Serial Optical Coherence Tomography Research Articles

Reproducibility of Retinal Nerve Fiber Layer and Macular Ganglion Cell Layer Thickness Measurements by Optical Coherence Tomography in Myopic Eyes.

In myopic eyes, reproducibility of circumpapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer thickness measurement by optical coherence tomography (OCT) showed excellent reproducibility except for the temporal quadrant RNFL thickness measurement. The aim of this study was to evaluate the long-term reproducibility of circumpapillary RNFL and macular ganglion cell-inner plexiform layer (GCIPL) thickness measurements using OCT in myopic eyes. Sixty-five eyes with moderate-to-high myopia (spherical equivalent <-3.0 D, myopia group) and 53 eyes with low-to-no myopia (spherical equivalent ≥-3.0 D, control group) without ocular disorders, such as glaucoma or retinal diseases, were included. Three serial OCT scans recorded at 1-year intervals were analyzed. Reproducibility was evaluated using within-subject SD (Sw), coefficient of variation (CVw), and intraclass correlation coefficient (ICC). Mean±SD refractive error was -0.30±0.80 and -6.26±2.45 D for control and myopia groups, respectively. The myopia group had thinner superior, inferior, and nasal quadrant RNFL, thicker temporal quadrant RNFL, and thinner GCIPL than the control group (P<0.05), except for the minimum and superotemporal GCIPL thicknesses (P>0.05). The myopia group had lower reproducibility in temporal quadrant RNFL thickness (Sw, 2.57 μm; CVw 3.27%; ICC, 0.979) than the control group (Sw, 1.80 μm; CVw 2.59%; ICC, 0.989), whereas in other sectors of RNFL and all GCIPL parameters, comparable reproducibility was observed between the 2 groups. Long-term reproducibility of RNFL and GCIPL thickness measurements in moderate-to-high myopia was comparable to that of low-to-no myopia, except RNFL thickness in the temporal quadrant. These findings should be considered when detecting RNFL and GCIPL changes.

Impact of the Antithrombotic Effects of Prasugrel on Mid-Term Vascular Healing in Acute Coronary Syndrome vs. Stable Coronary Artery Disease.

The impact of antiplatelet drug effects on mid-term local arterial responses following percutaneous coronary intervention (PCI) remains uncertain. We evaluated the impact of the platelet reactivity of prasugrel on mid-term vascular healing between acute coronary syndrome (ACS) and stable coronary artery disease (CAD).Methods and Results:We conducted a prospective, 12-center study in 125 patients with ACS and 126 patients with stable CAD who underwent PCI with an everolimus-eluting stent (EES) and received dual antiplatelet therapy (DAPT) with prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed immediately after PCI and at the 9-month follow-up to assess the association of P2Y12reaction units (PRU) with the frequency of malapposed or uncovered struts and intrastent thrombi (IST). The incidence of abnormal mid-term OCT findings did not different between the ACS and CAD arms, regardless of clinical presentation, except that uncovered struts were more frequent in the ACS than CAD arm. PRU at PCI was significantly associated with the frequency of IST at follow-up, but not with uncovered and malapposed struts. PRU at PCI was the only independent predictor of IST detected at follow-up (odds ratio 1.009). In patients undergoing EES implantation and receiving prasugrel, achieving an adequate antiplatelet effect at the time of stent implantation may regulate thrombus formation throughout the follow-up period.

Optic Neuritis-Independent Retinal Atrophy in Neuromyelitis Optica Spectrum Disorder.

