Clinical Characteristics Associated With Secondary Generalization in Patients With Ocular Myasthenia Gravis: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Ocular myasthenia gravis (OMG) is an autoimmune disorder resulting in ocular symptoms such as diplopia and ptosis. The proportion of patients who convert to secondary generalized myasthenia gravis (SGMG) reported in the literature has been varied. The aim of this systematic review was to determine the clinical characteristics of patients with OMG and the proportion of SGMG conversion. METHODS: We conducted an electronic database search for randomized controlled trials, prospective nonrandomized studies, observational studies, and retrospective studies in EMBASE, CENTRAL, MEDLINE, and Web of Science. We included studies with patients with OMG who initially presented with ocular symptoms and signs only and were seen in clinical practice, reporting on the characteristics and outcomes of SGMG. We excluded studies with pediatric and congenital myasthenia gravis populations. Eligible studies included articles written in any language and containing data on patients with OMG. The main outcome measured was the proportion of patients with OMG who converted to SGMG and risk factors associated with secondary generalization of OMG. Two independent reviewers screened titles and abstracts and extracted data from full texts, reporting findings according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodology was evaluated using the Joanna Briggs Institute critical appraisal forms. PROSPERO registration number: CRD2021285257. RESULTS: Thirty-one studies were included in the quantitative and qualitative analysis. The proportion of generalization ranged from 11% to 84%. The pooled proportion was 39% (95% CI 32%-47%, I 2 = 95.86%, p < 0.001 unweighted, low certainty). The pooled risk ratio of female sex for conversion to SGMG was 1.06 (95% CI 0.96-1.17, I 2 = 0% p = 0.614, 21 studies included, very low certainty), and the pooled risk ratio of acetylcholine receptor (AChR) positivity was 1.30 (95% CI 1.05-1.56, I 2 = 0% p = 0.455, 16 studies included, very low certainty). DISCUSSION: Risk factors such as female sex and anti-AChR positivity have been identified to have possible associations with SGMG, but there are not enough quality observational studies. There is a need for a prospective global database of patients with OMG, including all countries with different populations.

Clinical characteristics of ocular myasthenia gravis and outcomes of secondary generalisation: a systematic review protocol.

OBJECTIVE: We aim to systematically assess the clinical characteristics of ocular myasthenia gravis (OMG) and report on the proportion of patients who develop secondary generalised myasthenia gravis (SGMG). INTRODUCTION: OMG is an autoimmune neuromuscular junction disorder resulting in ptosis and diplopia. A proportion of patients with OMG develop weakness in their limbs, respiratory or bulbar muscles, that is, convert to SGMG. The proportion of patients converting to SGMG reported in the literature have been varied. We therefore aim to systematically assess the clinical characteristics of OMG and outcomes of SGMG reported in the literature to date. INCLUSION CRITERIA: Studies describing a population of adults with OMG, that is, MG with ocular symptoms and signs only, seen consecutively through a clinical service, reporting on patient characteristics and the outcome of SGMG. Studies on paediatric and congenital myasthenia gravis will be excluded. METHODS: We will conduct an electronic database search for randomised controlled trials, prospective non-randomised studies, observational studies and retrospective studies in MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Web of Science. Exploratory database search was conducted on 1 December 2021. Eligibility criteria will include quantitative and qualitative articles written in any language and containing data on OMG. Additional studies will be identified by reviewing bibliographies of retrieved articles. Two independent reviewers will screen titles and abstracts and extract data from full texts, reporting outcomes according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data extraction of key characteristics will be completed using customised forms. Methodological quality will be assessed using the Joanna Briggs Institute critical appraisal forms. ETHICS AND DISSEMINATION: Ethical approval is not required for this review, as it will only include published data. Findings will be published in a peer-reviewed journal and disseminated across ophthalmic networks. PROSPERO REGISTRATION NUMBER: CRD42021285257.

Optical aberrations following implantation of multifocal intraocular lenses: a systematic review and meta-analysis protocol.

INTRODUCTION: Multifocal intraocular lens (IOLs) are used to restore vision at different focal distances. The technology of multifocal IOLs is continually advancing. Optical aberrations a property of lenses that causes spreading of light over a region resulting in a blurred or distorted image. This study aims to systematically review investigator measured and patient reported optical aberrations following implantation of multifocal IOLs during phacoemulsification surgery to treat presbyopia in adults. METHODS AND ANALYSIS: We will conduct an electronic database search for randomised controlled trials, prospective non-randomised studies, observational studies in Ovid MEDLINE, Ovid EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus and ClinicalTrials.gov in March 2021. Eligibility criteria will include quantitative articles written in English and containing data on optical aberrations. Two independent reviewers will screen titles and abstracts and extract data from full texts, reporting outcomes according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data extraction of key characteristics will be completed using customised forms. Methodological quality will be assessed using Cochrane Handbook 6.2. ETHICS AND DISSEMINATION: Ethics approval is not required for this review, as it will only include published data. Findings will be published in a peer-reviewed journal and disseminated across ophthalmic networks. We anticipate that the findings of this work will be of interest to multiple stakeholders: people who have undergone cataract surgery, eye health professionals, ophthalmic surgeons, device manufacturers and policy-makers. It will also inform researchers to where there are gaps in evidence and identify areas for future research. PROSPERO REGISTRATION NUMBER: CRD42021271050.

