睑板腺功能障碍相关干眼的局部药物治疗

Topical pharmacologic treatment of dry eye disease associated with meibomian gland dysfunction

摘要

干眼是影响全球数百万人的常见多因素眼表疾病，随着社会的快速发展其发病率不断上升。睑板腺功能障碍引发的泪膜结构、性状和眼表稳态改变，是导致干眼的主要因素之一，治疗方式包括药物、物理及手术干预。其中局部药物治疗可选择抗菌药、含脂人工泪液、抗炎药、促泪液分泌剂、激素眼用制剂及全氟己基辛烷等新型药物。本文就睑板腺功能障碍相关干眼的局部药物治疗进行综述。

Abstract

Dry eye is a common multifactorial ocular surface disease that affects millions of people worldwide, and its incidence is increasing with the rapid development of society. Alterations in tear film structure, properties, and ocular surface homeostasis triggered by meibomian gland dysfunction are one of the major factors contributing to dry eye. Treatment modalities include pharmacologic, physical, and surgical interventions. Topical pharmacotherapy options include antimicrobials, lipid-containing artificial tears, anti-inflammatory agents, tear secretion promoters, hormonal ophthalmic preparations, and novel drugs such as perfluorohexyloctane. This article reviews the topical pharmacologic treatment of dry eye associated with meibomian gland dysfunction.

关键词

睑板腺功能障碍 / 干眼 / 泪膜脂质层 / 全氟己基辛烷

Key words

Meibomian gland dysfunction / Dry eye disease / Tear film lipid layer / Perfluorohexane

参考文献

[1] Liu S , Yang G , Li QN , et al. Safety and efficacy of topical diquafosol for the treatment of dry eye disease: an updated meta-analysis of randomized controlled trials[J]. Indian Journal of Ophthalmology, 2023, 71(4): 1304-1315. doi: 10.4103/IJO.IJO_268_23

[2] 亚洲干眼协会中国分会, 海峡两岸医药卫生交流协会眼科学专业委员会眼表与泪液病学组, 中国医师协会眼科医师分会眼表与干眼学组 . 中国干眼专家共识: 治疗(2020年)[J]. 中华眼科杂志, 2020, 56(12): 907-913. doi: 10.3760/cma.j.cn112142-20200925-00618

[3] Sheppard JD , Nichols KK . Dry eye disease associated with meibomian gland dysfunction: focus on tear film characteristics and the therapeutic landscape[J]. Ophthalmology and Therapy, 2023, 12(3): 1397-1418. doi: 10.1007/s40123-023-00669-1

[4] Rolando M , Zierhut M , Barabino S . Should we reconsider the classification of patients with dry eye disease[J]. Ocular Immunology and Inflammation, 2021, 29(3): 521-523. doi: 10.1080/09273948.2019.1682618

[5] Rolando M , Merayo-lloves J . Management strategies for evaporative dry eye disease and future perspective[J]. Current Eye Research, 2022, 47(6): 813-823. doi: 10.1080/02713683.2022.2039205

[6] Lam SM , Tong L , Duan XR , et al. Extensive characterization of human tear fluid collected using different techniques unravels the presence of novel lipid amphiphiles[J]. Journal of Lipid Research, 2014, 55(2): 289-298. doi: 10.1194/jlr.M044826

[7] Agarwal P , Craig JP , Rupenthal ID . Formulation considerations for the management of dry eye disease[J]. Pharmaceutics, 2021, 13(2): 207. doi: 10.3390/pharmaceutics13020207

[8] Khanal S , Bai YQ , Nao W , et al. Human meibum and tear film derived cholesteryl and wax esters in meibomian gland dysfunction and tear film structure[J]. The Ocular Surface, 2022, 23: 12-23. doi: 10.1016/j.jtos.2021.10.009

[9] 蒋冬冬, 靳荷 . 睑板腺功能障碍相关干眼的诊疗进展[J]. 国际眼科杂志, 2021, 21(7): 1209-1212. doi: 10.3980/j.issn.1672-5123.2021.7.16

