Ocular Safety Research Articles

OCTN2- and ATB0,+-targeted nanoemulsions for improving ocular drug delivery

Traditional eye drops are administered via topical instillation. However, frequent dosing is needed due to their relatively rapid precorneal removal and low ocular bioavailability. To address these issues, stearoyl L-carnitine-modified nanoemulsions (SC-NEs) were fabricated. The physicochemical properties of SC-NEs in terms of size, morphology, zeta potential, encapsulation efficiency, and in vitro drug release behavior were characterized. The cellular uptake and mechanisms of SC-NEs were comprehensively studied in human corneal epithelial cells and the stearoyl L-carnitine ratio in SC-NEs was optimized. The optimized SC-NEs could target the novel organic cation/carnitine transporter 2 (OCTN2) and amino acid transporter B (0 +) (ATB0,+) on the corneal epithelium, which led to superior corneal permeation, ocular surface retention ability, ocular bioavailability. Furthermore, SC-NEs showed excellent in vivo anti-inflammatory efficacy in a rabbit model of endotoxin-induced uveitis. The ocular safety test indicated that the SC-NEs were biocompatible. In general, the current study demonstrated that OCTN2 and ATB0,+-targeted nanoemulsions were promising ophthalmologic drug delivery systems that can improve ocular drug bioavailability and boost the therapeutic effects of drugs for eye diseases.Graphical

Imatinib@glycymicelles entrapped in hydrogel: preparation, characterization, and therapeutic effect on corneal alkali burn in mice.

Imatinib (IMB) is a type of tyrosine kinase inhibitor with great application potential for inhibiting corneal neovascularization (CNV), but its poor water solubility limits its application in eye disease treatment. In this study, novel IMB@glycymicelles entrapped in hydrogel (called IMB@glycymicelle-hydrogel) were prepared, characterized, and evaluated for their therapeutic effects on corneal alkali burn in mice. Imatinib could be successfully loaded in glycymicelles using glycyrrhizin as a nanocarrier with an optimized weight ratio of IMB:nanocarrier. The apparent solubility of IMB was significantly improved from 61.69 ± 5.55μg/mL to bare IMB to 359,967.62 ± 20,059.42μg/mL to IMB@glycymicelles. Then, the IMB@glycymicelles were entrapped in hydrogel fabricated with hydroxypropyl methylcellulose and sodium hyaluronate (HA) to prolong retention time on the ocular surface. Rabbit eye tolerance tests showed that IMB@glycymicelle-hydrogel possessed good ocular safety profiles. In a mouse model of corneal alkali burns, the topical administration of IMB@glycymicelle-hydrogel showed strong efficacy by prompting corneal wound healing, recovering corneal sensitivity, relieving corneal opacities, and inhibiting CNV, and these efficacy evaluation parameters were better than those of the positive drug HA. Overall, these results demonstrated that IMB@glycymicelle-hydrogel may be a promising candidate for the effective treatment of alkali ocular damage.

Advancing ocular safety research: A comprehensive examination of benzocaine acute exposure without animal testing

Benzocaine is a widely employed local anaesthetic; however, there is a notable dearth of preclinical and clinical evidence regarding its safety in ophthalmological products. To address this, a comprehensive strategy incorporating in silico and in vitro methodologies was proposed for assessing benzocaine's ocular toxicity without animal testing. To collect the in silico evidence, the QSAR Toolbox (v4.5) was used. A single exposure to two benzocaine concentrations (2% and 20%) was evaluated by in vitro methods. Hen’s Egg Chorioallantoic Membrane Test (HET-CAM) was performed to evaluate the effects on the conjunctiva. To study corneal integrity, Short Time Exposure test (STE) and Bovine Corneal Opacity and Permeability (BCOP) assay, followed by histopathological analysis, were carried out. Results from both in silico and in vitro methodologies categorize benzocaine as non-irritating. The histopathological analysis further affirms the safety of using benzocaine in eye drops, as no alterations were observed in evaluated corneal strata. This research proposes a useful combined strategy to provide evidence on the safety of local anaesthetics and particularly show that 2% and 20% benzocaine solutions do not induce eye irritation or corneal damage, supporting the potential use of benzocaine in the development of ophthalmic anesthetic products.

