Investigation of the effect of latanoprostene bunod and latanoprost on peripapillary optical coherence tomography angiography.

This study evaluated the effects of α2-adrenergic agonist, prostaglandin F2α analog, and EP2 receptor agonist on tunicamycin-induced endoplasmic reticulum (ER) stress and fibrosis in human trabecular meshwork (TM) cells. Human TM cells were treated with tunicamycin for 24 h, followed by cotreatment with brimonidine (BRI), latanoprost (LAT), or omidenepag (OMD). Immunocytochemistry was used to assess expressions of collagen type I alpha 1 chain (COL1A1), fibronectin, F-actin, and alpha-smooth muscle actin (α-SMA). Western blotting was performed to evaluate levels of C/EBP homologous protein (CHOP), 78-kDa glucose-regulated protein (GRP78), and splicing X-box binding protein-1 (sXBP-1). Real-time qPCR was used to examine the mRNA expressions of COL1A1, connective tissue growth factor (CTGF), fibronectin, α-SMA, CHOP, GRP78, and sXBP-1. Expressions of COL1A1, CTGF, F-actin, fibronectin, α-SMA, CHOP, GRP78, and sXBP-1 significantly increased after tunicamycin treatment. BRI cotreatment significantly downregulated the mRNA and protein expressions of GRP78, and LAT or OMD cotreatment significantly reduced the CHOP and sXBP-1 expressions compared to the tunicamycin-treated group. BRI, LAT, or OMD cotreatment significantly attenuated cellular cytoskeletal changes and the increase of fibrosis markers such as COL1A1, CTGF, fibronectin, and α-SMA. In addition, COL1A1 mRNA expression was significantly lowered with LAT or OMD cotreatment compared to the BRI-cotreated group. Cotreatment with α2-adrenergic agonist, prostaglandin F2α analog, or EP2 receptor agonist alleviates tunicamycin-induced ER stress in human TM cells.

Objective:To evaluate the effects of latanoprostene bunod on intraocular pressure (IOP) and pupil diameter (PD) in normal cats and cats with feline congenital glaucoma (FCG).Animals Studied:Five normal and 5 FCG cats.Procedures:This masked, controlled crossover study comprised a 1-day Pre-treatment phase followed by two 10-day Treatment phases, each followed by a 10-day Recovery phase. During treatment, all cats received twice daily 0.005% latanoprost (LAT) or 0.024% latanoprostene bunod (LBN) in a randomized eye. Following Recovery, the same eye was treated with the opposite drug. Contralateral eyes served as saline-treated controls. Intraocular pressure and PD measurements were performed three times daily during all study phases. Data were analyzed via constrained longitudinal data analysis models.Results:Neither drug significantly reduced IOP in normal cats. In FCG cats, statistically significant reductions in mean (95% CI) IOP were observed relative to controls 4 h after LAT and LBN treatment (−5.5 mmHg [−8.4, −2.5], p < .001, −7.2 mmHg [−10.2, −4.3], p < .001, respectively). These differences represented 28.4% and 37.9% IOP reductions, respectively. Mean IOP reduction after 4 h was significantly greater with LBN treatment compared to LAT (−1.8 mmHg [−3.2, −0.4], p = .012). However, these IOP reductions were not considered clinically significant. Both drugs similarly reduced PD in normal and FCG cats.Conclusions:Transient IOP reduction was observed after topical administration of LAT and LBN in FCG cats; and mean IOP difference was statistically significantly greater in LBN-treated eyes. However, the apparent enhanced hypotensive effect of LBN is not clinically significant.

