Hydroxypropyl-Methylcellulose and GlicoPro^® Eyedrops in the Treatment of Dry Eye Disease: In Vitro and Clinical Study.

IF 2.6 3区医学 Q2 OPHTHALMOLOGY

Ophthalmology and Therapy Pub Date : 2025-04-01 Epub Date: 2025-03-01 DOI:10.1007/s40123-025-01101-6

Edoardo Villani, Giuseppe Campagna, Valentina Gentili, Elisa Imelde Postorino, Paola Genovese, Paola Palino, Gloria Maini, Alice Carbucicchio, Eleonora Ferioli, Paolo Nucci, Roberta Rizzo, Pasquale Aragona

{"title":"Hydroxypropyl-Methylcellulose and GlicoPro® Eyedrops in the Treatment of Dry Eye Disease: In Vitro and Clinical Study.","authors":"Edoardo Villani, Giuseppe Campagna, Valentina Gentili, Elisa Imelde Postorino, Paola Genovese, Paola Palino, Gloria Maini, Alice Carbucicchio, Eleonora Ferioli, Paolo Nucci, Roberta Rizzo, Pasquale Aragona","doi":"10.1007/s40123-025-01101-6","DOIUrl":null,"url":null,"abstract":"Introduction: Artificial tear substitutes are key elements in the first-line treatment of dry eye disease (DED). We hypothesized that GlicoPro®, a new multimolecular complex based on proteins, sulfured and unsulfured glycosaminoglycans and opiorphin, was able to significantly improve the effect of hydroxypropyl-methylcellulose (HPMC) eyedrops in treating DED.Methods: We performed an in vitro experiment and a clinical study, comparing an HPMC + GlicoPro®-based to an HPMC-based ophthalmic formulation (similar kinematic viscosity and comparable HPMC concentration). An in vitro dry eye model was established by inducing hyperosmolarity in the base medium of human corneal epithelial cells HCE-2. After treatment with ophthalmic formulations, the expression levels of inflammatory cytokines and enzymes (IL-20, IL-1β, TNF-α, IL-6, IL-8, MMP-9, and MCP-1) was measured by real-time polymerase chain reaction. Moreover, we performed a single-blind randomized 1:1 clinical trial, aimed to compare the efficacy of the two formulations instilled four times per day (QID), in treating mild-to-moderate DED. Symptoms (Ocular Surface Disease Index and Symptom Assessment iN Dry Eye), clinical signs, and ocular surface imaging data were assessed at baseline and after 1 and 3 months of treatment.Results: In vitro experiment: under hyperosmotic conditions, corneal epithelial cells upregulated the expression of inflammatory cytokines IL-20, IL-1β, TNF-α, IL-6, and IL-8. Treatment with HPMC + GlicoPro® significantly decreased the expression of all inflammatory markers tested, including cytokines, MMP-9, and MCP-1 (P < 0.05).Clinical study: the HPMC + GlicoPro® formulation showed a significantly higher effect in improving symptoms (overall treatment effect: P < 0.001), tear film stability, and markers of inflammation on corneal confocal microscopy (P < 0.01).Conclusions: Both in vitro and clinical data provided evidence supporting the role of GlicoPro® in improving the effect of HPMC in DED treatment.Clinical trial registration: NCT06726525.","PeriodicalId":19623,"journal":{"name":"Ophthalmology and Therapy","volume":" ","pages":"787-803"},"PeriodicalIF":2.6000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920458/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ophthalmology and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40123-025-01101-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/1 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: Artificial tear substitutes are key elements in the first-line treatment of dry eye disease (DED). We hypothesized that GlicoPro^®, a new multimolecular complex based on proteins, sulfured and unsulfured glycosaminoglycans and opiorphin, was able to significantly improve the effect of hydroxypropyl-methylcellulose (HPMC) eyedrops in treating DED.

Methods: We performed an in vitro experiment and a clinical study, comparing an HPMC + GlicoPro^®-based to an HPMC-based ophthalmic formulation (similar kinematic viscosity and comparable HPMC concentration). An in vitro dry eye model was established by inducing hyperosmolarity in the base medium of human corneal epithelial cells HCE-2. After treatment with ophthalmic formulations, the expression levels of inflammatory cytokines and enzymes (IL-20, IL-1β, TNF-α, IL-6, IL-8, MMP-9, and MCP-1) was measured by real-time polymerase chain reaction. Moreover, we performed a single-blind randomized 1:1 clinical trial, aimed to compare the efficacy of the two formulations instilled four times per day (QID), in treating mild-to-moderate DED. Symptoms (Ocular Surface Disease Index and Symptom Assessment iN Dry Eye), clinical signs, and ocular surface imaging data were assessed at baseline and after 1 and 3 months of treatment.

