Ocular Damage Research Articles

Photothermal-Responsive Soluble Microneedle Patches for Meibomian Gland Dysfunction Therapy.

Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye disease, presenting a challenge for targeted treatment. Traditional topical ocular drug delivery methods often fail to effectively reach the meibomian glands (MGs). To address this, the study has developed a soluble microneedles (MN) patch comprising poly(vinyl alcohol), cyclodextrin modified polyacrylic acid, and new indocyanine green. This innovative MN patch facilitates the transdermal release of peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, such as rosiglitazone in response to near-infrared ray induced temperature changes. By safely optimizing temperature, the patch effectively liquefied meibum lips, thereby alleviating duct obstruction while releasing the drug. MN patches exhibit sufficient mechanical strength for effective skin penetration, and its biosafety for eyelid application has been rigorously assessed in vitro and in vivo. The therapeutic efficiency of rosiglitazone loaded MN (ROSI-MN) treatment for MGD is evaluated in high-fat mice. After three months of treatments, ROSI-MN administration significantly alleviated MGD clinical manifestations, including ocular surface damage, lipid deposits, glandular hypertrophy, and inflammatory infiltration, ultimately improving the microstructure and biofunction of MGs. In conclusion, the soluble MN patches hold promise as an effective drug delivery strategy for treating ocular surface diseases beyond MGD.

The effect of water consumption on the aqueous layer of the tear film

Background: Tear deficient dry eye is a condition of insufficient tear production and may cause discomfort and visual disturbances, and if untreated, may cause ocular surface damage. While various treatment options have been explored and are available, these are usually costly and invasive.Aim: This study aimed to investigate the effect of water consumption on the aqueous layer of the tear film.Setting: University of KwaZulu-Natal Eye Clinic.Methods: A quantitative experimental design was implemented on 85 healthy participants of both genders aged between 18 and 34 years old. Pre-screening procedures, followed by baseline Schirmer 1 readings were obtained on all participants. The participants thereafter consumed water in relation to their body mass. Schirmer 1 test was re-administered at time intervals of 15, 30, 45 and 60 min after water consumption.Results: The mean baseline Schirmer 1 result prior to water consumption was 9.95 mm ± 4.52 mm. The mean Schirmer 1 results, at 15, 30, 45 and 60 min, following water consumption were 14.56 ± 5.82, 16.82 ± 5.44, 13.49 ± 4.82 and 11.54 mm ± 4.22 mm, respectively with a P-value of 0.000.Conclusion: This study showed that water consumption has a statistically significant increase on the aqueous tear volume.Contribution: Water consumption has been shown to increase aqueous tear production and may serve as a more affordable option to reduce dry eye symptoms.

Intestinal neutrophil extracellular traps promote gut barrier damage exacerbating endotoxaemia, systemic inflammation and progression of diabetic retinopathy in type 2 diabetes.

Within the small intestine, neutrophils play an integral role in preventing bacterial infection. Upon interaction with bacteria or bacteria-derived antigens, neutrophils initiate a multi-staged response of which the terminal stage is NETosis, formation of protease-decorated nuclear DNA into extracellular traps. NETosis has a great propensity to elicit ocular damage and has been associated with diabetic retinopathy and diabetic macular oedema (DME) progression. Here, we interrogate the relationship between gut barrier dysfunction, endotoxaemia and systemic and intestinal neutrophilia in diabetic retinopathy. In a cohort of individuals with type 2 diabetes (n=58) with varying severity of diabetic retinopathy and DME, we characterised the abundance of circulating neutrophils by flow cytometry and markers of gut permeability and endotoxaemia by plasma ELISA. In a mouse model of type 2 diabetes, we examined the effects of diabetes on abundance and function of intestinal, blood and bone marrow neutrophils, gut barrier integrity, endotoxaemia and diabetic retinopathy severity. Pharmacological inhibition of NETosis was achieved by i.p. injection of the peptidyl arginine deiminase 4 inhibitor (PAD4i) GSK484 daily for 4 weeks between 6 and 7 months of type 2 diabetes. In human participants, neutrophilia was unique to individuals with type 2 diabetes with diabetic retinopathy and DME and was accompanied by heightened circulating markers of gut permeability. At late-stage diabetes, neutrophilia and gut barrier dysfunction were seen in db/db mice. The db/db mice exhibited an increase in stem-like pre-neutrophils in the intestine and bone marrow and a decrease in haematopoietic vascular reparative cells. In the db/db mouse intestine, enhanced loss of gut barrier integrity was associated with elevated intestinal NETosis. Inhibition of NETosis by the PAD4i GSK484 resulted in decreased abundance of premature neutrophils in the intestine and blood and resulted in neutrophil retention in the bone marrow compared with vehicle-treated db/db mice. Additionally, the PAD4i decreased senescence within the gut epithelium and yielded a slowing of diabetic retinopathy progression. Severity of diabetic retinopathy and DME were associated with peripheral neutrophilia, gut barrier dysfunction and endotoxaemia in the human participants. db/db mice exhibited intestinal neutrophilia, specifically stem-like pre-neutrophils, which was associated with elevated NETosis and decreased levels of vascular reparative cells. Chronic inhibition of NETosis in db/db mice reduced intestinal senescence and NETs in the retina. These changes were associated with reduced endotoxaemia and an anti-inflammatory bone marrow milieu with retention of pre-neutrophils in the bone marrow and increased gut infiltration of myeloid angiogenic cells. Collectively, PAD-4i treatment decreased gut barrier dysfunction, restoring physiological haematopoiesis and levels of haematopoietic vascular reparative cells.