A limited number of studies have investigated the presence of ongoing disease activity independent of clinical relapses in neuromyelitis optica spectrum disorder (NMOSD), and data are conflicting. The objective of our study was to examine whether patients with aquaporin-4 (AQP4)-IgG seropositive NMOSD exhibit progressive retinal neuroaxonal loss, independently of optic neuritis (ON) attacks. In this single-center, longitudinal study, 32 AQP4-IgG+ NMOSD patients and 48 healthy controls (HC) were followed with serial spectral-domain optical coherence tomography and visual acuity (VA) assessments. NMOSD patients with ON less than 6 months before baseline were excluded, whereas data from patients with ON during follow-up were censored at the last visit before ON. VA worsening was defined as a decrease in monocular letter acuity ≥5 letters for high-contrast VA and ≥7 letters for low-contrast VA. Analyses were performed with mixed-effects linear regression models adjusted for age, sex, and race. The median follow-up duration was 4.2 years (interquartile range: 1.8-7.5). Relative to HC, NMOSD eyes had faster peripapillary retinal nerve fiber layer (pRNFL) (β = -0.25 µm/year faster, 95% confidence interval [CI]: -0.45 to -0.05, P = 0.014) and GCIPL thinning (β = -0.09 µm/year faster, 95% CI: -0.17 to 0, P = 0.05). This difference seemed to be driven by faster pRNFL and GCIPL thinning in NMOSD eyes without a history of ON compared with HC (GCIPL: β = -0.15 µm/year faster; P = 0.005; pRNFL: β = -0.43 µm/year faster, P < 0.001), whereas rates of pRNFL (β: -0.07 µm/year, P = 0.53) and GCIPL (β = -0.01 µm/year, P = 0.90) thinning did not differ between NMOSD-ON and HC eyes. Nine NMOSD eyes had VA worsening during follow-up. In this longitudinal study, we observed progressive pRNFL and GCIPL atrophy in AQP4-IgG+ NMOSD eyes unaffected by ON. These results support that subclinical involvement of the anterior visual pathway may occur in AQP4-IgG+ NMOSD.

Correlation of Ocular Biometric Parameters and Macular Ganglion Cell Layer in Normal Eyes

ABSTRACT Purpose To determine the association between ocular biometric parameters and macular ganglion cell layer (MGCL) thickness in normal eyes. Methods This observational cohort study was conducted with 76 eyes of 76 healthy subjects. Keratometry, pachymetry, corneal volume, iridocorneal angle were measured with Sirius (CSO, Florence, Italy); axial length, anterior chamber depth, anterior chamber volume, corneal diameter were measured with IOL Master (Carl Zeiss Meditec, Dublin, California). For all participants, serial horizontal Spectralis Domain Optical Coherence Tomography (SD-OCT, Heidelberg Engineering, GmbH, Dossenheim, Germany) scans of the macula and peripapillary retinal nerve fiber layer (RNFL) analysis were obtained using SD-OCT. The relationship between numerical variables was given by Pearson correlation coefficient. Results The mean age of the subjects was 36.3 ± 11.9 years (between 19 and 70 y). Fifty-one patients were female (67.1%) and twenty-five patients were male (32.9%). MGCL was found to be correlated with anterior chamber depth, anterior chamber volume, iridocorneal angle, axial length and white to white (p = .015 r = 0.594, p = .002 r = 0.365, p = .013 r = 0.299, p = .004 r = 0.335, p = .013 r = 0.289, respectively). In addition, MGCL was correlated positively with the mean global and superotemporal RNFL (p ≤ 0.005). However, neither central corneal thickness nor keratometry values were found to be correlated with MGCL. Conclusion The results of this study showed that MGCL thickness is affected by ocular biometric parameters. Therefore, these parameters should be taken into consideration when interpreting MGCL thickness measurements in the diagnosis of glaucoma.

Effects of the PCSK9 antibody alirocumab on coronary atherosclerosis in patients with acute myocardial infarction: a serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study–Rationale and design of the PACMAN-AMI trial

The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown. To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI4 mm) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI. In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI4 mm, and OCT-derived minimal FCT, will be assessed 52 weeks post randomization. The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI. NCT03067844.

Is the effect of atorvastatin 60 mg on stabilization of lipid-rich plaque equivalent to that of rosuvastatin 10 mg? A serial optical coherence tomography combined with intravascular ultrasound imaging.

