Management of meibomian gland dysfunction: a review

      Abstract

      Meibomian gland dysfunction is the leading cause of evaporative dry eye disease and is one of the most common conditions encountered by eye care providers. The disorder is characterized by obstruction of the meibomian gland terminal ducts and/or changes in their glandular secretion, resulting in changes in tear film stability, inflammation, and symptoms of irritation. There is no gold standard treatment for meibomian gland dysfunction, but rather a diversity of options. Conservative measures include warm compresses and lid hygiene, but there is growing interest and need for medical treatments and procedures. Potential medical treatments include antibiotics, nonsteroidal and steroidal anti-inflammatory agents, essential fatty acid supplementation, hormone therapy, and control of Demodex infestation. Procedures include intraductal meibomian gland probing, the use of electronic heating devices, intense pulsed light therapy, and intranasal neurostimulation. We provide an update on meibomian gland dysfunction treatments based on recent studies.

      Keywords

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      References

        • Aghai Z.H.
        • Kode A.
        • Saslow J.G.
        • et al.
        Azithromycin suppresses activation of nuclear factor-kappa B and synthesis of pro-inflammatory cytokines in tracheal aspirate cells from premature infants.
        Pediatr Res. 2007; 62: 483-488
        • Akyol-Salman I.
        • Azizi S.
        • Mumcu U.Y.
        • Ateş O.
        • Baykal O.
        Comparison of the efficacy of topical N-acetyl-cysteine and a topical steroid-antibiotic combination therapy in the treatment of meibomian gland dysfunction.
        J Ocul Pharmacol Ther. 2012; 28: 49-52
        • Albietz J.M.
        • Schmid K.L.
        Intense pulsed light treatment and meibomian gland expression for moderate to advanced meibomian gland dysfunction.
        Clin Exp Optom. 2018; 101: 23-33
        • Amparo F.
        • Dastjerdi M.H.
        • Okanobo A.
        • et al.
        Topical interleukin 1 receptor antagonist for treatment of dry eye disease: a randomized clinical trial.
        JAMA Ophthalmol. 2013; 131: 715-723
        • Arciniega J.C.
        • Uchiyama E.
        • Butovich I.A.
        Disruption and destabilization of meibomian lipid films caused by increasing amounts of ceramides and cholesterol.
        Invest Ophthalmol Vis Sci. 2013; 54: 1352-1360
        • Aronowicz J.D.
        • Shine W.E.
        • Oral D.
        • Vargas J.M.
        • McCulley J.P.
        Short term oral minocycline treatment of meibomianitis.
        Br J Ophthalmol. 2006; 90: 856-860
        • Asbell P.
        • Maguire M.
        • Pistilli M.
        • et al.
        n-3 fatty acid supplementation for the treatment of dry eye disease (DREAM Study Research Group).
        N Engl J Med. 2018; 378: 1681-1690
        • Balci O.
        • Gulkilik G.
        Assessment of efficacy of topical azithromycin 1.5 per cent ophthalmic solution for the treatment of meibomian gland dysfunction.
        Clin Exp Optom. 2018; 101: 18-22
        • Basta-Juzbasić A.
        • Subić J.S.
        • Ljubojević S.
        Demodex folliculorum in development of dermatitis rosaceiformis steroidica and rosacea-related diseases.
        Clin Dermatol. 2002; 20: 135-140
        • Bhandari V.
        • Reddy J.K.
        Blepharitis: always remember demodex.
        Middle East Afr J Ophthalmol. 2014; 21: 317-320
        • Bhargava R.
        • Kumar P.
        • Kumar M.
        • Mehra N.
        • Mishra A.
        A randomized controlled trial of omega-3 fatty acids in dry eye syndrome.
        Int J Ophthalmol. 2013; 6: 811-816
        • Blackie C.A.
        • Coleman C.A.
        • Holland E.J.
        The sustained effect (12 months) of a single-dose vectored thermal pulsation procedure for meibomian gland dysfunction and evaporative dry eye.
        Clin Ophthalmol. 2016; 10: 1385-1396
        • Borchman D.
        • Foulks G.N.
        • Yappert M.C.
        • et al.
        Human meibum lipid conformation and thermodynamic changes with meibomian-gland dysfunction.
        Invest Ophthalmol Vis Sci. 2011; 52: 3805-3817
        • Brignole-Baudouin F.
        • Baudouin C.
        • Aragona P.
        • et al.
        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 Ophthalmol. 2011; 89: e591-e597
        • Brinton M.
        • Kossler A.L.
        • Patel Z.M.
        • et al.
        Enhanced tearing by electrical stimulation of the anterior ethmoid nerve.
        Invest Ophthalmol Vis Sci. 2017; 58: 2341-2348
        • Butovich I.A.
        • Millar T.J.
        • Ham B.M.
