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Hot towels: The bedrock of Meibomian gland dysfunction treatment – A review

  • Morten Schjerven Magno
    Correspondence
    Corresponding author at: University of Oslo, PO Box 1072, 0316 Blindern, Oslo, Norway.
    Affiliations
    Department of Ophthalmology, Sørlandet Hospital Arendal, Arendal, Norway

    Department of Plastic and Reconstructive Surgery, Oslo University Hospital, Oslo, Norway

    Department of Ophthalmology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

    Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway

    Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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  • Jonatan Olafsson
    Affiliations
    Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway

    Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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  • Marie Beining
    Affiliations
    Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway

    Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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  • Emily Moschowits
    Affiliations
    Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
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  • Neil Lagali
    Affiliations
    Department of Ophthalmology, Institute for Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden

    Department of Ophthalmology, Sørlandet Hospital Arendal, Arendal, Norway
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  • James S. Wolffsohn
    Affiliations
    School of Optometry, College of Health & Life Sciences, Aston University, Birmingham, United Kingdom
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  • Jennifer P. Craig
    Affiliations
    School of Optometry, College of Health & Life Sciences, Aston University, Birmingham, United Kingdom

    Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, New Zealand
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  • Jelle Vehof
    Affiliations
    Department of Ophthalmology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

    Department of Ophthalmology, Vestfold Hospital Trust, Tønsberg, Norway

    Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

    Dutch Dry Eye Clinic, Emmastraat 21, 6881SN, Velp, the Netherlands
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  • Darlene A. Dartt
    Affiliations
    Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, 20 Staniford St., Boston, MA 02114, United States
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  • Tor P. Utheim
    Affiliations
    Department of Ophthalmology, Sørlandet Hospital Arendal, Arendal, Norway

    Department of Plastic and Reconstructive Surgery, Oslo University Hospital, Oslo, Norway

    Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway

    Department of Ophthalmology, Sørlandet Hospital Arendal, Arendal, Norway

    Department of Ophthalmology, Oslo University Hospital, Oslo, Norway

    Department of Ophthalmology, Stavanger University Hospital, Oslo, Norway

    Department of Ophthalmology, Vestre Viken Hospital Trust, Drammen, Norway

    Department of Computer Science, Oslo Metropolitan University, Oslo, Norway

    Department of Clinical Medicine, Faculty of Medicine, University of Bergen, Bergen, Norway

    Department of Quality and Health Technology, The Faculty of Health Sciences, University of Stavanger, Stavanger, Norway

    Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway

    National Centre for Optics, Vision and Eye Care, Department of Optometry, Radiography and Lighting Design, Faculty of Health Sciences, University of South-Eastern Norway, Kongsberg, Norway

    Department of Health and Nursing Science, The Faculty of Health and Sport Sciences, University of Agder, Grimstad, Norway

    The Norwegian Dry Eye Clinic, Oslo, Norway
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Open AccessPublished:October 28, 2022DOI:https://doi.org/10.1016/j.clae.2022.101775

      Abstract

      Background

      Meibomian gland dysfunction (MGD) reduces quality-of-life and hinders work productivity of millions of patients, with high direct and indirect societal costs. Thickened meibum obstructs the glands and disrupts ocular surface health. Heating the eyelids to soften and express meibum from the glands can be beneficial. The most accessible method for eyelid warming uses heated, wet towels. However, the efficacy of this treatment is reliant on the methodology, and evidence-based best-practice recommendations are needed.

      Purpose

      To evaluate the literature on hot towels in MGD treatment and recommend a best-practice protocol for future research and patient treatment.

      Methods

      Studies were identified through PubMed on the May 28, 2021, with the search terms: (warm* OR heat* OR thermal* OR towel OR wet towel) AND (meibomian OR MGD OR eyelid OR “dry eye” OR DED). All relevant original articles with English full-text were included.

      Results

      The search yielded 903 results, of which 22 met the inclusion criteria. Across studies, hot towels were found to be effective at reducing ocular symptoms. However, without reheating, the temperature quickly fell below the therapeutic range, which was deemed to be between 40 °C and 47 °C. Towels heated to around 45 °C and reheated every-two minutes were most effective at increasing eyelid temperature, comparable or better than several commercially available eyelid warming devices. No adverse effects were reported in the studies.

      Conclusion

      Hot towel treatment effectively warms the eyelids and reduces ocular symptoms, but must be standardized, and towels reheated to achieve maximum benefit. Future research should assess patient satisfaction with different hot towel treatment methods that reheat or replace the towel at least every-two minutes, to establish which methods yield the greatest compliance. Guidelines or clinical recommendations that do not mention the need for regular reheating during hot towel compress treatment should be updated to include this.

