Intravoxel incoherent motion as a surrogate marker of perfused vascular density in rat brain.

Intravoxel incoherent motion (IVIM) MRI has emerged as a valuable technique for the assessment of tissue characteristics and perfusion. However, there is limited knowledge about the relationship between IVIM-derived measures and changes at the level of the vascular network. In this study, we investigated the potential use of IVIM MRI as a noninvasive tool for measuring changes in cerebral vascular density. Variations in quantitative immunohistochemical measurements of the vascular density across different regions in the rat brain (cortex, corpus callosum, hippocampus, thalamus, and hypothalamus) were related to the pseudo-diffusion coefficient D* and the flowing blood fraction f in healthy Wistar rats. We assessed whether region-wise differences in the vascular density are reflected by variations in the IVIM measurements and found a significant positive relationship with the pseudo-diffusion coefficient (p < 0.05, ß = 0.24). The effect of cerebrovascular alterations, such as blood-brain barrier (BBB) disruption on the perfusion-related IVIM parameters, is not well understood. Therefore, we investigated the effect of BBB disruption on the IVIM measures in a rat model of metabolic and vascular comorbidities (ZSF1 obese rat) and assessed whether this affects the relationship between the cerebral vascular density and the noninvasive IVIM measurements. We observed increased vascular permeability without detecting any differences in diffusivity, suggesting that BBB leakage is present before changes in the tissue integrity. We observed no significant difference in the relationship between cerebral vascular density and the IVIM measurements in our model of comorbidities compared with healthy normotensive rats.

Investigation of the effects of gestational diabetes and hypertension on retinal and choroidal microvascular circulation using swept-source optical coherence tomography angiography.

PURPOSE: The aim of this study was to investigate the microvascular changes in the retina and choroid in gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) and to compare the results with those of healthy pregnant subjects. METHODS: Twenty-nine pregnant subjects with coexisting GDM and PIH (group 1) and 36 healthy pregnant subjects (group 2) were enrolled in the study. All subjects were examined by optical coherence tomography (OCT) and angiography (OCTA). The retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), choroidal thickness (CT), superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC) vascular density (VD), and foveal avascular zone (FAZ) were measured. RESULTS: We observed that the values of CT and VD were lower in group 1 than in group 2. No significant difference was found between groups in RT, FAZ area and CC VD. SCP and DCP VD values were higher in group 2 in all quadrants. We observed a significant increase in FAZ area and CC VD with increasing systolic blood pressure. No correlation was observed between diastolic blood pressure and FBS with other parameters. In group 1, FAZ area was significantly higher in the diet-treated group than in the insulin-treated group. CONCLUSION: Monitoring and treatment of pregnant women with PIH and GDM is important because of the risks that may occur during pregnancy. We believe that changes in microvascular circulation can be detected noninvasively with OCTA, even in the absence of clinical or retinal findings.

Changes in retinal and choroidal thickness and vascular density in patients with systemic lupus erythematosus: Assessed by optical coherence tomography angiography.

OBJECTIVE: The aim was to investigate the changes in retinal and choroidal thickness and vascular density in patients with systemic lupus erythematosus (SLE) using optical coherence tomography angiography (OCTA). METHODS: Twenty-nine patients with SLE (29 eyes) and 25 control subjects (25 eyes) were enrolled. SLE activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Retinal thickness (RT), inner retinal thickness (IRT), outer retinal thickness (ORT), choroidal thickness (ChT), retinal superficial vascular density (SVD), retinal deep vascular density (DVD), choriocapillary vascular density (CCVD), foveal avascular zone (FAZ), superficial FAZ (sFAZ), and deep FAZ (dFAZ) were measured using OCTA. The retinal and choroidal thickness and vascular density between the control group and SLE group were compared. The relationships between SLEDAI scores and the retinal and choroidal thickness and vascular density in SLE group were analyzed. RESULTS: The SVD was significantly increased, and the DVD and CCVD were significantly decreased in the SLE group compared to the control group (p < .05). The results of receiver operating characteristic (ROC) showed that the area under the curve (AUC) values of SVD, DVD, and CCVD were 0.873, 0.729, and 0.727, indicating a high accuracy in discriminating patients with SLE from controls. Correlation analysis showed that the SLEDAI scores were positively correlated with dFAZ (r = 0.589, p = .001) and FAZ (r = 0.451, p = .018), and negatively correlated with DVD (r = -0.491, p = .009) and CCVD (r = -0.521, p = .005). CONCLUSIONS: DVD and CCVD were decreased in the SLE and might be related to the disease activity. SVD, DVD, and CCVD may hold promise in the discovery of biomarkers for diagnosing SLE.

