J Ocul Pharmacol Ther [JOURNAL]
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200 papers
Intracameral Concentration and Safety Profile of High Concentration Ganciclovir Eyedrop in a Rabbit Model.
Lee J, Choi JA
J Ocul Pharmacol Ther · 2026 Apr · PMID 42046481 · Publisher ↗
PURPOSE: This study aimed to evaluate the efficacy and safety of topically administered ganciclovir (GC) eye drops at varying concentrations. METHODS: Fifteen New Zealand white rabbits were divided into 5 groups ( = 3 pe...
PURPOSE: This study aimed to evaluate the efficacy and safety of topically administered ganciclovir (GC) eye drops at varying concentrations. METHODS: Fifteen New Zealand white rabbits were divided into 5 groups ( = 3 per group): control (saline), 0.15%, 2%, 4%, and 8% GC eye drops. GC eye drops were applied to both eyes 4 times a day for 10 days. The concentration of GC in the aqueous humor was measured using liquid chromatography-tandem mass spectrometry. Ocular toxicity scores were graded using slit-lamp microscopy. Specular microscopy was performed after final instillation. Corneal tissues were analyzed for scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Intraocular pressure (IOP) was also measured. RESULTS: The mean GC concentrations in aqueous humor were significantly increased in a dose-dependent manner: 0.15% (40.75 ± 18.54 ng/mL), 2% (287.66 ± 114.67 ng/mL), 4% (855.70 ± 408.22 ng/mL), and 8% (1916.85 ± 985.97 ng/mL) ( = 0.004, K-W test). Total ocular surface toxicity scores rose with increasing concentrations, with the most pronounced toxicity observed in the 8% group. Specular microscopy and SEM showed no significant differences in endothelial cell density or morphology. TEM revealed increased cell vacuoles in the 8% group, though intercellular junctions remained intact. There were no significant differences in IOP values across all groups. CONCLUSIONS: Topical GC achieved effective ocular penetration, reaching concentrations above the 50% inhibitory dose for cytomegalovirus replication at 2% or higher. Dose-dependent ocular surface toxicity was observed, particularly at higher concentrations. However, no structural or cellular damage to the corneal endothelium was detected.
Comparison of Rebamipide Clear Solution and Diquafosol Eyedrops in Dry Eye Disease with Short Tear Break-up Time: A Retrospective, Comparative Observational Study.
Hwang HS, Lee JE, So HR … +2 more , Kim HS, Kim EC
J Ocul Pharmacol Ther · 2026 Apr · PMID 42036940 · Publisher ↗
PURPOSE: To compare the efficacy of 2% rebamipide clear solution and 3% diquafosol eyedrops in dry eye disease (DED) patients with short tear break-up time (tBUT). METHODS: This nonrandomized retrospective, comparative o...
PURPOSE: To compare the efficacy of 2% rebamipide clear solution and 3% diquafosol eyedrops in dry eye disease (DED) patients with short tear break-up time (tBUT). METHODS: This nonrandomized retrospective, comparative observational study included 120 eyes (60 patients) divided into Group 1 (2% rebamipide, 60 eyes) and Group 2 (3% diquafosol, 60 eyes). Evaluations at baseline, 1 month, and 3 months included Ocular Surface Disease Index Questionnaire (OSDI), Schirmer I, noninvasive tBUT (NItBUT), corneal/conjunctival staining score, meiboscore, meibum expressibility and quality, lipid thickness, tear meniscus height (TMH), impression cytology, and goblet cell density. The primary endpoint was NItBUT change at 3 months. RESULTS: Both groups showed significant improvement ( < 0.025, Bonferroni correction) in DED signs and symptoms at 1 and 3 months compared with baseline. Changes from baseline were comparable between groups for OSDI, NItBUT, corneal and conjunctival staining score, meiboscore, meibum expressibility and quality, lipid thickness, impression cytology, and goblet cell density ( > 0.05). At 3 months, group 2 showed greater increases in aqueous-related parameters than group 1 (for Schirmer I, adjusted mean differences 1.31 mm, 95% CI: 0.49-2.13, = 0.002; for TMH, adjusted mean differences 0.05 mm, 95% CI: 0.01-0.09, = 0.014). CONCLUSION: In patients with short tBUT DED, both rebamipide clear solution and diquafosol eyedrops showed comparable improvement in the primary endpoint, NItBUT at 3 months, as well as in other ocular surface parameters. Under standard dosing regimens, however, diquafosol was associated with greater increases in Schirmer I test values and TMH than rebamipide clear solution.
Investigation of Corneal Epithelial Tight Junction Disruption and Barrier Function Impairment Induced by Benzalkonium Chloride.
