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BMC Ophthalmology Jun 2023Micropulse transscleral laser treatment (mTLT) is the latest alternative intraocular pressure (IOP) lowering approach for glaucoma patients. This meta-analysis aims to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Micropulse transscleral laser treatment (mTLT) is the latest alternative intraocular pressure (IOP) lowering approach for glaucoma patients. This meta-analysis aims to evaluate the efficacy and safety of mTLT and continuous wave transscleral cyclophotocoagulation (CW-TSCPC) for the treatment of glaucoma.
METHODS
We searched the PubMed, Embase, and Cochrane Library of Systematic Reviews databases from January 2000 to July 2022 to identify studies that, evaluated the efficacy and safety of mTLT in glaucoma. There were no restrictions regarding study type, patient age, or type of glaucoma. We analysed the reduction in IOP and the number of anti-glaucoma medications (NOAM), retreatment rates, and complications between mTLT and CW-TSCPC treatment. Publication bias was conducted for evaluating bias. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA 2020) reporting guideline.
RESULTS
We identified 6 eligible studies of which only 2 RCTs and 386 participants with various types of glaucoma at different stages were ultimately included. The results revealed significant IOP decreases after mTLT up to 12 months and significant NOAM reductions at 1 month (WMD=-0.30, 95% CI -0.54 to 0.06), and 3 months (WMD=-0.39, 95% CI -0.64 to 0.14) in mTLT compared to CW-TSCPC. Moreover, the retreatment rates (Log OR=-1.00, 95% CI -1.71 to -0.28), hypotony (Log OR=-1.21, 95% CI -2.26 to -0.16), prolonged inflammation or uveitis (Log OR=-1.63, 95% CI -2.85 to -0.41), and worsening of visual acuity (Log OR=-1.13, 95% CI -2.19 to 0.06) occurred less frequently after mTLT.
CONCLUSION
Our results demonstrated that mTLT could lower the IOP until 12 months after treatment. mTLT seems to have a lower risk of retreatment after the first procedure, and mTLT is superior to CW-TSCPC with respect to safety. Studies with longer follow-up durations and larger sample sizes are necessary in the future.
TRIAL REGISTRATION NUMBER
INPLASY202290120.
Topics: Humans; Glaucoma; Intraocular Pressure; Retreatment; Databases, Factual; Lasers
PubMed: 37308944
DOI: 10.1186/s12886-023-03017-w -
BMJ Open Apr 2023To compare the efficacy and safety of tube shunt implantation with trabeculectomy in the treatment of patients with glaucoma. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the efficacy and safety of tube shunt implantation with trabeculectomy in the treatment of patients with glaucoma.
METHODS
A systematic literature search was performed for studies comparing tube with trabeculectomy in patients with glaucoma (final search date: 27 February 2022). Comparisons between tube and trabeculectomy were grouped by the type of tube (Ahmed, Baerveldt, Ex-PRESS and XEN). The primary endpoints included intraocular pressure (IOP), IOP reduction (IOPR), IOPR percentage (IOPR%), complete success rate (CSR), qualified success rate (QSR) and adverse events (AEs).
RESULTS
Forty-nine studies were included in this meta-analysis and presented data for 3795 eyes (Ahmed: 670, Baerveldt: 561, Ex-PRESS: 473, XEN: 199, trabeculectomy: 1892). Ahmed and Ex-PRESS were similar to trabeculectomy in terms of IOP outcomes and success rate (Ahmed vs trabeculectomy: IOPR%: mean difference (MD)=1.34 (-5.35, 8.02), p=0.69; Ex-PRESS vs trabeculectomy: IOPR%: MD=0.12 (-3.07, 3.31), p=0.94). The IOP outcomes for Baerveldt were worse than those for trabeculectomy (IOPR%: MD=-7.51 (-10.68, -4.35), p<0.00001), but the QSR was higher. No significant difference was shown for the CSR. XEN was worse than trabeculectomy in terms of IOP outcomes (IOPR%: MD=-7.87 (-13.55, -2.18), p=0.007), while the success rate was similar. Ahmed and Ex-PRESS had a lower incidence of AEs than trabeculectomy. Baerveldt had a lower incidence of bleb leakage/wound leakage, hyphaema and hypotonic maculopathy than trabeculectomy but a higher incidence of concurrent cataracts, diplopia/strabismus and tube erosion. The incidence of AEs was similar for the XEN and trabeculectomy procedures.
