掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

Purpose:

To investigate the impact of foveal glial tissue on the anatomical and functional results after macular hole (MH) surgery.

Methods:

This study included 141 consecutive eyes that underwent successful vitrectomy for full-thickness MH between January 2015 and December 2022. The best-corrected visual acuity (BCVA) and the length of outer retinal defects were evaluated preoperatively and at 6 months postoperatively. MH with retinal detachment, recurrent MH, and traumatic MH were excluded. Multiple regression analyses were conducted on outer retinal restoration and visual acuity using foveal glial tissue size, surgical technique of internal limiting membrane (ILM) peeling or inverted ILM flap, and high myopia as explanatory variables.

Results:

Analyses revealed that the foveal glial tissue significantly limited the outer nuclear layer (ONL), external limiting membrane (ELM) restoration, and ellipsoid zone (EZ) restoration as well as BCVA improvement (r = −0.380, p < 0.001; r = −0.314, p = 0.035; r = −0.530, p = 0.015; r = −0.00027, p = 0.001; respectively). Meanwhile, the surgical technique and high myopia did not significantly affect the restoration of ONL, ELM, EZ, and BCVA after surgery.

Conclusion:

Foveal glial tissue after MH surgery attenuated ONL, ELM, and EZ restoration as well as BCVA improvement.

DOI： 10.1097/iae.0000000000004294

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To examine the effects of hydrogen water on retinal blood flow (RBF) dysregulation in diabetes, we evaluated changes in RBF in response to flicker stimulation and systemic hyperoxia in diabetic mice. METHODS: Twelve type 2 diabetic mice were divided into a group that received non-hydrogen water (n = 6, control group) and the other that received hydrogen-rich water (0.6-0.8 mM) (n = 6, HRW group) from six weeks of age. Body weight, blood glucose, intraocular pressure, and blood pressure were evaluated from eight to 14 weeks of age. RBF was measured in the vascular area of the optic disc as mean blur rate using laser speckle flowgraphy in the resting state and response to flicker stimulation and hyperoxia. We evaluated glial activation and oxidative stress based on immunofluorescence expression. RESULTS: At 14 weeks, blood glucose level was significantly lower in the HRW group, though still elevated. RBF changes improved significantly in the HRW group compared with the control group from eight weeks of age and persisted throughout the study. Immunofluorescent expression of glial fibrillary acidic protein, particularly in the outer plexiform layer, was significantly decreased in the HRW group. Among oxidative stress markers, 3-nitrotyrosine was significantly suppressed in the HRW group. CONCLUSIONS: Hydrogen-rich water intake significantly improved RBF dysregulation in diabetic mice. Hydrogen may improve impaired neurovascular coupling function in diabetic mice by suppressing gliosis and oxidative stress in the retina. TRANSLATIONAL RELEVANCE: This study highlights the potential of oral intake of hydrogen-rich water to mitigate retinal dysfunction in diabetic mice.

DOI： 10.1167/tvst.13.10.36

PubMed

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To evaluate retinal blood flow (RBF) regulation in response to RBF stress in maturity-onset diabetes of the young type 3 (MODY3) pigs. STUDY DESIGN: Case-control study. METHODS: MODY3 pigs (diabetes mellitus [DM] group, n = 8) transfected with the human mutant hepatocyte nuclear factor-1⍺ and normal pigs of the same age (normal group, n = 8) were used as subjects. After confirming DM onset, the experiment was performed under inhalation anesthesia with isoflurane at 2 months of age before the cataract progressed. Ocular blood flow was assessed by calculating the optic papillary mean blur rate using laser speckle flowgraphy, modified for pig eye measurements. After baseline ocular blood flow measurements, flicker stimulation (12 Hz, 3 min) was applied, and ocular blood flow was measured over time. RESULTS: Blood glucose was 81.8 ± 5.1 mg/dL in the normal group and 311.4 ± 23.1 mg/dL in the DM group (mean ± standard error). The percent change in ocular blood flow at 3 min after flicker stimulation was +31.0 ± 10.9% in the normal group and -6.6 ± 6.5% in the DM group compared to the preload value, and the difference was statistically significant (Mann-Whitney test, P = 0.015). CONCLUSION: RBF response to flicker stimulation is reduced at 2 months of age in MODY3 pigs, suggesting that retinal neurovascular coupling is impaired from the early onset of DM.

DOI： 10.1007/s10384-024-01073-3

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We assessed the short-term effects of switching from intravitreal aflibercept (IVA) to intravitreal faricimab (IVF) on ocular blood flow in patients with treatment-resistant diabetic macular edema (DME). The medical records of 15 patients with DME who had received IVA injection ≥ 3 months before were retrospectively reviewed. The best-corrected visual acuity, central macular thickness (CMT) on optical coherence tomography, and mean blur rate (MBR) of all disc areas on laser speckle flowgraphy were measured before, 1 week after, and 4 weeks after IVA and IVF, respectively. The changes in visual acuity showed no significant difference after switching from IVA to IVF (P = 0.732). The mean CMT decreased significantly during the follow-up period (both P < 0.001). MBR showed no significant difference during the follow-up period (P = 0.26). However, it decreased significantly 4 weeks after IVF (P = 0.01) compared with the baseline value, but not 4 weeks after IVA (P = 0.074). A significant association was observed between decreased MBR and decreased CMT in patients who received IVF (correlation coefficient: 0.501, P = 0.005) but not in those who received IVA (P = 0.735). Thus, IVF maintained ocular blood flow reduction, although no significant differences in visual acuity and CMT changes were observed compared to IVA.

DOI： 10.1038/s41598-024-63435-8

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To report a case of cyclic esotropia successfully treated with prismatic correction. OBSERVATIONS: A 9-year-old girl presented with intermittent esotropia and diplopia occurring over the previous 4 months. The patient had 30 prism diopters (PD) of esotropia at both distance and near. Ocular motility testing, other ophthalmic examinations, and brain magnetic resonance imaging revealed no abnormalities. At the third visit, the patient had 6 PD of intermittent esotropia without diplopia, and the eye position diary demonstrated esotropia every other day, which led to a diagnosis of cyclic esotropia with a 48-h cycle. The cyclic pattern persisted for 9 months following the initial visit. However, during a subsequent regular visit, the patient reported a newfound ability to self-adjust from "esotropic" days to "straight" days by tightly closing the eyes immediately after waking up in the morning, particularly when wishing to avoid strabismus. To address the condition, we affixed a Fresnel membrane prism on the glasses to compensate for the latent deviation on a "straight" day. During the subsequent 18 months, the esotropia completely resolved, and the patient was followed up with gradual decreases in prism power. CONCLUSIONS AND IMPORTANCE: Correcting latent deviation using a prism lens is a simple approach without potential side effects. The present findings suggest that this approach is a viable treatment option for cyclic esotropia during its early and periodic stages.

DOI： 10.1016/j.ajoc.2024.102055

PubMed

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: In patients with diabetic macular edema (DME) from YOSEMITE/RHINE, dual angiopoietin-2/vascular endothelial growth factor-A (VEGF-A) inhibition with faricimab resulted in visual/anatomic improvements with extended dosing. The SWAN trial (jRCTs031230213) will assess the efficacy, durability, and safety of faricimab during the treatment maintenance phase in patients with DME using a treat-and-extend (T&E)-based regimen adapted to clinical practice and the characteristics of patients achieving extended dosing intervals. METHODS: SWAN is a 2-year, open-label, single-arm, interventional, multicenter trial enrolling adults with center-involving DME. All patients will receive three initial faricimab 6.0 mg doses every 4 weeks (Q4W). From week 12 onwards, in patients without active DME, dosing intervals will be extended in 8-week increments up to Q24W. In contrast, patients with active DME (central subfield thickness [CST] >325 μm and intraretinal fluid [IRF] or subretinal fluid [SRF] resulting in vision loss/disease aggravation) will receive a dose within a day and the dosing interval will be shortened by 4 weeks to a minimum of Q8W relative to the previous dosing interval. Recruitment commenced in August 2023 across a planned 16 sites in Japan. RESULTS: The primary endpoint is change in best-corrected visual acuity (BCVA) from baseline at 1 year (averaged over weeks 52, 56, and 60). Key secondary endpoints include: change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire scores over time; proportion of patients with BCVA (decimal visual acuity) ≥0.5, ≥0.7, ≥1.0, or ≤0.1; proportion of patients with absence of DME, and IRF and/or SRF over time. Safety endpoints include incidence/severity of ocular/nonocular adverse events. CONCLUSIONS: The SWAN trial is expected to provide evidence to support individualized faricimab dosing regimens, with the potential to reduce the burden of frequent treatments on patients, caregivers, and healthcare systems.

DOI： 10.1371/journal.pone.0311484

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Acute syphilitic posterior placoid chorioretinitis (ASPPC) is a rare form of ocular syphilis. However, its pathophysiology is not fully understood. Laser speckle flowgraphy (LSFG) can facilitate the non-invasive evaluation of blood flow and allow investigations into the effects of treatments in various ocular diseases. We report a case of ASPPC that presented with symptoms only in the right eye but showed bilateral disease in LSFG. OBSERVATIONS: A 54-year-old man presented with decreased vision and visual field defects in the right eye 2 days prior to the initial visit. Fundoscopy images showed a typical yellowish placoid lesion in the macular area, and optical coherence tomography showed disruption of the outer retinal layers and nodular appearance of the retinal pigment epithelium. Fluorescence angiography showed excessive leakage of the placoid lesion characterized by hypofluorescent dots in the inner area ("leopard spotting"). The patient was diagnosed with unilateral ASPPC based on multiple imaging and serological tests. Penicillin was administered for 2 weeks, and the patient showed improvement in symptoms and restoration of the retinal structure. The mean blur rate of the right/left eye was 2.1/5.9 arbitrary units (AU) before treatment and increased to 4.5/9.3 AU 6 months after treatment. CONCLUSIONS AND IMPORTANCE: Despite the absence of typical imaging signs and symptoms in the left eye, both eyes may have been affected with different degrees of severity. Thus, LSFG may facilitate the evaluation of treatment effects and the prediction of ocular inflammatory diseases in the early stages.

DOI： 10.1016/j.ajoc.2023.101880

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本眼科手術学会  

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記述言語：日本語   出版者・発行元：(公社)日本眼科手術学会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.exer.2023.109548

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Diabetic retinopathy (DR) is a leading cause of blindness in the working population. Because novel therapeutic intervention require testing, there is an urgent need for reliable animal models that faithfully replicate DR. Pig eyes have many similarities to human eyes anatomically and physiologically. Thus, attempts have been made to establish porcine models of DR by surgical, pharmaceutical or genetical induction of insulin deficiency, and dietary intervention. A previous study reported a transgenic pig model of maturity onset diabetes of the young type 3 (MODY3) developed signs of severe DR such as hemorrhage and proliferative tissue at the surface of the retina. However, the course of development of DR has not been studied in detail in this model. The purpose of this study was to investigate the early phase of DR in a MODY3. MODY3 and wild-type (WT) pigs underwent fundus photography and fluorescein angiogram (FA) before they developed cataracts. Animals were euthanized at age 1, 4, 7, and 10 months. Whole-mount retina and 10-μm thick paraffinized sections were stained with isolectin B4, and vessel density was determined by MATLAB software. At 4 and 7 months, retinal arterioles were immediately cannulated, and vasomotor action was measured by incubation with bradykinin and sodium nitroprusside. In the MODY3 pigs, fasting blood sugar levels gradually increased up to 500 mg/dL. Vascular tortuosity and yellowish spindle-shaped lesions were confirmed in MODY3 pigs at the age of 7 months; however, no microaneurysms were detected on FA. Compared with age-matched WT pigs, MODY3 pigs showed a significant decrease in blood vessel density in the intermediate and deep vascular plexus at 4 and 7 months of age and a slight decrease in capillary density in the superficial vascular plexus at 7 months of age. In MODY3 pigs, electron microscopy revealed thickening of the capillary basement membrane and leukostasis in the major blood vessels at 10 months of age. Bradykinin-induced dilation of retinal arterioles was diminished in MODY3 pigs as early as 7 months of age. Within 1 year after birth, MODY3 pigs show all typical early vascular lesions of diabetes except for microaneurysm formation. This pilot study suggests that the MODY3 pigs may serve as a suitable DR model to test effects of newly developed compounds on DR.

DOI： 10.1016/j.exer.2022.109379

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We retrospectively compared the stability of intraocular lenses (IOLs) routinely used at our institution by measuring IOL position after phacovitrectomy for rhegmatogenous retinal detachment (RRD). Patients with RRD who underwent phacovitrectomy with gas tamponade received one of three IOLs: 6-mm, single-piece NS-60YG (NIDEK, 15 eyes); 6-mm, single-piece XY1 (HOYA, 11 eyes); or 7-mm, three-piece X-70 (Santen, 11 eyes). Various parameters associated with the anterior chamber, lens, and IOL were measured by swept-source anterior segment optical coherence tomography (CASIA2; Tomey Corp) before and 1 week and 1 month after surgery. IOL position was determined as follows: IOL position = (postoperative aqueous depth [AQD] - preoperative AQD)/lens thickness. We found no significant difference in axial length between the IOLs (p = 0.97). At 1 week, IOL position was as follows: NS-60YG, 0.32; XY1, 0.24; and X-70, 0.26 (p &lt; 0.05). The respective IOL positions at 1 month were 0.35, 0.27, and 0.28 (p &lt; 0.01). These results indicated the smallest anterior shift with NS-60YG. To replicate the anterior shift of IOL position ex vivo, biomechanical measurement was performed. NS-60YG resisted more displacement force than the other IOLs. Thus, in eyes undergoing phacovitrectomy for RRD, NS-60YG was the most stable of the three IOLs studied.

DOI： 10.3390/jcm11123438

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

糖尿病患者が良好な視覚を保って天寿を全うできることが我々眼科医の目標であり,使命である.近年の薬剤・手術器具・各種の画像診断機器の目覚ましい発展により,糖尿病網膜症診療も進化してきた.診断では,光干渉断層計(OCT)の登場により糖尿病黄斑浮腫の定量的評価が可能となり,さらに光干渉断層血管撮影(OCTA)により血管の描出も非侵襲的に施行可能となった.治療に関しては小切開硝子体手術と抗血管内皮増殖因子(VEGF)療法によりパラダイムシフトが起きた.しかしながら,このような進化をもってしても糖尿病網膜症患者の失明をゼロにすることは難しく,早期診断・早期治療の必要性を痛感する.著者は長年,眼循環研究に携わり,高血糖に長期間曝露され続けた網膜血管の障害が糖尿病網膜症の本態であることに着目し,網膜循環が糖尿病網膜症の発症に先行して障害されることを見出した.これを発展させ,網膜循環を定量的に評価することで早期診断を可能とし,低侵襲な網膜症診療を実現させたいと考え,新たな研究に挑戦している.I.糖尿病網膜症診断の低侵襲化 網膜血流測定は網膜循環を定量化(数値化)できるため,糖尿病網膜症の所見を呈する以前からの異常を可視化でき,網膜症の低侵襲早期診断法として有用である.しかし,定常状態の網膜血流は個体差が大きいことも事実であり,糖尿病網膜症に伴う網膜血流障害の新しい評価法の確立が必要である.網膜血流は神経・グリアにより緻密に制御されており,その機構は網膜神経-血管連関(NVC)と呼ばれている.糖尿病網膜症においても早期からNVCの異常が起こると考えられてきたが,低侵襲的な負荷による網膜血流の変化率を数値化してNVCを定量化できれば,個体差による影響を最小化することが可能と考えられた.NVCを評価できるフリッカ刺激(血流増加)および高酸素負荷(血流低下)の2つの生理的負荷試験を行い,網膜血流測定による糖尿病網膜症における微細なNVC障害の検出を試みた.まず2型糖尿病モデルマウスの網膜血流をレーザースペックルフローグラフィ(LSFG)で経時的に評価した.観察期間中において,糖尿病マウスの網膜血流は定常状態では変化しない一方,生理的負荷試験の反応性は早期から減弱し,網膜症早期に起こる微細なNVC障害を低侵襲的かつ定量的に捉えることができた.さらに電気生理学および組織学的検討も行い,2型糖尿病ではNVC異常が網膜神経機能障害に先行して病態が進行すると考えられた.NVCを標的とする生理的負荷試験を用いた網膜血流測定により,糖尿病網膜症の低侵襲早期診断および早期介入が可能となると考えている.II.糖尿病網膜症治療の低侵襲化 網膜症の低侵襲治療開発には,標的分子,薬剤型,ドラッグデリバリーシステムなどを熟考しなければならない.著者は各分野の専門家との共同研究を進め,(1)血糖降下剤内服,(2)サプリメント内服,(3)ナノ粒子点眼,(4)ワクチン治療による糖尿病網膜症への改善効果について検討した.大規模臨床研究で網膜症への抑制効果が証明されたフェノフィブラートをナノ粒子化することにより眼内移行性を高め,点眼で後眼部への深達を可能とした.このフェノフィブラートナノ点眼は2型糖尿病動物モデルのNVC悪化を抑制し,新規糖尿病網膜症治療法としての有用性を確認した.また糖尿病治療薬であるsodium-glucose cotransporter 2(SGLT2)阻害薬やサプリメント投与,さらには抗ペプチドワクチン治療でも糖尿病動物モデルでのNVC改善効果が確認されており,これらの知見から新しい低侵襲糖尿病網膜症治療戦略を提唱したい.(著者抄録)

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study aimed to investigate the relationship between ocular vascular resistance parameters, evaluated by laser speckle flowgraphy (LSFG), and systemic atherosclerosis, renal parameters and cardiac function in acute coronary syndrome (ACS) patients. We evaluated 53 ACS patients between April 2019 and September 2020. LSFG measured the mean blur rate (MBR) and ocular blowout time (BOT) and resistivity index (RI). 110 consequent patients without a history of coronary artery disease who visited ophthalmology as a control group. Significant positive correlations were observed between ocular RI and systemic parameters in ACS patients, including intima-media thickness (r = 0.34, P = 0.015), brachial-ankle pulse-wave velocity (r = 0.41, P = 0.002), cystatin C (r = 0.32, P = 0.020), and E/e' (r = 0.34, P = 0.013). Ocular RI was significantly higher in the ACS group than in the control group in male in their 40 s (0.37 ± 0.02 vs. 0.29 ± 0.01, P < 0.001) and 50 s (0.36 ± 0.02 vs. 0.30 ± 0.01, P = 0.01). We found that the ocular RI was associated with systemic atherosclerosis, early renal dysfunction, and diastolic cardiac dysfunction in ACS patients, suggesting that it could be a useful non-invasive comprehensive arteriosclerotic marker.

DOI： 10.1038/s41598-021-04196-6

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

We investigated the effect of fenofibrate nano-eyedrops (FenoNano) on impaired retinal blood flow regulation in type 2 diabetic mice. Six-week-old db/db mice were randomly divided into an untreated group (n = 6) and treated group, which received FenoNano (n = 6). The longitudinal changes in retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice treated with FenoNano (n = 6) or the vehicle (n = 6) from ages 8-14 weeks. The retinal blood flow was assessed using laser speckle flowgraphy. We also evaluated the expressions of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQP4) and the phosphorylation of peroxisome proliferator-activated receptor alpha (PPAR-α) by immunofluorescence. In db/db mice treated with FenoNano, both responses were restored from 8 to 14 weeks of age compared with the diabetic mice treated with the vehicle. At 14 weeks of age, the impaired regulation of retinal blood flow during systemic hyperoxia and flicker stimulation improved to about half of that in the db/db mice treated with FenoNano compared with the db/m control group (n = 5). FenoNano prevented the activation of VEGF and GFAP expression and increased the AQP4 expression and the phosphorylation of PPAR-α detected by immunofluorescence compared with the diabetic mice treated with the vehicle eyedrop. Our results suggested that the fenofibrate nano-eyedrops prevent retinal glial dysfunction via the phosphorylation of PPAR-α and improves the retinal blood flow dysregulation in type 2 diabetic mice.

DOI： 10.3390/pharmaceutics14020384

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

We investigated the effect of tofogliflozin, a sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i), on retinal blood flow dysregulation, neural retinal dysfunction, and the impaired neurovascular coupling in type 2 diabetic mice. Tofogliflozin was added to mouse chow to deliver 5 mg/kg/day and 6-week-old mice were fed for 8 weeks. The longitudinal changes in the retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice that received tofogliflozin (n =6) or placebo (n = 6) from 8 to 14 weeks of age. We also evaluated glial activation and vascular endothelial growth factor (VEGF) expression by immunofluorescence. Tofogliflozin treatment caused a sustained decrease in blood glucose in db/db mice from 8 weeks of the treatment. In tofogliflozin-treated db/db mice, both responses improved from 8 to 14 weeks of age, compared with vehicle-treated diabetic mice. Subsequently, the electroretinography implicit time for the oscillatory potential was significantly improved in SGLT2i-treated db/db mice. The systemic tofogliflozin treatment prevented the activation of glial fibrillary acidic protein and VEGF protein expression, as detected by immunofluorescence. Our results suggest that glycemic control with tofogliflozin significantly improved the impaired retinal neurovascular coupling in type 2 diabetic mice with the inhibition of retinal glial activation.

DOI： 10.3390/ijms23031362

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Prorenin is viewed as an ideal target molecule in the prevention of diabetic retinopathy. However, no drugs are available for inhibiting activation of prorenin. Here, we tested the effect of a prorenin peptide vaccine (VP) in the retina of a murine model of type 2 diabetes (T2D). To choose the optimal vaccine, we selected three different epitopes of the prorenin prosegment (E1, E2, and E3) and conjugated them to keyhole limpet hemocyanin (KLH). We injected C57BL/6J mice twice with KLH only (as a control vaccine), E1 conjugated with KLH (E1-KLH), E2-KLH, or E3-KLH and compared antibody titers. E2-KLH showed the highest antibody titer and specific immunoreactivity of anti-sera against prorenin, so we used E2-KLH as VP. Then, we administered injections to the non-diabetic db/m and diabetic db/db mice, as follows: db/m + KLH, db/db + KLH, and db/db + VP. Retinal blood flow measurement with laser speckle flowgraphy showed that the impaired retinal circulation response to both flicker light and systemic hyperoxia in db/db mice improved with VP. Furthermore, the prolonged implicit time of b-wave and oscillatory potentials in electroretinography was prevented, and immunohistochemical analysis showed reduced microglial activation, gliosis, and vascular leakage. The enzyme-linked immunosorbent spot assay confirmed vaccinated mice had no auto-immune response against prorenin itself. The present data suggest that vaccination against prorenin is an effective and safe measure against the early pathological changes of diabetic retinopathy in T2D.

DOI： 10.1371/journal.pone.0262568

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: We investigated the effect of long-term administration of supplement with trapa bispinosa roxb. extract (TBE) and lutein on the susceptibility of retinal blood flow regulation in type 2 diabetic mice. Methods: Six-week-old db/db mice were randomly divided into the untreated group (n = 6) and the treated group received the supplement with TBE and lutein (n = 6). The longitudinal changes in retinal blood flow responses to systemic hyperoxia and a flicker stimulation were evaluated every 2 weeks in diabetes db/db mice from age 8 to 14 weeks. The retinal blood flow was assessed using laser speckle flowgraphy. We also evaluated the expressions of glial fibrillary acid protein (GFAP) and vascular endothelial growth factor (VEGF) by immunofluorescence. Results: The resting retinal blood flow was steady and comparable between two groups throughout the study. In db/db mice with supplement, both blood flow responses were restored from 8 to 14 weeks of age compared with diabetic mice treated with the placebo. Supplement prevented the activation of GFAP and decreased the expression of VEGF detected by immunofluorescence compared with the diabetic mice treated with placebo. Conclusion: We found that the long-term administration of supplement with TBE and lutein improved the impaired regulation of retinal blood flow in response to systemic hyperoxia and flicker stimulation, suggesting that these supplements can prevent diabetic retinopathy by improving abnormal neurovascular coupling in type 2 diabetic mice.

DOI： 10.3389/fphys.2022.788034

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Pro re nata (PRN) regimen using anti-vascular endothelial growth factor (VEGF) agent is popular for the treatment of diabetic macular edema (DME). We investigated the influence of waiting time (WT) and interval between the date of recurrence of edema and re-injection on treatment efficacy. METHODS: This retrospective study conducted at 7 sites in Japan enrolled patients who received intravitreal injection of ranibizumab (IVR) and aflibercept (IVA) in 1+PRN regimen. Enrolled patients were divided into 2 groups: prompt group (less than 1 week) and deferred group (3 weeks or more). Central retinal thickness (CRT) and best corrected visual acuity (BCVA) were measured every month for 1 year. RESULTS: CRT in the deferred group was significantly higher than that in the prompt group at 2, 5, 6, 7, and 12 months (p < 0.05). BCVA in the prompt group was significantly better than that in the deferred group at 7, 10, and 12 months (p < 0.05). CONCLUSION: The prompt group was superior in anatomical and functional improvement of DME in anti-VEGF therapy than the deferred group. Our data suggests that shorter WT is recommended for better visual prognosis in the treatment for DME.

