Eye Model Research Articles

The Influence that the Complexity of the Three-Dimensional Eye Model Used to Generate Simulated Eye-tracking Data Has on the Gaze Estimation Errors Achieved Using the Data

The Influence that the Complexity of the Three-Dimensional Eye Model Used to Generate Simulated Eye-tracking Data Has on the Gaze Estimation Errors Achieved Using the Data

The Topical Novel Formulations of Interferon α-2в Effectively Inhibit HSV-1 Keratitis in the Rabbit Eye Model and HSV-2 Genital Herpes in Mice.

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans.

Harnessing Standing Sound Waves to Treat Intraocular Blood Cell Accumulation.

Certain ocular conditions result from the non-physiological presence of intraocular particles, leading to visual impairment and potential long-term damage. This happens when the normally clear aqueous humor becomes less transparent, thus blocking the visual axis and by intraocular pressure elevation due to blockage of the trabecular meshwork, as seen in secondary open-angle glaucoma (SOAG). Some of these "particle-related pathologies" acquire ocular conditions like pigment dispersion syndrome, pseodoexfoliation and uveitis. Others are trauma-related, such as blood cell accumulation in hyphema. While medical and surgical treatments exist for SOAG, there is a notable absence of effective preventive measures. Consequently, the prevailing clinical approach predominantly adopts a "wait and see" strategy, wherein the focus lies on managing secondary complications and offers no treatment options for particulate matter disposal. We developed a new technique utilizing standing acoustic waves to trap and direct intraocular particles. By employing acoustic trapping at nodal regions and controlled movement of the acoustic transducer, we successfully directed these particles to specific locations within the angle. Here, we demonstrate control and movement of polystyrene (PS) particles to specific locations within an in vitro eye model, as well as blood cells in porcine eyes (ex vivo). The removal of particles from certain areas can facilitate the outflow of aqueous humor (AH) and help maintain optimal intraocular pressure (IOP) levels, resulting in a non-invasive tool for preventing secondary glaucoma. Furthermore, by controlling the location of trapped particles we can hasten the clearance of the AH and improve visual acuity and quality more effectively. This study represents a significant step towards the practical application of our technique in clinical use.

Wavefront Changes during a Sustained Reading Task in Presbyopic Eyes.

The objective of this study was to assess the effect of sustained reading on the temporal changes in the wavefront error in the presbyopic eye. The wavefront aberration of the eyes was measured using an IRX3 Shack-Hartmann aberrometer before and after (immediately, 5 min, and 10 min after) a reading task. Temporal changes in C20, C40, and C3-1 coefficient values of the eyes were plotted, showing a predominant number of V-shaped patterns (for C40 and C3-1) and inverse V-shaped patterns (for C20) among the study group, and the percentages (between 27 and 73%) were reported. The median of the total RMS of aberrations and the RMS of HOA (higher-order aberrations), which included comatic (3rd order) and spherical-like aberrations (4th and 6th order), increased immediately after finishing the near-vision reading task and then decreased. The median of RMS of comatic aberrations had a similar pattern of variations, while the median of RMS of spherical-like aberrations displayed an opposite pattern. Simulating the aberration changes due to lens decentration caused by relaxed zonules during 4 D accommodation in an eye model demonstrated that the expected range of changes for the vertical coma and spherical aberrations are in the order of 0.001 and 0.01 μm, respectively, which could justify why the observed changes were not statistically significant. The observed dynamic changes in HOA might be linked to the biomechanical characteristics and alterations in the displacement of the crystalline lens following prolonged near-vision tasks in presbyopic people. Although some predominant patterns under some conditions were shown, they exhibit considerable inter-subject and inter-ocular variability. This might be due to slight misalignments while fixating on the internal extended object in the aberrometer.

