Search Results (29)

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

Purpose: To investigate whether trabecular aspiration (TA) has an effective medium-term intraocular pressure (IOP)-lowering and medication-saving effect in patients with pseudoexfoliation glaucoma (PEG). In addition, a subgroup analysis of patients with or without a previous trabeculectomy was performed. Methods: Records of 290 consecutive eyes with PEG that underwent TA between 2006 and 2012 at the Department of Ophthalmology, Mainz, Germany, were retrospectively analyzed with a follow-up period of 3 years. The main outcomes were IOP and the need for further medical treatment. Results: Of the 290 eyes with PEG that received TA, 167 eyes from 127 patients met the inclusion criteria. Among these eyes, 128 received TA and cataract surgery (Phaco-TA) without having had a trabeculectomy (group I) before, 29 had Phaco-TA after a previous trabeculectomy (group II) and 10 underwent stand-alone TA after a previous trabeculectomy (group III). In the whole cohort, the median IOP decreased immediately after TA and remained significantly lower compared to the baseline throughout the period of 36 months. Likewise, the median number of antiglaucoma drugs was reduced over the whole period. At the same time, in group I, the median IOP and the number of antiglaucoma drugs were reduced over 36 months. In contrast, in the post-trabeculectomy groups (group II and III), the median IOP and the number of antiglaucoma drugs could not be reduced. While most of the patients that received Phaco-TA with or without a previous trabeculectomy (group I and II) did not require further surgical intervention during the follow-up period, almost all patients receiving stand-alone TA after a previous trabeculectomy (group III) needed surgical therapy, most of them between the second and the third year following TA. Conclusions: Phaco-TA has an effective medium-term pressure-lowering and medication-saving effect, especially in patients without a previous trabeculectomy. In trabeculectomized eyes, the effect of TA is limited but still large enough to delay more invasive surgical interventions in some patients. Full article

Background: This study analyzed the effects of topical anti-glaucoma medications on the surgical outcomes of endoscopic dacryocystorhinostomy (EDCR) in nasolacrimal duct obstruction (NLDO). Methods: This retrospective study included patients who underwent EDCR for NLDO between September 2012 and April 2021. Thirty patients with topical anti-glaucoma medications and 90 age- and sex-matched controls were included. Results: The success rate of EDCR was higher in the control group than in the anti-glaucoma group (97.8% vs. 86.7%, p = 0.034). Univariate and multivariate logistic regression analyses identified prostaglandin analogs as the most influential risk factor for EDCR success among anti-glaucoma medication ingredients (p = 0.005). The success rate of the group containing all four anti-glaucoma medication ingredients was statistically significant (p = 0.010). The success rate was significantly different in the group of patients who used anti-glaucoma medication for >24 months (p = 0.019). When multiplying the number of drug ingredients by the duration in months, the group > 69 showed a significantly decreased success rate (p = 0.022). Multivariate logistic regression analysis identified the number of anti-glaucoma medications as the most significant risk factor for EDCR success (odds ratio, 0.437; 95% confidence interval, 0.247 to 0.772; p = 0.004). Conclusions: The authors suggest that the anti-glaucoma medications might cause NLDO and increase the failure rate after EDCR. Therefore, when performing EDCR in patients using topical anti-glaucoma medications, surgeons should consider the possibility of increased recurrence after EDCR in clinical outcomes. Full article

Glaucoma is a leading cause of irreversible blindness and is characterized by increased intraocular pressure (IOP) and progressive optic nerve damage. The current therapeutic approaches for glaucoma management, such as eye drops and oral medications, face challenges including poor bioavailability, low patient compliance, and limited efficacy. In recent years, nanotechnology has emerged as a promising approach to overcome these limitations and revolutionize glaucoma treatment. In this narrative review, we present an overview of the novel nanotechnologies employed in the treatment of primary open-angle glaucoma. Various nanosystems, including liposomes, niosomes, nanoparticles, and other nanostructured carriers, have been developed to enhance the delivery and bioavailability of antiglaucoma drugs. They offer advantages such as a high drug loading capacity, sustained release, improved corneal permeability, and targeted drug delivery to the ocular tissues. The application of nanotechnologies in glaucoma treatment represents a transformative approach that addresses the limitations of conventional therapies. However, further research is needed to optimize the formulations, evaluate long-term safety, and implement these nanotechnologies into clinical practice. With continued advancements in nanotechnology, the future holds great potential for improving the management and outcomes of glaucoma, ultimately preserving vision and improving the lives of millions affected by this debilitating disease. Full article

