Possibilities of restoring precorneal tear film in patients with dry eye syndrome: results of an observational clinical program

Hyaluronic acid (HA) is a key component of the treatment of dry eye syndrome. The cross-linked HA has improved mechanical and rheological properties compared to conventional HA, which ensures a longer stay on the eye surface. Modern products with cross-linked HA provide longer-lasting hydration and with a lower frequency of instillations. However, for effective treatment of dry eye syndrome (DES), it is important to additionally stabilize the lipid layer of the tear film (TF) to reduce its evaporation. Okostill Ultralong is a new generation of longacting moisturizing eye drops due to its innovative composition which has an effect on all layers of the TF. It contains three active ingredients: cross-linked high molecular weight HA, phospholipids and propylene glycol.

Purpose of the work: to study the efficacy and evaluate the safety of using Ocostill Ultralong in patients with mild to moderate DES in comparison with Gilan Comfort (0.18% sodium hyaluronate solution).

Material and methods. The clinical observation included 80 patients (160 eyes) with mild and moderate DES. The patients were randomized into 2 groups, in which the efficacy and safety of two tear substitutes with different formulations were compared 40 min after the first instillation and after 30 days of daily use.

Results. After long-term use (30 days) of moisturizing drops of a three-component composition containing phospholipids and cross-linked HA, patients noted a decrease in the severity of dry eye sensations by 69%, a feeling of “sand” in the eyes by 88.6%, lacrimation by 90%, and hyperemia by 81%. Also in this group, was noted an increasing TF stability in 34.5% in the short term and in 41.7% after 30 days of regular use.

Conclusion. The combined effect of 3 components in the composition of moisturizing drops: cross-linked HA, phospholipids and propylene glycol, helps to stabilize the TF by affecting all its layers (lipid, aqueous, mucin). The stability of the TF increases by more than 40% and there was a decrease of clinical manifestations of DES.

1. Jones L, Downie LE, Korb D, et al. TFOS DEWS II Management and therapy report. Ocular Surface. 2017; 15: 575–628. doi: 10.1016/j.jtos.2017.05.006

2. Brzheskiy V.V., Egorova G.B., Egorov E.A. Dry eye syndrome and ocular surface diseases: clinic, diagnosis, treatment. Moscow: GEOTAR-Media; 2016 (In Russ.).

3. Brzheskiy V.V., Bobryshev V.A. Possibilities of reparative therapy in the treatment of patients with xerotic changes in the cornea. Ophthalmology reports. 2024; 17 (1): 63–70 (In Russ.). doi: 10.17816/OV625682

4. Brzheskiy V.V., Drozdova E.A., Bobryshev V.A., Berdnikova E.V., Golubev S. Yu. New possibilities for reparative therapy of dry eye syndrome. Vestnik oftal’mologii. 2024; 140 (1): 58–64 (In Russ.). https://doi.org/10.17116/oftalma202414001158

5. Posarelli C, Passani A, Del Re, et al. Cross-linked hyaluronic acid as tear film substitute. Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics. 2019; 35 (7): 381–7. https://doi.org/10.1089/jop.2018.0151

6. Schiraldi C, La Gatta A, De Rosa M. Biotechnological production and application of hyaluronan. In: Elnashar M, editor. Biopolymers. Sciyo; 2010: 387–412. http://dx.doi.org/10.5772/286

7. Rosenbaum D, Peric S, Holecek M, Ward HE. Hyaluronan in radiation-induced lung disease in the rat. Radiat Res. 1997 May; 147 (5): 585–91. PMID: 9146704.

8. Brzheskiy V.V., Bobryshev V.A., Kim G.G. The evolution of artificial tears based on hyaluronic acid. Medicinskij sovet. 2023; 17 (23): 303–9 (In Russ.). doi:10.21518/ms2023-430

9. Becker LC, Bergfeld WF, Belsito DV, et al. Final report of the safety assessment of hyaluronic acid, potassium hyaluronate, and sodium hyaluronate. Intern J Toxicol. 2009; 28 (4S): 5–67. doi:10.1177/1091581809337738

10. Brzheskiy V.V., Кim G.G., Bobryshev V.А. Modern possibilities of tear film stability restoration. Russian journal of clinical ophthalmology. 2024; 24 (3): 151–7 (In Russ.). doi: 10.32364/2311-7729-2024-24-3-7

11. Fallacara A, Manfredini S, Durini E, Vertuani S. Hyaluronic acid fillers in soft tissue regeneration. Facial Plast Surg. 2017; 33: 87–96. doi:10.1055/s-0036-1597685

12. Schramm C, Spitzer MS, Henke-Fahle S, et al. The crosslinked biopolymer hyaluronic acid as an artificial vitreous substitute. Invest Ophthalmol Vis Sci. 2012; 53: 613–21. doi: 10.1167/iovs.11-7322

13. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II Definition and classification report. Ocular Surf. 2017 Jul; 15 (3): 276–83. doi: 10.1016/j.jtos.2017.05.008

14. Schiffman R, Christianson D, Jacobsen G, et al. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000 May; 118 (5): 615–21. doi: 10.1001/archopht.118.5.615

15. Norn MS. Dessication of the precorneal film. I. Corneal wetting time. Acta Ophthalmol (Copenh). 1969; 47 (4): 865–80. doi: 10.1111/j.1755-3768.1969.tb03711.x