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The Cochrane Database of Systematic... Jun 2022Glaucoma is a group of optic neuropathies characterized by progressive degeneration of the retinal ganglion cells, axonal loss and irreversible visual field defects.... (Review)
Review
BACKGROUND
Glaucoma is a group of optic neuropathies characterized by progressive degeneration of the retinal ganglion cells, axonal loss and irreversible visual field defects. Glaucoma is classified as primary or secondary, and worldwide, primary glaucoma is a leading cause of irreversible blindness. Several subtypes of glaucoma exist, and primary open-angle glaucoma (POAG) is the most common. The etiology of POAG is unknown, but current treatments aim to reduce intraocular pressure (IOP), thus preventing the onset and progression of the disease. Compared with traditional antiglaucomatous treatments, rho kinase inhibitors (ROKi) have a different pharmacodynamic. ROKi is the only current treatment that effectively lowers IOP by modulating the drainage of aqueous humor through the trabecular meshwork and Schlemm's canal. As ROKi are introduced into the market more widely, it is important to assess the efficacy and potential AEs of the treatment.
OBJECTIVES
To compare the efficacy and safety of ROKi with placebo or other glaucoma medication in people diagnosed with open-angle glaucoma (OAG), primary open-angle glaucoma (POAG) or ocular hypertension (OHT).
SEARCH METHODS
We used standard Cochrane methods and searched databases on 11 December 2020.
SELECTION CRITERIA
We included randomized clinical trials examining commercially available ROKi-based monotherapy or combination therapy compared with placebo or other IOP-lowering medical treatments in people diagnosed with (P)OAG or OHT. We included trials where ROKi were administered according to official glaucoma guidelines. There were no restrictions regarding type, year or status of the publication.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Two review authors independently screened studies, extracted data, and evaluated risk of bias by using Cochrane's RoB 2 tool. MAIN RESULTS: We included 17 trials with 4953 participants diagnosed with (P)OAG or OHT. Fifteen were multicenter trials and 15 were masked trials. All participants were aged above 18 years. Trial duration varied from 24 hours to 12 months. Trials were conducted in the USA, Canada and Japan. Sixteen trials were funded by pharmaceutical companies, and one trial provided no information about funding sources. The trials compared ROKi monotherapy (netarsudil or ripasudil) or combination therapy with latanoprost (prostaglandin analog) or timolol (beta-blocker) with placebo, timolol, latanoprost or netarsudil. Reported outcomes were IOP and safety. Meta-analyses were applied to 13 trials (IOP reduction from baseline) and 15 trials (ocular AEs). Of the trials evaluating IOP, seven were at low risk, three had some concerns, and three were at high risk of bias. Three trials found that netarsudil monotherapy may be superior to placebo (mean difference [MD] 3.11 mmHg, 95% confidence interval [CI] 2.59 to 3.62; I = 0%; 155 participants; low-certainty evidence). Evidence from three trials found that timolol may be superior to netarsudil with an MD of 0.66 mmHg (95% CI 0.41 to 0.91; I = 0%; 1415 participants; low-certainty evidence). Evidence from four trials found that latanoprost may be superior to netarsudil with an MD of 0.97 mmHg (95% CI 0.67 to 1.27; I = 4%; 1283 participants; moderate-certainty evidence). Evidence from three trials showed that, compared with monotherapy with latanoprost, combination therapy with netarsudil and latanoprost probably led to an additional pooled mean IOP reduction from baseline of 1.64 mmHg (95% CI -2.16 to -1.11; 1114 participants). Evidence from three trials showed that, compared with monotherapy with netarsudil, combination therapy with netarsudil and latanoprost probably led to an additional pooled mean IOP reduction from baseline of 2.66 mmHg (95% CI -2.98 to -2.35; 1132 participants). The certainty of evidence was moderate. One trial showed that, compared with timolol monotherapy, combination therapy with ripasudil and timolol may lead to an IOP reduction from baseline of 0.75 mmHg (95% -1.29 to -CI 0.21; 208 participants). The certainty of evidence was moderate. Of the trials assessing total ocular AEs, three were at low risk, four had some concerns, and eight were at high risk of bias. We found very low-certainty evidence that netarsudil may lead to more ocular AEs compared with placebo, with 66 more ocular AEs per 100 person-months (95% CI 28 to 103; I = 86%; 4 trials, 188 participants). We found low-certainty evidence that netarsudil may lead to more ocular AEs compared with latanoprost, with 29 more ocular AEs per 100 person-months (95% CI 17 to 42; I = 95%; 4 trials, 1286 participants). We found moderate-certainty evidence that, compared with timolol, netarsudil probably led to 21 additional ocular AEs (95% CI 14 to 27; I = 93%; 4 trials, 1678 participants). Data from three trials (1132 participants) showed no evidence of differences in the incidence rate of AEs between combination therapy with netarsudil and latanoprost and netarsudil monotherapy (1 more event per 100 person-months, 95% CI 0 to 3); however, the certainty of evidence was low. Similarly, we found low-certainty evidence that, compared with latanoprost, combination therapy with netarsudil and latanoprost may cause 29 more ocular events per 100 person-months (95% CI 11 to 47; 3 trials, 1116 participants). We found moderate-certainty evidence that, compared with timolol monotherapy, combination therapy with ripasudil and timolol probably causes 35 more ocular events per 100 person-months (95% CI 25 to 45; 1 trial, 208 participants). In all included trials, ROKi was reportedly not associated with any particular serious AEs.
