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Acta Ophthalmologica Dec 2023Glaucoma 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... (Meta-Analysis)
Meta-Analysis
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.
Topics: Humans; Benzalkonium Compounds; Intraocular Pressure; Travoprost; Latanoprost; Ophthalmic Solutions; Goblet Cells; Prostaglandins F, Synthetic; Antihypertensive Agents; Glaucoma; Preservatives, Pharmaceutical; Conjunctiva; Prostaglandins, Synthetic; Blindness
PubMed: 38037546
DOI: 10.1111/aos.15808 -
Korean Journal of Ophthalmology : KJO Oct 2022Netarsudil is a Rho kinase inhibitor and the first new class of clinically useful ocular hypotensive agents. In this study, we conducted a systematic literature review... (Meta-Analysis)
Meta-Analysis
PURPOSE
Netarsudil is a Rho kinase inhibitor and the first new class of clinically useful ocular hypotensive agents. In this study, we conducted a systematic literature review and meta-analysis to summarize and synthesize the available evidence on the efficacy and safety of fixed-dose combination (FDC) therapy with netarsudil/latanoprost in patients with glaucoma.
METHODS
We identified relevant studies in PubMed, Ovid Medline, Embase, and Cochrane Central until April 2021. The quality of the studies and the level of evidence were assessed using the Risk of Bias tool. Efficacy was measured as the mean difference in reducing intraocular pressure (IOP), and safety was assessed by the risk of conjunctival hyperemia (CH) due to FDC therapy, netarsudil monotherapy, or latanoprost monotherapy.
RESULTS
Four studies met the predefined eligibility criteria and were included in the meta-analysis. The mean difference in the reduction in IOP after 2 weeks and 4 to 6 weeks of drug administration was -2.41 mmHg (95% confidence interval [CI], -2.95 to -1.87) and -1.77 mmHg (95% CI, -2.31 to -1.87), respectively, in patients receiving FDC therapy versus those receiving latanoprost monotherapy. On the other hand, latanoprost monotherapy had a greater effect in reducing IOP than netarsudil monotherapy after 4 to 6 weeks of administration (mean difference, 0.95 mmHg; 95% CI, 0.43 to 1.47). The risk of CH was significantly higher with both FDC therapy and netarsudil monotherapy compared to latanoprost monotherapy in week 12, where the relative ratio was 3.01 (95% CI, 1.95 to 4.66) and 2.33 (95% CI, 1.54 to 3.54), each.
CONCLUSIONS
Netarsudil/latanoprost FDC therapy has a significantly greater effect on reducing IOP than latanoprost alone. The symptoms of CH were mostly mild, and only a few glaucoma patients discontinued the medication owing to CH in earlier clinical trials. Therefore, it would be beneficial to consider the administration of netarsudil/latanoprost FDC therapy in patients with glaucoma.
Topics: Antihypertensive Agents; Benzoates; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Prostaglandins F, Synthetic; Timolol; Treatment Outcome; beta-Alanine; rho-Associated Kinases
PubMed: 35989070
DOI: 10.3341/kjo.2022.0061 -
Indian Journal of Ophthalmology May 2022The objective of this meta-analysis was to evaluate the effect of prostaglandin analogues (PGA) on central corneal thickness (CCT) in patients with glaucoma. Key... (Meta-Analysis)
Meta-Analysis Review
The objective of this meta-analysis was to evaluate the effect of prostaglandin analogues (PGA) on central corneal thickness (CCT) in patients with glaucoma. Key electronic databases were searched for randomized controlled trials (RCTs) involving the CCT effects of prostaglandin use for glaucoma. Primary outcome measures were the mean difference in the CCT measurement from baseline to the last available assessment. Intraocular pressure and other corneal changes were recorded as secondary. Efficacy estimates were measured by their weighted mean difference (WMD) with 95% confidence intervals (CI's) by using the random-effects model for primary and secondary outcomes Trial sequential analysis was used to determine if the current evidence was sufficient and conclusive. Eight RCTs met our inclusion criteria. A total of 879 patients were included. The overall effect showed that PGA's had a significant CCT lowering effect (WMD = -7.04, 95%CI: -10.07 to -4.00, P < 0.00001). We pooled results of 5 RCT's on Travoprost (WMD = -10.44, 95%CI: -16.80 to -4.08, P = 0.001), seven trials on Latanoprost (WMD = -4.73, 95% CI: -9.70 to 0.25, P = 0.06), and three trials on Bimatoprost (WMD = -11.88, 95%CI: -21.03 to -2.73, P = 0.01). The WMD across groups in >6 months of PGA use was -11.37 (95%CI: -17.17 to -5.58, P = 0.0001), and in <6 months of PGAs group was -8.35 (95% CI: -12.01 to -4.69, P < 0.00001), suggesting a longitudinal effect of PGAs on CCT. In conclusion, Bimatoprost and Travoprost caused a statistically significant reduction in the thickness of central cornea. Though only a few studies were included, the narrow confidence intervals and adequate sample size suggest that these findings are valid.
