Gilaise® Amino – a new combination of sodium hyaluronate and the amino acids L-lysine and L-leucine in eye drops

Dry eye syndrome (DES) is a multifactorial disease of the ocular surface caused by reduced tear secretion, excessive tear evaporation, and sometimes a combination of these key factors. According to the report of the TFOS DEWS II working group on dry eye research, in 2017 all cases of DGS were classified into two groups: meibomian gland dysfunction and dryness associated with increased tear evaporation [1]. This prompted the pharmaceutical industry to develop artificial tears containing sodium hyaluronate, as well as lipid-based formulations such as liposomes, emulsions, and ointments.

Numerous global studies on DSC indicate that the prevalence of the condition in the adult population ranges from 18 to 37%; this depends on the age group, gender of respondents, indoor air quality in homes and offices (industrial or agricultural regions), and climatic zones (heat, wind, or cold, dry air) [2]. In various studies, the number of women with DSC exceeded that of men by a factor of 1.33–1.74. The number of women with DSC in the age group >45 years increases significantly due to changes in the function of the meibomian glands during menopause [1, 3]. Age is also a very important factor in the pathogenesis of DSC, as the homeostasis of the ocular surface changes over the years: tear production and mucin secretion by goblet cells decrease, and tear film instability increases due to the use of systemic medications — such as antihypertensives, antidepressants, anxiolytics, and hormonal agents. We must not forget the group of patients with glaucoma who regularly use antiglaucoma eye drops. These drops contain not only active substances that disrupt the mucin layer and lipid emulsion on the ocular surface, but also preservatives and a buffer solution, which further reduce the stability of the tear film [3].
Patients with SSO complain of dryness, a foreign body sensation, and redness of the eyes; sometimes they are bothered by stinging and excessive tearing. It is precisely this tearing that misleads the patient, as people do not associate excessive tearing with SSO. This occurs due to the patient’s lack of awareness regarding the pathological tear-production reflex, the composition and stability of the tear film, as well as the mechanisms for retaining tears on the eye’s surface. In severe cases of SSO, not only is there a deficiency in tear volume and quality, but also an inflammatory process in the conjunctival and corneal epithelium, which exacerbates tearing and discomfort.
On the surface of the corneal epithelial membrane lies the glycocalyx—a mixture of the protein mucin, electrolytes, and water molecules; this is a positively charged layer which retains water on the negatively charged corneal epithelial membrane. Receptor protein molecules and glycoproteins on the epithelial surface in patients with SSO are in a state of damage and degradation, leading to reduced mucin adhesion and tear film stability [2]. This pathological cycle can be broken by using agents to restore tear volume and the protein layer on the epithelial surface. The latter task can be accomplished by a combined medical device in the form of Gilays® Amino eye drops, which contain sodium hyaluronate and the amino acids L-lysine and L-leucine. The combination of sodium hyaluronate, which contains numerous hydroxyl and carboxyl hydrophilic groups, with amino acids helps maintain the tear film and promotes the regeneration of glycoprotein molecules on the corneal epithelial membrane.
The aim of the study is to determine the efficacy of Gilays ® Amino in men and women with dry eye syndrome of various age groups and separately in a group of patients with glaucoma.

Materials and Methods

The study included 60 patients with SSO: Group 1 – 20 patients (40 eyes) aged 20–45 years (8 men, 12 women); Group 2 – 22 patients (44 eyes) aged ≥46 years (5 men, 17 women); Group 3 – 18 patients with glaucoma (7 men, 11 women). Among the glaucoma patients, 10 patients received monotherapy with the prostaglandin analog travoprost 0.004%,
while 8 patients used a fixed combination of travoprost 0.004% with the β-blocker timolol 0.5%. Inclusion criteria for patients in the study: complaints of dryness, redness, stinging, foreign body sensation, and excessive tearing in bright light and windy conditions; tear stability according to the Norn test (tear film break-up time using 2% fluorescein) <5 s (the average of three measurements was used); tear production volume according to the Schirmer test (without anesthesia) ≤10 mm in 5 min (Fig. 2). The condition of the corneal epithelium was assessed using the instillation fluorescein test on a scale from 0 to 3, where 0 indicates no staining of the epithelium, 1 indicates mild damage (staining of < ⅓ of the epithelium), 2 – moderate (>⅓, but less than half of the epithelial area is stained), 3 – significant (more than half of the epithelium is stained with fluorescein). These tests were performed before treatment and 4 and 8 weeks after the start of treatment.

