{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:48:15Z","timestamp":1791964095808,"version":"4.3.4"},"reference-count":42,"publisher":"Aboutscience Srl","issue":"1","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Grhta"],"abstract":"<jats:p>Introduction: Dry eye disease (DED) is a multifactorial, immune-mediated inflammatory condition affecting the ocular surface and lacrimal glands. Multiple ciclosporin-based therapies with different formulations are currently available in Europe, although clear guidance on their optimal use remains limited. The aim of this study was to determine the main unmet needs and the current management landscape of ciclosporin-based therapies, from the perspective of clinical experts using multi-criteria decision analysis (MCDA).Methods: A systematic literature review was conducted to gather evidence for each of the MCDA framework criteria. An international expert panel of seven clinical specialists in DED from four European countries independently weighted the criteria and scored the non-comparative criteria in the evidence matrix. Results were presented and discussed in a group online session.Results: DED is a highly prevalent, chronic inflammatory disease associated with significant visual and functional burden. Its management is not uniform and often involves a stepwise approach. Recent ciclosporin-based treatment alternatives address some unmet needs; however, others\u2014such as the need for greater standardization of diagnostic tools and improved objective markers of inflammation\u2014remain to be addressed. Highest importance was assigned to Efficacy\/effectiveness (4.7 \u00b1 0.5), Quality of evidence (4.7 \u00b1 0.5), and Safety\/tolerability (4.6 \u00b1 0.5) criteria, highlighting the relevance of treatment-related outcomes in clinical decision-making.Conclusions: The expert opinion, based on MCDA, enabled the identification of key value drivers and unmet needs in the current management of DED based on ciclosporin-based therapies. These early insights may contribute to promoting future work to support informed, evidence-based decision-making.<\/jats:p>","DOI":"10.33393\/grhta.2026.3766","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:23:35Z","timestamp":1791962615000},"page":"260-268","source":"Crossref","is-referenced-by-count":0,"title":["Determining value and the contribution of ciclosporin-based therapies in dry eye disease: a European expert MCDA pilot study"],"prefix":"10.33393","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8336-4314","authenticated-orcid":false,"given":"Sajjad","family":"Ahmad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Figueiredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Labetoulle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Messmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7006-8359","authenticated-orcid":false,"given":"Stefan","family":"Schrader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Philipp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2010-1701","authenticated-orcid":false,"given":"Jose Manuel","family":"Benitez del Castillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"18642","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"21280","doi-asserted-by":"crossref","unstructured":"Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017;15(3):276-283. https:\/\/doi.org\/10.1016\/j.jtos.2017.05.008 PMID:28736335","DOI":"10.1016\/j.jtos.2017.05.008"},{"key":"21281","doi-asserted-by":"crossref","unstructured":"Jones L, Craig JP, Markoulli M, et al.; TFOS Collaborator Group. TFOS DEWS III: management and therapy. Am J Ophthalmol. 