Preservative-free Latanoprost Research Articles

Efficacy and Safety of a Preservative-Free Latanoprost Cationic Emulsion in Patients with Open-Angle Glaucoma and Concurrent Ocular Surface Disease: A Randomized Phase 2 Study.

Purpose: To compare intraocular pressure (IOP), ocular surface disease (OSD) parameters, and safety in patients with open-angle glaucoma (OAG)/ocular hypertension (OH) and concurrent OSD treated with preservative-free latanoprost 0.005% cationic emulsion (PF-latanoprost-E) or travoprost-Z 0.004% ophthalmical solution containing a soft preservative system. Methods: Patients with OAG/OH and OSD were randomized to treatment with PF-latanoprost-E or travoprost-Z nightly for 3 months. Outcomes included mean diurnal IOP reduction; OSD endpoints, including symptom improvement, tear break-up time (TBUT), and corneal fluorescein staining (CFS) score; and safety after 1 and 3 months. Results: A total of 105 patients were randomized, 51 to PF-latanoprost-E and 54 to travoprost-Z. IOP reductions (LS mean differences) at 3 months were numerically greater in the PF-latanoprost-E than in the travoprost-Z group at 8AM (7.2 versus 6.0 mmHg), 10AM (6.7 versus 5.9 mmHg), and 4PM (6.0 versus 5.4 mmHg). LS mean changes in IOP from baseline in both groups at 1 and 3 months, however, were comparable. Mean ± SD CFS scores on the Ora scale at month 3 showed significantly greater reductions in the PF-latanoprost-E than in the travoprost-Z group (-1.07 ± 1.863 versus -0.16 ± 2.553 P = 0.0461). The mean TBUT at month 3 showed similar improvements in both groups (1.1 versus 1.0 s, P > 0.05). OSD symptoms improved but did not differ significantly in the two groups. Overall safety was comparable in both groups. Conclusion: PF-latanoprost-E effectively and safely lowered IOP and improved OSD parameters in patients with OAG/OH. These findings provide evidence for the beneficial effects of this new formulation of latanoprost in glaucoma patients with OSD.

A phase III, multicentre, randomised, investigator-masked, cross-over, comparative, non-inferiority trial evaluating the efficacy and tolerability of generic preservative-free Latanoprost (Polpharma S.A.) compared to Xalatan® (Pfizer) in patients with ocular hypertension or primary open-angle glaucoma

BackgroundPrimary open-angle glaucoma (POAG), often associated with increased intraocular pressure (IOP), can lead to permanent damage of the optic nerve, concomitant visual field loss, and blindness. Latanoprost, a prostaglandin F2α analogue, reduces IOP and is used to treat glaucoma. In this clinical trial, we evaluated the efficacy of Latanoprost Polpharma, a generic preservative-free latanoprost 0.05 mg/ml eye drops solution, in lowering IOP when compared to the originator Xalatan® (latanoprost 0.005% ophthalmic solution, Pfizer).MethodsThis was a Phase III, multicentre, randomized, investigator-masked, cross-over, comparative, non-inferiority trial carried out in 5 sites in Hungary and Russia. The primary endpoint was to evaluate the non-inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP on Day 1 (baseline) and Day 29. The secondary endpoints included efficacy, ocular tolerance, safety, and usability. We recruited adult patients (18–75 years) with open-angle glaucoma or ocular hypertension.ResultsForty-nine patients were randomised and received at least one dose of the test or reference product. A virtually identical reduction of the mean diurnal IOP of 7.04 ± 2.14 mmHg or 7.17 ± 2.11 mmHg was found after treatment with test or reference product, respectively (N = 44). In the intention to treat analysis, the reduction was 7.29 ± 2.53 mmHg (95% CI: 6.55–8.04) or 7.43 ± 2.78 mm Hg (95%CI: 6.61–8.24) after treatment with test or reference product, respectively (N = 47). There were no serious adverse events.ConclusionsLatanoprost Polpharma was shown to be non-inferior to Xalatan®. Both investigational products were equally well tolerated and safe. The data show a trend in favour of the test product with regards to the severity of hyperaemia and to the velocity of remission of ocular discomfort. Latanoprost Polpharma, being preservative-free, also avoids the cytotoxicity of benzalkonium chloride, the side effects of which may affect patient compliance and lower the quality of life.Trial registrationThe study had the ethical and regulatory approval from the National Institute of Pharmacy and Nutrition (OGYEI, OGYEI/41,779- 11/2018) and the Ethics Committee for Clinical Pharmacology (KFEB) of Hungary and from the Ministry of Healthcare of the Russian Federation (MOH of Russia) prior to the beginning of the study (642/25.12.2018) (clinical trial identification number: 848,300,144/0103/1 - POP03; IND number/EudraCT number: 2018-001727-39).