Topical Application of Perchlorate: A Toxicity Study in Rats.

To investigate the ocular safety profile of topical perchlorate as a potential preventive treatment for nasolacrimal obstruction associated with excessive use of radioactive iodine therapy. Nine Wistar male rats (18 eyes) were randomly assigned to receive an ocular application (topical eye drop on the OD, 3 times a day for 5 days) consisting of either: 1) sterile saline solution, 2) 30 mg/ml NaClO4 or 3) 30 mg/ml KClO4. The rat eyes were examined daily for corneal cloudiness/clarity, discharge, mucous secretions, conjunctival injection, eyelid erythema, and/or changes in behavior. Seven days after the first dose, the rats were euthanized and OU were harvested, fixed, embedded in paraffin, and stained with H&E and Masson's trichrome using standard techniques. The data collected over the 7 days revealed no behavior changes or ocular complications in any of the 3 study groups. Pathologic analysis of the corneas revealed normal findings on all groups without signs of inflammation, fibrosis, or any other abnormality, and no difference between the treated and control eyes. The findings of this study suggest that the use of topical perchlorate is safe to use on eyes in high concentrations. The efficacy of this compound in minimizing fibrosis of the nasolacrimal sac and duct warrants further study.

Short-term outcomes of treatment switch to faricimab in patients with aflibercept-resistant neovascular age-related macular degeneration

PurposeTo report short-term outcomes of treatment switch to faricimab in real-world patients with aflibercept-resistant neovascular age-related macular degeneration (AMD).MethodsSingle-center, retrospective cohort study with chart-review using electronic injection database, electronic medical records, and optical coherence tomography (OCT) data from May to September 2023.ResultsA total of 50 eyes of 46 patients were analyzed. Faricimab treatment led to absence of fluid in 32% of the eyes and a reduction of fluid in 84% of the eyes. There was a statistically significant decrease in central retinal thickness (CRT) and pigment epithelial detachment (PED) height in those that responded to the switch (median difference: − 31 μm, IQR: 55, p < 0.0001 and median difference: − 21 μm, IQR: 36, p < 0.0001, respectively) and a statistically significant increase in CRT (median difference: + 19 μm, IQR: 20, p = 0.0143) and no change in PED height (median difference: + 22 μm, IQR: 64, p = 0.1508) in those that did not.Best-corrected visual acuity (BCVA) showed marginal decrease with low statistical significance. No ocular or systemic safety events were observed.ConclusionsOur findings suggest that switching to faricimab is generally safe and effective in patients with neovascular AMD who are otherwise difficult to treat and have residual fluid despite frequent injections with aflibercept. We observed a high rate of morphological response to the treatment switch, improvement of anatomical parameters with about one-third of patients having dry macula following a single injection, and a marginal change in BCVA. Sustainability of these results requires further investigation.Study registrationClinicalTrials.gov registration number: NCT06124677. Date of registration: 09/11/2023, retrospectively registered.

Is multiple wavelength diode laser for facial contouring safe?

The multiple wavelength diode laser (MWDL) is a sophisticated device designed to target deeper skin layers by emitting various wavelengths. Its unique feature is the ability to deliver heat to specific depths within the tissue using different wavelengths while simultaneously cooling the skin surface. Recent research by Choi etal. suggests that wavelengths of 755 and 810 nm can induce carbonization in hair follicles, while the 1064 nm wavelength penetrates deeper into tissues. MWDL has been proposed for fat redistribution in aging, but concerns have been raised regarding ocular safety and potential tissue damage, particularly when used near the eyes. Studies have shown ocular injuries during cosmetic laser procedures, emphasizing the need for robust ocular protection and safety protocols. Additionally, there are reports of internal ischemic necrosis and burns, highlighting the importance of precise energy settings and parameter management. While MWDL shows promise, further research and comprehensive guidelines are needed to ensure safe and effective usage in clinical practice.

