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Yu M, Hwang HH, Wiggs JL, Pasquale LR, Kang JH. Association between Diabetes and Exfoliation Syndrome. OPHTHALMOLOGY SCIENCE 2024; 4:100436. [PMID: 38250562 PMCID: PMC10797545 DOI: 10.1016/j.xops.2023.100436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 10/22/2023] [Accepted: 11/13/2023] [Indexed: 01/23/2024]
Abstract
Topic This systematic review and meta-analysis summarizes the existing evidence for the association of diabetes mellitus (DM) and exfoliation syndrome (XFS). Clinical Relevance Understanding and quantifying these associations may aid clinical guidelines or treatment strategies and shed light on disease pathogenesis. The role of DM in determining XFS risk may also be of interest from an individual or public health perspective. Methods The study protocol was preregistered on the International Prospective Register of Systematic Reviews with registration number CRD42023429771. We systematically searched PubMed and Embase from inception to June 15, 2023. Screening and full-text review were conducted by 2 independent reviewers. All observational studies reporting an age-adjusted odds ratio (OR) and 95% confidence interval (CI) for the association between DM and XFS among adults were included. Quantitative synthesis involved a random-effects meta-analysis using the DerSimonian-Laird method to generate a pooled OR. Risk of bias was evaluated using the Newcastle-Ottawa Scale. Results Fourteen studies (9 cross-sectional and 5 case-control) comprising 47 853 participants were included in the systematic review and meta-analysis. Random-effects meta-analysis indicated no overall association between DM and XFS (OR 0.94; 95% CI, 0.73–1.21; I 2 = 68.5%). However, subgroup analysis revealed a significant inverse association among individuals ≥ 65 years (OR 0.71; 95% CI, 0.54–0.93) versus individuals < 65 years (OR 1.22; 95% CI, 0.80–1.87; P effect modification = 0.04). The relation between DM and XFS was also inverse in case-control studies (OR 0.75; 95% CI, 0.58–0.97) but was nonsignificant in cross-sectional studies (OR 1.17; 95% CI, 0.83–1.66; P effect modification = 0.04). Overall risk of bias was low, with tests for publication bias showing P ≥ 0.06. Conclusion This meta-analysis suggests no association between DM and XFS overall, with possible inverse associations of DM with XFS in older populations. However, given the substantial heterogeneity and borderline significance for publication bias, these findings should be interpreted with caution. Our results give insight into the unique etiology and clinical relevance of XFS while proposing the need for larger longitudinal and genetic biomarker studies. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Affiliation(s)
- Megan Yu
- Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Hannah H. Hwang
- Department of Ophthalmology, Weill Cornell Medicine, New York, New York
| | - Janey L. Wiggs
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts
| | - Louis R. Pasquale
- Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jae H. Kang
- Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
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Kang JH, Zeleznik O, Frueh L, Lasky-Su J, Eliassen AH, Clish C, Rosner BA, Pasquale LR, Wiggs JL. Prediagnostic Plasma Metabolomics and the Risk of Exfoliation Glaucoma. Invest Ophthalmol Vis Sci 2022; 63:15. [PMID: 35951322 PMCID: PMC9386645 DOI: 10.1167/iovs.63.9.15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Purpose The etiology of exfoliation glaucoma (XFG) is poorly understood. We aimed to identify a prediagnostic plasma metabolomic signature associated with XFG. Methods We conducted a 1:1 matched case-control study nested within the Nurses' Health Study and Health Professionals Follow-up Study. We collected blood samples in 1989-1990 (Nurses' Health Study) and 1993-1995 (Health Professionals Follow-up Study). We identified 205 incident XFG cases through 2016 (average time to diagnosis from blood draw = 11.8 years) who self-reported glaucoma and were confirmed as XFG cases with medical records. We profiled plasma metabolites using liquid chromatography-mass spectrometry. We evaluated 379 known metabolites (transformed for normality using probit scores) using multiple conditional logistic models. Metabolite set enrichment analysis was used to identify metabolite classes associated with XFG. To adjust for multiple comparisons, we used number of effective tests (NEF) and the false discovery rate (FDR). Results Mean age of cases (n = 205) at diagnosis was 71 years; 85% were women and more than 99% were Caucasian; controls (n = 205) reported eye examinations as of the matched cases' index date. Thirty-three metabolites were nominally significantly associated with XFG (P < 0.05), and 4 metabolite classes were FDR-significantly associated. We observed positive associations for lysophosphatidylcholines (FDR = 0.02) and phosphatidylethanolamine plasmalogens (FDR = 0.004) and inverse associations for triacylglycerols (FDR < 0.0001) and steroids (FDR = 0.03). In particular, the multivariable-adjusted odds ratio with each 1 standard deviation higher plasma cortisone levels was 0.49 (95% confidence interval, 0.32-0.74; NEF = 0.05). Conclusions In plasma from a decade before diagnosis, lysophosphatidylcholines and phosphatidylethanolamine plasmalogens were positively associated and triacylglycerols and steroids (e.g., cortisone) were inversely associated with XFG risk.