CONCLUSION
Compared with trabeculectomy, both Ahmed and Ex-PRESS appear to be associated with similar ocular hypotensive effects and lower incidences of AEs. However, Baerveldt and XEN cannot achieve sufficient reductions in IOP outcomes similar to those of trabeculectomy.
PROSPERO REGISTRATION NUMBER
CRD42021257852.
Topics: Humans; Trabeculectomy; Glaucoma Drainage Implants; Treatment Outcome; Glaucoma; Intraocular Pressure
PubMed: 37080625
DOI: 10.1136/bmjopen-2022-065921 -
The Cochrane Database of Systematic... Feb 2017Glaucoma is a leading cause of irreversible blindness worldwide and the second most common cause of blindness after cataracts. The primary treatment for glaucoma aims to... (Review)
Review
BACKGROUND
Glaucoma is a leading cause of irreversible blindness worldwide and the second most common cause of blindness after cataracts. The primary treatment for glaucoma aims to lower intraocular pressure (IOP) with the use of topical medicines. Topical medication instillation techniques, such as eyelid closure and nasolacrimal occlusion when instilling drops, have been proposed as potential methods to increase ocular absorption and decrease systemic absorption of the drops.
OBJECTIVES
To investigate the effectiveness of topical medication instillation techniques compared with usual care or another method of instillation of topical medication in the management of glaucoma or ocular hypertension.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), MEDLINE Ovid (1946 to 8 December 2016), Embase Ovid (1947 to 8 December 2016), PubMed (1948 to 8 December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 8 December 2016), International Pharmaceutical Abstracts Database (1970 to 8 December 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 13 May 2013), ClinicalTrials.gov (www.clinicaltrials.gov) (searched 8 December 2016) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) (searched 8 December 2016). We did not use any date or language restrictions in the electronic searches for trials.
SELECTION CRITERIA
We included randomized controlled trials which had compared any topical medication instillation technique with usual care or a different method of instillation of topical medication.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened records from the searches for eligibility, assessed the risk of bias, and extracted data. We followed methods recommended by Cochrane.
MAIN RESULTS
We identified two trials (122 eyes of 61 participants) that had evaluated a topical medication instillation technique. We also identified two ongoing trials. Both included trials used a within-person design and administered prostaglandin monotherapy for glaucoma or ocular hypertension. Because the trials evaluated different instillation techniques and assessed different outcomes, we performed no meta-analysis.One trial, conducted in the US, evaluated the effect of eyelid closure (one and three minutes) versus no eyelid closure on lowering IOP. At one to two weeks' follow-up, reduction in IOP was similar in the eyelid closure group and the no eyelid closure group (mean difference (MD) -0.33 mmHg, 95% confidence interval (CI) -0.8 to 1.5; 51 participants; moderate-certainty evidence).The second trial, conducted in Italy, evaluated the effect of using an absorbent cloth to wipe excess fluid after instillation (fluid removal) versus not using an absorbent cloth (no removal) on reducing dermatologic adverse events. At four months' follow-up, eyelashes were shorter among eyes in the fluid removal group compared with the no fluid removal group (MD -1.70 mm, 95% CI -3.46 to 0.06; 10 participants; low-certainty evidence). Fewer eyes showed skin hyperpigmentation in the eyelid region towards the nose in the fluid removal group compared with the no removal group (RR 0.07, 95% CI 0.01 to 0.84; 10 participants; low-certainty evidence); however, the difference was uncertain in the eyelid region towards the temples (RR 0.44, 95% CI 0.07 to 2.66; 10 participants; low-certainty evidence). The effect hypertrichosis (excessive hair growth) was uncertain between groups (RR 1.00, 95% CI 0.17 to 5.98; 10 participants; low-certainty evidence).Neither trial reported other outcomes specified for this review, including the proportion of participants with IOP less than 21 mmHg; participant-reported outcomes related to the ease, convenience, and comfort of instillation techniques; physiologic measurements of systemic absorption; escalation of therapy; mean change in visual fields; optic nerve progression; mean change in best-corrected visual acuity; proportion in whom glaucoma developed; quality of life outcomes; or cost-effectiveness outcomes. Neither trial reported data at follow-up times of more than four months.
