Dry Eye Disease: From Causes to Patient Care and Clinical Collaboration-A Narrative Review

Pasquale Aragona¹, Stefano Barabino², Antonio Di Zazzo³, Giuseppe Giannaccare⁴, Edoardo Villani⁵, Francesco Aiello⁶, Elena Antoniazzi⁷, Stefano Bonini⁸, Emilia Cantera⁹, Gianpaolo Carlini¹⁰, Chiara Chierego¹¹, Rossella Colabelli¹², Romina Fasciani¹³, Antonella Franch¹⁴, Giovanna Gabbriellini¹⁵, Caterina Maria Rita Gagliano^{16

17}, Andrea Leonardi¹⁸, Angelo Macrì¹⁹, Rita Mencucci²⁰, Luigi Mosca¹³, Vincenzo Orfeo²¹, Antonio Pinna²², Augusto Pocobelli¹², Romolo Protti²³, Paolo Rama²⁴, Laura Rania²⁵, Miguel Rechichi²⁶, Pierangela Rubino²⁷, Andrea Russo²⁸, Vincenzo Scorcia²⁹, Leopoldo Spadea³⁰, Marco Trentadue³¹, Salvatore Troisi³², Piera Versura³³, Maurizio Rolando³⁴

Affiliations

¹ Department of Biomedical Sciences, Ophthalmology Clinic, University of Messina, Messina, Italy.
² Ocular Surface and Dry Eye Center, Ospedale L. Sacco, University of Milan, Milan, Italy.
³ Cornea Service, Department of Ophthalmology, University of Rome Campus Biomedico, Campus Bio-Medico University Hospital Foundation, Via Alvaro del Portillo 200, 00128, Rome, RM, Italy. a.dizazzo@policlinicocampus.it.
⁴ Eye Clinic, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy.
⁵ Eye Clinic, San Giuseppe Hospital, IRCCS Multimedica, University of Milan, Milan, Italy.
⁶ Ophthalmology Unit, Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
⁷ IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
⁸ Cornea Service, Department of Ophthalmology, University of Rome Campus Biomedico, Campus Bio-Medico University Hospital Foundation, Via Alvaro del Portillo 200, 00128, Rome, RM, Italy.
⁹ Israelitic Hospital, Rome, Italy.
¹⁰ ASL Napoli 1 Centro, Naples, Italy.
¹¹ Ophthalmic Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
¹² UOC Oftalmologia-Banca degli Occhi, San Giovanni Addolorata Hospital, Rome, Italy.
¹³ Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy.
¹⁴ Fondazione Banca Degli Occhi del Veneto Onlus, Department of Ophthalmology, SS Giovanni and Paolo Hospital, Venice, Italy.
¹⁵ Ophthalmology Unit, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.
¹⁶ Department of Medicine and Surgery, Kore University of Enna, Enna, Italy.
¹⁷ "G.B. Morgagni" Foundation, Catania, Italy.
¹⁸ Ophthalmology Unit, Department of Neuroscience, University of Padua, Padua, Italy.
¹⁹ IRCCS San Martino Polyclinic Hospital, Genoa, Italy.
²⁰ Eye Clinic, Department of Neuroscience, Psychology, Pharmacology and Child Health, University of Florence, Florence, Italy.
²¹ Ophthalmology Unit, "Clinica Mediterranea", Naples, Italy.
²² Ophthalmology Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy.
²³ Ophthalmic Unit, San Biagio Hospital, Domodossola (VB), Italy.
²⁴ Department of Ophthalmology, IRCCS Policlinico San Matteo, Pavia, Italy.
²⁵ Department of Ophthalmology, Istituto per la Sicurezza Sociale, San Marino State Hospital, Cailungo, San Marino.
²⁶ Centro Polispecialistico Mediterraneo, Sellia Marina (CZ), Italy.
²⁷ Ophthalmology Unit, Department of General and Specialized Surgery, University Hospital of Parma, Via Gramsci 14, 43126, Parma, Italy.
²⁸ Eye Clinic, Department of Neurological and Vision Sciences, University of Brescia, Piazzale Spedale Civili, 1, 25100, Brescia, Italy.
²⁹ Department of Ophthalmology, University "Magna Græcia" of Catanzaro, Viale Europa, 88100, Catanzaro, Italy.
³⁰ Eye Clinic, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.
³¹ Azienda Ospedaliera "Ospedale Consorziale Policlinico", Bari, Italy.
³² Eye Department, AOU "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy.
³³ Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, Sant'Orsola-Malpighi University Hospital of Bologna, Bologna, Italy.
³⁴ Ocular Surface and Dry Eye Center, Vista Vision and ISPRE Ophthalmics, Genoa, Italy.

