How latanoprost changed glaucoma management.

Glaucoma is currently considered one of the leading causes of severe visual impairment and blindness worldwide. Topical medical therapy represents the treatment of choice for many glaucoma patients. Introduction of latanoprost, 25 years ago, with an entirely new mechanism of action from that of the antiglaucoma drugs used up to that time was a very important milestone. Since then, due mainly to their efficacy, limited systemic side effects and once daily dosing, prostaglandin analogues (PGAs) have become as the first-choice treatment for primary open-angle glaucoma. PGAs are in general terms well tolerated, although they are associated with several mild to moderate ocular and periocular adverse events. Among them, conjunctival hyperemia, eyelash changes, eyelid pigmentation, iris pigmentation and hypertrichosis around the eyes are the most prevalent. The objective of this paper is to review the role of PGAs in the treatment of glaucoma over the 25 years since the launch of Latanoprost and their impact on clinical practice outcomes.

Comparing the effect of benzalkonium chloride-preserved, polyquad-preserved, and preservative-free prostaglandin analogue eye drops on cultured human conjunctival goblet cells.

PURPOSE: To investigate the effect of benzalkonium chloride (BAK)-preserved latanoprost and bimatoprost, polyquad (PQ)-preserved travoprost, and preservative-free (PF) latanoprost and tafluprost, all prostaglandin analogues (PGAs), on human conjunctival goblet cell (GC) survival. Furthermore, to investigate the effect of BAK-preserved and PF latanoprost on the cytokine secretion from GC. METHODS: Primary human conjunctival GCs were cultivated from donor tissue. Lactate dehydrogenase (LDH) and tetrazolium dye colorimetric (MTT) assays were used for the assessment of GC survival. A cytometric bead array was employed for measuring secretion of interleukin (IL)-6 and IL-8 from GC. RESULTS: BAK-preserved latanoprost and bimatoprost reduced cell survival by 28% (p = 0.0133) and 20% (p = 0.0208), respectively, in the LDH assay compared to a negative control. BAK-preserved latanoprost reduced cell proliferation by 54% (p = 0.003), BAK-preserved bimatoprost by 45% (p = 0.006), PQ-preserved travoprost by 16% (p = 0.0041), and PF latanoprost by 19% (p = 0.0001), in the MTT assay compared to a negative control. Only PF tafluprost did not affect the GCs in either assay. BAK-preserved latanoprost caused an increase in the secretion of pro-inflammatory IL-6 and IL-8 (p = 0.0001 and p = 0.0019, respectively) compared to a negative control, which PF latanoprost did not. CONCLUSION: BAK-preserved PGA eye drops were more cytotoxic to GCs than PQ-preserved and PF PGA eye drops. BAK-preserved latanoprost induced an inflammatory response in GC. Treatment with PF and PQ-preserved PGA eye drops could mean better tolerability and adherence in glaucoma patients compared to treatment with BAK-preserved PGA eye drops.

The use of benzalkonium chloride in topical glaucoma treatment: An investigation of the efficacy and safety of benzalkonium chloride-preserved intraocular pressure-lowering eye drops and their effect on conjunctival goblet cells.