Retinal Ganglion Cell Function and Perfusion following Intraocular Pressure Reduction with Preservative-Free Latanoprost in Patients with Glaucoma and Ocular Hypertension.

(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.

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

Aims/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.Conclusions: 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.

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.

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

PurposeTo 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. MethodsPrimary 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. ResultsBAK-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. ConclusionBAK-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.

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

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 invitro and invivo drug permeability studies. 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 invitro using a reconstructed human corneal epithelium tissue. Then, invivo pharmacokinetic studies were performed on pigmented rabbits, for which LAT concentration was measured in the aqueous humour (AH) and iris-ciliary body (ICB). Invitro, the cumulative transport of LAT was linear between 1h and 4h 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 2h and 12h and was significantly lower than that of preserved latanoprost and PF SF latanoprost at 4 and 8h (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 1h 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 3h. BAK did not influence the corneal penetration of latanoprost in invitro and invivo 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.

COMfort Eye Trial (COMET) results - a non-inferiority, randomized, investigator-masked, two-parallel group, phase III clinical trial, to evaluate the efficacy and safety of a preservative free formulation of latanoprost versus a reference drug (Xalatan®) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT)

ABSTRACT Aim To prove non-inferiority of preservative-free (PF) latanoprost versus benzalkonium chloride (BAK) containing latanoprost in lowering intraocular pressure (IOP) in primary open-angle glaucoma (POAG) or ocular hypertension (OHT) patients. Design and methods This phase III, randomized, investigator-masked trial primarily aimed to demonstrate non-inferiority of YSLT PF latanoprost 50 μg/ml (Yonsung GmbH) to latanoprost (Xalatan®) 50 μg/ml (Pfizer) in reducing IOP from Baseline to Week 12. Secondary aims included conjunctival hyperemia evaluation and difference in ocular comfort levels. Total 130 patients with POAG or OHT were enrolled and randomized (1:1 ratio) to receive YSLT or latanoprost, instilling eye drops daily for 12 weeks. Results At Week 12, mean diurnal IOP reduction was −7.67 ± 2.104 mmHg for YSLT PF latanoprost and −7.77 ± 2.500 for latanoprost. The 97.5% confidence interval of between-treatment group difference in IOP reduction from Baseline to Week 12 was [−0.846, +∞), not crossing the non-inferiority margin of −1.5 mmHg. A low incidence of mild topical treatment emergent adverse events (TEAEs) was observed in both groups, while no serious TEAEs were reported. Conclusions YSLT eye drops demonstrated non-inferiority to latanoprost in reducing IOP. Both products were well tolerated without serious TEAEs reported.

Persistence and adherence with Latanoprost: A Danish register-based cohort study in older patients with glaucoma.

This study aims to assess the association between switching patterns and adherence/persistence in Danish patients over the age of 65, who started their first-ever glaucoma treatment with latanoprost eye drops. Patients were assigned to three different cohorts: (1) switchers, (2) non-switchers, and (3) preservative-free latanoprost (Monoprost®) users. Patients were followed for 1 year until the end of data coverage or censoring. Study covariates were used to compute the propensity score. In the adjusted analysis, the propensity score was added to the model as an independent variable. The Cox regression model was used to calculate the hazard ratio (HR) of discontinuation for the three cohorts (the non-switchers cohort was the reference level) in both adjusted and unadjusted analyses. Non-switchers had a statistically significant lower adherence (proportion of days covered, PDC 92%) than switchers (PDC 96%; p < 0.001) and users of Monoprost® (PDC 99%; p < 0.001). Switchers had a 53% lower risk of treatment discontinuation compared to the reference group within 1 year after the first redemption of latanoprost in both unadjusted (HR 0.47; 95% Confidence interval, 95% CI: 0.41-0.53; p < 0.001) and adjusted (HR 0.47; 95% CI: 0.42-0.53; p < 0.001) analyses. In comparison to the non-switchers, Monoprost® users had a 78% lower risk for the above result in both unadjusted (HR 0.22; 95% CI: 0.17-0.28; p < 0.001) and adjusted (HR 0.22; 95% CI: 0.17-0.29; p < 0.001) analyses. This study found increased adherence and persistence in latanoprost users among those who redeemed preservative-free latanoprost (Monoprost®) and among those who switched between different latanoprost formulations.