This study aimed to compare the effect of atorvastatin 60 (AT60) mg to that of rosuvastatin 10 (RT10) mg on the morphological changes in lipid-rich plaques (LRPs) and plaque volume, using serial optical coherence tomography (OCT) and intravascular ultrasound imaging (IVUS). Intensive lipid lowering therapy by statin provides more clinical benefit compared to that of moderate lipid lowering therapy. Fifty patients who underwent OCT and IVUS at baseline, 6, and 12 months were grouped by statin therapy into the AT60 mg (n = 27) and RT10 mg (n = 23) groups. The relationships between absolute and percentage changes in biomarkers and fibrous cap thickness (FCT) during follow-up were investigated using a simple regression analysis. At 6 months, the mean low-density lipoprotein cholesterol level reduced from 113.5 to 65.5 mg/dl (AT60 mg group) and 100.2 to 72.2 mg/dl (RT10 mg groups). A continuous increase in FCT from baseline to 12 months was observed in both groups (p < .001, p < .001, respectively). Mean lipid arc significantly decreased in both AT60 mg (189.0 ± 55.9°, 170.9 ± 60.2°, 155.6 ± 50.6°, p < .001) and RT10 mg (160.0 ± 45.6°, 151.2 ± 48.5°, 141.1 ± 52.9°, p = .010) groups. Plaque burden did not change significantly in both groups. Lipid-lowering therapy effect with AT60 mg was equivalent to that of RT10 mg in terms of change in plaque morphology. AT60 mg showed more intensive low-density lipid cholesterol level reduction compared to RT10 mg while RT10 mg was effective in increasing the high-density lipid cholesterol level. Both statin therapies could effectively stabilize LRPs.

Impact of Endothelial Shear Stress on Absorption Process of Resorbable Magnesium Scaffold: A BIOSOLVE-II Substudy

Background/purposeLocal hemodynamic forces such as endothelial shear stress (ESS) may have an influence on appropriate neointimal healing, vessel remodeling, and struts' absorption process following second-generation drug-eluting resorbable magnesium scaffold (RMS, Magmaris, Biotronik AG, Buelach, Switzerland) placement. The aim of this study was to investigate the impact of ESS assessed by optical coherence tomography (OCT)-based computational fluid dynamic (CFD) simulations on absorption process and coronary lumen dimension after Magmaris implantation. Methods and resultsA total of 22 patients who were enrolled in the BIOSOLVE-II trial and underwent serial OCT assessment immediately after Magmaris implantation and at 6- and 12-month follow-up were included. We evaluated qualitative OCT findings frame by frame, and CFD simulations were performed to calculate the ESS at 3-dimensional (3D) reconstructed arteries. For quantitative calculation, the average ESS within each 1-mm section was classified into three groups: low (<1.0 Pa), intermediate (1.0–2.5 Pa), or high (>2.5 Pa). A significant difference of percentage remnants of scaffold was observed among the 3 groups at 12-month follow-up (P = 0.001) but not at 6-month follow-up. Low-ESS segment at baseline resulted in a greater lumen change of −1.857 ± 1.902 mm2 at 1 year compared to −1.277 ± 1.562 mm2 in the intermediate-ESS segment (P = 0.017) and − 0.709 ± 1.213 mm2 in the high-ESS segment (P = 0.001). ConclusionAfter Magmaris implantation, the presence of higher ESS might be associated with slower strut absorption process but less luminal loss.

Modulation of Retinal Atrophy With Rituximab in Multiple Sclerosis.

To investigate the effects of rituximab on retinal atrophy in patients with relapsing-remitting multiple sclerosis (RRMS), we performed serial optical coherence tomography (OCT) scans among a cohort of patients with RRMS on rituximab and compared rates of ganglion cell + inner plexiform layer (GCIPL) atrophy to those observed among age- and sex-matched glatiramer acetate (GA)-and natalizumab-treated patients with RRMS and healthy controls (HCs). In this observational study, patients with RRMS treated with a single disease-modifying therapy and HCs were followed with serial OCT for a median duration of 2.8 years. Participants with uncontrolled hypertension, diabetes mellitus, or glaucoma, and eyes with optic neuritis ≤6 months prior to baseline OCT, or during follow-up, were excluded. Statistical analyses were performed using linear mixed-effects regression. During the overall follow-up period, rates of GCIPL atrophy were -0.28 ± 0.11 µm/y among rituximab-treated patients with RRMS (n = 35). This was similar to GA-treated (n = 49; -0.33 ± 0.05 µm/y; p = 0.69) and natalizumab-treated patients (n = 88; -0.17 ± 0.10 µm/y; p = 0.13) and faster than HCs (n = 78; -0.15 ± 0.03 µm/y; p = 0.006). Rituximab-treated patients exhibited 0.55 ± 0.23 µm/y faster rates of GCIPL atrophy during the first 12 months of treatment, relative to afterwards (n = 25; p = 0.02), during which period GCIPL atrophy rates were -0.14 ± 0.13 µm/y. Retinal atrophy in RRMS is modulated by rituximab. Greater attenuation of retinal atrophy may occur after 12 months of rituximab treatment, following which time GCIPL atrophy rates are similar to those observed among natalizumab-treated patients with RRMS and HCs. Our findings raise the possibility that the neuroprotective therapeutic response with rituximab in RRMS may take up to 12 months, which should be confirmed by larger studies. This study provides Class IV evidence on the difference in rate of change of the GCIPL thickness in patients with RRMS comparing rituximab to other disease-modifying therapies.

