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Acta Ophthalmologica Nov 2020Preservatives contained in glaucoma eye drops have been shown to have a deleterious impact on the ocular surface. We aimed to assess the association between preservative...
Preservative-free versus preserved glaucoma eye drops and occurrence of glaucoma surgery. A retrospective study based on the French national health insurance information system, 2008-2016.
PURPOSE
Preservatives contained in glaucoma eye drops have been shown to have a deleterious impact on the ocular surface. We aimed to assess the association between preservative exposure and the occurrence of further glaucoma surgery among patients with glaucoma or ocular hypertension in France.
METHODS
The study concerned all patients who first received glaucoma eye drop treatments in a French medical-administrative database (EGB) between 2008 and 2015. Three groups were created according to the level of preservative exposure during the whole follow-up: '0% preservatives', 'mixed' and '100% preservatives'. The occurrence of glaucoma surgery was estimated according to preservative exposure indicators in Cox multivariate models adjusted on age, sex, number of glaucoma eye drops simultaneously used, systemic antihypertensive treatment and duration of treatment.
RESULTS
The sample consisted of 12 454 patients. The median (interquartile range) follow-up was 4.1 (1.7-6.1) years. A total of 231 (1.9%) patients underwent glaucoma surgery during follow-up. On multivariable analysis, the risk of glaucoma surgery was increased for the 'mixed' group (hazard ratio [HR] = 3.94 [95% CI, 1.54-10.05]) and for the '100% preservative' group (HR = 7.97 [95% CI, 3.07-20.67]) when compared with the 0% preservative group.
CONCLUSION
We found an association between exposure to glaucoma eye drop preservatives and the prevalence of further glaucoma surgery. While these data might be used to support the consideration of routine use of preservative-free drops, in the absence of a randomized clinical trial, they cannot prove a direct cause-and-effect relationship between preservative-free glaucoma eye drops and further glaucoma surgery.
Topics: Aged; Antihypertensive Agents; Female; Filtering Surgery; Follow-Up Studies; France; Glaucoma; Humans; Incidence; Intraocular Pressure; Male; National Health Programs; Ophthalmic Solutions; Preservatives, Pharmaceutical; Retrospective Studies
PubMed: 32232968
DOI: 10.1111/aos.14410 -
Folia Morphologica 2022Glaucoma 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....
BACKGROUND
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.
MATERIALS AND METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
Topics: Animals; Antihypertensive Agents; Cornea; Guinea Pigs; Humans; Latanoprost; Male; Preservatives, Pharmaceutical; Prostaglandins, Synthetic
PubMed: 33438192
DOI: 10.5603/FM.a2020.0146 -
Journal of Optometry 2024To investigate the effect of benzalkonium chloride (BAK)-preserved latanoprost and bimatoprost, polyquad (PQ)-preserved travoprost, and preservative-free (PF)...
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.
Topics: Humans; Benzalkonium Compounds; Travoprost; Latanoprost; Ophthalmic Solutions; Goblet Cells; Bimatoprost; Cloprostenol; Interleukin-8; Prostaglandins F, Synthetic; Antihypertensive Agents; Preservatives, Pharmaceutical; Prostaglandins, Synthetic
PubMed: 37788596
DOI: 10.1016/j.optom.2023.100481 -
Scientific Reports Jul 2021Given that nonadherence is related to subject characteristics and drug tolerance and preserved eye drops tend to be more intolerable than preservative-free ones, we... (Comparative Study)
Comparative Study Randomized Controlled 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.
Topics: Aged; Drug Administration Schedule; Female; Glaucoma, Open-Angle; Humans; Intention to Treat Analysis; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Preservatives, Pharmaceutical; Treatment Adherence and Compliance; Treatment Outcome
PubMed: 34294842
DOI: 10.1038/s41598-021-94574-x -
Journal of Ocular Pharmacology and... Apr 2022Data are presented from ophthalmology clinics in Spain participating in the VISIONARY study, examining the effectiveness, tolerability, and safety of the... (Observational Study)
Observational Study
Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy: Results from the VISIONARY Study Population in Spain.
Data are presented from ophthalmology clinics in Spain participating in the VISIONARY study, examining the effectiveness, tolerability, and safety of the preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in the treatment of OAG and OHT. An observational, multicenter prospective study examined treatment outcomes following a switch to PF tafluprost/timolol FC in adult OAG/OHT patients demonstrating insufficient response to beta-blocker or prostaglandin analog (PGA) monotherapy. Primary end point was mean change in intraocular pressure (IOP) from baseline at month 6. Changes in the severity of ocular signs and symptoms were also assessed. Overall, 92 patients (51.1% female) were included. Mean (standard deviation) age was 68.3 (12.1) years. Mean IOP was reduced from 21.9 mmHg at baseline to 16.7 mmHg at month 6 (22.3% decrease; < 0.0001). Significant IOP reductions were observed at weeks 4 and 12 ( < 0.0001). Baseline PGA and beta-blocker users demonstrated mean month 6 IOP reductions of 5.5 mmHg (23.5%; < 0.001) and 3.5 mmHg (14.6%; = 0.029), respectively. Severity of conjunctival hyperemia, dry eye, irritation, itching, foreign body sensation, and eye pain was significantly reduced. Three treatment-related adverse events were reported, all were nonserious and mild/moderate in severity. In real-world clinical practice, PF tafluprost/timolol FC treatment provided significant IOP reductions over 6 months and was well tolerated among OAG/OHT patients showing poor response to PGA or beta-blocker monotherapy. IOP-lowering efficacy and improvements in ocular signs and symptoms were evident from week 4 and maintained over the 6-month study period. Trial Registration: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number EUPAS22204.
