Search Results (38)

Background/Objectives: The corneal epithelium plays a vital role in maintaining corneal transparency and ocular surface integrity. Chronic topical use of antiglaucoma medications may induce epithelial changes, especially with the concurrent use of multiple agents. This study aimed to evaluate the association between the number and class of antiglaucoma medications and central corneal epithelial thickness (CET), measured using a spectral-domain optical coherence tomography (SD-OCT) device. Methods: This cross-sectional study included 456 eyes from 242 adults (median age 72 years), grouped by the number of antiglaucoma agents used (0–4 medications). All pharmacologically treated participants had received the same regimen for ≥6 months. CET was measured using SD-OCT (SOLIX, Optovue). Generalized estimating equations (GEEs) accounted for inter-eye correlation. Two models were constructed: one evaluating specific medication effects and another assessing CET reduction per additional drug used. Age and sex were included as covariates. Results: CET progressively decreased with the number of medications, ranging from 53 µm in controls to 48 µm with quadruple therapy. Multivariable GEE analysis confirmed a cumulative thinning effect, with each additional medication associated with further CET reduction (β = −2.83 to −9.17 µm, p < 0.001). Latanoprost exerted the most pronounced single-drug effect (β = −3.01 µm, p < 0.001). Age was a modest negative predictor, while sex showed no significant effect. Conclusions: The cumulative number and specific class of antiglaucoma medications have a significant impact on corneal epithelial thickness. These results emphasize the need for vigilant ocular surface evaluation in patients on multi-drug regimens and propose CET as a surrogate marker for the burden of topical therapy. Full article

Background/Objectives: Latanoprost is a leading active pharmaceutical ingredient belonging to the synthetic prostaglandin F2α analogs, widely used as a first-line treatment for open-angle glaucoma and increased intraocular pressure. This study addresses the critical need for an accurate and precise chromatographic method that is capable of simultaneously quantifying latanoprost and six latanoprost-related substances in antiglaucoma eye drops. This will be crucial for patient safety and treatment efficacy. This method enables the separation of latanoprost isomers, (15S)-latanoprost, latanoprost enantiomer, and 5,6-trans latanoprost from latanoprost signal. Furthermore, it is specific for the well-known latanoprost degradants—the major latanoprost acid and the minor 15-ketolatanoprost—as well as synthetic derivatives, such as triphenylphosphine oxide (TPPO) and propan-2-yl 5-(diphenylphosphoryl)pentanoate (IDPP). Using forced degradation studies using high temperatures, UV light, alkalis, acids, and oxidizing agents, the degradation profiles of the drugs were characterized and the method’s stability-indicating power was confirmed. Methods: Separation was achieved on a stationary combined system comprising chiral and cyano columns. Reverse-phase gradient elution and UV 210 nm detection were employed. The novel method was validated according to the European Medicines Agency International Council for Harmonisation Q2 Validation of analytical procedures—Scientific guideline. Results: The method was shown to be linear in the range of 40–60 µg/mL for latanoprost and 0.05–2.77 µg/mL for related substances, confirmed by a correlation coefficient of r = 0.999. Recoveries for latanoprost were obtained within the range of 98.0–102.0% for assays and 90.0–110.0% for impurities. The detection and quantification limits for latanoprost were 0.025 µg/mL and 0.35 µg/mL, respectively. Conclusions: The analytical procedure developed is adequately sensitive, precise, and accurate compared to existing methods. The method can be reliably used to control the critical quality attributes of low-dose latanoprost products, ensuring their required high pharmaceutical quality, which translates into improvements in patient care. This advancement holds significant implications for enhancing the therapeutic management of glaucoma, ensuring drug safety and efficacy. Full article