Hypoxia-induced inflammation: Profiling the first 24-hour posthypoxic plasma and central nervous system changes.

Central nervous system and visual dysfunction is an unfortunate consequence of systemic hypoxia in the setting of cardiopulmonary disease, including infection with SARS-CoV-2, high-altitude cerebral edema and retinopathy and other conditions. Hypoxia-induced inflammatory signaling may lead to retinal inflammation, gliosis and visual disturbances. We investigated the consequences of systemic hypoxia using serial retinal optical coherence tomography and by assessing the earliest changes within 24h after hypoxia by measuring a proteomics panel of 39 cytokines, chemokines and growth factors in the plasma and retina, as well as using retinal histology. We induced severe systemic hypoxia in adult C57BL/6 mice using a hypoxia chamber (10% O2) for 1 week and rapidly assessed measurements within 1h compared with 18h after hypoxia. Optical coherence tomography revealed retinal tissue edema at 18h after hypoxia. Hierarchical clustering of plasma and retinal immune molecules revealed obvious segregation of the 1h posthypoxia group away from that of controls. One hour after hypoxia, there were 10 significantly increased molecules in plasma and 4 in retina. Interleukin-1β and vascular endothelial growth factor were increased in both tissues. Concomitantly, there was significantly increased aquaporin-4, decreased Kir4.1, and increased gliosis in retinal histology. In summary, the immediate posthypoxic period is characterized by molecular changes consistent with systemic and retinal inflammation and retinal glial changes important in water transport, leading to tissue edema. This posthypoxic inflammation rapidly improves within 24h, consistent with the typically mild and transient visual disturbance in hypoxia, such as in high-altitude retinopathy. Given hypoxia increases risk of vision loss, more studies in at-risk patients, such as plasma immune profiling and in vivo retinal imaging, are needed in order to identify novel diagnostic or prognostic biomarkers of visual impairment in systemic hypoxia.

Influence of dual antiplatelet therapy duration on neointimal condition after second-generation drug-eluting stent implantation

Guidelines recommend shorter duration (1–12 months) for dual antiplatelet therapy (DAPT) in the second-generation drug-eluting stent (DES) era. However, whether shorter DAPT duration affects stent strut conditions and neointimal characteristics at mid-term follow-up remains uncertain. Therefore, we studied the relation between DAPT duration and vascular healing response as assessed by optical coherence tomography (OCT). This study was retrospective observational study. Participants comprised 64 patients who underwent serial OCT at both 9 and 18 months after DES implantation. All patients received DAPT until the 9-month follow-up then were divided into two groups: 49 patients who continued DAPT (longer DAPT group); and 15 patients who stopped taking the P2Y12 inhibitor and were treated with aspirin alone (shorter DAPT group) at the 18-month follow-up. Using OCT, we evaluated and compared stent strut conditions and neointimal characteristics between groups at both 9 and 18 months after stent implantation. Baseline clinical and procedural parameters were mostly similar between groups. At the 18-month follow-up, no in-stent thrombus assessed by OCT was observed in either group. No significant differences in OCT characteristics or measurements of neointima were seen between groups at 9- or 18-month follow-ups. Neointimal volume increased from 9 to 18 months in both groups, with a similar degree of neointimal proliferation in both groups (shorter DAPT group, 0.23 ± 0.29 mm3/mm; longer DAPT group, 0.19 ± 0.27 mm3/mm; P = 0.56). In conclusion, interrupting DAPT 9 months after second-generation DES implantation did not affect the development of in-stent thrombus, neointimal proliferation or stent strut coverage at 18-month follow-up compared with continuing DAPT.