DOI： 10.3390/jcm10245738

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

<title>Abstract</title>Many studies have demonstrated that rhegmatogenous retinal detachment (RRD) leads to impaired retinal circulation. However, the involvement of inflammation in the RRD-induced worsening of retinal circulation was obscure. This retrospective observational study included 150 patients with primary RRD (macula-on, n = 63; macula-off, n = 87) who underwent 25-gauge microincision vitrectomy surgery (25G MIVS). Total retinal blood flow was represented by the mean blur rate (MBR) of the optic nerve head vessel, measured by laser speckle flowgraphy preoperatively and until 6 months postoperatively. Aqueous humor samples were obtained during surgery to determine cytokine concentrations by enzyme-linked immunosorbent assay. At 3 and 6 months postoperatively, there were no significant differences between eyes with macula-on RRD and fellow eyes. However, in macula-off RRD, MBR remained significantly lower in RRD eyes 6 months postoperatively (<italic>P</italic> &lt; 0.05). Log-transformed levels of soluble intercellular adhesion molecule-1 (sICAM-1) were negatively correlated with relative MBR (r-MBR, RRD eye/fellow eye) before surgery (<italic>r</italic> =  − 0.47, <italic>P</italic> = 0.01) in macula-on, but not macula-off, RRD. Six months postoperatively, r-MBR correlated significantly with sICAM-1 levels (<italic>r</italic> =  − 0.36, <italic>P</italic> = 0.02) in macula-off RRD. ICAM-1 may play a role in RRD-induced deterioration of retinal circulation.

DOI： 10.1038/s41598-021-94993-w

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その他リンク： http://www.nature.com/articles/s41598-021-94993-w

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

<title>Abstract</title>We investigated and compared the susceptibility of retinal blood flow regulation and neural function in mice developing type 2 diabetes. The longitudinal changes in retinal neuronal function and blood flow responses to a 10-min systemic hyperoxia and a 3-min flicker stimulation were evaluated every 2 weeks in diabetic db/db mice and nondiabetic controls (db/m) from age 8 to 20 weeks. The retinal blood flow and neural activity were assessed using laser speckle flowgraphy and electroretinography (ERG), respectively. The db/db mice had significantly higher blood glucose levels and body weight. The resting retinal blood flow was steady and comparable between two groups throughout the study. Hyperoxia elicited a consistent decrease, and flicker light an increase, in retinal blood flow in db/m mice independent of age. However, these flow responses were significantly diminished in db/db mice at 8 weeks old and then the mice became unresponsive to stimulations at 12 weeks. Subsequently, the ERG implicit time for oscillatory potential was significantly increased at 14 weeks of age while the a-wave and b-wave amplitudes and implicit times remained unchanged. The deficiencies of flow regulation and neurovascular coupling in the retina appear to precede neural dysfunction in the mouse with type 2 diabetes.

DOI： 10.1038/s41598-021-97651-3

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その他リンク： https://www.nature.com/articles/s41598-021-97651-3

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To investigate the efficacy and safety of a treat-and-extend (T&E) regimen using aflibercept (Eylea) for diabetic macular edema (DME). STUDY DESIGN: Prospective, open-label, multicenter, single-arm, nonblinded clinical study. METHODS: Forty eyes of 40 patients with DME received a T&E regimen of intravitreal aflibercept injection (IAI) with the longest treatment interval set to 16 weeks and adjunct focal/grid laser for 1 year. An intent-to-treat analysis was performed using the same last-observation-carried-forward method. A per-protocol analysis was also performed for patients who completed a 1-year T&E regimen. The primary endpoints were mean changes in best-corrected visual acuity (BCVA) and central subfield macular thickness (CST) from baseline. Secondary endpoints included IAI-interval extension and resultant IAI numbers and the association between an early response to IAI and final BCVA gain at 1 year. RESULTS: Thirty-one patients (77.5%) completed the 1-year aflibercept T&E regimen. In these per-protocol participants, the mean CST improvement/reduction was 187.3 ± 145.0 µm (P < .001), but the mean BCVA gain was limited to 4.3 ± 12.2 letters (P = .782). Subanalysis revealed that eyes that gained ≥ 4 letters (median at week 12) after the initial 3 consecutive IAIs (induction phase) achieved greater vision improvement (13.8 ± 9.5 letters) than did the residual eyes (- 4.3 ± 9.2 letters) at 1 year (P < .001). Treatment intervals were extended to 12 and 16 weeks in 16.1% (5/31) and 45.2% (14/31) of the patients, respectively. The mean IAI number was 7.0 ± 1.1. CONCLUSIONS: The results of this study suggest that although the BCVA improvement might be somewhat less than that of frequent treatment, a T&E aflibercept regimen with the longest treatment interval set to 16 weeks is a realizable rational strategy for DME treatment over 1 year.

DOI： 10.1007/s10384-021-00820-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We developed a new method to retrieve a dropped nucleus of the lens via a small incision using bipolar pencils, the kebab technique, to solve the lack of small-gauge fragmatomes, and the expense and toxicity of perfluorocarbon liquids (PFCL). A total of 8 eyes in 6 patients underwent this technique and were reviewed. After vitrectomy, the dropped nucleus of the lens was lifted from the retina by adhesion with a bipolar pencil, and phacoemulsification was performed while rotating the lens. The outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP), and corneal endothelial cell density before and after surgery. Surgical indications included zonular weakness, trauma, acute angle closure attack, and phacolytic glaucoma. At 1 month, BCVA improved from a mean (standard deviation, SD) 1.67 logMAR (0.90) to 1.14 logMAR (1.01). The mean preoperative IOP was 24.5 (16.8) mmHg and postoperative IOP was 11.0 (2.8) mmHg. The mean preoperative corneal endothelial cell count was 2600 (322) cells/mm2 (one eye was unmeasurable) and postoperative corneal endothelial cell count was 2387 (431) cells/mm2. There were no postoperative complications. The retrieval of a dropped nucleus of the lens using a bipolar pencil enables small incisions without using PFCL.

DOI： 10.1038/s41598-021-87022-3

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記述言語：英語  

Purpose: To report the changes over time in ocular blood flow quantified by laser speckle flowgraphy (LSFG) in a treated large retinal arterial macroaneurysm (RAM). Observations: A 72-year old female presented with sudden decreased vision in the left eye. Fundus examination revealed a RAM and vitreous hemorrhage (VH), which worsened over one month. A vitrectomy was performed to remove the VH, with 20% sulfur hexafluoride injected into the vitreous cavity. The VH recurred two weeks later and the RAM was found to have enlarged from one-quarter disc diameter (DD) to three DDs during a second vitrectomy. The RAM subsequently shrunk spontaneously to one DD without recurrent VH during the following 2 weeks. Beginning 4 weeks after the second vitrectomy we performed serial LSFG examinations of the RAM and found that the mean blur rate (MBR) of the RAM and retinal flow volume (RFV) in both the feeding arteriole and draining venule decreased as the RAM continued to involute. Conclusions and importance: MBR and arteriolar and venular RFV measured by LSFG decreased with RAM involution. Longitudinal followup of blood flow by LSFG may be useful for noninvasive evaluation of the stability of RAMs.

DOI： 10.1016/j.ajoc.2021.101022

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This prospective, open-label, single-arm, non-randomized clinical trial, assessed the efficacy of a 2-year treat-and-extend (T&E) regimen involving intravitreal aflibercept injection (IAI), with the longest treatment interval set to 16 weeks, and adjunct focal/grid laser in diabetic macula edema (DME) patients. We examined 40 eyes (40 adults) with fovea-involving DME from 8 Japanese centers between April 2015 and February 2017. Participants received IAI with an induction period featuring monthly injections and a subsequent T&E period featuring 8-16-week injection interval, adjusted based on optical coherence tomography findings. The primary endpoints were mean changes in the best-corrected visual acuity (BCVA) and central subfield macular thickness (CST) from baseline. Thirty patients (75%) completed the 2-year follow-up. The mean BCVA and CST changed from 60.5 ± 15.6 letters and 499.2 ± 105.6 µm at baseline to 66.6 ± 17.1 letters (P = 0.217) and 315.2 ± 79.0 µm (P < 0.001), respectively, after 2 years. The treatment interval was extended to 12 and 16 weeks in 6.7% and 66.7% of patients, respectively, at the end of 2 years. The T&E aflibercept regimen with the longest treatment interval set to 16 weeks, with adjunct focal/grid laser may be a rational 2-year treatment strategy for DME.

DOI： 10.1038/s41598-021-83811-y

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）  

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担当区分：最終著者,　責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

<title>Abstract</title>This study aimed to evaluate longitudinal changes in retinal blood flow in response to flicker stimulation and systemic hyperoxia in mice using a laser speckle flowgraphy (LSFG-Micro). The retinal blood flow in vascular area surrounding the optic nerve head was measured in 8-week-old male mice every 2 weeks until age 20-week. The coefficient of variation of retinal blood flow under resting condition was analyzed every 2 weeks to validate the consistency of the measurement. On day 1 of the experiment, retinal blood flow was assessed every 20 s for 6 min during and after 3 min flicker light (12 Hz) stimulation; on day 2, retinal blood flow was measured every minute for 20 min during and after 10 min systemic hyperoxia; and on day 3, electroretinography (ERG) was performed. Body weight, systemic blood pressure, and ocular perfusion pressure increased significantly with age, but the resting retinal blood flow and ERG parameters remained unchanged. Retinal blood flow significantly increased with flicker stimulation and decreased with systemic hyperoxia, independent of age. The LSFG-Micro provides consistent and reproducible retinal blood flow measurement in adult mice. Longitudinal assessments of retinal blood flow in response to flicker stimulation and systemic hyperoxia may be useful indexes for noninvasive monitoring of vascular function in retinas.

DOI： 10.1038/s41598-020-75296-y

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その他リンク： http://www.nature.com/articles/s41598-020-75296-y

記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Pancreatic duodenum homeobox 1 (Pdx1) expression is crucial for pancreatic organogenesis and is a key regulator of insulin gene expression. Hairy and enhancer of split 1 (Hes1) controls tissue morphogenesis by maintaining undifferentiated cells. Hes1 encodes a basic helix loop helix (bHLH) transcriptional repressor and functionally antagonizes positive bHLH genes, such as the endocrine determination gene neurogenin-3. Here, we generated a new pig model for diabetes by genetic engineering Pdx1 and Hes1 genes. RESEARCH DESIGN AND METHODS: A transgenic (Tg) chimera pig with germ cells carrying a construct expressing Hes1 under the control of the Pdx1 promoter was used to mate with wild-type gilts to obtain Tg piglets. RESULTS: The Tg pigs showed perinatal death; however, this phenotype could be rescued by insulin treatment. The duodenal and splenic lobes of the Tg pigs were slender and did not fully develop, whereas the connective lobe was absent. β cells were not detected, even in the adult pancreas, although other endocrine cells were detected, and exocrine cells functioned normally. The pigs showed no irregularities in any organs, except diabetes-associated pathological alterations, such as retinopathy and renal damage. CONCLUSION: Pdx1-Hes1 Tg pigs were an attractive model for the analysis of pancreatic development and testing of novel treatment strategies for diabetes.

DOI： 10.1136/bmjdrc-2020-001792

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Evaluate the effect of foveal leaking microaneurysms (MAs) on the required number of intravitreal ranibiz-umab (IVR) injections in the treatment of center-involving diabetic macular edema (DME) when treated with focal/grid laser. DESIGN: A pilot study of prospective, nonrandomized, multicenter clinical trial. METHODS: This study enrolled 21 eyes with DME for which pro re nata IVR injections were combined with short-pulse focal/grid laser. At 12 months, best-corrected visual acuity (BCVA), central subfield macular thickness (CMT), and the required number of IVRs to maintain CMT < 300 µm were compared between eyes with or without foveal leaking MAs, termed the MA(+) and MA(-) groups, respectively. RESULTS: Significant CMT improvements (p < 0.0001) and increased BCVA of 4.0 ± 8.5 letters were observed at 12 months. The MA(-) group required significantly fewer IVRs than did the MA(+) group (mean: 4.9 ± 3.0 vs. 8.6 ± 3.0; p = 0.0306). In the latter 6 months of the 1-year follow-up, 50% (4/8) of MA(-) eyes did not require any IVR administration to sustain CMT < 300 µm. CONCLUSIONS: A combination therapy of short-pulse focal/grid laser and reduced IVR injections appeared noninferior to previous reports of IVR monotherapy. Further large-scale investigations are warranted.

DOI： 10.1159/000492005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00417-017-3803-x

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記述言語：英語  

Purpose: To investigate whether benzo(e)pyrene (B(e)P), a toxicant in cigarette smoke, affects the endothelium-dependent nitric oxide (NO)-induced vasodilation of the retinal arterioles, and whether oxidative stress, distinct protein kinase signaling pathways, and endoplasmic reticulum (ER) stress are associated with the B(e)P-induced effect on the retinal arterioles. Methods: In this in vitro study, porcine retinal arterioles were isolated, cannulated, and pressurized without flow. These vessels were treated with intraluminal administration of B(e)P or B(e)P plus blockers for 180 minutes. Diametric changes to agonists were recorded by videomicroscopy. Results: Intraluminal treatment with 100 μM B(e)P for 180 minutes significantly reduced the arteriolar vasodilation caused by the endothelium-dependent NO-mediated agonists bradykinin and A23187 but not that caused by endothelium-independent NO donor sodium nitroprusside. The adverse effects of B(e)P on the vasodilatory action of bradykinin were prevented by the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) inhibitor apocynin, the c-Jun N-terminal kinase (JNK) inhibitor SP600125, the p38 mitogen-activated protein kinase inhibitor SB203580, genistein, resveratrol (RSV), and the ER stress inhibitor 4-phenylbutyrate (4-PBA). The xanthine oxidase inhibitor allopurinol did not alter the effect of B(e)P on the vasodilatory action induced by bradykinin. Conclusions: B(e)P decreases the endothelium-dependent NO-induced vasodilation in the retinal arterioles through the production of superoxide from NADPH oxidase, which is linked to JNK and p38 kinase. The results suggested that ER stress is instrumental in B(e)P-induced endothelial dysfunction and that genistein and RSV might preserve endothelial function.

DOI： 10.1167/iovs.17-21925

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記述言語：英語  

Purpose: To identify any significant correlations between retinal circulatory parameters and serum concentrations of omentin-1, a novel adipokine produced by adipocytes, in patients suffering from type 2 diabetes mellitus. Methods: Eighty-seven patients suffering from type 2 diabetes and incipient diabetic retinopathy (DR) were analyzed and further divided into two groups according to sex. We compared the patients' retinal circulatory parameters measured with laser Doppler velocimetry and serum omentin-1 concentrations. Results: The plasma omentin-1 concentrations were related positively to the retinal blood flow (RBF) (r = 0.212; P = 0.048) and primarily with female sex (r = 0.288; P = 0.06) and negatively to the retinal arterial vascular resistance (RVR) (r = -0.218; P = 0.043). Moreover, the plasma omentin-1 concentration was modestly but not significantly positively related to the blood velocity. Multiple regression analysis showed that the serum omentin-1 level contributed independently and negatively to the RVR. Conclusions: Increased concentrations of plasma omentin-1 might be linked to elevated RBF levels probably through elevated blood velocity in patients suffering from type 2 diabetes with incipient DR, especially in female patients, which warrants further investigation.

DOI： 10.1167/iovs.17-22030

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記述言語：英語  

Laser speckle flowgraphy (LSFG) is an ophthalmologic equipment that qualitatively detects the blood flow of the optic nerve head, which is known to be related with cerebral microcirculation. LSFG can also measure the mean blur rate, which quantitatively calculates the blood flow. We aimed to assess the utility of LSFG in the evaluation of cerebral perfusion during aortic surgery under hypothermic circulatory arrest with retrograde and antegrade cerebral perfusion. Two patients underwent total arch replacement for aneurysm. The blood flow of the optic nerve head was monitored with LSFG and the mean blur rate value was measured during the surgery. The LSFG could detect the blood flow quantitatively in the optic nerve head during both retrograde and antegrade cerebral perfusion; and the value was correlated with rSO2 value.

DOI： 10.1007/s11748-016-0727-z

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記述言語：英語  

BACKGROUND: The correlation between the short- and long-term effects of intravitreal ranibizumab (IVR) on macular edema after branch retinal vein occlusion (BRVO) remains unclear. We assessed the correlation between the short- and long-term effects of IVR on macular edema after BRVO. METHODS: Twenty-one eyes with macular edema after BRVO were enrolled in this prospective observational study. We measured the foveal thickness (FT) and the best-corrected visual acuity (BCVA) before, 1 day after, and 1 month after IVR (0.5 mg) and then at least every 2 months thereafter until 6 months after the injection. If the macular edema recurred, another injection was administered. The primary endpoint was the change from baseline in the BCVA (ΔVA). RESULTS: The mean logarithm of the minimum angle of resolution VA improved significantly (p = 0.01, p < 0.0001, respectively) after 1 day from 0.65 ± 0.28 to 0.51 ± 0.21 (20/89 to 20/63, Snellen equivalent) and after 6 months to 0.29 ± 0.24 (20/39, Snellen equivalent). The mean FT decreased significantly (p < 0.0001) after 1 day from 482 ± 85 μm to 349 ± 75 μm and after 6 months to 305 ± 84 μm. The 1-day VA was significantly (r = 0.68, p = 0.0007) positively correlated with the 6-month VA. The 1-day ΔVA was significantly (r = 0.79, p < 0.0001) positively correlated with the 6-month ΔVA. CONCLUSIONS: The short-term effects of IVR may predict the long-term effects of IVR in macular edema secondary to BRVO. TRIAL REGISTRATION: Trial registration number: UMIN000027003 . Retrospectively registered. (April/15/2017).

DOI： 10.1186/s12886-017-0485-4

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記述言語：英語  

DOI： 10.1053/j.jvca.2016.09.012

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記述言語：英語  

Purpose: To evaluate the retinal microcirculation using a segmental-scanning Doppler optical coherence tomography (DOCT) flowmeter in a patient with Takayasu's arteritis (TA) with aortic valve regurgitation (AR). Observations: We measured the retinal blood velocity (V), retinal blood flow (RBF), and retinal blood velocity profiles (RBVP) of the major retinal arterioles using a DOCT flowmeter. The arteries were measured at the straight portion 1 disc diameter from the optic disc. Horizontal velocity profiles were extracted to evaluate the RBVP during one cardiac cycle. A patient with TA with stage 2 Takayasu retinopathy (TR) and AR, had normal RBF and V, and the RBVP had a parabolic pattern in the systolic phase. However, the V was very slow and the RBVP had an abnormal pattern in the diastolic phase. Conclusions and importance: The current study showed for the first time that segmental-scanning DOCT flowmeter enables evaluation of an abnormal flow pattern of the RVBP in the retinal arterioles in a patient with TA and AR. Measurement of the retinal arterial blood flow may detect aortic valve dysfunction and shed light on the pathogenesis of TR.

DOI： 10.1016/j.ajoc.2016.12.020

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記述言語：英語  

BACKGROUND: The short-term effects of intravitreal ranibizumab (IVR) on diabetic macular edema (DME) remains unclear. We assessed the short-term effects of IVR on DME. METHODS: Eighteen eyes of 14 patients with DME were enrolled in this prospective interventional case series. After intravitreal ranibizumab was injected into treatment-naïve eyes with DME, we measured the foveal thickness (FT) before and 2 h, 1 day, 1 week, and 1 month later and the best-corrected visual acuity (BCVA) at all times except 2 h and compared the changes to baseline (ΔFT and ΔVA). RESULTS: The mean FT decreased significantly (p < 0.0001) from 452 ± 77 to 429 ± 65 microns after 2 h. The mean logarithm of the minimum angle of resolution BCVA improved significantly (p = 0.032) after 1 month from 0.41 ± 0.24 to 0.32 ± 0.21 (20/51 to 20/42, Snellen equivalent). The ΔFT after 2 h was significantly (r = 0.53, p = 0.025) correlated with the ΔFT after 1 month. The ΔVA after 1 day was significantly (r = 0.59, p = 0.01) correlated with the ΔVA after 1 month. CONCLUSIONS: The structural effects of IVR for DME occurred within 2 h, whereas the functional effects occurred after 1 month. The short-term effects (within 1 day) of IVR may predict the therapeutic outcome 1 month after IVR in patients with DME. TRIAL REGISTRATION: The trial registration number: UMIN000026118 (Feb/13/2017). Retrospectively registered.

DOI： 10.1186/s12886-017-0420-8

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記述言語：英語  

PURPOSE: The effect of combination therapy using intravitreal ranibizumab (IVR) injections and short pulse focal/grid laser photocoagulation was evaluated for the treatment of diabetic macular edema (DME). METHODS: The current investigation was a preliminary single-arm, open-label, prospective clinical study conducted on 21 eyes at 4 sites in Japan. Treatment protocol consisted of two phases. The induction IVR phase included two monthly IVRs followed by PRN IVR phase in which additional IVR was administered if the central macular thickness (CMT) exceeded 300 μm. One week after each IVR in both phases, short pulse focal/grid laser was delivered to treat residual leakage outside of the fovea (>500 μm) and reduce edema fluid influx. At the 6-month endpoint, the effects of treatment were examined in terms of best corrected visual acuity (BCVA), CMT, and required number of IVR injections in eyes with or without perifoveal leaking microaneurysms (MAs). RESULTS: In eyes with initial BCVA ≤70 letters, mean BCVA was significantly ameliorated by 7.0 ± 7.4 letters (P = 0.0324) and mean CMT improved significantly by 174.8 ± 105.0 µm (P = 0.0005). Both BCVA improvement (P = 0.8693) and CMT reduction (P = 0.9336) were comparable between MA(-) and MA(+) groups. The MA(-) group required significantly fewer PRN-IVR injections than did the MA(+) group over the 6-month study period (mean 3.4 ± 1.6 vs. 5.3 ± 0.9, median 3.0 vs. 5.5; P = 0.0229). CONCLUSIONS: Short pulse focal/grid laser photocoagulation could reduce the number of IVR injections required to resolve macular edema and increase BCVA in a possible mechanism of reduced influx of edema fluid into the foveal area in eyes without apparent perifoveal microaneurysms.

DOI： 10.1007/s10384-016-0483-8

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記述言語：英語  

Purpose: Because blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells, we investigated the effects of fluid shear stress on cultured human corneal epithelial cells (HCECs). Methods: The HCECs were exposed to shear stress (0, 1.2, 12 dyne/cm2) with the parallel-plate type of flow chamber. Wound healing, cellular proliferation, growth factor expression, TGF-β1 concentration in the culture supernatant, and phosphorylation of SMAD2 were investigated. Results: Monolayers of HCECs exposed to shear stress had delayed wound healing and decreased proliferation compared with those of the static control (0 dyne/cm2). With increasing shear stress, TGF-β1 expression and phosphorylation of SMAD2 increased significantly, but the levels of total TGF-β1 in the culture supernatant decreased significantly. Delayed wound healing, decreased proliferation, and phosphorylation of the SMAD2 by shear stress were canceled out with a TGF-β receptor inhibitor. Conclusions: Fluid shear stress on the HCECs affected TGF-β signaling, which was associated with delayed wound healing. Mechanical stress by blinking might involve TGF-β signaling, and activation of TGF-β might be a key factor in wound healing of the corneal epithelium. Further studies should investigate the molecular mechanism of shear stress-induced activation of TGF-β.

DOI： 10.1167/iovs.16-20638

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記述言語：英語  

Purpose: To characterize the morphology of neovascularization at the disc (NVD) and neovascularization elsewhere (NVE) in treatment-naïve or previously treated proliferative diabetic retinopathy (PDR) patients using optical coherence tomography (OCT) angiography. Methods: En face OCT angiograms of NVD/NVE in 40 eyes of 33 patients with PDR were acquired using RTVue XR Avanti OCT. The morphology of NVD/NVE on OCT angiograms was evaluated, and the activity was determined by biomicroscopy and fluorescein angiography (FA). In 12 eyes that were treated or treatment-naïve, changes in the morphology and vessel area of NVD/NVE before and after panretinal photocoagulation (PRP) were investigated. Results: Twenty eyes had treatment-naïve PDR, whereas 20 eyes were previously treated with PRP. All treatment-naïve NVD/NVE had remarkable (i.e., active) leakage in early-phase FA. Ninety-five percent of treatment-naïve NVD/NVE observed by OCT angiography had exuberant vascular proliferation (EVP), identified as irregular proliferation of fine (smaller-caliber) new vessels; whereas, the presence of EVP in previously treated eyes (13/20) was significantly less than in treatment-naïve eyes (65% vs. 95%, P = 0.043). The remaining seven treated eyes had pruned NVD/NVE without EVP, observed as fibrotic changes or faint (inactive) leakage in FA. The vessel areas of NVD/NVE significantly decreased following PRP (n = 12, P = 0.019), and NVD/NVE morphology showed pruning and decreased EVP. Conclusions: Exuberant vascular proliferation on OCT angiograms should be considered as an active sign of neovascularization; therefore, morphologic evaluation of neovascularization using OCT angiography may be useful to estimate the activity of each neovascularization in eyes with PDR.

