Lipid Layer Research Articles

An Esterase-Responsive SLC7A11 shRNA Delivery System Induced Ferroptosis and Suppressed Hepatocellular Carcinoma Progression.

Ferroptosis has garnered attention as a potential approach to fight against cancer, which is characterized by the iron-driven buildup of lipid peroxidation. However, the robust defense mechanisms against intracellular ferroptosis pose significant challenges to its effective induction. In this paper, an effective gene delivery vehicle was developed to transport solute carrier family 7 member 11 (SLC7A11) shRNA (shSLC7A11), which downregulates the expression of the channel protein SLC7A11 and glutathione peroxidase 4 (GPX4), evoking a surge in reactive oxygen species production, iron accumulation, and lipid peroxidation in hepatocellular carcinoma (HCC) cells, and subsequently leading to ferroptosis. This delivery system is composed of an HCC-targeting lipid layer and esterase-responsive cationic polymer, a poly{N-[2-(acryloyloxy)ethyl]-N-[p-acetyloxyphenyl]-N} (PQDEA) condensed shSLC7A11 core (G-LPQDEA/shSLC7A11). After intravenous (i.v.) injection, G-LPQDEA/shSLC7A11 quickly accumulated in the tumor, retarding its growth by 77% and improving survival by two times. This study is the first to construct a gene delivery system, G-LPQDEA/shSLC7A11, that effectively inhibits HCC progression by downregulating SLC7A11 expression. This underscores its therapeutic potential as a safe and valuable candidate for clinical treatment.

Evaluation of tear film in patients with AIDS without opportunistic ocular infections in the era of COVID-19: A case-control study.

The assessment of tear film and ocular surface conditions in patients with acquired immunodeficiency syndrome (AIDS) has been poorly studied thus far. We aim to assess tear film parameters, ocular surface characteristics, and dry eye disease (DED) symptoms of patients with AIDS who did not undergo highly active antiretroviral treatment (HAART). This case-control study included 154 age-, sex-, and ethnicity-matched healthy controls and patients with AIDS. All participants underwent comprehensive ocular surface assessment and subjective DED symptomology evaluation. Data were collected between March 2022 and July 2022. HAART-naïve patients with AIDS had a shorter noninvasive tear film breakup time (median 3.76 vs. 8.54 s), thinner tear film lipid layer thickness (median 73.00 vs. 91.00 nm), and lower Schirmer I test values (median 5.00 mm/5 min vs. 12.00 mm/5 min) (all P < 0.001). Moreover, higher corneal fluorescein staining scores (median 1.00 vs. 0.00) and higher upper, lower, and total meibomian gland grades were observed in AIDS patients (all P < 0.05). Negative correlations between the blood viral load and the Ocular Surface Disease Index score ( r = -3.50, P = 0.027) and the Schirmer I test score ( r = -0.374, P = 0.017) were detected in patients with AIDS. Altered tear film status was observed in individuals with HAART-naïve AIDS, even when there were no other ocular symptoms present. Therefore, patients with AIDS should be encouraged to undergo comprehensive ocular surface examinations to detect any subclinical tear film alterations occurring.

Real-time tracking of the adsorption of bovine serum albumin on lipid layer and its effect on lipolysis by optical interferometry

The model proteins bovine serum albumin (BSA) and lipid layer were used to study the effect of proteins on lipolysis. A lipid layer with an interference effect was constructed by loading the triolein into the silica colloidal crystal (SCC) film. The ordered porous layer interferometry (OPLI) system was used to track the changes in lipid layer mass caused by lipase hydrolysis to achieve real-time lipolysis detection. The real-time tracking of the adsorption of BSA on the lipid layer by converting the migration of interference fringes caused by the change of the lipid layer into the optical thickness change (ΔOT). The effect of BSA on the early and late stages of lipolysis was studied, and lipases containing 5 mg/mL BSA degraded the lipid layer 3.4 times faster than lipases containing 0.1 mg/mL BSA in the later stages. This study deepens the understanding of protein-lipid interactions in complex digestive environments.

Implicit model to capture electrostatic features of membrane environment.