2025;279:289-386. https:\/\/doi.org\/10.1016\/j.ajo.2025.05.039 PMID:40467022","DOI":"10.1016\/j.ajo.2025.05.039"},{"key":"21282","doi-asserted-by":"crossref","unstructured":"Rouen PA, White ML. Dry eye disease: prevalence, assessment and management. Home Healthcare Now. 2018;36. https:\/\/doi.org\/10.1097\/NHH.0000000000000652","DOI":"10.1097\/NHH.0000000000000652"},{"key":"21283","doi-asserted-by":"crossref","unstructured":"Messmer EM, Ahmad S, Benitez Del Castillo JM, et al. A panel of European dry eye disease experts. Management of inflammation in dry eye disease: recommendations from a European panel of experts. Eur J Ophthalmol. 2023;33(3):1294-1307. https:\/\/doi.org\/10.1177\/11206721221141481 PMID:36471573","DOI":"10.1177\/11206721221141481"},{"key":"21284","doi-asserted-by":"crossref","unstructured":"Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II epidemiology report. Ocul Surf. 2017;15(3):334-365. https:\/\/doi.org\/10.1016\/j.jtos.2017.05.003 PMID:28736337. CrossMark reports an erratum (or similar issue). The CrossMark type is \"hasReview\". Additional information can be found at https:\/\/doi.org\/10.3410\/f.731193574.793554006. https:\/\/doi.org\/10.1016\/j.jtos.2025.01.006 PMID:39828133","DOI":"10.1016\/j.jtos.2017.05.003"},{"key":"21285","doi-asserted-by":"crossref","unstructured":"Jones L, Downie LE, Korb D, et al. TFOS DEWS II management and therapy report. Ocul Surf. 2017;15(3):575-628. https:\/\/doi.org\/10.1016\/j.jtos.2017.05.006 PMID:28736343","DOI":"10.1016\/j.jtos.2017.05.006"},{"key":"21286","doi-asserted-by":"crossref","unstructured":"Goldberg DF, Malhotra RP, Schechter BA, et al. A phase 3, randomized, double-masked study of OTX-101 ophthalmic solution 0.09% in the treatment of dry eye disease. Ophthalmology. 2019;126(9):1230-1237. https:\/\/doi.org\/10.1016\/j.ophtha.2019.03.050 PMID:30965064","DOI":"10.1016\/j.ophtha.2019.03.050"},{"key":"21287","doi-asserted-by":"crossref","unstructured":"Moreno-Calder\u00f3n A, Tong TS, Thokala P. Multi-criteria decision analysis software in healthcare priority setting: a systematic review. PharmacoEconomics. 2020;38(3):269-283. https:\/\/doi.org\/10.1007\/s40273-019-00863-9 PMID:31820294","DOI":"10.1007\/s40273-019-00863-9"},{"key":"21288","doi-asserted-by":"crossref","unstructured":"Wahlster P, Goetghebeur M, Kriza C, et al. Balancing costs and benefits at different stages of medical innovation: a systematic review of multi-criteria decision analysis (MCDA). BMC Health Serv Res. 2015;15(1):262. https:\/\/doi.org\/10.1186\/s12913-015-0930-0 PMID:26152122","DOI":"10.1186\/s12913-015-0930-0"},{"key":"21289","doi-asserted-by":"crossref","unstructured":"Goetghebeur MM, Wagner M, Khoury H, et al. Bridging health technology assessment (HTA) and efficient health care decision making with multi-criteria decision analysis (MCDA): applying the EVIDEM framework to medicines appraisal. Med Decis Making. 2012;32(2):376-388. https:\/\/doi.org\/10.1177\/0272989X11416870 PMID:21987539","DOI":"10.1177\/0272989X11416870"},{"key":"21290","doi-asserted-by":"crossref","unstructured":"Thokala P, Devlin N, Marsh K, et al. Multiple criteria decision analysis for health care decision making\u2014an introduction: report 1 of the ISPOR MCDA Emerging Good Practices Task Force. Value Health. 2016;19(1):1-13. https:\/\/doi.org\/10.1016\/j.jval.2015.12.003 PMID:26797229","DOI":"10.1016\/j.jval.2015.12.003"},{"key":"21291","doi-asserted-by":"crossref","unstructured":"Marsh K, IJzerman M, Thokala P, et al.; ISPOR Task Force. Multiple criteria decision analysis for health care decision making\u2014emerging good practices: report 2 of the ISPOR MCDA Emerging Good Practices Task Force. Value Health. 2016;19(2):125-137. https:\/\/doi.org\/10.1016\/j.jval.2015.12.016 PMID:27021745","DOI":"10.1016\/j.jval.2015.12.016"},{"key":"21292","unstructured":"Ministerio de Sanidad. Agencia Espa\u00f1ola de Medicamentos y Productos Sanitarios (AEMPS). FICHA T\u00c9CNICA: Cequa 0,9 mg\/ml colirio en soluci\u00f3n en envase unidosis. 