Invasive dental treatment and acute vascular events: A systematic review and meta-analysis.

BACKGROUND: Acute infection/inflammation increases the risk of acute vascular events (AVEs). Invasive dental treatments (IDTs) trigger short-term acute inflammation. PURPOSE: The aim of this work is to critically appraise the evidence linking IDTs and AVEs. DATA SOURCES: Six bibliographical databases were searched up to 31 August 2021. A systematic review following PRISMA guidelines was performed. STUDY SELECTION: Intervention and observational studies reporting any AVEs following IDT were included. DATA EXTRACTION: Two reviewers independently extracted data and rated the quality of studies. Data were pooled using fixed-effect, inverse variance weights analysis. RISK OF BIAS: Risk of bias was assessed by the Newcastle-Ottawa Quality Assessment Scale for observational studies and the Cochrane Handbook-Rob 2.0 for randomized controlled trials. DATA SYNTHESIS: In 3 out of 16 clinical studies, a total of 533,175 participants, 124,344 myocardial infarctions, and 327,804 ischaemic strokes were reported. Meta-analysis confirmed that IDT did not increase incidence ratios (IR) for combined vascular events either at 1-4 weeks (IR of 1.02, 95% CIs: 0.92 to 1.13) and at 5-8 weeks (IR of 1.04, 95% CIs: 0.97 to1.10) after treatment. LIMITATIONS: A high level of heterogeneity (study designs and time point assessments) was found. CONCLUSION: Patients who received IDT exhibited no substantial increase in vascular risk over 8 weeks post treatment.

Risk of intraocular pressure elevation after topical steroids in children and adults: A systematic review.

Topical steroids may induce a rise in intraocular pressure. The risk may increase with prolonged use, high frequency of administration, young age, higher ocular penetrance and higher anti-inflammatory potency. We aimed to study this relationship by comparing published rates of intraocular pressure elevation following administration of topical steroids and compared the risk of higher versus lower dosage regimes, high- versus low-potency/penetration steroids and adults versus children. Data sources used were Ovid Embase, Ovid Medline, the Cochrane Central Register of Controlled Trials, Web of Science, Scopus, CINHAL Plus and LILACS. Eligible studies were randomised controlled trials of topical steroids versus any other topical steroid, nonsteroidal anti-inflammatory drugs, placebo or vehicle, or a different mode of administration administered for 7 days or longer that reported intraocular pressure elevation from baseline as >10, 6-15 or >15 mm Hg in adults or children. Risks of bias were reviewed using the GRADE quality approach. Data were extracted into the software package, RevMan, Version 5 (Cochrane Collaboration). In total, 43 studies were included. Meta-analysis was not possible. Topical steroids of lower anti-inflammatory potency, and with reduced intraocular penetration, are associated with reduced incidence of intraocular pressure elevation. A comparison of data in children and adults is limited by the use of different reporting systems. The principal obstacle to meta-analysis is the different reporting systems used to categorise intraocular pressure elevation. We recommend future studies should report intraocular pressure elevation >10 mm Hg from baseline to allow meta-analysis of data.

Glaucoma Control Strategies in Sub-Saharan Africa: A Review of the Clinical and Health Economic Evidence.