Membrane protein structure prediction and design are challenging due to the complexity of capturing the interactions in the lipid layer, such as those arising from electrostatics. Accurately capturing electrostatic energies in the low-dielectric membrane often requires expensive Poisson-Boltzmann calculations that are not scalable for membrane protein structure prediction and design. In this work, we have developed a fast-to-compute implicit energy function that considers the realistic characteristics of different lipid bilayers, making design calculations tractable. This method captures the impact of the lipid head group using a mean-field-based approach and uses a depth-dependent dielectric constant to characterize the membrane environment. This energy function Franklin2023 (F23) is built upon Franklin2019 (F19), which is based on experimentally derived hydrophobicity scales in the membrane bilayer. We evaluated the performance of F23 on five different tests probing (1) protein orientation in the bilayer, (2) stability, and (3) sequence recovery. Relative to F19, F23 has improved the calculation of the tilt angle of membrane proteins for 90% of WALP peptides, 15% of TM-peptides, and 25% of the adsorbed peptides. The performances for stability and design tests were equivalent for F19 and F23. The speed and calibration of the implicit model will help F23 access biophysical phenomena at long time and length scales and accelerate the membrane protein design pipeline.

Application of three-dimensional visualization technology in phacoemulsification benefits the dry eye symptoms of patients after cataract surgery.

To investigate the effects of the three-dimension visualization system on dry eye in patients after cataract phacoemulsification. Seventy-one patients (104 eyes) were enrolled in this study and assigned to the conventional microscopic group (CM group) or three-dimension group (3D group). Ocular Surface Disease Index, The Schirmer I test (SIt), lipid layer thickness (LLT), noninvasive tear breakup time (NIBUT) and other factors associated with dry eye were recorded before and 1 week and 1 month after surgery. The operation time and intraoperative light intensity (ILI) were also recorded. The ILI in the 3D group was significantly lower than that in the CM group (33% vs. 60%, p < 0.01). There was an interaction (group and time) effect for first NIBUT (NIBUT-F), average NIBUT (NIBUT-Ave), tear meniscus height (TMH) and the score of eye redness (Pinteraction < 0.05). The main effects of group on SIt, LLT, NIBUT-F, NIBUT-Ave and the score of eye redness were significant (Pgroup < 0.05). In the CM group, SIt, LLT, NIBUT-F, NIBUT-Ave, TMH were lower than those of the 3D group, the score of eye redness was higher than that of the 3D group at 1 week and 1 month after surgery (all p < 0.05). The changes in NIBUT-F and NIBUT-Ave between before surgery and 1 week after surgery showed negative correlations with ILI (p < 0.01). Compared with microscopic surgery, the 3D visualization system can provide better tear film stability for patients after cataract surgery.

Changes of dry eye parameters after small incision lenticule extraction surgery in patients with different ocular surface disease index scores

To evaluate the changes of dry eye parameters after small incision lenticule extraction (SMILE) surgery in patients with different ocular surface disease index (OSDI) scores. Prospective research. Participants were divided into two groups: Group A, OSDI < 13; and Group B, OSDI ≥ 13. The OSDI scores, tear meniscus height (TMH), first non-invasive tear film break-up time (NIBUT-First), and meibomian gland loss (MGL, %) were recorded at postoperative 1 -week and 1-month.113 eyes (57 patients) were enrolled, 70 eyes in Group A, and 43 eyes in Group B. In Group A, the OSDI scores significantly increased at 1-week and 1-month postoperative (all P < 0.001); the TMH, NIBUT-First and lipid layer grade significantly decreased at postoperative 1-week (P = 0.003, 0.005, 0.007, 0.004, respectively), but returned to preoperative level at 1-month postoperative. In Group B, only the lipid layer grade significantly decreased at postoperative 1-week (P < 0.05). Patients with different preoperative OSDI scores may experience different changes early after SMILE surgery. Patients with OSDI scores < 13 may experience more dramatic changes in dry eye symptoms which would resolve, while subjective complains could still exists at 1 month after surgery.

The effect of incomplete blinking rate on corneal epithelial remodeling after trans-PRK surgery: a six-month study.

