補償光学適用光干渉断層計を用いた黄斑上膜における錐体細胞とミュラー細胞の形態評価

京都大学新制・課程博士博士(医学)甲第25171号医博第5057号京都大学大学院医学研究科医学専攻(主査)教授 花川 隆, 教授 林 康紀, 教授 高橋 淳学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Retinal arterial macroaneurysm rupture caused by dissection-like change in the vessel wall

[Purpose] To highlight a potential pathogenetic mechanism of retinal arterial macroaneurysm. [Observations] A 79-year-old woman presented with a ruptured retinal arterial macroaneurysm in the right eye. One year after treatment, high-resolution multimodal imaging with optical coherence tomography (OCT), OCT angiography, and adaptive optics scanning light ophthalmoscope showed that a narrow passage developed in the vessel wall of the pre-existing retinal arterial macroaneurysm and another macroaneurysm had developed adjacent to the pre-existing one. [Conclusions and Importance] These images suggest the pathogenesis of retinal arterial macroaneurysm (RAM) associated with crack-like changes in the retinal arterial wall, similar to pathologies seen in systemic arteries

MACULAR BLOOD FLOW CHANGES IN BRANCH RETINAL VEIN OCCLUSION EXAMINED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY VARIABLE INTERSCAN TIME ANALYSIS

Purpose: To examine the relationship between changes in retinal blood flow and the recurrence of macular edema in eyes with branch retinal vein occlusion. Methods: This observational study included 32 eyes in 32 patients (18 men and 14 women) with branch retinal vein occlusion who visited the Department of Ophthalmology at Kyoto University Hospital (February 2021–November 2021). At the time of inclusion in the study, each patient underwent optical coherence tomography angiography on a macular area measuring 4 × 4 mm2. For variable interscan time analysis, different interscan times were set at 7.6 (IST7.6) and 20.6 ms (IST20.6) for the optical coherence tomography angiography. The parafoveal vessel densities were measured sectorally at IST7.6 and IST20.6, and their relationship with the longitudinal changes evident in the retinal thicknesses during the variable interscan time analysis examination and 2 months later was evaluated. Results: The parafoveal vessel densities in the affected sector was significantly greater at IST20.6 than at IST7.6 (P = 0.011). At 2 months after the variable interscan time analysis examination, 6 patients (19%) showed recurrence of macular edema involving the fovea. The difference in the parafoveal vessel densities (IST20.6 − IST7.6) in the affected sector was significantly associated with longitudinal retinal thickening in the corresponding parafovea (P = 0.020) and fovea (P = 0.014). Conclusion: In eyes with branch retinal vein occlusion, optical coherence tomography angiography variable interscan time analysis facilitated the detection of retinal blood flow changes that might be predictive for the recurrence of macular edema

Human Foveal Cone and Müller Cells Examined by Adaptive Optics Optical Coherence Tomography

Purpose: The purpose of this study was to image and investigate the foveal microstructure of human cone and Müller cells using adaptive optics-optical coherence tomography. Methods: Six healthy subjects underwent the prototype adaptive optics-optical coherence tomography imaging, which allowed an axial resolution of 3.4 µm and a transverse resolution of approximately 3 µm. The morphological features of the individual retinal cells observed in the foveola were qualitatively and quantitatively evaluated. Results: In the six healthy subjects, the image B-scans showed hyper-reflective dots that were densely packed in the outer nuclear layer. The mean number, diameter, and density of hyper-reflective dots in the foveola were 250.8 ± 59.6, 12.7 ± 59.6 µm, and 6966 ± 1833/mm², respectively. These qualitative and quantitative findings regarding the hyper-reflective dots were markedly consistent with the morphological features of the foveal cone cell nuclei. Additionally, the images showed the funnel-shaped hyporeflective bodies running vertically and obliquely between the inner and external limiting membranes, illustrating the cell morphology of the foveal Müller cells. Conclusions: Using adaptive optics, we succeeded in visualizing cross-sectional images of the individual cone and Müller cells of the human retina in vivo. Translational Relevance: Adaptive optics-optical coherence tomography would help to improve our understanding of the pathogenesis of macular diseases