DOI： 10.1167/iovs.16-20210

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記述言語：英語  

Purpose: To report the detailed macular morphology documented by spectral-domain optical coherence tomography (SD-OCT) in a patient with retinitis pigmentosa (RP) and diabetic retinopathy (DR). Observations: A 54-year-old man with a hemoglobin A1c level of 11.4% was referred for decreased visual acuity (VA) bilaterally (right eye, 20/100; left eye, 20/40). Funduscopy showed typical retinal findings of RP bilaterally. The macular area of both fundi showed retinal dot-and-blot hemorrhages, hard exudates. Time-domain OCT revealed macular edema in the right eye. The patient was diagnosed with RP accompanied by DR bilaterally. Five years after the first visit, the BCVAs remained 20/100 in the right eye and 20/40 in the left eye. SD-OCT showed that the retinas were thinner temporal to the maculas. The external limiting membrane line (ELM) and the ellipsoid zone of the photoreceptors line (EZ) was not visible in the foveal region in the right eye and temporal to the macula in both eyes. The image revealed the characteristic intraretinal and intrachoroidal hyrerreflective foci, the number of which increased corresponding to the extent of the disappearance of the ELM and EZ line with thinning of the outer nuclear layer (ONL). In addition, the image also showed a great number of the hyperreflective foci in the ONL and the choriocapillaris in the foveal region in the right eye compared with the left eye. Conclusions: In the current case, the SD-OCT findings suggested that the characteristic hyrerreflective foci clinically observed in the fundi of a patient with RP accompanied by DR are present in the retinal layers and the choroid. In addition, the foci in the retinal and choroidal layers in the foveal region may increase as vision declines corresponding to the disappearance of the ELM and EZ line.

DOI： 10.1016/j.ajoc.2016.04.002

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1167/iovs.15-19038

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

Purpose: To report a case of posttraumatic hypotonic maculopathy who received transscleral suturing of ciliary body guided by anterior segment optical coherence tomography (AS-OCT). Case: A 60-year-old male was referred to us for luxated intraocular lens (lOL). He has suffered penetrating injury in the right eye 23 years before. He received IOL implantation 9 years later. The IOL luxated 5 years later after blunt trauma. He received IOL implantation 5 months before. He had visual acuity of 1.2 with intraocular pressure (IOP) of 9 mmHg. Findings and Clinical Course: Visual acuity was 0.5 right with IOP of 5 mmHg. The right eye showed findings of hypotensive maculopathy. Gonioscopy showed cyclodialysis from 2 to 4:30 o'clock in the right eye. AS-OCT showed the presence of cyclodialysis in a wider range than was observed by conventional gonioscopy. The right eye received trasscleral suturing of ciliary body. Cyclodialysis and hypotony maculopathy disappeared after surgery with visual acuity of 1.0 and IOP of 10 mmHg. Conclusion: AS-OCT was useful in the evaluation of traumativc cyclodialysis before and after surgery.

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記述言語：英語  

Purpose: To investigate the role of endothelin-1 (ET-1) in retinal glial cells in regulating retinal blood flow (RBF) during hyperoxia in cats. Methods: We measured the vessel diameter (D), blood velocity (V), and blood flow (F) simultaneously in first-order retinal arterioles using a laser Doppler velocimetry system. The animals were under general anesthesia during hyperoxia (100% oxygen) for 10 minutes 24 hours after intravitreal injection of L-2-aminoadipic acid (LAA), a gliotoxic compound, or diluted hydrochloric acid (0.01 N) used as the vehicle control. We also measured the changes in the RBF after intravitreal injection of BQ-123, a specific ET type A receptor antagonist, in LAA-treated eyes. To examine if endothelin-converting enzyme-1 (ECE-1), as an ET-1-generating enzyme located in retinal glial cells, immunohistochemical examinations with costaining of antiglial fibrillary acidic protein (GFAP) antibody and anti-ECE-1 antibody were performed in whole-mount retinas. Results: During hyperoxia, the decreases in D, V, and F in response to hyperoxia were attenuated significantly (P < 0.01 for all comparisons) in the LAA-treated eyes compared with the vehicle control (LAA, D, -8.5 ± 1.5%; V, -13.8 ± 1.5%; F, -27.8 ± 3.0% versus vehicle control, D, -16.8 ± 1.3%; V, -26.3 ± 2.0%; F, -48.9 ± 2.4%). In LAA-treated eyes, intravitreal injections of BQ-123 did not change the rate of hyperoxia-induced RBF compared to LAA-treated eyes. The anti-ECE-1 antibody was costained with anti-GFAP antibody in the whole-mount retinas. Conclusions: The current findings suggest that retinal glial ET-1 may play an important role in regulating RBF during hyperoxia in cats.

DOI： 10.1167/iovs.16-19599

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記述言語：英語  

PURPOSE: To assess the short-term effect of intravitreal ranibizumab (IVR) on macular edema after branch retinal vein occlusion. METHODS: Twenty-three eyes with macular edema after branch retinal vein occlusion were enrolled in a prospective observational study. After administering one IVR injection (0.5 mg) for the first time, the authors measured the foveal thickness (FT) before and 2 hours, 1 and 3 days, 1 week, and 1 month later and the best-corrected visual acuity at all times except 2 hours, and determined the changes from baseline (ΔFT and ΔVA). RESULTS: The mean FT decreased significantly (P < 0.0001) from 522 ± 131 μm to 458 ± 96 μm after 2 hours. The mean logarithm of the minimum angle of resolution (logMAR) visual acuity improved significantly (P < 0.05) after 1 day from 0.69 ± 0.40 to 0.55 ± 0.34 (20/98-20/70, Snellen equivalent). The ΔFT after 2 hours was significantly positively correlated with the ΔFT after 1 week (r = 0.76, P < 0.001) and 1 month (r = 0.67, P < 0.001). The ΔVA after 1 day was correlated positively with the ΔVA after 1 week (r = 0.80, P < 0.001) and 1 month (r = 0.59, P < 0.01). CONCLUSION: Structural and functional effects of IVR for branch retinal vein occlusion occurred within 1 day. The short-term effects of IVR may predict the outcome of the therapy at 1 week and 1 month after IVR in macular edema secondary to branch retinal vein occlusion.

DOI： 10.1097/IAE.0000000000000991

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記述言語：英語  

Purpose: To clarify the area of retinoschisis by X-linked juvenile retinoschisis (XLRS) using swept-source optical coherence tomography (SS-OCT) en face images. Observations: We report two cases of XLRS in the same family. The patients presented with bilateral blurred vision. The posterior segment examination showed a spoked-wheel pattern in the macula. SS-OCT cross-sectional images revealed widespread retinal splitting at the level of the inner nuclear layer bilaterally. We diagnosed XLRS. To evaluate the area of retinoschisis, we obtained en face SS-OCT images, which clearly visualized the area of retinoschisis seen as a sunflower-like structure in the macula. Conclusion and Importance: We report the findings on en face SS-OCT images from patients with XLRS. The en face images using SS-OCT showed the precise area of retinoschisis compared with the SS-OCT thickness map and are useful for managing patients with XLRS.

DOI： 10.1016/j.ajoc.2016.03.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. We quantitatively analyzed the features of a radial peripapillary capillary (RPC) network visualized using wide-field montage optical coherence tomography (OCT) angiography in healthy human eyes.
METHODS. Twenty eyes of 20 healthy subjects were recruited. En face 3 3 3-mm OCT angiograms of multiple locations in the posterior pole were acquired using the RTVue XR Avanti, and wide-field montage images of the RPC were created. To evaluate the RPC density, the montage images were binarized and skeletonized. The correlation between the RPC density and the retinal nerve fiber layer (RNFL) thickness measured by an OCT circle scan was investigated.
RESULTS. The RPC at the temporal retina was detected as far as 7.6 +/- 0.7 mm from the edge of the optic disc but not around the perifoveal area within 0.9 +/- 0.1 mm of the fovea. Capillary-free zones beside the first branches of the arterioles were significantly (P &lt; 0.0001) narrower than those beside the second ones. The RPC densities at 0.5, 2.5, and 5 mm from the optic disc edge were 13.6 +/- 0.8, 11.9 +/- 0.9, and 10.4 +/- 0.9 mm(-1). The RPC density also was correlated significantly (r = 0.64, P &lt; 0.0001) with the RNFL thickness, with the greatest density in the inferotemporal region.
CONCLUSIONS. Montage OCT angiograms can visualize expansion of the RPC network. The RPC is present in the superficial peripapillary retina in proportion to the RNFL thickness, supporting the idea that the RPC may be the vascular network primarily responsible for RNFL nourishment.

DOI： 10.1167/iovs.15-18877

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記述言語：英語  

PURPOSE: The visual outcome after vitrectomy for proliferative diabetic retinopathy (PDR) is often poor. Bilateral vitrectomy has been especially associated with a poor visual prognosis in patients with PDR. The authors investigated the systemic risk factors for PDR requiring bilateral vitrectomy compared with unilateral vitrectomy. METHODS: The authors retrospectively reviewed 86 consecutive patients with Type 2 diabetes mellitus with PDR who underwent vitrectomy. These patients were divided into 2 groups: bilateral vitrectomy within 1 year (n = 25) and unilateral vitrectomy (n = 61). The authors compared the systemic risk factors: age, sex, duration of diabetes, hemoglobin A1c, body mass index, estimated glomerular filtration rate, uric albumin, hypertension, dyslipidemia, history of ischemic heart disease, arteriosclerosis obliterans, and smoking. RESULTS: There were significantly more cases with severe renal dysfunction in the bilateral vitrectomy group compared with the unilateral one (estimated glomerular filtration rate <30 mL/minute/1.73 m; bilateral cases = 5/25; unilateral cases = 2/61; P = 0.02). CONCLUSION: The authors found that severe renal dysfunction may be a risk factor in PDR requiring bilateral vitrectomy, indicating that careful attention needs to be paid to prevent the progression of diabetic retinopathy to severe PDR in the other eye if patients have severe unilateral PDR and severe renal dysfunction.

DOI： 10.1097/IAE.0000000000000886

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記述言語：英語  

PURPOSE: To study retinal blood flow (RBF) measurement reproducibility using segmental-scanning Doppler optical coherence tomography (DOCT) in vitro in glass capillaries and in vivo in anesthetized cats. METHODS: As a preliminary study, the flow rates of human blood through glass capillaries were changed by using an infusion pump and measured at 13 preset velocities by DOCT. For in vivo measurement, the cats were anesthetized using sevoflurane. The flow in the parent vessel was compared with the sum of the flow values in the two daughter vessels. The RBF was measured using two different instruments: bidirectional laser Doppler velocimetry (LDV) and DOCT. The reproducibility of the measurements was assessed by calculating the coefficients of variation (CVs) for repeated measurements of RBF at the superior retinal arterioles and venules. RESULTS: In vitro, the flow velocities measured by DOCT agreed well with the preset velocities. In vivo, the flow in the parent vessel agreed with the sum of the flow values in the two daughter vessels. In addition, there were no significant differences in the mean averaged CVs of the RBF in both the arterioles and venules between LDV and DOCT. CONCLUSIONS: The newly developed segmental-scanning DOCT revealed the accuracy of the measurement in in vitro glass capillaries and reproducibility of the measurements of blood velocity in both the retinal arterioles and venules in anesthetized cats.

DOI： 10.1167/iovs.15-18303

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記述言語：英語  

The aim of the current pilot study is to investigate the efficacy of a novel enhanced vitreous imaging (EVI) in primary macular holes (MHs) using a spectral-domain optical coherence tomography (SD-OCT). Thirty-four eyes of 32 consecutive patients with a MH were examined in one time cross-sectional study. The vitreomacular interface was assessed using SD-OCT with conventional and EVI technique. Twenty-three of the 34 eyes did not show a Weiss ring, and in 22 of those, we observed a MH with an open roof or operculum and a detached posterior vitreous cortex with conventional vitreous imaging. Using EVI-OCT, we visualized the reflection of the posterior vitreous with a vitreopapillary attachment. One of the 23 eyes without a Weiss ring had a central round retinal defect without an operculum, and the conventional SD-OCT showed an empty vitreous, suggesting a complete posterior vitreous detachment. However, the EVI-OCT revealed the reflection of the posterior vitreous, and the cortex appeared to still be completely attached. In all the 23 eyes without a Weiss ring, EVI-OCT detected the reflection of the posterior vitreous and vitreopapillary attachment. In all 11 eyes with a Weiss ring (stage 4 hole), EVI-OCT showed an optically empty space in the posterior vitreous cavity without a vitreopapillary attachment. EVI-OCT may be a new reliable method for preoperative evaluations to determine the presence or absence of a complete posterior vitreous detachment in macular diseases with an indistinct Weiss ring.

DOI： 10.1007/s10792-015-0126-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1167/iovs.15-18813

記述言語：英語  

PURPOSE: To examine the long-term effects of cigarette smoking on retinal circulation in patients with type 2 diabetes. METHODS: Seventy-four patients with type 2 diabetes mellitus and minimal (no or mild nonproliferative) diabetic retinopathy (DR) were evaluated. These patients with type 2 diabetes were divided into three groups based on their smoking history: current smokers (n = 19), past smokers (n = 20), and never smoked (n = 35). The retinal circulatory parameters were measured with laser Doppler velocimetry and were compared among the groups. RESULTS: There were significant decreases in the retinal blood flow (RBF; 8.9 ± 2.9 vs. 11.6 ± 3.1 μL/min, P = 0.009) with decreased blood velocity (V; 29.6 ± 6.8 vs. 37.8 ± 9.0 mm/s, P = 0.003) but no difference in the vessel diameter (D; 112.0 ± 11.9 vs. 113.7 ± 8.6 μm, P = 0.57) in the current smokers compared with those who never smoked. There were no differences in the RBF, blood V, and vessel D in the past smokers compared with those who never smoked and current smokers. Multiple regression analysis showed that the creatinine level was correlated negatively with the RBF and that current smoking was significantly and independent correlated with decreased RBF. CONCLUSIONS: Our results indicated that the blood V and RBF in the retinal arterioles may decrease in patients with type 2 diabetes who are chronic smokers, suggesting that chronic smoking may be associated with decreased RBF, probably via lower blood V in the retinal arterioles in early-phase DR.

DOI： 10.1167/iovs.15-18813

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: To determine whether water-dispersible hesperetin (WD-Hpt) can prevent degeneration of ganglion cell neurons in the ischemic retina. METHODS: Ischemia reperfusion (I/R) injury was induced by increasing the intraocular pressure of mice to 110 mmHg for 40 min. Mice received daily intraperitoneal injections with either normal saline (NS, 0.3 ml/day) or WD-Hpt (0.3 ml, 200 mg/kg/day). Reactive oxygen species (ROS) was assessed by dihydroethidium and nitrotyrosine formation. Inflammation was estimated by microglial morphology in the retina. Lipopolysaccharide (LPS)-stimulated BV-2 cells were used to explore the anti-inflammatory effect of WD-Hpt on activated microglia by quantifying the expression of IL-1β using real-time quantitative reverse transcription-polymerase chain reaction. Ganglion cell loss was assessed by immunohistochemistry of NeuN. Glial activation was quantified with glial fibrillary acidic protein (GFAP) immunoreactivity. Apoptosis was evaluated with a terminal deoxynucleotidyl transferase (TUNEL) assay and immunohistochemistry of cleaved caspase-3. Phosphorylation of extracellular signal-regulated kinase (p-ERK) was surveyed by western blotting. RESULTS: WD-Hpt decreased I/R-induced ROS formation. WD-Hpt alleviated microglial activation induced by I/R and reduced mRNA levels of IL-1β in LPS-stimulated BV-2. I/R resulted in a 37% reduction in the number of ganglion cells in the NS-treated mice, whereas the reduction was only 5% in the WD-Hpt-treated mice. In addition, WD-Hpt mitigated the immunoreactivity of GFAP, increased expression of cleaved caspase-3, increased number of TUNEL positive cells and p-ERK after I/R. CONCLUSIONS: WD-Hpt protected ganglion cells from I/R injury by inhibiting oxidative stress and modulating cell death signaling. Moreover, WD-Hpt had an anti-inflammatory effect through the suppression of activated microglia.

DOI： 10.1007/s10384-015-0415-z

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記述言語：英語  

PURPOSE: To report a case of retinal cavernous hemangioma documented by spectral domain optical coherence tomography and retro-mode retinal imaging by confocal scanning laser ophthalmoscope. METHODS: Clinical examination, fluorescein angiography, spectral domain optical coherence tomography, and scanning laser ophthalmoscope retro-mode imaging were performed. RESULTS: Fundus examination of the left eye of an asymptomatic 39-year-old woman showed an irregularly elevated dark red lesion with a cluster of various-sized saccular aneurysms. The retinal cavernous hemangioma lesions were in the upper vascular arcade. A late-phase fluorescein angiography image showed a typical finding, known as fluorescence capping, characterized by incomplete perfusion because of plasma-erythrocyte separation, which was seen in some larger aneurysms. Spectral domain optical coherence tomography showed that various-sized dilated cystic spaces corresponded to the aneurysms. The image showed the horizontal line, which corresponded to the fluorescence capping in some larger aneurysms. Scanning laser ophthalmoscope retro-mode images showed the individual sizes and septum of the aneurysms. The image also showed the characteristic dots-and-lines pattern around the retinal cavernous hemangioma at the corresponding area of inner retinoschisis attributed to the aneurysms without outer retinoschisis on the spectral domain optical coherence tomography images. CONCLUSION: Spectral domain optical coherence tomography and scanning laser ophthalmoscope retro-mode imaging may be useful for evaluating the pathophysiologic features and the full extent of the retinal cavernous hemangioma.

DOI： 10.1097/ICB.0000000000000267

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記述言語：英語  

PURPOSE: To report the detailed changes in the macular morphology documented by spectral domain optical coherence tomography in a 74-year-old woman with macular hole (MH) formation after vitreomacular detachment with an operculum. METHODS: History and clinical examinations included slit-lamp biomicroscopy, best-corrected visual acuity, color fundus photography, and spectral domain optical coherence tomography. RESULTS: The patient was referred for decreased vision in the left eye (visual acuity, right eye, 20/20; left eye, 20/50). Spectral domain optical coherence tomography showed a full-thickness MH in the left eye. The right eye had a lamellar MH, and the photoreceptor inner/outer segment line was uninterrupted beneath the central fovea. The right eye had vitreomacular detachment with a small round operculum suggestive of an elevated inner foveal retina. Thirty-seven months after the initial visit, the patient returned with visual acuity in the right eye that had decreased to 20/50 and a full-thickness MH had developed in the presence of vitreomacular detachment. An epiretinal membrane appeared nasal to the fovea, and the macular surface had a triangular dimple beneath the membrane. A large retinal schisis developed nasal to the hole. A tightrope-like structure bridged the MH edges. CONCLUSION: In this case, the MH resulted from the tangential traction caused by the epiretinal membrane after vitreomacular detachment developed; the MH was accompanied by a small round operculum, a retinal dimple beneath the membrane, and a tightrope-like structure that bridged the hole edges. The operculum likely comprised a detached inner foveal retina alone and did not include retinal photoreceptor cells.

DOI： 10.1097/ICB.0000000000000158

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To investigate how glial cells participate in retinal circulation during flicker stimulation in cats.
METHODS. Using laser Doppler velocimetry, we measured the vessel diameter and blood velocity simultaneously and calculated the retinal blood flow (RBF) in feline first-order retinal arterioles. Twenty-four hours after intravitreal injections of L-2-aminoadipic acid (LAA), a gliotoxic compound, and the solvent of 0.01 N hydrochloric acid as a control, we examined the changes in RBF in response to 16-Hz flicker stimulation for 3 minutes. We also measured the changes in RBF 2 hours after intravitreal injection of Nx-propyl-L-arginine (L-NPA), a selective neuronal nitric oxide synthase inhibitor, in LAA-treated eyes. To evaluate the effects of LAA on retinal neuronal function, ERGs were monitored. Immunohistochemical examinations were performed.
RESULTS. In LAA-treated eyes, histologic changes selectively occurred in retinal glial cells. There were no significant reductions in amplitude or elongation of implicit time in ERG after LAA injections compared with controls. In control eyes, the RBF gradually increased and reached the maximal level (53.5% +/- 2.5% increase from baseline) after 2 to 3 minutes of flicker stimulation. In LAA-treated eyes, the increases in RBF during flicker stimulation were attenuated significantly compared with controls. In LAA-treated eyes 2 hours after injection of L-NPA, flicker-evoked increases in RBF decreased significantly compared with LAA-treated eyes.
CONCLUSIONS. The current results suggested that increases in RBF in response to flicker stimulation were regulated partly by retinal glial cells.

DOI： 10.1167/iovs.15-17676

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3109/02713683.2014.971930.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.exer.2015.07.008

記述言語：英語  

PURPOSE: We evaluated the effect of hemodialysis on the choroidal thickness in patients with and without diabetes who have end-stage kidney disease (ESKD). METHODS: Forty-one patients with ESKD were recruited and divided into two groups: those with ESKD due to diabetic nephropathy (DM group, 37 eyes of 20 patients) and those with nondiabetic ESKD (NDM group, 40 eyes of 21 patients). Using spectral-domain optical coherence tomography (SD-OCT), the subfoveal choroidal thickness (SCT) was measured before and after hemodialysis, and the change ratio (ΔSCT [%]) was calculated. RESULTS: The SCT decreased in all eyes after hemodialysis. The ΔSCT value in the DM group (-12.6 ± 2.7%) was significantly (P = 0.00027) larger than that in the NDM group (-6.9 ± 2.3%). Moreover, the ΔSCT per body fluid removal (BFR [L]) in the DM group was significantly (P = 0.013) greater than in the NDM group. In the DM group, the mean ΔSCT in the eyes treated with panretinal photocoagulation (PRP; n = 19) was significantly (P = 0.035) larger than that in eyes not treated with PRP (n = 18). The relationship between the ΔSCT and BFR was not significant (R² = 0.0038, P = 0.80) in the DM group but was significant (R² = 0.54, P = 0.00013) in the NDM group. CONCLUSIONS: The current results may reflect that systemic fluid accumulation has a greater effect on the diabetic choroid, probably due to damage to the choroidal vasculature, in patients with ESKD.

DOI： 10.1167/iovs.15-16719

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記述言語：英語  

Ripasudil (K-115) is a novel Rho kinase inhibitor with a potent intraocular pressure-lowering effect. However, it is unclear whether ripasudil affects the retinal blood flow (RBF). We investigated the effect of ripasudil on feline retinal microcirculation. Ripasudil (5 μM, 50 μM or 5 mM; n = 5 each concentration) or vehicle (PBS; n = 5) was injected intravitreally. The vessel diameter (D) and blood velocity (V) were measured by laser Doppler velocimetry simultaneously in the first-order retinal arterioles and the RBF was calculated. The measurements started 5 min before the injection and were performed every 10 min for 120 min. After the intravitreal injection, the retinal circulatory parameters did not change significantly in PBS or 5 μM of ripasudil. The blood V and RBF increased significantly compared to baseline, whereas the vessel D did not change significantly in 50 μM and 5 mM of ripasudil. The V in 50 μM, and the V and RBF in 5 mM of ripasudil significantly increased compared to those in PBS. Intravitreal administration of ripasudil increased the blood V and RBF in cats, suggesting that ripasudil has the potential to improve the retinal blood flow.

