Latent mutations in the ancestries of alleles under selection.

We consider a single genetic locus with two alleles A1 and A2 in a large haploid population. The locus is subject to selection and two-way, or recurrent, mutation. Assuming the allele frequencies follow a Wright-Fisher diffusion and have reached stationarity, we describe the asymptotic behaviors of the conditional gene genealogy and the latent mutations of a sample with known allele counts, when the count n1 of allele A1 is fixed, and when either or both the sample size n and the selection strength |α| tend to infinity. Our study extends previous work under neutrality to the case of non-neutral rare alleles, asserting that when selection is not too strong relative to the sample size, even if it is strongly positive or strongly negative in the usual sense (α→-∞ or α→+∞), the number of latent mutations of the n1 copies of allele A1 follows the same distribution as the number of alleles in the Ewens sampling formula. On the other hand, very strong positive selection relative to the sample size leads to neutral gene genealogies with a single ancient latent mutation. We also demonstrate robustness of our asymptotic results against changing population sizes, when one of |α| or n is large.

Patch formation driven by stochastic effects of interaction between viruses and defective interfering particles.

Defective interfering particles (DIPs) are virus-like particles that occur naturally during virus infections. These particles are defective, lacking essential genetic materials for replication, but they can interact with the wild-type virus and potentially be used as therapeutic agents. However, the effect of DIPs on infection spread is still unclear due to complicated stochastic effects and nonlinear spatial dynamics. In this work, we develop a model with a new hybrid method to study the spatial-temporal dynamics of viruses and DIPs co-infections within hosts. We present two different scenarios of virus production and compare the results from deterministic and stochastic models to demonstrate how the stochastic effect is involved in the spatial dynamics of virus transmission. We compare the spread features of the virus in simulations and experiments, including the formation and the speed of virus spread and the emergence of stochastic patchy patterns of virus distribution. Our simulations simultaneously capture observed spatial spread features in the experimental data, including the spread rate of the virus and its patchiness. The results demonstrate that DIPs can slow down the growth of virus particles and make the spread of the virus more patchy.

The Conjunctival Microbiome and Dry Eye: What We Know and Controversies.

ABSTRACT: Dry eye disease is a common multifactorial condition that may be idiopathic or associated with autoimmune conditions, such as Sjogren syndrome. Commensal microorganisms modify immune responses, so it is relevant to understand how they modify such immune-mediated diseases. Microbiota in the gut regulate inflammation in the eye, and conversely, severe inflammation of the ocular surface results in alteration of gut microbiome. The conjunctiva microbiome can be analyzed using 16S or shotgun metagenomics. The amount of microbial DNA in ocular surface mucosa relative to human DNA is limited compared with the case of the intestinal microbiome. There are challenges in defining, harvesting, processing, and analyzing the microbiome in the ocular surface mucosa. Recent studies have shown that the conjunctiva microbiome depends on age, presence of local and systemic inflammation, and environmental factors. Microbiome-based therapy, such as the use of oral probiotics to manage dry eye disease, has initial promising results. Further longitudinal studies are required to investigate the alteration of the conjunctival microbiome after local therapy and surgery.

Effectiveness of simulation models and digital alternatives in training ophthalmoscopy: A systematic review.

PURPOSE: Traditional direct ophthalmoscopy (TDO) is the oldest method of fundus examination; however, it has fallen out of use due to its technical difficulty and limitations to clinical utility, amidst the advent of potentially better options. A spectrum of new technologies may help in addressing the shortcomings of TDO: simulation mannequins with non-tracked TDO, simulation models with tracked TDO, and smartphone ophthalmoscopy (SFO). METHODOLOGY: A systematic search of PubMed, Embase, and Cochrane databases for all studies evaluating usage of simulation mannequins/models and SFO in ophthalmology education was performed, from inception till April 2023 with no language restriction. We ensured that we included all possible relevant articles by performing backward reference searching of included articles and published review articles. RESULTS: We reviewed studies on non-tracked TDO (n = 5), tracked TDO (n = 3) and SFO (n = 12). Non-tracked TDO and SFO were superior in training competency relative to control (TDO on real eyes). Intriguingly, tracked TDO was non superior to controls. SFO appears to enhance the learning effectiveness of ophthalmoscopy, due to real-time projection of the retina view, permitting instantaneous and targeted feedback. Learners reported improved ergonomics, including a wider field of view and more comfortable viewing distance. Retention of images and recordings permitted the audit of learning and paves the way for storage of such images in patients' electronic medical record and rapid dissemination for specialist referral. CONCLUSIONS: Smartphone ophthalmoscopy (SFO) permits integration of both the practice and learning of ophthalmoscopy, and the auditing of both. These advantages over traditional methods (with simulation or otherwise) may lead to a paradigm shift in undergraduate ophthalmology education. However, the nascency of SFO necessitates preservation of traditional techniques to tide through this period of transition.

