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Ophthalmic & Physiological Optics : the... Jul 2024To synthesise evidence across studies on factors associated with pathologic myopia (PM) onset and progression based on the META-analysis for Pathologic Myopia (META-PM)... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To synthesise evidence across studies on factors associated with pathologic myopia (PM) onset and progression based on the META-analysis for Pathologic Myopia (META-PM) classification framework.
METHODS
Findings from six longitudinal studies (5-18 years) were narratively synthesised and meta-analysed, using odds ratio (OR) as the common measure of association. All studies adjusted for baseline myopia, age and sex at a minimum. The quality of evidence was rated using the Grades of Recommendation, Assessment, Development and Evaluation framework.
RESULTS
Five out of six studies were conducted in Asia. There was inconclusive evidence of an independent effect (or lack thereof) of ethnicity and sex on PM onset/progression. The odds of PM onset increased with greater axial length (pooled OR: 2.03; 95% CI: 1.71-2.40; p < 0.001), older age (pooled OR: 1.07; 1.05-1.09; p < 0.001) and more negative spherical equivalent refraction, SER (OR: 0.77; 0.68-0.87; p < 0.001), all of which were supported by an acceptable level of evidence. Fundus tessellation was found to independently increase the odds of PM onset in a population-based study (OR: 3.02; 2.58-3.53; p < 0.001), although this was only supported by weak evidence. There was acceptable evidence that greater axial length (pooled OR: 1.23; 1.09-1.39; p < 0.001), more negative SER (pooled OR: 0.87; 0.83-0.92; p < 0.001) and higher education level (pooled OR: 3.17; 1.36-7.35; p < 0.01) increased the odds of PM progression. Other baseline factors found to be associated with PM progression but currently supported by weak evidence included age (pooled OR: 1.01), severity of myopic maculopathy (OR: 3.61), intraocular pressure (OR: 1.62) and hypertension (OR: 0.21).
CONCLUSIONS
Most PM risk/prognostic factors are not supported by an adequate evidence base at present (an indication that PM remains understudied). Current factors for which an acceptable level of evidence exists (limited in number) are unmodifiable in adults and lack personalised information. More longitudinal studies focusing on uncovering modifiable factors and imaging biomarkers are warranted.
Topics: Humans; Myopia, Degenerative; Disease Progression; Risk Factors; Refraction, Ocular
PubMed: 38563652
DOI: 10.1111/opo.13312 -
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 -
Cureus Jul 2023Steroids are commonly used in children for the treatment of various medical conditions. However, systemic steroids can lead to the development of ocular hypertension... (Review)
Review
Steroids are commonly used in children for the treatment of various medical conditions. However, systemic steroids can lead to the development of ocular hypertension (OHT), an increase in intraocular pressure. Limited literature is available on the systemic route of steroid administration in children and the development of this side effect. For literature writing and review, a thorough research was conducted across various platforms, such as PubMed, PubMed Central (PMC), Medline, and Cochrane Database of Systematic Reviews (CDSR). After all the screening processes and quality checks, 12 articles were finalized for review writing. The aim was to explore if OHT development is a common side effect developed in children on systemic steroid use for various medical conditions and if any particular risk factors were present among children that lead to its development. The results indicate that OHT is a common side effect of systemic steroid use in children. Children may or may not present with the symptoms of raised intraocular pressure. The development of OHT occurs within one month of the beginning of the steroid treatment in most of the reviewed studies. Several risk factors associated with developing this side effect were also found. In conclusion, systemic steroid use in children leads to the development of OHT. Awareness among healthcare professionals regarding this potential association is necessary. This information can be used to develop guidelines for serial ocular examinations in children on prolonged systemic steroid use.
PubMed: 37602115
DOI: 10.7759/cureus.42112 -
Journal of Ophthalmic Inflammation and... Nov 2022To compare the outcomes and complications of different surgical interventions for secondary glaucoma in pediatric uveitis. (Review)
Review
PURPOSE
To compare the outcomes and complications of different surgical interventions for secondary glaucoma in pediatric uveitis.
METHODS
Systematic review following the PRISMA standards. Main inclusion criteria were surgery for secondary glaucoma in pediatric uveitis at a mean age of 16 years or below, a mean follow-up period of at least 1 year after surgery, and at least 10 eyes per surgical intervention per study. We used the GRADE approach to assess study quality. Primary outcomes were intraocular pressure (IOP) and number of IOP lowering medications before and after surgery. Secondary outcomes were success rate and complications.