ENGLISH SUMMARY: Glaucoma is a leading cause of the global prevalence of irreversible blindness. The pathogenesis of glaucoma is not entirely known, but the major risk factors include advancing age, genetic predisposition, and increased intraocular pressure (IOP). The only evidence-based treatment is a lowering of IOP through the use of eye drops, laser procedures, or surgical interventions. Although laser treatment is gaining recognition as a first-choice treatment option, the most common approach for managing glaucoma is IOP-lowering eye drops. A major challenge in the treatment is the occurrence of adverse events and poor adherence. In this context, the ocular surface is an area of great concern, as most glaucoma patients have dry eye disease (DED), which is largely caused by eye drops. Preservation with benzalkonium chloride (BAK) is a controversial topic due to its potential role as a significant cause of DED. A systematic review and meta-analyses investigate potential differences in efficacy and safety between BAK-preserved and BAK-free anti-glaucomatous eye drops (I). Many of the included studies report on ocular surface damage caused by the application of BAK-preserved eye drops. However, the meta-analyses addressing hyperemia, number of ocular adverse events, and tear break-up time did not identify any significant differences. The latter is likely due to varying measurement methods, different endpoints, and study durations. It is, therefore, possible that the large variations between the studies conceal differences in the safety profiles. The efficacy meta-analysis finds that there are no differences in the IOP-lowering effect between BAK-preserved and BAK-free eye drops, indicating that BAK is not necessary for the effectiveness of eye drops. To promote more homogeneous choices of endpoints and methods when evaluating BAK-preserved and BAK-free glaucoma treatments, a Delphi consensus statement was performed. In this study, glaucoma experts and ocular surface disease experts reached consensus on the key factors to consider when designing such studies (II). The hope is to have more studies with comparable endpoints that can systematically show the potentially adverse effects of BAK. The preclinical studies in the current Ph.D. research focus on conjunctival goblet cells (GCs). GCs are important for the ocular surface because they release the mucin MUC5AC, which is an essential component of the inner layer of the tear film. BAK preservation may damage the GCs and result in a low GC density, leading to an unstable tear film and DED. The most commonly used IOP-lowering drugs are prostaglandin analogs (PGAs). Thus, the conducted studies investigate the effect of PGAs preserved in different ways on GCs. BAK-preserved latanoprost is cytotoxic to primary cultured human conjunctival GCs and results in a scattered expression of MUC5AC, in contrast to negative controls, where MUC5AC is localized around the cell nucleus (III). Preservative-free (PF) latanoprost is not cytotoxic and does not affect the MUC5AC expression pattern. Furthermore, BAK-preserved travoprost is found to be cytotoxic in a time-dependent manner, while Polyquad®-preserved travoprost does not affect GC survival at any measured time point (IV). Both Polyquad and BAK induce scattered expression of MUC5AC. The cytotoxicity of BAK-preserved PGA eye drops is higher compared to the safer profile of PF and Polyquad-preserved PGA eye drops (V). Additionally, PF latanoprost does not increase the release of the inflammatory markers interleukin (IL)-6 and IL-8, unlike BAK-preserved latanoprost. A review highlights the active and inactive components of IOP-lowering eye drops (VI). Several preclinical and clinical studies have identified adverse effects of BAK. Although other components, such as the active drug and phosphates, can also cause adverse events, the review clearly states that BAK alone is a major source of decreased tolerability. The conclusion of this thesis is that BAK preservation is unnecessary and harmful to the ocular surface. The preclinical studies demonstrate that GCs die when exposed to BAK. Furthermore, they find that BAK induces a pro-inflammatory response. The review included in the thesis concludes that BAK should be phased out of eye drops for chronic use. Overall, the inclusion of BAK poses a risk of developing DED and poor adherence, which can ultimately lead to disease progression and blindness.

Effect of retrobulbar prostaglandin analog injection on orbital fat in rats.

PURPOSE: Periorbital fat atrophy is a known side effect of topical prostaglandin analogs (PA). This side effect may have implications in the treatment of diseases like thyroid orbitopathy. In this in vivo study we aimed to evaluate the effects of retrobulbar injection of three different PAs on orbital fat. METHODS: Eighteen adult male Wistar-albino rats were divided into three groups of six animals. 0.1 ml of 0.03% bimatoprost, 0.005% latanoprost, or 0.005% travoprost was injected into the right orbits and saline was injected into the left orbits, as controls. Both orbits were exenterated after 3 weeks. Histological cross-sections were analyzed using ImageJ image analysis software. Intraconal adipocyte density was calculated. RESULTS: There was no significant difference in the adipocyte density between the PA injected orbits and the control side in each of the three groups. When calculations from all three groups were analyzed together, again the difference in the adipocyte density between the PA injected orbits and the control side was not significant. CONCLUSION: No significant fat atrophy was noted in this rat model three weeks after retrobulbar injection of PAs. To evaluate retrobulbar injection of PA as a potential therapy for orbital diseases with fat proliferation, in vivo studies in different animal models, higher concentrations of PA, or longer follow-up duration are required.