2024. https:\/\/cima.aemps.es\/cima\/dochtml\/ft\/89655\/FT_89655.html (Accessed February 2026)"},{"key":"21293","unstructured":"European Medicines Agency (EMA). CHMP. EPAR. ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS: Vevizye 1 mg\/mL eye drops, solution. 2024. https:\/\/ec.europa.eu\/health\/documents\/community-register\/2024\/20240919163740\/anx_163740_en.pdf (Accessed February 2026)"},{"key":"21294","doi-asserted-by":"crossref","unstructured":"Periman LM, Mah FS, Karpecki PM. A review of the mechanism of action of cyclosporine A: the role of cyclosporine A in dry eye disease and recent formulation developments. Clin Ophthalmol. 2020;14:4187-4200. https:\/\/doi.org\/10.2147\/OPTH.S279051 PMID:33299295","DOI":"10.2147\/OPTH.S279051"},{"key":"21295","doi-asserted-by":"crossref","unstructured":"McDonald M, Patel DA, Keith MS, et al. Economic and humanistic burden of dry eye disease in Europe, North America, and Asia: a systematic literature review. Ocul Surf. 2016;14(2):144-167. https:\/\/doi.org\/10.1016\/j.jtos.2015.11.002 PMID:26733111","DOI":"10.1016\/j.jtos.2015.11.002"},{"key":"21296","doi-asserted-by":"crossref","unstructured":"Boboridis KG, Messmer EM, Ben\u00edtez-Del-Castillo J, et al. Patient-reported burden and overall impact of dry eye disease across eight European countries: a cross-sectional web-based survey. BMJ Open. 2023;13(3):e067007. https:\/\/doi.org\/10.1136\/bmjopen-2022-067007 PMID:36931668","DOI":"10.1136\/bmjopen-2022-067007"},{"key":"21297","doi-asserted-by":"crossref","unstructured":"Messmer EM. Pathophysiology of dry eye disease and novel therapeutic targets. Exp Eye Res. 2022;217:108944. https:\/\/doi.org\/10.1016\/j.exer.2022.108944 PMID:35077753","DOI":"10.1016\/j.exer.2022.108944"},{"key":"21298","doi-asserted-by":"crossref","unstructured":"Verjee MA, Brissette RA, Starr CE. Dry eye disease: early recognition with guidance on management and treatment for primary care family physicians. Ophthalmol Ther. 2020;877-888. https:\/\/doi.org\/10.1007\/s40123-020-00308-z","DOI":"10.1007\/s40123-020-00308-z"},{"key":"21299","doi-asserted-by":"crossref","unstructured":"Lam D, Chong K, Shih K, et al. Optimizing diagnosis and management of dry eye disease: a practical framework for Hong Kong. Ophthalmol Ther. 2025;14(5):815-833. https:\/\/doi.org\/10.1007\/s40123-025-01129-8 PMID:40138170","DOI":"10.1007\/s40123-025-01129-8"},{"key":"21300","doi-asserted-by":"crossref","unstructured":"Messmer E, Chan C, Asbell P, et al. Comparing the needs and preferences of patients with moderate and severe dry eye symptoms across four countries. BMJ Open Ophthalmol. 2019;4(1):e000360. https:\/\/doi.org\/10.1136\/bmjophth-2019-000360 PMID:31909193","DOI":"10.1136\/bmjophth-2019-000360"},{"key":"21301","doi-asserted-by":"crossref","unstructured":"Pinto-Fraga J, Enr\u00edquez-de-Salamanca A, Calonge M, et al. Severity, therapeutic, and activity tear biomarkers in dry eye disease: an analysis from a phase III clinical trial. Ocul Surf. 2018;16(3):368-376. https:\/\/doi.org\/10.1016\/j.jtos.2018.05.001 PMID:29772277","DOI":"10.1016\/j.jtos.2018.05.001"},{"key":"21302","doi-asserted-by":"crossref","unstructured":"Sullivan BD, Whitmer D, Nichols KK, et al. An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci. 2010;51(12):6125-6130. https:\/\/doi.org\/10.1167\/iovs.10-5390 PMID:20631232","DOI":"10.1167\/iovs.10-5390"},{"key":"21303","doi-asserted-by":"crossref","unstructured":"Bilkhu P, Sivardeen Z, Chen C, et al. Patient-reported experience of dry eye management: an international multicentre survey. Cont Lens Anterior Eye. 