Topical Instillation Research Articles

Efficacy of Pretreatment with Preservative-Free Topical Bromfenac in Improving Post-Intravitreal-Injection Pain: A Prospective Pilot Study.

(1) Background: To determine the analgesic effect of pretreatment topical bromfenac instillation in patients undergoing intravitreal anti-VEGF treatment. (2) Methods: A prospective, non-randomized pilot study was conducted in patients scheduled to receive repeated intravitreal anti-VEGF injections at a single tertiary hospital. Before the planned second injection, the patients received topical bromfenac eye drops twice a day for 3 days. At 1, 6, and 24 h after the first and second injections, the post-injection pain scores were determined using the numerical rating scale (NRS) telephonically. (3) Results: A total of 28 patients were enrolled in this study. After the first intravitreal injection, the NRS pain scores were 4.04 ± 1.90 at 1 h, 1.57 ± 1.75 at 6 h, and 0.93 ± 1.27 at 24 h. The pain scores after the second intravitreal injection significantly decreased at each measurement time point (p = 0.002, 0.055, and 0.004, respectively) compared to the first injection. (4) Conclusions: The use of topical bromfenac eye drops before intravitreal injection can lead to a significant improvement in injection-related pain scores, which is the basis for a future large-scale randomized comparative study.

Resveratrol, an Inhibitor Binding to VEGF, Restores the Pathology of Abnormal Angiogenesis in Retinopathy of Prematurity (ROP) in Mice: Application by Intravitreal and Topical Instillation.

Retinopathy of prematurity (ROP) is a severe eye disease leading to blindness. Abnormal vessel formation is the pathological hallmark of neovascular ROP. In forming vessels, vascular endothelial growth factor (VEGF) is an important stimulator. The current anti-ROP therapy has focused on bevacizumab, a monoclonal antibody against VEGF, and pazopanib, a tyrosine kinase inhibitor on the VEGF receptor (VEGFR). Several lines of evidence have proposed that natural compounds may be more effective and safer for anti-VEGF function. Resveratrol, a common natural compound, binds to VEGF and blocks its interaction with VEGFR, thereafter suppressing angiogenesis. Here, we evaluate the efficacy of intravitreal injection, or topical instillation (eye drops), of resveratrol into the eyes of mice suffering from oxygen-induced retinopathy, i.e., developing ROP. The treatment of resveratrol significantly relieved the degree of vascular distortion, permeability and hyperplasia; the efficacy could be revealed by both methods of resveratrol application. In parallel, the treatments of resveratrol inhibited the retinal expressions of VEGF, VEGFR and CD31. Moreover, the applied resveratrol significantly relieved the damage caused by oxygen radicals through upregulating the level of superoxide dismutase (SOD) and downregulating the level of malondialdehyde (MDA) in the retina. Taken together, the potential therapeutic benefit of resveratrol in pro-angiogenic diseases, including retinopathy, can be considered.

Ocular Hypotensive Properties and Biochemical Profile of QLS-101, a Novel ATP-Sensitive Potassium (KATP) Channel Opening Prodrug.

PurposeTo characterize the ocular hypotensive and pharmacological properties of QLS-101, a novel ATP-sensitive potassium (KATP) channel opening prodrug.MethodsOcular hypotensive properties of QLS-101 were evaluated by measuring IOP with a handheld rebound tonometer after daily topical ocular instillation of 0.2% (n = 5) or 0.4% QLS-101 (n = 10) in C57BL/6J mice. KATP channel specificity was characterized in HEK-293 cells stably expressing human Kir6.2/SUR2B subunits and assessed for off-target interactions using a receptor binding screen. Conversion of QLS-101 prodrug to its active moiety, levcromakalim, was evaluated in vitro using human ocular tissues and plasma samples and after incubation with human phosphatase enzymes (2.0 nM-1.0 µM).ResultsC57BL/6J mice treated once daily with 0.2% QLS-101 exhibited significant (P < 0.01) IOP reductions of 2.1 ± 0.4 mmHg after five days; however, a daily attenuation of the effect was noted by 23h post-dose. By comparison, treatment with 0.4% QLS-101 lowered IOP by 4.8 ± 0.7 mm Hg (P < 0.0001) which was sustained for 24 hours. Unlike levcromakalim, QLS-101 failed to induce KATP channel activity in HEK-Kir6.2/SUR2B cells consistent with its development as a prodrug. No off-target receptor effects were detected with either compound. In vitro ocular tissue conversion of QLS-101 prodrug was identified in human iris, ciliary body, trabecular meshwork, and sclera. Alkaline phosphatase was found to convert QLS-101 (mean Km = 630 µM, kcat = 15 min−1) to levcromakalim.ConclusionsQLS-101 is a novel KATP channel opening prodrug that when converted to levcromakalim shows 24-hour IOP lowering after once-daily topical ocular administration.

