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Stepwise Approach to the Diagnosis and Management of Dry Eye and Ocular Surface Disease

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      References

        • Stapleton F.
        • Alves M.
        • Bunya V.Y.
        • et al.
        TFOS DEWS II epidemiology report.
        Ocul Surf. 2017; 15: 334-365https://doi.org/10.1016/j.jtos.2017.05.003
      1. The definition and classification of dry eye disease: Report of the definition and classification subcommittee of the International Dry Eye Workshop (2007).
        Ocul Surf. 2007; 5: 75-92
        • Jones L.
        • Downie L.E.
        • Korb D.
        • et al.
        TFOS DEWS II management and therapy report.
        Ocul Surf. 2017; 15: 575-628https://doi.org/10.1016/j.jtos.2017.05.006
        • Gomes J.A.P.
        • Azar D.T.
        • Baudouin C.
        • et al.
        TFOS DEWS II iatrogenic report.
        Ocul Surf. 2017; 15: 511-538https://doi.org/10.1016/j.jtos.2017.05.004
        • Fraunfelder F.T.
        • Sciubba J.J.
        • Mathers W.D.
        The role of medications in causing dry eye.
        J Ophthalmol. 2012; 2012: 285851https://doi.org/10.1155/2012/285851
        • Vitale S.
        • Goodman L.A.
        • Reed G.F.
        • et al.
        Comparison of the NEI-VFQ and OSDI questionnaires in patients with Sjögren’s syndrome-related dry eye.
        Health Qual Life Outcomes. 2004; 2: 44https://doi.org/10.1186/1477-7525-2-44
        • Schiffman R.M.
        • Christianson M.D.
        • Jacobsen G.
        • et al.
        Reliability and validity of the ocular surface disease index.
        Arch Ophthalmol. 2000; 118: 615-621https://doi.org/10.1001/archopht.118.5.615
        • Chalmers R.L.
        • Begley C.G.
        • Caffery B.
        Validation of the 5-item dry eye questionnaire (DEQ-5): discrimination across self-assessed severity and aqueous tear deficient dry eye diagnoses.
        Cont Lens Anterior Eye. 2010; 33: 55-60https://doi.org/10.1016/j.clae.2009.12.010
        • Akowuah P.K.
        • Adjei-Anang J.
        • Nkansah E.K.
        • et al.
        Comparison of the performance of the dry eye questionnaire (DEQ-5) to the ocular surface disease index in a non-clinical population.
        Cont Lens Anterior Eye. 2021; : 101441https://doi.org/10.1016/j.clae.2021.101441
        • Blackie C.
        • Albou-Ganem C.
        • Korb D.
        Questionnaire assists in dry eye disease diagnosis. Four-question survey helps evaluate patients’ dry eye symptoms to improve screening.
        Ocul Surg News. 2012;
        • Ngo W.
        • Situ P.
        • Keir N.
        • et al.
        Psychometric properties and validation of the standard patient evaluation of eye dryness questionnaire.
        Cornea. 2013; 32: 1204-1210https://doi.org/10.1097/ICO.0b013e318294b0c0
        • Wolffsohn J.S.
        • Arita R.
        • Chalmers R.
        • et al.
        TFOS DEWS II diagnostic methodology report.
        Ocul Surf. 2017; 15: 539-574https://doi.org/10.1016/j.jtos.2017.05.001
        • Shimazaki J.
        Definition and diagnostic criteria of dry eye disease: historical overview and future directions.
        Invest Ophthalmol Vis Sci. 2018; 59: DES7-12https://doi.org/10.1167/iovs.17-23475
        • Baudouin C.
        • Aragona P.
        • Van Setten G.
        • et al.
        Diagnosing the severity of dry eye: a clear and practical algorithm.
        Br J Ophthalmol. 2014; 98: 1168-1176https://doi.org/10.1136/bjophthalmol-2013-304619
        • Veres A.
        • Tapasztó B.
        • Kosina-Hagyó K.
        • et al.
