OCTA in macular intraretinal microvascular abnormalities: Retinal vascular density remodeling after panretinal photocoagulation.

PURPOSE: To describe a case of macular intraretinal microvascular abnormality (IRMA) detected with Optical Coherence Tomography Angiography (OCTA) and to show its remodeling and vascular density changes after panretinal photocoagulation (PRP) during an 18-month follow-up. METHODS: Case report. RESULTS: A 22-year-old female patient with proliferative diabetic retinopathy was found to have a small hyperreflective formation with posterior shadow cone and signal flow, located at the temporal margin of the fovea avascular zone (FAZ), identified as macular IRMA with OCTA. Her best-corrected-visual acuity was 20/20. Four months later the macular IRMA was larger and, in its context, there was also an increase in the flow area in B-scan. The patient underwent PRP and after 18 months we observed a regression of macular IRMA and an increase in the superficial capillary plexus vessel density in all sectors in comparison to baseline. CONCLUSION: OCTA is a non-invasive tool that recognize macular IRMA in diabetic retinopathy patient and it could be helpful to follow their qualitative and quantitative vascular evolution over time.

Associations between angiogenic factors and intravoxel incoherent motion-derived parameters in diffusion-weighted magnetic resonance imaging of breast cancer.

ABSTRACT: Intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) can be used to estimate perfusion-related parameters, but these parameters may differ, based on the curve-fitting algorithm used for IVIM. Microvessel density (MVD) and vascular endothelial growth factor (VEGF) status are used as angiogenic factors in breast cancer. We aimed to investigate the relationship between MVD, VEGF, and intravoxel incoherent motion (IVIM)-derived parameters, obtained by 4 curve-fitting algorithms, in patients with invasive breast cancers.This retrospective study investigated IVIM-derived parameters, D (ie, tissue diffusivity), D∗ (ie, pseudodiffusivity), and f (ie, perfusion fraction), of 55 breast cancers, using 10 b values (range, 0-800 s/mm2) and 4 curve-fitting algorithms: algorithm 1, linear fitting of D and f first, followed by D∗; algorithm 2, linear fitting of D and f and nonlinear fitting of D∗; algorithm 3, linear fitting of D and f, linear fitting of D∗, and ignoring D contribution for low b values; and algorithm 4, full nonlinear fitting of D, f, and D∗. We evaluated whole-tumor histograms of D, f, and D∗ for their association with MVD and VEGF.D∗10, D∗25, D∗50, D∗mean, D∗75, D∗90, f10, and f25, derived using algorithm 3, were associated with VEGF expression (P = .043, P = 0.012, P = .019, P = .024, P = .044, P = .041, P = .010, and P = .005, respectively). However, no correlation existed between MVD and IVIM-derived parameters.Perfusion-related IVIM parameters obtained by curve-fitting algorithm 3 may reflect VEGF expression.

Cell - Vessel Mismatch in Glaucoma: Correlation of Ganglion Cell Layer Soma and Capillary Densities.

Purpose: The purpose of this study was to characterize the relationship between retinal ganglion cell layer (GCL) soma density and capillary density in glaucomatous eyes. Methods: Six glaucoma subjects with known hemifield defects and 6 age-matched controls were imaged with adaptive optics - optical coherence tomography (AO-OCT) at 6 locations: 3 degrees, 6 degrees, and 12 degrees temporal to the fovea above and below the midline. GCL soma density and capillary density were measured at each location. Coefficients of determination (pseudo R2) and slopes between GCL soma and capillary density were determined from mixed-effects regressions and were compared between glaucoma and control subjects, between more and less affected hemifield in subjects with glaucoma, and between subjects with early and moderate glaucoma, both in a local, bivariate model and then a global, multivariable model controlling for eccentricity and soma size. Results: The global correlation between GCL soma and capillary density was stronger in control versus subjects with glaucoma (R2 = 0.59 vs. 0.22), less versus more affected hemifields (R2 = 0.55 vs. 0.01), and subjects with early versus moderate glaucoma subjects (R2 = 0.44 vs. 0.18). When controlling for eccentricity and soma size, we noted an inverse soma-capillary density local relationship in subjects with glaucoma (-388 ± 190 cells/mm2 per 1% change in capillary density, P = 0.046) and more affected hemifields (-602 ± 257 cells/mm2 per 1% change in capillary density, P = 0.03). Conclusions: An inverted soma-capillary density local relationship in areas affected by glaucoma potentially explains weaker global correlations observed between GCL soma and capillary density, suggesting cell-vessel mismatch is associated with the disease.

