To compare the efficacy of morning and evening latanoprost/timolol fixed-combination (LTFC) dosing in patients with primary open-angle glaucoma (POAG) and ocular hypertension.
In this double-blind, randomized clinical trial, 63 untreated Chinese patients with POAG and ocular hypertension were enrolled. All patients received LTFC and were randomized (1:1) to group 1, morning (8 AM) dosing, or group 2, evening (8 PM) dosing. Vehicle drops were used in the morning or evening, accordingly, to preserve masking. Patients were treated for 4 weeks. Outcomes included mean reduction of the 24-hour intraocular pressure (IOP) and IOP fluctuation from baseline after a 4-week treatment.
Fifty-six patients were included in the final analysis. In both groups, the posttreatment IOP values were significantly lower than those at baseline at each 24-hour measuring time point. A significant difference between the groups in IOP reduction from baseline was observed at the 9:30 AM time point (4.01 ± 2.62 vs. 2.42 ± 3.23 mm Hg, evening dosing versus morning dosing group; P = 0.048). Both groups showed decreased IOP fluctuation after treatment. However, the morning dosing group had a significantly greater decrease in diurnal IOP fluctuation than that of the evening dosing group (2.04 ± 2.32 mm Hg vs. 0.50 ± 1.70 mm Hg, respectively; P = 0.012).
Both morning and evening LTFC dosing can effectively reduce 24-hour IOP and IOP fluctuation. Morning dosing is more likely to effectively control diurnal IOP fluctuations.
This multicenter, double-blind, randomized clinical trial generates robust evidence on the optimal LTFC dosing regimen to help clinical decision-making in the treatment of raised IOP.

Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F2α and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application. Meanwhile, the FP receptor selective agonist latanoprost is not suitable to treat PPH due to its poor solubility and fast clearance. Here, we present two cryo-EM structures of the FP receptor bound to carboprost and latanoprost-FA (the free acid form of latanoprost) at 2.7 Å and 3.2 Å resolution, respectively. The structures reveal the molecular mechanism of FP receptor selectivity for both endogenous prostaglandins and clinical drugs, as well as the molecular mechanism of G protein coupling preference by the prostaglandin receptors. The structural information may guide the development of better prostaglandin drugs.

Glaucoma is the third leading cause of blindness worldwide and is primarily characterized by elevated intraocular pressure (IOP). Common risk factors such as age, myopia, ocular trauma, and hypertension all increase the risk of elevated IOP. Prolonged high IOP not only causes physiological discomfort like headaches, but also directly damages retinal cells and leads to retinal ischemia, oxidative imbalance, and accumulation of reactive oxygen species (ROS) in the retina. This oxidative stress causes the oxidation of proteins and unsaturated lipids, leading to peroxide formation and exacerbating retinal damage. While current clinical treatments primarily target reducing IOP through medication or surgery, there are currently no effective methods to mitigate the retinal cell damage associated with glaucoma. To address this gap, we developed a novel nanoemulsion to co-delivery latanoprost and α-tocopherol (referred to as LA@VNE later) that prolongs ocular retention and enhances retinal permeability through localized administration. By encapsulating latanoprost, an IOP-lowering drug, and α-tocopherol, a potent antioxidant, we effectively reduced ROS accumulation (>1.5-fold in vitro and 2.5-fold in vivo), retinal ganglion cell (RGC) apoptosis (>9 fold), and inflammatory cell infiltration (>1.6 fold). Our approach showed strong biocompatibility and significant potential for clinical translation, providing a promising platform for the treatment of glaucoma.

This prospective, observer-masked, randomized clinical trial was conducted between December 2018 and June 2021 at Eye Hospital, China Academy of Chinese Medical Sciences. A total of 45 glaucoma patients from Beijing, China, were enrolled in this clinical trial to compare the short-term efficacy of primary single-selective laser trabeculoplasty (SLT) to 0.005% latanoprost eye drops for the treatment of 24-h intraocular pressure (IOP) in patients with newly diagnosed primary open angle glaucoma (POAG) and ocular hypertension (OHT). Both SLT and latanoprost significantly decreased mean 24-h IOP and peak IOP, although the latanoprost group effect was more potent when compared to the SLT group (both Ps < 0.05). Compared with the SLT group, the latanoprost group had a significant and stable decrease in IOP after treatment. The latanoprost group had a more pronounced reduction in IOP at weeks 4 and 12 (P < 0.05) but had no difference at week 1 (P = 0.097). As a first-line treatment, both SLT and latanoprost eye drops are effective in newly diagnosed POAG and OHT patients. However, the latanoprost eye drops may be better in decreasing mean and peak 24-h IOP and thus controlling 24-h IOP fluctuation compared to SLT.