        Understanding and analyzing meibomian lipids--a review.
        Curr Eye Res. 2008; 33: 405-420
        • Byun Y.
        • Kim T.
        • Kwon S.M.
        • et al.
        Efficacy of combined 0.05% cyclosporine and 1% methylprednisolone treatment for chronic dry eye.
        Cornea. 2012; 31: 509-513
        • Calder P.C.
        Polyunsaturated fatty acids, inflammation, and immunity.
        Lipids. 2001; 36: 1007-1024
        • Cermak J.M.
        • Krenzer K.L.
        • Sullivan R.M.
        • Dana M.R.
        • Sullivan D.A.
        Is complete androgen insensitivity syndrome associated with alterations in the meibomian gland and ocular surface?.
        Cornea. 2003; 22: 516-521
        • Chayet A.
        • Friedman N.
        • Butron Valdez K.
        • Robledo Silva N.
        • Loudin J.
        • Baba S.
        A nonrandomized, open-label study to evaluate the effect of nasal stimulation on tear production in subjects with dry eye disease.
        Clin Ophthalmol. 2016; 10: 795-804
        • Cheng A.M.S.
        • Sheha H.
        • Tseng S.C.G.
        Recent advances on ocular Demodex infestation.
        Curr Opin Ophthalmol. 2015; 26: 295-300
        • Craig J.P.
        • Chen Y.-H.
        • Turnbull P.R.K.
        Prospective trial of intense pulsed light for the treatment of meibomian gland dysfunction.
        Invest Opthalmol Vis Sci. 2015; 56: 1965-1970
        • Crawford G.H.
        • Sciacca J.R.
        • James W.D.
        Tea tree oil: cutaneous effects of the extracted oil of Melaleuca alternifolia.
        Dermatitis. 2004; 15: 59-66
        • Dell S.J.
        • Gaster R.N.
        • Barbarino S.C.
        • Cunningham D.
        Prospective evaluation of intense pulsed light and meibomian gland expression efficacy on relieving signs and symptoms of dry eye disease due to meibomian gland dysfunction.
        Clin Ophthalmol. 2017; 11: 817-827
        • Dinarello C.A.
        Interleukin-1 in the pathogenesis and treatment of inflammatory diseases.
        Blood. 2011; 117: 3720-3732
        • Dougherty J.M.
        • McCulley J.P.
        • Silvany R.E.
        • Meyer D.R.
        The role of tetracycline in chronic blepharitis. Inhibition of lipase production in staphylococci.
        Invest Ophthalmol Vis Sci. 1991; 32: 2970-2975
        • Duerden J.M.
        • Tiffany J.M.
        Lipid synthesis in vitro by rabbit meibomian gland tissue and its inhibition by tetracycline.
        Biochim Biophys Acta. 1990; 1042: 13-18
        • English F.P.
        • Nutting W.B.
        Demodicosis of ophthalmic concern.
        Am J Ophthalmol. 1981; 91: 362-372
        • Enríquez-de-Salamanca A.
        • Castellanos E.
        • Stern M.E.
        • et al.
        Tear cytokine and chemokine analysis and clinical correlations in evaporative-type dry eye disease.
        Mol Vis. 2010; 16: 862-873
        • Epitropoulos A.T.
        • Donnenfeld E.D.
        • Shah Z.A.
        • et al.
        Effect of oral re-esterified omega-3 nutritional supplementation on dry eyes.
        Cornea. 2016; 35: 1185-1191
        • Esmaeli B.
        • Harvey J.T.
        • Hewlett B.
        Immunohistochemical evidence for estrogen receptors in meibomian glands.
        Ophthalmology. 2000; 107: 180-184
        • Fadlallah A.
        • Rami H.E.L.
        • Fahd D.
        • et al.
        Azithromycin 1.5% ophthalmic solution: efficacy and treatment modalities in chronic blepharitis.
        Arq Bras Oftalmol. 2012; 75: 178-182
        • Federici T.J.
        The non-antibiotic properties of tetracyclines: clinical potential in ophthalmic disease.
        Pharmacol Res. 2011; 64: 614-623
        • Feng Y.
        • Feng G.
        • Peng S.
        • Li H.
        The effects of hormone replacement therapy on dry eye syndromes evaluated by Schirmer test depend on patient age.
        Contact Lens Anterior Eye. 2016; 39: 124-127
        • Fini M.E.
        • Girard M.T.
        Expression of collagenolytic/gelatinolytic metalloproteinases by normal Cornea.
        Invest Ophthalmol Vis Sci. 1990; 31: 1779-1788
        • Finis D.
        • Hayajneh J.
        • König C.
        • Borrelli M.
        • Schrader S.
        • Geerling G.
        Evaluation of an automated thermodynamic treatment (LipiFlow®) system for meibomian gland dysfunction: a prospective, randomized, observer-masked trial.
