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Acta Ophthalmologica Feb 2022Diabetic macular oedema (DME) is considered a chronic inflammatory disease associated with aberrations in many intraocular cytokines. Studies assessing the role of these... (Meta-Analysis)
Meta-Analysis
Diabetic macular oedema (DME) is considered a chronic inflammatory disease associated with aberrations in many intraocular cytokines. Studies assessing the role of these cytokines as biomarkers in the diagnosis and management of DME have demonstrated inconsistent findings. We quantitatively summarized data related to 116 candidate aqueous and vitreous inflammatory cytokines as biomarkers in DME. A systematic search without year limitation was performed up to 19 October 2020. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with DME. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with DME and controls. Data were extracted from 128 studies that included 4163 study eyes with DME and 1281 control eyes. Concentrations (standard mean difference, 95% confidence interval and p-value) of aqueous IL-6 (1.28, 0.57-2.00, p = 0.004), IL-8 (1.06, 0.74-1.39, p < 0.00001), MCP-1 (1.36, 0.57-2.16, p = 0.0008) and VEGF (1.31, 1.01-1.62, p < 0.00001) and vitreous VEGF (2.27, 1.55-2.99, p < 0.00001) were significantly higher in patients with DME (n = 4163) compared to healthy controls (n = 1281). No differences, failed sensitivity analyses or insufficient data were found between patients with DME and healthy controls for the concentrations of the remaining cytokines. This analysis implicates multiple cytokine biomarker candidates other than VEGF in DME and clarifies previously reported inconsistent associations. As the therapeutic options for DME expand to include multiple agents with multiple targets, it will be critical to manage the treatment burden with tailored therapy that optimizes outcomes and minimizes treatment burden. Intraocular cytokines have the promise of providing a robust individualized assessment of disease status and response to therapy. We have identified key candidate cytokines that may serve as biomarkers in individualized treatment algorithms.
Topics: Aqueous Humor; Biomarkers; Cytokines; Diabetic Retinopathy; Humans; Inflammation; Macular Edema; Vitreous Body
PubMed: 33945678
DOI: 10.1111/aos.14891 -
The Cochrane Database of Systematic... Nov 2020Diabetic macular edema (DME) is secondary to leakage from diseased retinal capillaries with thickening of central retina, and is an important cause of poor central... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic macular edema (DME) is secondary to leakage from diseased retinal capillaries with thickening of central retina, and is an important cause of poor central visual acuity in people with diabetic retinopathy. Intravitreal steroids have been used to reduce retinal thickness and improve vision in people with DME.
OBJECTIVES
To assess the effectiveness and safety of intravitreal steroid therapy compared with other treatments for DME.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase on 15 May, 2019. We also searched reference lists, Science Citation Index, conference proceedings, and relevant trial registers. We conducted a top up search on 21 October, 2020.
SELECTION CRITERIA
We included randomized controlled trials that evaluated any type of intravitreal steroids as monotherapy against any other intervention (e.g. observation, laser photocoagulation, anti-vascular endothelial growth factor (antiVEGF) for DME.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study eligibility and risk of bias and extracted data. Where appropriate, we performed meta-analyses.