DETECTION AND CHARACTERISTICS OF UNRUPTURED RETINAL ARTERIAL MACROANEURYSMS

Purpose: To determine the presence of unruptured retinal arterial macroaneurysms (RAMs) and to examine the characteristics of the detected lesions. Methods: This retrospective observational study included the affected and contralateral eyes of 50 patients (100 eyes) with symptomatic, unilateral, ruptured RAMs who visited the Department of Ophthalmology at the Kyoto University Hospital (April 2014–April 2020) and were followed up for at least 6 months after the onset. The presence and characteristics of unruptured RAMs were examined by reviewing the findings of color fundus photography and infrared scanning laser ophthalmoscopy performed before the onset or during the follow-up period. Results: Unruptured RAMs were detected in six of the 50 patients. Some patients had bilateral or multiple unruptured RAMs, and a total of 12 unruptured RAMs were detected in eight eyes of the six patients. Among the detected lesions, eight exhibited a longitudinal increase in their diameter during the follow-up period, whereas six exhibited ruptures. Conclusion: Unruptured RAM is not an uncommon retinal vascular abnormality and can enlarge and progress to ruptured RAM

Widefield Choroidal Thickness of Eyes with Central Serous Chorioretinopathy Examined by Swept-Source OCT

PURPOSE: To examine widefield (WF) changes in the choroidal thickness of eyes with central serous chorioretinopathy (CSC). DESIGN: An observational study. PARTICIPANTS: Twenty-two patients with treatment naïve unilateral CSC (20 men and two women) and 28 normal eyes of 28 age-matched healthy participants (21 men and seven women). METHODS: We performed enhanced depth imaging (EDI) of swept-source optical coherence tomography (SS-OCT) with a viewing angle of vertical 20 mm × horizontal 23 mm. Moreover, we developed a grid consisting of nine subfields, with diameters of 3 mm, 9 mm, and 18 mm; inner and outer rings enclosed by circles with diameters of 3 mm and 9 mm and 9 mm and 18 mm, respectively, which were divided into four superotemporal, inferotemporal, superonasal, and inferonasal subfields. MAIN OUTCOME MEASURES: WF changes in choroidal thickness. RESULTS: The mean duration from the presumed onset of CSC was 6.8 ± 3.1 months during the examination. Compared with normal eyes, the choroidal thickness of patients with CSC was significantly greater in all subfields (P<0.020 for fellow eyes; P<0.001 for eyes with CSC). Compared with fellow eyes, the choroidal thicknesses of eyes with CSC were significantly greater, except for the outer superotemporal and inferonasal subfields (P<0.001 for all inner subfields; and P<0.001 for outer superonasal and inferotemporal subfields). In areas with dilated vortex veins, choroidal thickening was observed from the vicinity of the vortex vein ampulla to the macula along the courses of the veins. Choroidal thickenings on the dominant side were significantly greater than those on the non-dominant side (P=0.015 for the nasal subfield of the inner ring; P=0.003 and <0.001 for temporal subfields of the inner and outer rings, respectively). CONCLUSIONS: EDI of SS-OCT imaging facilitated the analysis of WF changes in choroidal thickness not only in both controls and patients with CSC. Local factors of the affected vortex vein and systemic risk factors may be involved in the pathogenesis of CSC

Preliminary Clinical Evaluation of Toxicity and Efficacy of A New Astaxanthin-rich Haematococcus pluvialis Extract

Astaxanthin (Ax), a carotenoid ubiquitously distributed in microorganisms, fish, and crustaceans, has been known to be a potent antioxidant and hence exhibit various physiological effects. We attempted in these studies to evaluate clinical toxicity and efficacy of long-term administration of a new Ax product, by measuring biochemical and hematological blood parameters and by analyzing brain function (using CogHealth and P300 measures). Ax-rich Haematococcus pluvialis extracts equivalent to 4, 8, 20 mg of Ax dialcohol were administered to 73, 38, and 16 healthy adult volunteers, respectively, once daily for 4 weeks to evaluate safety. Ten subjects with age-related forgetfulness received an extract equivalent to 12 mg in a daily dosing regimen for 12 weeks to evaluate efficacy. As a result, no abnormality was observed and efficacy for age-related decline in cognitive and psychomotor functions was suggested