Evaluation of retinal vascular density and related factors in youth myopia without maculopathy using OCTA.

To evaluate the retinal vascular flow density changes of myopic eyes of young adults using optical coherence tomography angiography and the factors affecting these changes. In this cross-sectional study, 90 eyes of 45 participants were analyzed and divided into three groups: mild, moderate, and high myopia (without pathological changes). Macular and radial peripapillary capillary flow densities were measured using optical coherence tomography angiography. Their relationships with the axial length, the spherical equivalent of the refractive error, and age were analyzed using analysis of variance, Pearson's correlation coefficient, and multivariate linear regression analysis. Superficial and deep macular vascular densities were significantly decreased in the high myopia group compared to the other groups. In the high myopia group, the nasal peripapillary flow density decreased, whereas the flow density inside the disc increased. The axial length negatively correlated with the superficial and deep macular vascular density, but positively correlated with the vascular density inside the disc. The spherical equivalent of the refractive error negatively correlated with the macular vascular density. The retinal vascular density decreased in the high myopia group. Hence, the microvascular network inside the disc may have a compensatory action in the hypoxic setting of high myopia.

Longer Axial Length Potentiates Relationship of Intraocular Pressure and Peripapillary Vessel Density in Glaucoma Patients.

Purpose: The purpose of this study was to investigate how axial length (AL) changes the relationship of intraocular pressure (IOP) with peripapillary vessel density (pVD) in glaucoma versus non-glaucomatous eyes. Methods: A population-based, cross-sectional study of 2127 African Americans aged 40 years and older in Inglewood, California, were imaged with 6 × 6-mm optic disc optical coherence tomography angiography scans. There were 1028 healthy subjects (1539 eyes) and 65 subjects with glaucoma (86 eyes) who met inclusion criteria. A multivariable linear mixed effects regression model investigated the relationship of IOP on pVD after controlling for signal strength, retinal nerve fiber layer thickness, and age. These results were stratified by AL groups. Results: Higher IOP was a significant predictor of lower pVD among subjects with glaucoma (P = 0.009), but not among healthy subjects (P = 0.26). After stratifying by the sample median AL (23.46 mm), higher IOP was associated with lower pVD among subjects with glaucoma with longer AL (≥ 23.46 mm, P = 0.005), but not among those in the shorter AL (< 23.46 mm, P = 0.45). IOP was not significantly associated with pVD among healthy subjects in either AL stratum. Conclusions: Among subjects with glaucoma with longer AL, IOP was significantly associated with pVD. This relationship was not seen among subjects with glaucoma with shorter AL or non-glaucomatous subjects in either AL group. These findings support the hypothesis that disturbed retinal autoregulation may be present in subjects with glaucoma with longer AL. Longitudinal studies are needed to further investigate whether axial elongation increases glaucoma risk by compromising retinal autoregulation.

SRSF-1 and microvessel density immunohistochemical analysis by semi-automated tissue microarray in prostate cancer patients with diabetes (DIAMOND study).