Preliminary study of cyclosporine A/Lifitegrast subconjunctival sustained-release drug membrane in the treatment of dry eyes

BackgroundDry eyes can cause discomfort. To treat dry eye disease, cyclosporine A (CsA) and Lifitegrast are two eye drugs approved by the U.S. Food and Drug Administration (FDA). However, frequent use of eye drops can be challenging and lead to poor compliance, especially in elderly patients. Therefore, this study aimed to develop a drug sustained-release vector and explore its therapeutic effect in animal models of dry eye.MethodsFirstly, drug membranes loaded with both CsA and Lifitegrast using a carrier called poly(lactate-co-ε-caprolactone) (P(LLA-CL)) were prepared and evaluated for their physicochemical properties, release behavior in vitro, and safety in vivo. Next, a rabbit dry eye model using a 0.1% benzalkonium chloride (BAC) solution was developed and treated by drug-loaded micro membranes. We observed and recorded conjunctival hyperemia, corneal staining, corneal edema, corneal neovascularization, conjunctival goblet cells and hematoxylin and eosin (H&E) staining. Finally, we detected the MUC5AC and MMP-9 by immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA).ResultsThe composite film released both CsA and Lifitegrast for at least one month. Compared to the blank membrane group, conjunctival hyperemia, corneal fluorescein staining, corneal edema, corneal neovascularization and conjunctival goblet cells recovered faster in the drug membrane group, and the difference was statistically significant. At the molecular level, the drug membrane group showed an increase in mucin density and a significant anti-inflammatory effect.ConclusionsThe implantation of CsA/Lifitegrast loaded P(LLA-CL) membrane under the subconjunctival of the rabbit eye is safe. The study suggests that this subconjunctival administration could be developed into a minimally invasive delivery system to help patients with dry eye disease who require multiple daily eyedrops but have poor compliance.

Calcium-sensing receptor (CaSR) modulates ocular surface chloride transport and its inhibition promotes ocular surface hydration

PurposeOcular surface hydration is critical for eye health and its impairment can lead to dry eye disease. Extracellular calcium-sensing receptor (CaSR) is regulator of ion transport in epithelial cells expressing cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. CFTR is also a major ion channel in ocular surface epithelia, however the roles of CaSR in ocular surface are not well studied. This study aims to investigate expression and functional roles of CaSR in ocular surface. MethodsCaSR immunostaining was performed in mouse and human cornea and conjunctiva. Ocular surface potential difference (OSPD) and tear fluid volume measurements were performed in mice with topically applied cinacalcet (CaSR activator) and NPS-2143 (CaSR inhibitor). ResultsCaSR is expressed in corneal and conjunctival epithelia of mice and humans. Topically administered CaSR activator cinacalcet inhibits cAMP agonist forskolin-induced Cl− secretion and CFTR activity up to 90 %. CaSR inhibitor NPS-2143 stimulates CFTR-mediated Cl− secretion in mouse ocular surface, after which cAMP agonist forskolin had minimal additional secretory effects. Single dose NPS-2143 treatment (as an eye drop) increases tear fluid volume in mice by ∼60 % compared to vehicle treatment. NPS-2143 effect on tear volume lasts at least 8 h after single dose. ConclusionsCaSR is a key regulator of ocular surface ion transport and CaSR inhibition promotes Cl− and tear secretion in the ocular surface. If they are found to be effective in in dry eye models, CaSR inhibitors (currently in clinical development) can potentially be repurposed as novel prosecretory treatments for dry eye disease.

A Standardized Extract of Green-Cotyledon Small Black Soybean (EYESOY®) Ameliorates Dry Eye Syndrome in an Animal Model

Purpose Dry eye syndrome is a common ocular disease that causes morbidity, high healthcare burden, and decreased quality of life. In this study, we evaluated the beneficial effects of a standardized extract of small black soybean (EYESOY®) in a benzalkonium chloride (BAC)-induced murine model of dry eye. Methods Experimental dry eye was induced by instillation of 0.02% BAC on the right eye of the Sprague-Dawley rats. Saline solution or EYESOY were administered orally every day for 8 weeks. Results EYESOY significantly improved tear volume in the cornea compared with that in the BAC group. Moreover, EYESOY inhibited damage to the corneal epithelial cells and lacrimal glands by suppressing the oxidative and inflammatory responses in a mouse dry eye model. It also increased the goblet cell density and mucin integrity in the conjunctiva. Conclusions Our results suggest that EYESOY has the potential to alleviate dry eye syndrome.

