Journal of Ocular Pharmacology and Therapeutics

Purpose: In many epithelia, including the corneal endothelium, intracellular/extracellular stresses break down the perijunctional actomyosin ring (PAMR) and zonula occludens-1 (ZO-1) at the apical junctions. This study aims to grade the severity of damage to PAMR and ZO-1 through machine learning. Methods: Immunocytochemical images of PAMR and ZO-1 were drawn from recent studies on the corneal endothelium subjected to hypothermia and oxidative stress. The images were analyzed for their morphological (e.g., Hu moments) and textural features (based on gray-level co-occurrence matrix [GLCM] and Gabor filters)...

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Purpose: Bevacizumab-bvzr (Zirabev® ), a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor and a biosimilar to bevacizumab, is approved for intravenous administration for various indications worldwide. The objectives of this study were to evaluate the ocular toxicity, systemic tolerability, and toxicokinetics (TKs) of bevacizumab-bvzr following repeat intravitreal (IVT) injection to cynomolgus monkeys. Methods: Male monkeys were administered saline, vehicle, or bevacizumab-bvzr at 1...

Losartan is an angiotensin II receptor blocker (ARB) that impedes transforming growth factor (TGF) beta signaling by inhibiting activation of signal transduction molecule extracellular signal-regulated kinase (ERK). Studies supported the efficacy of topical losartan in decreasing scarring fibrosis after rabbit Descemetorhexis, alkali burn, and photorefractive keratectomy injuries, and in case reports of humans with scarring fibrosis after surgical complications. Clinical studies are needed to explore the efficacy and safety of topical losartan in the prevention and treatment of corneal scarring fibrosis, and other eye diseases and disorders where TGF beta has a role in pathophysiology...

Purpose: Proliferative vitreoretinopathy (PVR) is currently treated surgically. Reliable pharmaceutical options would be desirable, and numerous drugs have been proposed. This in vitro study is intended to systematically compare and determine the most promising candidates for the treatment of PVR. Methods: A structured literature review was conducted in the "PubMed" database to identify previously published agents proposed for medical treatment of PVR -36 substances that met the inclusion criteria. Toxicity and antiproliferative effects were evaluated on primary human retinal pigment epithelial (hRPE) using colorimetric viability assays...

Purpose: The induction of retinal progenitor cell (RPC) proliferation is a strategy that holds promise for alleviating retinal degeneration. However, the mechanisms that can stimulate RPC proliferation during repair remain unclear. Xenopus tailbud embryos successfully regrow functional eyes within 5 days after ablation, and this process requires increased RPC proliferation. This model facilitates identification of mechanisms that can drive in vivo reparative RPC proliferation. This study assesses the role of the essential H+ pump, V-ATPase, in promoting stem cell proliferation...

Purpose: To compare the duration of vascular endothelial growth factor (VEGF) suppression in the aqueous humor of macaque eyes after intravitreal injection of brolucizumab and aflibercept. Methods: Clinical dose of intravitreal brolucizumab (IVBr; 6.0 mg/50 μL) or intravitreal aflibercept (IVA; 2 mg/50 μL) was injected into the right eye of each of 8 macaques. Aqueous humor samples (150 μL) from both eyes were obtained just before injection and on days 1, 3, 7, 14, 21, 28, 42, 56, 84, and 112 after IVBr injection or IVA injection...

Inflammation is an important driver of dry eye disease (DED) pathogenesis. An initial insult that results in the loss of tear film homeostasis can initiate a nonspecific innate immune response that leads to a chronic and self-sustaining inflammation of the ocular surface, which results in classic symptoms of dry eye. This initial response is followed by a more prolonged adaptive immune response, which can perpetuate and aggravate inflammation and result in a vicious cycle of chronic inflammatory DED. Effective anti-inflammatory therapies can help patients exit this cycle, and effective diagnosis of inflammatory DED and selection of the most appropriate treatment are therefore key to successful DED management and treatment...