MAIN RESULTS
We included 10 trials (4348 participants, 4505 eyes). These trials compared intravitreal steroid therapies versus other treatments, including intravitreal antiVEGF therapy, laser photocoagulation, and sham injection. Most trials had an overall unclear or high risk of bias. One trial (701 eyes ) compared intravitreal dexamethasone implant 0.7mg with sham. We found moderate-certainty evidence that dexamethasone leads to slightly more improvement of visual acuity than sham at 12 months (mean difference [MD] -0.08 logMAR, 95% confidence interval [CI] -0.12 to -0.05 logMAR). Regarding improvement of three or more lines of visual acuity, there was moderate-certainty evidence in favor of dexamethasone at 12 months, but the CI covered the null value (risk ratio (RR) 1.39, 95% CI 0.91 to 2.12). Regarding adverse events, dexamethasone increased by about four times the risk of cataract progression and the risk of using intraocular pressure (IOP)-lowering medications compared to sham (RR 3.89, 95% CI 2.75 to 5.50 and RR 4.54, 95% CI 3.19 to 6.46, respectively; moderate-certainty evidence); about 4 in 10 participants treated with dexamethasone needed IOP-lowering medications. Two trials (451 eyes) compared intravitreal dexamethasone implant 0.7mg with intravitreal antiVEGF (bevacizumab and ranibizumab). There was moderate-certainty evidence that visual acuity improved slightly less with dexamethasone compared with antiVEGF at 12 months (MD 0.07 logMAR, 95% CI 0.04 to 0.09 logMAR; 2 trials; 451 participants/eyes; I = 0%). The RR of gain of three or more lines of visual acuity was inconsistent between trials, with one trial finding no evidence of a difference between dexamethasone and bevacizumab at 12 months (RR 0.99, 95% CI 0.70 to 1.40; 1 trial; 88 eyes), and the other, larger trial finding the chances of vision gain were half with dexamethasone compared with ranibizumab (RR 0.50, 95% CI 0.32 to 0.79; 1 trial; 432 participants). The certainty of evidence was low. Cataract progression and the need for IOP-lowering medications increased more than 4 times with dexamethasone implant compared to antiVEGF (moderate-certainty evidence). One trial (560 eyes) compared intravitreal fluocinolone implant 0.19mg with sham. There was moderate-certainty evidence that visual acuity improved slightly more with fluocinolone at 12 months (MD -0.04 logMAR, 95% CI -0.06 to -0.01 logMAR). There was moderate-certainty evidence that an improvement in visual acuity of three or more lines was more common with fluocinolone than with sham at 12 months (RR 1.79, 95% CI 1.16 to 2.78). Fluocinolone also increased the risk of cataract progression (RR 1.63, 95% CI 1.35 to 1.97; participants = 335; moderate-certainty evidence), which occurred in about 8 in 10 participants, and the use of IOP-lowering medications (RR 2.72, 95% CI 1.87 to 3.98; participants = 558; moderate-certainty evidence), which were needed in 2 to 3 out of 10 participants. One small trial with 43 participants (69 eyes) compared intravitreal triamcinolone acetonide injection 4 mg with sham. There may be a benefit in visual acuity at 24 months (MD -0.11 logMAR, 95% CI -0.20 to -0.03 logMAR), but the certainty of evidence is low. Differences in adverse effects were poorly reported in this trial. Two trials (615 eyes) compared intravitreal triamcinolone acetonide injection 4mg with laser photocoagulation and reached discordant results. The smaller trial (31 eyes followed up to 9 months) found more visual acuity improvement with triamcinolone (MD -0.18 logMAR, 95% CI -0.29 to -0.07 logMAR), but a larger, multicenter trial (584 eyes, 12-month follow-up) found no evidence of a difference regarding change in visual acuity (MD 0.02 logMAR, 95% CI -0.03 to 0.07 logMAR) or gain of three or more lines of visual acuity (RR 0.85, 95% CI 0.55 to 1.30) (overall low-certainty evidence). Cataract progression was about three times more likely (RR 2.68, 95% CI 2.21 to 3.24; moderate-certainty evidence) and the use of IOP-lowering medications was about four times more likely (RR 3.92, 95% CI 2.59 to 5.96; participants = 627; studies = 2; I = 0%; moderate-certainty evidence) with triamcinolone. About 1 in 3 participants needed IOP-lowering medication. One small trial (30 eyes) compared intravitreal triamcinolone acetonide injection 4mg with intravitreal antiVEGF (bevacizumab or ranibizumab). Visual acuity may be worse with triamcinolone at 12 months (MD 0.18 logMAR, 95% CI 0.10 to 0.26 logMAR); the certainty of evidence is low. Adverse effects were poorly reported in this trial. Four trials reported data on pseudophakic participants, for whom cataract is not a concern. These trials found no decrease in visual acuity in the second treatment year due to cataract progression.
AUTHORS' CONCLUSIONS
Intravitreal steroids may improve vision in people with DME compared to sham or control. Effects were small, about one line of vision or less in most comparisons. More evidence is available for dexamethasone or fluocinolone implants when compared to sham, and the evidence is limited and inconsistent for the comparison of dexamethasone with antiVEGF treatment. Any benefits should be weighed against IOP elevation, the use of IOP-lowering medication and, in phakic patients, the progression of cataract. The need for glaucoma surgery is also increased, but remains rare.