Development of an Ex Vivo Porcine Eye Model for Exploring the Pathogenicity of Acanthamoeba.

Acanthamoeba, a widely distributed free-living amoeba found in various environments, is an opportunistic pathogen responsible for causing Acanthamoeba keratitis, a condition that may lead to blindness. However, identifying the pathogenicity of Acanthamoeba is challenging due to its complex life cycle, ability to adapt to different environments, variable virulence factors, and intricate interactions with the host immune system. Additionally, the development of an effective model for studying Acanthamoeba pathogenicity is limited, hindering a comprehensive understanding of the mechanisms underlying its virulence and host interactions. The aim of this study was to develop an ex vivo model for Acanthamoeba infection using porcine eyeballs and to evaluate the pathogenicity of the Acanthamoeba isolates. Based on slit lamp and biopsy analysis, the developed ex vivo model is capable of successfully infecting Acanthamoeba within 3 days. Histopathological staining revealed that clinical isolates of Acanthamoeba exhibited greater corneal stroma destruction and invasion in this model than environmental isolates. Our results highlight the importance of an ex vivo porcine eye model in elucidating the pathogenesis of Acanthamoeba infection and its potential implications for understanding and managing Acanthamoeba-related ocular diseases.

Fosfenopril Attenuates Inflammatory Response in Diabetic Dry Eye Models by Inhibiting the TLR4/NF-κB/NLRP3 Signaling Pathway.

The purpose of this study was to investigate the involvement of the TLR4/NF-κB/NLRP3 signaling pathway and its underlying mechanism in diabetic dry eye. Two models of diabetic dry eye were established in high glucose-induced human corneal epithelial (HCE-T) cells and streptozotocin (STZ)-induced C57BL/6 mice, and the TLR4 inhibitor fosfenopril (FOS) was utilized to suppress the TLR4/NF-κB/NLRP3 signaling pathway. The expression changes in TLR4, NF-κB, NLRP3, and IL-1β, and other factors were detected by Western blot and RT‒qPCR, the wound healing rate was evaluated by cell scratch assay, and the symptoms of diabetic mice were evaluated by corneal sodium fluorescein staining and tear secretion assay. In the diabetic dry eye model, the transcript levels of TLR4, NF-κB, NLRP3, and IL-1β were raised, and further application of FOS, a TLR4 inhibitor, downregulated the levels of these pathway factors. In addition, FOS was found to be effective in increasing the wound healing rate of high glucose-induced HCE-T cells, increasing tear production, and decreasing corneal fluorescence staining scores in diabetic mice, as measured by cell scratch assay, corneal sodium fluorescein staining assay, and tear production. The current study found that the TLR4/NF-κB/NLRP3 signaling pathway regulates diabetic dry eye in an in vitro and in vivo model, and that FOS reduces the signs of dry eye in diabetic mice, providing a new treatment option for diabetic dry eye.

Efficacy of RCI001 as a therapeutic candidate of dry eye disease in a modified mixed dry eye model

