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Ophthalmic Research 2023Prostaglandin analogs (PGAs) are first-line antiglaucoma agents that appear to either decrease or increase central cornea thickness (CCT), creating controversy regarding... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prostaglandin analogs (PGAs) are first-line antiglaucoma agents that appear to either decrease or increase central cornea thickness (CCT), creating controversy regarding the benefits of PGAs in treating CCT.
PURPOSE
We performed the first meta-analysis of observational studies to evaluate the effects of PGAs on CCT in patients with glaucoma or ocular hypertension (OHT).
METHODS
This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. A literature search was performed of the PubMed, Embase, Cochrane Library, System for Information on Grey Literature in Europe (Open Grey), and ClinicalTrials.gov databases and the references of retrieved studies. Only observational studies were included in the meta-analysis. The final CCT of patients and 95% confidence interval (CI) of each study were extracted. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ). A fixed-effects model was used to calculate the weighted mean difference (WMD) and 95% CI. Subgroup analyses based on several stratified factors such as public bias (Begg's test) and sensitivity analyses were performed.
RESULTS
Five cohort, 5 case-control, and three cross-sectional studies including 2,722 subjects were included. The pooled effect of all thirteen studies showed that PGAs reduced the CCT of patients with glaucoma or OHT slightly but significantly (WMD = -9.37; 95% CI [-12.18, -6.57]; p = 0.00; I2 = 45.5%). Significant effects were also observed in all three study designs: cohort (WMD = -5.17; 95% CI [-9.52, -0.82]), case-control (WMD = -15.31; 95% CI [-22.66, -7.97]), and cross-sectional (WMD = -8.65; 95% CI [-17.30, -0.01]). In addition, subgroup analysis of exposure time showed the effect of PGAs to be more obvious in the first (WMD = -5.81; 95% CI [-9.49, -2.14]) and second (WMD = -13.73; 95% CI [-20.19, -7.28]) years.
CONCLUSIONS
The pooled effects of previously reported studies suggest that PGA use can reduce the CCT of patients with glaucoma or OHT slightly but significantly, with this effect more pronounced in the first 2 years. These findings suggest that clinicians must closely monitor changes in CCT in the first 2 years of PGA use to identify cases of intraocular pressure misestimation and the efficacy of PGAs.
Topics: Humans; Cross-Sectional Studies; Glaucoma, Open-Angle; Cornea; Glaucoma; Ocular Hypertension; Intraocular Pressure; Tonometry, Ocular; Prostaglandins, Synthetic
PubMed: 36455536
DOI: 10.1159/000528461 -
European Journal of Ophthalmology Sep 2023This review focuses on utility of artificial intelligence (AI) in analysis of biofluid markers in glaucoma. We detail the accuracy and validity of AI in the exploration...
PURPOSE
This review focuses on utility of artificial intelligence (AI) in analysis of biofluid markers in glaucoma. We detail the accuracy and validity of AI in the exploration of biomarkers to provide insight into glaucoma pathogenesis.
METHODS
A comprehensive search was conducted across five electronic databases including Embase, Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science. Studies pertaining to biofluid marker analysis using AI or bioinformatics in glaucoma were included. Identified studies were critically appraised and assessed for risk of bias using the Joanna Briggs Institute Critical Appraisal tools.
RESULTS
A total of 10,258 studies were screened and 39 studies met the inclusion criteria, including 23 cross-sectional studies (59%), nine prospective cohort studies (23%), six retrospective cohort studies (15%), and one case-control study (3%). Primary open angle glaucoma (POAG) was the most commonly studied subtype (55% of included studies). Twenty-four studies examined disease characteristics, 10 explored treatment decisions, and 5 provided diagnostic clarification. While studies examined at entire metabolomic or proteomic profiles to determine changes in POAG, there was heterogeneity in the data with over 175 unique, differentially expressed biomarkers reported. Discriminant analysis and artificial neural network predictive models displayed strong differentiating ability between glaucoma patients and controls, although these tools were untested in a clinical context.