Comparative Study of Ocular Pharmacokinetics of Topical 0.3% Gatifloxacin Eye Gel and Solution in Rabbits.

Few articles have reported drug concentrations of different ophthalmic dosage forms in the ocular tissues. This study aimed to determine the ocular pharmacokinetics of gatifloxacin 0.3% eye gel (GTX-Gel) and gatifloxacin 0.3% eye solution (GTX-Sol) at different time intervals after topical instillation in rabbits. A total of 126 healthy New Zealand rabbits were included, of which six rabbits did not receive antibiotics (control group). The remaining rabbits were randomly divided into four groups. GTX-Gel and GTX-Sol (50 μL) were topically instilled every hour in groups A1 and B1, respectively, and every two hours in groups A2 and B2, respectively, for 12 h. Ocular tissues were collected 2, 4, 8, 12, and 24 h after administration. Gatifloxacin concentration was measured using high-performance liquid chromatography coupled with tandem mass spectrometry. The drug reached peak concentrations (Cmax) in all tissues at 8–12 h. With the same administration frequency, the Cmax was higher with GTX-Gel than with GTX-Sol (p < 0.05). Except for the iris-ciliary body, other ocular tissues did not show significant difference (p > 0.05) in gatifloxacin concentration between either pair of groups. Gatifloxacin ophthalmic gel was found to attain significantly higher concentrations than the ophthalmic solution in ocular tissues.

Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye Disorders.

PurposeTo evaluate the therapeutic benefit of a novel peptide, ALM201, in ocular pathologic vascularization.DesignExperimental study in mouse, rat, and rabbit animal models.ParticipantsTen-week-old Lister Hooded male rats, 8-week-old Brown Norway male rats, 9-day-old C57BL/6J mice, and 12-month-old New Zealand male rabbits.MethodsCorneal vascularization was scored for vessel density and vessel distance to suture in a rat corneal suture model. Ocular penetration and biodistribution were evaluated by matrix-assisted laser desorption/ionization mass spectrometry imaging after topical ALM201 application to rabbit eyes. A mouse choroidal sprouting assay, with aflibercept as positive control, was used to evaluate choroidal neovascularization (CNV) in the posterior segment tissue. Efficacy of topical ALM201 was assessed using a rat laser CNV model of neovascular age-related macular degeneration.Main Outcome MeasuresClinical scoring and histologic analysis of vascularized corneas, sprouting area, lesion size, and vessel leakiness in posterior segments.ResultsAssessment of ALM201 treatment in the rat corneal suture model showed a significant decrease in vessel density (P = 0.0065) and vessel distance to suture (P = 0.021) compared with vehicle control (phosphate-buffered saline [PBS]). Infiltration of inflammatory cells into the corneal stroma also was reduced significantly compared with PBS (724.5 ± 122 cells/mm2 vs. 1837 ± 195.9 cells/mm2, respectively; P = 0.0029). Biodistribution in rabbit eyes confirmed ALM201 bioavailability in anterior and posterior ocular segments 1 hour after topical instillation. ALM201 treatment significantly suppressed choroid vessel sprouting when compared with PBS treatment (44.5 ± 14.31 pixels vs. 120.9 ± 33.37 pixels, respectively; P = 0.04) and was not inferior to aflibercept (65.63 ± 11.86 pixels; P = 0.7459). Furthermore, topical ALM201 significantly improved vessel leakiness (leakage scores: 2.1 ± 0.7 vs. 2.9 ± 0.1; P = 0.0274) and lesion size (144,729 ± 33,239 μm3 vs. 187,923 ± 28,575 μm3; P = 0.03) in the rat laser CNV model when compared with topical PBS vehicle.ConclusionsALM201 is a promising novel molecule with anti-inflammatory and antivascularization activity and is a strong candidate to meet the clinical need of a new, topically delivered therapeutic agent for treating inflammation and pathologic vascularization in the anterior and posterior segments of the eye.

