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International Journal of Molecular... Apr 2024Melatonin's cytoprotective properties may have therapeutic implications in treating ocular diseases like glaucoma and age-related macular degeneration. Literature data... (Review)
Review
Melatonin's cytoprotective properties may have therapeutic implications in treating ocular diseases like glaucoma and age-related macular degeneration. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. This study aims to summarize the screened articles on melatonin's clinical, pharmacological, and formulation evaluation in treating ocular disorders. The identification of relevant studies on the topic in focus was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. The studies were searched in the following databases and web search engines: Pubmed, Scopus, Science Direct, Web of Science, Reaxys, Google Scholar, Google Patents, Espacenet, and Patentscope. The search time interval was 2013-2023, with the following keywords: melatonin AND ocular OR ophthalmic AND formulation OR insert AND disease. Our key conclusion was that using melatonin-loaded nano-delivery systems enabled the improved permeation of the molecule into intraocular tissues and assured controlled release profiles. Although preclinical studies have demonstrated the efficacy of developed formulations, a considerable gap has been observed in the clinical translation of the results. To overcome this failure, revising the preclinical experimental phase might be useful by selecting endpoints close to clinical ones.
Topics: Humans; Melatonin; Eye; Glaucoma; Face; Databases, Factual
PubMed: 38612812
DOI: 10.3390/ijms25073999 -
Statistics in Medicine Sep 2011Mixed treatment comparison (MTC) meta-analyses estimate relative treatment effects from networks of evidence while preserving randomisation. We extend the MTC framework... (Meta-Analysis)
Meta-Analysis Review
Mixed treatment comparison (MTC) meta-analyses estimate relative treatment effects from networks of evidence while preserving randomisation. We extend the MTC framework to allow for repeated measurements of a continuous endpoint that varies over time. We used, as a case study, a systematic review and meta-analysis of intraocular pressure (IOP) measurements from randomised controlled trials evaluating topical ocular hypotensives in primary open-angle glaucoma or ocular hypertension because IOP varies over the day and over the treatment course, and repeated measurements are frequently reported. We adopted models for conducting MTC in WinBUGS (The BUGS Project, Cambridge, UK) to allow for repeated IOP measurements and to impute missing standard deviations of the raw data using the predictive distribution from observations with standard deviations. A flexible model with an unconstrained baseline for IOP variations over time and time-invariant random treatment effects fitted the data well. We also adopted repeated measures models to allow for class effects; assuming treatment effects to be exchangeable within classes slightly improved model fit but could bias estimated treatment effects if exchangeability assumptions were not valid. We enabled all timepoints to be included in the analysis, allowing for repeated measures to increase precision around treatment effects and avoid bias associated with selecting timepoints for meta-analysis.The methods we developed for modelling repeated measures and allowing for missing data may be adapted for use in other MTC meta-analyses.
Topics: Antihypertensive Agents; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Randomized Controlled Trials as Topic; Software
PubMed: 21728183
DOI: 10.1002/sim.4284 -
Biomedical Engineering Online Dec 2023Artificial intelligence (AI) has shown excellent diagnostic performance in detecting various complex problems related to many areas of healthcare including... (Review)
Review
Artificial intelligence (AI) has shown excellent diagnostic performance in detecting various complex problems related to many areas of healthcare including ophthalmology. AI diagnostic systems developed from fundus images have become state-of-the-art tools in diagnosing retinal conditions and glaucoma as well as other ocular diseases. However, designing and implementing AI models using large imaging data is challenging. In this study, we review different machine learning (ML) and deep learning (DL) techniques applied to multiple modalities of retinal data, such as fundus images and visual fields for glaucoma detection, progression assessment, staging and so on. We summarize findings and provide several taxonomies to help the reader understand the evolution of conventional and emerging AI models in glaucoma. We discuss opportunities and challenges facing AI application in glaucoma and highlight some key themes from the existing literature that may help to explore future studies. Our goal in this systematic review is to help readers and researchers to understand critical aspects of AI related to glaucoma as well as determine the necessary steps and requirements for the successful development of AI models in glaucoma.
Topics: Humans; Artificial Intelligence; Deep Learning; Glaucoma; Machine Learning; Ophthalmology
PubMed: 38102597
DOI: 10.1186/s12938-023-01187-8 -
Medicine Jul 2019To evaluated and compared the efficacy and safety of 3 prostaglandin analogues (0.005% latanoprost, 0.004% travoprost, and 0.03% bimatoprost) in treatment of primary... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluated and compared the efficacy and safety of 3 prostaglandin analogues (0.005% latanoprost, 0.004% travoprost, and 0.03% bimatoprost) in treatment of primary open-angle glaucoma (POAG) or ocular hypertension (OHT).