Background: Different drugs have been approved to reduce the intraocular pressure. However, most of them contain preservatives to maintain sterility and these can be toxic to the ocular surface. The aim was to determine the patterns of use of antiglaucoma agents and ophthalmic preservatives in a group of patients from Colombia. Methods: A cross-sectional study that identified ophthalmic antiglaucoma agents from a population database of 9.2 million. Sociodemographic and pharmacological variables were considered. Descriptive and bivariate analyses were performed. Results: A total of 38,262 patients were identified, with a mean age of 69.2 ± 13.3 years, and 58.6% were women. A total of 98.8% were prescribed antiglaucoma drugs in multidose containers. The most widely used were prostaglandin analogs (59.9%), especially latanoprost (51.6%) and β-blockers (59.2%). A total of 54.7% of patients received combined management, especially with fixed-dose combination (FDC) drugs (41.3%). A total of 94.1% used antiglaucoma drugs with preservatives (benzalkonium chloride, 68.4%). Conclusions: The pharmacological treatment of glaucoma was very heterogeneous, but the most commonly used therapeutic groups were in accordance with the recommendations of clinical practice guidelines but with differences by sex and age. Most of the patients were exposed to preservatives, especially benzalkonium chloride, but the wide use of FDC drugs can minimize toxicity on the ocular surface. Full article

To date, the ophthalmic application of liquid crystalline nanostructures (LCNs) has not been thoroughly reconnoitered, yet they have been extensively used. LCNs are primarily made up of glyceryl monooleate (GMO) or phytantriol as a lipid, a stabilizing agent, and a penetration enhancer (PE). For optimization, the D-optimal design was exploited. A characterization using TEM and XRPD was conducted. Optimized LCNs were loaded with the anti-glaucoma drug Travoprost (TRAVO). Ex vivo permeation across the cornea, in vivo pharmacokinetics, and pharmacodynamic studies were performed along with ocular tolerability examinations. Optimized LCNs are constituted of GMO, Tween^® 80 as a stabilizer, and either oleic acid or Captex^® 8000 as PE at 25 mg each. TRAVO-LNCs, F-1-L and F-3-L, showed particle sizes of 216.20 ± 6.12 and 129.40 ± 11.73 nm, with EE% of 85.30 ± 4.29 and 82.54 ± 7.65%, respectively, revealing the highest drug permeation parameters. The bioavailability of both attained 106.1% and 322.82%, respectively, relative to the market product TRAVATAN^®. They exhibited respective intraocular pressure reductions lasting for 48 and 72 h, compared to 36 h for TRAVATAN^®. All LCNs exhibited no evidence of ocular injury in comparison to the control eye. The findings revealed the competence of TRAVO-tailored LCNs in glaucoma treatment and suggested the potential application of a novel platform in ocular delivery. Full article

The paper presents the results of a 24-month-long observation comparing the effectiveness and safety of two micro-invasive glaucoma surgery (MIGS) devices: Hydrus Microstent and iStent Trabecular Bypass in combination with cataract phacoemulsification in the treatment of open-angle glaucoma. We also analyzed the impact of preoperative factors on achieving surgical success in both surgical methods. The prospective, comparative, non-randomized study included 65 glaucoma surgeries. In 35 patients (53.8%), an iStent implant procedure was performed, while 30 patients (46.2%) underwent a Hydrus implant procedure. The demographic data was similar in both treatment groups. At 24 months after surgery, the mean IOP in the iStent group was 15.9 ± 3.0 mmHg and in the Hydrus group 16.2 ± 1.8 mmHg. The difference between the mean iStent vs Hydrus after two years of treatment was −0.3 (p = 0.683). At the 24 month follow-up, the average change in the number of antiglaucoma medications used was 71.7% in the iStent group and 79.6% in the Hydrus group. The difference in mean percentage change between groups was 7.9% in favor of Hydrus. Patients under the age of 70 may benefit from a greater risk reduction in the Hydrus group (HR = 0.81), while those over the age of 70 may benefit from a risk reduction in the iStent group (HR = 1.33). IOP cases with >18 mmHg before the surgery have a better chance of surgical success with the Hydrus method (HR = 0.28), and with IOP < 18 mmHg in the iStent group (HR = 1.93). Cases with more drugs (≥3 drugs) are more favorable in the Hydrus group (HR = 0.23), while those with a maximum of two drugs have a better prognosis in the iStent group (HR = 2.23). The most common postoperative complication was the presence of erythrocytes in the anterior chamber (AC), found in 40.0% of operated eyes in the Hydrus group. The profile of observed complications and significant improvement in visual acuity allows us to consider both implants as a safe way of treating patients with early or moderate glaucoma and co-existing cataracts. Full article

