Modern Technologies in Demodex Blepharitis Diagnosis and Therapy (Review)

Blepharitis associated with Demodex infestation is a widespread condition, its complications include eyelid margin deformities, corneal erosions, and ulcers.

The review considers the epidemiological and pathogenetic aspects, along with new trends in Demodex blepharitis diagnosis and treatment, and represents the comparative characteristics of current diagnostic modalities, including traditional light microscopy, lateral eyelash retraction and rotation, as well as intravital imaging technologies, such as confocal microscopy and optical coherence tomography. Improving imaging techniques using machine learning was found to enable to improve early diagnosis availability and provide early initiation of etiotropic therapy. The review analyzes the preparations for conservative treatment of Demodex blepharitis,representing them with regard to the specificity of pharmacological effects and systemic safety, special attention being given to the problems of toxicity and shelf-life expectancy of drugs. Combination drugs and different laser exposure effects on Demodex mites and eyelid margin structures were stated to be prospective and understudied treatment approaches. We demonstrated the heterogeneity of approaches to efficacy assessment of diagnostic and therapeutic methods that makes actual the necessity of developing a standardized scale of Demodex blepharitis severity; the scale reflecting both clinical characteristics and instrumental findings. The authors concluded that the development of noninvasive imaging techniques and the shortest and safest therapeutic algorithms would enable to switch over to a whole new level of therapy efficacy for patients with Demodex blepharitis.

1. Maychuk Yu.F., Yani E.V. New approaches in the treatment of blepharitis. Kataraktal’naya i refraktsionnaya khirurgiya 2012; 12(1): 59–62.
2. Egorov E.A., Romanova T.B., Rybakova E.G., Oganezova Zh.G. Modern approaches to the prevention and treatment of secondary dry eye syndrome. RMZh. Klinicheskaya oftal’mologiya 2017; 17(1): 61–64.
3. Belousova N.U., Poltanova T.I. Demodex vs human (literature review). Ural’skiy meditsinskiy zhurnal 2019; 12(180): 126–132.
4. Dergacheva N.N., Medvedev I.B. Clinical-laboratory assessment of the effectiveness of drugs based on metronidazole and tar in the treatment of demodectic blepharitis. Modern Technologies in Ophtalmology 2020; 4(35): 185–186, https://doi.org/10.25276/2312-4911-2020-4-185-186.
5. Sidorenko E.E., Nazarenko A.O., Sukhanova I.V., Migel’ D.V., Abramova T.V. Demodecosis of the eyelids — modern aspects of treatment. Quantum Satis 2021; 4(1–4): 47–51.
6. Lindsley K., Matsumura S., Hatef E., Akpek E.K. Interventions for chronic blepharitis. Cochrane Database Syst Rev 2012; 2012(5):CD005556, https://doi.org/10.1002/14651858.CD005556.pub2.
7. Navel V., Mulliez A., Benoist d’Azy C., Baker J.S., Malecaze J., Chiambaretta F., Dutheil F. Efficacy of treatments for Demodex blepharitis: a systematic review and meta-analysis. Ocul Surf 2019; 17(4): 655–669, https://doi.org/10.1016/j.jtos.2019.06.004.
8. Holzchuh F.G., Hida R.Y., Moscovici B.K., Villa Albers M.B., Santo R.M., Kara-José N., Holzchuh R. Clinical treatment of ocular Demodex folliculorum by systemic ivermectin. Am J Ophthalmol 2011; 151(6): 1030–1034.e1, https://doi.org/10.1016/j.ajo.2010.11.024.
9. Liu J., Sheha H., Tseng S.C. Pathogenic role of Demodex mites in blepharitis. Curr Opin Allergy Clin Immunol 2010; 10(5): 505–510, https://doi.org/10.1097/ACI.0b013e32833df9f4.
10. Ting D.S.W., Pasquale L.R., Peng L., Campbell J.P., Lee A.Y., Raman R., Tan G.S.W., Schmetterer L., Keane P.A., Wong T.Y. Artificial intelligence and deep learning in ophthalmology. Br J Ophthalmol 2019; 103(2): 167–175, https://doi.org/10.1136/bjophthalmol-2018-313173.
11. Liu X., Fu Y., Wang D., Huang S., He C., Yu X., Zhang Z., Kong D., Dai Q. Uneven index: a digital biomarker to prompt Demodex blepharitis based on deep learning. Front Physiol 2022; 13: 934821, https://doi.org/10.3389/fphys.2022.934821.