Retinal vascular density as a potential biomarker of diabetic cerebral small vessel disease.

AIM: The retina and brain share similar anatomical and physiological features. Thus, retinal imaging by optical coherence tomography angiography (OCTA) might be a potential tool for the early diagnosis of diabetic cerebral small vessel disease (CSVD). In this study, we aimed to evaluate retinal vascular density (VD) in diabetic CSVD by OCTA imaging and explore the associations between retinal VD and cerebral magnetic resonance imaging (MRI) markers and cognitive function. METHODS: In total, 131 patients were enrolled, including CSVD (n = 43) and non-CSVD groups (n = 88). The VD and foveal avascular zone of the retinal capillary plexus were measured with OCTA. A brain MRI was performed. RESULTS: MRI imaging showed that in the diabetic CSVD group, white matter hyperintensities (WMHs), particularly deep WMHs (58.82%), are the most common MRI marker, followed by cerebral microbleeds in the subtentorial and cortical areas (34.78%). The CSVD group showed increases in the prevalence of cognitive dysfunction (p = .034) and depression (p = .033) and decreases in visuospatial/executive ability and delayed recall ability. In the CSVD group, VDs of the macular superficial vascular plexus (32.93 ± 7.15% vs. 36.97 ± 6.59%, p = .002), intermediate capillary plexus (20.87 ± 4.30% vs. 23.08 ± 4.30%, p = .005) and deep capillary plexus (23.54 ± 5.00% vs. 26.05 ± 4.20%, p = .003) were lower than those of the non-CSVD group. Multiple linear regression analysis showed that VD of the macular superficial vascular plexus was independently associated with cerebral microbleeds. Meanwhile, VD of the macular intermediate capillary plexus was associated with white matter lacunar infarcts after adjustment. CONCLUSIONS: Diabetic CSVDs are characterized by MRI markers, including deep WMHs and cerebral microbleeds, and showed impaired cognition with decreased visuospatial/executive ability and delayed recall ability. OCTA imaging revealed a significant decrease in retinal microvascular perfusion in diabetic CSVD, which was related to MRI markers and cognitive function. OCTA might be a valuable potential measurement for the early diagnosis of CSVD.

Decreased retinal vascular density is associated with cognitive impairment in CADASIL: an optical coherence tomography angiography study.

PURPOSE: This study aimed to assess alterations in retinal vascular density in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients using optical coherence tomography angiography (OCTA) and investigate their association with MRI and cognitive features. METHODS: Twenty-five patients with CADASIL and forty healthy controls were evaluated by Cirrus HD-OCT 5000 with AngioPlex OCTA to determine changes in macular retinal vasculature. Retinal vasculature parameters between two groups were compared. The MRI lesion burden and neuropsychological scales were also examined in patients. The association between OCTA parameters and MRI/cognitive features was evaluated using partial Spearman rank correlation. RESULTS: The vessel density and perfusion density of whole image in macular region (vessel density: t = - 2.834, p = 0.005; perfusion density: t = - 2.691, p = 0.007) were significantly decreased in patients with CADASIL. Moreover, vessel density of whole image in macular region was negatively associated with Fazekas scores (ρ = - 0.457; p = 0.025) and the number of lacunar infractions (ρ = - 0.425, p = 0.038) after adjustment for age. Decreased macular vessel density and perfusion density of whole image were also associated with MoCA scores (vessel density: ρ = 0.542, p = 0.006; perfusion density: ρ = 0.478, p = 0.018) and other domain-specific neuropsychological tests (p < 0.05) after adjustment for age. CONCLUSION: Decreased retinal vascular density was associated with increased MRI lesion burden and cognitive impairment in patients with CADASIL. Our findings suggest that the degree of retinal vascular involvement, as demonstrated by OCTA, may be consistent with the severity of MRI lesions and the degree of cognitive impairment in patients.