DOI： 10.1016/j.exer.2015.07.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: To show that noninvasive in vivo corneal confocal microscopy (IVCM) can make more accurate imaging of the corneal subbasal nerve plexus possible. This diagnostic technique monitors the status of diabetic peripheral neuropathy. However, it is difficult to accurately confirm the corneal area captured by IVCM, which can induce measurement errors. Because the whorl-like characteristic pattern of the corneal subbasal nerve plexus is in the inferocentral cornea, we evaluated whether IVCM images of the whorl-like patterns can accurately evaluate the corneal nerve fibers in diabetic neuropathy. METHODS: Forty-seven patients with diabetes (DM group) and 21 healthy control subjects underwent IVCM examination to compare the characteristics of the corneal subbasal nerve plexus around the central cornea (conventional method) and the whorl-like pattern in the inferocentral cornea (study method). We measured the total corneal nerve fiber and branch length (CNFL). RESULTS: The total CNFL were significantly shorter in the DM group than in the control group and tended to decrease with progression of diabetic retinopathy, nephropathy, neuropathy, and decreased corneal sensation. There was a significant positive correlation between the CNFL values obtained with the conventional method and those obtained with the study method. The coefficient of variation of the CNFL values in the study method was significantly smaller than in the conventional method. CONCLUSIONS: Our findings indicated that IVCM measurements of the whorl-like patterns may accurately define the extent of corneal nerve damage in order to monitor diabetic peripheral neuropathy.

DOI： 10.1167/iovs.15-16609

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記述言語：英語  

PURPOSE: To evaluate how optical coherence tomography (OCT) angiography depicts clinical fundus findings in patients with diabetic retinopathy (DR). DESIGN: Prospective study evaluating imaging technology. METHODS: Forty-seven eyes of 25 patients with DR were scanned using a high-speed 840-nm-wavelength spectral-domain optical coherence tomography instrument (RTVue XR Avanti; Optovue, Inc, Fremont, California, USA). Blood flow was detected using the split-spectrum amplitude-decorrelation angiography algorithm. Fluorescein angiography (FA) images were also obtained in all eyes and the ability to visualize microaneurysms, retinal nonperfused areas, and neovascularization was compared with that of the en face OCT angiograms. RESULTS: In 42 eyes, microaneurysms detected by FA near the macula appeared as focally dilated saccular or fusiform capillaries on OCT angiograms of the superficial and/or deep capillary plexus. Retinal nonperfused areas visualized by FA appeared as lesions with no or sparse capillaries on OCT angiograms. Area measurement of retinal nonperfusion near the macula in 7 eyes revealed a difference between the extent of nonperfused areas in superficial and deep plexuses. In 4 eyes, the vascular structures of neovascularization at the optic disc were clearly visualized on OCT angiograms. Decreases and re-increases of flow in new vessels were quantified in an eye treated with anti-vascular endothelial growth factor. CONCLUSIONS: OCT angiography can clearly visualize microaneurysms and retinal nonperfused areas and enables closer observation of each layer of the retinal capillaries. Quantitative information on new vessels can also be obtained. OCT angiography may be clinically useful to evaluate the microvascular status and therapeutic effect of treatments for DR.

DOI： 10.1016/j.ajo.2015.04.021

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE:

To study the relationship between retinal microcirculation and serum adiponectin, an important adipocytokine secreted by adipocytes, concentrations in patients with type 2 diabetes mellitus.
METHODS:

Using a laser Doppler velocimetry system, we simultaneously measured the retinal blood flow (RBF) values and retinal vessel diameter and blood velocity in 64 consecutive Japanese patients (mean age ± SD, 59.8 ± 10.4 years) with type 2 diabetes with no or mild nonproliferative diabetic retinopathy. We compared the values with the RBF and serum adiponectin concentrations in these patients. The patients were divided into two groups based on sex (33 males, 31 females).
RESULTS:

The plasma adiponectin concentrations were correlated positively with the retinal vessel diameter (r = 0.480; P = 0.005), retinal blood velocity (r = 0.399; P = 0.02), and RBF (r = 0.518; P = 0.002) and correlated negatively with the retinal arterial vascular resistance (r = -0.598; P = 0.0002) in males, but not females, with type 2 diabetes with early-stage diabetic retinopathy. Multiple regression analysis showed that the plasma adiponectin level was independently and positively correlated with RBF and negatively correlated with retinal arterial vascular resistance.
CONCLUSIONS:

Our results indicated that a high concentration of serum adiponectin may be associated with increased RBF, probably via the increased blood velocity and dilated vessel diameter in males with type 2 diabetes with early-phase diabetic retinopathy.

DOI： 10.1167/iovs.15-16447

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of the current pilot study is to investigate the efficacy of a novel enhanced vitreous imaging (EVI) in primary macular holes (MHs) using a spectral-domain optical coherence tomography (SD-OCT). Thirty-four eyes of 32 consecutive patients with a MH were examined in one time cross-sectional study. The vitreomacular interface was assessed using SD-OCT with conventional and EVI technique. Twenty-three of the 34 eyes did not show a Weiss ring, and in 22 of those, we observed a MH with an open roof or operculum and a detached posterior vitreous cortex with conventional vitreous imaging. Using EVI-OCT, we visualized the reflection of the posterior vitreous with a vitreopapillary attachment. One of the 23 eyes without a Weiss ring had a central round retinal defect without an operculum, and the conventional SD-OCT showed an empty vitreous, suggesting a complete posterior vitreous detachment. However, the EVI-OCT revealed the reflection of the posterior vitreous, and the cortex appeared to still be completely attached. In all the 23 eyes without a Weiss ring, EVI-OCT detected the reflection of the posterior vitreous and vitreopapillary attachment. In all 11 eyes with a Weiss ring (stage 4 hole), EVI-OCT showed an optically empty space in the posterior vitreous cavity without a vitreopapillary attachment. EVI-OCT may be a new reliable method for preoperative evaluations to determine the presence or absence of a complete posterior vitreous detachment in macular diseases with an indistinct Weiss ring.

DOI： 10.1007/s10792-015-0126-y

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To study the relationship between retinal microcirculation and serum adiponectin, an important adipocytokine secreted by adipocytes, concentrations in patients with type 2 diabetes mellitus.
METHODS. Using a laser Doppler velocimetry system, we simultaneously measured the retinal blood flow (RBF) values and retinal vessel diameter and blood velocity in 64 consecutive Japanese patients (mean age +/- SD, 59.8 +/- 10.4 years) with type 2 diabetes with no or mild nonproliferative diabetic retinopathy. We compared the values with the RBF and serum adiponectin concentrations in these patients. The patients were divided into two groups based on sex (33 males, 31 females).
RESULTS. The plasma adiponectin concentrations were correlated positively with the retinal vessel diameter (r = 0.480; P = 0.005), retinal blood velocity (r = 0.399; P = 0.02), and RBF (r = 0.518; P = 0.002) and correlated negatively with the retinal arterial vascular resistance (r = -0.598; P = 0.0002) in males, but not females, with type 2 diabetes with early-stage diabetic retinopathy. Multiple regression analysis showed that the plasma adiponectin level was independently and positively correlated with RBF and negatively correlated with retinal arterial vascular resistance.
CONCLUSIONS. Our results indicated that a high concentration of serum adiponectin may be associated with increased RBF, probably via the increased blood velocity and dilated vessel diameter in males with type 2 diabetes with early-phase diabetic retinopathy.

DOI： 10.1167/iovs.15-16447

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1167/iovs.14-15854

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. To investigate how neuronal nitric oxide synthase (nNOS) contributes to regulation of the retinal circulation during rest and flicker stimulation in cats.
METHODS. Using laser Doppler velocimetry, we measured the vessel diameter and blood velocity simultaneously and calculated the retinal blood flow (RBF) in feline first-order retinal arterioles. After intravitreal injections of N omega-Nitro-L-arginine methyl ester (L-NAME), a nonselective NOS inhibitor, and N omega-propyl-L-arginine (L-NPA), a selective nNOS inhibitor, we continuously monitored the retinal circulation without any perturbations for 2 hours. We then examined the changes in the RBF in response to 16-Hz flicker stimuli for 3 minutes at 2 hours after intravitreal injection of phosphate-buffered saline (PBS) as a control, L-NAME, L-NPA, and thromboxane A2 (TXA2) analogue U46619 as a basal tone-adjusted control.
RESULTS. After intravitreal injection of L-NAME and L-NPA, the baseline RBF decreased gradually in a dose-dependent manner. In the PBS group, the RBF increased gradually and reached a maximal level after 2 to 3 minutes of flicker stimuli. After 3 minutes of 16-Hz flicker stimuli, the RBF increased by 53.5% +/- 3.4% compared with baseline. In the L-NAME and L-NPA groups, the increases in RBF during flicker stimulation were attenuated significantly compared with the PBS group. In the TXA2 group, the reduction in the flicker-induced increase in RBF was comparable to that in the PBS group.
CONCLUSIONS. The current results suggested that increased RBF in response to flicker stimulation may be mediated by nitric oxide (NO) production via nNOS activation.

DOI： 10.1167/iovs.14-15854

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1177/1470320314551442

記述言語：英語  

INTRODUCTION: To determine if the serum prorenin level is useful for detecting ocular disease in a non-diabetic population. MATERIALS AND METHODS: We enrolled non-diabetic men (n = 402) and women (n = 349) in our study. We used the antibody-activating direct enzyme kinetic assay of human prorenin to determine serum prorenin levels. We performed multiple regression analysis to determine the factors that affect serum prorenin levels, such as: age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, fasting blood sugar, and HbA1c or estimated glomerular filtration rate. Our study subjects were divided into groups by their ophthalmologic diagnosis. One-way analysis of variance (ANOVA) was performed to detect a significant difference in the serum prorenin levels among the groups. RESULTS: There were no significant differences in serum prorenin levels among the ocular diseases and disorders. The DBP was negatively correlated with serum prorenin levels in men (r = - 0.1992; p = 0.021) and in women (r = - 0.2067; p = 0.031). CONCLUSION: Considering the current results and those of previous studies together, we found that the prorenin value is useful solely for predicting development of diabetic retinopathy in adults.

DOI： 10.1177/1470320314551442

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: To evaluate how the growth of neovascularization elsewhere (NVE) was delineated in an eye with hemicentral retinal vein occlusion (CRVO) using optical coherence tomography (OCT) angiography. PATIENTS AND METHODS: We examined a 64-year-old man diagnosed with hemi-CRVO. The area around the occluded vein was scanned using a spectral-domain OCT device (RTVue XR Avanti). Blood flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Color fundus photography, fluorescein angiography (FA), and OCT angiography examinations were performed at the first visit and at 3 and 6 months postpresentation. RESULTS: At the first visit, FA revealed delayed retinal venous filling and extensive areas of capillary nonperfusion. The patient underwent a trial of intravitreal ranibizumab injection (0.5 mg/0.05 mL) for the treatment of macular edema. At 3 months postpresentation, there was no NVE around the occluded vein in the en-face SSADA image, but at 6 months, NVE appeared on the occluded veins. The en-face SSADA image showed the NVE structure in the fibrovascular membrane on the occluded vein more clearly than FA images. CONCLUSION: OCT angiography clearly visualized the sprouting of NVE in an eye with hemi-CRVO. New findings of the vascular structure of NVE in hemi-CRVO were revealed using the en-face SSADA algorithm.

DOI： 10.2147/IMCRJ.S93702

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記述言語：英語  

PURPOSE: The purpose of this study was to investigate the effects of aging on anteroposterior tortuosity of the retinal vein at the arteriovenous (AV) crossing in healthy subjects. METHODS: We examined 48 eyes of 24 healthy older Japanese subjects (>60 years), and, as controls, 42 eyes of 21 healthy younger Japanese subjects (<30 years). Retinal vein images at the AV crossing were obtained by optical coherence tomography. The depth of the vein was measured vertically from the outer border of the retinal pigment epithelium to the outer vein wall. We defined "m" as the deepest point of the vein at the AV crossing and "M" as the shallowest point. To evaluate the anteroposterior tortuosity of the retinal vein, we calculated the ratio m/M. RESULTS: Mean m, M, and m/M in older subjects were 76.5 ± 13.1 µm, 142.7 ± 21.2 µm, and 0.52 ± 0.09, respectively. In younger control subjects, the values were 64.1 ± 12.6 µm, 139.9 ± 22.4 µm, and 0.46 ± 0.06. The values of "M" were not significantly different between groups, whereas both "m/M" and "m" were significantly (p = 0.021) lower in the older subjects than in the younger subjects. CONCLUSION: Anteroposterior tortuosity of the retinal vein was evaluated based on the maximum and minimum retinal vein depth measurements at the AV crossing using optical coherence tomography. Anteroposterior tortuosity of the retinal vein at the AV crossing is increased with age.

DOI： 10.3109/02713683.2014.971930

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記述言語：英語  

PURPOSE: To clarify the vasodilatory mechanism of unoprostone isopropyl (UI), we examined its effects on the retinal microvascular diameter to determine the dependence on the endothelium and/or smooth muscle to reveal the signaling mechanisms involved in this vasomotor activity. METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded the diametric responses to UI. RESULTS: The retinal arterioles dilated in response to UI in a dose-dependent (100 pM-10 µM) manner. The nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) inhibited UI-induced vasodilation. The large-conductance Ca2+-activated K channel (BKCa channel) blocker iberiotoxin also inhibited UI-induced vasodilation. The residual vasodilation after L-NAME was eliminated with co-administration of iberiotoxin. CONCLUSIONS: UI elicits dilation of the retinal arterioles mediated by NO release and BKCa channel activation.

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE:

To investigate the effect of intravitreal bevacizumab (IVB) injections for macular edema secondary to acute branch retinal vein occlusion on the retinal microcirculation.
METHODS:

The study was a prospective, interventional case series. Central macular thickness using spectral-domain optical coherence tomography and retinal blood flow (RBF) in untreated eyes with macular edema secondary to acute branch retinal vein occlusion in occluded (V1) and opposite venules in affected eyes (V2) and the equivalent venules in contralateral eyes (V3), using laser Doppler velocimetry during follow-up and after IVB injection, were measured.
RESULTS:

In 33 eyes with acute branch retinal vein occlusion of <2 months of duration at the first visit, changes in the retinal microcirculation for 1 month was observed; the macular edema improved spontaneously, and the RBF was unchanged in 15 of 33 eyes, and the RBF increased by 23.3% in 18 eyes with persistent macular edema. Twenty-four eyes received an IVB injection (1.25 mg per 0.05 mL). The RBF did not change significantly during follow-up. In 8 of 24 eyes (33%) with improved macular edema 3 months after the treatment, the average RBF values before injection were significantly higher compared with that of eyes with recurrent edema.
CONCLUSION:

One IVB injection might have little effect on the retinal microcirculation in patients with macular edema secondary to acute branch retinal vein occlusion at least 3 months after the injection. However, the increased RBF in the occluded venules before injection might be associated with improved macular edema after the IVB injection.

DOI： 10.1097/IAE.0000000000000172

記述言語：英語  

PURPOSE: To investigate the effect of intravitreal bevacizumab (IVB) injections for macular edema secondary to acute branch retinal vein occlusion on the retinal microcirculation. METHODS: The study was a prospective, interventional case series. Central macular thickness using spectral-domain optical coherence tomography and retinal blood flow (RBF) in untreated eyes with macular edema secondary to acute branch retinal vein occlusion in occluded (V1) and opposite venules in affected eyes (V2) and the equivalent venules in contralateral eyes (V3), using laser Doppler velocimetry during follow-up and after IVB injection, were measured. RESULTS: In 33 eyes with acute branch retinal vein occlusion of <2 months of duration at the first visit, changes in the retinal microcirculation for 1 month was observed; the macular edema improved spontaneously, and the RBF was unchanged in 15 of 33 eyes, and the RBF increased by 23.3% in 18 eyes with persistent macular edema. Twenty-four eyes received an IVB injection (1.25 mg per 0.05 mL). The RBF did not change significantly during follow-up. In 8 of 24 eyes (33%) with improved macular edema 3 months after the treatment, the average RBF values before injection were significantly higher compared with that of eyes with recurrent edema. CONCLUSION: One IVB injection might have little effect on the retinal microcirculation in patients with macular edema secondary to acute branch retinal vein occlusion at least 3 months after the injection. However, the increased RBF in the occluded venules before injection might be associated with improved macular edema after the IVB injection.

DOI： 10.1097/IAE.0000000000000172

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: Prostacyclin (PGI2) is usually described as an endoEDRFsthelium-derived relaxing factor, but the vasoreactivity to PGI2 in the retinal arterioles and the underlying mechanisms are not fully understood. We examined the effects of PGI2 on the retinal microcirculation using beraprost sodium (BPS), a stable PGI2 analogue, and the signaling mechanisms involved in this vasomotor activity. METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded the diametric responses to BPS. RESULTS: Beraprost sodium elicited dose-dependent (0.1 pM-0.1 μM) vasodilation of the retinal arterioles that was abolished by the PGI2 receptor (IP) antagonist CAY10441. Beraprost sodium-induced vasodilation decreased by 50% after the endothelium was removed and was inhibited by the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) comparable with denudation. Inhibition of soluble guanylyl cyclase by 1H-1,2,4-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and blockage of protein kinase A (PKA) by Rp-8-Br-cAMPS were comparable to L-NAME. Beraprost sodium-induced vasodilation was also inhibited by the nonselective potassium channel inhibitor, tetraethylammonium, and the adenosine triphosphate-sensitive potassium (KATP) channel blocker, glibenclamide. Residual vasodilation in the presence of glibenclamide decreased further with subsequent application of ODQ. CONCLUSIONS: Beraprost sodium, a stable PGI2 analogue, causes vasodilation of the retinal arterioles mediated via the IP receptor. The current findings suggest that BPS elicits endothelium-dependent and -independent dilation of the retinal arterioles mediated by NO induced by activation of PKA in the endothelium and the KATP channel activation in the vascular smooth muscle, respectively.

DOI： 10.1167/iovs.14-14902

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although sphingosine 1-phosphate (S1P), a bioactive lipid derived from activated platelets, has a variety of physiologic effects on vessels, no reports have described the effect of S1P on the retinal circulation. We examined the effect and underlying mechanism of the vasomotor action of S1P on porcine retinal arterioles. The porcine retinal arterioles were isolated, cannulated, and pressurized without flow for in vitro study. S1P-induced diameter changes were recorded using videomicroscopic techniques. S1P elicited concentration-dependent (1 nM-10 μM) vasoconstriction of the retinal arterioles that was abolished by the S1P receptor 2 (S1PR2) antagonist JTE-013. S1P-induced vasoconstriction was abolished by the Rho kinase (ROCK) inhibitor H-1152 and was inhibited partly by the protein kinase C (PKC) inhibitor Gö-6983. The inhibition of phospholipase C by U73122 and L-type voltage-operated calcium channels (L-VOCCs) by nifedipine inhibited S1P-induced vasoconstriction; a combination of both inhibitors abolished S1P-induced vasoconstriction. Furthermore, inhibition of myosin light chain kinase (MLCK) by ML-9 significantly blocked S1P-induced vasoconstriction; further coadministration of ML-9 with H-1152 or Gö-6983 abolished S1P-induced vasoconstriction. The current data suggest that S1P elicits vasoconstriction of the retinal arterioles via S1PR2 in vascular smooth muscle cells and this vasoconstriction may be mediated by the Ca2+ -sensitive pathway via activation of PKC leading to activation of ROCK and the Ca2+ -dependent pathway via activation of L-VOCCs resulting in activation of MLCK.

DOI： 10.1016/j.exer.2014.01.011

記述言語：英語  

Although sphingosine 1-phosphate (S1P), a bioactive lipid derived from activated platelets, has a variety of physiologic effects on vessels, no reports have described the effect of S1P on the retinal circulation. We examined the effect and underlying mechanism of the vasomotor action of S1P on porcine retinal arterioles. The porcine retinal arterioles were isolated, cannulated, and pressurized without flow for in vitro study. S1P-induced diameter changes were recorded using videomicroscopic techniques. S1P elicited concentration-dependent (1 nM-10 μM) vasoconstriction of the retinal arterioles that was abolished by the S1P receptor 2 (S1PR2) antagonist JTE-013. S1P-induced vasoconstriction was abolished by the Rho kinase (ROCK) inhibitor H-1152 and was inhibited partly by the protein kinase C (PKC) inhibitor Gö-6983. The inhibition of phospholipase C by U73122 and L-type voltage-operated calcium channels (L-VOCCs) by nifedipine inhibited S1P-induced vasoconstriction; a combination of both inhibitors abolished S1P-induced vasoconstriction. Furthermore, inhibition of myosin light chain kinase (MLCK) by ML-9 significantly blocked S1P-induced vasoconstriction; further coadministration of ML-9 with H-1152 or Gö-6983 abolished S1P-induced vasoconstriction. The current data suggest that S1P elicits vasoconstriction of the retinal arterioles via S1PR2 in vascular smooth muscle cells and this vasoconstriction may be mediated by the Ca2+ -sensitive pathway via activation of PKC leading to activation of ROCK and the Ca2+ -dependent pathway via activation of L-VOCCs resulting in activation of MLCK.

DOI： 10.1016/j.exer.2014.01.011

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記述言語：英語  

PURPOSE: To investigate the regulatory mechanisms responsible for autoregulation of retinal blood flow (RBF) during periods of decreased ocular perfusion pressure (OPP). METHODS: The effects of acute reductions in OPP on RBF were assessed using laser Doppler velocimetry in cats. The OPP decreased from 90 to 40 mm Hg by increasing the IOP (elevated IOP) or by decreasing the systemic blood pressure via exsanguination (systemic hypotension). The contributions of nitric oxide (NO), adenosine, and/or N-methyl-D-aspartic acid (NMDA) in regulation of the retinal arteriolar hemodynamics during decreased OPP was determined at 120 minutes after intravitreal injection of various inhibitors or PBS. RESULTS: Following PBS injection, the flow velocity decreased in proportion to the decrease in OPP; however, the retinal arteriolar diameter gradually increased. Consequently, the RBF was maintained near baseline levels when the OPP exceeded 70 mm Hg but decreased significantly (P < 0.01) when the OPP fell to less than or equal to 60 mm Hg due to elevated IOP or systemic hypotension. Adenosine receptor blocker 8-(p-sulfophenyl)theophylline, significantly (P < 0.01) enhanced decreases in RBF induced by elevated IOP and systemic hypotension at OPP from 80 to 40 mm Hg, whereas NO synthase inhibitor N(G)-nitro-L-arginine-methyl ester and NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid only significantly (P < 0.01) enhanced reductions in RBF induced by elevated IOP. CONCLUSIONS: These results indicate that adenosine contributes to autoregulation of RBF during systemic hypotension, whereas adenosine, NO, and NMDA receptors autoregulate the RBF after elevated IOP. Different vasoregulatory factors might contribute to autoregulation of RBF after decreases in OPP induced by elevated IOP and systemic hypotension.

DOI： 10.1167/iovs.13-12591

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE:

To investigate the regulatory mechanisms responsible for autoregulation of retinal blood flow (RBF) during periods of decreased ocular perfusion pressure (OPP).
METHODS:

The effects of acute reductions in OPP on RBF were assessed using laser Doppler velocimetry in cats. The OPP decreased from 90 to 40 mm Hg by increasing the IOP (elevated IOP) or by decreasing the systemic blood pressure via exsanguination (systemic hypotension). The contributions of nitric oxide (NO), adenosine, and/or N-methyl-D-aspartic acid (NMDA) in regulation of the retinal arteriolar hemodynamics during decreased OPP was determined at 120 minutes after intravitreal injection of various inhibitors or PBS.
RESULTS:

Following PBS injection, the flow velocity decreased in proportion to the decrease in OPP; however, the retinal arteriolar diameter gradually increased. Consequently, the RBF was maintained near baseline levels when the OPP exceeded 70 mm Hg but decreased significantly (P < 0.01) when the OPP fell to less than or equal to 60 mm Hg due to elevated IOP or systemic hypotension. Adenosine receptor blocker 8-(p-sulfophenyl)theophylline, significantly (P < 0.01) enhanced decreases in RBF induced by elevated IOP and systemic hypotension at OPP from 80 to 40 mm Hg, whereas NO synthase inhibitor N(G)-nitro-L-arginine-methyl ester and NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid only significantly (P < 0.01) enhanced reductions in RBF induced by elevated IOP.
CONCLUSIONS:

These results indicate that adenosine contributes to autoregulation of RBF during systemic hypotension, whereas adenosine, NO, and NMDA receptors autoregulate the RBF after elevated IOP. Different vasoregulatory factors might contribute to autoregulation of RBF after decreases in OPP induced by elevated IOP and systemic hypotension.