        Ocul Surf. 2014; 12: 146-154
        • Finis D.
        • König C.
        • Hayajneh J.
        • Borrelli M.
        • Schrader S.
        • Geerling G.
        Six-Month effects of a thermodynamic treatment for MGD and implications of meibomian gland atrophy.
        Cornea. 2014; 33: 1265-1270
        • Foulks G.N.
        • Borchman D.
        • Yappert M.
        • Kakar S.
        Topical azithromycin and oral doxycycline therapy of meibomian gland dysfunction: a comparative clinical and spectroscopic pilot study.
        Cornea. 2013; 32: 44-53
        • Freedberg I.M.
        • Tomic-Canic M.
        • Komine M.
        • Blumenberg M.
        Keratins and the keratinocyte activation cycle.
        J Invest Dermatol. 2001; 116: 633-640
        • Gangoiti P.
        • Camacho L.
        • Arana L.
        • et al.
        Control of metabolism and signaling of simple bioactive sphingolipids: Implications in disease.
        Prog Lipid Res. 2010; 49: 316-334
        • Gao Y.-Y.
        • Di Pascuale M.A.
        • Elizondo A.
        • Tseng S.C.G.
        Clinical treatment of ocular demodecosis by lid scrub with tea tree oil.
        Cornea. 2007; 26: 136-143
        • Gao Y.-Y.
        • Di Pascuale M.A.
        • Li W.
        • et al.
        In vitro and in vivo killing of ocular Demodex by tea tree oil.
        Br J Ophthalmol. 2005; 89: 1468-1473
        • Gao Y.-Y.
        • Xu D.
        • Huang L.-J.
        • Wang R.
        • Tseng S.C.G.
        Treatment of ocular itching associated with ocular demodicosis by 5% tea tree oil ointment.
        Cornea. 2012; 31: 14-17
        • Geerling G.
        • Tauber J.
        • Baudouin C.
        • et al.
        The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Management and Treatment of Meibomian Gland Dysfunction.
        Invest Opthalmol Vis Sci. 2011; 52: 2050-2064
        • Georgala S.
        • Katoulis A.C.
        • Kylafis G.D.
        • Koumantaki-Mathioudaki E.
        • Georgala C.
        • Aroni K.
        Increased density of Demodex folliculorum and evidence of delayed hypersensitivity reaction in subjects with papulopustular rosacea.
        J Eur Acad Dermatol Venereol. 2001; 15: 441-444
        • Goldberg D.J.
        Current trends in intense pulsed light.
        J Clin Aesthet Dermatol. 2012; 5: 45-53
        • Greene J.B.
        • Jeng B.H.
        • Fintelmann R.E.
        • Margolis T.P.
        Oral azithromycin for the treatment of meibomitis.
        JAMA Ophthalmol. 2014; 132: 121-122
        • Greiner J.V.
        A single LipiFlow ® thermal pulsation system treatment improves meibomian gland function and reduces dry eye symptoms for 9 months.
        Curr Eye Res. 2012; 37: 272-278
        • Greiner J.V.
        Long-term (12-month) improvement in meibomian gland function and reduced dry eye symptoms with a single thermal pulsation treatment.
        Clin Exp Ophthalmol. 2013; 41: 524-530
        • Greiner J.V.
        Long-term (3 Year) effects of a single thermal pulsation system treatment on meibomian gland function and dry eye symptoms.
        Eye Contact Lens Sci Clin Pract. 2016; 42: 99-107
        • Greiner J.V.
        • Glonek T.
        • Korb D.R.
        • Booth R.
        • Leahy C.D.
        Phospholipids in meibomian gland secretion.
        Ophthalmic Res. 1996; 28: 44-49
        • Gumus K.
        • Schuetzle K.L.
        • Pflugfelder S.C.
        Randomized controlled crossover trial comparing the impact of sham or intranasal tear neurostimulation on conjunctival goblet cell degranulation.
        Am J Ophthalmol. 2017; 177: 159-168
        • Gupta P.K.
        • Vora G.K.
        • Matossian C.
        • Kim M.
        • Stinnett S.
        Outcomes of intense pulsed light therapy for treatment of evaporative dry eye disease.
        Can J Ophthalmol. 2016; 51: 249-253
        • Hagen K.
        • Bedi R.
        • Blackie C.
        • Christenson-Akagi K.J.
        Comparison of a single-dose vectored thermal pulsation procedure with a 3-month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction.
        Clin Ophthalmol. 2018; 12: 161-168
        • Hannun Y.A.
        • Obeid L.M.
        Principles of bioactive lipid signalling: Lessons from sphingolipids.
        Nat Rev Mol Cell Biol. 2008; 9: 139-150
        • Hoeprich P.D.
        • Warshauer D.M.
        Entry of four tetracyclines into saliva and tears.