Chorioretinal biomarkers in hypothalamic amenorrhea.

PURPOSE: The aim of our study was to evaluate changes in the retinal and choriocapillaris circulations in patients with hypothalamic amenorrhea. METHODS: Prospective, cross-sectional observational study on 25 patients (50 eyes) diagnosed with hypothalamic amenorrhea and 25 age-matched healthy women. Optical coherence tomography angiography (OCTA) was used to evaluate the vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris VD layers in whole 6.4 × 6.4-mm image and in fovea grid-based image. In patients' group, systemic parameters were collected: body mass index (BMI), endometrial rhyme thickness, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, insulin, and cortisol. RESULTS: SCP and DCP did not show any statistical difference when comparing patients and controls (all p > 0.05). Differently, choriocapillaris VD in the whole region showed a non-significant tendency toward higher values in the patients group in both eyes (p = 0.038 for right eye [RE], p = 0.044 for left eye [LE]). Foveal choriocapillaris VD was higher in hypothalamic amenorrhea women vs. healthy controls (66.0 ± 2.4 vs. 63.7 ± 6.6%, p = 0.136 for RE; 65.0 ± 2.4 vs. 61.6 ± 7.0%, p = 0.005 for LE). Focusing on correlation with systemic parameters, SCP and DCP foveal density had a medium/high effect size with endometrial rhyme, along with DCP in the fovea area vs. cortisol and SCP in the whole area vs. FSH. CONCLUSION: When comparing hypothalamic amenorrhea patients to healthy subjects, OCTA detected changes in the choriocapillaris layer, showing increased VD in the early stage of the systemic pathology, suggesting that microvascular "compaction" could be a first phase of hypoestrogenism adaptation.

Anatomical changes in idiopathic epiretinal membrane at 2-year follow-up assessed using spectral domain optical coherence tomography and optical coherence tomographic angiography.

PURPOSE: To evaluate anatomical changes in the low-stage partial attachment-type idiopathic epiretinal membrane (iERM) over 2 years. METHODS: Data from patients with low-stage partial attachment-type iERM (stage 2) were analyzed. The main outcome measures were anatomical changes, including changes in the foveal avascular zone (FAZ) area, vessel density (VD) in the vascular plexus, and thickness of retinal sublayers during the follow-up period. RESULTS: Thirty patients (mean age: 68±12 years) were included in the study. The FAZ area on the superficial vascular plexus (SVP) significantly decreased from baseline (0.12±0.08 mm2) to month 24 (0.10±0.08 mm2, p=0.024). However, the FAZ area on the deep vascular plexus (DVP) did not significantly decrease from baseline (0.15±0.13 mm2) to month 24 (0.14±0.14 mm2, p=0.099). VDs on both the SVP and DVP did not show significant change from baseline (29.51±8.14% vs. 28.35±5.63%) to month 24 (29.79±9.77%, p=0.564 vs. 28.17±5.75%, p=0.417). Parafoveal ganglion cell and inner plexiform layer (GCIPL) thickness decreased from baseline (108.77±13.61 µm) to month 24 (103.03±15.54 µm, p=0.004). The central total retinal layer thickness did not significantly change from baseline (396.07±64.86 µm) to month 24 (392.04±72.72 µm, p=0.570). CONCLUSION: Even in low-stage ERM, inner retinal changes, including GCIPL thickness, occurred during follow-up periods, which might be owing to degenerative changes or centrifugal movement.

Optical coherence tomography angiography evaluation of retinal and choroidal microvascular changes in pregnant women with a history of unexplained recurrent spontaneous abortions.