Disclosing long-term tolerance, efficacy and penetration properties of hyaluronic acid-coated latanoprost-loaded liposomes as chronic glaucoma therapy.

Frequent topical administration of hypotensive eye drops in glaucoma patients may lead to the development of dry eye disease (DED) symptoms, because of tear film destabilization and the adverse effects associated with antiglaucoma formulations. To address all this, in the current study preservative-free latanoprost-loaded (0.005% w/v) synthetic phosphatidylcholine (1,2-dioleoyl-sn-glycero-3-phosphocholine 0.75% w/v, 1,2-dimyristoyl-sn-glycero-3-phosphocholine 0.25% w/v) liposomes dispersed in the mucoadhesive polymer hyaluronic acid (0.2% w/v), containing the osmoprotective ingredients betaine (0.40% w/v) and leucine (0.90% w/v) (LAT-HA-LIP), have been prepared and further characterised. Permeation and retention evaluations on a validated ex vivo porcine eye model revealed that the active metabolite latanoprost acid was quantified only starting from LAT-HA-LIP once passing conjunctiva, sclera and choroid compared to the marketed latanoprost (0.005% w/v) benchmark (MF). The liposomal formulation outperformed MF when applied to the corneal tissue. Additionally, distribution and interactions within corneal and scleral tissues were investigated by means of two-photon microscopy with liposomal formulations containing coumarin-6. Furthermore, acute and chronic tolerance studies on rabbits revealed no signs of discomfort or ocular damage. Schirmer's test, tear osmolarity, tear breakup time (TBUT) and fluorescence staining evaluated through the Oxford grading scale, were assessed as DED diagnostic parameters over a 25-day monitoring period; LAT-HA-LIP consistently maintained levels comparable to physiological solution (0.9% w/v NaCl) used as control, with a slight increase of TBUT values from day 15 (6.00±0.63s for control, 7.00±0.78s for LAT-HA-LIP at day 15, p=0.0066). A daily topical application of LAT-HA-LIP for 15 consecutive days, effectively lowered IOP in a sustained way (2.51-3.88mmHg mean IOP reduction over the 5-15-day period). These results highlight the clinical relevance of the proposed technological platform, able to provide IOP reduction during the simulated long-term administration and simultaneous ocular surface protection with potential for the treatment of glaucoma.

Changes in tear cytokine and lactoferrin levels in postmenopausal women with primary acquired nasolacrimal duct obstruction complicated with obstructed meibomian gland dysfunction