2022;45(1):101450. https:\/\/doi.org\/10.1016\/j.clae.2021.101450 PMID:33941501","DOI":"10.1016\/j.clae.2021.101450"},{"key":"21304","doi-asserted-by":"crossref","unstructured":"Hossain P, Siffel C, Joseph C, et al. Patient-reported burden of dry eye disease in the UK: a cross-sectional web-based survey. BMJ Open. 2021;11(3):e039209. https:\/\/doi.org\/10.1136\/bmjopen-2020-039209 PMID:33664064","DOI":"10.1136\/bmjopen-2020-039209"},{"key":"21305","doi-asserted-by":"crossref","unstructured":"Roy NS, Wei Y, Kuklinski E, et al. The growing need for validated biomarkers and endpoints for dry eye clinical research. Invest Ophthalmol Vis Sci. 2017;58(6):BIO1-BIO19. https:\/\/doi.org\/10.1167\/iovs.17-21709 PMID:28475698","DOI":"10.1167\/iovs.17-21709"},{"key":"21306","doi-asserted-by":"crossref","unstructured":"Thulasi P, Djalilian AR. Update in current diagnostics and therapeutics of dry eye disease. Ophthalmology. 2017;124(11S):S27-S33. https:\/\/doi.org\/10.1016\/j.ophtha.2017.07.022 PMID:29055359","DOI":"10.1016\/j.ophtha.2017.07.022"},{"key":"21307","unstructured":"European Medicines Agency (EMA). CHMP. EPAR. ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS: IKERVIS 1 mg\/mL eye drops, emulsion. 2015. https:\/\/ec.europa.eu\/health\/documents\/community-register\/2015\/20150319131066\/anx_131066_en.pdf (Accessed February 2026)"},{"key":"21308","doi-asserted-by":"crossref","unstructured":"Goetghebeur MM, Wagner M, Khoury H, et al. Evidence and value: impact on DecisionMaking \u2013 the EVIDEM framework and potential applications. BMC Health Serv Res. 2008;8(1):270. https:\/\/doi.org\/10.1186\/1472-6963-8-270 PMID:19102752","DOI":"10.1186\/1472-6963-8-270"},{"key":"21309","doi-asserted-by":"crossref","unstructured":"Domingo C, Fernandez M, Garin N, et al. Determining what represents value in the treatment of refractory or unexplained chronic cough from the perspective of key stakeholders in Spain using multi-criteria decision analysis. Appl Health Econ Health Policy. 2023;21(1):119-130. https:\/\/doi.org\/10.1007\/s40258-022-00770-9 PMID:36319945","DOI":"10.1007\/s40258-022-00770-9"},{"key":"21310","doi-asserted-by":"crossref","unstructured":"Abad MR, Alerany C, Alsina L, et al. Determining value in the treatment of activated PI3K\u03b4 syndrome in Spain: a multi-criteria decision analysis from the perspective of key stakeholders. Glob Reg Health Technol Assess. 2024;11(1):124-130. https:\/\/doi.org\/10.33393\/grhta.2024.3041 PMID:38784663","DOI":"10.33393\/grhta.2024.3041"},{"key":"21311","doi-asserted-by":"crossref","unstructured":"Ngorsuraches S, Lai TC, Habermann R, et al. Using a patient-centered multi-criteria decision analysis to assess the value of multiple sclerosis treatments in the US: a study protocol. PharmacoEconom Open. 2024;8(5):773-781. https:\/\/doi.org\/10.1007\/s41669-024-00509-3 PMID:38982030","DOI":"10.1007\/s41669-024-00509-3"},{"key":"21312","doi-asserted-by":"crossref","unstructured":"Badia X, Aguar\u00f3n A, Fern\u00e1ndez A, et al. Patient involvement in reflective multi-criteria decision analysis to assist decision making in oncology. Int J Technol Assess Health Care. 2019;35(1):56-63. https:\/\/doi.org\/10.1017\/S0266462318003641 PMID:30730288","DOI":"10.1017\/S0266462318003641"},{"key":"21313","doi-asserted-by":"crossref","unstructured":"Barrio P, Ezzeldin M, Bruguera P, et al. Methadone for the treatment of prescription opioid dependence. A retrospective chart review. Adicciones. 