Eye Drops Research Articles

Phase 1 Study of Tivozanib Eye Drops in Healthy Volunteers and Patients with Neovascular Age-related Macular Degeneration

PurposeTo evaluate the safety, pharmacokinetics, and exploratory efficacy of tivozanib eye drops in healthy volunteers and patients with neovascular age-related macular degeneration (nAMD). DesignThis multicenter, group-sequential dose escalation phase 1 study consisted of a placebo-controlled, double-masked study of healthy volunteers (Cohorts 1 and 2) and an open-label study of nAMD patients (Cohort 3). ParticipantsHealthy volunteers: Japanese or White men aged 20 to <50 years. Patients with nAMD with central subfield thickness ≥300 μm and best-corrected visual acuity score ≥23 letters in the study eye. MethodsIn the single-dose cohort of healthy men (Cohort 1: Steps 1–5), 1 or 2 tivozanib eye drops (30 μL/drop, 5-minute interval; 0.5, 1.0, and 2.0 w/v%) or placebo were administered in 1 eye once. In the multiple-dose cohort of healthy men (Cohort 2: Steps 1–6), 1 or 2 tivozanib eye drops (0.5, 1.0, and 2.0 w/v%) or placebo were administered 3 times daily (TID) in 1 eye for 21 days. In the multiple-dose cohort of nAMD patients (Cohort 3, Steps 1–3), 1 or 2 tivozanib eye drops (0.5 and 1.0 w/v%) were administered TID in 1 affected eye for 21 days. Main Outcome MeasuresThe safety outcome measures included adverse events (AEs). The pharmacokinetic outcome was serum tivozanib concentration. Among the exploratory efficacy outcomes, central subfield thickness (CST) was evaluated. ResultsIn total, 40, 48, and 28 participants were enrolled in Cohorts 1, 2, and 3, respectively. Serious AEs did not occur in Cohorts 1–3. The most frequent AE in multiple-dose cohorts was reversible punctate keratitis: placebo arm, 8.3% (healthy men, 1/12); tivozanib arm, 47.2% (healthy men, 17/36) and 14.3% (nAMD, 4/28). Serum tivozanib exposure increased dose-dependently and was similar in healthy men and patients with nAMD. In patients with nAMD, mean CST changes from baseline to Day 22 were −27.6 ± 54.88 (0.5 w/v%; 1 drop, TID), −35.6 ± 49.64 (1.0 w/v%; 1 drop, TID), and −43.7 ± 55.19 μm (1.0 w/v%; 2 drops, TID). ConclusionsTivozanib eye drops showed a favorable safety profile in healthy Japanese and White men and Japanese patients with nAMD.

Controlled release of vitamin A palmitate from crosslinked cyclodextrin organic framework for dry eye disease therapy

Controlled release drug delivery systems of eye drops are a promising ophthalmic therapy with advantages of good patient compliance and low irritation. However, the lack of a suitable drug carrier for ophthalmic use limits the development of the aforementioned system. Herein, the crosslinked cyclodextrin organic framework (COF) with a cubic porous structure and a uniform particle size was synthesized and applied to solidify vitamin A palmitate (VAP) by using the solvent-free method. The VAP@COF suspension eye drops were formulated by screening co-solvents, suspending agents, and stabilizing agents to achieve a homogeneous state and improve stability. According to the in vitro release study, the VAP@COF suspension exhibited a controlled release of VAP within 12 h. Both the ex vivo corneal contact angle and in vivo fluorescence tracking indicated that the VAP@COF suspension prolonged the VAP residence time on the ocular surface. This suspension accelerated the recovery of the dry eye disease (DED) model in New Zealand rabbits. Furthermore, the suspension was non-cytotoxic to human corneal epithelial cells and non-irritation to rabbit eyes. In summary, the particulate COF is an eye-acceptable novel carrier that sustains release and prolongs the VAP residence time on the ocular surface for DED treatment