HPLC-DAD method for concurrent estimation of netarsudil, latanoprost and benzalkonium chloride: Stability indicating study, impurity separation, assay of ophthalmic preparations and greenness/whiteness valuation

The first line of glaucoma treatment focuses on reducing intraocular pressure (IOP) through the prescription of topical prostaglandin analogues, such as latanoprost (LAT). Topical ophthalmic medicines have low bioavailability due to their rapid elimination from the ocular surface. Nanotechnology offers innovative ways of enhancing the ocular bioavailability of antiglaucoma agents while reducing administration frequency. This study aims to combine LAT-loaded synthetic phosphatidylcholine liposomes with hyaluronic acid (0.2% w/v) and the osmoprotectants betaine (0.40% w/v) and leucine (0.90% w/v) (LAT-HA-LIP) to extend the hypotensive effect of LAT while protecting the ocular surface. LAT-HA-LIP was prepared as a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, cholesterol and α-tocopherol acetate. LAT-HA-LIP exhibited high drug-loading capacity (104.52 ± 4.10%), unimodal vesicle sizes (195.14 ± 14.34 nm) and a zeta potential of -13.96 ± 0.78 mV. LAT-HA-LIP was isotonic (284.00 ± 1.41 mOsm L−1), had neutral pH (7.63 ± 0.01) and had suitable surface tension (44.07 ± 2.70 mN m−1) and viscosity (2.69 ± 0.15 mPa s−1) for topical ophthalmic administration. LAT-HA-LIP exhibited optimal in vitro tolerance in human corneal and conjunctival epithelial cells. No signs of ocular alteration or discomfort were observed when LAT-HA-LIP was instilled in albino male New Zealand rabbits. Hypotensive studies revealed that, after a single eye drop, the effect of LAT-HA-LIP lasted 24 h longer than that of a marketed formulation and that relative ocular bioavailability was almost three times higher (p < 0.001). These findings indicate the potential ocular protection and hypotensive effect LAT-HA-LIP offers in glaucoma treatment.Graphical abstract

The temporal change in concentration of a novel medicine, Latanoprost (LP), was evaluated in the aqueous humor of rats (6-8-week-old Jcl:Wister rats) when delivered in a very-high-molecular-weight hyaluronic acid (vHiHA) eye drop. Animals were randomly assigned to three treatment groups (LP + vHiHA (LPvHiHA), commercial LP (cLP), and diluted LP (dLP)) and after instilling the eye drops, the aqueous humor (AH) was collected at 0.5, 1, 2, 4, and 6 h to measure the LP concentration using an enzyme-linked immunosorbent assay (ELISA). Although the LP concentration in the LPvHiHA eye drop formulation was 3.57 times lower than in the commercial eye drops used (cLP), the LP concentration in the AH following LPvHiHA administration reached a value close to that of cLP. The cLP was diluted to the same concentration of LP as in the LPvHiHA eye drops for the dLP group, but the LP concentration in the AH of these animals was lower than that of the LPvHiHA rats at all time points. The higher LP concentration in the AH of the LPvHiHA rats suggests that vHiHA may aid the transport of LP across the ocular surface epithelium.

Abstract A gradient high-performance liquid chromatography (HPLC) method has been developed to determine the concentrations of latanoprost (LP) and latanoprost free acid (LPA) in aqueous solutions. It is novel due to a combination of its simplicity, speed, and detection capability in aqueous solutions for both active drug (LPA) and prodrug (LP). This method is applicable for the research and development of novel drug delivery devices and quality control assays for experimental and commercial laboratory settings, as it allows for a high sample throughput. Samples were chromatographed across a C18 + 2.7 µm 4.6 × 7.5 mm reversed-phase column with gradient elution using a mobile phase of aqueous acetic acid (pH 3.1) and acetonitrile with 0.1% acetic acid. UV spectrophotometry was used to monitor the eluents at 210 nm. Drug concentrations from 1.0 to 150 μg mL−1 were tested, with good linearity observed across the range. LPA had a signature peak at approximately 4.82 min (SD &lt; 0.08) and LP at 9.27 min (SD &lt; 0.07). For both drug and pro-drug, LOD and LOQ were 1.0 and 2.5 μg mL−1, respectively. This assay which accurately measures both prodrug and drug in a single injection, has significant applicability in determining the release kinetics of novel LP drug delivery systems.