BackgroundEpiphora and secondary ocular surface damage are increasingly impairing the quality of life of people, particularly elderly women. We aimed to investigate the changes in tear cytokine and lactoferrin levels in postmenopausal women with primary acquired nasolacrimal duct obstruction (PANDO) complicated with obstructed meibomian gland dysfunction (OMGD) and preliminary explore the pathological mechanisms of OMGD in patients with PANDO.MethodsThe prospective study involved 43 and 41 postmenopausal women with and without PANDO, respectively. Based on the presence or absence of OMGD, the participants were subdivided. Tear fluid was collected from affected eyes of all participants using Schirmer I test and tested for cytokine concentrations (interleukin (IL)-6, IL-8, IL-1β, interferon-gamma, tumour necrotic factor (TNF)-α, IL-10, epidermal growth factor (EGF)) using the Multiplex Luminex Assay. Tear lactoferrin levels was determined using ELISA.ResultsIn the PANDO with OMGD group, the IL-8, IL-1α, IL-1β, and macrophage inflammatory protein-1α levels were significantly higher than those in the other groups. The IL-6 and TNF-α levels were significantly higher than those in the controls. The lactoferrin level in the PANDO with OMGD group was lower than that in the Non-PANDO with OMGD group. The IL-10 and EGF levels were not significantly different among the groups.ConclusionThe level of pro-inflammatory factors in the tears of patients with PANDO complicated with OMGD was significantly increased, which is likely to cause further damage to ocular surface. Anti-inflammatory therapy may help protect ocular surface in postmenopausal women with PANDO.

Investigation of the Ocular Response and Corneal Damage Threshold of Exposure to 28 GHz Quasi-millimeter Wave Exposure.

Electromagnetic radiation energy at millimeter wave frequencies, typically 30 GHz to 300 GHz, is ubiquitously used in society in devices for telecommunications; radar and imaging systems for vehicle collision avoidance, security screening, and medical equipment; scientific research tools for spectroscopy; industrial applications for non-destructive testing and precise measurement; and military and defense applications. Understanding the biological effects of this technology is essential. We have been investigating ocular responses and damage thresholds comparing various frequencies using rabbit eyes and dedicated experimental apparatus. In this study we investigated the 28 GHz quasi-millimeter wave band (wavelength: 10.7 mm), a candidate for 5G communication. Similar to millimeter wave frequencies, ocular damage from exposure to 28 GHz for 6 min (400 mW cm-2) included corneal epithelial damage, corneal edema, and opacity. The incident power density threshold, indicating a 50% probability of ocular damage from exposure for 6 min, was found to be 359 mW cm-2 for 28 GHz. Comparing the ocular exposure area for various millimeter wave frequencies (40, 75, 95 GHz) and 28 GHz quasi-millimeter waves using a thermosensitive liquid crystal capsule, we found that for millimeter waves, even at identical incident power densities, the ocular exposure area decreases as the frequency increases (lens effect). However, this lens effect was not observed at 28 GHz, where the entire anterior segment area was exposed to radio waves.

ASSESSING THE IMPACT OF LEVATOR RESECTION BY ANTERIOR APPROACH WITH AND WITHOUT UPPER LID BLEPHAROPLASTY ON DRY EYE SYNDROME

Background: Dry eye disease is a multifactorial condition that significantly affects tear film homeostasis, resulting in ocular discomfort and surface damage. Surgical interventions like upper eyelid blepharoplasty, often performed for aesthetic and functional purposes, can disrupt the tear film, particularly when combined with levator resection. Understanding the impact of these procedures on dry eye parameters is crucial for optimizing patient outcomes, especially in populations predisposed to dry eye symptoms due to age or other risk factors. Objective: To evaluate and compare the effects of upper eyelid blepharoplasty with levator resection versus levator resection alone on dry eye parameters, focusing on tear film stability and subjective symptoms. Methods: This prospective study included 120 eyes from 120 patients diagnosed with acquired ptosis, equally divided into two groups: one undergoing upper eyelid blepharoplasty combined with levator resection and the other undergoing levator resection alone. Dry eye parameters, including tear break-up time (TBUT), Schirmer's test, and Ocular Surface Disease Index (OSDI) scores, were assessed preoperatively, and at 1 and 3 months postoperatively. The surgeries were performed under local anesthesia, and postoperative evaluations excluded the use of lubricants to ensure unbiased tear film assessments. Results: In the blepharoplasty with levator resection group, the mean preoperative TBUT decreased from 15.27 ± 2.62 seconds to 14.32 ± 2.89 seconds at 1 month, followed by partial recovery to 14.87 ± 2.72 seconds at 3 months. Schirmer’s test values dropped from 14.88 ± 2.12 mm preoperatively to 13.87 ± 2.29 mm at 1 month, improving to 14.60 ± 2.13 mm at 3 months. The OSDI score increased from 48.05 ± 19.12 preoperatively to 48.95 ± 19.24 at 1 month and improved to 46.55 ± 19.13 at 3 months. In contrast, the levator resection alone group showed stable dry eye parameters, with preoperative TBUT, Schirmer’s test, and OSDI scores remaining consistent at 1 and 3 months. Conclusion: Upper eyelid blepharoplasty with levator resection temporarily exacerbates dry eye symptoms and reduces tear film stability, with partial recovery by 3 months. Levator resection alone did not significantly impact dry eye parameters, underscoring the role of blepharoplasty-specific interventions in these changes. Proactive patient counseling and early postoperative management are essential for mitigating transient discomfort.