        Antimicrob Agents Chemother. 1974; 5: 330-336
        • Holland E.J.
        • Luchs J.
        • Karpecki P.M.
        • et al.
        Lifitegrast for the treatment of dry eye disease: results of a phase III, randomized, double-masked, placebo-controlled trial (OPUS-3).
        Ophthalmology. 2017; 124: 53-60
        • Holzchuh F.G.
        • Hida R.Y.
        • Moscovici B.K.
        • et al.
        Clinical treatment of ocular Demodex folliculorum by systemic ivermectin.
        Am J Ophthalmol. 2011; 151: 1030-1034
        • Igami T.Z.
        • Holzchuh R.
        • Osaki T.H.
        • Santo R.M.
        • Kara-Jose N.
        • Hida R.Y.
        Oral azithromycin for treatment of posterior blepharitis.
        Cornea. 2011; 30: 1145-1149
        • Jensen A.A.
        • Higginbotham E.J.
        • Guzinski G.M.
        • Davis I.L.
        • Ellish N.J.
        A survey of ocular complaints in postmenopausal women.
        J Assoc Acad Minor Phys. 2000; 11: 44-49
        • Jiang X.
        • Lv H.
        • Song H.
        • et al.
        Evaluation of the safety and effectiveness of intense pulsed light in the treatment of meibomian gland dysfunction.
        J Ophthalmol. 2016; 2016: 1-8
        • Jin X.
        • Lin Z.
        • Liu Y.
        • Lin L.
        • Zhu B.
        Hormone replacement therapy benefits meibomian gland dysfunction in perimenopausal women.
        Medicine (Baltimore). 2016; 95: e4268
        • Kangari H.
        • Eftekhari M.H.
        • Sardari S.
        • et al.
        Short-term consumption of oral omega-3 and dry eye syndrome.
        Ophthalmology. 2013; 120: 2191-2196
        • Kashkouli M.B.
        • Fazel A.J.
        • Kiavash V.
        • Nojomi M.
        • Ghiasian L.
        Oral azithromycin versus doxycycline in meibomian gland dysfunction: a randomised double-masked open-label clinical trial.
        Br J Ophthalmol. 2015; 99: 199-204
        • Kenrick C.J.
        • Alloo S.S.
        The limitation of applying heat to the external lid surface: a case of recalcitrant meibomian gland dysfunction.
        Case Rep Ophthalmol. 2017; 8: 7-12
        • Khandelwal P.
        • Liu S.
        • Sullivan D.A.
        Androgen regulation of gene expression in human meibomian gland and conjunctival epithelial cells.
        Mol Vis. 2012; 18: 1055-1067
        • Kheirkhah A.
        • Casas V.
        • Li W.
        • Raju V.K.
        • Tseng S.C.G.
        Corneal manifestations of ocular Demodex infestation.
        Am J Ophthalmol. 2007; 143: 743-749
        • Kim J.H.
        • Chun Y.S.
        • Kim J.C.
        Clinical and immunological responses in ocular demodecosis.
        J Korean Med Sci. 2011; 26: 1231-1237
        • Knop E.
        • Knop N.
        • Millar T.
        • Obata H.
        • Sullivan D.A.
        The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland.
        Invest Ophthalmol Vis Sci. 2011; 52: 1938-1978
        • Koo H.
        • Kim T.H.
        • Kim K.W.
        • Wee S.W.
        • Chun Y.S.
        • Kim J.C.
        Ocular surface discomfort and Demodex: effect of tea tree oil eyelid scrub in Demodex blepharitis.
        J Korean Med Sci. 2012; 27: 1574-1579
        • Korb D.R.
        • Blackie C.A.
        Case report.
        Eye Contact Lens Sci Clin Pract. 2013; 39: e1-e3
        • Krenzer K.L.
        • Reza Dana M.
        • Ullman M.D.
        • et al.
        Effect of androgen deficiency on the human meibomian gland and ocular surface.
        J Clin Endocrinol Metab. 2000; 85: 4874-4882
        • Lacey N.
        • Kavanagh K.
        • Tseng S.C.G.
        Under the lash: Demodex mites in human diseases.
        Biochem (Lond). 2009; 31: 2-6
        • Lam H.
        • Bleiden L.
        • de Paiva C.S.
        • Farley W.
        • Stern M.E.
        • Pflugfelder S.C.
        Tear cytokine profiles in dysfunctional tear syndrome.
        Am J Ophthalmol. 2009; 147: 198-205.e1
        • Lane S.S.
        • DuBiner H.B.
        • Epstein R.J.
        • et al.
        A new system, the LipiFlow, for the treatment of meibomian gland dysfunction.
        Cornea. 2012; 31: 396-404
        • Lee H.
        • Chung B.
        • Kim K.S.
        • Seo K.Y.
        • Choi B.J.