Fukuda M, Sasaki Y, Kiyoi T … +5 more , Ishida H, Sasaki M, Kubo E, Masuoka T, Sasaki H
J Ocul Pharmacol Ther · 2026 Apr · PMID 42025447 · Publisher ↗
PURPOSE: This study investigated the effects of benzalkonium chloride (BAK), a commonly used ophthalmic preservative, on corneal epithelial barrier function. METHODS: Separate animals were assigned to the control and BAK...
PURPOSE: This study investigated the effects of benzalkonium chloride (BAK), a commonly used ophthalmic preservative, on corneal epithelial barrier function. METHODS: Separate animals were assigned to the control and BAK groups. Rabbits received a topical instillation of 0.02% BAK solution every 5 min for a total of 5 doses (20 min). Corneal resistance (CR) was quantitatively measured at 30, 60, and 120 min after the final instillation using a corneal resistance device (CRD). Corneal epithelial damage was evaluated using fluorescein staining, histopathological analysis using hematoxylin and eosin (HE) staining, and immunofluorescence staining for the tight junction protein Zonula occludens-1 (ZO-1). The results were compared with those of the saline-treated control eyes. RESULTS: In the BAK-treated group, CR measured using the CRD method was 82.50 ± 8.92%, 74.17 ± 10.19%, and 76.67 ± 8.35% ( = 6) at 30, 60, and 120 min after the final instillation, respectively. These values were significantly lower than those of the control group at the corresponding time points (100.00 ± 3.34%, 99.17 ± 3.96%, and 101.67 ± 4.08%, respectively; = 6) ( < 0.0125). Fluorescein staining revealed mild superficial punctate keratopathy in most BAK-treated eyes, whereas the control eyes remained intact. HE staining revealed partial loss of superficial epithelial cells in the BAK group. Immunofluorescence analysis demonstrated that ZO-1 was continuously expressed along the corneal epithelial cell borders in control corneas, whereas ZO-1 expression was discontinuous and fragmented in corneas after BAK exposure. In addition, semiquantitative evaluation of the tissue sections indicated that BAK exposure altered ZO-1 localization. CONCLUSIONS: BAK disrupts the tight junctions of the corneal epithelium, thereby reducing barrier function. These findings emphasize the importance of evaluating preservative toxicity in ophthalmic formulations to ensure safety of the ocular surface. Although this is a pilot study, it provides important insights into the physiological mechanisms of BAK-induced corneal epithelial damage.
Dose-Dependent Corneal Epithelial and Neural Toxicity of Topical Proparacaine: An and Study.
Ju S, Kim J, Park JY … +4 more , Song JY, Chung SH, Kim HS, Byun YS
J Ocul Pharmacol Ther · 2026 Apr · PMID 42014347 · Publisher ↗
PURPOSE: To evaluate the dose-dependent toxicity of topical proparacaine (PPC) on the corneal epithelium and nerve fibers using both and models. METHODS: Human corneal epithelial cells were used for cell viability and...
PURPOSE: To evaluate the dose-dependent toxicity of topical proparacaine (PPC) on the corneal epithelium and nerve fibers using both and models. METHODS: Human corneal epithelial cells were used for cell viability and scratch assays. Male Sprague-Dawley rats received topical PPC (0.5%, 0.1%, 0.01%) for 2 weeks. Apoptosis was assessed by TUNEL assay, intraepithelial nerve density by anti-βIII tubulin immunohistochemistry, and corneal NGF, substance , and CGRP levels by ELISA. Corneal epithelial wound healing was also evaluated. RESULTS: PPC demonstrated dose-dependent cytotoxicity, with the CC between 2% (0.0625%) and 2% (0.125%). PPC concentrations ≥ 2% (0.03125%) significantly inhibited epithelial wound gap closure . , PPC 0.5% induced significant apoptosis in corneal epithelium and markedly reduced intraepithelial nerve density compared with controls ( = 0.015 and 0.001, respectively). Corneal NGF levels were significantly reduced in the PPC 0.1% and 0.5% groups, whereas corneal substance levels were significantly reduced only in the PPC 0.5% group. Corneal epithelial wound healing was significantly delayed with PPC 0.5% ( = 0.01), but not with PPC 0.1% or 0.01%. CONCLUSIONS: Repeated application of PPC at the clinical concentration (0.5%) induced corneal epithelial and neural toxicity, whereas diluted concentrations (0.1% and 0.01%) showed no significant adverse effects. These findings highlight the risk of toxicity associated with repeated use of clinical concentration PPC, while also suggesting the potential utility of dilute formulations in select clinical scenarios.