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. Full article

Rho-associated kinase (ROCK) inhibitors have gained popularity as novel treatment options in the management of glaucoma and corneal endothelial disorders. Among the various ocular side effects, reticular corneal epithelial edema has been most frequently reported, mainly after treatment with netarsudil. To explain the potential mechanisms, we comparatively analyzed the effects of ripasudil and netarsudil on corneal endothelial and epithelial function in vitro. Primary human corneal endothelial and epithelial cells were incubated with netarsudil dihydrochloride and ripasudil hydrochloride dihydrate for up to 7 days. Gene and protein expression analyses were performed by real-time PCR and immunocytochemistry. Functional assays assessed the cell migration, proliferation, viability, Na⁺/K⁺-ATPase activity, transcellular electrical resistance, and FITC–dextran permeability. Reticular bullous corneal epithelial edema was observed in a patient following netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (Roclanda^®) for elevated intraocular pressure. In the subsequent laboratory analyses, both netarsudil and ripasudil were found to improve the corneal endothelial pump and barrier function, but they showed differential effects on corneal epithelial cells. Whereas ripasudil improved the epithelial barrier function by upregulating major components of the tight and adherens junctions and reducing paracellular permeability, netarsudil had no or even adverse effects on the epithelial barrier properties by downregulating the expression levels of cell-junction-associated genes. The expression changes normalized after discontinuation of ROCK inhibitors. The findings support the concept that ROCK inhibitors can act as a double-edged sword by having beneficial effects on corneal endothelial cells and adverse effects on epithelial cells. Full article

In open-angle glaucoma, the increase in intraocular pressure (IOP) is caused by an increased resistance to aqueous humour outflow in the trabecular meshwork. Since genetic variability of matrix metalloproteinase (MMP) genes may influence extracellular matrix remodelling, we investigated their association with glaucoma risk and/or response to treatment. The retrospective part of the study included patients with primary open-angle glaucoma and ocular hypertension (OHT); in the prospective part of the study, newly diagnosed patients with POAG or OHT were randomised to receive either latanoprost or selective laser trabeculoplasty (SLT) as the initial treatment. The reduction in IOP was measured 6 weeks after treatment. The following MMP single nucleotide polymorphisms were genotyped: MMP2 rs243865, rs243849, and rs7201; MMP3 rs3025058; MMP9 rs17576, rs17577, rs20544, and rs2250889; MMP14 rs1042704, rs1042704, and rs743257. Logistic regression was used to calculate odds ratios to assess the association between MMP polymorphism and risk of POAG or OHT, glaucoma phenotypes and response to treatment. Only carriers of the MMP3 rs3025058 TT genotype had a significantly higher risk of OHT, more advanced glaucoma, and a higher C/D ratio in the additive and dominant models. None of the investigated MMP polymorphisms were associated with response to treatment with latanoprost and SLT in our study population. Full article

Background/Objectives: This study aims to evaluate the computed tomography (CT) scans of glaucoma patients using prostaglandin analogs (PGA) in one eye, investigate findings associated with prostaglandin-associated periorbitopathy (PAP), and compare these findings with those of the contralateral eyes. Methods: Patients with open-angle glaucoma who had CT images of the orbital region taken for another reason at least one month after starting PGA treatment in one eye were included in the study. Enophthalmos measurements from thin-slice CT images, along with 3D volume measurements of orbital fat tissue, periorbital muscles, and the optic nerve, were performed. Ophthalmological examination findings and treatment information were collected. The values were compared with those of the contralateral eyes of the same patients not using PGA. Intraclass correlation coefficients (ICCs) were computed to evaluate measurement repeatability. Results: Forty patients were included in the study. Among them, 29 (72.5%) used latanoprost, 9 (22.5%) used bimatoprost, and 2 (5%) used travoprost. The mean enophthalmos values on the treated side (15.5 ± 2.0 mm) were lower than on the untreated side (16.1 ± 1.4 mm), but this difference was not statistically significant (p = 0.07). In 29 patients (72.5%), enophthalmos measurements were smaller on the treated side, with 7 patients (17.5%) showing a difference of 2 mm or more. No significant correlation was found between the duration of PGA use and enophthalmos measurements (p = 0.768 r = −0.048). Additionally, no significant differences were found in orbital fat volume, total extraocular muscle volume, and optic nerve volume (p > 0.05). ICC values demonstrated excellent reliability (ICC > 0.75) for all measurements. Conclusions: We did not find significant differences in enophthalmos measurements, orbital fat volume, total muscle volume, and optic nerve volume between the PGA-treated and untreated eyes. Full article