        • Kim T.
        Effects of topical loteprednol etabonate on tear cytokines and clinical outcomes in moderate and severe meibomian gland dysfunction: randomized clinical trial.
        Am J Ophthalmol. 2014; 158: 1172-1183.e1
        • Lee H.
        • Min K.
        • Kim E.K.
        • Kim T.-I.
        Minocycline controls clinical outcomes and inflammatory cytokines in moderate and severe meibomian gland dysfunction.
        Am J Ophthalmol. 2012; 154: 949-957
        • Lee J.H.
        • Min K.
        • Kim S.K.
        • Kim E.K.
        • Kim T.
        Inflammatory cytokine and osmolarity changes in the tears of dry eye patients treated with topical 1% methylprednisolone.
        Yonsei Med J. 2014; 55: 203-208
        • Lemp M.A.
        Advances in understanding and managing dry eye disease.
        Am J Ophthalmol. 2008; 146: 350-356.e1
        • Li D.-Q.
        • Lokeshwar B.L.
        • Solomon A.
        • Monroy D.
        • Ji Z.
        • Pflugfelder S.C.
        Regulation of MMP-9 production by human corneal epithelial cells.
        Exp Eye Res. 2001; 73: 449-459
        • Li J.
        • O’Reilly N.
        • Sheha H.
        • et al.
        Correlation between ocular Demodex infestation and serum immunoreactivity to Bacillus proteins in patients with facial rosacea.
        Ophthalmology. 2010; 117: 870-877.e1
        • Liu A.
        • Ji J.
        Omega-3 essential fatty acids therapy for dry eye syndrome: a meta-analysis of randomized controlled studies.
        Med Sci Monit. 2014; 20: 1583-1589
        • Liu Y.
        • Kam W.R.
        • Ding J.
        • Sullivan D.A.
        One man’s poison is another man’s meat: using azithromycin-induced phospholipidosis to promote ocular surface health.
        Toxicology. 2014; 320: 1-5
        • Liu R.
        • Rong B.
        • Tu P.
        • et al.
        Analysis of cytokine levels in tears and clinical correlations after intense pulsed light treating meibomian gland dysfunction.
        Am J Ophthalmol. 2017; 183: 81-90
        • Liu J.
        • Sheha H.
        • Tseng S.C.
        Pathogenic role of Demodex mites in blepharitis.
        Curr Opin Allergy Clin Immunol. 2010; 10: 505-510
        • Le Loët X.
        • Nordström D.
        • Rodriguez M.
        • et al.
        Effect of anakinra on functional status in patients with active rheumatoid arthritis receiving concomitant therapy with traditional disease modifying antirheumatic drugs: evidence from the OMEGA Trial.
        J Rheumatol. 2008; 35: 1538-1544
        • Ma X.
        • Lu Y.
        Efficacy of intraductal meibomian gland probing on tear function in patients with obstructive meibomian gland dysfunction.
        Cornea. 2016; 35: 725-730
        • Määttä M.
        • Kari O.
        • Tervahartiala T.
        • et al.
        Tear fluid levels of MMP-8 are elevated in ocular rosacea—treatment effect of oral doxycycline.
        Graefes Arch Clin Exp Ophthalmol. 2006; 244: 957-962
        • Macsai M.S.
        The role of omega-3 dietary supplementation in blepharitis and meibomian gland dysfunction (an AOS thesis).
        Trans Am Ophthalmol Soc. 2008; 106: 336-356
        • Maisch N.M.
        • Kochupurackal J.G.
        • Sin J.
        Azithromycin and the risk of cardiovascular complications.
        J Pharm Pract. 2014; 27: 496-500
        • Malhotra C.
        • Singh S.
        • Chakma P.
        • Jain A.K.
        Effect of oral omega-3 fatty acid supplementation on contrast sensitivity in patients with moderate meibomian gland dysfunction.
        Cornea. 2015; 34: 637-643
        • Mantelli F.
        • Moretti C.
        • Micera A.
        • Bonini S.
        Conjunctival mucin deficiency in complete androgen insensitivity syndrome (CAIS).
        Graefes Arch Clin Exp Ophthalmol. 2007; 245: 899-902
        • Maskin S.L.
        Intraductal meibomian gland probing relieves symptoms of obstructive meibomian gland dysfunction.
        Cornea. 2010; 29: 1145-1152
        • Maskin S.L.
        • Testa W.R.
        Growth of meibomian gland tissue after intraductal meibomian gland probing in patients with obstructive meibomian gland dysfunction.
        Br J Ophthalmol. 2018; 102: 59-68
        • McCulley J.P.
        • Shine W.
        A compositional based model for the tear film lipid layer.
        Trans Am Ophthalmol Soc. 1997; 95: 79-88
        • Nakayama N.
        • Kawashima M.
        • Kaido M.