Comparison of In Vitro Corneal Permeation and In Vivo Ocular Bioavailability in Rabbits of Three Marketed Latanoprost Formulations.

BACKGROUND AND OBJECTIVE: All latanoprost formulations currently available for the treatment of glaucoma or ocular hypertension contain the same concentration of latanoprost (0.005%) but differ in excipients, which may affect corneal drug permeability or stability. This study aimed at comparing corneal penetration of three marketed latanoprost solutions with different excipient formulations in in vitro and in vivo drug permeability studies. METHODS: Three latanoprost formulations were tested under good laboratory practice conditions: a formulation containing benzalkonium chloride (BAK) but no surfactant (Preserved latanoprost); the same formulation except preservative-free (PF) without BAK or surfactant (SF) (PF SF latanoprost); and a different formulation without BAK but containing a non-ionic surfactant (MGHS 40 at 5%) combined with thickening agents (Carbomer 974P, Macrogol 4000) (PF latanoprost). Corneal permeation of latanoprost acid (LAT) was first determined in vitro using a reconstructed human corneal epithelium tissue. Then, in vivo pharmacokinetic studies were performed on pigmented rabbits, for which LAT concentration was measured in the aqueous humour (AH) and iris-ciliary body (ICB). RESULTS: In vitro, the cumulative transport of LAT was linear between 1 h and 4 h for preserved latanoprost and PF SF latanoprost, and LAT concentrations matched exactly at each timepoint. By contrast, the permeation of PF latanoprost was linear between 2 h and 12 h and was significantly lower than that of preserved latanoprost and PF SF latanoprost at 4 and 8 h (p < 0.001). In rabbits, the concentrations of LAT in AH and ICB were not statistically different between preserved latanoprost and PF SF latanoprost at each timepoint, except at 1 h in ICB (p = 0.005). By comparison, the LAT concentration of PF latanoprost was statistically (p < 0.05) lower than that of preserved latanoprost and PF SF latanoprost in AH and ICB from 0.5 to 3 h. CONCLUSION: BAK did not influence the corneal penetration of latanoprost in in vitro and in vivo studies. The formulation containing a non-ionic surfactant resulted in lower and slower ocular penetration compared with preserved or PF SF formulations. This raises questions about the relevance of BAK and some surfactants in enhancing corneal penetration of ocular formulations.

Persistence of the carteolol hydrochloride/latanoprost fixed-combination ophthalmic solution, compared with the other ß-blocker/prostanoid FP receptor agonist fixed-combination ophthalmic solutions.

PURPOSE: To investigate the treatment persistence of carteolol hydrochloride/latanoprost fixed-combination ophthalmic solution (CAR/LAT) and other ß-blocker/prostanoid FP receptor agonist fixed-combination ophthalmic solutions (BB/FP) in the treatment of glaucoma. STUDY DESIGN: Retrospective observational cohort study. METHODS: A retrospective observational cohort study using JMDC Claims Database. Patients aged 20 years or older diagnosed with glaucoma between February 1, 2017, and March 31, 2020, and prescribed CAR/LAT or another BB/FP were included. RESULTS: A total of 16,612 patients (7423 in the CAR/LAT group and 9189 in the other BB/FP group) were included. The cumulative treatment persistence rate at the end of follow-up was 42.0% (64.9% at 1 year, 53.4% at 2 years, 45.0% at 3 years, and 42.0% at 4 years) in the CAR/LAT group and 34.7% (54.8% at 1 year, 43.6% at 2 years, 37.1% at 3 years, and 34.7% at 4 years) in the other BB/FP group. Treatment persistence was significantly longer in the CAR/LAT group compared to that in the other BB/FP group (hazard ratio 0.747, p < 0.0001). Over the treatment period, the number of patients who discontinued treatment was 3281 (44.2%) in the CAR/LAT group and 4926 (53.6%) in the other BB/FP group; the median duration of treatment was 135 days and 97 days, respectively. CONCLUSION: The study results suggest that persistence rates vary depending on the BB/FP and CAR/LAT appears to be more persistent than other BB/FP.

