brimonidine + ripasudil (gra alfa / Graalfa / K232)

Therapeutic efficacy and systemic pharmacokinetics of a dual-drug hydrogel contact lens for sustained glaucoma therapy.

Varshitha Vangol V, Sankararajan Umadevi U

Conventional topical therapy for glaucoma is limited by poor ocular bioavailability, rapid precorneal drug loss, frequent dosing and systemic absorption through the nasolacrimal pathway, which may reduce therapeutic efficacy and increase the risk of adverse effects. Drug-eluting hydrogel contact lenses have emerged as a promising strategy to overcome these limitations by enabling sustained ocular drug delivery. This study aimed to evaluate the therapeutic efficacy, ocular biocompatibility and systemic pharmacokinetic profile of an optimized dual-drug-loaded HEMA-based hydrogel contact lens delivering timolol maleate (TM) and brimonidine tartrate (BT) for sustained glaucoma management. Optimized hydrogel contact lenses composed of 2-hydroxyethyl methacrylate (HEMA), N, N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP) and ethylene glycol dimethacrylate (EGDMA) were fabricated by UV photopolymerization and loaded with TM and BT (4 mg/mL each). Ocular biocompatibility was assessed using the modified Draize irritation test. Therapeutic efficacy was evaluated in a steroid-induced ocular hypertension New Zealand White rabbit model by monitoring intraocular pressure (IOP) for 24 h. Systemic drug exposure was determined by validated high-performance liquid chromatography (HPLC) analysis of plasma samples, while ocular safety was further confirmed through histopathological examination. The optimized hydrogel lens exhibited excellent ocular biocompatibility, with a maximum Draize score of 0.33 ± 0.12 that resolved completely within 48 h and no histopathological evidence of ocular tissue damage. In hypertensive rabbits, the dual-drug hydrogel lens maintained normotensive IOP (16.1 ± 0.8 mmHg) for 24 h, representing a 43.5% reduction from baseline and significantly outperforming conventional eye drops beyond 4 h (p < 0.01). Plasma concentrations of both TM and BT remained below the limit of quantification (<2.0 ng/mL) throughout the study, whereas conventional eye drops produced measurable systemic exposure (TM: 18.4 ± 2.1 ng/mL; BT: 8.2 ± 1.2 ng/mL), demonstrating effective minimization of systemic drug absorption. The optimized dual-drug-loaded hydrogel contact lens provided sustained intraocular pressure reduction, excellent ocular biocompatibility and negligible systemic drug exposure compared with conventional topical therapy. These findings highlight its potential as a sustained ocular drug-delivery platform capable of improving therapeutic efficacy, reducing systemic adverse effects and enhancing long-term treatment adherence in glaucoma management. Further long-term preclinical investigations and clinical studies are warranted to support clinical translation.

Management of brimonidine-associated uveitis and conjunctivitis.

Amrani Yasmina Y, Ameli Shervine S, Verhulst Karen K, Dugauquier Artemise A

Post-acne Erythema: A Systematic Review of Randomized Controlled Trials on the Comparative Efficacy and Safety of Interventions Across Clinical, Instrumental, and Patient-Reported Outcomes.

Alhussain Ahmed A, Majrashi Mohammad M, Omar AlMubarak Khalid K, Faleh Alqahtani Rayan R et al.

Post-acne erythema (PAE) is a persistent acne sequela without an established standard treatment. This systematic review evaluated the comparative efficacy and safety of interventions tested in randomized trials. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception through August 1, 2026. Randomized parallel-group and split-face trials reporting erythema outcomes were eligible. Risk of bias was assessed with the Cochrane Risk of Bias 2 (RoB 2) tool. Heterogeneity precluded meta-analysis, and available findings were synthesized narratively. Nine trials involving 301 participants contributed 11 pairwise comparisons. Against untreated or blank controls, favorable effects were reported for picosecond alexandrite laser, narrow-spectrum vascular intense pulsed light (IPL), and non-cross-linked hyaluronic acid mesotherapy. A 577-nm semiconductor laser showed interim instrumental benefit, but blinded assessors found no final between-side difference. In active-treatment and add-on comparisons, narrow-spectrum IPL was favored over broad-spectrum IPL, neodymium-doped yttrium aluminum garnet (Nd) laser added to low-dose isotretinoin was favored over isotretinoin alone, and 577-nm pro-yellow laser was favored over topical brimonidine. Botulinum toxin type A was favored over broadband light at the earliest assessment only. Fractional laser and pulsed dye laser did not differ significantly, while delicate pulsed light and Q-switched 1064-nm Nd laser showed no sustained difference at the final assessment. Adverse events were mild and transient, although pigmentation and blistering occurred with one broad-spectrum IPL protocol. Five trials had some concerns, and four had high overall risk of bias. Trials suggested potential benefits, but small samples, heterogeneity, short follow-up, and reporting limitations precluded identification of a preferred treatment. Larger, prospectively registered trials using blinded assessment and standardized outcomes are needed.

Association of Topical Therapy and Surgical Management with Corneal Parameters in Congenital PAX6-Related Classical Aniridia: a Cross-Sectional Study.

Li Yubo Y, Grünauer-Kloevekorn Clara C, Csidey Mária M, Náray Annamária A et al.

This study aimed to investigate associations of topical therapy and surgical management with the severity of aniridia-associated keratopathy (AAK), limbal stem cell deficiency (LSCD) and corneal microstructural alterations in patients with PAX6-related congenital aniridia (CA). This cross-sectional study included eyes with genetically confirmed CA. Medical history, including preservative-free artificial tears, antiglaucoma medications (beta-blockers, brimonidine, carbonic anhydrase inhibitors, prostaglandin analogues), and ocular surgery was recorded. AAK and LSCD were graded. Anterior segment optical coherence tomography (AS-OCT) assessed epithelial and total corneal thickness, while in vivo confocal microscopy (IVCM) assessed subbasal nerve plexus parameters, Langerhans cell density (LCD), and stromal keratocyte density. Associations were analyzed using generalized estimating equations. Sixty-one eyes of 31 patients were analyzed. More advanced AAK and LSCD were associated with more frequent preservative-free artificial tear use. Antiglaucoma medications were associated with differences in corneal thickness, keratocyte and Langerhans cell densities, and subbasal nerve plexus parameters. Prostaglandin analogue use was associated with a heterogeneous pattern, including higher corneal nerve fiber density and length, higher middle stromal keratocyte density, and lower LCD. Previous ocular surgery showed limited associations with corneal microstructural parameters but was associated with lower corneal nerve network complexity. All findings were exploratory and hypothesis-generating. Topical therapy use is associated with differences in corneal structural and cellular parameters in congenital aniridia. Preservative-free artificial tear use is associated with more advanced AAK and LSCD, while antiglaucoma medications are associated with differences in corneal thickness, keratocyte and Langerhans cell densities, and corneal nerve parameters. Prostaglandin-treated eyes show a heterogeneous pattern of associations with corneal microstructural parameters. Given the cross-sectional design, whether these treatment-associated differences reflect medication effects, underlying disease severity, treatment selection, concomitant therapies, or residual confounding cannot be determined. These findings require longitudinal confirmation.