Topical instillation of cell-penetrating peptide-conjugated melphalan blocks metastases of retinoblastoma

Retinoblastoma is the most common primary intraocular malignancy in infancy with a metastases-related death risk. However, a safe and convenient treatment without enucleation is still an unmet clinical need. In this work, a cell-penetrating peptide, 89WP, was conjugated with melphalan (89WP-Mel), which achieved high tumor inhibition effects as intravitreally injected melphalan via topical instillation for the first time. Notably, the “outside-in” diffusion of instilled 89WP-Mel created a protective shield surrounding the eye, efficiently preventing tumor metastases, while the mice treated with intravitreally injected melphalan suffered more brain metastases related death. The ocular absorption of 89WP-conjugated melphalan and other small molecules, both hydrophobic and hydrophilic, occurred via non-corneal pathway with high safety and a prolonged residence duration in retina up to 24 h. The present work paves a new avenue for simultaneous intraocular tumor inhibition and extraocular metastases prevention in a safe and convenient way via topical instillation.

Efficacy and Patient Tolerability of Omidenepag Isopropyl in the Treatment of Glaucoma and Ocular Hypertension.

Current therapeutic approaches for glaucoma aim to reduce intraocular pressure (IOP), which is the only available and reliable strategy proven to control the risk of disease development and progression. Omidenepag isopropyl (OMDI) is a novel topical ocular hypotensive agent that was launched onto the market for the treatment of glaucoma and ocular hypertension (OHT). After topical instillation and during corneal penetration, OMDI is converted into the active metabolite omidenepag (OMD), which behaves as a non-prostaglandin, selective E-prostanoid subtype 2 (EP2) receptor agonist. The topical administration of 0.002% OMDI once-daily (QD) possesses a 20–35% IOP-lowering effect, comparable to that of prostaglandin analogs targeting F-prostanoid (FP) receptor QD, which are the current first-line for pharmaceutical reduction of IOP. However, the mechanism of action and adverse events (AEs) of OMDI are different from those of FP receptor agonists. OMDI reduces IOP by enhancing both conventional trabecular and uveoscleral outflow facilities without complications of prostaglandin-associated periorbitopathy (PAP) seen with FP receptor agonists. Moreover, OMDI was also effective and well-tolerated in non-/poor responders to latanoprost and showed a stable IOP-lowering effect for one year, and its concomitant use with timolol enhanced the IOP-lowering effect. OMDI demonstrated acceptable safety and tolerability with good adherence and can be used in almost every patient. However, OMDI has some AEs such as conjunctival hyperemia, corneal thickening, macular edema/cystoid macular edema and ocular inflammation. Moreover, OMDI is contraindicated in patients who are allergic to the product, in aphakic or pseudophakic eyes, and in combination with tafluprost eye drops. If used appropriately in the right patients, OMDI could be an effective treatment option for glaucoma and OHT as a first-line alternative to FP agonists. Here, we summarize the results of clinical studies of OMDI and discuss its efficacy and patient tolerability in glaucoma and OHT in this review.

Validation of a preclinical dry eye model in New Zealand white rabbits during and following topical instillation of 1% ophthalmic atropine sulfate.

BackgroundThe objective of this study was to validate an animal model for dry eye during and after the administration of 1% ophthalmic atropine sulfate (OAS) in New Zealand white (NZW) rabbits.MethodsOAS (1%) was applied three times per day to 30 eyes of 15 healthy NZW rabbits. Sacrifice, enucleation, and lacrimal gland removal took place on days 15, 21, and 30 (OAS group). A second group (n = 5) was used as control. Clinical evaluations took place on days 3, 10, 15, 18, 21, 24 and 30. The primary endpoints were: Schirmer I test, tear break‐up time (TBUT), and corneal fluorescein staining. As secondary endpoints, clinical changes including intraocular pressure, and histopathology were evaluated.ResultsWhile OAS was administered, the Schirmer I test showed a statistically significant reduction for OAS group versus control (p < 0.001), and versus basal production (p < 0.001). TBUT showed statistically significant differences between groups (days 3 and 10; p = 0.001) and versus basal values (day 3; p < 0.001). Fluorescein staining showed a statistically significant difference (day 3; p = 0.001). The most frequent clinical finding was conjunctival hyperemia (76.9% OAS vs. 20% control). For histopathology, all OAS subjects presented some degree of inflammation (86.7% minimal; 13.3% mild) whereas the control presented only 30% minimal inflammation. Goblet cell density showed no difference.ConclusionsThe effectiveness of the OAS dry eye model in NZW rabbits as reported in previous studies was confirmed, provided that the application of the drug is maintained throughout the intervention; it is not a viable model after OAS administration is suspended.

