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Seminars in Ophthalmology 2018To review the application of the PACK-CXL and to identify different treatment protocols according to the pathogens associated with keratitis. (Review)
Review
PURPOSE
To review the application of the PACK-CXL and to identify different treatment protocols according to the pathogens associated with keratitis.
METHODS
A systematic review of 21 articles. The primary outcome was the healing of a corneal ulcer, defined as epithelization, blocking corneal melting. The secondary end-point was the recovery of visual acuity.
RESULTS
We studied a total of 145 eyes. Infectious keratitis was associated with bacteria in 80 eyes (55.55%), fungus in 24 eyes (16.67%), and protozoa in 13 (8.97%). In 26 (18%), the microbiological culture was negative or not performed. The mean time of re-epithelization was 25.70±29.83days (1-180). A total of 27 patients needed corneal transplantation. The overall probability of blocking corneal melting was 84.13%. Three different protocols for each group of pathogens have been proposed.
CONCLUSION
PACK-CXL still has a limit in its spread. In the future, we hope that each pathogen will be treated with the most efficient and least invasive protocols available.
Topics: Corneal Transplantation; Cross-Linking Reagents; Eye Infections, Bacterial; Humans; Keratitis; Photochemotherapy; Photosensitizing Agents; Riboflavin; Ultraviolet Rays; Visual Acuity
PubMed: 27093581
DOI: 10.3109/08820538.2015.1123731 -
Clinical Breast Cancer Aug 2020Epidemiologic studies focusing on the association between 1-carbon metabolism-related vitamins (ie, folate, vitamin B, vitamin B, vitamin B) and breast cancer risk have... (Meta-Analysis)
Meta-Analysis
Epidemiologic studies focusing on the association between 1-carbon metabolism-related vitamins (ie, folate, vitamin B, vitamin B, vitamin B) and breast cancer risk have reported inconsistent findings. We conducted a systematic search of the reported data and performed a meta-analysis of prospective case-control and cohort studies to derive a more precise evaluation. The PubMed and EMBASE databases were searched to identify eligible studies. A total of 27 studies involving 49,707 cases and 1,274,060 individuals were included in the meta-analysis. The results indicated that a high intake of folate, vitamin B, and vitamin B might decrease the risk of breast cancer. The corresponding pooled relative risks (RRs) for the highest intake compared with the lowest were 0.93 (95% confidence interval [CI], 0.88-0.99; P = .018), 0.94 (95% CI, 0.89-1.00; P = .037) and 0.90 (95% CI, 0.82-0.99; P = .026). No significant association between vitamin B and breast cancer risk was found (RR, 0.99; 95% CI, 0.94-1.04; P = .604). Further study showed that folate and vitamin B might decrease the risk of estrogen receptor-negative (ER)/progesterone receptor-negative (PR) breast cancer but not ER/PR breast cancer. The dose-response meta-analysis indicated a significant linearity relationship between folate intake and a reduced risk of ER/PR breast cancer. An increment of folate intake (100 μg/d) corresponded to a 7% deceased risk of ER/PR breast cancer (RR, 0.93; 95% CI, 0.89-0.98; P = .007). In conclusion, a high intake of 1-carbon metabolism-related vitamins might contribute to the prevention of breast cancer, especially ER/PR breast cancer.
Topics: Breast; Breast Neoplasms; Case-Control Studies; Diet Surveys; Female; Folic Acid; Humans; Prospective Studies; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Riboflavin; Risk Assessment; Risk Factors; Vitamin B 12; Vitamin B 6
PubMed: 32241696
DOI: 10.1016/j.clbc.2020.02.012 -
Journal of Neuromuscular Diseases 2021Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid...
BACKGROUND
Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has been extensively researched, interventional trials of pharmacological therapies are lacking.
OBJECTIVE
We collated evidence for the effectiveness of pharmacological and gene-based treatments for hereditary peripheral neuropathies.