OBJECTIVE: To study the association between insulin receptors (isoforms α and ß), insulin growth factor-1 (IGF1) and serine/arginine splicing factor 1 (SRSF-1) in patients with prostate cancer (PC) and diabetes. MATERIALS AND METHODS: We retrospectively analyzed data from 368 patients who underwent surgery for PC or benign prostatic hyperplasia (BPH) between 2010 and 2020 at the Department of Urology, University of Catania. Tissue microarray slides were constructed and they were stained for androgen receptor (AR), insulin receptor-α and -ß, IGF1 (IGF1-R), Ki-67, and prostate specific membrane antigen (PSMA) expression using validated score. RESULTS: The final cohort was represented by 100 patients with BPH and 268 with PC, with a median age of 68 years. We found that SRSF-1 expression was associated with AR (odds ratio [OR]: 1.66), PSMA (OR: 2.13), Ki-67 (OR: 5.99), insulin receptor (IR)-α (OR: 2.38), IR-ß (OR: 3.48), IGF1-R (OR: 1.53), and microvascular density (MVD) was associated with PSMA (OR: 3.44), Ki-67 (OR: 2.23), IR-α (OR: 2.91), IR-ß (OR: 3.02), IGF1-R (OR: 2.95), and SRSF-1 (OR: 2.21). In the sub cohort of PC patients, we found that SRSF-1 expression was associated with AR (OR: 2.34), Ki-67 (OR: 6.77), IR-α (OR: 2.7), and MVD (OR: 1.98). At the Kaplan-Meier analysis, SRSF-1+ patients had worse 5- and 9-year biochemical recurrence (36% and 6%) respect to SRSF-1- (67% and 7%; p < .01) and similarly MVD+ patients (44% and 7%) respect to MVD- (64% and 8%; p < .01). Restricting the analysis only in patients with PC and diabetes, we found that SRSF-1+ was associated with Ki-67+ (OR: 8.75; p < .05) and MVD+ (OR: 7.5; p < .05). CONCLUSIONS: PC exhibits widespread heterogeneity in protein expression. In particular, the expressions of the SRSF-1 protein and of the MVD are associated with a worse prognosis and in particular with a greater cell proliferation. These results, although preliminary, may offer new future scientific insights with the aim of highlighting possible genetic alterations linked to a greater expression of SRSF-1 and associated with a worse prognosis.

Multiparametric magnetic resonance imaging features of a canine glioblastoma model.

PURPOSE: To assess glioblastoma multiforme (GBM) formation with similar imaging characteristics to human GBM using multiparametric magnetic resonance imaging (MRI) in an orthotopic xenograft canine GBM model. MATERIALS AND METHODS: The canine GBM cell line J3T1 was subcutaneously injected into 6-week-old female BALB/c nude mice to obtain tumour fragments. Tumour fragments were implanted into adult male mongrel dog brains through surgery. Multiparametric MRI was performed with conventional MRI, diffusion-weighted imaging, and dynamic susceptibility contrast-enhanced perfusion-weighted imaging at one week and two weeks after surgery in a total of 15 surgical success cases. The presence of tumour cells, the necrotic area fraction, and the microvessel density (MVD) of the tumour on the histologic specimen were assessed. Tumour volume, diffusion, and perfusion parameters were compared at each time point using Wilcoxon signed-rank tests, and the differences between tumour and normal parenchyma were compared using unpaired t-tests. Spearman correlation analysis was performed between the imaging and histologic parameters. RESULTS: All animals showed a peripheral enhancing lesion on MRI and confirmed the presence of a tumour through histologic analysis (92.3%). The normalized perfusion values did not show significant decreases through at least 2 weeks after the surgery (P > 0.05). There was greater cerebral blood volume and flow in the GBM than in the normal-appearing white matter (1.46 ± 0.25 vs. 1.13 ± 0.16 and 1.30 ± 0.22 vs. 1.02 ± 0.14; P < 0.001 and P < 0.001, respectively). The MVD in the histologic specimens was correlated with the cerebral blood volume in the GBM tissue (r = 0.850, P = 0.004). CONCLUSION: Our results suggest that the canine GBM model showed perfusion imaging characteristics similar to those of humans, and it might have potential as a model to assess novel technical developments for GBM treatment.

Prognostic Value of Microvessel Density in Non-Hodgkin Lymphoma: A Meta-Analysis.

BACKGROUND: Angiogenesis in non-Hodgkin lymphoma (NHL) has been investigated by a variety of studies. However, the correlation between angiogenesis and the occurrence or prognosis of NHL patients remains controversial. METHODS: We performed a systematic and comprehensive retrieval of relevant literatures from PubMed, EMBASE, and Web of Science databases. The quality of the eligible studies was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Fifteen eligible studies containing a total of 1373 NHL patients were included in this study. All the eligible studies were high-quality studies scoring ≥6 points. MVD was not different between NHL and control (SMD = 0.281, 95% CI: -1.410 to 1.972, p = 0.745). High MVD was associated with advanced disease stage (OR = 1.580, 95% CI: 1.080-2.311, p = 0.018) and unfavorable OS (HR = 1.656, 95% CI: 1.366-2.009, p = 0.000) but not with PFS (HR = 1.349, 95% CI: 0.852-2.136, p = 0.201). CONCLUSION: This meta-analysis demonstrated that high MVD was related to advanced disease stage and associated with unfavorable OS of NHL patients.