BackgroundTo evaluate the therapeutic effects of topical RCI001 (RCI) and compare its efficacy with that of 1% prednisolone acetate (PDE) and 5% Lifitegrast in a modified mixed dry eye disease (DED) model.MethodsThe environmental DED model was induced in BALB/c mice in a dry chamber with scopolamine. The eyes of the mice were treated topically with phosphate buffered saline (PBS), PDE, Lifitegrast or RCI twice daily for 1 week. Ocular surface staining (OSS), tear secretion, inflammatory cytokines in the ocular surface and lacrimal gland, and immunofluorescence staining in the conjunctiva and cornea(CC) were assessed.ResultsThe RCI group demonstrated better improvement of OSS and tear secretion than the PBS group (OSS, PBS: 13.0 ± 1.6, RCI: 9.4 ± 3.0; tear secretion, PBS: 5.0 ± 0.4 mm, RCI: 7.0 ± 0.3 mm, each P < 0.001) and better clinical efficacy than PDE and Lifitegrast groups on Day 7 (improvement rate of OSS, RCI: 32.45%, Lifitegrast: 13.13%, PDE: 12.25%). The RCI group resulted in significantly lower expression of oxidative stress markers in the CC than the PBS group (4-HNE, NOX2, and NOX4 in the conjunctiva; NOX2 in the cornea, each P < 0.05). However, the PDE and Lifitegrast groups did not show significant differences compared with the PBS group. There were no significant differences of inflammatory cytokines in the ocular surface and lacrimal gland between all groups.ConclusionTopical RCI001 showed excellent therapeutic effects in environmental DED models by stimulating tear secretion, modulating oxidative stress and improving corneal epithelial healing compared to 1% PDE and 5% Lifitegrast.

Enhancing Corneal Drug Penetration Using Penetratin for Ophthalmic Suspensions.

Eye drops, including solutions and suspensions, are essential dosage forms to treat ophthalmic diseases, with poorly water-soluble drugs typically formulated as ophthalmic suspensions. In addition to low bioavailability, suspensions exhibit limited efficacy, safety, and usability due to the presence of drug particles. Improving bioavailability can reduce the drug concentrations and the risk of problems associated with suspended drug particles. However, practical penetration enhancers capable of improving bioavailability remain elusive. Herein, we focused on penetratin (PNT), a cell-penetrating peptide (CPP) that promotes active cellular transport related to macromolecule uptake, such as micropinocytosis. According to the in vitro corneal uptake study using a reconstructed human corneal epithelial tissue model, LabCyte CORNEA-MODEL24, PNT enhanced the uptake of Fluoresbrite® YG carboxylate polystyrene microspheres without covalent binding. In an ex vivo porcine eye model, the addition of 10 µM PNT to rebamipide ophthalmic suspension markedly improved the corneal uptake of rebamipide; however, the addition of 100 µM PNT was ineffective due to potentially increased particle size by aggregation. This article provides basic information on the application of PNT as a penetration enhancer in ophthalmic suspensions, including the in vitro and ex vivo studies mentioned above, as well as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay and storage stability at different pH values.

Comparison of SRK/T with Kane formula for prediction of refractive outcome after phacoemulsification: Insights from a South Asian patient group

BackgroundPhacoemulsification stands as the most commonly conducted ocular procedure. Biometry represents an art with numerous generations of formulas introduced to enhance refractive prediction accuracy. The Sanders Retzlaff Kraff theoretical (SRK/T), a third-generation formula that merges linear regression and a theoretical eye model, and the Kane formula, a fourth-generation formula incorporating theoretical optics, regression, and artificial intelligence, embody our focal points. Our aim is to compare post-operative refractive outcomes utilizing SRK/T and Kane formulae for calculating intraocular lens (IOL) power in senile cataract patients undergoing phacoemulsification featuring a hydrophilic acrylic, monofocal IOL. MethodsThis prospective, interventional institutional study engaged 70 patients, totaling 74 eyes. They were categorized into two groups: Group A employed the SRK/T for IOL power calculation, while Group B used the Kane formula. Quantel Medical® A-scan biometer was employed. A comparison was drawn between both formulae in terms of mean absolute error (MAE) and median absolute error (MedAE), with the utilization of IBM SPSS 20 and a significance level of p < 0.05. ResultsThe MAE for the SRK/T and Kane formulae stood at 0.18 ± 0.82 D and 0.24 ± 0.94 D, respectively, while the MedAE recorded values of 0.16 D and 0.155 D, correspondingly (p < 0.05). ConclusionWithin this South Asian cohort of senile cataract patients, the SRK/T formula demonstrated a marginally improved refractive outcome, evidenced by a reduced mean absolute error.