Enzyme-instructed self-assembly of peptide-drug conjugates in tear fluids for ocular drug delivery

In vivo self-assembly of small molecules offers an excellent opportunity for targeted and long-term accumulation of a therapeutic agent at the lesion site. Here we demonstrate the strategy of enzyme-instructed self-assembly (EISA) by designing a phosphorylated peptide-drug (IBF-HYD-GFFpY) precursor through the ester bond to release active drugs at the target site. Meanwhile, the in vivo assembly can be achieved by the catalysis of alkaline phosphatase (ALP) in the tear fluid for ocular drug delivery efficiently. The in vitro enzymatic experiments indicate that the dephosphorylation of IBF-HYD-GFFpY occurs firstly with the yield of IBF-HYD-GFFY which subsequently self-assembles into the supramolecular hydrogel to afford sustained drug release over 96 h. In the treatment of lipopolysaccharide (LPS)-activated Raw 264.7 macrophages, IBF-HYD-GFFpY exerts the more potent anti-inflammatory efficacy than that of free ibuprofen (IBF) at the concentration of 200 μM. Moreover, the aqueous solution of IBF-HYD-GFFpY via topical instillation hardly causes ocular irritation, and displays longer precorneal retention compared to the conventional eye drop formulation. In addition, in the in vivo study, a rabbit model of endotoxin-induced uveitis (EIU) evidences the comparable therapeutic efficacy of IBF-HYD-GFFpY eye drops with that of clinically used 0.1 wt% diclofenac (DIC) sodium eye drops by the reduction of macrophage and leukocyte influx. This work, in situ EISA in the tear microenvironment directing in vivo self-assembly of small molecules, may guide a powerful approach for developing enzymatic self-assembled molecules as an efficient delivery system of ocular drugs.

Polymeric Drug Delivery Devices: Role in Cornea and External Disease.

The field of ophthalmic drug delivery is undergoing rapid changes not only in the evolution of pharmacologic agents but also in the novel drug delivery vehicles. The ocular surface has limitations to drug penetration because of the presence of tight junctions between basal epithelial cells, which limits the amount of drug that can be absorbed after topical instillation. In addition, nasolacrimal drainage reduces the precorneal residence time significantly. Contact lenses (CLs) have been considered as possible carriers for topical medications because they reside on the ocular surface for a sufficient length of time, and pharmacologic agents may be copolymerized with hydrogels allowing controlled drug diffusion. This strategy reduces the frequency of dosage while improving compliance. Modification of drug delivery vehicles is essential to allow sustained release of the drug from a polymeric complex, facilitate stability and residence time of the drug on the precorneal tear film, and improve penetration into biologic membranes. This review focuses on updates in CL-based and non-CL-based strategies in ophthalmic drug delivery.

The Effect of Limbal Mesenchymal Stem Cell Secretome on Corneal Expression of Interleukin-1 in Experimental Model of Corneal Alkali Injury

Background: To investigate the effect of limbal mesenchymal stem cells secretome (L-MSCS) on corneal expression of Interleukin-1 (IL-1) in alkali ocular chemical injury animal model. Methods: Secretome was collected from limbal mesenchymal stem cells of corneoscleral tissue of healthy male rabbit. Rabbits were exposed to NaOH. The research subjects consisted of 3 groups, normal control group, Balance saline solution (BSS) group, and L-MSCS group. The level of corneal expression of IL-1 by immunohistochemical staining were analyzed. Results: After seven days administration of topical instillation of L-MSCS, the mean level of IL-1 expression with immunoreactive score (IRS) was 3,2 in normal group, 5,4 in BSS group, and 5,1 in L-MSCS group. The level of IL-1 expression in L-MSCS group was lower than BSS group. There was no difference in IL-1 expression between L-MSCS group and the BSS group (p>0.05) but a significant difference was found between normal group and BSS group, normal group and L-MSCS group, and between the three groups (p<0.05). Conclusions: Topical instillation of L-MSCS has a potential effect on decrease the level of IL-1 expression in the 7th day of chemical ocular injury animal model even though the difference was not statistically significant.