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. Full article

Increased intraocular pressure (IOP) is the most important risk factor for glaucoma. The role of IOP fluctuation, independently from elevated IOP, has not yet been confirmed in glaucoma. We investigated the effects of IOP fluctuation itself on retinal neurodegeneration. Male rats were treated with IOP-lowering eyedrops (brinzolamide and latanoprost) on Mondays and Thursdays (in the irregular instillation group) or daily (in the regular instillation group), and saline was administered daily in the normal control group for 8 weeks. The IOP standard deviation was higher in the irregular instillation group than the regular instillation group or the control group. The degree of oxidative stress, which was analyzed by labeling superoxide, oxidative DNA damage, and nitrotyrosine, was increased in the irregular instillation group. Macroglial activation, expressed by glial fibrillary acidic protein in the optic nerve head and retina, was observed with the irregular instillation of IOP-lowering eyedrops. Microglial activation, as indicated by Iba-1, and the expression of TNF-α did not show a significant difference between the irregular instillation and control groups. Expression of cleaved caspase-3 was upregulated and the number of retinal ganglion cells (RGCs) was decreased in the irregular instillation group. Our findings indicate that IOP fluctuations could be induced by irregular instillation of IOP-lowering eyedrops and this could lead to the degeneration of RGCs, probably through increased oxidative stress and macrogliosis. Full article

We tested five chemically and metabolically stable prostaglandin (PG) receptor agonists in a mouse model of dexamethasone-induced ocular hypertension (OHT). Whilst all compounds significantly (p < 0.05, ANOVA) lowered intraocular pressure (IOP) after twice-daily bilateral topical ocular dosing (5 µg/dose) over three weeks, the time course and magnitude of the responses varied. The onset of action of NS-304 (IP-PG receptor agonist) and rivenprost (EP4-PG receptor agonist) was slower than that of misoprostol (mixed EP2/EP3/EP4-PG receptor agonist), PF-04217329 (EP2-PG receptor agonist), and butaprost (EP2-PG receptor agonist). The rank order of IOP-lowering efficacies aligned with the onset of actions of these compounds. Peak IOP reductions relative to vehicle controls were as follows: misoprostol (74.52%) = PF-04217329 (74.32%) > butaprost (65.2%) > rivenprost (58.4%) > NS-304 (55.3%). A literature survey indicated that few previously evaluated compounds (e.g., latanoprost, timolol, pilocarpine, brimonidine, dorzolamide, cromakalim analog (CKLP1), losartan, tissue plasminogen activator, trans-resveratrol, sodium 4-phenyl acetic acid, etc.) in various animal models of steroid-induced OHT were able to match the effectiveness of misoprostol, PF-04217329 or butaprost. Since a common feature of the latter compounds is their relatively high affinity and potency at the EP2-PG receptor sub-type, which activates the production of intracellular cAMP in target cells, our studies suggest that drugs selective for the EP2-PG receptor may be suited to treat corticosteroid-induced OHT. Full article

(1) Background: Given the global prevalence of glaucoma and the crucial role of intraocular pressure (IOP) reduction in the management of the disease, understanding the immediate effects on retinal structure and function is essential. (2) Methods: This study aimed to assess the effects of preservative-free latanoprost on morphological and functional parameters in treatment-naïve patients with ocular hypertension and open-angle glaucoma. (3) Results: This study showed a significant reduction in IOP by an average of 30.6% after treatment with preservative-free latanoprost. Despite the significant reduction in IOP, no statistically significant changes were observed in the electroretinogram (ERG) nor the optical coherence tomography/angiography (OCT/OCTA) parameters compared to baseline. An exploration of the correlation between IOP changes and various parameters revealed a significant association solely with the macular IPL/INL plexus vessel density (VD) measured with OCTA. (4) Conclusions: This finding suggests a possible association between IOP reduction and changes in the macular microcirculation and provides valuable insights into the differential effects of latanoprost. Acknowledging the study limitations, this study emphasizes the need for larger, longer-term investigations to comprehensively assess the sustained effects of preservative-free latanoprost on both IOP and retinal parameters. In addition, exploring systemic factors and conducting subgroup analyses could improve personalized approaches to glaucoma treatment. Full article