METHODS
We searched several databases for randomised controlled trials (RCT), observational studies and case reports of therapies in hereditary peripheral neuropathies. Two investigators extracted and analysed the data independently, assessing study quality using the Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence in conjunction with the Jadad scale.
RESULTS
Of the 2046 studies initially identified, 119 trials met our inclusion criteria, of which only 34 were carried over into our final analysis. Ascorbic acid was shown to have no therapeutic benefit in CMT1A, while a combination of baclofen, naltrexone and sorbitol (PXT3003) demonstrated some efficacy, but phase III data are incomplete. In TTR-related amyloid polyneuropathy tafamidis, patisiran, inotersen and revusiran showed significant benefit in high quality RCTs. Smaller studies showed the efficacy of L-serine for SPTLC1-related hereditary sensory neuropathy, riboflavin for Brown-Vialetto-Van Laere syndrome (SLC52A2/3) and phytanic acid-poor diet in Refsum disease (PHYH).
CONCLUSIONS
The 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies.
Topics: Amyloid Neuropathies, Familial; Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy; Humans
PubMed: 32773395
DOI: 10.3233/JND-200546 -
The Cochrane Database of Systematic... Mar 2021Keratoconus is the most common corneal dystrophy. It can cause loss of uncorrected and best-corrected visual acuity through ectasia (thinning) of the central or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Keratoconus is the most common corneal dystrophy. It can cause loss of uncorrected and best-corrected visual acuity through ectasia (thinning) of the central or paracentral cornea, irregular corneal scarring, or corneal perforation. Disease onset usually occurs in the second to fourth decade of life, periods of peak educational attainment or career development. The condition is lifelong and sight-threatening. Corneal collagen crosslinking (CXL) using ultraviolet A (UVA) light applied to the cornea is the only treatment that has been shown to slow progression of disease. The original, more widely known technique involves application of UVA light to de-epithelialized cornea, to which a photosensitizer (riboflavin) is added topically throughout the irradiation process. Transepithelial CXL is a recently advocated alternative to the standard CXL procedure, in that the epithelium is kept intact during CXL. Retention of the epithelium offers the putative advantages of faster healing, less patient discomfort, faster visual rehabilitation, and less risk of corneal haze.
OBJECTIVES
To assess the short- and long-term effectiveness and safety of transepithelial CXL compared with epithelium-off CXL for progressive keratoconus.
SEARCH METHODS
To identify potentially eligible studies, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature database (LILACS); ClinicalTrials.gov; and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not impose any date or language restrictions. We last searched the electronic databases on 15 January 2020.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which transepithelial CXL had been compared with epithelium-off CXL in participants with progressive keratoconus.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
We included 13 studies with 723 eyes of 578 participants enrolled; 13 to 119 participants were enrolled per study. Seven studies were conducted in Europe, three in the Middle East, and one each in India, Russia, and Turkey. Seven studies were parallel-group RCTs, one study was an RCT with a paired-eyes design, and five studies were RCTs in which both eyes of some or all participants were assigned to the same intervention. Eleven studies compared transepithelial CXL with epithelium-off CXL in participants with progressive keratoconus. There was no evidence of an important difference between intervention groups in maximum keratometry (denoted 'maximum K' or 'Kmax'; also known as steepest keratometry measurement) at 12 months or later (mean difference (MD) 0.99 diopters (D), 95% CI -0.11 to 2.09; 5 studies; 177 eyes; I = 41%; very low certainty evidence). Few studies described other outcomes of interest. The evidence is very uncertain that epithelium-off CXL may have a small (data from two studies were not pooled due to considerable heterogeneity (I = 92%)) or no effect on stabilization of progressive keratoconus compared with transepithelial CXL; comparison of the estimated