DOI： 10.1167/iovs.13-12591

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s10792-012-9707-1

記述言語：英語  

Familial exudative vitreoretinopathy (FEVR) is a rare hereditary vitreoretinal disease that occurs in young patients and results in an avascular peripheral retina, retinal neovascularization, and tractinal retinal detachment. Patients occasionally have concurrent macular diseases. However, the vitreomacular relationship in FEVR remains unclear. We report two cases, a 22-year-old woman (case 1) and a 14-year-old boy (case 2) with FEVR who have the characteristic findings of the disease in the vitreomacular interface and the macular morphology, observed using spectral-domain optical coherence tomography (SD-OCT). In case 1, the best-corrected visual acuity (BCVA) was 20/20 bilaterally. SD-OCT showed a perifoveal posterior vitreous detachment (PVD) with vitreofoveal adhesion in the left eye. In case 2, SD-OCT showed a perifoveal PVD in the right eye (BCVA, 20/30) with numerous small deposits that appeared as rod-shaped attachments perpendicular to the parafoveal face without intraretinal and subretinal materials beneath the posterior hyaloid face that corresponded to white material on the fundus examination. Fluorescein angiography showed a circumferential peripheral avascular area and peripheral neovascularization in both cases. These SD-OCT findings suggested that a perifoveal PVD and small deposits, which appeared as rod-shaped attachments perpendicular to the parafoveal face in patients with FEVR, may carry the risk of macular disease and decreased visual acuity.

DOI： 10.1007/s10792-012-9707-1

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE:
To investigate the relationship between retinal fractal dimensions (Dfs) and retinal circulation, which is impaired in early-stage diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM).
METHODS:
Using a laser Doppler velocimetry system, we measured the retinal vessel diameter (D) and blood velocity (V) and calculated the retinal blood flow (RBF) in the retinal arterioles and venules in 106 eyes (106 patients, mean age ± standard deviation, 58.7 ± 9.8 years). Patients with type 2 DM had no (n = 86) or mild nonproliferative DR (n = 20). The Dfs were measured on the retinal photographs using a semiautomatic computer-based program.
RESULTS:
The average D, V, and RBF in the retinal arterioles and venules were, respectively, 107.9 ± 13.3 and 139.4 ± 20.1 µm, 33.2 ± 7.0 and 22.6 ± 6.1 mm/s and 9.3 ± 2.9 and 10.4 ± 3.8 µl/min. The average Df was 1.4276 ± 0.0193. There was no association between the Df and any retinal circulatory parameters of the retinal arterioles. In contrast, we found significant correlations between the Df and the vessel D (r = 0.37, p = 0.0002) and RBF (r = 0.22, p = 0.026) in the retinal venules.
CONCLUSION:
The Df might be associated with changes in the retinal circulation in patients with type 2 DM.

DOI： 10.3109/02713683.2013.805232.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016

記述言語：英語  

The vascular endothelium responds to shear stress generated by blood flow and changes functions to regulate blood flow and maintain tissue homeostasis. Recently, we found that arteriolar high shear stress leads to increased expression of vasodilatory and antithrombotic genes in human retinal microvascular endothelial cells (HRMECs). However, it is unknown whether low shear stress, which is induced by hypoperfusion particularly in the retinal venules where leukocyte-endothelial interactions mainly occur, affects the retinal endothelial function. We studied the effect of low shear stress on proinflammatory gene expression in HRMECs. The cells were cultured on glass plates and exposed to laminar shear stresses of 0 (static), 1.5 (relatively low flow), and 15 dyne/cm(2) (relatively high flow) for 24 h using parallel plate-type flow-loading devices. The mRNA expressions of adhesion molecules, cytokines and chemokines, and procoagulant factors were evaluated using real-time reverse-transcription polymerase chain reaction. HRMECs exposed to 1.5 dyne/cm(2) significantly up-regulated the mRNA expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. The cells exposed to 1.5 dyne/cm(2) of stress also had increased cytokine/chemokine mRNA expression, i.e., interleukin (IL)-6, IL-8, platelet-derived growth factor-B, and monocyte chemotactic protein-1. Procoagulant factors, i.e., tissue factor and plasminogen activator inhibitor-1 mRNA, increased significantly with exposure to 1.5 dyne/cm(2) of stress. Our results showed that relatively low shear stress causes up-regulation of proinflammatory genes in HRMECs, suggesting that decreased shear stress due to vascular hypoperfusion might change the phenotypic characterization of the retinal vascular endothelium and be associated with leukocyte-endothelial interactions.

DOI： 10.1016/j.exer.2013.10.001

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記述言語：英語  

PURPOSE: To investigate the relationship between retinal fractal dimensions (Dfs) and retinal circulation, which is impaired in early-stage diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM). METHODS: Using a laser Doppler velocimetry system, we measured the retinal vessel diameter (D) and blood velocity (V) and calculated the retinal blood flow (RBF) in the retinal arterioles and venules in 106 eyes (106 patients, mean age ± standard deviation, 58.7 ± 9.8 years). Patients with type 2 DM had no (n = 86) or mild nonproliferative DR (n = 20). The Dfs were measured on the retinal photographs using a semiautomatic computer-based program. RESULTS: The average D, V, and RBF in the retinal arterioles and venules were, respectively, 107.9 ± 13.3 and 139.4 ± 20.1 µm, 33.2 ± 7.0 and 22.6 ± 6.1 mm/s and 9.3 ± 2.9 and 10.4 ± 3.8 µl/min. The average Df was 1.4276 ± 0.0193. There was no association between the Df and any retinal circulatory parameters of the retinal arterioles. In contrast, we found significant correlations between the Df and the vessel D (r = 0.37, p = 0.0002) and RBF (r = 0.22, p = 0.026) in the retinal venules. CONCLUSION: The Df might be associated with changes in the retinal circulation in patients with type 2 DM.

DOI： 10.3109/02713683.2013.805232

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記述言語：英語  

DOI： 10.1001/jamaophthalmol.2013.4686

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The difference in preferences and trends of treatment in each country are important to plan an international interventional clinical study in eastern Asia. Accordingly, we compared the preferences and trends in treatment of diabetic retinopathy in Korea and Japan. METHODS: We obtained answers to questionnaires (49 questions) from 91 ophthalmologists of the Korean Retina Society and 120 ophthalmologists of the Japanese Society of Ophthalmic Diabetology in June/July, 2012. Some of the questions were modified from The Preferences and Trends (PAT) survey of American Society of Retina Specialists. RESULTS: The first choice for a patient with vision of 20/25, clinically significant diabetic macular edema and clear evidence of intraretinal fluid on spectral domain OCT were intravitreal anti-vascular endothelial growth factor agent (31%) in Korea and sub-Tenon steroid (22%) in Japan. The management for a patient with refractory neovascular glaucoma who has closed angle and persistent intraocular pressure elevation (>50 mmHg) were glaucoma drainage implant surgery (74%) in Korea and trabeculectomy (57%) in Japan. CONCLUSION: There were differences in preferences and trends of treatment for diabetic retinopathy between Korea and Japan. The differences need to be considered when planning international clinical studies.

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記述言語：英語  

PURPOSE: Adiponectin, an important adipocytokine secreted by adipocytes, has anti-inflammatory and atheroprotective effects on vascular tissue via the adiponectin receptor (adipoR). However, the action of adiponectin in the retinal microcirculation is unknown. We examined the direct effect and underlying mechanism of the vasomotor action of adiponectin in porcine retinal arterioles. METHODS: Porcine retinal arterioles (internal diameter, 60-90 μm) were isolated, cannulated, and pressurized (55 cmH2O) without flow in this in vitro study. Videomicroscopic techniques were used to record changes in diameter in response to adiponectin. RESULTS: The retinal arterioles dilated in a dose-dependent (0.125-7.5 μg/mL) manner in response to adiponectin. The vasodilation decreased significantly after removal of the endothelium. N(G)-nitro-L-arginine methyl ester (a nitric oxide [NO] synthase inhibitor), 1H-1,2,4-oxadia-zolo[4,3-a]quinoxalin-1-one (a soluble guanylyl cyclase inhibitor), but not wortmannin (a phosphatidylinositol 3-kinase inhibitor) inhibited the effect of adiponectin-induced vasodilation comparable with that of denudation. Pretreatment with compound C, an activated protein kinase (AMPK) inhibitor, partially but significantly reduced vasodilation. Incubation with GW6471, a peroxisome proliferator-activated receptor blocker, did not significantly inhibit vasodilation by adiponectin. AdipoR1 and adipoR2 immunoreactions were observed in the endothelium of retinal arterioles. CONCLUSIONS: Adiponectin elicits mainly endothelium-dependent dilation of the retinal arterioles. Endothelium-dependent vasodilation likely induced by adiponectin results from NO via activation of guanylyl cyclase that is partially dependent on AMPK activity. Understanding the effect of adiponectin on the retinal vasculature may help improve potential therapies for retinal vascular disorders, especially diabetic retinopathy in patients with type 2 diabetes mellitus.

DOI： 10.1167/iovs.13-11756

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE:

Adiponectin, an important adipocytokine secreted by adipocytes, has anti-inflammatory and atheroprotective effects on vascular tissue via the adiponectin receptor (adipoR). However, the action of adiponectin in the retinal microcirculation is unknown. We examined the direct effect and underlying mechanism of the vasomotor action of adiponectin in porcine retinal arterioles.
METHODS:

Porcine retinal arterioles (internal diameter, 60-90 μm) were isolated, cannulated, and pressurized (55 cmH2O) without flow in this in vitro study. Videomicroscopic techniques were used to record changes in diameter in response to adiponectin.
RESULTS:

The retinal arterioles dilated in a dose-dependent (0.125-7.5 μg/mL) manner in response to adiponectin. The vasodilation decreased significantly after removal of the endothelium. N(G)-nitro-L-arginine methyl ester (a nitric oxide [NO] synthase inhibitor), 1H-1,2,4-oxadia-zolo[4,3-a]quinoxalin-1-one (a soluble guanylyl cyclase inhibitor), but not wortmannin (a phosphatidylinositol 3-kinase inhibitor) inhibited the effect of adiponectin-induced vasodilation comparable with that of denudation. Pretreatment with compound C, an activated protein kinase (AMPK) inhibitor, partially but significantly reduced vasodilation. Incubation with GW6471, a peroxisome proliferator-activated receptor blocker, did not significantly inhibit vasodilation by adiponectin. AdipoR1 and adipoR2 immunoreactions were observed in the endothelium of retinal arterioles.
CONCLUSIONS:

Adiponectin elicits mainly endothelium-dependent dilation of the retinal arterioles. Endothelium-dependent vasodilation likely induced by adiponectin results from NO via activation of guanylyl cyclase that is partially dependent on AMPK activity. Understanding the effect of adiponectin on the retinal vasculature may help improve potential therapies for retinal vascular disorders, especially diabetic retinopathy in patients with type 2 diabetes mellitus.

DOI： 10.1167/iovs.13-11756

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

OBJECTIVE: To study the relationship between retinal microcirculation and renal function in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Using a laser Doppler velocimetry system, we obtained the retinal blood flow (RBF) values by simultaneously measuring the retinal vessel diameter and blood velocity. To determine if the RBF is affected in the presence of renal dysfunction, we also evaluated the renal function using the estimated glomerular filtration rate calculated by age and serum creatinine level. RESULTS: We recruited 169 eyes of 169 consecutive Japanese patients with type 2 diabetes, no or minimal diabetic retinopathy, and normo/microalbuminuria (mean age ± SD, 59.0 ± 11.1 years). We divided the patients into four groups based on the stage of chronic kidney disease (CKD) (non-CKD, n = 99; CKD stage 1, n = 22; stage 2, n = 27; stage 3, n = 21). We found significant (P = 0.035) decreases in RBF with decreased vessel diameter (P = 0.017) but no difference in blood velocity (P = 0.54) in stage 3 CKD compared with the non-CKD group. Multiple regression analysis showed that the CKD stage was significantly (P = 0.02) and independently associated with decreased RBF. CONCLUSIONS: Our results indicated that the vessel diameter and RBF in the retinal arterioles decrease in patients with type 2 diabetes with stage 3 CKD, suggesting that impaired renal function might be associated with decreased RBF, probably via constriction of the retinal arterioles, in early-phase diabetic retinopathy.

DOI： 10.2337/dc12-0864

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記述言語：英語  

PURPOSE: Elevated plasma concentration of homocysteine, a sulfur-containing amino acid, is an emerging risk factor for cardiovascular diseases. Recent epidemiologic studies have confirmed that elevated homocysteine levels are associated with ocular vascular diseases; however, the direct effect of homocysteine on ocular microvascular reactivity remains unknown. We investigated whether homocysteine affects endothelium-dependent nitric oxide (NO)-mediated dilation of retinal arterioles and whether oxidative stress and distinct protein kinase signaling pathways are involved in the homocysteine-mediated effect. METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Diameter changes were recorded using videomicroscopy techniques. RESULTS: Intraluminal treatment with homocysteine (1 mM, 180 minutes) significantly attenuated arteriolar dilation in response to the endothelium-dependent NO-mediated agonists bradykinin and A23187 but not in response to the endothelium-independent NO donor sodium nitroprusside. In the presence of the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), the nicotinamide adenine dinucleotide phosphate-oxidase (NAD(P)H oxidase inhibitor apocynin, p38 kinase inhibitor SB203580, and peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone, the detrimental effect of homocysteine on bradykinin-induced dilation was prevented; however, neither the xanthine oxidase inhibitor allopurinol, the JNK inhibitor SP600125, or pioglitazone with PPAR-γ inhibitor GW9662 had that effect. CONCLUSIONS: Homocysteine inhibits endothelium-dependent NO-mediated dilation in the retinal arterioles by producing superoxide from NAD(P)H oxidase, which appears to be linked with p38 kinase. By impairing endothelium-dependent NO-mediated vasoreactivity, homocysteine potentially facilitates development of retinal vascular diseases. In addition, pioglitazone can prevent homocysteine-induced endothelial dysfunction possibly by activating PPAR-γ.

DOI： 10.1167/iovs.12-11082

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: Cilostazol, a selective inhibitor of phosphodiesterase 3, has antiplatelet aggregation and peripheral vasodilation effects. We examined the effects of cilostazol on the retinal microvascular diameter to determine its dependence on the endothelium and/or smooth muscle to reveal the signaling mechanisms involved in this vasomotor activity. METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded the diametric responses to cilostazol. RESULTS: The retinal arterioles dilated in response to cilostazol in a dose-dependent (100 pM-10 μM) manner; the dilation decreased by 60% after endothelial removal. The nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), inhibited cilostazol-induced vasodilation comparable to denudation. Inhibition of soluble guanylyl cyclase and blockade of protein kinase A (PKA) were comparable to L-NAME. Compound C, an AMP-activated protein kinase (AMPK) inhibitor, partially inhibited cilostazol-induced vasodilation, which exhibited a weaker inhibitory effect on cilostazol-induced vasodilation than blockade of PKA. The large-conductance Ca²⁺-activated K channel (BK(Ca) channel) blocker, iberiotoxin, also inhibited cilostazol-induced vasodilation. The residual vasodilation decreased further with co-administration of L-NAME and iberiotoxin. CONCLUSIONS: Cilostazol elicits endothelium-dependent and -independent dilation of the retinal arterioles mediated by NO release and BK(Ca) channel activation, respectively. Endothelial nitric oxide synthase (eNOS) phosphorylation via the cAMP/PKA and AMPK pathways and consequent activation of the soluble guanylyl cyclase/cyclic guanosine monophosphate pathway might play an important role in cilostazol-induced vasodilation of the retinal arterioles.

DOI： 10.1167/iovs.12-10115

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: To evaluate systemic endothelial function in patients with branch retinal vein occlusion (BRVO). METHODS: Twenty-seven patients with BRVO (BRVO group, 8 men, 19 women; mean age, 65.4 ± 1.3), 10 patients with systemic hypertension and no other systemic or ocular disease (hypertension group, 6 men, 4 women; mean age, 70.4 ± 2.2), and 10 healthy volunteers (healthy group, 3 men, 7 women; mean age, 63.8 ± 2.1) were enrolled. We excluded patients with diabetes mellitus and current smokers. Using high-resolution ultrasonographic imaging, we evaluated the brachial artery (mm) to evaluate the flow-mediated vasodilation (FMD) by measuring the diameter of the brachial artery during reperfusion after arterial occlusion. RESULTS: There were no significant differences among the three groups in age (p = 0.98), sex (p = 0.21), or the baseline diameter of the brachial artery (p = 0.11). The group-averaged FMD value decreased significantly in the BRVO group (4.6 ± 0.4%) compared to the hypertension group (8.0 ± 0.8%, p < 0.01) and the healthy group (6.9 ± 0.6%, p < 0.05). Multiple logistic regression analysis identified lower FMD as an independent risk factor for BRVO. CONCLUSIONS: The results suggested that BRVO is associated with generalized endothelial dysfunction and that impaired systemic endothelial function may be associated with BRVO.

DOI： 10.3109/02713683.2012.738460

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: To analyze the vitreomacular interface in idiopathic full-thickness macular holes (MHs) using spectral-domain optical coherence tomography. DESIGN: Prospective cross-sectional case series. METHODS: Ninety-one eyes of 86 consecutive patients with a MH were examined by spectral-domain optical coherence tomography. The vitreomacular interface was assessed and the presence or absence of an operculum was analyzed. RESULTS: Fifty-two eyes had a stage 2 MH, 12 eyes a stage 3 MH, and 27 eyes a stage 4 MH. No posterior hyaloid membrane was detected in any eyes with a stage 4 MH. In 35 (54.7%) of the 64 eyes with an MH without a complete posterior vitreous detachment (PVD), we saw a perifoveal PVD with vitreofoveal adhesion and partial dehiscence of the raised inner retina with an outer retinal separation in the MHs. In 24 (37.5%) of the 64 eyes without a complete PVD, an operculum, which is a hyperreflective structure of the foveal retina, was in front of the MH. The posterior hyaloid membrane was separated completely but adhered to the optic disc. In 2 (3.1%) of the 64 eyes without a complete PVD, the posterior hyaloid membrane was separated from the macula without an operculum. In 3 (4.7%) of the 64 eyes without a complete PVD, vitreofoveal adhesion on both edges of the hole was connected to the taut posterior hyaloid membrane without an operculum. CONCLUSIONS: The vitreomacular interface had 4 configurations in MHs without a complete PVD. Approximately 55% of cases with an open roof in the eyes without a complete PVD may be at risk for progression to operculum formation (loss of retinal tissue).

DOI： 10.1016/j.ajo.2012.05.024

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

The purpose of this study was to investigate the roles of endothelium-derived factors in the retinal arteriolar responses to acute severe elevation in systemic blood pressure (BP) in cats. Acute elevation of mean arterial BP by 60% for 5 min was achieved by inflating a balloon-tipped catheter in the descending aorta. The retinal arteriolar diameter, flow velocity, wall shear rate (WSR) and blood flow (RBF) changes during BP elevation were assessed with laser Doppler velocimetry 2 h after intravitreal injections of nitric oxide (NO) synthase inhibitor l-NAME, cyclooxygenase inhibitor indomethacin, endothelin-1 receptor antagonists (BQ-123 for type A and BQ-788 for type B), or Rho kinase inhibitor fasudil. BP elevation caused a marked increase in retinal arteriolar flow velocity and WSR with slight vasoconstriction, resulting in an increase in RBF. The increases in velocity, WSR and RBF, but not diameter, were correlated with the increase in ocular perfusion pressure. With l-NAME or indomethacin, the increase in RBF upon BP elevation was significantly attenuated due to enhanced retinal arteriolar vasoconstriction. In contrast, BQ-123 and fasudil potentiated the increased RBF. BQ-788 had no effect on arteriolar diameter and hemodynamics. Our data suggest that acute elevation of BP by 60% leads to an increase in RBF due to the release of NO and prostanoids probably through a shear stress-induced vasodilation mechanism. The release of endothelin-1 and Rho kinase activation help to limit RBF augmentation by counteracting the vasodilation. It appears that the retinal endothelium, by releasing vasoactive substances, contributes to RBF regulation during acute severe elevation of systemic blood pressure.

DOI： 10.1016/j.exer.2012.08.007

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記述言語：英語  

PURPOSE: Our aim was to evaluate the effects of topical carteolol on retinal arterial blood flow (RBF) in patients with primary open-angle glaucoma. METHODS: Sixteen patients received carteolol topically for 90 days. Changes in RBF in the major retinal artery were evaluated using laser Doppler velocimetry at baseline and after 30, 60, and 90 days. Patients were divided into groups based on changes in RBF; retinal arterial blood column diameter, blood velocity, and ocular perfusion pressure (OPP) were compared. RESULTS: Overall, no significant changes in RBF were observed. Twelve patients had unchanged and four decreased RBF. In patients with unchanged RBF, no significant changes in diameter, velocity, and OPP were observed. In patients with decreased RBF, the diameter did not change significantly; velocity decreased from baseline on day 90 (p = 0.041); OPP did not change significantly, but the values on days 30, 60, and 90 were lower than in patients with unchanged RBF. CONCLUSIONS: Although carteolol preserved RBF, some patients had decreased RBF with low blood pressure, suggesting that carteolol decreases RBF in some patients with decreased ocular perfusion after the topical instillation of carteolol.

DOI： 10.1007/s10384-012-0156-1

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: To investigate the relationship between the choroidal thickness and choroidal blood flow in healthy young subjects. DESIGN: Retrospective, cross-sectional study. METHODS: We examined 25 eyes of 25 healthy young Japanese subjects. The subfoveal choroidal thickness was measured by enhanced depth imaging optical coherence tomography (EDI-OCT). The total choroidal blood flow and subfoveal choroidal blood flow were evaluated by pulsatile ocular blood flow using Langham OBF computerized tonometry and the choroidal blood flow using laser Doppler flowmetry. The refractive error, intraocular pressure, and axial length were also measured. RESULTS: The mean refractive error was -3.4 ± 3.1 diopters, mean intraocular pressure 15.3 ± 1.7 mm Hg, and axial length 25.4 ± 2.0 mm. The subfoveal choroidal thickness was correlated positively (r = 0.785, P < .01) with the refractive error and negatively (r = -0.735, P < .001) with the axial length. No significant correlation was found between the subfoveal choroidal thickness and the pulsatile ocular blood flow or choroidal blood flow. CONCLUSION: Our results suggested that there were no significant correlations between the subfoveal choroidal thickness and the total choroidal blood flow and the subfoveal choroidal blood flow in healthy young subjects; however, decreased subfoveal choroidal thickness was associated with decreased refractive error and axial length.

DOI： 10.1016/j.ajo.2011.11.005

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記述言語：英語  

PURPOSE: Although recent clinical trials have demonstrated that fenofibrate is effective for treating diabetic retinopathy, the mechanism of this beneficial effect remains unclear. In the current study, we examined the effect of the vasomotor action of fenofibrate on porcine retinal arterioles. METHODS: Porcine retinal arterioles (internal diameter, 60-90 μm) were isolated, cannulated, and pressurized (55 cmH(2)O) without flow in vitro. Video-microscopic techniques recorded the diameter responses to fenofibrate. RESULTS: The retinal arterioles dilated in a dose-dependent manner in response to fenofibrate (10 nM to 30 μM). This vasodilation significantly decreased after the endothelium was removed. N(ω)-nitro-L-arginine methyl ester (a nitric oxide [NO] synthase inhibitor), 1H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one (a soluble guanylyl cyclase inhibitor), wortmannin (a phosphatidylinositol [PI] 3-kinase inhibitor), and compound C (an AMP-activated protein kinase inhibitor) attenuated the effect of fenofibrate-induced vasodilation to an extent comparable to that produced by denudation. Pretreatment with GW6471, a peroxisome proliferator-activated receptor-α blocker, did not significantly inhibit fenofibrate-induced vasodilation. CONCLUSIONS: Fenofibrate primarily elicited endothelium-dependent dilation of the retinal arterioles. The current findings suggested that fenofibrate-induced endothelium-dependent vasodilation is mediated by the release of NO, which probably mediates dilation via activation of guanylyl cyclase, the PI3-kinase pathway, and the AMP-activated protein kinase pathway. Understanding the vasodilatory effect of fenofibrate on the retinal microvasculature may improve potential therapy for diabetic retinopathy.