The In Vivo Effect of a Prostaglandin on the Conjunctival Goblet Cells

Introduction To evaluate the density of conjunctival goblet cells (GCs) from in vivo confocal microscopy (IVCM) and impression cytology (IC) and mucin expression in ten glaucomatous patients treated with preservative-free latanoprost (Monoprost®) Methods Ten glaucomatous patients (10 eyes) were enrolled. Conjunctiva was examined clinically and morphologically by IVCM and IC. Both IVCM and IC were performed at baseline, and after the 1st and 4th month of Monoprost® therapy. GC density (GCD) in cells⁄mm2 was the main outcome measurement. Results At baseline, mean GCD was 147+/-78 cells/mm2 for IVCM and 114+/-62 cells/mm2 for IC GCD. At month one, mean GCD was 149+/-69 and 120+/-56 measured with IVCM and IC, respectively (p=0.31 for IVCM and p=0.40 for IC). At month four, GCD increased to 162+/-81 and 134+/-61 measured with IVCM and IC, respectively (p=0.02 for IVCM and p=0.02 for IC). Conclusion Treatment with preservative-free (PF) latanoprost was associated with an increase in conjunctival GCD in glaucomatous eyes. Further studies are mandatory to verify this finding because its validation may have important consequences in the medical management of glaucoma.

Effect of preservative-free and preserved prostaglandin analogues on the histology of cornea of adult male guinea pigs following repeated exposure.

Glaucoma is a group of eye diseases that can cause vision loss. Prostaglandin analogues (PGAs) are known to be first-line treatment for patients with glaucoma. Latanoprost is a good, efficient and well-tolerated PGA that is currently available as latanoprost with benzalkonium chloride (BAC) (Xalatan) and preservative-free (PF) prostaglandin analogue latanoprost (Monopost). Lately, using PF anti-glaucoma agents has been considered an essential procedure for enhancing glaucoma care. This study aimed to analyse the histological changes within the corneal tissue with the use of currently available preserved prostaglandins-derived eye drops and PF prostaglandin analogue. In this study, 40 male guinea pigs were divided into four equal groups. Control group, Latanoprost with 0.02% BAC-treated group, Recovery group and PF latanoprost-treated group. After 2 months, the corneal tissues of guinea pigs were prepared for light and electron microscopic studies; morphometric and statistical studies were performed. Our results indicated that guinea pigs treated with latanoprost with BAC exhibited ocular surface changes: there was epithelial thinning with desquamation, the stroma showed irregularly arranged collagen fibres and small keratocytes. Morphometrically, there was a marked decrease in the thickness of epithelium and number of keratocytes. Negative periodic acid Schiff (PAS) reaction was observed in some parts of the epithelial basement membrane. The epithelium gave a strong positive immunoreactivity for Bcl-2-associated X protein (BAX). Guinea pigs left to recover exhibited improvement, while treatment of animals with PF latanoprost resulted in nearly normal corneal structure. In conclusion, PF prostaglandin anti-glaucoma medication seems to be better and have protective effect on cornea of male guinea pigs than prostaglandins with BAC preservative.

Impact of benzalkonium chloride-preserved and preservative-free latanoprost eye drops on cultured human conjunctival goblet cells upon acute exposure and differences in physicochemical properties of the eye drops

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

Efficacy and safety of newly developed preservative-free latanoprost 0.005% eye drops versus preserved latanoprost 0.005% in open angle glaucoma and ocular hypertension: 12-week results of a randomized, multicenter, controlled phase III trial.

To evaluate the therapeutic efficacy, safety and tolerability of newly developed preservative-free (PF) latanoprost generic [TJO-002] and compare it with benzalkonium chloride (BAK)-preserved latanoprost [Xalatan®] in patients with primary open angle glaucoma (POAG) and ocular hypertension (OHT). Included patients were aged ≥19y with POAG/OHT. After a washout period, patients with IOP 21-35 mm Hg at 9 a.m. were enrolled. After a full ophthalmic and glaucoma examination, 144 patients with POAG and OHT participated in this study. Subjects were randomly assigned either PF latanoprost (74 eyes) or BAK-preserved latanoprost (70 eyes). All subjects were examined at 4, 8, and 12wk after first administration. At each follow-up visit, IOP was measured at 9 a.m. and 5 p.m. and compliance was assessed. Throughout the study, all adverse events were recorded and monitored by the masked investigators who measured IOP. Both groups showed a statistically significant decrease of average diurnal IOP at 12wk compared to baseline (-7.21±3.10 mm Hg in the PF latanoprost group and -7.02±3.17 mm Hg in the BAK latanoprost group, both P<0.0001). There was no statistically significant diurnal IOP variation between the groups. In terms of tolerability, pruritus, burning/stinging, and sticky eye sensation, severity was significantly lower in the PF latanoprost group than in the BAK latanoprost group (P<0.05). PF latanoprost has at least similar efficacy in terms of IOP reduction and better tolerability compared with BAK latanoprost.