A Systematic Review of Tear Vascular Endothelial Growth Factor and External Eye Diseases.

We aim to summarize the current evidence of Vascular endothelial growth factors (VEGF)s in external eye diseases and determine whether serum and plasma VEGF levels are associated with tear and ocular surface tissues. A systematic search of PUBMED and EMBASE was conducted using PRISMA guidelines between October 2022 and November 2023, with no restriction on language or publication date. Search terms included relevant MESH terms. These studies were evaluated for quality, and an assessment of the risk of bias was also carried out. Extracted data were then visually represented through relevant tables or figures. The initial literature search yielded 777 studies from PUBMED, 944 studies from EMBASE, and 10 studies from manual searches. Fourteen eligible studies were identified from 289 articles published from 2000 to 2023 in the English language or with English translations, including rabbit models, murine models, and human-derived samples. Most studies were retrospective in nature and case-control studies. Various common external eye diseases, such as dry eye disease (DED) and allergic eye disease were investigated. Despite limitations and small sample sizes, researchers have found elevated tissue levels of the VEGF in the vascularized cornea, especially in animal models, but there is no evidence of clear changes in the tear concentrations of VEGF in DED and allergic eye disease. Tear VEGF is associated with corneal vascularization. Anti-VEGF therapies may have the potential to manage such conditions.

Two-Photon and Multiphoton Microscopy in Anterior Segment Diseases of the Eye.

Two-photon excitation microscopy (TPM) and multiphoton fluorescence microscopy (MPM) are advanced forms of intravital high-resolution functional microscopy techniques that allow for the imaging of dynamic molecular processes and resolve features of the biological tissues of interest. Due to the cornea's optical properties and the uniquely accessible position of the globe, it is possible to image cells and tissues longitudinally to investigate ocular surface physiology and disease. MPM can also be used for the in vitro investigation of biological processes and drug kinetics in ocular tissues. In corneal immunology, performed via the use of TPM, cells thought to be intraepithelial dendritic cells are found to resemble tissue-resident memory T cells, and reporter mice with labeled plasmacytoid dendritic cells are imaged to understand the protective antiviral defenses of the eye. In mice with limbal progenitor cells labeled by reporters, the kinetics and localization of corneal epithelial replenishment are evaluated to advance stem cell biology. In studies of the conjunctiva and sclera, the use of such imaging together with second harmonic generation allows for the delineation of matrix wound healing, especially following glaucoma surgery. In conclusion, these imaging models play a pivotal role in the progress of ocular surface science and translational research.

Polymorphisms in Lymphotoxin-Alpha as the "Missing Link" in Prognosticating Favourable Response to Omega-3 Supplementation for Dry Eye Disease: A Narrative Review.

Elements of inflammation are found in almost all chronic ocular surface disease, such as dry eye disease. The chronicity of such inflammatory disease speaks to the dysregulation of innate and adaptive immunity. There has been a rising interest in omega-3 fatty acids to attenuate inflammation. While many cell-based (in vitro) studies verify the anti-inflammatory effects of omega-3, different human trials report discordant outcomes after supplementation. This may be due to underlying inter-individual differences in inflammatory cytokine metabolism (such as tumor necrosis factor alpha (TNF-α)), in which genetic differences might play a role, such as polymorphisms in the lymphotoxin alpha (LT-α) gene. Inherent TNF-α production affects omega-3 response and is also associated with LT-α genotype. Therefore, LT-α genotype might predict omega-3 response. Using the NIH dbSNP, we analyzed the relative frequency of LT-α polymorphisms among various ethnicities, each weighted by the genotype's probability of positive response. While the probability of response for unknown LT-α genotypes are 50%, there is greater distinction in response rates between various genotypes. Hence, there is value in genetic testing to prognosticate an individual's response to omega-3.

Impact of Exposomes on Ocular Surface Diseases.