Seasonal expressions of VEGF and its receptors VEGFR1 and VEGFR2 in the prostate of the wild ground squirrels (Spermophilus dauricus).

As a vital male accessory reproductive gonad, the prostate requires vascular endothelial growth factors for promoting its growth and development. In this study, we investigated the localizations and expressions of vascular endothelial growth factor (VEGF) and its receptors including VEGF-receptor1 (VEFGR1) and VEGF-receptor2 (VEGFR2) in the prostate of the wild ground squirrels during the breeding and the non-breeding seasons. The values of total prostate weight and volume in the breeding season were higher than those in the non-breeding season. Histological observations showed that the exocrine lumens of the prostate expanded in the breeding season and contracted in the non-breeding season. The mRNA expression levels of VEGF and VEGFR2 in the prostate were higher in the breeding season than those in the non-breeding season, but the mRNA expression level of VEGFR1 had no significant change between the breeding and non-breeding seasons. Immunohistochemical results revealed that VEGF, VEGFR1 and VEGFR2 were presented in epithelial and stromal cells during the breeding and non-breeding seasons. In addition, the microvessels of the prostate were widely distributed and the number of microvessels increased obviously in the breeding season, while decreased sharply in the non-breeding season. These results suggested that expression levels of VEGF and VEGFR2 might be correlated with seasonal changes in morphology and functions of the prostate, and VEGF might serve as pivotal regulators to affect seasonal changes in the prostate functions of the wild male ground squirrels via an autocrine/paracrine pathway.

Perfusion microvessel density in the cerebral cortex of septic rats is negatively correlated with endothelial microparticles in circulating plasma.

In sepsis, endothelial microparticles (EMPs) released from endothelial cells (ECs) participate in microcirculation dysfunction through pro-coagulant and pro-inflammatory effects, which can lead to sepsis-associated brain dysfunction. However, the relationship between EMPs and cerebral cortical perfusion microvessel density has not been explored. A closed cranial window was created in rats who were tended to until the cerebral cortex edema caused by preparation of the cranial window subsided, and the microvessel density was stable. A cecal ligation and puncture (CLP) sepsis procedure was then performed on day 6, post-surgery. At 12 and 24 h after the CLP, cerebral cortical perfusion microvessel density was measured with optical coherence tomography angiography (OCTA), followed by measurement of EMPs to evaluate the relationship between these factors. Microvessel density changed from 46.38 % ± 7.65 % on the day of surgery to 35.87 % ± 11.05 % on the second day and 36.71 % ± 11.38 % on the third day after surgery, and then increased daily. The microvessel density decreased to 27.20 % ± 8.50 % 24 h after CLP, which was significantly lower than that immediately and 12 h after CLP (P < 0.001). EMPs increased progressively at 12 and 24 h after CLP. Moreover, there was a negative correlation between EMPs and microvessel density (r=-0.56, P = 0.01). Edema and microvessel density decreased in the local cerebral cortex of the window and then gradually recovered after cranial window surgery. In sepsis, the perfusion microvessel density of the cerebral cortex negatively correlated with the EMPs. Therefore, the perfusion microvessel density can be indirectly evaluated by detecting the plasma EMP level.

Intra-skeletal vascular density in a bipedal hopping macropod with implications for analyses of rib histology.