Long-term ocular surface stability in conjunctivolimbal autograft and ocular surface safety in the donor eyes.

The current study is aimed to present the long-term results of the patients who underwent conjunctivolimbal autograft (CLAU) as the primary operation in unilateral limbal stem cell deficiency and the ocular surface safety of the donor eyes. The patients were followed up for fiveyears or longer. The records of all patients who underwent CLAU as the primary operation were retrospectively analyzed. Additional ocular surface operations, ocular surface stability, best-corrected visual acuity (BCVA), and ocular surface status of the donor eyes were investigated. The mean age of the patients at the time of transplantation was 35.07 ± 12.9 (12-60). Twenty-nine eyes of 29 patients were followed up for an average of 97.82 ± 34.45 (60-186) months. Additional ocular surface operation was required in 27.58% (8/29) of the eyes in order to achieve a stable ocular surface. Ocular surface stability was achieved in 82.75% (24/29) of the eyes at the end of the follow-up period. BCVA increased from 1.78 ± 0.82 to 0.91 ± 0.92 logMAR at the last visit (p < 0.001). Corneal ectasia and vascularization developed in one donor eye in the fifth postoperative year. CLAU tissues provide ocular surface stability with a successful vision result in the long term. CLAU theoretically carries risks including limbal stem cell deficiency in the donor eye. In the long-term follow-up of donor eyes after CLAU, ectasia and limbal stem cell deficiency were observed in one eye.

Chinese expert consensus on the diagnosis and treatment of contact lens-associated dry eye (2024)

The number of contact lens wearers in China is increasing rapidly. Long-term contact lens wearing may induce or exacerbate tear film instability, and consequently affect the visual quality, ocular surface safety, and compliance of the wearers. To promote the safety and effectiveness of contact lens fitting, and to improve the visual quality and satisfaction of contact lens wearers, the Society of Contact Lens Safety Monitoring & Vision Health of Chinese Health Association has targeted to develop an expert consensus on the diagnosis and treatment of contact lens-associated dry eye. By referring to relevant literature and summarizing clinical experience, the clinical experts in corneal disease, pediatric ophthalmology and optometry have made repeated discussions to form this consensus, including the definition, pathological mechanisms, influencing factors, evaluation, prevention and treatment of contact lens-associated dry eye, for the reference of optometrists and ophthalmologists.

Prevalence of ocular morbidity among industrial workers of Eastern Nepal

Objectives: The study aimed to investigate the prevalence of ocular morbidity among industrial workers. Materials and Methods: A descriptive cross-sectional study was carried out in four industries of Koshi Province. The demographic information gathered encompassed details such as age and gender. Employment-related factors included the nature of work, years of experience, and the type of industry. Economic considerations, such as monthly pay scale and job responsibilities, were also explored. Educational background and awareness of ocular hazards in the workplace, along with knowledge about safety devices, constituted crucial components of the survey. Comprehensive ocular examinations, along with assessments for color vision, contrast sensitivity, and stereopsis, were carried out on-site in collaboration with the outreach team of Biratnagar Eye Hospital. A structured schedule was administered through face-to-face interviews and documented. Results: In the present study, A total of 359 industrial workers were screened; among them, 321 (89%) were male, and 38 (11%) were Female, with a mean age of 43.72 ± 10.18. The majority of them were from 40 to 49 years of age group 135 (37.6%). The overall prevalence of ocular morbidity among the workers was 289, (80.50%). The highest rate of ocular morbidity was seen in sugar industry 98, (89.9%) followed by the jute industry 85, (80.18%), the soap industry 59, (74.68%), and the dairy industry 47, (72.30%). Presbyopia 166, (46.23%) emerged as the most common ocular morbidity among all workers. A history of ocular injuries was found in 115, (32%) of workers, and only 19% of workers used ocular safety devices. The main reason for not using ocular safety devices was due to unavailability (65%). Conclusion: The research highlights a significant prevalence of ocular morbidity among industrial workers, with presbyopia emerging as the most common ocular disorder.