Pulsed Ultrasound-Mediated Drug Delivery Enhancement Through Human Sclera.

The purpose of this study was to characterize whether pulsed ultrasound (PUS) affects transscleral drug delivery. Fluorescein sodium (NaF, 376 Da) and fluorescein isothiocyanate-conjugated dextran 40 (FD-40, 40 kDa) were used as model drugs. Human sclera grafts were placed in modified Franz diffusion cells and were treated by PUS (1 megahertz [MHz], 0.71W/cm2, duty cycle 30%, application time 5minutes) once or repeatedly under various conditions to assess permeation enhancement and reservoir effect. The safety of PUS application was assessed on human sclera grafts ex vivo and rabbit eyes in vivo by histology and temperature measurements. Single PUS application yielded a significant increase in FD-40 permeation (P< 0.05). Repeated PUS applications led to a further enhancement in FD-40 permeation and also significantly promoted NaF permeation (more than 8.51-fold, P< 0.05). The human scleral permeability was temporarily modified by PUS, as evidenced by the increased scleral permeability during PUS application and the unchanged permeability coefficients at steady state. The reservoir effect of human sclera was also enhanced by PUS application. Cavitation was detected under PUS. A minor increase in graft temperature rise (<1°C) and no ocular damage was caused by PUS. PUS is an efficient and safe method to enhance model drugs to transport across human sclera by increasing the scleral permeability transiently and improving the reservoir effect. The enhancement was correlated with the molecule size and further promoted by the repeated PUS application. Our study provides proof of concept for using PUS to enhance drug delivery to the posterior eye segment.

A comprehensive update on over the counter artificial tears.

Artificial tears play a critical role in the management of dry eye disease (DED), providing patient symptomatic relief and improving ocular surface health. Its clinical importance has driven pharmaceutical innovation in terms of its formula and ingredients. The following article is an overview of the artificial tear products on the market. The artificial tears on the market vary in terms of their active ingredients, inactive ingredients, preservatives, and formulation. The particular chemical composition of ingredients and formulation plays a clinical role in treating ocular pathology. Conversely, certain ingredients can cause more ocular damage than other ingredients. Upon review of the artificial tears on the market, the authors conclude that clinicians should consider the products' composition when designating a treatment for DED. Different artificial tear composition may benefit specific causes of DED such as evaporative, aqueous-deficient, glaucoma, ocular surface tumors, corneal ulcers, and viral conjunctivitis.

Therapeutic Potential of Combined 5% Lifitegrast and Tocopherol Eye Drops in Managing Inflammation and Oxidative Stress in Murine Dry Eye.

Background/Objectives: This study aimed to evaluate the therapeutic effects of combined 5% lifitegrast (LF) and tocopherol (TCP) eye drops in a murine experimental dry eye (EDE) model. Methods: Female C57BL/6 were divided into seven groups: untreated controls, EDE control, EDE + 0.05% cyclosporin A (CsA), EDE + tocopherol (TCP), EDE + 5% LF, EDE + 5% LF + TCP (once daily), and EDE + 5% LF + TCP (twice daily). Clinical parameters (tear volume, tear break-up time (TBUT), corneal fluorescein staining score (CFSS), tear film lipid layer grade (TFLLG)) were assessed on days 7 and 14. Goblet cell density in the conjunctiva, CD4+ IFN-γ+ T cells, interleukin levels, reactive oxygen species (ROS) levels, and corneal apoptotic cells were analyzed on day 14. Results: Monotherapy with 0.05% CsA and LF showed improvements in all clinical parameters compared to the EDE control (p < 0.05). Combination therapy groups demonstrated superior improvements in clinical parameters compared to the EDE control, 0.05% CsA, and 5% LF groups. CD4+ IFN-γ+ T cell percentages and ROS levels in the cornea and conjunctiva were markedly reduced in the combination groups compared with the 0.05% CsA and 5% LF groups (p < 0.01). Furthermore, corneal apoptotic cells significantly decreased in the combination groups compared to the 0.05% CsA and TCP groups (p < 0.05). Conclusions: Combined 5% LF and TCP eye drops improved tear film parameters and reduced inflammatory and oxidative stress markers. The combination therapy can mitigate ocular surface damage by managing inflammation and oxidative stress in dry eye.