        Imaging lid-parallel conjunctival folds with OCT and comparing its grading with the slit lamp classification in dry eye patients and normal subjects.
        Invest Ophthalmol Vis Sci. 2011; 52: 2945-2951https://doi.org/10.1167/iovs.10-5505
        • Lamberts D.W.
        • Foster C.S.
        • Perry H.D.
        Schirmer test after topical anesthesia and the tear meniscus height in normal eyes.
        Arch Ophthalmol. 1979; 97: 1082-1085https://doi.org/10.1001/archopht.1979.01020010536004
        • Vanley G.T.
        • Leopold I.H.
        • Gregg T.H.
        Interpretation of tear film breakup.
        Arch Ophthalmol. 1977; 95: 445-448https://doi.org/10.1001/archopht.1977.04450030087010
        • Potvin R.
        • Makari S.
        • Rapuano C.J.
        Tear film osmolarity and dry eye disease: a review of the literature.
        Clin Ophthalmol. 2015; 9: 2039-2047https://doi.org/10.2147/OPTH.S95242
        • Messmer E.M.
        • von Lindenfels V.
        • Garbe A.
        • et al.
        Matrix metalloproteinase 9 testing in dry eye disease using a commercially available point-of-care immunoassay.
        Ophthalmology. 2016; 123: 2300-2308https://doi.org/10.1016/j.ophtha.2016.07.028
        • Ohashi Y.
        • Ishida R.
        • Kojima T.
        • et al.
        Abnormal protein profiles in tears with dry eye syndrome.
        Am J Ophthalmol. 2003; 136: 291-299https://doi.org/10.1016/s0002-9394(03)00203-4
        • Latkany R.
        • Lock B.G.
        • Speaker M.
        Tear film normalization test: a new diagnostic test for dry eyes.
        Cornea. 2006; 25: 1153-1157https://doi.org/10.1097/01.ico.0000240085.21105.51
        • Begley C.
        • Caffery B.
        • Chalmers R.
        • et al.
        Review and analysis of grading scales for ocular surface staining.
        Ocul Surf. 2019; 17: 208-220https://doi.org/10.1016/j.jtos.2019.01.004
        • Dogru M.
        • Tsubota K.
        Pharmacotherapy of dry eye.
        Expert Opin Pharmacother. 2011; 12: 325-334https://doi.org/10.1517/14656566.2010.518612
        • Miljanović B.
        • Trivedi K.A.
        • Dana M.R.
        • et al.
        Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women.
        Am J Clin Nutr. 2005; 82: 887-893https://doi.org/10.1093/ajcn/82.4.887
        • Asbell P.A.
        • Maguire M.G.
        • Pistilli M.
        • 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: 1681-1690https://doi.org/10.1056/NEJMoa1709691
        • Liu J.
        • Dong Y.
        • Wang Y.
        Vitamin D deficiency is associated with dry eye syndrome: a systematic review and meta-analysis.
        Acta Ophthalmol. 2020; 98: 749-754https://doi.org/10.1111/aos.14470
        • Finis D.
        • König C.
        • Hayajneh J.
        • et al.
        Six-month effects of a thermodynamic treatment for MGD and implications of meibomian gland atrophy.
        Cornea. 2014; 33: 1265-1270https://doi.org/10.1097/ICO.0000000000000273
        • Thode A.R.
        • Latkany R.A.
        Current and emerging therapeutic strategies for the treatment of meibomian gland dysfunction (MGD).
        Drugs. 2015; 75: 1177-1185https://doi.org/10.1007/s40265-015-0432-8
        • Pucker A.D.
        • Ng S.M.
        • Nichols J.J.
        Over the counter (OTC) artificial tear drops for dry eye syndrome.
        Cochrane Database Syst Rev. 2016; 2: CD009729https://doi.org/10.1002/14651858.CD009729.pub2
        • Berdy G.J.
        • Abelson M.B.
        • Smith L.M.
        • et al.
        Preservative-free artificial tear preparations. Assessment of corneal epithelial toxic effects.