A Rabbit Dry Eye Model Induced by Subcutaneous Scopolamine

Purpose To establish and characterize a dry eye model in New Zealand rabbits by subcutaneous injections of scopolamine hydrobromide (SCOP). Methods Twenty New Zealand male rabbits were injected subcutaneously SCOP for 14 consecutive days; subcutaneous saline was used as a negative control. The correlated clinical parameters of ocular surface dryness were detected in vivo using tear secretion and corneal fluorescein staining. The expression of IL-1β and TNF-α on the ocular surface and in lacrimal glands were analyzed by real-time PCR and western blot on the 14th day. The expression of Mucin-5 subtype AC (MUC5AC) was detected by Immunofluorescence staining in conjunctival tissue. Results The SCOP-treated rabbits exhibited significantly decreased aqueous tear secretion and increased corneal fluorescein staining scores over time. Both the mRNA expression levels and the protein expression levels of IL-1β and TNF-α were significantly increased after SCOP treatment compared with those after saline treatment. The loss of conjunctival MUC5AC was found in the SCOP-injected rabbits. Some infiltrated inflammatory cells and atrophic acinar cells were observed in the lacrimal gland after SCOP treatment. The disordered structures of the ocular surface and lacrimal glands were also observed. Conclusions This study showed that repeated subcutaneous SCOP injections successfully elicited some of the typical dry eye symptoms commonly seen in humans.

Quantitative investigation on the effects of eyeball geometry, blood perfusion and natural convection in retinal laser surgery

The photothermal effects of laser on tissue are widely used in ophthalmology to treat retinal diseases. The accurate modelling of retinal laser surgery will prove valuable guidance for clinic treatment. There are several important issues should be carefully evaluated during retinal laser surgery modelling, including the eye geometry (whole eye or fundus only, retinal pigment epithelium layer incorporated or not), blood perfusion and natural convection. In previous publications, the existence of the anterior part of eyeball and retinal pigment epithelium layer is neglected to simply the eye geometry due to low laser light absorption (anterior part of eyeball) or small volume occupation (retinal pigment epithelium layer), respectively. However, the justification of this treatment has not been conducted. In this study, we will quantitatively investigate these factors systemically in a large pulse duration range that covers all the retinal laser surgery used in clinic. To do this, we present a bioheat transfer model for the simulation of the thermal response of the eye to laser irradiation. In the simulation, the 3D whole-eye geometry is considered. The Pennes bioheat transfer equation is adopted for the whole-eye temperature modelling. Simultaneously, we treat the fundus as a multilayered medium that all primary components, including RPE layer, are considered for first time in whole eye modelling. Our model calculates the thermal responses of the eye during laser retinal surgery with the pulse duration from nanosecond to tens of second. The effects of eye geometry, blood perfusion and natural convection are clearly clarified based on the laser pulse duration and incident energy used. The results show that neglecting the anterior part of eyeball will introduce the computational error more than 27 %. The existence of the retinal pigment epithelium layer should always be considered in retinal laser surgery modelling in all pulse durations used in clinic, otherwise more than 20 % computational error will be generated. When the pulse duration is longer than 10s, the effect of blood perfusion and natural convection in vitreous body should both be considered.

Simulation of Changes in Tensile Strain by Airbag Impact on Eyes After Trabeculectomy by Using Finite Element Analysis.