Ocular surface diseases (OSDs) are significant causes of ocular morbidity, and are often associated with chronic inflammation, redness, irritation, discomfort, and pain. In severe OSDs, loss of vision can result from ocular surface failure, characterised by limbal stem cell deficiencies, corneal vascularisation, corneal opacification, and surface keratinisation. External and internal exposomes are measures of environmental factors that individuals are exposed to, and have been increasingly studied for their impact on ocular surface diseases. External exposomes consist of external environmental factors such as dust, pollution, and stress; internal exposomes consist of the surface microbiome, gut microflora, and oxidative stress. Concerning internal exposomes, alterations in the commensal ocular surface microbiome of patients with OSDs are increasingly reported due to advancements in metagenomics using next-generation sequencing. Changes in the microbiome may be a consequence of the underlying disease processes or may have a role in the pathogenesis of OSDs. Understanding the changes in the ocular surface microbiome and the impact of various other exposomes may also help to establish the causative factors underlying ocular surface inflammation and scarring, the hallmarks of OSDs. This review provides a summary of the current evidence on exposomes in various OSDs.

Impact of Microplastics on the Ocular Surface.

Plastics are synthetic materials made from organic polymers that are ubiquitous in daily living and are especially important in the healthcare setting. However, recent advances have revealed the pervasive nature of microplastics, which are formed by degradation of existing plastic products. Although the impact on human health has yet to be fully characterised, there is increasing evidence that microplastics can trigger inflammatory damage, microbial dysbiosis, and oxidative stress in humans. Although there are limited studies investigating their effect on the ocular surface, studies of microplastics on other organs provide some insights. The prevalence of plastic waste has also triggered public outcry, culminating in the development of legislation aimed at reducing microplastics in commercial products. We present a review outlining the possible sources of microplastics leading to ocular exposure, and analyse the possible mechanisms of ocular surface damage. Finally, we examine the utility and consequences of current legislation surrounding microplastic regulation.

The ocular surface and diabetes, the other 21st Century epidemic.

Diabetes Mellitus (DM) is a chronic metabolic disorder characterized by sustained hyperglycemia, potentially leading to life-threatening health problems. While the complication of diabetic retinopathy has been extensively studied, less attention has been given to the impact of diabetes on ocular surface health. In fact diabetic keratopathy is potentially sight-threatening and may also provide diagnostic and management cues for other diabetic systemic complications. In this review, we provide an overview of the recent understanding of diabetic ocular surface disease, including neuropathy, dry eye, and other morphological changes of the cornea. Additionally, we will touch on several areas that have been covered less in published literature. This includes ocular surface complications in pre-diabetic states and differences in ocular surface disease between human diabetics and animal models of diabetes. Recent advances in experimental models of diabetic ocular surface complications are highlighted. The latest methods for diagnosis, management, and monitoring of DM-related ocular surface disease are also evaluated. Specifically, the advantages and limitations of cornea in vivo confocal microscopy, as well as its accessibility and potential alternatives are discussed. Additionally, future directions for research are described based on findings with promising clinical value. This includes the emergence of protein microarray technology that may be potentially applied to the diagnosis and management of diabetic ocular surface disease.

Topical Omega-3 Fatty Acids Eyedrops in the Treatment of Dry Eye and Ocular Surface Disease: A Systematic Review.

Dry eye is a common inflammatory condition of the ocular surface. While oral omega-3 supplementation for its treatment has been extensively studied, recent large-scale studies have cast doubt on their efficacy. However, efficacy of topical omega-3 has yet to be reviewed. We performed a systematic search of PubMed, Embase, and Cochrane databases for all studies evaluating topical omega-3 in dry eye. Five human and five animal studies were included. Of the five human studies, two were on dry eye disease (DED), one was on contact lens discomfort, and two were on patients undergoing corneal collagen crosslinking. In humans, there is promising evidence for improved ocular surface staining and tear break-up time compared to controls, equivocal evidence for improvements to ocular surface symptoms and meibomian gland dysfunction, and no effect on increasing tear production. Data from animal models largely agree with these findings, and further reveal decreased inflammatory cytokines and monocyte infiltration. Our review suggests that topical omega-3 is a promising treatment for dry eye, but also points to the paucity of evidence in this field. Further trials in humans are required to characterize effects of topical omega-3 and optimize its dosage.