PMID: 40434534
PMCID: PMC12167426
DOI: 10.1007/s40123-025-01161-8

Review

Dry Eye Disease: From Causes to Patient Care and Clinical Collaboration-A Narrative Review

Pasquale Aragona et al. Ophthalmol Ther. 2025 Jul.

. 2025 Jul;14(7):1411-1428.

doi: 10.1007/s40123-025-01161-8. Epub 2025 May 28.

Authors

Affiliations

¹ Department of Biomedical Sciences, Ophthalmology Clinic, University of Messina, Messina, Italy.
² Ocular Surface and Dry Eye Center, Ospedale L. Sacco, University of Milan, Milan, Italy.
³ Cornea Service, Department of Ophthalmology, University of Rome Campus Biomedico, Campus Bio-Medico University Hospital Foundation, Via Alvaro del Portillo 200, 00128, Rome, RM, Italy. a.dizazzo@policlinicocampus.it.
⁴ Eye Clinic, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy.
⁵ Eye Clinic, San Giuseppe Hospital, IRCCS Multimedica, University of Milan, Milan, Italy.
⁶ Ophthalmology Unit, Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
⁷ IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
⁸ Cornea Service, Department of Ophthalmology, University of Rome Campus Biomedico, Campus Bio-Medico University Hospital Foundation, Via Alvaro del Portillo 200, 00128, Rome, RM, Italy.
⁹ Israelitic Hospital, Rome, Italy.
¹⁰ ASL Napoli 1 Centro, Naples, Italy.
¹¹ Ophthalmic Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
¹² UOC Oftalmologia-Banca degli Occhi, San Giovanni Addolorata Hospital, Rome, Italy.
¹³ Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy.
¹⁴ Fondazione Banca Degli Occhi del Veneto Onlus, Department of Ophthalmology, SS Giovanni and Paolo Hospital, Venice, Italy.
¹⁵ Ophthalmology Unit, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.
¹⁶ Department of Medicine and Surgery, Kore University of Enna, Enna, Italy.
¹⁷ "G.B. Morgagni" Foundation, Catania, Italy.
¹⁸ Ophthalmology Unit, Department of Neuroscience, University of Padua, Padua, Italy.
¹⁹ IRCCS San Martino Polyclinic Hospital, Genoa, Italy.
²⁰ Eye Clinic, Department of Neuroscience, Psychology, Pharmacology and Child Health, University of Florence, Florence, Italy.
²¹ Ophthalmology Unit, "Clinica Mediterranea", Naples, Italy.
²² Ophthalmology Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy.
²³ Ophthalmic Unit, San Biagio Hospital, Domodossola (VB), Italy.
²⁴ Department of Ophthalmology, IRCCS Policlinico San Matteo, Pavia, Italy.
²⁵ Department of Ophthalmology, Istituto per la Sicurezza Sociale, San Marino State Hospital, Cailungo, San Marino.
²⁶ Centro Polispecialistico Mediterraneo, Sellia Marina (CZ), Italy.
²⁷ Ophthalmology Unit, Department of General and Specialized Surgery, University Hospital of Parma, Via Gramsci 14, 43126, Parma, Italy.
²⁸ Eye Clinic, Department of Neurological and Vision Sciences, University of Brescia, Piazzale Spedale Civili, 1, 25100, Brescia, Italy.
²⁹ Department of Ophthalmology, University "Magna Græcia" of Catanzaro, Viale Europa, 88100, Catanzaro, Italy.
³⁰ Eye Clinic, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.
³¹ Azienda Ospedaliera "Ospedale Consorziale Policlinico", Bari, Italy.
³² Eye Department, AOU "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy.
³³ Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, Sant'Orsola-Malpighi University Hospital of Bologna, Bologna, Italy.
³⁴ Ocular Surface and Dry Eye Center, Vista Vision and ISPRE Ophthalmics, Genoa, Italy.