Effect of postoperative subconjunctival corticosteroid injections in a multimodal approach for the treatment of severe symblepharon

Aims/Purpose: To report on the impact of additional subconjunctival corticosteroid injections in a subsequent multimodal treatment of a challenging case of symblepharon following a Roper Hall Grade III chemical burn.History and signs: A 42‐year‐old male patient was referred due to multiple failed treatment attempts for his corneal disease and severe symblepharon formation. The initial cause of the accident was a chemical burn on the right eye (OD) caused by potassium hydroxide. At the time of referral, extensive ocular surface damage was present with corneal vascularization, fibrovascular pannus, persistent central corneal ulcer, distichiasis, upper eyelid nasal entropion, and limbal stem cell deficiency (LSCD), with visual acuity reduced to finger counting.Results: To treat this patient's condition, we adopted a multimodal three‐step approach. The first step was to reconstruct the fornix, with additional preoperatively intensive topical therapy with autologous serum drops and antibiotic eye drops to reepithelialize the corneal ulcer. In the crucial postoperative period, we administered a subconjunctival injection of 0.5ml betamethasone and a week later 1ml triamcinolone to prevent recurrence of symblepharon. The healing process went well and there were no further signs of symblepharon recurrence three months later. To improve tissue modulation, we administered a subconjunctival injection of triamcinolone again to achieve a more lasting effect and planned step two, which included a limbal stem cell transplant and lastly a penetrating keratoplasty as the final step.Conclusions: There are numerous therapeutic approaches to treat symblepharon, which are primarily based on surgical procedures and these remain an important cornerstone for the chances of recovery. In addition to surgical treatment, postoperative adjustment is also crucial for success. With our new approach we took action in the fibrosis formation process by administering early postoperative subconjunctival injections, this to achieve better bioavailability.

A hyaluronic acid-modified cyclodextrin self-assembly system for the delivery of β-carotene in the treatment of dry eye disease.

Dry eye disease (DED) is a multifactorial ocular disease, the core mechanism of which is the tear film instability caused by ocular oxidative stress damage and inflammation. Although various pharmaceutical agents are available for DED treatment, their effectiveness is often limited by the eyes' unique biological barriers, and the long-term use of steroid hormones can lead to several adverse effects. This study reported a nano-supramolecular delivery system consisting of a polycyclodextrin (PCD), hyaluronic acid (HA) and the natural compound β-carotene (BC) for the DED treatment. Our findings indicate that the HA/PCD@BC eye drops effectively distribute on the ocular surface, retain BC, and significantly enhance the corneal penetration of BC. The excellent biocompatibility of HA/PCD@BC was demonstrated through viability testing on different cell lines, the Draize eye test, as well as the hematoxylin-eosin staining (H&E) sections of cornea and conjunctiva. Both in vitro oxidative stress assays and in vivo DED model evaluations demonstrated that the HA/PCD@BC delivery system significantly reduced abnormal oxidative stress levels on the ocular surface, inhibited the secretion of inflammatory factors, and increased the secretion of tear film stabilizing mucin. These effects collectively improved pathological changes in eye tissues and minimized damage to the ocular surface. It is of particular importance to note that HA/PCD@BC eye drops showed superior efficacy in comparison to cyclosporine A (CsA), an FDA-approved first-line drug. To sum up, the HA/PCD@BC nanodelivery system provides a natural, safe and effective therapeutic strategy for the treatment of DED and various ocular diseases.