Remote-controlled dexamethasone-duration on eye-surface with a micelle-magnetic nanoparticulate co-delivery system for dry eye disease

Dexamethasone (DEX) is used to treat ocular surface diseases. However, regulating DEX duration in tears while preventing its absorption into the anterior chamber is critical for balancing its therapy effects and the side effects. In this study, a novel magnetic nanoparticle (MNP)-micelle (MC) co-delivery system (MMDS) was developed. The MC moiety in the MMDS served as the carrier for DEX and the MNP part endowed the MMDS with magnetic-responsive properties. To extend its residency, the MMDS was magnetically attracted by an external magnet after instilling, which acted as a precorneal drug-depot enabling a sustainable release of DEX in tears. With combination of magnet treatment, the topical instillation of MMDS@DEX significantly prolonged the DEX-retention in tears and increased the DEX-concentration in the cornea and conjunctiva, as well as concurrently reduced the DEX-level in the aqueous humor, when compared with the commercial DEX eye drop treatment. The combination of MMDS@DEX and magnet treatment exerted significantly better therapeutic effects against DED with smaller side effects than conventional treatments including DEX suspension, commercial DEX eye drops, as well as the MMDS@DEX treatment alone. The present work provided a new method for the effective delivery of DEX to ocular surface tissues while reducing its side effects, which will be beneficial to the treatments of a wide range of ocular surface diseases.

Dry eye syndrome associated with traumatic keratitis

Dry eye syndrome (DES) is an urgent problem in healthcare practice worldwide. Various diseases of the eye are of particular importance for the development of this syndrome. A special place among the diseases leading to symptomatic DES with ocular surface lesion belongs to corneal injuries of traumatic origin. The frequency of post-traumatic complications of the eye, especially the cornea, remains high due to its anatomical location. And often these patients are at risk of secondary DES. For the pathogenesis of DES after ke­ratitis, ultrastructural changes in the cells of different corneal layers and the toxic effect on the tear film layers of preservative-containing drugs used in the treatment of keratitis are important. The purpose of the study was to assess the severity of secondary DES in patients after traumatic keratitis and the effectiveness of hyaluronic acid combined with antioxidants in the treatment of this pathology. An ophthalmological examination, functional tests were made, and the Ocular Surface Disease Index was used to evaluate the symptoms and severity of the disease. The criteria for the effectiveness of the therapy with hyaluronic acid in combination with vitamins A and E four times a day were: reduction of corneal syndrome, increase in the tear film break-up time, a decrease in subjective discomfort. Clinical observation of patients with DES after traumatic keratitis showed that the use of hyaluronic acid can result in a significant reduction or complete disappearance of subjective symptoms of the disease, sustained improvement in vision and increased stability of the tear film. The use of these eye drops makes it possible to reach compliance and shorten the treatment period.

Breaking Barriers: Nanomedicine-Based Drug Delivery for Cataract Treatment.

Cataract is a leading cause of blindness globally, and its surgical treatment poses a significant burden on global healthcare. Pharmacologic therapies, including antioxidants and protein aggregation reversal agents, have attracted great attention in the treatment of cataracts in recent years. Due to the anatomical and physiological barriers of the eye, the effectiveness of traditional eye drops for delivering drugs topically to the lens is hindered. The advancements in nanomedicine present novel and promising strategies for addressing challenges in drug delivery to the lens, including the development of nanoparticle formulations that can improve drug penetration into the anterior segment and enable sustained release of medications. This review introduces various cutting-edge drug delivery systems for cataract treatment, highlighting their physicochemical properties and surface engineering for optimal design, thus providing impetus for further innovative research and potential clinical applications of anti-cataract drugs.