12. Alexander J.O. Arthropods and human skin. Germany: Springer-Verlag; 1984.
13. Schaller M. Carl Gustav Theodor Simon (1810–1857). In: C. Löser, G. Plewig, W.H.C. Burgdorf (eds.). Pantheon of dermatology: outstanding historical figures. Berlin, Heidelberg: Springer; 2013; p. 1039–1045.
14. Trattler W., Karpecki P., Rapoport Y., Sadri E., Schachter S., Whitley W.O., Yeu E. The prevalence of Demodex blepharitis in US eye care clinic patients as determined by collarettes: a pathognomonic sign. Clin Ophthalmol 2022; 16: 1153–1164, https://doi.org/10.2147/OPTH.S354692.
15. Wilkin J.K. Oral thermal-induced flushing in erythematotelangiectatic rosacea. J Invest Dermatol 1981; 76(1): 15–18, https://doi.org/10.1111/1523-1747.ep12524458.
16. Kulac M., Ciftci I.H., Karaca S., Cetinkaya Z. Clinical importance of Demodex folliculorum in patients receiving phototherapy. Int J Dermatol 2008; 47(1): 72–77, https://doi.org/10.1111/j.1365-4632.2007.03336.x.
17. Tighe S., Gao Y.Y., Tseng S.C. Terpinen-4-ol is the most active ingredient of tea tree oil to kill Demodex mites. Transl Vis Sci Technol 2013; 2(7): 2, https://doi.org/10.1167/tvst.2.7.2.
18. Bitton E., Aumond S. Demodex and eye disease: a review. Clin Exp Optom 2021; 104(3): 285–294, https://doi.org/10.1111/cxo.13123.
19. Zheltikova T.M. Demodicosis: myths and reality. Pediatriya. Prilozhenie k zhurnalu Consilium Medicum 2011; 3: 73.
20. Maychuk D.Yu. Blepharitis — demodicosis, allergy, infection — how is it all connected? Novoe v oftal’mologii 2013; 3: 42–47.
21. Damian C., Danuta I.K.B. Eyelid demodicosis. Rossiyskiy oftal’mologicheskiy zhurnal 2014; 7(4): 107–110.
22. Adaskevich V.P. Demodecosis: etiology, pathogenesis, clinical forms, diagnostics, treatment. Dermatovenerologiya. Kosmetologiya 2015; 1(01): 60–71.
23. Hu L., Zhao Y., Niu D., Gong X., Yang R. De novo transcriptome sequencing and differential gene expression analysis of two parasitic human Demodex species. Parasitol Res 2019; 118(12): 3223–3235, https://doi.org/10.1007/s00436-019-06461-0.
24. English F.P., Nutting W.B. Feeding characteristics in demodectic mites of the eyelid. Aust J Ophthalmol 1981; 9(4): 311–313, https://doi.org/10.1111/j.1442-9071.1981.tb00928.x.
25. English F.P., Zhang G.W., McManus D.P., Campbell P. Electron microscopic evidence of acarine infestation of the eyelid margin. Am J Ophthalmol 1990; 109(2): 239–240, https://doi.org/10.1016/s0002-9394(14)76003-9.
26. Köksal M., Kargi S., Tayşi B.N., Uğurbaş S.H. A rare agent of chalazion: demodectic mites. Can J Ophthalmol 2003; 38(7): 605–606, https://doi.org/10.1016/s0008-4182(03)80117-5.
27. Lacey N., Delaney S., Kavanagh K., Powell F.C. Mite-related bacterial antigens stimulate inflammatory cells in rosacea. Br J Dermatol 2007; 157(3): 474–481, https://doi.org/10.1111/j.1365-2133.2007.08028.x.
28. Valenton M.J., Okumoto M. Toxin-producing strains of Staphylococcus epidermidis (albus). Isolates from patients with staphylococcic blepharoconjunctivitis. Arch Ophthalmol 1973; 89(3): 186–189, https://doi.org/10.1001/archopht.1973.01000040188004.
29. Seal D., Ficker L., Ramakrishnan M., Wright P. Role of staphylococcal toxin production in blepharitis. Ophthalmology 1990; 97(12): 1684–1688, https://doi.org/10.1016/s0161-6420(90)32361-8.