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Affiliation(s)
- Jae H Kang
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
| | - Oana Zeleznik
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
| | - Lisa Frueh
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
| | - Jessica Lasky-Su
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
| | - A Heather Eliassen
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
- Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States
| | - Clary Clish
- Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, United States
| | - Bernard A Rosner
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States
| | - Louis R Pasquale
- Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York, United States
| | - Janey L Wiggs
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, United States
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Zehavi-Dorin T, Nahum N, Ben-Artsi E, Levkovitch-Verbin H. Exfoliation syndrome: association with systemic diseases-the Maccabi glaucoma study. Graefes Arch Clin Exp Ophthalmol 2021; 259:3027-3034. [PMID: 34169352 DOI: 10.1007/s00417-021-05241-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 05/05/2021] [Accepted: 05/11/2021] [Indexed: 11/28/2022] Open
Abstract
PURPOSE To investigate the relationship between exfoliation syndrome (XFS) and systemic diseases. METHODS A population-based, retrospective study with control group was conducted using the electronic medical database of Maccabi Health Services, the second largest Health Maintenance Organization (HMO) in Israel. Study population included Maccabi members from January 2003 to April 2016. Cases consisted of patients diagnosed with XFS regardless of glaucoma. The control group included Maccabi members without XFS, matched on age, sex, and ancestry, that were examined by an ophthalmologist within the last year. MAIN OUTCOME MEASURES Associations between XFS and systemic diseases. RESULTS We identified 16,388 patients with XFS, in whom 40.3% (n = 6613) had glaucoma. The control group included 14,015 patients. Mean age was 78.3 ± 8.9 years and 76.2 ± 8.5 years for the XFS and control group, respectively. In unconditional logistic regression analyses, after adjusting for age, sex, and ancestry, XFS was significantly associated with risk of cardiovascular diseases including hypertension (OR 1.07, 95% CI 1.01-1.13, p = 0.02), myocardial infarction (OR 1.21, 95% CI 1.17-1.31, p < 0.0001), and congestive heart failure (OR 1.70, 95% CI 1.55-1.88, p < 0.0001) as well as higher risk for high creatinine (OR 1.28, 95% CI 1.2-1.37, p < 0.0001). Diabetes mellitus and body mass index were inversely associated with XFS (OR 0.70, 95% CI 0.67-0.73, p < 0.0001 and OR 0.88, 95% CI 0.84-0.93, p < 0.0001, respectively). Overall cancer diagnoses were more common in the XFS group (OR 1.05, 95% CI 1.0-1.1, p = 0.05). XFS was associated with more hospitalizations (mean 5 ± 5.3 hospitalizations in the XFS group and 3.3 ± 4.0 in the controls, p < 0.0001). CONCLUSION XFS is significantly associated with cardiovascular systemic diseases (in a population living in Israel and predominantly born in Russia).