CONCLUSION
The use of AI models could inform glaucoma diagnosis with high sensitivity and specificity. While insight into differentially expressed biomarkers is valuable in pathogenic exploration, no clear pathogenic mechanism in glaucoma has emerged.
Topics: Humans; Artificial Intelligence; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Glaucoma; Glaucoma, Open-Angle; Prospective Studies; Proteomics; Retrospective Studies
PubMed: 36426575
DOI: 10.1177/11206721221140948 -
Therapeutic Advances in Ophthalmology 2022The global burden of hypertension is constantly increasing with adverse cardiovascular and ocular sequelae. The association between elevated blood pressure and choroidal...
BACKGROUND
The global burden of hypertension is constantly increasing with adverse cardiovascular and ocular sequelae. The association between elevated blood pressure and choroidal thickness (CT), as assessed via optical coherence tomography (OCT), is poorly understood.
OBJECTIVES AND DESIGN
Studies including hypertensive adults and normotensive controls undergoing OCT were evaluated for inclusion in this meta-analysis. The primary endpoint was CT difference between hypertensive and normotensive adults.
DATA SOURCES AND METHODS
We conducted a systematic review and after searching 1011 results from MEDLINE, ClinicalTrials.gov, medRxiv and Cochrane Library, six studies were deemed eligible and were pooled according to a random-effect model.
RESULTS
A statistically significant reduction in choroidal thickness was found in hypertensive adults ( = 454) as compared with normotensive controls ( = 365) [mean difference: -0.77; 95% confidence intervals: (-1.20, -0.34); = 0.0004]. The main limitations of this meta-analysis are the relatively small population included and the high statistical heterogeneity ( = 87%) among the various studies. Of note, after excluding one study the heterogeneity was markedly reduced.
CONCLUSION
Choroidal thickness is reduced among hypertensive subjects compared with normotensive controls. This finding mandates further examination in the context of long-term clinical outcomes.
PubMed: 36388726
DOI: 10.1177/25158414221132825 -
EMBO Molecular Medicine Dec 2022Spontaneous bleeds are a leading cause of death in the pediatric JAG1-related liver disease Alagille syndrome (ALGS). We asked whether there are sex differences in...
Spontaneous bleeds are a leading cause of death in the pediatric JAG1-related liver disease Alagille syndrome (ALGS). We asked whether there are sex differences in bleeding events in patients, whether Jag1 mice display bleeds or vascular defects, and whether discovered vascular pathology can be confirmed in patients non-invasively. We performed a systematic review of patients with ALGS and vascular events following PRISMA guidelines, in the context of patient sex, and found significantly more girls than boys reported with spontaneous intracranial hemorrhage. We investigated vascular development, homeostasis, and bleeding in Jag1 mice, using retina as a model. Jag1 mice displayed sporadic brain bleeds, a thin skull, tortuous blood vessels, sparse arterial smooth muscle cell coverage in multiple organs, which could be aggravated by hypertension, and sex-specific venous defects. Importantly, we demonstrated that retinographs from patients display similar characteristics with significantly increased vascular tortuosity. In conclusion, there are clinically important sex differences in vascular disease in ALGS, and retinography allows non-invasive vascular analysis in patients. Finally, Jag1 mice represent a new model for vascular compromise in ALGS.
Topics: Female; Male; Animals; Mice; Alagille Syndrome; Sex Characteristics; Retina; Risk Factors
PubMed: 36345711
DOI: 10.15252/emmm.202215809 -
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 -
PloS One 2022Pediatric conditions can lead to significant caregiver burden and poor quality of life (QoL). This systematic review describes research relating to caregiver burden and...