Antioxidant nanoemulsion loaded with latanoprost enables highly effective glaucoma treatment.

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.

Pharmacokinetic and Ocular Toxicity Evaluation of Latanoprost Ophthalmic Solution, 0.005%, with Preservative Level Reduced to Below the Limit of Quantitation.

Purpose: The systemic and ocular pharmacokinetics (PK), and ocular toxicity of benzalkonium chloride (BAK)-free TearClear latanoprost ophthalmic solution, 0.005% formulation (TC-002) were evaluated. TC-002 is designed to selectively capture BAK at the time of drug administration; therefore, the dose delivered to the eye contains no quantifiable level of preservative. Methods: The systemic and ocular PK of TC-002 were compared to a BAK containing reference listed drug (RLD, Xalatan™) over a 24-h period, after a single topical ocular dose to 1 eye of male Dutch Belted (DB) rabbits (n = 3/timepoint). Latanoprost acid concentrations were measured in plasma and ocular tissues. The ocular toxicity was evaluated in a separate study and included toxicokinetic evaluation of TC-002 after once daily topical ocular dosing into each eye of DB rabbits (n = 8/group) for at least 28 days. Toxicity endpoints included ophthalmic and clinical evaluations, necropsy, and microscopic evaluation of ocular tissues. Results: Average ratios of Cmax values for TC-002/RLD ranged from 0.6 to 1.6, and Cmax and area under the concentration-time curve of last observed concentration (AUClast) exposures to latanoprost acid were similar (<2-fold) between the 2 treatments. In the 28-day study, the Tmax was achieved in both groups in <0.5 h. There were no abnormal ocular findings. Conclusions: TC-002 with no quantifiable preservative or BAK-containing RLD exhibited similar ocular and systemic PK profiles. TC-002 was well tolerated and comparable to RLD. TC-002 retains the safety and PK characteristics of RLD without the added concern of long-term exposure of the eye to preservatives.

Prostaglandin analogs in ophthalmology.

Glaucoma is a major cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) is currently the only approach to prevent further optic nerve head damage. Pharmacotherapy is the mainstay of treatment for glaucoma patients. In recent years, a significant milestone in glaucoma treatment has been a transition to prostaglandin analogs (PGAs) as the first line of drugs. The rapid shift from traditional ß-blockers to PGAs is primarily due to their excellent efficacy, convenient once-a-day usage, better diurnal control of IOP, and systemic safety profiles. This review article aims to provide information regarding the various PGAs in practice and also the newer promising drugs.

Effects of topical prostaglandin therapy on corneal layers thickness in primary open-angle glaucoma patients using anterior segment optical coherence tomography.