      Keywords

      1. Introduction

      Meibomian gland dysfunction (MGD) is the most common cause of dry eye disease (DED), affecting several hundred million people worldwide [
      • Schaumberg D.A.
      • Nichols J.J.
      • Papas E.B.
      • Tong L.
      • Uchino M.
      • Nichols K.K.
      The international workshop on meibomian gland dysfunction: report of the subcommittee on the epidemiology of, and associated risk factors for.
      ]. MGD is hallmarked by increased tear evaporation, hyperosmolarity and symptoms of dry eye, including discomfort, visual disruption, and eyelid tenderness [
      • Chhadva P.
      • Goldhardt R.
      • Galor A.
      Meibomian gland disease: the role of gland dysfunction in dry eye disease.
      ]. The healthy eye is protected by the tear film, which provides a physical and immunological barrier against microorganisms, pollutants, and other stressors [
      • Barabino S.
      • Chen Y.
      • Chauhan S.
      • Dana R.
      Ocular surface immunity: homeostatic mechanisms and their disruption in dry eye disease.
      ,
      • Akpek E.K.
      • Gottsch J.D.
      Immune defense at the ocular surface.
      ]. The tear film is made up of two main layers, the inner mucoaqueous layer and the outer lipid layer (Fig. 1) [
      • Willcox M.D.P.
      • Argueso P.
      • Georgiev G.A.
      • Holopainen J.M.
      • Laurie G.W.
      • Millar T.J.
      • et al.
      TFOS DEWS II Tear Film Report.
      ]. The meibomian glands, located in the tarsal plates of the eyelids produce the meibum that makes up the outer lipid layer which stabilizes, reduces the surface tension of, and prevents the evaporation of the aqueous tear fluid [
      • 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.
      ].
      Figure thumbnail gr1
      Fig. 1Schematic drawing of the anterior segment of the eye and ocular adnexa with the overlying tear film. The tear film is made up of two distinct layers, with three major components; mucin (1), aqueous tears (2), and lipids (3) secreted by the goblet cells, lacrimal gland, and meibomian glands, respectively. Illustration by Sara Nøland.
      In MGD, the loss of healthy meibum production and function leads to lipid layer deterioration, which causes the tear film to become unstable, resulting in DED [
      • 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.
      ]. The clinical presentation of MGD is often characterized by altered meibum secretion, meibomian gland dropout, and orifice plugging [
      • Chhadva P.
      • Goldhardt R.
      • Galor A.
      Meibomian gland disease: the role of gland dysfunction in dry eye disease.
      ]. Meibum in healthy adults has a transition temperature of around 28 °C [
      • Borchman D.
      • Foulks G.N.
      • Yappert M.C.
      • Bell J.
      • Wells E.
      • Neravetla S.
      • et al.
      Human meibum lipid conformation and thermodynamic changes with meibomian-gland dysfunction.
      ]. This is low enough to keep the meibum mostly fluid during normal conditions, where the ocular surface and eyelids maintain a temperature of between 33 °C and 36 °C [
      • Butovich I.A.
      • Millar T.J.
      • Ham B.M.
      Understanding and analyzing meibomian lipids–a review.
      ,
      • Borchman D.
      The optimum temperature for the heat therapy for meibomian gland dysfunction.
      ,
      • Abreau K.
      • Callan C.
      • Kottaiyan R.
      • Zhang A.
      • Yoon G.
      • Aquavella J.V.
      • et al.
      Temperatures of the Ocular Surface, Lid, and Periorbital Regions of Sjogren's, Evaporative, and Aqueous-Deficient Dry Eyes Relative to Normals.
      ]. The meibum can then freely flow onto the ocular surface from the main secretory duct where it is stored [
      • 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.
      ]. In MGD, the increased viscosity, higher melting point of the meibum, and hyper-keratinization of the ductal epithelium together lead to the obstruction of the terminal ducts, which halts the secretion of healthy meibum [
      • Asbell P.A.
      • Stapleton F.J.
      • Wickstrom K.
      • Akpek E.K.
      • Aragona P.
      • Dana R.
      • et al.
      The international workshop on meibomian gland dysfunction: report of the clinical trials subcommittee.
      ]. Generally, the chemical structure of the meibum from patients suffering from MGD is more ordered than healthy meibum and has a hydrocarbon chain stiffness halfway between olive oil and butter [
      • Borchman D.
      • Foulks G.N.
      • Yappert M.C.
      • Bell J.
      • Wells E.
      • Neravetla S.
      • et al.
      Human meibum lipid conformation and thermodynamic changes with meibomian-gland dysfunction.
      ]. To achieve the same level of disorder and liquidity as healthy meibum at 36 °C, meibum from patients with MGD requires a temperature of 38.5 °C on average [
      • Borchman D.
      The optimum temperature for the heat therapy for meibomian gland dysfunction.
      ]. This may explain the poor meibum secretion observed in this patient group [
      • Ong B.L.
      • Larke J.R.
      Meibomian gland dysfunction: some clinical, biochemical and physical observations.
      ,
      • Nagymihalyi A.
      • Dikstein S.
      • Tiffany J.M.
      The influence of eyelid temperature on the delivery of meibomian oil.
      ,
      • Terada O.
      • Chiba K.
      • Senoo T.
      • Obara Y.
      Ocular surface temperature of meibomia gland dysfunction patients and the melting point of meibomian gland secretions.
      ]. This abnormal secretion in turn leads to glandular atrophy, dropout, and decreased gland function [
      • Nichols K.K.
      • Foulks G.N.
      • Bron A.J.
      • Glasgow B.J.
      • Dogru M.
      • Tsubota K.
      • et al.
      The international workshop on meibomian gland dysfunction: executive summary.
      ]. Excreting this thickened meibum, therefore, plays a vital role in the treatment of MGD [
      • Geerling G.
      • Tauber J.
      • Baudouin C.
      • Goto E.
      • Matsumoto Y.
      • O'Brien T.
      • et al.
      The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction.
      ]. This can be accomplished by delivering localized heat to warm the meibum beyond its melting point and applying pressure to express the softened meibum.
      For warming of the eyelids, the application of a warm compress for five to fifteen minutes, followed by brief eyelid hygiene between once and four times daily is often recommended [
      • Geerling G.
      • Tauber J.
      • Baudouin C.
      • Goto E.
      • Matsumoto Y.
      • O'Brien T.
      • et al.
      The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction.
      ]. The most accessible method for warm compress treatment is the use of a wetted and heated towel that is placed over the eyelids to provide direct, moist heat to the eyelids [
      • Geerling G.
      • Tauber J.
      • Baudouin C.
      • Goto E.
      • Matsumoto Y.
      • O'Brien T.
      • et al.
      The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction.
      ]. Despite the long clinical tradition of recommending this treatment to patients, limited research has been performed to standardize this practice. Recently, several studies were published focusing on the ever-increasing number of alternative modalities for eyelid warming. These include commercially available dry-heat eyelid masks, steam-based systems, and in-office treatment systems [
      • Arita R.
      • Morishige N.
      • Sakamoto I.
      • Imai N.
      • Shimada Y.
      • Igaki M.
      • et al.
      Effects of a warm compress containing menthol on the tear film in healthy subjects and dry eye patients.
      ,
      • Badawi D.
      A novel system, TearCare((R)), for the treatment of the signs and symptoms of dry eye disease.
      ,
      • Bilkhu P.S.
      • Naroo S.A.
      • Wolffsohn J.S.
      Effect of a commercially available warm compress on eyelid temperature and tear film in healthy eyes.
      ,
      • Lane S.S.
      • DuBiner H.B.
      • Epstein R.J.
      • Ernest P.H.
      • Greiner J.V.
      • Hardten D.R.
      • et al.
      A new system, the LipiFlow, for the treatment of meibomian gland dysfunction.
      ,
      • Ngo W.
      • Srinivasan S.
      • Jones L.
      An Eyelid Warming Device for the Management of Meibomian Gland Dysfunction.
      ,
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      ,
      • Tan J.
      • Ho L.
      • Wong K.
      • La A.
      • Lee S.
      • Park S.
      • et al.
      The effects of a hydrating mask compared to traditional warm compresses on tear film properties in meibomian gland dysfunction.
      ,
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Villani E.
      • Garoli E.
      • Canton V.
      • Pichi F.
      • Nucci P.
      • Ratiglia R.
      Evaluation of a novel eyelid-warming device in meibomian gland dysfunction unresponsive to traditional warm compress treatment: an in vivo confocal study.
      ]. In these studies, a wide range of hot towel warm compress techniques were used as control groups, with no clear standardization or repeatability [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ]. By critically reviewing the current literature on hot towel compresses in the treatment of MGD, this review aims to establish a best-practice for hot towel treatment and recommend a standard methodology for the application of hot towel treatment as a control in future studies. As hot towel compresses are the most widely available and affordable treatment option, a large number of patients worldwide are reliant on this treatment. Standardization of methodology could both help patients achieve the best possible results from treatment and improve the quality of research on eyelid warming devices, further advancing the field.

      2. Methods

      A search was conducted on PubMed on the 28th of May 2021 using the following search terms: (warm* OR heat* OR thermal* OR towel OR wet towel) AND (meibomian OR MGD OR eyelid OR “dry eye” OR DED). All search results were evaluated by a single author, first by title and later by abstract to ensure relevance to the topic and satisfaction of the inclusion criteria. The inclusion criteria for this review were: original, peer-reviewed studies with available English full text that investigated hot towel warm compresses to treat MGD. Only articles clearly describing the use of a towel/cloth-based method of warm compress treatment were included, studies on commercial devices or which did not describe the method of warm compress treatment were excluded. Further, case reports, review articles, and non-peer-reviewed literature were excluded. The methodology is illustrated in Fig. 2.
      Figure thumbnail gr2
      Fig. 2Flow chart of PubMed search methodology.