AUTHORS' CONCLUSIONS
The current evidence suggests that in people diagnosed with OHT or (P)OAG, the hypotensive effect of netarsudil may be inferior to latanoprost and slightly inferior to timolol. Combining netarsudil and latanoprost probably further reduces IOP compared with monotherapy. Netarsudil as mono- or combination therapy may result in more ocular AEs. However, the certainty of evidence was very low or low for all comparisons except timolol. In general, AEs were described as mild, transient, and reversible upon treatment discontinuation. ROKi was not associated with any particular serious AEs. Future trials of sufficient size and follow-up should be conducted to provide reliable information about glaucoma progression, relevant IOP measurements and a detailed description of AEs using similar terminology. This would ensure the robustness and confidence of the results and assess the intermediate- and long-term efficacy and safety of ROKi.
Topics: Glaucoma, Open-Angle; Humans; Ocular Hypertension; Randomized Controlled Trials as Topic; Treatment Outcome; rho-Associated Kinases
PubMed: 35686679
DOI: 10.1002/14651858.CD013817.pub2 -
European Journal of Ophthalmology Nov 2023To compare the VEGF levels in the aqueous humor of patients with Primary Open Angle Glaucoma (POAG) and non-glaucomatous eyes and reveal any potential statistically...
PURPOSE
To compare the VEGF levels in the aqueous humor of patients with Primary Open Angle Glaucoma (POAG) and non-glaucomatous eyes and reveal any potential statistically significant correlations.
METHODS
We searched PubMed, from inception to December 31, 2021. Key search terms included VEGF and Glaucoma. All relevant studies that evaluated the VEGF levels in patients with POAG and in the control group were included in this systematic review. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines were followed. Data were extracted independently by 2 authors. Heterogeneity was statistically quantified by Q, H, and statistics, and a meta-analysis was performed using the random-effects model.
RESULTS
Seven cross-sectional studies were included in the meta-analysis. 144 eyes were enrolled in the POAG group and 162 eyes in the control group. The random effect model showed no statistically significant difference between the two groups (SMD =0.284, 95% CI = -0.173 to 0.741; P = 0.223), but we noticed a trend towards elevated VEGF levels in the aqueous humor of POAG patients. Significant heterogeneity was detected (= 74.1%, P = 0.001).
CONCLUSIONS
This systematic review and meta-analysis indicates a trend towards elevated VEGF-A levels in the aqueous humor of patients with POAG and suggests a potential neuroprotective role of VEGF in patients with POAG. Future studies are required to evaluate the exact role of VEGF in POAG.
PubMed: 37038334
DOI: 10.1177/11206721231168146 -
Medicine Jul 2018Migraine is increasingly being reported as a risk factor for primary open angle glaucoma (POAG). However, studies aimed to investigate this association yielded... (Meta-Analysis)
Meta-Analysis Review
Migraine is increasingly being reported as a risk factor for primary open angle glaucoma (POAG). However, studies aimed to investigate this association yielded conflicting results. To assess the consistency of the data on the topic, we performed a systematic review and meta-analysis. A systematic literature search from Embase, Web of Science, and PubMed was performed to identify relevant studies on the relationship between migraine and POAG. Random effects models were used to estimate the pooled relative risks (RRs) with 95% confidence intervals (95% CIs) in this meta-analysis. A total of 11 studies meeting the inclusion criteria were included in this meta-analysis. Our findings showed an RR of developing POAG of 1.24 (95% CI = 1.12-1.37) in migraine patients. No evidence of significant heterogeneity was detected across studies (P = .071; I = 41.7%). This association was not modified by the glaucoma type of the included patients. A significant association was observed in case-control design studies, but not in cohort design studies. Little evidence of publication bias was found. The findings of this meta-analysis suggest that migraine can significantly increase the risk of the development of POAG. However, the cohort study design failed to identify this association. Whether migraines can significantly increase the risk of developing POAG is still controversial.