Comparison of ocular surface assessment and adherence between preserved and preservative-free latanoprost in glaucoma: a parallel-grouped randomized trial

Given that nonadherence is related to subject characteristics and drug tolerance and preserved eye drops tend to be more intolerable than preservative-free ones, we conducted a phase 4, parallel-grouped, investigator-blind, active-control, randomized, multicenter study. A total of 51 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomly assigned to the preserved latanoprost group (n = 26) and the preservative-free latanoprost group (n = 25). The efficacy variables were corneal/conjunctival staining grade, Ocular Surface Disease Index (OSDI), adherence at 12 weeks after the first administration; corneal/conjunctival staining grade at 4 weeks; and IOP, tear break-up time (TBUT), and hyperemia score at 4 and 12 weeks. The safety variables included visual acuity and drug tolerance questionnaire results. There was no statistically significant difference in corneal/conjunctival staining grade, OSDI, or TBUT between the groups at 4 and 12 weeks. However, the adherence rate was higher and the hyperemia score was lower in the preservative-free group than in the preserved group. The severity and duration of stinging/burning sensation were lower in the preservative-free group than in the preserved group. Overall, preservative-free latanoprost showed better ocular tolerance assessed by hyperemia scores and stinging/burning symptoms following higher adherence than preserved latanoprost.

Efficacy and Safety of Preservative-free Latanoprost Eyedrops Compared with Preserved Prostaglandin Analogues in Patients with Open-angle Glaucoma.

PurposeTo evaluate the safety and efficacy of preservative-free (PF) latanoprost in glaucoma patients.MethodsIn this prospective, open-label, observational study, a total of 27 primary open-angle glaucoma patients who used benzalkonium chloride-preserved prostaglandin analogues for at least 6 months were enrolled. After changing the eye drops to PF lataprost, the intraocular pressure (IOP) and ocular surface symptoms and signs were evaluated in all patients on days 0 (first visit, D0), 45 (D45), and 90 (D90).ResultsMean IOP remained stable during the study period (14.0 ± 2.4 mmHg at D0, 13.9 ± 2.0 mmHg at D45, 13.7 ± 2.2 mmHg at D90; p = 0.603). Mean deviation, pattern standard deviation, and best-corrected visual acuity were similar before and after eye drops replacement. Bulbar conjunctival hyperemia, corneal staining, and conjunctival staining were significantly decreased over 90 days (p = 0.025, p < 0.001, p = 0.020, respectively). The ocular surface disease index score showed a statistically significant improvement from 26.4 ± 18.5 at D0 to 19.8 ± 17.0 at D45 and 15.7 ± 15.6 at D90 (p < 0.001). In the evaluation of ocular tolerability, burning symptoms and dryness were significantly decreased (p = 0.001, p = 0.040).ConclusionsThe effects of PF latanoprost on reducing IOP were comparable with those of benzalkonium chloride-preserved prostaglandin analogues, but side effects on the ocular surface were much less pronounced when PF latanoprost was used. With this efficacy, PF latanoprost could slow the progression of glaucoma by increasing patient compliance.

Comparison of the Safety and Efficacy between Preserved and Preservative-Free Latanoprost and Preservative-Free Tafluprost.

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

Preserved Versus Preservative-Free Latanoprost for the Treatment of Glaucoma and Ocular Hypertension: A Post Hoc Pooled Analysis.