DOI： 10.1167/iovs.11-8841

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: To investigate whether plasma pentosidine, a well-defined advanced glycation end product, is associated with retinal hemodynamic abnormalities in patients with type 2 diabetes. DESIGN: Prospective cross-sectional study. METHODS: Forty-two eyes with type 2 diabetes mellitus were evaluated. The type 2 diabetic eyes were divided into 2 groups: 22 eyes (22 patients; mean age, 61 years) with nondiabetic retinopathy (NDR) and 20 eyes (20 patients; mean age, 61 years) with mild nonproliferative diabetic retinopathy (NPDR). We used a retinal laser Doppler system to measure the arterial diameter, velocity, and blood flow in the major temporal retinal arteries. The pulsatility ratio, a resistive index expressed as the peak systolic to the end diastolic velocity ratio, was calculated from the blood velocity traces. Plasma pentosidine was measured in 42 patients with diabetes using a commercially available competitive enzyme-linked immunosorbent assay. RESULTS: The pulsatility ratio significantly increased in patients with NPDR (4.8 ± 1.5) compared with patients with NDR (3.7 ± 0.8) (P = .0061). No differences in velocity, diameter, or blood flow were seen between the 2 groups. Plasma pentosidine levels also increased significantly (P = .0085) in patients with NPDR (0.057 ± 0.015) compared to patients with NDR (0.047 ± 0.012). The pulsatility ratio was correlated positively with the plasma pentosidine levels in patients with NPDR (Pearson correlation, r = 0.45, P = .044). Multiple regression analysis showed that the plasma pentosidine level was significantly associated with the pulsatility ratio (standardized coefficient, 0.62; P = .009). CONCLUSIONS: The vascular rigidity of the retinal arteries may increase with increasing plasma pentosidine in patients with type 2 diabetes with retinopathy.

DOI： 10.1016/j.ajo.2011.10.020

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記述言語：英語  

OBJECTIVE: Retinal endothelial dysfunction is a key in the etiogenesis of diabetic retinopathy (DR), in patients with type 2 diabetes mellitus (DM). Brachial artery flow-mediated vasodilation (FMD) is a marker of endothelial function associated with production of endogenous nitric oxide. Using FMD, we investigated the relationship between macrovascular function and DR. METHODS: We studied 74 patients with type 2 DM, including non-DR (NDR) (n = 30); mild nonproliferative DR (NPDR) (n = 16); moderate NPDR (n = 10); severe NPDR (n = 10); and proliferative DR (PDR) (n = 8); and 21 age-matched controls. We measured FMD in each group. Retinal blood flow and pulsatility ratios were measured using laser Doppler velocimetry. RESULTS: FMD decreased significantly in patients with DM compared with healthy control subjects. No significant differences were found in FMD among the NDR, mild NPDR, and moderate NPDR groups. FMD decreased significantly in the severe NPDR and PDR groups compared with the NDR group. FMD was significantly and negatively correlated with duration of DM and pulsatility ratio. CONCLUSION: Systemic endothelial dysfunction appears to be associated with DR and vascular abnormalities in patients with type 2 DM.

DOI： 10.3109/02713683.2012.654883

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記述言語：英語  

PURPOSE: Physiological shear stress is higher in the retinal microcirculatory network than in other organs. The effects of laminar shear stress on gene expression in human retinal microvascular endothelial cells (HRMECs) was investigated. METHODS: Cultured HRMECs on glass plates were exposed to a laminar shear stress of 0, 1.5, 6, 15, 30, 60, or 100 dyne/cm(2) for 24 hours and to 60 dyne/cm(2) for 0, 1, 3, 6, 12, 24, or 48 hours. The mRNA expressions of endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), and thrombomodulin (TM) in the HRMECs were evaluated using real-time reverse transcription polymerase chain reaction. RESULTS: The HRMECs elongated and aligned parallel with the flow direction based on the shear stress and exposure times. The expression of eNOS mRNA gradually increased and became saturated at 60 dyne/cm(2); ET-1 mRNA expression increased at 1.5 dyne/cm(2) but decreased below that of the static control at shear stresses of 30 dyne/cm(2) or more. TM mRNA expression in response to shear stress increased linearly from 0 to 100 dyne/cm(2). A shear stress of 60 dyne/cm(2) for 6 hours or more promoted eNOS and TM mRNA expression but suppressed ET-1 mRNA expression in HRMECs. CONCLUSIONS: Long-term exposure to a physiological shear stress in the retinal arterioles up-regulated eNOS and TM mRNA expressions and downregulated ET-1 mRNA expression in HRMECs. These results suggest that shear stress may be associated with the vasoregulatory and antithrombotic properties of retinal vessels under physiological conditions present during retinal circulation.

DOI： 10.1167/iovs.11-7686

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. The aim of this study was to determine whether NOX2, one of the homologs of NADPH oxidase, plays a role in neuronal cell death during retinal ischemia.
METHODS. Ischemia reperfusion (I/R) injury was generated in C57/BL6 and NOX2(-/-) mice by increasing the intraocular pressure (IOP) to 110 mm Hg for 40 minutes followed by reperfusion. Quantitative PCR and Western blot analysis were performed to measure NOX2 expression. Reactive oxygen species (ROS) formation was assessed by dihydroethidium imaging of superoxide formation and Western blot analysis for tyrosine nitration. TUNEL assay was performed to determine cell death at 3 days after I/R. Survival of neurons within the ganglion cell layer (GCL) was assessed at 7 days after I/R by confocal morphometric imaging of retinal wholemounts immunostained with NeuN antibody. Activation of mitogen-activated protein kinases and nuclear factor kappa B (NF-kappa B) was measured by Western blot analysis.
RESULTS. NOX2 mRNA and protein and ROS were significantly increased in wild-type I/R retinas. This effect was associated with a 60% decrease in the number of GCL neurons and a 10-fold increase in TUNEL-positive cells compared with the fellow sham control eyes. Phosphorylation of ERK and NF-kappa B was significantly increased in wild-type I/R retinas. Each of these effects was markedly attenuated in the NOX2-/-retina (P &lt; 0.01).
CONCLUSIONS. These data demonstrate that the deletion of NOX2 can reduce I/R-induced cell death and preserve retinal GCL neurons after I/R injury. The neuronal cell injury caused by I/R is associated with the activation of ERK and NF-kappa B signaling mechanisms. (Invest Ophthalmol Vis Sci. 2011;52:8123-8131) DOI:10.1167/iovs.11-8318

DOI： 10.1167/iovs.11-8318

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記述言語：英語  

The aim was to determine whether serum prorenin levels affect the development of diabetic retinopathy (DR) in type 2 diabetes. Baseline serum prorenin levels were measured in 196 patients (85 males, 111 females) with type 2 diabetes without DR using the antibody-activating direct prorenin assay. The fundi were checked regularly. The participants were divided into two groups based on the serum prorenin levels (high and low). We used Kaplan-Meyer analysis to detect differences in the development of DR between the two groups within the same gender. Kaplan-Meyer analysis showed that males with a high serum prorenin level tended to develop DR earlier and more frequently than males with a low prorenin level ( p = 0.004 by the log rank test). However, there was no difference in the development of DR between high and low groups in females (p = 0.58). Serum prorenin levels in males with type 2 diabetes could be a new prognostic indicator of the development of DR.

DOI： 10.1177/1470320310391327

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記述言語：英語  

PURPOSE: Pioglitazone, a peroxisome proliferator-activated receptor (PPAR)-γ agonist, has anti-inflammatory and atheroprotective effects on vascular tissue and may reduce cardiovascular risk in patients with diabetes. The effect of pioglitazone on the retinal microvascular diameter was examined, and it was determined whether the effect depends on the endothelium and/or potassium channels in smooth muscle to reveal the signaling mechanisms involved in this vasomotor activity. METHODS: Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded diametric responses to pioglitazone. RESULTS: The retinal arterioles dilated in a concentration-dependent (10 nM-10 μM) manner in response to pioglitazone and decreased by 60% after endothelium removal. The nitric oxide (NO) synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) inhibited pioglitazone-induced vasodilation comparable to denudation. Inhibition of soluble guanylyl cyclase (1H-1,2,4-oxadiazolo[4,3-a]quinoxalin-1-one), blockade of phosphatidylinositol (PI) 3-kinase (wortmannin), and pretreatment with compound C, an AMP-activated protein kinase (AMPK) inhibitor, were comparable to l-NAME. Pioglitazone-induced vasodilation also was inhibited by a nonselective K(+) channel blocker, tetraethylammonium, and a voltage-gated K(+) (Kv) inhibitor, 4-aminopyridine (4-AP). Treatment with intraluminal and extraluminal GW9662, a PPAR-γ antagonist, similarly inhibited pioglitazone-induced vasodilation. Co-administration of l-NAME and 4-AP almost eliminated pioglitazone-induced vasodilation. CONCLUSIONS: Pioglitazone elicits endothelium-dependent and -independent dilation of retinal arterioles mediated by NO release and Kv channel activation, respectively. The NO-mediated dilation pathway probably occurs via activation of guanylyl cyclase, PI3-kinase/Akt, and AMPK signaling. Understanding the effect of pioglitazone on retinal vasculature may provide new insights into therapeutic advances for treating diabetic retinopathy.

DOI： 10.1167/iovs.10-6826

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記述言語：英語  

PURPOSE: To estimate the rate of macular hole formation in fellow eyes with a perifoveal posterior vitreous detachment (PVD) and early stage 1 intrafoveal lesions in patients with a unilateral idiopathic full-thickness macular hole (MH) using optical coherence tomography (OCT). DESIGN: Retrospective observational case series. METHODS: Fellow eyes of consecutive patients with a unilateral full-thickness MH were examined on OCT. A subset of fellow eyes with a perifoveal PVD had been followed to investigate the rates of macular hole formation in fellow eyes with early stage 1 intrafoveal lesions. RESULTS: Of 176 patients with a unilateral full-thickness MH, 42 fellow eyes (42 patients) with a perifoveal PVD were identified. During follow-up, a foveolar detachment was seen in 16 eyes, and 4 eyes had a foveal pseudocyst alone. In the 16 eyes with a foveolar detachment, 9 eyes had concurrent inner foveal splits. Within another 2 years of follow-up, OCT showed that 5 of 16 fellow eyes (31%) with a foveolar detachment developed a second full-thickness MH and 5 of 9 fellow eyes with a foveolar detachment and inner foveal splits developed a second full-thickness MH. Two of 4 eyes with a foveal pseudocyst alone developed vitreofoveal separation without hole formation. The remaining 2 eyes with a foveal pseudocyst alone remained stable at the last follow-up visit. CONCLUSIONS: Fellow eyes with a foveolar detachment and a perifoveal PVD may be at high risk, and fellow eyes with a foveolar detachment and inner foveal splits might be at higher risk for progression to macular hole formation.

DOI： 10.1016/j.ajo.2011.01.011

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記述言語：英語  

PURPOSE: To compare the accuracy and repeatability of Fourier-domain optical coherence tomography (FD-OCT) with ultrasonic pachymetry (USP) and a rotating Scheimpflug camera for measuring the central corneal thickness (CCT). METHODS: The CCT was measured in 30 subjects (30 normal corneas) by the same examiner using RTVue-100 FD-OCT with an anterior segment adaptor, Pentacam rotating Scheimpflug camera, and SP-2000 USP. Two examiners obtained one FD-OCT measurement from 10 eyes of 5 subjects to assess interexaminer reproducibility. RESULTS: The mean CCT (±SD) measured by FD-OCT, USP, and the Pentacam were 530 ± 33, 544 ± 34, and 552 ± 35 μm, respectively. Significant correlations were found between FD-OCT and USP (r = 0.97; P < 0.0001), FD-OCT and Pentacam (r = 0.97; P < 0.0001), and USP and Pentacam (r = 0.96; P < 0.0001). Pairwise comparisons showed that the FD-OCT CCT measurement was significantly thinner than those of the other 2 methods (P < 0.001 for all comparisons). Regarding intraexaminer repeatability, the intraclass correlation coefficients ranged between 0.97 and 0.98. There was high repeatability of the CCT measurements with all methods. FD-OCT also had high interexaminer reproducibility (intraclass correlation coefficient = 0.98). CONCLUSIONS: RTVue-100 FD-OCT may be a useful alternative for measuring the CCT; however, it significantly underestimates the CCT compared with the USP and the Pentacam with slight differences. Although highly correlated, the measurements are not directly interchangeable in clinical practice.

DOI： 10.1097/ICO.0b013e3181d00800

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

DOI： 10.1007/s10384-011-0001-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: To determine the anatomical morphology of Stage 1-A impending macular holes characterized by a yellow spot using spectral-domain optical coherence tomography to study the fellow eyes of patients diagnosed with a full-thickness macular hole or eyes with a typical yellow spot with metamorphopsia. METHODS: Prospective observational case series of 45 patients with a full-thickness macular hole or a foveolar yellow spot with metamorphopsia. Visual acuity assessment, biomicroscopic examination, and spectral-domain optical coherence tomography were performed. Clinical ophthalmologic examinations were repeated, including spectral-domain optical coherence tomography, in the eyes with a foveolar yellow spot at 1-month interval. RESULTS: We examined 43 fellow eyes of 43 patients with a macular hole and 2 eyes of 2 patients with a foveolar yellow spot. Five fellow eyes had a yellow spot. Spectral-domain optical coherence tomography clearly showed the reflectivity of the perifoveal posterior vitreous detachment with vitreofoveal adhesion in the 7 eyes with a yellow spot; the foveal microstructure had a triangular foveolar detachment of the cone outer segment tip line, of which only 2 eyes (29%) had foveal splits during the observational period, 3 eyes (43%) had a foveal perpendicular line, and 4 eyes (57%) showed progression to vitreofoveal separation before the development of inner splits or pseudocysts. In those 7 eyes, the 2 eyes (29%) with foveal splits progressed to a full-thickness macular hole. The 38 fellow eyes without a yellow spot had no foveolar detachment. CONCLUSION: The foveolar detachment of the cone outer segment tip line might be responsible for the yellow spot seen in Stage 1-A macular holes.

DOI： 10.1097/IAE.0b013e3181e7997b

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記述言語：英語  

PURPOSE: To report the detailed vitreomacular morphology of a case of progressive enlargement and macular detachment secondary to and several years after the development of bilateral giant macular holes using optical coherence tomography. METHODS: Using optical coherence tomography, both eyes of a patient with bilateral giant macular holes were examined. RESULTS: A 33-year-old woman had bilateral giant macular holes at the first visit. At the 5-year follow-up visit, the macular hole had enlarged centrifugally in the right eye, and a macular detachment developed beyond the arcade vessels in the left eye. Optical coherence tomography showed retinoschisis in the right eye around the edges of the hole and a macular detachment in the left eye with vitreoretinal adhesion temporal to both holes. CONCLUSION: These optical coherence tomography findings suggested that vitreomacular traction at the temporal edge of the hole may have resulted in progressive centrifugal enlargement of the hole in both eyes and then the macular detachment occurred in the left eye.

DOI： 10.1097/ICB.0b013e3181f047b6

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記述言語：英語  

PURPOSE: To evaluate the differences in retinal circulation in eyes of patients with type 2 diabetes with no or early-stage diabetic retinopathy compared with control eyes. METHODS: Seventy-five nondiabetic eyes and 194 eyes with type 2 diabetes mellitus were evaluated. The type 2 diabetic eyes were classified into two groups: 139 eyes (139 patients) without diabetic retinopathy (NDR) and 55 eyes (55 patients) with mild nonproliferative diabetic retinopathy (NPDR). The retinal circulatory parameters were measured with laser Doppler velocimetry, and the factors that affect retinal hemodynamics were determined in a cross-sectional population of patients with type 2 diabetes. RESULTS: The group-averaged blood velocity (V) and retinal blood flow (RBF) in the NDR and mild NPDR groups were significantly (P < 0.01) lower than in the non-DM group. The diameter and wall shear rate were also significantly (P < 0.05) lower in the NDR group than in the nondiabetic control eyes. Multiple regression analysis showed that the RBF was independently and negatively correlated with serum low-density lipoprotein and creatinine. HbA1c was significantly (P < 0.05) higher in participants in the lowest RBF quartile than in the highest quartiles. CONCLUSIONS: The results indicate that the RBF may decrease in patients with type 2 diabetes without retinopathy and in those with mild retinopathy.

DOI： 10.1167/iovs.10-5364

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記述言語：英語  

A 65-year-old patient complained of central metamorphopsia and presented an intraretinal cyst with a yellow ring in the fovea of the right eye. His best-corrected visual acuity was 20/32 in that eye. Optical coherence tomography (OCT) 3 showed an enlarged pseudocyst at the outer retina of a stage 1B macular hole; the foveal roof was intact where the vitreous was attached reflecting a perifoveal posterior vitreous detachment. Six months later, OCT 3 showed bridging by centripetal protrusion in the outer fovea inside the pseudocyst with a residual defect in the foveal photoreceptor layer. Eighteen months after the initial visit, spectral-domain OCT showed bridging of the outer retina inside the pseudocyst at the hyper-reflective line representing the external limiting membrane; the roof of the pseudocyst was more elevated with posterior hyaloid adhesion and there was a smaller residual defect in the foveal photoreceptor layer. This case demonstrates that spontaneous closure in the outer retina may develop in some cases of stage 1B macular holes without vitreofoveal separation.

DOI： 10.1007/s10792-010-9363-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To investigate perifoveal capillary blood flow velocity and retinal thickness at the central fovea in patients with branch retinal vein occlusion (BRVO) and macular edema and to assess their relation with visual acuity and visual prognosis. Methods: Eighteen patients with BRVO and 16 healthy volunteers were compared. Perifoveal capillary blood flow velocity was measured on fluorescein angiograms with a scanning laser ophthalmoscope by the tracing method. Retinal thickness was measured at the central fovea by optical coherence tomography. Best-corrected visual acuity (BCVA) was determined. Results: BCVA differed significantly between patients and controls (P &lt
0.0001). Among patients, BCVA was negatively correlated with perifoveal capillary blood flow velocity by univariate analysis (r = -0.7916, P &lt
0.0001), and positively correlated with retinal thickness at the central fovea (r = 0.8970, P &lt
0.0001). Multivariate analysis showed that retinal thickness at the central fovea was the only independent determinant of BCVA (P &lt
0.0001). Conclusions: In patients with BRVO, BCVA was more strongly influenced by retinal thickness at the central fovea than by perifoveal capillary blood flow velocity. © 2010 Japanese Ophthalmological Society (JOS).

DOI： 10.1007/s10384-010-0834-9

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記述言語：英語  

PURPOSE: To investigate the effects of acute hyperglycemia on retinal microcirculation and endothelial function in cats and removal of superoxide to prevent retinal endothelial dysfunction from hyperglycemia. METHODS: Hyperglycemia was induced by intravenous injection of 25% glucose to maintain the plasma glucose concentration at 30 mM. Laser Doppler velocimetry was used to measure the vessel diameter (D) and blood velocity (V) simultaneously and calculated retinal blood flow (RBF) in second-order retinal arterioles in cats. Intravitreous, endothelial-dependent vasodilator bradykinin (BK) and endothelium-independent vasodilator sodium nitroprusside (SNP) were administered into the vitreous cavity to evaluate endothelial function in the retinal arterioles. To control osmolality, 25% mannitol was administered the same way. Systemic hyperoxia was induced to noninvasively examine endothelial function during hyperglycemia. To determine the effect of the superoxide on the hyperglycemia-induced changes in the retinal circulation, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) was administered in drinking water for 14 days before the experiment. RESULTS: The D, V, and RBF increased with acute hyperglycemia and mannitol compared with baseline. BK-induced increases in D, V, and RBF significantly declined, whereas SNP-induced increases were unattenuated during acute hyperglycemia. Return of the decreased RBF to baseline after cessation of systemic hyperoxia was significantly (P < 0.05) inhibited by acute hyperglycemia. TEMPOL significantly (P < 0.05) prevented a decrease in the BK-induced increase in RBF during hyperglycemia. CONCLUSIONS: The results suggest that acute hyperglycemia increases RBF via increased osmolality and may cause retinal endothelial dysfunction partially via increased oxidative stress. Systemic hyperoxia can be used to noninvasively evaluate retinal endothelial function during hyperglycemia.

DOI： 10.1167/iovs.09-4070

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

OBJECTIVE: To report the case of a stage 1 macular hole and the sequential intrafoveal changes with spectral-domain optical coherence tomography (SD-OCT). DESIGN: Single, observational case report. PARTICIPANT: A 51-year-old woman with a stage 1A macular hole that progressed to a stage 2 macular hole. METHODS: Clinical ophthalmologic examinations were repeated, including SD-OCT, during follow-up at intervals of several weeks. MAIN OUTCOME MEASURES: Sequential intrafoveal tomographic alterations in a patient with a stage 1 macular hole. Foveal splits in the inner retina progressed to an enlarged pseudocyst that disrupted the outer retinal layer (ORL) resulting from the vitreous traction associated with a perifoveal posterior vitreous detachment (PPVD). RESULTS: The patient was referred for decreased vision in the left eye. Her best-corrected visual acuity was 20/32 in the left eye. The SD-OCT showed intrafoveal splits of a typical stage 1A macular hole with a PPVD. Two weeks later, a small, triangularly shaped foveal detachment was detected beneath the central fovea. Four weeks after the initial visit, the splits expanded and the foveal surface was elevated anteriorly; a columnar structure between the splits beneath the central fovea was seen. Eight weeks after the initial visit, the columnar structure was pulled from the outer retina with formation of the PPVD; the structure had shortened anteriorly and formed a cone-shaped structure under the roof. Eleven weeks after the initial visit, the cone-shaped structure shortened and became smaller under the inner roof, and the ORL was separated completely. The anatomic features of the foveal pseudocyst were comparable with that of a typical stage 1B macular hole. Eighteen weeks after the initial visit, the cone-shaped structure disappeared under the inner roof. Thirty weeks after the initial visit, the roof opened with formation of the PPVD. The foveal anatomic features of the full-thickness macular hole became comparable with that of a typical stage 2 macular hole. CONCLUSIONS: These OCT findings suggested that the cone-shaped structure was pulled from the outer retina by anteroposterior vitreous traction. This may cause a progressively enlarging pseudocyst that disrupts the ORL in some cases of stage 1 macular holes. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

DOI： 10.1016/j.ophtha.2009.09.022

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記述言語：英語  

Although it is important to investigate the effects of normal aging on the ocular circulation, few studies have examined the effects of aging on the retinal microcirculation in healthy subjects. The purpose of this study was to evaluate the effects of aging on the retinal microcirculation in healthy men. Forty-five healthy men were divided into three groups based on age (young, middle-aged, elderly). We measured vessel diameter and blood velocity and calculated the retinal blood flow (RBF) and wall shear rate (WSR) in the retinal arteries. We performed pulse wave analysis obtained from the retinal blood velocity measurements. We also divided the subjects into two groups based on the presence or absence of prehypertension defined as 120-139/80-89 mmHg. No significant differences in vessel diameter, blood velocity, RBF, and WSR were seen among the groups. Pulse wave analysis showed significant increases in upstroke time (UT) in elderly men compared with young men (P < 0.05). Multiple regression analysis showed that the UT was correlated with age in all subjects. A significant difference was seen only in the UT between subjects with and without prehypertension. The UT calculated from the retinal blood velocity profile is associated significantly with aging, suggesting that measurement of the UT may detect the changes in the retinal and the systemic vessels with increasing age. The UT is the only parameter that increased significantly in subjects with prehypertension compared with those without prehypertension, suggesting that the UT may indicate the effects of prehypertension on the retinal arterioles.