Advancements in Retinoblastoma Treatment: Unraveling the Potential of Intravitreal Chemotherapy.

Retinoblastoma necessitates urgent attention due to itspotential fatality if untreated. Multiple treatment options are available and should be employed according to size, location, and the extent of dissemination. This reviewemphasizes the need for increased awareness, advanced diagnostic tools, and innovative treatmentapproaches, especially intravitreal chemotherapy (IVitC) to address the diverse manifestations and aggressive nature of retinoblastoma.Timely diagnosis and commitment to treatment are pivotal, as delays and reluctance to undergo enucleationcontribute to unfavorable outcomes. The evolving treatment landscape, spanning from traditionalinterventions to modern targeted therapies such as intravitreal melphalan, holds promise for improvedoutcomes. While the intravitreal approach presents challenges, ongoing research aims to establish itsdefinitive role in retinoblastoma treatment. In the treatment of retinoblastoma, IVitCraises considerations about side effects. The risk of tumor spread beyond the eye is rare, emphasising thepotential of IVitC in carefully selected cases. Intravitreal injections exhibit fewer localadverse effects compared to intra-arterial chemotherapy, with careful measures reducing significant ocularcomplications. The evaluation of ocular toxicity, particularly with melphalan, underscores the importance ofa nuanced approach to achieve the right balance between therapeutic efficacy and ocular safety. This comprehensive analysis of studies on IVitC and its ocular and systemic complications provides valuable insights for enhanced patient care. The review concludes with a focus on balancingsafety and efficacy in local chemotherapeutic drugs, highlighting the need for thoughtful measures andcontinued research to optimise treatment modalities globally.

Ocular safety of hydroxychloroquine when used as prophylaxis against COVID-19 in healthcare workers at a tertiary care center in India

Ocular safety of hydroxychloroquine when used as prophylaxis against COVID-19 in healthcare workers at a tertiary care center in India

Safety-in-use test of facial cosmetic products on normal and self-assessed sensitive skin subjects.

Safety-in-use (SIU) studies are commonly used by the cosmetic Industry to confirm the skin and ocular compatibility of cosmetic products under realistic in-use conditions. There are only limited case studies published about the design, outcome and interpretation of product SIU studies. A series of SIU case studies is presented to demonstrate the considerations in study design and how the methodology can help in supporting skin and ocular safety profile of facial cosmetic products within a population of different ethnicities with normal and self-perceived sensitive skin. In a series of four single-blinded SIU studies, more than 250 female study subjects of different ethnicities and with normal and self-assessed sensitive skin were asked to use different facial cosmetic products including lotions, essences and cleansers according to the instructed usage conditions of these products. Each study was specifically designed according to product usage scenarios and target consumer groups. The primary measures of safety were based on dermal evaluations by a dermatologist for erythema and dryness/scaling and by an ophthalmologist for any visible signs of an ocular condition on eyelids, conjunctivae and cornea. The study subjects were also asked for any self-perceived skin or eye reactions. Dermal and ocular irritation potential of the products under realistic product usage conditions was evaluated according to the measures. Across all studies, objectively and self-assessed mean scores for skin and eye effects did not indicate any cumulative response of the investigated products over the study period. As a suitable tool for assessing and establishing the skin and eye compatibility of facial cosmetic products, SIU studies can be designed according to specific consumer groups, skin types and product usage scenarios to better predict realistic in-use conditions. It can demonstrate the safe use of the investigated products for people of different ethnicities, skin types and with normal or self-assessed sensitive skin, single product use or regimen use. The test results are consistent with the inherently low irritation potential of the products.