Topics: Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Glaucoma; Glaucoma, Open-Angle; Humans; Prostaglandins A; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Travoprost
PubMed: 35502015
DOI: 10.4103/ijo.IJO_1971_21 -
Ageing Research Reviews Feb 2022The association between F-isoprostanes and Alzheimer's disease (AD) has been controversially discussed in the literature since the 1990s. However, no systematic review... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The association between F-isoprostanes and Alzheimer's disease (AD) has been controversially discussed in the literature since the 1990s. However, no systematic review has been performed so far.
METHODS
A systematic review of observational studies on the associations of F-isoprostanes and the specific biomarker 8-iso-prostaglandin F with AD were conducted. Random-effects model meta-analyses were performed.
RESULTS
29 studies were included in the systematic review, including four longitudinal studies. In an overall meta-analysis of the 25 cross-sectional studies, F-isoprostane levels were statistically significantly associated with AD (Hedge's g [95% confidence interval]: 1.00 [0.69-1.32]). When studies were grouped by biomarker and sample specimen, F-isoprostane and 8-iso-prostaglandin F levels were statistically significantly elevated in tissue samples of the frontal lobe of AD patients. Moreover, F-isoprostane levels in cerebrospinal fluid and 8-iso-prostaglandin F levels in blood samples of AD patients were significantly increased. Meta-analyses of the few longitudinal studies did not reach statistical significance.
DISCUSSION
Increased concentrations of F-isoprostanes were found in AD patients. However, due to the lack of adjustment in most cross-sectional case-control studies, results must be interpreted carefully. In addition, the causality of the association is uncertain because evidence from well-conducted longitudinal studies was conflicting, and further longitudinal studies are required to reinforce the results.
Topics: Alzheimer Disease; Cross-Sectional Studies; Dinoprost; F2-Isoprostanes; Humans; Isoprostanes; Oxidative Stress
PubMed: 34954419
DOI: 10.1016/j.arr.2021.101552 -
PloS One 2021Prostaglandins are thought to be important mediators in the initiation of human labour, however the evidence supporting this is not entirely clear. Determining how, and...