proportions of eyes with decreases or increases of 2 or more diopters in maximum K at 12 months from one study with 61 eyes was RR 0.32 (95% CI 0.09 to 1.12) and RR (non-event) 0.86 (95% CI 0.74 to 1.00), respectively (very low certainty). We did not estimate an overall effect on corrected-distance visual acuity (CDVA) because substantial heterogeneity was detected (I = 70%). No study evaluated CDVA gain or loss of 10 or more letters on a logarithm of the minimum angle of resolution (logMAR) chart. Transepithelial CXL may result in little to no difference in CDVA at 12 months or beyond. Four studies reported that either no adverse events or no serious adverse events had been observed. Another study noted no change in endothelial cell count after either procedure. Moderate certainty evidence from 4 studies (221 eyes) found that epithelium-off CXL resulted in a slight increase in corneal haze or scarring when compared to transepithelial CXL (RR (non-event) 1.07, 95% CI 1.01 to 1.14). Three studies, one of which had three arms, compared outcomes among participants assigned to transepithelial CXL using iontophoresis versus those assigned to epithelium-off CXL. No conclusive evidence was found for either keratometry or visual acuity outcomes at 12 months or later after surgery. Low certainty evidence suggests that transepithelial CXL using iontophoresis results in no difference in logMAR CDVA (MD 0.00 letter, 95% CI -0.04 to 0.04; 2 studies; 51 eyes). Only one study examined gain or loss of 10 or more logMAR letters. In terms of adverse events, one case of subepithelial infiltrate was reported after transepithelial CXL with iontophoresis, whereas two cases of faint corneal scars and four cases of permanent haze were observed after epithelium-off CXL. Vogt's striae were found in one eye after each intervention. The certainty of the evidence was low or very low for the outcomes in this comparison due to imprecision of estimates for all outcomes and risk of bias in the studies from which data have been reported.
AUTHORS' CONCLUSIONS
Because of lack of precision, frequent indeterminate risk of bias due to inadequate reporting, and inconsistency in outcomes measured and reported among studies in this systematic review, it remains unknown whether transepithelial CXL, or any other approach, may confer an advantage over epithelium-off CXL for patients with progressive keratoconus with respect to further progression of keratoconus, visual acuity outcomes, and patient-reported outcomes (PROs). Arrest of the progression of keratoconus should be the primary outcome of interest in future trials of CXL, particularly when comparing the effectiveness of different approaches to CXL. Furthermore, methods of assessing and defining progressive keratoconus should be standardized. Trials with longer follow-up are required in order to assure that outcomes are measured after corneal wound-healing and stabilization of keratoconus. In addition, perioperative, intraoperative, and postoperative care should be standardized to permit meaningful comparisons of CXL methods. Methods to increase penetration of riboflavin through intact epithelium as well as delivery of increased dose of UVA may be needed to improve outcomes. PROs should be measured and reported. The visual significance of adverse outcomes, such as corneal haze, should be assessed and correlated with other outcomes, including PROs.
Topics: Adult; Bias; Collagen; Corneal Pachymetry; Cross-Linking Reagents; Dextrans; Disease Progression; Epithelium, Corneal; Female; Humans; Iontophoresis; Keratoconus; Male; Photosensitizing Agents; Randomized Controlled Trials as Topic; Riboflavin; Ultraviolet Therapy; Visual Acuity; Young Adult
PubMed: 33765359
DOI: 10.1002/14651858.CD013512.pub2 -
Cornea Jul 2022Corneal collagen cross-linking (CXL) is an effective treatment to slow down keratoconus (KC) progression in adults. Several studies have also shown efficacious outcomes...
PURPOSE
Corneal collagen cross-linking (CXL) is an effective treatment to slow down keratoconus (KC) progression in adults. Several studies have also shown efficacious outcomes in pediatric populations, yet no systematic analysis has been performed and no accepted definition for progression is available in children after CXL. This study aimed to establish the most commonly used criteria for progression and to conduct a systematic review of the literature with pooled analysis to assess children's keratoconus progression after CXL.
