Impact of Novel Incorporation of CT-based Segment Mapping into a Conjugated Gradient Algorithm on Bone SPECT Imaging: Fundamental Characteristics of a Context-specific Reconstruction Method

Objective(s): The latest single-photon emission computed tomography (SPECT)/computed tomography (CT) reconstruction system, referred to as xSPECT Bone™, is a context-specific reconstruction system utilizing tissue segmentation information from CT data, which is called a zone map. The aim of this study was to evaluate theeffects of zone-map enhancement incorporated into the ordered-subset conjugated gradient minimization (OSCGM) reconstruction method on SPECT images.Methods: Image quality with zone-map enhanced OSCGM (OSCGMz) and nonenhanced OSCGM methods was compared using various reconstruction parameters. The compartment phantom had 3 radioactive sections with CT values of about 1000, 250, and 0 HU. SPECT data were acquired using a lowenergy high-resolution (LEHR) collimator, with a 256×256 matrix and 2.4-mm pixel size. The performances of the 2 reconstruction methods (OSCGM vs.OSCGMz) were evaluated on the basis of %error, coefficient of variation (%CV), and normalized mean squared error (NMSE), and adequate iterative update numbers were determined. The relative CV representing the ratio of smoothed images to non-smoothed images was calculated to evaluate the effects of the Gaussian filter on each section set with different CT values.Results: On comparing the OSCGM and OSCGMz methods, it was found that the %error of the OSCGMz method tended to show convergence with fewer updates, especially in the high CT value section mimicking bone absorption. In the watersection, the %CV of the OSCGMz method was lower than that of the OSCGM method. The NMSE minimum values for the OSCGM and OSCGMz methods were obtained at 30 and 20 updates, respectively. The relative CV for the OSCGMzmethod in the water section decreased remarkably according to the size of the full width at half maximum (FWHM) of the Gaussian filter.Conclusion: The zone-map enhancement contributed to SPECT reconstruction for the reproduction of radioactive concentrations in bone tissues, using a low number of OSCGM updates. Our findings indicated that the incorporation of zone maps into SPECT reconstruction might improve image quality

PAX6-positive microglia evolve locally in hiPSC-derived ocular organoids

Microglia are the resident immune cells of the central nervous system (CNS). They govern the immunogenicity of the retina, which is considered to be part of the CNS; however, it is not known how microglia develop in the eye. Here, we studied human-induced pluripotent stem cells (hiPSCs) that had been expanded into a self-formed ectodermal autonomous multi-zone (SEAM) of cells that partially mimics human eye development. Our results indicated that microglia-like cells, which have characteristics of yolk-sac-like linage cells, naturally develop in 2D eye-like SEAM organoids, which lack any vascular components. These cells are unique in that they are paired box protein 6 (PAX6)-positive, yet they possess some characteristics of mesoderm. Collectively, the data support the notion of the existence of an isolated, locally developing immune system in the eye, which is independent of the body’s vasculature and general immune system

Diagnosis of choroidal disease with deep learning-based image enhancement and volumetric quantification of optical coherence tomography

Purpose: The purpose of this study was to quantify choroidal vessels (CVs) in pathological eyes in three dimensions (3D) using optical coherence tomography (OCT) and a deep-learning analysis. Methods: A single-center retrospective study including 34 eyes of 34 patients (7 women and 27 men) with treatment-naïve central serous chorioretinopathy (CSC) and 33 eyes of 17 patients (7 women and 10 men) with Vogt-Koyanagi-Harada disease (VKH) or sympathetic ophthalmitis (SO) were imaged consecutively between October 2012 and May 2019 with a swept source OCT. Seventy-seven eyes of 39 age-matched volunteers (26 women and 13 men) with no sign of ocular pathology were imaged for comparison. Deep-learning-based image enhancement pipeline enabled CV segmentation and visualization in 3D, after which quantitative vessel volume maps were acquired to compare normal and diseased eyes and to track the clinical course of eyes in the disease group. Region-based vessel volumes and vessel indices were utilized for disease diagnosis. Results: OCT-based CV volume maps disclose regional CV changes in patients with CSC, VKH, or SO. Three metrics, (i) choroidal volume, (ii) CV volume, and (iii) CV index, exhibit high sensitivity and specificity in discriminating pathological choroids from healthy ones. Conclusions: The deep-learning analysis of OCT images described here provides a 3D visualization of the choroid, and allows quantification of features in the datasets to identify choroidal disease and distinguish between different diseases. Translational Relevance: This novel analysis can be applied retrospectively to existing OCT datasets, and it represents a significant advance toward the automated diagnosis of choroidal pathologies based on observations and quantifications of the vasculature

VEGF regulates local inhibitory complement proteins in the eye and kidney

10.1172/JCI86418Journal of Clinical Investigation1271199-21

Suppression and Regression of Choroidal Neovascularization in Mice by a Novel CCR2 Antagonist, INCB3344

