Optical Coherence Tomography Angiography Predicts Visual Outcomes for Craniopharyngioma in Children by Quantifying Choroidal Capillaries

Purpose: To predict the prognosis of craniopharyngioma in children by optical coherence tomography angiography (OCTA).Methods: We evaluated if the relationship between preoperative OCTA of the choroidal capillary density (CCD) and visual outcome continued over long-term visual recovery in 38 patients undergoing craniopharyngioma resection. Patients were evaluated 3 times: 1 week before surgery (Visit1), followed-up at 6–10 weeks (Visit2), and 9–15 months (Visit3) after surgery.Results: In total 38 patients (70 eyes) with craniopharyngiomas, which included 20 (52.6%) boys and 18 (47.4%)girls, the mean age was 11.8 ± 2.7 years (range: 6–18 years). The age (p = 0.71), gender (p = 1.00), mean refractive error (p = 0.55), and axial length (p = 0.23) of 38 normal volunteers (76 eyes) were matched. After surgery, the cross-compression of patients was relieved. The average visual acuity change in the normal CCD group was 0.07 ± 0.02; the average visual acuity change in the low CCD group was 0.01 ± 0.01, p < 0.001. Preoperative CCD value is related to the preoperative BCVA (p < 0.001), and the visual function after the long-term follow-up (9–15 months) (p < 0.001). The prognosis of CCD has the same trend as the BCVA. Further correlation analysis shows that CCD and BCVA are significantly correlated (r = 0.878; p < 0.001). CCD has a weak but significant correlation both with MD (r = 0.19; p < 0.001) and PSD (r = −0.21; p <0.001). A natural cutoff of CCD is approximately 38%. With the normal CCD group the maximum improvement of BCVA exceeds 0.3 post-operatively, compared to eyes in the low CCD group that improve by <0.03, and worse after surgery.Conclusions: Long-term vision recovery after surgical decompression of craniopharyngiomas in children can be predicted by preoperative by OCTA. Patients with normal CCD before surgery showed a tendency to improve vision; this trend of improvement persisted in subsequent follow-ups. The CCD baseline natural cutoff value for predicting visual prognosis before and after surgery is about 38%.

Implication of satellite cell behaviors in capillary growth via VEGF expression-independent mechanism in response to mechanical loading in HeyL-null mice

Angiogenesis and muscle satellite cell (SC)-mediated myonuclear accretion are considered essential for the robust response of contraction-induced muscle hypertrophy. Moreover, both myonucleus and SCs are physically adjacent to capillaries and are the major sites for the expression of proangiogenic factors, such as VEGF, in the skeletal muscle. Thus, events involving the addition of new myonuclei via activation of SCs may play an important role in angiogenesis during muscle hypertrophy. However, the relevance among myonuclei number, capillary density, and angiogenesis factor is not demonstrated. The Notch effector HeyL is specifically expressed in SCs in skeletal muscle and is crucial for SC proliferation by inhibiting MyoD in overload-induced muscle hypertrophy. Here, we tested whether the addition of new myonuclei by SC in overloaded muscle is associated with angiogenic adaptation by reanalyzing skeletal muscle from HeyL knockout (KO) mice, which show blunted responses of SC proliferation, myonucleus addition, and overload-induced muscle hypertrophy. Reanalysis confirmed blunted SC proliferation and myonuclear accretion in the plantaris muscle of HeyL-KO mice 9 weeks after synergist ablation. Interestingly, the increase in capillary-fiber ratio observed in WT mice was impaired in HeyL-KO mice. In both WT and HeyL-KO mice, the expression of VEGFA and VEGFB was similarly increased in response to overload. In addition, the expression pattern of TSP-1, a negative regulator of angiogenesis, was also not changed between WT and HeyL-KO mice. Collectively, these results suggest that SCs activation-myonuclear accretion plays a crucial role in angiogenesis during overload-induced muscle hypertrophy via independent of angiogenesis regulators.

Chronic effects of blast injury on the microvasculature in a transgenic mouse model of Alzheimer’s disease related Aβ amyloidosis