IntroductionTo compare the tolerability and efficacy of a preservative-containing latanoprost (PCL) to a preservative-free formulation of latanoprost (PFL) in patients with open-angle glaucoma or ocular hypertension.MethodsA pooled analysis was performed of data from five published studies. The primary outcome was tolerability as evaluated by the severity of hyperemia. The secondary objectives were patient tolerance based on a composite ocular surface disease (OSD) score arising from ocular signs and symptoms, patient and investigator satisfaction, and a comparison of IOP-lowering efficacy.ResultsThere were three randomized controlled trials and two observational studies included in the analysis. Conjunctival hyperemia improved significantly in 25.6% (388) of patients switched to the PFL group versus 11.7% (117) of patients switched to the PCL group (p < 0.001). PFL was two times superior to PCL in reducing ocular hyperemia (odds ratio = 1.96; p < 0.001). The mean OSD composite score decreased by 32.2% in patients switched to the PFL group and 14.1% in the PCL group (p < 0.001). At 3 months, the mean IOP was similar between groups (p = 0.312).ConclusionThis post hoc pooled analysis confirmed the findings of the individual studies that PFL is as efficacious at reducing IOP as PCL but better tolerated. After switching to PFL, there was twice the improvement in the OSD composite score. PFL was twice as effective at reducing ocular hyperemia and other ocular signs. These findings suggest that PFL has features that may improve patient compliance, thereby potentially improving the IOP-lowering efficacy on a long-term basis.

Real-World Study on Patient Satisfaction and Tolerability After Switching to Preservative-Free Latanoprost.

PurposePatient satisfaction is important in the treatment of glaucoma. Suboptimal compliance and impaired long-term outcome are a likely result of poor tolerability. The present multicentre, international, transverse, epidemiological survey was conducted to assess the satisfaction of patients who had received preservative-free latanoprost (PFL) for at least 3 months.Patients and MethodsA total of 1872 patients from 6 European countries, treated with PFL for at least 3 months, were included in this survey. Prior to PFL treatment, patients were to be treatment naïve or currently treated for their glaucoma. During a single routine consultation, patients completed a questionnaire concerning global satisfaction and satisfaction based on tolerability.ResultsIn total, 76.2% had been previously treated; 69.4% had received preserved and 6.8% preservative-free (PF) topical treatment. After 3 months of PFL treatment, a large majority of patients (95.3%) were satisfied or very satisfied with their PFL treatment and were, overall, significantly (p<0.0001) more satisfied with PFL than with their previous treatment; 4.2% were either unsatisfied or very unsatisfied. Overall, 97.3% of originally treatment-naïve patients were satisfied (50.1%) or very satisfied (47.2%) with their PFL. Ocular surface disease was diagnosed in 9.2% of patients (n=173) and was mainly mild (76.9%). Patient satisfaction with PFL was very high. ConclusionPFL may be considered a valuable first-choice treatment in glaucoma patients.

Preservative-free versus preserved latanoprost eye drops for reducing intraocular pressure: a non-inferiority phase III randomized, multi-center, single-blind, parallel-group controlled trial

Background: The aim of this study was to test the non-inferiority of preservative-free (PF) latanoprost 50 μg/mL multi-dose ophthalmic solution versus the marketed benzalkonium chloride (BAK)-preserved latanoprost 50 μg/mL ophthalmic solution in patients with open-angle glaucoma and patients with ocular hypertension.&#x0D; Methods: This was a prospective, national, randomized, multi-center, observer-blind, parallel-group controlled clinical trial. Patients were randomized to receive either PF or BAK-preserved latanoprost once daily for 12 weeks. The primary endpoint was the change in intraocular pressure (IOP) at 8:00 AM in the affected eye between the end of the treatment (week 12) and the baseline (week 0). Secondary measurements were taken at weeks 2 and 6, with IOP being recorded at 8:00 AM, 12:00 PM, and 4:00 PM.&#x0D; Results: A total of 158 patients were included in the per protocol (PP) population (77 in the PF latanoprost treatment arm and 81 patients in the BAK-preserved latanoprost treatment arm). PF latanoprost was non-inferior to BAK-preserved latanoprost in reducing IOP at 8:00 AM in the study eye from the baseline (week 0) to the end of the treatment (week 12). The point estimate of the between-treatment difference was 0.1 mmHg (95% confidence interval: -0.646, 0.847). Mean between-group differences in IOP reduction from the baseline to each of the secondary measurements were also similar between the two treatment arms. The two treatments were well tolerated and had comparable adverse event profiles.&#x0D; Conclusions: PF latanoprost was non-inferior to BAK-preserved latanoprost in reducing IOP in patients with open-angle glaucoma or ocular hypertension. Both treatments were well tolerated.

Efficacy of Preservative-free Latanoprost in Normal-tension Glaucoma with Mild to Moderate Dry Eye

Efficacy of Preservative-free Latanoprost in Normal-tension Glaucoma with Mild to Moderate Dry Eye