METHODS
PubMed, Embase, Cochrane library, Web of science, CNKI, Wanfang, and Vip database, published between January 1, 2000 and June 1, 2018, were systematically examined for randomized controlled trials (RCT) based on prostaglandin analogues for POAG or OHT treatment. Statistical analyses including weighted mean difference (WMD) calculation and odds ratio (OR) were performed using Review Manager Software version 5.3.
RESULT
The 17 studies were included in this analysis (N = 2433 participants) with 1∼12 months' follow-ups. The difference of intraocular pressure (IOP) reduction between latanoprost and travoprost group had not significant; there was significant difference of IOP reduction between latanoprost and bimatoprost group in the third month and sixth month; Travoprost was significantly different from bimatoprost in reducing IOP in the third month. Travoprost revealed an elevated risk of conjunctival hyperemia compared with latanoprost. An elevated risk of conjunctival hyperemia and growth of lashes compared with latanoprost. Bimatoprost shows lower ocular tolerability with higher incidence of side effects such as conjunctival hyperemia.
CONCLUSIONS
0.03% bimatoprost appears more effective following long time use (3 and 6 month post-treatment) for IOP control compared to 0.005% latanoprost, and is more effective compared to 0.004% travoprost after being used for a certain period of time (3 months post-treatment); nevertheless, 0.005% latanoprost is better tolerated in patients with POAG or OHT.
Topics: Bimatoprost; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Prostaglandins, Synthetic; Randomized Controlled Trials as Topic; Travoprost
PubMed: 31348303
DOI: 10.1097/MD.0000000000016597 -
The British Journal of Ophthalmology Aug 2020Of the side effects of prostaglandin analogues (PGAs), uveitis and cystoid macular oedema (CME) have significant potential for vision loss based on postmarket reports.... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Of the side effects of prostaglandin analogues (PGAs), uveitis and cystoid macular oedema (CME) have significant potential for vision loss based on postmarket reports. Caution has been advised due to concerns of macular oedema and uveitis. In this report, we researched and summarised the original data suggesting these effects and determined their incidence.
METHODS
Preferred Reporting Items for Systematic review and Meta-Analyses guidelines were followed. Studies evaluating topical PGAs in patients with ocular hypertension or open angle glaucoma were included. MEDLINE, PubMed, EMBASE, CINAHL, Web of Science, Cochrane Library, LILACS and ClinicalTrials.gov were searched between 1946 and 2019. Experimental studies, animal studies and randomised studies with other intraocular pressure-lowering eye drops were excluded.
RESULTS
214 studies (28 232 patients) met the inclusion criteria. Using prospective data, the incidence of uveitis and CME among PGA users were 62/28 232 (0.22%) and 25/28 232 (0.09%), respectively. A higher frequency of both uveitis and CME were found among latanoprost users compared with bimatoprost. There were 21 case studies reporting CME including 48 eyes in 43 patients. 47 of 48 eyes (97.9%) had previous incisional ocular surgery. 8 eyes were re-challenged, of which 7 (87.5%) recurred. 7 case studies reported uveitis in 15 eyes of 10 patients. 7 of 15 eyes (46.7%) were either pseudophakic or aphakic. 6 eyes were re-challenged, and all 6 (100%) recurred.
CONCLUSIONS
Cases of uveitis or CME revealed a confounding effect of ocular surgery, aphakia or subluxed intraocular lens. PGAs may be used in non-surgical patients without concern of causing CME or uveitis. The incidences of PGA-associated CME and uveitis are rare with limited prospective studies on the cause-effect relationship.
Topics: Administration, Ophthalmic; Bimatoprost; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Macular Edema; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins, Synthetic; Uveitis
PubMed: 32532763
DOI: 10.1136/bjophthalmol-2019-315280 -
Biology Direct Oct 2023The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56... (Meta-Analysis)
Meta-Analysis Review
The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. These drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. However, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. Genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. The present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 recommendations. The literature search was conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science and Public Health Genomics and Precision Health Knowledge Base up to June 14th, 2023. The search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. The results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. Moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG.PROSPERO registration: CRD42023434867.
Topics: Humans; Glaucoma, Open-Angle; Antihypertensive Agents; Genome-Wide Association Study; Timolol; Genotype
PubMed: 37833756
DOI: 10.1186/s13062-023-00423-4 -
The Cochrane Database of Systematic... Mar 2023Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be associated with significant complications that uncommonly cause permanent vision loss. Complications include elevated intraocular pressure, corneal blood staining, anterior and posterior synechiae, and optic nerve atrophy. People with sickle cell trait or disease may be particularly susceptible to increases in intraocular pressure and optic atrophy. Rebleeding is associated with an increase in the rate and severity of complications.
OBJECTIVES
To assess the effectiveness of various medical interventions in the management of traumatic hyphema.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 3); MEDLINE Ovid; Embase.com; PubMed (1948 to March 2022); the ISRCTN registry; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The last date of the search was 22 March 2022.