Topics: Adult; Aged; Antihypertensive Agents; Drug Combinations; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Ocular Hypertension; Preservatives, Pharmaceutical; Prospective Studies; Prostaglandins; Prostaglandins A; Prostaglandins F; Prostaglandins, Synthetic; Spain; Timolol
PubMed: 35230148
DOI: 10.1089/jop.2021.0099 -
Journal of Cataract and Refractive... Jun 2022To compare the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) and steroidal eyedrops for inflammation management after cataract surgery using slitlamp... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of a preservative-free nonsteroidal anti-inflammatory drug and preservative-free corticosteroid after uneventful cataract surgery: multicenter, randomized, evaluator-blinded clinical trial.
PURPOSE
To compare the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) and steroidal eyedrops for inflammation management after cataract surgery using slitlamp indicators.
SETTING
11 eye centers in South Korea.
DESIGN
Randomized prospective multicenter study with a blinded evaluator.
METHOD
In 125 (250 eyes) patients who underwent cataract surgery, bromfenac sodium hydrate 0.1% (NSAID group) was applied twice a day in 1 eye, whereas the other eye was treated with fluorometholone 0.1% (steroid group), 4 times a day for 4 weeks postoperatively. The primary efficacy outcome was the presence of anterior chamber cells and flare at 1 week postoperatively. Anterior chamber cells and flare at 4 to 8 weeks, corrected distance visual acuity, central corneal thickness, conjunctival hyperemia, dry eye parameters, foveal thickness, and ocular and visual discomfort were evaluated as secondary outcomes.
RESULTS
At week 1, residual anterior chamber inflammation was not statistically significantly different between the groups (-1.03 ± 1.27 vs -0.95 ± 1.24, P = .4850). However, the NSAID group recovered from conjunctival hyperemia more rapidly than the steroid group (0.30 ± 0.52 vs 0.44 ± 0.81, P = .0144 at week 1). The increase in central corneal thickness in the NSAID group was less than that in the steroid group 1 week postoperatively (7.87 ± 22.46 vs 29.47 ± 46.60 μm, P < .0001). The change in foveal thickness in the NSAID group was significantly less than that in the steroid group (18.11 ± 68.19 vs 22.25 ± 42.37 μm, P = .0002). Lower levels of postoperative ocular and visual discomfort were reported in the NSAID group than in the steroid group under treatment.
CONCLUSIONS
Preservative-free bromfenac was as effective as preservative-free fluorometholone eyedrops in anterior chamber inflammation control and showed better signs and symptoms after cataract surgery.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Cataract; Cataract Extraction; Fluorometholone; Humans; Hyperemia; Inflammation; Ophthalmic Solutions; Phacoemulsification; Postoperative Complications; Preservatives, Pharmaceutical; Prospective Studies; Treatment Outcome
PubMed: 34629379
DOI: 10.1097/j.jcrs.0000000000000841 -
International Journal of Molecular... Nov 2022Prostaglandin analogues (PGAs), including bimatoprost (BIM), are generally the first-line therapy for glaucoma due to their greater efficacy, safety, and convenience of...
Cytotoxicity, Mitochondrial Functionality, and Redox Status of Human Conjunctival Cells after Short and Chronic Exposure to Preservative-Free Bimatoprost 0.03% and 0.01%: An In Vitro Comparative Study.
Prostaglandin analogues (PGAs), including bimatoprost (BIM), are generally the first-line therapy for glaucoma due to their greater efficacy, safety, and convenience of use. Commercial solutions of preservative-free BIM (BIM 0.03% and 0.01%) are already available, although their topical application may result in ocular discomfort. This study aimed to evaluate the in vitro effects of preservative-free BIM 0.03% vs. 0.01% in the human conjunctival epithelial (HCE) cell line. Our results showed that long-term exposure to BIM 0.03% ensues a significant decrease in cell proliferation and viability. Furthermore, these events were associated with cell cycle arrest, apoptosis, and alterations of ΔΨ. BIM 0.01% does not exhibit cytotoxicity, and no negative influence on conjunctival cell growth and viability or mitochondrial activity has been observed. Short-time exposure also demonstrates the ability of BIM 0.03% to trigger reactive oxygen species (ROS) production and mitochondrial hyperpolarisation. An in silico drug network interaction was also performed to explore known and predicted interactions of BIM with proteins potentially involved in mitochondrial membrane potential dissipation. Our findings overall strongly reveal better cellular tolerability of BIM 0.01% vs. BIM 0.03% in HCE cells.
