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The Cochrane Database of Systematic... Feb 2020Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of... (Review)
Review
BACKGROUND
Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) medications are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGF medications for the control of intraocular pressure (IOP) in NVG.
OBJECTIVES
To assess the effectiveness of intraocular anti-VEGF medications, alone or with one or more type of conventional therapy, compared with no anti-VEGF medications for the treatment of NVG.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register); MEDLINE; Embase; PubMed; and LILACS to 22 March 2019; metaRegister of Controlled Trials to 13 August 2013; and two additional trial registers to 22 March 2019. We did not use any date or language restrictions in the electronic search for trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of people treated with anti-VEGF medications for NVG.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the search results for trials, extracted data, and assessed risk of bias, and the certainty of the evidence. We resolved discrepancies through discussion.
MAIN RESULTS
We included four RCTs (263 participants) and identified one ongoing RCT. Each trial was conducted in a different country: China, Brazil, Egypt, and Japan. We assessed the trials to have an unclear risk of bias for most domains due to insufficient information. Two trials compared intravitreal bevacizumab combined with Ahmed valve implantation and panretinal photocoagulation (PRP) with Ahmed valve implantation and PRP. We did not combine these two trials due to substantial clinical and statistical heterogeneity. One trial randomised participants to receive an injection of either an intravitreal anti-VEGF medication or placebo at the first visit, followed by non-randomised treatment according to clinical findings after one week. The last trial randomised participants to PRP with and without ranibizumab, but details of the study were unavailable for further analysis. Two trials that examined IOP showed inconsistent results. One found inconclusive results for mean IOP between participants who received anti-VEGF medications and those who did not, at one month (mean difference [MD] -1.60 mmHg, 95% confidence interval [CI] -4.98 to 1.78; 40 participants), and at one year (MD 1.40 mmHg, 95% CI -4.04 to 6.84; 30 participants). Sixty-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 60% without anti-VEGF medications. In another trial, those who received anti-VEGF medications were more likely to reduce their IOP than those who did not receive them, at one month (MD -6.50 mmHg, 95% CI -7.93 to -5.07; 40 participants), and at one year (MD -12.00 mmHg, 95% CI -16.79 to -7.21; 40 participants). Ninety-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 50% without anti-VEGF medications. The certainty of a body of evidence was low for this outcome due to limitations in the design and inconsistency of results between studies. Post-operative complications included anterior chamber bleeding (3 eyes) and conjunctival hemorrhage (2 participants) in the anti-VEGF medications group, and retinal detachment and phthisis bulbi (1 participant each) in the control group. The certainty of evidence is low due to imprecision of results and indirectness of evidence. No trial reported the proportion of participants with improvement in visual acuity, proportion of participants with complete regression of new iris vessels, or the proportion of participants with relief of pain and resolution of redness at four- to six-week, or one-year follow-up.
AUTHORS' CONCLUSIONS
Currently available evidence is uncertain regarding the long-term effectiveness of anti-VEGF medications, such as intravitreal ranibizumab or bevacizumab or aflibercept, as an adjunct to conventional treatment in lowering IOP in NVG. More research is needed to investigate the long-term effect of these medications compared with, or in addition to, conventional surgical or medical treatment in lowering IOP in NVG.
Topics: Endothelial Growth Factors; Glaucoma, Neovascular; Humans; Intraocular Pressure; Randomized Controlled Trials as Topic; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 32027392
DOI: 10.1002/14651858.CD007920.pub3 -
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 -
Investigative Ophthalmology & Visual... May 2021Glaucoma remains a poorly understood disease, and identifying biomarkers for early diagnosis is critical to reducing the risk of glaucoma-related visual impairment and...
PURPOSE
Glaucoma remains a poorly understood disease, and identifying biomarkers for early diagnosis is critical to reducing the risk of glaucoma-related visual impairment and blindness. The aim of this review is to provide current metabolic profiles for glaucoma through a summary and analysis of reported metabolites associated with glaucoma.
METHODS
We searched PubMed and Web of Science for metabolomics studies of humans on glaucoma published before November 11, 2020. Studies were included if they assessed the biomarkers of any types of glaucoma and performed mass spectrometry-based or nuclear magnetic resonance-based metabolomics approach. Pathway enrichment analysis and topology analysis were performed to generate a global view of metabolic signatures related to glaucoma using the MetaboAnalyst 3.0.