All patients were asked to complete a questionnaire consisting of 12 questions, modeled after the Ocular Surface Disease Index (OSDI) [4]. The results were scored on a scale from 0 to 100 points. The study included patients with moderate to severe symptoms of SSO, corresponding to a score of ≥30 on the assessment scale. The survey was conducted once before enrolling patients in the trial. Patients had not used artificial tears or sodium hyaluronate preparations for the past 3 months.
For the treatment of DSC, Gilays® Amino eye drops were prescribed twice daily throughout the entire observation period. Statistical analysis was performed using SPSS for Windows (ver. 23), yielding numerical values for the arithmetic mean (m) and standard deviation (SD) (Table). Pre- and post-treatment indicators were compared using Student’s t-test; a difference was considered statistically significant at a p-value <0.05.

Results
In Group 1, among patients aged 20–45 years with a daily computer screen exposure of 6–8 hours, the level of complaints on the OSDI scale was moderate and amounted to 39.17 ± 9.12; baseline tear status indicators were as follows: Norn test – 4.52 ± 1. 27 s, Schirmer test – 15.76 ± 2.93 mm, fluorescein test – 2.02 ± 1.04. Only the Schirmer test was within normal limits, indicating preserved tear volume in participants of this age group.
After 4 weeks of treatment, the results were as follows: Norn test – 5.76 ± 1.41 s (p > 0.05), Schirmer test – 16.32 ± 3.14 mm (p > 0.05), fluorescein test – 2.38±0.29 (p>0.05), indicating a trend toward improved tear stability and quality of the corneal glycocalyx. The degree of damage to the corneal epithelium was insignificant and remained virtually unchanged.
The second stage of measuring tear stability and tear production was conducted 8 weeks after the start of treatment (1 patient dropped out of the study during this period). The Norn test result was 7.89±2.73 s, which differed significantly from the baseline value (p<0.05). The Schirmer test and fluorescein test values after 8 weeks of treatment were within normal limits and amounted to 16.89 ± 2.73 mm (p > 0.05) and 1.95 ± 1.12 (p > 0.05), respectively . These results may indicate good reparative capabilities of the corneal epithelium, presumably due to mucin production, in individuals aged 20–45 years following the use of Gilays®Amino eye drops despite significant visual strain during the workday.