      3. Results

      3.1 Overview of existing literature

      The search term (warm* OR heat* OR thermal* OR towel OR wet towel) AND (meibomian OR MGD OR eyelid OR “dry eye” OR DED) yielded 903 results, spanning from April 1948 to May 2021. Review article and case reports were filtered out, leaving 688 studies to be assessed for relevance by title and abstract. At this step, 623 articles were excluded, leaving 65 full-text articles to be evaluated. Of these, 22 articles were selected for this review based on the content of the full text. A majority of the 43 studies that were excluded in this last step either clearly stated the use of a commercially available eyelid warming device, not hot towels, or failed to provide any information on the type of warm compress used. One article was excluded as the group receiving hot towel treatment was pooled with other treatments and no clinical measures were reported separately for this group [
      • Ambaw Y.A.
      • Fuchs D.
      • Raida M.
      • Mazengia N.T.
      • Torta F.
      • Wheelock C.E.
      • et al.
      Changes of tear lipid mediators after eyelid warming or thermopulsation treatment for Meibomian gland dysfunction.
      ]. The final 22 articles included in this review were published between April 2003 [
      • Olson M.C.
      • Korb D.R.
      • Greiner J.V.
      Increase in tear film lipid layer thickness following treatment with warm compresses in patients with Meibomian gland dysfunction.
      ] and September 2020 [
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ], and were conducted in 10 different countries: (USA [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Olson M.C.
      • Korb D.R.
      • Greiner J.V.
      Increase in tear film lipid layer thickness following treatment with warm compresses in patients with Meibomian gland dysfunction.
      ,
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ,
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      ,
      • Blackie C.A.
      • McMonnies C.W.
      • Korb D.R.
      Warm compresses and the risks of elevated corneal temperature with massage.
      ,
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ,
      • Solomon J.D.
      • Case C.L.
      • Greiner J.V.
      • Blackie C.A.
      • Herman J.P.
      • Korb D.R.
      Warm compress induced visual degradation and Fischer-Schweitzer polygonal reflex.
      ], Japan [
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ], China [
      • Lam A.K.
      • Lam C.H.
      Effect of warm compress therapy from hard-boiled eggs on corneal shape.
      ], Germany [
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      ,
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      ], Singapore [
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Zhao Y.
      • Veerappan A.
      • Yeo S.
      • Rooney D.M.
      • Acharya R.U.
      • Tan J.H.
      • et al.
      Clinical trial of thermal pulsation (LipiFlow) in Meibomian gland dysfunction with preteatment meibography.
      ,
      • Lam S.M.
      • Tong L.
      • Duan X.
      • Acharya U.R.
      • Tan J.H.
      • Petznick A.
      • et al.
      Longitudinal changes in tear fluid lipidome brought about by eyelid-warming treatment in a cohort of Meibomian gland dysfunction.
      ,
      • Yeo S.
      • Tan J.H.
      • Acharya U.R.
      • Sudarshan V.K.
      • Tong L.
      Longitudinal changes in tear evaporation rates after eyelid warming therapies in Meibomian gland dysfunction.
      ], Canada [
      • Lacroix Z.
      • Leger S.
      • Bitton E.
      Ex vivo heat retention of different eyelid warming masks.
      ,
      • Bitton E.
      • Lacroix Z.
      • Leger S.
      In-vivo heat retention comparison of eyelid warming masks.
      ], Korea [
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ], Thailand [
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ], Australia [
      • Tan J.
      • Ho L.
      • Wong K.
      • La A.
      • Lee S.
      • Park S.
      • et al.
      The effects of a hydrating mask compared to traditional warm compresses on tear film properties in meibomian gland dysfunction.
      ], and Ireland [

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]). Seven of the included studies used hot, wet towel compresses as the only eyelid warming technique [
      • Olson M.C.
      • Korb D.R.
      • Greiner J.V.
      Increase in tear film lipid layer thickness following treatment with warm compresses in patients with Meibomian gland dysfunction.
      ,
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      ,
      • Blackie C.A.
      • McMonnies C.W.
      • Korb D.R.
      Warm compresses and the risks of elevated corneal temperature with massage.
      ,
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ,
      • Solomon J.D.
      • Case C.L.
      • Greiner J.V.
      • Blackie C.A.
      • Herman J.P.
      • Korb D.R.
      Warm compress induced visual degradation and Fischer-Schweitzer polygonal reflex.
      ,
      • Lam A.K.
      • Lam C.H.
      Effect of warm compress therapy from hard-boiled eggs on corneal shape.
      ,
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ]. Twelve studies compared the effect of towels to other eyelid warming therapies [
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      ,
      • Tan J.
      • Ho L.
      • Wong K.
      • La A.
      • Lee S.
      • Park S.
      • et al.
      The effects of a hydrating mask compared to traditional warm compresses on tear film properties in meibomian gland dysfunction.
      ,
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ,
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      ,
      • Zhao Y.
      • Veerappan A.
      • Yeo S.
      • Rooney D.M.
      • Acharya R.U.
      • Tan J.H.
      • et al.
      Clinical trial of thermal pulsation (LipiFlow) in Meibomian gland dysfunction with preteatment meibography.
      ,
      • Lacroix Z.
      • Leger S.
      • Bitton E.
      Ex vivo heat retention of different eyelid warming masks.
      ,
      • Bitton E.
      • Lacroix Z.
      • Leger S.
      In-vivo heat retention comparison of eyelid warming masks.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. These therapies included the use of latent moist heat devices [
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      ,
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ,
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      ], commercially available eye masks or warm compresses [
      • Tan J.
      • Ho L.
      • Wong K.
      • La A.
      • Lee S.
      • Park S.
      • et al.
      The effects of a hydrating mask compared to traditional warm compresses on tear film properties in meibomian gland dysfunction.
      ,
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ,
      • Lacroix Z.
      • Leger S.
      • Bitton E.
      Ex vivo heat retention of different eyelid warming masks.
      ,
      • Bitton E.
      • Lacroix Z.
      • Leger S.
      In-vivo heat retention comparison of eyelid warming masks.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ], and in-office, vectored thermal pulsation treatment [