        • Arita R.
        • Tsubota K.
        Analysis of meibum before and after intraductal meibomian gland probing in eyes with obstructive meibomian gland dysfunction.
        Cornea. 2015; 34: 1206-1208
        • Nelson J.D.
        • Shimazaki J.
        • Benitez-del-Castillo J.M.
        • et al.
        The international workshop on meibomian gland dysfunction: report of the definition and classification subcommittee.
        Invest Ophthalmol Vis Sci. 2011; 52: 1930-1937
        • Nichols K.K.
        • Foulks G.N.
        • Bron A.J.
        • et al.
        The international workshop on meibomian gland dysfunction: executive summary.
        Invest Opthalmol Vis Sci. 2011; 52: 1922-1929
        • Olenik A.
        • Luxan S.
        • Quintana S.
        • et al.
        Benefits of omega-3 fatty acid dietary supplementation on health-related quality of life in patients with meibomian gland dysfunction.
        Clin Ophthalmol. 2014; 8: 831
        • Opitz D.L.
        • Tyler K.F.
        Efficacy of azithromycin 1% ophthalmic solution for treatment of ocular surface disease from posterior blepharitis.
        Clin Exp Optom. 2011; 94: 200-206
        • Papageorgiou P.
        • Clayton W.
        • Norwood S.
        • Chopra S.
        • Rustin M.
        Treatment of rosacea with intense pulsed light: significant improvement and long-lasting results.
        Br J Dermatol. 2008; 159: 628-632
        • Paranjpe V.
        • Tan J.
        • Nguyen J.
        • et al.
        Clinical signs of meibomian gland dysfunction (MGD) are associated with changes in meibum sphingolipid composition.
        Ocul Surf. 2019; 17: 318-326
        • Peck T.
        • Olsakovsky L.
        • Aggarwal S.
        Dry eye syndrome in menopause and perimenopausal age group.
        J Midlife Health. 2017; 8: 51-54
        • Pelletier J.S.
        • Capriotti K.
        • Stewart K.S.
        • Capriotti J.A.
        Demodex blepharitis treated with a novel dilute povidone-iodine and DMSO system: a case report.
        Ophthalmol Ther. 2017; 6: 361-366
        • Perry H.D.
        • Doshi-Carnevale S.
        • Donnenfeld E.D.
        • Solomon R.
        • Biser S.A.
        • Bloom A.H.
        Efficacy of commercially available topical cyclosporine A 0.05% in the treatment of meibomian gland dysfunction.
        Cornea. 2006; 25: 171-175
        • Post C.F.
        • Juhlin E.
        Demodex folliculorum and blepharitis.
        Arch Dermatol. 1963; 88: 298-302
        • Prabhasawat P.
        • Tesavibul N.
        • Mahawong W.
        A randomized double-masked study of 0.05% cyclosporine ophthalmic emulsion in the treatment of meibomian gland dysfunction.
        Cornea. 2012; 31: 1386-1393
        • Rashid S.
        • Jin Y.
        • Ecoiffier T.
        • Barabino S.
        • Schaumberg D.A.
        • Dana M.R.
        Topical omega-3 and omega-6 fatty acids for treatment of dry eye.
        Arch Ophthalmol. 2008; 126: 219-225
        • Raulin C.
        • Hellwig S.
        • Schönermark M.P.
        Treatment of a nonresponding port-wine stain with a new pulsed light source (PhotoDerm VL).
        Lasers Surg Med. 1997; 21: 203-208
        • Robciuc A.
        • Hyötyläinen T.
        • Jauhiainen M.
        • Holopainen J.M.
        Ceramides in the pathophysiology of the anterior segment of the eye.
        Curr Eye Res. 2013; 38: 1006-1016
        • Rubel D.M.
        • Freeman S.
        • Southwell I.A.
        Tea tree oil allergy: what is the offending agent? Report of three cases of tea tree oil allergy and review of the literature.
        Australas J Dermatol. 1998; 39: 244-247
        • Schaumberg D.A.
        • Buring J.E.
        • Sullivan D.A.
        • Dana M.R.
        Hormone replacement therapy and dry eye syndrome.
        JAMA. 2001; 286: 2114-2119
        • Schirra F.
        • Richards S.M.
        • Liu M.
        • Suzuki T.
        • Yamagami H.
        • Sullivan D.A.
        Androgen regulation of lipogenic pathways in the mouse meibomian gland.
        Exp Eye Res. 2006; 83: 291-296
        • Schirra F.
        • Richards S.M.
        • Sullivan D.A.
        Androgen influence on cholesterogenic enzyme mRNA levels in the mouse meibomian gland.
        Curr Eye Res. 2007; 32: 393-398
        • Schultz C.
        Safety and efficacy of cyclosporine in the treatment of chronic dry eye.