Prostaglandins are thought to be important mediators in the initiation of human labour, however the evidence supporting this is not entirely clear. Determining how, and which, prostaglandins change during pregnancy and labour may provide insight into mechanisms governing labour initiation and the potential to predict timing of labour onset. The current study systematically searched the existing scientific literature to determine how biofluid levels of prostaglandins change throughout pregnancy before and during labour, and whether prostaglandins and/or their metabolites may be useful for prediction of labour. The databases EMBASE and MEDLINE were searched for English-language articles on prostaglandins measured in plasma, serum, amniotic fluid, or urine during pregnancy and/or spontaneous labour. Studies were assessed for quality and risk of bias and a qualitative summary of included studies was generated. Our review identified 83 studies published between 1968-2021 that met the inclusion criteria. As measured in amniotic fluid, levels of PGE2, along with PGF2α and its metabolite 13,14-dihydro-15-keto-PGF2α were reported higher in labour compared to non-labour. In blood, only 13,14-dihydro-15-keto-PGF2α was reported higher in labour. Additionally, PGF2α, PGF1α, and PGE2 were reported to increase in amniotic fluid as pregnancy progressed, though this pattern was not consistent in plasma. Overall, the evidence supporting changes in prostaglandin levels in these biofluids remains unclear. An important limitation is the lack of data on the complexity of the prostaglandin pathway outside of the PGE and PGF families. Future studies using new methodologies capable of co-assessing multiple prostaglandins and metabolites, in large, well-defined populations, will help provide more insight as to the identification of exactly which prostaglandins and/or metabolites consistently change with labour. Revisiting and revising our understanding of the prostaglandins may provide better targets for clinical monitoring of pregnancies. This study was supported by the Canadian Institutes of Health Research.
Topics: Amniotic Fluid; Body Fluids; Databases, Factual; Dinoprost; Female; Humans; Labor Onset; Labor, Obstetric; Oxytocics; Plasma; Pregnancy; Prostaglandins; Prostaglandins E; Prostaglandins F; Serum; Urine
PubMed: 34793529
DOI: 10.1371/journal.pone.0260115 -
The British Journal of Ophthalmology May 2022To assess the comparative efficacy of latanoprostene bunod (LBN), a novel prostaglandin analogue (PGA), to other medications for open-angle glaucoma and ocular... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
To assess the comparative efficacy of latanoprostene bunod (LBN), a novel prostaglandin analogue (PGA), to other medications for open-angle glaucoma and ocular hypertension on lowering intraocular pressure (IOP).
METHODS
A systematic literature review adapted from the Li (Ophthalmology, 2016) study was conducted. Medline, Embase and PubMed were searched for randomised controlled trials published between 1 January 2014 and 19 March 2020. Studies had to report IOP reduction after 3 months for at least two different treatments among placebo, PGAs (bimatoprost 0.01%, bimatoprost 0.03%, latanoprost, LBN, tafluprost, unoprostone) or apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide, levobunolol, timolol, travoprost. A Bayesian network meta-analysis was performed to provide the relative effect in terms of mean difference (95% credible interval) of IOP reduction and ranking probabilities. Surface under the cumulative ranking curve (SUCRA) was generated.
RESULTS
A total of 106 trials were included with data for 18 523 participants. LBN was significantly more effective than unoprostone (-3.45 (-4.77 to -2.12)). Although relative effect was not significative, compared with other PGAs, LBN numerically outperformed latanoprost (-0.70 (-1.83 to 0.43)) and tafluoprost (-0.41 (-1.87 to 1.07)), was similar to bimatoprost 0.01% (-0.02(-1.59 to 1.55)) and was slightly disadvantaged by bimatoprost 0.03% (-0.17 (-1.42 to 1.07)). LBN was significantly more efficient than the beta-blockers apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide and timolol. According to SUCRA, LBN was ranked second after bimatoprost 0.03%, followed by bimatoprost 0.01%.
CONCLUSION
LBN was significantly more effective than the PGA unoprostone and most of the beta-blockers. Compared with the most widely used PGAs, LBN numerically outperformed latanoprost and travoprost and was similar to bimatoprost 0.01%.