PURPOSE: To study retinal and choroidal microcirculation by optical coherence tomography angiography (OCTA) in pregnant women with unexplained recurrent spontaneous abortion (RSA) and to compare them with healthy pregnant and nonpregnant subjects. METHODS: Pregnant women with an unexplained history of RSA (group 1), healthy pregnant (group 2), and healthy non-pregnant women (group 3) were included in the study. After a thorough ophthalmologic examination:best-corrected visual acuity, intraocular pressure,slit-lamp biomicroscopy, fundus examination,autorefractometer, biometry, and axial length measurement; OCT and OCTA measurements were performed with Swept Source OCT-Angiography (Topcon Co, Japan). RESULTS: The nonpregnant group had higher values for central foveal superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density (VD) and lower values for superior, inferior, and mean VD compared with pregnant groups (p < 0.001). Choriocapillaris values (CC) VD were higher in groups 1 and 2 than in group 3 (p < 0.001). The group with unexplained RSA had a relatively smaller FAZ (foveal avascular zone) area than the group of healthy pregnant women (p:0.047). There were no statistically significant differences between groups in the retina, retinal nerve fiber layer, ganglion cell layer, and choroidal thickness (p > 0.05). CONCLUSION: Although our study did not identify any etiology in pregnant women with RSA, we observed detectable differences in FAZ area and vessel density values using OCTA, when comparing them with healthy pregnant women and healthy nonpregnant controls. We believe that OCTA, as used in many pathologies such as diabetic and hypertensive retinopathy and retinal vascular occlusion, can also be extended to unexplained RSA both to detect etiology and to monitor treatment in studies with a larger number of patients.

Investigation of Gastrointestinal Toxicities Associated with Concurrent Abdominal Radiation Therapy and the Tyrosine Kinase Inhibitor Sunitinib in a Mouse Model.

Tyrosine kinase inhibitors (TKIs) may be combined with radiation therapy (RT) to enhance tumor control; however, increased incidences of gastrointestinal (GI) toxicity have been reported with this combination. We hypothesize that toxicity is due to compromised intestinal healing caused by inhibition of vascular repair and proliferation pathways. This study explores underlying tissue toxicity associated with abdominal RT and concurrent sunitinib in a mouse model. Four groups of CD-1 mice were treated with 12 Gy abdominal RT, oral sunitinib, abdominal RT + sunitinib, or sham treatment. Mice received oral sunitinib or the vehicle via gavage for 14 days. On day 7, mice were irradiated with 12 Gy abdominal RT or sham treated. Mice were euthanized on day 14 and intestinal tract was harvested for semiquantitative histopathologic evaluation and immunohistochemical quantification of proliferation (Ki67) and vascular density (CD31). Non-irradiated groups had stable weights while abdominal irradiation resulted in weight loss, with mice receiving RT + SUN having greater weight loss than mice receiving RT alone. Semiquantitative analysis showed significant increases in inflammation in irradiated groups. The difference in the density of CD31+ cells was significantly increased in RT alone compared to SUN alone. Ki67+ density was not significant. In summary, we identify a lack of angiogenic response in irradiated GI tissues when abdominal RT is combined with a TKI, which may correlate with clinical toxicities seen in canine and human patients receiving combined treatment.

Analysis of Macular Vascularization Using Optical Coherence Tomography Angiography in Patients with Obstructive Sleep Apnea Syndrome: A Prospective Clinical Study.

Background and Objectives: Given the conflicting data available in the literature, this study aimed to investigate the impact of obstructive sleep apnea syndrome (OSAS) on the macular vascular density (VD) and perfusion density (PD). Materials and Methods: Based on the obstructive apnea-hypopnea index (OAHI), 61 prospectively recruited patients were assigned to either a control group (n = 12; OAHI < 5/h) or an OSAS group (n = 49; OAHI ≥ 5/h). The macular VD and PD of the superficial and deep capillary plexuses (SCP and DCP, respectively) were measured in the parafoveolar and perifoveolar areas using Zeiss PLEX Elite 9000 (6 × 6 mm). The values were compared between the control and OSAS groups. Results: Compared with the control group, the OSAS group demonstrated an increased VD of the DCP in the parafoveolar and perifoveolar areas and PD of the DCP in the perifoveolar area. No significant differences in either the macular VD or PD of the SCP were observed. There was no correlation between the OAHI and macular VD or PD. Conclusions: This study indicates that collateral vessel formation and possible retinal vasodilation occur in the DCP of patients with OSAS.

Changes in retinal vascular density measured by optical coherence tomography angiography in patients with carotid artery stenosis after carotid artery stenting and angioplasty.

