L-Carnitine and Short Chain Ester in Tears from Patients with Dry Eye

Purpose: to evaluate the effectiveness of approaches to tear substitution in dry eye syndrome (DES) patients before cataract phacoemulsification (CPE). Material and methods. 60 DES and cataract patients who received preoperative therapy — tear substitute instillations (4 times a day, 1 month), were examined before CPE. They were divided into 2 groups each of which was subdivided into two subgroups. Group 1 included 30 mild DES patients with lipid deficiency who had a negative lipid interference test, meibomian gland dysfunction (MGD), and aqua deficiency absence (Schirmer-1 test > 15 mm). The subgroup 1.1 (15 patients) received 0.18 % sodium hyaluronate (SH) instillations (Gilan comfort), while the other subgroup 1.2 received “fat-water” type emulsion instillations. Group 2 consisted of 30 moderate DES patients with lipid-aqua deficiency, who also had negative lipid interference test, MGD, and aqua deficiency presence. Subgroup 2.1 (15 patients) received 0.3 % sodium hyaluronate (SH) instillations (Gilan ultra comfort), while subgroup 2.2 patients received “fat-water” type emulsion instillations. We evaluated: the OSDI points, and tear break-up time (TBUT). Results. As a result of therapy, a positive effect of the therapy on OSDI and TBUT was observed in all subgroups. In group 1 , OSDI decrease and TBUT increase were more pronounced in subgroup 1.1 patients, however, this difference between subgroups was not statistically significant. In group 2, OSDI decrease and TBUT increase were more pronounced and statistically significant in subgroup 2.1 patients. Conclusion. In patients with mild DES and lipid deficiency, 0.18 % SH (Gilan comfort) demonstrated a positive effect on OSDI and TBUT comparable to the “fat-water” type emulsion. In moderate DES patients with lipid-aqua deficiency, 0.3 % SH (Gilan ultra comfort) demonstrated a statistically significant and more pronounced positive effect on OSDI and TBUT than the “fat-water” type emulsion.

Purpose: To evaluate tear film osmolarity in patients with systemic lupus erythematosus (SLE). Methods: A total of 55 eyes from 55 patients with SLE and 47 eyes from 47 age- and gender-matched healthy individuals were included in this study. Tear film osmolarity was evaluated with a lab-on-a-chip technique (TearLab; TearLab Corporation, San Diego, CA) in SLE patients in comparison with healthy individuals, and results were correlated to clinically available diagnostic tests for dry eye, such as tear film break-up time (BUT), Schirmer’s test, and Ocular Surface Disease Index (OSDI). Results: The mean tear film osmolarity in the SLE patients and healthy individuals was 306.02 ± 13.27 mOsm/L and 300.74 ± 9.11 mOsm/L, respectively, which made for a statistically significant difference (p = 0.020). In the SLE group, tear film osmolarity was negatively correlated with the Schirmer’s test score and the BUT value (r = −0.295 p = 0.029 and r = 0.347 p = 0.009, respectively), whereas tear film osmolarity was not correlated with OSDI score (r = −0.182 p = 0.183). Conclusions: This study revealed that tear film hyperosmolarity and abnormal tear film function are associated with SLE.