Effect of Topically Applied 0.5% Apraclonidine Versus 0.5% Timolol Maleate on Intraocular Pressure of Healthy Horses

This study aims to assess the effect of topical 0.5% apraclonidine on Intraocular pressure (IOP) in horses and compare the effects of timolol maleate 0.5% with 0.5% apraclonidine in the equine eye. Twenty healthy female thoroughbred horses were used. Horses were divided into two groups. Ten horses received single dose of 0.2 mL of 0.5% apraclonidine in one randomly selected eye and the contralateral eye received single dose of 0.2 mL of artificial tears. In the second group, 10 horses received single dose of 0.2 mL of 0.5% timolol maleate in one eye and the opposite eye received single dose of placebo (0.2 mL of artificial tears). Intraocular pressure was measured using rebound tonometer at the baseline and 30, 60, 120, 240, 360 minutes, and 24 hours after topical ophthalmic drops instillation. Any ocular side effects were recorded at each time point. Mean (SD) baseline IOPs of the treated and placebo eyes were 26.2(3.1) and 23.5(3.4) in apraclonidine group, and 25.7(2.6) and 23.2(3.3) in timolol group. In the apraclonidine group, significant reduction in the mean IOP started after 60 minutes (P= .005) and was still present after 24 hours (P < .001). In timolol group, IOP was reduced in the treated eyes, but this reduction was only significant in the treated eyes at T24h (P= .03). The highest reduction in IOP in timolol group was observed at T360 (21.0(2.2); 14.7%). Mean IOP was decreased prominently by apraclonidine compared to timolol in treated eyes. In conclusion, single dose of topical 0.5% apraclonidine reduced IOP significantly among normal horses in the present study. Further investigations are necessary for evaluating efficacy and safety of apraclonidine in horses.

Nanotechnology-based formulations to amplify intraocular bioavailability.

Conventional drug delivery formulations, such as eye drops and ointments, are mainly administered by topical instillation. The topical delivery of ophthalmic drugs is a challenging endeavor despite the eye is easily accessible. Unique and complex barriers, serving as protection against extrinsic harmful factors, hamper therapeutic intraocular drug concentrations. Bioavailability for deeper ocular tissues of the anterior segment of the eye is exceptionally low. As the bioavailability of the active substance is the major hurdle to overcome, dosing is increased, so the side effects do. Both provoke patient poor compliance, confining the desired therapeutic outcome. The incidence and severity of adverse reactions amplify evenly in the case of chronic treatments. Current research focuses on the development of innovative delivery strategies to address low ocular bioavailability and provide safe and convenient dosing schemes. The main objective of this review is to explore and present the latest developments in ocular drug delivery formulations for the treatment of the pathology of the anterior segment of the eye. Nanotechnology-based formulations, that is, organic nanoparticles (liposomes, niosomes/discosomes, dendrimers, nanoemulsions, nanosuspensions, nanoparticles/nanospheres) and inorganic nanoparticles, nanoparticle-laden therapeutic contact lenses, in situ gelling systems, and ocular inserts, are summarized and presented accordingly.

Authors′ response_123

We thank the authors for their interest and comments with regard to the use of chloroquine nasal drops in mild COVID-191. Therapeutic applications for COVID-19 has been a rapidly evolving area and it is quite true that the initial promise of chloroquine and hydroxychloroquine (CQN and HCQ) has not stood the test of evolving evidence over time. This particular study was conducted in April-May 2020 when Covid was just emerging in the world, and many of the insights of today were not available. It also is in tandem with other evidence accumulated over time to indicate that CQN delivered intranasally, is similar to systemically administered CQN and HCQ,2 in not being demonstrated as effective in patients with established COVID-19 infection. The statement of conveniently understating adverse events is unwarranted. Of the 30 patients, seven had adverse events which were no worse than mere irritants (local nasal irritation from topical nasal drops instillation), and which did not deter them from continuing the treatment. One other patient was non-compliant to the treatment. These facts have been stated as observed. The observations on toxicity and mortality of systemic HCQ as per the quoted systemic reviews,23 do not apply to nasal CQN. The post-hoc analysis on Ct values as pre-exposure prophylaxis in non-infected patients receiving nasal CQN/ placebo was not a planned observation and the numbers are therefore not suitably powered for this observation. It was however, of significant promise at the time of the observations when no appropriate treatment or vaccines were available. The observation is only in the context of prophylactic treatment before infection, and can certainly not be of any greater relevance than as a hypothesis generating observation which needs further testing. In current times, the availability of effective and safe vaccines would seem to eclipse and override any potential role of nasal CQN for prophylaxis. This is the nature of parallel and competing advances in science.