Development and evaluation of hot-melt–extruded diquafosol tetrasodium formulations for ophthalmic inserts: A design of experiments approach

This study aimed to develop, optimize, and evaluate hot-melt–extruded ophthalmic inserts capable of sustained release of diquafosol tetrasodium (DQS) via a design of experiments approach. DQS, a tear stimulant for dry eye management, faces challenges of frequent administration and low bioavailability. The developed insert uses biodegradable polymers in varied proportions to achieve sustained release. Optimized through mixture design, the insert completely dissolved within 24 h and maintained a stable drug content, thickness, and surface pH over three months at room temperature. In vitro corneal permeation studies on excised rabbit corneas demonstrated increased bioavailability, suggesting a reduced dosing frequency compared with conventional eye drops. Therefore, this insert has potential to enhance treatment outcomes by improving patient compliance and providing sustained drug effects.

Integrated high-throughput drug screening microfluidic system for comprehensive ocular toxicity assessment

Traditional experimental methodologies suffer from a few limitations in the toxicological evaluation of the preservatives added to eye drops. In this study, we overcame these limitations by using a microfluidic device. We developed a microfluidic system featuring a gradient concentration generator for preservative dosage control with microvalves and micropumps, automatically regulated by a programmable Arduino board. This system facilitated the simultaneous toxicological evaluation of human corneal epithelial cells against eight different concentrations of preservatives, allowing for quadruplicate experiments in a single run. In our study, the IC50 values for healthy eyes and those affected with dry eyes syndrome showed an approximately twofold difference. This variation is likely attributable to the duration for which the preservative remained in contact with corneal cells before being washed off by the medium, suggesting the significance of exposure time in the cytotoxic effect of preservatives. Our microfluidic system, automated by Arduino, simulated healthy and dry eye environments to study benzalkonium chloride toxicity and revealed significant differences in cell viability, with IC50 values of 0.0033% for healthy eyes and 0.0017% for dry eyes. In summary, we implemented the pinch-to-zoom feature of an electronic tablet in our microfluidic system, offering innovative alternatives for eye research.

Ouabain, ATPase inhibitor, potentially enhances the effect of polyhexamethylene biguanide on Acanthamoeba castellanii

Acanthamoeba, a free-living amoeba, is commonly found in various natural environments, such as rivers and soil, as well as in public baths, swimming pools, and sewers. Acanthamoeba can cause severe illness such as granulomatous amoebic encephalitis and Acanthamoeba keratitis (AK) in humans. AK, the most recognized disease, can cause permanent visual impairment or blindness by affecting the cornea. AK commonly affects contact lens wearers who neglect proper cleaning habits. The symptoms of AK include epithelial and stromal destruction, corneal infiltrate, and intense ocular pain, occasionally necessitating surgical removal of the entire eyeball. Current AK treatment involves the hourly application of eye drops containing polyhexamethylene biocide (PHMB). However, studies have revealed their ineffectiveness against drug-resistant strains. Acanthamoeba can form cysts as a survival mechanism in adverse environments, though the exact mechanism remains unknown. Our experiments revealed that sodium P-type ATPase (ACA1_065450) is closely linked to encystation. In addition, various encystation buffers, such as MgCl2 or NaCl, induced the expression of P-type ATPase. Furthermore, we used ouabain, an ATPase inhibitor, to inhibit the Na+/K+ ion pump, consequently decreasing the encystation rate of Acanthamoeba. Our primary objective is to develop an advanced treatment for AK. We anticipate that the combination of ouabain and PHMB may serve as an effective therapeutic approach against AK in the future.

