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Impact of LDL Cholesterol on Microvascular Versus Macrovascular Disease: A Mendelian Randomization Study.
Emanuelsson, F, Nordestgaard, BG, Tybjærg-Hansen, A, Benn, M
Journal of the American College of Cardiology. 2019;(11):1465-1476
Abstract
BACKGROUND Low-density lipoprotein cholesterol (LDL-C) is causally associated with a high risk of coronary artery disease. Whether this also holds for a spectrum of peripheral vascular diseases is unknown. OBJECTIVES The purpose of this study was to determine whether high LDL-C causally relates to risk of retinopathy, neuropathy, chronic kidney disease (CKD), and peripheral arterial disease (PAD) in the general population. METHODS One-sample Mendelian randomization (MR) of 116,419 Danish individuals, 2-sample MR on summary-level data from the Global Lipid Genetics Consortium (GLGC) (n = 94,595) and the UK Biobank (n = 408,455), and meta-analysis of randomized statin trials (n = 64,134) were performed. RESULTS Observationally, high LDL-C did not associate with high risk of retinopathy or neuropathy. There were stepwise increases in risk of CKD and PAD with higher LDL-C (both p for trend <0.001), with hazard ratios of 1.05 (95% confidence interval [CI]: 0.97 to 1.13) for CKD, and 1.41 (95% CI: 1.23 to 1.62) for PAD in individuals with LDL-C above the 95th percentile versus below the 50th percentile. In genetic, causal analyses in the Copenhagen studies, the risk ratio of disease for a 1 mmol/l higher LDL-C was 1.06 (95% CI: 0.24 to 4.58) for retinopathy, 1.05 (95% CI: 0.64 to 1.72) for neuropathy, 3.83 (95% CI: 2.00 to 7.34) for CKD, and 2.09 (95% CI: 1.30 to 2.38) for PAD. Summary-level data from the GLGC and the UK Biobank for retinopathy, neuropathy, and PAD gave similar results. For CKD, a 1-mmol/l lower LDL-C conferred a higher eGFR of 1.95 ml/min/1.73 m2 (95% CI: 1.88 to 2.02 ml/min/1.73 m2) observationally, 5.92 ml/min/1.73 m2 (95% CI: 4.97 to 6.86 ml/min/1.73 m2) genetically, and 2.69 ml/min/1.73 m2 (95% CI: 1.48 to 3.94 ml/min/1.73 m2) through statin therapy. CONCLUSIONS High LDL-C was not causally associated with risk of retinopathy and neuropathy; however, high LDL-C was observationally and genetically associated with high risks of PAD and CKD, suggesting that LDL-C is causally involved in the pathogenesis of these diseases.
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Test performance of optical coherence tomography angiography in detecting retinal diseases: a systematic review and meta-analysis.
Faes, L, Bodmer, NS, Locher, S, Keane, PA, Balaskas, K, Bachmann, LM, Schlingemann, RO, Schmid, MK
Eye (London, England). 2019;(8):1327-1338
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Abstract
OBJECTIVE To investigate the diagnostic accuracy of optical coherence tomography angiography (OCTA) in detecting vascular characteristics of chorio-retinal disease. METHODS Evidence acquisition: We searched Web of Science, Scopus, and Medline by the citation of references and complemented these electronic searches by checking the list of references of included and review articles. Screening, selection, assessment, and extraction was performed in parallel by two authors. RESULTS Evidence synthesis: Systematic review and exploratory meta-analysis. The ten studies that contributed to the meta-analysis enrolled 440 eyes and allowed constructing ten two-by-two tables. The tables reported on detection of choroidal neovascularization (CNV) in eyes suffering from either age-related macular degeneration (4), central serous chorioretinopathy (2), myopia (2), foveomacular vitelliform dystrophy (1), or a mixed cohort suffering from multiple retinal diseases (1). Of the ten studies, six used a cohort and four a case-control design. We found a pooled sensitivity of 0.90 (95% confidence intervals (CIs): 0.82-0.95) and a pooled specificity of 0.97 (95% CI: 0.89-0.99). Corresponding positive and negative likelihood ratios were 32.3 (95% CI: 7.4-141.6) and 0.10 (95% CI: 0.06-0.20), respectively. No pooling was possible for retinal vascular parameters of diabetic retinopathy, polypoidal choroidal vasculopathy, or detection of CNV activity. CONCLUSIONS The results of highly biased and heterogeneous studies assessing the diagnostic performance of OCTA highlight the need for further analyses of methodologically sound and sufficiently sized clinical evaluations.