[10] Gurlevik U , Karakoyun A , Yasar E . Does Sjogren̓s syndrome affect only the lacrimal gland in the eye Time to replace the missing stones[J]. Indian Journal of Ophthalmology, 2021, 69(1): 53-57. doi: 10.4103/ijo.IJO_2383_19

[11] Chhadva P , Goldhardt R , Galor A . Meibomian gland disease the role of gland dysfunction in dry eye disease[J]. Ophthalmology, 2017, 124(11): S20-S26. doi: 10.1016/j.ophtha.2017.05.031

[12] 李威, 张斌 . 优化脉冲光联合睑板腺按摩治疗睑板腺功能障碍的临床效果观察[J]. 山东大学耳鼻喉眼学报, 2021, 35(2): 105-109. doi: 10.6040/j.issn.1673-3770.0.2020.341

[13] 亚洲干眼协会中国分会, 海峡两岸医药卫生交流协会眼科学专业委员会眼表与泪液病学组, 中国医师协会眼科医师分会眼表与干眼学组 . 中国睑板腺功能障碍专家共识:定义和分类(2023年)[J]. 中华眼科杂志, 2023, 59(4): 256-261. doi: 10.3760/cma.j.cn112142-20230114-00023.

[14] 狄宇 . 干眼炎症反应机制及抗炎治疗的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(2): 144-150. doi: 10.6040/j.issn.1673-3770.0.2020.484

[15] Holland EJ , Jackson MA , Donnenfeld E , et al. Efficacy of lifitegrast ophthalmic solution, 5.0%, in patients with moderate to severe dry eye disease: a post hoc analysis of 2 randomized clinical trials[J]. JAMA Ophthalmology, 2021, 139(11): 1200-1208. doi: 10.1001/jamaophthalmol.2021.3943

[16] Malmin A , Thomseth VM , Frland PT , et al. Associations between serial intravitreal injections and dry eye[J]. Ophthalmology, 2023, 130(5): 509-515. doi: 10.1016/j.ophtha.2023.01.009

[17] Capasso L , Abbinante G , Coppola A , et al. Recent evidence of tea tree oil effectiveness in blepharitis treatment[J]. BioMed Research International, 2022, 2022(1): 9204251. doi: 10.1155/2022/9204251

[18] Jacobi C , Doan S , Pavel V , et al. Different approach to Manage Demodex Blepharitis - initial and maintenance treatment[J]. Current Eye Research, 2022, 47(3): 352-360. doi: 10.1080/02713683.2021.1978099

[19] Liu WT , Gong L . Anti-demodectic effects of okra eyelid patch in Demodex blepharitis compared with tea tree oil[J]. Experimental and Therapeutic Medicine, 2021, 21(4): 338. doi: 10.3892/etm.2021.9769

[20] Navel V , Mulliez A , Benoit d̓Azy C , et al. Efficacy of treatments for demodex blepharitis: a systematic review and meta-analysis[J]. The Ocular Surface, 2019, 17(4): 655-669. doi: 10.1016/j.jtos.2019.06.004

[21] Sabeti S , Kheirkhah A , Yin J , et al. Management of meibomian gland dysfunction: a review[J]. Survey of Ophthalmology, 2020, 65(2): 205-217. doi: 10.1016/j.survophthal.2019.08.007

[22] Stroman DW , Mintun K , Epstein AB , et al. Reduction in bacterial load using hypochlorous acid hygiene solution on ocular skin[J]. Clin Ophthalmol, 2017, 11: 707-714. doi: 10.2147/opth.s132851

[23] Correia S , Poeta P , Hébraud M , et al. Mechanisms of quinolone action and resistance: where do we stand[J]. Journal of Medical Microbiology, 2017, 66(5): 551-559. doi: 10.1099/jmm.0.000475

[24] 许海嘉, 李蓓, 范罕英, 等 . 药物联合物理疗法治疗MGD所致干眼的疗效观察[J]. 国际眼科杂志, 2019, 19(10): 1787-1790. doi: 10.3980/j.issn.1672-5123.2019.10.36

[25] 孙圣书, 黄悦 . 抗生素治疗睑板腺功能障碍的研究进展[J]. 国际眼科杂志, 2022, 22(5): 827-832. doi: 10.3980/j.issn.1672-5123.2022.5.26