Dry eye syndrome is a global problem of the modern world. Overload of information, rapid urbanization, and a busy lifestyle lead to non-compliance with work and rest schedules, including increased visual loads, decreased stress resistance in conditions of time deficit, leading to a deficiency of vital substances in the body. All the above are risk factors for the development of dry eye syndrome and affect the course of this disease. It is a well-known fact that balanced nutrition, regular intake of vitamins and microelements with food, and compliance with work and rest schedules play a role in the prevention and elimination of clinical manifestations of these conditions. This article presents the results of using the biologically active food supplement “DOPPELHERZ® V.I.P. OFTALMOVIT No. 30” (manufacturer Queisser Pharma GmbH & Co. KG, Germany) in the treatment of dry eye syndrome. The purpose of the study: to evaluate the effect of the dietary supplement “DOPPELHERZ® V.I.P. OFTALMOVIT no. 30” in the treatment of dry eye syndrome. Material and methods. The study included 90 students with dry eye syndrome, aged 18 to 26 years. Patients of group I (control) did not receive any dietary supplements; group II (study group) received the dietary supplement “DOPPELHERZ® V.I.P. OFTALMOVIT”. Results. OSDI questionnaire — in the study group, the severity of dry eye syndrome: “before” moderate n = 38, severe n = 22, “1 month” moderate n = 43, severe n = 17, “2 months” mild n = 11, moderate n = 43, severe n = 6, in the control group no changes ( p = 0.368). Norn’s test: the study group showed an increase in tear film breakup time ( p < 0.001), no changes were recorded in the control group ( p = 0.285). Lacrimal meniscus height: the study group showed an increase in the height of the lacrimal meniscus, which indicates an improvement in the functional properties of the tear film and a decrease in dry eye syndrome ( p < 0.001), no changes were recorded in the control group ( p = 0.105). Schirmer tests 1 and 2: the study group showed an increase in the tear film breakup time, which indicates an improvement in the functional properties of the tear film and a decrease in dry eye syndrome, no changes were recorded in the control group (RSH1 = 0.587, RSH2 = 0.293). CISS questionnaire: a gradual decrease in the severity of asthenopia signs was observed in the study group ( p < 0.001), no changes were recorded in the control group ( p = 0.125). Pupillography: in the study group, regression of accommodation tension was recorded, more pronounced after 2 months ( p < 0.001), in the control group there was a change in accommodation tension, which can be associated with the alternating predominance of sympathetic and parasympathetic wagging ( p < 0.05). Discussion. The concept of dry eye syndrome treatment includes etiopathogenetic, non-specific and symptomatic therapy. An integral link in the strategy of pathogenetic treatment of dry eye syndrome is the targeted introduction of vitamins and microelements into the diet. Conclusion. Based on the results of the study, as well as on the data of foreign and domestic authors, dietary supplements can serve as an additional source of vitamins and microelements, the deficiency of which is one of the components of the causes of dry eye syndrome pathogenesis. Considering the above, we can recommend taking the dietary supplement “DOPPELHERTS ® V.I.P. OFTALMOVIT” 1 capsule once a day for 2 months in the complex therapy of patients with dry eye syndrome.

Introduction. The officinal dosage of dexamethasone solution (0.1%) has a marked localized antiinflammatory effect. But the widespread use of this dose in the management of dry eye diseases is limited by the risk of damage to the cornea. Therefore, the authors developed a solution containing 0.01% dexamethasone phosphate in combination with 6% polyvinylpyrolidone and 1.5%–5.5% dextrose [3]. Aim. To study the effects of this novel anti-inflammatory solution on corneal inflammatory processes. Materials and methods. This study included a cohort of 25 patients (50 eyes) with corneal–conjunctival xerosis. Lower tear meniscus index, precorneal tear film production, stability and osmolarity, and the degree of staining of the ocular surface epithelium with vital solutions were assessed prior to the treatment and on day 28 of the study. The presence of the cytokines IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-1Ra, TNF-α, INF-α, and INF-γ in patients’ tear fluid and blood plasma was quantified using ELISA. All patients were asked to complete a questionnaire to evaluate subjective signs of xerosis of the ocular surface. Results. Statistically significant increases in tear meniscus index, precorneal tear film stability, and main and total tear production, with a significant decrease in tear film osmolarity were observed by day 28 of the study. In addition, positive changes in objective parameters relating to the ocular surface epithelium were further confirmed by the patients’ evaluations of their quality of life. Furthermore, the degree of staining of the ocular surface epithelium with vital solutions also decreased. Conclusions. The results of the study demonstrate the high level of effectiveness of the developed medication as a treatment for dry eye diseases of various etiologies.