We studied the kinetic phenomenon of an airbag impact on eyes after trabeculectomy using finite element analysis (FEA), a computerized method for predicting how an object reacts to real-world physical effects and showing whether an object will break, to sequentially determine the responses at various airbag deployment velocities. A human eye model was used in the simulations using the FEA program PAM-GENERISTM (Nihon ESI, Tokyo, Japan). A half-thickness incised scleral flap was created on the limbus and the strength of its adhesion to the outer sclera was set at 30%, 50%, and 100%. The airbag was set to hit the surface of the post-trabeculectomy eye at various velocities in two directions: perpendicular to the corneal center or perpendicular to the scleral flap (30° gaze-down position), at initial velocities of 20, 30, 40, 50, and 60 m/s. When the airbag impacted at 20 m/s or 30 m/s, the strain on the cornea and sclera did not reach the mechanical threshold and globe rupture was not observed. Scleral flap lacerations were observed at 40 m/s or more in any eye position, and scleral rupture extending posteriorly from the scleral flap edge and rupture of the scleral flap resulting from extension of the corneal laceration through limbal damage were observed. Even in the case of 100% scleral flap adhesion strength, scleral flap rupture occurred at 50 m/s impact velocity in the 30° gaze-down position, whereas in eyes with 30% or 50% scleral flap adhesion strength, scleral rupture was observed at an impact velocity of 40 m/s or more in both eye positions. An airbag impact of ≥40 m/s might induce scleral flap rupture, indicating that current airbags may induce globe rupture in the eyes after trabeculectomy. The considerable damage caused by an airbag on the eyes of short-stature patients with glaucoma who have undergone trabeculectomy might indicate the necessity of ocular protection to avoid permanent eye damage.

Optics of spectacle lenses intended to treat myopia progression.

This is a review of the optics of various spectacle lenses that have been used in myopia control over the last 60 years, with emphasis on approximately the last 15 years.Myopia has become an increasing health problem worldwide, particularly in some East Asian countries. This has led to many attempts to slow its progression in children and reduce its endpoint value. This review is concerned with the optics of spectacle lenses for use in myopia control, from bifocal lenses to multisegment and diffusion optics lenses. Treatments are based on theories of the onset or progression of myopia. These include the hypotheses that eye growth and myopia in susceptible children may be stimulated by (1) poor accommodation response and the consequent hyperopic defocus with near vision tasks, (2) relative hyperopic peripheral refraction, and (3) high retinal image contrast as occurs in urban environments. Using spectacle lenses to slow myopia progression has a history of about 60 years. The review is laid out in approximately the order in which different types of lenses have been introduced: bifocals, conventional progressive addition lenses, undercorrection with single-vision lenses, specialized progressive addition lenses, defocus-incorporated multiple segments, diffusion optics, and concentric bifocals. In the review, some of the lenses are combined with an eye model to determine refractive errors for peripheral vision for the stationary eye and for foveal vision for the rotating eye. Numbers are provided for the reported success of particular designs in retarding myopia progression, but this is not an epidemiological paper, and there is no critical review of the findings. Some of the recent treatments, such as multiple segments, appear to reduce the eye growth and myopia progression by better than 50% over periods of up to 2 years.

Studies on cationic ocular emulsions containing bipartitioned oil droplets to codeliver cyclosporin A and etodolac.

Background: To prepare ocular emulsions containing bipartitioned oil droplets to entrap cyclosporin A (0.05% w/w) and etodolac (0.2% w/w) by using castor, olive and silicon oils. Methods: The physicochemical characterizations of prepared emulsions were performed. The drug's biodistribution profiles and pharmacokinetic parameters from emulsions were checked using the ultraperformance liquid chromatography-tandemmass spectrometry method in the ocular tissues of the healthy rabbit eye model. Results: The emulsions displayed 365.13±7.21nm size and 26.45±2.09mV zeta potential. The ferrying of two drugs after releasing from emulsions occurred across corneal/conjunctival tissues to enter the vitreous and sclera following a single drop administration into the rabbit's eyes. Conclusion: The dual drug-loaded emulsions weremore likely to produce synergistic anti-inflammatory activity for managing moderate-to-severe dry eye disease.

Silk Fibroin Formed Bioadhesive Ophthalmic Gel for Dry Eye Syndrome Treatment.