An injectable thermoresponsive-hydrogel for lamellar keratoplasty: In-situ releases celastrol and hampers corneal scars

Corneal stromal fibrosis is a common cause of visual impairment resulting from corneal injury, inflammation and surgery. Therefore, there is an unmet need for inhibiting corneal stromal fibrosis. However, bioavailability of topical eye drops is very low due to the tear and corneal barriers. In situ delivery offers a unique alternative to improve efficacy and minimize systemic toxicity. Herein, a drug delivery platform based on thermoresponsive injectable hydrogel/nano-micelles composite with in situ drug-controlled release and long-acting features is developed to prevent corneal scarring and reduce corneal stromal fibrosis in lamellar keratoplasty. The in-situ gelation hydrogels enabled direct delivery of celastrol to the corneal stroma. In vivo evaluation with a rabbit anterior lamellar keratoplasty model showed that hydrogel/micelles platform could effectively inhibit corneal stromal fibrosis. This strategy achieves controlled and prolonged release of celastrol in the corneal stroma of rabbit. Following a single corneal interlamellar injection, celastrol effectively alleviated fibrosis via mTORC1 signal promoting autophagy and inhibiting TGF-β1/Smad2/3 signaling pathway. Overall, this strategy demonstrates promise for the clinical application of celastrol in preventing corneal scarring and reducing corneal stromal fibrosis post-lamellar keratoplasty, highlighting the potential benefits of targeted drug delivery systems in ocular therapeutics.

TO STUDY THE ROLE OF TEAR FILM MATRIX METALLOPROTEINASE-9 (MMP-9) IN THE DIAGNOSIS AND MANAGEMENT OF INFLAMMATORY DRY EYE DISEASE USING POINT TO CARE RAPID MMP-9 IMMUNOASSAY KIT

Purpose: To study the role of Matrix Metalloproteinase-9 (MMP-9) in the tear film for the diagnosis and management of inflammatory dry eye disease using point to care Rapid MMP-9 immunoassay kit. Methods: This prospective interventional study was conducted at a tertiary eye care centre in a duration of two years. 300 eyes (Right Eye) of 300 patients with Dry Eye Disease (DED) were included in the study. After assessing the signs and grade of dry eye clinically, the patients were subjected to MMP-9 immunoassay of the tear film. The tear MMP-9 immunoassay results were interpreted using qualitative (positive or negative) and quantitative (reagent band density on a four-point scale: 0 = negative 1 = weakly positive 2 = moderately positive 3 = strongly positive) methods. The patients who were tested negative for MMP-9 were treated with eye drop Carboxy methyl cellulose (CMC) 0.5% thrice a day, while those who were tested positive for MMP-9 were given eye drop Cyclosporine 0.05 % twice a day in addition to lubricants. Treatment and follow up was done for a period of six months and the response to treatment was re-assessed at the end of first week, first month, three months and six months. Result: At presentation among 120 MMP-9 positive patients, 34%(41) were mild positive, 45%(54) were moderate positive, 21%(25) were severe positive. 88.98%(105) of 120, MMP-9 positive patients became mild positive and 10.8% converted to MMP-9 negative at the end of six months follow up. In MMP-9 positive group, mean reduction in OSDI from baseline 33.46 ± 13.47 to 11.86 ± 2.99, mean increase in Schirmer from baseline 9.22 ± 1.64 to 13.15 ± 2.42 and mean increase in TBUT from baseline 8.68 ± 1.11 to 11.33 ± 1.36 were observed at the end of six month follow up. Conclusion: In this study, we found that there is a positive correlation between the MMP-9 immunoassay results with that of the severity of the signs and symptoms of DED. It was also observed that patients who were in MMP-9 positive group were found to have higher OSDI, lower Schirmer and TBUT values at baseline andthey showed significant improvement in the scores of dry eye with anti-inflammatory drops.Hence, topical anti-inflammatory eye drops plays a major role in the management of patients with severe DED.

The Protective Effect of Rho-Associated Kinase Inhibitor Eye Drops (Ripasudil) on Corneal Endothelial Cells After Cataract Surgery: A Prospective Comparative Study.