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Zhao Y.
      • Veerappan A.
      • Yeo S.
      • Rooney D.M.
      • Acharya R.U.
      • Tan J.H.
      • et al.
      Clinical trial of thermal pulsation (LipiFlow) in Meibomian gland dysfunction with preteatment meibography.
      ]. A summary of important characteristics of all included trials is presented in Table 1.
      Table 1Overview of included studies.
      First authorYearStudy DesignSubjects*Important Characteristics
      Olson MC
      • Olson M.C.
      • Korb D.R.
      • Greiner J.V.
      Increase in tear film lipid layer thickness following treatment with warm compresses in patients with Meibomian gland dysfunction.
      2003Single-visit20 MGDTowels were wetted and microwaved to 40 °C. The compress was reheated every 2 min by replacement of the towel. Unheated towels served as controls.
      Matsumoto Y
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      2006Open-label prospective10 MGDPatients were given thermometers and asked to heat water to 60 °C. Towels were warmed in the water and applied while cooling. Used as control group for moist hot air device.
      Lam AKC
      • Lam A.K.
      • Lam C.H.
      Effect of warm compress therapy from hard-boiled eggs on corneal shape.
      2007Single-visit25 HealthyTowels were wetted and wrapped around a hot egg. Temperature was between 40 °C and 50 °C. Study included control groups with either unheated egg or hot egg not touching the eye.
      Solomon JD
      • Solomon J.D.
      • Case C.L.
      • Greiner J.V.
      • Blackie C.A.
      • Herman J.P.
      • Korb D.R.
      Warm compress induced visual degradation and Fischer-Schweitzer polygonal reflex.
      2007Single-visit24 DEDTowels were wetted and microwaved to reach 45 °C. Replaced every 2 min. Towel applied to one eye only, control eye was allowed to stay open.
      Blackie CA
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      2008Single-visit32 HealthyTowels were wetted and microwaved to reach 45 °C. Group A had no reheating. In group B and C, the towel was replaced every 2 min, however group C aimed the compress towards the lower lid. All three groups treated only one eye, with the contralateral eye closed.
      Pult H
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      2012Single-visit20 HealthyTowels were warmed in heated water to achieve 41 °C. Not reheated. Control for Blephasteam.
      Blackie CA
      • Blackie C.A.
      • McMonnies C.W.
      • Korb D.R.
      Warm compresses and the risks of elevated corneal temperature with massage.
      2013Single-visit12 HealthyTowels were wetted and microwaved to reach 45 °C. Replaced every 2 min. Towel applied to one eye only, the closed, contralateral eye was used as control.
      Sim HS
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      2014Single-masked RCT24 MGDTowels were heated in “warm” water. Patients were encouraged to reheat when “they feel it get cooler”. Use of artificial tears and Blephagel was encouraged. Control group for EyeGiene and Blephasteam.
      Lam SM
      • Lam S.M.
      • Tong L.
      • Duan X.
      • Acharya U.R.
      • Tan J.H.
      • Petznick A.
      • et al.
      Longitudinal changes in tear fluid lipidome brought about by eyelid-warming treatment in a cohort of Meibomian gland dysfunction.
      2014Follow-up study10 MGD**Follow-up on sub-population of Sim et al. Clinical performance deemed equivalent to Blephasteam and EyeGiene and tear lipidome analysis conducted on pooled data for all three groups.
      Arita R
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      2015Open-label, crossover10 HealthyTowels were wetted and microwaved on 500 W for 30 sec. Not reheated. The study compared single application of hot towels, Azuki no Chikara, Eye Hot R, Hot Eye Mask, and Memoto Este, and 2 weeks use of either hot towels or Azuki no Chikara.
      Korb DR
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      2015Single-masked RCT13 LDDETowels were warmed in “maximum comfortable” warm water. Patients were encouraged to keep a bowl of warm water and reheat when it began to cool. Control group for combination treatment that did not include lid warming.
      Lacroix Z
      • Lacroix Z.
      • Leger S.
      • Bitton E.
      Ex vivo heat retention of different eyelid warming masks.
      2015Single-visit, Ex-vivoN/ATowels were warmed in tap water microwaved for 20 sec to reach 43 °C. Not reheated. Placed on a Styrofoam board. Compared with MGDRx, The Eye Doctor, MediBeads, Tranquileyes, and Eye-ssential.
      Murakami DK
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      2015Single-visit5 HealthyTowels were wetted, bundled, and microwaved for 1.5 min to reach 47 °C. New towel unbundled and used every 2 min. Compared with MGDRx, MediBeads, Eye-ssential, Tranquileyes XR, EyeGiene, Blephasteam, and rice bag.
      Bitton E
      • Bitton E.
      • Lacroix Z.
      • Leger S.
      In-vivo heat retention comparison of eyelid warming masks.
      2016Single-visit12 HealthyTowels were warmed in tap water that was microwaved for 20 sec to reach 39 °C. Not reheated. Compared with MGDRx, The Eye Doctor, MediBeads, Tranquileyes, and Eye-ssential.
      Zhao Y
      • Zhao Y.
      • Veerappan A.
      • Yeo S.
      • Rooney D.M.
      • Acharya R.U.
      • Tan J.H.
      • et al.
      Clinical trial of thermal pulsation (LipiFlow) in Meibomian gland dysfunction with preteatment meibography.
      2016Follow-up study22 MGD**Follow-up on sub-population of Sim et al. Used as control group for LipiFlow.
      Yeo S
      • Yeo S.
      • Tan J.H.
      • Acharya U.R.
      • Sudarshan V.K.
      • Tong L.
      Longitudinal changes in tear evaporation rates after eyelid warming therapies in Meibomian gland dysfunction.
      2016Follow-up study22 MGD**Follow-up on sub-population of Sim et al. Assessed tear film evaporation rates at baseline and 12-weeks.
      Lee H
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      2017Single-group prospective32 MGDThe patients were instructed to use a 40–45 °C warm towel. Not reheated. Combined with a lid cleanser and weekly in-office meibomian gland squeezing.
      Tan J
      • Tan J.
      • Ho L.
      • Wong K.
      • La A.
      • Lee S.
      • Park S.
      • et al.
      The effects of a hydrating mask compared to traditional warm compresses on tear film properties in meibomian gland dysfunction.
      2018Single-visit31 MGDTowels were warmed in hot water to reach a maximum temperature of 42 °C. Replaced every 2 min. Compared with Bruder compress.
      Tichenor AA
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      2019Open-label RCT17 CLDETowels were warmed in “hot faucet water”. Not reheated. Control for Bruder Compress.
      Kremers I
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      2020Single-visit41 Healthy, 31 MGDTowels were heated in warm water to reach approximately 40 °C. Replaced every 20 sec, 2 min, or 5 min in different groups. Compared with Blephasteam and sauna.
      Murphy O