Topics: Amides; Antihypertensive Agents; Bayes Theorem; Betaxolol; Bimatoprost; Brimonidine Tartrate; Carteolol; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Network Meta-Analysis; Ocular Hypertension; Prostaglandins A; Prostaglandins F, Synthetic; Timolol; Travoprost
PubMed: 33397657
DOI: 10.1136/bjophthalmol-2020-317262 -
International Journal of Molecular... May 2020Isoprostanes are physiopathologic mediators of oxidative stress, resulting in lipid peroxidation. 8-isoprostane seems particularly useful for measuring oxidative stress... (Meta-Analysis)
Meta-Analysis
Isoprostanes are physiopathologic mediators of oxidative stress, resulting in lipid peroxidation. 8-isoprostane seems particularly useful for measuring oxidative stress damage. However, no reference range values are available for 8-isoprosante in exhaled breath condensate (EBC) of healthy adults, enabling its meaningful interpretation as a biomarker. We conducted this systematic review and meta-analysis according to the protocol following PROSPERO (CRD42020146623). After searching and analyzing the literature, we included 86 studies. After their qualitative synthesis and risk of bias assessment, 52 studies were included in meta-analysis. The latter focused on studies using immunological analytical methods and investigated how the concentrations of 8-isoprostane differ based on gender. We found that gender had no significant effect in 8-isoprostane concentration. Among other studied factors, such as individual characteristics and factors related to EBC collection, only the device used for EBC collection significantly affected measured 8-isoprostane concentrations. However, adjustment for the factors related to EBC collection, yielded uncertainty whether this effect is due to the device itself or to the other factors. Given this uncertainty, we estimated the reference range values of 8-isoprostane stratified by gender and EBC collection device. A better standardization of EBC collection seems necessary; as well more studies using chemical analytical methods to extend this investigation.
Topics: Asthma; Biomarkers; Breath Tests; Dinoprost; Exhalation; Female; Healthy Volunteers; Humans; Inflammation; Lung; Male; Nitric Oxide; Oxidative Stress; Reference Values; Sex Factors
PubMed: 32481492
DOI: 10.3390/ijms21113822 -
Toxicology Letters Aug 2020Oxidative stress is defined as an imbalance between the production and elimination of reactive oxygen species (ROS) are associated with various inflammation-related... (Meta-Analysis)
Meta-Analysis
Oxidative stress is defined as an imbalance between the production and elimination of reactive oxygen species (ROS) are associated with various inflammation-related human disease. ROS can oxidize lipids, which subsequently undergo fragmentation to produce F2-isoprostanes (F2-IsoPs). Eight-isoprostane is one of the most extensively studied F2-IsoPs and the most commonly used biomarker for the assessment of oxidative stress in human studies. This urinary biomarker is quantified using either chemical or immunological techniques. A "physiological" range for 8-isoprostanes is needed to use this biomarker as a measure of excess oxidative stress originating from occupational exposures. However, ranges reported in the literature are inconsistent. We designed a standardized protocol of a systematic review and meta-analysis to assess baseline values for 8-isoprostane concentrations in urine of healthy adults and identify determinants of their inter- and intra-individual variability. We searched PubMed from journal inception and up to April 2019, and screened articles for studies containing F2-IsoPs concentrations in urine for healthy adult participants. We grouped studies in three biomarker groups: "8-isoprostane", "Isoprostanes" "15- F2t-Isoprostane". We computed geometric mean (GM) and geometric standard deviation (GSD) as the basis for the meta-analysis. Of the initial 1849 articles retrieved, 63 studies were included and 107 subgroups within these study populations were identified. We stratified the subgroups analyzed with the chemical methods by body mass index (BMI) reported. We provide pooled GM values for urinary 8-isoprostane concentrations in healthy adults, separately for chemical and immunological analysis in this review. The interquartile range (IQR) in subgroups with a mean BMI below 25 measured using chemical methods was 0.18 to 0.40 μg/g creatinine. We show that there is a significant positive association between BMI and urinary 8-isoprostane concentrations. We recommend adjusting urinary 8-isoprostane concentrations in spot urine with creatinine, quantifying 8-isoprostane with chemical analytical methods, and reporting results as median and quartiles. This will help in comparing results across studies.
