記述言語：英語  

DOI： 10.1007/s10384-025-01219-x

PubMed

記述言語：英語  

DOI： 10.1167/iovs.66.6.56

PubMed

DOI： 10.4103/tjo.TJO-D-25-00001

Web of Science

記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: Neovascular age-related macular degeneration (nAMD) with type 2 macular neovascularization (MNV) has a relatively good responsiveness to anti-vascular endothelial growth factor (anti-VEGF) therapy compared to type 1 MNV. This study aimed to analyze the treatment outcomes of nAMD patients with type 2 MNV and identify factors associated with fluid recurrence. Study Design: Retrospective observational study. Methods: This study included treatment-naïve nAMD patients with type 2 MNV but without type 1 MNV, who received 3-monthly anti-VEGF injections as the loading phase and were followed up for over 2 years. The treatment outcomes were compared between proactive (PA) and reactive regimen (RA) groups. In addition, we investigated the factors associated with fluid recurrence in the RA group. Results: This retrospective study included 65 eyes from 65 patients. Best-corrected visual acuity (BCVA) and central macular thickness significantly improved in both the PA and RA groups. Although there was no significant difference between the two groups, the RA group showed a trend towards better BCVA. The presence of fluid three or four months after the initial injection was associated with fluid recurrence in the RA group (p = 0.02). Conclusion: For nAMD patients with type 2 MNV, a proactive regimen is generally preferred. However, for nAMD patients with type 2 MNV achieving fluid resolution after the loading phase, it may be possible to maintain BCVA and reduce the number of anti-VEGF injections by following a reactive regimen.

DOI： 10.1007/s10384-025-01178-3

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PubMed

記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: The Retinitis Pigmentosa Progression and Inflammatory Marker Registry (RP-PRIMARY) is intended as a prospective observational study aimed at establishing sensitive outcome measures to detect the efficacy of anti-inflammatory agents in future clinical trials. The following is the RP-PRIMARY study protocol. Study Design: Prospective, multicenter study. Methods: We will recruit 100 patients with typical RP (any genetic mutation) and the following characteristics: age 20–70 years; mean retinal sensitivity ≥ 10 dB at 12 central points on Humphrey 10-2 visual field tests; central foveal thickness ≤ 250 μm on optical coherence tomography (OCT); and no ocular complications unrelated to RP or serious systemic complications. Early Treatment Diabetic Retinopathy Study (ETDRS). visual acuity, Humphrey 10-2 visual field tests, OCT, and fundus autofluorescence imaging will be performed every 3 months for 2 years. Inflammatory indices such as aqueous flare values, high-sensitivity C-reactive protein (CRP), serum IL-8, and CD14/16 inflammatory monocyte proportion will be measured every year. The primary endpoint will be the progression rate of retinal sensitivity loss on the Humphrey 10-2 visual field tests. The secondary endpoints will be the rate of decline of each parameter and its association with inflammatory indices. Standard-operation-procedure documents were prepared for all study procedures, and consultations with the regulatory agency were conducted to ensure the data reliability for future use in clinical trials. Conclusions: Detailed registry data on the natural history and inflammatory profile of RP will be useful in designing study protocols for anti-inflammatory therapy for RP and as natural history data for drug applications.

DOI： 10.1007/s10384-025-01179-2

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PubMed

出版者・発行元：株式会社医学書院  

DOI： 10.11477/mf.037055790790040446

CiNii Research

記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞目的:眼科受診を契機に確定診断に至った伝染性単核球症の1例について報告する。症例:症例は10歳,女性。3週間前から持続する両側上眼瞼腫脹を主訴に初診。初診時,両側涙腺部に軽度の腫脹を認め,右眼に1mm×2mm,左眼に3mm×3mmの皮下腫瘤を触知した。MRIにて両側涙腺軽度腫大を認め,採血では異型リンパ球増加,AST,ALT上昇を伴っていた。小児科を受診し,頸部リンパ節腫脹,肝臓腫大を認め,抗EBウイルスIgM抗体陽性であったことから,伝染性単核球症の確定診断に至った。安静を指示し,2週間で症状は軽快した。結論:伝染性単核球症が眼瞼腫脹を主訴に眼科を初診する場合があり,注意が必要である。