Recently, many new types of cosmetic illegal additives have been screened in the market. Most of the new additives were new drugs or analogues with very similar structures to other prohibited additives, which were difficult to be identified by liquid chromatography-mass spectrometry (LC-MS) only. Therefore, a new strategy is proposed, which is chromatographic separation combined with nuclear magnetic resonance spectroscopy (NMR) structural identification. The suspected samples were screened by ultra-high-performance liquid chromatography tandem high-resolution mass spectrometry (UPLC-Q-TOF-MS), followed by purification and extraction through silica-gel column chromatography and preparative high-performance liquid chromatography (HPLC). Finally, the extracts were identified unambiguously by NMR as bimatoprost and latanoprost, which were identified to be new cosmetic illegal additives in eyelash serums in China. Meanwhile, bimatoprost and latanoprost were quantified by high-performance liquid chromatography tandem triple quadrupole mass spectrum (HPLC-QQQ-MS/MS). The quantitative method demonstrated good linearity in the range of approximately 0.25-50 ng/mL (R2 > 0.9992), with limit of detection (LOD) and limit of quantification (LOQ) values of 0.01 and 0.03 mg/kg, respectively. The accuracy, precision, and reproducibility were confirmed to be acceptable.

UNASSIGNED: Prostaglandin analogs have been found to have more versatile uses: treatment of open-angle glaucoma, high intraocular pressure, vitiligo, and other treatments. And prostaglandin analogs have been found to have an important role in the hair growth cycle. However, prostaglandin analogs have not been sufficiently studied for hair (including hair, eyelashes, and eyebrows) regeneration. In this study, a systematic review and meta-analysis of topical prostaglandin analogs on hair loss was performed.
UNASSIGNED: The purpose of this meta-analysis is to determine the efficacy and safety of topical prostaglandin analogs for treating hair loss.
UNASSIGNED: We searched PubMed, Embase, and Cochrane Library databases comprehensively. Data were pooled using Review Manager 5.4.1, and subgroup analyses were performed if necessary.
UNASSIGNED: There were six randomized controlled trials included in this meta-analysis. All studies compared prostaglandin analogs with placebo, and one trial consisted of two sets of data. The results showed that prostaglandin analogs could significantly improve the hair length and density (p < 0.001). As far as adverse events are concerned, there was no significant difference between the experimental group and the control group.
UNASSIGNED: In patients with hair loss, the topical prostaglandin analogs have better therapeutic efficacy and safety than placebo. However, the best dose and frequency of experimental treatment require further studies.

Glaucoma is a chronic disease that requires lifelong treatment, whereas, discomfort caused by frequent medication may affect the quality of life. Moreover, the therapeutic efficacy of traditional local administration was unsatisfactory due to the rapid ocular clearance mechanism and the ocular barrier. Herein, a triple crosslinked micelle-hydrogel lacrimal implant with low polymer content was fabricated for localized and prolonged therapy of glaucoma. Latanoprost and timolol were simultaneously entrapped in the PEG-PLA micelles with high encapsulation efficiency and further loaded into the triple crosslinked hydrogel, facilitating a double sustained release of drugs. Subsequently, the implant was constructed by a unique molecular orientation fixation technology, which enables the implant to be fixed in the lacrimal duct. The triple crosslinked micelle-hydrogel lacrimal implant manifested a distinguished physicochemical characterization to sustain the release of latanoprost and timolol. In vitro release experiment demonstrated the duration of two drugs was extended for up to 28 days. The in vivo test of elevated intraocular pressure (IOP) in a rabbit model revealed that the IOP-lowering effects were sustained longer than 28 days as expected. The relative pharmacological availability (PA) of lacrimal implants was 5.7 times greater than that of the eye drops. The results of the studies on ocular irritation and histological examination demonstrated the good safety of the lacrimal implant. In conclusion, the triple crosslinked micelle-hydrogel lacrimal implant could effectively lower the IOP with splendid compatibility, demonstrating the promising prospect in the long-term noninvasive treatment of glaucoma.