Evaluation of Stromal Riboflavin Penetration Using Slit-Lamp-Based Digital Image Processing in an Iontophoresis Model.
Coskun A, Senturk F, Aygün B … +3 more , Alıcı C, Kaba D, Eski İS
J Ocul Pharmacol Ther · 2026 Apr · PMID 41981933 · Publisher ↗
PURPOSE: To evaluate the effect of different iontophoresis current intensities on stromal riboflavin penetration for transepithelial corneal cross-linking (CXL) and to develop a simple, accessible, and quantitative image...
PURPOSE: To evaluate the effect of different iontophoresis current intensities on stromal riboflavin penetration for transepithelial corneal cross-linking (CXL) and to develop a simple, accessible, and quantitative image-processing workflow for its objective assessment using digital slit-lamp biomicroscopy. METHODS: bovine corneas ( = 3 per group) were allocated to five groups: untreated control, topical riboflavin, and iontophoresis at 1, 3, or 5 mA for 5 min. After treatment, cobalt-blue-excited slit-lamp images were obtained. Stromal fluorescence was quantified using a Python-OpenCV workflow that converted images to hue-saturation-value space and applied segmentation-based masking to generate a fluorescence score (FS). For validation, stromal extracts were analyzed spectrophotometrically at 370 nm to determine riboflavin concentration. Finally, the association between FS and spectrophotometric riboflavin levels was examined to evaluate the utility of slit-lamp fluorescence as a noninvasive surrogate measure. RESULTS: Mean FS increased in a current-dependent manner. Iontophoresis enhanced stromal loading, producing mean FS values of 1.04 ± 0.17 (1 mA/5 min), 1.82 ± 0.13 (3 mA/5 min), and 2.53 ± 0.25 (5 mA/5 min), with higher currents also promoting a more homogeneous stromal distribution. Based on the linear FS-concentration relationship, these values corresponded to increasing stromal riboflavin concentrations. A strong linear correlation ( = 0.96) between FS and spectrophotometrically calculated riboflavin concentration demonstrated that slit-lamp-derived fluorescence accurately predicts stromal riboflavin content. CONCLUSION: The proposed digital slit-lamp analysis provides a simple, objective, and reproducible method for quantifying stromal riboflavin fluorescence. The strong correlation between FS and spectrophotometric measurements supports its use as a noninvasive surrogate for stromal riboflavin assessment. With further validation, this approach may enable real-time monitoring and optimization of transepithelial CXL protocols.
Eyes on New Product Development.
Novack GD
J Ocul Pharmacol Ther · 2026 May · PMID 41981713 · Publisher ↗
Abstract loading — click title to view on PubMed.
Eyes on New Product Development.
Novack GD
J Ocul Pharmacol Ther · 2026 Apr · PMID 41974608 · Publisher ↗
Abstract loading — click title to view on PubMed.
SDF-1 Inhibition Attenuates VEGF-Driven Retinal Leukostasis and Neovascularization in Ischemic Retinopathy.
Ye Y, Long J, Hu P … +4 more , Shen J, Gong J, Lu X, Long D
J Ocul Pharmacol Ther · 2026 Apr · PMID 41963275 · Publisher ↗
PURPOSES: Ischemic retinopathies are characterized by hypoxia-driven inflammation and pathological neovascularization (NV), with vascular endothelial growth factor (VEGF) as a central mediator. Incomplete responses to an...
