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：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To evaluate retinal circulation in eyes with central retinal artery occlusion (CRAO). METHODS: The best-corrected visual acuity (BCVA), fluorescein angiography (FA), and laser speckle flowgraphy (LSFG) values were measured at the first visit in 42 patients with CRAO (42 eyes; mean age, 66.0±14.0 years. LSFG was performed at baseline, 1 week, and 1, 3, and 6 months; the difference between the mean blur rate vessel area and mean blur rate tissue area (MV-MT), reflecting the retinal vessel blood flow, was measured. FA measured the arteriovenous passage (AV) time. Time-course changes in the MV-MT and BCVA and the relationship between MV-MT and final BCVA were examined. RESULTS: MV-MT was significantly correlated with AV time (P<0.001). The MV-MT increased significantly after 1, 3, and 6 months (P<0.001). The VA improved significantly until 1 month (P<0.01). Multivariate analysis showed a significant correlation between the baseline BCVA (P<0.001) and MV-MT at 1 month (P=0.01) and the final BCVA. Age and MV-MT were significantly negatively correlated at 1 month (P<0.001). CONCLUSIONS: The retinal circulation improved significantly within 1 month; younger patients had better retinal circulation improvement. The baseline BCVA and retinal circulation within 1 month were correlated with the final BCVA.

DOI： 10.1097/IAE.0000000000004264

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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 the association between the time from onset to initial treatment and changes in visual acuity or the number of treatments in patients with branch retinal vein occlusion (BVO). DESIGN: Retrospective. METHODS: Thirty-nine eyes of 39 consecutive patients with untreated acute-phase BVO who visited the University of Tokyo Hospital and were followed up for at least one year were included. The patients were initially treated with anti-vascular endothelial growth factor (VEGF) therapy and additional pro re nata therapy within six months of onset. The patients were classified according to the time from disease onset to the first treatment (group A: 28 days or less, group B: over 28 days). RESULTS: The mean (SD) age was 73 ± 8 years, and 19 patients were male. The mean (SD) time to the first treatment was 31.6 ± 17.9 days. The mean (SD) logMAR visual acuity at first treatment was 0.37 ± 0.30. After 12 months of treatment, the mean (SD) logMAR change was - 0.15 ± 0.23, and the mean number (SD) of treatments was 3.1 ± 1.7. No significant association was observed between the timing of treatment initiation and changes in logMAR visual acuity. Patients in group A and central macular thickness at the initial visit were independently associated with the greater number of treatments at one year (p = 0.03 and p = 0.01, respectively). CONCLUSIONS: At one year, the time between onset and the start of anti-VEGF therapy for BVO was not associated with subsequent visual acuity changes. Meanwhile, it may have significant association with the number of treatments.

DOI： 10.1007/s10792-024-03272-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This retrospective study aimed to investigate the progression of central retinal vein occlusion (CVO) prior to treatment initiation and its impact on prognosis. Of the 54 studied eyes with acute CVO, the average logMAR visual acuity (VA) at the initial visit was 0.65 ± 0.49 with an average time to treatment of 14.9 ± 14.5 days. VA at the initial treatment was identified as a stronger predictor of VA at the final visit compared to VA at the first visit or other factors. Patients who received treatment more than 28 days after the initial visit experienced a significant decline in VA compared to those treated within 28 days (0.21 ± 0.35 vs. 0.04 ± 0.13, p = 0.006). Additionally, patients who were treated between 15 and 28 days showed a greater decrease in VA compared to those treated within 14 days (0.12 ± 0.46 vs. 0.018 ± 0.02, p = 0.026). These findings from the current retrospective analysis suggesting that there is a possibility of VA decline at the initial treatment associating with worse prognosis even when treatment is administered within a month should be further investigated in the prospective study. Also, it may be crucial to consider frequent monitoring of acute CVO patients for initiating treatment at the optimal timing.

DOI： 10.1038/s41598-024-67925-7

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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 long-term visual outcomes after initial treatment with combined photodynamic therapy (PDT) or aflibercept treat-and-extend (TAE) monotherapy in patients with pachychoroid neovasculopathy (PNV). METHODS: Patients diagnosed with PNV, initially treated with PDT combined with anti-vascular endothelial growth factor (VEGF) or intravitreal aflibercept (IVA) monotherapy in the TAE protocol and followed up for at least 6 months, were included in the study. Medical records were retrospectively reviewed. Survival analysis was performed, in which deterioration in logMAR visual acuity by 0.1 or 0.3 is defined as "death." The annual number of treatments was also analyzed. Sub-analysis was performed on 33 patients diagnosed with PNV without polypoidal lesions. RESULTS: This study included 46 patients (23 in the initial combined PDT group and 23 in the IVA TAE group). Mean age, sex, mean baseline logMAR visual acuity, or duration of observation (3.6 ± 3.2 years vs. 3.1 ± 1.9 years) in both groups were comparable. As for visual outcome, no significant differences were found in survival analysis based on worsening of 0.1 or 0.3 logMAR (3-year survival; 26% vs. 26%, 91% vs. 90%, respectively). Meanwhile, the additional number of anti-VEGF injections per year was significantly lower in the initial combined PDT group than in the IVA TAE group (1.0 ± 1.3 vs. 4.1 ± 1.5, p < 0.0001). No significant differences were found in the number of additional PDTs per year (0.07 ± 0.20 vs. 0.02 ± 0.09, p = 0.27). Similar results were found in a sub-analysis of 33 patients without polyps. CONCLUSION: In the treatment of PNV, regardless of the presence of polyps, the long-term visual outcomes were similar between the initial combined PDT and IVA TAE monotherapy. However, the annual number of anti-VEGF injections was lower in the initial combined PDT group than in the aflibercept TAE group, whereas that of PDT was comparable.

DOI： 10.1007/s00417-024-06387-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Recent evidence suggests that venous congestion at the vortex vein significantly contributes to the development of central serous chorioretinopathy (CSCR), and sclera is observed to be thicker in affected eyes. This study aims to investigate whether eyes with CSCR exhibit stiff corneas, measured using Corneal Visualization Scheimflug Technology (Corvis ST), which may serve as an indicator of scleral stiffness. METHODS: This retrospective case-control study comprises 52 eyes from 33 patients diagnosed with CSCR and 52 eyes from 32 normal controls without CSCR. We compared biomechanical parameters measured with Corvis ST and anterior scleral thickness measured using anterior segment swept-source optical coherence tomography between the two groups. RESULTS: Age, sex, axial length, intraocular pressure, and central corneal thickness showed no significant differences between the two groups (p > 0.05, linear mixed model). Three biomechanical parameters-peak distance, maximum deflection amplitude, and integrated inverse radius-indicated less deformability in CSCR eyes compared to control eyes. The stress-strain index (SSI), a measure of stiffness, and anterior scleral thickness (AST) at temporal and nasal points were significantly higher in the CSCR eyes. SSI and AST were not correlated, yet both were significantly and independently associated with CSCR in a multivariate logistic regression model. CONCLUSIONS: Eyes affected by CSCR have stiffer corneas, irrespective of thicker scleral thickness. This suggests that stiffer sclera may play a role in the pathogenesis of CSCR.

DOI： 10.1007/s00417-024-06378-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Long-term results of photodynamic therapy (PDT) combined with vascular endothelial growth factor (VEGF) inhibitors for pachychoroid neovasculopathy (PNV) are not yet clear. METHODS: This study is a retrospective, observational case series. We retrospectively examined untreated PNV cases (22 cases, 22 eyes, mean age of 71.0 years) who underwent PDT therapy in combination with VEGF inhibitors followed by additional treatments with pro re nata protocol. Visual acuity, number of treatments, and time to recurrence were examined. In addition, foveal choroidal thickness and choroidal vascularity index (CVI) were evaluated in 13 of 22 patients who were followed up with SpectralisOCTR from baseline. RESULTS: Fifteen (68%) cases had polyps at baseline. LogMAR visual acuity averaged 0.24 ± 0.20 (range, - 0.079 to 0.82) at baseline and significantly improved after 1, 2, and 3 years (p = 0. 004, 0.0003, 0.002, respectively). Fourteen patients (64%) recurred, with an average time to recurrence of 1.8 ± 0.9 years. Foveal choroidal thickness decreased significantly after 1 year (average from 326 μm to 263 μm) and remained unchanged up to 3 years (255 μm). CVI also decreased after 1 year (average from 0.62 to 0.61) and remained unchanged until 3 years later (0.60). CONCLUSIONS: We examined the 3-year course of PDT in combination with the VEGF inhibitor for untreated PNV. Visual acuity was improved, foveal choroidal thickness and CVI were decreased after 3 years.

DOI： 10.1007/s00417-024-06499-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To describe clinical characteristics of a retinal finding termed mound-like epiretinal material (MOLEM), and distinguish it from epiretinal proliferation, a similar epiretinal finding previously described in various pathologies. METHODS: Five eyes from five patients were retrospectively identified from medical records. Clinical findings and images, including fundus photographs and optical coherence tomography (OCT), were reviewed. RESULTS: All eyes displayed mound-like material with uniform and low-to-moderate reflectivity on an otherwise intact retinal surface detected on OCT. No eyes presented with concurrent pathology typically observed in cases of epiretinal proliferation, such as lamellar/full-thickness macular hole, epiretinal membrane, vitreomacular traction, or uveitis. Two eyes exhibited central serous chorioretinopathy, but there was no association of MOLEM with serous retinal detachment. In three out of five eyes, MOLEM appeared simultaneously with posterior vitreous detachment (PVD). Some lesions underwent irregular transformations over months and occasionally disappeared. While all cases were monitored without intervention, no visual decline or complications attributed to MOLEM were detected. CONCLUSION: MOLEM represents a novel clinical finding, characterized by transient morphological changes without symptoms and potential association with PVD. It may occur in eyes lacking macular diseases linked with epiretinal proliferation, a similar yet distinct lesion. The incidence, etiology, and clinical significance of MOLEM warrant further investigation by accumulating comparable cases, although the lesion appears benign and self-limiting.

DOI： 10.1097/ICB.0000000000001570

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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：(公財)日本眼科学会  

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記述言語：英語   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   掲載種別：研究論文（学術雑誌）  

To analyze the long-term visual outcomes of pachychoroid spectrum diseases (PSD). Retrospective study. We reviewed the medical charts of consecutive patients with PSD, including focal choroidal excavation (FCE), pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), and pachychoroid neovasculopathy (PNV). The patients initially visited the Tokyo University Hospital from January 2008 to March 2021. Survival analyses were performed, in which loss of vision was defined as visual acuity (VA) of 0.2 logarithm of minimal angle of resolution (logMAR) or worse, 0.5 logMAR or worse, or VA worsening by 0.3 logMAR or greater. Moreover, we further investigated factors associated with visual prognosis, particularly in the CSC group. A total of 741 eyes of 638 patients were included in this analysis. The CSC or PNV group showed significantly worse visual prognosis than the FCE&PPE group for VA to 0.2 logMAR or worse (P = 0.0117 or 0.0001, respectively) and for VA worsening by 0.3 logMAR or greater (P = 0.0283 or 0.0037, respectively). In the CSC group, unlike age, sex, or treatment history, the accumulative duration of subfoveal fluid existence ≥ 12 months (continuous or intermittent) was significantly associated with visual prognosis (P < 0.0001). Among PSD, CSC and PNV were associated with a higher risk of vision loss in the long term than FCE and PPE. The duration of subretinal fluid existence was identified as a significant factor affecting long-term visual outcomes in CSC.

DOI： 10.1038/s41598-023-49153-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To characterize and compare macular vessel density in central retinal artery occlusion (CRAO) eyes with retinal arterial cannulation and CRAO eyes with standard treatment. This study was Cross-sectional, observational study. Twenty-two eyes with nonarteric CRAO which underwent retinal arterial cannulation and 19 eyes with nonarteric CRAO with standard treatment were included. Optical coherent tomography angiography (OCTA)-based macular vessel density and visual acuity were examined. The dynamic ranged-based normalized rates of vessel density was compared within each group at the first visit to the clinic and 7 days after the onset. Macular vessel density in cannulation group was significantly better at 7 days after the onset than that at the first visit (3.73 ± 3.02 mm-1 vs. 7.89 ± 1.02 mm-1, P = 0.0001), while there wasn't significant improvement of macular vessel density in standard treatment group at 7 days after the onset (2.13 ± 1.62 mm-1 vs. 2.89 ± 0.22 mm-1, P = 0.067). At one month after the onset, mean LogMAR visual acuity in CRAO eyes with cannulation significantly improved compared with that at the first visit after the onset (1.678 vs. 0.979, P = 0.00012). Macular vessel density loss in CRAO eyes was improved by retinal arterial cannulation. Early intervention of retinal arterial cannulation is useful for minimizing visual impairment in CRAO eyes.

DOI： 10.1038/s41598-023-46267-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Limited information regarding the anatomical and visual prognosis of macular telangiectasia (MacTel) type 2 in the Asian population is currently available. Herein, we conducted a retrospective longitudinal analysis of Japanese patients diagnosed with MacTel type 2. Disease progression was evaluated using the Simple MacTel Classification developed by Chew EY et al. in 2023, and its association with visual changes was analyzed. Sixteen eyes of eight Japanese patients were included in the study, with an average follow-up period of 8.2 ± 3.9 years (range, 2.2-14.0). At the initial visit, 7 (44%) and 5 (31%) eyes were classified as Grade 2 (central ellipsoid zone break) and Grade 3 (noncentral pigment), respectively. The proportion of eyes that progressed by 1 or 2-steps in grade after 1, 3, 5, 8, and 12 years was 0%, 14%, 43%, 70%, and 100%, or 0%, 7%, 7%, 30%, and 75%, respectively. The visual acuity significantly deteriorated during the follow-up period, particularly in the two eyes with full-thickness macular holes (FTMH). Three out of 7 patients exhibited low serum serine concentrations, although no apparent correlation with anatomical or visual outcomes was observed. Overall, this cohort demonstrated chronic disease progression, both anatomically and functionally, in eyes with MacTel type 2, with FTMH potentially associated with greater visual loss.

DOI： 10.1038/s41598-023-46394-4

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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：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To evaluate the relationship between retinal haemorrhages detected on Ultra-widefield (UWF) red channel images and perfusion status in eyes with acute central retinal vein occlusion (CRVO). METHODS: UWF fundus images were split into green and red channels using ImageJ software. The retinal haemorrhages were calculated quantitatively with both the green and red channel images, resulting in green channel haemorrhages (GCH) and red channel haemorrhages (RCH). The nonperfusion area (NPA) was also calculated from fluorescein angiography in each eye. The relationships between both the GCH and RCH with the NPA were investigated. RESULTS: Thirty-two eyes of 32 patients with acute CRVO (18 men, 14 women) were included. The mean GCH and RCH values were 10.4% ± 8.2% and 1.7% ± 1.7%, respectively. The mean NPA was 39.2% ± 28.8%. Significant correlations were seen between the GCH and NPA (r = 0.38; P = 0.022) and RCH and NPA (r = 0.44; P = 0.010, linear regression analysis). Multivariate analysis suggested that only the RCHs were correlated significantly with the NPA. CONCLUSIONS: Retinal haemorrhages detected by UWF red channel imaging were less compared to green channel imaging and associated closely with retinal NPAs in eyes with acute CRVO. UWF red channel imaging allowed us to identify ischaemia-related haemorrhage.