Drug-eluting contact lenses (DECLs) incorporated with poly(lactic-co-glycolic acid) (PLGA) and various model drugs (ketotifen fumarate, bimatoprost and latanoprost) were fabricated using nanoelectrospray (nES) approach. The resulting DECLs demonstrated outstanding optical transmittance within the optical zone, indicating that the employed coating procedure did not compromise visual acuity under the prescribed spraying parameters. In vitro drug release assessments of the model drugs (ketotifen fumarate (KF), bimatoprost (BIM), and latanoprost (LN)) revealed a strong correlation between the model drug's hydrophobicity and the duration of drug release. Changing the drug loading of the more hydrophilic model drugs, BIM and KF, showed no impact on the drug release kinetics of DECLs loaded with BIM and KF. However, for the hydrophobic model drug, LN, the highest LN loading led to the most extended drug release. The conventional steam sterilisation method was found to damage the PLGA coating on the DECLs fabricated by nES. An alternative sterilisation strategy, such as radiation sterilisation may need to be investigated in the future study to minimise potential harm to the coating.

To evaluate the ocular surface of patients treated with latanoprost (LT) 0.005% who switched to latanoprostene bunod (LBN) 0.024%. A prospective and nonrandomized clinical study of a case series was performed, including patients with chronic open-angle glaucoma who were on previous LT-only treatment and, after a washout period, switched to LBN, with a 3-month follow-up. The main parameter to be evaluated was the ocular surface disease index (OSDI) test. In addition, best-corrected visual acuity (BCVA), intraocular pressure (IOP), biomicroscopic aspect of the ocular surface, measuring tear breakup time, fluorescein staining (grading performed on Oxford scale) and Schirmer I test were evaluated. A total of 36 patients (72 eyes) were included, 21 women (58.3%) and 15 men (41.7%, with a mean age of 65.6 ± 10.9 years (37-86). The initial OSDI score was 17.8 ± 12.1 and improved to 11.1 ± 10.5 (p < 0.01). From the data evaluated at biomicroscopy, an improvement was observed in the Oxford scale from 0.6 ± 0.7 to 0.2 ± 0.8 (p: 0.01), but no statistically significant changes were observed in the break-up time (BUT) and Schirmer. BCVA remained stable, as did IOP, which was initially 13.4 ± 2.1 mm Hg and, after performing the LBN treatment change, went to 13.1 ± 1.7 mm Hg. After the change of treatment from LT 0.005% to LBN 0.024%, the patients had an improvement in the ocular surface, maintaining control of their IOP. The need to investigate possible beneficial mechanisms on the ocular surface in glaucoma patients treated with LBN, potentially related to nitric oxide, is raised. Patients treated with LT 0.005% who switched to LBN 0.024% had an improvement in ocular surface symptoms and signs, keeping IOP under control.Latanoprostene bunod (LBN) 0.024% may have beneficial effects on the ocular surface, which should be further studied. Zanutigh V, Galetto L, Valvecchia F, et al. Ocular Surface Evaluation after Switch from Latanoprost 0.005% to Latanoprostene Bunod 0.024%. J Curr Glaucoma Pract 2023;17(4):205-209.

Trabecular meshwork (TM) fibrosis is a crucial pathophysiological process in the development of primary open-angle glaucoma. Pirfenidone (PFD) is a new, broad-spectrum antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis. This study investigated the inhibitory effect of PFD on TM fibrosis and evaluated its efficacy in lowering intraocular pressure (IOP). Human TM cells were isolated, cultured, and characterized. Cell Counting Kit-8 was used to evaluate the proliferation and toxicity of different concentrations of PFD on normal or fibrotic TM cells. TM cells were treated with transforming growth factor beta-2 (TGF-β2) in the absence or presence of PFD. Western blotting and immunofluorescence analyses were used to analyze changes in the TM cell cytoskeleton and extracellular matrix (ECM) proteins, including alpha-smooth muscle actin (α-SMA), F-actin, collagen IV (COL IV), and fibronectin (FN). An ocular hypertension (OHT) mouse model was induced with Ad-TGF-β2C226/228S and then treated with PFD or latanoprost (LT) eye drops to confirm the efficacy of PFD in lowering IOP. PFD inhibited the proliferation of fibrotic TM cells in a dose-dependent manner and inhibited TGF-β2-induced overexpression of α-SMA, COL IV, and FN in TM cells. PFD stabilized F-actin. In vivo, PFD eye drops reduced the IOP of the OHT models and showed no significant difference compared with LT eye drops. PFD inhibited TGF-β2-induced TM cell fibrosis by rearranging the disordered cytoskeleton and decreasing ECM deposition, thereby enhancing the aqueous outflow from the TM outflow pathway and lowering IOP, which provides a potential new approach to treating glaucoma. Our work with pirfenidone provides a new approach to treat glaucoma.