PMID: 40434534
PMCID: PMC12167426
DOI: 10.1007/s40123-025-01161-8

Abstract

Dry eye disease (DED) is a common condition of the ocular surface that affects tens of millions of people worldwide. It is often characterized by decreased tear production or increased evaporation, resulting in a wide range of signs and symptoms. This review provides a comprehensive analysis of the literature related to DED, detailing causes, diagnostic tests, and medical management. Several mechanisms contribute to the maintenance of the physiological integrity of the ocular surface, and their dysfunction may result in noticeable symptoms. Accurate diagnosis is therefore essential, even when physiological function is only minimally impaired or no clear pathological signs are present. The review emphasizes the importance of addressing the underlying causes through a combination of treatment options, lifestyle changes, and enhanced communication between patients and healthcare providers to break the cycle of inflammation and tear instability. It aims to raise awareness among patients, healthcare professionals, and researchers regarding the diagnosis and treatment of DED, while also highlighting recent advancements and future challenges in its management.

Keywords: Dry eye disease; Hyperosmolarity; Inflammation; Ocular surface diseases; Patients; Quality of life; Symptoms; Therapy.

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Conflict of interest statement

Declarations. Conflict of Interest: Antonio Pinna received honoraria from Thea Pharma Inc. and Bausch & Lomb for educational activity related to the topics of this manuscript. Andrea Leonardi is a consultant for Alcon, FAES Farma, FIDIA, Santen Pharmaceutical Co. Ltd., Laboratoires Théa, SIFI, URSA-pharma. Pasquale Aragona, Stefano Barabino, Antonio Di Zazzo, Giuseppe Giannaccare, Edoardo Villani, Francesco Aiello, Elena Antoniazzi, Stefano Bonini, Emilia Cantera, Gianpaolo Carlini, Chiara Chierego, Rossella Colabelli, Romina Fasciani, Antonella Franch, Giovanna Gabbriellini, Caterina Maria Rita Gagliano, Angelo Macrì, Rita Mencucci, Luigi Mosca, Vincenzo Orfeo, Augusto Pocobelli, Romolo Protti, Paolo Rama, Laura Rania, Miguel Rechichi, Pierangela Rubino, Andrea Russo, Vincenzo Scorcia, Leopoldo Spadea, Marco Trentadue, Salvatore Troisi, Piera Versura, and Maurizio Rolando have nothing to disclose. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Figures

**Fig. 1**
Extrinsic and intrinsic factors that contribute to the vicious circle of dry eye disease (DED)

**Fig. 2**
Dry eye disease—risk factors, symptoms, and diagnostic approach. The upper portion of the illustration depicts the main risk factors of DED alongside its common symptoms. The lower portion focuses on diagnostic techniques, including low-tech (left column, boxes A–D) and high-tech methods (right column, boxes E–H). The illustration also highlights the importance of differential diagnosis with blepharitis (box I) and new diagnostic approaches such as tear fluid analysis for biomarkers (box J). F fluorescein, RP rose bengal, LG lissamine green, *BUT* break-up time, *NIBUT* non-invasive break-up time, *TMH* tear meniscus height, *IgE* immunoglobulin E, *MMP-9* matrix metalloproteinase-9

**Fig. 3**
Stepwise therapeutic approach for dry eye disease. This illustration outlines a stepwise approach to the treatment of DED, beginning with patient education and lifestyle modification, progressing through basic therapy with eyelid hygiene and artificial tears, and advancing to pharmacologic and non-pharmacologic interventions according to severity. A multidisciplinary approach is always essential to address systemic and psychological comorbidities and ensure comprehensive care. HA hyaluronic acid, *NAAGA* N-acetyl-aspartyl-glutamic acid

See this image and copyright information in PMC

References

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1. Rouen PA, White ML. Dry eye disease: prevalence, assessment, and management. Home Healthc Now. 2018;36(2):74–83. 10.1097/NHH.0000000000000652. - PubMed
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1. Barabino S, et al. Updated definition and classification of dry eye disease: renewed proposals using the nominal group and Delphi techniques. London: SAGE Publications; 2021. 10.1177/1120672120960586. - PubMed
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Dry Eye Disease: From Causes to Patient Care and Clinical Collaboration-A Narrative Review

Affiliations

Dry Eye Disease: From Causes to Patient Care and Clinical Collaboration-A Narrative Review

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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