DOI： 10.1038/s41433-022-02337-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The current study aims to investigate the postoperative refractive outcomes in eyes that underwent the flanged intrascleral IOL fixation combined with vitrectomy with or without gas/air tamponade. METHODS: We divided the eyes into two groups (Group A; eyes that underwent flanged intrascleral IOL fixation with gas/air tamponade, Group B; eyes that underwent flanged intrascleral IOL fixation without gas/air tamponade). The predicted spherical equivalent (SE) refraction values were calculated using the SRK/T formula. Then, the prediction error (PE) was calculated by subtracting the predicted SE refraction from the postoperative objective SE refraction and the absolute prediction error (AE) was calculated as the absolute value of the PE for each eye. RESULTS: A total of 68 eyes were included in the current study. There was a significant correlation between the predicted and postoperative SE refraction in both groups (Group A, r = 0.968, p<0.0001, Group B, r = 0.943, p<0.0001, linear regression analysis). The PE demonstrated a mild myopic shift after the flanged intrascleral IOL fixation in both groups (Group A, -0.40 ± 0.96 D, Group B, -0.59 ± 0.95 D). There was no significant difference in PE and AE between the two groups (p=0.44, p=0.70, Wilcoxon rank sum test). CONCLUSION: The postoperative SE refraction after flanged intrascleral IOL fixation was not influenced by gas/air tamponade.

DOI： 10.1097/IAE.0000000000003860

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Association for Research in Vision and Ophthalmology (ARVO)  

DOI： 10.1167/tvst.12.5.5

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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 the time courses of morphologic changes in the transplanted grafts, including the retinal layer, the ellipsoid zone (EZ) and the visual acuity (VA) after autologous retinal transplantation (ART) in patients with primary large macular holes (MHs). DESIGN: Single-center, retrospective cohort study. SUBJECTS: The study included 17 eyes of 17 patients who had undergone ART. All patients fulfilled the following criteria: (1) MH was the only disease-causing anatomic abnormality of the macula; (2) they could be followed up for at least 12 months after ART surgery; (3) they had no other systemic disorders; and (4) the MH was > 400 μm in diameter. METHODS: Data of all patients who underwent assessment of the VA and spectral-domain (SD)-OCT at 1, 3, 6, and 12 months after surgery were analyzed. The morphologic features of the graft and the EZ were measured by SD-OCT. MAIN OUTCOME MEASURES: Changes in the morphologic features of the graft (graft thickness, overall graft area, graft length, area of outer retina, and EZ) and VA over 1 year after surgery. RESULTS: Closure of the MH was achieved in all patients. The VA was 0.59 ± 0.27 (logarithm of the minimal angle of resolution units) at 1-year postsurgery compared with 0.84 ± 0.22 before surgery (P < 0.05). The retinal layers gradually became smoothly connected. Although a decrease in graft thickness and overall graft area was observed, the length and area of the outer retina were maintained throughout the follow-up period. The presence of the EZ was observed in 9 patients (52.9%) and our analyses revealed significantly greater improvement of VA in these patients than in those without the EZ (P < 0.05). Moreover, the incidence of macular edema (ME) was higher in the group without the EZ (P = 0.04; chi-square test). CONCLUSION: Patients showed significant improvements of the VA. Morphologically, the layers were gradually connected to each other, and the outer retina was particularly maintained. Especially, patients in whom an EZ was restored in the graft showed a low prevalence of ME and greater improvement of the VA. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

DOI： 10.1016/j.oret.2022.12.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We investigated the effect of the number of laser shots applied on the myopic variables to elucidate the mechanism of myopia development in laser-treated retinopathy of prematurity (ROP) eyes. METHODS: A total of 33 eyes of 17 infants with ROP who underwent laser treatment were included in the analysis. Cycloplegic retinoscopic refraction testing was carried out and the spherical equivalent (SE) was calculated. Relationships between SE and various variables (including the number of laser shots applied) were examined. In addition, an age-matched control group without ROP was prepared and ocular structural parameters were compared. RESULTS: Although there was no statistical difference in axial length (AL) between two groups (p = 0.88), SE was significantly more myopic in the ROP group (p < 0.001). SE was associated with AL, corneal refraction (CR), and crystalline lens power (CLP) in the ROP group. Of these three factors (AL, CR, and CLP), CLP and the number of laser shots applied were significantly correlated (p = 0.003); however, no correlations were observed between the number of laser shots and AL or CR (p = 0.15 and 0.10, respectively). Very similar tendency was observed in the analysis of the difference between right and left eyes in each child. CONCLUSIONS: In laser-treated ROP eyes, AL, CR, and CLP were related to the degree of myopia. Moreover, the number of shots applied also affected the myopic status in laser-treated ROP eyes. Among AL, CR, and CLP, only CLP was correlated with the laser shots applied.

DOI： 10.1186/s40942-023-00456-x

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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：(公財)日本眼科学会  

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記述言語：英語   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：金原出版(株)  

＜文献概要＞巨大な黄斑円孔もしくは難治性黄斑円孔により,網膜自家移植術を受け5年以上の経過を観察することができた3例3眼を報告する。移植術を受けた際の平均年齢,平均術後観察期間,平均最小黄斑円孔径,平均視力はそれぞれ,62.3歳(男性3),67±6ヵ月,902±176μm,0.12±0.09であった。一方,最終受診時の移植網膜厚,移植網膜内のEZ長,術後視力は,それぞれ209±51μm,112±8μm,0.40±0.4であった。経過観察中に,移植片の離脱,強度の術後炎症をきたした症例はみられなかった。網膜自家移植術の術後経過は長期に安定しており,難治性の黄斑円孔に対して有効な手術治療と考えられる。

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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 the clinical validity of the Guided Progression Analysis definition (GPAD) and cluster-based definition (CBD) with the Humphrey Field Analyzer (HFA) 10-2 test in retinitis pigmentosa (RP). METHODS: Ten non-progressive RP visual fields (VFs) (HFA 10-2 test) were simulated for each of 10 VFs of 111 eyes (10 simulations × 10 VF sequencies × 111 eyes = 111,000 VFs; Dataset 1). Using these simulated VFs, the specificity of GPAD for the detection of progression was determined. Using this dataset, similar analyses were conducted for the CBD, in which the HFA 10-2 test was divided into four quadrants. Subsequently, the Hybrid Definition was designed by combining the GPAD and CBD; various conditions of the GPAD and CBD were altered to approach a specificity of 95.0%. Subsequently, actual HFA 10-2 tests of 116 RP eyes (10 VFs each) were collected (Dataset 2), and true positive rate, true negative rate, false positive rate, and the time required to detect VF progression were evaluated and compared across the GPAD, CBD, and Hybrid Definition. RESULTS: Specificity values were 95.4% and 98.5% for GPAD and CBD, respectively. There were no significant differences in true positive rate, true negative rate, and false positive rate between the GPAD, CBD, and Hybrid Definition. The GPAD and Hybrid Definition detected progression significantly earlier than the CBD (at 4.5, 5.0, and 4.5 years, respectively). CONCLUSIONS: The GPAD and the optimized Hybrid Definition exhibited similar ability for the detection of progression, with the specificity reaching 95.4%.

DOI： 10.1371/journal.pone.0291208

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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 the repeatability of macular hole (MH) diameter measurement on en face slab optical coherence tomography (OCT) reflectance images and assess its potential to predict visual acuity (VA). Methods: We enrolled 27 eyes with full-thickness MHs in this study. Preoperative en face slab OCT reflectance images were obtained. Image binarization, ellipse approximation, and uncorrected measurement of minimum diameter, min(ef_uc), and maximum diameter, max(ef_uc), were performed using ImageJ. In addition, magnification-corrected diameters were calculated as min(ef) and max(ef) using the Littman and modified Bennett formulas. Spectral-domain OCT horizontal images were used as the conventional method for the analysis: min(conv) and max(conv). The inter-rater reliability of the method was evaluated by calculating the intraclass correlation coefficient (ICC). The following relationships were analyzed: (1) between logMAR VA and min(ef_uc), min(ef), and min(conv); and (2) between logMAR VA and max(ef_uc), max(ef), and max(conv). Results: The min(ef) and max(ef) values were 439.4 ± 240.5 µm and 720.7 ± 346.1 µm, respectively. The ICC values were 0.985 and 0.999 for min(ef) and max(ef), and 0.885 and 0.909 for min(conv) and max(conv), respectively. Multivariate analysis suggested that min(ef), but not min(ef_uc) or min(conv), was associated with pre- and postoperative logMAR VA. Furthermore, max(ef), but not max(ef_uc) or max(conv), was also closely correlated with pre- and postoperative logMAR VA. Conclusions: The MH diameter measured by our method is highly reproducible and closely associated with VA compared to that measured by the conventional method. Translational Relevance: The MH diameter measured by this modality might serve as an accurate biomarker to predict visual function in eyes with MH.

DOI： 10.1167/tvst.11.10.13

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Anastomosis on graft retina was studied after autologous retinal transplantation (ART) on 26 eyes with primary and refractory macular holes. Angiogenesis and anastomosis were seen in 35% of the eyes with successful ART, likely contributing to the survival of the transplanted retina.

DOI： 10.1016/j.oret.2022.05.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To characterize the findings of eyes with choroidal vascular hyperpermeability (CVH), a hallmark of central serous chorioretinopathy (CSC), using multimodal imaging and investigate the locational agreement between these findings and CVH. METHODS: Among patients with CSC in either eye, eyes with CVH identified using indocyanine green angiography without exudative changes were included. All eyes were examined using funduscopy, fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT), short-wavelength or near-infrared autofluorescence (SWAF or NIRAF). The locational agreement between CVH and imaging findings was evaluated for each modality. The relative index on how they overlapped was calculated as the overlapping index. Binarized images, particularly for NIRAF, were also evaluated. RESULTS: This study included 69 CVH sites in 33 eyes of 28 patients. Pachydrusen was detected in 36% of CVH sites. FA revealed hyperfluorescent areas in 39% of CVH sites. OCT findings identified 65% of CVH sites, but the overlapping index was 5%. SWAF imaging identified 89% of CVH sites, but they exhibited variable autofluorescence. NIRAF imaging revealed hypoautofluorescence findings in all CVH sites. When binarized, near-infrared autofluorescent dark dots (NADD) were observed in all CVH sites. Overlapping indices before and after binarization were 78% and 98%, respectively. The NADD area corresponded well with that of CVH (intraclass correlation coefficient, 0.987 [95% confidence interval, 0.952-0.995]). CONCLUSIONS: Hypoautofluorescent findings revealed on NIRAF imaging, especially after binarization processing, corresponded well with CVH sites. These multimodal imaging results might help investigate the anatomical or locational characteristics of CVH in patients with CSC.

DOI： 10.1097/IAE.0000000000003593

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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  

DOI： 10.1007/s00417-022-05717-3

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その他リンク： https://link.springer.com/article/10.1007/s00417-022-05717-3/fulltext.html

記述言語：英語  

Purpose: To evaluate an outbreak of endophthalmitis caused by Fusarium oxysporum after cataract surgery. Methods: In the present study, we conducted a retrospective review of the medical records of cases of endophthalmitis that developed after cataract surgery. All eyes underwent phacoemulsification and intraocular lens implantation (PEA + IOL) at a single eye clinic on the same date. Symptoms of endophthalmitis occurred 21.5 ± 3.4 days after the cataract surgery. Results: Nine eyes of 9 patients with fungal endophthalmitis (5 males and 4 females) were enrolled in the current study. The mean age of the patients was 63.4 ± 8.5 years. Soon after the diagnosis of endophthalmitis, pars plana vitrectomy (PPV) had been performed in all the eyes. However, because there was no response to the first PPV plus antibacterial drug therapy, we performed repeat PPV for all the eyes, combined with IOL removal and antifungal therapy (natamycin eye drops plus oral voriconazole or fosfluconazole). After the antifungal drug therapy, no recurrence of endophthalmitis was observed in any of the operated eyes, and good visual outcomes were obtained. Fusarium oxysporum was identified by culture and sequencing analysis. Conclusion: Early diagnosis and appropriate, adequate treatment are needed for successful management of fungal endophthalmitis.

DOI： 10.1016/j.ajoc.2022.101397

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To evaluate the 1-year visual outcomes and anatomic responses of Japanese patients who received intravitreal brolucizumab (IVBr) injections for polypoidal choroidal vasculopathy (PCV). This was a retrospective study of 17 treatment-naïve eyes with PCV that were treated with IVBr. We evaluated the best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT) and number of injections for 1 year. The eradication of polypoidal lesions was also evaluated using by indocyanine green angiography during the 1-year follow-up. Non-infectious intraocular inflammation developed in two (11.8%) eyes; 15 eyes were assessed at the 1-year follow-up examination. The mean BCVA improved significantly from 0.28 at baseline to 0.13 (P < 0.05) at 1 year. The CMT and CCT decreased significantly after 1 year. The mean number of injections was 6.4 ± 0.13. The rate of complete resolution of polypoidal lesions at 1 year was 93.3%. A dry macula was achieved in 13 eyes (86.6%) after the loading phase and in 11 eyes (73.3%) at 1 year. The IVBr injections appeared to be effective for improving both functional and anatomic outcomes in Japanese patients with PCV, with a high regression rate of polypoidal lesions.

DOI： 10.1038/s41598-022-12216-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/OBJECTIVES: To investigate the association between visual acuity (VA) and visual field (VF) and its reproducibility in patients with retinitis pigmentosa (RP). SUBJECTS/METHODS: The study cohort comprised 227 eyes of 227 patients with RP. The reproducibility of two Humphrey VF tests (10-2 Swedish Interactive Threshold Algorithm [SITA] tests) performed within a period of 3 months was calculated using the root mean squared error (RMSE) of each VF test point's sensitivity. The association between the logarithm of the minimum angle of resolution (logMAR) VA and VF sensitivity was investigated. Additionally, the relationship between RMSE and age, fixation loss, false positives, false negatives, and logMAR VA was determined. RESULTS: The association between visual sensitivity and VA was most tight at the fovea, and it became weak toward the peripheral region in an eccentric manner. VF reproducibility appreciably increased as VA decreased. In particular, reproducibility was significantly decreased when logMAR VA was >0.5 compared with logMAR VA ≤ 0. CONCLUSION: Reproducibility of VF tests decreases with a decrease in VA. Careful consideration is necessary when a patient's logMAR VA is >0.5.

DOI： 10.1038/s41433-022-02043-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To analyze the vessel density around the optic nerve head (ONH) by optical coherence tomography angiography (OCTA) in patients with retinitis pigmentosa (RP), and to evaluate its correlation with visual functions. METHODS: Thirty-eight eyes with RP with visual field constriction within the central 10° were enrolled. The mean (± SD) age of the patients was 43.7 ± 15.1 years. In addition to visual acuity (VA) measurements and visual field tests (Humphrey Field Analyzer 10-2 test), we also measured the vessel density at the macula by OCTA (superficial and deep vessel density: sVD(m) and dVD(m)) and in multiple layers around the ONH (vessel density in the radial peripapillary capillary [RPC] layer and in the nerve head [NH] layer: VDrpc and VDnh). The vessel density was calculated by binarizing the OCTA images. The associations between the logMAR VA and mean deviation (MD) values and the variables of central retinal thickness (CRT), sVD(m), dVD(m), VDrpc, VDnh, and also the size of the foveal avascular zone were investigated. RESULTS: The mean logMAR VA was 0.16 ± 0.34 and the MD value was - 17.2 ± 10.3 dB; the MD value was significantly related to the logMAR VA (p = 0.0028). Multivariate analysis with AICc model selection suggested only dVD(m) was associated with logMAR VA. On the other hand, the optimal model for the MD value included the CRT, dVD(m), and VDnh. CONCLUSION: The vessel density in the deep layer around the ONH was significantly associated with the visual field deterioration in patients with RP.

DOI： 10.1007/s00417-021-05288-9

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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：Nature Research  

The purpose of this study was to report the incidence of elevated intraocular pressure (IOP) after intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) in Japanese patients with age-related macular degeneration (AMD). A retrospective study of chart review of patients who underwent ≥ 10 intravitreal anti-VEGF injections between April 2009 and December 2019 was conducted. Elevated IOP was defined as IOP ≥ 25 mmHg at one visit. Cases with elevated IOP resulting from IVI were identified. Furthermore, the association between elevated IOP and some parameters, as the risk factors that influence elevated IOP, was investigated. A total of 402 eyes of 370 patients were included in this study. Twenty-eight eyes of 26 patients (7.0%) were identified as cases with elevated IOP after IVI. The mean time of elevation after baseline was 50.6 ± 26.5 months. History of glaucoma (p = 0.021
odds ratio, 5.85), treatment modality (p = 0.019
odds ratio, 6.32), and total number of injections (p = 0.003
odds ratio, 1.03) were significantly associated with elevated IOP. A late complication of elevated IOP is associated with IVI in patients with AMD. Particularly, history of glaucoma and treat and extend regimen with frequent injections were found to be risk factors of elevated IOP.