Latanoprost (LTP) is a prostaglandin F2α analog used to lower intraocular pressure in glaucoma treatment administered daily as eye drops. In this study, a universal model based on poly(l-lactide-co-glycolide-co-trimethylene carbonate) with shape memory was proposed for the development of a solid biodegradable formulation with prolonged release administered intraconjunctivally, intravitreally, subconjunctivally, and subcutaneously. Solution casting and electron beam (EB) irradiation were applied to the matrix formulation. The properties of the native matrix and matrices degraded in a PBS buffer (pH 7.4) were monitored by NMR, DSC, GPC, and SEM. Water uptake (WU) and weight loss (WL) were also analyzed. LTP was released over 113 days in a tri-phasic and sigmoidal pattern without a burst effect and with a relatively long second release phase, in which changes were observed in the glass transition temperature, molecular weight (Mn), WU, and WL. EB irradiation decreased the initial Mn, increased WU, and accelerated LTP release with a shortened lag phase. This provides the opportunity to partially eliminate the use of drops at the start of treatment. SEM observations indicated that surface erosion is the prevalent degradation mechanism. The proposed model is an interesting solution during a preliminary study to develop final medicinal products that provide high adherence.

Background Acrofacial vitiligo (AFV) represents a therapeutic challenge for dermatologists. Aim and objectives To investigated the efficacy of microneedling (MN) and topical latanoprost (LT) 0.005% in the treatment of AFV. Patients and methods A total of 72 patients with AFV were divided into two groups. Group A (n=36) received topical LT 0.005% twice daily, preceded by MN sessions at 2-week intervals, for a total duration of 12 weeks. Group B (n=36) received topical LT 0.005% alone for 12 weeks. Participants were evaluated by vitiligo area and severity index (VASI) at 2-week intervals for 12 weeks, and at 12 weeks after stopping the treatment. Results In group A, 12-week VASI [0.45 (0.18, 0.64)] was significantly lower than the baseline VASI [0.5 (0.21, 0.67); P=0.003]. In group B, the 12-week VASI was the same as the baseline VASI [0.43 (0.25, 1)]. Repigmentation was achieved in 18/36 (50%) of patients in group A and 0/36 (0.0%) in group B. Repigmentation was rated as excellent in 2/36 (5.56%), very good in 2/36 (5.56%), good in 4/36 (11.12%), and fair in 10/36 (27.76%) of the cases. Conclusion Combined therapy with MN and topical LT 0.005% resulted in variable degrees of repigmentation in 50% of patients with AFV.

It is difficult to follow changes in the intraocular pressure (IOP) in glaucomatous eyes comprehensively because of the limited number of outpatient examinations. We report our findings in a case of normal tension glaucoma (NTG) in which frequent self-measurements of the IOP were used to evaluate the IOP-lowering effect of different medications. A 50-year-old man with NTG had a nasal step visual field defect in his right eye and was being treated with 0.005% latanoprost (LAT) ophthalmic solution (XALATAN®). The patient was diagnosed with NTG. The patient had a mean IOP in the right eye of 10.9 ± 1.5 mm Hg (68 measurements in 1 month, Period A) during treatment with 0.005% LAT ophthalmic solution. During the second month (Period B), the mean IOP in the same eye was 9.8 ± 1.7 mm Hg (59 measurements) with treatment with a LAT and carteolol fixed combination (LCFC). And during the third month (Period C), the mean IOP was 7.4 ± 1.1 mm Hg (57 measurements) on the same right eye after the addition of brimonidine and brinzolamide fixed combination ophthalmic solution to the LCFC ophthalmic solution. Comparisons of the IOPs between Periods A and B and between B and C showed that the reductions in the IOP were significant. We conclude that frequent self-measurements of the IOP can determine that small changes of the IOPs are significant.