SELECTION CRITERIA
Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. We included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical interventions or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions on age, gender, severity of the closed-globe trauma, or level of visual acuity at time of enrollment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane and assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included 23 randomized and seven quasi-randomized studies with a total of 2969 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest. We found no evidence of an effect on visual acuity for any intervention, whether measured within two weeks (short term) or for longer periods. In a meta-analysis of two trials, we found no evidence of an effect of aminocaproic acid on long-term visual acuity (RR 1.03, 95% confidence interval (CI) 0.82 to 1.29) or final visual acuity measured up to three years after the hyphema (RR 1.05, 95% CI 0.93 to 1.18). Oral tranexamic acid appeared to provide little to no benefit on visual acuity in four trials (RR 1.12, 95% CI 1.00 to 1.25). The remaining trials evaluated the effects of various interventions on short-term visual acuity; none of these interventions was measured in more than one trial. No intervention showed a statistically significant effect (RRs ranged from 0.75 to 1.10). Similarly, visual acuity measured for longer periods in four trials evaluating different interventions was also not statistically significant (RRs ranged from 0.82 to 1.02). The evidence supporting these findings was of low or very low certainty. Systemic aminocaproic acid reduced the rate of recurrent hemorrhage (RR 0.28, 95% CI 0.13 to 0.60), as assessed in six trials with 330 participants. A sensitivity analysis omitting two studies not using an intention-to-treat analysis reduced the strength of the evidence (RR 0.43, 95% CI 0.17 to 1.08). We obtained similar results for topical aminocaproic acid (RR 0.48, 95% CI 0.20 to 1.10) in two trials with 131 participants. We assessed the certainty of the evidence as low. Systemic tranexamic acid had a significant effect in reducing the rate of secondary hemorrhage (RR 0.33, 95% CI 0.21 to 0.53) in seven trials with 754 participants, as did aminomethylbenzoic acid (RR 0.10, 95% CI 0.02 to 0.41), as reported in one study. Evidence to support an associated reduction in risk of complications from secondary hemorrhage (i.e. corneal blood staining, peripheral anterior synechiae, elevated intraocular pressure, and development of optic atrophy) by antifibrinolytics was limited by the small number of these events. Use of aminocaproic acid was associated with increased nausea, vomiting, and other adverse events compared with placebo. We found no evidence of an effect on the number of adverse events with the use of systemic versus topical aminocaproic acid or with standard versus lower drug dose. The number of days for the primary hyphema to resolve appeared to be longer with the use of systemic aminocaproic acid compared with no use, but this outcome was not altered by any other intervention. The available evidence on usage of systemic or topical corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to the small numbers of participants and events in the trials. We found no evidence of an effect between a single versus binocular patch on the risk of secondary hemorrhage or time to rebleed. We also found no evidence of an effect on the risk of secondary hemorrhage between ambulation and complete bed rest.
AUTHORS' CONCLUSIONS
We found no evidence of an effect on visual acuity of any of the interventions evaluated in this review. Although the evidence was limited, people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhage. However, hyphema took longer to clear in people treated with systemic aminocaproic acid. There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema, other than possibly to reduce the rate of secondary hemorrhage. The potentially long-term deleterious effects of secondary hemorrhage are unknown. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.
Topics: Humans; Adrenal Cortex Hormones; Aminocaproic Acid; Antifibrinolytic Agents; Aspirin; Glaucoma; Hyphema; Mydriatics; Tranexamic Acid
PubMed: 36912744
DOI: 10.1002/14651858.CD005431.pub5 -
European Journal of Medical Research Mar 2023Glaucoma is a chronic neurodegenerative process of the optic nerve that is the leading cause of blindness worldwide, and early diagnosis of the disease could greatly... (Meta-Analysis)
Meta-Analysis Review
Glaucoma is a chronic neurodegenerative process of the optic nerve that is the leading cause of blindness worldwide, and early diagnosis of the disease could greatly affect patients' prognoses. The pathophysiology of glaucoma is complicated by a combination of genetic and epigenetic factors. Deciphering the early diagnostic biomarkers in glaucoma could attenuate the disease's global burden and help us understand the exact mechanisms involved in glaucoma. The microRNAs are members of a larger family of non-coding RNAs that play an essential role in the epigenetic basis of glaucoma. A systematic study and meta-analysis of diagnostic microRNAs in glaucoma, jointly with network analysis of target genes, were carried out on published papers assessing differentially expressed microRNAs in human subjects. In total, 321 articles were found, and, after screening, six studies were eligible for further analysis. 52 differentially expressed microRNAs were found, of which 28 and 24 were up-regulated and down-regulated, respectively. Only 12 microRNAs were qualified for meta-analysis, with overall sensitivity and specificity of 80% and 74%, respectively. Then, using network analysis, it became apparent that the VEGF-A, AKT1, CXCL12, and HRAS genes were the most important targets for the microRNAs. Perturbations in WNT signaling, protein transport, and extracellular matrix organization pathways were discovered to be important in the etiology of glaucoma using the community detection approach. This study tries to uncover the promising microRNAs and their target genes that govern the epigenetics of glaucoma.