Human ribs are thought to be less affected by mechanical strain at the microscopic level than limb bones, implying that rib remodelling better reflects bone physiological homeostasis. Here, we test the hypothesis that rib tissue will be well vascularized and thus enhance susceptibility to metabolic influence. An intra-skeletal comparison of bone vascular canal density was conducted using a macropod animal model adapted to bipedal habitual hopping. The right humerus, ulna, radius, femur, tibia, fibula, a mid-thoracic and upper-thoracic rib of an eastern grey kangaroo (Macropus giganteus) were sectioned at the midshaft, from which histological sections were prepared. Bone vascularity from a maximum of 12 mm2 of sub-periosteal parallel-fibred and lamellar bone was recorded, resulting in a total of 2047 counted vessels. Vascular canal density data were corrected by cortical width, maximum length, and midshaft circumference robusticity indices computed for each bone. The fibula consistently had the highest vascular canal density, even when corrected for maximum length, cortical width and midshaft circumference robusticities. This was followed by the mid- and upper-thoracic ribs. Vascularity differences between bones were relatively consistent whether vascular canal density was controlled for by cortical width or midshaft circumference robusticities. Vascular canal density and robusticity indices were also positively and negatively correlated (p < 0.05). Results confirm that the ribs are well vascularized, which facilitates bone metabolic processes such as remodelling, but the fibula also appears to be a well vascularized bone. Future research investigating human bone metabolism will benefit from examining thoracic rib or fibula samples.

Assessment of tissue perfusion of pancreatic cancer as potential imaging biomarker by means of Intravoxel incoherent motion MRI and CT perfusion: correlation with histological microvessel density as ground truth.

BACKGROUND/OBJECTIVES: The aim of this study was to compare intravoxel incoherent motion (IVIM) diffusion weighted (DW) MRI and CT perfusion to assess tumor perfusion of pancreatic ductal adenocarcinoma (PDAC). METHODS: In this prospective study, DW-MRI and CT perfusion were conducted in nineteen patients with PDAC on the day before surgery. IVIM analysis of DW-MRI was performed and the parameters perfusion fraction f, pseudodiffusion coefficient D*, and diffusion coefficient D were extracted for tumors, upstream, and downstream parenchyma. With a deconvolution-based analysis, the CT perfusion parameters blood flow (BF) and blood volume (BV) were estimated for tumors, upstream, and downstream parenchyma. In ten patients, intratumoral microvessel density (MVDtumor) and microvessel area (MVAtumor) were analyzed microscopically in resection specimens. Correlation coefficients between IVIM parameters, CT perfusion parameters, and histological microvessel parameters in tumors were calculated. Receiver operating characteristic (ROC) analysis was performed for differentiation of tumors and upstream parenchyma. RESULTS: ftumor significantly positively correlated with BFtumor (r = 0.668, p = 0.002) and BVtumor (r = 0.672, p = 0.002). There were significant positive correlations between ftumor and MVDtumor/ MVAtumor (r ≥ 0.770, p ≤ 0.009) as well as between BFtumor and MVDtumor/ MVAtumor (r ≥ 0.697, p ≤ 0.025). Correlation coefficients between ftumor and MVDtumor/ MVAtumor were not significantly different from correlation coefficients between BFtumor and MVDtumor/ MVAtumor (p ≥ 0.400). Moreover, f, BF, BV, and permeability values (PEM) showed excellent performance in distinguishing tumors from upstream parenchyma (area under the ROC curve ≥0.874). CONCLUSIONS: The study shows that IVIM derived ftumor and CT perfusion derived BFtumor similarly reflect vascularity of PDAC and seem to be comparably applicable for the evaluation of tumor perfusion for tumor characterization and as potential quantitative imaging biomarker. TRIAL REGISTRATION: DRKS, DRKS00022227, Registered 26 June 2020, retrospectively registered. https://www.drks.de/drks_web/navigate.do?navigationId=trial . HTML&TRIAL_ID=DRKS00022227.

Acidosis induces synovial fibroblasts to release vascular endothelial growth factor via acid-sensitive ion channel 1a.

