CONTEMPORARY THERAPEUTIC APPROACHES TO DRY EYE SYNDROME: A SYSTEMATIC REVIEW OF CLINICAL EVIDENCE WITH IMPLICATIONS FOR OCULAR HEALTH AND QUALITY OF LIFE
Abstract
Background: Dry Eye Syndrome (DES), or Dry Eye Disease (DED), is a common, multifactorial condition affecting the tear film and ocular surface. It causes symptoms such as discomfort, visual disturbances, and inflammation. Treatments range from artificial tears and anti-inflammatory drops to newer approaches like light-based therapies, electrotherapy, and biological tear substitutes.
Objective: This systematic review evaluates current pharmacological and non-pharmacological treatments for DES, focusing on clinical effectiveness, safety, and evidence quality - particularly from randomized controlled trials.
Methods: A comprehensive search was performed in major databases for studies published between January 2010 and April 2025. Included studies were in English, involved human subjects with DES, and assessed specific treatments with measurable outcomes (e.g., tear production, symptom severity). Eligible studies included randomized controlled trials, observational studies, and systematic reviews with meta-analyses. Two reviewers independently screened and selected studies, data were extracted and analyzed descriptively due to heterogeneity.
Results: A wide range of therapies were identified. Artificial tears, especially preservative-free and hyaluronic acid-based, consistently improved symptoms and tear stability. Cyclosporine A showed moderate anti-inflammatory effects. Biological tear substitutes, like autologous serum and platelet-rich plasma, benefited severe cases. Non-pharmacological treatments such as intense pulsed light (IPL), low-level light therapy, electrotherapy, and acupuncture improved outcomes in meibomian gland dysfunction. Omega-3 and curcumin supplements had mixed but promising effects.
Conclusions: DES management should be personalized and multimodal. Although many treatments show benefits, variations in study designs limit comparability. More standardized, high-quality research is needed to guide evidence-based care.
References
Akpek, E. K., Sheppard, J. D., Hamm, A., Angstmann-Mehr, S., & Krösser, S. (2024). Efficacy of a new water-free topical cyclosporine 0.1% solution for optimizing the ocular surface in patients with dry eye and cataract. Journal of Cataract and Refractive Surgery, 50(6), 644–650. https://doi.org/10.1097/j.jcrs.0000000000001423
Belalcázar-Rey, S., Sánchez Huerta, V., Ochoa-Tabares, J. C., Altamirano Vallejo, S., Soto-Gómez, A., Suárez-Velasco, R., García-Félix, F., Baiza-Durán, L., Olvera-Montaño, O., & Muñoz-Villegas, P. (2021). Efficacy and Safety of Sodium Hyaluronate/chondroitin Sulfate Preservative-free Ophthalmic Solution in the Treatment of Dry Eye: A Clinical Trial. Current Eye Research, 46(7), 919-929. https://doi.org/10.1080/02713683.2020.1849733
Downie, L. E., Hom, M. M., Berdy, G. J., El-Harazi, S., Verachtert, A., Tan, J., Liu, H., Carlisle-Wilcox, C., Simmons, P., & Vehige, J. (2020). An artificial tear containing flaxseed oil for treating dry eye disease: A randomized controlled trial. The Ocular Surface, 18(1), 148–157. https://doi.org/10.1016/j.jtos.2019.11.004
D’Souza, S., James, E., Koul, A., Modak, D., Kundu, G., & Shetty, R. (2023). A randomized controlled study evaluating outcomes of intense pulsed light and low-level light therapy for treating meibomian gland dysfunction and evaporative dry eye. Indian Journal of Ophthalmology, 71(4), 1608–1612. https://doi.org/10.4103/IJO.IJO_2834_22
Efficacy and Safety of OC-01 (Varenicline Solution) Nasal Spray on Signs and Symptoms of Dry Eye Disease—ClinicalKey. (b.d.).