Juxtapapillary Deep-Layer Microvasculature Dropout and Retinal Nerve Fiber Layer Thinning in Glaucoma

We sought to characterize juxtapapillary (JP) and non-JP microvasculature dropout in patients with primary open-angle glaucoma and to compare their rate of retinal nerve fiber layer (RNFL) thinning. Retrospective cohort study. A total of 141 eyes with primary open-angle glaucoma with ≥4 serial optical coherence tomography (OCT) images after initial OCT angiography for ≥2 years were included. Based on OCT angiography imaging, the 3 groups were matched by age and visual field mean deviation: JP group (parapapillary deep-layer microvasculature dropout in contact with the optic disc boundary, n=47), non-JP group (dropout not reaching the optic disc boundary, n=47), and no-dropout group (lacking the dropout, n=47). The RNFL thinning rate was compared among the 3 groups. The rate of RNFL thinning tended to be fastest in the JP group followed by the non-JP group and no-dropout group in all areas except the temporal and nasal sectors. Post hoc analysis revealed that the JP group had significantly faster RNFL thinning than did the no-dropout group in the global area and the inferotemporal and inferonasal sectors (P < .05). When subgroup analysis was performed for subjects in which the main sector of dropout was the inferotemporal sector, the JP group had significantly faster RNFL thinning than the other 2 groups in the corresponding inferotemporal sector (P < .001). Eyes with JP microvasculature dropout showed faster RNFL thinning than eyes without dropout. These findings suggest that deep-layer microvasculature dropout, especially in contact with the optic disc boundary, is associated with rapid glaucoma progression.

Long-term clinical, angiographic, and optical coherence tomography findings of Mg-based bioresorbable scaffold in patients with acute coronary syndrome.

This study sought to evaluate the clinical outcomes of patients treated with magnesium-based bioresorbable scaffolds (MgBRS) in the context of acute coronary syndromes (ACS) at long-term follow-up (24 months). The study also aims to investigate the MgBRS performance by angiography and the healing and bioresorption pattern by optical coherence tomography (OCT) at 18 months. Between December 2016 and December 2018, a total of 90 patients admitted for ACS and treated with MgBRS (Magmaris, Biotronik AG, Bülach, Switzerland) were enrolled in a multicenter prospective study. Clinical follow-up was performed in all patients at 24 months and angiographic and OCT follow-up in 51.5% of patients at 18 months. Serial OCT was available in 33 patients (36.7%). At a 2-year follow-up, 88.8% were free of symptoms, no cardiac death was reported, and the device-oriented composite event (DOCE): consisting of cardiac death, target vessel myocardial infarction, and target lesion revascularization (TLR) was 13.3%. Stent thrombosis and TLR were observed in 2.2 and 11.1%, respectively. Binary restenosis was observed in 21.7% of cases and in-stent late lumen loss was 0.61 ± 0.75 mm. By serial OCT imaging, the minimal lumen area was significantly reduced greater than 40% (from 6.12 ± 1.59 to 3.5± 1.55 mm2, p< .001). At follow-up, area stenosis was 44.33 ± 23.07% and half of the patients presented indiscernible struts. The principal observed mechanism of restenosis was scaffold collapse. At long-term follow-up, MgBRS implantation in ACS patients showed a high rate of DOCE, mainly caused by clinically driven TLR. MgBRS restenosis was caused by scaffold collapse in most of the cases.

The incidence, natural history, and predictive factors for tissue protrusion after drug-eluting stent implantation.

Although tissue protrusion (TP) between the stent struts after stent implantation has been implicate as a potential factor of stent failure, the incidence, natural history, and predictive factor of TP after stent implantation remains unclear. This prospective study evaluated the fate of TP after drug-eluting stent (DES) deployment using optical coherence tomography (OCT). This study analyzed TP for 42 lesions after DES in which three serial OCTs, including preprocedure, postprocedure, and 1-month after the procedure were performed. TP was classified into the five groups: (a) persistent, (b) progressive, (c) healed, (d) regressive, and (e) late-acquired. Immediately after the procedure, 100 TPs in 37 lesions (88%) were identified. Of those, 53 (53%) were persistent, 3 (3%) were progressive, 20 (20%) were healed, and 24 (24%) were regressed at 1-month follow-up. Seven TPs in five patients (13%) were observed only at 1-month follow-up (late-acquired). In lesions with late-acquired TP, calcified nodule was identified as an underlying plaque morphology on preprocedural OCT. A serial OCT analysis found TP occurred not only immediately after DES implantation, but also 1-month after DES implantation.