DOI： 10.1016/j.exer.2009.07.019

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記述言語：日本語  

PURPOSE: To evaluate the retinal arteriolar circulation, morphology and sensitivity of an area in branch retinal artery occlusion (BRAO) using sequential investigation with laser Doppler velocimetry (LDV), optical coherence tomography (OCT) and microperimetry (MP-1). CASE REPORT: A 45-year-old woman was referred for decreased vision in the right eye with a visual acuity (VA) of 0.1. At the initial examination, retinal whitening and thickening were noted in the affected area. Fluorescein angiography revealed slightly delayed retinal filling time but no obstruction of arteries. Ophthalmoscopic and fluorescein angiographic examinations revealed incomplete branch retinal artery occlusion. OCT showed retinal thickening superior to the macula. MP-1 perimetry showed scotoma in the upper macula. LDV revealed a lower absolute value of retinal arterial blood flow (RBF) (7.5 microl/min) in the right eye. Laboratory test results showed iron deficiency anemia which probably induced the BRAO. The patient was treated with ocular massage and intravenous mannitol. The next day, VA improved to 1.2 and RBF normalized to 13.9 microl/min. On follow-up 2 months after the initial visit, OCT revealed retinal thinning and inner retinal atrophy; MP-1 showed improvement in retinal sensitivity overlaying the area of branch retinal artery occlusion following resolution of retinal edema. The RBV decreased to 6.0 microl/min, showing a marked decrease due to narrowing of the artery. CONCLUSION: In this case of acute transient BRAO, sequential LDV was performed and the quantitative retinal circulation was useful in evaluating the treatment and helped the prognosis of visual function in BRAO.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. Activation of the endothelin (ET) system has been implicated in the pathogenesis of retinal ischemic disease. Although ET-1, the predominant endogenous isoform of ET, has been shown to cause constriction of retinal vessels, the expression and functional significance of its synthesis and the involved specific ET receptors in retinal arterioles remain unknown. The authors examined the roles of ET(A) and ET(B) receptors and of endothelin-converting enzyme (ECE)-1 in ET-1-induced vasomotor responses of single retinal arterioles.
METHODS. To exclude systemic confounding effects, porcine retinal arterioles were isolated for vasoreactivity and molecular studies.
RESULTS. Isolated and pressurized retinal arterioles developed basal tone and constricted in a manner dependent on concentration to ET-1. ET-1 precursor big ET-1 elicited time-dependent vasoconstriction over 20 minutes, which was blocked by the ECE-1 inhibitor phosphoramidon. ET(A) receptor antagonist BQ123 inhibited most (approximately 90%) of vasoconstrictions to ET-1 and big ET-1. ET(B) receptor agonist sarafotoxin also elicited concentration-dependent constriction of retinal arterioles but with significantly less potency than ET-1. ET(B) receptor antagonist BQ788 abolished vasoconstriction to sarafotoxin but only slightly reduced responses to ET-1 and big ET-1. Protein and mRNA expressions of ET(A), ET(B), and ECE-1 were detected in retinal arterioles. Immunohistochemistry revealed ET(A) and ET(B) receptors predominantly in smooth muscle and ECE-1 predominantly in endothelium and smooth muscle.
CONCLUSIONS. ET-1 elicits constriction of retinal arterioles predominantly through the activation of smooth muscle ET(A) receptors. Endogenous production of ET-1 from vascular ECE-1 is sufficient to evoke ET(A) receptor-dependent constriction in retinal arterioles. (Invest Ophthalmol Vis Sci. 2009;50:3329-3336) DOI: 10.1167/iovs.08-3129

DOI： 10.1167/iovs.08-3129

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記述言語：日本語  

PURPOSE: To report the long-term clinical course of a case of juvenile retinitis pigmentosa (RP) with bilateral cystoid macular edema (CME) which was subjected to sequential investigation with laser Doppler flowmetry (LDF) to evaluate the choroidal blood flow (CBF) in the foveal region. CASE: A 17-year-old man with RP was referred for a full examination. His best-corrected visual acuity (VA) was 1.0 in the right eye and 0.9 in the left eye. At the initial examination, retinal pigment epithelium degeneration and obvious CME were noted in the both eyes. LDF revealed a CBF of 19.8 (a. u.) in the right eye and 14.2 (a. u.) in the left. Three years and 6 months later, the VA decreased to 0.8 in the right eye and 0.4 in the left, and the CBF decreased to about 50% of the initial values in either eye. Vitrectomy was performed for bilateral CME. 6 years and 2 months after the initial visit, the VA decreased to 0.1 in the right eye and 0.05 in the left eye, showing a marked decrease of the CBF to 2.5 (a. u.) in the right eye and 1.6 (a. u.) in the left eye, about 12% of the initial values. CONCLUSION: We describe a case of bilateral CME due to RP in which sequential LDF was performed. We theorize that the worsening of VA and the decrease of CBF advanced simultaneously and gradually in our patient.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

To quantitatively assess the arteriovenous distribution of hemodynamic parameters throughout the microvascular network of the human retina, we constructed a retinal microcirculatory model consisting of a dichotomous symmetric branching system. This system is characterized by a diameter exponent of 2.85, instead of 3 as dictated by Murray's law, except for the capillary networks. The value of 2.85 was the sum of a fractal dimension (1.70) and a branch exponent (1.15) of the retinal vasculature. Following the feeding artery (central retinal artery), each bifurcation was recursively developed at a distance of an individual branch length [L(r)=7.4r1.15] by a centrifugal scheme. The venular tree was formed in the same way. Using this model, we evaluated hemodynamic parameters, including blood pressure, blood flow, blood velocity, shear rate, and shear stress, within the retinal microcirculatory network as a function of vessel diameter. The arteriovenous distributions of blood pressure and velocity in the simulation were consistent with in vivo measurements in the human retina and other vascular beds of small animals. We therefore conclude that the current theoretical model was useful for quantifying hemodynamics as a function of vessel diameter within the retinal microvascular network. © 2009 Japanese Society of Biorheology.

DOI： 10.1007/s12573-009-0012-1

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記述言語：英語  

PURPOSE: The aim of this study was to determine the short-term effects of topical tafluprost, a novel prostaglandin F(2) derivative, on feline retinal circulation. METHODS: Seventeen (17) adult cats were anesthetized with enflurane and mechanically ventilated. One (1) drop of tafluprost (0.0015%; n = 8), latanoprost (0.005%; n = 5), or control vehicle (n = 4) was instilled in 1 eye and the fellow eye was untreated. We measured the intraocular pressure (IOP), vessel diameter, and blood velocity simultaneously for 120 min in the large retinal arterioles and calculated the retinal blood flow (RBF) with a laser Doppler velocimetry system. RESULTS: Tafluprost 0.0015% significantly increased RBF (maximum change, 42.8 +/- 4.2% [mean +/- standard error of the mean; P < 0.01) and blood velocity (maximum change, 24.1 +/- 3.3%; P < 0.01) for 120 min after instillation; there was no significant change in vessel diameter. Latanoprost 0.005% significantly increased RBF (maximum change, 31.7 +/- 3.4%; P < 0.05); there was no significant change in vessel diameter and blood velocity. There were no significant differences in the IOP reduction among the three groups. CONCLUSIONS: We observed, for the first time, that topical tafluprost significantly increased RBF in cats, suggesting that dual-action tafluprost may be a beneficial antiglaucomatous agent for reducing IOP and increasing RBF.

DOI： 10.1089/jop.2007.0065

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記述言語：英語  

PURPOSE: To investigate whether nitric oxide (NO) regulates retinal circulation during and after induction of hyperoxia in cats. METHODS: Hyperoxia was induced for 10 minutes with 100% oxygen. The vessel diameter and blood velocity were measured simultaneously in second-order retinal arterioles by laser Doppler velocimetry; the retinal blood flow (RBF) and wall shear rate (WSR) were calculated during and after hyperoxia. PBS, L-NAME, D-NAME, BQ-123, BQ-788, and 7-nitroindazole (7-NI) were administered before induction of hyperoxia. RESULTS: In the PBS group, vessel diameter, blood velocity, and RBF decreased during hyperoxia and returned to baseline within 10 minutes after hyperoxia ended. WSR decreased transiently and then returned to baseline by the delayed constriction of retinal arterioles during hyperoxia. In the l-NAME and BQ-788 groups, the decreases in RBF during hyperoxia did not differ from those in the PBS group. However, the recovery of RBF after hyperoxia ended was attenuated significantly until 20 minutes after hyperoxia ended in both groups compared with the PBS group (P < 0.05). In the BQ-123 group, the intravitreous injection of BQ-123 caused less reduction of blood velocity and RBF during hyperoxia compared with that in the PBS group, whereas the RBF immediately returned to baseline after hyperoxia. D-NAME and 7-NI did not affect RBF in response to hyperoxia. CONCLUSIONS: The current results indicate that NO contributes to RBF recovery after hyperoxia, probably through the action of endothelial NOS via the ETB receptor in the vascular endothelium of the retinal arterioles, suggesting that the RBF response to hyperoxia may be used to evaluate the endothelial function of the retinal arterioles.

DOI： 10.1167/iovs.07-1667

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記述言語：英語  

PURPOSE: To determine the role of prorenin in the pathogenesis of retinal neovascularization, we evaluated the inhibitory effect of the handle region peptide (HRP) on retinal neovascularization. METHODS: Neonatal C57BL6 mice were exposed to 75% oxygen from postnatal day 7 (P7) to P12 and placed in room air. The animals received HRP (1.0 or 0.1 mg/kg/day), captopril (10 mg/kg/day), or normal saline from P12 to P17. Following enucleation of the eyes, the retina was dissected for whole-mount retinal sections and semiquantitative analysis of mRNA of vascular endothelial growth factor (VEGF), placental growth factor (PIGF), fms-like tyrosine kinase 1 (Flt-1), fetal liver kinase 1 (Flk-1), angiopoietin 2 (Ang2), and tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (Tie2). RESULTS: The average numbers of neovascular nuclei in retinopathy of prematurity treated with normal saline, captopril, and HRP (0.1 or 1.0 mg/kg/day) were 37.2+/-8.6, 7.7+/-3.4, 39.5+/-7.3, and 6.5+/-2.7, respectively. HRP (1.0 mg/kg/day) and captopril inhibited neovascularization in rhodamine-perfused retina; HRP (0.1 mg/kg/day) did not. Semiquantitative analysis of mRNA for angiogenic factors showed that HRP (1.0 mg/kg/day) inhibited overexpression of PIGF, Flt-1, and Ang2. CONCLUSIONS: HRP inhibits retinal neovascularization by interfering with nonproteolytic activation of prorenin, indicating that prorenin may promote retinal neovascularization.

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記述言語：英語  

PURPOSE: Elevated levels of C-reactive protein (CRP), a proinflammatory marker, are associated with systemic vascular disorders. In addition, clinical studies have implicated that elevated CRP is an independent risk factor for diabetic retinopathy and age-related macular degeneration. However, the direct effect of CRP on ocular microvascular reactivity remains unknown. The authors examined whether CRP can affect endothelium-dependent nitric oxide (NO)-mediated dilation of retinal arterioles and whether oxidative stress and distinct protein kinase signaling pathways are involved in the CRP-mediated effect. METHODS: Porcine retinal arterioles (internal diameter, 71 +/- 2 microm) were isolated and pressurized without flow for in vitro study. Diameter changes were recorded using videomicroscopic techniques. Dihydroethidium (DHE) was used to detect superoxide production. RESULTS: Intraluminal treatment with a clinically relevant concentration of CRP (7 microg/mL, 60 minutes) significantly attenuated arteriolar dilation to endothelium-dependent NO-mediated agonists bradykinin and A23187 but not to endothelium-independent NO donor sodium nitroprusside. In the presence of superoxide scavenger TEMPOL, NAD(P)H oxidase inhibitor apocynin, p38 kinase inhibitor SB203580, simvastatin, or Rho-kinase inhibitor Y-27632, the detrimental effect of CRP on bradykinin-induced dilation was prevented. DHE staining showed that CRP produced TEMPOL-sensitive superoxide production in the arteriolar endothelium. CONCLUSIONS: CRP inhibits endothelium-dependent NO-mediated dilation in retinal arterioles by producing superoxide from NAD(P)H oxidase, which appears to be linked with p38 kinase and RhoA/Rho-kinase activation. By impairing endothelium-dependent NO-mediated vasoreactivity, CRP can potentially facilitate the development of retinal vascular diseases. In addition, statins are beneficial by preserving endothelial function, possibly through inactivation of the RhoA/Rho-kinase pathway.

DOI： 10.1167/iovs.07-1387

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. Resveratrol, a polyphenolic phytoalexin found in grapes and red wine, has been shown to exert cardiovascular benefits, but its action in the retinal microcirculation remains unknown. In this study, the direct effect and the underlying mechanism of the vasomotor action of resveratrol were examined in retinal arterioles.
METHODS. Porcine retinal arterioles were isolated, cannulated, and pressurized without flow for in vitro study. Resveratrolinduced diameter changes were recorded by videomicroscopic techniques.
RESULTS. Retinal arterioles (65 +/- 3 mu m) dilated dose dependently in response to resveratrol (1-50 mu M). The removal of the endothelium reduced this dilation by 50%. Inhibition of nitric oxide (NO) synthase (by L-NAME; N-G-nitro-L-arginine methyl ester) and blockade of soluble guanylyl cyclase (by ODQ; 1H-1,2,4-oxadiazolo[4,3-a]quinoxalin-1-one) produced similar inhibition as that produced by denudation. However, the resveratrol response was not affected by indomethacin (a cyclooxygenase inhibitor) and sulfaphenazole (an epoxygenase inhibitor). Intraluminal administration of an extracellular signal-regulated kinase (ERK) inhibitor (PD98059), but not an estrogen receptor blocker (ICI 182780), also reduced vasodilation by 50%. A nonselective K+ channel blocker, tetraethylammonium (TEA), and a large-conductance Ca2+ -activated K+(BKCa) channel inhibitor, iberiotoxin, produced identical inhibition of resveratrol-induced dilation. However, the dilation was insensitive to the inhibitors of ATP-sensitive K+ channels and voltage-gated K (+) channels. Coadministration of L-NAME and iberiotoxin almost abolished the vasodilation induced by resveratrol.
CONCLUSIONS. Resveratrol elicits endothelium-dependent and - independent dilation of retinal arterioles. Endothelium-dependent dilation is mediated by the released NO, probably via NO synthase ( NOS) activation by the ERK pathway and the subsequent activation of soluble guanylyl cyclase. The activation of BKCa channels in smooth muscle contributes to the endothelium-independent dilation caused by resveratrol. A better understanding of the action of resveratrol on retinal vasculature may help shed light on its therapeutic potential for retinal vascular disease.

DOI： 10.1167/iovs.07-0094

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: To evaluate serum prorenin levels in preterm infants with or without retinopathy of prematurity (ROP). DESIGN: Noncomparative retrospective case control study. METHODS: Serum prorenin levels in children with a gestational age younger than 36 weeks were measured with antibody-activating direct enzyme kinetic assay. RESULTS: The mean prorenin concentrations were higher in preterm infants with ROP than in infants without ROP at every time point: from 26 to 30 weeks, 2326 +/- 334 microg/ml (mean +/- SE [standard error]) (n = 3) and 1164 +/- 234 microg/ml (n = 3), respectively (P < .05); from 31 to 35 weeks, 1760 +/- 496 microg/ml (n = 10) and 957.1 +/- 139 microg/ml (n = 25) (P < .05); from 36 to 40 weeks, 958.2 +/- 194.2 microg/ml (n = 23) and 470.1 +/- 32.6 microg/ml (n = 67) (P < .01); and from 41 to 45 weeks, 575.8 +/- 148.4 (n = 9) and 385.6 +/- 47.9 (n = 13), which is not significantly different. CONCLUSIONS: Prorenin levels in preterm infants can predict which infants will develop ROP.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

PURPOSE. Results in a prior study have demonstrated that systemic administration of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor simvastatin to healthy subjects reduces intraocular pressure and increases retinal blood flow. However, it remains unclear whether simvastatin can directly elicit dilation of retinal microvessels. In the current study, the direct effect and the underlying mechanism of the vasomotor action of simvastatin in retinal arterioles was studied.
METHODS. Porcine retinal arterioles (similar to 75 mu m internal diameter) were isolated, cannulated, and pressurized (55 cmH(2)O) without flow for in vitro study. Diameter changes in response to simvastatin were recorded using videomicroscopic techniques.
RESULTS. Retinal arterioles dilated dose dependently to simvastatin (1 nM to 10 mu M). This vasodilation was significantly reduced after removal of the endothelium. The nitric oxide (NO) synthase inhibitor L-NAME (N-G-nitro-L-arginine methyl ester) markedly inhibited the vasodilation, and combined administration of L-NAME with cyclooxygenase inhibitor indomethacin mimicked the effect of denudation. Blockade of soluble guanylyl cyclase by ODQ (1H-[1,2,4] oxadiazolo[4,3,-a] quinoxalin-1-one) produced a similar inhibitory effect as that by L-NAME. In contrast, the dilation was unaffected by cytochrome-P450 epoxygenase inhibitor sulfaphenazole. Intraluminal incubation of vessels with mevalonate, an immediate metabolite of HMG-CoA reductase, partially inhibited vasodilation to simvastatin. The Rho kinase inhibitor Y-27632 abolished the antagonistic effect of mevalonate.
CONCLUSIONS. Simvastatin elicits mainly an endothelium-dependent, NO-mediated dilation of retinal arterioles via activation of guanylyl cyclase; cyclooxygenase plays a relatively minor role. It appears that inhibition of the mevalonate-Rho kinase pathway in endothelial cells contributes in part to the simvastatin-induced vasodilation. A better understanding of the action of statins on retinal vasculature may help shed light on its therapeutic potential in retinal vascular disease.

DOI： 10.1167/iovs.06-0856

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記述言語：英語  

PURPOSE: To evaluate the effect of interferon (IFN) therapy on retinal microcirculation. METHODS: Thirty-six patients with chronic hepatitis C who were treated with high-dose IFN were included in this prospective study. The changes in vessel diameter and blood velocity were measured, and the retinal blood flow (RBF) and wall shear rate (WSR) were calculated in the retinal arteries before and 2, 4, 8, 16, and 24 weeks after IFN therapy by using laser Doppler velocimetry. RESULTS: Retinal blood velocity, RBF, and WSR significantly (P < 0.0001) increased in all patients, as early as 2 weeks after IFN therapy. The increase in RBF was independently correlated with a decrease in the red blood cell count. In 22 (61%) of the 36 patients asymptomatic retinopathy developed during treatment. In patients with retinopathy, the blood velocity and WSR increased, but the vessel diameter did not change, whereas the vessel diameter increased but the blood velocity and WSR did not change in patients without retinopathy 2 weeks after IFN therapy. Multiple logistic regression analysis showed that patient age and the change in WSR at week 2 were risk factors for the development of IFN-induced retinopathy. CONCLUSIONS: RBF increases in association with IFN therapy in patients with chronic hepatitis C. In addition, the increased WSR in patients with retinopathy indicates that retinal vascular endothelial dysfunction may be associated with IFN-induced retinopathy, because wall shear stress should be constant under physiologic conditions.

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記述言語：日本語  

Ocular circulation is regulated to maintain the homeostasis of retinal function in response to physiological stimulus. It is important to understand the mechanism of the regulation of ocular circulation under physiological conditions because the impairment of ocular circulation should cause severe retinal disorders. We previously investigated the physiological mechanism of ocular circulation in response to hypoxia, hypercapnia, and acute increased systemic blood pressure. In addition, it was reported that transpupillary thermotherapy might change ocular blood flow in patients with age-related macular degeneration. However, it still remains unclear whether the increased ocular tissue temperature may be associated with alteration of the ocular blood flow. Therefore, we examined the effect of ocular warming on retinal blood flow (RBF) and subfoveal choroidal blood flow (CBF) in humans. Ocular warming was induced in 10 healthy volunteers using an ocular warming lamp for 10 minutes. The RBF in the retinal artery and vein and the CBF in the foveal region were examined with a retinal laser Doppler velocimetry system and a laser Doppler flowmeter, respectively. Ocular warming increased RBF in the retinal artery and vein but decreased CBF in the foveal region. The CBF in the foveal region may contribute to maintaining a constant retinal temperature in response to ocular warming.

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Purpose: Nitric oxide (NO) plays an important role in homeostatic vasodilation and the regulation of blood flow. On the other hand, excess release of NO causes various vascular complications. There are only a few reports on the relationship between plasma NO levels and microvascular complications, especially diabetic retinopathy (DR) in patients with type 2 diabetes. The purpose of this study was to determine the relationship between plasma NO levels and DR.
Methods: In a prospective study, blood samples were obtained from 36 patients with diabetes and no diabetic retinopathy (NDR), 43 patients with nonproliferative diabetic retinopathy (NPDR), 18 patients with proliferative diabetic retinopathy (PDR), and 40 subjects without diabetes mellitus, who served as controls. The levels of plasma NOx (nitrite and nitrate), the stable metabolites of NOx were measured by high-performance liquid chromatography with the Griess method.
Results: The plasma NOx levels were 92.8 +/- 16.0, 70.2 +/- 6.8, 90.3 +/- 9.1, and 53.8 +/- 6.1 mu mol/l in patients with NDR, NPDR, or PDR, and in the controls, respectively. The plasma NO, levels in the three diabetic groups were significantly higher than those in the control group (P &lt; 0.05 in each case).
Conclusion: The increased plasma NO levels in patients with type 2 diabetes indicate that NO may be associated with the pathogenesis of DR.

DOI： 10.1007/s10384-006-0344-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Purpose: To evaluate quantitatively the effects of bucillamine on the entrapment of leukocytes in the retinal microcirculation of diabetic rats.
Methods: 13 male Brown Norway rats were injected with streptozotocin (STZ). After the animals developed diabetes, they were divided into two groups. Group 1(n = 7) received fresh drinking water without bucillamine. and group 2 (n = 6) received fresh drinking water supplemented with bucillamine (200 mg/kg per day). Rats that were not injected with STZ and received water without bucillamine served as controls (n = 6). Four weeks after the injection of STZ, the leukocytes in the retina were observed by acridine orange digital fluorography. The number of leukocytes trapped in the retinal vessels was compared among the three groups.
Results: In the untreated diabetic rats, the number of trapped leukocytes was significantly higher than in control rats or bucillamine-treated diabetic rats (P &lt; 0.05).
Conclusions: We demonstrated an inhibitory effect of bucillamine on leukocyte entrapment in the retinal vessels of diabetic rats. Bucillamine may have therapeutic efficacy in preventing the development of diabetic retinopathy.

DOI： 10.1007/s10384-005-0322-9

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記述言語：英語  

OBJECTIVE: To investigate the effect of systemic administration of simvastatin on the retinal circulation. METHODS: The effects of systemic administration of simvastatin on the retinal circulation after 90 minutes and after 7 days were studied in a placebo-controlled, double-masked, clinical trial among 12 healthy men. We used laser Doppler velocimetry to measure vessel diameter and blood velocity and calculated the blood flow in retinal arteries and veins. We also measured the intraocular pressure and the plasma nitrite/nitrate levels, the stable end products of nitric oxide metabolism. RESULTS: There were no significant changes in any retinal circulatory parameters at 90 minutes after administration of simvastatin. Daily administration of simvastatin for 7 days significantly increased blood velocity and blood flow in retinal arteries and veins but did not significantly change vessel diameter. The intraocular pressure significantly decreased at 90 minutes and at 7 days after administration of simvastatin. Simvastatin also significantly increased the plasma nitrite/nitrate levels. CONCLUSION: Simvastatin induced an increase in blood velocity and blood flow in retinal arteries and veins, increased the plasma nitrite/nitrate levels, and decreased the intraocular pressure, probably through the increase in nitric oxide.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: To evaluate wall shear stress (WSS) on retinal microcirculation noninvasively. METHODS: Retinal vessel diameter (D) and mean centerline blood velocity (V(max, mean)) were measured in the retinal arterioles and venules at first- and second-order branches in 13 subjects using laser Doppler velocimetry (LDV). Retinal blood flow (RBF) and wall shear rate (WSR) were calculated using these two parameters. Blood viscosity at the calculated shear rate was also measured using a cone-plate viscometer. WSS was calculated as the product of the WSR and the blood viscosity. RESULTS: In the first-order branches, the averaged D, V(max, mean), RBF, and WSR(mean) were 108 +/- 13 microm, 41 +/- 10 mm/s, 11 +/- 4 microL/min, and 1539 +/- 383 s(-1) in the arterioles and 147 +/- 13 microm, 23 +/- 3 mm/s, 12 +/- 4 microL/min, and 632 +/- 73 s(-1) in the venules, respectively. The apparent blood viscosities at the measured shear rates were 3.5 +/- 0.3 centipoise (cP) in the arterioles and 3.8 +/- 0.4 cP in the venules. Therefore, the averaged WSS was 54 +/- 13 dyne/cm2 in the arterioles and 24 +/- 4 dyne/cm2 in the venules. The WSS in the second-order arterioles was significantly lower than that in the first-order branches (P = 0.002), but the WSS in the first-order venules was similar to that in the second-order venules. CONCLUSIONS: The authors demonstrated that the WSS in the retinal vessels could be evaluated noninvasively in humans using LDV and cone-plate viscometry. This system may be useful for further clinical investigation of the role of shear stress in the pathogenesis of various retinal disorders.

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記述言語：日本語  

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To determine the changes in the pulse amplitude (PA) and the pulsatile ocular blood flow (POBF) after scleral buckling (SB). Methods: Retrospectively, we studied 24 patients (average age, 52 years) who had undergone SB to repair a retinal detachment in one eye. The patients were divided into two groups: those in whom SB had been performed less than 6 months earlier (n = 10), and those in whom the procedure had been performed more than 6 months previously (n = 14). In each group, the PA and the POBF were determined with a computerized tonometry system, and the values in the SB eyes were compared with those in the control fellow eyes. Results: Within 6 months postoperatively, the mean PA in the SB eyes (0.66 ± 0.30 mmHg) was significantly lower than that in the control eyes (1.43 ± 0.34 mmHg
P &lt
0.05). The mean POBF in the SB eyes (349.5 ± 154.1 μl/min) was also significantly lower than that in the control eyes (631.0 ± 226.6 μl/min
P &lt
0.05). After more than 6 months postoperatively, there were no significant differences in the PA or the POBF between the SB eyes (1.08 ± 0.49 mmHg and 612.4 ± 341.2 μl/min, respectively) and the control eyes (1.50 ± 0.51 mmHg and 589.5 ± 278.4 μl/min, respectively). Conclusions: These results indicate that the choroidal blood flow decreases after SB but returns to normal levels after 6 months. © Japanese Ophthalmological Society 2005.