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Anti-vascular endothelial growth factor treatment for retinal conditions: a systematic review and meta-analysis.
Pham, B, Thomas, SM, Lillie, E, Lee, T, Hamid, J, Richter, T, Janoudi, G, Agarwal, A, Sharpe, JP, Scott, A, et al
BMJ open. 2019;(5):e022031
Abstract
OBJECTIVES To evaluate the comparative effectiveness and safety of intravitreal bevacizumab, ranibizumab and aflibercept for patients with choroidal neovascular age-related macular degeneration (cn-AMD), diabetic macular oedema (DMO), macular oedema due to retinal vein occlusion (RVO-MO) and myopic choroidal neovascularisation (m-CNV). DESIGN Systematic review and random-effects meta-analysis. METHODS Multiple databases were searched from inception to 17 August 2017. Eligible head-to-head randomised controlled trials (RCTs) comparing the (anti-VEGF) drugs in adult patients aged ≥18 years with the retinal conditions of interest. Two reviewers independently screened studies, extracted data and assessed risk of bias. RESULTS 19 RCTs involving 7459 patients with cn-AMD (n=12), DMO (n=3), RVO-MO (n=2) and m-CNV (n=2) were included. Vision gain was not significantly different in patients with cn-AMD, DMO, RVO-MO and m-CNV treated with bevacizumab versus ranibizumab. Similarly, vision gain was not significantly different between cn-AMD patients treated with aflibercept versus ranibizumab. Patients with DMO treated with aflibercept experienced significantly higher vision gain at 12 months than patients receiving ranibizumab or bevacizumab; however, this difference was not significant at 24 months. Rates of systemic serious harms were similar across anti-VEGF agents. Posthoc analyses revealed that an as-needed treatment regimen (6-9 injections per year) was associated with a mortality increase of 1.8% (risk ratio: 2.0 [1.2 to 3.5], 2 RCTs, 1795 patients) compared with monthly treatment in cn-AMD patients. CONCLUSIONS Intravitreal bevacizumab was a reasonable alternative to ranibizumab and aflibercept in patients with cn-AMD, DMO, RVO-MO and m-CNV. The only exception was for patients with DME and low visual acuity (<69 early treatment diabetic retinopathy study [ETDRS] letters), where treatment with aflibercept was associated with significantly higher vision gain (≥15 ETDRS letters) than bevacizumab or ranibizumab at 12 months; but the significant effects were not maintained at 24 months. The choice of anti-VEGF drugs may depend on the specific retinal condition, baseline visual acuity and treatment regimen. PROSPERO REGISTRATION NUMBER CRD42015022041.
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Optical coherence angiography: A review.
Wylęgała, A, Teper, S, Dobrowolski, D, Wylęgała, E
Medicine. 2016;(41):e4907
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Abstract
BACKGROUND Retinal vascular diseases are one of the most common causes of blindness in the developed world. Optical Coherence Tomography Angiography (OCT-A) is a new noninvasive method that uses several algorithms to detect blood movement. This enables the creation of high-resolution vascular images with contrast depicting motionless tissue. METHODS This review presents the results of articles relevant to age-related macular degeneration (AMD), diabetic retinopathy (DR), and OCT-A. The OCT-A technique can successfully be used in the diagnosis of neovascularization, retinal vein occlusion (RVO) and retinal artery occlusion (RAO), vessel abnormalities and even anterior segment neovascularization. OCT-A can also be applied to compute data such as vessel density, and flow index in both superficial and deep plexuses. RESULTS Many studies have compared fluorescein angiography with OCT-A. Other studies have reported differences in vascular density in AMD patients and have compared them with people having healthy eyes. Although OCT-A offers rapid picture acquisition, high repeatability and resolution, it also has many drawbacks. The most common are: motion artifacts, projections from overlying vessels and limited field of view.An interesting new application is the possibility to assess changes during antivascular endothelial growth factor (anti-VEGF) therapy. Another function of OCT-A is the possible application in the study of choriocapillaries in many fields of ocular pathology. CONCLUSION OCT-A is a new promising method that allows the visualization of the retinal vascular network and the counting of blood flow parameters. This technique provides reliable images useful in clinical routines.