AUTHORS' CONCLUSIONS
Evidence to evaluate the effectiveness of topical medication instillation techniques for treatment of glaucoma is lacking. It is unclear what, if any, effects instillation techniques have on topical medical therapy for glaucoma.
Topics: Administration, Ophthalmic; Antihypertensive Agents; Bimatoprost; Eyelashes; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Ophthalmic Solutions; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Travoprost
PubMed: 28218404
DOI: 10.1002/14651858.CD010520.pub2 -
Journal of Ophthalmology 2018Prostaglandin analogues (PGAs) are first-line medical therapy for primary open angle glaucoma (POAG) and ocular hypertension (OHT). Intraocular pressure (IOP) lowering... (Review)
Review
TOPIC
Prostaglandin analogues (PGAs) are first-line medical therapy for primary open angle glaucoma (POAG) and ocular hypertension (OHT). Intraocular pressure (IOP) lowering effects in full responders are known to be 25-33% for this class; however, partial responders and nonresponders do exist. In clinical trials or prospective series, discontinuation and washout of PGAs is necessary to evaluate true change in IOP from novel surgeries and medical therapies.
CLINICAL RELEVANCE
To identify all relevant papers with pertinent data on washout of PGAs and quantify the duration and long-term effect of reported PGA washout periods in glaucoma and OHT patients.
METHODS
A systematic review and meta-analysis was conducted to investigate the long-term effects on IOP after discontinuation of topical PGAs POAG and OHT patients. The main search was conducted in MEDLINE/PubMed, EMBASE, Cochrane Library, CINAHL, Web of Science, and BIOSIS Previews and conference proceedings.
RESULTS
1055 papers were identified, 548 were independently screened by two physicians., and 56 papers were analyzed for washout durations. The mean washout was found to be 4.56 weeks (±1.25), with the mode and median being 5 weeks. Five studies were analyzed as randomized control trials in which latanoprost was discontinued for 4 weeks prior to restarting another intraocular pressure-lowering drug. Meta-analysis revealed a 4-week discontinuation of latanoprost, on average, subjects returned to their baseline IOP.
CONCLUSION
A significant IOP-lowering effect of latanoprost was not observed beyond 4 weeks, suggesting this may be an appropriate washout period for latanoprost. We could not identify appropriate washout periods for either travoprost or bimatoprost, although a majority of articles had 4-week washout durations for the two drugs. Despite the widespread use of this class of medication, there is a paucity of literature on the effects of PGA washout in patients that are treatment naïve to other topical medications.
PubMed: 30363694
DOI: 10.1155/2018/3190684 -
The Cochrane Database of Systematic... Jan 2015Primary congenital glaucoma (PCG) manifests within the first few years of a child's life and is not associated with any other systemic or ocular abnormalities. PCG... (Review)
Review
BACKGROUND
Primary congenital glaucoma (PCG) manifests within the first few years of a child's life and is not associated with any other systemic or ocular abnormalities. PCG results in considerable morbidity even in developed countries. Several surgical techniques for treating this condition, and lowering the intraocular pressure (IOP) associated with it, have been described.