Cataract surgery poses a risk to corneal endothelial cells. This study aimed to assess the protective effect of rho-associated kinase inhibitor eye drop (ripasudil) on corneal endothelial cells after cataract surgery over 12months. We conducted a prospective, non-randomized, non-blinded comparative study including 43 patients divided into two groups: the ripasudil group (22 patients, 23 eyes) and the control group (21 patients, 21 eyes). All patients had grade 3 nuclear cataract and underwent uneventful phacoemulsification with intraocular lens implantation. In the ripasudil group, one drop of ripasudil hydrochloride hydrate (Glanatec® ophthalmic solution 0.4%) was administered three times a day for 5days. Outcome measures included central corneal thickness (CCT) and endothelial cell density (ECD), which were evaluated preoperatively and 12months postoperatively. In the ripasudil group, the median ECD was 2398 (interquartile range [IQR] 410, 2201-2611) cells/mm2 at baseline and 2262 (IQR 298, 2195-2493) cells/mm2 at 12months postoperatively. In the control group, the median ECD was 2503 (IQR 390, 2340-2730) cells/mm2 at baseline and 2170 (IQR 324, 2049-2373) cells/mm2 at 12months postoperatively. Endothelial cell loss (ECL) was 12.8% in the control group, significantly reduced to 4.5% in the ripasudil group (p = 0.001*). CCT (p = 0.042), age (p = 0.383), sex (p = 0.944), and duration of surgery (p = 0.319) were not significant factors. No adverse effects were observed in either of the groups. Incorporating ripasudil into postoperative management could help maintain corneal endothelial cell integrity and reduce cell loss after cataract surgery, potentially decreasing the need for endothelial transplantation in patients who have undergone intraocular surgeries.

A Case of Bilateral Conjunctivitis in a Seven-Year-Old Shih-Tzu Dog

Background: Conjunctivitis is an inflammation of the conjunctiva that is common in dog, which also known as pink eyes. Conjunctivitis can be caused by infectious agents such as bacteria, chlamydia, and virus, and can also be induced by allergies or due to trauma. Bilateral infection may indicate they are caused by an infectious agent or allergy. Purpose: This study aims to provide veterinarians with insight into the treatment of conjunctivitis cases and the factors that hinder therapy. Case: A seven-year-old female Shih-Tzu dog has had eye problems for six months since April 2023. Physical examination revealed redness in the left and right eyes with mucopurulent exudate. Laboratory examination using an impression smear followed by cytology confirmed inflammation in the eye with many neutrophil cells and coccus-shaped bacteria. The dog was diagnosed with bacterial conjunctivitis with a good prognosis. Case Management: The therapy consisted of the administration of topical antibiotics in the form of Erlamycetin plus® (chloramphenicol and dexamethasone) eye drops for five days, followed by Erlamycetin® (chloramphenicol) eye ointment. Conclusion: After 12 days of therapy, there was no redness in the dog’s eyes and only a small amount of exudate was observed. However, on day 14, the owner reported that exudates were observed in the dog’s eyes. The therapy resulted in improvements but was not optimal because the owner did not consistently follow the recommendations.

Formulation and Evaluation of Ocular in situ Gel of Framycetin Sulfate

The aim of the present study was to formulate and optimize Framycetin sulfate in situ gels for the used for treatment of ocular eye infection .it was formulated as ocular in situ gel forming eye drop are using polymers such as carbopol 940 as a gelling agent in combination of suitable preservatives. It is a newer approach to improve easy to eye instillation residence time and enhance bioavailability, prolonged and sustained drug release. in-situ gel formulation using a suitable phase transition polymer to effectively deliver the drug into eyes with sustained and prolonged release and enhanced drug bioavailability. It is observed from the formulation F3 which shown drug content 96.16 % and have good gelling capacity. Thus, it can be concluded that the drug given in the form of ocular in situ gel of Framycetin sulfate providing better patient compliance and an effective mode of treatment.

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.

New suture probe canaloplasty combined with suprachoroidal collagen implantation.