Purpose: This study evaluated if tauroursodeoxycholic acid (TUDCA) alleviates pro-inflammatory and endoplasmic reticulum (ER) stress-mediated visual deficits in diabetic tie2-TNF transgenic mice via Takeda G protein-coupled receptor 5 (TGR5) receptor signaling. Methods: Adult tie2-TNF transgenic or age-matched C57BL/6J (wildtype, WT) mice were made diabetic and treated subcutaneously with TUDCA. After 4 weeks, visual function, vascular permeability, immunohistology, and molecular analyses were assessed. Human retinal endothelial cells (HRECs) silenced for TGR5, followed by TNF and high glucose (HG) stress-mediated endothelial permeability, and transendothelial migration of activated leukocytes were assessed with TUDCA in vitro ...

Purpose: To investigate the ocular pharmacokinetic properties of intravitreally injected aflibercept in rabbits after using brinzolamide 1%/timolol maleate 0.5% fixed-combination eye drops. Methods: The right eye of 5 rabbits was topically administered 30 μL of brinzolamide and timolol maleate eye drops twice a day (q12h). The 2 eyes of each rabbit were injected with 1.0 mg (0.025 cc) of aflibercept on the 2nd day after instilling the eye drops. The intraocular pressure of the rabbits was measured before injection and sampling...

Purpose: Povidone-iodine (PVI), also known as Betadine, is a widely used antiseptic agent used in several fields of medicine. In ophthalmology, it is applied as a preoperative antiseptic to prevent infectious complications that can result from surgical procedures. PVI's safety and efficacy have been extensively studied and represented in the literature; however, the incidence of adverse effects has been reported in conjunction. The aim of this paper is to compile information regarding PVIs use, safety profile, adverse effects, and possible alternatives through a review of the existing literature...

An intracameral (IC) injection directly delivers the drug into the anterior chamber of the eye. This targeted drug delivery technique overcomes the ocular barriers and offers a high therapeutic concentration of medication at the desired site and consequently better clinical outcomes. IC drug delivery is a safe and effective modality with many advantages over topical delivery. These include excellent bioavailability, reduced systemic risk, and minimal ocular toxicity. Agents delivered via IC injection have shown promising results against infection, inflammation, ocular hypertension, and neovascularization...

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Purpose: To investigate the characteristics of sustained drug release systems established by an arginine-glycine-aspartic acid (RGD) peptide hydrogel and mitomycin C (MMC) in vitro , and verify their antiscar effects in rat ocular injury model. Methods: Low, medium, and high loading doses of MMC were added to 5 mL 0.25%, 0.5%, and 1% wt RGD peptide hydrogel, respectively, to prepare 9 ratios of MMC-RGD systems. Drug release characteristics of the systems in phosphate-buffered saline solution were investigated by plotting the drug release curves and fitting them with mathematical models in OriginPro8...

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Purpose: Umbilical cord blood serum (UCBS) is an effective adjunctive treatment along with conventional therapy in ocular surface disorders (OSDs). It aids in rapid ocular surface restoration thereby achieving epithelial integrity, in addition to improvement in subjective and objective parameters. The study aims to compare the efficacy of human umbilical cord blood serum and autologous serum (AS) in treatment of OSD. Methods: A prospective randomized study was conducted on 101 eyes diagnosed with OSD resulting from dry eye disease (DED; n  = 40), acute chemical burn (ACB; n  = 21), and ocular allergy (OA; n  = 40)...

Purpose: A new class of ocular steroids designed to mitigate steroid-induced intraocular pressure (IOP) elevation while maintaining anti-inflammatory activity was developed. Herein is described the discovery and preclinical characterization of ROCK'Ster compound 1 . Methods: Codrugs consisting of a Rho kinase inhibitor (ROCKi) and a corticosteroid were synthesized. Compounds were initially screened in vitro for ROCKi activity and anti-inflammatory activity against the proinflammatory interleukin 23 and bacterial lipopolysaccharide (LPS) pathways...

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Purpose: To investigate the antifibrotic effect of ZD6474 in human pterygium fibroblasts (HPFs) and angiogenesis in human umbilical vein endothelial cells (HUVECs) compared with mitomycin C (MMC). Methods: Pterygium and tenon fibroblasts were isolated from patients undergoing surgery to culture HPFs and human tenon fibroblasts (HTFs). The effects of ZD6474 on HPF, HTF, and HUVEC proliferation and migration were detected using CCK8 and wound-healing assays, respectively. Fibrosis and epithelial-mesenchymal transformation (EMT) were evaluated by western blotting [transforming growth factor beta (TGF-β)1/2 and snail] and immunofluorescence (vimentin and α-smooth muscle actin)...

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