Hori, Y., Oka, K., & Inai, M. (2022). Efficacy and Safety of the Long-Acting Diquafosol Ophthalmic Solution DE-089C in Patients with Dry Eye: A Randomized, Double-Masked, Placebo-Controlled Phase 3 Study. Advances in Therapy, 39(8), 3654–3667. https://doi.org/10.1007/s12325-022-02194-2
Jongkhajornpong, P., Lekhanont, K., Rattanasiri, S., Numthavaj, P., McKay, G., Attia, J., & Thakkinstian, A. (2024). Efficacy of 100% autologous platelet-rich plasma and 100% autologous serum in dry eye disease: A randomised controlled trial. BMJ Open Ophthalmology, 9(1), e001857. https://doi.org/10.1136/bmjophth-2024-001857
Moon, S. Y., Chung, H. S., Lee, J. H., Lee, H., Tchah, H., & Kim, J. Y. (2024). Effectiveness of cyclosporine nanoemulsion eye drops in patients with mild-to-moderate dry eyes: Objective and subjective evaluation. BMC Ophthalmology, 24, 401. https://doi.org/10.1186/s12886-024-03620-5
Oydanich, M., Maguire, M. G., Pistilli, M., Hamrah, P., Greiner, J. V., Lin, M. C., & Asbell, P. A. (2020). Effects of Omega-3 Supplementation on Exploratory Outcomes in the DREAM Study. Ophthalmology, 127(1), 136–138. https://doi.org/10.1016/j.ophtha.2019.07.009
Pan, Q., Angelina, A., Marrone, M., Stark, W. J., & Akpek, E. K. (2017). Autologous serum eye drops for dry eye. The Cochrane Database of Systematic Reviews, 2017(2), CD009327. https://doi.org/10.1002/14651858.CD009327.pub3
Pan, Q., Angelina, A., Zambrano, A., Marrone, M., Stark, W. J., Heflin, T., Tang, L., & Akpek, E. K. (2013). Autologous serum eye drops for dry eye. The Cochrane database of systematic reviews, 8, CD009327. https://doi.org/10.1002/14651858.CD009327.pub2
Park, Y., Kim, H., Kim, S., & Cho, K. J. (2022). Effect of low-level light therapy in patients with dry eye: A prospective, randomized, observer-masked trial. Scientific Reports, 12, 3575. https://doi.org/10.1038/s41598-022-07427-6
Quan, N. G., Leslie, L., & Li, T. (2023). Autologous Serum Eye Drops for Dry Eye: Systematic Review. Optometry and Vision Science, 100(8), 564–571. https://doi.org/10.1097/OPX.0000000000002042
Wang, Y., Yuan, J., Wen, Y., Li, S., Tian, L., & Jie, Y. (2025). Clinical observation of esculin and digitalisglycosides eye drops with 0.3% sodium hyaluronate eye drops for dry eye disease: A randomized controlled trial. Scientific Reports, 15, 5747. https://doi.org/10.1038/s41598-025-90074-4
Yang, Y.-J., Lee, W.-Y., Kim, Y., & Hong, Y. (2021). A Meta-Analysis of the Efficacy of Hyaluronic Acid Eye Drops for the Treatment of Dry Eye Syndrome. International Journal of Environmental Research and Public Health, 18(5), 2383. https://doi.org/10.3390/ijerph18052383
Zhang, X., Zhang, B., Peng, S., Zhang, G., Ma, J., & Zhu, W. (2022). Effectiveness of acupuncture at acupoint BL1 (Jingming) in comparison with artificial tears for moderate to severe dry eye disease: A randomized controlled trial. Trials, 23, 605. https://doi.org/10.1186/s13063-022-06486-4
Ang, B. C. H., Sng, J. J., Wang, P. X. H., Htoon, H. M., & Tong, L. H. T. (2017). Sodium Hyaluronate in the Treatment of Dry Eye Syndrome: A Systematic Review and Meta-Analysis. Scientific Reports, 7, 9013. https://doi.org/10.1038/s41598-017-08534-5
Bhargava, R., Pandey, K., Ranjan, S., Mehta, B., & Malik, A. (2023). Omega-3 fatty acids supplements for dry eye—Are they effective or ineffective? Indian Journal of Ophthalmology, 71(4), 1619–1625. https://doi.org/10.4103/IJO.IJO_2789_22
Calonge, M., Sahyoun, M., Baillif, S., Gain, P., Paw, E., Mearza, A., & Cochener, B. (2023). Sodium hyaluronate 0.30% ocular gel versus sodium hyaluronate 0.18% eye drop in the treatment of moderate to severe dry eye disease. European Journal of Ophthalmology, 33(1), 188–195. https://doi.org/10.1177/11206721221096321