DOI： 10.1007/s10384-004-0161-0

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記述言語：英語  

PURPOSE: To examine the relation between intima-media thickness (IMT) in the common carotid artery, which is generally recognized as a marker of early atherosclerosis, and retinal circulatory parameters. METHODS: The vessel diameter and blood velocity of retinal arterioles were measured with laser Doppler velocimetry (LDV) in 33 patients with coronary artery disease (CAD), because they were thought to have general atherosclerosis. The retinal blood flow (RBF) and wall shear rate (WSR), an index of wall shear stress in retinal vessels, were calculated from the two parameters. The carotid IMT was evaluated with B-mode ultrasonography. RESULTS: The patients were divided into two groups: those with an IMT >0.70 mm and those with an IMT < or =0.70 mm. The blood velocity, WSR, and upstroke time in the retinal arterioles were significantly higher in the group with an IMT >0.70 mm compared with the group with an IMT < or =0.70 mm. There were no significant differences in vessel diameter and RBF between the groups. Positive correlations were found between the carotid IMT and blood velocity (r = 0.51, P = 0.002) and WSR (r = 0.60, P = 0.0001). Multiple regression analysis showed that the retinal WSR and blood velocity correlated independently with the IMT in patients with CAD. CONCLUSIONS: The present findings from this pilot study suggest that the retinal circulatory parameters measured by LDV may be associated with systemic atherosclerosis. These results support recent studies showing an association between retinal microvascular changes and cardiovascular disease.

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記述言語：英語  

OBJECTIVE: To examine the effect of ocular warming on retinal blood flow (RBF) and subfoveal choroidal blood flow (CBF) in humans. METHODS: Ocular warming was induced in 10 healthy volunteers using an ocular warming lamp for 10 minutes. The ocular surface temperature was measured before and after warming. The RBF in the retinal artery and vein and the CBF in the foveal region were examined with a retinal laser Doppler velocimetry system and a laser Doppler flowmeter, respectively. Ocular blood flow measurements were performed before and 3, 6, and 9 minutes after warming. RESULTS: The ocular surface temperature significantly increased just after warming and returned to baseline 10 minutes later. Three minutes after warming, the mean +/- SE RBF significantly increased in the retinal artery (14.2% +/- 3.5%, P = .01) and vein (15.8% +/- 3.6%, P = .006). Six minutes after warming, the RBF returned to baseline in the artery and vein. Three and 6 minutes after warming, the mean +/- SE CBF significantly decreased 16.6% +/- 4.2% and 24.2% +/- 4.7%, respectively (P = .001 for both). Nine minutes after warming, the measurements returned to baseline. CONCLUSIONS: The RBF increased and the CBF decreased in the foveal region after cessation of ocular warming in healthy young volunteers. The CBF in the foveal region may contribute to maintaining a constant retinal temperature in response to ocular warming.

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: To investigate whether nitric oxide (NO) contributes to the regulation of retinal circulation during hypercapnia in cats. METHODS: NG-nitro-L-arginine-methylester (L-NAME; n=8), a NOS inhibitor; NG-nitro-D-arginine-methylester (D-NAME; n=6), the inactive isomer; or phosphate-buffered saline (PBS; n=8) was injected intravitreously into the cat's eye. A selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI; n=6), was injected intraperitoneally. Hypercapnia was induced for 10 minutes by inhalation of 5% carbon dioxide with 21% oxygen and 74% nitrogen. The vessel diameter and blood velocity were measured simultaneously in large retinal arterioles in cats by laser Doppler velocimetry and the retinal blood flow (RBF) calculated. Retinal vascular resistance (RVR) was also estimated. RESULTS: In the PBS group, the vessel diameter (9.5% +/- 2.7%, P<0.05), blood velocity (15.6% +/- 4.4%, P<0.05), and RBF (37.2% +/- 3.7%, P<0.05) increased, and the RVR decreased (-26.0% +/- 2.7%, P<0.05) during hypercapnia. In the L-NAME group, those changes were greatly suppressed in response to hypercapnia. D-NAME was inactive with regard to RBF during hypercapnia. The RBF responses to hypercapnia after the 7-NI injection were significantly attenuated compared with those before 7-NI injection (P<0.05). CONCLUSIONS: These results indicate that NO contributes to the increase in RBF during hypercapnia. Furthermore, the NO synthesized by the action of nNOS may participate in regulation of RBF during hypercapnia.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: To describe a newly developed stabilized retinal laser Doppler instrument, to report the reproducibility of retinal blood flow measurements, and to present examples of its clinical application. DESIGN: Experimental study. METHODS: The intrasession, intersession, and interobserver reproducibility of retinal blood flow measurements obtained using the Canon Laser Blood Flowmeter model CLBF 100 was assessed. Intrasession: the coefficients of variation (CV) for repeated measurements (5X) of retinal vessel diameter (D), time-average centerline blood velocity (V(av)), and blood flow (F) were calculated at 18 sites along temporal retinal arteries and 18 sites along temporal retinal veins using both eyes in six healthy volunteers. Intersession: the correlation coefficients and average differences between two sets of measurements at the same 36 retinal sites made by one examiner on two different days were calculated. Interobserver: the correlation coefficients and average differences between two sets of measurements at nine sites (five arterial and four venous) in five eyes of five of the volunteers made by two examiners on the same day were calculated. Results from two patients, one with branch retinal vein occlusion (BRVO), and one with central retinal vein occlusion (CRVO), are used to illustrate abnormal retinal circulatory characteristics. RESULTS: intrasession: CV (mean +/- SD) for D, V(av), and F were 5.5% +/- 2.2%, 13.1% +/- 6.3%, and 13.8% +/- 4.7% in arteries and 3.5% +/- 2.1%, 11.9% +/- 5.9%, and 12.7% +/- 5.5% in veins. Intersession/interobserver: strong correlations between measurements made by one examiner on two different days and by two examiners on the same day were found in D, V(av), and F. Average differences in F were 16.4% +/- 12.8% for intersession and 12.6% +/- 7.0% for interobserver comparisons. Results from the patient with BRVO show marked differences in flow characteristics in the affected quadrant compared with an unaffected quadrant in the same eye, and to the fellow eye. Results from the patient with CRVO show a dramatic improvement in flow characteristics after clearing of the occlusion. CONCLUSIONS: The reproducibility results and the fact that blood flow is measured in actual units of microl/min indicate that the instrument can be used for reliable comparison of blood flow characteristics at different retinal vascular sites in the same eye, at comparable sites in both eyes, and for comparison between patients and healthy control subjects.

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: To investigate how nitric oxide (NO) contributes to the regulation of retinal circulation during rest and hypoxia in cats. METHODS: N(G)-nitro-L-arginine-methyl ester (L-NAME; n = 7), an NO synthase inhibitor; N(G)-nitro-D-arginine methyl ester (D-NAME; n = 6), the inactive isomer; or phosphate-buffered saline (PBS; n = 7) was injected intravitreously. Hypoxia was induced in the cats by the administration of 10% oxygen. Vessel diameter and blood velocity were measured simultaneously in the anesthetized cats with a laser Doppler velocimetry system, and the retinal blood flow (RBF) and wall shear rate (WSR) were calculated as an index of shear stress on the retinal vessel wall. RESULTS: After intravitreous injection of L-NAME, the vessel diameter (-8.1% +/- 2.0%, P < 0.01), velocity (-17.0% +/- 3.7%, P < 0.01), and RBF (-29.4% +/- 4.6%, P < 0.01) significantly decreased compared with the preinjection level. In the PBS group, maximum increases above the prehypoxia diameter (13.7% +/- 3.5%, P < 0.01), velocity (39.5% +/- 8.6%, P < 0.01), RBF (73.9% +/- 10.6%, P < 0.01), and WSR (28.3% +/- 7.1%, P < 0.01) were observed during hypoxia. In the L-NAME group, those changes substantially decreased in response to hypoxia. D-NAME was inactive with regard to RBF during rest and hypoxia. CONCLUSIONS: These results suggest that NO may be continuously produced in the retina during rest and contributes to increased RBF during hypoxia. In addition, the increased WSR during hypoxia indicates that NO plays an important role in retinal hypoxic hyperemia through a flow-induced mechanism.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

PURPOSE: The purpose of this study was to investigate the response of the retinal arteriole to an acute increase in systemic blood pressure (BP). METHODS: Sixteen healthy volunteers underwent a 5-minute cold pressor test (CPT) on the left hand. Retinal blood flow (RBF) was determined using a laser Doppler velocimetry system that enables simultaneous measurements of blood velocity and vessel diameter in a retinal artery every 30 seconds for the duration of the CPT. The mean arterial BP (MABP) was measured every 30 seconds during the test. RESULTS: The MABP immediately increased and reached the maximum level (from 85.1 +/- 2.7 to 103.7 +/- 5.0 mm Hg; P < 0.01) 1.5 +/- 0.2 minutes after the CPT began. The peak increase in velocity (from 30.6 +/- 1.3 to 46.1 +/- 2.1 mm/sec; P < 0.01) occurred at 1.6 +/- 0.2 minutes, resulting in an increase in RBF (from 10.1 +/- 1.0 to 14.3 +/- 1.4 microL/min; P < 0.01). The peak decrease in diameter (115.8 +/- 5.0 to 105.1 +/- 5.0 microm; P < 0.01) occurred at 2.9 +/- 0.3 minutes and the RBF returned to the baseline value. The increases in MABP significantly correlated with the decreases in diameter (r = -0.674, P = 0.0059). CONCLUSIONS: The CPT caused an acute increase in MABP that was associated with a transient increase in RBF and blood velocity, followed by constriction of the retinal arterioles and return of RBF to baseline. The results suggest that constriction of the retinal arterioles plays an important role in the maintenance of RBF in response to an acute increase in systemic BP.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

- Background: The pathogenesis of idiopathic macular hole is unclear. We studied the morphologic features of idiopathic macular holes using a modification of the scanning laser ophthalmoscope (SLO). - Methods: Seventy-two eyes of 57 patients with macular hole (40 women, 17 men
age 66.1 ± 6.4, years, mean ± SD) were included in this study. The macular holes were classified according to the Gass classification (1988). The changes around the macular holes were recorded by SLO using both a confocal aperture with a helium-neon laser (633 nm) and a ring aperture (dark-field mode) with a diode laser (780 nm) to detect fine morphologic features. - Results: We successfully observed minute retinal wrinkling, i.e., radiating striae (fold type) and a dome configuration (dome type), around the macular holes using the SLO dark-field mode with a diode laser, which provides a deeper retinal image because of the longer wavelength laser and the indirect mode. A helium-neon laser with a confocal aperture sometimes failed to disclose the fine retinal wrinkles. Most of the stage 2 macular holes were of the fold type. The smaller the hole, the higher the prevalence of the fold type. As the holes progressed in size, the prevalence of the dome type increased. The radiating retinal folds disappeared after successful vitreous surgery. - Conclusion: The SLO dark-field mode with a diode laser might be useful for clear observation of fine retinal features around macular holes. The retinal folds probably indicate the presence of traction on the macula and hence may be good markers for macular repair after vitreous surgery.

DOI： 10.1007/s004170050104

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Royal College of Ophthalmologists  

Purpose. To determine the short- and long-term effects of betaxolol and timolol on human retinal circulation. Methods. In a double-masked, randomised, placebo-controlled study we evaluated the effects of both a one-drop application and a twice-daily 2-week application of either topical 0.5% betaxolol hydrochloride or topical 0.5% timolol maleate on the retinal circulation in 12 healthy volunteers. Laser Doppler velocimetry was used to detect changes in the retinal venous blood flow. Results. In both betaxolol- and timolol-treated eyes, intraocular pressure decreased significantly compared with baseline values after both 90 min and 2 weeks. In betaxolol-treated eyes, retinal blood flow did not change significantly after 90 min, but increased significantly (14 ± 9%
p = 0.02) compared with baseline after 2 weeks. In timolol-treated eyes, retinal blood flow decreased significantly (18 ± 5%: p = 0.04) compared with baseline after 90 min, and also decreased significantly (14 ± 6%
p = 0.04) compared with baseline after 2 weeks. Conclusions. Retinal blood flow increases as a long-term effect of betaxolol and decreases as both a short- and long-term effects of timolol.

DOI： 10.1038/eye.1998.216

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The effects of topically applied timolol (a nonselective beta-blocker) and UF-021 (a prostaglandin-related compound) on pulsatile ocular blood flow (POBF) were investigated in 9 healthy volunteers. One drop of either UF-021 or timolol was instilled in one randomly selected eye and the fellow eye received physiologic saline. Before and 90 min after drop instillation, we measured intraocular pressure (IOP), POBF, heart rate (HR) and blood pressure (BP). After a washout interval of at least 1 week, the other drug was instilled in the previously treated eye. IOP, POBF, HR, and PB were measured following the same protocol. After timolol administration, IOP and POBF decreased significantly in the treated eye (26%, p = 0.01, and 13%, p = 0.02, respectively) and in the fellow eye (11%, p = 0.01, and 11%, p = 0.03, respectively). HR also decreased (10%, p = 0.03), but BP did not change significantly. After UF-021 administration, no significant changes were found in IOP, POBF, HR, or BP. Our results suggest that in normal subjects timolol decreases POBF in both the treated and the untreated eyes, whereas UF-021 has no action on either IOP or POBF. © 1997 S. Karger AG, Basel.

DOI： 10.1159/000268008

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PubMed

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記述言語：日本語   著書種別：学術書

記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：日本白内障学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J02566&link_issn=&doc_id=20210621350011&doc_link_id=10.14938%2Fcataract.13-011&url=https%3A%2F%2Fdoi.org%2F10.14938%2Fcataract.13-011&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(公社)日本医師会  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：日本眼光学学会  

網膜血管造影検査の意義を考えてみると、蛍光眼底造影検査(FA)および血管造影検査(OCTA)などの網膜血管造影検査はあくまでも血流が流れている部分と流れていない部分を区別する方法である。一方、眼血流測定法は、血流情報を数値化して評価できることにより、軽度の血流低下などを早期に検出できる可能性がある。これまでに臨床で用いられてきたレーザードップラー法やレーザースペックル法などの網膜血流量評価法に加えて、近年の光干渉断層計(OCT)技術を応用したドップラーOCT血流計が開発された。本稿では、これまでの眼循環測定法と比較しながらドップラーOCTの測定原理と今後の臨床応用への期待について述べる。(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J02611&link_issn=&doc_id=20180122560003&doc_link_id=10.11432%2Fjpnjvissci.38.93&url=https%3A%2F%2Fdoi.org%2F10.11432%2Fjpnjvissci.38.93&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

黄斑浮腫は糖尿病網膜症や網膜静脈閉塞症などさまざまな病態で引き起こされるが、その基本病態に眼循環障害も関与している。これまでの眼循環測定にはレーザードップラー法やレーザースペックル法などが用いられ、黄斑浮腫の診断や治療効果の判定に役立てられてきた。さらに最近ではOCTアンギオグラフィーも臨床応用され、さらに詳しい検討がなされている。特に網膜毛細血管網の3次元的解析により、浅層よりも深層毛細血管網の障害が黄斑浮腫の病態に関与する可能性が示唆されている。(著者抄録)

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記述言語：日本語   出版者・発行元：(公社)日本眼科医会  

糖尿病網膜症・黄斑浮腫は眼循環がその病態に深く関与する代表的疾患である。眼循環測定法としては蛍光眼底造影検査に加え、レーザードップラー法やレーザースペックル法などの定量的測定法が開発され、さらに最近では造影剤を用いない網膜血管造影法としてOCTアンギオグラフィーも登場した。定量的測定法の結果から、糖尿病網膜症早期には網膜血流の低下が示唆されていたが、最近のOCTアンギオグラフィーから得られる知見もこれを支持するものと現時点では考えられる。眼循環評価には測定法の問題に加え血糖コントロールや腎機能など全身因子の関与があることも忘れてはならない。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

最近めざましく進歩している眼底イメージングについて,特に網膜血管に焦点を絞り,血管構築(造影検査)と循環動態(血流測定)の2つの観点から,最近のテクノロジーの進歩と臨床応用への可能性についてまとめたい。(著者抄録)

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

目的:低眼圧症に対し,前眼部光干渉断層計(AS-OCT)により毛様体解離の範囲を同定した後,強膜毛様体縫合術を行った症例の報告。症例:60歳男性が右眼の眼内レンズ脱臼で紹介受診した。23年前に金属片により右眼が受傷し,その9年後に眼内レンズが挿入された。その5年後に鈍性外傷で眼内レンズが脱臼し,無水晶体眼になった。5ヵ月前に眼内レンズ縫着を受けた。矯正視力は1.2,眼圧は9mmHgであった。所見と経過:右眼視力は0.5,眼圧は5mmHgで,眼内レンズの状態に異常はなく,眼底に黄斑浮腫など低眼圧症の所見があった。隅角鏡検査で右眼の隅角に2時半から4時にかけての隅角解離と毛様体解離があった。AS-OCTでは,毛様体解離は隅角鏡検査よりも広い範囲にあった。その後,強膜毛様体縫合術を行った。術後のAS-OCTで毛様体解離は消失し,矯正視力は1.0,眼圧は10mmHgになり,網脈絡膜皺襞など低眼圧黄斑症の所見が消失した。結論:AS-OCTは,外傷性の毛様体解離の術前術後の評価に有用であった。(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J01537&link_issn=&doc_id=20160907210024&doc_link_id=10.11477%2Fmf.1410211955&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410211955&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：医歯薬出版(株)  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(株)医学出版  

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記述言語：日本語   出版者・発行元：金原出版(株)  

近年、眼科診療において、OCT信号の位相変化や強度変化を基に、血流の三次元画像を表示する"OCT angiography"と総称される技術が考案され、神経組織に埋もれる微小血管構造の画像化が可能となった。また、laser speckle flowgraphyは、眼底の血流分布を二次元カラーマップとして表示できる血流画像解析法で、同一部位における経時的変化の比較によく用いられる。これら2つの非侵襲的眼底造影法について、その原理と臨床応用例などについて詳しく説明した。

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J00293&link_issn=&doc_id=20160714150006&doc_link_id=10.18888%2FJ00293.2016367775&url=https%3A%2F%2Fdoi.org%2F10.18888%2FJ00293.2016367775&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(株)日本臨床社  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(株)全日本病院出版会  

高血圧網膜症は、持続する高血圧により、網膜血管が障害され、網膜に出血や滲出斑を呈する疾患である。また、高血圧の程度や罹病期間により、高血圧網膜症のみならず、さまざまな高血圧性眼底変化を認めることも知られている。眼底検査で観察される網膜血管は、非侵襲的に観察できる生体内で唯一の血管であることからも、高血圧診療における眼底検査や蛍光眼底検査は重要である。この稿では、高血圧網膜症も含めた高血圧性眼底変化について解説し、血圧の変動による血流の自己調節autoregulationについて、我々の研究も含め紹介する。(著者抄録)

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記述言語：日本語   出版者・発行元：金原出版(株)  

両眼の先天無眼球症の女児に対し、地方の一般眼科医が早期治療を行った。眼瞼幅5mmで、睫毛、涙丘を認め、生後1日のCTで眼球、視神経は認めないが外眼筋を認めた。他に明らかな先天異常はなかった。生後13日より両結膜嚢内へのコンフォーマー挿入を開始し、生後5ヵ月までは2週間に1回、6ヵ月以降は4週間に1回の診察を行い、可能であればコンフォーマーのサイズ変更を行った。生後9ヵ月以降は家庭でのコンフォーマーの付け外しと洗浄を指導した。1歳0ヵ月時に眼瞼幅15mmとなり、幅15mm、高さ12mmのコンフォーマーを挿入中である。本例は生後直後に眼形成専門医と連絡を取って治療方針を決定し、出生した地域病院で早期治療を行った。患者は通院の負担が少なく頻繁なコンフォーマーサイズ変更を行うことができ、結膜嚢と眼窩の良好な発育が得られた。なお、本邦における2000年以降の無眼球症関連の報告は5報で、一般病院での治療報告はなかった。

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：日本緑内障学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

Web of Science

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

Web of Science

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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担当区分：筆頭著者   記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：メディカル葵出版  

記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J01784&link_issn=&doc_id=20150407200004&doc_link_id=%2Fah9atgke%2F2015%2F003203%2F005%2F0331-0337%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fah9atgke%2F2015%2F003203%2F005%2F0331-0337%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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担当区分：筆頭著者   記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：医学書院  

記述言語：日本語   出版者・発行元：医学書院  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2015095575

記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

目的:糖尿病性腎症による末期腎不全を合併した糖尿病黄斑浮腫(DME)が、腎移植または血液透析の導入で改善した5症例を経験したので報告する。症例:腎移植となった症例は43歳、男性。DMEに両眼トリアムシノロンTenon嚢下注(STTA)、左眼bevacizumab硝子体注(IVB)施行したが著効せず、中心窩網膜厚(CMT)は右眼464μm、左眼394μm、小数視力は右眼(0.2)、左眼(0.5)であった。生体腎移植が施行され、全身の溢水状態は改善し、体重は20kg減少した。腎移植3ヵ月後、CMTは右眼275μm、左眼285μmに減少し、視力は両眼(0.8)へ改善した。血液透析が導入された4例(平均年齢62.8歳)では、5眼でDMEを認めた。嚢胞様黄斑浮腫(CME)、漿液性網膜剥離(SRD)をそれぞれ4眼で認めた。2眼でSTTA施行、1眼でIVB施行されたが、著効は示さず、透析導入前の平均CMTは550.8μmであった。透析導入後、平均4.6ヵ月で全例にDMEの改善が認められ、CME、SRDも全例で消失した。透析導入後の平均CMTは298.6μmであった。結論:腎移植や血液透析による全身溢水状態の改善が、DMEの改善にも繋がることが示唆された。(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J01784&link_issn=&doc_id=20150227170021&doc_link_id=http%3A%2F%2Famcor.asahikawa-med.ac.jp%2Fmodules%2Fxoonips%2Fdetail.php%3Fid%3D2015170533&url=http%3A%2F%2Famcor.asahikawa-med.ac.jp%2Fmodules%2Fxoonips%2Fdetail.php%3Fid%3D2015170533&type=%88%AE%90%EC%88%E3%89%C8%91%E5%8Aw%81F%88%AE%90%EC%88%E3%89%C8%91%E5%8Aw%8Aw%8Fp%90%AC%89%CA%83%8A%83%7C%83W%83g%83%8A_AMCoR&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80003_3.gif

記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病合併症学会  

我々は臨床研究において、2型糖尿病患者では網膜症発症前からすでに網膜血流が低下していることを見出し、この血流低下を改善させることによって網膜症の発症・進展を予防するという新しい治療戦略を考えている。日常臨床で広く用いられている内服薬の中で、網膜循環を改善させる作用を有する薬剤をスクリーニングするため、摘出網膜血管を用いたex vivo実験を行い、シンバスタチンやピオグリタゾンなどの薬剤や、サプリメントとして用いられるレスベラトロール、さらには抗生活習慣ホルモンであるアディポネクチンが、網膜動脈を拡張させることを報告した。我々の研究成果より、網膜循環改善に着目した内服薬の選択という、新しい網膜症治療戦略を開拓できる可能性が示唆された。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J01784&link_issn=&doc_id=20140425300003&doc_link_id=%2Fah9atgke%2F2014%2F003104%2F004%2F0493-0496%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fah9atgke%2F2014%2F003104%2F004%2F0493-0496%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：日本糖尿病眼学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

目的:東アジアにおける大規模臨床試験の計画を見据えて,日韓の糖尿病網膜症治療の現状について比較調査を行う.対象と方法:2012年6〜7月に日本糖尿病眼学会会員および韓国網膜硝子体学会会員を対象にアンケートを行い,日本120名,韓国91名の回答を得た.アンケート作成には,American Society of Retina SpecialistsのPreferences and Trends(PAT)surveyを参考にした.結果:局所性黄斑浮腫に対する第一選択として最も多かった回答は日本で副腎皮質ステロイドテノン【嚢】下注射(22%),韓国で抗血管内皮増殖因子薬硝子体内注射(31%),PAT surveyで局所光凝固(68%)であった.血管新生緑内障に対する手術では日本は線維柱帯切除術(57%)が多かったが,韓国ではほとんどが緑内障インプラント手術(74%)であった.結論:日本,韓国間で糖尿病網膜症の治療方針に差異がみられた.今後両者にとって納得のいくプロトコールで,意義のある臨床研究デザインをよく考える必要があると思われた.(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J01049&link_issn=&doc_id=20130913400004&doc_link_id=1520009407091126016&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1520009407091126016&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif