Iron accumulation in the retina is associated with the development of age-related macular degeneration (AMD). IV iron is a common method to treat iron deficiency anemia in adults, and its retinal manifestations have not hitherto been identified. To assess whether IV iron formulations can be retina-toxic, we generated a mouse model for iron-induced retinal damage. Male C57BL/6J mice were randomized into groups receiving IV iron-sucrose (+Fe) or 30% sucrose (−Fe). Iron levels in neurosensory retina (NSR), retinal pigment epithelium (RPE), and choroid were assessed using immunofluorescence, quantitative PCR, and the Perls’ iron stain. Iron levels were most increased in the RPE and choroid while levels in the NSR did not differ significantly in +Fe mice compared to controls. Eyes from +Fe mice shared histological features with AMD, including Bruch’s membrane (BrM) thickening with complement C3 deposition, as well as RPE hypertrophy and vacuolization. This focal degeneration correlated with areas with high choroidal iron levels. Ultrastructural analysis provided further detail of the RPE/photoreceptor outer segment vacuolization and Bruch’s membrane thickening. Findings were correlated with a clinical case of a 43-year-old patient who developed numerous retinal drusen, the hallmark of AMD, within 11 months of IV iron therapy. Our results suggest that IV iron therapy may have the potential to induce or exacerbate a form of retinal degeneration. This retinal degeneration shares features with AMD, indicating the need for further study of AMD risk in patients receiving IV iron treatment.
Single-nucleotide polymorphisms and rare mutations in factor H (FH; official name, CFH ) are associated with age-related macular degeneration and atypical hemolytic uremic syndrome, a form of thrombotic microangiopathy. Mice with the FH W1206R mutation (FH R/R ) share features with human atypical hemolytic uremic syndrome. Herein, we report that FH R/R mice exhibited retinal vascular occlusion and ischemia. Retinal fluorescein angiography demonstrated delayed perfusion and vascular leakage in FH R/R mice. Optical coherence tomography imaging of FH R/R mice showed retinal degeneration, edema, and detachment. Histologic analysis of FH R/R mice revealed retinal thinning, vessel occlusion, as well as degeneration of photoreceptors and retinal pigment epithelium. Immunofluorescence showed albumin leakage from blood vessels into the neural retina, and electron microscopy demonstrated vascular endothelial cell irregularity with narrowing of retinal and choroidal vessels. Knockout of C6, a component of the membrane attack complex, prevented the aforementioned retinal phenotype in FH R/R mice, consistent with membrane attack complexemediated pathogenesis. Pharmacologic blockade of C5 also rescued retinas of FH R/R mice. This FH R/R mouse strain represents a model for retinal vascular occlusive disorders and ischemic retinopathy. The results suggest complement dysregulation can contribute to retinal vascular occlusion and that an anti-C5 antibody might be helpful for C5-mediated thrombotic retinal diseases.
PurposeDense deposit disease (DDD) is caused by dysregulation of the alternative pathway of the complement cascade and characterized by electron-dense deposits in the kidney glomerular basement membrane (GBM) and drusen in Bruch's membrane (BrM). Complement factor H (fH) and factor properdin (fP) regulate complement activation; fH inhibits alternative pathway (AP) activation, whereas fP promotes it. We report pathologic changes in eyes of an fH and fP double-mutant mouse, which we previously showed have dense deposits in the GBM and early mortality from nephropathy.MethodsfHm/m, fP−/−, and fHm/m/fP−/− mice were generated on a C57BL/6–129J background. Fundus imaging at 8 weeks of age was followed by analysis via light and electron microscopy. Retinal function was assessed by electroretinography (ERG). Complement levels and localization were tested by immunohistochemistry and ELISA. Retinas of fHm/m/fP−/− mice treated with intraperitoneal injections of an anti-C5 antibody were compared to those of age- and genotype-matched mice injected with an isotype control antibody.ResultsfHm/m/fP−/− mice suffered early-onset retinal hypopigmented spots detected using in vivo retinal photography, and histologic examination showed basal laminar deposits (BLamD), degeneration of the photoreceptors, and RPE vacuolization. ERG showed diminished retinal function. The anti-C5 antibody was retina-protective.ConclusionsThis unique mouse represents a new model of complement-mediated rapid-onset DDD, and could be useful in exploring the pathologic changes associated with BLamD in age-related macular degeneration.