In Group 2, which consisted of patients aged ≥46 years, predominantly women, the baseline level of subjective dryness on the OSDI scale was 58.26±21.27, indicating significant eye discomfort. The Norn test score was 3.18±1.51 s —lower than that in younger patients (4.52±1.27 s).
After 4 weeks of treatment, the Norn test time increased significantly to 6.76 ± 1.05 s (p < 0.05); after 8 weeks, it remained virtually unchanged at 6.99 ± 3.08 s (p < 0.05 compared to the baseline value). Tear production as measured by the Schirmer test was significantly reduced at the start of the study and amounted to 6.69 ± 2.94 mm; after 4 weeks of treatment, this value improved non-significantly to 9.73 ± 3.19 mm (p > 0.05) .
Complaints of a foreign body sensation persisted in 5 patients, which necessitated changing the instillation regimen of Gilays® Amino drops to 3 times daily for all patients in this group; this treatment continued from the 5th to the 8th week, after which a significant increase in the Schirmer test was observed—to 14.52±1.02 mm (p<0.05) . The fluorescein test in Group 2 was 3.30 ± 0.21 before treatment, 3.63 ± 0.16 after 4 weeks of treatment (p > 0.05), and 2.50 ± 0.53 after administration of the drops 3 times daily (p > 0.05). Thus, patients in the middle-aged and older age groups likely require three-times-daily administration of the study drops to stabilize tear production, improve the mucin layer, regenerate the glycocalyx, and maintain tear film volume.
Among the participants in Group 3, 16 individuals showed, upon biomicroscopic examination of the conjunctiva, erosion and hyperemia of the mucosal surface, as well as significant dilation of the conjunctival and superficial episcleral vessels—a finding typical of prolonged prostaglandin exposure to ocular vessels. The subjective sensation of dryness and discomfort on the OSDI scale was the highest among all groups and amounted to 63.81±17.22.
The baseline value of the Norn test was the lowest at 1.54 ± 1.17 s (with a normal range of ≥5 s), while the Schirmer test, conversely, was the highest (18.13 ± 5.72 mm); this indicates excessive tear production but low tear stability on the ocular surface. The fluorescein test showed the highest value—3.05 ± 1.01: numerous punctate areas of damaged epithelium were observed.
After 4 weeks of using Gilays®Amino twice daily, the results of the Norn and Schirmer tests improved slightly and amounted to 1.68 ± 1.22 s (p > 0.05) and 20.95 ± 8.24 mm (p > 0.05), respectively . From the 5th to the 8th week of treatment, Gilays® Kea—an isotonic ophthalmic ointment based on vaseline oil and 0.4% sodium hyaluronate—was prescribed for additional tear stabilization. Patients used Gilays® Kea was used by patients once daily in the evening, 10 minutes after instillation of antiglaucoma eye drops.
By the end of the 8th week of treatment, complaints of tearing and a foreign body sensation had decreased. The Norn test showed virtually no change and was 2.89±1.15 s (p<0.05), which can be explained by the prolonged effect of prostaglandins and preservatives on the corneal glycocalyx. The Schirmer test also remained virtually unchanged at 19.68 ± 7.17 mm (p > 0.05), while the fluorescein test decreased slightly to 2.74 ± 0.43 (p > 0.05). Although the data on positive dynamics are not statistically significant, they may indicate good therapeutic potential for the combination of sodium hyaluronate with the amino acids L-lysine and L-leucine in Gilays®Amino eye drops.

Conclusions
During the study, patients aged 20–45 years with SSO (Group 1) were found to have preserved tear volume on the Schirmer test and tear film instability on the Norton test and fluorescein test. After 4 weeks of treatment, these objective indicators changed insignificantly, but after 8 weeks, a significant improvement in the Norton test was observed even during prolonged computer use.
Group 2 (patients aged ≥46 years) was characterized by a significant decrease in tear stability and volume; women aged 46–55 years reported particular discomfort. The use of Gilays®Amino twice daily for 1 month did not provide complete subjective comfort or restore the Norna and Schirmer test results. In contrast, the administration of drops 3 times daily for the second month was accompanied by stabilization of the tear film (according to the Norn test) and an increase in tear production (according to the Schirmer test).
In patients with glaucoma (Group 3), tear instability was combined with simultaneous excessive tear production, as evidenced by Schirmer test results within the normal range despite a short tear film break-up time according to the Norn test. In this group, the combined use of Gilays® Amino eye drops and Gilays® Kea ointment during the second month of treatment was accompanied by stabilization of the tear film (as measured by the Norn test).

Gilaise® Amino is a new medical device in the form of preservative-free eye drops designed to relieve symptoms of dry eyes. Sodium hyaluronate, in combination with amino acids, forms a protective film on the surface of the eye, providing protection and hydration. Sodium hyaluronate “adheres” to the surface of the eye, forming a structure that binds water molecules, while the presence of amino acids helps improve its distribution and adhesion to the corneal surface, thereby promoting hydration and protection of the cornea. Thanks to these properties, Gilays® Amino helps break the vicious cycle of ocular surface damage in cases of SSO.

The list of references is available from the editorial office