This real-world analysis was performed on administrative databases to evaluate characteristics, therapies, and related economic burden of glaucoma in Italy. Adults with at least 1 prescription for ophthalmic drops (ATC class S01E: antiglaucoma preparations, miotics) during data availability period (January 2010−June 2021) were screened, then patients with glaucoma were included. First date of ophthalmic drops prescription was the index date. Included patients had at least 12 months of data availability before index-date and afterwards. Overall, 18,161 glaucoma-treated patients were identified. The most frequent comorbidities were hypertension (60.2%), dyslipidemia (29.7%) and diabetes (17%). During available period, 70% (N = 12,754) had a second-line therapy and 57% (N = 10,394) a third-line therapy, predominantly ophthalmic drugs. As first-line, besides 96.3% patients with ophthalmic drops, a small proportion reported trabeculectomy (3.5%) or trabeculoplasty (0.4%). Adherence to ophthalmic drops was found in 58.3% patients and therapy persistence reached 78.1%. Mean total annual cost per patient was €1,725, mostly due to all-cause drug expenditure (€800), all-cause hospitalizations (€567) and outpatient services (€359). In conclusion, glaucoma-treated patients were mostly in monotherapy ophthalmic medications, with an unsatisfying adherence and persistence (<80%). Drug expenditures were the weightiest item among healthcare costs. These real-life data suggest that further efforts are needed to optimize glaucoma management. Full article

Glaucoma is a degenerative, chronic ocular disease that causes irreversible vision loss. The major symptom of glaucoma is high intraocular pressure, which happens when the flow of aqueous humor between the front and back of the eye is blocked. Glaucoma therapy is challenging because of the low bioavailability of drugs from conventional ocular drug delivery systems such as eye drops, ointments, and gels. The low bioavailability of antiglaucoma agents could be due to the precorneal and corneal barriers as well as the low biopharmaceutical attributes of the drugs. These limitations can be overcome by employing nanoparticulate drug delivery systems. Over the last decade, there has been a lot of interest in chitosan-based nanoparticulate systems to overcome the limitations (such as poor residence time, low corneal permeability, etc.) associated with conventional ocular pharmaceutical products. Therefore, the main aim of the present manuscript is to review the recent research work involving the chitosan-based nanoparticulate system to treat glaucoma. It discusses the significance of the chitosan-based nanoparticulate system, which provides mucoadhesion to improve the residence time of drugs and their ocular bioavailability. Furthermore, different types of chitosan-based nanoparticulate systems are also discussed, namely nanoparticles of chitosan core only, nanoparticles coated with chitosan, and hybrid nanoparticles of chitosan. The manuscript also provides a critical analysis of contemporary research related to the impact of this chitosan-based nanomedicine on the corneal permeability, ocular bioavailability, and therapeutic performance of loaded antiglaucoma agents. Full article

Glaucoma is a group of eye diseases consisting of optic nerve damage with corresponding loss of field vision and blindness. Hydrogen sulfide (H₂S) is a gaseous neurotransmitter implicated in various pathophysiological processes. It is involved in the pathological mechanism of glaucomatous neuropathy and exerts promising effects in the treatment of this disease. In this work, we designed and synthetized new molecular hybrids between antiglaucoma drugs and H₂S donors to combine the pharmacological effect of both moieties, providing a heightened therapy. Brinzolamide, betaxolol and brimonidine were linked to different H₂S donors. The H₂S-releasing properties of the new compounds were evaluated in a phosphate buffer solution by the amperometric approach, and evaluated in human primary corneal epithelial cells (HCEs) by spectrofluorometric measurements. Experimental data showed that compounds 1c, 1d and 3d were the hybrids with the best properties, characterized by a significant and long-lasting production of the gasotransmitter both in the aqueous solution (in the presence of L-cysteine) and in the intracellular environment. Because, to date, the donation of H₂S by antiglaucoma H₂S donor hybrids using non-immortalized corneal cells has never been reported, these results pave the way to further investigation of the potential efficacy of the newly synthesized compounds. Full article