Glaucoma is the leading cause of irreversible blindness, and its treatment is attracting widespread attention. Drug-loaded lacrimal suppositories can effectively treat xerophthalmia, but there is little research on the treatment of glaucoma with drug-loaded lacrimal suppositories. This article explored and expanded the non-pharmacological model of lacrimal suppository therapy for glaucoma by using a combination of lacrimal suppository and medication. The drug-loaded lacrimal suppository was rationally designed through the conjugation of gelatin with polyamide (PAM) via the formation of amide linkages, followed by Schiff base reaction grafting with latanoprost. In vitro drug release studies showed that latanoprost released from drug-loaded lacrimal embolus had sustained-release properties with a release time of 33 days and a drug release volume of 82.6%. The biological evaluation of drug-loaded lacrimal thrombus was carried out by IOP test, retinal potential test, and retinal H&E staining. The results showed that the IOP decreased to 27.125 ± 1.1254 mmHg, and the a and b waves of retinal potential increased to 4.39 ± 0.16 μV and 67.9 ± 2.17 μV, respectively. It indicated that latanoprost lacrimal suppository has a good therapeutic effect on glaucoma.

UNASSIGNED: As monotherapy is insufficient for some patients, the existing fixed-dose combination (FDC) requires two or more daily administrations with declining adherence. The present study compared the efficacy and safety of netarsudil/latanoprost FDC with monotherapy of its individual components in patients with glaucoma.
UNASSIGNED: A systematic literature search was performed for studies comparing netarsudil/latanoprost fixed-dose combination (FDC) vs. monotherapy in patients with glaucoma. The primary endpoints included intraocular pressure (IOP), intraocular pressure reduction percentage (IOPR%) and adverse events (AEs).
UNASSIGNED: Three randomized controlled trial studies (RCTs) involving 1,692 patients (FDC: 556, netarsudil: 577, latanoprost: 559) were included in this meta-analysis. FDC was more effective than netarsudil, with significantly lower diurnal IOP over three time points (8:00 a.m., 10:00 a.m., 4:00 p.m.), mean diurnal IOP (MD = -2.36 [-3.08, -1.63], P < 0.00001) and higher IOPR% (MD = 9.60 [7.86, 11.33], P < 0.00001). When comparing FDC with latanoprost, both mean diurnal IOP (MD = -1.64 [-2.05, -1.23], P < 0.00001) and diurnal IOP across 3 time points were significantly lower with FDC than with latanoprost, while FDC induced significantly higher IOPR% (MD = 6.09 [4.40, 7.77], P < 0.00001). Incidence of total AEs was similar between netarsudil and FDC, but higher with FDC than with latanoprost.
UNASSIGNED: Netarsudil/latanoprost FDC appears to be superior to netarsudil or latanoprost alone, with better ocular hypotensive effects. However, there are concerns that netarsudil/latanoprost FDC was associated with a significantly higher incidence of AEs specifically compared with latanoprost.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311956.

Glaucoma is a common eye disease and a major cause of blindness. We designed brinzolamide (Brla)- and latanoprost (Ltp)-loaded nano-lipoidal carriers (NLCs) for glaucoma treatment. Brla and Ltp-loaded NLCs were designed and characterized by assessing the zeta potential, polydispersity index, X-ray diffraction and scanning electron microscopy images, and particle size. Drug release was assessed by in vitro and ex vivo methods to determine transcorneal permeation, ocular irritation, and cell viability. Moreover, Brla- and Ltp-loaded NLCs were assessed in terms of the management of raised intraocular pressure (IOP). The size of Brla- and Ltp-loaded NLCs was <200 nm, the drug entrapment efficiency was 97.5%, and the zeta potential was 35.33 mv. The transcorneal permeation levels of Blra and Ltp after 8 h were 50.5% and 49.4%, respectively; after 24 h, they were 81.4% and 84.2%, respectively. However, NLCs are not cytotoxic. Moreover, Brla+Ltp-treated NLCs effectively reduced IOP in glaucoma patients. Therefore, Brla+Ltp-loaded NLCs showed promising effects against glaucoma.