PURPOSE: To evaluate the effects of latanoprost, bimatoprost, and travoprost eye drops and their preservatives on each corneal layer thickness in patients with primary open-angle glaucoma (POAG). METHODS: We retrospectively analyzed 79 eyes of 79 patients with POAG who were receiving prostaglandin therapy. Patients were divided into three subgroups according to monotherapy with latanoprost, bimatoprost, and travoprost during a mean of 43.14 ± 19.12 months follow-up period. In addition, the central corneal epithelial thickness (CET), central corneal stromal thickness (CST), and total central corneal thickness (CCT) were measured by anterior segment optical coherence tomography (AS-OCT) at baseline and every six months after treatment initiation at each visit between 9 and 12 o'clock in the morning. Furthermore, intraocular pressure (IOP) was measured with Goldmann applanation tonometry (GAT) after AS-OCT measurements at each visit. RESULTS: All three groups were not significantly different in age, gender, follow-up period, and mean intraocular pressure values (p > 0.05 for all). The reduction of CCT in the latanoprost, bimatoprost, and travoprost groups was 6.53 ± 3.17, 18.59 ± 8.42, and 10.1 ± 1.13 µm, respectively. The decrease in CST values was 4.65 ± 1.54, 15.84 ± 7.47, 9.69 ± 1.45 µm, and CET values were 1.88 ± 1.66, 2.75 ± 0.73, 0.41 ± 0.54 µm in all groups, respectively. A statistically significant thinning was observed in all corneal layers (p < 0.05) except the CST values in the latanoprost group and CET values in the travoprost group. However, no significant difference was found in the average reduction of CET, CST, and CCT values among the three groups (p > 0.05). CONCLUSION: Topical treatment with latanoprost, bimatoprost, and travoprost affects each layer of the cornea separately according to the active and protective substances contained in these eye drops. On the other hand, the thinning effect on the corneal layers was similar in these three drugs because there was no significant difference between the three groups in the total amount of thinning of the corneal layers during the follow-up period.

Use of a Cationic Emulsion of Latanoprost to Treat Glaucoma Patients with Ocular Surface Disease: A Preclinical Review.

Prostaglandin analogue topical medications are one of the most effective therapeutic approaches for the chronic management of glaucoma and ocular hypertension, through the reduction of elevated intra ocular pressure (IOP). While many of the first generations of anti-glaucoma eye drops were preserved with benzalkonium chloride, their repeated use may induce chronic ocular surface toxicity that leads to ocular surface disease (OSD) signs and symptoms. As a result, soft-preservatives and preservative-free formulations have been developed with the goal to avoid the long-term iatrogenic toxicity of the preservative agents. In addition, it has been suggested that OSD and its associated inflammation may negatively impact the efficacy of the IOP-lowering medications, including treatment adherence and compliance. Hence, it may be particularly interesting that glaucoma medications can concomitantly protect and "heal" the ocular surface and its environment while lowering elevated IOP, for the greater benefit of glaucoma patients. The objective of the present review is to briefly present the preclinical data of the cationic oil-in-water emulsion of latanoprost (latanoprost-CE) to shed some light on its mechanisms of action. It overall supports the following hypothesis: the restoration of a healthy ocular surface environment and treatment of the OSD signs and symptoms will allow for an improved elevated IOP reduction and glaucoma management. This would be achieved with a once daily dosing regimen to preserve glaucoma patients' vision, ocular surface, and quality-of-life and wellness.

A triple crosslinked micelle-hydrogel lacrimal implant for localized and prolonged therapy of glaucoma.

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.

Preparation and performance of latanoprost-loaded hydrogels as a lacrimal suppository for the 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.

Trends in development and quality assessment of pharmaceutical formulations - F2α analogues in the glaucoma treatment.

The ocular delivery route presents a number of challenges in terms of drug administration and bioavailability. The low bioavailability following topical ophthalmic administration shows that there is a clear need for in-depth research aimed at finding both more efficacious molecules and formulations precisely targeted at the site of action. Continuous technological development will eventually result in improved bioavailability, lower dosages, reduced toxicity, fewer adverse effects, and thus better patient compliance and treatment efficacy. Technological development, as well as increasingly stringent quality requirements, help stimulate analytical progress. This is also clearly evident in the case of medicinal products used in the treatment of glaucoma, which are the subject of this review. Impurity profiling of PGF2α analogues, either in the pure substance or in the finished formulation, is a crucial step in assessing their quality. The development of specific, accurate and precise stability-indicating analytical methods for determining the content and related substances seems to be an important issue in relation to this tasks. A total of 27 official and in-house analytical methods are presented that are used for the analysis of latanoprost, travoprost and bimatoprost. The conditions for chromatographic separation with UV or MS/MS detection and the available results obtained during method validation are described. In addition, several aspects are discussed, with particular emphasis on the instability of the analogues in aqueous solution and the phenomenon of isomerism, which affects a potentially large number of degradation products.