Pediatric conditions can lead to significant caregiver burden and poor quality of life (QoL). This systematic review describes research relating to caregiver burden and QoL of caregivers of pediatric glaucoma patients. A systematic database search of Embase, Medline, PsycINFO, CINAHL, Web of Science, and the three journals within the Association for Research in Vision and Ophthalmology (ARVO) was conducted in October 2021. Publications underwent abstract and full-text screening and were included if they reported pediatric caregivers' QoL using quantitative or qualitative methods. Review articles, publications not in English, and articles focusing on adult glaucoma patients were excluded. Studies then underwent risk of bias assessment and data extraction. Of the 105 publications identified, 8 publications with 667 participants were included in the review. Studies indicated significantly higher burden and poor QoL in caregivers. Female sex, lower education level, lower income, and working status of caregivers were associated with poorer QoL and greater burden. Additionally, more severe and longer duration of the child's disease negatively impacted these measures of caregiver wellbeing. Additionally, studies found significant improvement in caregiver QoL after patients underwent surgery with combined trabeculotomy-trabeculectomy. In conclusion, few studies have investigated the impact of pediatric glaucoma on caregivers. This review of the existing studies found poor QoL and high levels of caregiver burden within this population. Given the lifelong nature of pediatric glaucoma, there is a need for further longitudinal research focusing on the caregivers of these pediatric patients. Long-term follow-up would allow for a greater understanding of how caregiver QoL changes over the course of the disease.
Topics: Adult; Humans; Female; Child; Quality of Life; Caregiver Burden; Caregivers; Income; Glaucoma
PubMed: 36288373
DOI: 10.1371/journal.pone.0276881 -
The Cochrane Database of Systematic... Oct 2022Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such... (Review)
Review
BACKGROUND
Dry eye disease (DED), arising from various etiologic factors, leads to tear film instability, ocular surface damage, and neurosensory changes. DED causes symptoms such as ocular dryness, burning, itching, pain, and visual impairment. Given their well-established anti-inflammatory effects, topical steroid preparations have been widely used as a short-term treatment option for DED. Because of potential risks of ocular hypertension, cataracts, and infections associated with the long-term use of topical steroids, published trials comparing the efficacy and safety of topical steroids (versus placebo) have mostly been of short duration (three to eight weeks).
OBJECTIVES
To evaluate the effectiveness and safety of topical corticosteroids compared with no treatment, placebo, other steroidal or non-steroidal therapies, or a combination of therapies for DED.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 8); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The date of the last search was 20 August 2021.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which topical corticosteroids, alone or in combination with tobramycin, were compared with no treatment, artificial tears (AT), vehicles, AT plus tobramycin, or cyclosporine A (CsA).
DATA COLLECTION AND ANALYSIS
We applied standard Cochrane methodology.
MAIN RESULTS
We identified 22 RCTs conducted in the USA, Italy, Spain, China, South Korea, and India. These RCTs reported outcome data from a total of 4169 participants with DED. Study characteristics and risk of bias All trials recruited adults aged 18 years or older, except one trial that enrolled children and adolescents aged between 3 and 14 years. Half of these trials involved predominantly female participants (median 79%, interquartile range [IQR] 76% to 80%). On average, each trial enrolled 86 participants (IQR 40 to 158). The treatment duration of topical steroids ranged between one week and three months; trial duration lasted between one week and six months. Eight trials were sponsored exclusively by industry, and four trials were co-sponsored by industry and institutional or governmental funds. We assessed the risk of bias of both subjective and objective outcomes using RoB 2, finding nearly half of the trials to be at high risk of bias associated with selective outcome reporting. Findings Of the 22 trials, 16 evaluated effects of topical steroids, alone or in combination with tobramycin, as compared with lubricants (AT, vehicle), AT plus tobramycin, or no treatment. Corticosteroids probably have a small to moderate effect on improving patient-reported symptoms by 0.29 standardized mean difference (SMD) (95% confidence interval [CI] 0.16 to 