METHODS
A systemic literature review combined with pooled analysis was performed on full-length studies of KC after CXL treatment in a pediatric population and the methods used to report progression were analyzed.
RESULTS
Thirty-seven studies (2078 eyes) were identified on the rates of KC progression after CXL. The most common method to report progression was increased Kmax, Kmean, or Ksteep by ≥1.0 diopter (78.3% of studies). Using these criteria, the mean pooled progression rate after epithelium-off CXL was 9.9% (95% confidence interval: 6.1% -14.6%, total pooled sample size: 1508 eyes) with high heterogeneity between studies [I 2 = 86.48% (95% confidence interval: 80.98 - 90.39), P < 0.0001].
CONCLUSIONS
When considering KC progression after CXL in children, with an increase in Kmax, Kmean, or Ksteep ≥ 1.0 diopter, the progression risk was roughly 10%. We encourage clear quantitative reporting of KC progression in future studies evaluating CXL efficacy in pediatric populations.
Topics: Adult; Child; Collagen; Corneal Topography; Cross-Linking Reagents; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Riboflavin; Ultraviolet Rays; Visual Acuity
PubMed: 34294638
DOI: 10.1097/ICO.0000000000002808 -
Journal of Neuromuscular Diseases 2021Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intolerance, myalgia and progressive muscle weakness. Effective...
BACKGROUND
Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intolerance, myalgia and progressive muscle weakness. Effective treatments for some of these diseases are available, but while our understanding of the pathogenesis of metabolic myopathies related to glycogen storage, lipid metabolism and β-oxidation is well established, evidence linking treatments with the precise causative genetic defect is lacking.
OBJECTIVE
The objective of this study was to collate all published evidence on pharmacological therapies for the aforementioned metabolic myopathies and link this to the genetic mutation in a format amenable to databasing for further computational use in line with the principles of the "treatabolome" project.
METHODS
A systematic literature review was conducted to retrieve all levels of evidence examining the therapeutic efficacy of pharmacological treatments on metabolic myopathies related to glycogen storage and lipid metabolism. A key inclusion criterion was the availability of the genetic variant of the treated patients in order to link treatment outcome with the genetic defect.
RESULTS
Of the 1,085 articles initially identified, 268 full-text articles were assessed for eligibility, of which 87 were carried over into the final data extraction. The most studied metabolic myopathies were Pompe disease (45 articles), multiple acyl-CoA dehydrogenase deficiency related to mutations in the ETFDH gene (15 articles) and systemic primary carnitine deficiency (8 articles). The most studied therapeutic management strategies for these diseases were enzyme replacement therapy, riboflavin, and carnitine supplementation, respectively.
CONCLUSIONS
This systematic review provides evidence for treatments of metabolic myopathies linked with the genetic defect in a computationally accessible format suitable for databasing in the treatabolome system, which will enable clinicians to acquire evidence on appropriate therapeutic options for their patient at the time of diagnosis.
Topics: Glycogen; Glycogen Storage Disease Type II; Humans; Lipid Metabolism; Metabolism, Inborn Errors; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Muscle Weakness; Mutation
PubMed: 33720849
DOI: 10.3233/JND-200621 -
Seminars in Ophthalmology 2016To describe the infectious complications and the group of pathogens involved in the infection following corneal crosslinking, the visual outcome, and the treatment... (Review)
Review
AIM
To describe the infectious complications and the group of pathogens involved in the infection following corneal crosslinking, the visual outcome, and the treatment proposed.
METHODS
A Medline (National Library of Medicine, Bethesda, MD, USA) search from October 2000 to October 2013 was performed to identify all articles describing infectious keratitis following corneal crosslinking treatment. Nineteen articles were selected. Ten articles reported infectious complications of corneal crosslinking treatment were included. Nine articles were excluded, because seven described sterile keratitis, one article was in German, and one reported general complication without describing the infection complication.