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Affiliation(s)
- Tzukit Zehavi-Dorin
- Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Nofar Nahum
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Elad Ben-Artsi
- Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Hani Levkovitch-Verbin
- Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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Scharfenberg E, Rauscher FG, Meier P, Hasenclever D. Pseudoexfoliation syndrome: analysis of systemic comorbidities of 325 PEX-positive patients compared with 911 PEX-negative patients. Graefes Arch Clin Exp Ophthalmol 2019; 257:2471-2480. [PMID: 31420731 DOI: 10.1007/s00417-019-04438-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 07/31/2019] [Accepted: 08/08/2019] [Indexed: 02/07/2023] Open
Abstract
PURPOSE Pseudoexfoliation syndrome (PEX) is an age-related systemic elastic fibrillopathy disorder featuring an excessive production and accumulation of elastic fibre components in the extracellular matrix and is associated with impaired protective mechanisms against oxidative and cellular stress. PEX is diagnosed solely by ophthalmologists; however, PEX deposits have been detected in the connective tissues of many extraocular organ systems. This large, retrospective case-control study investigates whether patients with PEX have an increased risk of extraocular comorbidities. METHODS Cases and controls were drawn from consecutive patients over 50 years of age undergoing in-house ophthalmological operations under general anaesthesia or in standby preparedness for general anaesthesia. The participants were grouped based solely on PEX-positive (n = 325) or PEX-negative (n = 911) status. The same teams of ophthalmologists and anaesthesiologists uniformly documented every known systemic comorbidity of each patient through two independent rounds of standard anamnestic procedure and protocols in preparation for general anaesthesia. For the purpose of this study, every systemic comorbidity was registered from these forms and subsequently categorized into 17 disease groups based on the International Classification of Diseases (ICD-10) of the World Health Organization (WHO). Odds ratios (ORs) comparing comorbidities in cases and controls were adjusted for age and gender using logistic regression. RESULTS After adjustment for multiple testing, patients with PEX had an increased odds ratio for respiratory OR 2.1 [1.4; 3.0], cardiac OR 2.5 [1.6; 4.2], vascular OR 2.0 [1.4; 2.8], and urogenital conditions OR 2.3 [1.4; 3.7]. Renal and psychiatric comorbidities were nominally significant. While no substantially higher frequency was found for hernias, aneurysms, aortic dissection, or varicose veins among PEX-positive patients, higher rates of cardiac valve disorders and benign prostate hyperplasia were found among the PEX-positive individuals. CONCLUSION In addition to confirming an increased risk of respiratory, cardiovascular, and urogenital comorbidities, our data found an increased risk of cardiac valve disorders and benign prostate hyperplasia among PEX-positive patients, which may be manifestations of the underlying systemic elastotic fibrillopathy and warrants further exploration, including future histological study.
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Affiliation(s)
- Elizabeth Scharfenberg
- Department of Ophthalmology, Leipzig University Hospital, Liebigstrasse 10-14, 04103, Leipzig, Germany
| | - Franziska G Rauscher
- Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, Härtelstrasse 16-18, 04107, Leipzig, Germany.
| | - Petra Meier
- Department of Ophthalmology, Leipzig University Hospital, Liebigstrasse 10-14, 04103, Leipzig, Germany
| | - Dirk Hasenclever
- Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, Härtelstrasse 16-18, 04107, Leipzig, Germany
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Outcomes after cataract surgery in eyes with pseudoexfoliation: Results from the Veterans Affairs Ophthalmic Surgery Outcomes Data Project. Can J Ophthalmol 2017; 52:61-68. [DOI: 10.1016/j.jcjo.2016.07.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Revised: 06/03/2016] [Accepted: 07/18/2016] [Indexed: 01/29/2023]
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Tryggvason G, Jonasson F, Cotch MF, Li CM, Hoffman HJ, Themann CL, Eiriksdottir G, Sverrisdottir JE, Harris TB, Launer LJ, Gudnason V, Petersen H. Hearing in older adults with exfoliation syndrome/exfoliation glaucoma or primary open-angle glaucoma. Acta Ophthalmol 2016; 94:140-6. [PMID: 26547142 PMCID: PMC4764451 DOI: 10.1111/aos.12914] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Accepted: 09/22/2015] [Indexed: 02/06/2023]
Abstract
PURPOSE To determine whether adults, aged 66-96 years, with exfoliation syndrome (XFS)/exfoliation glaucoma (XFG), or primary open-angle glaucoma (POAG) have poorer hearing than controls of similar age. METHODS Case (XFS/XFG and POAG) and control status was diagnosed in the Reykjavik Glaucoma Studies (RGS) using slit-lamp examination, visual field testing and optic disc photographs; the RGS data were merged with the Age, Gene/Environment Susceptibility-Reykjavik Study that collected hearing data using air-conduction, pure-tone thresholds obtained at 0.5, 1, 2, 3, 4, 6 and 8 kHz categorized by better ear and worse ear, based on pure-tone averages (PTAs) calculated separately for low and middle frequencies (PTA512 - mean of thresholds at 0.5, 1 and 2 kHz) and high frequencies (PTA3468 - mean of thresholds at 3, 4, 6 and 8 kHz). Multivariable linear regression was used to test for differences in PTAs between cases and controls. RESULTS The mean age for 158 XFS/XFG cases (30.4% male) was 77.4 years, 95 POAG cases (35.8% male) was 77.9 years, and 123 controls (46.3% male) was 76.8 years. Using multivariable linear regression analysis, there were no consistent, statistically significant differences in PTAs between the two case groups and controls in either the low- or high-frequency range, even when stratified by age group. CONCLUSION Among the older individuals examined in this study hearing loss is highly prevalent and strongly associated with male gender and increasing age. As we did not find consistent statistically significant difference in hearing between cases and controls the diagnosis of XFS/XFG or POAG does not as such routinely call for audiological evaluation.