        Arch Ophthalmol. 1992; 110: 528-532https://doi.org/10.1001/archopht.1992.01080160106043
        • Ervin A.-M.
        • Law A.
        • Pucker A.D.
        Punctal occlusion for dry eye syndrome.
        Cochrane Database Syst Rev. 2017; 6: CD006775https://doi.org/10.1002/14651858.CD006775.pub3
        • Sall K.
        • Stevenson O.D.
        • Mundorf T.K.
        • et al.
        Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group.
        Ophthalmology. 2000; 107: 631-639https://doi.org/10.1016/s0161-6420(99)00176-1
        • O’Neil E.C.
        • Henderson M.
        • Massaro-Giordano M.
        • et al.
        Advances in dry eye disease treatment.
        Curr Opin Ophthalmol. 2019; 30: 166-178https://doi.org/10.1097/ICU.0000000000000569
        • Tauber J.
        • Schechter B.A.
        • Bacharach J.
        • et al.
        A Phase II/III, randomized, double-masked, vehicle-controlled, dose-ranging study of the safety and efficacy of OTX-101 in the treatment of dry eye disease.
        Clin Ophthalmol. 2018; 12: 1921-1929https://doi.org/10.2147/OPTH.S175065
        • Matossian C.
        • Trattler W.
        • Loh J.
        Dry eye treatment with topical cyclosporine 0.1% in chondroitin sulfate ophthalmic emulsion.
        Clin Ophthalmol. 2021; 15: 1979-1984https://doi.org/10.2147/OPTH.S308088
        • Sheppard J.D.
        • Donnenfeld E.D.
        • Holland E.J.
        • et al.
        Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with topical cyclosporine 0.05.
        Eye Contact Lens. 2014; 40: 289-296https://doi.org/10.1097/ICL.0000000000000049
        • Haber S.L.
        • Benson V.
        • Buckway C.J.
        • et al.
        Lifitegrast: a novel drug for patients with dry eye disease.
        Ther Adv Ophthalmol. 2019; 11https://doi.org/10.1177/2515841419870366
        • Marsh P.
        • Pflugfelder S.C.
        Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjögren syndrome.
        Ophthalmology. 1999; 106: 811-816https://doi.org/10.1016/S0161-6420(99)90171-9
        • Foulks G.N.
        • Borchman D.
        • Yappert M.
        • et al.
        Topical azithromycin therapy for meibomian gland dysfunction: clinical response and lipid alterations.
        Cornea. 2010; 29: 781-788https://doi.org/10.1097/ICO.0b013e3181cda38f
        • Yoo S.-E.
        • Lee D.-C.
        • Chang M.-H.
        The effect of low-dose doxycycline therapy in chronic meibomian gland dysfunction.
        Korean J Ophthalmol. 2005; 19: 258https://doi.org/10.3341/kjo.2005.19.4.258
        • Foulks G.N.
        • Borchman D.
        • Yappert M.
        • et al.
        Topical azithromycin and oral doxycycline therapy of meibomian gland dysfunction: a comparative clinical and spectroscopic pilot study.
        Cornea. 2013; 32: 44-53https://doi.org/10.1097/ICO.0b013e318254205f
        • Drew V.J.
        • Tseng C.-L.
        • Seghatchian J.
        • et al.
        Reflections on dry eye syndrome treatment: therapeutic role of blood products.
        Front Med. 2018; 5: 33https://doi.org/10.3389/fmed.2018.00033
        • Anitua E.
        • Muruzabal F.
        • Tayebba A.
        • et al.
        Autologous serum and plasma rich in growth factors in ophthalmology: preclinical and clinical studies.
        Acta Ophthalmol. 2015; 93: e605-e614https://doi.org/10.1111/aos.12710
        • Sanchez-Avila R.M.
        • Merayo-Lloves J.
        • Muruzabal F.
        • et al.
        Plasma rich in growth factors for the treatment of dry eye from patients with graft versus host diseases.