Results: In vitro experiment: under hyperosmotic conditions, corneal epithelial cells upregulated the expression of inflammatory cytokines IL-20, IL-1β, TNF-α, IL-6, and IL-8. Treatment with HPMC + GlicoPro^® significantly decreased the expression of all inflammatory markers tested, including cytokines, MMP-9, and MCP-1 (P < 0.05).

Clinical study: the HPMC + GlicoPro^® formulation showed a significantly higher effect in improving symptoms (overall treatment effect: P < 0.001), tear film stability, and markers of inflammation on corneal confocal microscopy (P < 0.01).

Conclusions: Both in vitro and clinical data provided evidence supporting the role of GlicoPro^® in improving the effect of HPMC in DED treatment.

Clinical trial registration: NCT06726525.

查看原文本刊更多论文

羟丙基甲基纤维素和GlicoPro®滴眼液治疗干眼症：体外和临床研究

人工泪液替代品是干眼病（DED）一线治疗的关键因素。我们假设GlicoPro®是一种基于蛋白质、含硫和无硫糖胺聚糖和opiorphin的新型多分子复合物，能够显著改善羟丙基甲基纤维素（HPMC）滴眼液治疗DED的效果。方法：我们进行了体外实验和临床研究，比较了基于HPMC + GlicoPro®的与基于HPMC的眼科配方（相似的运动粘度和相似的HPMC浓度）。通过在人角膜上皮细胞HCE-2的基础培养基中诱导高渗，建立离体干眼模型。用眼用制剂治疗后，采用实时聚合酶链反应法测定炎症因子和酶（IL-20、IL-1β、TNF-α、IL-6、IL-8、MMP-9、MCP-1）的表达水平。此外，我们进行了一项单盲随机1:1临床试验，旨在比较两种制剂每天灌注四次（QID）治疗轻中度DED的疗效。在基线和治疗1个月和3个月后评估症状（干眼眼表疾病指数和症状评估）、临床体征和眼表成像数据。结果：体外实验：在高渗条件下，角膜上皮细胞上调炎症因子IL-20、IL-1β、TNF-α、IL-6、IL-8的表达。HPMC + GlicoPro®治疗可显著降低所有炎症标志物的表达，包括细胞因子、MMP-9和MCP-1 (P)临床研究：HPMC + GlicoPro®配方在改善症状方面的效果显著更高（总体治疗效果：P）结论：体外和临床数据均支持GlicoPro®改善HPMC治疗DED效果的作用。临床试验注册：NCT06726525。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Ophthalmology and Therapy OPHTHALMOLOGY-

CiteScore

4.20

自引率

3.00%

发文量

157

审稿时长

6 weeks

期刊介绍： Aims and Scope Ophthalmology and Therapy is an international, open access, peer-reviewed (single-blind), and rapid publication journal. The scope of the journal is broad and will consider all scientifically sound research from preclinical, clinical (all phases), observational, real-world, and health outcomes research around the use of ophthalmological therapies, devices, and surgical techniques. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/series, trial protocols and short communications such as commentaries and editorials. Ophthalmology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. Rapid Publication The journal’s publication timelines aim for a rapid peer review of 2 weeks. If an article is accepted it will be published 3–4 weeks from acceptance. The rapid timelines are achieved through the combination of a dedicated in-house editorial team, who manage article workflow, and an extensive Editorial and Advisory Board who assist with peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid, efficient communication of the latest research and reviews, fostering the advancement of ophthalmic therapies. Open Access All articles published by Ophthalmology and Therapy are open access. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning authors will always have an editorial contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. Digital Features and Plain Language Summaries Ophthalmology and Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’. For examples of digital features please visit our showcase page https://springerhealthcare.com/expertise/publishing-digital-features/ Publication Fees Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of €5250/$6000/£4300. The journal will consider fee discounts and waivers for developing countries and this is decided on a case by case basis. Peer Review Process Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria. At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials, and Letters which are generally reviewed by one member of the Editorial Board. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case-by-case basis and should be sent to the journal editor. Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors’ or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. Authors should disclose details of preprint posting during the submission process or at any other point during consideration in one of our journals. Once the manuscript is published, it is the author’s responsibility to ensure that the preprint record is updated with a publication reference, including the DOI and a URL link to the published version of the article on the journal website. Please follow the link for further information on preprint sharing: https://www.springer.com/gp/authors-editors/journal-author/journal-author-helpdesk/submission/1302#c16721550 Copyright Ophthalmology and Therapy''s content is published open access under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0. Contact For more information about the journal, including pre-submission enquiries, please contact christopher.vautrinot@springer.com.