Background Altered cerebrovascular function and accumulation of amyloid-β (Aβ) after traumatic brain injury (TBI) can contribute to chronic neuropathology and increase the risk for Alzheimer’s disease (AD). TBI due to a blast-induced shock wave (bTBI) adversely affects the neurovascular unit (NVU) during the acute period after injury. However, the chronic effects of bTBI and Aβ on cellular components of the NVU and capillary network are not well understood. Methods We exposed young adult (age range: 76–106 days) female transgenic (Tg) APP/PS1 mice, a model of AD-like Aβ amyloidosis, and wild type (Wt) mice to a single bTBI (~ 138 kPa or ~ 20 psi) or to a Sham procedure. At 3-months or 12-months survival after exposure, we quantified neocortical Aβ load in Tg mice, and percent contact area between aquaporin-4 (AQP4)-immunoreactive astrocytic end-feet and brain capillaries, numbers of PDGFRβ-immunoreactive pericytes, and capillary densities in both genotypes. Results The astroglia AQP4-capillary contact area in the Tg-bTBI group was significantly lower than in the Tg-Sham group at 3-months survival. No significant changes in the AQP4-capillary contact area were observed in the Tg-bTBI group at 12-months survival or in the Wt groups. Capillary density in the Tg-bTBI group at 12-months survival was significantly higher compared to the Tg-Sham control and to the Tg-bTBI 3-months survival group. The Wt-bTBI group had significantly lower capillary density and pericyte numbers at 12-months survival compared to 3-months survival. When pericytes were quantified relative to capillary density, no significant differences were detected among the experimental groups, for both genotypes. Conclusion In conditions of high brain concentrations of human Aβ, bTBI exposure results in reduced AQP4 expression at the astroglia-microvascular interface, and in chronic capillary proliferation like what has been reported in AD. Long term microvascular changes after bTBI may contribute to the risk for developing chronic neurodegenerative disease later in life.

Sex features of cutaneous microvasculature in healthy working-age people

Aim. To study sex characteristics of cutaneous microvascular structure and function in a cohort of healthy working-age people without cardiovascular diseases.Material and methods. The study included 35 healthy men (42±4 years) and 34 women (41 ±5 years). The cardiovascular system was assessed in all patients. The microcirculatory bed of the skin was investigated by the following non-invasive methods: 1) computerized video capillaroscopy; 2) laser Doppler flowmetry; 3) photoplethysmography.Results. According to computerized video capillaroscopy in men, compared with women, there was a smaller number of both functioning capillaries (78 vs 86 capillaries/mm2, respectively (p<0,05)) and their total number (100 vs 120 capillaries/mm2, respectively (p<0,001)). Against the background of a decrease in capillary density in men, there was a higher skin interstitial hydration — 113 vs 96 gm (p<0,005) in men than in women. At the level of precapillary arterioles, where humoral tone regulation prevails. Laser Doppler flowmetry revealed lower pulse amplitude in men than in women — 0,87 vs 1,02 pf, respectively (p<0,05), which indicates a lower arterial blood inflow to exchange microvessels. Against this background, the constrictor response of precapillary arterioles to a sympathetic nervous system stimulation in men is higher than in women — 45% vs 40%, respectively (p<0,05). At the level of large arterioles, where neural tone regulation prevails, photoplethysmography revealed lower augmentation index standardized at a heart rate in men (-4,6 vs 1,7%, respectively, p<0,05), which indicates lower rigidity of muscular vessels in men.Conclusion. In working-age healthy people, sex differences are noted at all cutaneous microvascular levels, which must be taken into account when planning studies.

Long-term reproducibility of optical coherence tomography angiography in healthy and stable glaucomatous eyes

Background/aimsTo assess and compare long-term reproducibility of optic nerve head (ONH) and macula optical coherence tomography angiography (OCTA) vascular parameters and optical coherence tomography (OCT) thickness parameters in stable primary open-angle glaucoma (POAG), glaucoma suspect and healthy eyes.MethodsEighty-eight eyes (15 healthy, 38 glaucoma suspect and 35 non-progressing POAG) of 68 subjects who had at least three visits within 1–1.5 years with OCTA and OCT imaging (Angiovue; Optovue, Fremont, California, USA) on the same day were included. A series of vascular and thickness parameters were measured including macular parafoveal vessel density (pfVD), ONH circumpapillary capillary density (cpCD), macular parafoveal ganglion cell complex (pfGCC) and ONH circumpapillary retinal nerve fibre layer (cpRNFL). A random effects analysis of variance model was used to estimate intraclass correlation (ICC) coefficients and long-term variability estimates.ResultsICC was lower for OCTA (pfVD 0.823 (95% CI 0.736 to 0.888) and cpCD 0.871 (0.818 to 0.912)) compared with OCT (pfGCC 0.995 (0.993 to 0.997) and cpRNFL 0.975 (0.964 to 0.984)). Within-subject test–retest SD was 1.17% and 1.22% for pfVD and cpCD, and 0.57 and 1.22 µm for pfGCC and cpRNFL. Older age and lower signal strength index were associated with decreasing long-term variability of vessel densities.ConclusionsOCTA-measured macula and ONH vascular parameters have good long-term reproducibility, supporting the use of this instrument for longitudinal analysis. OCTA long-term reproducibility is less than OCT-measured thickness reproducibility. This needs to be taken into consideration when serial OCTA images are evaluated for change.Trial registration numberNCT00221897.