30. Gao Y.Y., Di Pascuale M.A., Li W., Liu D.T., Baradaran-Rafii A., Elizondo A., Kawakita T., Raju V.K., Tseng S.C. High prevalence of Demodex in eyelashes with cylindrical dandruff. Invest Ophthalmol Vis Sci 2005; 46(9): 3089–3094, https://doi.org/10.1167/iovs.05-0275.
31. Gao Y.Y., Di Pascuale M.A., Li W., Baradaran-Rafii A., Elizondo A., Kuo C.L., Raju V.K., Tseng S.C. In vitro and in vivo killing of ocular Demodex by tea tree oil. Br J Ophthalmol 2005; 89(11): 1468–1473, https://doi.org/10.1136/bjo.2005.072363.
32. English F.P. Demodex folliculorum and oedema of the eyelash. Br J Ophthalmol 1971; 55(11): 742–746, https://doi.org/10.1136/bjo.55.11.742.
33. Chen D., Wang J., Sullivan D.A., Kam W.R., Liu Y. Effects of terpinen-4-ol on meibomian gland epithelial cells in vitro. Cornea 2020; 39(12): 1541–1546, https://doi.org/10.1097/ICO.0000000000002506.
34. Muntz A., Purslow C., Wolffsohn J.S., Craig J.P. Improved Demodex diagnosis in the clinical setting using a novel in situ technique. Cont Lens Anterior Eye 2020; 43(4): 345–349, https://doi.org/10.1016/j.clae.2019.11.009.
35. Zhong J., Tan Y., Li S., Peng L., Wang B., Deng Y., Yuan J. The prevalence of Demodex folliculorum and Demodex brevis in cylindrical dandruff patients. J Ophthalmol 2019; 2019: 8949683, https://doi.org/10.1155/2019/8949683.
36. Mastrota K.M. Method to identify Demodex in the eyelash follicle without epilation. Optom Vis Sci 2013; 90(6): e172–e174, https://doi.org/10.1097/OPX.0b013e318294c2c0.
37. Randon M., Liang H., El Hamdaoui M., Tahiri R., Batellier L., Denoyer A., Labbé A., Baudouin C. In vivo confocal microscopy as a novel and reliable tool for the diagnosis of Demodex eyelid infestation. Br J Ophthalmol 2015; 99(3): 336–341, https://doi.org/10.1136/bjophthalmol-2014-305671.
38. Sattler E.C., Maier T., Hoffmann V.S., Hegyi J., Ruzicka T., Berking C. Noninvasive in vivo detection and quantification of Demodex mites by confocal laser scanning microscopy. Br J Dermatol 2012; 167(5): 1042–1047, https://doi.org/10.1111/j.1365-2133.2012.11096.x.
39. Messmer E.M., Torres Suárez E., Mackert M.I., Zapp D.M., Kampik A. Konfokale In-vivo-Mikroskopie bei Blepharitis [In vivo confocal microscopy in blepharitis]. Klin Monbl Augenheilkd 2005; 222(11): 894–900, https://doi.org/10.1055/s-2005-858798.
40. Welzel J., Lankenau E., Birngruber R., Engelhardt R. Optical coherence tomography of the human skin. J Am Acad Dermatol 1997; 37(6): 958–963, https://doi.org/10.1016/s0190-9622(97)70072-0.
41. Sokolova T.V., Golitsyna M.V., Malyarchuk A.P., Lopatina Yu.V. Diagnosis of demodicosis: pro and con. Klinicheskaya dermatologiya i venerologiya 2022; 21(3): 383–389, https://doi.org/10.17116/klinderma202221031383.
42. Kubanov A.A., Gallyamova Yu.A., Grevtseva A.S. Features of the clinical picture of demodicosis. Lechashchiy vrach 2015; 11: 24.
43. Maier T., Sattler E., Braun-Falco M., Ruzicka T., Berking C. High-definition optical coherence tomography for the in vivo detection of Demodex mites. Dermatology 2012; 225(3): 271–276, https://doi.org/10.1159/000345364.
44. Katalevskaya E.A., Sizov A.Yu., Gilemzianova L.I. Artificial intelligence algorithm for segmentation of pathological structures on optical coherence tomography scans. Russian Journal of Telemedicine and E-Health 2022; 8(3): 21–27, https://doi.org/10.29188/2712-9217-2022-8-3-21-27.
