Journal of Ocular Pharmacology and Therapeutics

Extend Phase 2A study to evaluate additional concentrations of H-1337 and dosing frequencies, and to compare them with a positive control.

Phase 2B, randomized, double-masked, active-controlled, dose–response study of 28 days of four treatments: H-1337 0.6% b.i.d., 1.0% b.i.d., or 1.0% q.d. (1.0% in the morning with H-1337 vehicle in the evening), and timolol maleate 0.5% b.i.d.

Two hundred one subjects with open-angle glaucoma or ocular hypertension at eight private practice sites in the United States.

Diurnal intraocular pressure (IOP) over 28 days of dosing.

Non-inferiority to timolol in change from baseline in IOP at Day 1 and Day 28.

Mean reduction in IOP was 4–7 mmHg for the H-1337 groups and 5–8 mmHg for the timolol group. Non-inferiority to timolol for H-1337 1.0% b.i.d. [upper limit of 95% confidence interval (CI) strictly lower than 1.5 mmHg] was met at 6/9 time points (Day 1: h 8 and 12; Day 28: h 2, 4, 8, and 12). Similar comparative efficacy was seen for the other H-1337 treatment groups. The most common adverse event observed was hyperemia, reported in 54.0% (27/50) for H-1337 1.0% q.d., 33.3% (17/51) for H-1337 0.6% b.i.d., 41.2% (21/51) for H-1337 1.0% b.i.d., and 8.2% (4/49) for timolol.

H-1337 in doses of 0.6% b.i.d., 1.0% q.d., and 1.0% b.i.d. had ocular hypotensive efficacy in the range of timolol, although not within the strict Phase 3 non-inferiority margins, which would have required a larger sample size.

Refractive surgery may exacerbate the existing dry eye symptoms in patients with dry eye syndrome. Therefore, we explore the therapeutic and protective effects of using optimal intense pulsed light (IPL) therapy combined with meibomian gland expression (MGX) before and after surgery on post-laser corneal refractive surgery dry eyes.

This was a prospective, self-controlled, single-center clinical trial. Using optimal IPL therapy and MGX, a total of 68 patients with mild-to-moderate evaporative dry eye or meibomian gland dysfunction who underwent refractive surgery received 2 sessions of treatment. The treatment was administered once a week preoperatively and once a week postoperatively. Baseline measurements were taken before optimal IPL therapy and MGX, and the parameters were assessed at 1 week and 1 month after surgery.

Out of 68 patients, 54 patients received small-incision lenticule extraction (SMILE), while 14 patients received femtosecond laser-assisted in situ keratomileusis (FS-LASIK) (results primarily reflect SMILE outcomes due to sample imbalance). In the SMILE group, significant improvement was already observed in uncorrected/corrected distance visual acuity (P = 1.42 × 10⁻³), meibomian gland expressibility score (MGYSS) (P = 0.01), and meibum yielding secretion score (MGS) (P = 5.39 × 10⁻⁴) between 1 week before and after the surgery. First noninvasive breakup time (NIBUTf) (P = 8.98 × 10⁻³), average noninvasive breakup time (NIBUTav) (P = 2.30 × 10⁻⁴), and meibomian gland dropout score (bottom) (P = 9.05 × 10⁻³) were observed to have significant improvement till 1 month after the surgery. Patients in the FS-LASIK group exhibited a comparable trend of change.

IPL treatment combined with MGX may improve ocular discomfort and dry eye symptoms in MGYSS, MGS, NIBUTf, NIBUTav, and meibomian gland dropout score (bottom) for patients with post-laser corneal refractive surgery dry eyes in short term.

To analyze the differential expression of inflammatory proteins in the tear fluid of patients with polypoidal choroidal vasculopathy (PCV) or neovascular age-related macular degeneration (nAMD).

A total of 19 patients with PCV, 17 patients with nAMD, and 18 normal controls (NC) aged ≥50 years were enrolled. Tear samples were collected, and the expression levels of 92 inflammatory proteins were quantified using Olink technology. Differentially expressed proteins (DEPs) among the groups were analyzed, with particular attention to consistency with previous findings from aqueous humor studies.

Olink analysis revealed extensive DEPs among PCV, nAMD, and NC groups. Compared with NC, the PCV group exhibited significant upregulation of VEGFA, Interleukin (IL) -18, IL-1α, IL-8, IL-7, Monocyte chemotactic protein (MCP)-2, and Neurturin (NRTN), along with downregulation of Tumor necrosis factor (TNF) and IL-10. The nAMD group showed a more pronounced pro-inflammatory profile, with upregulation of VEGFA, IL-18, IL-8, IL-1α, IL-7, Fibroblast growth factor (FGF)-19, MCP-1, Matrix metalloproteinase (MMP)-10, NRTN, Stem cell factor (SCF), Osteoprotegerin (OPG), Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), MMP-1, MCP-2, Fms-related tyrosine kinase 3 ligand (Flt3L), Tumor Necrosis Factor - like Weak Inducer of Apoptosis (TWEAK), Caspase (CASP)-8, and Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), and downregulation of IL-10 and IL-12β. Comparison between PCV and nAMD indicated that IL-12β and Hepatocyte growth factor (HGF) were specifically upregulated in PCV, whereas SCF, VEGFA, Flt3L, OPG, MCP-1, T-cell surface glycoprotein CD8α (CD8α), Cystatin D (CST5), MMP-1, TNFRSF9, Transforming growth factor-α (TGF-α), 4E-BP1, and CASP-8 were significantly downregulated in PCV relative to nAMD. Boxplot analysis confirmed that Flt3L, IL-18, IL-1α, IL-7, IL-8, MCP-1, MMP-1, OPG, SCF, and VEGFA were specifically elevated in nAMD compared with both PCV and NC groups, while IL-10 was specifically suppressed in PCV.