Prostaglandin-Associated Periorbitopathy Symptom Alleviation After Switching Prostaglandin F Receptor Agonist to EP2 Receptor Agonist in Patients with Glaucoma.

Purpose: Prostaglandin-associated periorbitopathy in patients with glaucoma is reportedly not caused by EP2 agonist, but it has been a cosmetic problem with prostaglandin F receptor (FP) agonists. In this study, patients with prostaglandin-associated periorbitopathy on FP agonists were switched to EP2 agonist and changes were investigated. Methods: Patients complaining of prostaglandin-associated periorbitopathy were included. The FP agonist was switched to EP2 agonist (omidenepag isopropyl), and patients were followed up for 7 months. Frontal photographs were taken at every visit, and objective changes in deepening of the upper eyelid sulcus were assessed by three observers. Subjective questionnaires (self-awareness of deepening of the upper eyelid sulcus, eyelid/peri-eyelid skin pigmentation, eyelash elongation, and conjunctival hyperemia) were acquired at the start and the endpoint. Factors associated with the change of prostaglandin-associated periorbitopathy were investigated using logistic regression analysis. Results: Included were 23 eyes of 23 patients (17 women; 60.6 years). At 7 months, objective deepening of the upper eyelid sulcus improved by 76%. The subjective questionnaires showed that deepening of the upper eyelid sulcus improved in 95%, eyelid/peri-eyelid skin pigmentation in 76%. The less extent of myopia was a significant factor in the eyes with improved eyelid/peri-eyelid skin pigmentation. After switching, no change in intraocular pressure or visual acuity was observed (P ≥ 0.22). Conclusion: Switching to omidenepag isopropyl increased patient satisfaction and might be the first step to lightening deepening of the upper eyelid sulcus and eyelid/peri-eyelid skin pigmentation. It was suggested that pigmentation may be more easily improved in nonmyopic eyes.

The effectiveness and tolerability of fixed-dose combination netarsudil 0.02%/latanoprost 0.005% at a tertiary glaucoma center.

PURPOSE: To assess real-world effectiveness and tolerability of fixed-dose combination netarsudil 0.02%/latanoprost 0.005% (FCNL) in management of glaucoma patients in a tertiary eye care center. METHODS: This retrospective cohort study included glaucoma patients initiated on FCNL from January 2018 to July 2021 with at least 1-month follow-up. Demographic and clinical data were collected at baseline and at follow-up visits through 12 months. Patient-solicited side effects were recorded at each visit. Maximum glaucoma pharmacotherapy was defined as surgery/laser being the next treatment option following an intensive pharmacotherapy regimen, or when pharmacotherapy could not be increased due to allergy/intolerance or all pharmacologic mechanisms already being in use. RESULTS: Seventy-nine eyes of 47 patients were included. Mean age was 67.7 ± 14.7 years. Baseline IOP was 18.7 ± 4.9 mmHg; mean change in IOP (∆IOP) each study visit compared to baseline ranged from - 1.6 ± 3.5 to - 4.4 ± 4.1 mmHg (all p < 0.05). The eyes on maximum glaucoma pharmacotherapy (73.4%) had similar ∆IOP compared to those on non-maximal therapy at each visit (p > 0.2 for all). Forty-three (54.4%) eyes were switched from a prostaglandin analog alone, producing a 1-month IOP reduction of - 4.7 ± 3.9 mmHg at 1 month which remained significant at each visit for the 12-month study period (all p < 0.05). Across all study visits, conjunctival hyperemia was documented in 26 (32.9%) eyes. Subjective blurry vision was reported in 22 (27.8%) eyes without significant worsening of visual acuity at any visit (all p > 0.05). Six (7.6%) and 7 (8.9%) eyes required further medical or surgical/laser intervention, respectively. Kaplan-Meier analysis revealed no significant difference in the need for subsequent medical or surgical intervention between those on maximum and non-maximal pharmacotherapy (p > 0.4). CONCLUSION: FCNL was well-tolerated and demonstrated a significant and sustained reduction in IOP, even as last-line therapy before incisional or laser surgery in those on maximum glaucoma pharmacotherapy. FCNL is a viable treatment option for glaucomatous eyes before consideration of surgical intervention.