PURPOSE: The aim of this study was to compare the effect of carotid artery stenting and angioplasty (CASA) on retinal vascular density (VD) in patients with severe carotid stenosis with a healthy control group and to evaluate using optical coherence tomography angiography (OCTA). METHODS: For this prospective study, eyes on the operated side constituted the ipsilateral eye group, and the other eye constituted the contralateral eye group. 40 eyes of 40 patients with ipsilateral eye of carotisid artery stenosis (CAS), 34 eyes on contralateral side, and 30 healthy eyes (control group) were included in this study. We performed quantitative OCTA analyses of retinal VD changes, before and after CASA. The main outcome measures were the quantitative changes of VD of superficial capillary plexus (SCP) and deep capillary plexus (DCP). RESULTS: We evaluated the VD of ipsilateral eyes and contralateral eyes separately before and after the procedure. All patients did not have visual symptoms. There was no significant difference in the VD of SCP in all groups before the procedure. No significant change was observed in all groups when the VD of the SCP was compared before and after the procedure. The VD of the DCP in the ipsilateral and contralateral group improved significantly after CASA. CONCLUSION: OCTA could noninvasively detect retinal VD improvements after CASA in CAS patients. Quantitative changes in VD evaluated using OCTA are thought to be early indicators in the diagnosis of CAS and in the follow-up of treatment success.

Vascular changes of the peripapillary choroidal area in the thyroid orbitopathy.

PURPOSE: The aim of this study was to investigate the peripapillary choroidal vascular changes in thyroid orbitopathy (TO). METHODS: The study included 20 eyes of 10 patients with active TO (aTO), 30 eyes of 15 patients with inactive TO (inaTO) and 30 eyes of 30 healthy subjects. The peripapillary choroidal vascular change was assessed with peripapillary choroidal vascular index (pCVI), peripapillary choroidal luminal area (pLA), peripapillary choroidal stromal area (pSA), peripapillary total choroidal area (pTCA). RESULTS: Compared to the control group, there was a reduction in the nasal and temporal areas of pCVI in both the aTO and inaTO groups (aTO vs control: nasal p = 0.001 and temporal p = 0.004; inaTO vs control: nasal p = 0.007 and temporal p < 0.001), while the inferior area was lower only in the inaTO group (p = 0.001). Compared to the other groups, the inaTO group exhibited a decrease pSA (vs aTO: total p = 0.004, inferior p = 0.02 and vs control: total p = 0.01, inferior p = 0.03), pLA (vs aTO: total p = 0.02, inferior p = 0.02, temporal p < 0.001 and vs control: total p = 0.002, inferior p < 0.001, temporal p < 0.001) and pTCA (vs aTO: total p = 0.009, inferior p = 0.01, temporal p < 0.001 and vs control: total p = 0.003, inferior p = 0.001, temporal p < 0.001). CONCLUSION: The horizontal area (nasal and temporal area) of the peripapillary choroidal vascular structure may be more sensitive than the vertical area in TO patients. The first affected quadrant of RPC-VD in the active TO may be the inferior quadrant. Structural or vascular choroidal changes may occur during the chronic or post-active phase of the disease.

Comparison of macular and optic disc vessel density in thyroid orbitopathy: a comparative octa study.

PURPOSE: To determine the microvascular and structural changes in the peripapillary and macular areas observed in patients with active thyroid orbitopathy(TO) before and after steroid treatment and compare with inactive TO and the control group by optical coherence tomography angiography (OCTA). MATERIAL AND METHOD: This cross-sectional study included 34 eyes of 17 active TO patients, 108 eyes of 54 inactive TO patients, and 60 eyes of 30 healthy controls. Central macular thickness (CMT), ganglion cell layer-inner plexiform layer (GCL-IPL) thickness, central choroidal thickness (CCT), retinal nerve fiber layer (RNFL) thickness, choroidal thickness in the peripapillary region, superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris vessel densities were determined by OCTA in before and after 12-week steroid treatment of active TO cases, inactive TO and control groups. RESULTS: Between the three groups in macula OCTA, a statistically significant difference was observed in the inferior and nasal quadrants in SCP (all p = 0.01) and only in the temporal quadrant choriocapillaris (p = 0.005). In peripapillary OCTA, a statistically significant difference was found only in the central choriocapillaris (p = 0.03). In the comparison of the active group before and after treatment, there was a statistically significant decrease in CMT and CCT; a statistically significant increase was observed in GCL-IPL (all p < 0.01). There was a statistically significant decrease in SCP and DCP only in the central (all p < 0.01). There was a statistically significant increase was found in the lower quadrant macular SCP vessel density and mean macular DCP in post-treatment measurements (p = 0.01 and p = 0.03, respectively). Peripapillary SCP and DCP vessel density was increased after treatment (p < 0.01). CONCLUSION: Active TO group had lower vessel density than inactive group and after treatment, vessel density was increased. Non-invasive quantitative analysis of retinal and optic disc perfusion using OCTA could be useful in early treatment before complications occur and monitoring patients with TO.