Design and Development of Nanoparticle-loaded In-situ Gel for Enhanced and Sustained Ophthalmic Delivery

Background: Flurbiprofen, a non-selective COX inhibitor utilized for managing mild to moderate pain and inflammation, operates through reversible inhibition of both COX-1 and COX-2 pathways. However, as a BCS class II drug, it exhibits limited aqueous solubility, leading to suboptimal ocular bioavailability and a brief corneal contact. Objective: The goal of this study was to amplify the aqueous solubility of Flurbiprofen by formu-lating it into a nanosuspension, which was subsequently incorporated into an in-situ gelling sys-tem so as to extend the ocular residence time and to achieve sustained drug release. Methods: Nanosuspensions were crafted through the anti-solvent precipitation ultra-sonication method. The assessment included parameters, such as particle size, surface morphology, XRD, and FT-IR. The optimized nanosuspension was then incorporated into a pH-sensitive in-situ gel. Results: The developed formulation was stable and showed enhanced contact time, minimizing the frequency of administration. Morphological analysis unveiled spherical drug nanoparticles in the nanosuspension without any signs of aggregation, supported by high-resolution transmission electron microscopy. The ex vivo permeation studies showed a drug release of 83.48%, indicating good permeation and histopathology, and isotonicity indicated no ocular irritation and tissue damage. Conclusion: The design and development of Flurbiprofen nanosuspension were found to be liq-uid at the formulated pH and formed gel due to changes in bonds between polymers. In-situ ocu-lar gels minimize the risk of systemic absorption of the drug, as they are designed to stay local-ized on the ocular surface and within the eye. An optimum point can be reached in the shortest time with minimum efforts to achieve desirable rheological and in-vitro release properties for in-situ gelling systems.

Impact of particulate matter and air pollution on ocular surface disease: A systematic review of preclinical and clinical evidence.

Exposure to particulate matter (PM) and air pollution has been implicated in the etiology of ocular surface diseases (OSD). The purpose of this systematic review is to evaluate and synthesize peer-reviewed literature on the impact of PM exposure on the ocular surface, integrating results from preclinical in vitro and in vivo studies with clinical findings to provide a comprehensive understanding of molecular mechanisms, physiological effects, clinical implications, and potential therapies to target acute and chronic PM-induced ocular toxicity. A systematic literature search was performed using PubMed and EMBASE over the period from 2009 to 2024 following the recommendations for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. 102 studies were identified that met the inclusion/exclusion criteria. All studies were assessed for the risk of bias and qualitative data were analyzed. Preclinical studies using models of corneal and conjunctival cells found that exposure to PM and similar air pollutants resulted in apoptosis, primarily via inflammatory and oxidative stress pathways as well as allergic and immune responses. Animal models resulted in phenotypes reminiscent of that of dry eye disease, presenting with reduced tear volumes and ocular surface damage. These results were corroborated by clinical studies, which reported that patients commonly presented with symptoms of itching, burning, and irritation, and ocular surface signs correlated with a diagnosis of dry eye disease, conjunctivitis, and allergic eye disease. This systematic review provides a comprehensive summary of our current understanding of PM exposure on the ocular surface, highlighting the correlation between exposure to PM and ocular surface dysfunction.

Keratoconjunctivitis sicca in intact Aksaray Malakli breed dogs: Evaluation of 50 cases.

Keratoconjunctivitis sicca (KCS) is characterized by decreased aqueous tear film components, leading to ocular surface damage. Diagnosis involves clinical examination, Schirmer Tear Test (STT1), and Tear Film Break-Up Time (TFBUT) measurement. This retrospective study aimed to assess dry eye syndrome in intact, purebred, Aksaray Malakli breed dogs, and investigate potential associations with hereditary ocular diseases due to inbreeding for phenotype preservation. Fifty healthy, purebred, intact Aksaray Malakli dogs of varying ages and sexes, all exhibiting conjunctival hyperemia and mucoid ocular discharge. Dogs with chronic diseases, systemic medication, or ongoing ophthalmic treatment were excluded. Demographic data, ophthalmic examination results, and ocular anomalies were recorded. STT1 and TFBUT assessments were performed to measure tear production and film stability. STT1 values were scored from 1 (normal) to 4 (severe dry eye), and TFBUT ≥20 s was considered normal. Statistical analyses were used to evaluate correlations and differences. The correlation between age and STT1 values (r = -.182, p = .206) was not statistically significant. Mean STT1 was higher in females than males, though not significantly (p = .849). Dogs without third eyelid gland prolapse had significantly higher STT1 and TFBUT measurements compared to those with prolapse (p = .027). No significant sex difference was found in the frequency of third eyelid prolapse (p = .289). A significant positive correlation was observed between STT1 and TFBUT (r = .924; p < .001). Aksaray Malakli dogs, particularly those with third eyelid gland prolapse, are predisposed to mild to moderate KCS. These findings suggest the need for further clinical and genetic investigations to better understand and manage dry eye syndrome in this breed.