0.42) as compared with lubricants (moderate certainty evidence). Topical steroids also likely have a small to moderate effect on lowering corneal staining scores by 0.4 SMDs (95% CI 0.18 to 0.62) (moderate certainty evidence). However, steroids may increase tear film break-up time (TBUT) slightly (mean difference [MD] 0.70 s, 95% CI 0.06 to 1.34; low certainty evidence) but not tear osmolarity (MD 1.60 mOsm/kg, 95% CI -10.47 to 13.67; very low certainty evidence). Six trials examined topical steroids, either alone or in combination with CsA, against CsA alone. Low certainty evidence indicates that steroid-based interventions may have a small to moderate effect on improving participants' symptoms (SMD -0.33, 95% CI -0.51 to -0.15), but little to no effect on corneal staining scores (SMD 0.05, 95% CI -0.25 to 0.35) as compared with CsA. The effect of topical steroids compared to CsA alone on TBUT (MD 0.37 s, 95% CI -0.13 to 0.87) or tear osmolarity (MD 5.80 mOsm/kg, 95% CI -0.94 to 12.54; loteprednol etabonate alone) is uncertain because the certainty of the evidence is low or very low. None of the included trials reported on quality of life scores. Adverse effects The evidence for adverse ocular effects of topical corticosteroids is very uncertain. Topical corticosteroids may increase participants' risk of intraocular pressure (IOP) elevation (risk ratio [RR] 5.96, 95% CI 1.30 to 27.38) as compared with lubricants. However, when compared with CsA, steroids alone or combined with CsA may decrease or increase IOP elevation (RR 1.45, 95% CI 0.25 to 8.33). It is also uncertain whether topical steroids may increase risk of cataract formation when compared with lubricants (RR 0.34, 95% CI 0.01 to 8.22), given the short-term use and study duration (four weeks or less) to observe longer-term adverse effects. AUTHORS' CONCLUSIONS: Overall, the evidence for the specified review outcomes was of moderate to very low certainty, mostly due to high risk of bias associated with selective results reporting. For dry eye patients whose symptoms require anti-inflammatory control, topical corticosteroids probably provide small to moderate degrees of symptom relief beyond lubricants, and may provide small to moderate degrees of symptom relief beyond CsA. However, the current evidence is less certain about the effects of steroids on improved tear film quality or quantity. The available evidence is also very uncertain regarding the adverse effects of topical corticosteroids on IOP elevation or cataract formation or progression. Future trials should generate high certainty evidence to inform physicians and patients of the optimal treatment strategies with topical corticosteroids in terms of regimen (types, formulations, dosages), duration, and its time-dependent adverse profile.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Male; Adrenal Cortex Hormones; Cataract; Cyclosporine; Dry Eye Syndromes; Glucocorticoids; Loteprednol Etabonate; Lubricant Eye Drops; Randomized Controlled Trials as Topic; Tobramycin
PubMed: 36269562
DOI: 10.1002/14651858.CD015070.pub2 -
Eye (London, England) Jun 2023The objective of this systematic review is to identify how reporting of micro-invasive glaucoma surgery (MIGS) procedure complications are reported in randomised... (Review)
Review
The objective of this systematic review is to identify how reporting of micro-invasive glaucoma surgery (MIGS) procedure complications are reported in randomised controlled trials (RCTs) and the quality of this reporting compared to the CONSORT extension for harms. RCTs evaluating MIGS procedures were identified from a database of systematic reviews and from recent literature. Trials were evaluated in comparison to the CONSORT extension for harms to quantify the quality of harms reporting. Simple descriptive statistics were calculated for the CONSORT checklist. 21 trials were identified as eligible for inclusion, 14 were evaluating iStent, one Trabectome, three Hydrus, one Cypass, one Preseflo MicroShunt and one Excimer laser trabeculotomy. The average number of CONSORT for Harms checklist items fulfilled by the studies was 10 out of 16. No studies used a validated instrument to report severity of harms and only 4 had a list or definition of adverse events. An analysis of harm was conducted by 19 of 21 studies (90%). Appropriate metrics were used for reporting rates of adverse events in 19 of 21 studies but in only 4 studies was there an attempt to give these adverse events a grade of seriousness. In conclusion, most studies evaluating MIGS procedures do make an effort to acknowledge harms data, however this is not done uniformly well or in the same manner. A validated instrument to report severity and a standard list of complications for MIGS surgery would go a long way to helping this.