A latanoprost cationic emulsion (STN1013001) vs. other latanoprost formulations (Latanoprost) in open angle glaucoma/ocular hypertension and ocular surface disease: an Italian cost-utility analysis.

BACKGROUND: STN1013001 is an innovative latanoprost cationic emulsion for open-angle glaucoma/ocular hypertension (OAG/OHT) and ocular surface disease (OSD). METHODS AND FINDINGS: A 5-year, 7 health states, 1-year cycle early Markov model-supported cost-utility analysis (CUA) of STN1013001 vs. other latanoprost formulations (Latanoprost) followed the Italian National Health Service (INHS) perspective.One-way, probabilistic and scenario sensitivity analyses tested the uncertainty of the baseline results. Value of information analysis (VOIA) investigated the potential cost-effectiveness of collecting further evidence. RESULTS: Over 5 years, the Markov model-supported CUA predicts STN1013001 to be potentially highly cost-effective vs. Latanoprost (+€57.60 cost at €2020 values; +0.089 Quality-Adjusted Life Years).The Incremental Cost-Utility Ratio (€647.65) falls well below the lower limit of the acceptability range proposed for Italy (€25,000-€40,000).Sensitivity analyses confirmed the robustness of the baseline findings. VOIA highlighted that further information might only be cost-effective for OAG/OHT utilities and OSD-related disutility. CONCLUSION: STN1013001 is potentially highly cost-effective and strongly dominant vs. Latanoprost for OAG/OHT+OSD patients from the INHS perspective. These findings should be re-assessed using the data from the ongoing Phase III trial (NCT04133311) comparing the efficacy and safety of STN1013001 vs. Latanoprost and with future real-world CUAs upon the availability of STN1013001 on the Italian market.

[Xalacom: possibilities and advantages of the drug in the treatment of patients with glaucoma]. / Ksalakom: vozmozhnosti i preimushchestva preparata v terapii glaukomy.

The strategy of glaucoma therapy is aimed at preserving visual functions and ensuring an acceptable quality of life for patients. To achieve this strategic goal, clinicians in their practice use drugs that affect the main factor in the progression of the disease - intraocular pressure (IOP), aiming to reduce it to an individual target level. It is not always possible to achieve optimal IOP values with monotherapy. Many patients require a combination of drugs from different pharmacological groups. Xalacom is a fixed drug with good tolerability and t hypotensive effect. This review focuses on the benefits of this drug for the treatment of glaucoma.

[Neuroprotective properties of latanoprost]. / Neiroprotektornye svoistva latanoprosta.

Glaucoma is the main cause of irreversible blindness in the world. Latanoprost - an ester prodrug of prostaglandin F2α (PGF2α) - was the first prostaglandin analogue used to treat glaucoma. The review shows that latanoprost possesses direct neuroprotective properties such as blocking the entry of calcium ions into neurons and inhibiting the action of caspase-3, inhibiting the activity of cyclooxygenase and activation of polypeptide 2B1 (OATP2B1) and Klotho protein. It is emphasized that when the drug is instilled into the eye, the concentration of the drug inside the vitreous body is twice as high as what is required to ensure the survival of retinal ganglion cells.