Assessing the impact of PCSK9 inhibition on coronary plaque phenotype with optical coherence tomography: rationale and design of the randomized, placebo-controlled HUYGENS study.

Technological advances in arterial wall imaging permit the opportunity to visualize coronary atherosclerotic plaque with sufficient resolution to characterize both its burden and compositional phenotype. These modalities have been used extensively in clinical trials to evaluate the impact of lipid lowering therapies on serial changes in disease burden. While the findings have unequivocally established that these interventions have the capacity to either slow disease progression or promote plaque regression, depending on the degree of lipid lowering achieved, their impact on plaque phenotype is less certain. More recently optical coherence tomography (OCT) has been employed with a number of studies demonstrating favorable effects on both fibrous cap thickness (FCT) and the size of lipid pools within plaque in response to statin treatment. The phase 3, multi-center, double-blind HUYGENS study will assess the impact of incremental lipid lowering with the proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor, evolocumab, on plaque features using serial OCT imaging, in statin-treated patients following an acute coronary syndrome (ACS). Subjects with non-ST-elevation ACS (n=150) will be randomized 1:1 into two groups to receive monthly injections of evolocumab 420 mg or placebo. The primary endpoint is the effect of evolocumab on coronary atherosclerotic plaques will be assessed by OCT at baseline and at week 50. The HUYGENS study will determine whether intensified lipid lowering therapy with evolocumab in addition to maximally tolerated statin therapy will have incremental benefits on high-risk features of coronary artery plaques. This study was registered on Clinicaltrials.gov (NCT03570697).

Predictors for Rapid Progression of Coronary Calcification: An Optical Coherence Tomography Study.

BackgroundThe role of coronary calcification in cardiovascular events and plaque stabilization is still being debated, and factors involved in the progression of coronary calcification are not fully understood. This study aimed to identify the predictors for rapid progression of coronary calcification.Methods and ResultsPatients with serial optical coherence tomography imaging at baseline and at 6 months were selected. Changes in the calcification index and predictors for progression of calcification were studied. Calcification index was defined as the product of the mean calcification arc and calcification length. Rapid progression of calcification was defined as an increase in the calcification index above the median value. Among 187 patients who had serial optical coherence tomography imaging, 235 calcified plaques were identified in 105 patients (56.1%) at baseline. After 6 months, the calcification index increased in 95.3% of calcified plaques from 132.0 to 178.2 (P<0.001). In multivariable analysis, diabetes mellitus (odds ratio [OR], 3.911; P<0.001), chronic kidney disease (OR, 2.432; P=0.037), lipid‐rich plaque (OR, 2.698; P=0.034), and macrophages (OR, 6.782; P<0.001) were found to be independent predictors for rapid progression of coronary calcification. Interestingly, rapid progression of calcification was associated with a significant reduction of inflammatory features (thin‐cap fibroatheroma; from 21.2% to 11.9%, P=0.003; macrophages; from 74.6% to 61.0%, P=0.001).ConclusionsDiabetes mellitus, chronic kidney disease, lipid‐rich plaque, and macrophages were independent predictors for rapid progression of coronary calcification. Baseline vascular inflammation and subsequent stabilization may be related to rapid progression of calcification.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01110538.

Residual thrombus following plaque disruption contributes to rapid plaque progression: in-vivo serial optical coherence tomography imaging

Residual thrombus following plaque disruption contributes to rapid plaque progression: in-vivo serial optical coherence tomography imaging