Latanoprost (LAT) has been shown to have a hypertrichoticeffect,which makes it a promising candidate for alopecia treatments. Forthe first time, LAT has been encapsulated in nanotransfersomes inorder to increase its efficacy. Ex vivo skin biodistributionwas studied by confocal laser microscopy both in human scalp and pigskin. Results showed that nanotransfersomes increase the penetrationof two different fluorochromes, with similar patterns in both species,compared with fluorochrome solutions containing no nanotransfersomes.Nanotransfersomes were stable under accelerated conditions (40 °C/75%RH) and long-term conditions (25 °C/60% RH) for up to 1 year,with no differences in vesicle size and polydispersity when LAT wasloaded. Nanotransfersomes increased the LAT cell proliferation effectin HaCaT cell via MAPK signaling pathway. Collectively, our resultsdemonstrate LAT-nanotransfersomes formulation could be a promisingtherapy for hair growth disorders.

Novel chitosan - graphene quantum dots composite for therapeutic delivery and tracking through enzymatic stimuli response

The trabecular meshwork (TM) is the main site of drainage of the aqueous humor, and its dysfunction leads to intraocular pressure elevation, which is one of the main risk factors of glaucoma. We aimed to compare the effects on cytoskeleton organization and extracellular matrix (ECM) of latanoprost (LT) and a Rho-kinase inhibitor (ROCKi) on a transforming growth factor beta2 (TGF-β2)-induced glaucoma-like model developed from primary culture of human TM cells (pHTMC). The TGF-β2 stimulated pHTMC were grown and incubated with LT or a ROCKi (Y-27632) for 24 h. The expression of alpha-smooth muscle actin (αSMA) and fibronectin (FN), and phosphorylation of the myosin light chain (MLC-P) and Cofilin (Cofilin-P) were evaluated using immunofluorescence and Western blot. The architectural modifications were studied in a MatrigelTM 3D culture. TGF-β2 increased the expression of αSMA and FN in pHTMC and modified the cytoskeleton with cross-linked actin network formation. LT did not alter the expression of αSMA but decreased FN deposition. The ROCKi decreased TGF-β2-induced αSMA and FN expression, as well as MLC-P and Cofilin-P, and stimulated the cells to recover a basal cytoskeletal arrangement. In the preliminary 3D study, pHTMC organized in a mesh conformation showed the widening of the TM under the effect of Y-27632. By simultaneously modifying the organization of the cytoskeleton and the ECM, with fibronectin deposition and overexpression, TGF-β2 reproduced the trabecular degeneration described in glaucoma. The ROCKi was able to reverse the TGF-β2-induced cytoskeletal and ECM rearrangements. LT loosened the extracellular matrix but had no action on the stress fibers.

Abstract PurposeTo investigate the impact on human conjunctival goblet cell (GC) survival and mucin release for benzalkonium chloride (BAK) preserved and preservative‐free (PF) 0.005% (w/v) latanoprost (LT) eye drops, and to compare the eye drops’ physicochemical properties.MethodsGC cultures were established from human conjunctival donor tissue. The impact of eye drops on GC survival was assessed using lactate dehydrogenase (LDH) and tetrazolium dye (MTT) colorimetric assays. Mucin release was evaluated through mucin‐specific immunostaining. pH‐value, osmolality, drop mass and surface tension for all LT eye drops were measured.ResultsAfter application with PF‐LT for 30 minutes (min), the GC survival was maintained (p = 0.7043), while all BAK‐LT eye drops reduced survival to approximately 70% (p&lt;0.0001). Following application with PF‐LT for 30 min, mucin was found around the GC nucleus, as seen in the vehicle control, indicating no secretion. In contrast, BAK‐LT caused diffuse staining of mucin, similar to the secretagogue histamine, indicating stimulation of secretion. The pH of the BAK‐LT and PF‐LT eye drops were 6.0‐6.9 and 6.8, respectively. The osmolality was 258‐288 mOsm/kg for the BAK‐LT eye drops and 276 for PF‐LT eye drop. The mean drop mass was 26‐31 mg for the BAK‐LT eye drops and 30mg for PF‐LT. The surface tension was lower for all BAK‐LT eye drops (31.1‐32.1 mN/m) compared to PF‐LT (42 mN/m).ConclusionsPF‐LT compared to various branded and generic LT preparations containing BAK should be used to improve goblet cell tolerability and ocular surface health.