Evaluation of Lycium Shawii Schult &amp; Roem Eye Drops as a Novel Treatment for Old Corneal Scars in Rabbits

Purpose: to evaluate the efficacy of eye drops extracted from Lycium Shawii Roem&amp;Schult leaves in treating old corneal scars in rabbit corneas. A corneal scar is a condition in which the cornea becomes opaque. The cornea is a transparent, avascular tissue. Corneal opacity/scar is the fifth leading causes of blindness and vision impairment worldwide.&#x0D; Methods: In a randomized controlled trial. twelve European pigmented rabbits with a twenty four eyes with a mean weight of 1.12 kg (Standared Deviation ± 0.16 kg), aged 5 to 6 months old, were subjected to a partial thickness (120–180 μm) sterile surgical excision on the anterior central part of the cornea with a 7 mm diameter. After the surgical procedures, we waited six weeks for stable old corneal scars to develop, after that rabbits received topical drops as one eye drops three times per day for two months, lycium shawii leaves extract for treatment group (10%; n=12), placebo (normal saline 9% ;n=10) for control group. Therapy effects on corneal scar and ocular safety were evaluated by slit-lamp microscope, Modified Fantes haze scale for grading.&#x0D; Results: The treatment group showed a significant reduction in corneal scar (P &lt;0.000), mean 2.75 score , standard deviation ± 0.45, and a 68.75% improvement in corneal clarity (P &lt;0.000), mean 0.25 score, standard deviation ± 0.45.&#x0D; Conclusion: The therapy is effective and safe in treating old corneal scar in rabbit and restores the transparency without ocular toxicity even after 2.5 years of follow up.

Safety and efficacy of intravitreal injection of conbercept for the treatment of patients with choroidal neovascularization secondary to pathological myopia: Results from the SHINY study.

To evaluate the safety and efficacy of intravitreal injections of 0.5 mg conbercept in patients with choroidal neovascularization secondary to pathological myopia (pmCNV). The 177 pmCNV patients were randomly assigned in a 3:1 ratio to receive conbercept or sham injection, respectively. The conbercept group receive conbercept intravitreal injections administered on a pro re nata (PRN) basis after 3 monthly loading doses. The sham group received three consecutive monthly sham injections and then one conbercept injection followed by PRN conbercept intravitreal injections. At month 3, the mean BCVA for the two groups were improved by 12.0 letters (conbercept group, from 54.05 letters to 66.05 letters) and 0.6 letters (sham group, from 49.77 letters to 50.33 letters), respectively (p < 0.001). The mean central retinal thickness (CRT) at month 3 in the two groups decreased 62.0 μm (conbercept group, from 348.90 μm to 286.18 μm) and 4.4 μm (sham group, from 347.86 μm to 343.47 μm) (p < 0.001). At month 9, the mean BCVA improved by 13.3 letters in the conbercept group and 11.3 letters in the sham group. The mean CRT decreased 73.6 μm in the conbercept group and 55.9 μm in the sham group (p < 0.001). The most common ocular adverse events were associated with intravitreal injections, such as conjunctival haemorrhage and increased intraocular pressure. Intravitreal injections of 0.5 mg conbercept provided improvement in visual and anatomical outcomes in pmCNV patients with low rates of ocular and nonocular safety events.

Micro-interaction of montmorillonite-loaded nanoparticles with mucin promotes retention of betaxolol hydrochloride on the ocular surface and the tear film microenvironment

