. Curr Eye Res2019; 44: 1299–1305.
98.
Yazdani-Ibn-TazMKHanMMJonuscheitS, et al.Patient-reported severity of dry eye and quality of life in diabetes. Clin Ophthalmol2019; 13: 217–224.
99.
PetropoulosINAlamUFadaviH, et al.Corneal nerve loss detected with corneal confocal microscopy is symmetrical and related to the severity of diabetic polyneuropathy. Diabetes Care2013; 36: 3646–3651.
100.
FerdousiMKaltenieceAAzmiS, et al.Diagnosis of neuropathy and risk factors for corneal nerve loss in type 1 and type 2 diabetes: a corneal confocal microscopy study. Diabetes Care2021; 44: 150–156.
101.
TummanapalliSSWillcoxMDPIssarT, et al.Tear film substance P: a potential biomarker for diabetic peripheral neuropathy. Ocul Surf2019; 17: 690–698.
102.
DolmanPJ. Grading severity and activity in thyroid Eye disease. Ophthalmic Plast Reconstr Surg2018; 34: S34–S40.
103.
AchtsidisVTentolourisNTheodoropoulouS, et al.Dry eye in graves ophthalmopathy: correlation with corneal hypoesthesia. Eur J Ophthalmol2013; 23: 473–479.
104.
AbelsonMBHollyFJ. A tentative mechanism for inferior punctate keratopathy. Am J Ophthalmol1977; 83: 866–869.
UsubaFSde Medeiros-RibeiroACNovaesP, et al.Dry eye in rheumatoid arthritis patients under TNF-inhibitors: conjunctival goblet cell as an early ocular biomarker. Sci Rep2020; 10: 14054.
107.
MarsovszkyLNemethJReschMD, et al.Corneal langerhans cell and dry eye examinations in ankylosing spondylitis. Innate Immun2014; 20: 471–477.
108.
GarrettSJenkinsonTKennedyLG, et al.A new approach to defining disease status in ankylosing spondylitis: the bath ankylosing spondylitis disease activity Index. J Rheumatol1994; 21: 2286–2291.
109.
GhalamkarpourFBaradaran-RafiiASadoughiMM, et al.Ocular findings in patients with psoriasis: is it related to the side effects of treatment or to psoriasis itself? A case-control study. J Dermatolog Treat2020; 31: 27–32.
110.
RehalBModjtahediBSMorseLS, et al.Ocular psoriasis. J Am Acad Dermatol2011; 65: 1202–1212.
111.
LeeCYChenHCLinHW, et al.Increased risk of keratopathy after psoriasis: a nationwide population-based study. PLoS One2018; 13: e0201285.
112.
ChimentiMSTriggianesePSalandriG, et al.A multimodal Eye assessment in psoriatic arthritis patients sine-psoriasis: evidence for a potential association with systemic inflammation. J Clin Med2020; 9: 719.
113.
RentkaANagyAHarsfalviJ, et al.Association between objective signs and subjective symptoms of dry eye disease in patients with systemic sclerosis. Rheumatol Int2017; 37: 1835–1845.
114.
BawazirMChaSIslamNM, et al.Labial salivary gland assessment in idiopathic pulmonary fibrosis patients with sicca symptoms. Oral Surg Oral Med Oral Pathol Oral Radiol2021; 132: 434–440.
115.
Gonzalez-HuezoMSDelgado-AyalaLYOsorio-NunezAL, et al.Autoimmune associations in a Mexican cohort with primary biliary cholangitis. Rev Gastroenterol Mex (Engl Ed2019; 84: 130–135.
CitirikMBerkerNKacarS, et al.Ocular findings in patients with autoimmune liver disease. Ocul Immunol Inflamm2012; 20: 438–442.
118.
BartaZCzompaLRentkaA, et al.Evaluation of objective signs and subjective symptoms of dry eye disease in patients with inflammatory bowel disease. Biomed Res Int2019; 2019: 8310583.
119.
CraigJPNelsonJDAzarDT, et al.TFOS DEWS II report executive summary. Ocul Surf2017; 15: 802–812.
120.
MossSEKleinRKleinBE. Prevalence of and risk factors for dry eye syndrome. Arch Ophthalmol2000; 118: 1264–1268.
121.
Al-MohtasebZSchachterSShen LeeB, et al.The relationship between dry eye disease and digital screen use. Clin Ophthalmol2021; 15: 3811–3820.
122.
JonesLDownieLEKorbD, et al.TFOS DEWS II management and therapy report. Ocul Surf2017; 15: 575–628.
123.