Ocular safety of 222-nm far-ultraviolet-c full-room germicidal irradiation: A 36-month clinical observation.

The ocular safety of 222-nm far-ultraviolet-C (UV-C) irradiation, widely recognized for its germicidal properties, was evaluated in a clinical setting to assess its long-term health effects on the human eye. This prospective observational study involved a 36-month follow-up of physicians working in an ophthalmic examination room equipped with 222-nm UV-C lamps. Initially, a 12-month observation showed no signs of acute or chronic ocular damage. To further substantiate these findings, the study period was extended to 36 months, during which four participants underwent regular ocular examinations, including assessments of visual acuity, refractive error, and corneal endothelial cell density. The irradiation dose was meticulously controlled to remain within the previous threshold limit of 22 mJ/cm2 over an 8-h period, as advised by the ACGIH prior to 2022. Results indicated no significant changes in these parameters, suggesting no clinically significant ocular hazards associated with prolonged exposure to 222-nm UV-C irradiation under real-world conditions. Additionally, no delayed side effects, such as pterygium, keratopathies, or cataracts, were observed. Our study supports the safe use of 222-nm UV-C for microbial disinfection in occupied environments and provides a robust foundation for updated safety guidelines.

Pooled results from two pivotal randomized controlled clinical trials: ESSENCE-1 and ESSENCE-2 to assess efficacy and safety of a water-free ciclosporin 0.1% formulation for the treatment of dry eye disease.

This pooled analysis of two pivotal studies (ESSENCE-1 and ESSENCE-2) evaluated treatment effects of a water-free ciclosporin 0.1% solution in dry eye disease (DED) patients in the overall population and in subgroups according to sex, age, and baseline severity of disease. In these randomized, multicenter, double-masked, vehicle-controlled studies patients received ciclosporin 0.1% or vehicle (1:1 ratio) in both eyes twice daily for 85 and 29 days, respectively. Total and central corneal fluorescein staining (tCFS; cCFS; NEI scale, 0-15) were assessed at Day 15 and 29. Other endpoints included conjunctival staining and blurred vision scores. Safety and tolerability parameters comprised adverse events, ophthalmic examinations and drop comfort assessments. In total 1162 patients were included in the analysis (585 ciclosporin 0.1%; 577 vehicle). Patients age (mean [SD]: 58.3 [15.23] years) and gender distribution (73% females) are consistent with DED epidemiology.Change from baseline (LS mean [SE]) in tCFS significantly improved compared tovehicle, both at Day 15 (ciclosporin: -3.24 [0.112]; vehicle -2.71 [0.113];Δ= -0.52[0.144], p=0.0003) and Day 29 (ciclosporin: ‑3.83 [0.115]; vehicle:‑3.30 [0.116];Δ: ‑0.53 [0.147], p=0.0003). 56.8% and 66.4% of patients responded to ciclosporin0.1% with a tCFS improvement of ≥ 3 scores on Day 15 and 29, respectively. Aconsistent effect on tCFS favoring ciclosporin over vehicle was observed in allsubgroups. Improvements favoring ciclosporin were seen in cCFS andconjunctival staining in the overall population and in blurred vision score inpatients with significant corneal staining. Incidence of ocular adverse events was13.2% in both treatment groups. Mild instillation site reactions were reported by7.9% patients in the ciclosporin group. Discontinuation rates were low with 2.6%and 2.1% in ciclosporin and vehicle groups. Ciclosporin 0.1% was ratedcomfortable upon instillation by 84.7% of patients. The pooled analysis confirmed that the water-free ciclosporin 0.1% solution is effective in improving ocular surface staining after 2 weeks of treatment to a clinically relevant extent in more than 50% of patients in the overall population and subgroups. With an early onset and good tolerability, the product has the potential to address an unmet medical need in DED. NCT03292809 on 21-July-2017;NCT04523129 on 20-August-2020 KEY MESSAGES: What Was Known: Ciclosporin eye drops are a standard of care in dry eye disease (DED) therapy notcontrolled by artificial tears. A novel water-free ciclosporin 0.1% ophthalmicsolution with improved efficacy has recently been commercialized in the UnitedStates and approved in the European Union. The water-free cyclosporine 0.1% solution showed consistent and early improvement of ocular surface damage in patients with moderate and severe dry eye disease as well as in subgroups according to age and sex. Responder analysis showed the clinical relevance of these improvements in more than 50 % of treated patients after 2 weeks of treatments. This eye drop formulation was well tolerated and no new safety signals were detected.