RESULTS
Fourteen studies fulfilled the inclusion criteria, in which one (n = 11) or more (n = 3) surgical interventions were described, comprising in total six different procedures. According to the GRADE criteria, the quality of the studies was low to very low, in particular because of the small size and the applied study designs. All surgical interventions provided a significant decrease in IOP and number of IOP lowering medications. The success rates during follow-up varied widely, with the lowest rates of success after cyclophotocoagulation. The most frequently reported complications were ocular hypertension, hypotony, and hyphema, with an indication for a reoperation in more than one-third of the cases. Permanent vision loss was infrequently seen and was attributed to prolonged hypotony.
CONCLUSIONS
The described surgical interventions are able to prevent blindness by lowering a medically uncontrolled IOP to an acceptable level. Therefore, there is a crucial role for surgical intervention in these children. Based on the present studies, no preferences can be made. Given the reported complications, more research with larger sample sizes and direct comparisons is needed to determine the most successful glaucoma treatment in children with uveitis.
PubMed: 36344704
DOI: 10.1186/s12348-022-00313-2 -
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 -
Ophthalmology Science Dec 2023To provide standardized confidence limits of the transient pattern electroretinogram (tPERG) P50 and N95 and steady state pattern electroretinogram (ssPERG) amplitudes...
TOPIC
To provide standardized confidence limits of the transient pattern electroretinogram (tPERG) P50 and N95 and steady state pattern electroretinogram (ssPERG) amplitudes in normal controls as compared to ocular hypertension (OHT), glaucoma suspect (GS), or early manifest glaucoma (EMG) eyes.
CLINICAL RELEVANCE
The identification of standardized confidence limits in the context of pattern electroretinogram (PERG) might overcome the high intrinsic variability of the measure, and it might lead to a more intuitive understanding of the results as well as to an easier comparison of data from multiple tests, sites, and operators.
METHODS
The study protocol was prospectively registered on the International Prospective Register of Systematic Reviews (ID: CRD42022370032). A literature search was conducted on PubMed, Web of Science, and Scopus. Studies comparing PERG raw data in normal control eyes as compared to OHT, GS, or EMG were included. The risk of bias was assessed using the National Institute for Health and Clinical Excellence quality assessment tool. The main outcome was the P50, N95, and ssPERG amplitude difference between the control and the study groups' eyes. The standardized mean difference was calculated as a measure of the effect size for the primary outcome. A subanalysis was conducted based on the type of electrodes adopted for the PERG measurements (invasive vs. noninvasive).
RESULTS
Of the 4580 eligible papers, only 23 were included (1754 eyes). Statistically significant amplitude differences were found in the P50, N95, and ssPERG amplitudes between normal controls and OHT, GS, and EMG eyes. The highest standardized mean difference values were observed in the ssPERG amplitude in all 3 sets of comparison. The subanalysis did not reveal any statistically significant differences between invasive and noninvasive recording strategies.
CONCLUSIONS
The use of standardized values as the main outcome measures in the context of the PERG data analysis is a valid approach, normalizing several confounding factors which have affected the clinical utility of PERG both for individual patients and in clinical trials. Steady state PERG apparently better discriminates diseased eyes compared to tPERG. The adoption of skin-active electrodes is able to adequately discriminate between healthy and diseased statuses.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found after the references.
PubMed: 37334035
DOI: 10.1016/j.xops.2023.100322 -
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 -
The Cochrane Database of Systematic... Apr 2018Glaucoma is a leading cause of blindness worldwide. It results in a progressive loss of peripheral vision and, in late stages, loss of central vision leading to... (Review)
Review
BACKGROUND
Glaucoma is a leading cause of blindness worldwide. It results in a progressive loss of peripheral vision and, in late stages, loss of central vision leading to blindness. Early treatment of glaucoma aims to prevent or delay vision loss. Elevated intraocular pressure (IOP) is the main causal modifiable risk factor for glaucoma. Aqueous outflow obstruction is the main cause of IOP elevation, which can be mitigated either by increasing outflow or reducing aqueous humor production. Cyclodestructive procedures use various methods to target and destroy the ciliary body epithelium, the site of aqueous humor production, thereby lowering IOP. The most common approach is laser cyclophotocoagulation.