[26] Mah FS , Karpecki PM . Review of loteprednol etabonate 0.5%/tobramycin 0.3% in the treatment of blepharokeratoconjunctivitis[J]. Ophthalmology and Therapy, 2021, 10(4): 859-875. doi: 10.1007/s40123-021-00401-x

[27] 胡晓娟, 卢丽丽, 刘猛 . 睑板腺按摩联合抗生素滴眼液治疗睑板腺功能障碍性干眼的效果[J]. 医学信息, 2020, 33(14): 76-79. doi: 10.3969/j.issn.1006-1959.2020.14.022

[28] Jerkins G , Greiner JV , Tong L , et al. A comparison of efficacy and safety of two lipid-based lubricant eye drops for the management of evaporative dry eye disease[J]. Clinical Ophthalmology, 2020, 14: 1665-1673. doi: 10.2147/OPTH.S256351

[29] Chan TCY , Chow SSW , Wan KHN , et al. Update on the association between dry eye disease and meibomian gland dysfunction[J]. Medical Journal, 2019, 25(1): 38-47. doi: 10.12809/hkmj187331

[30] Labetoulle M , Benitez-del-castillo JM , BARABINO S , et al. Artificial tears: biological role of their ingredients in the management of dry eye disease[J]. International Journal of Molecular Sciences, 2022, 23(5): 2434. doi: 10.3390/ijms23052434

[31] 陆菁, 刘辰, 吴晋晖, 等 . 人工泪液成分的最新研究及进展[J]. 中南药学, 2022, 20(11): 2635-2641. doi: 10.7539/j.issn.1672-2981.2022.11.031

[32] Li Y , Cui L , Lee HS , et al. Comparison of 0.3% hypotonic and isotonic sodium hyaluronate eye drops in the treatment of experimental dry eye[J]. Current Eye Research, 2017, 42(8): 1108-1114. doi: 10.1080/02713683.2017.1297462

[33] Liu Z , Chen D , Chen X , et al. Trehalose induces autophagy against inflammation by activating TFEB signaling pathway in human corneal epithelial cells exposed to hyperosmotic stress[J]. Investigative Ophthalmology & Visual Science, 2020, 61(10): 26. doi: 10.1167/iovs.61.10.26

[34] Goldstein MH , Silva FQ , Blender N , et al. Ocular benzalkonium chloride exposure: problems and solutions[J]. Eye (London, England), 2022, 36(2): 361-368. doi: 10.1038/s41433-021-01668-x

[35] Kallab M , Szegedi S , Hommer N , et al. Correction to: topical low dose preservative-free hydrocortisone reduces signs and symptoms in patients with chronic dry eye: a randomized clinical trial[J]. Advances in Therapy, 2020, 37(1): 342-343. doi: 10.1007/s12325-019-01190-3

[36] Prinz J , Maffulli N , Fuest M , et al. Efficacy of topical administration of corticosteroids for the management of dry eye disease: systematic review and meta-analysis[J]. Life, 2022, 12(11): 1932. doi: 10.3390/life12111932

[37] Messmer EM , Ahmad S , Del Castillo JMB , et al. Management of inflammation in dry eye disease: recommendations from a European panel of experts[J]. European Journal of Ophthalmology, 2023, 33(3): 1294-1307. doi: 10.1177/11206721221141481

[38] Boboridis KG , Konstas AGP . Evaluating the novel application of cyclosporine 0.1% in ocular surface disease[J]. Expert Opinion on Pharmacotherapy, 2018, 19(9): 1027-1039. doi: 10.1080/14656566.2018.1479742

[39] Rhim JW , Eom Y , Yoon EG , et al. Efficacy of a 0.05% cyclosporine atopical nanoemulsion in dry eyes with obstructive meibomian gland dysfunction[J]. Japanese Journal of Ophthalmology, 2022, 66(3): 254-263. doi: 10.1007/s10384-022-00906-3