Topics: Glaucoma, Open-Angle; Humans; Incidence; Migraine Disorders; Risk Factors
PubMed: 29995778
DOI: 10.1097/MD.0000000000011377 -
International Journal of Ophthalmology 2022To assess the differences in average and sectoral peripapillary retinal nerve fiber layer (pRNFL) thickness using spectral domain optical coherence tomography (SD-OCT)...
Optical coherence tomography evaluation of retinal nerve fiber layer thickness in non-arteritic anterior ischemic optic neuropathy and primary open angle glaucoma: a systematic review and Meta-analysis.
AIM
To assess the differences in average and sectoral peripapillary retinal nerve fiber layer (pRNFL) thickness using spectral domain optical coherence tomography (SD-OCT) in patients with non-arteritic anterior ischemic neuropathy (NAION) compared with those with primary open angle glaucoma (POAG).
METHODS
A comprehensive literature search of the PubMed, Cochrane Library, and Embase databases were performed prior to October, 2021. Studies that compared the pRNFL thickness in NAION eyes with that in POAG eyes with matched mean deviation of the visual fields were included. The weighted mean difference (WMD) with 95% confidence interval (CI) was used to pool continuous outcomes.
RESULTS
Ten cross-sectional studies (11 datasets) comprising a total of 625 eyes (278 NAION eyes, 347 POAG eyes) were included in the qualitative and quantitative analyses. The pooled results demonstrated that the superior pRNFL was significantly thinner in NAION eyes than in POAG eyes (WMD=-6.40, 95%CI: -12.22 to -0.58, =0.031), whereas the inferior pRNFL was significant thinner in POAG eyes than in NAION eyes (WMD=11.10, 95%CI: 7.06 to 15.14, ≤0.001). No difference was noted concerning the average, nasal, and temporal pRNFL thickness (average: WMD=1.45, 95%CI: -0.75 to 3.66, =0.196; nasal: WMD=-2.12, 95%CI: -4.43 to 0.19, =0.072; temporal: WMD=-1.24, 95%CI: -3.96 to 1.47, =0.370).
CONCLUSION
SD-OCT based evaluation of inferior and superior pRNFL thickness can be potentially utilized to differentiate NAION from POAG, and help to understand the different pathophysiological mechanisms between these two diseases. Further longitudinal studies and studies using eight-quadrant or clock-hour classification method are required to validate the obtained findings.
PubMed: 36017036
DOI: 10.18240/ijo.2022.08.22 -
PloS One 2017The relationship between hypothyroidism and primary open angle glaucoma (POAG) has attracted intense interest recently, but the reported results have been controversial.... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The relationship between hypothyroidism and primary open angle glaucoma (POAG) has attracted intense interest recently, but the reported results have been controversial. This meta-analysis was carried out to determine the association between hypothyroidism and POAG.
METHODS
The literature was identified from three databases (Web of Science, Embase, and PubMed). The meta-analyses were performed using random-effects models, with results reported as adjusted odds ratios (ORs) with 95% confidence intervals (CI 95%).
RESULTS
A total of 11 studies meeting the inclusion criteria were included in the final meta-analysis. The pooled OR based on 11 risk estimates showed a statistically significant increased risk of POAG prevalence among individuals with hypothyroidism (OR = 1.64, 95% CI = 1.27-2.13). Substantial heterogeneity among these studies was detected (P < 0.001; I2 = 83.2%). Sub-group analysis revealed that the cohort studies and case-control studies showed a significant association between hypothyroidism and POAG, which was not observed in cross-sectional studies. There was no significant publication bias in this study.
CONCLUSIONS
The findings of this meta-analysis indicate that individuals with hypothyroidism have an increased risk of developing POAG.
Topics: Glaucoma, Open-Angle; Humans; Hypothyroidism; Risk Factors
PubMed: 29069095
DOI: 10.1371/journal.pone.0186634 -
PloS One 2014To determine the association between diabetes mellitus (DM) and primary open-angle glaucoma (POAG). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the association between diabetes mellitus (DM) and primary open-angle glaucoma (POAG).
METHODS
This is a systematic review and meta-analysis of case-control and cohort studies. The literature search included two databases (PubMed and Embase) and the reference lists of the retrieved studies. Separate meta-analyses for case-control studies and cohort studies were conducted using random-effects models, with results reported as adjusted odds ratios (ORs) and relative risks (RRs), respectively.
