In Vivo Evaluation of the Visual Pathway in Streptozotocin-Induced Diabetes by Diffusion Tensor MRI and Contrast Enhanced MRI.

Visual function has been shown to deteriorate prior to the onset of retinopathy in some diabetic patients and experimental animal models. This suggests the involvement of the brain's visual system in the early stages of diabetes. In this study, we tested this hypothesis by examining the integrity of the visual pathway in a diabetic rat model using in vivo multi-modal magnetic resonance imaging (MRI). Ten-week-old Sprague-Dawley rats were divided into an experimental diabetic group by intraperitoneal injection of 65 mg/kg streptozotocin in 0.01 M citric acid, and a sham control group by intraperitoneal injection of citric acid only. One month later, diffusion tensor MRI (DTI) was performed to examine the white matter integrity in the brain, followed by chromium-enhanced MRI of retinal integrity and manganese-enhanced MRI of anterograde manganese transport along the visual pathway. Prior to MRI experiments, the streptozotocin-induced diabetic rats showed significantly smaller weight gain and higher blood glucose level than the control rats. DTI revealed significantly lower fractional anisotropy and higher radial diffusivity in the prechiasmatic optic nerve of the diabetic rats compared to the control rats. No apparent difference was observed in the axial diffusivity of the optic nerve, the chromium enhancement in the retina, or the manganese enhancement in the lateral geniculate nucleus and superior colliculus between groups. Our results suggest that streptozotocin-induced diabetes leads to early injury in the optic nerve when no substantial change in retinal integrity or anterograde transport along the visual pathways was observed in MRI using contrast agent enhancement. DTI may be a useful tool for detecting and monitoring early pathophysiological changes in the visual system of experimental diabetes non-invasively

Manganese (Mn)-enhanced MRI of anterograde Mn transport along the visual pathway in streptozotocin (STZ) and sham control (CTRL) groups.

<p>(Left panel) Mn-enhanced MRI of the visual brain nuclei at 1 month after systemic STZ or CTRL administration, and 1 day after intravitreal MnCl₂ injection into the right eye. The regions of interest (ROI) for quantitative measurements were illustrated on both sides of the lateral geniculate nucleus (LGN), superior colliculus (SC) and visual cortex (VC) in yellow (arrows). Note the signal enhancements in the left lateral geniculate nucleus and left superior colliculus of both groups; (Right panel) Quantitative comparisons of Mn signal enhancements in the visual brain nuclei. Significantly higher signal intensities were found in the left LGN and SC than the right ones in both STZ and CTRL groups (Post-hoc Sidak’s multiple comparisons correction tests, p<0.01). No apparent difference in signal intensity was found between left and right VC in either group (Post-hoc Sidak’s multiple comparisons correction tests, p>0.05). No apparent difference in Mn enhancement was found in the lateral geniculate nucleus, the superior colliculus or the visual cortex between the two groups (Post-hoc Sidak’s multiple comparisons correction tests, p>0.05).</p

Chromium (Cr)-enhanced MRI of the retina in the streptozotocin (STZ) and sham control (CTRL) groups.

<p>(Top panel) Cr-enhanced MRI of the retina at 1 month after systemic STZ or CTRL administration, and 1 day after intravitreal Cr injection into the left eye. The regions of interest (ROI) for quantitative measurements were illustrated on both sides of the retina in yellow. Note the signal enhancements in the left retina of both groups (arrows); (Bottom panel) Quantitative comparisons of Cr signal enhancements in the retina. Significantly higher signal intensities were found in the left retina than the right retina of both STZ and CTRL groups (Post-hoc Sidak’s multiple comparisons correction tests, p<0.001). No apparent difference was found in Cr enhancement in the retina between the two groups. (Post-hoc Sidak’s multiple comparisons correction tests, p>0.05.)</p

Body weights of streptozotocin-induced diabetic rats (STZ) and sham control (CTRL) rats before, and at 3, 5, 7, 14, 21 and 28 days after experimental model induction via systemic drug injection.

<p>Both groups increased their body weights over time (Repeated measures ANOVA, p<0.0001), whereas the STZ group consistently showed lower weight gain than the CTRL group after systemic drug administration (Post-hoc Sidak’s multiple comparisons correction tests, *p<0.0001).</p

Blood glucose level at 1 month after streptozotocin (STZ) or sham control (CTRL) treatment.

<p>(Two-tailed unpaired Student’s t-test between STZ and CTRL groups, *p<0.05.)</p

Diffusion tensor MRI of white matter integrity in the prechiasmatic optic nerve (ON), optic tract (OT) and anterior commissure (AC) (arrows).

<p>(Top row) Color-encoded fractional anisotropy (FA) directionality maps; (Middle row) FA value maps; (Bottom row) Illustrations of the regions of interest (ROI) in yellow at the corresponding Bregma locations for quantitative analyses. Note the relatively lower FA in the optic nerves of the streptozotocin (STZ) group compared to the sham control (CTRL) group. Color ball illustrates the corresponding principal diffusion directions in the color-encoded FA directionality map: blue: caudal-rostral; red: left-right; and green: dorsal-ventral.</p

Clinical survey of 3680 iris tumors based on patient age at presentation.

OBJECTIVE: To report the spectrum of iris lesions based on patient age at presentation. DESIGN: Retrospective, nonrandomized, single-center case series. PARTICIPANTS: We included 3680 iris tumors in 3451 patients. METHODS: Chart review. MAIN OUTCOME MEASURES: Diagnostic category based on age. RESULTS: The mean age at presentation was 48 years and there were 449 (12%) tumors in children (≤20 years), 788 (21%) in young adults (21-40 years), 1308 (36%) in mid adults (41-60 years), and 1135 (31%) in senior adults (\u3e60 years). Of 3680 tumors, the diagnostic category was cystic (n = 768; 21%) or solid (n = 2912; 79%). The cystic tumors originated from iris pigment epithelium (IPE; n = 672; 18%) or iris stroma (n = 96; 3%). The solid tumors included melanocytic (n = 2510; 68%) and nonmelanocytic (n = 402; 11%). The melanocytic tumors comprised nevus (n = 1503; 60%), melanocytoma (n = 68; 3%), melanoma (n = 645; 26%), and melanocytosis (n = 64; 3%). Of 2510 melanocytic tumors, the first and second most common diagnoses by age (children, young adult, mid adult, senior adult) were nevus (53%, 57%, 63%, and 63%, respectively) and melanoma (17%, 27%, 26%, and 27%, respectively). The nonmelanocytic tumors included categories of choristomatous (n = 4; CONCLUSIONS: In an ocular oncology practice, the spectrum of iris tumors includes cystic (21%) and solid (79%) tumors. The solid tumors were melanocytic (68%) or nonmelanocytic (11%). At all ages, the most common specific diagnoses were nevus (42%), IPE cyst (19%), and melanoma (17%)