45. Takhchidi Kh.P., Gliznitsa P.V., Svetozarskiy S.N., Bursov A.I., Shusterzon K.A. Color fundus photograph labeling improves macular pathology recognition using deep learning. Vestnik Rossiyskogo gosudarstvennogo meditsinskogo universiteta 2021; 4: 29–35, https://doi.org/10.24075/vrgmu.2021.040.
46. Katalevskaya E.A., Katalevskiy D.Yu., Tyurikov M.I., Velieva I.A., Bol’shunov A.V. Future of artificial intelligence for the diagnosis and treatment of retinal diseases. Russian Journal of Clinical Ophthalmology 2022; 22(1): 36–43, https://doi.org/10.32364/2311-7729-2022-22-1-36-43.
47. Sitnova A.V., Svetozarskiy S.N. Modern technologies in diagnosis of fungal keratitis (review). Sovremennye tehnologii v medicine 2023; 15(2): 73–84, https://doi.org/10.17691/stm2023.15.2.07.
48. Ting D.S.J., Foo V.H., Yang L.W.Y., Sia J.T., Ang M., Lin H., Chodosh J., Mehta J.S., Ting D.S.W. Artificial intelligence for anterior segment diseases: emerging applications in ophthalmology. Br J Ophthalmol 2021; 105(2): 158–168, https://doi.org/10.1136/bjophthalmol-2019-315651.
49. Salahouddin T., Petropoulos I.N., Ferdousi M., Ponirakis G., Asghar O., Alam U., Kamran S., Mahfoud Z.R., Efron N., Malik R.A., Qidwai U.A. Artificial intelligence-based classification of diabetic peripheral neuropathy from corneal confocal microscopy images. Diabetes Care 2021; 44(7): e151–e153, https://doi.org/10.2337/dc20-2012.
50. Preston F.G., Meng Y., Burgess J., Ferdousi M., Azmi S., Petropoulos I.N., Kaye S., Malik R.A., Zheng Y., Alam U. Artificial intelligence utilising corneal confocal microscopy for the diagnosis of peripheral neuropathy in diabetes mellitus and prediabetes. Diabetologia 2022; 65(3): 457–466, https://doi.org/10.1007/s00125-021-05617-x.
51. Bao X.L., Sun Y.J., Zhan X., Li G.Y. Orbital and eyelid diseases: The next breakthrough in artificial intelligence? Front Cell Dev Biol 2022; 10: 1069248, https://doi.org/10.3389/fcell.2022.1069248.
52. Samuelson J. Why metronidazole is active against both bacteria and parasites. Antimicrob Agents Chemother 1999; 43(7): 1533–1541, https://doi.org/10.1128/AAC.43.7.1533.
53. Paichitrojjana A., Chalermchai T. Comparison of in vitro killing effect of Thai herbal essential oils, tea tree oil, and Metronidazole 0.75% versus Ivermectin 1% on Demodex folliculorum. Clin Cosmet Investig Dermatol 2023; 16: 1279–1286, https://doi.org/10.2147/CCID.S414737.
54. Krasnyuk I.I. Jr, Naryshkin S.R., Belyackaya A.V., Tarasov V.V., Stepanova O.I., Krasnyuk I.I., Grih V.V., Ovsyannikova L.V., Mazyarkin E.V., Vorob’yov A.N. Metronidazole — 60 years of use. Vestnik Voronezhskogo gosudarstvennogo universiteta. Seriya: Khimiya. Biologiya. Farmatsiya 2020; 1: 81–90.
55. Sattler E.C., Hoffmann V.S., Ruzicka T., Braunmühl T.V., Berking C. Reflectance confocal microscopy for monitoring the density of Demodex mites in patients with rosacea before and after treatment. Br J Dermatol 2015; 173(1): 69–75, https://doi.org/10.1111/bjd.13783.
56. Ávila M.Y., Martínez-Pulgarín D.F., Rizo Madrid C. Topical ivermectin-metronidazole gel therapy in the treatment of blepharitis caused by Demodex spp.: a randomized clinical trial. Cont Lens Anterior Eye 2021; 44(3): 101326, https://doi.org/10.1016/j.clae.2020.04.011.