DOI： 10.1038/s41598-021-91832-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To compare the foveal microstructures, such as the prevalence of epiretinal proliferation (EP) and residual ellipsoid zone (EZ), in eyes with lamellar macular hole (LMH), epiretinal retinal membrane (ERM) foveoschisis and macular pseudohole (MPH), and to investigate the association of the foveal microstructure with visual functions. METHOD: In addition to the prevalence of EP, we calculated the residual EZ index within 1mm and 3 mm (rEZ1 and rEZ3) in all examined eyes. Comparisons were conducted to baseline characteristics (logMAR visual acuity [logMAR VA], metamorphopsia score [Mave], central retinal thickness [CRT], the prevalence of EP, rEZ1 and rEZ3) between MPH, ERM foveoschisis and LMH subgroups. The relationships (1) between logMAR VA and each of age, type (MPH, ERM foveoschisis and LMH), the prevalence of EP, rEZ1, rEZ3, spherical equivalent (SE) and CRT and (2) between Mave and each of variables were investigated. RESULTS: Fifty-one eyes of 48 patients were enroled. The mean age was 65.2 ± 11.1 years. Ten eyes were diagnosed as LMH, 22 eyes as ERM foveoschisis and 19 eyes as MPH, respectively. There was a significant difference in CRT only between LMH and ERM foveoschisis (p = 0.023). There was a tendency toward significance in rEZ1 between LMH and ERM foveoschisis (p = 0.057), but not in rEZ3. The optimal model for logMAR VA included age, rEZ1, SE and CRT. On the other hand, the optimal model for Mave included the prevalence of EP, rEZ1 and SE. CONCLUSION: Microstructural observations are useful to predict visual functions in LMH, ERM foveoshisis and MPH.

DOI： 10.1038/s41433-021-01818-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: A method of evaluating central visual field (VF) progression in eyes with retinitis pigmentosa (RP) has still to be established. We previously reported the potential merit of applying a binomial test to pointwise linear regression (binomial PLR) in glaucoma progression. In the current study, we investigated the usefulness of binomial PLR in eyes with RP. Methods: A series of 10 VFs (VF 1-10, Humphrey field analyzer, 10-2 test) from 196 eyes of 103 patients with RP were collected retrospectively. The PLR was performed by regressing the total deviation of all test points with the complete series of 10 VFs. The accuracy (positive predictive value, negative predictive value, and false-positive rate) and the time required to detect VF progression with shorter VF series (from VF 1-5 to VF 1-9) were compared across the binomial PLR, a permutation analysis of PLR (PoPLR), and a mean deviation (MD) trend analysis. Results: In evaluating VF progression, the binomial PLR was comparable with the PoPLR and MD trend analyses in its positive predictive value (0.55 to 0.95), negative predictive value (0.67 to 0.92), and false-positive rate (0.01 to 0.05). The binomial PLR required significantly less time to detect VF progression (5.0 ± 2.0 years) than the PoPLR and MD trend analyses (P < 0.01, P < 0.001, respectively). Conclusions: The application of a binomial PLR achieved reliable and earlier detection of central VF progression in eyes with RP. Translational Relevance: A binomial PLR was useful in assessing VF progression in RP.

DOI： 10.1167/tvst.10.13.15

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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：英語   掲載種別：研究論文（学術雑誌）  

Non-vascularized pigment epithelial detachments (PED) are usually associated with dry age-related macular degeneration (AMD). In this study, we aimed to investigate the correlation between visual function and morphologic parameters. Seventeen eyes of eleven patients with non-vascularized AMD were enrolled. In addition to conventional optical coherence tomography (OCT), polarization-sensitive optical coherence tomography (PS-OCT) measurements were performed by evaluating the regularity of retinal pigment epithelium (RPE) entropy within the PED area. Retinal sensitivity was measured with MP-3 microperimetry, and retinal sensitivities within (RSin) and outside (RSout) the PED area were calculated. The relationship between OCT parameters and visual function was analyzed. As a result, there was a significant difference between the RSin and RSout (p < 0.001, Wilcoxon signed rank test). Moreover, RSin was significantly related to logMAR VA (p = 0.033, linear mixed model). The regularity of RPE entropy was significantly related to visual acuity and RSin (p = 0.00038, p = 0.031, linear mixed model), although neither the height nor area of PED correlated with visual function. Our results suggest that retinal sensitivity is significantly deteriorated within the PED area and RPE entropy measured with PS-OCT was closely related to visual function in eyes with non-vascularized PED.

DOI： 10.1038/s41598-021-96151-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: This study investigated the relationship between retinal artery angle and visual function in eyes with idiopathic epiretinal membrane (ERM). Methods: Ultra-wide field fundus imaging was conducted to analyze ERM and normal contralateral eyes. In addition to the logMAR visual acuity (VA) measurement, the average of the vertical and horizontal metamorphopsia scores (Mave) was measured using m-Charts for each eye. We calculated the retinal artery angle (Yugami correlated angle [YCA]) in all the examined eyes using ImageJ software. The YCAs were then compared between the ERM and normal contralateral eyes. Additionally, the relationship between YCA and visual function was investigated in the ERM eyes. Results: Data from 40 patients with ERM were analyzed. The mean age of the participants was 67.1 ± 8.1 years. The YCA was significantly smaller in the ERM eyes, compared with the contralateral eyes (P < 0.001, respectively; Wilcoxon signed rank test). Among age, axial length, YCAs, central retinal thickness (CRT), and central choroidal thickness (CCT), the optimal model for logMAR VA included age, YCA, and CRT. On the other hand, the optimal model for Mave included YCA and CCT. Conclusions: The retinal artery angle may be useful for predicting visual function in eyes with ERM. Translational Relevance: Our established quantitative measurements in fundus photography have potential clinical use in predicting visual function in ERM.

DOI： 10.1167/tvst.10.9.35

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIMS: To validate a deep learning algorithm to diagnose glaucoma from fundus photography obtained with a smartphone. METHODS: A training dataset consisting of 1364 colour fundus photographs with glaucomatous indications and 1768 colour fundus photographs without glaucomatous features was obtained using an ordinary fundus camera. The testing dataset consisted of 73 eyes of 73 patients with glaucoma and 89 eyes of 89 normative subjects. In the testing dataset, fundus photographs were acquired using an ordinary fundus camera and a smartphone. A deep learning algorithm was developed to diagnose glaucoma using a training dataset. The trained neural network was evaluated by prediction result of the diagnostic of glaucoma or normal over the test datasets, using images from both an ordinary fundus camera and a smartphone. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AROC). RESULTS: The AROC with a fundus camera was 98.9% and 84.2% with a smartphone. When validated only in eyes with advanced glaucoma (mean deviation value < -12 dB, N=26), the AROC with a fundus camera was 99.3% and 90.0% with a smartphone. There were significant differences between these AROC values using different cameras. CONCLUSION: The usefulness of a deep learning algorithm to automatically screen for glaucoma from smartphone-based fundus photographs was validated. The algorithm had a considerable high diagnostic ability, particularly in eyes with advanced glaucoma.

DOI： 10.1136/bjophthalmol-2020-318107

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記述言語：英語  

Purpose: To report the clinical findings of the patients with retinal pigment epithelium (RPE) aperture secondary to age-related macular degeneration (AMD). Methods: A retrospective data analysis was conducted of patients at the University of Tokyo Hospital eye clinic, from the year September 1st, 2012 to 2019. Review of the medical records of patients with RPE aperture accompanied by AMD was performed. We investigated age, best-corrected visual acuity (BCVA), images of spectral domain optical coherence tomography, short-wave fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography, and retinal sensitivity measured with microperimetry. The change in visual acuity or the area of the aperture during the follow-up period was analyzed. Results: Five eyes of 5 patients (4 men, one woman) were included in the analysis. The mean age at presentation was 78.6 ± 9.1 years. The average length of follow-up was 23.6 ± 17.9 months. The RPE apertures appeared as round, either at the apex or at the base of PED, with no evidence of accompanying CNV but subretinal detachment (SRD) above the aperture. On FAF, the apertures appeared as sharply demarcated round areas of hypoautofluorescence. The FA revealed sharply demarcated round areas of window defects in the early and mid-phase with leakage in the late phase corresponding to SRD. The area of apertures enlarged during the follow-up period. Mean BCVA got worse from 0.20 logMAR at the initial presentation to 0.39 logMAR at the last visit. The retinal sensitivity was reduced but partly preserved above the area of aperture. Conclusions and importance: RPE aperture was found in some patients with drusenoid PED secondary to AMD. It enlarged during follow-up. Visual acuity was declined. Retinal sensitivity was decreased but partly preserved.

DOI： 10.1016/j.ajoc.2021.101083

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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 retinal sensitivity of highly myopic eyes without choroidal neovascularisation (CNV) or patchy chorioretinal atrophy (PCA) and investigated its association with anatomical characteristics including melanin distribution at the retinal pigment epithelium (RPE), which was evaluated with polarisation-sensitive optical coherence tomography (PS-OCT). DESIGN: Retrospective consecutive observational cohort study. METHODS: We included highly myopic eyes (refractive error ≤-8.0 dioptres or axial length of ≥26.5 mm) from patients at the University of Tokyo Hospital. Retinal sensitivity was measured by microperimetry at 25 sectors within 6 degrees from the fovea. Depolarisation value, which reflected melanin pigmentation, was measured by a clinical prototype of PS-OCT and was parameterised as polarimetric entropy. Retinal sensitivity or entropy at the RPE in high myopia was compared with emmetropic control subjects. The association of retinal sensitivity with age, axial length, entropy, or choroidal thickness was assessed in per-eye and per-sector analysis. RESULTS: Twenty-three highly myopic eyes (age, 66.6±12.3 years) were included. The average retinal sensitivity was 25.3±3.0 dB, which was significantly decreased compared with the control (p<0.0001). The average entropy at the RPE in the highly myopic eyes was significantly lower than in the control (p<0.0001). Univariate analysis followed by multivariate analysis showed that besides age, axial length or choroidal thickness, RPE entropy was independently associated with retinal sensitivity (β=4.4; 95% CI 0.5 to 8.3; p=0.03). CONCLUSIONS: Decreased depolarisation at the RPE measured with PS-OCT, which reflected altered melanin pigmentation, was independently associated with reduced retinal sensitivity in patients with early stages of myopic maculopathy without CNV or PCA.

DOI： 10.1136/bjophthalmol-2021-318890

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim was to establish and evaluate a new clustering method for visual field (VF) test points to predict future VF in retinitis pigmentosa. A Humphrey Field Analyzer 10-2 test was clustered using total deviation values from 858 VFs. We stratified 68 test points into 24 sectors. Then, mean absolute error (MAE) of the sector-wise regression with them (S1) was evaluated using 196 eyes with 10 VF sequences and compared to pointwise linear regression (PLR), mean sensitivity of total area (MS) and also another sector-wise regression basing on VF mapping for glaucoma (29 sectors; S2). MAE with S1 were smaller than with PLR when between the first-third and first-seventh VFs were used. MAE with the method were significantly smaller than those of S2 when between the first-sixth and first-ninth VFs were used. The MAE of MS was smaller than those with S1 only when first to 3rd and first to 4th VFs were used; however, the prediction accuracy became far larger than any other methods when larger number of VFs were used. More accurate prediction was achieved using this new sector-wise regression than with PLR. In addition, the obtained cluster was more useful than that for glaucoma to predict progression.

DOI： 10.1038/s41598-021-89233-0

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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 the associations between visual function and the optical coherence tomography (OCT) parameters in eyes with idiopathic epiretinal membrane (ERM). Methods: Thirty-nine consecutive eyes with ERM were enrolled. In addition to OCT parameters, such as central retinal thickness (CRT), the area of gap between the ERM and the retinal surface (SUKIMA) was newly defined and calculated from the vertical and horizontal OCT images (SUKIMAv and SUKIMAh). The average of SUKIMAv and SUKIMAh (SUKIMAave) was used for the statistical analysis. The vertical and horizontal metamorphopsia scores (MV, MH) and the average of MV and MH (Mave) were also used for the analysis. Results: The Mave was not significantly associated with logMAR visual acuity (VA) (P = 0.57, linear regression analysis). Analysis using second-order bias-corrected Akaike information criterion model selection identified the age, CRT, and SUKIMAave as being associated with logMAR VA. On the other hand, among the OCT parameters, SUKIMAave and CRT were associated with the Mave. In addition, there was a significant relationship between SUKIMAh and MV (P = 0.011) and between SUKIMAv and MH (P = 0.0014). Conclusions: We identified SUKIMA as a novel OCT parameter that is useful to predict both VA and metamorphopsia in patients with ERM.

DOI： 10.1167/iovs.62.6.6

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記述言語：英語  

DOI： 10.1016/j.jcjo.2020.08.004

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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：Association for Research in Vision and Ophthalmology Inc.  

PURPOSE. The purpose of this study was to compare the results of near-infrared autofluorescence (NIRAF) and short-wavelength autofluorescence (SWAF) imaging of eyes with resolved central serous chorioretinopathy (CSC) and to assess the retinal sensitivity (RS) in areas with abnormal autofluorescence (AF) using white-on-white (WW) and blue-onyellow (BY) perimetries. METHODS. We examined 20 consecutive eyes with resolved CSC. We calculated the areas of abnormal AF detected by SWAF and NIRAF imaging as SWAF-area and NIRAF-area, respectively, and the number of measurement points within and outside abnormal SWAF and NIRAF regions were counted. The results of WW and BY perimetries were superimposed on the AF images, and the mean overall RS within and outside abnormal SWAF and NIRAF regions were calculated using both WW and BY perimetries (W-RSin-SWAF, W-RSout-SWAF, W-RSin-NIRAF, W-RSout-NIRAF, B-RSin-SWAF, BRSout- SWAF, B-RSin-NIRAF, and B-RSout-NIRAF, respectively). RESULTS. The mean age of the participants was 54.1 years. The SWAF-area was significantly smaller than the NIRAF-area (P &lt
0.0001, Wilcoxon signed rank test). A ?2 test suggested a significant relationship between the number of measurement points within/outside abnormal SWAF and NIRAF regions (P &lt
0.0001). In the results of measurement by WW perimetry, there was a significant difference between WRSin- NIRAF and W-RSout-NIRAF (P &lt
0.0001), but not between W-RSin-SWAF and WRSout- SWAF (P = 0.060, Wilcoxon rank sum test). In contrast, on BY perimetry, there were significant differences between both B-RSin-SWAF and B-RSout-SWAF and between B-RSin-NIRAF and B-RSout-NIRAF (P &lt
0.0001). CONCLUSIONS. NIRAF was useful for predicting impaired RS in eyes with resolved CSC.

DOI： 10.1167/IOVS.62.3.36

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We investigated the anatomical differences in the choroidal structure between pregnant women in the first trimester of pregnancy and age-matched healthy nonpregnant women using enhanced depth imaging optical coherence tomography (EDI-OCT) and choroidal binarization analysis. The main parameters measured in the two study groups, namely, pregnant women in the first trimester and healthy nonpregnant women, were choroidal thickness and the choroidal luminal area. Binarization of the EDI-OCT images from each patient was performed, and the choroidal vascularity index (CVI) was calculated. The correlations between the baseline characteristics of the subjects and the CVI were investigated using linear mixed model analysis. As a result, there was no statistically significant difference in the mean age, best-corrected visual acuity, axial length, central retinal thickness, subfoveal choroidal thickness, systolic blood pressure (BP), or diastolic BP between the two study groups. Conversely, a significant difference was observed in the CVI (P = 0.012) between the two groups. The multivariate analysis identified a significant correlation between the CVI and the systolic BP (P = 0.0044, linear mixed test). Taken together, a larger choroidal luminal area was associated with a higher systolic BP, especially in the first trimester of pregnancy. Our findings may provide further insight into the choroidal changes that occur during pregnancy.

