Pathological progression of genetic Creutzfeldt–Jakob disease with a PrP V180I mutation

13301甲第4678号博士（医学）金沢大学博士論文本文Full 以下に掲載：Prion 12(1) pp54-62 2018. Taylor&Francis. 共著者：Akio Akagi, Yasushi Iwasaki, Maya Mimuro, Tetsuyuki Kitamoto, Masahito Yamada, Mari Yoshid

Pachychoroid neovasculopathy and age-related macular degeneration.

Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV). As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD. This is because its characteristics have yet to be well described. To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD. Pachychoroid neovasculopathy was observed in 39 individuals (19. 5%), which corresponds to one fourth of neovascular AMD. Patients with pachychoroid neovasculopathy were significantly younger (p = 5. 1 × 10[−5]) and showed a greater subfoveal choroidal thickness (p = 3. 4 × 10[−14]). Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p = 0. 029), CFH rs800292 (p = 0. 013) and genetic risk score calculated from 11 AMD susceptibility genes (p = 3.8 × 10[−3]). Current results implicate that the etiologies of the two conditions must be different. Thus, it will be necessary to distinguish these two conditions in future studie

Focal choroidal excavation in eyes with central serous chorioretinopathy.

[Purpose]To study the prevalence and 3-dimensional (3-D) tomographic features of focal choroidal excavations in eyes with central serous chorioretinopathy (CSC) using swept-source optical coherence tomography (OCT). [Design]Prospective, cross-sectional study. [Methods]We examined 116 consecutive eyes with CSC with a prototype 3-D swept-source OCT. 3-D images of the shape of the macular area, covering 6 × 6 mm2, were reconstructed by segmentation of the outer surface of the retinal pigment epithelium (RPE). [Results]The 3-D swept-source OCT detected focal choroidal excavations in 9 eyes (7.8%). The 3-D scanning protocol, coupled with en face scans, allowed for clear visualization of the excavation morphology. In 5 eyes with focal excavations, unusual choroidal tissue was found beneath the excavation, bridging the bottom of the excavation and the outer choroidal boundary. Additionally, 3 of those 5 eyes showed a suprachoroidal space below the excavation, as if the outer choroidal boundary is pulled inward by this bridging tissue. The focal choroidal excavations were located within fluorescein leakage points and areas of choroidal hyperpermeability. Eyes with focal choroidal excavations were more myopic (−4.42 ± 2.92 diopters) than eyes without excavations (−0.27 ± 1.80 diopters, P = .001). Subfoveal choroidal thickness was significantly thinner (301.3 ± 60.1 μm) in eyes with focal excavations than in eyes without the excavations (376.6 ± 104.8 μm, P = .036). [Conclusions]Focal choroidal excavations were present in 7.8% of eyes with CSC. In these eyes, focal choroidal excavations may have formed from RPE retraction caused by focal scarring of choroidal connective tissue

Coagulation and fibrinolysis abnormalities in familial amyloid polyneuropathy

Objective: Familial amyloid polyneuropathy (FAP) is an autosomal dominant form of hereditary amyloidosis. Several studies reported coagulation factor X deficiency and excessive fibrinolysis in immunoglobulin light chain amyloidosis. However, few have investigated coagulation and fibrinolysis in FAP. The objective of this study was to determine abnormalities in plasma biomarkers of coagulation and fibrinolysis in FAP. Methods: We prospectively recruited eight FAP patients with transthyretin mutations and ten age-matched control patients with other neuropathies in our university. We examined plasma biomarkers of coagulation and fibrinolysis including prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin/fibrinogen degradation products, D-dimer, α2-antiplasmin, antithrombin, plasminogen, thrombin-antithrombin complex, plasmin-α2-antiplasmin complex, prothrombin fragment 1+2, and coagulation factor X. The MannWhitney U test was performed for statistical comparisons between FAP and control groups. Results: FAP patients exhibited significantly decreased levels of coagulation factor X, plasminogen and α2-antiplasmin, and significantly increased levels of prothrombin fragment 1+2 compared to control patients. Conclusion: Our results indicate abnormalities of coagulation and fibrinolysis in FAP patients. © 2012 Informa UK, Ltd

Relationship between retinal morphological findings and visual function in age-related macular degeneration.