To present the modified surgery technique of new suture probe canaloplasty with a specially prepared monofilament 4.0 polypropylene suture combined with suprachoroidal drainage (ScD) and collagen sheet implantation for non-penetrating glaucoma surgery. Prospective study with a twelve months follow-up. A standard 4/0 polypropylene suture (ProleneTM by Ethicon; thickness: approximately 250m) is cut and shaped with an ophthalmic knife (MANI® Crescent Knife, Mani Inc 8-3 Kiyohara Industrial Park, Utsunomiya, Tochigi 321-3231, Japan) to create a blunt end without sharp or compressed edges. This improves suture probe canaloplasty by providing a more stable and smoother probing device. Schlemm's canal is prepared using the standard technique of canaloplasty with suprachoroidal drainage. Then, instead of using the canaloplasty microcatheter or the previously published 6/0 double-helix suture, Schlemm's canal is probed with the blunt ending of the 4/0 Prolene suture. After successful 360-degree probing, a doubled 10/0 polypropylene tension suture is threaded through the tip of the 4/0 suture. The 4/0 suture is then pulled back and the 10/0 tension sutures are tied at both ends to tension Schlemm's canal. A special collagen sheet (Ologen®) is placed in suprachoroidal space, and the scleral flap is firmly sewed. 115 eyes were included in this prospective study. In 113 cases the Schlemm's canal could completely be probed with the suture probe and canaloplasty with ScD and collagen sheet implantation succeeded. In two cases the intervention was transformed to 360-degree suture trabeculotomy due to an intraoperative cheese-wiring. Twelve months after successful new suture probe canaloplasty with ScD and Collagen Implantation the IOP had decreased by 37.1% (from 21.6 ± 6.0mmHg with 3.3 different IOP lowering eye drops to 13.5 ± 3.5mmHg with 1.0 eye drops). 16 Patients did not achieve sufficient IOP levels and underwent 360-degree suture trabeculotomy during the follow-up. One patient had to be treated with further glaucoma surgery to achieve a sufficient IOP level. Complications were hyphema, postoperative IOP elevation and transient hypotony. No serious or sight-threatening complications occurred. New suture probe canaloplasty with ScD and collagen sheet implantation yields the opportunity to conduct a cost-effective canaloplasty easier and less complicated than with the previously described method with the twisted 6/0 suture. The safety profile and IOP lowering effect is comparable. In cases where complete probing fails, there is still the opportunity to switch to suture trabeculotomy over the majorly probed part of Schlemm's canal. The pressure lowering effect of the deep sclerectomy with ScD and suprachoroidal collagen sheet implant seems to have an additional impact on the sufficient pressure lowering procedure.

تحضير وتقييم جل العين الموضعي بآلية تحفيز مزدوجة لتوصيل جاتيفلوكساسين وبيتاميثازون فوسفات الصوديوم

Background: Bacterial infections of the eye are treated by administering ophthalmic solutions containing corticosteroids and antibacterial agents. The main challenges faced when used for topical instillation are precorneal fast clearance and multiple applications, particularly with gatifloxacin. Objectives: To develop an ocular gel that utilizes both ion-induced and thermal-sensitive mechanisms to achieve gelation. Methods: We prepared and compared formulations containing different percentages of poloxamer 407 and gellan gum (F1–F24) in terms of gelation temperature, gelling capacity, gelation time, and permeation. We tested the optimum formulation for isotonicity and irritation in rabbits. Results: The formulations' pH varied from 6.7 to 7.3. Formulations that passed the gelation temperature test successfully were F6, F7, F9, and F10. For both drugs (F6, F7, F9, and F10), the drug content percentages ranged from 98.64% to 99.95%. In situ, gels (F6, F7, F9, and F10) showed pseudoplastic shear-thinning rheological behavior, which means that their viscosity decreased as the angular velocity went up. F7, which contains 17% poloxamer and 0.5% gellan gum, had 15 seconds of gelation time at 34oC and remained in gel form for 270 min. It was isotonic and did not change the size or shape of RBCs when topically applied. The rabbit's eyes did not experience irritation due to the extended release of both drugs. Conclusions: The new in situ gel formulation may be a superior alternative to the traditional eye drops of gatifloxacin and betamethasone for ocular infections.