To evaluate the impact of incomplete blink rate on corneal epithelial thickness after transepithelial photorefractive keratectomy (Trans-PRK) surgery. Trans-PRK patients were divided into two groups based on preoperative incomplete blinking rates, namely rates ≤0.5 (41 right eyes, group A) and rates >0.5 (65 right eyes, group B). We used anterior segment optical coherence tomography to measure the corneal epithelial thickness (CET) and lipiview to measure the number of blinks, incomplete blinking rate, and lipid layer thickness (LLT). In both groups, CET decreased at 1 week and 1 month, and the thicknesses in the IT, T, and ST regions exceeded the preoperative levels. Three months after Trans-PRK, the thickness exceeded the preoperative levels and continued to increase during subsequent follow-ups. The blinking times and LLT in both groups decreased at 1 week and gradually increased but did not return to preoperative levels. Group A maintained an incomplete blinking rate of over 0.5 at all postoperative periods. The incomplete blinking rate of group B remained above 0.5 postoperatively, although there was an improvement compared with preoperative rates. Both groups showed a correlation between changes in CET and incomplete blinking rate. There was a correlation between changes in LLT and the incomplete blinking rate after surgery. Both groups showed uneven corneal epithelia thickening, which became more pronounced approaching the peripheral areas. In addition, changes in CET after surgery were positively correlated with the incomplete blinking rate in both patient groups. There was a negative correlation between postoperative LLT and incomplete blinking rate.

New Insights into the Molecular Structure of Tear Film Lipids Revealed by Surface X-ray Scattering.

The tear film lipid layer (TFLL) is a unique biological membrane that serves a pivotal role in the maintenance of ocular surface health. Reaching an overarching understanding of the functional principle of the TFLL has been hampered by a lack of insights into the structural and functional roles played by individual lipid classes. To bridge this knowledge gap, we herein focus on studying films formed by principal lipid classes by surface scattering methods. Through grazing incidence X-ray diffraction and X-ray reflectivity studies, we reveal quantitative data about the lattice distances, molecular tilt angles, and mono/multilayer thickness and density profiles for central TFLL lipid classes under close to simulated physiological conditions. In addition, we discuss the correlation of the results to those obtained previously with the natural lipid composition of meibum.

The effects of eyelash extensions on the ocular surface

PurposeTo investigate the effects of eyelash extensions on the ocular surface. MethodsThis prospective study included 32 participants with eyelash extensions in both eyes. Symptoms and clinical parameters such as conjunctival vascular density, tear meniscus height (TMH), noninvasive tear break-up time, bulbar redness, meibography, lipid layer thickness, and corneal staining were assessed in the right eyes. These measurements were taken at baseline and 1 h, 1 day, 1 week, and 1 month after eyelash extensions were applied. ResultsAt 1 h after eyelash extensions, ocular symptoms were reported by 27 participants (84.44 %), the most common being foreign body sensation (59.38 %). However, the Ocular Surface Disease Index scores were not statistically different between baseline, 1 week, and 1 month after eyelash extension (P > 0.05). TMH increased significantly at 1 h after eyelash extensions, from 0.27 ± 0.08 mm (baseline) to 0.29 ± 0.07 mm (P = 0.02). Subsequently, TMH decreased and was the lowest at 1 week at 0.24 ± 0.08 mm. First tear break-up time and average tear break-up time decreased to the lowest at 1 week after eyelash extension, with 8.36 ± 4.6 s and 10.71 ± 4.99 s, respectively, both of which were statistically different from baseline (P < 0.05). Corneal staining score was highest at 1 h after eyelash extensions at 0.78 ± 1.34. However, there were no significant differences in the conjunctival vascular density, bulbar redness, meiboscore, or lipid layer thickness. ConclusionThis study demonstrates that eyelash extensions can lead to an imbalance in ocular surface homeostasis, resulting in corneal epithelial defects and short-term decreased tear film stability.

Evaluation of tear meniscus height and lipid layer patterns in the tear film in domestic cats: An observational study.