        Eur J Ophthalmol. 2020; 30: 94-103https://doi.org/10.1177/1120672118818943
        • Alio J.L.
        • Rodriguez A.E.
        • Ferreira-Oliveira R.
        • et al.
        Treatment of dry eye disease with autologous platelet-rich plasma: a prospective, interventional, non-randomized study.
        Ophthalmol Ther. 2017; 6: 285-293https://doi.org/10.1007/s40123-017-0100-z
        • Wang Y.
        • Carreno-Galeano J.T.
        • Singh R.B.
        • et al.
        Long-term outcomes of punctal cauterization in the management of ocular surface diseases.
        Cornea. 2021; 40: 168-171https://doi.org/10.1097/ICO.0000000000002384
        • Yokoi N.
        • Inatomi T.
        • Kinoshita S.
        Surgery of the conjunctiva.
        in: Dev Ophthalmol. vol. 41. KARGER, Basel2008: 138-158https://doi.org/10.1159/000131086
        • Dell S.J.
        • Gaster R.N.
        • Barbarino S.C.
        • et al.
        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: 817-827https://doi.org/10.2147/OPTH.S130706
        • Finis D.
        • Hayajneh J.
        • König C.
        • et al.
        Evaluation of an automated thermodynamic treatment (LipiFlow®) system for meibomian gland dysfunction: a prospective, randomized, observer-masked trial.
        Ocul Surf. 2014; 12: 146-154https://doi.org/10.1016/j.jtos.2013.12.001
        • Tauber J.
        • Owen J.
        • Bloomenstein M.
        • et al.
        Comparison of the iLUX and the LipiFlow for the Treatment of Meibomian Gland dysfunction and symptoms: a randomized clinical trial.
        Clin Ophthalmol. 2020; 14: 405-418https://doi.org/10.2147/OPTH.S234008
        • Kislan T.
        New, targeted technology for treating the root cause of dry eye disease (DED).
        (MiBo Medical n.d. Avilable at:) (Accessed February 28, 2021)
        • Karpecki P.
        • Wirta D.
        • Osmanovic S.
        • et al.
        A prospective, post-market, multicenter trial (CHEETAH) suggested TEARCARE® system as a safe and effective blink-assisted eyelid device for the treatment of dry eye disease.
        Clin Ophthalmol. 2020; 14: 4551-4559https://doi.org/10.2147/OPTH.S285953
        • Maskin S.L.
        Intraductal meibomian gland probing relieves symptoms of obstructive meibomian gland dysfunction.
        Cornea. 2010; 29: 1145-1152https://doi.org/10.1097/ICO.0b013e3181d836f3
        • Epstein I.J.
        • Rosenberg E.
        • Stuber R.
        • et al.
        Double-masked and unmasked prospective study of terpinen-4-ol lid scrubs with microblepharoexfoliation for the treatment of demodex blepharitis.
        Cornea. 2020; 39: 408-416https://doi.org/10.1097/ICO.0000000000002243
        • Ji M.H.
        • Moshfeghi D.M.
        • Periman L.
        • et al.
        Novel extranasal tear stimulation: pivotal study results.
        Transl Vis Sci Technol. 2020; 9: 23https://doi.org/10.1167/tvst.9.12.23
        • Cohn G.S.
        • Corbett D.
        • Tenen A.
        • et al.
        Randomized, controlled, double-masked, multicenter, pilot study evaluating safety and efficacy of intranasal neurostimulation for dry eye disease.
        Invest Ophthalmol Vis Sci. 2019; 60: 147https://doi.org/10.1167/iovs.18-23984
        • Wirta D.
        • Vollmer P.
        • Paauw J.
        • et al.
        Efficacy and safety of OC-01 (Varenicline) nasal spray on signs and symptoms of dry eye disease: the ONSET-2 phase 3, randomized trial.
        Ophthalmology. 2021; S0161-6420: 00836-00838https://doi.org/10.1016/j.ophtha.2021.11.004
        • Goyal S.
        • Hamrah P.
        Understanding neuropathic corneal pain--gaps and current therapeutic approaches.