TanriverdiCNurozler TabakciBDonmezS. Longitudinal assessment of meibomian glands and tear film layer in systemic isotretinoin treatment. Eur J Ophthalmol2021; 11206721211018361. https://doi.org/10.1177/11206721211018361
124.
LeeYBKohJWHyonJY, et al.Sleep deprivation reduces tear secretion and impairs the tear film. Invest Ophthalmol Vis Sci2014; 55: 3525–3531.
125.
RummenieVTMatsumotoYDogruM, et al.Tear cytokine and ocular surface alterations following brief passive cigarette smoke exposure. Cytokine2008; 43: 200–208.
126.
ThorntonJKellySPHarrisonRA, et al.Cigarette smoking and thyroid eye disease: a systematic review. Eye (Lond2007; 21: 1135–1145.
127.
NgoWSrinivasanSHoutmanD, et al.The relief of dry eye signs and symptoms using a combination of lubricants, lid hygiene and ocular nutraceuticals. J Optom2017; 10: 26–33.
128.
OuslerG3rdDevriesDKKarpeckiPM, et al.An evaluation of retaine ophthalmic emulsion in the management of tear film stability and ocular surface staining in patients diagnosed with dry eye. Clin Ophthalmol2015; 9: 235–243.
129.
BorchmanD. The optimum temperature for the heat therapy for meibomian gland dysfunction. Ocul Surf2019; 17: 360–364.
130.
LamSMTongLDuanX, et al.Longitudinal changes in tear fluid lipidome brought about by eyelid-warming treatment in a cohort of meibomian gland dysfunction. J Lipid Res2014; 55: 1959–1969.
131.
TauberJOwenJBloomensteinM, et al.Comparison of the iLUX and the LipiFlow for the treatment of meibomian gland dysfunction and symptoms: a randomized clinical trial. Clin Ophthalmol2020; 14: 405–418.
132.
CourseyTGde PaivaCS. Managing sjogren's syndrome and non-sjogren syndrome dry eye with anti-inflammatory therapy. Clin Ophthalmol2014; 8: 1447–1458.
133.
MaIHChenLWTuWH, et al.Serum components and clinical efficacies of autologous serum eye drops in dry eye patients with active and inactive sjogren syndrome. Taiwan J Ophthalmol2017; 7: 213–220.
134.
TzamalisAMatsouAAnastasopoulosE, et al.Treatment of spontaneous corneal perforation secondary to undiagnosed sjogren's syndrome using regenerating agent and autologous serum eye drops. Eur J Ophthalmol2021; 31: NP17–NP21.
135.
MatsuoTTsuchidaYMorimotoN. Trehalose eye drops in the treatment of dry eye syndrome. Ophthalmology2002; 109: 2024–2029.
136.
TsubotaKGotoEFujitaH, et al.Treatment of dry eye by autologous serum application in sjogren's syndrome. Br J Ophthalmol1999; 83: 390–395.
137.
MarshPPflugfelderSC. Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in sjogren syndrome. Ophthalmology1999; 106: 811–816.
138.
SheppardJDDonnenfeldEDHollandEJ, et al.Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with topical cyclosporine 0.05%. Eye Contact Lens2014; 40: 289–296.
139.
KorenfeldMNicholsKKGoldbergD, et al.Safety of KPI-121 ophthalmic suspension 0.25% in patients with dry eye disease: a pooled analysis of 4 multicenter, randomized, vehicle-controlled studies. Cornea2021; 40: 564–570.
140.
BaudouinCde la MazaMSAmraneM, et al.One-Year efficacy and safety of 0.1% cyclosporine a cationic emulsion in the treatment of severe dry eye disease. Eur J Ophthalmol2017; 27: 678–685.
141.
MoawadPShammaRHassaneinD, et al.Evaluation of the effect of topical tacrolimus 0.03% versus cyclosporine 0.05% in the treatment of dry eye secondary to sjogren syndrome. Eur J Ophthalmol2022; 32: 673–679.
142.
WanKHChenLJYoungAL. Efficacy and safety of topical 0.05% cyclosporine Eye drops in the treatment of dry eye syndrome: a systematic review and meta-analysis. Ocul Surf2015; 13: 213–225.
143.
NicholsKKDonnenfeldEDKarpeckiPM, et al.Safety and tolerability of lifitegrast ophthalmic solution 5.0%: pooled analysis of five randomized controlled trials in dry eye disease. Eur J Ophthalmol2019; 29: 394–401.
144.
PerezVLPflugfelderSCZhangS, et al.Lifitegrast, a novel integrin antagonist for treatment of dry eye disease. Ocul Surf2016; 14: 207–215.
145.