Chu, Y.-C., & Huang, C.-C. (2024). Role of Lutein Supplements in the Management of Dry Eye Syndrome: A Systematic Review. International Journal for Vitamin and Nutrition Research, 95(1), Artykuł 1. https://doi.org/10.31083/IJVNR36626
de Paiva, C. S., Pflugfelder, S. C., Ng, S. M., & Akpek, E. K. (2019). Topical cyclosporine A therapy for dry eye syndrome. The Cochrane Database of Systematic Reviews, 2019(9), CD010051. https://doi.org/10.1002/14651858.CD010051.pub2
Hu, W.-L., Yu, H.-J., Pan, L.-Y., Wu, P.-C., Pan, C.-C., Kuo, C.-E., Tseng, Y.-J., & Hung, Y.-C. (2021). Laser Acupuncture Improves Tear Film Stability in Patients with Dry Eye Disease: A Two-Center Randomized-Controlled Trial. Journal of Alternative and Complementary Medicine, 27(7), 579–587. https://doi.org/10.1089/acm.2020.0524
Kapil, D., Bari, A., Sharma, N., Velpandian, T., Sinha, R., Maharana, P., Kaur, M., & Agarwal, T. (2025). Role of oral bio-enhanced curcumin in dry eye disease. Indian Journal of Ophthalmology, 73(Suppl 3), S428- S434. https://doi.org/10.4103/IJO.IJO_1572_24
Kasetsuwan, N., Chantaralawan, K., Reinprayoon, U., & Uthaithammarat, L. (2020). Efficacy of topical bevacizumab 0.05% eye drops in dry eye disease: A double-masked, randomized trial. PLoS ONE, 15(6), e0234186. https://doi.org/10.1371/journal.pone.0234186
Kim, B. H., Kim, M. H., Kang, S. H., & Nam, H. J. (2018). Optimizing acupuncture treatment for dry eye syndrome: A systematic review. BMC Complementary and Alternative Medicine, 18, 145. https://doi.org/10.1186/s12906-018-2202-0
Liu, S.-H., Saldanha, I. J., Abraham, A. G., Rittiphairoj, T., Hauswirth, S., Gregory, D., Ifantides, C., & Li, T. (2022). Topical corticosteroids for dry eye. The Cochrane Database of Systematic Reviews, 2022(10), CD015070. https://doi.org/10.1002/14651858.CD015070.pub2
Nosch, D. S., Joos, R. E., & Job, M. (2021). Prospective randomized study to evaluate the efficacy and tolerability of Ectoin® containing Eye Spray (EES09) and comparison to the liposomal Eye Spray Tears Again® (TA) in the treatment of dry eye disease. Contact Lens and Anterior Eye, 44(3), 101318. https://doi.org/10.1016/j.clae.2020.04.003
Protzko, E. E., Segal, B. A., Korenfeld, M. S., Krösser, S., & Vittitow, J. L. (2024). Long-Term Safety and Efficacy of Perfluorohexyloctane Ophthalmic Solution for the Treatment of Patients With Dry Eye Disease: The KALAHARI Study. Cornea, 43(9), 1100–1107. https://doi.org/10.1097/ICO.0000000000003418
Qin, G., Chen, J., Li, L., Zhang, Q., Xu, L., Yu, S., He, W., He, X., & Pazo, E. E. (2023). Efficacy of intense pulsed light therapy on signs and symptoms of dry eye disease: A meta-analysis and systematic review. Indian Journal of Ophthalmology, 71(4), 1316–1325. https://doi.org/10.4103/IJO.IJO_2987_22
Trivli, A., Karmiris, E., Dalianis, G., Ruggeri, A., & Terzidou, C. (2023). Evaluating the efficacy of Quantum Molecular Resonance (QMR) electrotherapy in mixed-type dry eye patients. Journal of Optometry, 16(2), 128–134. https://doi.org/10.1016/j.optom.2022.06.003
White, D. E., Hendrix, L. H., Sun, L., Tam, I., Macsai, M., & Gibson, A. A. (2023). Matching-adjusted indirect comparison of phase 3 clinical trial outcomes of OC-01 (varenicline solution) nasal spray and lifitegrast 5% ophthalmic solution for the treatment of dry eye disease. Journal of Managed Care & Specialty Pharmacy, 29(1), 10.18553/jmcp.2022.22208. https://doi.org/10.18553/jmcp.2022.22208
Wirta, D. L., Galor, A., Aune, C. A., Vollmer, P. M., Liang, E., Meides, A. S., & Krösser, S. (2025). Long-Term Safety and Efficacy of a Water-Free Cyclosporine 0.1% Ophthalmic Solution for Treatment of Dry Eye Disease: ESSENCE-2 OLE. Cornea, 44(6), 692–700. https://doi.org/10.1097/ICO.0000000000003567
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