(1) Background: The current study aimed to compare two of the most frequently prescribed preservative-free (PF) antiglaucoma drops, (Latanoprost PF vs. Bimatoprost PF) in promoting OSD in patients with POAG. (2) Methods: In this prospective study, 44 eyes from 44 participants were included. In the control group we enrolled 24 eyes, 11 eyes treated only with Latanoprost PF were enrolled in the Latanoprost PF group, and 9 eyes treated only with Bimatoprost PF in the Bimatoprost PF group. In all eyes, we evaluated the ocular levels of MMP-9 using the InflammaDry kit. We also performed Schirmer’s test and the TBUT test. (3) Results: We found elevated ocular levels of MMP-9 (>40 ng/mL) in the Bimatoprost PF group (88.89% of the participants) compared to the control (8.33%) and the Latanoprost PF group (27.27%), and the difference was statistically significant (p < 0.001). The Schirmer’s test values were statistically significantly lower in the Bimatoprost PF group compared to the other two groups. Additionally, the TBUT values were lower in the Bimatoprost PF group compared to the control group, and the difference was statistically significant. (4) Conclusions: Latanoprost PF eye drops treat the ocular surface better and they do not induce overexpression of MMP-9, a molecule that is related to OSD. Full article

Eyelashes, in addition to fulfilling eye-protective functions, generate an aesthetic impact. Latanoprost is a prostaglandin analog, commonly used for the treatment of glaucoma and intraocular hypertension. The side effect reported most often is the stimulation of eyelash growth. The aim of this study was to evaluate the efficacy and safety of latanoprost in inducing eyelash growth and darkening. Thirty healthy volunteers were recruited in a 3-month, randomized, double-blind, placebo-controlled pilot study. A transparent eyelash mascara was used as a vehicle. The placebo group (n = 15) received only the vehicle, and the latanoprost group (n = 15) received the vehicle + 0.005% latanoprost. The participants were asked to apply the latanoprost topically to the eyelashes while avoiding entry into the eye, daily at night. The latanoprost group showed a significant increase in eyelash length and color change, while the placebo group maintained eyelash length and color throughout the study. The intraocular pressures of all the participants were maintained in normal ranges (10–20 mmHg). Topical application of both the placebo and the latanoprost medications was well tolerated; none of the participants withdrew, generated side effects, or developed any ophthalmic pathology. In conclusion, latanoprost is effective and safe to stimulate the growth of eyelashes. Full article

Background: Androgenetic alopecia (AGA) and alopecia areata (AA) are the most common types of non-cicatricial alopecia. Both diseases have limited effective therapeutic options and affect patient quality of life. Pharmacogenetic tests can help predict the most appropriate treatment option by evaluating the single nucleotide polymorphisms (SNPs) corresponding to genes related to alopecia. The objective of the study was to evaluate and compare selected SNPs and genes in AA and AGA patients from Romania and Brazil. Materials and Methods: We performed a retrospective study regarding the associations between AA and AGA and 45 tag SNPs of 15 genes in 287 Romanian and 882 Brazilian patients. The DNA samples were collected from oral mucosa using a swab. The SNPs were determined by the qPCR technique. Each genetic test displays the subject’s genotype of the selected gene and the prediction of a successful treatment (e.g., genotype AA of the GR-alpha gene is related to a predisposition to normal sensibility to topical glucocorticoid, and, therefore, glucocorticoids should be effective). Results: The GR-alpha, GPR44-2, SULT1A1, and CRABP2 genes were statistically significantly different in Brazil compared to Romania. The SULT1A1 activity that predicts the response to minoxidil treatment showed in our analysis that minoxidil is recommended in half of the cases of AGA and AA. Patients with AGA and a high expression of SRD5A1 or PTGFR-2 may benefit from Dutasteride or Latanoprost treatment, respectively. Most of the studied genes showed no differences between the two populations. Conclusions: The DNA analysis of the patients with alopecia may contribute to a successful treatment. Full article

Latanoprost (LTP) is a prostaglandin F_2α 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 (M_n), WU, and WL. EB irradiation decreased the initial M_n, 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. Full article