Topics: Anti-Inflammatory Agents; Bevacizumab; Bias; Confidence Intervals; Dexamethasone; Diabetic Retinopathy; Drug Implants; Fluocinolone Acetonide; Glucocorticoids; Humans; Intravitreal Injections; Macular Edema; Randomized Controlled Trials as Topic; Ranibizumab; Steroids; Triamcinolone; Vascular Endothelial Growth Factor A; Visual Acuity; Vitreous Body
PubMed: 33206392
DOI: 10.1002/14651858.CD005656.pub3 -
Romanian Journal of Ophthalmology 2020Endogenous endophthalmitis, EE, a less common form of endophthalmitis, occurs when the microorganisms spread to the eye through the bloodstream, from a septic focus...
Endogenous endophthalmitis, EE, a less common form of endophthalmitis, occurs when the microorganisms spread to the eye through the bloodstream, from a septic focus elsewhere in the body, that breaches into the integrity of the eyeball itself. The etiopathogenesis of endogenous endophthalmitis has changed over the past two decades, the aim of this review being to study the changing trends in causative organism in the era of modern antibiotics.
Topics: Anti-Bacterial Agents; Bacteria; Endophthalmitis; Eye Infections, Bacterial; Humans; Vitreous Body
PubMed: 32685775
DOI: No ID Found -
Acta Ophthalmologica Mar 2021Inflammatory cytokines are involved in the pathogenesis of neovascular age-related macular degeneration (nAMD) and have been shown to be useful as diagnostic and... (Meta-Analysis)
Meta-Analysis
Inflammatory cytokines are involved in the pathogenesis of neovascular age-related macular degeneration (nAMD) and have been shown to be useful as diagnostic and predictive biomarkers. Given the heterogeneity of data within the literature, we aimed to quantitatively summarize data related to inflammatory cytokines in nAMD. A systematic search without year limitation was performed up to 13 April 2020. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with nAMD. Data were extracted from 95 studies that encompassed 3105 study eyes with nAMD and 1209 control eyes. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with nAMD and controls. Among the 4314 eyes in 95 studies, aqueous concentrations (standard mean difference, 95% confidence interval and p-value) of MCP-1 (0.43, 0.09 to 0.77 and p = 0.01), MIG (0.63, 0.31 to 0.94 and p = 0.0001), TGF-β (0.45, 0.07 to 0.82 and p = 0.02) and VEGF (0.64, 0.31 to 0.98 and p = 0.0001) were significantly higher in patients with nAMD compared to healthy controls. No differences, failed sensitivity analyses or insufficient data were found between patients with nAMD and healthy controls for the concentrations of the remaining cytokines and with all vitreous samples. Previous studies had shown conflicting associations with nAMD for all 27 cytokines assessed. Our analysis indicates multiple candidate cytokines other than VEGF that are implicated in nAMD and adds clarity to the previous literature. This will help focus translational research in nAMD investigating biomarkers and therapeutic targets.
Topics: Aqueous Humor; Biomarkers; Cytokines; Humans; Inflammation; Vitreous Body; Wet Macular Degeneration
PubMed: 32602185
DOI: 10.1111/aos.14537 -
Acta Ophthalmologica Dec 2020Asteroid hyalosis is defined by the presence of white, snowball-like non-crystalline vitreous opacities that move with the vitreous and appear to be anchored to its... (Meta-Analysis)
Meta-Analysis
Asteroid hyalosis is defined by the presence of white, snowball-like non-crystalline vitreous opacities that move with the vitreous and appear to be anchored to its matrix. Asteroid hyalosis commonly occurs in the absence of other identifiable ocular abnormalities and is usually an incidental finding. The vitreous opacities are usually invisible to the patient and asymptomatic, but asteroid hyalosis can be a significant obstacle to the examination of the fundus. The prevalence increases dramatically with age. The aetiology is unknown. We systematically reviewed the literature for epidemiological data, qualitatively reviewed available studies, conducted meta-analyses with demographical stratifications, evaluated temporal changes and estimated the future prevalence using forecasting analysis. Nine eligible studies were identified with data on 104 569 individuals. The overall population prevalence of asteroid hyalosis was 0.75% (95% confidence interval: 0.39-1.21%); however, the prevalence was highly age-dependent, ranging from 0.27% (95% confidence interval 0.12-0.49%) in individuals aged 0-39 years and gradually increasing to 3.07% (95% confidence interval 1.90-4.50%) in individuals aged ≥80 years. Male gender was an additional risk factor (odds ratio 1.80, 95% confidence interval 1.32-2.45, p = 0.00017). The estimated global prevalence was 10.7 million subjects in year 1950, which is expected to increase to 41.5 million in year 2020 and 91.2 million in year 2100. The prevalence of asteroid hyalosis is relevant because it impacts the utility of diagnostic strategies, especially screening methods for conditions such as diabetic retinopathy.