Anti-inflammatory iron chelator, DIBI, reduces leukocyte-endothelial adhesion and clinical symptoms of LPS-induced interstitial cystitis in mice

BACKGROUND: Interstitial cystitis (IC) is a prevalent and debilitating chronic inflammatory disease of the urinary bladder. Currently there are no fully effective therapeutic agents available, in part due to the still obscure pathogenesis of IC. Lipopolysaccharide (LPS) also known as endotoxin from Gram negative bacteria elicits IC in mice and has formed the basis of model systems for investigation. Excess free iron plays an important role in inflammation through generation of reactive oxygen species (ROS). The novel iron chelator DIBI has been shown to sequester excess free iron and dampen excess inflammatory responses to systemic LPS administration and also to Gram negative bacterial infections. OBJECTIVE: The overall objective of this study was to evaluate the effects of DIBI on LPS induced IC in mice. Leukocyte activation, endothelial adhesion and functional capillary density were assessed by intravital microscopy of the bladder microcirculation following a single intravesical LPS administration with or without intravesical DIBI treatment. Clinical IC symptoms were also assessed through behavioral and pain threshold force measurements. METHODS: Four groups of female BALB/c mice (n = 5–6/group) were randomized in this study: control group, IC group without therapy, IC group with DIBI therapy and control group with DIBI therapy. The groups were examined using intravital microscopy (IVM) of the bladder for leukocyte-endothelial interactions (adherent leukocytes, temporarily interacting leukocytes) and functional capillary density (FCD). A modified behavioral score by Boucher et al. and Von-Frey-Aesthesiometry were used to evaluate key behavioral indices related to pain and visceral pain perception. RESULTS: LPS introduced intravesically induced an early (≤2h) inflammation of the bladder evidenced by leukocyte activation and adhesion to bladder capillary walls. Intravesical DIBI therapy of mice 30min following LPS administration and assessed after 1.5h treatment showed a significant decrease in the number of adherent leukocytes compared to IC animals without DIBI treatment. DIBI treated mice showed a significantly lowered increase in behavioral distress scores compared to IC mice without therapy. Untreated IC mice exhibited a significantly decreased threshold force value for evoked pain response and DIBI treatment improved the threshold pain response. A significant inverse correlation was found for the two pain and suffering evaluation methods results. CONCLUSION: DIBI reduced inflammatory endothelial leukocyte adhesion and key indices related to pain and suffering over those observed in untreated IC mice. Our findings suggest a potential therapeutic role for DIBI for IC treatment.

Macular and submacular choroidal microvasculature in patients with primary open-angle glaucoma and high myopia

AimsTo characterise the influence of primary open-angle glaucoma (POAG) and high myopia (HM) on the macular and choroidal capillary density (CD).MethodsTwo hundred and seven eyes were enrolled, including 80 POAG without HM, 50 POAG with HM, 31 HM without POAG and 46 normal controls. A fovea-centred 6×6 mm optical coherence tomography angiography scan was performed to obtain the CD of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris. Macular and choroidal CDs were compared among the groups and the association of CDs with visual field mean deviation (MD) was determined using linear regression models.ResultsCompared with normal eyes, SCP CD was decreased in the POAG without HM group (p<0.05), while DCP CD was significantly decreased in the HM without POAG group (p<0.05). Both SCP and DCP CDs were significantly decreased in the POAG with HM group (p<0.05). CD reduction occurred mainly in the outer rather than inner ring of the 6×6 mm scan size. In multivariate regression analysis, worse MD was associated with lower CD in the outer ring of the SCP in all the HM eyes (p<0.05).ConclusionsPOAG and HM reduced macular CD in different layers of the retinal capillary plexus and both particularly in the outer ring of the 6×6 mm scans. Furthermore, assessment of the CD in the outer ring of the SCP may facilitate the diagnosis of glaucoma in eyes with HM.

Early neurovascular retinal changes detected by swept-source OCT in type 2 diabetes and association with diabetic kidney disease

Purpose To evaluate retinal thickness and capillary density in patients with type 2 diabetes (T2D) and their association with diabetic kidney disease (DKD) using swept-source optical coherence tomography (SS-OCT). Methods A cross-sectional study was conducted with T2D patients with mild or no diabetic retinopathy (DR) and nondiabetic controls. Inner retinal layer thickness was measured with SS-OCT. Retinal capillary density and the foveal avascular zone (FAZ) were measured with SS-OCT angiography (OCTA). SS-OCT parameters were compared in patients with and without diabetic kidney disease (DKD) and nondiabetic controls. Results 131 DKD eyes showed decreased ganglion cell layer plus (GCL+) (p = 0.005 TI; p = 0.022 I), retinal nerve fiber layer (RNFL) (p = 0.003), and central retinal thickness (CRT) (p = 0.032), as well as foveal avascular zone (FAZ) enlargement (p = 0.003) and lower capillary density in the superficial vascular plexus (p = 0.016, central quadrant), compared to controls. No statistically significant changes were found between diabetic patients without significant DKD and controls. Conclusion Our findings suggest early neurovascular damage in patients with T2D; these changes were more significant in patients with DKD. Larger longitudinal studies are warranted to determine the role of early neurovascular damage in the pathophysiology of severe DR.