Topics: Humans; MicroRNAs; Glaucoma; Prognosis; Early Diagnosis
PubMed: 36973823
DOI: 10.1186/s40001-023-01093-8 -
American Journal of Ophthalmology Mar 2024Many studies have examined the ocular pulse amplitude (OPA) to better understand its physiology and clinical relevance, but the papers are scattered, not consistently... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Many studies have examined the ocular pulse amplitude (OPA) to better understand its physiology and clinical relevance, but the papers are scattered, not consistently indexed, and sometimes difficult to locate. We aimed to identify and summarize the relevant published evidence on OPA and, in a meta-analysis, outline specific differences of this parameter between healthy individual, primary open-angle glaucoma, normal-tension glaucoma, ocular hypertension, and cataract patients.
DESIGN
Systematic review and meta-analysis.
METHODS
A thorough literature search and data extraction were conducted by 2 reviewers independently. Reports on OPA measured by the dynamic contour tonometry in conjunction with different ocular and systemic diseases or potential influencing factors were included.
RESULTS
Of the 527 initially found reports, 97 met the inclusion criteria assessing 31 clinical conditions. A meta-analysis based on 6850 eyes and 106 study arms (68.8%) revealed differences in mean OPA values in millimeters of mercury between various entities. Among healthy eyes, the OPA was 2.58 mm Hg (95% CI: 2.45-2.71), whereas OPA values were higher in glaucoma (unspecified glaucoma 2.73 mm Hg, 95% CI: 2.38-3.08; normal-tension glaucoma 2.66 mm Hg, 95% CI: 2.36-2.97; and primary open-angle glaucoma 2.92 mm Hg, 95% CI: 2.75-3.08). Although ocular hypertension showed the highest OPA values (3.53 mm Hg, 95% CI: 3.05-4.01), the lowest values were found in cataract eyes (2.26 mm Hg, 95% CI: 1.57-2.94).
CONCLUSION
We found different OPA values characteristic of different clinical entities, with above-normal values in glaucoma and ocular hypertension and lower values in cataract patients. Our work is intended for clinicians and researchers who want to get a quick overview of the available evidence or who need statistical data on OPA distributions in individual diseases.
Topics: Humans; Intraocular Pressure; Glaucoma, Open-Angle; Healthy Volunteers; Blood Pressure; Glaucoma; Ocular Hypertension; Tonometry, Ocular; Low Tension Glaucoma; Cataract
PubMed: 37898282
DOI: 10.1016/j.ajo.2023.10.014 -
Current Medical Research and Opinion Aug 2019We compared the benefits and harms of topical interventions for ocular perfusion pressure in open angle glaucoma. We searched the databases MEDLINE, EMBASE and CENTRAL... (Meta-Analysis)
Meta-Analysis
We compared the benefits and harms of topical interventions for ocular perfusion pressure in open angle glaucoma. We searched the databases MEDLINE, EMBASE and CENTRAL for randomized controlled trials comparing topical hypotensive agents in glaucoma. Of the 9433 citations identified, 10 randomized controlled trials were included. We summarized data using random effects meta-analysis for post-treatment mean ocular perfusion pressure and using relative risk for adverse events. Ten trials (416 patients) were included. The quality of included trials was low to moderate. There was a higher post-treatment ocular perfusion pressure with bimatoprost compared to timolol (1 trial, 32 patients, mean difference - 4.00 mmHg, 95% confidence interval -7.01 to -0.99, = .009); heterogeneity was not significant ( = 41%, = 13.55, = .09). Prostaglandins as a class had higher post-treatment mean ocular perfusion pressure compared to alternative interventions (5 trials, 147 patients, mean difference 2.19 mmHg, 95% confidence interval 0.67-3.70, = .005); heterogeneity in the subgroup analysis was not significant ( = 10%, = 4.47, = .35). Adverse events were found to be significant in only one of the studies comparing latanoprost to brimonidine, relative risk 3.67 (standard error 0.59, = .03). We identified low to moderate quality evidence describing post-intervention mean ocular perfusion pressure in open angle glaucoma. Bimatoprost increases mean ocular perfusion pressure when compared to timolol. As a class, prostaglandins increase mean ocular perfusion pressure. Prostaglandins may provide beneficial ocular perfusion pressure profiles compared to alternative agents.
Topics: Administration, Topical; Antihypertensive Agents; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30880485
DOI: 10.1080/03007995.2019.1595553