Acid-sensitive ion channel 1a (ASIC1a) is a member of the extracellular H+ activated cation channel family. Studies have shown that tissue acidification contributes to the formation of microvessels in rheumatoid arthritis (RA) synovial tissue, but its underlying mechanisms remain unclear. The purpose of this study was to investigate the role of tissue acidification in microvascular formation of arthritic synovial tissue and the effect of ASIC1a on vascular endothelial growth factor (VEGF) release from arthritic synovial tissue. Our results indicate that ASIC1a expression, VEGF expression, and microvessel density (MVD) are elevated in RA synovial tissue and adjuvant arthritis (AA) rat synovial tissue. When AA rats were treated with ASIC1a-specific blocker psalmotoxin-1 (PcTx-1), the expression of ASIC1a, VEGF expression, and MVD were all reduced. Acidification of RA synovial fibroblasts (RASF) can promote the release of VEGF. PcTx-1 and ASIC1a-short hairpin RNA can inhibit acid-induced release of VEGF. In addition, the ASIC1a overexpression vector can promote acid-induced VEGF release. This indicates that extracellular acidification induces the release of VEGF by RASF via ASIC1a. These findings suggest that blocking ASIC1a mediates the release of VEGF from synoviocytes may provide a potential therapeutic strategy for RA therapy.

RETINAL SENSITIVITY AND VESSEL DENSITY AFTER MACULAR HOLE SURGERY WITH THE SUPERIOR INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE.

PURPOSE: To evaluate retinal vessel density and retinal sensitivity (RS) after macular hole surgery with the superior inverted internal limiting membrane flap technique. METHODS: Retrospective, observational case series. Twenty-one patients with idiopathic macular hole underwent 27-gauge vitrectomy with the superior inverted internal limiting membrane flap technique and triamcinolone acetonide. Measurements included RS, which was measured with microperimetry, as well as retinal vessel density in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), which was measured with optical coherence tomography angiography. All parameters were evaluated in the superior and inferior sectors of the macula preoperatively and 1, 3, and 6 months postoperatively. RESULTS: Six months postoperatively, retinal thickness in the inferior sector was unchanged, but retinal thickness in the superior sector decreased significantly (P < 0.01). SCP vessel density in both sectors was unchanged at all postoperative time points. DCP vessel density in both sectors increased very significantly at 3 months (P < 0.01) and returned to baseline at 6 months. RS in the inferior sector increased by 47% 3 months postoperatively and by 61% 6 months postoperatively (P < 0.05 and P < 0.001, respectively), but RS in the superior sector increased only at 6 months postoperatively and only by 22% (P < 0.05). CONCLUSION: Lower recovery of RS in the superior sector suggests that internal limiting membrane peeling might affect the postoperative visual function.

Reduced vessel density in deep capillary plexus correlates with retinal layer thickness in choroideremia.

BACKGROUND: To assess retinal layer thickness in choroideremia (CHM) and to reveal its correlation with optical coherence tomography (OCT) angiography (OCTA) findings. METHODS: The study was designed as an observational, cross-sectional clinical series of patients with CHM, which included 14 CHM eyes and 14 age-matched controls. Multimodal imaging included OCT and OCTA. The vessel density (VD) of superficial capillary (SCP), deep capillary (DCP) and choriocapillaris (CC) plexuses was analysed by OCTA. The apparently preserved retinal islet and atrophic regions were investigated separately. Main outcome measures were as follows: best-corrected visual acuity (BCVA), total retinal layers, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), ellipsoid zone-retinal pigment epithelium (EZ-RPE) layer, choroidal thickness and VDs of SCP, DCP and of CC. RESULTS: Mean BCVA was 0.0±0.0 LogMAR in both groups. GCL, ONL, EZ-RPE and choroid were significantly thinned in CHM, particularly in the atrophic region. OPL was unaffected in the apparently preserved islet, whereas INL and IPL were similarly thinned in the atrophic and apparently preserved retina. DCP appeared severely affected in both regions, while CC was only altered in the atrophic retina. Significant correlations were found between OCT and OCTA parameters. CONCLUSIONS: Our study showed severe alterations in both outer and inner retinal layers of patients with CHM. The extended retinal involvement might be the consequence of neuronal and vascular trophic factor reduction produced by the primarily altered RPE and/or secondary Müller glial cell reaction.

The Effect of Software Versions on the Measurement of Retinal Vascular Densities Using Optical Coherence Tomography Angiography.