Tear fluid analysis represents a feasible and noninvasive approach to investigate the pathogenesis of PCV and nAMD.

Ambroxol is a high-potency inhibitor of voltage-gated sodium channels Nav1.7 and Nav1.8 responsible for nociceptive and neuropathic pain. This study investigated the analgesic property of ambroxol on corneal pain in rats as well as its toxicity on human corneal epithelial cells.

Inhibition of corneal sensation (CS) by ambroxol hydrochloride (AH) in Sprague–Dawley rats was assessed by Cochet–Bonnet esthesiometer. Rat corneal pain was induced by administering 5 M NaCl drops to the eyes, and eye wiping rates were recorded to reflect pain intensity. Subsequently, a rat neuropathic corneal pain (NCP) model was created by first removing the corneal epithelium and then provoking pain with 2 M NaCl. The analgesic property of 0.5% AH eye drop was assessed in rats by reductions in eye wiping rates. In cultured human corneal epithelial cells, the adverse effects of AH on cell migration and viability were studied by cell scratch and Cell Counting Kit-8 tests.

It was noted that 0.5% AH could significantly inhibit CS, and 0.5% AH is efficacious in suppressing rat corneal pain as well as heightened nociceptor sensitivity from repetitive stimulation from irritants. At concentrations up to 30 μM, AH does not affect corneal epithelial cell migration, cell proliferation, and viability.

Selective blockage of key nociceptors of the cornea by ambroxol is effective in suppressing corneal pain and heightened nociceptor excitability, leading to modulation of NCP. Sparing certain CS could translate into more protection to the ocular surface. No overt toxicity of ambroxol was seen in cultured human corneal epithelial cells in this study.

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.

This study compared the efficacy and safety of MTX versus steroids and placebo in treating scleritis.

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.

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 (P = 0.003). However, its effect on visual acuity was insignificant (P = 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.

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.

To investigate the mechanisms underlying the protective effects of piperine on retinal pigment epithelium (RPE) cells under high-glucose and hypoxic conditions.

A model of diabetes was established by treating D407 cells with high glucose (25 mM) and hypoxia (5% O₂ for 24 h). The mRNA and protein expression levels of the long noncoding RNA (lncRNA), plasmacytoma variant translocation 1 (PVT1), miR-128, pigment epithelium-derived factor (PEDF), and vascular endothelial growth factor C (VEGFC) were assessed by RT–qPCR, western blotting, and immunofluorescence staining. Wound-healing assays were performed to evaluate cell migration. The role of PVT1 was explored using siRNA-mediated knockdown, and the interactions among lncRNA PVT1, miR-128, and VEGFC were predicted and validated by dual-luciferase reporter assays.

Under high-glucose and hypoxic conditions, lncRNA PVT1 and VEGFC mRNA transcription were upregulated, whereas miR-128 and PEDF mRNA expression were downregulated. VEGFC protein levels were increased, PEDF protein levels were decreased, and cell migration was impaired. Treatment with piperine or knockdown of lncRNA PVT1 via siRNA partially reversed these effects. Dual-luciferase reporter assays further confirmed the interactions among PVT1, miR-128, and VEGFC.

Piperine may protect RPE cells by modulating the lncRNA PVT1/miR-128 signaling pathway and promoting PEDF expression.

The apelin/APJ system represents a promising VEGF-independent therapeutic target for treating retinopathy of prematurity (ROP), given its selective upregulation in pathological retinal neovasculature. We aimed to identify clinically translatable APJ antagonists that suppress pathological neovascularization without VEGF-related side effects.

We employed a hypoxia-induced zebrafish ROP model to recapitulate pathological neovascularization, combined with structure-based virtual screening of 2,506 FDA-approved drugs targeting the APJ receptor (PDB ID: 6KNM). Lead compounds were evaluated through in vitro angiogenesis assays (human umbilical vascular endothelial cells [HUVEC] tube formation, migration, and invasion) and in vivo efficacy testing.

Among 21 initial hits, octreotide (X-3) showed the most potent anti-angiogenic activity, with an IC₅₀ of 0.016 µM in HUVECs. Mechanistically, X-3 selectively downregulated APJ expression without altering VEGF/VEGFR levels. Functional assays confirmed its ability to suppress endothelial tube formation, migration, and invasion.

Our findings identified octreotide as a novel APJ antagonism with high translational potential, offering a dual advantage—targeting pathological neovascularization while preserving physiological VEGF signaling. These findings support its repurposing as a precision therapy for ROP and other ocular neovascular disorders.