Ocular Drug Delivery into the Eyes Using Drug-Releasing Soft Contact Lens

The impact of visual impairment, such as blindness, on quality of life is immeasurable. However, effective ocular drug delivery into the eyes has not yet been established, primarily due to the impermeability imposed by the blood–retinal barrier (BRB) based on the tight junctions and efflux transporters at the endothelium or the epithelium in oral or intravenous administration, as well as the dilution with tear fluid and excretion through the nasolacrimal duct in eye drop administration. Furthermore, intravitreous injections induce pain and fear in patients. Unmet medical needs persist in ocular diseases such as age-related macular degeneration and diabetic retinopathy. Therefore, innovative non-invasive administration methods should be developed. Drug-releasing soft contact lenses (DR-SCLs) affixed to the eye’s surface can continuously and locally deliver their loaded drugs to the eyes. The use of DR-SCLs is expected to greatly enhance the bioavailability and patient adherence to the drug regimen. It is known that several solute carrier (SLC) transporters are expressed in various parts of the eyes, including the cornea, the ciliary body, and the bulbar conjunctiva. Carrier-mediated transport through SLC transporters may occur in addition to passive diffusion. Moreover, nanoparticles can be loaded into DR-SCLs, offering various intelligent approaches based on modifications to induce receptor-mediated endocytosis/transcytosis or to control the loaded drug release within this delivery system. In this perspective review, I discuss the implementation and potential of DR-SCL-mediated ocular drug delivery, particularly focusing on low-molecular-weight compounds because of their fine distribution in living body, ease of handling, and ease of manufacturing.

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

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. 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 14days and subjected to synchronous fluorescence spectroscopy. Phytotherapy was achieved by topical instillation of 20µl of water extracts of pomegranate peel or green tea powders. 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. 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 new preservative-free ophthalmic formulation of bilastine 0.6% preserves the ocular surface epithelial integrity in a comparative in vitro study

Allergic conjunctivitis (AC) is the most common form of allergic eye disease and an increasingly prevalent condition. Topical eye drop treatments are the usual approach for managing AC, although their impact on the ocular surface is not frequently investigated. The aim of this study was to perform a comparative physicochemical characterization, and in vitro biological evaluations in primary conjunctival and corneal epithelial cells of the new multidose preservative-free bilastine 0.6% and main commercially available eye drops. MTT assay was used to measure cell viability; oxidative stress was analyzed with a ROS-sensitive probe; and apoptosis was evaluated monitoring caspase 3/7 activation. Differences in pH value, osmolarity, viscosity and phosphate levels were identified. Among all formulations, bilastine exhibited pH, osmolarity and viscosity values closer to tear film (7.4, 300 mOsm/l and ~ 1.5–10 mPa·s, respectively), and was the only phosphates-free solution. Single-dose ketotifen did not induce ROS production, and single-dose azelastine and bilastine only induced a mild increase. Bilastine and single-dose ketotifen and azelastine showed high survival rates attributable to the absence of preservative in its formulation, not inducing caspase-3/7-mediated apoptosis after 24 h. Our findings support the use of the new bilastine 0.6% for treating patients with AC to preserve and maintain the integrity of the ocular surface.

Corneal Complications Related to Dupilumab Use.

The aim of this report is to describe atypical corneal complications associated with dupilumab use. This is a series of four cases of adult patients with infiltrative or ulcerative keratitis secondary to dupilumab use. All four patients in this series were prescribed dupilumab for the treatment of atopic dermatitis and developed infiltrative or ulcerative corneal lesions. In all cases, corneal disease was successfully managed with immediate discontinuation of dupilumab and topical steroid treatment. In two cases, the patient also received antibiotic eye drops for infection precautions. Although dupilumab is most commonly associated with conjunctivitis, physicians should be aware of potential severe corneal complications for early identification and intervention.