BACKGROUND: The goal of the study was to determine the effect of different software versions on the measurement of retinal vessel densities using optical coherence tomography angiography (OCTA) in normal subjects. METHODS: Thirty-two eyes of eighteen healthy subjects were imaged using two OCTA devices: the Optovue RTVue and the Zeiss Cirrus. The macular 3 × 3 mm scan protocol was used. The images acquired using the Optovue OCTA device were exported using two different software versions in the system and compared to the images acquired through the Zeiss OCTA. In addition, the Optovue OCTA images were exported after manual adjustment of the segmentation boundaries according to the intraretinal layer definition. The densities of the superficial vascular plexus (SVP) and deep vascular plexus (DVP) were measured using fractal analysis by box-counting (Dbox). RESULTS: Both the vessel densities of the SVP and DVP acquired using the Optovue OCTA device were significantly different when compared to those from the Zeiss OCTA device (all, P <.05). No significant difference was found between the vessel densities of the SVP exported using both the new and old versions of Optovue (P >.05). However, the DVP exported using the new Optovue software version was significantly different compared to those exported using the old version (P <.05). The vessel densities of the SVP and DVP were related among the Optovue OCTA software versions and manual adjustment method (r ranged from 0.55 to 0.77; all P <.05). CONCLUSION: This is the first study to determine that different software versions with various intraretinal layer segmentation methods affect the vessel density measurements of the SVP and DVP.

Microaneurysm density in residual oedema after anti-vascular endothelial growth factor therapy for diabetic macular oedema.

PURPOSE: To investigate the relationship between microaneurysm (MA) density and residual oedema after intravitreal injection of an anti-vascular endothelial growth factor agent for the treatment of diabetic macular oedema (DMO). METHODS: Patients with DMO were divided into those with residual oedema (RO) and those with no residual oedema (NRO) by the presence and absence of oedema at 1 month after intravitreal injection of either aflibercept or ranibizumab. We then compared MA density, best corrected visual acuity (BCVA), central retinal thickness (CRT) and size of the severely thickened area, as indicated by a white area (WA) on optical coherence tomography. RESULTS: We examined 48 eyes in the RO group and 25 eyes in the NRO group (n = 73). In both groups, the CRT and WA size significantly decreased and BCVA improved at 1 month and thereafter. CRT was significantly higher and BCVA was poor in the RO group at 1 and 3 months, while WA size was larger at 1, 3 and 6 months compared with the NRO group (p < 0.05). The number of injections in the RO group (3.62 ± 1.75) was larger than the NRO group (1.89 ± 0.97; p < 0.0001). At 1 and 6 months, the MA density in the area with persistent oedema was significantly higher than in the area with improved oedema (1 month: p = 0.0001, 6 months: p = 0.029). CONCLUSION: High MA density and extensive swelling may be characteristic of RO following treatment for DMO with intravitreal injection of either aflibercept or ranibizumab.

Microvascular retinal alterations in rhegmatogenous retinal detachment after pneumatic retinopexy.

PURPOSE: To evaluate the macular microvascularity with optical coherence tomography angiography (OCTA) in rhegmatogenous retinal detachment (RRD) which were successfully treated with pneumatic retinopexy (PR). METHODS: Thirty eyes of thirty patients who were treated with PR (12 eyes with macula-off RRD and 18 eyes with macula-on RRD) were included in this prospective study. OCTA was used to evaluate the macular perfusion changes postoperatively at 1 and 3 months. The fellow eyes (30 eyes) were used as control for comparison. Parafoveal retinal thickness (RT) and best-corrected visual acuity (BCVA) were evaluated. RESULTS: Vessel density (VD) in SCP, DCP and choriocapillaris plexus (CCP) flow area was significantly lower in the macula-off group one month after the PR (p < 0.001). In the macula-off group, VD in SCP, DCP and CCP flow area significantly increased at months 3 (p < 0.001, p < 0.001, p = 0.009). The inner RT, RT and FAZ decreased three months after PR (p < 0.001, p = 0.001, <0.001). The FAZ was significantly larger in the macula-off group at third months after PR (p < 0.001). The inner RT was higher in the macula-off group at third month (p = 0.012). There was no significant difference between the groups in means of final VD, CCP flow area and RT. There was also a negative correlation between the final BCVA (logMAR) and FAZ at month 3 (r = 0.776, p = 0.003). CONCLUSION: Optical coherence tomography angiography evaluation of macular capillary plexuses may be useful for predicting vascular structural changes in patients undergoing PR.