DOI： 10.1038/s41598-021-84204-x

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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 the three-dimensional distribution and associating demographic factors of depolarization, using polarization-sensitive optical coherence tomography (PS-OCT), to evaluate melanin pigmentation in the retinal pigment epithelium (RPE) and choroid in healthy eyes. Methods: In total, 39 unaffected healthy eyes of 39 subjects were examined using a PS-OCT clinical prototype. The degree of depolarization, expressed as the polarimetric entropy, was assessed in the RPE, the superficial and the total choroid layer, especially in the center, the inner, or the outer areas centered at the fovea. The values and their association with the demographic data were analyzed. Near-infrared fundus autofluorescence (NIRAF) was also used, in the same manner, for the comparison. Twenty-eight of 39 eyes were measured twice to evaluate intrasession repeatability. Results: Both the polarimetric entropy in the RPE and the gray level in NIRAF, decreased from the center to the periphery (P < 0.001). The polarimetric entropy in the RPE was significantly associated with age in each area (P ≤ 0.001). In the RPE and the superficial choroid, the polarimetric entropy was negatively associated with axial length in each area (P ≤ 0.002). The intraclass correlation coefficient of the polarimetric entropy in the same session was excellent in each area of the RPE, superficial choroid, or total choroid layer (0.94-0.98). Conclusions: The distribution of fundus melanin pigment-related depolarization was evaluated using PS-OCT. The depolarization was associated with the subjects' demographic data, such as age or axial length. Translational Relevance: The presented information in healthy eyes provides an essential basis for the investigation into a variety of chorioretinal pathologies.

DOI： 10.1167/tvst.10.2.30

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cone-rod dystrophy (CORD) is one of the inherited retinal diseases that result in central visual field deterioration and decreased visual acuity (VA). In CORD patients, impaired photoreceptor cells are observed as the disruption of ellipsoid zone (EZ) on optical coherence tomography (OCT) images. In the present study, we calculated the index of residual EZ (rEZ) to quantify the function of photoreceptor cells and investigated the correlation between rEZ index and visual functions. Twenty-six eyes of 13 patients with clinical suspicion of CORD were examined. Visual field was tested with the Humphrey Visual Field Analyzer (HFA 10-2 program). We simultaneously obtained OCT images and calculated the area of decreased EZ intensity (EZa). Using the binarized OCT images, the percentage of the rEZ in a 3 × 3 mm area surrounding the macula was analyzed. To clarify interrator reproducibility, intraclass correlation coefficient (ICC) was calculated. Moreover, we investigated the association between OCT parameters and VA as well as the mean deviation (MD) value measured with HFA. The mean age of the patients was 48.5 ± 16.9 years. The mean central retinal thickness was 122.7 ± 73.2 μm. The mean EZa and rEZ were 22.2 ± 23.6 μm2 and 0.35 ± 0.31, respectively. The ICC of each rEZ index was 0.91 (95% CI: 0.89 < ICC < 0.93). Multivariate analysis indicated rEZ was significantly related to logMAR VA (p = 0.05) and rEZ and EZa were associated with the MD value (p = 0.014 and p = 0.009, linear mixed model). Furthermore, rEZ was also associated with photopic a- and b-wave amplitudes (p = 0.027 and p = 0.0024, respectively, linear mixed model). Taken together, the current results suggested the usefulness of rEZ quantification for predicting visual functions in CORD patients.

DOI： 10.1177/1120672121990561

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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 autofluorescence (AF) signal measured with ultra-wide field imaging and visual functions in patients with cone-rod dystrophy (CORD). A retrospective chart review was performed for CORD patients. We performed the visual field test and fundus autofluorescence (FAF) measurement and visualized retinal structures with optical coherence tomography (OCT) on the same day. Using binarised FAF images, we identified a low FAF area ratio (LFAR: low FAF/30°). Relationships between age and logMAR visual acuity (VA), central retinal thickness (CRT), central choroidal thickness (CCT), mean deviation (MD) value, and LFAR were investigated. Thirty-seven eyes of 21 CORD patients (8 men and 13 women) were enrolled. The mean patient age was 49.8 years. LogMAR VA and MD were 0.52 ± 0.47 and - 17.91 ± 10.59 dB, respectively. There was a significant relationship between logMAR VA and MD (p = 0.001). LogMAR VA significantly correlated with CRT (p = 0.006) but not with other parameters. Conversely, univariate analysis suggested a significant relationship between MD and LFAR (p = 0.001). In the multivariate analysis, LFAR was significantly associated with MD (p = 0.002). In conclusion, it is useful to measure the low FAF area in patients with CORD. The AF measurement reflects the visual field deterioration but not VA in CORD.

DOI： 10.1038/s41598-021-81597-7

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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 cases with a retinal pigment epithelium (RPE) aperture using polarization-sensitive optical coherence tomography (PS-OCT). STUDY DESIGN: Retrospective consecutive case series. METHODS: A retrospective study that included three eyes (three patients) with RPE aperture and age-related macular degeneration (AMD) evaluated at the Macular Clinic in Tokyo University Hospital. A three-dimensional dataset of depolarization information was obtained with a clinical prototype of PS-OCT. RESULTS: All patients were categorized as intermediate AMD. RPE apertures were identified with PS-OCT as discontinuities of depolarization in the RPE layer of the pigment epithelial detachment (PED). A nonuniform decrease of depolarization in the RPE layer was also observed around the aperture. Two findings were observed above the aperture, intraretinal focal areas with high reflectivity and increased depolarization and subretinal bands with moderate reflectivity and low depolarization. Retinal sensitivity according to fundus microperimetry measured at 25 points was significantly associated with the degree of depolarization at the corresponding area (r-square = 0.60, p = 0.0001). CONCLUSION: The RPE aperture was characterized as a round discontinuity of depolarization. The findings with PS-OCT suggest atrophic changes in the overlying RPE of the PED. The degree of depolarization was associated with retinal sensitivity. The current results indicate that RPE apertures developed within the spectrum of atrophic AMD.

DOI： 10.1007/s10384-020-00787-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: A smoking habit can cause various health problems encompassing retinal diseases including central serous chorioretinopathy (CSC). The aim of the current study was to investigate the effect of smoking on the choroidal structure in patients with CSC. METHODS: The choroidal vascular index (CVI) was calculated using the binarized OCT images. Baseline parameters (age, refractive error [SE], subfoveal choroidal thickness [SFCT] and CVI) were compared between smokers and non-smokers using Wilcoxon rank sum test. Moreover, the associations between SFCT and the baseline parameters were analyzed using a multivariate linear regression followed by the AICc model selection. RESULTS: Among 75 CSC patients, 45 patients were smokers and 30 patients were non-smokers. No significant differences in age and SE were seen between the smoking group and the non-smoking group. A significant difference in the SFCT was seen between two groups (382.0 ± 68.2 μm in the smoking group vs. 339.3 ± 52.3 μm in the non-smoking group, p = 0.0038), while no significant difference was observed in the CVI (p = 0.32). The optimal model for SFCT included the variables of age, SE and past history of smoking among the baseline parameters. Additionally, increased pack years was associated with increased SFCT. CONCLUSION: Cigarette smoking was associated with an increased SFCT in patients with CSC. Thicker choroid in smoking CSC patients may be an important modulator of the disease.

DOI： 10.1371/journal.pone.0249073

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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 usefulness of red channel fundus imaging to detect the ischemic status in eyes with central retinal vein occlusion (CRVO). METHODS: Ultra-widefield (UWF) fundus images were obtained from 42 eyes with CRVO. Twenty-one eyes were ischemic, and 21 eyes were non-ischemic. Rubeosis was found in 11 ischemic eyes. UWF images were split into red and green channels using ImageJ software. Both the color and red channel images were used to predict the presence or absence of ischemia when examined by masked graders. The sensitivity and specificity of UWF imagings for the detection of ischemia were calculated in Group A (total 42 eyes), Group B (32 eyes excluding non-rubeotic ischemic CRVO) and Group C (31 eyes excluding rubeotic ischemic CRVO), respectively. Moreover, a linear mixed model was conducted to investigate the relationship between the type of images and the accuracy of prediction in each group. RESULTS: No significant difference in the sensitivity of color fundus imaging was seen between Group A and Group B. By contrast, a significant difference in the sensitivity of red channel imaging was seen between Group A and Group B (p = 0.031). The accuracies of the predictions were not associated with the type of image in Group A and Group B, but were significantly associated in Group C (p = 0.026). CONCLUSIONS: UWF red channel imaging enabled more accurate detection of the ischemic status, compared with color fundus images, especially in non-rubeotic CRVO eyes.

DOI： 10.1371/journal.pone.0260383

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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 the minimum number of visual fields (VFs) required to precisely predict future VFs in eyes with retinitis pigmentosa (RP). METHODS: A series of 12 VFs (Humphrey Field Analyzer 10-2 test (8.9 years in average) were analysed from 102 eyes of 52 patients with RP. The absolute error to predict the 12th VF using the prior 11 VFs was calculated in a pointwise manner, using the linear regression, and the 95% CI range was determined. Then, using 3-10 initial VFs, next VFs (4th to 11th VFs, respectively) were also predicted. The minimum number of VFs required for the mean absolute prediction error to reach the 95% CI was identified. Similar analyses were iterated for the second and third next VF predictions. Similar analyses were conducted using mean deviation (MD). RESULTS: In the pointwise analysis, the minimum number of VFs required to reach the 95% CI for the 12th VF was five (first and second next VF predictions) and six (third next VF prediction). For the MD analysis, three (first and second next VF predictions) and four (third next VF prediction) VFs were required to reach 95% CI for the 12th VF. CONCLUSIONS: The minimum number of VFs required to obtain accurate predictions of the future VF was five or six in the pointwise analysis and three or four in the analysis with MD.

DOI： 10.1136/bmjophth-2021-000900

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To investigate the association between serum soluble fms-like tyrosine kinase-1 (sFlt-1) and the choroidal structure during the pregnancy. METHODS AND ANALYSIS: This prospective study enrolled 24 eyes of 12 consecutive healthy pregnant women. Each participant was evaluated during the first, second and third trimester of pregnancy and the postpartum period. The central choroidal thickness (CCT) and Choroidal Vascular Index (CVI) were measured using enhanced depth-imaging optical coherence tomography. Moreover, serum sFlt-1 and vascular endothelial growth factor (VEGF) concentrations were measured manually using ELISA. The association between choroidal structural parameters and serum sFlt-1/VEGF was analysed using a linear mixed model. RESULTS: The CCT was significantly thicker in the second and third trimester than the postpartum period (p<0.05). In contrast, there was no significant difference in the CVI throughout pregnancy or the postpartum period. Serum sFlt-1 levels were significantly higher during pregnancy than the postpartum period (p<0.05), whereas the serum VEGF levels were significantly lower during pregnancy than the postpartum period (p<0.05). Furthermore, serum sFlt-1 levels were significantly associated with CCT throughout pregnancy (p=0.011, linear mixed model). On the contrary, sFlt-1 levels was not associated with the CVI during the pregnancy. CONCLUSION: Our results suggest that serum sFlt-1 might have an influence on the choroidal thickness during the pregnancy.

DOI： 10.1136/bmjophth-2021-000888

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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 the visual outcomes of vitrectomy for lamellar macular hole (LMH) and epiretinal membrane (ERM) foveoschisis and to investigate the prognostic factor for postoperative visual acuity. METHODS: We retrospectively reviewed 15 LMH and 17 ERM foveoschisis eyes that had undergone a standard three-port pars plana vitrectomy with (12 eyes) or without (20 eyes) cataract surgery. Best-corrected visual acuity (BCVA) at postoperative three months and the final visit were compared to the preoperative measurements. We investigated the relationship between BCVA at the final visit and baseline parameters (age, preoperative BCVA, the presence of epiretinal proliferation [EP] and ellipsoid zone [EZ] disruption). The best explanatory variables for the final BCVA were investigated using the corrected Akaike information criterion (AICc) model selection. RESULTS: The mean age was 67.2 years. The mean follow-up duration was 30.7 months. Fifteen of 32 examined eyes were diagnosed as LMH and 17 eyes as ERM foveoschisis. Twelve eyes in LMH had EP and 13 eyes showed the disruption of EZ integrity. In total, BCVA significantly improved at 3 months postoperatively (p = 0.0013). A significant improvement was observed in ERM foveoschisis (p = 0.0085) but not in LMH group (p = 0.071). Comparing the BCVA between the baseline and the final visit, significant improvements were observed in total, ERM foveoschisis and LMH group (p<0.001, p<0.001 and p = 0.026, respectively). The optimal model for BCVA at the final visit included preoperative BCVA and the presence of EZ disruption (p<0.001 and p<0.001, respectively). CONCLUSION: Our results suggested that the final BCVA was dependent on preoperative BCVA and the presence of EZ disruption. Surgical indications might be warranted for LMHs with EZ disruption.

DOI： 10.1371/journal.pone.0247509

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担当区分：責任著者  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Short wavelength automated perimetry (SWAP) is known for detecting the early reduction of retinal sensitivity (RS) in glaucoma. It's application in retinal diseases have also been discussed previously. We investigated the difference in RS measured between standard white-on-white automated perimetry (WW) and blue-on-yellow SWAP in central serous chorioretinopathy (CSC). The overall RS (W-RS, S-RS) as well as the RS inside and outside of the serous retinal detachment (SRD) region were investigated in 26 eyes of 26 CSC patients using WW and SWAP. The central retinal thickness, central choroidal thickness, SRD area (SRDa), and SRD height at the fovea were measured using optic coherence tomography. RS inside the SRD region was lower than that of outside for both perimetries (both p < 0.001). The difference between RS inside and outside of the SRD region was greater in SWAP compared to WW (p < 0.001). Univariate analysis revealed significant correlations between SRDa and both W-RS and S-RS (both p < 0.001); moreover, multivariate analysis indicated that only S-RS was selected as the optimal model for SRDa. Our study demonstrated that SWAP was detected the decrease in RS more accurately than WW in CSC. These results may suggest the usefulness of SWAP for detecting change of retinal function in CSC.

DOI： 10.1038/s41598-020-73569-0

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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 the outcomes of autologous neurosensory retinal transplant as a primary treatment for patients with large chronic macular holes and evaluate the safety and feasibility of the procedure. DESIGN: Retrospective study, consecutive case series. METHODS: We reviewed seven patients with a primary chronic large macular hole, who underwent autologous neurosensory retinal transplant. Mean preoperative minimum and maximum hole diameters were 643 µm and 1214 µm, respectively. Changes in visual acuity were measured postsurgery, and optical coherence tomography, fluorescein angiography, and microperimetry-3 were analyzed after the procedure. RESULTS: Closure of the macular hole was achieved in all seven eyes in the study. At 1 year post-surgery, there was significant improvement in mean visual acuity (LogMAR 1.10 vs. 0.68, P = 0.001). Optical coherence tomography showed that all grafts had formed attachments to the retinal epithelial cells of the recipient retina. Mean preoperative ellipsoid zone defect was 1,089 ± 403.8 µm (range, 918-1,329 µm) which further decreased to 921 ± 129.1 µm (range, 670-1,201 µm) at final follow up (P = 0.09). Microperimetry-3 testing indicated retinal sensitivity in the graft in five eyes. CONCLUSION: Autologous retinal transplantation may help rebuild the macular structure resulting in functional improvement for eyes with primary chronic large macular hole.