RESULTS
Thirteen studies--seven case-control studies and six population-based cohort studies--were included in this meta-analysis. The pooled RR of the association between DM and POAG based on the risk estimates of the six cohort studies was 1.40 (95% CI, 1.25-1.57). The pooled OR of the association between DM and POAG based on the risk estimates of the seven case-control studies was 1.49 (95% CI, 1.17-1.88). There was considerable heterogeneity among the case-control studies that reported an association between DM mellitus and POAG (P<0.001) and no significant heterogeneity among the cohort studies (P = 0.377). After omitting the case-control study that contributed significantly to the heterogeneity, the pooled OR for the association between DM and POAG was 1.35 (95% CI, 1.06-1.74).
CONCLUSIONS
Individuals with DM have an increased risk of developing POAG.
Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glaucoma, Open-Angle; Humans; Male; Middle Aged; Odds Ratio; Risk Factors
PubMed: 25137059
DOI: 10.1371/journal.pone.0102972 -
Acta Ophthalmologica May 2018To assess the efficacy and safety of different regimens, including monotherapy and double therapy, for primary open-angle glaucoma (POAG) or ocular hypertension. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To assess the efficacy and safety of different regimens, including monotherapy and double therapy, for primary open-angle glaucoma (POAG) or ocular hypertension.
METHODS
We searched PubMed, EMBASE and clinicaltrials.gov for studies that fit our inclusion criteria in this network meta-analysis. Randomized controlled trials that report data on efficacy and safety of medications for POAG or ocular hypertension are included. Data on intra-ocular pressure (IOP) lowering effect and incidence of adverse events including hyperaemia and ocular discomfort were extracted and used in mixed-comparison analysis.
RESULTS
This study includes 72 randomized trials. Data were available on 12 medical treatments of POAG or ocular hypertension. Of 66 possible comparisons of outcome efficacy, 15 treatments were compared directly. Compared to prostaglandin analogues (PGA), beta-blockers (BB) showed relatively weaker ability to lower IOP, followed by α2-adrenergic agonists (AA) and carbonic anhydrase inhibitors (CAI). For dual therapy, regimens composed of a combination of PGA with another treatment demonstrated more powerful IOP lowering efficacy, while the combination of two non-PGA drugs had lower efficacy in controlling IOP than PGA alone. There was no statistical significance in combinations that did not include PGA on efficacy of IOP control. In terms of tolerance, PGA alone leads to more severe hyperaemia than any other monotherapy regimen, while BBs have the lowest effect on the incidence of hyperaemia. Most dual therapy regimens containing PGA also lead to serious hyperaemia, with the exception of PGA + AA. Compared to regimens containing PGA, those with BB are less likely to cause hyperaemia.
CONCLUSION
Our network meta-analysis showed that PGAs provide best IOP lowering effect among all the monotherapy regimen. Combination of PGA and other category of drugs leads to better IOP decrease. Combination of BB and another non-PGA drug may have less ocular side-effects than PGA alone.
Topics: Antihypertensive Agents; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Network Meta-Analysis; Ocular Hypertension
PubMed: 29144028
DOI: 10.1111/aos.13568 -
Acta Ophthalmologica Sep 2018A common question of patients to their physician is what they can do themselves against glaucoma, except taking their daily medication. However, for ophthalmologists, it... (Review)
Review
PURPOSE
A common question of patients to their physician is what they can do themselves against glaucoma, except taking their daily medication. However, for ophthalmologists, it is often hard to give their patients an advice on their dietary intake. To help ophthalmologists in answering this question, an overview of the current scientific literature on the association of nutrients with glaucoma is presented.
METHODS
A comprehensive systematic review was conducted in which articles published up to September 2017 were identified in PubMed and reference lists. Nutrients were categorized into minerals and trace elements, nutrition with antioxidative properties and omega-fatty acids.
RESULTS
The literature search revealed a total of 407 articles of which a total of 46 met the inclusion criteria. Most of these articles studied the effect of nutrients on open-angle glaucoma. Many trace elements have been investigated in the literature, but the most interesting are selenium and iron (both may increase the risk of glaucoma). Investigated nutrients with antioxidative properties and omega-fatty acids included glutathione, nitric oxide, carotenoids, flavonoids, and omega-3 and omega-6 fatty acids. Of these, glutathione, nitric oxide, and flavonoids had a significant protective effect on glaucoma.