Methotrexate Therapy Promotes Cell Coverage and Stability in in-Stent Neointima

Anti-proliferative drugs released from drug-eluting stents delay cell coverage and vascular healing, which increases the risk of late stent thrombosis. We assessed the potential effects of systemic methotrexate (MTX) on cell coverage, vascular healing and inflammation activation in vivo and in vitro. We applied MTX in the right common carotid artery in a rabbit stenting model to determine the impact on cell coverage and inflammation activation using a serial optical coherence tomography (OCT) analysis and elucidated the molecular mechanism of MTX in human umbilical vein endothelial cells (HUVECs). Low-dose MTX promoted the development of cell coverage and vascular healing, which was associated with fewer uncovered struts (%) and cross-sections with any uncovered struts (%) at 4 weeks of stenting. The MTX group also exhibited lower rates of heterogeneity, microvessels and per-strut low-signal-intensity layers, indicating neointimal instability at 12 weeks of stenting. In vitro, low-dose MTX strongly inhibited HUVEC apoptosis, promoted proliferation and inhibited inflammatory activation by targeting the phosphoinositide 3-kinase (PI3K)/AKT signalling pathway. Low-dose MTX may be a key means of promoting early cell coverage via the inhibition of the inflammatory response and stability of neointima by targeting inflammatory pathways after stent implantation.

Optical Coherence Tomography Predictors for a Favorable Vascular Response to Statin Therapy.

BackgroundSpecific plaque phenotypes that predict a favorable response to statin therapy have not been systematically studied. This study aimed to identify optical coherence tomography predictors for a favorable vascular response to statin therapy.Methods and ResultsPatients who had serial optical coherence tomography imaging at baseline and at 6 months were included. Thin‐cap area (defined as an area with fibrous cap thickness <200 μm) was measured using a 3‐dimensional computer‐aided algorithm, and changes in the thin‐cap area at 6 months were calculated. A favorable vascular response was defined as the highest tertile in the degree of reduction of the thin‐cap area. Macrophage index was defined as the product of the average macrophage arc and length of the lesion with macrophage infiltration. Layered plaque was defined as a plaque with 1 or more layers of different optical density. In 84 patients, 140 nonculprit lipid plaques were identified. In multivariable analysis, baseline thin‐cap area (odds ratio [OR] 1.442; 95% CI, 1.024–2.031, P=0.036), macrophage index (OR, 1.031; 95% CI, 1.002–1.061, P=0.036), and layered plaque (OR, 2.767; 95% CI, 1.024–7.479, P=0.045) were identified as the significant predictors for a favorable vascular response. Favorable vascular response was associated with a decrease in the macrophage index.ConclusionsThree optical coherence tomography predictors for a favorable vascular response to statin therapy have been identified: large thin‐cap area, high macrophage index, and layered plaque. Favorable vascular response to statin was correlated with signs of decreased inflammation.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01110538.

Serum ceramide levels are altered in multiple sclerosis

Background: Sphingolipids are myelin components and inflammatory signaling intermediates. Sphingolipid metabolism may be altered in people with multiple sclerosis (PwMS), but existing studies are limited by small sample sizes. Objectives: To compare the levels of serum ceramides between PwMS and healthy controls (HCs) and to determine whether ceramide levels correlate with disability status, as well as optical coherence tomography (OCT)-derived rates of retinal layer atrophy. Methods: We performed targeted lipidomics analyses for 45 ceramides in PwMS (n = 251) and HCs (n = 68). For a subset of PwMS, baseline and 5-year Expanded Disability Status Scale (EDSS) assessments (n = 185), or baseline and serial spectral-domain OCT (n = 180) were assessed. Results: Several ceramides, including hexosylceramides, lactosylceramides, and dihydroceramides, were altered in PwMS compared with HCs. Higher levels of Cer16:0 were associated with higher odds of EDSS worsening at 5 years in univariable (odds ratio (OR) = 3.84, 95% confidence interval (CI) = 1.41–10.43) and multivariable analyses accounting for age, sex, and race (OR = 2.97, 95% CI = 1.03–8.59). Each 1 ng/mL higher concentration of Hex-Cer22:0 and DH-HexCer22:0 was associated with accelerated rates (μm/year) of ganglion cell + inner plexiform layer (–0.138 ± 0.053, p = 0.01; –0.158 ± 0.053, p = 0.003, respectively) and peripapillary retinal nerve fiber layer thinning (–0.305 ± 0.107, p = 0.004; –0.358 ± 0.106, p = 0.001, respectively). Conclusion: Ceramide levels are altered in PwMS and may be associated with retinal neurodegeneration and physical disability.

In vivo evaluation of coronary arteritis by serial optical coherence tomography in large vessel vasculitis

<i>In vivo</i> evaluation of coronary arteritis by serial optical coherence tomography in large vessel vasculitis