DOI： 10.1097/IAE.0000000000002693

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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 the relationship between the number of laser shots applied during laser photocoagulation treatment and the degree of myopia at 3 years in children with laser-treated retinopathy of prematurity (ROP). METHOD: A total of 68 eyes of 34 infants who had developed prethreshold ROP and were treated by diode laser therapy were included in the current study. Cycloplegic retinoscopic refraction testing was performed in the children at the age of 3 years, and the spherical equivalent (SE) was calculated for all the examined eyes. The number of laser shots that had been applied was compared between the eyes with and without high myopia (SE < - 5 diopters (D)). In addition, the relationship between the difference in the SE values between the two eyes in each infant and the difference in the number of laser shots applied between the two eyes was also analyzed. RESULTS: The number of laser shots applied was significantly higher for the eyes with high myopia than for those without high myopia (p = 0.0088), and the number of laser shots applied was significantly positively correlated with the degree of myopia (p < 0.001). A significant correlation was also observed between the differences in the SE values between the two eyes and the differences in the number of laser shots applied between the two eyes (p = 0.0013). CONCLUSION: The number of laser shots applied in photocoagulation treatment for ROP is significantly associated with the degree of myopia seen subsequently in the children.

DOI： 10.1007/s00417-020-04946-8

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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 the usefulness of the retinal sensitivity in branch retinal vein occlusion (BVO) with macular edema (ME) following the anti-vascular endothelial growth factor (anti-VEGF) treatment. METHODS: Best-corrected visual acuity (BCVA), microperimetry, and optical coherence tomography (OCT) measurements were carried out in 20 patients with BVO with ME, at baseline and 1 month after the anti-VEGF treatment. The relationships among BCVA, mean retinal sensitivity (MS), macular volume (MV), central retinal thickness (CRT), integrity of ellipsoid zone (EZ), mean retinal sensitivity in the most affected quadrant (qMS), and macular volume in the most affected quadrant (qMV) were investigated. In addition, the relationships among the change in BCVA at 1 month (ΔBCVA1m), mean sensitivity in the most affected quadrant at 1 month (ΔqMS1m), MV in the most affected quadrant at 1 month (ΔqMV1m), and CRT at 1 month (ΔCRT1m) were analyzed. The optimal model for BCVA at 3 months after the treatment (BCVA3m) was identified. RESULTS: There was not a significant difference in BCVA (paired Wilcoxon test, p = 0.058) between at baseline and after the treatment, but there were significant differences in MS, MV, CRT, qMS, and qMV (p < 0.05). There was a significant relationship between ΔqMS1m and ΔMV1m, ΔCRT1m, and ΔqMV1m, respectively. ΔMS1m or ΔqMS1m and BCVA at baseline and ΔBCVA1m were selected as explanatory variables in the optimal model for BCVA3m. CONCLUSION: Retinal sensitivity was related to retinal structure, whereas this was not the case with BCVA. In addition, retinal sensitivity was useful to predict BCVA after anti-VEGF therapy.

DOI： 10.1007/s00417-020-04759-9

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記述言語：英語  

Purpose: To describe the findings of long-term follow-up of a case of amyloidosis-associated chorioretinopathy by multimodal imagings, including optical coherence tomography (OCT). Observations: A 47-year-old woman who had been diagnosed as having systemic amyloidosis was found to have a best corrected visual acuity of 20/13 in both eyes at the age of 41, which subsequently decreased to 20/100 in the left eye and 20/20 in the right eye at age 47. Visual field examination demonstrated worsening of the central scotoma during the follow-up period. Funduscopic examination revealed bilateral white deposits along the choroidal vessels, which became more pronounced over time, along with diffuse pigmentary changes. The fluorescein angiography and indocyanine green angiography findings were consistent not only with atrophic lesions, but also with amyloid deposition (i.e., staining of the vessels).At the baseline, macula OCT revealed a thick hyporeflective band at the choriocapillaris, however, at the last follow-up, it revealed an absent ellipsoid zone, and bilateral progressive retinal pigment epithelium irregularities in both eyes. Conclusions: Patients diagnosed as having amyloidosis-related chorioretinopathy may have maintained visual function at the first detection of retinal amyloid deposition, and a number of years may elapse before the patient manifests visual deterioration.

DOI： 10.1016/j.ajoc.2020.100846

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: The purpose of this study was to investigate the association between fundus autofluorescence (FAF) and visual field (VF) sensitivities in eyes with retinitis pigmentosa (RP). We also investigated the model we developed to predict VF sensitivity using the FAF ring and its prediction accuracy. Methods: The training dataset consisted of 51 eyes of 28 patients, and the testing dataset consisted of 42 eyes of 25 patients with RP. VF and FAF measurements were conducted using the Humphrey Field Analyzer (HFA) 10-2 test and Optos. The HFA 10-2 test was divided into three sectors according to the association with the FAF (IN, ON, and OUT). Moreover, concentric curves were drawn at 1-degree intervals outside the FAF ring and OUT was divided into six sectors (from OUT1 to OUT6 toward the periphery). Finally, the total deviation (TD) value was predicted using age and visual acuity (VA) in the whole field, and each of the eight sectors was compared. Results: The TD value decreased significantly from IN, ON, and then toward OUT6. The absolute prediction error with the FAF ring (average, 7.6 dB) was significantly smaller than that without the FAF ring (average, 8.7 dB). The absolute prediction error with the FAF ring was significantly smaller in the central areas (IN, 4.4 dB and ON, 5.3 dB) than those in the peripheral areas (OUT1-6, 6.8-9.1 dB). Conclusions: VF sensitivity decreases in association with the FAF ring. We developed a model to predict 10-2 VF sensitivity values using the FAF ring, which enabled us to predict 10-2 TD values.

DOI： 10.1167/iovs.61.10.51

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To identify the functional outcome and evaluate the morphologic changes of patients with pachychoroid neovasculopathy (PNV) undergoing intravitreal anti-vascular endothelial growth factor (VEGF) combined with photodynamic therapy (PDT) at the 1-year follow-up. METHODS: We retrospectively studied all the treatment-naïve PNV patients who were scheduled to undergo combination therapy between September 2017 and November 2018. All the patients received three consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab as loading doses. Full-dose PDT was performed within 1 week of the first injection. Retreatment was allowed if evidence of clinical deterioration or the presence of fluid on spectral-domain optical coherence tomography examination performed at the 1-month follow-up was noted. The best-corrected visual acuity (BCVA) was compared before treatment and at 3, 6, and 12 months after the initial treatment. Changes in the central foveal thickness (CFT), central choroidal thickness (CCT), and retreatment rate during the maintenance phase were also evaluated. RESULTS: Eleven eyes were enrolled in this study. Significantly, better BCVA was observed at 12 months than at baseline (P = 0.010). The mean CFT significantly decreased from 331 ± 93 to 237 ± 72 μm at 12 months (P < 0.001). The mean CCT also significantly decreased from 361 ± 74 to 310 ± 83 μm at 12 months (P < 0.001). The mean number of injections per eye was 3.9 ± 1.3 during the follow-up period. A total of 45.5% (5 /11) of the patients required retreatment during the maintenance phase. CONCLUSION: Anti-VEGF combined with full-dose PDT was well tolerated and appeared to be effective treatment for patients with treatment-naïve PNV. Combination therapy might also reduce the treatment burden with fewer injections in patients with PNV.

DOI： 10.1007/s00417-020-04661-4

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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 early changes of vascular lesions and their associations with the early responses to combined photodynamic therapy (PDT) in eyes with polypoidal choroidal vasculopathy (PCV). METHODS: This study evaluated 19 eyes of 19 patients with PCV who underwent PDT combined with anti-vascular endothelial growth factor injections and were followed for 3 months. All subjects were examined 1 week and 1, 2, and 3 months after combined PDT. "Active" cases were defined as recurrence or persistence of serous retinal detachment or subretinal hemorrhage detected within 3 months. Branching vascular networks (BVNs) were evaluated by optical coherence tomography angiography (OCTA) and polyps by indocyanine-green angiography. RESULTS: In total, 16%, 58%, 84%, and 89% of eyes displayed BVNs 1 week, 1, 2, and 3 months after PDT, respectively. BVNs were detected significantly more often 1 month after PDT in the "active" group than "inactive" group (89% vs. 30%, p = 0.020). There were significantly higher overall proportions of BVNs detected by OCTA in the "active" group than "inactive" group (p = 0.0058). CONCLUSION: In most cases, BVNs disappeared once and gradually appeared again within 3 months. Detecting BVNs using OCTA from early phases could be a helpful biomarker to assess the early responses to PDT in eyes with PCV.

DOI： 10.1007/s10792-020-01299-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We investigated long-term treatment responses in patients with treatment-naïve polypoidal choroidal vasculopathy (PCV) undergoing photodynamic therapy (PDT) with intravitreal ranibizumab (IVR). The medical charts of 14 patients with treatment-naïve PCV who underwent PDT with IVR were retrospectively reviewed. Patients were followed up and treated with additional IVR for ≥3 years. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), greatest linear dimension (GLD) on angiography, polyp regression and central choroidal thickness (CCT) were assessed. Associations between these functional or anatomic outcomes with age, baseline CCT, baseline GLD or choroidal vascular hyperpermeability (CVH) were investigated using univariate and multivariate analysis. Mean logMAR BCVA improved significantly at 3 years (0.34 ± 0.24 to 0.12 ± 0.29, p = 0.003). Greater BCVA improvement and longer time to first recurrence was significantly associated with CVH. Fewer number of IVR retreatment within 3 years was associated with thicker baseline CCT. Mean CCT significantly decreased at 3 years (217 ± 33 µm to 197 ± 48 µm, p = 0.003). Greater decrease of CCT was significantly associated both with greater number of IVR retreatment within 3 years and absence of CVH. These results showed that pachychoroid characteristics at baseline was associated long-term functional and anatomic outcomes in patients with treatment-naïve PCV who had undergone combination PDT and IVR.

DOI： 10.1038/s41598-020-65346-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Lysosome-associated membrane protein 2 plays an important role in autophagy and lysosomal function and its mutation is responsible for pathogenesis of Danon disease, which can cause retinopathy, though its pathophysiological contribution to retinal dysfunction remains unclear. The purpose of our research is to report the first case of Japanese Danon disease retinopathy and to understand how LAMP2 dysfunction contributes to pathogenesis of retinopathy. METHODS: One case underwent ophthalmic examination including slit-lamp exam, fundus imaging, visual field testing, and electroretinogram. In molecular biological study, relative messenger RNA expression levels of three splicing variants of Lamp2 or LAMP2 in wild type mouse retina and retinal pigment epithelium, human retinal pigment epithelium cell line adult retinal pigment epithelium-19 were quantified. LAMP2 was knocked down by small interfering RNA in adult retinal pigment epithelium-19 and its effect to LC3, an autophagy marker, was assessed by Western blotting. Intracellular localization of LAMP2 and LC3 in untreated and LAMP2-knocked-down adult retinal pigment epithelium-19 was analyzed by confocal microscopy. RESULTS: Our case manifested cone dystrophy in both eyes. In mice, expression of Lamp2a and Lamp2b was significantly higher in retinal pigment epithelium than that in neural retina. Expression of Lamp2a and Lamp2b were significantly higher than that of Lamp2c in mouse retinal pigment epithelium. Adult retinal pigment epithelium-19 cells showed similar LAMP2 expression pattern to mouse retinal pigment epithelium. LAMP2 knockdown in adult retinal pigment epithelium-19 reduced LC3-II amount and the number and size of autophagosome. DISCUSSION: We report a Japanese case of Danon disease retinopathy, and our study implies that LAMP2 plays an important role in autophagosome formation in retinal pigment epithelium.

DOI： 10.1177/1120672119832183

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To compare 5-year clinical results of non-Descemet stripping automated endothelial keratoplasty (nDSAEK) and DSAEK. METHODS: A retrospective chart review involving patients with non-Fuchs-type bullous keratoplasty who underwent nDSAEK or DSAEK 5 years before the review was performed on demographics, graft survival rate, endothelial cell density (ECD), best-corrected visual acuity (BCVA), and complications. RESULTS: Fifty eyes (nDSAEK 28, DSAEK 22) were included in this study. Common indications for surgery were bullous keratopathy due to glaucoma, cataract surgeries, or laser iridotomy. The graft survival rates in nDSAEK and DSAEK eyes at 1, 3, and 5 years were 0.75 and 0.86, 0.67 and 0.81, and 0.59 and 0.74, respectively. The mean donor ECDs of nDSAEK and DSAEK eyes were 2638 and 2503 cells/mm, respectively; these decreased to 1654 and 1406, 1503 and 1218, and 1108 and 1020 cells/mm at 1, 3, and 5 years, respectively. The mean preoperative BCVAs of nDSAEK and DSAEK eyes were 1.08 and 1.11 LogMAR, respectively; these improved to 0.238 and 0.190, 0.126 and 0.157, and 0.097 and 0.070 LogMAR at 1, 3, and 5 years, respectively. The most common complication was intraocular pressure elevation. There were no statistically significant differences between nDSAEK and DSAEK in graft survival rates, changes in ECD and BCVA, or the occurrence of postoperative complications, with the exception of the change in ECD at 2 years (1173 and 1193 cells/mm, P = 0.0159). CONCLUSIONS: Our 5-year clinical results of nDSAEK and DSAEK did not show significant differences at almost all points.

DOI： 10.1097/ICO.0000000000002211

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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 the effect of elongated photoreceptor outer segment length on the visual prognosis of patients with chronic central serous chorioretinopathy after treatment using half-dose and half-fluence photodynamic therapy (reduced PDT). METHODS: The study included 36 eyes of 36 patients with chronic central serous chorioretinopathy who underwent reduced PDT and were followed up for at least 1 year. Spectral domain optical coherence tomography measurement was conducted at baseline and 12 months after reduced PDT. Thereafter, the association between the best-corrected visual acuity (BCVA) at 12 months after reduced PDT and 7 baseline variables (age, symptom duration, BCVA, outer nuclear layer thickness, elongated photoreceptor outer segment length, height of subretinal detachment, and subfoveal choroidal thickness) was evaluated. Multivariate analyses using the model selection with the corrected Akaike Information Criterion index were performed. RESULTS: The optimal model for BCVA at 12 months only included baseline BCVA (coefficient = 0.90, P < 0.0001) and baseline elongated photoreceptor outer segment length (coefficient = -0.0016, P = 0.034), but not outer nuclear layer thickness. CONCLUSION: Elongated photoreceptor outer segment length was significantly associated with BCVA prognosis in patients with chronic central serous chorioretinopathy after reduced PDT and can be useful for predicting residual photoreceptor function during the active phase of chronic central serous chorioretinopathy.

DOI： 10.1097/IAE.0000000000002445

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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：KARGER  

Background:Choroidal osteoma is a rare, benign, ossifying intraocular tumor of unknown etiology. While patients with choroidal osteoma usually show distinct large yellowish subretinal lesions, some could have small lesions, making the differential diagnosis difficult. We experienced 2 cases of small symptomatic unilateral osteoma approximately 1.0-mm disc diameter in size.Methods:Retrospective medical charts of 2 patients with small symptomatic unilateral osteoma were reviewed. Fundus examination, spectral domain enhanced-depth optical coherence tomography (EDI-OCT), fluorescein angiography, indocyanine green angiography, B-scan ultrasonography (USG), and X-ray computed tomography (CT) were performed.Results:Case 1: a case of a 41-year-old male. Fundus examination revealed a yellowish-white lesion of 1.0-mm disc diameter in size. EDI-OCT of the lesion shows sub-RPE elevation. B-scan USG was not definite for diagnosis. Thin-slice (2 mm) CT scan revealed a choroidal osteoma. Case 2: a case of a 70-year-old male. Fundus examination revealed a yellowish-white lesion of 0.9-mm disc diameter. EDI-OCT showed sub-RPE elevation without serous retinal detachment and horizontal lamellar-like structure within the lesion. B-scan USG suggested acoustic shadowing, but it was unclear. The thin-slice CT scan confirmed bony tissue at the lesion.Conclusions:We report 2 cases of small choroidal osteoma. Diagnosis of small yellowish subretinal lesions is sometimes difficult. Characteristic findings with EDI-OCT may sometimes suggest this disease, and thin-slice CT could help to diagnose choroidal osteoma.