Optical coherence tomography angiography measurements in multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Recent literature on multiple sclerosis (MS) demonstrates the growing implementation of optical coherence tomography-angiography (OCT-A) to discover potential qualitative and quantitative changes in the retina and optic nerve. In this review, we analyze OCT-A studies in patients with MS and examine its utility as a surrogate or precursor to changes in central nervous system tissue. METHODS: PubMed and EMBASE were systematically searched to identify articles that applied OCT-A to evaluate the retinal microvasculature measurements in patients with MS. Quantitative data synthesis was performed on all measurements which were evaluated in at least two unique studies with the same OCT-A devices, software, and study population compared to controls. A fixed-effects or random-effects model was applied for the meta-analysis based on the heterogeneity level. RESULTS: The study selection process yielded the inclusion of 18 studies with a total of 1552 evaluated eyes in 673 MS-associated optic neuritis (MSON) eyes, 741 MS without optic neuritis (MSNON eyes), and 138 eyes without specification for the presence of optic neuritis (ON) in addition to 1107 healthy control (HC) eyes. Results indicated that MS cases had significantly decreased whole image superficial capillary plexus (SCP) vessel density when compared to healthy control subjects in the analyses conducted on Optovue and Topcon studies (both P < 0.0001). Likewise, the whole image vessel densities of deep capillary plexus (DCP) and radial peripapillary capillary (RPC) were significantly lower in MS cases compared to HC (all P < 0.05). Regarding optic disc area quadrants, MSON eyes had significantly decreased mean RPC vessel density compared to MSNON eyes in all quadrants except for the inferior (all P < 0.05). Results of the analysis of studies that used prototype Axsun machine revealed that MSON and MSNON eyes both had significantly lower ONH flow index compared to HC (both P < 0.0001). CONCLUSIONS: This systematic review and meta-analysis of the studies reporting OCT-A measurements of people with MS confirmed the tendency of MS eyes to exhibit reduced vessel density in the macular and optic disc areas, mainly in SCP, DCP, and RPC vessel densities.

Subserosal vascular density predicts oncological features of T2 gallbladder cancer.

PURPOSE: Tumor sidedness (hepatic side vs. peritoneal side) reportedly predicts microvascular invasion and survival outcomes of T2 gallbladder cancer, although the actual histopathological mechanism is not fully understood. METHODS: The clinical relevance of tumor sidedness was revisited in 84 patients with gallbladder cancer using histopathological analysis of the vascular density of the gallbladder wall. RESULTS: Hepatic-side tumor location was associated with overall survival (OS) (hazard ratio [HR], 13.62; 95% confidence interval [CI], 2.09-88.93) and recurrence-free survival (RFS) (HR, 8.70; 95% CI, 1.36-55.69) in T2 tumors. The Adjusted Kaplan-Meier curve indicated a clear survival difference between T2a (peritoneal side) and T2b (hepatic side) tumors (P = 0.006). A review of 56 pathological specimens with gallbladder cancer and 20 control specimens demonstrated that subserosal vascular density was significantly higher on the hepatic side of the gallbladder, regardless of the presence of cancer (P < 0.001). Multivariate analysis also confirmed that higher subserosal vascular density was significantly associated with poor OS (HR, 1.73; 95% CI, 1.10-2.73 per 10 microscopic fields) and poor RFS (HR, 1.62; 95% CI, 1.06-2.49) in T2  gallbladder cancer. CONCLUSION: Higher subserosal vascular density may account for the higher incidence of cancer spread and the poor prognosis of T2b gallbladder cancer.

Time course study of optical coherence tomography angiography in patients with methanol induced optic neuropathy.

INTRODUCTION: In countries where alcoholic beverages are legally prohibited, methanol toxicity usually occurs due to ingesting homemade alcoholic drinks. The initial ophthalmologic symptoms of methanol toxicity typically appear 6-48 h after ingestion, and the severity of symptoms varies widely from mild and painless decreased vision to no-light perception vision. METHODS: This prospective study examines 20 patients with acute methanol poisoning within 10 days of use. Patients underwent ocular examinations, BCVA (Best Corrected Visual Acuity) recording, and OCTA (Optical Coherence Tomography Angiography) of the macula and optic disc. BCVA measurement and imaging were repeated one month and three months after intoxication. RESULTS: There was a statistically significant reduction in superficial parafoveal vascular density (P-value = 0.026), inner retinal thickness (P-value = 0.022), RNFL (Retinal Nerve Fiber Layer) thickness (P-value = 0.031), and an increase in cup to disc ratio (P-value < 0.001), and central visual acuity (P-value = 0.002) in this time course. However, there was no statistically significant difference in FAZ (Foveal Avascular Zone) area (P-value = 0.309), FAZ perimeter (P-value = 0.504), FD-300 (Foveal density, vascular density within a 300 µm wide region of the FAZ) (P-value = 0.541), superficial vascular density (P-value = 0.187), deep foveal vascular density (P-value = 0.889), deep parafoveal vascular density (P-value = 0.830), choroidal flow area (P-value = 0.464), total retinal thickness (P-value = 0.597), outer retinal thickness (P-value = 0.067), optic disc whole image vascular density (P-value = 0.146), vascular density inside the disc (P-value = 0.864), or peripapillary vascular density (P-value = 0.680) at different times. CONCLUSION: Over time, methanol poisoning can cause changes in retinal layers thickness, vasculature, and optic nerve head. The most important changes include cupping of the optic nerve head, reduction in RNFL thickness, and inner retinal thickness.

Distribution of the Retinal Microcirculation Based on the Morphology of Peripapillary Atrophy in High Myopia.

INTRODUCTION: The objective of this study was to evaluate the retinal microvasculature of the optic nerve head and macula in high myopia (HM), investigate the association between the vascular parameters and peripapillary atrophy (PPA) deformation, and assess and identify the PPA morphology changes during the development of HM. METHODS: One hundred sixty-seven right eyes from 167 HM patients were enrolled in this cross-sectional study. Using the optical coherence tomography angiography (OCTA) and fundus camera, we evaluated the following parameters: radian and type of PPA, intrapapillary vascular density (IVD), peripapillary vascular density (PVD), macular vascular density (MVD), and foveal avascular zone (FAZ). Based on the PPA radian, subjects were divided into four groups: the non-PPA, temporal PPA, advanced PPA, and annular PPA. At the same time, the above parameters were compared between the groups using analysis of variance (ANOVA) and least significant difference test. RESULTS: Total enrolled patients were divided into the non-PPA group (22 eyes), temporal-PPA group (70 eyes), advanced-PPA group (60 eyes), and annular-PPA group (15 eyes). The results showed that the PVD in the annular-PPA group was smaller than that in the non-PPA group, especially in the superonasal, nasosuperior, nasoinferior, inferotemporal, temporoinferior, and superotemporal directions (F = 4.059, 5.014, 2.830, 4.798, 5.892, 3.439; p < 0.05). Notably, the PVD showcased the highest value in temporal, followed by that in superior and inferior, and the lowest in the nasal. Concerning the fovea deep macular vascular density, FAZ area, and subfoveal choroidal thickness in the annular-PPA group, they were less than those of the rest of the groups (p < 0.05). CONCLUSION: The retinal microvasculature differed significantly in HM according to the PPA morphology. In addition to PVD and SFCT, the PPA can also affect FAZ. Finally, we speculated that PVD demonstrated better predictability of myopic progression than MVD.

Imaging the effect of the circadian light-dark cycle on the glymphatic system in awake rats.