Among participants of comparison of age-related macular degeneration treatments trials, the use of oral iron supplements was associated with retinal/subretinal hemorrhage in a dose-response manner. Unindicated iron supplementation may be detrimental in patients with wet age-related macular degeneration.
BACKGROUND:Prostate cancer is the most common malignancy among men more than fifty years of age (Cancer foundation of India). Imaging may help in clarifying several important issues in localized prostate cancer. MRI provides the best depiction of the contours of the prostate as well as its internal zonal anatomy. Recent evidence suggests that multi-parametric MRI could improve the accuracy of diagnostic assessment in prostate cancer. In addition, MRI also allows functional assessment with techniques such as diffusion-weighted MRI (DWI), MR spectroscopy (MRS), and dynamic contrast enhanced MRI (DCE-MRI). Strong opinions are held about the need for endorectal coil imaging. Endorectal coils provide large gains in signal with reductions in noise, most noticeably at 1.5 T; however, endorectal coils are uncomfortable and expensive. At 3 T, the need for endorectal coils has been debated. Clearly, the highest-quality MRI results from the combined use of endorectal coils and phased array body coils at 3 T. Prostate cancer is associated with proportionately lower levels of citrate and higher levels of choline and creatine than are seen in benign prostatic hyperplasia (BPH) or in normal prostate tissue. This difference can be detected by magnetic resonance spectroscopic imaging (MRSI). MRSI uses a strong magnetic field to obtain metabolic information (spectra) that identifies the relative concentrations of various metabolites in the cell cytoplasm and the extracellular space. This technique can identify metabolic differences in prostate tissue (BPH, prostate cancer, and normal prostate tissue).
Introduction: In 2019-20, the American College of Radiology (ACR) introduced Ovarian-Adnexal Reporting and Data System Magnetic Resonance Imaging (O-RADS MRII). Application of the O-RADS MRI in routine clinical practice can increase lesion characterization accuracy, promote better interdisciplinary communication, and help in personalized patient management of adnexal masses. Aim: To assess the diagnostic performance of the ACR O-RADS MRI scoring system for the predicting malignancy in adnexal mass in routine clinical radiology practice by using histology/ imaging findings during a minimum 4 month follow-up as the reference standard. Materials and Methods: In this single- tertiary center prospective cohort study done in Jorhat Medical College, Assam, 42 patients with 46 adnexal masses who underwent MRI between April 2020 and June 2021 were assessed. The ACR O-RADS MR scores were assigned using the MRI protocol with a dynamic study. Sensitivity, specificity, positive and negative predictive values along with the area under the Receiver Operating Characteristic (ROC) curve were calculated (cut-off score ≥4 was considered malignancy,). Histopathologic diagnosis or >4 months followup imaging findings was the reference standard used. Logistic regression analysis of MRI parameters used in identifying malignant masses was assessed. Statistical analysis was done using 95% confidence intervals (CIs). The p-values <0.05 was considered statistically significant. Results: The mean age of subjects in the study was 35.9 (range 10-75 years), and 84.8% of adnexal masses (39) were premenopausal. Malignancy was more common in postmenopausal patients (57.1%). Of 46 lesions, 13 (33.3%) were malignant. The ACR O-RADS-MR scoring system, using a dynamic MRI protocol, showed 92.3% sensitivity and 87.8%specificity in malignancy prediction. The area under the ROC curve for predicting malignancy was 0.962. The positive and negative predictive values were 75% and 89.1%, respectively. Conclusion: In a teaching hospital in assam, the O-RADS MRI scoring system, based on a dynamic MRI protocol demonstrated good sensitivity, specificity and area under the Receiver Operator Characteristic (ROC) curve in identifying malignant adnexal masses. The ACR O-RADS MRI system enables standardized MRI reporting with uniform lexicon and interpretation guide on adnexal masses.This will help to improve communication between radiologists and referring physician and in patient management, particularly in indeterminate masses on ultrasound.
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