RESULTS
A total number of infections reported included 10 eyes. The infectious keratitis was associated with bacteria in five eyes (50%): gram-positive bacteria in three eyes (30%) (staphylococcus epidermidis, S. aureus and streptococcus salivarius plus S. oralis, respectively) and gram-negative bacteria in two eyes (20%) (E. coli; P. aeruginosa); there was herpes virus in two eyes, fungus in two eyes (Fusarium and Microsporidia) (20%), and Acanthamoeba in one eye (10%).
CONCLUSIONS
Only 10 cases of infectious keratitis following corneal crosslinking are published. The most virulent pathogens were Pseudomonas aeruginosa and Acanthamoeba. Less virulent organisms were Escherichia coli and S. epidermidis. Two cases of herpes keratitis were described, suggesting the possibility of systemic antiviral prophylaxis before corneal crosslinking treatment. The most common risk factor of infections identified was postoperative incorrect patient behavior.
Topics: Adult; Collagen; Corneal Stroma; Cross-Linking Reagents; Eye Infections; Humans; Keratitis; Photosensitizing Agents; Postoperative Complications; Riboflavin; Risk Factors; Ultraviolet Rays; Visual Acuity; Young Adult
PubMed: 25392046
DOI: 10.3109/08820538.2014.962176 -
Nutrition Reviews May 2024Riboflavin (vitamin B2) is a water-soluble micronutrient considered to be a precursor of the nucleotides flavin adenine dinucleotide and flavin mononucleotide. This...
CONTEXT
Riboflavin (vitamin B2) is a water-soluble micronutrient considered to be a precursor of the nucleotides flavin adenine dinucleotide and flavin mononucleotide. This vitamin makes up mitochondrial complexes and participates as an enzymatic cofactor in several mechanisms associated with energy metabolism.
OBJECTIVE
This systematic review collected and discussed the most relevant results on the role of riboflavin in the energy metabolism of lipids, proteins, and carbohydrates.
DATA SOURCES
A systematic search was carried out in the PubMed-Medline, Scopus, Embase, and Web of Science databases using the PICOS (Population, Intervention, Comparison, Outcome, Study design) strategy.
DATA EXTRACTION
The screening of studies went through 2 stages following predefined eligibility criteria. The information extracted covered reference details, study design, population characteristics, experimental model, treatment parameters and dosage, route of administration, duration of treatment, and results found.
DATA ANALYSIS
The risk of bias was assessed using the SYRCLE Risk of Bias (RoB) tool for in vivo studies and the QUIN tool adapted for in vitro studies, utilizing 10 domains, including selection bias, performance bias, detection bias, attrition bias, reporting bias, and other biases, to evaluate the methodological quality of the included studies.
CONCLUSION
This review concludes that riboflavin regulates energy metabolism by activating primary metabolic pathways and is involved in energy balance homeostasis.
PubMed: 38719205
DOI: 10.1093/nutrit/nuae041 -
Neuromuscular Disorders : NMD Mar 2021Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder with a dramatic clinical presentation. It was recently discovered that MADD may...
Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder with a dramatic clinical presentation. It was recently discovered that MADD may present at an advanced age. The clinical and laboratory data of an index patient and patients previously diagnosed at our institution were collected. A systematic review of previous studies retrieved from the PubMed, MEDLINE, and Embase databases published by February 1, 2020 was performed to collect patients with very-late-onset MADD (VLO-MADD, onset age > 60 years) globally and patients with late-onset MADD (LO-MADD, onset age < 60 years) in Taiwan. The clinical characteristics of the VLO-MADD patients were compared to those of LO-MADD patients. We report a patient with VLO-MADD who developed the first symptom at the age of 61 years. The patient presented with a Reye-like syndrome after taking aspirin for coronary artery disease. Repeated bouts of weakness were noted. Two variants of c.250 G > A (;) 419C > T were observed in the ETFDH gene. Another four patients with VLO-MADD were identified globally. Eighteen patients with LO-MADD were collected from our department and previously reported patients in Taiwan. There was no difference in the clinical symptoms (except for the onset age) or laboratory data between these two groups. Homozygous variants were not observed in any patients in the VLO-MADD group but were detected in 12 patients (66.6%) in the LO-MADD group (p = 0.014). Patients with MADD may first show symptoms in their 6th decade or beyond. The disease course may lead to erroneous diagnoses in this age group.