Changes of tear lipid mediators after eyelid warming or thermopulsation treatment for meibomian gland dysfunction.

Meibomian gland dysfunction (MGD) represents a major cause of dry eye and ocular discomfort. Lipid mediators, often termed oxylipins, can be produced enzymatically or non-enzymatically, and may modulate inflammatory processes in MGD. Here, we aimed to assess the longitudinal changes of lipid mediators after various eyelid treatments (eyelid warming and thermopulsation) over 12 weeks. Secondly, we aimed to assess the chirality of mono-hydroxyl lipid mediators from tears of MGD and healthy participants. Tears lipid mediators were extracted from Schirmer's strips and levels were quantified by liquid chromatography mass spectrometry (LC-MS) techniques. We quantified 33 lipid mediators in the tear, 18 of which (including 11-HETE, 20-OH-LTB4, and 15-oxoETE) were reduced significantly after treatment. Changes in concentrations of 10-HDoHE (r = 0.54) and 15-oxoETE (r = 0.54) were correlated to the number of meibomian gland plugs at baseline, so increased severity of MGD was associated with treatment-induced change in lipid mediators. The chiral analysis demonstrated that 5(S)-HETE, 12(S)-HETE, 15(S)-HETE, 14(S)-HDoHE, 17(S)-HDoHE and 11(R)-HETE were produced with significant enantiomeric excess (ee %) in controls compared to patients, due to enantiomer selective enzymatic action, whereas most lipid mediators were racemates in patients, due to dominance of oxidative effects which have no enantiomeric preference. Treatment of MGD restored the concentrations of 15(S)-HETE, 14(S)-HDoHE and 17(S)-HDoHE with significant ee values, suggesting reduction in oxidative action. Overall, MGD therapy reduced pro-inflammatory molecules generated by lipoxygenase and oxidative stress.

Impossibility of Consistent Distance Estimation from Sequence Lengths Under the TKF91 Model.

We consider the problem of distance estimation under the TKF91 model of sequence evolution by insertions, deletions and substitutions on a phylogeny. In an asymptotic regime where the expected sequence lengths tend to infinity, we show that no consistent distance estimation is possible from sequence lengths alone. More formally, we establish that the distributions of pairs of sequence lengths at different distances cannot be distinguished with probability going to one.

A Review on Evidence-Based Treatments for Meibomian Gland Dysfunction.

OBJECTIVES: To evaluate recent studies on available therapies for meibomian gland dysfunction (MGD). METHODS: A literature search on recent publications, within the last five years, concerning treatment options for MGD was performed. RESULTS: A total of 35 articles were reviewed after curation by the authors for relevance. In general, all modalities of treatments were shown to have clinical efficacy in alleviating dry eye signs and symptoms, although the extent of improvement and persistency of outcomes varied between the different treatments. Evidence from published studies demonstrate that thermal pulsation produces the longest lasting effect per treatment, but it also incurs the highest per-treatment cost. Reusable methods for warm compress with lipid/semi-fluorinated alkane-containing eye drops are recommended as first-line treatment for mild-to-moderate dry eye patients, because this option is most technically feasible and cost-effective in clinical practice. Intense pulsed light (IPL) therapy and thermal pulsation may be suitable as second line for patients unresponsive to warm compress therapy; however, their respective limitations need to be considered. For refractory MGD with features of periductal fibrosis or severe blepharitis, supplementary treatment with meibomian gland probing or oral antibiotics may be used. CONCLUSIONS: All eight forms of treatments, including self-applied eyelid warming, thermal pulsation, IPL, MG probing, antibiotics, lipid-containing eye drops, and perfluorohexyloctane, were effective against MGD, although with varying extent of clinical improvements. A better understanding on the mechanisms of actions may guide physicians to make better treatment decisions targeting the root causes.

A New Perspective on Dry Eye Classification: Proposal by the Asia Dry Eye Society.