2016;29(1):55-60. https:\/\/doi.org\/10.20882\/adicciones.832 PMID:27391853","DOI":"10.20882\/adicciones.832"},{"key":"21314","doi-asserted-by":"crossref","unstructured":"Rold\u00e1n \u00daB, Badia X, Marcos-Rodr\u00edguez JA, et al. Multi-criteria decision analysis as a decision-support tool for drug evaluation: a pilot study in a pharmacy and therapeutics committee setting. Int J Technol Assess Health Care. 2018;34(5):519-526. https:\/\/doi.org\/10.1017\/S0266462318000569 PMID:30348241","DOI":"10.1017\/S0266462318000569"},{"key":"21315","doi-asserted-by":"crossref","unstructured":"Thokala P, Madhavan G. Stakeholder involvement in multi-criteria decision analysis. Cost Eff Resour Alloc. 2018;16(S1)(suppl 1):0. https:\/\/doi.org\/10.1186\/s12962-018-0120-0 PMID:30455597","DOI":"10.1186\/s12962-018-0120-0"},{"key":"21316","doi-asserted-by":"crossref","unstructured":"Gaievskyi S, Delfrate N, Ragazzoni L, et al. Use of multi-criteria decision analysis (MCDA) to support decision-making during health emergencies: a scoping review. Front Public Health. 2025;13:1584026. https:\/\/doi.org\/10.3389\/fpubh.2025.1584026 PMID:40416669","DOI":"10.3389\/fpubh.2025.1584026"},{"key":"21317","doi-asserted-by":"crossref","unstructured":"Gilabert-Perramon A, Torrent-Farnell J, Catalan A, et al. Drug evaluation and decision making in Catalonia: development and validation of a methodological framework based on multi-criteria decision analysis (MCDA) for orphan drugs. Int J Technol Assess Health Care. 2017;33(1):111-120. https:\/\/doi.org\/10.1017\/S0266462317000149 PMID:28434413","DOI":"10.1017\/S0266462317000149"},{"key":"21318","doi-asserted-by":"crossref","unstructured":"Gongora-Salazar P, Rocks S, Fahr P, et al. The use of multi-criteria decision analysis to support decision making in healthcare: an updated systematic literature review. Value Health. 2023;26(5):780-790. https:\/\/doi.org\/10.1016\/j.jval.2022.11.007 PMID:36436791","DOI":"10.1016\/j.jval.2022.11.007"},{"key":"21319","doi-asserted-by":"crossref","unstructured":"de Andr\u00e9s-Nogales F, Casado M\u00c1, Trillo JL, et al. A multiple stakeholder multi-criteria decision analysis in diabetic macular edema management: the MULTIDEX-EMD study. PharmacoEconom Open. 2020;4(4):615-624. https:\/\/doi.org\/10.1007\/s41669-020-00201-2 PMID:32100249","DOI":"10.1007\/s41669-020-00201-2"},{"key":"21320","doi-asserted-by":"crossref","unstructured":"Mezei F, Tsiasiotis E, Basile M, et al. Shaping the future of DHT assessment: insights on industry challenges, developer needs, and a harmonized, European HTA framework. J Mark Access Health Policy. 2025;13(3):46. https:\/\/doi.org\/10.3390\/jmahp13030046 PMID:40989745","DOI":"10.3390\/jmahp13030046"},{"key":"21321","doi-asserted-by":"crossref","unstructured":"Radaelli G, Lettieri E, Masella C, et al. Implementation of eunethta core model\u00ae in Lombardia: the VTS framework. Int J Technol Assess Health Care. 2014;30(1):105-112. https:\/\/doi.org\/10.1017\/S0266462313000639 PMID:24451150","DOI":"10.1017\/S0266462313000639"}],"container-title":["Global and Regional Health Technology Assessment"],"original-title":[],"link":[{"URL":"https:\/\/journals.aboutscience.eu\/index.php\/grhta\/article\/download\/3766\/5368","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.aboutscience.eu\/index.php\/grhta\/article\/download\/3766\/5369","content-type":"application\/epub+zip","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.aboutscience.eu\/index.php\/grhta\/article\/download\/3766\/5368","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:24:22Z","timestamp":1791962662000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.aboutscience.eu\/index.php\/grhta\/article\/view\/3766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,13]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,7,15]]}},"URL":"https:\/\/doi.org\/10.33393\/grhta.2026.3766","relation":{},"ISSN":["2283-5733","2284-2403"],"issn-type":[{"value":"2283-5733","type":"electronic"},{"value":"2284-2403","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10,13]]}}}