OBJECTIVES
To compare the effectiveness and safety of different surgical techniques for PCG.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 23 June 2014.
SELECTION CRITERIA
We included all randomized and quasi-randomized trials in which different types of surgical interventions were compared in children under five years of age with PCG.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures specified by The Cochrane Collaboration.
MAIN RESULTS
We included a total of six trials (four randomized and two quasi-randomized) with 102 eyes in 61 children. Two trials were conducted in the USA and one trial each in Egypt, Israel, Lebanon and Saudi Arabia. All trials included children aged younger than one year when diagnosed with PCG, and followed them for periods ranging from six months to five years.No two trials compared the same pair of surgical interventions, so we did not perform any meta-analysis. One trial compared trabeculotomy versus goniotomy; a second trial compared combined trabeculectomy-trabeculotomy with mitomycin C versus trabeculectomy-trabeculotomy with mitomycin C and deep sclerectomy; a third trial compared combined trabeculotomy-trabeculectomy versus trabeculotomy; a fourth trial compared one goniotomy versus two goniotomies; a fifth trial compared trabeculotomy versus viscocanalostomy; and the sixth trial compared surgical goniotomy versus neodymium-YAG laser goniotomy. For IOP change and surgical success (defined by IOP achieved), none of the trials reported a difference between pairs of surgical techniques. However, due to the limited sample sizes for all trials (average of 10 children per trial), the evidence as to whether a particular surgical technique is effective and which surgical technique is better still remains uncertain. Adverse events, such as choroidal detachment, shallow anterior chamber and hyphema, were reported from four trials. None of the trials reported quality of life or economic data.These trials were neither designed nor reported well overall. Two trials were quasi-randomized trials and judged to have high risk of selection bias; four trials were at unclear or high risk for performance bias and detection bias; and we judged one trial to have high risk of attrition bias due to high proportions of losses to follow-up. Due to poor study design and reporting, the reliability and applicability of evidence remain unclear.
AUTHORS' CONCLUSIONS
No conclusions could be drawn from the trials included in this review due to paucity of data. More research is needed to determine which of the many surgeries performed for PCG are effective.
Topics: Child, Preschool; Glaucoma; Glaucoma Drainage Implants; Humans; Infant; Infant, Newborn; Mitomycin; Postoperative Complications; Randomized Controlled Trials as Topic; Sclera; Trabecular Meshwork; Trabeculectomy
PubMed: 25636153
DOI: 10.1002/14651858.CD008213.pub2 -
The Cochrane Database of Systematic... Jan 2023Uveitis is a term used to describe a group of intraocular inflammatory diseases. Uveitis is the fifth most common cause of vision loss in high-income countries, with the... (Review)
Review
BACKGROUND
Uveitis is a term used to describe a group of intraocular inflammatory diseases. Uveitis is the fifth most common cause of vision loss in high-income countries, with the highest incidence of disease in the working-age population. Corticosteroids are the mainstay of treatment for all subtypes of non-infectious uveitis. They can be administered orally, topically with drops, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation.
OBJECTIVES
To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE Ovid, Embase, PubMed, LILACS, and three trials registries to November 2021. SELECTION CRITERIA: We included randomized controlled trials comparing either fluocinolone acetonide (FA) or dexamethasone (DEX) intravitreal implants with standard-of-care therapy or sham procedures, with at least six months of follow-up after treatment. We included studies that enrolled participants of all ages, who had chronic non-infectious posterior uveitis, intermediate uveitis, or panuveitis with vision that was better than hand-motion.
DATA COLLECTION AND ANALYSIS
We applied standard Cochrane methodology.