Guimaraes de SouzaRYuZSternME, et al.Suppression of Th1-mediated keratoconjunctivitis Sicca by LifitegrastJ Ocul Pharmacol Ther2018; 34: 543–549.
146.
HollandEJWhitleyWOSallK, et al.Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials. Curr Med Res Opin2016; 32: 1759–1765.
147.
DieckmannGFregniFHamrahP. Neurostimulation in dry eye disease-past, present, and future. Ocul Surf2019; 17: 20–27.
148.
CohnGSCorbettDTenenA, et al.Randomized, controlled, double-masked, multicenter, pilot study evaluating safety and efficacy of intranasal neurostimulation for dry eye disease. Invest Ophthalmol Vis Sci2019; 60: 147–153.
JiMHMoshfeghiDMPerimanL, et al.Novel extranasal tear stimulation: pivotal study results. Transl Vis Sci Technol2020; 9: 23.
151.
BavingerJCDeLossKMianSI. Scleral lens use in dry eye syndrome. Curr Opin Ophthalmol2015; 26: 319–324.
152.
DimitRGireAPflugfelderSC, et al.Patient ocular conditions and clinical outcomes using a PROSE scleral device. Cont Lens Anterior Eye2013; 36: 159–163.
153.
Brito-ZeronPRetamozoSKostovB, et al.Efficacy and safety of topical and systemic medications: a systematic literature review informing the EULAR recommendations for the management of sjogren's syndrome. RMD Open2019; 5: e001064.
154.
YavuzSAsfurogluEBicakcigilM, et al.Hydroxychloroquine improves dry eye symptoms of patients with primary sjogren's syndrome. Rheumatol Int2011; 31: 1045–1049.
155.
YoonCHLeeHJLeeEY, et al.Effect of hydroxychloroquine treatment on Dry Eyes in subjects with primary sjogren's syndrome: a double-blind randomized control study. J Korean Med Sci2016; 31: 1127–1135.
156.
WangSQZhangLWWeiP, et al.Is hydroxychloroquine effective in treating primary Sjogren's syndrome: a systematic review and meta-analysis. BMC Musculoskelet Disord2017; 18: 186.
157.
WillekePSchluterBBeckerH, et al.Mycophenolate sodium treatment in patients with primary Sjogren syndrome: a pilot trial. Arthritis Res Ther2007; 9: R115.
158.
van WoerkomJMKruizeAAGeenenR, et al.Safety and efficacy of leflunomide in primary Sjogren's syndrome: a phase II pilot study. Ann Rheum Dis2007; 66: 1026–1032.
159.
SouzaFBPorfirioGJAndrioloBN, et al.Rituximab effectiveness and safety for treating primary Sjogren's syndrome (pSS): systematic review and meta-analysis. PLoS One2016; 11: e0150749.
160.
MeijerJMMeinersPMVissinkA, et al.Effectiveness of rituximab treatment in primary Sjogren's syndrome: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum2010; 62: 960–968.
161.
MarietteXRavaudPSteinfeldS, et al.Inefficacy of infliximab in primary Sjogren's syndrome: results of the randomized, controlled trial of remicade in primary Sjogren's syndrome (TRIPSS). Arthritis Rheum2004; 50: 1270–1276.
162.
ZandbeltMMde WildePvan DammeP, et al.Etanercept in the treatment of patients with primary Sjogren's syndrome: a pilot study. J Rheumatol2004; 31: 96–101.
163.
MeinersPMVissinkAKroeseFG, et al.Abatacept Treatment reduces disease activity in early primary Sjogren's syndrome (open-label proof of concept ASAP study). Ann Rheum Dis2014; 73: 1393–1396.
164.
HolzchuhRVilla AlbersMBOsakiTH, et al.Two-year outcome of partial lacrimal punctal occlusion in the management of dry eye related to Sjogren syndrome. Curr Eye Res2011; 36: 507–512.
165.
SuJZZhengBLiuXJ, et al.Quality of life and patient satisfaction after submandibular gland transplantation in patients with severe dry eye disease. Ocul Surf2019; 17: 470–475.
166.
MurubeJMurubeEChenZhuoL, et al.Subcutaneous abdominal artificial tears pump-reservoir for severe Dry Eye. Orbit2003; 22: 29–40.
167.
De AndresJGarcia-DelpechSPerezVL, et al.Bilateral infusion pump implants as therapy for refractory corneal ulcers in a patient with CREST syndrome: an interdisciplinary approach. Arch Ophthalmol2008; 126: 964–967.
168.
ShaferBFuerstNMMassaro-GiordanoM, et al.The use of self-retained, cryopreserved amniotic membrane for the treatment of Sjogren syndrome: a case series. Digit J Ophthalmol2019; 25: 21–25.