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      2020Single-masked RCT12 MGDSubjects were instructed to boil 200 ml of water and let it cool in an open bowl for 10 min. This aimed to produce a water temperature of between 39 °C and 50 °C. The towel was heated in the water and reheated every 2 min. Control for MGDRx and OPTASE compresses.
      Kasetsuwan N
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      2020Single-masked RCT22 MGD with glaucomaParticipants were provided with a video demonstration. The subjects were instructed to use hot towel compresses for 5 min, then lid massage with baby shampoo. Control for LipiFlow combined with lid hygiene. Desired temperature, method of heating, or reheating schedule not described.
      *Subjects receiving hot towels treatment as primary treatment, **Sub-population of Sim et al.
      MGD: participants with meibomian gland dysfunction, DED: dry eye disease, CLDE: contact lens associated dry eye, LDDE: lipid deficient dry eye, RCT: randomized control trial.

      3.2 Thermal properties and efficacy of hot towel treatment

      Studies varied in the types of towels used, method of heating, and desired temperature. As shown in Table 1, eight studies relied on microwaves to heat the towels [
      • Olson M.C.
      • Korb D.R.
      • Greiner J.V.
      Increase in tear film lipid layer thickness following treatment with warm compresses in patients with Meibomian gland dysfunction.
      ,
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ,
      • Blackie C.A.
      • McMonnies C.W.
      • Korb D.R.
      Warm compresses and the risks of elevated corneal temperature with massage.
      ,
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ,
      • Solomon J.D.
      • Case C.L.
      • Greiner J.V.
      • Blackie C.A.
      • Herman J.P.
      • Korb D.R.
      Warm compress induced visual degradation and Fischer-Schweitzer polygonal reflex.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ,
      • Lacroix Z.
      • Leger S.
      • Bitton E.
      Ex vivo heat retention of different eyelid warming masks.
      ,
      • Bitton E.
      • Lacroix Z.
      • Leger S.
      In-vivo heat retention comparison of eyelid warming masks.
      ], while five used hot water to heat towels to a certain temperature [
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      ,
      • Tan J.
      • Ho L.
      • Wong K.
      • La A.
      • Lee S.
      • Park S.
      • et al.
      The effects of a hydrating mask compared to traditional warm compresses on tear film properties in meibomian gland dysfunction.
      ,
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. An additional six studies used hot water to heat the towels but did not specify a desired temperature [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      ,
      • Zhao Y.
      • Veerappan A.
      • Yeo S.
      • Rooney D.M.
      • Acharya R.U.
      • Tan J.H.
      • et al.
      Clinical trial of thermal pulsation (LipiFlow) in Meibomian gland dysfunction with preteatment meibography.
      ,
      • Lam S.M.
      • Tong L.
      • Duan X.
      • Acharya U.R.
      • Tan J.H.
      • Petznick A.
      • et al.
      Longitudinal changes in tear fluid lipidome brought about by eyelid-warming treatment in a cohort of Meibomian gland dysfunction.
      ,
      • Yeo S.
      • Tan J.H.
      • Acharya U.R.
      • Sudarshan V.K.
      • Tong L.
      Longitudinal changes in tear evaporation rates after eyelid warming therapies in Meibomian gland dysfunction.
      ]. Finally, two studies did not provide details on how towels were heated [
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ], and one study used a hot egg to warm the towels [
      • Lam A.K.
      • Lam C.H.
      Effect of warm compress therapy from hard-boiled eggs on corneal shape.
      ].
      Several of the included articles investigated the thermal properties of hot towel compresses. Table 2 provides further details on these trials [
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      ,
      • Olson M.C.
      • Korb D.R.
      • Greiner J.V.
      Increase in tear film lipid layer thickness following treatment with warm compresses in patients with Meibomian gland dysfunction.
      ,
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ,
      • Blackie C.A.
      • McMonnies C.W.
      • Korb D.R.
      Warm compresses and the risks of elevated corneal temperature with massage.
      ,
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ,
      • Lam A.K.
      • Lam C.H.
      Effect of warm compress therapy from hard-boiled eggs on corneal shape.
      ,
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      ,
      • Lacroix Z.
      • Leger S.
      • Bitton E.
      Ex vivo heat retention of different eyelid warming masks.
      ,
      • Bitton E.
      • Lacroix Z.
      • Leger S.
      In-vivo heat retention comparison of eyelid warming masks.
      ]. Most of these single-visit studies on healthy subjects examined the changes in eyelid temperature with the application of hot towel compress [
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      ,
      • Olson M.C.
      • Korb D.R.
      • Greiner J.V.
      Increase in tear film lipid layer thickness following treatment with warm compresses in patients with Meibomian gland dysfunction.
      ,
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ,
      • Blackie C.A.
      • McMonnies C.W.
      • Korb D.R.
      Warm compresses and the risks of elevated corneal temperature with massage.
      ,
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ,
      • Lam A.K.
      • Lam C.H.
      Effect of warm compress therapy from hard-boiled eggs on corneal shape.
      ,
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      ,
      • Bitton E.
      • Lacroix Z.
      • Leger S.
      In-vivo heat retention comparison of eyelid warming masks.
      ]. Six of the nine studies examining thermal properties used cotton cloths, folded 3–4 times [
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      ,
      • Olson M.C.
      • Korb D.R.
      • Greiner J.V.
      Increase in tear film lipid layer thickness following treatment with warm compresses in patients with Meibomian gland dysfunction.
      ,
      • Blackie C.A.
      • McMonnies C.W.
      • Korb D.R.
      Warm compresses and the risks of elevated corneal temperature with massage.
      ,
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ,
      • Lacroix Z.
      • Leger S.
      • Bitton E.
      Ex vivo heat retention of different eyelid warming masks.
      ,
      • Bitton E.
      • Lacroix Z.
      • Leger S.
      In-vivo heat retention comparison of eyelid warming masks.
      ], while Murakami used microfiber towels in a bundle [
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ]. The last two studies did not specify the type of towel/cloth [
      • Lam A.K.
      • Lam C.H.
      Effect of warm compress therapy from hard-boiled eggs on corneal shape.
      ,
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      ]. One study compared, ex-vivo, the heat retaining properties of different warm compresses, including hot towels [
      • Lacroix Z.
      • Leger S.
      • Bitton E.
      Ex vivo heat retention of different eyelid warming masks.
      ]. The cotton facecloth was wetted in room-temperature water, folded three times, and heated for 20 s in a microwave oven. This yielded an initial temperature of around 43 °C, but fell below 40 °C after 2 min and the towel had a temperature of less than 30 °C after 10 min [
      • Lacroix Z.
      • Leger S.
      • Bitton E.
      Ex vivo heat retention of different eyelid warming masks.
      ]. This rapid drop in temperature was also shown when applied to healthy subjects in a subsequent trial [
      • Bitton E.
      • Lacroix Z.
      • Leger S.
      In-vivo heat retention comparison of eyelid warming masks.
      ]. In this trial, Bitton et al. found that when applied over closed eyes, a cotton facecloth similarly folded three times would fall from 39.2 °C to below 35 °C after the first two minutes of application and fall further, to under 30 °C, by the end of the 12 min period [
      • Bitton E.
      • Lacroix Z.
      • Leger S.
      In-vivo heat retention comparison of eyelid warming masks.
      ].
      Table 2Temperature profiles of application methods.
      First authorDescriptionTempReheatingDurationTemperature profile
      Olson MC

      • Olson M.C.
      • Korb D.R.
      • Greiner J.V.
      Increase in tear film lipid layer thickness following treatment with warm compresses in patients with Meibomian gland dysfunction.
      Cotton cloth, folded four times.40 °CEvery 2 min30 minInitial cloth temperature was 40 °C. The temperature fell quickly, but due to replacement of the towel, the applied compresses were above 38 °C for the duration of treatment.
      Blackie CA

      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      Cotton cloth, folded four times.45 °CA: NO

      B: Every 2 min

      C: Every 2 min
      A: 15 min

      B: 30 min

      C: 30 min
      Maximum inner eyelid temperature in A was 38.8 °C, B was 40.4 °C, and C was 40.8 °C. Both B and C achieved 40 °C within the first 6 min, and remained above 40 °C for the duration of treatment.
      Blackie CA

      • Blackie C.A.
      • McMonnies C.W.
      • Korb D.R.
      Warm compresses and the risks of elevated corneal temperature with massage.
      Cotton cloth, folded four times.45 °CEvery 2 min30 minThe outer eyelid temperature rose to 42.2 °C after 6 min and was maintained above 40 °C for the duration of the treatment. The cornea reached a maximum temperature of 39.4 °C after 8 min, but never exceeded 40 °C.
      Murakami DK

      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      Microfiber towels, folded and bundled47 °CEvery 2 min10 minThe inner lower eyelid temperature rose to about 40 °C. The bundle method gave a consistent and distributed temperature of about 40 °C at both the inner and outer eyelid surfaces.
      Kremers I

      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      Unspecified towel/cloth40 °CEvery 20 sec, 2 min or 5 min10 minEyelid temperature increase was 3.2 °C when reheated every 20 s, 2.0 °C every 2 min, and 1.4 °C every 5 min, in healthy subjects. In patients with MGD, the increase was 2.7 °C when reheated every 2 min and 1.4 °C every 5 min.
      Lam AKC

      • Lam A.K.
      • Lam C.H.
      Effect of warm compress therapy from hard-boiled eggs on corneal shape.
      Wet cloth40–50 °CNO5 minRaised eyelid temperature 3 °C within first minute, remained above 36 °C until the end of application.
      Pult H

      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      Cotton cloth, folded three times41 °CNO10 minRaised eyelid temperature to 38.2 °C within first minute, then temperature dropped at a rate of 0.44 °C/min.
      Bitton E

      • Bitton E.
      • Lacroix Z.
      • Leger S.
      In-vivo heat retention comparison of eyelid warming masks.
      Cotton facecloth, folded to three layers.39.2 °CNO12 minInitial cloth temperature was 39.2 °C. The temperature fell about 4 °C within the first two minutes, and ended at 29.2 °C.
      Lacroix Z