The effect of swimmer position during prone ventilation on the onset of brachial plexus injury in the intensive care unit: A multiprofessional clinical study protocol.

Prone positioning improves oxygenation in adults with acute respiratory distress syndrome (ARDS) and has been extensively applied in intensive care units (ICU) during the COVID-19 pandemic. Although some complications due to the manoeuvre are well known, brachial plexus injury after prone positioning is reported as a rare complication and the phenomenon could be either very rare or underestimated. This study aimed to evaluate the effect of swimmer position during prone ventilation on the onset of brachial plexus injury in patients admitted to ICU for ARDS. The study will also evaluate the safety of prolonged prone positioning collecting data on any adverse events occurred. A prospective, observational cohort study will be conducted in a tertiary level ICU in the metropolitan area of Milano (Italy) specialized in advanced treatment of patients with ARDS. This observational study will report clinical data on the electromyography (EMG) and the muscle strength assessment, including comorbidities and cardio-respiratory status. A baseline EMG will be performed within 2 h from the first pronation manoeuvre and immediately at the end of each pronation cycle. The functional assessment of patients will be also performed at the end of ICU stay and at hospital discharge. The primary outcome is to estimate the prevalence of brachial plexus injury in patients with ARDS placed in the swimmer position during prone ventilation. Secondary outcomes will also include the safety of the manoeuvre by evaluation of all adverse events classified as skin or ocular damage, loss of tube and vascular access and new pressure ulcers. The findings of this study will contribute to understand the possible benefits/harms of prone ventilation performed using swimmer position. Eventually, this will call for the development of specific and tailored rehabilitation programs for patients with upper limb injuries during ICU stay, including also timely follow-up upon ICU-discharge.

Ophthalmic Formulations for the Treatment of Allergic Conjunctivitis and Their Effect on the Ocular Surface: A Review of Safety and Tolerability Assessments in Clinical Trials.

Allergic conjunctivitis (AC) is the most common allergic eye disorder. Antiallergic eyedrops are the first line of pharmacological treatment. However, the application of antiallergic eyedrops can potentially alter tear homeostasis and affect the ocular surface, which may result in iatrogenic diseases such as dye eye disease (DED). Long-term treatment of AC with eyedrops containing preservatives and other components may increase the risk of DED and ocular surface damage. Here, we examined 20 clinical trials published during the past ten years with antihistamine ophthalmic formulations in the treatment of AC, to evaluate the extent of evidence about their safety and tolerability. Remarkably, we find that most trials lack an evaluation of the critical ocular surface parameters, such as tear film break-up time, tear volume, corneal and conjunctival damage, and inflammation, to properly assess the state of the ocular surface state after prolonged treatment. There is a need to increase awareness of the use of specific formulations that do not increase the risk of iatrogenic DED.

Transient Cortical Blindness After Coronary Artery Bypass Surgery: A Case Report

: Transient cortical blindness (TCB) is an unusual postoperative complication following cardiac surgery. In this report, we present the case of a 54-year-old female who developed TCB after undergoing coronary artery bypass grafting (CABG) surgery. Her vision gradually improved over the course of two months post-operation. No causative ocular damage was found upon ophthalmologic examination, and assessments of related arteries (carotid, vertebral, and ophthalmic) were entirely normal. Following the onset of blindness, a non-contrast computed tomography scan showed bilateral subarachnoid hyperdensities in the occipital and parietal lobes. Magnetic resonance imaging was performed to confirm the presence of cerebral hemorrhage, but no pathology was detected. While the exact mechanism of TCB remains unclear, recognizing this potential complication after CABG is crucial.