Topics: Adult; Biomarkers; Dinoprost; Environmental Exposure; Humans; Oxidative Stress; Smoking; Xenobiotics
PubMed: 32320775
DOI: 10.1016/j.toxlet.2020.04.006 -
Journal of the American Academy of... Mar 2018
Review
Topics: 11-beta-Hydroxysteroid Dehydrogenases; Alopecia Areata; Anthralin; Bimatoprost; Cyclopropanes; Dermatologic Agents; Drug Therapy, Combination; Eyebrows; Eyelashes; Facial Dermatoses; Humans; Latanoprost; Minoxidil; Photosensitizing Agents; Prostaglandins F, Synthetic
PubMed: 28987491
DOI: 10.1016/j.jaad.2017.09.054 -
Journal of Dairy Science May 2017Presynchronization of cows with 2 injections of prostaglandin administered 14 d apart (Presynch-Ovsynch) is a widely adopted procedure to increase pregnancy per... (Meta-Analysis)
Meta-Analysis
Evaluation of prostaglandin F versus prostaglandin F plus gonadotropin-releasing hormone as Presynch methods preceding an Ovsynch in lactating dairy cows: A meta-analysis.
Presynchronization of cows with 2 injections of prostaglandin administered 14 d apart (Presynch-Ovsynch) is a widely adopted procedure to increase pregnancy per artificial insemination (P/AI) at first service. Recently, a presynchronization protocol including GnRH and PGF (Double-Ovsynch; GnRH, 7 d, PGF, 3 d, GnRH) followed 7 d later by an Ovsynch protocol was introduced to overcome the limitations of PGF-based protocols for presynchronization of anovular cows and to precisely set up cows on d 7 of the estrous cycle when the Ovsynch is initiated. A systematic review of the literature and a meta-analytical assessment was performed with the objective to compare the reproductive performance of lactating dairy cows presynchronized with these 2 protocols for the first timed AI (TAI) considering parity-specific effects. A fixed or a random effects meta-analysis was used based on the heterogeneity among the experimental groups. Reproductive outcomes of interest were P/AI measured on d 32 (28-42) and pregnancy loss between d 32 and 60 (42-74) of gestation. A total of 25 articles with 27 experimental groups from 63 herds including 21,046 cows submitted to first TAI using either a Presynch-Ovsynch or a Double-Ovsynch protocol were reviewed. Results for P/AI were then categorized by parity if available. Information was available for P/AI for 7,400 and 10,999 primiparous and multiparous cows, respectively. Information regarding pregnancy loss was available for 7,477 cows. In the random effects model for all cows, the overall proportion of P/AI was 41.7% [95% confidence interval (CI): 39.1-44.3; n = 8,213] and 46.2% (95% CI: 41.9-50.5; n = 12,833) on d 32 after TAI for Presynch-Ovsynch and Double-Ovsynch, respectively. In the random effects model for primiparous cows, the overall proportion of P/AI was 43.4% (95% CI: 36.2-47.7; n = 2,614) and 51.4% (95% CI: 47.4-55.4; n = 4,786) on d 32 after TAI for Presynch-Ovsynch and Double-Ovsynch, respectively. In the random effects model for multiparous cows, the overall proportion of P/AI was 39.2% (95% CI: 36.2-42.3; n = 3,411) and 41.4% (95% CI: 36.4-46.4; n = 7,588) on d 32 after TAI for Presynch-Ovsynch and Double-Ovsynch, respectively. The overall proportion of pregnancy loss was 11.3% (95% CI: 7.6-15.7; n = 3,247) and 11.7% (95% CI: 9.3-14.3; n = 4,230) on d 60 after AI for Presynch-Ovsynch to and Double-Ovsynch, respectively. Substantial heterogeneity existed among the experimental groups regarding P/AI and pregnancy loss. In summary, a benefit was detected for P/AI in primiparous cows presynchronized with a Double-Ovsynch protocol for the first TAI, but this benefit was not observed in multiparous cows.
Topics: Abortion, Veterinary; Animals; Cattle; Dinoprost; Estrus Synchronization; Female; Gonadotropin-Releasing Hormone; Insemination, Artificial; Lactation; Progesterone
PubMed: 28318589
DOI: 10.3168/jds.2016-11956