PURPOSES: Ischemic retinopathies are characterized by hypoxia-driven inflammation and pathological neovascularization (NV), with vascular endothelial growth factor (VEGF) as a central mediator. Incomplete responses to anti-VEGF therapy suggest involvement of additional hypoxia-regulated pathways. This study investigated the contribution of stromal cell-derived factor-1 (SDF-1) to VEGF-driven retinal vascular pathology. METHODS: SDF-1 expression, leukostasis, vascular nonperfusion (NP), and NV were assessed in oxygen-induced retinopathy, VEGF transgenic mice, and VEGF-injected mice. The SDF-1 aptamer NOX-A12 was administered alone or in combination with aflibercept. Retinal vascular pathology was quantified by immunofluorescence, and vitreous albumin levels were measured to assess vascular leakage. RNA sequencing was performed in VEGF-stimulated human umbilical vein endothelial cells treated with SDF-1. RESULTS: SDF-1 expression was increased in ischemic retinas and in models of sustained VEGF overexpression (Rho P35, 2.43 ± 1.34; Tet/Opsin/VEGF (TVOP), 0.27 ± 0.31; C57 VEGF, 0.13 ± 0.14; retinopathy of prematurity, 3.06 ± 0.65; = 0.0004, 0.0005, < 0.0001, <0.0001). SDF-1 aptamer plus aflibercept more effectively suppressed retinal leukostasis (24 h, 84.2 ± 13.8 vs 122.2 ± 20.8; 72 h, 22 ± 10.5 vs 52.6 ± 13.1; Rho/VEGF P21, 20.2 ± 7.79 vs 37.4 ± 9.07; Rho/VEGF P35, 20.8 ± 7.63 vs 39.7 ± 8.83; TVOP, 35.3 ± 9.16 vs 170.6 ± 40.9, all < 0.0001), NP area (80.92 ± 3.82 vs 51.53 ± 11.13; < 0.0001), hypoxia (0.23 ± 0.10 vs 0.82 ± 0.09; < 0.0001), and NV (0.01 ± 0.01 vs 0.07 ± 0.01; < 0.0001) than aflibercept alone, without additional effects on choroidal NV or vitreous albumin levels. Transcriptomic analysis revealed enrichment of pathways related to leukocyte transendothelial migration, focal adhesion, tight junctions, and extracellular matrix organization. CONCLUSION: SDF-1 functions as a cooperative mediator of VEGF-driven retinal vascular pathology. Dual targeting of SDF-1 and VEGF enhances suppression of ischemic retinal injury and NV.
Advanced Medicinal Treatment for Keratoconus: A Systematic Review of New Drugs and Formulations.
Hu S, Li X, Zhang X … +3 more , Bu F, Huang T, Zhou X
J Ocul Pharmacol Ther · 2026 Apr · PMID 41951565 · Publisher ↗
Keratoconus is a progressive ocular disorder characterized by the cornea gradually thinning and protruding into a conical shape, resulting in distorted vision. The underlying pathogenesis of keratoconus is multifactorial...
Keratoconus is a progressive ocular disorder characterized by the cornea gradually thinning and protruding into a conical shape, resulting in distorted vision. The underlying pathogenesis of keratoconus is multifactorial and involves a loss of corneal collagen cross-linking, leading to structural instability and the conical deformation of the cornea. Currently, the mainstay treatments for keratoconus include surgical interventions, such as corneal cross-linking, and the use of contact lenses for vision correction. However, there are no approved direct pharmacological treatments available. In this review, we provide an overview of innovative medical therapies that target various pathogenic mechanisms of keratoconus. These treatments aim to enhance collagen cross-linking, reduce corneal degradation, and modulate inflammatory factors. Advances in drug formulations and delivery vehicles have played a significant role in the development of these novel treatments. Some of these therapies are in advanced stages of clinical development, demonstrating promising results, while others remain in preclinical stages. In addition to directly targeting the pathogenesis of keratoconus, preventive measures, such as medical treatments that reduce eye rubbing or mitigate corneal hydrops, have shown potential in halting disease progression and alleviating symptoms. This review aims to update the current landscape of medical treatments for keratoconus, offering insights into future noninvasive therapeutic approaches for managing this condition.
Study on the Effect of Atropinesterase on Intraocular Atropine Metabolism.
Han T, Wang Y, Peng X … +2 more , Huang T, Zhou X
J Ocul Pharmacol Ther · 2026 Apr · PMID 41936537 · Publisher ↗
PURPOSE: Atropine is an important medicine for myopia control in clinical practice, yet individual therapeutic responses vary widely, potentially due to differences in metabolic processes. Atropinesterase (AE), the enzym...
PURPOSE: Atropine is an important medicine for myopia control in clinical practice, yet individual therapeutic responses vary widely, potentially due to differences in metabolic processes. Atropinesterase (AE), the enzyme catalyzing atropine hydrolysis, may critically influence its bioavailability and efficacy. This study investigated the role of AE in intraocular atropine metabolism. METHODS: In total, 28 New Zealand White rabbits were screened for plasma AE activity using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). From these, 14 rabbits [7 AE-positive (AE+) and 7 AE-negative (AE-)] were selected for the drug administration study. A single 50-μL dose of 1% atropine sulfate was administered topically to the right conjunctival sac of each animal. Then 24 h post-administration, ocular tissues (including cornea, iris, retina, choroid, aqueous humor, vitreous, and anterior/posterior sclera) were collected. Tissue atropine concentrations were quantified by validated HPLC-MS/MS methods. For statistical analysis, tissue-specific atropine distributions were evaluated using generalized linear mixed-effects models. RESULTS: Briefly, 35.71% of rabbits were identified as AE+. AE activity significantly reduced atropine levels in aqueous humor ( = 0.001), iris ( = 0.030), choroid ( = 0.031), and vitreous ( = 0.001) in AE+ rabbits than in AE- rabbits. In both AE- and AE+ eyes, the top 3 atropine-concentrated tissues were anterior sclera, cornea, and posterior sclera. CONCLUSIONS: AE markedly accelerates intraocular atropine metabolism, leading to significant concentration disparities across ocular tissues. The metabolic principle revealed in rabbits-that higher enzymatic activity limits drug availability-likely applies to humans and offers a new perspective on interindividual efficacy variations of atropine in myopic children.
