Changes of the retinal and choroidal vasculature in cerebral small vessel disease

Cerebral small vessel disease (CSVD) is associated with changes in the retinal vasculature which can be assessed non-invasively with much higher resolution than the cerebral vasculature. To detect changes at a microvascular level, we used optical coherence tomography angiography which resolves retinal and choroidal vasculature. Participants with CSVD and controls were included. White matter lesions were determined on magnetic resonance imaging (MRI). The retinal and choroidal vasculature were quantified using swept-source optical coherence tomography angiography. Data were analysed using linear regression. We included 30 participants (18 females; patients, n = 20; controls, n = 10) with a mean age of 61 ± 10 years. Patients had a higher mean white matter lesion index and number of lesions than controls (p ≤ 0.002). The intraindividual deviation of choriocapillaris reflectivity differed significantly between age-matched patients (0.234 ± 0.012) and controls (0.247 ± 0.011; p = 0.029). Skeleton density of the deep retinal capillaries was significantly associated with the number of lesions on MRI (β = − 5.3 × 108, 95%-confidence interval [− 10.3 × 108; − 0.2 × 108]) when controlling for age. The choroidal microvasculature and the deep retinal vascular plexus, as quantified by optical coherence tomography angiography, are significantly altered in CSVD. The value of these findings in diagnosing or monitoring CSVD need to be assessed in future studies

Impact of visual impairment on physical activity in early and late age-related macular degeneration.

BACKGROUND:Modifiable risk factors for age-related macular degeneration (AMD) include smoking, nutrition and likely physical activity (PA). Levels of PA, however, are impacted by any visual impairment which makes the assessment of any association with AMD difficult. PURPOSE:To assess the impact of visual impairment under both high and low luminance conditions on levels of PA in early and late AMD. METHODS:Ninety participants with early to late AMD underwent a clinical assessment including conventional best-corrected visual acuity, low luminance visual acuity, contrast sensitivity and the Moorfields acuity test. PA was recorded using a wrist-worn accelerometer (GENEActiv, Activeinsights) on seven consecutive days. Patient characteristics were compared with the Wilcoxon rank-sum test and determinants of moderate-to-vigorous-PA (MVPA) were assessed using linear regression models. RESULTS:Mean age was 73.9 ± 8.5 years (range 50-89) and 47 subjects (52.2%) were women. Average MVPA time was longer in the early (355.1 ± 252.0 minutes/week) compared to the late AMD group (162.2 ± 134.6 minutes/week; p<0.001). Using linear regression, age [β = -0.25; 95% confidence interval (CI): -12.9; -0.8, p = 0.028] and AMD stage (β = -0.28; 95% CI: -230.9, -25.0; p = 0.015) but not visual impairment on any of the employed tests were associated with MVPA (minutes/week). CONCLUSIONS:We found late AMD to be associated with reduced PA. As performance on any of the visual tests was not associated with PA, this association cannot entirely be explained by functional impairment. More research is needed to further explore the association of PA and AMD as PA may be a potentially modifiable risk factor

Structural retinal changes in cerebral small vessel disease

Cerebral small vessel disease (CSVD) is an important contributor to cognitive impairment and stroke. Previous research has suggested associations with alterations in single retinal layers. We have assessed changes of all individual retinal layers in CSVD using high-resolution optical coherence tomography (OCT) for the first time. Subjects with recent magnetic resonance imaging (MRI) underwent macular and peripapillary retinal imaging using OCT for this case-control study. Number and volume ratio index (WMRI) of white matter lesions (WML) were determined on MRI. Data were analyzed using multiple linear regression models. 27 CSVD patients and 9 control participants were included. Ganglion cell layer (GCL) volume was significantly reduced in patients with CSVD compared to age-matched controls (p = 0.008). In patients with CSVD, larger foveal outer plexiform layer (OPL) volume and decreased temporal peripapillary retinal nerve fiber layer (RNFL) thickness were significantly associated with a higher WMRI in linear regression when controlling for age (p ≤ 0.033). Decreased foveal GCL volume and temporal-inferior RNFL thickness at Bruch's membrane opening (MRW), and increased temporal MRW were associated with a higher WML burden (p ≤ 0.037). Thus, we identified alterations in several OCT layers in individuals with CSVD (GCL, OPL, MRW and RNFL). Their potential diagnostic value merits further study

Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques

<div><p>Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10–12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated.</p></div

Fetal growth as assessed by predicted gestational ages.

<p>The predicted gestational age (pGA) as described by Tarantal [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006378#ppat.1006378.ref035" target="_blank">35</a>] from each of the pregnancies is plotted against the actual day of gestation estimated from breeding activity and animal menstrual records. The pGA was derived from the average of BPD+FL (dashed lines), or the HC (solid lines). <b>A</b> (animal 827577) and <b>B</b> (animal 660875), first trimester infection. <b>C</b> (animal 357676) and <b>D</b> (animal 598248), late second/early third trimester infection.</p

Study layout and viral RNA burden in pregnant rhesus fluids.

<p>(<b>A</b>) Schematic representation of the timeline of infection, sampling for maternal viral burden, and experimental cesarean section, for all animals in the study. Animals received a ZIKV challenge in the first or late second/early third trimesters of pregnancy, and blood and other fluid samples were collected according to the schedule indicated in detail in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006378#ppat.1006378.s001" target="_blank">S1 Fig</a>. (<b>B</b>) ZIKV viral load in pregnant macaque fluids. Viral RNA loads (vRNA copies/ml) measured in plasma, urine, saliva, and amniotic fluid presented individually for the four pregnant animals. The day post-inoculation is indicated below each graph, and gestational age (days) for each animal is indicated above (term = 165±10 days). Limit of assay quantification is 100 copies/mL. Limit of detection is 33 copies/mL. Colors for individual animals are continued through the rest of the Figures, including the Supplementary Figures.</p

Complete blood counts (CBCs) and serum chemistries for pregnant macaques infected with ZIKV.

<p>Animals were infected with 10⁴ PFU of ZIKV. Animals infected in the first or third trimesters are represented by color coding (<b>A</b>) as presented in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006378#ppat.1006378.g001" target="_blank">Fig 1</a>. All animals had CBC analysis performed on EDTA blood and chemistry analysis performed on serum at -7, -3, 0, 1–10 and additional indicated dpi. <b>B.</b> AST blood chemistries, <b>C.</b> ALT serum chemistries, <b>D.</b> CK serum chemistries, <b>E.</b> WBC counts, <b>F.</b> % lymphocytes, <b>G.</b> red blood cell (RBC) counts.</p

Immunohistochemical localization of ZIKV in fetal [and maternal] tissues.

<p>(<b>A</b>) Immunofluorescent staining for ZIKV NS2B (red) and macrophage marker CD163 (green) in fetal axillary lymph node with a high vRNA burden. The white scale bar = 100 μm. (<b>B</b>) H&E stained near section of the tissue presented in 9A. (<b>C</b>) Nonspecific immunostaining with control isotypes for ZIKV NS2B and CD163.</p