MAIN RESULTS
We included data from four trials (683 participants, 907 eyes) that compared corticosteroid implants with either sham or standard-of-care therapy. Study characteristics and risk of bias Of the two trials that compared corticosteroid implants with sham procedure, one examined a 0.18 mg FA implant, and the other, a 0.7 mg DEX implant. The other two trials compared a 0.59 mg FA implant with standard-of-care therapy, which included systemic corticosteroids and immunosuppressive medications, if needed. We assessed the four trials to be at either low risk, or with some concerns of risk of bias across all domains. Findings Using sham procedure as control, combined results at the six-month primary time point suggested that corticosteroid implants may decrease the risk of uveitis recurrence by 60% (relative risk [RR] 0.40, 95% confidence interval [CI] 0.30 to 0.54; 2 trials, 282 participants; low-certainty evidence); and lead to a greater improvement in best-corrected visual acuity (BCVA; mean difference [MD] 0.22 logMAR, 95% CI 0.13 to 0.31; 1 trial, 153 participants; low-certainty evidence). Evidence based on a single-study report (146 participants) suggested that steroid implants may have no effects on visual functioning quality of life, measured on the National Eye Institute 25-Item Visual Function Questionnaire (MD 2.85, 95%CI -3.64 to 9.34; 1 trial, 146 participants; moderate-certainty evidence). Using standard-of care therapy as control, combined estimates at the 24-month primary time point suggested that corticosteroid implants were likely to decrease the risk of recurrence of uveitis by 54% (RR 0.46, 95% CI 0.35 to 0.60; 2 trials, 619 eyes). Combined estimates at 24 months also suggested that steroid implants may have little to no effects on BCVA (MD 0.05 logMAR, 95% CI -0.02 to 0.12; 2 trials, 619 eyes; low-certainty evidence). Evidence based on a single-study report (232 participants) suggested that steroid implants may have minimal clinical effects on visual functioning (MD 4.64, 95% CI 0.13 to 9.15; 1 trial, 232 participants; moderate-certainty evidence); physical functioning (SF-36 physical subscale MD 2.95, 95% CI 0.55 to 5.35; 1 trial, 232 participants; moderate-certainty evidence); or mental health (SF-36 mental subscale MD 3.65, 95% CI 0.52 to 6.78; 1 trial, 232 participants; moderate-certainty evidence); but not on EuroQoL (MD 6.17, 95% CI 1.87 to 10.47; 1 trial, 232 participants; moderate-certainty evidence); or EuroQoL-5D scale (MD 0.02, 95% CI -0.04 to 0.08; 1 trial, 232 participants; moderate-certainty evidence). Adverse effects Compared with sham procedures, corticosteroid implants may slightly increase the risk of cataract formation (RR 2.69, 95% CI 1.17 to 6.18; 1 trial, 90 eyes; low-certainty evidence), but not the risk of cataract progression (RR 2.00, 95% CI 0.65 to 6.12; 1 trial, 117 eyes; low-certainty evidence); or the need for surgery (RR 2.98, 95% CI 0.82 to 10.81; 1 trial, 180 eyes; low-certainty evidence), during up to 12 months of follow-up. These implants may increase the risk of elevated intraocular pressure ([IOP] RR 2.81, 95% CI 1.42 to 5.56; 2 trials, 282 participants; moderate-certainty evidence); and the need for IOP-lowering eyedrops (RR 1.85, 95% CI 1.05 to 3.25; 2 trials, 282 participants; moderate-certainty evidence); but not the need for IOP-lowering surgery (RR 0.72, 95% CI 0.13 to 4.17; 2 trials, 282 participants; moderate-certainty evidence). Evidence comparing the 0.59 mg FA implant with standard-of-care suggested that the implant may increase the risk of cataract progression (RR 2.71, 95% CI 2.06 to 3.56; 2 trials, 210 eyes; low-certainty evidence); and the need for surgery (RR 2.98, 95% CI 2.33 to 3.79; 2 trials, 371 eyes; low-certainty evidence); along with the risk of elevated IOP (RR 3.64, 95% CI 2.71 to 4.87; 2 trials, 605 eyes; moderate-certainty evidence); and the need for medical (RR 3.04, 95% CI 2.36 to 3.91; 2 trials, 544 eyes; moderate-certainty evidence); or surgical interventions (RR 5.43, 95% CI 3.12 to 9.45; 2 trials, 599 eyes; moderate-certainty evidence). In either comparison, these implants did not increase the risk for endophthalmitis, retinal tear, or retinal detachment (moderate-certainty evidence). AUTHORS' CONCLUSIONS: Our confidence is limited that local corticosteroid implants are superior to sham therapy or standard-of-care therapy in reducing the risk of uveitis recurrence. We demonstrated different effectiveness on BCVA relative to comparators in people with non-infectious uveitis. Nevertheless, the evidence suggests that these implants may increase the risk of cataract progression and IOP elevation, which will require interventions over time. To better understand the efficacy and safety profiles of corticosteroid implants, we need future trials that examine implants of different doses, used for different durations. The trials should measure core standard outcomes that are universally defined, and measured at comparable follow-up time points.