The glymphatic system functions in the removal of potentially harmful metabolites and proteins from the brain. Dynamic, contrast-enhanced MRI was used in fully awake rats to follow the redistribution of intraventricular contrast agent entrained to the light-dark cycle and its hypothetical relationship to the sleep-waking cycle, blood flow, and brain temperature in specific brain areas. Brain areas involved in circadian timing and sleep-wake rhythms showed the lowest redistribution of contrast agent during the light phase or time of inactivity and sleep in rats. Global brain redistribution of contrast agent was heterogeneous. The redistribution was highest along the dorsal cerebrum and lowest in the midbrain/pons and along the ventral surface of the brain. This heterogeneous redistribution of contrast agent paralleled the gradients and regional variations in brain temperatures reported in the literature for awake animals. Three-dimensional quantitative ultrashort time-to-echo contrast-enhanced imaging was used to reconstruct small, medium, and large arteries and veins in the rat brain and revealed areas of lowest redistribution overlapped with this macrovasculature. This study raises new questions and theoretical considerations of the impact of the light-dark cycle, brain temperature, and blood flow on the function of the glymphatic system.

Optical coherence tomography angiography analysis of changes in the retina and the choroid after hemodialysis for end stage kidney disease.

PURPOSE: To study effects of hemodialysis (HD) on retinal and choroidal vasculature in patients with end-stage kidney disease (ESKD) using optical coherence tomography angiography (OCTA). METHODS: In this prospective study, we investigated eyes of patients undergoing hemodialysis for ESKD from Mondor University Hospital. Only one eye/patient was considered. Subfoveal choroidal thickness (SCT) was measured on enhanced-depth imaging optical coherence tomography (EDI-OCT) before and after the hemodialysis session. OCTA was used to extract retinal vascular density (superficial and deep capillary plexus, SCP, DCP) and choriocapillaris non-perfusion. Clinical, demographic and biological parameters (Blood B-Nitric Peptid rate prior to HD session) were reviewed. RESULTS: Twenty patients (mean age 53.2 ± 13.6 years, 10 males and 10 females) were included in this prospective study. SCT significantly decreased after the HD session (234.3 ± 56.14 µm before HD to 211.9 ± 60.79 µm after hemodialysis (Wilcoxon signed-rank test, p = 0.003)). Non-perfusion in the choriocapillaris significantly increased after HD (41.65 ± 3.58 before HD, 42.95 ± 3.19 after HD, p = 0.036) while no significant modification of the vascular density was observed in the retinal vasculature (SCP, DCP) around the macular zone or the optic nerve. An increased plasma B-Nitric Peptide (BNP) level prior to the onset of the HD session was significantly correlated with the decrease of the SCT (r = 0.45, p = 0.043). CONCLUSION: Hemodialysis in patients with ESKD is associated with a significant decrease in SCT and an increase in non-perfusion in the choriocapillaris on OCTA. A High BNP level prior to the onset of the hemodialysis appears to be correlated with the decrease in SCT.

The choroidal microvasculature of the parapapillary area as a biomarker of glaucoma development in the fellow eye of patients with unilateral glaucoma.

PURPOSE: To investigate the factors associated with the development of glaucoma in the healthy eyes of unilateral glaucoma patients. MATERIALS AND METHODS: This was a retrospective observational case series study. All participants had unilateral primary open-angle glaucoma at the initial visit and were divided into two groups: one in which the fellow eyes developed glaucoma during the follow-up period and one in which the fellow eyes remained healthy. A complete ophthalmic examination, including best-corrected visual acuity testing, slit-lamp examination, intraocular pressure measurement, retinal nerve fiber layer and optic disk photographs, a 30-2 visual field test, and optical coherence tomography with angiography, was performed over a follow-up period of at least 3 years. RESULTS: A total of fifty-six patients were enrolled, and over the course of the study period, 11 patients developed glaucoma in the fellow eyes, while the fellow eyes of 45 patients remained healthy. At the baseline, the glaucomatous eye had a larger area of beta parapapillary atrophy, lower parapapillary choroidal vascular density (pCVD) within the area, and a lower prevalence of microvascular dropout than normal fellow eyes (P < 0.001, 0.013, 0.001, respectively). In the multivariate analysis, a reduced pCVD in the gamma parapapillary atrophy (γPPA) region was significantly associated with the development of glaucoma in normal eyes (odds ratio, 0.566; 95% CI, 0.342, 0.935; P = 0.026). CONCLUSIONS: The pCVD within the γPPA region at baseline is the risk factor for the development of glaucoma in the normal fellow eye of patients with unilateral glaucoma.