The 2017 consensus report of the Asia Dry Eye Society (ADES) on the definition and diagnosis of dry eyes described dry eye disease as "Dry eye is a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage." The report emphasized the instability of tear film and the importance of visual dysfunction in association with dry eyes, highlighting the importance of the evaluation of tear film stability. This report also discussed the concept of tear film-oriented therapy, which stemmed from the definition, and which is centered on provision of insufficient components in each tear film layer and ocular surface epithelium. The current ADES report proposes a simple classification of dry eyes based on the concept of tear film-oriented diagnosis and suggests that there are three types of dry eye: aqueous-deficient, decreased wettability, and increased evaporation. It is suggested that these three types respectively coincide with the problems of each layer: aqueous, membrane-associated mucins, and lipid/secretory mucin. Although each component cannot be quantitatively evaluated with the current technology, a practical diagnosis based on the patterns of fluorescein breakup is recommended. The Asia Dry Eye Society classification report suggests that for a practical use of the definition, diagnostic criteria and classification system should be integrated and be simple to use. The classification system proposed by ADES is a straightforward tool and simple to use, only through use of fluorescein, which is available even to non-dry eye specialists, and which is believed to contribute to an effective diagnosis and treatment of dry eyes.

Systematic Review on Therapeutic Strategies to Minimize Corneal Stromal Scarring After Injury.

OBJECTIVES: To evaluate recent studies on available and experimental therapies in preventing or minimizing corneal stromal scarring after injury. METHODS: We performed an Entrez PubMed literature search using keywords "cornea," "scarring," "haze," "opacity," "ulcer," "treatments," "therapies," "treatment complications," and "pathophysiology" resulting in 390 articles of which 12 were analyzed after filtering, based on English language and publication within 8 years, and curation for relevance by the authors. RESULTS: The 12 articles selected included four randomized control trials (RCTs) (two were double-blinded placebo-controlled RCTs, one was a prospective partially masked RCT, and one was an open-label RCT), two retrospective observational studies, and six laboratory-based studies including two studies having in vivo and in vitro experiments, one was in vivo study, one was ex vivo study, and the last two were in vitro studies. The current mainstay for preventing or minimizing corneal scarring involves the use of topical corticosteroids and local application of mitomycin C. However, supportive evidence for their use in clinical practice from well-designed RCTs is lacking. Laboratory studies on topical rosiglitazone therapy, vitamin C prophylaxis, gene therapy, and stem cell therapy have shown promising results but have yet to be translated to clinical research. CONCLUSION: There is a need for more robust randomized controlled trials to support treatments using topical corticosteroids and mitomycin C. Furthermore, their clinical efficacy and safety profile should be compared with new treatments that have shown promising results in the laboratory setting. Ultimately, the goal should be to personalize cornea scarring treatment according to the most effective treatment for the specific underlying pathology.

Coping with dry eyes: a qualitative approach.

BACKGROUND: Dry eye is a common problem that affects many people worldwide, reducing quality of life and impacting daily activities. A qualitative approach often used in medicine and other disciplines is used to evaluate how people with dry eye cope with this impact. METHODS: Six focus group sessions were conducted at the Singapore National Eye Centre (SNEC), premises of an eye research institute. These focus groups consist of a spectrum of dry eye sufferers (30 women, 8 men, aged 61 ± 11.8 years). Standard methods of coding followed by determination of themes were adhered to. Where classification was difficult, consensus was made between 3 assessors. RESULTS: Audio-recorded transcripts were coded in 10 themes by 3 assessors independently. Four of the themes involved traditional measures such as lid warming, cleansing, lubrication and oral dietary supplements. The other themes discovered were Traditional Chinese Medicine, modification of eye-care habits (e.g. wearing sunglasses), environmental humidity, lifestyle (e.g. sleeping habits), psychological attitude, and lastly sharing and communication. CONCLUSION: Holistic coping strategies were found to be prominent in dry eye sufferers from these focus groups, and people tend to find personalised ways of coping with the impact of dry eye on daily living.

Tear Lactoferrin and Features of Ocular Allergy in Different Severities of Meibomian Gland Dysfunction.