ObjectiveTo investigate the short-term impact on human conjunctival goblet cell (GC) survival and mucin release of acute exposure to benzalkonium chloride (BAK) preserved and preservative-free (PF) 0.005% (w/v) latanoprost (LT)...

In this study, we investigated the effect of preservative-free (PF) 0.0015% tafluprost (TA), to the preservative containing (PC) and the PF 0.005% latanoprost (LA) in Korean subjects. This study was conducted as a multi-center, randomized, investigator-blind, active controlled, parallel-group, clinical trial in adult patients (≥19 years) with open-angle glaucoma (OAG) and ocular hypertension (OHT). After a washout period, patients with an IOP between 15 and 35 mmHg were enrolled and evaluated the efficacy, safety, and compliance at 4, 8 and 12 weeks after the first administration. A total of 137 OAG and OHT patients were randomized. Statistically significant reductions in IOP were observed in all groups. Twelve weeks after each eye drop instillation, the mean IOP reduction was −4.59 ± 2.70 mmHg (−24.57 ± 13.49%) in the PC-LA group, −4.52 ± 2.17 mmHg (−24.41 ± 11.38%) in the PF-LA, and −3.14 ± 2.83 mmHg (−17.22 ± 14.57%) in the PF-TA group. The PF-LA showed significantly better responsiveness than did PF-TA. PF-LA was better tolerated than was PC-LA. There were no adverse events that led to cessation of eye drop use in any of the groups. In conclusion, IOP decreased similarly across the groups. PF-LA may provide a good choice for OAG patients with ocular surface diseases.

Experimental studies have shown that aqueous extract of Pleurotus tuber-regium (PT) caused a reduction in steroid induced ocular hypertension in feline models and a contractile effect on isolated bovine iris. A comparative thin layer chromatographic study and Ultraviolet-Visible spectrophotometric analysis (TLC-UVS) of PT in comparison with known antiglaucoma drugs (0.5% betaxolol, 0.5% timolol maleate, 2% pilocarpine, and 0.005% latanoprost) was carried out to identify their similarities. Graded concentrations (5mg/ml, 10mg/ml, 20mg/ml and 40mg/ml) of PT were spotted along with the drugs on prepared glass plates. Silica type 60 gel served as the stationary phase while a solvent system of 50ml chloroform and 50ml absolute ethanol was used as the solvent system. On completion, comparison was made between the extracts and the drugs based on their migration speeds and retardation factors. Further analytic studies were carried out on the filtrates gotten from thin layer chromatography with an Ultraviolet-Visiblespectrophotometer. Thin layer chromatographic (TLC) analysis showed that the extracts compared favorably with the drugs under study, particularly with timolol maleate and latanoprost, as they had similar migration distances and retardation factors (R ). f Spectrophotometry revealed that the extract has an absorption spectrum within the ultra-violet wavelength range with a λmax of 260nm, this is comparable to the known absorption spectra of the anti-glaucoma drugs. PT may likely have similar substances with known anti glaucoma drugs. This is a preliminary evaluation of the crude aqueous extract of PT. Key Words: Antiglaucoma drugs, Chromatographic Analysis, Pharmacodynamics, Pleurotus tuber-regium.