Dataset Information

Tear biomarkers in latanoprost and bimatoprost treated eyes.

ABSTRACT:

Purpose

Prostaglandin analogues (PGA's) are the mainstay and first line of treatment in current glaucoma practise. Though latanoprost and bimatoprost are the most commonly used PGA's with minimal side effects at lower concentrations like bimaotoprost 0.01%, direct comparison of their cytokine/MMP profile in tears has not been evaluated earlier. The study intends to ascribe PGA to the upregulation of MMPs, Cytokines and Chemokines mediating varied pathways to result in side effects of the drugs.

Methods

Tear sample collection was done from outer canthus of 30 eyes of 30 patients (primary open angle glaucoma (n = 26 and n' = 20), normal tension glaucoma (n = 4 and n' = 10), in latanoprost (n) 0.005% and bimatoprost (n') 0.01% group respectively, with a mean age of 62±10.5 years) on >6 months of PGA use using Tear floTM Schirmer filter strip. Tear samples from 30 eyes of 30 cataract patients without drug treatment were used as the control. Gelatinolytic activity of MMP-9 and MMP-2 were examined by substrate gelatine zymography MMP-1 and TIMP-1 concentrations from tears samples with PGAs were evaluated by ELISA while cytokine concentration in the eluted tears was evaluated using a convenient bioplex kit assay (Milliplex MAP kit, HCYTMAG-60K-PX41, Millipore, Massachusetts, United States). The mean duration of use of PGA in both groups did not differ significantly (median 1.3 years in bimatoprost and 1.1 years in latanoprost eyes, p = 0.6).

Results

The tear MMP-9 expression was higher in eyes receiving latanoprost while the MMP-2 expression was higher in eyes receiving bimatoprost with MMP1 protein levels being higher in the former. Latanoprost treated eyes had marginally elevated tear cytokines involved in tissue remodelling while bimatoprost eyes showed elevated cytokines regulating allergic pathways.

Conclusion

Differential cytokine and MMP expression indicates differential signalling pathways mediating different cellular effects (evident as clinical and side effects) with the two drugs which can be explored further.

SUBMITTER: Reddy S

PROVIDER: S-EPMC6078293 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Tear biomarkers in latanoprost and bimatoprost treated eyes.

Reddy Shweta S Sahay Prity P Padhy Debananda D Sarangi Sarada S Suar Mrutyunjay M Modak Rahul R Rao Aparna A

PloS one 20180806 8

<h4>Purpose</h4>Prostaglandin analogues (PGA's) are the mainstay and first line of treatment in current glaucoma practise. Though latanoprost and bimatoprost are the most commonly used PGA's with minimal side effects at lower concentrations like bimaotoprost 0.01%, direct comparison of their cytokine/MMP profile in tears has not been evaluated earlier. The study intends to ascribe PGA to the upregulation of MMPs, Cytokines and Chemokines mediating varied pathways to result in side effects of the ...[more]

PMID: 30080906

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Project description:BACKGROUND:The purpose of this study was to evaluate the intraocular pressure (IOP)-lowering efficacy and safety of bimatoprost 0.01% or 0.03% as monotherapy in patients treated with latanoprost 0.005% monotherapy who require additional IOP lowering for their ocular hypertension or open-angle glaucoma. METHODS:Two prospective, investigator-masked, randomized, parallel-group, multicenter studies enrolled patients with baseline IOP ?20 mmHg after ?30 days of latanoprost 0.005% monotherapy. Patients were randomized to 12 weeks of study treatment (study 1, bimatoprost 0.01% once daily or bimatoprost 0.01% once daily plus brimonidine 0.1% three times daily; study 2, bimatoprost 0.03% once daily or bimatoprost 0.03% once daily plus fixed-combination brimonidine 0.2%/timolol 0.5% twice daily). Patient evaluations at weeks 4 and 12 included IOP at 8 am, 10 am, and 4 pm and safety assessments. Results in the monotherapy study arms (bimatoprost 0.01% or 0.03%) are presented. RESULTS:Latanoprost-treated baseline mean diurnal IOP (± standard error of the mean) was 22.2±0.3 mmHg and 22.1±0.4 mmHg in the bimatoprost 0.01% and bimatoprost 0.03% treatment arms, respectively (P=0.957). In both treatment arms, mean (± standard error of the mean) reduction in IOP from latanoprost-treated baseline was statistically significant at each time point at both follow-up visits (P<0.001), ranging from 3.7±0.4 (17.0%) mmHg to 4.4±0.4 (19.9%) mmHg with bimatoprost 0.01% and from 2.8±0.5 (12.8%) mmHg to 3.9±0.5 (16.7%) mmHg with bimatoprost 0.03%. Mean percentage IOP reduction from latanoprost-treated baseline was numerically greater with bimatoprost 0.01% than with bimatoprost 0.03% throughout follow-up. The incidence of conjunctival hyperemia of mild or greater severity increased from latanoprost baseline after 12 weeks of treatment only in the bimatoprost 0.03% treatment arm. CONCLUSION:Many patients who do not reach their target IOP on latanoprost can achieve additional IOP lowering and maintain monotherapy by replacing latanoprost with bimatoprost. Reductions in IOP from latanoprost baseline were larger with bimatoprost 0.01% than with bimatoprost 0.03%, and bimatoprost 0.01% had a more favorable tolerability profile.