This work developed a triple-encapsulated nano-delivery system for topical and long-term glaucoma treatment. We encapsulated betaxolol hydrochloride (BH), a glaucoma drug loaded in refined acid-treated montmorillonite (RAMt), in hyaluronic acid/chitosan (HA/CS) cross-linked nanoparticles with high encapsulation efficiency and further wrapped them with Eudragit (ED) films to achieve dual sustained release. RAMt-BH-HA/CS@ED NPs exhibited excellent physicochemical properties for the sustained release of betaxolol hydrochloride. In vitro release experiments were performed, and the results showed that the drug release lasted for up to 8 h. Then, particle surface hydrophobicity experiments showed that the nanoparticles had both hydrophilic and hydrophobic properties. The ocular safety of the nanoparticles was confirmed by the chick embryo allantoic membrane assay and the rabbit blink frequency test. In the mucin-nanoparticle interaction experiments, the interaction between the nanoparticles and the mucin solution with high pH and low concentration (simulating the aqueous layer microenvironment of tears) was stronger than that with low pH and high concentration (simulating the tear mucin layer microenvironment of tears). Therefore, the nanoparticles showed excellent retention properties in tears and cornea. In vivo experiments in a rabbit model of elevated intraocular pressure demonstrated that the IOP-lowering effect was sustained for more than 12 hours. In conclusion, nanoparticles effectively lower IOP with excellent tolerability, and offer promising applications for long-term treatment of glaucoma.

Ocular Mucoadhesive and Biodegradable Sponge-Like Inserts for the Sustained and Controlled Delivery of Voriconazole; Preparation, D-optimal Factorial Optimization and in-vivo Evaluation

The aim of this study was to formulate and optimize by statistical means mucoadhesive and biodegradable sponge-like inserts loaded with voriconazole (VCZ) which increases the contact time of the drug with the eye and sustain its release from the formula in a controlled manner. This avoids the pulsed effect reported for the drug suspension and results in reducing the number of drug instillations in the eye with the result of enhancing the patient compliance. Also, the sponge like nature of the insert reduces the foreign body sensation caused by other ocular solid dosage forms. They were prepared using casting/freeze-drying technique using five polymers namely high molecular weight chitosan (CH), sodium alginate (AL), sodium carboxy methyl cellulose (CMC), gellan gum (GG) and xanthan gum (XG). The prepared inserts were subjected to evaluations of their visual appearance, weight variation, drug content, surface pH, in-vitro release (percent drug released after 1h (Q1 (%)), mean dissolution time (MDT) and dissolution efficiency (DE)) in addition to kinetic analysis of the release data, water uptake, mucoadhesion and rheology of the forming plain polymer solution at the maximum rate of shear. The independent variables of the D-optimal factorial design were the polymer type and concentration while Q1 (%), MDT, DE, % water uptake after 15 minutes and rheology at the maximum rate of shear were chosen as dependant variables. The performed optimization process using design expert software showed an optimum formula consisting of 2 % GG. It showed slow release behavior compared to the drug suspension. FTIR and DSC studies showed that there is no interaction between VCZ and GG. The optimum formula has good in-vitro mucoadhesive properties and pH in the safe ocular range. Moreover, it showed promising in-vivo results of rapid hydration and gelling in addition to good mucoadhesive behavior when instilled in the eye, high ocular safety and biocompatibility, sustained antifungal activity in comparison to the drug suspension and finally biodegradation. So, it may be taken into consideration as an outstanding carrier for the ocular delivery of VCZ.

Double-Masked, Vehicle-Controlled, Randomized, Phase II Study of the Ocular Hypotensive Activity and Safety of VVN539 Ophthalmic Solution