Topics: Humans; Checklist; Glaucoma; Ophthalmology; Trabeculectomy; Randomized Controlled Trials as Topic
PubMed: 36253459
DOI: 10.1038/s41433-022-02268-z -
PloS One 2022For primary angle-closure and angle-closure glaucoma, the fact that refractive error sometimes deviates from predictions after intraocular lens (IOL) implantation is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
For primary angle-closure and angle-closure glaucoma, the fact that refractive error sometimes deviates from predictions after intraocular lens (IOL) implantation is familiar to cataract surgeons. Since controversy remains in the accuracy of IOL power calculation formulas, both traditional and network meta-analysis on formula accuracy were conducted in patients with primary angle-closure conditions.
METHODS
A comprehensive literature search was conducted through Aug 2022, focusing on studies on intraocular lens power calculation in primary angle-closure (PAC) and primary angle-closure glaucoma (PACG). A systemic review and network meta-analysis was performed. Quality of studies were assessed. Primary outcomes were the mean absolute errors (MAE) and the percentages of eyes with a prediction error within ±0.50 diopiters (D) or ±1.00 D (% ±0.50/1.00 D) by different formulas.
RESULTS
Six retrospective studies involving 419 eyes and 8 formulas (Barrett Universal II, Kane, SRK/T, Hoffer Q, Haigis, Holladay I, RBF 3.0 and LSF) were included. SRK/T was used as a reference as it had been investigated in all the studies included. Direct comparison showed that none of the involved formula outperformed or was defeated by SRK/T significantly in terms of either MAE or % ±0.50/1.00 D (all P>0.05). Network comparison and ranking possibilities disclosed BUII, Kane, RBF 3.0 with statistically insignificant advantage. No significant publication bias was detected by network funnel plot.
CONCLUSIONS
No absolute advantage was disclosed among the formulas involved in this study for PAC/PACG eyes. Further carefully designed studies are warranted to evaluate IOL calculation formulae in this target population.
TRAIL REGISTRATION
Registration: PROSEPRO ID: CRD42022326541.
Topics: Biometry; Glaucoma, Angle-Closure; Humans; Lenses, Intraocular; Network Meta-Analysis; Optics and Photonics; Phacoemulsification; Refraction, Ocular; Retrospective Studies
PubMed: 36240196
DOI: 10.1371/journal.pone.0276286 -
Meta-Analysis of Dyslipidemia and Blood Lipid Parameters on the Risk of Primary Open-Angle Glaucoma.Computational and Mathematical Methods... 2022We aimed to explore the effect of blood lipid parameters on the risk of primary open-angle glaucoma (POAG) by meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aimed to explore the effect of blood lipid parameters on the risk of primary open-angle glaucoma (POAG) by meta-analysis.
METHODS
The databases of PubMed, Scopus, CNKI, and Wanfang were systematically searched from inception to April 2022, and the relevant research literature was obtained, screened, and analyzed.
RESULTS
A total of 15 studies were included in this meta-analysis, including 11 reporting dyslipidemia and risk of POAG and 5 reporting specific lipid level and risk of POAG. Dyslipidemia increased the risk of POAG with an odd ratio (OR) of 1.25 (95% CI: 1.23, 1.26). Total triglyceride and total cholesterol were not related to the prevalence of POAG, but high-density lipoprotein cholesterol was significantly negatively correlated with the risk of POAG with an OR of 0.96 (95% CI: 0.94, 0.99).
CONCLUSION
Dyslipidemia is a risk factor for POAG. Given the small sample size and significant interstudy heterogeneity, additional studies are needed to establish this conclusion.
Topics: Cholesterol; Dyslipidemias; Glaucoma, Open-Angle; Humans; Lipids; Lipoproteins, HDL; Risk Factors; Triglycerides
PubMed: 36188106
DOI: 10.1155/2022/1122994