Topics: Eye Diseases; Global Health; Humans; Prevalence; Vitreous Body
PubMed: 32410360
DOI: 10.1111/aos.14465 -
JAMA Network Open Feb 2020Diagnosing posterior chamber ocular abnormalities typically requires specialist assessment. Point-of-care ultrasonography (POCUS) performed by nonspecialists, if... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Diagnosing posterior chamber ocular abnormalities typically requires specialist assessment. Point-of-care ultrasonography (POCUS) performed by nonspecialists, if accurate, could negate the need for urgent ophthalmologist evaluation.
OBJECTIVE
This meta-analysis sought to define the diagnostic test characteristics of emergency practitioner-performed ocular POCUS to diagnose multiple posterior chamber abnormalities in adults.
DATA SOURCES
PubMed (OVID), MEDLINE, EMBASE, Cochrane, CINAHL, and SCOPUS were searched from inception through June 2019 without restrictions. Conference abstracts and trial registries were also searched. Bibliographies of included studies and relevant reviews were manually searched, and experts in the field were queried.
STUDY SELECTION
Included studies compared ocular POCUS performed by emergency practitioners with a reference standard of ophthalmologist evaluation. Pediatric studies were excluded. All 116 studies identified during abstract screening as potentially relevant underwent full-text review by multiple authors, and 9 studies were included.
DATA EXTRACTION AND SYNTHESIS
In accordance with PRISMA guidelines, multiple authors extracted data from included studies. Results were meta-analyzed for each diagnosis using a bivariate random-effects model. Data analysis was performed in July 2019.
MAIN OUTCOMES AND MEASURES
The outcomes of interest were diagnostic test characteristics of ocular POCUS for the following diagnoses: retinal detachment, vitreous hemorrhage, vitreous detachment, intraocular foreign body, globe rupture, and lens dislocation.
RESULTS
Nine studies (1189 eyes) were included. All studies evaluated retinal detachment, but up to 5 studies assessed each of the other diagnoses of interest. For retinal detachment, sensitivity was 0.94 (95% CI, 0.88-0.97) and specificity was 0.94 (95% CI, 0.85-0.98). Sensitivity and specificity were 0.90 (95% CI, 0.65-0.98) and 0.92 (95% CI, 0.75-0.98), respectively, for vitreous hemorrhage and were 0.67 (95% CI, 0.51-0.81) and 0.89 (95% CI, 0.53-0.98), respectively, for vitreous detachment. Sensitivity and specificity were high for lens dislocation (0.97 [95% CI, 0.83-0.99] and 0.99 [95% CI, 0.97-1.00]), intraocular foreign body (1.00 [95% CI, 0.81-1.00] and 0.99 [95% CI, 0.99-1.00]), and globe rupture (1.00 [95% CI, 0.63-1.00] and 0.99 [95% CI, 0.99-1.00]). Results were generally unchanged in sensitivity analyses of studies with low risk of bias.
CONCLUSIONS AND RELEVANCE
This study suggests that emergency practitioner-performed ocular POCUS is an accurate test to assess for retinal detachment in adults. Its utility in diagnosing other posterior chamber abnormalities is promising but needs further study.
Topics: Eye Diseases; Humans; Point-of-Care Systems; Posterior Eye Segment; Retinal Detachment; Ultrasonography
PubMed: 32074291
DOI: 10.1001/jamanetworkopen.2019.21460