RESULTS
In total, 18 articles were included in this review, among which 13 studies were focused on open-angle glaucoma (OAG). Seventeen metabolites related to OAG were repeatedly identified, including seven amino acids (arginine, glycine, alanine, lysine, methionine, phenylalanine, tyrosine), two phosphatidylcholine (PC aa C34:2, PC aa C36:4), three complements (acetylcarnitine, propionylcarnitine, butyrylcarnitine), carnitine, glutamine, hypoxanthine, spermine, and spermidine. The pathway analysis implied a major role of amino metabolism in OAG pathophysiology and revealed the metabolic characteristics between different biological samples.
CONCLUSIONS
In this review, we summarize existing metabolomic studies related to glaucoma biomarker identification and point out a series of metabolic disorders in OAG patients, providing information on the molecular mechanism changes in glaucoma. Additional studies are needed to validate existing findings, and future research will need to explore the potential overlap between different biological fluids.
Topics: Biomarkers; Glaucoma, Open-Angle; Humans; Metabolome; Metabolomics
PubMed: 33956051
DOI: 10.1167/iovs.62.6.9 -
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 -
The Cochrane Database of Systematic... Apr 2023Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of... (Review)
Review
BACKGROUND
Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) medications are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGF medications for the control of intraocular pressure (IOP) in NVG.
OBJECTIVES
To assess the effectiveness of intraocular anti-VEGF medications, alone or with one or more types of conventional therapy, compared with no anti-VEGF medications for the treatment of NVG.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register); MEDLINE; Embase; PubMed; and LILACS to 19 October 2021; metaRegister of Controlled Trials to 19 October 2021; and two additional trial registers to 19 October 2021. We did not use any date or language restrictions in the electronic search for trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of people treated with anti-VEGF medications for NVG.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the search results for trials, extracted data, and assessed risk of bias, and the certainty of the evidence. We resolved discrepancies through discussion.
MAIN RESULTS
We included five RCTs (356 eyes of 353 participants). Each trial was conducted in a different country: two in China, and one each in Brazil, Egypt, and Japan. All five RCTs included both men and women; the mean age of participants was 55 years or older. Two RCTs compared intravitreal bevacizumab combined with Ahmed valve implantation and panretinal photocoagulation (PRP) with Ahmed valve implantation and PRP alone. One RCT randomized participants to receive an injection of either intravitreal aflibercept or placebo at the first visit, followed by non-randomized treatment according to clinical findings after one week. The remaining two RCTs randomized participants to PRP with and without ranibizumab, one of which had insufficient details for further analysis. We assessed the RCTs to have an unclear risk of bias for most domains due to insufficient information to permit judgment. Four RCTs examined achieving control of IOP, three of which reported our time points of interest. Only one RCT reported our critical time point at one month; it found that the anti-VEGF group had a 1.3-fold higher chance of achieving control of IOP at one month (RR 1.32, 95% 1.10 to 1.59; 93 participants) than the non-anti-VEGF group (low certainty of evidence). For other time points, one RCT found a three-fold greater achievement in control of IOP in the anti-VEGF group when compared with the non-anti-VEGF group at one year (RR 3.00; 95% CI:1.35 to 6.68; 40 participants). However, another RCT found an inconclusive result at the time period ranging from 1.5 years to three years (RR 1.08; 95% CI: 0.67 to 1.75; 40 participants). All five RCTs examined mean IOP, but at different time points. Very-low-certainty evidence showed that anti-VEGFs were effective in reducing mean IOP by 6.37 mmHg (95% CI: -10.09 to -2.65; 3 RCTs; 173 participants) at four to six weeks when compared with no anti-VEGFs. Anti-VEGFs may reduce mean IOP at three months (MD -4.25; 95% CI -12.05 to 3.54; 2 studies; 75 participants), six months (MD -5.93; 95% CI -18.13 to 6.26; 2 studies; 75 participants), one year (MD -5.36; 95% CI -18.50 to 7.77; 2 studies; 75 participants), and more than one year (MD -7.05; 95% CI -16.61 to 2.51; 2 studies; 75 participants) when compared with no anti-VEGFs, but such effects remain uncertain. Two RCTs reported the proportion of participants who achieved an improvement in visual acuity with specified time points. Participants receiving anti-VEGFs had a 2.6 times (95% CI 1.60 to 4.08; 1 study; 93 participants) higher chance of improving visual acuity when compared with those not receiving anti-VEGFs at one month (very low certainty of evidence). Likewise, another RCT found a similar result at 18 months (RR 4.00, 95% CI 1.33 to 12.05; 1 study; 40 participants). Two RCTs reported the outcome, complete regression of new iris vessels, at our time points of interest. Low-certainty evidence showed that anti-VEGFs had a nearly three times higher chance of complete regression of new iris vessels when compared with no anti-VEGFs (RR 2.63, 95% CI 1.65 to 4.18; 1 study; 93 participants). A similar finding was observed at more than one year in another RCT (RR 3.20, 95% CI 1.45 to 7.05; 1 study; 40 participants). Regarding adverse events, there was no evidence that the risks of hypotony and tractional retinal detachment were different between the two groups (RR 0.67; 95% CI: 0.12 to 3.57 and RR 0.33; 95% CI: 0.01 to 7.72, respectively; 1 study; 40 participants). No RCTs reported incidents of endophthalmitis, vitreous hemorrhage, no light perception, and serious adverse events. Evidence for the adverse events of anti-VEGFs was low due to limitations in the study design due to insufficient information to permit judgments and imprecision of results due to the small sample size. No trial reported the proportion of participants with relief of pain and resolution of redness at any time point.