Is Methotrexate a Superior Alternative to Steroids or Placebo for Scleritis? A Systematic Review and Meta-Analysis on Efficacy and Safety.
Chen KY, Chan HC, Chan CM
J Ocul Pharmacol Ther · 2026 Mar · PMID 41931384 · Publisher ↗
BACKGROUND: Scleritis is a severe, painful inflammatory condition affecting the sclera. If untreated, scleritis can lead to significant ocular complications. Corticosteroids are often considered for the initial treatment...
BACKGROUND: Scleritis is a severe, painful inflammatory condition affecting the sclera. If untreated, scleritis can lead to significant ocular complications. Corticosteroids are often considered for the initial treatment of non-infectious scleritis. However, for steroid-resistant cases, cases requiring prolonged therapy, or to reduce steroid dependence, immunosuppressive agents, including methotrexate (MTX), are employed. OBJECTIVES: This study compared the efficacy and safety of MTX versus steroids and placebo in treating scleritis. METHODS: A comprehensive literature search was conducted via different databases. The search results were screened against prespecified eligibility criteria. The risk of bias in the included studies was appraised using the Newcastle-Ottawa Quality Scale and the risk of bias in nonrandomized studies with intervention (ROBINS-I). Data were then systematically extracted and analyzed. RESULTS: The literature search yielded 558 records, of which 11 studies that met the eligibility criteria were included. MTX in scleritis treatment demonstrated significant efficacy for inflammation control ( = 0.003). However, its effect on visual acuity was insignificant ( = 0.689). Safety analysis revealed lower adverse event rates than azathioprine and insignificant differences with mycophenolate, with comparable discontinuation rates. Treatment response varies by scleritis subtype, with higher efficacy in non-necrotizing anterior scleritis. CONCLUSION: The study revealed MTX's clinical significance in managing noninfectious scleritis. Significant results were observed in inflammation control and tolerability; however, the lack of randomized comparator studies limits conclusions regarding MTX's superiority over steroids or placebo. Future controlled trials are needed to confirm comparative effectiveness and refine treatment guidelines.
Eyes on New Product Development #128.
Novack GD
J Ocul Pharmacol Ther · 2026 Mar · PMID 41931383 · Publisher ↗
Abstract loading — click title to view on PubMed.
Eyes on New Product Development.
Novack GD
J Ocul Pharmacol Ther · 2026 Jun · PMID 41912384 · Publisher ↗
Abstract loading — click title to view on PubMed.
Standardization of Autologous Serum Eye Drops Preparation Practices in France: Delphi Method.
Champmartin L, Lannoy D, Coulomb M … +4 more , Jost J, Robert PY, Rocher M, Ratsimbazafy V
J Ocul Pharmacol Ther · 2026 Mar · PMID 41896184 · Publisher ↗
PURPOSE: Dry eye disease affects quality of life and generates significant health care costs. Severe forms, refractory to conventional treatments, are responsible for visual impairment and disability. Autologous serum ey...
PURPOSE: Dry eye disease affects quality of life and generates significant health care costs. Severe forms, refractory to conventional treatments, are responsible for visual impairment and disability. Autologous serum eye drops (ASEDs) are proven to be a therapeutic alternative. We carried out a national inventory of ASEDs preparation practices that highlights low supply (13 producer centers in France) and preparation heterogeneity. The general objective was to develop a national consensus-based protocol for ASEDs preparation in French university hospitals using a Delphi method, with the goal of improving ASEDs quality, safety, and supply. METHODS: Method for consensus reaching is Delphi method. Four protocol parts are covered: blood sampling and controls, preparing and packaging the eye drops, postproduction controls, and storage and conservation. Expert panel are hospital pharmacists. Steps were as follows: questionnaire construction, mailing with link access to Google Forms, response analyses, consensus rate calculation, result synthesis, and anonymous referral to experts. RESULTS: With 12 answering experts, after 4 rounds: out of 39 proposals initially submitted, the work resulted in a 26 validated item protocol at the final. In sampling and controls: 15 items were validated, 5 dropped. Preparation: 5 were validated, 1 dropped. Postcompounding Control: 3 were validated, 4 dropped. Storage and Conservation: 3 were validated. The four rounds took 86 days. CONCLUSIONS: A standardized protocol for ASEDs preparation was proposed. This could improve the supply of care across the country. Method strengths are a consultation of dedicated experts on the draft questionnaire of the Delphi survey and qualified experts on the topic, anonymity avoiding opinion leader.