Topics: Humans; Adrenal Cortex Hormones; Cataract; Glaucoma; Panuveitis; Quality of Life; Steroids; Uveitis; Uveitis, Intermediate; Randomized Controlled Trials as Topic
PubMed: 36645716
DOI: 10.1002/14651858.CD010469.pub3 -
EClinicalMedicine Jul 2022Glaucoma and chronic kidney disease (CKD) are prevalent and debilitating conditions, with common pathogenic pathways like oxidative stress and fluid dysregulation. We...
BACKGROUND
Glaucoma and chronic kidney disease (CKD) are prevalent and debilitating conditions, with common pathogenic pathways like oxidative stress and fluid dysregulation. We evaluated if there is a bidirectional association between them, as previous studies have yielded conflicting results.
METHODS
In this systematic review and meta-analysis, we searched PubMed, Embase and Cochrane Library from inception until 15 June 2021, including full-length English articles published in peer-reviewed journals reporting on glaucoma and CKD as either exposure or outcome, among participants aged ≥18 years. We pooled overall summary estimates of odds ratios using random-effect meta-analysis and conducted subgroup meta-analyses and univariate meta regression. We assessed risk of bias using the Newcastle-Ottawa Scale (NOS) and quality of evidence using the GRADE framework. Our article is PROSPERO-registered and adherent to both PRISMA and MOOSE guidelines. This review is registered with PROSPERO (CRD42021262846).
FINDINGS
We identified 14 articles comprising of 3 retrospective cohort studies and 12 cross-sectional studies from 2,428 records, including 1,978,254 participants. Risk of bias was low to moderate. Participants with CKD at baseline had higher pooled odds of glaucoma (odds ratio[OR]=1.18, 95% confidence interval[CI]=1.04-1.33, I=66%, N=12) compared to participants without CKD. The association remained significant in subgroups of longitudinal studies, participants with diabetes, East Asian studies and primary open-angle glaucoma. In the reverse direction, participants with glaucoma at baseline had over three-fold higher odds of incident CKD compared to participants without glaucoma after 10-15 years of follow-up in longitudinal studies (OR=3.67, 95% CI=2.16-6.24, I=75%, N=2). All studies adjusted for age and sex, while most studies adjusted for comorbidities such as diabetes and hypertension. Meta-regression identified ethnicity (East Asians vs Non-East Asians) as a significant effect moderator. Associations were robust to trim-and-fill adjustment for publication bias, single-study influence and cumulative meta-analyses.
INTERPRETATION
Our meta-analysis suggests a bidirectional relationship between glaucoma and CKD, particularly among East Asians. Further studies are required to elucidate underlying mechanisms and account for differential association by ethnicity.
FUNDING
Ching-Yu Cheng is supported by Clinician Scientist Award (NMRC/CSA-SI/0012/2017) of the Singapore Ministry of Health's National Medical Research Council.