(1) Aims of the study: calculating the underreporting ratio for two different medications, a fixed combination of 0.5% timolol + 0.2% brimonidine + 2.0% dorzolamide (antiglaucoma) and a fixed combination of sodium hyaluronate 0.1% + chondroitin sulfate 0.18% (artificial tears) for characterizing the features influencing the reporting of adverse drug reactions (ADRs) in spontaneous reporting. (2) Methods: The underreporting ratio was calculated by comparing the adverse drug reactions reported in the spontaneous reporting database for every 10,000 defined daily doses marketed and the adverse drug reactions from an active surveillance study for every 10,000 defined daily doses used for different drugs (antiglaucoma and artificial tears). The factors related to the report in spontaneous reporting through statistical tests were also determined. (3) Results: The underreporting ratio of spontaneous reporting was 0.006029% for antiglaucoma and 0.003552% for artificial tears. Additionally, statistically significant differences were found for severity, unexpected adverse drug reactions, and incidence of adverse drug reactions in females when compared with spontaneous reporting and active surveillance. (4) Conclusions: The underreporting ratio of ADRs related to ophthalmic medications indicates worry since the cornerstone of pharmacovigilance focuses on spontaneous reporting. Additionally, since underreporting seems to b selective, the role of certain aspects, such as gender, seriousness, severity, and unexpected ADRs, must be considered in future research. Full article

Pharmacological inhibition of the enzyme activity targeting carbonic anhydrases (CAs) demonstrated antiglaucoma and anticancer effects through pH control. Recently, we reported a series of indole-based benzenesulfonamides as potent CA inhibitors. The present study aimed to evaluate the antitumor effects of these compounds against various cancer cell lines, including breast cancer (MDA-MB-231, MCF-7, and SK-BR-3), lung cancer (A549), and pancreatic cancer (Panc1) cells. Overall, more potent cytotoxicity was observed on MCF-7 and SK-BR-3 cells than on lung or pancreatic cancer cells. Among the 15 compounds tested, A6 and A15 exhibited potent cytotoxic and antimigratory activities against MCF-7 and SK-BR-3 cells in the CoCl₂-induced hypoxic condition. While A6 and A15 markedly reduced the viability of control siRNA-treated cells, these compounds could not significantly reduce the viability of CA IX-knockdown cells, suggesting the role of CA IX in their anticancer activities. To assess whether these compounds exerted synergism with a conventional anticancer drug doxorubicin (DOX), the cytotoxic effects of A6 or A15 combined with DOX were analyzed using Chou−Talalay and Bliss independence methods. Our data revealed that both A6 and A15 significantly enhanced the anticancer activity of DOX. Among the tested pairs, the combination of DOX with A15 showed the strongest synergism on SK-BR-3 cells. Moreover, this combination further attenuated cell migration compared to the respective drug. Collectively, our results demonstrated that A6 and A15 suppressed tumor growth and cell migration of MCF-7 and SK-BR-3 cells through inhibition of CA IX, and the combination of these compounds with DOX exhibited synergistic cytotoxic effects on these breast cancer cells. Therefore, A6 and A15 may serve as potential anticancer agents alone or in combination with DOX against breast cancer. Full article

Microhook trabeculotomy (μLOT), recently developed by Tanito belongs to minimally invasive glaucoma surgery and contributes to intraocular pressure (IOP) control in eyes with glaucoma resistant to medical therapy. In this study, we aimed to investigate the effectiveness and safety of μLOT for uveitic glaucoma. The medical records of consecutive 36 eyes from 30 patients who underwent μLOT and were followed up over post-operative 1 year were reviewed. The surgical success (IOP = 5–20 mmHg and ΔIOP ≥ 20% with additional anti-glaucoma drugs) was achieved in 67% of eyes at post-operative 12 months. The median IOP significantly decreased from 30.5 mmHg pre-operatively to 15 mmHg at 12 months post-operatively (p = 0.001), and the median glaucoma drug score changed from 5 pre-operatively to 2.5 at 12 months post-operatively (p = 0.301). Intraocular inflammation scores at post-operative 6 weeks did not show a significant worsening as compared to pre-operatively, and 8 (22%) eyes exhibited exacerbation of inflammation during the 12-month follow-up period. Post-operative complications were confirmed in 58% of eyes, but most of them were mild and transient or successfully managed. With its favorable benefit–risk profile, μLOT would be an option worth considering as the first glaucoma surgery for uveitic glaucoma. Full article

A series of benzenesulfonamides incorporating pyrazole- and pyridazinecarboxamides decorated with several bulky moieties has been obtained by original procedures. The new derivatives were investigated for the inhibition of four physiologically crucial human carbonic anhydrase (hCA, EC 4.2.2.1.1) isoforms, hCA I and II (cytosolic enzymes) as well as hCA IX and XII (transmembrane, tumor-associated isoforms). Examples of isoform-selective inhibitors were obtained for all four enzymes investigated here, and a computational approach was employed for explaining the observed selectivity, which may be useful in drug design approaches for obtaining inhibitors with pharmacological applications useful as antiglaucoma, diuretic, antitumor or anti-cerebral ischemia drugs. Full article