OBJECTIVES
To assess the effectiveness and safety of cyclodestructive procedures for the management of non-refractory glaucoma (i.e. glaucoma in an eye that has not undergone incisional glaucoma surgery). We also aimed to compare the effect of different routes of administration, laser delivery instruments, and parameters of cyclophotocoagulation with respect to IOP control, visual acuity, pain control, and adverse events.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 8); Ovid MEDLINE; Embase.com; LILACS; the metaRegister of Controlled Trials (mRCT) and ClinicalTrials.gov. The date of the search was 7 August 2017. We also searched the reference lists of reports from included studies.
SELECTION CRITERIA
We included randomized controlled trials of participants who had undergone cyclodestruction as a primary treatment for glaucoma. We included only head-to-head trials that had compared cyclophotocoagulation to other procedural interventions, or compared cyclophotocoagulation using different types of lasers, delivery methods, parameters, or a combination of these factors.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results, assessed risks of bias, extracted data, and graded the certainty of the evidence in accordance with Cochrane standards.
MAIN RESULTS
We included one trial (92 eyes of 92 participants) that evaluated the efficacy of diode transscleral cyclophotocoagulation (TSCPC) as primary surgical therapy. We identified no other eligible ongoing or completed trial. The included trial compared low-energy versus high-energy TSCPC in eyes with primary open-angle glaucoma. The trial was conducted in Ghana and had a mean follow-up period of 13.2 months post-treatment. In this trial, low-energy TSCPC was defined as 45.0 J delivered, high-energy as 65.5 J delivered; it is worth noting that other trials have defined high- and low-energy TSCPC differently. We assessed this trial to have had low risk of selection bias and reporting bias, unclear risk of performance bias, and high risk of detection bias and attrition bias. Trial authors excluded 13 participants with missing follow-up data; the analyses therefore included 40 (85%) of 47 participants in the low-energy group and 39 (87%) of 45 participants in the high-energy group.Control of IOP, defined as a decrease in IOP by 20% from baseline value, was achieved in 47% of eyes, at similar rates in the low-energy group and the high-energy groups; the small study size creates uncertainty about the significance of the difference, if any, between energy settings (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.64 to 1.65; 79 participants; low-certainty evidence). The difference in effect between energy settings based on mean decrease in IOP, if any exists, also was uncertain (mean difference (MD) -0.50 mmHg, 95% CI -5.79 to 4.79; 79 participants; low-certainty evidence).Decreased vision was defined as the proportion of participants with a decrease of 2 or more lines on the Snellen chart or one or more categories of visual acuity when unable to read the eye chart. Twenty-three percent of eyes had a decrease in vision. The size of any difference between the low-energy group and the high-energy group was uncertain (RR 1.22, 95% CI 0.54 to 2.76; 79 participants; low-certainty evidence). Data were not available for mean visual acuity and proportion of participants with vision change defined as greater than 1 line on the Snellen chart.The difference in the mean number of glaucoma medications used after cyclophotocoagulation was similar when comparing treatment groups (MD 0.10, 95% CI -0.43 to 0.63; 79 participants; moderate-certainty evidence). Twenty percent of eyes were retreated; the estimated effect of energy settings on the need for retreatment was inconclusive (RR 0.76, 95% CI 0.31 to 1.84; 79 participants; low-certainty evidence). No data for visual field, cost effectiveness, or quality-of-life outcomes were reported by the trial investigators.Adverse events were reported for the total study population, rather than by treatment group. The trial authors stated that most participants reported mild to moderate pain after the procedure, and many had transient conjunctival burns (percentages not reported). Severe iritis occurred in two eyes and hyphema occurred in three eyes. No instances of hypotony or phthisis bulbi were reported. The only adverse outcome that was reported by the treatment group was atonic pupil (RR 0.89 in the low-energy group, 95% CI 0.47 to 1.68; 92 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
There is insufficient evidence to evaluate the relative effectiveness and safety of cyclodestructive procedures for the primary procedural management of non-refractory glaucoma. Results from the one included trial did not compare cyclophotocoagulation to other procedural interventions and yielded uncertainty about any difference in outcomes when comparing low-energy versus high-energy diode TSCPC. Overall, the effect of laser treatment on IOP control was modest and the number of eyes experiencing vision loss was limited. More research is needed specific to the management of non-refractory glaucoma.