To assess safety and ocular hypotensive efficacy of VVN539 ophthalmic solution in a first-in-human study. Multicenter, double-masked, randomized, vehicle-controlled, dose-response, parallel-comparison study. Sixty-eight subjects with ocular hypertension (OHT) or open-angle glaucoma enrolled at 5 private practices. After washout of ocular hypotensive medications as required, the subjects were randomized to receive either VVN539 ophthalmic solution 0.02%, 0.04%, or vehicle once-daily (QD) in the morning (5 days), once-daily in the evening (6 days) and then twice-daily (6 days). Comparison of VVNM539 to its vehicle in mean intraocular pressure (IOP) at each diurnal time point (8:00am, 10:00am, and 4:00pm) at visit 4 (day 7), visit 5 (day 14), and visit 6 (day 21). Mean IOP decreased throughout dosing in the active groups to between 18 and 20 mmHg in both active groups, to between 22 to 23 mmHg in the vehicle group. VVN539 0.04% was statistically superior to vehicle at all 9 diurnal time points (QD AM, QD PM, and twice daily, P ≤ 0.0109). VVN539 0.02% was statistically superior to vehicle at only 6 of 9 diurnal time points (selected QD times and twice daily). The most common ocular treatment-emergent adverse event was conjunctival hyperemia (11 [47.8%], 10 [4.5%], and 1 [4.3%]), followed by ocular hyperemia (3 [13.0%], 5 [22.7%] and 0), respectively. There were no clinically significant changes of note in visual acuity, biomicroscopy, dilated ophthalmoscopy, blood chemistry, hematology, or cardiovascular measures. In conclusion, the results of this initial phase II study indicate that VVN539 ophthalmic solution showed clinically and statistically significant ocular hypertensive activity and was relatively well tolerated for the treatment of subjects with primary open-angle glaucoma or OHT. Additional studies will be required for a more complete evaluation of the utility of VVN539 ophthalmic solution. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The efficacy and ocular safety following aflibercept, conbercept, ranibizumab, bevacizumab, and laser for retinopathy of prematurity: a systematic review and meta-analysis

BackgroundRetinopathy of prematurity (ROP) is typically treated with laser photocoagulation and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF). To the best of our knowledge, most systematic reviews have focused on comparing anti-VEGF against laser treatment while comparisons between different anti-VEGF agents are lacking. Thus, we conducted this meta-analysis to compare the efficacy and safety of different anti-VEGF agents or laser after primary ROP therapy.MethodsWe conducted a comprehensive search across multiple databases up to November 2022. We included studies that used anti-VEGF or laser for ROP with comparable cohorts.ResultsOverall, 44 studies were included in this meta-analysis. When comparing anti-VGEF with laser, we found that the anti-VEGF group had a significantly higher retreatment rate (RR = 1.56, 95%CI = [1.06, 2.31], p = 0.03), a longer time from treatment to retreatment (WMD = 5.99 weeks, 95%CI = [4.03, 7.95], p < 0.001), a lower retinal detachment rate (RR = 0.55, 95%CI = [0.30, 0.91], p = 0.02), higher spherical equivalent (WMD = 1.69D, 95%CI = [0.61, 2.77], p = 0.002), lower myopia rate (RR = 0.69, 95%CI = [0.50, 0.97], p = 0.03) and lower anisometropia rate (RR = 0.44, 95%CI = [0.29, 0.67], p = 0.0001). In comparisons between ranibizumab and bevacizumab, the intravitreal ranibizumab (IVR) group was associated with higher recurrence rate (RR = 2.02, 95%CI = [1.49, 2.73], p < 0.0001), higher retreatment rate (RR = 1.70, 95%CI = [1.17, 2.47], p = 0.0006), and lower high myopia rate (RR = 0.31, 95%CI = [0.12, 0.77], p = 0.01). Similarly, when compared to aflibercept and conbercept, the IVR cohort also demonstrated higher recurrence and retreatment rates. While no significant differences were observed in any of the variables included in the statistical analysis in the comparison between bevacizumab and aflibercept.ConclusionsAnti-VEGF was associated with higher retreatment and lesser incidence of myopia as compared to laser. Laser therapy was linked to more complications like retinal detachment and myopia. Ranibizumab exhibited higher recurrence and retreatment rates compared to bevacizumab, aflibercept, and conbercept.