Topics: Acyl-CoA Dehydrogenase; Adult; Age of Onset; Aged; Cohort Studies; Female; Homozygote; Humans; Male; Middle Aged; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Muscle, Skeletal; Mutation; Riboflavin; Taiwan; Young Adult
PubMed: 33589341
DOI: 10.1016/j.nmd.2021.01.006 -
Ophthalmology Aug 2021To evaluate the safety and efficacy of transepithelial corneal cross-linking in comparison with the established epithelium-off technique for corneal ectasia. (Meta-Analysis)
Meta-Analysis
TOPIC
To evaluate the safety and efficacy of transepithelial corneal cross-linking in comparison with the established epithelium-off technique for corneal ectasia.
CLINICAL RELEVANCE
Considerable debate exists regarding whether transepithelial and epithelium-off cross-linking are comparable in their safety and efficacy.
METHODS
We searched 16 electronic databases, including Medline, Embase, Web of Science, and the grey literature, current to July 8, 2020, for randomized controlled trials comparing transepithelial and epithelium-off cross-linking for corneal ectasia. We excluded studies evaluating cross-linking for nonectatic indications, as well as non-randomized controlled trials. Our primary outcome was the change in maximal keratometry (K) at 12 months after cross-linking, and we considered additional topographic, visual, and safety outcomes. We summarized our analyses by calculating weighted mean differences (MDs) with associated 95% confidence intervals (CIs) for continuous outcomes and relative risks (RRs) with corresponding 95% CIs for dichotomous outcomes. We conducted trial sequential analysis to determine whether the required information size was met for each outcome. The quality of individual trials was evaluated using the Cochrane Collaboration's risk of bias assessment tool, and the evidence was assessed at an outcome level using the Grading of Recommendations Assessment, Development, and Evaluation methodology.
RESULTS
Twelve studies totaling 966 eyes were eligible. A significant difference was found between transepithelial and epithelium-off cross-linking groups in the change in K at 12 months (MD, 0.75; 95% CI, 0.23-1.28; P = 0.004; primary outcome) and at longest follow-up (MD, 1.20; 95% CI, 0.62-1.77; P < 0.001; secondary outcome) after treatment. No significant difference was found between the 2 groups when examining uncorrected distance visual acuity (MD, 0.04; 95% CI, -0.06 to 0.14; P = 0.386) or corrected distance visual acuity (MD, 0.01; 95% CI, -0.06 to 0.09; P = 0.732). Transepithelial cross-linking was associated with significantly fewer complications than the epithelium-off approach (RR, 0.22; 95% CI, 0.06-0.79; P = 0.020), although it was associated with an increased rate of disease progression at 12 months after treatment (RR, 4.49; 95% CI, 1.24-16.25; P = 0.022). The required information size was met for our primary outcome and trial sequential analysis supported the conventional meta-analysis. The quality of evidence was rated as moderate using the Grading of Recommendations Assessment, Development, and Evaluation methodology.
DISCUSSION
The efficacy of transepithelial cross-linking remains inferior to the epithelium-off approach, although it is significantly safer.
Topics: Collagen; Corneal Stroma; Cross-Linking Reagents; Debridement; Dilatation, Pathologic; Epithelium, Corneal; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Randomized Controlled Trials as Topic; Riboflavin; Ultraviolet Rays; Visual Acuity
PubMed: 33383093
DOI: 10.1016/j.ophtha.2020.12.023