It is well-known that diabetes is one of the major causes of dry eye disease (DED). As DED can lead to serious ocular surface complications such as punctate keratitis, corneal erosion, corneal scarring, corneal perforation and visual loss, research is ongoing to investigate ways of improving the diagnosis of DED in patients with diabetes. This thesis investigated the role of inflammatory cytokines and metabolic proteins in tear fluid as a non-invasive, objective measure of inflammation in the diagnosis of type 2 diabetes (T2D)-related DED. In this thesis, a number of studies were performed to investigate potential tear fluid biomarkers and comparing them to the established clinical and laboratory measures used in DED diagnosis. It was important to evaluate the clinical behaviours of eye care professionals, such as ophthalmologists and optometrists with respect to the diagnosis and management of diabetes-related DED (Chapter 3). Thus, the online survey was conducted among 194 eye care professionals who work in the UK and Mongolia, to evaluate and compare their preferences for specific clinical procedures used to diagnose the presence of DED in diabetes. For example, how these may differ, depending on the practitioners' profession (ophthalmologist and optometrist) and the countries they work in. This study is the first time that the awareness of eye care professionals in the diagnosis and the management of diabetes-related DED in different regions of the world has been investigated. The results of the survey showed that eye care professionals in both countries have similar practice behaviours for diagnosing and treating diabetes-related DED. That is, ophthalmologists in the UK and in Mongolia have similar practice behaviours in diagnosing diabetes-related DED, and its severity, as for optometrists in the UK. Before commencing the studies to analyse protein biomarkers in tear fluids, it was important to establish the best possible means of sampling and storing tear samples, along with the optimal method of analysing them (Chapter 4). Therefore, a study was conducted to investigate the methodology of tear sampling, storage, analysis, sample centrifugation duration and speed. For tear biomarker assessment, a pilot study investigating the detectability of metabolic proteins in 1 μl tears was conducted (Chapter 5). This study is the first time that metabolic proteins such as Leptin, Insulin, C-peptide, GIP and active Ghrelin, have been shown to be detected in human tears collected from “healthy” individuals using Luminex Xmap technology. The results of this study showed that Leptin could be used in the future as a potential diagnostic biomarker of ocular surface disorders and, possibly, in determining the effects of metabolic disorders, as it has a low intra-subject confidence interval (CI) and a high intra-class correlation coefficient (ICC). A pilot study investigating the correlation between the presence of tear fluid inflammatory cytokines and tear fluid stability (assessed using tear evaporation rate [TER]; and non-invasive tear break-up time [NITBUT]) in healthy subjects was carried out (Chapter 6). This study also investigated the effect of time of day on TER and NITBUT values, and its possible correlation with tear cytokine concentrations in healthy subjects. The results revealed that the NITBUT and TER values had no significant variability over a day, or on different days, in healthy subjects, when the humidity and temperature of the examination room were constant. However, some tear fluid cytokine concentrations did show inter- and intra-day variability, without any consistent correlation with TER diurnal variation. Before commencing the study in a large cohort, a pilot study investigating the detectability of inflammatory cytokines and metabolic proteins in 1 μl tears collected from patients with type 2 diabetes (T2D; with and without DED) and DED-only (without T2D) was conducted (Chapter 7). The concentrations of 14 inflammatory cytokines, six metabolic proteins, ocular surface parameters, DED-related symptoms and quality of life (QoL) were evaluated and compared in a total of 122 subjects divided into four study groups as: T2D with DED, T2D-only (without DED), DED-only (without T2D) and healthy controls (Chapter 8). Overall, the results of this study showed that the ocular surface parameters and DED-related symptoms were similar for patients in the T2D+DED group and the DED-only group. In addition, patients in the T2D-only group had similar ocular surface parameters to healthy controls. Tear fluid Interleukin (IL)-6 and IL-8 concentrations were significantly higher in the T2D+DED group than the T2D-only group, DED-only group and healthy controls, which suggests that IL-6 and IL-8 could potentially be diagnostic biomarkers of T2D-related DED. These studies show that tear fluid biomarker analysis is feasible and it can be utilised in the objective diagnosis of T2D-related DED. This research helps to improve the understanding of the inflammatory mechanisms and markers of DED in T2D. However this complex process will require further research to identify the most appropriate biomarkers.

Dry eye disease (DED) is a multifactorial disorder in which tear fluid homeostasis is lost, resulting in increased tear film osmolarity and ocular surface irritation. In Asia, the short tear film breakup time-type DED, which has become a global problem in recent years, is common. While the mainstay of DED treatment in the West is the suppression of inflammation, the first goal of treatment is the stabilization of the tear film in Asia. To date, artificial tears and steroid eye drops have been the main treatment for DED. However, artificial tears require frequent administration of eye drops and thus pose adherence problems, while steroids have problems with side-effects (cataracts, increased intraocular pressure). This review evaluates the new generation therapies in Asia based on what is known about them and demonstrates that they are more effective for DED than traditional therapies such as artificial tears and steroids. Based on considerations, it is proposed that the optimal treatment for the short tear film breakup time-type DED is the initial application of mucin-secretion-enhancing eye drops (long-acting diquafosol) and oral supplements; and if additional treatment is needed, cyclosporine eye drops and the adjunctive therapies presented in this review are added.