PURPOSE: A review of the effectiveness, costs, and cost-effectiveness of detection and treatment strategies for glaucoma control in Sub-Saharan Africa (SSA) was conducted. METHODS: Detailed searches were performed using the Ovid Medline, Ovid Embase, The Cochrane Library, Web of Science, Scopus, and LILACS databases up to September 2016. The key Medical Subject Heading search terms used included glaucoma, diagnosis, treatment, effectiveness, costs, cost-effectiveness, and Sub-Saharan Africa. Effectiveness was measured as the proportion of study participants with an intra-ocular pressure less than or equal to 22 mmHg. RESULTS: A total of 5658 records were examined with 48 papers identified. The sensitivity and specificity of portable instruments or smartphone technologies to detect glaucomatous changes ranged from 58.3% to 93.8% and from 82.4% to 96.8%, respectively. The overall effect size for various glaucoma interventions was: 0.39 (95% confidence interval (CI) 0.27-0.54, I2 = 64.85, p = 0.036) for laser trabeculoplasty; 0.56 (95% CI 0.23-0.84, I2 = 85.74, p = 0.001) for drainage implant devices; 0.66 (95% CI 0.61-0.71, I2 = 0.00, p = 0.402) for medical management; and 0.73 (95% CI 0.65-0.80, I2 = 93.25, p = 0.000) for all other non-drainage tube surgical interventions, including trabeculectomy surgery and the use of anti-metabolites. The mean annual cost of anti-glaucoma drugs across SSA was USD 394, with a mean direct non-medication cost per year of USD 54, and a mean surgical cost per year of USD 283. CONCLUSIONS: While effective glaucoma control interventions exist, their widespread use and diffusion across SSA remain challenging principally due to low per capita income levels and high glaucoma treatment costs.

Use of hyaluronidase as an adjunct to local anaesthetic eye blocks to reduce intraoperative pain in adults.

BACKGROUND: Hyaluronidase has been used over many decades as an adjunct to local anaesthetic solution to improve the speed of onset of eye blocks and to provide better akinesia and analgesia. With the evolution of modern eye surgery techniques, fast onset and akinesia are not essential requirements anymore. The assumption that the addition of hyaluronidase to local anaesthetic injections confers better analgesia for the patient needs to be examined. There has been no recent systematic review to provide evidence that hyaluronidase actually improves analgesia. OBJECTIVES: To ascertain if adding hyaluronidase to local anaesthetic solutions for use in ophthalmic anaesthesia in adults results in a reduction of perceived pain during the operation and to assess harms, participant and surgical satisfaction, and economic impact. SEARCH METHODS: We carried out systematic searches in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and four other databases in June 2017. We searched the trial registers at www.ISRCTN.com, ClinicalTrials.gov and www.clinicaltrialsregister.eu for relevant trials. We imposed no language restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated the effect of hyaluronidase on pain experienced by adults during intraocular surgery using a rating scale. DATA COLLECTION AND ANALYSIS: Two review authors (HR and KA) independently extracted data and assessed methodological quality using standard procedures as expected by Cochrane. MAIN RESULTS: We included seven trials involving 500 participants that studied the effect of hyaluronidase on intraoperative pain. Four of the seven trials with 289 participants reported the primary outcome in a dichotomous manner, and we proceeded to meta-analyse the findings which showed a moderate heterogeneity that could not be explained (I2 = 41% ). The pooled risk ratio (RR) for these four trials was 0.83 with the 95% confidence interval ranging from 0.48 to 1.42. The reduction in intraoperative pain scores in the hyaluronidase group were not statistically significant. Among the three trials that reported the primary outcome in a continuous manner, the presence of missing data made it difficult to conduct a meta-analysis. To further explore the data, we imputed standard deviations for the other studies from another included RCT (Sedghipour 2012). However, this resulted in substantial heterogeneity between study estimates (I² = 76% ). The lack of reported relevant data in two of the three remaining trials made it difficult to assess the direction of effect in a clinical setting.Overall, there was no statistical difference regarding the intraoperative reduction of pain scores between the hyaluronidase and control group. All seven included trials had a low risk of bias.According to GRADE, we found the quality of evidence was low and downgraded the trials for serious risk of inconsistency and imprecision. Therefore, the results should be analysed with caution.Participant satisfaction scores were significantly higher in the hyaluronidase group in two high quality trials with 122 participants. Surgical satisfaction was also superior in two of three high quality trials involving 141 participants. According to GRADE, the quality of evidence was moderate for participant and surgical satisfaction as the trials were downgraded for imprecision due to the small sample sizes. The risk of bias in these trials was low.There was no reported harm due to the addition of hyaluronidase in any of the studies. No study reported on the cost of hyaluronidase in the context of eye surgery. AUTHORS' CONCLUSIONS: The effects of adding hyaluronidase to local anaesthetic fluid on pain outcomes in people undergoing eye surgery are uncertain due to the low quality of evidence available. A well designed RCT is required to address inconsistency and imprecision among the studies and to determine the benefit of hyaluronidase to improve analgesia during eye surgery. Participant and surgical satisfaction is higher with hyaluronidase compared to the control groups, as demonstrated in moderate quality studies. There was no harm attributed to the use of hyaluronidase in any of the studies. Considering that harm was only rarely defined as an outcome measure, and the overall small number of participants, conclusions cannot be drawn about the incidence of harmful effects of hyaluronidase. None of the studies undertook cost calculations with regards to use of hyaluronidase in local anaesthetic eye blocks.