[Background]: We aimed to study the retinal morphological findings associated with exudative age-related macular degeneration (AMD) and their association with visual prognosis. [Methods]: We retrospectively reviewed the medical records of 96 consecutive patients (96 eyes) with exudative AMD. Retinal structural changes were examined using optical coherence tomography (OCT). [Results]: Initial OCT examination showed cystoid macular edema in 18 eyes (18.8%), fibrin exudate in 56 eyes (58.3%), and hyperreflective foci within the neurosensory retina in 78 eyes (81.3%). Upon initial examination, an external limiting membrane (ELM) line was detected under the fovea in 64 eyes (66.7%). Using Pearson’s correlation analyses, final visual acuity (VA) was correlated with initial VA (r = 0.61, p < 0.001), age (r = 0.34, p < 0.001), initial total foveal thickness (r = 0.41, p < 0.001), presence of hyperreflective foci (r = 0.40, p < 0.001), and detection of a foveal ELM line (r = 0.55, p < 0.001). After multiple regression analysis, final VA correlated with initial VA (r = 0.48, p < 0.001), initial presence of hyperreflective foci (r = 0.23, p = 0.054), and detection of a foveal ELM line (r = 0.36, p = 0.008). [Conclusions]: In eyes with exudative AMD, final VA was most correlated with initial VA. In addition, the initial integrity of the foveal outer retina was partially correlated with the visual prognosis. The initial ELM condition was associated with good final VA, while the initial presence of hyperreflective foci in the foveal neurosensory retina was associated with poor final VA

Analysis of fundus shape in highly myopic eyes by using curvature maps constructed from optical coherence tomography.

PURPOSE: To evaluate fundus shape in highly myopic eyes using color maps created through optical coherence tomography (OCT) image analysis. METHODS: We retrospectively evaluated 182 highly myopic eyes from 113 patients. After obtaining 12 lines of 9-mm radial OCT scans with the fovea at the center, the Bruch's membrane line was plotted and its curvature was measured at 1-µm intervals in each image, which was reflected as a color topography map. For the quantitative analysis of the eye shape, mean absolute curvature and variance of curvature were calculated. RESULTS: The color maps allowed staphyloma visualization as a ring of green color at the edge and as that of orange-red color at the bottom. Analyses of mean and variance of curvature revealed that eyes with myopic choroidal neovascularization tended to have relatively flat posterior poles with smooth surfaces, while eyes with chorioretinal atrophy exhibited a steep, curved shape with an undulated surface (P<0.001). Furthermore, eyes with staphylomas and those without clearly differed in terms of mean curvature and the variance of curvature: 98.4% of eyes with staphylomas had mean curvature ≥7.8×10-5 [1/µm] and variance of curvature ≥0.26×10-8 [1/µm]. CONCLUSIONS: We established a novel method to analyze posterior pole shape by using OCT images to construct curvature maps. Our quantitative analysis revealed that fundus shape is associated with myopic complications. These values were also effective in distinguishing eyes with staphylomas from those without. This tool for the quantitative evaluation of eye shape should facilitate future research of myopic complications

Three-dimensional tomographic features of dome-shaped macula by swept-source optical coherence tomography.

[Purpose]To study the tomographic and pathomorphologic features of dome-shaped maculas with swept-source optical coherence tomography (OCT). [Design]Prospective, cross-sectional study. [Methods]The macular area of 51 highly myopic eyes (35 patients) with dome-shaped maculas was studied with swept-source OCT at 1050 nm. Three-dimensional (3-D) data sets were obtained with raster scanning covering a 12 × 8-mm2 area; 3-D images of the posterior pole were constructed by autosegmentation of the retinal pigment epithelium (RPE). [Results]In all reconstructed 3-D images of the RPE, 2 outward concavities were seen within the posterior staphyloma and a horizontal ridge was formed between these 2 concavities. In 42 of these eyes, this horizontal ridge was band shaped. The vertical OCT section through the fovea showed a convex configuration of RPE, but the horizontal section showed an almost flat RPE line. In 9 eyes, 3-D images showed a typical dome-shaped convexity within the staphyloma. OCT scans showed no outward protrusions in the external scleral surface, but marked scleral thinning was seen consistent with the 2 outward concavities of the RPE. The sclera of the fovea (518.6 ± 97.6 μm) was significantly thicker than that in all 4 quadrants of the parafoveal area (range, 277.2 to 360.3 μm; P < .001). [Conclusions]In highly myopic eyes with a dome-shaped macula, a horizontal ridge is formed within the posterior staphyloma by uneven thinning of the sclera