Background.The prevalence of dry eye syndrome (DES) tends to further increase due to the widespread introduction of keratorefractive surgeries, the active use of computers, air conditioners, contact vision correction devices, and the spread of general diseases of the body. Assessing the clinical effectiveness of modern moisturizing and lubricating solutions for eye protection is an urgent scientific task in the framework of improving the treatment of dry eye syndrome. Purpose. To evaluate the clinical efficacy of the medicine “Thealoz” in the treatment of patients with dry eye syndrome. Material and methods. 34 patients (68 eyes) took part in the study. All patients were divided into two groups: group 1 – mild degree of DES (grade I), 22 eyes (32.35 %); group 2 – moderate degree of DES (II degree), 46 eyes (67.65 %). For the treatment of dry eye syndrome, the medicine “Thealoz” was used – 1 drop 3 times a day, for 1 month. The observation period was 1 month. Results.After a month of using the medicine, patients in both groups noted a significant improvement in the condition of the ocular surface. Almost complete restoration of the tear film was noted in patients of both groups. Evaluation of the results of the Schirmer test showed a significant decrease in total and main tear production to normal values. Conclusion.The use of the medicine “Thealoz” in the treatment of mild and moderate dry eye syndrome for 1 month increases the stability of the tear film (up to 36 %) and thereby helps to reduce subjective and objective signs of xerosis of the ocular surface. Keywords:dry eye syndrome, keratoconjunctivitis, eye protection solution, trehalose

The cornerstone of managing dry eye syndrome (DES) remains the administration of artificial tear substitutes, the selection of which is challenging due to their extensive diversity. A rational therapeutic approach necessitates accounting for the nature of ocular surface changes and the severity of DES. According to TFOS DEWS II (2017) recommendations, DES may be categorized as evaporative DES due to increased tear film instability, corresponding to mild DES as per the classification of V.V. Brzeski et al. (2016), or aqueous-deficient DES, which corresponds to moderate, severe, and particularly severe forms of DES. Furthermore, the ADES (2020) guidelines describe an additional subtype of DES linked to reduced corneal wettability associated with membrane-associated mucin deficiency (e.g., conjunctival and corneal epitheliopathy). Based on these diagnostic frameworks, the treatment of mild evaporative DES typically involves the use of lipid-based agents that stabilize the lipid layer of the tear film or artificial tear substitutes that increase viscosity to counteract the excessive aqueous component of the tear film, with products such as hyaluronic acid (HA)-based formulations. In cases of aqueous-deficient DES, the treatment tactics focus on restoring the aqueous-mucin component of the tear film by utilizing agents that enhance viscosity. Such agents are commonly delivered as fixed combinations (FC) of HA and compounds that improve the qualitative and quantitative characteristics of the tear film. For severe epitheliopathy, it is advisable to incorporate additional agents that interact with the damaged epithelium to modify the ocular surface or employ reparative agents to facilitate tissue recovery. In mixed forms of DES, FC are suitable, including formulations that simultaneously replace both the lipid and aqueous-mucin layers of the tear film, osmoprotective agents, and components that directly influence the ocular surface epithelium. KEYWORDS: dry eye syndrome, evaporation, aqueous deficiency, mucin deficiency, hyaluronic acid, polyethylene glycol, triglycerides, carbomer, dexpanthenol. FOR CITATION: Yanchenko S.V., Odilov M.Yu., Kharibova E.A., Malyshev A.V., Teshaev Sh.Zh., Davlatov S.S., Shonazarov A. Differentiated approaches to correcting the condition of the ocular surface in dry eye syndrome: a literature review. Russian Journal of Clinical Ophthalmology. 2025;25(2):109–116 (in Russ.). DOI: 10.32364/2311-7729-2025-25-2-5

Exploring topical anti-glaucoma medication effects on the ocular surface in the context of the current understanding of dry eye

Tear Film and Ocular Surface Changes in a Rabbit Model of Neurotrophic Keratitis

To evaluate the tear film osmolality and electrolyte composition in healthy horses. 15 healthy adult horses. Each horse was manually restrained, and an ophthalmic examination, which included slit-lamp biomicroscopy, indirect ophthalmoscopy, and a Schirmer tear test, was performed. Tear samples were collected from both eyes with microcapillary tubes 3 times at 5-minute intervals. The tear samples for each horse were pooled, and the osmolality and electrolyte concentrations were measured. The mean (SD) was calculated for each variable to establish preliminary guidelines for tear film osmolality and electrolyte composition in healthy horses. The mean (SD) tear film osmolality was 283.51 (9.33) mmol/kg, and the mean (SD) sodium, potassium, magnesium, and calcium concentrations were 134.75 (10), 16.3 (5.77), 3.48 (1.97), and 1.06 (0.42) mmol/L, respectively. The sodium concentration in the tear film was similar to that in serum, whereas the potassium concentration in the tear film was approximately 4.75 times that of serum. Results provided preliminary guidelines with which tear samples obtained from horses with keratopathies can be compared. Measurement of tear film osmolality in these horses was easy and noninvasive. The tear film concentration of divalent cations was greater than expected and was higher than the divalent cation concentrations in the tear films of rabbits and humans. These data may be clinically useful for the diagnosis and monitoring of hyperosmolar ocular surface disease in horses.