SIGNIFICANCE: Meibomian gland dysfunction, but not atrophy, was associated with lower tear lactoferrin concentration, greater dry eye, and allergic symptoms, indicating greater inflammation and discomfort in patients with lower meibomian gland expressibility. PURPOSE: Meibomian gland dysfunction can potentially damage adjacent palpebral structures, which may induce inflammation in accessory lacrimal glands and affect lactoferrin secretion. This study aimed to examine the relationships between the severity of meibomian gland dysfunction with tear lactoferrin, conjunctival cell morphology, and clinical features of ocular allergy. METHODS: Forty subjects were divided into two groups based on the severity of meibomian gland plugging and expressibility and secondarily based on its atrophy. Dry eye and allergy questionnaires; slit-lamp examination, including lid telangiectasia; and meibography were performed. Tear lactoferrin concentration was measured using TearScan 270 MicroAssay. Impression cytology was performed on the upper palpebral conjunctiva, and goblet cell density and epithelial squamous metaplasia were quantified. RESULTS: Twenty-two subjects with meibomian gland dysfunction were categorized into severely obstructed group (case), whereas 19 subjects had minimal/no obstruction (comparison). Lower lactoferrin (1.3 ± 0.4 vs. 1.7 ± 0.4 mg/mL, P = .007), greater dry eye (7 [1 to 10] vs. 2 [0 to 5], P = .03), and allergy symptoms (9 [4 to 23] vs. 6 [0 to 9], P = .05) were found in the cases compared with the comparisons. There were no differences in conjunctival cell morphology between groups. The plugging score was correlated with lactoferrin concentration (ρ = -0.43, P = .006), dry eye (ρ = 0.36, P = .02), and allergic symptoms (ρ = 0.33, P = .04). Greater lid margin telangiectasia was associated with meibomian gland obstruction, but not atrophy. CONCLUSIONS: Meibomian gland activity/dysfunction, but not atrophy, may be associated with increased inflammation on the ocular surface. The inflammation may be sufficient to reduce tear lactoferrin production from damage to accessory lacrimal glands and/or meibomian gland and result in increased symptoms.

Association of long-term glycaemic control on tear break-up times and dry eye symptoms in Chinese patients with type 2 diabetes.

IMPORTANCE: Diabetes mellitus is known to be associated with dry eye syndrome (DES), but the effects of long-term glycaemic control on tear film metrics and dry eye symptoms are not known in the Chinese population. BACKGROUND: To evaluate tear film stability and dry eye symptoms and their associations with systemic risk factors in Chinese patients with type 2 diabetes mellitus (T2DM). DESIGN: Cross-sectional study set at the Lo Fong Siu Po Eye Centre (Grantham Hospital), Hong Kong. PARTICIPANTS: A total of 80 Chinese participants, aged 18 or above, with T2DM recruited from the specialist outpatient setting were included. METHODS: The Oculus Keratograph 5M (Oculus Inc., Wetzlar, Germany) was used to measure the non-invasive tear break-up time (NITBUT). Ocular symptoms were evaluated using the Ocular Surface Disease Index (OSDI). The association between OSDI, NITBUT and metabolic parameters relating to diabetes were evaluated using multiple linear regression. MAIN OUTCOME MEASURES: The associations between long-term glycaemic control and NITBUT and OSDI scores. RESULTS: Stepwise multiple linear regression analysis revealed glycated haemoglobin to be the only significant independent variable for NITBUT (R2 = 0.099, P = 0.014) and OSDI (R2 = 0.062, P = 0.044) after controlling for potential confounders. The age-adjusted prevalence of DES was 20% (95% confidence interval: 11-30%) in the Chinese T2DM population. The odds of DES for increasing percentage of glycated haemoglobin was 1.49 (95% confidence interval: 1.03-2.17, P = 0.04). CONCLUSIONS AND RELEVANCE: Our findings highlight the importance of good glycaemic control as a modifiable risk factor for both dry eye symptoms and tear film instability in patients with T2DM.

Topical Delivery of Senicapoc Nanoliposomal Formulation for Ocular Surface Treatments.

Topical ophthalmologic treatments have been facing great challenges with main limitations of low drug bioavailability, due to highly integrative defense mechanisms of the eye. This study rationally devised strategies to increase drug bioavailability by increasing ocular surface residence time of drug-loaded nanoliposomes dispersed within thermo-sensitive hydrogels (Pluronic F-127). Alternatively, we utilized sub-conjunctival injections as a depot technique to localize nanoliposomes. Senicapoc was encapsulated and sustainably released from free nanoliposomes and hydrogels formulations in vitro. Residence time increased up to 12-fold (60 min) with 24% hydrogel formulations, as compared to 5 min for free liposomes, which was observed in the eyes of Sprague-Dawley rats using fluorescence measurements. Pharmacokinetic results obtained from flushed tears, also showed that the hydrogels had greater drug retention capabilities to that of topical viscous solutions for up to 60 min. Senicapoc also remained quantifiable within sub-conjunctival tissues for up to 24 h post-injection.