DOI： 10.1159/000508846

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To compare the 1-year visual outcomes and anatomical responses of patients who received photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) injections with those of patients who received PDT combined with intravitreal aflibercept (IVA) injections for treating polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively studied all treatment-naïve patients with PCV who received PDT combined with either IVR or IVA. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), the number of additional injections, and the presence of polypoidal lesions, as indicated by indocyanine green angiography (ICGA), during 1 year were evaluated. RESULTS: Forty-four eyes were assessed at the 1-year follow-up examination. Of these, 23 were treated with PDT combined with IVR (PDT/IVR group), and 21 were treated with PDT combined with IVA (PDT/IVA group). In both groups, BCVA was shown to be significantly improved 1 year after the initial treatment. CMT and CCT were also significantly decreased after 1 year. There were no significant differences in the changes in BCVA or CMT between the two groups. However, the change in CCT in the PDT/IVA group was significantly larger than that of the PDT/IVR group (P < 0.001). The mean number of additional injections was 0.78 ± 0.21 in the PDT/IVR group and 0.57 ± 0.21 in the PDT/IVA group with no significant difference between the two groups (P = 0.45). The polyp regression rate at 12 months was 78.2% in the PDT/IVR group and 78.9% in the PDT/IVA group with no significant difference between the two groups. CONCLUSIONS: PDT combined with either IVR or IVA was well tolerated and appeared to improve both vision and anatomy in patients with PCV. PDT/IVA may have a more pronounced effect on macular choroidal thickness at 1-year follow-up.

DOI： 10.1371/journal.pone.0235213

PubMed

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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 investigate oneyear results of verteporfin photodynamic therapy (PDT) combined with antivascular endothelial growth factor (VEGF) agents for neovascular agerelated macular degeneration (AMD) with limited response to aflibercept. Patients and Methods: Medical charts of 22 eyes of 22 patients (17 men and 5 women) with neovascular AMD who were treated with PDT combined with aflibercept for recurrent or persistent disease activity after repetitive administration of afiibercept and followed at least one year were retrospectively reviewed. Results : The mean age was 74.7 ± 7.1 years. The mean BCVA was similar between the baseline and 1 year after combined PDT. Central foveal thickness and central choroidal thickness measured by optical coherence tomography significantly decreased at 1 year. 72.7% of the cases showed dry macula at one year. In 15 cases treated with pro re nata protocol, mean additional treatment number was 1.6 ± 1.9, and in 7 cases treated with treat and extend protocol, mean additional treatment number was 7.3 ± 2 . 3 . Additional P D T was performed in 2 of 22 cases. Conclusion':Although the effects may vary with each patient, PDT combined with anti-VEGF agents might be an option for patients after repetitive anti-VEGF treatment.

Scopus

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Early detection and treatment are important management strategies for neovascular age-related macular degeneration (AMD). The purpose of this study was to determine the sensitivity and specificity in detecting neovascular AMD using two wide-field imaging systems: ClarusTM (CLARUS 500™, Carl Zeiss Meditec AG, Jena, Germany) and Optos®(Optos California®, Optos PLC, Dunfermline, United Kingdom), compared to conventional digital fundus photographs. METHODS: We retrospectively analyzed 109 eyes of 73 consecutive patients with neovascular AMD, who underwent standard examination and multimodal imaging, including fundus photography, and optical coherence tomography (OCT). Unmasked graders utilized slit-lamp biomicroscopy and OCT to diagnose neovascular AMD. Masked graders evaluated ClarusTM, Optos®, and digital fundus photograph methods to determine the presence of choroidal neovascularization associated with AMD. Sensitivity and specificity analyses were performed using combined fundoscopy and OCT as the reference standard. RESULTS: Ninety eyes were diagnosed with neovascular AMD and the remaining 19 eyes were normal based on the reference standard. Of these, neovascular AMD was detected using ClarusTM in 94.4% (85/90). The sensitivities of Optos® and digital fundus photographs were 81.1% (73/90) and 87.8% (79/90), respectively. The specificities using ClarusTM, Optos®, and digital fundus photographs were 89.5% (17/19), 94.7% (18/19), and 89.5% (17/19), respectively. CONCLUSION: ClarusTM, with its ability to image high-resolution wide field fundus, was considered superior for diagnosing neovascular AMD with high sensitivity and specificity. It may be a useful screening tool for early detection of neovascular AMD, facilitating prompt referral and treatment.

DOI： 10.1371/journal.pone.0238072

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本視能訓練士協会  

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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：英語   掲載種別：研究論文（学術雑誌）  

Central serous chorioretinopathy (CSC) usually resolves spontaneously; however, in some patients, it can be chronic and visual impairment remains even after resolution of the serous retinal detachment. The impaired photoreceptor cells often present with disrupted ellipsoid zone (EZ) on optical coherence tomography (OCT). In this study, the integrity of EZ was quantified by calculating the index of residual EZ, identified on binarized OCT images from 25 eyes of 23 patients with resolved CSC. To estimate residual EZ, integrity of residual EZ with the central horizontal line on the fovea (rEZc) and average integrity of residual EZ within 3 × 3-mm macular area (rEZave) were investigated. The interrater reliability of the method was assessed using the intraclass correlation coefficient (ICC). The relationship between LogMAR VA and age, central retinal thickness, central choroidal thickness, rEZc, and rEZave were evaluated using the linear mixed model. Retinal sensitivity was measured with the MP-3 microperimeter and similar analyses were iterated for mean retinal sensitivity (MS). ICC values were 0.938 with rEZc and 0.979 with rEZave. rEZc was significantly related to LogMAR VA (p = 0.039). rEZave was significantly related to MS (p < 0.001). These results suggested potential usefulness of residual EZ to predict visual function in resolved CSC.

DOI： 10.1038/s41598-019-48825-7

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 investigate retinal sensitivity in eyes with angioid streaks (AS). METHODS: This study was a retrospective observational case series. A total of 13 eyes from 9 patients with AS underwent ophthalmologic examination, including fundus autofluorescence (FAF), spectral domain optical tomography (SD-OCT), and microperimetry. Retinal pigment epithelium (RPE) atrophy was assessed using FAF. Outer retinal atrophy, more specifically, disruption of the ellipsoid zone, was evaluated using SD-OCT images. The association between retinal sensitivity, RPE atrophy or outer retinal atrophy, and patient demographic characteristics or ophthalmologic findings were investigated. RESULTS: The mean area of outer retinal atrophy was 14.5 ± 12.9 mm2, significantly larger than the mean area of RPE atrophy (9.0 ± 9.0 mm2; P = 0.0028). The average retinal sensitivity in the area of RPE atrophy was 2.4 ± 5.6 dB, that in the area of outer retinal atrophy outside RPE atrophy was 14.6 ± 7.5 dB, and that in the area without any atrophy was 25.6 ± 5.1 dB. Reticular pseudodrusen (RPD) was observed in 5 eyes. Eyes with RPD showed a greater extent of both outer retinal atrophy and RPE atrophy than those without RPD and a greater decrease in mean retinal sensitivity. CONCLUSIONS: In eyes with AS, especially in those with RPD, large areas of outer retinal atrophy and RPE atrophy were observed, and the retinal sensitivity in the areas was correspondingly decreased.

DOI： 10.1007/s00417-019-04332-z

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 three middle-aged cases with choroidal neovascularization (CNV) associated with early-onset drusen documented with optical coherence tomography angiography (OCTA). METHODS: Three patients with bilateral early-onset drusen were referred to our hospital. Fundus examination, fluorescein angiography, indocyanine green angiography, OCTA, and other multimodal imaging were performed. RESULTS: Case 1 involved a 47-year-old woman who presented with sudden unilateral anorthopia. She had no previous systemic pathologies. Funduscopic examination and fluorescein angiography revealed bilateral large colloid drusen accompanied by unilateral mild subretinal hemorrhage. Indocyanine green angiography revealed CNV, although it was unclear in fluorescein angiography. Optical coherence tomography angiography also showed interconnecting CNV beneath the retinal pigment epithelium. Case 2 involved a 40-year-old woman with membranoproliferative glomerulonephritis Type 3 who presented with unilateral anorthopia. On fluorescein angiography, cuticular drusen secondary to membranoproliferative glomerulonephritis were seen in both eyes. An interconnecting vascular network was revealed with OCTA and indocyanine green angiography indicating Type 1 CNV in the affected eye. Case 3 involved a 47-year-old man without any medical or family history. Predominant large colloid drusen associated with cuticular drusen were seen in both eyes. Unilateral mild serosanguinous changes were accompanied in the macula, where Type 1 CNV was detected with OCTA. CONCLUSION: All our cases with early-onset drusen showed Type 1 CNV that was detected by indocyanine green angiography or OCTA. Optical coherence tomography angiography has a potential to help noninvasively diagnose CNV in the cases of EOD.

DOI： 10.1097/ICB.0000000000000856

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 assess precision and accuracy of a new objective algorithm using binarization in a software for identifying the hyperautofluorescent ring (AF ring) in retinitis pigmentosa (RP) compared with subjective visual inspection. Methods: Ultra-widefield AF images were obtained from 23 eyes of 13 patients with retinitis pigmentosa (RP). We defined the borders of the AF rings using semiautomatic binarization algorithm in Fiji software. We compared the degree of precision (intra- and interrater agreements) of this algorithm and that of subjective visual inspection (freehand method) using Jaccard indices (JIs). To compare the classification performance (whether 68 points of Humphrey Field Analyzer is classified as inside, on, or outside AF rings), we calculated percent agreement and weighted kappa statistic between the two methods. The relationship between the distance from the AF ring and retinal sensitivities was also investigated. Results: The binarization method showed significantly higher JIs than the freehand method (for interrater: 0.94-0.95 vs. 0.73-0.78, respectively, P = 0.002; for intrarater: 0.95 vs. 0.68-0.71, respectively, P = 0.005). Percent agreement for classification between the two methods were 0.94 and weighted kappa statistic was 0.94 (P < 0.001). The retinal sensitivities decreased significantly and eccentrically from 2° inside to 3° outside the AF ring. Conclusions: Defining the AF ring in RP using the binarization algorithm showed significantly higher precision and the same degree of accuracy compared with visual inspection. Translation Relevance: This novel method may enable quantitative analysis of the AF ring, an indicator of retinal function in RP.

DOI： 10.1167/tvst.8.1.20

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pachychoroid neovasculopathy (PNV) shares some anatomical features with other pachychoroid spectrum diseases, but little is known about the characteristics on the treatment with anti-vascular endothelial growth factor (VEGF). We investigated the effect of choroidal structure and responses to anti-VEGF on the prognosis of pachychoroid neovasculopathy (PNV) and other types of neovascular age-related macular degeneration (non-PNV). Twenty-one eyes with PNV and 34 eyes with non-PNV who had anti-VEGF treatment were retrospectively reviewed. Choroidal neovascularization (CNV) area at baseline was measured with fluorescein angiography (FAG). The luminal and stromal area in the choroid was measured by enhanced-depth-imaging (EDI) OCT at baseline and 1 month. The association between dry macula or LogMAR VA (visual acuity, VA) at 1 month and baseline values or changes in the luminal or stromal area at 1 month, baseline CNV area, or anti-VEGF drugs were analyzed in patients with or without PNV. In non-PNV, change of luminal area (coefficient = 7.0×10-5, p = 0.0001), baseline CNV area (coefficient = 0.18, p = 0.033), and aflibercept vs. ranibizumab (coefficient = 0.29, p = 0.0048) were chosen as predictors for dry macula by the model selection. Similarly, in non-PNV, change of luminal area (coefficient = 6.1×10-6, p = 0.033), baseline CNV area (coefficient = 0.034, p = 0.022), and aflibercept vs. ranibizumab (coefficient = 0.056, p = 0.0020) were chosen as predictors for greater VA improvement. In PNV, however, none of these factors was chosen as predictors for dry macula or VA improvement by the model selection. The result of the present study implied that structural response after anti-VEGF might be different between non-PNV and PNV in the treatment with anti-VEGF agents.

DOI： 10.1371/journal.pone.0212055

PubMed

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

目的:滲出型加齢黄斑変性exudative age-related macular degeneration(AMD)におけるラニビズマブ硝子体内注射intravitreal injection of ranibizumab(IVR)反応不良例に対するアフリベルセプト硝子体注射intravitreal injection of aflibercept(IVA)へ切り替え後、treat and extend(TAE)療法による1年後までの治療成績を検討した。対象:2013年2月〜2014年9月までに東大病院眼科にてIVAに切り替えを行ったラニビズマブ治療反応不良AMD症例のうち、IVAによるTAE療法を開始後、1年以上経過観察が可能であったAMDの連続症例94例96眼とした。結果:視力は、1〜2ヵ月で有意に改善し、以降12ヵ月まで維持された。中心窩網膜厚は、1〜3ヵ月後に減少し、以降12ヵ月まで維持された。また一度も滲出性変化の再燃を認めなかった症例は36例(37%)症例であった。結論:ラニビズマブ治療反応不良例に対し、アフリベルセプト治療に切り替え後、TAE療法を用い、1年後平均視力、中心窩網膜厚の有意な改善・維持を認めた。(著者抄録)

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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 the relationship between visual field (VF) loss and the rings of the ellipsoid zone (EZ) and autofluorescence (AF) in patients with retinitis pigmentosa (RP). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 28 eyes of 15 patients with a clinical diagnosis of RP. METHODS: The VF was measured at a 1-degree interval on the horizontal or vertical lines, within the central 10 degrees from fixation, using MP-3 microperimetry (Nidek Co. Ltd., Aichi, Japan), and the sensitivity deviation from the normative database was calculated. OCT was performed, and the EZ was identified. Fundus AF was also measured, and the AF ring was identified. The VF test points were categorized according to their relationship with the EZ line and AF ring. The relationship between mean retinal sensitivity deviations on both the horizontal and vertical lines and the diameters of the EZ line and the AF ring in the corresponding directions was analyzed. The relationship between visual sensitivity deviation and the locations against EZ line and AF rings was also investigated. MAIN OUTCOME MEASURES: The relationship between the visual sensitivity deviation and the locations against EZ line and AF rings. RESULTS: The diameter of the AF ring had a significantly stronger relationship with mean retinal sensitivity deviation compared with the diameter of the EZ line in both the horizontal and vertical directions. Test point location inside/on/outside the AF ring was significantly related to retinal sensitivity deviation independent of the location inside/outside the EZ line (P < 0.001, linear mixed model). CONCLUSIONS: Visual sensitivity damage is significantly associated with the EZ lines and AF rings. The development of the AF ring is related to the decrease of visual function independent of and stronger than the EZ line.

DOI： 10.1016/j.oret.2018.03.007

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: To evaluate the prevalence of and factors associated with age-related macular degeneration (AMD) in a rural population of southwestern Japan. METHODS: This population-based cross-sectional study of all residents aged 40 years or older was conducted on the island of Kumejima, Okinawa, Japan. Of 4632 eligible residents, 3762 completed a comprehensive questionnaire and underwent ocular examination (participant rate, 81.2%). A non-mydriatic fundus photograph was used to grade AMD lesions according to the Wisconsin protocol. Prevalence of AMD was calculated and factors associated with AMD were identified by logistic regression. RESULTS: Of 3068 subjects with gradable photographs, 469 had early AMD and 4 had late AMD. Age-adjusted prevalence was 13.4% for any AMD, 13.3% for early AMD and 0.09% for late AMD. In multivariate analysis, any AMD was positively associated with age (OR 1.04 per year, 95% CI 1.03 to 1.05), male sex (OR 1.42, 95% CI 1.14 to 1.75) and history of cataract surgery (OR 1.35, 95% CI 1.00 to 1.82) and was negatively associated with longer axial length (OR 0.85 per millimetre, 95% CI 0.74 to 0.96). Early AMD similarly showed significant associations with these same factors. CONCLUSIONS: Prevalence of early or late AMD in a southwestern island population of Japan was 13.4% or 0.09%. Our data suggest relatively high prevalence for early AMD and low prevalence for late AMD in this sample of rural Japanese population. Significant factors associated with any or early AMD were mostly similar to that of previous studies.