PURPOSE: To investigate the effect of an intravitreally administered CCR2 antagonist, INCB3344, on a mouse model of choroidal neovascularization (CNV). METHODS: CNV was induced by laser photocoagulation on Day 0 in wild type mice. INCB3344 or vehicle was administered intravitreally immediately after laser application. On Day 14, CNV areas were measured on retinal pigment epithelium (RPE)-choroid flat mounts and histopathologic examination was performed on 7 µm-thick sections. Macrophage infiltration was evaluated by immunohistochemistry on RPE-choroid flat mounts and quantified by flow cytometry on Day 3. Expression of vascular endothelial growth factor (VEGF) protein in RPE-choroid tissue was examined by immunohistochemistry and ELISA, VEGF mRNA in sorted macrophages in RPE-choroid tissue was examine by real-time PCR and expression of phosphorylated extracellular signal-regulated kinase (p-ERK 1/2) in RPE-choroid tissue was measured by Western blot analysis on Day 3. We also evaluated the efficacy of intravitreal INCB3344 to spontaneous CNV detected in Cu, Zn-superoxide dismutase (SOD1) deficient mice. Changes in CNV size were assessed between pre- and 1week post-INCB3344 or vehicle administration in fundus photography and fluorescence angiography (FA). RESULTS: The mean CNV area in INCB3344-treated mice decreased by 42.4% compared with the vehicle-treated control mice (p<0.001). INCB3344 treatment significantly inhibited macrophage infiltration into the laser-irradiated area (p<0.001), and suppressed the expression of VEGF protein (p = 0.012), VEGF mRNA in infiltrating macrophages (p<0.001) and the phosphorylation of ERK1/2 (p<0.001). The area of spontaneous CNV in Sod1⁻/⁻ mice regressed by 70.35% in INCB3344-treated animals while no change was detected in vehicle-treated control mice (p<0.001). CONCLUSIONS: INCB3344 both inhibits newly forming CNV and regresses established CNV. Controlling inflammation by suppressing macrophage infiltration and angiogenic ability via the CCR-2/MCP-1 signal may be a useful therapeutic strategy for treating CNV associated with age-related macular degeneration

Spontaneous separation of secondary epiretinal membrane after vitrectomy for retinal detachment

Purpose: While secondary epiretinal membranes (ERMs) are well-documented postoperative complications following rhegmatogenous retinal detachment (RRD) surgery, literature addressing the mechanisms of spontaneous resolution, particularly in cases involving vitrectomy, remain limited. In this case report, we describe the spontaneous resolution of secondary ERM in an amateur boxer following traumatic RRD surgery. Observations: Pars plana vitrectomy was performed for traumatic RRD in a 20-year-old man. Secondary ERM formation was observed one month after RRD surgery, resulting in retinal distortion. The ERM began to peel spontaneously and disappeared one year after surgery. His visual function did not deteriorate in the meantime. Conclusions and Importance: Spontaneous ERM separation is possible even after vitrectomy. This is the first published observation of the formation and spontaneous disappearance of secondary ERM after vitrectomy without intervention

An angiogenic role for adrenomedullin in choroidal neovascularization.

PURPOSE: Adrenomedullin (ADM) has been shown to take part in physiological and pathological angiogenesis. The purpose of this study was to investigate whether ADM signaling is involved in choroidal neovascularization (CNV) using a mouse model. METHODS AND RESULTS: CNV was induced by laser photocoagulation in 8-week-old C57BL/6 mice. ADM mRNA expression significantly increased following treatment, peaking 4 days thereafter. The expression of ADM receptor (ADM-R) components (CRLR, RAMP2 and RAMP 3) was higher in CD31(+)CD45(-) endothelial cells (ECs) than CD31(-)CD45(-) non-ECs. Inflammatory stimulation upregulated the expression of ADM not only in cell lines but also in cells in primary cultures of the choroid/retinal pigment epithelium complex. Supernatants from TNFα-treated macrophage cell lines potentiated the proliferation of ECs and this was partially suppressed by an ADM antagonist, ADM (22-52). Intravitreous injection of ADM (22-52) or ADM neutralizing monoclonal antibody (mAb) after laser treatment significantly reduced the size of CNV compared with vehicle-treated controls (p<0.01). CONCLUSIONS: ADM signaling is involved in laser-induced CNV formation, because both an ADM antagonist and ADM mAb significantly inhibited it. Suppression of ADM signaling might be a valuable alternative treatment for CNV associated with age-related macular degeneration

Vitrectomy without prone positioning for rhegmatogenous retinal detachments in eyes with inferior retinal breaks

<div><p>Purpose</p><p>To compare the anatomic and functional outcomes of pars plana vitrectomy (PPV) for treating rhegmatogenous retinal detachments (RRDs) between two groups with and without postoperative prone positioning.</p><p>Methods</p><p>This retrospective cohort study included 142 eyes of 142 patients with a primary RRD. All patients underwent PPV with 20% sulfur hexafluoride gas tamponade and were divided into two groups: the groups that did and did not maintain a prone position postoperatively. All patients were followed for more than 3 months. The main outcome measures were the best-corrected visual acuity (BCVA), retinal reattachment rate, and postoperative complications.</p><p>Results</p><p>Sixty-five eyes were included in the prone position group and 77 eyes in the group without prone positioning; the respective initial reattachment rates were 83.1% and 96.1%, a difference that reach significance (p = 0.011). In the eyes with inferior breaks, the initial reattachment rate was 94.7% (18 eyes) without prone positioning, which was significantly (p = 0.036) better than the 60% (6 eyes) initial reattachment rate in the group with prone positioning. In the eyes without inferior breaks, there was no significant difference in the initial reattachment rates between the two groups. The BCVAs at the 3-month postoperative visit did not differ significantly between the two groups. An epiretinal membrane (ERM) was observed postoperatively in 10 (13.0%) eyes in the group without prone positioning; no ERMs were seen postoperatively in eyes in which the internal limiting membrane (ILM) was peeled during PPV.</p><p>Conclusions</p><p>PPV without postoperative prone positioning is associated with a higher reattachment rate in eyes with a RRD, especially those with inferior retinal breaks. PPV with postoperative supine and lateral positioning might be beneficial to manage RRDs associated with inferior retinal breaks if ILM peeling is performed intraoperatively.</p></div

Risk factors for recurrence of RD in the subgroup of inferior breaks.

<p>Risk factors for recurrence of RD in the subgroup of inferior breaks.</p