Healthy vision in humans and animals requires a stable tear film. The environmental factor could affect the status of the tear film. Therefore, assessing the tear film in animals is essential to avoid visual system disturbance. The current research used a noninvasive device to evaluate the tear meniscus height (TMH) and lipid layer pattern (LLP) in domestic cats. In addition, the scores were compared with those of humans with healthy eyes. Fifty-four domestic cats (28 males and 26 females; mean ± SD = 13.9 ± 18.2 months) were randomly selected and included in the study. The cats were healthy, without any ocular disorders or diseases. Fifty-four healthy eye subjects (27 males and 27 females; mean ± SD = 25.6 ± 5.1 years) were randomly recruited and took part in the study for comparison. EASYTEAR View+ was used, for the first time, to assess the tear film parameters on the right eye of each subject. The examiner allowed a 5-minute gap between the tests. Each test was performed by the same examiner three times, followed by calculating the mean scores. Significant differences (Mann-Whitney U test) were found in the median scores of LLP (p = 0.009) between cats and subjects with healthy eyes. The median TMH score was higher in cats (0.18 mm) than in humans (0.14). However, no significant difference (Mann-Whitney U Test, p = 0.210) exists in the TMH scores between cats and humans. The LLP analysis indicated that a dense white-blue lipid layer (grade 4 or D; lipid layer thickness, LLT, = approximately 80 nm) was predominant in both cats (N = 24, 44.4%) and humans (N = 29, 53.7%). In comparison, variable colors lipid layer (grade 5 or E; LLT = 90-140 nm) was a minority in cats (N = 5, 9.3%) and common in humans (N = 16, 29.6%). The statistical analysis indicated medium correlations between cats' TMH and LLP scores (r = 0.431, p < 0.01) and between age and TMH scores in humans (r = 0.440, p < 0.01). In addition, it indicated a weak correlation (r = 0.291, p < 0.05) between the LLP scores in cats and humans. Assessing animals' tear film is essential to avoid any ocular disorders. EASYTEAR View+ is efficiently used to evaluate domestic cats' TMH and LLP. Cats have thicker lipid layers and longer TMH comparable to those reported for humans with healthy eyes.

Assessment of lipid layer patterns in domestic dogs and rabbits: an observational study.

Maintaining a stable tear film is crucial for having healthy human and animal vision. Animals are expected to have thicker lipid layers than humans due to living in high-temperature and humid environments. The study aimed to evaluate the lipid layer patterns (LLPs) in Arabian dogs and rabbits using a non-invasive, practical, and easy-to-use device and compare them to humans with healthy eyes. The study included 75 domestic Arabian dogs (42 males and 33 females; mean ± SD = 6.1 ± 12.7 months) and 75 rabbits (37 males and 38 females; mean ± SD = 3.1 ± 3.4 months). In addition, 75 individuals with healthy eyes (39 males and 36 females; mean ± SD = 25.7 ± 5.0 years) were included for comparison. EASYTEAR View+ assessed the LLP in each animal's and individual's right eye. The median LLP grades significantly differed between dogs and humans (Mann-Whitney U test, p < 0.001). Similarly, the LLP grades differed significantly between rabbits and humans (Mann-Whitney U test, p < 0.001). No significant difference (Mann-Whitney U test) in the LLP grades between dogs and rabbits was found. The analysis indicated that most dogs had either an A (34.7%) or a B grade (37.3%). Similarly, rabbits had predominantly A or 1 (46.7%) and B (30.7%) grades. On the other hand, humans had predominantly D (53.3%) and E (30.7%) grades. The EASYTEAR View+ has been employed to assess LLP in dogs and rabbits, and the measurements were compared to those of humans with normal ocular health. Dogs and rabbits have thinner lipid layers than healthy humans.

On the interactions between RNA and titrateable lipid layers: implications for RNA delivery with lipid nanoparticles.

Characterising the interaction between cationic ionisable lipids (CIL) and nucleic acids (NAs) is key to understanding the process of RNA lipid nanoparticle (LNP) formation and release of NAs from LNPs. Here, we have used different surface techniques to reveal the effect of pH and NA type on the interaction with a model system of DOPC and the CIL DLin-MC3-DMA (MC3). At only 5% MC3, differences in the structure and dynamics of the lipid layer were observed. Both pH and %MC3 were shown to affect the absorption behaviour of erythropoietin mRNA, polyadenylic acid (polyA) and polyuridylic acid (polyU). The adsorbed amount of all studied NAs was found to increase with decreasing pH and increasing %MC3 but with different effects on the lipid layer, which could be linked to the NA secondary structure. For polyA at pH 6, adsorption to the surface of the layer was observed, whereas for other conditions and NAs, penetration of the NA into the layer resulted in the formation of a multilayer structure. By comparison to simulations excluding the secondary structure, differences in adsorption behaviours between polyA and polyU could be observed, indicating that the NA's secondary structure also affected the MC3-NA interactions.