MicroRNA Therapy for Dry Eye Disease.

Purpose: We tested the role of microRNA-328 in dry eye disease (DED). Benzalkonium chloride (BAC) has been used to induce DED in animal models. We first demonstrated that both BAC and hyperosmotic stress induced overexpression of miR-328 in corneal cells and then tested whether anti-miR-328 could be a new therapy. Methods: BAC was instilled to both eyes of 41 rabbits and 19 mice from day 0 to 21 to induce DED. Animals of each species were divided to receive topical instillation of saline or anti-miR-328 eye drops between day 8 and 21. The DED signs were assessed by corneal fluorescein staining, histological examination, apoptosis of corneal cells, and inflammatory cytokines in rabbit eyes. For mice, only corneal fluorescein staining was assessed for the therapeutic effects. The corneal fluorescein staining scores ranged from 0 of no staining to 4 of coalescent. Results: For the rabbits, the staining score was significantly reduced (P = 0.038) after the 14-day anti-miR-328 treatment (n = 42 eyes), but the score was not improved by saline treatment (n = 40 eyes). Furthermore, rabbit eyes treated with anti-miR-328 had thicker corneal epithelium (P = 9.4 × 10-5), fewer apoptotic cells in corneal epithelium (P = 0.002), and stroma (P = 0.029) compared with the saline-treated eyes. Anti-miR-328 was more effective than saline to reduce the block of orifices of Meibomian glands, although such an effect was only marginally significant (P = 0.059). Similarly, anti-miR-328 was more effective than saline in reducing corneal staining in mouse eyes (P = 0.005). Conclusion: Overexpression of miR-328 may contribute to DED. Anti-miR-328 protects corneal cells and promotes re-epithelialization for DED treatment.

P027 CHRONIC MESH INFECTION AFTER TRANSVERSUS ABDOMINIS RELEASE FOR A MULTIRECURRENT COMPLEX VENTRAL HERNIA IN HIGH RISK PATIENT: CRITICAL ISSUES OF A LONG LASTING MANAGEMENT

Abstract Aim to point out the critical issues of the management of a challenging case of complex ventral hernia (CVH) in high risk patient Material and methods A 58-year-old female was referred to our Institution with a history of alcohol and smoking abuse, COPD and class I obesity. Four years before she underwent liver transplantation. In the next two years she had 2 VH repairs with polypropilene (PP) meshes. The postoperative course was complicated by a deep surgical site infection (SSI) and dehiscence. The wound resulted in a large R2 M3-L2 CWH with distorted anatomy. The patient experienced VH incarcerations and bowel obstructions. Clinical examination revealed no signs of infection and the CT scan showed partial loss of substance of the abdominal wall. Results The patient underwent posterior component separation with transversus abdominis release (PCS-TAR) and large PVDF mesh on top of a biosynthetic mesh implantation. The postoperative course was complicated after 14 days by a SSI causing a large wound dehiscence with underlying mesh exposure. The patient was readmitted and negative pressure wound therapy (NPWT) with topical wound solution instillation was initiated. After 1 month was followed up as an out-patient to continue traditional NPWT and removal of former PP remnants. NPWT was interrupted after 6 months and no signs of infection nor VH recurrence were recorded at 1 year. Conclusions the indication to PCS-TAR for such comorbid patient should be carefully evaluated. The use of a biosyntetic mesh could be debatable. The conservative management of a chronic infection could be the first-line option in case of macroporous mesh implantations.

The Impact of Clinical Atropine Use in Taiwanese Schoolchildren: Changes in Physiological Characteristics and Visual Functions.