DOI： 10.1136/bjophthalmol-2016-309980

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The purpose of the study was to investigate whether the structure-function relationship in glaucomatous and normative eyes is improved by considering photoreceptor layer thickness. Humphrey 10-2 visual fields (VF) and optical coherence tomography were carried out in 615 eyes of 391 subjects, including 100 eyes of 53 healthy controls and 515 eyes of 338 glaucoma patients. The relationship between mean VF sensitivity and the thickness of the retinal nerve fiber layer (RNFL) and ganglion cell layer and inner plexiform layer (GCL + IPL) was analyzed using linear mixed models, by glaucoma status and degree of myopia. The structure-function relationship was also analyzed by supplementing the RNFL and GCL + IPL thickness with the thicknesses of: (i) the inner nuclear layer and outer plexiform layer (INL + OPL); (ii) the outer nuclear layer and inner segment of photoreceptor layer (ONL + ISL); (iii) the outer segment layer of photoreceptor and retinal pigment epithelium (OSL + RPE). The model included total thickness of RNFL, GCL + IPL and OSL + RPE was highly more optimal than the model that only included the total thickness of RNFL and GCL + IPL, in all subsets of eyes by glaucoma status and degree of myopia.

DOI： 10.1038/s41598-018-28821-z

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of the current study is to investigate corneal biomechanical properties in detail using Ocular Response Analyzer (ORA) and Corvis ST (CST) tonometry and to analyze the association between corneal biomechanical properties and the frequency of intravitreal anti-vascular endothelial growth factor (VEGF) injections (FIV) in AS eyes with choroidal neovascularization (CNV). Twenty-eight eyes of 15 patients with AS were enrolled. Mean age of AS patients was 67.9 ± 9.8 years. ORA and CST measurements were carried out, in addition to comprehensive ophthalmic examinations. LogMAR visual acuity (VA) and ΔVA (the change of VA from baseline to the final visit) were calculated in each eye. Also, the relationships between FIV, and the variables of initial age at the observation period, axial length, and corneal biomechanical properties were investigated in eyes with AS using linear mixed model with model selection using AICc. In 28 AS eyes, 16 eyes underwent intravitreal anti-VEGF injections during follow-up period. Lower corneal hysteresis (CH), higher corneal resistant factor (CRF) and higher CST measured the DA ratio were associated with the increase of FIV in AS eyes (p = 0.01, p = 0.002, p = 0.027, respectively), suggesting the usefulness for monitoring of corneal biomechanical properties.

DOI： 10.1038/s41598-018-26430-4

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 investigate the relationship between choroidal structure and visual acuity after intravitreal aflibercept therapy for polypoidal choroidal vasculopathy (PCV). METHODS: We conducted a retrospective, single-centre and observational study including 18 eyes of 18 patients with PCV (73.8 ± 10.2 years of age) who were treated with three monthly intravitreal aflibercept injections followed by additional treatments in a treat-and-extend protocol. The cross-sectional images of the macula were obtained with enhanced depth imaging optical coherence tomography at baseline, at 3 months, and at 12 months. The choroidal layer was divided into luminal or stromal segments by applying binarization processing to calculate these areas. The relationships between age, spherical equivalent, best-corrected visual acuity (BCVA), baseline value, or changes in the luminal or the stromal areas, and the BCVA change at 12 months were analysed using multiple regression analyses and model selection procedures. RESULTS: Both stromal and luminal areas were decreased at 3 and 12 months compared to baseline areas (5% and 9% at 3 months, 6% and 12% at 12 months, p < 0.0001, p < 0.0001, p < 0.0001 and p < 0.0001, respectively). Greater improvement of visual acuity (VA) at 12 months was significantly associated with younger age, greater spherical equivalent, worse baseline BCVA, greater baseline luminal area, and smaller baseline stromal area. CONCLUSIONS: Choroidal structure might be useful as a new biomarker for potential Visual outcomes after intravitreal aflibercept therapy for PCV.

DOI： 10.1371/journal.pone.0197042

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The purpose of the study was to evaluate the 2-year outcome and predictive factors of treat-and-extend aflibercept in patients with eyes affected by typical neovascular age-related macula degenelation (t-AMD) or polypoidal choroidal vasculopathy (PCV), who were switched from ranibizumab. Patients and methods: The patients underwent three monthly aflibercept injections and subsequent administration following the treat-and-extend protocol. Sixty-two eyes of 62 patients were reviewed retrospectively. R statistical software was used for statistical analysis. Results: Twenty-two eyes were t-AMD and the remaining 40 eyes were PCV. There was no significant difference in the logarithm of the minimal angle of resolution visual acuity (VA) between baseline and 2 years after switching to aflibercept (0.40 vs 0.40; P=0.99). Multivariate analyses suggested that the following factors were significantly correlated with better VA at 2 years after switching to aflibercept: patients with PCV, the absence of intraretinal fluid at baseline, and better VA at baseline. Conclusion: In conclusion, VA was maintained and there was an anatomical improvement at 2 years in patients with t-AMD and PCV who were switched from ranibizumab to treat-and-extend aflibercept. PCV patients showed more favorable visual outcomes and less injections at 2 years compared to t-AMD patients. Intraretinal fluid and VA at baseline were predictors of VA at 2 years.

DOI： 10.2147/OPTH.S172115

PubMed

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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：Association of Folia Ophthalmologica Japonica  

Scopus

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記述言語：日本語   出版者・発行元：(公社)日本視能訓練士協会  

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記述言語：英語  

Purpose: We describe a sporadic case of unilateral pigmented paravenous retinochoroidal atrophy (PPRCA) with retinitis pigmentosa (RP) in the contralateral eye. Observations: a 24-year-old female aware of the narrowing of visual field was examined at our hospital. Funduscopic examination revealed left eye showing retinochroidal atrophy along the retinal veins with pigment accumulation while right eye showing peripheral diffuse retinal pigmented epithelium atrophy with bone spicule pigmentation. Fundus autofluorescence, electroretinogram, visual field test and optic coherent tomography were also performed and obtained results were compatible with funduscopic observation. Conclusions and importance: Simultaneous manifestation of PPRCA and RP observed in this case is rare and supports a shared genetic basis between the two diseases. Further genetic investigations are needed to elucidate the etiology and to properly manage PPRCA.

DOI： 10.1016/j.ajoc.2017.08.003

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本視能訓練士協会  

【目的】Outer Retinal tubulation(ORT)は、加齢黄斑変性のほか様々な網膜疾患の網膜外層にみられる管状病変である。今回、光干渉断層計(OCT)を用いてORTを撮像し、En face画像における病変の形状を観察した。【対象と方法】2015年12月から2016年4月までに東京大学医学部附属病院を受診し、黄斑変性にORTを認めた15例15眼を対象とした。Optovue社RTVueXRを使用し、En face画像でORTの形状を後ろ向きに検討した。【結果】En face画像では、ORTは外網状層に存在し、内部が低反射で外壁が網膜血管より肥厚した管状組織として認められた。ORTの形状は、分岐のない比較的小さな型(散在型11眼)と分岐を認める比較的大きな型(分岐型4眼)の2種に分類された。散在型と分岐型の間には、年齢、視力、屈折値の有意差は認められなかったが、ORTの存在期間は、分岐型が散在型に比べて有意に長かった(平均57.7ヵ月対31.9ヵ月、p<0.05)。【結論】OCTのEn Face画像を用いてORTを観察した。散在型と分岐型の2種の形状に特徴づけられた。分岐型ORTは、経過観察中にその形状が変化した。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01962&link_issn=&doc_id=20180306160030&doc_link_id=130006515552&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130006515552&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

The purpose of the current study was to investigate the association between visual function and retinal structure in central serous chorioretinopathy (CSC). In 22 eyes of 22 chronic CSC patients with serous retinal detachment at the macula, retinal sensitivity was measured using MP3 microperimetry (NIDEK, Japan) and mean sensitivity within two degrees (MS2), four degrees (MS4) and six degrees (MS6), as well as foveal sensitivity (MS0), were calculated. Retinal structure was measured using optical coherence tomography (OCT, Spectralis, Heidelberg). The relationship between visual function (LogMAR best-corrected visual acuity [LogMAR VA] and MS0, MS2, MS4, MS6) and serous retinal detachment height at the fovea (SRDH), central retinal thickness (CRT), macular volume (MV) and central choroidal thickness (CCT) was investigated. There were significant negative correlations between LogMAR VA and MS0 (p = 0.016), MS2 (p = 0.049). No significant relationship was observed between LogMAR VA and SRDH (p = 0.97) although there was a significant negative correlation between SRDH and MS2 (p = 0.028), MS4 (p = 0.049), MS6 (p = 0.023). In conclusion, in CSC, serous retinal detachment was significantly correlated with retinal sensitivity measured with MP3, but not with LogMAR VA.

DOI： 10.1038/s41598-017-16339-9

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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：NATURE PUBLISHING GROUP  

The purpose of the current study was to investigate the structure-function relationship in patients with retinitis pigmentosa (RP) using optical coherence tomography and the MP-3 microperimeter. Visual field (VF) measurements were carried out using MP-3 microperimetry and the Humphrey Field Analyzer (HFA, Carl-Zeiss, CA), 22 eyes of 11 patients with a clinical diagnosis of RP, both with the 10-2 test grid pattern. Optical coherence tomography (OCT, Spectralis, Heidelberg, Germany) was also performed and the ellipsoid zone (EZ) was identified in the OCT image. The mean (±SD) number of test points located within the EZ edge was 11.6 (±5.9). There was a significant relationship between mean retinal sensitivity measured with MP-3 and the area surrounded by the EZ circular line: AEZ (p < 0.05), but this was not the case with HFA (p > 0.05). The difference between retinal sensitivity inside and outside the EZ edge was significantly larger with MP-3 than with HFA (p < 0.001). Our findings suggest that retinal sensitivity measured with MP-3 better reflects the magnitude of structural damage observed with OCT, compared with HFA. Further, the difference in retinal sensitivity between the inside and outside EZ edge is significantly larger for the MP-3 test, compared with the HFA.

DOI： 10.1038/s41598-017-16143-5

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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 29 cases who were switched to aflibercept therapy for exudative age- related macular degeneration (AMD) and who showed stabilization following treatment at 12-week interval by treat-And-extend (TAE) method. Cases and Method: This study was made on 29 eyes of 29 cases of AMD. They were chosen out of 66 eyes of 66 cases who showed resistance to ranibizumab and were switched to aflibercept and who needed aflibercept at a 12-week-interval by TAE method. These 29 cases were evaluated regarding background factors, rate of recurrence, and central retinal thickness. Results: Ten cases showed recurrence after switching to aflibercept. Recurrence was independent of background factors or visual acuity before recurrence. Cases with recurrence showed greater value of central retinal thickness just before extending the interval of treatment to 12 weeks. Conclusion: In cases of AMD treated by aflibercept by TAE method, increased central retinal thickness may serve as a predictive factor for recurrence before extending the interval to 12 weeks.

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記述言語：日本語   出版者・発行元：(株)医学書院  

目的:滲出型加齢黄斑変性(AMD)に対してアフリベルセプトに切り替え,treat-and-extend(TAE)法で投与間隔を長期間延長できた29症例の報告。対象と方法:ラニビズマブに抵抗がある29例29眼を対象とした。本症例群は,過去43ヵ月間にラニビズマブを4週ごとに3回投与しても滲出性変化が消退しないためにアフリベルセプトに切り替えた66例66眼のうち,投与間隔を12週に延長できた症例である。本症例群について,背景因子,再発の有無,投与間隔を12週に延長する直前の中心窩網膜厚につき,診療録の記述に基づいて検索した。結果:再発は10眼に生じた。再発の有無は背景因子に関係せず,再発前後の視力に差がなかった。投与間隔を12週に延長する直前からの中心窩網膜厚は,再発群で大きかった。結論:加齢黄斑変性に対するアフリベルセプトのTAEによる投与では,投与間隔を12週に延長する直前からの中心窩網膜厚が再発の指標となる可能性がある。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01537&link_issn=&doc_id=20171005050019&doc_link_id=10.11477%2Fmf.1410212438&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410212438&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   掲載種別：研究論文（学術雑誌）   出版者・発行元：Association of Folia Ophthalmologica Japonica  

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記述言語：日本語   出版者・発行元：眼科臨床紀要会  

背景:強度近視の網膜内に脈絡膜血管が迷入した1例を経験したので報告する。症例:70歳、女性。4年前より左眼霧視を自覚し当科受診した。初診時左眼所見は、視力(0.3)、眼軸長は31.5mmで、前眼部は人工無水晶体、眼底に後部ぶどう腫、限局性網脈絡膜萎縮(CRA)、脈絡膜新生血管を認め、近視性新生血管黄斑症と診断した。光干渉断層計(OCT)でCRAの網膜外顆粒層に管状構造を認めた。OCTにて管状組織は、脈絡膜より網膜内に認めた後、再び脈絡膜中大血管層へ向かった。OCT angiographyにて同部位に灌流を示し、蛍光眼底造影にて管状組織に蛍光流入を認めた。以上より管状組織は、脈絡膜血管が網膜内に迷入したものと考えられた。結論:限局性CRAの網膜内の管状組織はOCTではouter retinal tubulationと類似していたが、OCT angiographyや蛍光眼底造影で判別した。(著者抄録)

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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 evaluate the effect of retinal fluid status at month 3 on visual and anatomic outcomes during the one-year follow-up period in patients with neovascular age-related macular degeneration, which were recalcitrant with intravitreal ranibizumab treatment.Subjects and Methods: Post-hoc analysis including 75 eyes received three initial monthly intravitreal aflibercept injections as introduction phase and subsequently received treat and extend treatment. We defined the recalcitrant group which had fluid at month 3, and the sensitive group which had no fluid. We analyzed the background and visual or anatomic outcome during the one-year follow-up period. Results: The background was similar between the two groups. Best-corrected logMAR visual acuity, central retinal thickness, and subfoveal choroidal thickness from baseline improved at month 12 in the total cohort. Compared to the recalcitrant group, the sensitive group showed better improvement at each time point. The patients in the recalcitrant group tended to receive more injections. Conclusions: Conversion to IVA was effective in patients with AMD resistant to ranibizumab. Fluid status at month 3 may predict visual or anatomic outcome, and the number of injections during the one-year follow-up period.