PubMed: 35747173
DOI: 10.1016/j.eclinm.2022.101498 -
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... Dec 2015Glaucoma is an optic neuropathy that leads to vision loss and blindness. It is the second most common cause of irreversible blindness worldwide. The main treatment for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glaucoma is an optic neuropathy that leads to vision loss and blindness. It is the second most common cause of irreversible blindness worldwide. The main treatment for glaucoma aims to reduce intraocular pressure (IOP) in order to slow or prevent further vision loss. IOP can be lowered with medications, and laser or incisional surgeries. Trabeculectomy is the most common incisional surgical procedure to treat glaucoma. Device-modified trabeculectomy is intended to improve drainage of the aqueous humor to lower IOP. Trabeculectomy-modifying devices include Ex-PRESS, Ologen, amniotic membrane, expanded polytetrafluoroethylene (E-PTFE) membrane, Gelfilm and others. However, the effectiveness and safety of these devices are uncertain.
OBJECTIVES
To assess the relative effectiveness, primarily with respect to IOP control and safety, of the use of different devices as adjuncts to trabeculectomy compared with standard trabeculectomy in eyes with glaucoma.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2014, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2014), EMBASE (January 1980 to December 2014), PubMed (1948 to December 2014), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 22 December 2014.
SELECTION CRITERIA
We included randomized controlled trials comparing devices used during trabeculectomy with trabeculectomy alone. We also included studies where antimetabolites were used in either or both treatment groups.
DATA COLLECTION AND ANALYSIS
We used standard procedures expected by Cochrane.
MAIN RESULTS
We found 33 studies that met our inclusion criteria, of which 30 were published as full-length journal articles and three as conference abstracts. Only five studies have been registered. The 33 studies included a total of 1542 participants with glaucoma, and compared five types of devices implanted during trabeculectomy versus trabeculectomy alone. Five studies reported the use of Ex-PRESS (386 participants), eight studies reported the use of Ologen (327 participants), 18 studies reported the use of amniotic membrane (726 participants), one study reported the use of E-PTFE (60 participants), and one study reported the use of Gelfilm (43 participants). These studies were conducted in North America, South America, Europe, Asia, and the Middle East. Planned participant follow-up periods ranged from three months to five years. The studies were reported poorly which limited our ability to judge risk of bias for many domains. Only two studies explicitly masked outcome assessment so, we rated 31 studies at high risk of detection bias.Low-quality evidence from three studies showed that use of Ex-PRESS compared with trabeculectomy alone may be associated with a slightly lower IOP at one year (mean difference (MD) -1.58 mm Hg, 95% confidence interval (CI) -2.74 to -0.42; 165 eyes). Cataract surgery and hyphema may be less frequent in the Ex-PRESS group than in the trabeculectomy-alone group (cataract surgery: risk ratio (RR) 0.32, 95% CI 0.14 to 0.74, 3 studies, low-quality evidence; hyphema: RR 0.33, 95% CI 0.12 to 0.94, 4 studies, low-quality evidence). The effect of whether Ex-PRESS prevents hypotony was uncertain (RR 0.92, 95% CI 0.63 to 1.33, 2 studies, very low-quality evidence). All these studies received funding from the device manufacturer.Very low-quality evidence from five studies suggests that use of Ologen compared with trabeculectomy alone is associated with slightly higher IOP at one year (MD 1.40 mm Hg, 95% CI -0.57 to 3.38; 177 eyes). The effect of Ologen on preventing hypotony was uncertain (RR 0.75, 95% CI 0.47 to 1.19, 5 studies, very low-quality evidence). Differences between the two treatment groups for other reported complications also were inconclusive.Low-quality evidence from nine studies suggests that use of amniotic membrane with trabeculectomy may be associated with lower IOP at one year compared with trabeculectomy alone (MD -3.92 mm Hg, 95% CI -5.41 to -2.42; 356 eyes). Low-quality evidence showed that use of amniotic membrane may prevent adverse events and complications, such as hypotony (RR 0.40, 95% CI 0.17 to 0.94, 5 studies, low-quality evidence).The report from the only E-PTFE study (60 eyes) showed no important differences for postoperative IOP at one year (MD -0.44 mm Hg, 95% CI -1.76 to 0.88) between the trabeculectomy + E-PTFE versus the trabeculectomy-alone groups. Hypotony was the only postoperative complication observed less frequently in the E-PTFE group compared to the trabeculectomy-alone group (RR 0.29, 95% CI 0.11 to 0.77).The one Gelfilm study reported uncertainty in the difference in IOP and complication rates between the two groups at one year; no further data were provided in the study report.