AUTHORS' CONCLUSIONS
Anti-VEGFs as an adjunct to conventional treatment could help reduce IOP in NVG in the short term (four to six weeks), but there is no evidence that this is likely in the longer term. Currently available evidence regarding the short- and long-term effectiveness and safety of anti-VEGFs in achieving control of IOP, visual acuity, and complete regression of new iris vessels in NVG is insufficient. More research is needed to investigate the effect of these medications compared with, or in addition to, conventional surgical or medical treatment in achieving these outcomes in NVG.
Topics: Female; Humans; Male; Middle Aged; Bevacizumab; Glaucoma, Neovascular; Ranibizumab; Vascular Endothelial Growth Factor A
PubMed: 37010901
DOI: 10.1002/14651858.CD007920.pub4 -
Journal Francais D'ophtalmologie May 2022There is currently a lack of high-quality research on the best dietary recommendations for patients with early glaucoma or at high risk for glaucoma. This meta-analysis... (Meta-Analysis)
Meta-Analysis
There is currently a lack of high-quality research on the best dietary recommendations for patients with early glaucoma or at high risk for glaucoma. This meta-analysis aims to clarify the relationship between vitamin intake and glaucoma risk. Electronic databases, including PubMed, EMbase, ScienceDirect, Cochrane Database, Clinicaltrials.gov, and Google Scholar, were searched for publications indexed as of September 18, 2021. Data were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The I index was used to assess heterogeneity. We performed five meta-analyses of existing studies to summarize the evidence on the association between vitamin intake and glaucoma risk. The initial search identified 689 studies, eight of which (262,189 patients) met the eligibility criteria for the meta-analysis. The data showed that high-dose intake of vitamins A (OR=0.63, 95%CI [0.53, 0.76]) and B (OR=0.71, 95%CI [0.64, 0.80]) but not vitamins C (OR=0.69, 95%CI [0.48, 1.01]), D (OR=0.90, 95%CI [0.45, 1.83]), or E (OR=0.91, 95%CI [0.71, 1.16]) was associated with a low prevalence of glaucoma. The results of this study demonstrated that high-dose intake of vitamins A and B, but not vitamins C, D, or E, was associated with a low prevalence of glaucoma.
Topics: Ascorbic Acid; Glaucoma; Humans; Odds Ratio; Vitamin A; Vitamins
PubMed: 35120728
DOI: 10.1016/j.jfo.2021.10.010 -
Acta Ophthalmologica May 2022Preservative-free topical medications have been introduced for glaucoma care to reduce ocular adverse events associated with preservatives. This is a systematic review...
Preservative-free topical medications have been introduced for glaucoma care to reduce ocular adverse events associated with preservatives. This is a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing the efficacy and safety of beta-blockers, or combination using beta-blockers, with and without preservatives. PubMed, EMBASE and Web of Science were examined. Risk of bias was assessed using the Cochrane Handbook for Systematic Reviews. The primary outcome was change in intraocular pressure (IOP) from baseline to final follow-up. Secondary outcomes included ocular and systemic side effects, and other clinical and quality of life outcomes. Of 242 records identified, seven RCTs (1125 patients) were included. The follow-up period ranged from one to 12 months. Timolol was used in five studies, and two studies used a combination (timolol with bimatoprost or dorzolamide). The difference in mean change (MD) in IOP between the preservative-free and the preserved drugs was statistically significant but not clinically relevant: (MD 0.29 mmHg, 95% confidence interval 0.07-0.51 mmHg, p = 0.010; moderate-certainty evidence). Regarding adverse events: Level of evidence for all ocular surface outcome was low or very low and reported in few studies. No significant difference was observed on ocular surface symptoms. Tear break-up time (TBUT) was better with preservative-free drops (p < 0.001). Schirmer's test was better in the preservative-free group (p < 0.001). Level of evidence for all ocular surface outcomes was low or very low. There was no difference in other secondary outcomes. We found no clinically relevant difference in mean change in IOP between the preserved and the preservative-free treatments. Data on adverse events used different methods and were incompletely reported. Although some measures of ocular surface health favoured preservative-free medications, more evidence is needed. The increasing use of preservative-free drops may be associated with better ocular surface and tolerability, but strong evidence from RCTs would be welcome.
Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Preservatives, Pharmaceutical; Timolol
PubMed: 34128326
DOI: 10.1111/aos.14926 -
PloS One 2023Glaucoma is a leading cause of irreversible blindness worldwide. Retinal ganglion cells (RGC), the neurons that connect the eyes to the brain, specifically die in...
PURPOSE
Glaucoma is a leading cause of irreversible blindness worldwide. Retinal ganglion cells (RGC), the neurons that connect the eyes to the brain, specifically die in glaucoma, leading to blindness. Elevated intraocular pressure (IOP) is the only modifiable risk factor, however, many patients progress despite excellent IOP control. Thus, alternative treatment strategies to prevent glaucoma progression are an unmet need. Citicoline has demonstrated neuroprotective properties in central neurodegenerative diseases. However, conclusive evidence of the effect of citicoline on glaucoma progression is missing. This systematic review investigates first-time the therapeutic potential of citicoline in glaucoma patients.
METHODS
The present study was conducted according to the PRISMA 2020 statement. PubMed, Web of Science, Google Scholar, and Embase were accessed in July 2023 to identify all clinical studies investigating the efficacy of citicoline on IOP, the mean deviation of the 24-2 visual field testing (MD 24-2), retinal nerve fibre layer (RNFL), and the pattern electroretinogram (PERG) P50-N95 amplitude in glaucoma patients. The risk of bias was assessed using the Review Manager 5.3 software (The Nordic Cochrane Collaboration, Copenhagen) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool.
RESULTS
Ten studies were eligible for this systematic review, including 424 patients. The mean length of the follow-up was 12.1 ± 11.6 months. The overall risk of bias was low to moderate. The mean age of the patients was 56.7 years. There were no significant differences in the IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude between patients receiving citicoline and the control group. There was no improvement from baseline to the last follow-up in IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude.
CONCLUSION
There is a lack of sufficient evidence to support that citicoline slows the progression of glaucoma.
Topics: Humans; Middle Aged; Cytidine Diphosphate Choline; Glaucoma, Open-Angle; Intraocular Pressure; Glaucoma; Retinal Ganglion Cells; Blindness
PubMed: 37768938
DOI: 10.1371/journal.pone.0291836 -
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 -
Cornea Mar 2020To identify risk factors for the development of ocular hypertension after keratoplasty.
PURPOSE
To identify risk factors for the development of ocular hypertension after keratoplasty.
METHODS
A systematic search in PubMed and Embase identified 67 relevant articles published between January 1990 and 2019. We preferentially searched for data on an intraocular pressure increase above 21 mmHg at 6 months or a threshold or time point close to that and reported whether the preoperative or intraoperative status of risk factors was defined. The results were presented in evidence tables, visualizing the direction of the association, whether univariate and/or multivariate analysis was performed, and the significance level (P < 0.05). Four researchers, blinded for the risk factors, independently assigned a level of evidence (definitely, probably, possibly, not associated). Consensus was met during group meetings.
RESULTS
From the 110 studied risk factors, pre-existing glaucoma, high preoperative IOP and combined keratoplasty with removal or exchange of an intraocular lens (IOL) were definitely associated with an increased risk. In addition, if the pre-or postoperative lens status was undefined, aphakia and pseudophakia with the IOL in the anterior or posterior chamber were also definitely associated with an increased risk when compared to phakia. Glaucoma in the contralateral eye, indication of bullous keratopathy, African American descent, preoperative treatment with cyclosporine or olopatadine 0.1%, postoperative treatment with prednisolone acetate 1%, and combined surgery in general (ie, the type of surgeries undefined in primary studies) were probably associated. Multiple other identified risk factors lack sufficient evidence and need additional investigation.
CONCLUSIONS
Risk factors with a definite association can help clinicians select patients at risk and adjust their follow-up and treatment. The other factors need further investigation.
Topics: Corneal Diseases; Humans; Intraocular Pressure; Keratoplasty, Penetrating; Ocular Hypertension; Postoperative Complications; Risk Assessment; Risk Factors; Visual Acuity
PubMed: 31764288
DOI: 10.1097/ICO.0000000000002209