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記述言語：日本語   出版者・発行元：(株)医学書院  

目的:ラニビズマブ抵抗性の滲出型加齢黄斑変性に対するアフリベルセプト切り替え治療導入後に滲出が残存した例について検討する。対象と方法:導入期毎月3回連続投与,維持期treat and extend投与した75眼を対象とし,導入期終了時に滲出性変化が残存した抵抗群,消失した反応群の背景因子,1年経過を後ろ向きに検討した。結果:背景因子に両群の差はなかった。視力はlogMARで抵抗群は維持,反応群では0.089改善した(p<0.001)。中心窩網膜厚は抵抗群で68μm(P<0.01),反応群で140μm改善した(p<0.001)。中心窩脈絡膜厚は抵抗群で維持,反応群で28μm菲薄化した(p<0.001)。投与回数は抵抗群10.95回,反応群8.89回と差があった(p<0.001)。結論:切り替え導入期終了時の滲出性変化の有無は1年成績に有意に関連した。(著者抄録)

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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：PUBLIC LIBRARY SCIENCE  

PURPOSE: To assess the thickness of the photoreceptor layer in the macular region in glaucomatous eyes. METHOD: Humphrey 10-2 visual field (VF) testing was carried out and mean threshold (mTH) was calculated in 118 eyes from 118 patients with open angle glaucoma. Macular optical coherence tomography (OCT) measurements (RS 3000, Nidek Co.ltd., Aichi, Japan) were also carried out in all eyes. Thickness measurements were recorded in the outer segment and retinal pigment epithelium (OS+RPE), the nerve fiber layer (NFL), the ganglion cell layer and inner plexiform layer (GCL+IPL), the inner nuclear layer and outer plexiform layer (INL+OPL) and the outer nuclear layer and inner segment (ONL+IS). The relationship between mTH and the thickness of these five different layers was investigated. Additionally, the influence of OS+RPE on mTH was investigated using partial correlation eliminating the effect of other variables of NFL, GCL+IPL, INL+OPL, ONL+IS, age, gender and axial length. RESULTS: The thickness of the OS+RPE layer was significantly decreased with the decrease of mTH (coefficient = 0.63 p <0.001). Partial correlation analysis suggested OS+RPE thickness is significantly (coefficient = 0.31, p <0.001) related to mTH, independent from NFL, GCL+IPL, INL+OPL, ONL+IS, age, gender and axial length. CONCLUSIONS: The thickness of the RPE+OS layer appears to be related to visual sensitivity in glaucoma.

DOI： 10.1371/journal.pone.0184064

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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：PUBLIC LIBRARY SCIENCE  

PURPOSE: The purpose of the current study is to investigate the test-retest reproducibility of visual fields (VFs) measured with the MP-3 microperimeter, in patients with retinitis pigmentosa (RP). METHOD: VFs were twice measured with the MP-3 and also the Humphrey Field Analyzer, using the 10-2 test grid pattern in both perimeters, in 30 eyes (15 right and 15 left eyes) of 18 RP patients (11 males and 7 females). Test-retest reproducibility was assessed using the mean absolute deviation (MAD) measure at all 68 points in the test grid. Reproducibility was also evaluated using the intraclass correlation coefficient (ICC) of VF sensitivities. RESULT: The mean sensitivity measured in the HFA 10-2 was significantly higher than that measured in the MP-3 in both the first and second VF tests (p <0.0001, linear mixed model). The MAD was 2.4±0.6 [1.1 to 3.6] dB for MP-3 and 2.4±0.9 [1.1 to 5.1] dB for HFA 10-2, which was not significantly different (p = 0.76, linear mixed model). The ICC value associated with the MP-3 VFs was 0.81±0.13 [0.49 to 0.98], which was significantly larger than that observed for the HFA 10-2 VFs: 0.77±0.19 [0.20 to 0.94] (p = 0.043, linear mixed model). CONCLUSION: The MP-3 microperimeter appears to be useful to evaluate central visual function in RP eyes, exhibiting test-retest reproducibility that is equal to, or better than, that observed in HFA 10-2 VFs.

DOI： 10.1371/journal.pone.0166666

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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：ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

As a part of the visual cycle, all-trans-retinol (all-trans-ROL), the major form of vitamin A in circulating blood, is transported to the retinal pigment epithelium (RPE). All-trans-ROL is essential for normal retina function. However, recent researches have shown that excessive retinol intake can cause increase of all-trans-retinal. This can lead to the accumulation of lipofuscin, which is important in the pathogenesis of retina degeneration disease, such as dry type age-related macular degeneration (AMD). Since there are few reports regarding the involvement of all-trans-ROL in exudative AMD, we investigated the effects of all-trans-ROL in vitro and in vivo. We evaluated vascular endothelial growth factor (VEGF) expression in ARPE-19 cells and THP-1 cells after all-trans-ROL treatment using ELISA and real-time RT-PCR. In-vitro tube formation assay was performed with HUVEC cells using the conditioned medium (CM) obtained from ARPE-19 cells treated with all-trans-ROL. Transcriptional activity of retinoic acid receptor (RAR) was evaluated using luciferase assay. In mice, VEGF expressions were investigated in the retina and RPE/choroid after three weeks of excessive oral retinol intake. Laser-induced choroidal neovascularization (CNV) models were evaluated after they were fed with various doses of retinol. VEGF mRNA expression and VEGF production were significantly increased in all-trans-ROL treated ARPE-19 cells, which were inhibited by an RAR antagonist LE540. In contrast, there were no significant changes in VEGF production in THP-1 cells. Transcriptional activity of RAR was upregulated by all-trans-ROL treatment in ARPE-19 cells. The CM, obtained from ARPE-19 cells treated with all-trans-ROL, induced more capillary-like tube formation than cells treated with control vehicles. In vivo, the high retinol diet group has increased VEGF expression in the RPE/choroid and larger lesion size was induced. Our results suggest that all-trans-ROL is a pro-angiogenic factor. Excessive retinoid intake may be a potential risk factor for exudative AMD.

DOI： 10.1016/j.exer.2015.01.005

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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：SPRINGER JAPAN KK  

PURPOSE: To investigate the association between vitreomacular adhesion (VMA) and the visual and anatomic outcomes of antivascular endothelial growth factor therapy for macular edema due to branch retinal vein occlusion (BRVO). METHODS: This study included 107 eyes of 107 patients with BRVO who underwent intravitreal injection of 1.25 mg bevacizumab. The presence of VMA was determined with spectral-domain optical coherence tomography (SD-OCT). All eyes underwent best-corrected visual acuity (BCVA) and central retinal thickness (CRT) measurements using SD-OCT immediately before the injection and at 3, 6, 9, and 12 months after the injection. The main outcome measures were changes in BCVA and CRT from baseline. RESULTS: The VMA(+) and VMA(-) groups consisted of 47 and 60 eyes, respectively, and patients' age differed significantly between the groups (P < 0.001). In both groups, BCVA and CRT improved after the injection. The VMA(+) group showed better improvement in BCVA than did the VMA(-) group (P = 0.0150), and the presence of VMA was associated with a greater decrease in CRT after adjusting for age (P = 0.0019). CONCLUSIONS: Presence of VMA may be associated with superior visual and anatomic outcome for intravitreal bevacizumab in the treatment of macular edema due to BRVO.

DOI： 10.1007/s10384-013-0302-4

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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  

The molecular mechanism that leads to age-related macular degeneration (AMD) is poorly understood. Gene expression profiling identified adrenomedullin (ADM) as a possible molecular target for the treatment of AMD and expression of ADM was upregulated in eyes with laser-induced choroidal neovascularization (CNV). In vivo experiments strongly indicated that ADM inhibits laser-induced CNV. In vitro tube formation assay demonstrated that neither ADM nor conditioned medium from the retinal pigment epithelial (RPE) cells, D407 cells, treated with ADM affected the capillary-formation of human umbilical vein endothelial cells. In contrast, in vitro macrophage migration assay clearly demonstrated that the conditioned medium of D407 inhibited macrophage migration. Furthermore, the expression of C-C motif chemokine 2 (CCL2) was significantly inhibited in D407 cells after ADM treatment. In vivo experiments using a laser-induced CNV model in ADM(+/-) mice demonstrated that CCL2 expression was upregulated in ADM(+/-) mice with concomitant increase in macrophage migration in the subretinal space. Additionally, the effect of ADM was abrogated in CCL2 knockout mice. These results suggest that administration of ADM inhibits macrophage migration in the subretinal space and leads to the suppression of laser-induced CNV in an animal model. The inhibition of macrophage migration occurred through the CCL2 from RPE. This study provides a novel potential therapeutic target for AMD which does not substantially disrupt VEGF-A signaling mediated vasculogenesis.

DOI： 10.1016/j.ajpath.2012.06.028

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/ATVBAHA.112.248021

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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: Several recent studies suggest that some chemokines/chemokine receptors are involved in choroidal neovascularization (CNV). CXCR3 was the focus of the present study because microarray analysis for murine laser-induced CNV model showed the increased expression of CXCR3. The purpose of this study was to evaluate the effect of CXCR3 on CNV. METHODS: Microarray analysis was performed for the mouse eyes with laser-induced CNV. CXCR3 expressions on the CNV were evaluated by immunohistochemistry and real-time RT-PCR. CNV was compared between CXCR3-deficient mice and wild-type mice, between mice treated with anti-CXCR3/anti-IP-10 neutralizing antibody and mice treated with control IgG. Macrophage recruitment into CNV was also investigated. Ocular expressions of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), C-C chemokine ligand-2 (CCL2), and complement component-3 (C3) were evaluated by real-time PCR. RESULTS: Microarray analysis and real-time RT-PCR revealed the elevation of CXCR3 and IP-10 in laser-treated mouse eyes compared with control eyes. Immunohistochemistry showed CXCR3 expression on the endothelial cells of CNV. Laser-induced CNV of CXCR3-deficient mice was significantly larger, with greater leakage in fluorescein angiography, and with greater macrophage-infiltration compared with wild-type mice (P < 0.01). Intravitreal injection of anti-CXCR3/anti-IP-10 neutralizing antibody exacerbated CNV. The CCL2 expression in the laser-treated eyes of CXCR3-deficient mice was higher than in those of wild-type mice (P < 0.05), whereas VEGF, PEDF, and C3 showed no differences. CONCLUSIONS: These results suggested that CXCR3 expressed on CNV could have an angiostatic effect on it.

DOI： 10.1167/iovs.11-8232

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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：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Oxidative stress is implicated in the pathologies of photoreceptor cells, and the protective role of antioxidant enzymes for photoreceptor cells have been well understood. However, their essentiality has remained unknown. In this study we generated photoreceptor-specific conditional knock-out (CKO) mice of glutathione peroxidase 4 (GPx4) and showed the critical role of GPx4 for photoreceptor cells. In the wild-type retina the dominant GPx4 expression was in the mitochondria, indicating the mitochondrial variant was the major GPx4 in the retina. In the GPx4-CKO mice, although photoreceptor cells developed and differentiated into rod and cone cells by P12, they rapidly underwent drastic degeneration and completely disappeared by P21. The photoreceptor cell death in the GPx4-CKO mice was associated with the nuclear translocation of apoptosis-inducing factor (AIF) and TUNEL-positive cells. Photoreceptor cells before undergoing apoptosis (P11) exhibited decreased mitochondrial biomass, decreased number of connecting cilia, as well as disorganized structure of outer segments. These findings indicate that GPx4 is a critical antioxidant enzyme for the maturation and survival of photoreceptor cells.

DOI： 10.1074/jbc.M111.335174

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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：SOC NEUROSCIENCE  

The molecular mechanisms underlying cell fate determination from common progenitors in the vertebrate CNS remain elusive. We previously reported that the OTX2 homeoprotein regulates retinal photoreceptor cell fate determination. While Otx2 transactivation is a pivotal process for photoreceptor cell fate determination, its transactivation mechanism in the retina is unknown. Here, we identified an evolutionarily conserved Otx2 enhancer of ∼500 bp, named embryonic enhancer locus for photoreceptor Otx2 transcription (EELPOT), which can recapitulate initial Otx2 expression in the embryonic mouse retina. We found that the RAX homeoprotein interacts with EELPOT to transactivate Otx2, mainly in the final cell cycle of retinal progenitors. Conditional inactivation of Rax results in downregulation of Otx2 expression in vivo. We also showed that NOTCH-HES signaling negatively regulates EELPOT to suppress Otx2 expression. These results suggest that the integrated activity of cell-intrinsic and -extrinsic factors on EELPOT underlies the molecular basis of photoreceptor cell fate determination in the embryonic retina.

DOI： 10.1523/JNEUROSCI.3109-11.2011

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Crx is a transcription factor which is predominantly expressed in developing and mature photoreceptor cells in the retina, and plays a crucial role in the terminal differentiation of both rods and cones. Crx is one of the earliest-expressed genes specifically in photoreceptor precursors, allowing us to trace photoreceptor precursor cells from embryonic stages to adult stage by visualizing Crx-expressing cells. In the current study, we generated a transgenic mouse line which expresses enhanced green fluorescence protein (EGFP) in the retina driven by the Crx promoter using bacterial artificial chromosome (BAC) transgenesis. EGFP-positive cells were observed in the presumptive photoreceptor layer in the retina at embryonic day 15.5 (E15.5), and continued to be expressed in developing and mature photoreceptor cells up to adult stage. We sorted EGFP-positive photoreceptor precursors at E17.5 using fluorescence-activated cell sorter (FACS), and subsequently performed microarray analysis of the FACS-sorted cells. We observed various photoreceptor genes, especially cone genes, are enriched in the EGFP-positive cells, indicating that embryonic cone photoreceptor precursors are enriched. In addition, we found that most of the EGFP-positive cells were post-mitotic cells. Thus, the transgenic line we established can serve as a useful tool to study both developing and mature photoreceptor cells, including embryonic cone precursors whose analysis has been difficult.

DOI： 10.1016/j.bbrc.2010.01.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To establish the genetic tools for conditional gene deletion in mouse retinal progenitors, we generated a Dkk3-Cre transgenic mouse line using bacterial artificial chromosome (BAC) transgenesis. Cre recombination efficiency in vivo was assayed by crossing this transgenic line, termed BAC-Dkk3-Cre, with the CAG-CAT-Z reporter line. This BAC-Dkk3-Cre line showed Cre recombinase activity in most retinal progenitors. Cre activity was detectable from embryonic day 10.5 (E10.5) and generally restricted to the retina during embryogenesis. To verify that BAC-Dkk3-Cre mice successfully circumvented lethality, we generated Otx2flox/flox/BAC-Dkk3-Cre+ mice as Otx2 conditional knockout mice. The Otx2flox/flox/BAC-Dkk3-Cre+ mice were viable, and their retina showed loss of mature cell-type markers of photoreceptor cells, bipolar cells, and horizontal cells, in contrast, amacrine-like cells noticeably increased. Thus, the BAC-Dkk3-Cre transgenic mouse line provides a powerful tool for generating conditional knockout mouse lines for studying loss of gene functions in the developing retina.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Sterile alpha motif (SAM) domains are approximately 70 residues long and have been reported as common protein-protein interaction modules. This domain is found in a large number of proteins, including Polycomb group (PcG) proteins and ETS family transcription factors. In this work, we report the cloning and functional characterization of a novel SAM domain-containing protein, which is predominantly expressed in retinal photoreceptors and the pineal gland and is designated mouse mr-s (major retinal SAM domain protein). RESULTS: mr-s is evolutionarily conserved from zebrafish through human, organisms through which the mechanism of photoreceptor development is also highly conserved. Phylogenetic analysis suggests that the SAM domain of mr-s is most closely related to a mouse polyhomeotic (ph) ortholog, Mph1/Rae28, which is known as an epigenetic molecule involved in chromatin modifications. These findings provide the possibility that mr-s may play a critical role by regulating gene expression in photoreceptor development. mr-s is preferentially expressed in the photoreceptors at postnatal day 3-6 (P3-6), when photoreceptors undergo terminal differentiation, and in the adult pineal gland. Transcription of mr-s is directly regulated by the cone-rod homeodomain protein Crx. Immunoprecipitation assay showed that the mr-s protein self-associates mainly through the SAM domain-containing region as well as ph. The mr-s protein localizes mainly in the nucleus, when mr-s is overexpressed in HEK293T cells. Moreover, in the luciferase assays, we found that mr-s protein fused to GAL4 DNA-binding domain functions as a transcriptional repressor. We revealed that the repression activity of mr-s is not due to a homophilic interaction through its SAM domain but to the C-terminal region. CONCLUSION: We identified a novel gene, mr-s, which is predominantly expressed in retinal photoreceptors and pineal gland. Based on its expression pattern and biochemical analysis, we predict that mr-s may function as a transcriptional repressor in photoreceptor cells and in pinealocytes of the pineal gland.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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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  

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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  

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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  

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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  

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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：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  

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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  

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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  

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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  

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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  

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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  

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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  

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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  

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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  

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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  

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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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：ELSEVIER SCIENCE BV  

DOI： 10.1016/j.mod.2009.06.179

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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  

J-GLOBAL

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