All-Trans Retinoic Acid Modulates MicroRNA-129-5p/Hypoxia-Inducible Factor-1α/Vascular Endothelial Growth Factor Signaling and Suppresses Ets-1 in Retinal Pigment Epithelial ARPE-19 Cells.
Chang YC, Yang YC, Chen PH … +2 more , Wu WC, Kao YH
J Ocul Pharmacol Ther · 2026 Mar · PMID 41873168 · Publisher ↗
PURPOSE: Proliferative vitreoretinopathy (PVR) is a vision-threatening complication of retinal detachment or ocular trauma characterized by the formation of contractile fibrotic membranes. Retinal pigment epithelium (RPE...
PURPOSE: Proliferative vitreoretinopathy (PVR) is a vision-threatening complication of retinal detachment or ocular trauma characterized by the formation of contractile fibrotic membranes. Retinal pigment epithelium (RPE) cells are central to PVR pathogenesis, driving maladaptive wound-healing responses. This study investigated the effects of all-trans retinoic acid (ATRA) on RPE cell proliferation, vascular endothelial growth factor (VEGF) secretion, and miR-129-5p biogenesis, alongside the downstream regulation of Ets-1 and the hypoxia-inducible factor-1α (HIF-1α)/VEGF axis. METHODS: Human ARPE-19 cells were treated with ATRA under quiescent or protein kinase C (PKC)-activated conditions. Proliferation, VEGF secretion, and miR-129-5p expression were quantified via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, enzyme-linked immunosorbent assay, and real-time quantitative PCR. Bioinformatic analysis, miR-129-5p mimic transfection, Western blotting, and protein ubiquitination assays were utilized to characterize the regulatory mechanisms. RESULTS: ATRA exerted a dose- and time-dependent cytostatic effect on ARPE-19 cells without inducing cytotoxicity. VEGF modulation was highly context-dependent: basal secretion exhibited a biphasic response (peaking at 10 M), whereas PKC-stimulated secretion was significantly suppressed. Mechanistically, ATRA promoted intracellular miR-129-5p accumulation, which directly silenced the profibrotic factor Ets-1. Paradoxically, miR-129-5p mimic transfection stabilized HIF-1α protein by reducing its polyubiquitination, thereby enhancing VEGF production. CONCLUSIONS: Our findings characterize miR-129-5p as a pivotal molecular switch orchestrating ATRA-mediated RPE modulation. By decoupling antifibrotic activity (Ets-1 suppression) from cytoprotective signaling (HIF-1α stabilization), this miR-129-5p/HIF-1α/VEGF axis balances the attenuation of pathological fibrosis with the preservation of homeostatic survival factors for retinal integrity, providing a nuanced therapeutic approach for PVR and the associated retinal disorders.
AG1295 Attenuates High-Glucose-Induced Proliferation, Migration, Phenotype Transition, and Interleukin-6 Expression in Human Corneal Stromal Fibroblasts.
Zheng Y, Jiang H, Wang J … +3 more , Zhang Q, Wan Q, Wang Y
J Ocul Pharmacol Ther · 2026 Mar · PMID 41852028 · Publisher ↗
PURPOSE: Up to 46%-64% of individuals with diabetes exhibit corneal abnormalities, including epithelial dysfunction and reduced sensitivity, which may gradually impair corneal transparency. Corneal fibroblasts regulate s...
PURPOSE: Up to 46%-64% of individuals with diabetes exhibit corneal abnormalities, including epithelial dysfunction and reduced sensitivity, which may gradually impair corneal transparency. Corneal fibroblasts regulate scar formation and play a critical role in maintaining corneal transparency. This study investigated the effects of high-glucose levels on fibroblasts and elucidated the underlying mechanisms. METHODS: Human corneal stromal fibroblasts were isolated by collagenase digestion of fresh corneal stromal lenticules, obtained from small incision corneal lens extraction surgery, and cultured with different glucose concentrations (5.5-30 mM). The phosphorylated platelet-derived growth factor receptor beta (p-PDGFRβ)/PDGFRβ) ratio, fibroblast proliferation, migration, fibrotic markers, and interleukin-6 (IL-6) expression were assessed. RESULTS: Human corneal stromal fibroblast proliferation increased with increasing glucose concentrations, and a glucose concentration of 30 mM was selected for subsequent high-glucose treatment experiments. The p-PDGFRβ/PDGFRβ ratio, fibroblast proliferation, migration, fibrotic markers, and IL-6 expression were enhanced in the high-glucose group compared with those in the control group. These effects were inhibited by treatment with AG1295, a PDGFRβ tyrosine kinase inhibitor. CONCLUSIONS: In patients with diabetes, fibroblasts may aggregate at sites of corneal injury, potentially promoting scar hyperplasia and reducing corneal transparency. These changes may be reversed by PDGFRβ phosphorylation inhibitors, suggesting new therapeutic avenues.