Topics: Glaucoma, Open-Angle; Humans; Intraocular Pressure; Laser Coagulation
PubMed: 29694684
DOI: 10.1002/14651858.CD009313.pub2 -
Clinical Ophthalmology (Auckland, N.Z.) 2022Starting in 2019, the Global Initiative for Asthma recommended the use of inhaled corticosteroids (ICS) as part of reliever combination therapy in patients 12 years of...
PURPOSE
Starting in 2019, the Global Initiative for Asthma recommended the use of inhaled corticosteroids (ICS) as part of reliever combination therapy in patients 12 years of age and older, thus dramatically increasing the population exposure to ICS. ICS and intranasal corticosteroids (INS) are commonly used for a variety of respiratory diseases. Chronic steroid use is a well-known risk factor for elevated intraocular pressure (IOP) and glaucoma regardless of route of administration. This study aimed to determine the reported risk of glaucoma, ocular hypertension (OHT) and IOP elevation associated with ICS and INS use.
MATERIALS AND METHODS
Systematic literature search in MEDLINE, EMBASE, Cochrane, CINAHL, BIOSIS, and Web of Science databases from the date of inception identified studies that assess ocular outcomes related to glaucoma in ICS and INS users. Study selection, risk of bias assessment and data extraction were done independently in duplicate. Meta-analysis assessed glaucoma incidence, OHT incidence and IOP changes in patients using ICS and INS. Study adhered to PRISMA guidelines. Study protocol was registered with PROSPERO: CRD42020190241.
RESULTS
Qualitative and quantitative analyses included 65 and 41 studies, respectively. Incidence of glaucoma was not significantly different in either ICS or INS users compared to control over 45,457 person-years of follow-up. Similarly, no significant difference in OHT incidence over 4431 person-years was detected. In studies reporting IOP, a significantly higher IOP was observed (0.69 mmHg) in 857 ICS or INS users compared to 615 controls. However, no significant increase in IOP was observed within ICS or INS users when compared to pre-treatment baseline.
CONCLUSION
Overall, use of ICS or INS does not significantly increase the incidence of glaucoma or OHT. However, ICS and INS patients had significantly higher IOPs compared to untreated patients. Awareness of these findings is significant in care of patients with additional risk factors for glaucoma.
PubMed: 35669010
DOI: 10.2147/OPTH.S358066 -
Journal of Glaucoma Aug 2023Cost-effectiveness analyses (CEAs) quantify and compare both costs and measures of efficacy for different interventions. As the costs of glaucoma management to patients,...
PURPOSE
Cost-effectiveness analyses (CEAs) quantify and compare both costs and measures of efficacy for different interventions. As the costs of glaucoma management to patients, payers, and physicians are increasing, we seek to investigate the role of CEAs in the field of glaucoma and how such studies impact clinical management.
METHODS
We adhered to the "Preferred Reporting Items for Systematic Reviews and Meta-analyses" guidelines for our systematic review structure. Eligible studies included any full-text articles that investigated cost-effectiveness or cost-utility as it relates to the field of open angle glaucoma management in the United States. Risk of bias assessment was conducted using the validated Joanna Briggs Institute Critical Appraisal Checklist for Economic Evaluations.
RESULTS
Eighteen studies were included in the review. Dates of publication ranged from 1983 to 2021. Most of the studies were published in the 2000s and performed CEAs in the domains of treatment/therapy, screening, and adherence for patients with primary angle open glaucoma. Of the 18 articles included, 14 focused on treatment, 2 on screening, and 2 on adherence. Most of these studies focused on the cost-effectiveness of different topical medical therapies, whereas only a few studies explored laser procedures, surgical interventions, or minimally invasive procedures. Economic models using decision analysis incorporating state-transition Markov cycles or Montecarlo simulations were widely used, however, the methodology among studies was variable, with a wide spectrum of inputs, measures of outcomes, and time horizons used.
CONCLUSION
Overall, we found that cost-effectiveness research in glaucoma in the United States remains relatively unstructured, resulting in unclear and conflicting implications for clinical management.
Topics: Humans; Glaucoma, Open-Angle; Cost-Benefit Analysis; Intraocular Pressure; Glaucoma; Cost-Effectiveness Analysis
PubMed: 37311022
DOI: 10.1097/IJG.0000000000002249