Mimicking the hair surface for neutron reflectometry.

The surface of human hair is normally hydrophobic as it is covered by a lipid layer, mainly composed of 18-methyleicosanoic acid (18-MEA). When the hair is damaged, this layer can be partially or fully removed and more hydrophilic, mainly negatively charged surfaces are formed with a wide variety of physical and chemical characteristics. The cosmetic industry is currently embracing the opportunity of increasing the sustainability of their hair-care products whilst improving product performance. To do this, it is vital to have a deeper understanding of the hair surface and how it interacts with hair-care ingredients. This work contributes to this by harnessing the potential of neutron reflectometry (NR) with scattering contrast variation to describe hierarchical adsorption. Three types of hair-mimetic surfaces have been produced: two "healthy hair" models to probe the role of lipid structure, and one "damaged hair" model, to consider the effect of the surface charge. Adsorption of hair-care ingredients has then been studied. The results for these relatively short lipid models indicate that a methyl branch has little effect on adsorption. The "damaged hair" studies, however, reveal the unexpected apparent adsorption of an anionic surfactant to a negative surface. This preferential adsorption of the otherwise solubilised neutral components demonstrates a facile route to selectively deliver a protective film on a damaged hair fibre, without the need for a cationic species. On a more general note, this study also demonstrates the feasibility of using NR to characterize such complex systems.

Липидный анализ слезной жидкости в диагностике дисфункции мейбомиевых желез

The tear film lipid layer plays a crucial role in maintaining ocular surface homeostasis by preventing excessive evaporation of the aqueous layer and reducing heat transfer from the corneal and conjunctival surface. The lipid composition of the tear film is unique and consists of two main layers: the outer (nonpolar lipids) and the inner (polar lipids). The thick outer layer of the tear film is composed of non-polar lipids that lack internal distributed charge, while the thin inner layer is formed by polar lipids with positive and negative charges at the ends of the molecule. Both types of lipids are synthesized in the meibomian glands (MG) and contribute to tear film stability. Meibomian gland dysfunction (MGD) alters the composition and physical properties of lipids, leading to pathological changes in both the MG and tear film. In meibomian gland dysfunction (MGD), the meibum thickens and acquires a higher melting point than normal. This leads to a decrease in the amount of nonpolar and amphiphilic lipids in the meibomian gland secretion and tear film. Consequently, the protective effect of the tear lipid layer is impaired, and its stability is compromised. Lipid mapping analyzes the lipid composition of biological samples, such as tear fluid, to study the mechanisms of the development and progression of various ocular surface diseases, including dry eye syndrome, MGD, and recurrent blepharoconjunctivitis. This method provides fundamental data on the properties of the tear film in various ocular surface diseases. It has the potential to establish hallmarks of disease course and develop personalized treatment approaches for specific clinical cases. KEYWORDS: tear, tear film lipids, ocular surface, meibomian gland dysfunction, lipid analysis. FOR CITATION: Takhauova L.R., Guseva A.A., Krylova A.A., Krivosheina O.I. Lipid analysis of tear fluid as a diagnostic tool for meibomian gland dysfunction. Russian Journal of Clinical Ophthalmology. 2024;24(2):83–87 (in Russ.). DOI: 10.32364/2311-7729-2024-24-2-7.

New Skin-Relevant Cell Coculture Model With Stratum Corneum-Like Layer.

Two-dimensional (2D) cell culture is an important tool in the discovery of skin-active agents. Fibroblasts and keratinocytes, more rarely fibroblast-keratinocyte cocultures, are usually used for that purpose, where test compounds are added by mixing with the overlaying growth medium. However, such an approach is suboptimal because it lacks the stratum corneum component. The stratum corneum acts as a selective gatekeeper and opposes the intradermal permeation of many compounds that are bioactive when placed in direct contact with cells. One solution is to use reconstituted epidermis, but this approach is costly and time consuming. Here, a model is proposed, where the simplicity and convenience of the 2D cell culture is combined with the advantage of a hydrophobic barrier reminiscent of the skin horny layer. This model was tested with skin-relevant solvents, as well as with "naked" hydrophilic and encapsulated compounds. Cell viability and collagen stimulation were used as readouts. The results showed that the incorporation of a stratum corneum-substitute barrier on top of a 2D cell culture reduced the cytotoxicity of a common cosmetic solvent, dimethyl isosorbide (DMI), in cell culture and modified the bioactivity of the added actives (magnesium ascorbyl phosphate [MAP] and oligomeric proanthocyanidins [OPCs]/levan biopolymer), which became dependent on their ability to penetrate through a lipidic layer. Taken together, these results indicate a better physiological relevance of this cell culture model in workflows aimed at the discovery and analysis of skin-active compounds than conventional 2D systems.