Project description:AimWithin the clinical setting, some patients have been identified as lacking in response to PGAs. This meta-analysis study aimed to evaluate the responsiveness of latanoprost, travoprost, bimatoprost, and tafluprost in OAG/OHT patients, latanoprost nonresponders (LNRs), and the IOP-reducing efficacy and safety.MethodsA literature search was conducted on PubMed, Embase, and the Cochrane Controlled Trials Register. The primary clinical endpoint was the number of responders at the end of the study. The secondary clinical endpoint was the IOP reduction at the endpoint from baseline. Safety evaluation included five common adverse events: conjunctival hyperemia, hypertrichosis, ocular burning, ocular itching, and foreign-body sensation.ResultsEleven articles containing ten RCTs were included in this meta-analysis study. The results highlighted that, in the OAG/OHT population, there was no statistically significant difference in the responsiveness of the four PGAs. Bimatoprost had a better IOP-reducing efficacy than latanoprost. There was no significant difference in the IOP-reducing efficacy of travoprost, latanoprost, and tafluprost. In LNRs, the responsiveness of bimatoprost, travoprost, and latanoprost did not show statistical differences. Bimatoprost reduced IOP with a greater extent than latanoprost and travoprost in LNRs, while there was no significant difference in the IOP-reducing efficacy of travoprost and latanoprost. No serious adverse events occurred with the treatment of the four PGAs. The prevalence of conjunctival hyperemia due to bimatoprost or tafluprost was significantly higher than that of latanoprost. Other adverse events had no significant difference between the four drugs.ConclusionThe existing studies cannot prove that latanoprost, travoprost, bimatoprost, and tafluprost have different responsiveness in OAG/OHT patients. Switching to bimatoprost or travoprost cannot achieve a significant improvement in responsiveness in LNRs. Bimatoprost has a better IOP-reducing efficacy than latanoprost and travoprost. No serious adverse events occurred during treatment with any medication we studied.

Project description:INTRODUCTION:The preservative benzalkonium chloride (BAK) is used to preserve several topical, intraocular pressure (IOP)-lowering glaucoma medications but can cause tolerability concerns that may lead to decreased adherence to treatment and ultimately diminish the effectiveness of IOP control. The study aimed to determine the efficacy and tolerability of BAK-free travoprost preserved with polyquaternium-1 in glaucoma patients switched from BAK-preserved latanoprost or bimatoprost. METHODS:This 12-week, open-label study was conducted in Europe between December 2011 and February 2013. We enrolled adult patients with open-angle glaucoma or ocular hypertension who were receiving BAK-preserved latanoprost 0.005% or bimatoprost 0.01% and, in the opinion of the investigator, would benefit from transition to BAK-free travoprost 0.004% preserved with polyquaternium-1 because of tolerability concerns. Assessments included IOP, proportion of patients with IOP ?18 mmHg, ocular surface status, hyperemia, patient treatment preference, and adherence. Adverse events were recorded throughout the study. RESULTS:Of the 202 patients screened, 187 patients were included in the intent-to-treat population (mean age, 66.6 years; range, 19-90 years). The mean IOP significantly reduced from baseline (17.0 mmHg) to week 6 (mean change, -1.17 mmHg; P<0.001) and week 12 (-1.16 mmHg; P<0.001). At week 12, more patients achieved IOP ?18 mmHg (81.2% versus 73.3% at baseline), and ocular surface disease severity improved from baseline to week 12. Most patients preferred BAK-free travoprost (74.9%) versus their previous medication and were very confident in their adherence (84.1%). Reduced visual acuity and eye pruritus were the most common adverse events (2.5% each). CONCLUSION:BAK-free travoprost 0.004% preserved with polyquaternium-1 was efficacious and well tolerated and may be an advantageous prostaglandin analog option for patients with open-angle glaucoma or ocular hypertension who are intolerant to BAK-preserved latanoprost or bimatoprost.

Project description:PurposeKeratoconus (KC) is a corneal ectasia characterized by structural changes, resulting in progressive thinning and biomechanical weakening that can lead to worsening visual acuity due to irregular astigmatism. Corneal collagen Crosslinking (CXL) and Intracorneal Ring Segment (ICRS) are widely used treatments in KC disease, but the alterations they cause in biomechanical mediators are still poorly understood. The aim of this study was to analyze the tear proteome profile before and after treatments to identify biomarkers altered by surgery.Materials and methodsAn observational, prospective, case-control pilot study was conducted, analyzing tear samples from KC patients by nano-liquid chromatography-mass spectrometry (nLC-MS/MS). Data are available via ProteomeXchange with identifier PXD035655. Patients with KC who underwent ICRS surgery (n = 4), CXL (n = 4), and healthy subjects (Ctrl, n = 4) were included in this study. Clinical parameters were measured and tear samples were collected before and 18 months after surgery. Proteins with ≥2 expression change and p-value < 0.05 between groups and times were selected to study their role in post-operative corneal changes.ResultsThese analyses led to the identification of 447 tear proteins, some of which were dysregulated in KC patients. In comparisons between the two surgical groups and Ctrls, the biological processes that were altered in KC patients at baseline were those that were dysregulated as a consequence of the disease and not of the surgical intervention. Among the biological processes seen to be altered were: immune responses, cytoskeleton components, protein synthesis and metabolic reactions. When comparing the two treatment groups (ICRS and CXL), the process related to cytoskeleton components was the most altered, probably due to corneal thinning which was more pronounced in patients undergoing CXL.ConclusionThe changes observed in tears after 18 months post-operatively could be due to the treatments performed and the pathology. Among the deregulated proteins detected, A-kinase anchor protein 13 (AKAP-13) deserves special attention for its involvement in corneal thinning, and for its strong overexpression in the tears of patients with more active KC and faster disease progression. However, it should be kept in mind that this is a pilot study conducted in a small number of patients.

Dataset Information

Tear biomarkers in latanoprost and bimatoprost treated eyes.

Purpose

Methods

Results

Conclusion

Publications

Tear biomarkers in latanoprost and bimatoprost treated eyes.

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