Systematic Literature Review on the Effect of Cenegermin on Corneal Sensation and Innervation in Patients with Neurotrophic Keratopathy.
Fung SSM, Campos C, Weiss J … +1 more , Yermilov I
J Ocul Pharmacol Ther · 2026 Mar · PMID 41852024 · Publisher ↗
PURPOSE: Neurotrophic keratopathy (NK) results from trigeminal nerve impairment, leading to loss of corneal sensation (CS), epithelial breakdown, and in advanced stages, stromal ulceration or perforation. Cenegermin, a r...
PURPOSE: Neurotrophic keratopathy (NK) results from trigeminal nerve impairment, leading to loss of corneal sensation (CS), epithelial breakdown, and in advanced stages, stromal ulceration or perforation. Cenegermin, a recombinant human nerve growth factor, is the first and only FDA-approved therapy for NK, although existing studies are limited by small sample sizes. This systematic literature review evaluated cenegermin's effects on CS and corneal innervation (CI) in patients with NK. METHODS: English-language studies published between August 2018 and June 2024 measuring CS or CI after cenegermin treatment for NK were identified through PubMed and Embase. For studies reporting quantitative data, sample size-based weighting was applied to each study's reported or derived mean change. Weighted means were calculated by NK stage or overall, where applicable. RESULTS: A total of 25 studies met the inclusion criteria. The pooled mean age was 61.8 years (range: 2-93 years). Most included patients with stage II (moderate; 19 studies) and stage III (severe; 17 studies) NK. Across 8 studies reporting quantitative CS outcomes and 3 studies reporting quantitative CI outcomes, the weighted mean improvement from baseline to 8 weeks post-treatment was 116.5% for CS (range: 78.3%-259.3%) and 64.5% for CI (range: 39.1%-188.9%). CONCLUSION: An 8-week course of cenegermin led to improvements in CS and CI in patients with NK, with greater relative gains observed among those patients with more severe disease. While study design heterogeneity and small sample sizes may limit the generalizability of these findings, the data support cenegermin's role in promoting corneal nerve regeneration.
Vitreous and Serum Levels of IL-1β and IL-33 in Proliferative Diabetic Retinopathy: Evaluation of Local Versus Systemic Inflammatory Signatures.
Çelik E, Polat E, Güven F … +3 more , Yılmaz A, Çelikkol A, Güzel S
J Ocul Pharmacol Ther · 2026 Mar · PMID 41841466 · Publisher ↗
PURPOSE: To compare vitreous and serum concentrations of interleukin (IL-1β) and interleukin-33 (IL-33) between eyes with proliferative diabetic retinopathy (PDR) and nondiabetic surgical controls, and to explore associa...
PURPOSE: To compare vitreous and serum concentrations of interleukin (IL-1β) and interleukin-33 (IL-33) between eyes with proliferative diabetic retinopathy (PDR) and nondiabetic surgical controls, and to explore associations between cytokine levels and clinical characteristics. METHODS: Eighty-four eyes of 84 consecutive patients were prospectively enrolled: 42 eyes with PDR undergoing pars plana vitrectomy for vitreous hemorrhage or tractional retinal detachment and 42 nondiabetic controls undergoing vitrectomy for idiopathic epiretinal membrane. Undiluted vitreous and paired venous blood samples were collected perioperatively. IL-1β and IL-33 levels were quantified by ELISA. RESULTS: Both vitreous and serum cytokine levels were significantly higher in PDR than in controls. Median vitreous IL-1β and IL-33 concentrations were 18.85 and 43.76 pg/mL in PDR versus 11.74 and 35.36 pg/mL in controls ( = 0.003 and < 0.001). The median serum IL-1β and IL-33 levels were 25.87 and 49.27 pg/mL in PDR compared with 20.73 and 34.09 pg/mL in controls ( = 0.009 and < 0.001). Serum concentrations exceeded vitreous levels across groups. Within the PDR cohort, vitreous and serum levels were correlated for IL-1β ( = 0.51, < 0.001) and IL-33 ( = 0.39, = 0.012). Duration of diabetic retinopathy showed a mild negative correlation with serum IL-1β ( = -0.32, = 0.037). CONCLUSIONS: PDR is characterized by concomitant intraocular and systemic upregulation of IL-1β and IL-33, with serum levels consistently exceeding vitreous concentrations and showing partial correlation between compartments. These findings support an IL-1-IL-33-associated inflammatory signature that spans both retinal and systemic levels and highlight IL-1β and IL-33 as potential biomarkers or candidate mediators in advanced PDR.