        Ophthalmol Eye Dis. 2014; 6: 37-42
        • Semba C.
        • Gadek T.
        Development of lifitegrast: a novel T-cell inhibitor for the treatment of dry eye disease.
        Clin Ophthalmol. 2016; 10: 1083-1094
        • Sha Y.
        • Markovic-Plese S.
        A role of IL-1R1 signaling in the differentiation of Th17 cells and the development of autoimmune diseases.
        Self Nonself. 2011; 2: 35-42
        • Sheppard J.D.
        • Scoper S.V.
        • Samudre S.
        Topical loteprednol pretreatment reduces cyclosporine stinging in chronic dry eye disease.
        J Ocul Pharmacol Ther. 2011; 27: 23-27
        • Sheppard J.D.
        • Torkildsen G.L.
        • Lonsdale J.D.
        • et al.
        Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study.
        Ophthalmology. 2014; 121: 475-483
        • Shine W.E.
        • McCulley J.P.
        • Pandya A.G.
        Minocycline effect on meibomian gland lipids in meibomianitis patients.
        Exp Eye Res. 2003; 76: 417-420
        • Sik Sarman Z.
        • Cucen B.
        • Yuksel N.
        • Cengiz A.
        • Caglar Y.
        Effectiveness of intraductal meibomian gland probing for obstructive meibomian gland dysfunction.
        Cornea. 2016; 35: 721-724
        • Solomon A.
        • Dursun D.
        • Liu Z.
        • Xie Y.
        • Macri A.
        • Pflugfelder S.C.
        Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease.
        Invest Ophthalmol Vis Sci. 2001; 42: 2283-2292
        • Souchier M.
        • Joffre C.
        • Gregoire S.
        • et al.
        Changes in meibomian fatty acids and clinical signs in patients with meibomian gland dysfunction after minocycline treatment.
        Br J Ophthalmol. 2008; 92: 819-822
        • Steagall R.J.
        • Yamagami H.
        • Wickham L.A.
        • Sullivan D.A.
        Androgen control of gene expression in the rabbit meibomian gland.
        Adv Exp Med Biol. 2002; 506: 465-476
        • Sullivan D.A.
        • Allansmith M.R.
        Hormonal modulation of tear volume in the rat.
        Exp Eye Res. 1986; 42: 131-139
        • Sullivan D.A.
        • Jensen R.V.
        • Suzuki T.
        • Richards S.M.
        Do sex steroids exert sex-specific and/or opposite effects on gene expression in lacrimal and meibomian glands?.
        Mol Vis. 2009; 15: 1553-1572
        • Sullivan D.A.
        • Sullivan B.D.
        • Evans J.E.
        • et al.
        Androgen deficiency, Meibomian gland dysfunction, and evaporative dry eye.
        Ann N Y Acad Sci. 2002; 966: 211-222
        • Sullivan D.A.
        • Sullivan B.D.
        • Ullman M.D.
        • et al.
        Androgen influence on the meibomian gland.
        Invest Ophthalmol Vis Sci. 2000; 41: 3732-3742
        • 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.
        Invest Opthalmol Vis Sci. 2008; 49: 1797-1808
        • Suzuki T.
        • Sullivan D.A.
        Estrogen stimulation of proinflammatory cytokine and matrix metalloproteinase gene expression in human corneal epithelial cells.
        Cornea. 2005; 24: 1004-1009
        • Syed Z.
        • Sutula F.
        Dynamic intraductal meibomian probing (DIMP): a novel approach to the treatment of meibomian gland dysfunction.
        Invest Ophthalmol Vis Sci. 2015; 56: 4761
        • Ta C.N.
        • Shine W.E.
        • McCulley J.P.
        • Pandya A.
        • Trattler W.
        • Norbury J.W.
        Effects of minocycline on the ocular flora of patients with acne rosacea or seborrheic blepharitis.
        Cornea. 2003; 22: 545-548
        • Tabbara K.F.
        • Al-Kharashi S.A.
        • Al-Mansouri S.M.
        • et al.
        Ocular levels of azithromycin.
        Arch Ophthalmol. 1998; 116: 1625-1628
        • Thode A.R.
        • Latkany R.A.
        Current and emerging therapeutic strategies for the treatment of meibomian gland dysfunction (MGD).
        Drugs. 2015; 75: 1177-1185
        • Tighe S.
        • Gao Y.-Y.
        • Tseng S.C.G.
        Terpinen-4-ol is the most active ingredient of tea tree oil to kill Demodex mites.
        Transl Vis Sci Technol. 2013; 2 (Article 2)
        • Toyos R.
        • McGill W.
        • Briscoe D.
        Intense pulsed light treatment for dry eye disease due to meibomian gland dysfunction; a 3-year retrospective study.
        Photomed Laser Surg. 2015; 33: 41-46
        • Vegunta S.
        • Patel D.