AUTHORS' CONCLUSIONS
Overall, the use of devices with standard trabeculectomy may help with greater IOP reduction at one-year follow-up than trabeculectomy alone; however, due to potential biases and imprecision in effect estimates, the quality of evidence is low. When we examined outcomes within subgroups based on the type of device used, our findings suggested that the use of an Ex-PRESS device or an amniotic membrane as an adjunct to trabeculectomy may be slightly more effective in reducing IOP at one year after surgery compared with trabeculectomy alone. The evidence that these devices are as safe as trabeculectomy alone is unclear. Due to various limitations in the design and conduct of the included studies, the applicability of this evidence synthesis to other populations or settings is uncertain. Further research is needed to determine the effectiveness and safety of other devices and in subgroup populations, such as people with different types of glaucoma, of various races and ethnicity, and with different lens types (e.g. phakic, pseudophakic).
Topics: Amnion; Biocompatible Materials; Collagen; Gelatin; Glaucoma; Glaucoma Drainage Implants; Glycosaminoglycans; Humans; Intraocular Pressure; Polytetrafluoroethylene; Randomized Controlled Trials as Topic; Trabeculectomy; Visual Acuity
PubMed: 26625212
DOI: 10.1002/14651858.CD010472.pub2 -
Biomedicine & Pharmacotherapy =... Jun 2022The endocannabinoid system (ECS) is a complex biological regulatory system. Its expression and functionality have been widely investigated in ocular tissues. Recent data... (Review)
Review
BACKGROUND
The endocannabinoid system (ECS) is a complex biological regulatory system. Its expression and functionality have been widely investigated in ocular tissues. Recent data have reported its modulation to be valid in determining an ocular hypotensive and a neuroprotective effect in preclinical animal models of glaucoma.
AIM
This study aimed to explore the available literature on cannabinoid receptor 1 (CBR), cannabinoid receptor 2 (CBR), and transient receptor potential vanilloid 1 (TRPV1) expression in the trabecular meshwork (TM), ciliary body (CB), and retina as well as their ocular hypotensive and neuroprotective effects in preclinical, in vivo, animal glaucoma models.
MATERIALS AND METHODS
The study adhered to both PRISMA and SYRCLE guidelines. Sixty-nine full-length articles were included in the final analysis.
RESULTS
Preclinical studies indicated a widespread distribution of CBR, CBR, and TRPV1 in the TM, CB, and retina, although receptor-, age-, and species-dependent differences were observed. CBR and CBR modulation have been shown to exert ocular hypotensive effects in preclinical models via the regulation of inflow and outflow pathways. Retinal cell neuroprotection has been achieved in several experimental models, mediated by agonists and antagonists of CBR, CBR, and TRPV1.
DISCUSSION
Despite the growing body of preclinical data regarding the expression and modulation of ECS in ocular tissues, the mechanisms responsible for the hypotensive and neuroprotective efficacy exerted by this system remain largely elusive. Research on this topic is advocated to further substantiate the hypothesis that the ECS is a new potential therapeutic target in the context of glaucoma.
Topics: Animals; Endocannabinoids; Glaucoma; Neurons; Receptors, Cannabinoid; Retina
PubMed: 35468582
DOI: 10.1016/j.biopha.2022.112981