Comparison in treatment effect according to the IPL treatment area in meibomian gland dysfunction patients

Aims/Purpose: We investigated whether there is a difference in the treatment effect according to the intense pulsed light (IPL) treatment site of meibomian gland dysfunction (MGD) patients.Methods: Patients who underwent 3 IPL treatment at 3‐week intervals were divided into groups A, B and C according to the treatment site (Group A, upper lid and lower lid; Group B, lower lid and lateral canthus; Group C, lower lid). Lid abnormality score (LAS), meibum expressibility (ME), meibum quality (MQ), lipid layer thickness (LLT), type I Schirmer test (ST), tear break‐up time (TBUT) test, and corneal staining scores (CFSs), and ocular surface disease index (OSDI) were obtained before the first and after the third IPL treatment.Results: Of 136 patients (136 eyes) were recruits, 45 (45 eyes) in group A, 56 (56 eyes) in group B, and 36 (36 eyes) in group C were included. LAS, ME, MQ, TBUT, CFS, and OSDI were significantly improved in group A, B, and C. The difference value of LAS before and after IPL treatment in group A and B were significantly greater than that of group C.Conclusions: Additional IPL treatment of upper lid and lateral canthus were considered to provide additional improvement in treating MGD patients.

Применение нового комбинированного препарата, содержащего среднецепочечные триглицериды, в лечении синдрома «сухого глаза»

Background: the outer layer of the tear film is composed of nonpolar lipids, including free fatty acid esters, triglycerides (TG), and cholesterol esters. Alterations in their qualitative and quantitative composition can result in evaporative dry eye, which requires pathogenic treatment. Somatic comorbidities, particularly type 2 diabetes (T2D), may act as a potential etiological factor. Aim: to assess the efficacy of a new complex medication containing medium chain TGs for the treatment of dry eye. Patients and Methods: a single-center, observational, single-stage, controlled single-sample, non-randomized study was conducted. Twenty-seven patients (mean age 52.5±0.5 years) were included in the study. Group 1 included 12 patients with dry eye and T2D. Group 2 included 15 patients with dry eye but no T2D. Patients received a complex medication containing medium chain TGs and carbomer for one month. In addition to standard and additional eye examinations, tearscopy and low-resolution mass spectrometry using LCQ Fleet (Thermo Scientific, Germany) were performed. Results: a reduction in the levels of TG and cholesterol was demonstrated in both groups. The reduction was more significant in group 1. A complex medication containing medium chain TGs and carbomer for one month improved functional indices in group 1 patients compared with baseline (p &lt;0.05). Corneal staining grade 1 was reported in 94% of group 1 patients. In group 2, corneal staining did not change significantly. Tearscopy revealed a significant improvement in the tear film lipid layer in group 1 (an increase in the lipid distribution coefficient and lipid thickness by 0.2 and 0.03, respectively) in comparison to group 2 (an increase by 0.1 and 0.02). Conclusions: decreased levels of TGs and cholesterol in T2D induce cellular dysfunction and inflammation in meibomian glands, thereby triggering dry eye development and/or worsening its course. In light of these considerations, complex medications containing TGs are necessary and reasonable. KEYWORDS: medium chain triglycerides, carbomer, meibomian gland dysfunction, dry eye, mass spectrometry, diabetes. FOR CITATION: Safonova T.N., Zaytseva G.V., Kravets K.Yu., Polyakov N.B. Novel complex medication containing medium chain triglycerides for the treatment of dry eye. Russian Journal of Clinical Ophthalmology. 2024;24(2):64–68 (in Russ.). DOI: 10.32364/2311- 7729-2024-24-2-4.