Isotretinoin-Induced Meibomian Gland Dysfunction: Rationale for Proactive Clinical Surveillance.
Prados-Carmona JJ, Prados-Carmona Á, Sánchez-Ventosa Á … +7 more , Villalba-González M, Díaz-Ramos JC, Palacín-Miranda E, Pérez-Angulo JG, López-Pérez MD, Villarrubia-Cuadrado A, Cano-Ortiz A
J Ocul Pharmacol Ther · 2026 Mar · PMID 41841457 · Publisher ↗
PURPOSE: We synthesized the current evidence on isotretinoin-induced Meibomian gland dysfunction (MGD), including underlying mechanisms, clinical manifestations, risk factors, management strategies, and the need for upda...
PURPOSE: We synthesized the current evidence on isotretinoin-induced Meibomian gland dysfunction (MGD), including underlying mechanisms, clinical manifestations, risk factors, management strategies, and the need for updated screening recommendations. METHODS: The review was conducted during November 2025, covering multiple databases including Semantic Scholar, PubMed, and others. The search yielded 1,046 records; after eligibility assessment, 53 studies were included. Clinical, preclinical, and review articles, as well as clinical guidelines were considered if they met predefined quality standards. RESULTS: Isotretinoin significantly impairs Meibomian gland function by suppressing PPARγ signalling, leading to reduced lipid secretion, glandular inflammation, and atrophy. These effects often precede overt symptoms, complicating early diagnosis. Risk factors include prolonged or high-dose therapy, pre-existing ocular surface disease, contact lens wear, and dermatologic or systemic comorbidities. Clinical manifestations range from mild dry eye symptoms to persistent ocular surface damage. Current management is largely palliative, and there is no validated therapy for reversing gland atrophy. Despite mounting evidence, existing clinical guidelines do not recommend ophthalmologic screening, potentially delaying diagnosis and intervention. CONCLUSION: Isotretinoin-induced MGD is a clinically significant and underrecognized adverse effect. The absence of routine ophthalmological screening and standardized monitoring protocols leaves high-risk patients vulnerable to irreversible gland damage. Proactive surveillance, structured prevention, and individualized management are essential to minimize long-term ocular complications. Among all strategies, infrared meibography may serve as an objective, non-invasive tool to monitor isotretinoin-induced Meibomian gland damage, guiding early intervention and treatment decisions. Further research is needed to establish optimal screening strategies and explore effective preventive and restorative therapies.
New Gel Eye Formulation Based on Aristoflex and Xanthan Gum in the Management of Glaucoma Disease: Nonclinical Studies.
Biswal S, Das D, Sahoo RN … +1 more , Parmanik A
J Ocul Pharmacol Ther · 2026 Mar · PMID 41830312 · Publisher ↗
PURPOSE: Glaucoma, a class of visual neuropathies, is caused by the progressive degeneration of retinal ganglion cells, resulting in vision loss. Acetazolamide, a carbonic anhydrase inhibitor, is typically used to treat...
PURPOSE: Glaucoma, a class of visual neuropathies, is caused by the progressive degeneration of retinal ganglion cells, resulting in vision loss. Acetazolamide, a carbonic anhydrase inhibitor, is typically used to treat glaucoma. To minimize its harmful effects, the current study aimed to develop an acetazolamide-loaded gel by combining natural polymers, such as sodium alginate and xanthan gum (XG), and cold-processable synthetic polymer Aristoflex (AF). METHODS: Design Expert software was used to identify the optimized formulation by analyzing drug release study and viscosity data. The selected gel was evaluated based on its physicochemical properties and other nonclinical evaluations. RESULTS: Optimized formulation yielded satisfactory results in physicochemical characterizations. The drug-excipient compatibility analysis revealed no drug-polymer interactions. and release studies showed release of up to 70% and 65%, respectively, in 6 h. The intraocular pressure of the rabbit decreased over a long period after applying the optimized gel compared with the marketed formulation. CONCLUSION: Therefore, the research provided a brief explanation that the combination of AF and XG can be utilized in gels owing to its high retention time and reduced harmful effects for ocular illnesses.
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