Taiwan is commonly noted for its high prevalence of myopia, as well as a long history of more than 20 years of using atropine to control myopia. However, the clinical implications are rarely discussed. This is a cross-sectional study investigating the influence of topical atropine instillation on ocular physiology, visual function, and visual discomfort in children. Aged 7 to 12 years, 212 schoolchildren were recruited and divided into the atropine group and the non-atropine group. Physiological characteristics such as pupil size and intraocular pressure were measured, and a variety of visual functions was also evaluated. A questionnaire was used to investigate the side effects and visual complaints caused by atropine treatment. There was a significant difference in pupil size (OD: 5.40 ± 0.90 vs. 6.60 ± 1.01 mm; OS: 5.42 ± 0.87 vs. 6.64 ± 1.00 mm, p < 0.001) between the two groups. Reductions in near visual acuity, accommodation, convergence ability, and stereopsis were observed in the atropine group. The horizontal pupil diameter enlarged, and visual functions were greatly affected after administration of topical atropine. The changes in visual function during atropine therapy need to be carefully monitored by clinicians, while patient compliance is usually the key to success.

Efficacy of Artificial Tears Based on an Extract of Artemia salina Containing Dinucleotides in a Rabbit Dry Eye Model.

(1) Background: Artemia salina is a brine shrimp containing high concentrations of dinucleotides, molecules with properties for dry eye treatment. For this reason, the purpose of the study was to evaluate the effect of the artificial tears based on an extract of Artemia salina in a rabbit dry eye model. (2) Methods: A prospective and randomized study was carried out. Twenty rabbits were divided into 4 groups (n = 5, each group): healthy rabbits, dry eye rabbits, dry eye rabbits treated with hypromellose (HPMC), and dry eye rabbits treated with Artemia salina. Dry eye was induced by the topical instillation of 0.2% benzalkonium chloride. The measurements were performed before and after the treatment for 5 consecutive days. (3) Results: The topical instillation of artificial tears containing Artemia salina showed beneficial effects on tear secretion, tear break-up time, corneal staining, the density of Goblet cells, heigh of mucin cloud secreted by these cells, and mRNA levels of IL-1β and MMP9 in conjunctival cells. Compared with the HPMC, there was a statistically significant improvement (p < 0.05) with the Artemia salina in all the variables under study, except for the conjunctival hyperemia, density of Goblet cells, and mRNA levels of IL-6. (4) Conclusions: The potential of artificial tears based on Artemia salina as a secretagogue agent for dry eye treatment was confirmed, opening the door for future clinical trials and studies to extrapolate the findings for dry eye patients.

The Effect of Limbal Mesenchymal Stem Cell Secretome on Corneal Neovascularization in Experimental Model of Corneal Alkali Injury

Background: To investigate the effect of limbal mesenchymal stem cell (L-MSC) secretome in inhibition of corneal neovascularization in animal model of alkali chemical injury Methods: Secretome was collected from limbal mesenchymal stem cells of corneoscleral tissue of healthy male rabbit. Rabbits were exposed to NaOH. The research subjects consisted of 3 groups, normal control group, Balance salt solution (BSS) group, and (L-MSC) secretome group. Clinical corneal neovascularization level, number of corneal neovascularization histopathologically with hematoxylin-eosin staining and VEGF expression by immunohistochemical staining were analyzed. Results: After seven days of administration of topical instillation of L-MSC secretome, neovascularization level in L-MSC group was lower than BSS group even though the difference was not statistically significant (p>0.05). The mean histopathological neovascular count in the L-MSC secretome group was lower than that BSS group even though the difference was not statistically significant (p>0.05) Conclusions: In conclusion, topical instillation of limbal mesenchymal stem secretome has a potential effect on inhibiton of corneal neovascularization even though not significant at day-7 in experimental alkali injury model.

Celastrol-based nanomedicine promotes corneal allograft survival

Effectively promoting corneal allograft survival remains a challenge in corneal transplantation. The emerging therapeutic agents with high pharmacological activities and their appropriate administration routes provide attractive solutions. In the present study, a celastrol-loaded positive nanomedicine (CPNM) was developed to enhance corneal penetration and to promote corneal allograft survival. The in vitro, in vivo and ex vivo results demonstrated the good performance of CPNM prolonging the retention time on ocular surface and opening the tight junction in cornea, which resulted in enhanced corneal permeability of celastrol. Both in vitro and in vivo results demonstrated that celastrol inhibited the recruitment of M1 macrophage and the expression of TLR4 in corneal allografts through the TLR4/MyD88/NF-κB pathway, thereby significantly decreasing secretion of multiple pro-inflammatory cytokines to promote corneal allograft survival. This is the first celastrol-based topical instillation against corneal allograft rejection to provide treatment more potent than conventional eye drops for ocular anterior segment diseases.Graphical