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Affiliation(s)
- Geir Tryggvason
- Department of Otolaryngology–Head and Neck Surgery, Oslo University Hospital, Oslo, Norway
| | - Fridbert Jonasson
- Department of Ophthalmology, Landspitali University Hospital, Reykjavik, Iceland
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - Mary Frances Cotch
- Division of Epidemiology and Clinical Applications, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, Maryland, USA
| | - Chuan-Ming Li
- Epidemiology and Statistics Program, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH), Bethesda, Maryland, USA
| | - Howard J. Hoffman
- Epidemiology and Statistics Program, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH), Bethesda, Maryland, USA
| | - Christa L. Themann
- Hearing Loss Prevention Team, National Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control and Prevention (CDC), Cincinnati, Ohio, USA
| | | | | | - Tamara B. Harris
- Laboratory of Population Sciences, National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, Maryland, USA
| | - Lenore J. Launer
- Laboratory of Population Sciences, National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, Maryland, USA
| | - Vilmundur Gudnason
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Icelandic Heart Association, Kopavogur, Iceland
| | - Hannes Petersen
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Department of Otolaryngology–Head and Neck Surgery, Landspitali University Hospital, Reykjavik, Iceland
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Gunes A, Yasar C, Tok L, Tok O. Prevalence of Pseudoexfoliation Syndrome in Turkish Patients with Senile Cataract. Semin Ophthalmol 2016; 32:297-301. [PMID: 26795697 DOI: 10.3109/08820538.2015.1068344] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
PURPOSE To investigate the prevalence of pseudoexfoliation syndrome (PEX) among Turkish patients with senile cataract. MATERIALS AND METHODS Records of 352 eyes of 352 patients who underwent cataract surgery were analyzed in this retrospective study. The presence of PEX, type of cataract, intraocular pressure (IOP), glaucoma, age-related macular degeneration, and systemic diseases (coronary artery disease, hypertension, diabetes mellitus) were recorded. RESULTS The overall prevalence of PEX syndrome was detected to be 11%. The mean age of PEX patients was significantly higher than without PEX (74.4 ± 7.2 years and 69.3 ± 11.4 years, respectively, p = 0.004). The most common cataract type in the PEX patients was mixed-type cataract determined in 51.2% of patients. IOP was significantly higher in eyes with PEX than in eyes without it (16.1 ± 4.5 mmHg and 14.7 ± 3.8 mmHg, respectively; p = 0.03). Moreover, the prevalence of age-related macular degeneration was found to be significantly higher, and prevalence of glaucoma slightly higher in PEX patients than without PEX. CONCLUSION Pseudoexfoliation syndrome is a common condition in Turkish people. PEX is associated with mixed type of cataract, age-related macular degeneration, and elevated IOP. Therefore, PEX patients should be checked for concomitant diseases.
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Affiliation(s)
- Alime Gunes
- a Department of Ophthalmology , Süleyman Demirel University, Faculty of Medicine , Isparta , Turkey
| | - Cigdem Yasar
- a Department of Ophthalmology , Süleyman Demirel University, Faculty of Medicine , Isparta , Turkey
| | - Levent Tok
- a Department of Ophthalmology , Süleyman Demirel University, Faculty of Medicine , Isparta , Turkey
| | - Ozlem Tok
- a Department of Ophthalmology , Süleyman Demirel University, Faculty of Medicine , Isparta , Turkey
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Sayin N, Kara N, Pekel G. Ocular complications of diabetes mellitus. World J Diabetes 2015; 6:92-108. [PMID: 25685281 PMCID: PMC4317321 DOI: 10.4239/wjd.v6.i1.92] [Citation(s) in RCA: 184] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 11/22/2014] [Accepted: 12/03/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus (DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and is becoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world's most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases.
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Mikropoulos DG, Mallini P, Michopoulou A, Giannopoulos T, Arranz-Marquez E, Koliakos GG, Konstas AGP. Asymmetric Dimethyloarginin (ADMA) Concentration in the Aqueous Humor of Patients with Exfoliation Syndrome or Exfoliative Glaucoma. Curr Eye Res 2013; 38:266-70. [DOI: 10.3109/02713683.2012.757325] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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