Albuminuria and retinal vessel density in diabetes without diabetic retinopathy: the Kailuan Eye Study.

BACKGROUND: Diabetic retinopathy and chronic kidney disease are both major complications of diabetes mellitus. We explored the relationship between retinal vessel density (VD) and albuminuria in diabetic patients without conventionally defined diabetic retinopathy. METHODS: The cross-sectional community-based Kailuan Diabetic Retinopathy Study included patients with type 2 diabetes without diabetic retinopathy who participated in the community-based longitudinal Kailuan study and who had undergone ocular fundus photography, kidney function assessment, and optical coherence tomographic angiography (OCT-angiography) for the assessment the retinal perfusion density (PD) and retinal VD. RESULTS: The study included 447 patients (mean age: 60.9 ± 9.7 years). Higher PD and VD were associated with a lower urinary albumin-creatinine ratio (uACR) (macular region: p = 0.007: standardized regression coefficient beta: -0.14; and p = 0.008, beta: -0.13, respectively; parafoveal region: p = 0.006, beta: -0.14; and p = 0.007, beta: -0.14, respectively) after adjusting for age and ocular axial length. In a reverse manner, higher uACR was associated with lower PD and VD (macular region: p = 0.009, beta: -0.14; and p = 0.01, beta: -0.14, respectively; parafoveal region: p = 0.008, beta: -0.14; and p = 0.01, beta: -0.14, respectively), after adjusting for diabetes duration, blood pressure, serum concentration of C-reactive protein and high-density lipoprotein cholesterol and ocular axial length. In a multivariable model, the prevalence of macroalbuminuria increased by 11% (95% CI: 2%, 18%) and 17% (95% CI: 3%, 30%), respectively, for each mm-1 decrease in VD and each unit decrease in PD. CONCLUSIONS AND RELEVANCE: After adjusting for systemic and ocular parameters, diabetic patients without diabetic retinopathy showed a reduction in OCT-angiographic retinal vascular measurements in association with systemic parameters indicating chronic kidney disease. Optical coherence tomographic (OCT)-angiographic retinal microvascular parameters may serve as markers for chronic kidney disease.

SUSPENDED SCATTERING PARTICLES IN MOTION MAY INFLUENCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY VESSEL DENSITY METRICS IN EYES WITH DIABETIC MACULAR EDEMA.

PURPOSE: To study the effect of the suspended scattering particles in motion (SSPiM) on optical coherence tomography angiography (OCTA) vessel density metrics in eyes with diabetic macular edema (DME). METHODS: Thirty-four eyes with DME from 27 patients (16 men and 11 women; 61.4 ± 9.6 years) with DME were included in this retrospective cohort study. Among these eyes, 19 (55.9%) showed the SSPiM artifact on OCTA. All participants received 3-mm and 6-mm optical coherence tomography angiography (OCTA) imaging. Perfusion density and skeletonized vessel density were calculated for the superficial capillary plexus (SCP) and the deep capillary plexus (DCP), and these were compared between eyes with and without SSPiM. Additionally, foveal vessel density in a 300-µm-wide region around the foveal avascular zone (FVD) was evaluated on 3-mm OCTA scans. The main outcome measures were vessel density in the SCP and the DCP. RESULTS: Among the 3-mm OCTA images, there was no statistically significant difference in SCP vessel density in eyes with and without SSPiM (P = 0.98). Vessel density in the DCP (P = 0.001 and P = 0.028 for perfusion and skeletonized vessel density, respectively) and FVD (P = 0.03) on 3-mm OCTA scans were significantly higher in DME eyes with SSPiM than in those without SSPiM. There were no statistically significant differences in vessel density in SCP and DCP between eyes with and without SSPiM based on 6-mm OCTA scans. CONCLUSION: The presence of SSPiM may lead to an overestimation of DCP vessel density in eyes with DME when 3-mm OCTA scans are used for analysis.