[40] Tauber J . A 6-week, prospective, randomized, single-masked study of lifitegrast ophthalmic solution 5% versus thermal pulsation procedure for treatment of inflammatory meibomian gland dysfunction[J]. Cornea, 2020, 39(4): 403-407. doi: 10.1097/ICO.0000000000002235

[41] Donnenfeld ED , Karpecki PM , Majmudar PA , et al. Safety of lifitegrast ophthalmic solution 5.0% in patients with dry eye disease: a 1-year, multicenter, randomized, placebo-controlled study[J]. Cornea, 2016, 35(6): 741-748. doi: 10.1097/ICO.0000000000000803

[42] Jain K , Jaju M , Yadav D . Efficacy and safety of topical 2% rebamipide ophthalmic suspension in dry eye disease at tertiary care centre[J]. Indian Journal of Ophthalmology, 2023, 71(4): 1598-1602. doi: 10.4103/IJO.IJO_2586_22

[43] Fukuoka S , Arita R . Tear film lipid layer increase after diquafosol instillation in dry eye patients with meibomian gland dysfunction: a randomized clinical study[J]. Scientific Reports, 2019, 9(1): 9091. doi: 10.1038/s41598-019-45475-7

[44] Katagiri A , Tsubota K , Mikuzuki L , et al. Diquafosol sodium reduces neuronal activity in trigeminal subnucleus caudalis in a rat model of chronic dry eye disease[J]. Neuroscience Letters, 2023, 792: 136939. doi: 10.1016/j.neulet.2022.136939

[45] 刘子彬, 张蕊, 李能, 等 . 3%地夸磷索钠滴眼液治疗睑板腺功能障碍相关性干眼[J]. 国际眼科杂志, 2022, 22(8): 1271-1276. doi: 10.3980/j.issn.1672-5123.2022.8.07

[46] Wang LX , Deng YP . Androgen and meibomian gland dysfunction: from basic molecular biology to clinical applications[J]. International Journal of Ophthalmology, 2021, 14(6): 915-922. doi: 10.18240/ijo.2021.06.18

[47] Goleiwoski B , Badarudin N , Eden J , et al. The effects of transdermal testosterone and oestrogen therapy on dry eye in postmenopausal women: a randomised, placebo-controlled, pilot study[J]. British Journal of Ophthalmology, 2017, 101(7): 926-932. doi: 10.1136/bjophthalmol-2016-309498

[48] Ibrahim MAA , Elwan WM . Role of topical dehydroepiandrosterone in ameliorating isotretinoin-induced Meibomian gland dysfunction in adult male albino rat[J]. Annals of Anatomy-Anatomischer Anzeiger, 2017, 211: 78-87. doi: 10.1016/j.aanat.2017.01.007

[49] Stollowich N , Vittitow J , Kissling R , et al. Oxygen-carrying capacity of perfluorohexyloctane, a novel eye drop for dry eye disease[J]. Current Therapeutic Research, 2023, 98: 100705. doi: 10.1016/j.curtheres.2023.100705

[50] Tauber J , Berdy GJ , Wirta DL , et al. NOV03 for dry eye disease associated with meibomian gland dysfunction results of the randomized phase 3 GOBI study[J]. Ophthalmology, 2023, 130(5): 516-524. doi: 10.1016/j.ophtha.2022.12.021

[51] Delicado-Miralle M , Velasco E , Díaz-Tahoces A , et al. Deciphering the action of perfluorohexyloctane eye drops to reduce ocular discomfort and pain[J]. Frontiers in Medicine, 2021, 8: 709712. doi: 10.3389/fmed.2021.709712

[52] Vittitow J , Kissling R , Decory H , et al. In vitro inhibition of evaporation with perfluorohexyloctane, an eye drop for dry eye disease[J]. Current Therapeutic Research, 2023, 98: 100704. doi: 10.1016/j.curtheres.2023.100704

[53] Tian L , Gao ZJ , Zhu L , et al. Perfluorohexyloctane eye drops for dry eye disease associated with meibomian gland dysfunction in Chinese patients: a randomized clinical trial[J]. JAMA Ophthalmology, 2023, 141(4): 385-392. doi: 10.1001/jamaophthalmol.2023.0270

基金资助

山西省青年科学研发项目(202203021212072)