Dry eye syndrome (DES), arising from various etiologic factors, leads to tear film instability and ocular surface damage. Given its anti-inflammatory effects, cyclosporine A (CsA) has been widely used as a short-term treatment option for DES. However, poor bioavailability and solubility of CsA in aqueous phase make the development of a cyclosporine A-based eye drop for ocular topical application a huge challenge. In this study, a novel strategy for preparing cyclosporine A-loaded silk fibroin nanoemulsion gel (CsA NBGs) was proposed to address these barriers. Additionally, the rheological properties, ocular irritation potential, tear elimination kinetics, and pharmacodynamics based on a rabbit dry eye model were investigated for the prepared CsA NBGs. Furthermore, the transcorneal mechanism across the ocular barrier was also investigated. The pharmacodynamics and pharmacokinetics of CsA NBGs exhibited superior performance compared to cyclosporine eye drops, leading to a significant enhancement in the bioavailability of CsA NBGs. Furthermore, our investigation into the transcorneal mechanism of CsA NBGs revealed their ability to be absorbed by corneal epithelial cells via the paracellular pathway. The CsA NBG formulation exhibits promising potential for intraocular drug delivery, enabling safe, effective, and controlled administration of hydrophobic drugs into the eye. Moreover, it enhances drug retention within the ocular tissues and improves systemic bioavailability, thereby demonstrating significant clinical translational prospects.

Analyzing Tear Fluid Composition by Synchronous Fluorescence for Diagnosing Dry Eye Disease and the Role of Phytotherapy Intervention

Purpose Tear fluid gained attention as a representative biological fluid. Its simple and non-invasive collection methods as well as richness of candidate biomarkers made it a potential diagnostic tool for different diseases such as dry eye. Synchronous fluorescence spectroscopy is a highly sensitive analytical tool that results in narrowing and enhanced peak resolution, and has a potential role in disease diagnosis, biomarker identification, and therapeutic monitoring. We applied synchronous fluorescence spectroscopy to monitor variations of tear fluid composition during the development of dry eye disease and to evaluate the potential effects of phytotherapy. Methods Dry eye model was induced in Chinchilla rabbits by instillation of 1% atropine sulfate ophthalmic solution. Then, the tear fluid was collected at 3, 7, and 14 days and subjected to synchronous fluorescence spectroscopy. Phytotherapy was achieved by topical instillation of 20 µl of water extracts of pomegranate peel or green tea powders. Results The fluorescence results revealed changes in the structure of tear fluid over time and the eye is subjected to toxification due to oxidative stress. In addition, dry eye disease was found to affect the metabolic/energetic state of the eye. On the other hand, phytotherapy led to enhancement of the metabolic/biosynthesis state due to activation of flavin adenine dinucleotide-associated proteins. Conclusion There was change in the electrical conductivity of tear fluid proteins. In the case of dry eyes, they became electrical insulators, while in the case of treatment with extracts, their electrical conductivity properties improved. The effects of phytotherapy can be related to the high content of ellagic acid and anthocyanin of pomegranate extract, while in green tea, they are related to catechins and phenolic compounds.

The influence of variations in ocular biometric and optical parameters on differences in refractive error.

To present a paraxial method to estimate the influence of variations in ocular biometry on changes in refractive error (S) at a population level and apply this method to literature data. Error propagation was applied to two methods of eye modelling, referred to as the simple method and the matrix method. The simple method defines S as the difference between the axial power and the whole-eye power, while the matrix method uses more accurate ray transfer matrices. These methods were applied to literature data, containing the mean ocular biometry data from the SyntEyes model, as well as populations of premature infants with or without retinopathy, full-term infants, school children and healthy and diabetic adults. Applying these equations to 1000 SyntEyes showed that changes in axial length provided the most important contribution to the variations in refractive error (57%-64%), followed by lens power/gradient index power (16%-31%) and the anterior corneal radius of curvature (10%-13%). All other components of the eye contributed <4%. For young children, the largest contributions were made by variations in axial length, lens and corneal power for the simple method (67%, 23% and 8%, respectively) and by variations in axial length, gradient lens power and anterior corneal curvature for the matrix method (55%, 21% and 14%, respectively). During myopisation, the influence of variations in axial length increased from 54.5% to 73.4%, while changes in corneal power decreased from 9.82% to 6.32%. Similarly, for the other data sets, the largest contribution was related to axial length. This analysis confirms that the changes in ocular refraction were mostly associated with variations in axial length, lens and corneal power. The relative contributions of the latter two varied, depending on the particular population.