Lacrimal Gland in Sjögren's Syndrome

Background. Currently, the health status of the population in the Aral Sea region should be considered with reference to long-term effects of environmental pollution – air, soil and drinking water containing toxic salts. As per results of the analysis of primary eye diseases in the Southern Aral Sea region, it was revealed that the main cause of conjunctivitis were chemical and physical exogenous irritation factors, such as dust, smoke and exposure to salt and sand storms that create a favorable environment for infection and development of secondary Dry Eye Syndrome. Purpose. To optimize treatment of secondary Dry Eye Syndrome (DES) in patients with chronic conjunctivitis in the South Aral Sea region. Materials and Methods. The research included 62 patients (120 eyes) with chronic conjunctivitis, aged 35–62 years, who had been observed in an outpatient clinic for the last 3 years, with signs of DES. All studied patients were divided into 2 groups by random sampling after preliminary adequate antibacterial and anti-inflammatory therapy. The control group (20 patients, 40 eyes) was instilled with Tsinosol antiseptic (composition: zinc sulphate, boric acid, Aseptic) – 2 drops 3 times a day, during 30 days. Patients of the main group (42 patients, 80 eyes) were instilled with Tsinosol antiseptic (2 drops 3 times a day) and Keratrop artificial tear (AT) eye drops (composition: sodium carmellose, glycerin, levocarnitine, erythrol, firma Aseptica) – 2 drops 3 times a day, during a month. All patients underwent standard ophthalmological tests, and special tests were carried out to verify DES, including Schirmer, Norn and Jones tests. Lower lacrimal meniscus height and the severity of the conjunctival fold were also determined. Results. Studies have shown that in the main group, both subjective and objective signs of the disease significantly decreased compared with the baseline and with the respective parameters of the control group, and a significant improvement in the stability of the tear film was noted. Conclusion. To optimize the therapy of secondary DES, it is necessary to include artificial tear eye drops in the treatment regimen in general, and consider using Keratrop eye drops in particular.

The aim of this review is to summarize the results of a consensus meeting held by a group of experts in dry eye disease (DED) to discuss the importance of tear substitutes in the treatment of DED. The meeting focused especially on the main characteristics of lacrimal substitutes, the development of in vitro models to investigate DED pathophysiology and treatment, the importance of conducting rigorous clinical trials, the requirements of the upcoming European Legislation on medical devices, the advances in the formulation of safer preservatives, the peculiarities of treatment in younger subjects, and the importance of an updated terminology for lacrimal substitutes. A literature search was conducted using MEDLINE, with different combinations of pertinent keywords, depending on the subject under discussion, such as "dry eye disease"; "tear substitutes"; "in vitro models"; "ocular surface"; "clinical trials"; "European Regulation"; "preservatives" "younger patients". Also, each author included in the discussion selected articles from their personal library. Using a consensus-based method called nominal group technique to reach a conclusion and proposal for a new classification of eye drops used to improve the tear film and ocular surface epithelia, the experts also conducted a round table meeting. The new terms proposed by the authors are "wetting agents", "multiple-action tear substitutes" or "ocular surface modulators". The new classification is needed to distinguish eye drops used to improve the tear film and ocular surface epithelia, in line with the new definition of DED, which recognizes the loss of ocular homeostasis, and the creation of a vicious circle of chronic inflammation and ocular damage as fundamental aspects of DED pathophysiology. Although tear substitutes have been historically used to provide eye lubrication to the ocular surface, recent advances in the pathophysiology of dry eye disease (DED) clarified that treatment should not just focus on tear film quality or quantity, but address the loss of homeostasis of the ocular surface, blocking the vicious circle of chronic inflammation and ocular damage. Given the scant comparative evidence on tear substitutes currently on the market, further studies should focus on developing new agents, considering the advantages provided by in vitro models, importance of conducting rigorous clinical trials, availability of less harmful preservatives and obligations related to the new European legislation on medical devices. Based on the discussion of these topics, a group of experts held a consensus meeting to identify new and more appropriate terms for different tear substitutes. The proposed terms are wetting agents, multiple-action tear substitutes and ocular surface modulators. Regardless of the agent used, it is important to note that tear substitutes represent one of many options for DED treatment, which should not overlook the psychological aspects of the disease and the peculiarities of younger subjects, who seem to have a higher risk for DED, possibly related to digital devices excessive use.

Seeing through tears: Understanding and managing dry eye disease.