      • Lacroix Z.
      • Leger S.
      • Bitton E.
      Ex vivo heat retention of different eyelid warming masks.
      Cotton facecloth, folded to three layers.43 °CNO12 minThe cloth remained above 40 °C for two min, then had a cooling rate of about −1°C/min over the next ten min.
      The clinical effect of this rapid fall in temperature in the hot towels that were not reheated was shown in study by Pult et al., investigating the change in outer eyelid temperature with application of either hot towel compresses or Blephasteam [
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      ]. This study found that upon application of the cotton cloth, folded three times, with an initial temperature of 41 °C, the outer eyelid temperature rose to 38 °C within the first minute but then steadily fell each minute after that, ending at 35 °C after ten minutes of application [
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      ]. This shows that when the towels are not reheated, the temperature falls too quickly to provide enough heat for more than a couple of minutes, potentially preventing the heat from diffusing throughout the whole thickness of the eyelid to warm the meibum sufficiently [
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      ].
      The cooling rate found in these studies highlights the importance of reheating the towels to provide effective eyelid warming. As most of the heat loss from the towel is due to conduction and convection, Newton’s law of cooling can be used to describe the temperature function [
      • Vollmer M.
      Newton's law of cooling revisited.
      ]. Simply stated, this means that the heat transfer from the object to its surroundings is proportional to the difference in temperature between the object and its environment [
      • Vollmer M.
      Newton's law of cooling revisited.
      ]. This explains why a towel heated to 50 °C will have a much greater drop in temperature within the first two minutes than the same towel heated to 40 °C, all else being equal. Therefore, simply having a higher initial temperature of the towel is not sufficient to maintain an adequate temperature over time, and reheating is necessary. This theoretical principle is reflected in the temperature curves shown in Fig. 3 a), which shows the temperatures of cotton towels reported in two studies that did not reheat the towels. Included in the graph is also the temperature range reported in a study where the cotton towel was heated to 40 °C and replaced every-two minutes [
      • Olson M.C.
      • Korb D.R.
      • Greiner J.V.
      Increase in tear film lipid layer thickness following treatment with warm compresses in patients with Meibomian gland dysfunction.
      ,
      • Lacroix Z.
      • Leger S.
      • Bitton E.
      Ex vivo heat retention of different eyelid warming masks.
      ,
      • Bitton E.
      • Lacroix Z.
      • Leger S.
      In-vivo heat retention comparison of eyelid warming masks.
      ]. Fig. 3 b) and c) present the inner and outer eyelid temperatures reported, respectively [
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ,
      • Blackie C.A.
      • McMonnies C.W.
      • Korb D.R.
      Warm compresses and the risks of elevated corneal temperature with massage.
      ,
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ].
      Figure thumbnail gr3
      Fig. 3Temperatures over time, interpolated from listed studies. The three graphs show the temperature of a) the physical towel used for treatment b) the outer eyelid, and c) the inner eyelid in studies with or without reheating of the compress during application. In the study by Olson et al. (a), towels were replaced every-two minutes with new preheated towels, thus the range represents the temperature range of the applied towels reported in the trial, not the temperature of any individual towel. For the studies labeled reheated, towels were replaced every-two minutes with either new preheated towels, or by applying a new towel from the bundle, effectively reheating the applied compress.
      With reheating or replacement of the towels, compresses are capable of producing a more even level of heat over time [
      • Olson M.C.
      • Korb D.R.
      • Greiner J.V.
      Increase in tear film lipid layer thickness following treatment with warm compresses in patients with Meibomian gland dysfunction.
      ]. A towel warmed to 40 °C and replaced every-two minutes maintained an applied temperature range of between 38 °C and 40 °C for a full 30-minute application [
      • Olson M.C.
      • Korb D.R.
      • Greiner J.V.
      Increase in tear film lipid layer thickness following treatment with warm compresses in patients with Meibomian gland dysfunction.
      ]. This is a major advantage over the towels that were not reheated, as the ability to provide steady heat over time is important for raising the inner eyelid temperature [
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ]. However, a limitation of these studies is the use of an already preheated towel to achieve reheating, which might not reflect the clinical setting where reheating of a single towel might be more likely.
      The importance of reheating on eyelid temperature was demonstrated in several studies [
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ,
      • Blackie C.A.
      • McMonnies C.W.
      • Korb D.R.
      Warm compresses and the risks of elevated corneal temperature with massage.
      ,
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ,
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      ]. In 2008, Blackie et al., compared three different regimens of eyelid warming, one without reheating and two groups where the cotton towels were replaced every-two minutes [
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ]. All three groups started with a towel with an initial temperature of 45 °C [
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ]. The group without reheating reached peak inner eyelid temperature after only four minutes, and this subsequently fell for the duration of application [
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ]. In the two groups where the towels were reheated every-two minutes, the inner eyelid reached 40 °C within 6 min and plateaued at this temperature for the remainder of the 30 min [
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ]. The same was shown for the outer eyelid temperature in a later trial by the same authors, where the outer eyelid temperature plateaued quickly and remained virtually unchanged during application [
      • Blackie C.A.
      • McMonnies C.W.
      • Korb D.R.
      Warm compresses and the risks of elevated corneal temperature with massage.
      ]. They also found that the central corneal temperature increased at a slower rate and did not exceed 40 °C [
      • Blackie C.A.
      • McMonnies C.W.
      • Korb D.R.
      Warm compresses and the risks of elevated corneal temperature with massage.
      ].
      A reheating and replacement interval of two minutes was found to be adequate for maintaining therapeutic heat [
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ]. A towel heated to 45 °C dropped by 2.3 °C after two minutes, remaining within therapeutic range [
      • Blackie C.A.
      • Solomon J.D.
      • Greiner J.V.
      • Holmes M.
      • Korb D.R.
      Inner eyelid surface temperature as a function of warm compress methodology.
      ]. Furthermore, a towel warmed to 40 °C increased eyelid temperature by 1.4 °C if changed every 5 min, 2.0 °C if changed every 2 min, and 3.2 °C if changed every 20 s in healthy subjects [
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      ]. In patients with MGD, the results were 1.4 °C when reheated every 5 min and 2.7 °C when reheated every 2 min [
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      ]. No adverse effects related to heating or thermal injuries were noted in any of the studies.
      Collectively, these findings indicate that reheating of the towel every 2 min is essential in providing safe, effective, and practical heating of the eyelid.

      3.3 Efficacy of hot towel therapy over time

      Eleven articles described eight studies with follow-up on patients undergoing hot towel compress treatment [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ,
      • Zhao Y.
      • Veerappan A.
      • Yeo S.
      • Rooney D.M.
      • Acharya R.U.
      • Tan J.H.
      • et al.
      Clinical trial of thermal pulsation (LipiFlow) in Meibomian gland dysfunction with preteatment meibography.
      ,
      • Lam S.M.
      • Tong L.
      • Duan X.
      • Acharya U.R.
      • Tan J.H.
      • Petznick A.
      • et al.
      Longitudinal changes in tear fluid lipidome brought about by eyelid-warming treatment in a cohort of Meibomian gland dysfunction.
      ,
      • Yeo S.
      • Tan J.H.
      • Acharya U.R.
      • Sudarshan V.K.
      • Tong L.
      Longitudinal changes in tear evaporation rates after eyelid warming therapies in Meibomian gland dysfunction.
      ,
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. The subjects undergoing hot towel treatment in Zhao et al. [
      • Zhao Y.
      • Veerappan A.
      • Yeo S.
      • Rooney D.M.
      • Acharya R.U.
      • Tan J.H.
      • et al.
      Clinical trial of thermal pulsation (LipiFlow) in Meibomian gland dysfunction with preteatment meibography.
      ], Yeo et al. [
      • Yeo S.
      • Tan J.H.
      • Acharya U.R.
      • Sudarshan V.K.
      • Tong L.
      Longitudinal changes in tear evaporation rates after eyelid warming therapies in Meibomian gland dysfunction.
      ], and Lam et al. [
      • Lam S.M.
      • Tong L.
      • Duan X.
      • Acharya U.R.
      • Tan J.H.
      • Petznick A.
      • et al.
      Longitudinal changes in tear fluid lipidome brought about by eyelid-warming treatment in a cohort of Meibomian gland dysfunction.
      ] are the same subjects as Sim et al. [
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ]. Important outcomes of the initial studies are summarized in Table 3. In many of these studies, hot towel compresses were used as controls to other treatments, and the application method was not well-described [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ,
      • Zhao Y.
      • Veerappan A.
      • Yeo S.
      • Rooney D.M.
      • Acharya R.U.
      • Tan J.H.
      • et al.
      Clinical trial of thermal pulsation (LipiFlow) in Meibomian gland dysfunction with preteatment meibography.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. This lack of a well-described method presents a limitation of these studies. Follow-up time varied between two weeks [
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ] and six months [
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ]. Across studies, the most frequently used treatment regime consisted of twice-daily, ten-minute treatment with a warm cotton towel that was either reheated when cooled, or not reheated. Most studies offered only a subjective description of the towel preparation and application method, such as the temperature of the towel being “warm” [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ,
      • Zhao Y.
      • Veerappan A.
      • Yeo S.
      • Rooney D.M.
      • Acharya R.U.
      • Tan J.H.
      • et al.
      Clinical trial of thermal pulsation (LipiFlow) in Meibomian gland dysfunction with preteatment meibography.
      ] and for the reheating; “rewarm it once it cools” [
      • Zhao Y.
      • Veerappan A.
      • Yeo S.
      • Rooney D.M.
      • Acharya R.U.
      • Tan J.H.
      • et al.
      Clinical trial of thermal pulsation (LipiFlow) in Meibomian gland dysfunction with preteatment meibography.
      ]. Only three trials provided information on the desired temperature, with one using a 60 °C hot towel that was not reheated [
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ], one using 40–45 °C and no reheating [
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ], and one study using towels of between 39 and 50 °C that were reheated every-two minutes [