        • Shen J.F.
        Combination therapy of intense pulsed light therapy and meibomian gland expression (IPL/MGX) can improve dry eye symptoms and meibomian gland function in patients with refractory dry eye.
        Cornea. 2016; 35: 318-322
        • Versura P.
        • Giannaccare G.
        • Campos E.C.
        Sex-steroid imbalance in females and dry eye.
        Curr Eye Res. 2015; 40: 162-175
        • Wladis E.J.
        Intraductal meibomian gland probing in the management of ocular rosacea.
        Ophthal Plast Reconstr Surg. 2012; 28: 416-418
        • Wladis E.J.
        • Bradley E.A.
        • Bilyk J.R.
        • Yen M.T.
        • Mawn L.A.
        Oral Antibiotics for Meibomian Gland-Related Ocular Surface Disease: A Report by the American Academy of Ophthalmology.
        Ophthalmology. 2016; 123: 492-496
        • Wojtowicz J.C.
        • Butovich I.
        • Uchiyama E.
        • Aronowicz J.
        • Agee S.
        • McCulley J.P.
        Pilot, prospective, randomized, double-masked, placebo-controlled clinical trial of an omega-3 supplement for dry eye.
        Cornea. 2011; 30: 308-314
        • Worda C.
        • Nepp J.
        • Huber J.C.
        • Sator M.O.
        Treatment of keratoconjunctivitis sicca with topical androgen.
        Maturitas. 2001; 37: 209-212
        • Yan X.
        • Qiao X.
        Emerging treatment options for meibomian gland dysfunction.
        Clin Ophthalmol. 2013; 7: 1797-1803
        • Yang W.-J.
        • Yang Y.-N.
        • Cao J.
        • et al.
        Risk factors for dry eye syndrome: a retrospective case-control study.
        Optom Vis Sci. 2015; 92: e199-e205
        • Yin Y.
        • Liu N.
        • Gong L.
        • Song N.
        Changes in the meibomian gland after exposure to intense pulsed light in meibomian gland dysfunction (MGD) patients.
        Curr Eye Res. 2018; 43: 308-313
        • Zhang L.
        • Su Z.
        • Zhang Z.
        • Lin J.
        • Li D.-Q.
        • Pflugfelder S.C.
        Effects of azithromycin on gene expression profiles of proinflammatory and anti-inflammatory mediators in the eyelid margin and conjunctiva of patients with meibomian gland disease.
        JAMA Ophthalmol. 2015; 133: 1117-1123
        • Zhao Y.
        • Veerappan A.
        • Yeo S.
        • et al.
        Clinical trial of thermal pulsation (LipiFlow) in meibomian gland dysfunction with preteatment meibography.
        Eye Contact Lens Sci Clin Pract. 2016; 42: 339-346

      Other Cited Material

      1. U.S. Food & Drug Administration. FDA Drug Safety Communication: Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms Safety Announcement. Page last updated Feb 14, 2018. Last accessed Jan 03, 2019.

        • Connor C.G.
        Symptomatic Relief of Dry Eye Assessed with the OSDI in Patients Using 5% Testosterone Cream. 2005 ARVO Annual Meeting Abstract.
        Invest Ophthalmol Vis Sci. 2006; 46: 2032
        • Schiffman R.M.
        • Bradford R.
        • Bunnell B.
        • et al.
        A multi-center, double-masked, randomized, vehicle-controlled, parallel group study to evaluate the safety and efficacy of testosterone ophthalmic solution in patients with meibomian gland dysfunction. 2006 ARVO Annual Meeting Abstract.
        Invest Ophthalmol Vis Sci. 2006; 47: 5608
        • Maskin S
        • Kantor K.
        Intraductal meibomian gland probing to restore gland functionality for obstructive meibomian gland dysfunction (MGD): Follow up of original meibomian gland probing cases.
        http://drmaskin.com/includes/meibomian-probing.pdf
        Date: 2011
        Date accessed: January 3, 2019
        • Pondelis N.
        • Dieckmann G.
        • Kataguiri P.
        • et al.
        Intranasal neurostimulator induces morphological changes in meibomian glands in patients with dry eye disease. 2017 ARVO Annual Meeting Abstract.
        Invest Ophthalmol Vis Sci. 2017; 58: 2235
        • Green KB
        • Kamat M.
        • Franke M.
        • et al.
        Tear total lipid concentration in patients with dry eye following intranasal neurostimulation. 2017 ARVO Annual Meeting Abstract.
        Invest Ophthalmol Vis Sci. 2017; 58: 2693
        • Watson M
        • Angjeli E.
        • Orrick B.
        • et al.
        Effect of the intranasal tear neurostimulator on meibomian glands. 2017 ARVO Annual Meeting Abstract.
        Invest Ophthalmol Vis Sci. 2017; 58: 4387