57. Kane N.S., Hirschberg B., Qian S., Hunt D., Thomas B., Brochu R., Ludmerer S.W., Zheng Y., Smith M., Arena J.P., Cohen C.J., Schmatz D., Warmke J., Cully D.F. Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin. Proc Natl Acad Sci U S A 2000; 97(25): 13949–13954, https://doi.org/10.1073/pnas.240464697.
58. Salem D.A., El-Shazly A., Nabih N., El-Bayoumy Y., Saleh S. Evaluation of the efficacy of oral ivermectin in comparison with ivermectin-metronidazole combined therapy in the treatment of ocular and skin lesions of Demodex folliculorum. Int J Infect Dis 2013; 17(5): e343–e347, https://doi.org/10.1016/j.ijid.2012.11.022.
59. Valvecchia F., Greco L., Perrone F., Logioco C., Caride G.G., Perrone L., Valvecchia G., Albertazzi R., Zanutigh V. Topical ivermectin ointment treatment of Demodex blepharitis: a 6-year retrospective study. Graefes Arch Clin Exp Ophthalmol 2024; 262(4): 1281–1288, https://doi.org/10.1007/s00417-023-06281-0.
60. Persi A., Rebora A. Metronidazole in the treatment of rosacea. Arch Dermatol 1985; 121(3): 307–308, https://doi.org/10.1001/archderm.1985.01660030027007.
61. Ayres S., Mihan R. Demodex folliculorum in rosacea. Arch Dermatol 1970; 101(6): 706, https://doi.org/10.1001/archderm.1970.04000060078024.
62. Gliznitsa P.V., Takhchidi Kh.P., Svetozarskiy S.N., Bursov A.I., Shusterzon K.A. Machine learning in the diagnosis and treatment of ophthalmic diseases. Head and neck Russian Journal 2022; 10(1): 83–90, https://doi.org/10.25792/HN.2022.10.1.83-90.
63. Capasso L., Abbinante G., Coppola A., Salerno G., De Bernardo M. Recent evidence of tea tree oil effectiveness in blepharitis treatment. Biomed Res Int 2022; 2022: 9204251, https://doi.org/10.1155/2022/9204251.
64. Riks I.A., Trufanov S.V., Boutaba R. Modern approaches to the treatment of meibomian gland dysfunction. Vestnik oftal’mologii 2021; 137(1): 130–136, https://doi.org/10.17116/oftalma2021137011130.
65. Thapa S., Lv M., Xu H. Acetylcholinesterase: a primary target for drugs and insecticides. Mini Rev Med Chem 2017; 17(17): 1665–1676, https://doi.org/10.2174/1389557517666170120153930.
66. de Oliveira G.P., Barreto D.L.C., Ramalho Silva M., Augusti R., Evódio Marriel I., Gomes de Paula Lana U., Takahashi J.A. Biotic stress caused by in vitro co-inoculation enhances the expression of acetylcholinesterase inhibitors by fungi. Nat Prod Res 2022; 36(16): 4266–4270, https://doi.org/10.1080/14786419.2021.1975701.
67. Mills C., Cleary B.J., Gilmer J.F., Walsh J.J. Inhibition of acetylcholinesterase by tea tree oil. J Pharm Pharmacol 2004; 56(3): 375–379, https://doi.org/10.1211/0022357022773.
68. Man Peles I., Zahavi A., Chemodanova E., Vardizer Y. Novel in-office technique for visual confirmation of Demodex infestation in blepharitic patients. Cornea 2020; 39(7): 858–861, https://doi.org/10.1097/ICO.0000000000002254.
69. Bulut A., Tanriverdi C. Anti-Demodex effect of commercial eyelid hygiene products. Semin Ophthalmol 2021; 36(8): 719–722, https://doi.org/10.1080/08820538.2021.1897859.
70. Jacobi C., Doan S., Pavel V., Chiambaretta F., Kärcher T. Different approach to manage Demodex blepharitis — initial and maintenance treatment. Curr Eye Res 2022; 47(3): 352–360, https://doi.org/10.1080/02713683.2021.1978099.
71. Lee Y.I., Seo M., Cho K.J. Demodex blepharitis: an analysis of nine patients. Korean J Parasitol 2022; 60(6): 429–432, https://doi.org/10.3347/kjp.2022.60.6.429.
72. Tharmarajah B., Coroneo M.T. Corneal effects of tea tree oil. Cornea 2021; 40(10): 1363–1364, https://doi.org/10.1097/ICO.0000000000002776.