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. One study provided the participants with video instruction to standardize the hot towel compress treatment [
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ]. However, beyond the application time being 5 min, no further information regarding technique was provided. An additional limitation was that three of the seven comparative studies were open label [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ], and one of the studies assessing treatment over time did not include a control group [
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ].
      Table 3Studies assessing treatment over time.
      First authorStudy DesignDescriptionReheatFrequencySymptomsTBUTCFSLLTSch. IVAMG ScoreOther Outcomes
      Matsumoto Y
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      Open-label prospective60 °C

      10 min
      NO2x/day for 2 wN.DN.DN.DRose Bengal scores did not change.
      Sim HS
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      Single-masked RCT“Warm”

      10 min
      When cooled2x/day for 3 moN.DN.DN.DNumber of plugged MGs did not change.
      Korb DR
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      Single-masked RCT“Maximum comfortable”

      8 min
      When cooled1x/day for 3 mo
      : Ocular Surface Disease Index (OSDI),
      /↑
      : Standard Patient Evaluation of Eye Dryness (SPEED),
      N.DN.DN.DN.DItching and eye rubbing improved.
      Arita R
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      Open-label, crossover“Warm”

      5 min
      NO2x/day for 2 wN.DN.DN.DN.DN.DTBUT improved only after single-application.
      Lee H
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      Single-group prospective40–45 °C

      5 min
      NO2x/day for 4 w
      : Ocular Surface Disease Index (OSDI),
      N.DN.DLid margin abnormalities and MGD stage improved.
      Tichenor AA
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      Open-label RCT“Warm”

      10 min
      NO2x/day for 1 mo
      : Ocular Surface Disease Index (OSDI),
      ,
      : Standard Patient Evaluation of Eye Dryness (SPEED),
      /↑
      : Visual Analog Scale (VAS) for ocular severity.
      N.DN.DUncomfortable CL wear time was reduced. 80 % were compliant with twice-daily hot towels.
      Murphy O

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      Single-masked RCT39–50 °C

      10 min
      Every 2 min2x/day for 2 w, then 1x/day for 6 w
      : Ocular Surface Disease Index (OSDI),
      N.DN.D78 % were compliant with treatment.
      Kasetsuwan N
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      Single-masked RCT5 minNot described2x/day for 6 mo
      : Ocular Surface Disease Index (OSDI),
      N.D12.5 % of total population was compliant with treatment at least once per day, 64.5 % conducted eyelid warming at least 5 days/week, on average.
      N.D: Not described, TBUT: Tear film breakup time, CFS: Cornea fluorescein staining, LLT: Lipid layer thickness, Sch. I: Schirmer I, VA: Visual acuity, MG: Meibomian gland, RCT: Randomized clinical trial.
      ↑: Significant improvement, —: No significant change.
      1 : Ocular Surface Disease Index (OSDI),
      2 : Standard Patient Evaluation of Eye Dryness (SPEED),
      3 : Visual Analog Scale (VAS) for ocular severity.
      Subjective symptoms of dry eye and ocular irritation were measured in seven of the eight studies with follow-up [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      ,
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. Symptom scores improved in all eight from baseline compared to the last follow-up for those receiving hot towel compresses. One study used three separate measures of symptoms: the Ocular Surface Disease Index (OSDI) and Standard Patient Evaluation of Eye Dryness (SPEED) at baseline and follow-up, and a daily assessment of dry eye severity using a visual analog scale (VAS) [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ]. The authors noted improvement in the daily symptom burden using VAS, while OSDI and SPEED scores were not significantly different from baseline at follow-up [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ]. Korb et al. used both the Standard Patient Evaluation of Eye Dryness (SPEED) and the OSDI questionnaire and found significant improvements in both scores at the 1-, 2-, and 3-month follow-ups [
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      ]. Three other trials also found a significant improvement in OSDI over time [
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. Taken together, these findings show a clear improvement in subjective symptoms over time with hot towel compresses.
      Seven out of the eight studies with a follow-up period reported tear film breakup time (TBUT) measures [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ,
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. Only the study with the largest sample receiving hot towel compresses noted improvement in TBUT [
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ]. The other six studies did not find significant change in TBUT upon application of hot towels [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. In these six studies, hot towel compresses were used as the control intervention for other eyelid warming devices, either commercially available or under development [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ].
      Other clinical measures of MGD were reported in a subset of trials. Corneal fluorescein staining was reported in four of the studies with follow-up [
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. Corneal fluorescein staining scores improved in two of these trials [
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. The remaining two studies showed no significant change in corneal fluorescein staining scores [
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ]. Another clinical parameter measured in four of the longitudinal studies was lipid layer thickness [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ]. Only one of these trials noted a change from baseline, with an improvement in lipid layer thickness after long-term hot towel treatment [
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ]. Further clinical measurements such as Schirmer I and meibomian gland scores and gradings were also reported in a smaller number of trials. None of the four studies measuring Schirmer I found any change from baseline at follow-up [
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. Five studies examined different aspects of meibomian gland scoring or meibum excretion [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      ,
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. Korb et al. explored the number of meibomian glands yielding liquid secretion and found no significant increase in the group receiving warm compress treatment [
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      ]. Three studies reported improvement in both meibum quality and expressibility [
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Lee H.
      • Kim M.
      • Park S.Y.
      • Kim E.K.
      • Seo K.Y.
      • Kim T.I.
      Mechanical Meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of Meibomian gland dysfunction.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. Tichenor et al., however, found no significant difference in meibomian gland score [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ].
      Across studies, although differing methods and study populations, hot towel compress treatment was consistently shown to effectively reduce symptoms of MGD, but the effect on clinical signs of MGD was more varied.