        Semin Ophthalmol. 2016; 31: 59-70https://doi.org/10.3109/08820538.2015.1114853
        • Nguyen M.T.B.
        • Thakrar V.
        • Chan C.C.
        EyePrintPRO therapeutic scleral contact lens: indications and outcomes.
        Can J Ophthalmol. 2018; 53: 66-70https://doi.org/10.1016/j.jcjo.2017.07.026
        • Arya S.K.
        • Bhala S.
        • Malik A.
        • et al.
        Role of amniotic membrane transplantation in ocular surface disorders.
        Nepal J Ophthalmol. 2010; 2: 145-153https://doi.org/10.3126/nepjoph.v2i2.3722
        • McDonald M.B.
        • Sheha H.
        • Tighe S.
        • et al.
        Treatment outcomes in the DRy Eye amniotic membrane (DREAM) study.
        Clin Ophthalmol. 2018; 12: 677-681https://doi.org/10.2147/OPTH.S162203
        • Zhang X.
        • Chen Q.
        • Chen W.
        • et al.
        Tear dynamics and corneal confocal microscopy of subjects with mild self-reported office dry eye.
        Ophthalmology. 2011; 118: 902-907https://doi.org/10.1016/j.ophtha.2010.08.033
        • Labbé A.
        • Liang Q.
        • Wang Z.
        • et al.
        Corneal nerve structure and function in patients with non-sjogren dry eye: clinical correlations.
        Invest Ophthalmol Vis Sci. 2013; 54: 5144-5150https://doi.org/10.1167/iovs.13-12370
        • Lin H.
        • Li W.
        • Dong N.
        • et al.
        Changes in corneal epithelial layer inflammatory cells in aqueous tear-deficient dry eye.
        Invest Ophthalmol Vis Sci. 2010; 51: 122-128https://doi.org/10.1167/iovs.09-3629
        • Chew C.K.
        • Jansweijer C.
        • Tiffany J.M.
        • et al.
        An instrument for quantifying meibomian lipid on the lid margin: the Meibometer.
        Curr Eye Res. 1993; 12: 247-254https://doi.org/10.3109/02713689308999470
        • Srinivasan S.
        • Menzies K.
        • Sorbara L.
        • et al.
        Infrared imaging of meibomian gland structure using a novel keratograph.
        Optom Vis Sci. 2012; 89: 788-794https://doi.org/10.1097/OPX.0b013e318253de93
        • Wise R.J.
        • Sobel R.K.
        • Allen R.C.
        Meibography: a review of techniques and technologies.
        Saudi J Ophthalmol. 2012; 26: 349-356https://doi.org/10.1016/j.sjopt.2012.08.007
        • Kobayashi A.
        • Yoshita T.
        • Sugiyama K.
        In vivo findings of the bulbar/palpebral conjunctiva and presumed meibomian glands by laser scanning confocal microscopy.
        Cornea. 2005; 24: 985-988https://doi.org/10.1097/01.ico.0000160976.88824.2b
        • Hosaka E.
        • Kawamorita T.
        • Ogasawara Y.
        • et al.
        Interferometry in the evaluation of precorneal tear film thickness in dry eye.
        Am J Ophthalmol. 2011; 151: 18-23.e1https://doi.org/10.1016/j.ajo.2010.07.019
        • Arita R.
        • Morishige N.
        • Fujii T.
        • et al.
        Tear interferometric patterns reflect clinical tear dynamics in dry eye patients.
        Invest Ophthalmol Vis Sci. 2016; 57: 3928-3934https://doi.org/10.1167/iovs.16-19788
        • Szczesna D.H.
        • Alonso-Caneiro D.
        • Iskander D.R.
        • et al.
        Predicting dry eye using noninvasive techniques of tear film surface assessment.
        Invest Ophthalmol Vis Sci. 2011; 52: 751-756https://doi.org/10.1167/iovs.10-5173
        • Fahim M.M.
        • Haji S.
        • Koonapareddy C.V.