CONCLUSION
Intake of selenium and iron may increase the risk of glaucoma, though, only few studies have been done on this topic. Nitric oxide present in other dark green leafy vegetables seems to have a beneficial effect on glaucoma. However, the evidence for an association of dietary intake with glaucoma is still not strong. More (longitudinal and randomized clinical trials) studies are required to make the presented findings clinically applicable.
Topics: Diet; Disease Progression; Feeding Behavior; Glaucoma; Global Health; Humans; Intraocular Pressure; Morbidity; Prognosis
PubMed: 29461678
DOI: 10.1111/aos.13662 -
Nutrients Mar 2018The aim of is to determine the association of vitamins with glaucoma by performing a systematic review and meta-analyses. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The aim of is to determine the association of vitamins with glaucoma by performing a systematic review and meta-analyses.
METHODS
Studies on the relation of vitamins and glaucoma published up to December 2017 were identified in the PubMed and Embase database. Data on vitamins (method of assessment), glaucoma (type and method of assessment), study characteristics and quality were recorded. In case of multiple studies for one nutrient a meta-analysis was performed.
RESULTS
A total of 629 articles were identified of which 36 were included in the systematic review. The meta-analysis included five of them (940 open-angle glaucoma (OAG) cases and 123,697 controls in total) and resulted in an odds ratio [95% confidence interval] (OR [95% CI]) of 0.58 [0.37-0.91] for dietary vitamin A, though heterogeneity was high (I² = 51%). After omitting studies that contributed significantly to the heterogeneity, the pooled OR [95% CI] was 0.45 [0.30-0.68] for dietary vitamin A on OAG (I² = 0%). For vitamin B1, C and E no significant association with OAG was found (OR [95% CI]: 0.84 [0.47-1.51]; 0.68 [0.38-1.22]; 0.95 [0.75-1.19]; respectively). However, after addressing heterogeneity, vitamin C showed a protective effect as well. Especially, foods high in these vitamins (e.g., dark green vegetables) were protective for OAG.
CONCLUSIONS
Dietary intake of vitamin A and C showed a beneficial association with OAG; however, findings on blood levels of vitamins do not show a clear relation with OAG.
Topics: Adult; Aged; Ascorbic Acid; Chi-Square Distribution; Diet; Glaucoma, Open-Angle; Humans; Middle Aged; Odds Ratio; Prevalence; Prognosis; Protective Factors; Risk Factors; Vitamin A
PubMed: 29547516
DOI: 10.3390/nu10030359 -
The British Journal of Ophthalmology Jan 2016Systematic review of published population based surveys to examine the relationship between primary open angle glaucoma (POAG) prevalence and demographic factors. A... (Meta-Analysis)
Meta-Analysis Review
Systematic review of published population based surveys to examine the relationship between primary open angle glaucoma (POAG) prevalence and demographic factors. A literature search identified population-based studies with quantitative estimates of POAG prevalence (to October 2014). Multilevel binomial logistic regression of log-odds of POAG was used to examine the effect of age and gender among populations of different geographical and ethnic origins, adjusting for study design factors. Eighty-one studies were included (37 countries, 216 214 participants, 5266 POAG cases). Black populations showed highest POAG prevalence, with 5.2% (95% credible interval (CrI) 3.7%, 7.2%) at 60 years, rising to 12.2% (95% CrI 8.9% to 16.6%) at 80 years. Increase in POAG prevalence per decade of age was greatest among Hispanics (2.31, 95% CrI 2.12, 2.52) and White populations (1.99, 95% CrI 1.86, 2.12), and lowest in East and South Asians (1.48, 95% CrI 1.39, 1.57; 1.56, 95% CrI 1.31, 1.88, respectively). Men were more likely to have POAG than women (1.30, 95% CrI 1.22, 1.41). Older studies had lower POAG prevalence, which was related to the inclusion of intraocular pressure in the glaucoma definition. Studies with visual field data on all participants had a higher POAG prevalence than those with visual field data on a subset. Globally 57.5 million people (95% CI 46.4 to 73.1 million) were affected by POAG in 2015, rising to 65.5 million (95% CrI 52.8, 83.2 million) by 2020. This systematic review provides the most precise estimates of POAG prevalence and shows omitting routine visual field assessment in population surveys may have affected case ascertainment. Our findings will be useful to future studies and healthcare planning.
Topics: Age Distribution; Aged; Aged, 80 and over; Ethnicity; Female; Glaucoma, Open-Angle; Global Health; Humans; Male; Middle Aged; Prevalence; Sex Distribution
PubMed: 26286821
DOI: 10.1136/bjophthalmol-2015-307223