73. Mohammad-Rabei H., Arabi A., Shahraki T., Rezaee-Alam Z., Baradaran-Rafii A. Role of blepharoexfoliation in Demodex blepharitis: a randomized comparative study. Cornea 2023; 42(1): 44–51, https://doi.org/10.1097/ICO.0000000000003046.
74. Cheng A.M., Sheha H., Tseng S.C. Recent advances on ocular Demodex infestation. Curr Opin Ophthalmol 2015; 26(4): 295–300, https://doi.org/10.1097/ICU.0000000000000168.
75. Zhang N., Wen K., Liu Y., Huang W., Liang X., Liang L. High prevalence of Demodex infestation is associated with poor blood glucose control in type 2 diabetes mellitus: a cross-sectional study in the guangzhou diabetic eye study. Cornea 2023; 42(6): 670–674, https://doi.org/10.1097/ICO.0000000000003116.
76. Cheung I.M.Y., Xue A.L., Kim A., Ammundsen K., Wang M.T.M., Craig J.P. In vitro anti-demodectic effects and terpinen-4-ol content of commercial eyelid cleansers. Cont Lens Anterior Eye 2018; 41(6): 513–517, https://doi.org/10.1016/j.clae.2018.08.003.
77. Fromstein S.R., Harthan J.S., Patel J., Opitz D.L. Demodex blepharitis: clinical perspectives. Clin Optom (Auckl) 2018; 10: 57–63, https://doi.org/10.2147/OPTO.S142708.
78. Rutherford T., Nixon R., Tam M., Tate B. Allergy to tea tree oil: retrospective review of 41 cases with positive patch tests over 4.5 years. Australas J Dermatol 2007; 48(2): 83–87, https://doi.org/10.1111/j.1440-0960.2007.00341.x.
79. Ambrogio F., Foti C., Cazzato G., Mortato E., Mazzoccoli S., De Caro A.P., Cassano N., Vena G.A., Calogiuri G., Romita P. Spreading allergic contact dermatitis to tea tree oil in an over-the-counter product applied on a wart. Medicina (Kaunas) 2022; 58(5): 561, https://doi.org/10.3390/medicina58050561.
80. Hsu D.-J., Huang H.-L., Sheu S.-C. Characteristics of air pollutants and assessment of potential exposure in spa centers druing aromatherapy. Env Eng Sci 2012; 29: 79–85, https://doi.org/10.1089/ees.2011.0004.
81. de Groot A.C., Schmidt E. Tea tree oil: contact allergy and chemical composition. Contact Dermatitis 2016; 75(3): 129–143, https://doi.org/10.1111/cod.12591.
82. McMahon M.A., Blair I.S., Moore J.E., McDowell D.A. Habituation to sub-lethal concentrations of tea tree oil (Melaleuca alternifolia) is associated with reduced susceptibility to antibiotics in human pathogens. J Antimicrob Chemother 2007; 59(1): 125–127, https://doi.org/10.1093/jac/dkl443.
83. Yasin M., Younis A., Javed T., Akram A., Ahsan M., Shabbir R., Ali M.M., Tahir A., El-Ballat E.M., Sheteiwy M.S., Sammour R.H., Hano C., Alhumaydhi F.A., El-Esawi M.A. River tea tree oil: composition, antimicrobial and antioxidant activities, and potential applications in agriculture. Plants (Basel) 2021; 10(10): 2105, https://doi.org/10.3390/plants10102105.
84. Nielsen J.B. What you see may not always be what you get — bioavailability and extrapolation from in vitro tests. Toxicol In Vitro 2008; 22(4): 1038–1042, https://doi.org/10.1016/j.tiv.2007.12.013.
85. Knop E., Knop N., Millar T., Obata H., Sullivan D.A. The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci 2011; 52(4): 1938–1978, https://doi.org/10.1167/iovs.10-6997c.
86. Han D., Kim H., Kim S., Park Y., Cho K.J. Comparative study on the effect of hyperthermic massage and mechanical squeezing in the patients with mild and severe meibomian gland dysfunction: an interventional case series. PLoS One 2021; 16(3):e0247365, https://doi.org/10.1371/journal.pone.0247365.