Topics: Humans; Bimatoprost; Preservatives, Pharmaceutical; Conjunctiva; Oxidation-Reduction
PubMed: 36430590
DOI: 10.3390/ijms232214113 -
Journal of Ocular Pharmacology and... 2014Glaucoma patients routinely take multiple medications, with multiple daily doses, for years or even decades. Benzalkonium chloride (BAK) is the most common preservative... (Review)
Review
Glaucoma patients routinely take multiple medications, with multiple daily doses, for years or even decades. Benzalkonium chloride (BAK) is the most common preservative in glaucoma medications. BAK has been detected in the trabecular meshwork (TM), corneal endothelium, lens, and retina after topical drop installation and may accumulate in those tissues. There is evidence that BAK causes corneal and conjunctival toxicity, including cell loss, disruption of tight junctions, apoptosis and preapoptosis, cytoskeleton changes, and immunoinflammatory reactions. These same effects have been reported in cultured human TM cells exposed to concentrations of BAK found in common glaucoma drugs and in the TM of primary open-angle glaucoma donor eyes. It is possible that a relationship exists between chronic exposure to BAK and glaucoma. The hypothesis that BAK causes/worsens glaucoma is being tested experimentally in an animal model that closely reflects human physiology.
Topics: Animals; Benzalkonium Compounds; Conjunctiva; Cornea; Glaucoma; Glaucoma, Open-Angle; Humans; Preservatives, Pharmaceutical; Species Specificity; Tissue Distribution; Trabecular Meshwork
PubMed: 24205938
DOI: 10.1089/jop.2013.0174 -
Korean Journal of Ophthalmology : KJO Jun 2021To evaluate the safety and efficacy of preservative-free (PF) latanoprost in glaucoma patients. (Observational Study)
Observational Study
PURPOSE
To evaluate the safety and efficacy of preservative-free (PF) latanoprost in glaucoma patients.
METHODS
In 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).
RESULTS
Mean 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).
CONCLUSIONS
The 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.
Topics: Antihypertensive Agents; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prospective Studies; Prostaglandins F, Synthetic; Prostaglandins, Synthetic
PubMed: 34120423
DOI: 10.3341/kjo.2021.0010 -
Korean Journal of Ophthalmology : KJO Aug 2015Chronic use of topical hypotensive agents induces several side effects caused by preservatives. The purpose of this study was to evaluate the effects of prostaglandin...
PURPOSE
Chronic use of topical hypotensive agents induces several side effects caused by preservatives. The purpose of this study was to evaluate the effects of prostaglandin analogs with varying concentrations of benzalkonium chloride (BAC), preservative-free (PF), and alternative preservatives on mouse corneal tissue.
METHODS
Thirty-five, 8- to 10-week-old female C57BL/6 mice (five mice for each group) were used for this study. To the control group, we applied normal saline, and to each drug-treated group we applied 0.02% BAC, bimatoprost 0.01% (with BAC 0.02%), latanoprost 0.005% (with BAC 0.02%), travoprost 0.004% (with 0.001% polyquad) or tafluprost 0.0015% with/without 0.001% BAC, once a day (9 p.m.) for 4 weeks. Corneal fluorescein staining was evaluated in all groups. After harvest, the corneal tissues were embedded in paraffin and then Hematoxylin-Eosin stain was performed for histopathological examination. Immunofluorescence staining was done against TNF-α, IL-6, HLA DR, pJNK, and pAkt.
RESULTS
In corneal fluorescein staining, severe punctate epithelial keratitis was seen in the groups of 0.02% BAC, 0.02% BAC containing bimatoprost 0.01% and latanoprost 0.005%. The surface desquamation, irregular surface, loss of cell borders, anisocytosis and stromal shrinkage were observed in the groups of BAC-containing eye drops. Moreover, the groups treated with BAC-containing eye drops have high inflammatory markers, significantly decreased cell viability-related signal, pAkt, and higher apoptosis-inducing signal, pJNK, than the control group. On the other hand, travoprost 0.004% and PF tafluprost 0.0015% have less cellular morphologic changes, lower inflammation, and higher cellular viability than BAC-containing formulations.
CONCLUSIONS
Corneal damage, increased inflammation and apoptosis and low cell viability were observed in BAC-containing groups. PF or alternatively preserved glaucoma medications seem to be a reasonable and viable alternative to those preserved with BAC.
Topics: Animals; Cell Survival; Conjunctiva; Disease Models, Animal; Epithelium, Corneal; Female; Glaucoma; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prostaglandins, Synthetic
PubMed: 26240512
DOI: 10.3341/kjo.2015.29.4.270