Changes in the precorneal tear film at various stages of keratoconus

This study assesses the changes in the state of the precorneal tear film in KC relative to the stages of the disease. The study included 50 patients (100 eyes) with bilateral non-operated KC from subclinical to stage IV. The following methods were used for a comprehensive assessment of the condition of the tear film: biomicroscopy of the anterior segment of the eye using vital dyes, functional tests (Norn, Schirmer, Jones tests), tearscopy of the lipid layer of the tear film with software processing of the results, OCT-meniscometry, as well as filling out the OSDI questionnaire by patients. The following significant changes were revealed as the KC stage progressed: an increase in the area of staining of the ocular surface with vital dyes, a decrease in the results of the Norn functional test and OCT-meniscometry, an increase in the areas of smaller thickness of lipids and areas of their complete absence according to tearscopy, as well as an increase in scores of the OSDI questionnaire. A comprehensive assessment of the condition of the tear film in KC indicates the relationship and the strengthening of the signs of DES as keratectasia progresses, and can be considered as justification for the need to prescribe tear replacement and reparative therapy that improves the condition of the ocular surface and stabilizes the precorneal tear film.

Novel anti‐evaporative lipid‐based formulation for dry eye disease treatment

Purpose: The majority of dry eye disease (DED) patients suffer from the tear film lipid layer (TFLL) instability issues associated with increased evaporation of water from the ocular surface. Therefore, we developed a liposomal formulation based on selected TFLL lipid classes that would restore the tear film stability and retard the evaporation of the aqueous tear fluid.Methods: The liposomal formulation was prepared by the thin film hydration method and subsequently characterized intermittently by standard techniques for at least 6 months. The mitochondrial metabolic activity (MTT) assay with human corneal epithelial (HCE) cells was utilized to assess the formulation toxicity in vitro. The evaporation resistance properties of the formulation were determined in vitro by the Langmuir trough methods, while a DED cellular model engendered by exposing the HCE cells to benzalkonium chloride (BAC) enabled additional assessment of the in vitro efficacy. In vivo safety was evaluated in rats and rabbits in one‐week studies. The conditions of the animal eyes were assessed by a non‐invasive biomicroscope, an optical coherence tomography, and histological staining of the dissected eyes.Results: The lipid‐based formulation with favourable pharmaceutical and functional properties (e.g., the evaporation resistance, and the promotion of HCE cell recovery after damage) was developed successfully, while also the physical stability of the formulation was found promising. No evidence of toxicity was observed during in vitro and in vivo experiments.Conclusions: The results suggest that the developed formulation is well‐tolerated and possesses properties and a safety profile compatible with ocular administration. Utilized in vitro efficacy models imply that the developed formulation is a promising candidate towards more efficient DED treatment. In vivo efficacy remains to be clarified in future studies.

Assessment of meibomian gland dysfunction and dry eye disease by using novel noninvasive ocular surface analyzer in people with type 2 diabetes

Abstract Objective: To assess meibomian gland dysfunction (MGD) and dry eye disease in people with type 2 diabetes using a novel noninvasive ocular surface analyzer. Materials and Methods: This prospective study was conducted in the Ophthalmology Department, Baqai Institute of Diabetology and Endocrinology, Baqai Medical University, Karachi, from June to December 2020. MGD is defined as increased lipids and proteins in the meibomian glands, leading to increased severity of dry eye disease symptoms. People with type 2 diabetes underwent an ocular surface examination; lipid layer thickness, noninvasive breakup time, tear meniscus height, grading of meibomian gland loss, and expression of meibum by a noninvasive analyzer. MGD was graded based on minimal to mild, moderate, and marked symptoms and divided into four subtypes. Result: A total of 46 diabetic subjects, 24 (52.2%) were males and 22 (47.8%) were females, with a median age of 55 (50–67.5) and 48 (41.5–55.25) years. Most of the subjects had mild gland opening for both the right and the left eye (50% and 54.3%). MGD score 1 was found in 12 (26.7%) and 11 (24.4%) subjects for the right and the left eye, respectively. Score 2 was observed mostly in the right eye 32 (71.1%) while score 3 was more frequent in the left eye 27 (60%). Notably, the conjunctival and ciliary levels were predominantly normal. Conclusion: Most of the participants had moderate to severe loss of the meibomian gland in both eyes.