        • et al.
        Fluorophotometry as a diagnostic tool for the evaluation of dry eye disease.
        BMC Ophthalmol. 2006; 6: 20https://doi.org/10.1186/1471-2415-6-20
        • Sacchetti M.
        • Lambiase A.
        • Schmidl D.
        • et al.
        Effect of recombinant human nerve growth factor eye drops in patients with dry eye: a phase IIa, open label, multiple-dose study.
        Br J Ophthalmol. 2020; 104: 127-135https://doi.org/10.1136/bjophthalmol-2018-312470
        • Meerovitch K.
        • Torkildsen G.
        • Lonsdale J.
        • et al.
        Safety and efficacy of MIM-D3 ophthalmic solutions in a randomized, placebo-controlled Phase 2 clinical trial in patients with dry eye.
        Clin Ophthalmol. 2013; 7: 1275-1285https://doi.org/10.2147/OPTH.S44688
        • Vijmasi T.
        • Chen F.Y.T.
        • Balasubbu S.
        • et al.
        Topical administration of lacritin is a novel therapy for aqueous-deficient dry eye disease.
        Invest Ophthalmol Vis Sci. 2014; 55: 5401-5409https://doi.org/10.1167/iovs.14-13924
        • Lambiase A.
        • Sullivan B.D.
        • Schmidt T.A.
        • et al.
        A two-week, randomized, double-masked study to evaluate safety and efficacy of lubricin (150 μg/mL) eye drops versus sodium hyaluronate (HA) 0.18% eye drops (Vismed®) in patients with moderate dry eye disease.
        Ocul Surf. 2017; 15: 77-87https://doi.org/10.1016/j.jtos.2016.08.004
        • Sosne G.
        • Dunn S.P.
        • Kim C.
        Thymosin β4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial.
        Cornea. 2015; 34: 491-496https://doi.org/10.1097/ICO.0000000000000379
        • Murri M.S.
        • Moshirfar M.
        • Birdsong O.C.
        • et al.
        Amniotic membrane extract and eye drops: a review of literature and clinical application.
        Clin Ophthalmol. 2018; 12: 1105-1112https://doi.org/10.2147/OPTH.S165553
        • Tauber J.
        • Wirta D.L.
        • Sall K.
        • et al.
        A randomized clinical study (SEECASE) to assess efficacy, safety, and tolerability of NOV03 for treatment of dry eye disease.
        Cornea. 2021; 40: 1132-1140https://doi.org/10.1097/ICO.0000000000002622
        • Clark D.
        • Tauber J.
        • Sheppard J.
        • et al.
        Early onset and broad activity of reproxalap in a randomized, double-masked, vehicle-controlled phase 2b trial in dry eye disease.
        Am J Ophthalmol. 2021; 226: 22-31https://doi.org/10.1016/j.ajo.2021.01.011
        • Lindstrom R.
        • Donnenfeld E.
        • Holland E.
        • et al.
        Safety and efficacy of ALG-1007 topical ophthalmic solution – A synthetic peptide that regulates inflammation, in patients with dry eye disease: an exploratory phase I, open-label, single-center clinical study.
        AJOCT. 2020; 3: 10https://doi.org/10.25259/AJOCT_1_2020
        • Spana C.
        • Taylor A.W.
        • Yee D.G.
        • et al.
        Probing the role of melanocortin type 1 receptor agonists in diverse immunological diseases.
        Front Pharmacol. 2018; 9: 1535https://doi.org/10.3389/fphar.2018.01535
      2. Azura Ophthalmics Announces Primary Endpoints Met in Phase 2 Trial of Investigational Treatment for Contact Lens Discomfort.
        (Available at:) (Accessed February 28, 2021)
        • Sarezky D.
        • Massaro-Giordano M.
        • Bunya V.Y.
        Novel diagnostics and therapeutics in dry eye disease.
        Adv Ophthalmol Optom. 2016; 1: 1-20https://doi.org/10.1016/j.yaoo.2016.03.016