      3.4 Safety assessment and adverse effects

      In two of the studies without extended follow-up, there was a significant drop in visual acuity and increased in subjective blur immediately after hot towel compress treatment [
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      ,
      • Solomon J.D.
      • Case C.L.
      • Greiner J.V.
      • Blackie C.A.
      • Herman J.P.
      • Korb D.R.
      Warm compress induced visual degradation and Fischer-Schweitzer polygonal reflex.
      ]. Solomon et al. also noted the presence of a Fischer-Schweitzer polygonal reflex in patients after a 30-minute hot-towel treatment and linked this to the reduced visual acuity [
      • Solomon J.D.
      • Case C.L.
      • Greiner J.V.
      • Blackie C.A.
      • Herman J.P.
      • Korb D.R.
      Warm compress induced visual degradation and Fischer-Schweitzer polygonal reflex.
      ]. This phenomenon consists of a honey-comb pattern on the cornea and commonly occurs after rubbing [
      • Schweitzer N.M.
      A fluorescein colored polygonal pattern in the human cornea. The reflectographic “Furchenbild” of Fischer.
      ]. Another study found that the pressing force negatively affected the corneal topography, when the hot towel was wrapped around an egg to increase the heat capacity [
      • Lam A.K.
      • Lam C.H.
      Effect of warm compress therapy from hard-boiled eggs on corneal shape.
      ]. One study by Blackie et al. also raised the issue of elevated corneal temperature as a possible adverse outcome, as 30 min of 45 °C hot towel increased the central corneal temperature to near 40 °C, the level they deemed to be the safe upper limit [
      • Blackie C.A.
      • McMonnies C.W.
      • Korb D.R.
      Warm compresses and the risks of elevated corneal temperature with massage.
      ]. Due to these findings, three of the studies with a follow-up period included measures of visual acuity, with one of these also measuring corneal topography [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      ]. All three studies found visual acuity to remain unchanged at all timepoints throughout the trials [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      ]. Tichenor et al. also found no warpage or change in corneal topography at any timepoint [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ].
      Compliance with hot towel compress treatment over time was reported in three studies [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. These studies demonstrated varying compliance, with more than 70 % of subjects complying with treatment in two studies [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ], but only 12.5 % conducted hot towel treatment once daily and 64.5 % at least 5 days per week in another study [
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ]. None of the studies reported any form of thermal injuries or patient complaints about the towels being too hot.
      In summation, the adverse effects noted in the trials without follow-up, were not found in the studies with follow-up. Long-term treatment with hot towels therefore appears safe as long as the towels are not heated beyond safe limits or applied with excessive force.

      3.5 Comparative studies and outcomes

      The single-visit studies that did not reheat the wet towels found that the heat retention and eyelid warming effect of hot towels were inferior to the commercially available alternatives [
      • Pult H.
      • Riede-Pult B.H.
      • Purslow C.
      A comparison of an eyelid-warming device to traditional compress therapy.
      ,
      • Lacroix Z.
      • Leger S.
      • Bitton E.
      Ex vivo heat retention of different eyelid warming masks.
      ,
      • Bitton E.
      • Lacroix Z.
      • Leger S.
      In-vivo heat retention comparison of eyelid warming masks.
      ]. However, when reheated, hot towels showed equivalent, or better, heating abilities than commercial options [
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ,
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      ]. Murakami et al. found that of the eight devices tested (the bundle method, EyeGiene, MediBeads, Eye-ssential, MGDRx Eyebag, a rice bag, Tranquileyes XR, and Blephasteam), the bundle method of hot towel treatment was the only method capable of heating the eyelids above 40 °C. Moreover, the bundle method provided consistent heat to both the outer and inner eyelid surface [
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ]. In short, the bundle method consists of wrapping five or six wetted and folded microfiber towels in a bundle and microwaving the bundle in a covered dish for about 1.5 min. The temperature of the outer towel should then be measured, with the targeted temperature being 47 °C, as described elsewhere [
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ]. It is important to note, however, that the temperature should not exceed 48–49 °C and the patient should be advised to wait before application if the towels are too hot. Although not described in the original publication, a simple way to test if the towels are too hot, is to touch them against the inside of the wrist to ensure that this does not provoke pain. The outer towel is then peeled off the bundle and applied for two min while the remaining towels in the bundle are left in the covered dish. Every-two minutes, the applied towel is placed aside and the next towel in the bundle is peeled off and applied, giving a total duration of application around ten to twelve minutes [
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ]. This procedure is illustrated in Fig. 4.
      Figure thumbnail gr4
      Fig. 4Illustration showing the bundle method, described by Murakami et al.
      [
      • Murakami D.K.
      • Blackie C.A.
      • Korb D.R.
      All warm compresses are not equally efficacious.
      ]
      , an application method for hot towel treatment shown effective at raising eyelid temperature. 1) A standard bundle consists of five or six folded towels that are then bundled together; 2) the bundle of towels is placed in a covered glass dish and heated in the microwave; 3) the towels are used one at a time. The outer towel is peeled off and applied, while the rest of the towels remain in the covered dish. Every-two minutes, the used towel is placed aside and a new towel is taken from the bundle 4) the towel should be placed over closed eyes with minimal pressure. Illustration by Sara Nøland.
      Towels warmed to 40 °C and changed every 20 s gave the same level of eyelid warming as one session of Blephasteam; however, when changed only every 2 or 5 min, they were significantly cooler [
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      ]. A 10-minute sauna at 85 °C was found to increase eyelid temperature similarly to applying hot towels [
      • Kremers I.
      • Hohberger B.
      • Bergua A.
      Infrared thermography: different options of thermal eyelid warming.
      ].
      Four prospective studies used hot towel treatment without reheating as comparators for other eyelid warming treatments [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ,
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ]. Kasetsuwan et al. found no difference in any measured parameter between the group allocated to six months of twice-daily hot towel compress treatment only and the group receiving a single LipiFlow treatment in addition to twice-daily hot towel compress treatment for six months [
      • Kasetsuwan N.
      • Suwajanakorn D.
      • Tantipat C.
      • Reinprayoon U.
      The efficacy between conventional lid hygiene and additional thermal pulsatile system in Meibomian gland dysfunction patients treated with long-term anti-glaucoma medications in a randomized controlled trial.
      ]. Another study found no difference between hot towels and the Bruder Moist Heat Compress in ocular surface parameters nor improvement in symptoms from contact lens wear [
      • Tichenor A.A.
      • Cox S.M.
      • Ziemanski J.F.
      • Ngo W.
      • Karpecki P.M.
      • Nichols K.K.
      • et al.
      Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.
      ]. Although there were no statistical comparisons between groups, two prospective studies found significant improvements from baseline in the groups receiving experimental treatment that was not observed in those receiving hot towel treatment [
      • Matsumoto Y.
      • Dogru M.
      • Goto E.
      • Ishida R.
      • Kojima T.
      • Onguchi T.
      • et al.
      Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction.
      ,
      • Arita R.
      • Morishige N.
      • Shirakawa R.
      • Sato Y.
      • Amano S.
      Effects of eyelid warming devices on tear film parameters in normal subjects and patients with Meibomian gland dysfunction.
      ].
      Four studies used hot towels that were reheated as controls to other MGD treatments [
      • Tan J.
      • Ho L.
      • Wong K.
      • La A.
      • Lee S.
      • Park S.
      • et al.
      The effects of a hydrating mask compared to traditional warm compresses on tear film properties in meibomian gland dysfunction.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,
      • Korb D.R.
      • Blackie C.A.
      • Finnemore V.M.
      • Douglass T.
      Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on Meibomian gland functionality in patients with lipid deficient/evaporative dry eye.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.

      ]. Three of them found no difference in clinical signs between the experimental treatment group and the hot towel control group [
      • Tan J.
      • Ho L.
      • Wong K.
      • La A.
      • Lee S.
      • Park S.
      • et al.
      The effects of a hydrating mask compared to traditional warm compresses on tear film properties in meibomian gland dysfunction.
      ,
      • Sim H.S.
      • Petznick A.
      • Barbier S.
      • Tan J.H.
      • Acharya U.R.
      • Yeo S.
      • et al.
      A randomized, controlled treatment trial of eyelid-warming therapies in Meibomian gland dysfunction.
      ,

      Murphy O, V OD, Lloyd-Mckernan A. The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis. Curr Eye Res 2020;45(5):563-75. doi:10.1080/02713683.2019.1686153.