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

Overview

Journal Ophthalmol Ther

Specialty Ophthalmology

Date 2025 Mar 2

PMID 40024993

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

Affiliations

Soon will be listed here.

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.

References

Stapleton F, Alves M, Bunya V, Jalbert I, Lekhanont K, Malet F . TFOS DEWS II Epidemiology Report. Ocul Surf. 2017; 15(3):334-365. DOI: 10.1016/j.jtos.2017.05.003. View

Craig J, Nichols K, Akpek E, Caffery B, Dua H, Joo C . TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017; 15(3):276-283. DOI: 10.1016/j.jtos.2017.05.008. View

Jones L, Downie L, Korb D, Benitez-Del-Castillo J, Dana R, Deng S . TFOS DEWS II Management and Therapy Report. Ocul Surf. 2017; 15(3):575-628. DOI: 10.1016/j.jtos.2017.05.006. View

Pucker A, Ng S, Nichols J . Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst Rev. 2016; 2:CD009729. PMC: 5045033. DOI: 10.1002/14651858.CD009729.pub2. View

Gentili V, Bortolotti D, Benedusi M, Alogna A, Fantinati A, Guiotto A . HelixComplex snail mucus as a potential technology against O3 induced skin damage. PLoS One. 2020; 15(2):e0229613. PMC: 7034816. DOI: 10.1371/journal.pone.0229613. View

Trapella C, Rizzo R, Gallo S, Alogna A, Bortolotti D, Casciano F . HelixComplex snail mucus exhibits pro-survival, proliferative and pro-migration effects on mammalian fibroblasts. Sci Rep. 2018; 8(1):17665. PMC: 6281574. DOI: 10.1038/s41598-018-35816-3. View

Mencucci R, Strazzabosco G, Cristofori V, Alogna A, Bortolotti D, Gafa R . GlicoPro, Novel Standardized and Sterile Snail Mucus Extract for Multi-Modulative Ocular Formulations: New Perspective in Dry Eye Disease Management. Pharmaceutics. 2021; 13(12). PMC: 8708832. DOI: 10.3390/pharmaceutics13122139. View

Tiwari C, Khan H, Grewal A, Dhankhar S, Chauhan S, Dua K . Opiorphin: an endogenous human peptide with intriguing application in diverse range of pathologies. Inflammopharmacology. 2024; 32(5):3037-3056. DOI: 10.1007/s10787-024-01526-8. View

Giannaccare G, Vaccaro S, Borselli M, Rossi C, Scalzo G, Scalia G . A Novel Ophthalmic Solution Containing Glicopro Complex for the Treatment of Patients with Dry Eye Disease: Results from a Pilot Study. J Clin Med. 2024; 13(5). PMC: 10932378. DOI: 10.3390/jcm13051447. View

10.

Ballesteros-Sanchez A, Sanchez-Gonzalez J, Tedesco G, Rocha-de-Lossada C, Murano G, Spinelli A . Evaluating GlicoPro Tear Substitute Derived from Snail Mucus in Alleviating Severe Dry Eye Disease: A First-in-Human Study on Corneal Esthesiometry Recovery and Ocular Pain Relief. J Clin Med. 2024; 13(6). PMC: 10971458. DOI: 10.3390/jcm13061618. View

11.

Wang H, Chen W, Huang Y, Hsu S, Tsao Y, Hsu Y . Interleukin-20 is involved in dry eye disease and is a potential therapeutic target. J Biomed Sci. 2022; 29(1):36. PMC: 9178884. DOI: 10.1186/s12929-022-00821-2. View

12.

Schiffman R, Christianson M, Jacobsen G, Hirsch J, Reis B . Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000; 118(5):615-21. DOI: 10.1001/archopht.118.5.615. View

13.

Bron A, Evans V, Smith J . Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea. 2003; 22(7):640-50. DOI: 10.1097/00003226-200310000-00008. View

14.

Schaumberg D, Gulati A, Mathers W, Clinch T, Lemp M, Nelson J . Development and validation of a short global dry eye symptom index. Ocul Surf. 2007; 5(1):50-7. DOI: 10.1016/s1542-0124(12)70053-8. View

15.

Villani E, Marelli L, Dellavalle A, Serafino M, Nucci P . Latest evidences on meibomian gland dysfunction diagnosis and management. Ocul Surf. 2020; 18(4):871-892. DOI: 10.1016/j.jtos.2020.09.001. View

16.

Efron N . Morphology of corneal nerves using confocal microscopy. Cornea. 2001; 20(4):374-84. DOI: 10.1097/00003226-200105000-00008. View

17.

Rajendraprasad R, Kwatra G, Batra N . Carboxymethyl Cellulose versus Hydroxypropyl Methylcellulose Tear Substitutes for Dry Eye Due to Computer Vision Syndrome: Comparison of Efficacy and Safety. Int J Appl Basic Med Res. 2021; 11(1):4-8. PMC: 8025960. DOI: 10.4103/ijabmr.IJABMR_399_20. View

18.

Zhang Y, Yang M, Zhao S, Nie L, Shen L, Han W . Hyperosmolarity disrupts tight junction TNF-α/MMP pathway in primary human corneal epithelial cells. Int J Ophthalmol. 2022; 15(5):683-689. PMC: 9091896. DOI: 10.18240/ijo.2022.05.01. View

19.

Cabral-Pacheco G, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuna J, Perez-Romero B, Guerrero-Rodriguez J . The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int J Mol Sci. 2021; 21(24). PMC: 7767220. DOI: 10.3390/ijms21249739. View

20.

Pflugfelder S, Farley W, Luo L, Chen L, de Paiva C, Olmos L . Matrix metalloproteinase-9 knockout confers resistance to corneal epithelial barrier disruption in experimental dry eye. Am J Pathol. 2005; 166(1):61-71. PMC: 1602302. DOI: 10.1016/S0002-9440(10)62232-8. View