Safety and efficacy of ranibizumab biosimilar (Razumab®) as a cost-effective alternative to the innovator molecule for macular disorders in real-world

: To report the clinical efficacy and safety of the intravitreal ranibizumab biosimilar molecule, Razumab® (IVRz) as an economic alternative to the innovator molecule (Lucentis) in macular diseases under real-world conditions.: A single‑ center, prospective study of 100 consecutive eyes undergoing three-monthly IVRz between April 2020 to March 2021 for a variety of macular disorders including diabetic macular edema (DME), neovascular age‑related macular degeneration (nAMD), retinal vein occlusion (RVO), and myopic choroidal neovascular membrane (mCNVM). The main outcome measures were changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), intraretinal-fluid (IRF), and subretinal-fluid (SRF) along with a safety analysis at weeks 4, 8, and 12 respectively. : Of the 100 eyes of 100 patients undergoing IVRz, a majority had DME (39 eyes; 39%) followed by RVO (34 eyes; 34%), nAMD (21 eyes; 21%), and mCNVM (6 eyes; 6%). Mean BCVA improved from baseline to weeks 4, 8, and 12 (P&amp;#60;0.001). A significant reduction in CST from the baseline was also noted at all the visits (P&amp;#60;0.001). On qualitative analysis, resolution of SRF and IRF was observed in 61.47% and 61.71% of eyes respectively. No serious ocular or systemic adverse events were noted.: Our real-world data suggests that IVRz therapy is safe and efficacious for the management of varied macular pathologies. The cost-effectiveness and systemic and ocular safety of this regulatory-approved biosimilar makes it a suitable alternative to the branded drug. Further comparative studies into the benefit-cost analysis of these biosimilar and branded agents are warranted to better understand the health economics of anti-vascular endothelial growth factor (anti-VEGF) therapy in chorioretinal disorders.

Topical Sustained-Release Dexamethasone-Loaded Chitosan Nanoparticles: Assessment of Drug Delivery Efficiency in a Rabbit Model of Endotoxin-Induced Uveitis.

Uveitis is an ocular illness that if not treated properly can lead to a total loss of vision. In this study, we evaluated the utility of HA-coated Dexamethasone-sodium-phosphate (DEX)-chitosan nanoparticles (CSNPs) coated with hyaluronic acid (HA) as a sustained ocular delivery vehicle for the treatment of endotoxin-induced-uveitis (EIU) in rabbits. The CSNPs were characterized for particle size, zeta potential, polydispersity, surface morphology, and physicochemical properties. Drug encapsulation, in vitro drug release, and transcorneal permeation were also evaluated. Finally, eye irritation, ocular pharmacokinetics, and pharmacodynamics were in vivo. The CSNPs ranged from 310.4 nm and 379.3 nm pre-(uncoated) and post-lyophilization (with HA-coated), respectively. The zeta potentials were +32 mV (uncoated) and -5 mV (HA-uncoated), while polydispersity was 0.178-0.427. Drug encapsulation and loading in the CSNPs were 73.56% and 6.94% (uncoated) and 71.07% and 5.54% (HA-coated), respectively. The in vitro DEX release over 12 h was 77.1% from the HA-coated and 74.2% from the uncoated NPs. The physicochemical properties of the CSNPs were stable over a 3-month period when stored at 25 °C. Around a 10-fold increased transcorneal-flux and permeability of DEX was found with HA-CSNPs compared to the DEX-aqueous solution (DEX-AqS), and the eye-irritation experiment indicated its ocular safety. After the ocular application of the CSNPs, DEX was detected in the aqueous humor (AH) till 24 h. The area under the concentrations curve (AUC0-24h) for DEX from the CSNPs was 1.87-fold (uncoated) and 2.36-fold (HA-coated) higher than DEX-AqS. The half-life (t1/2) of DEX from the uncoated and HA-coated NPs was 2.49-and 3.36-fold higher, and the ocular MRT0-inf was 2.47- and 3.15-fold greater, than that of DEX-AqS, respectively. The EIU rabbit model showed increased levels of MPO, TNF-α, and IL-6 in AH. Topical DEX-loaded CSNPs reduced MPO, TNF-α, and IL-6 levels as well as inhibited NF-κB expression. Our findings demonstrate that the DEX-CSNPs platform has improved the delivery properties and, hence, the promising anti-inflammatory effects on EIU in rabbits.