87. Golebiowski B., Badarudin N., Eden J., You J., Hampel U., Stapleton F. Does endogenous serum oestrogen play a role in meibomian gland dysfunction in postmenopausal women with dry eye? Br J Ophthalmol 2017; 101(2): 218–222, https://doi.org/10.1136/bjophthalmol-2016-308473.
88. Xiao J., Adil M.Y., Chen X., Utheim Ø.A., Ræder S., Tønseth K.A., Lagali N.S., Dartt D.A., Utheim T.P. Functional and morphological evaluation of meibomian glands in the assessment of meibomian gland dysfunction subtype and severity. Am J Ophthalmol 2020; 209: 160–167, https://doi.org/10.1016/j.ajo.2019.09.005.
89. Krenzer K.L., Dana M.R., Ullman M.D., Cermak J.M., Tolls D.B., Evans J.E., Sullivan D.A. Effect of androgen deficiency on the human meibomian gland and ocular surface. J Clin Endocrinol Metab 2000; 85(12): 4874–4882, https://doi.org/10.1210/jcem.85.12.7072.
90. Arita R., Fukuoka S. Therapeutic efficacy and safety of intense pulsed light for refractive multiple recurrent chalazia. J Clin Med 2022; 11(18): 5338, https://doi.org/10.3390/jcm11185338.
91. Murube J. Demodex hominis. Ocul Surf 2015; 13(3): 181–186, https://doi.org/10.1016/j.jtos.2015.04.002.
92. Ertaş R., Yaman O., Akkuş M.R., Özlü E., Avcı A., Ulaş Y., Ozyurt K., Atasoy M. The rapid effect of pulsed dye laser on Demodex density of facial skin. J Cosmet Laser Ther 2019; 21(3): 123–126, https://doi.org/10.1080/14764172.2018.1481509.
93. Prieto V.G., Sadick N.S., Lloreta J., Nicholson J., Shea C.R. Effects of intense pulsed light on sun-damaged human skin, routine, and ultrastructural analysis. Lasers Surg Med 2002; 30(2): 82–85, https://doi.org/10.1002/lsm.10042.
94. Fishman H.A., Periman L.M., Shah A.A. Real-time video microscopy of in vitro Demodex death by intense pulsed light. Photobiomodul Photomed Laser Surg 2020; 38(8): 472–476, https://doi.org/10.1089/photob.2019.4737.
95. Gupta P.K., Vora G.K., Matossian C., Kim M., Stinnett S. Outcomes of intense pulsed light therapy for treatment of evaporative dry eye disease. Can J Ophthalmol 2016; 51(4): 249–253, https://doi.org/10.1016/j.jcjo.2016.01.005.
96. Zhang X., Song N., Gong L. Therapeutic effect of intense pulsed light on ocular demodicosis. Curr Eye Res 2019; 44(3): 250–256, https://doi.org/10.1080/02713683.2018.1536217.
97. Temiz S.A., Durmaz K., Işık B., Ataseven A., Dursun R. The effect of 577-nm pro-yellow laser on Demodex density in patients with rosacea. J Cosmet Dermatol 2022; 21(1): 242–246, https://doi.org/10.1111/jocd.14085.
98. Altunisik N., Turkmen D., Sener S. Evaluation of the effect of 577-nm pro-yellow laser on Demodex intensity. J Cosmet Laser Ther 2021; 23(7-8): 221–224, https://doi.org/10.1080/14764172.2022.2075898.
99. Yalici-Armagan B., Elcin G. The decrease of Demodex density after Nd:YAG laser application for facial telengiactasias: a case report. Dermatol Ther 2020; 33(6): e14108, https://doi.org/10.1111/dth.14108.
100. Li J., Wei E., Reisinger A., French L.E., Clanner-Engelshofen B.M., Reinholz M. Comparison of different anti-Demodex strategies: a systematic review and meta-analysis. Dermatology 2023; 239(1): 12–31, https://doi.org/10.1159/000526296.
101. Yurekli A., Botsali A. The comparative in vitro killing activity of tea tree oil versus permethrin on Demodex folliculorum of rosacea patients. J Cosmet Dermatol 2022; 21(5): 2268–2272, https://doi.org/10.1111/jocd.14701.

Igonin G.S., Svetozarskiy S.N., Smetankin I.G. Modern Technologies in Demodex Blepharitis Diagnosis and Therapy (Review). Sovremennye tehnologii v medicine 2025; 17(3): 62, https://doi.org/10.17691/stm2025.17.3.06