記述言語：英語   出版者・発行元：Retina  

Purpose:To report the surgical outcome of fluid aspiration in intraretinal cysts as a novel treatment approach for the refractory cystoid macular edema associated with diabetic retinopathy.Methods:This retrospective consecutive case series examined eight patients with refractory cystoid macular edema who underwent intraretinal cyst fluid aspiration using a 38-gauge subretinal infusion needle during pars plana vitrectomy. This study reviewed changes in central retinal thickness, best-corrected visual acuity, and central sensitivity among patients followed up for 12 months postsurgery.Results:Central retinal thickness on optical coherence tomography (m) significantly improved at 12 months after surgery (308 ± 99) compared with before surgery (480 ± 141) (P < 0.005). During the follow-up period, cystoid macular edema relapsed in one eye. The best-corrected visual acuity (logarithm of the minimal angle of resolution) at 12 months postsurgery (0.23 ± 0.32, Snellen equivalent: 20/50) was significantly better than the preoperative best-corrected visual acuity (0.39 ± 0.29, Snellen equivalent: 20/63) (P < 0.01). The mean deviation value of central sensitivity did not significantly change between preoperative (-2.5 ± 2.1) and postoperative (-2.2 ± 2.2) assessments (P = 0.07).Conclusion:Fluid aspiration in intraretinal cysts may be a treatment option for refractory cystoid macular edema in eyes with diabetes.

DOI： 10.1097/IAE.0000000000004198

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PubMed

記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

目的:網膜色素変性症(RP)患者に処方された遮光眼鏡の特徴(色,視感透過率)と視機能との関連について検討した.対象と方法:2019～2022年に屋外用遮光眼鏡を処方したRP患者34例について,診療録を後ろ向きに調査した.視機能の指標として,視力良好眼の矯正視力(logMAR)と視力・視野検査の結果からFunctional Acuity Score(FAS),Functional Field Score(FFS),Functional Vision Score(FVS)を算出し,処方した遮光眼鏡の視感透過率との関連についてスコアを比較検討した.結果:平均年齢は63.0±11.3歳.処方した遮光眼鏡の色はブラウン系17例,グレー系9例,グリーン系8例であった.各視機能スコアの平均値は,視力良好眼のlogMAR値:0.49±11.3,FAS:71±25,FFS:33±16,FVS:26±18であった.すべての視機能スコアと視感透過率との間に有意な相関が認められた(p<0.01).結論:RP患者の遮光眼鏡のカラー選択はブラウン系が多かった.視機能スコアの低い患者ほど視感透過率の低いレンズを選択した.(著者抄録)

記述言語：英語   出版者・発行元：Pediatric Blood and Cancer  

Programs allowing access to investigational drugs and off-label drug use for serious diseases have often been applied to pediatric cancers. A clinical study conducted under the Japanese “Patient-Proposed Healthcare Services” evaluated the efficacy and safety of dabrafenib plus trametinib in children with BRAF V600 mutant glioma (jRCTs071210071). This study successfully provided unapproved and off-label medications to four enrolled patients, two with low-grade glioma and two with high-grade glioma (median age: 10.5 years), until regulatory approval. The timeframe and data collection from such access programs need to be optimized for pediatric patients in accordance with the healthcare system of each nation.

DOI： 10.1002/pbc.31510

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記述言語：英語   出版者・発行元：Investigative Ophthalmology and Visual Science  

PURPOSE. Autophagy and lysosomal degradation are vital processes that protect cells from oxidative stress. This study investigated the role of lysosome-associated membrane protein 2 (Lamp2), a lysosomal protein essential for autophagosome maturation and lysosome biogenesis, in maintaining retinal health under oxidative stress. METHODS. To induce oxidative stress, young Lamp2 knockout (KO) and wild-type mice received an intravenous injection of a low dose (10 mg/kg) of sodium iodate (NaIO3).We examined retinal histopathology and morphological changes in the RPE. The involvement of resident microglia or infiltrating macrophages was assessed using immunostaining, flow cytometry, and real-time PCR for chemokines and cytokines. RESULTS. After administering a low-dose NaIO3, Lamp2 KO mice showed significant RPE degeneration, whereas wild-type mice had minimal damage. Histological analysis and electron microscopy revealed significant thinning of the outer nuclear layer and loss of RPE epithelial polarity in Lamp2 KO mice. Additionally, there was a significant increase in ionized calcium-binding adaptor molecule 1-positive microglia and macrophages in the outer retina. Early proliferation of CD45lowMHC-IIlow resident microglia was followed by the infiltration of CD45highLy6Chigh monocytes and the engraftment of CD11b+CD45high monocyte-derived macrophages. Transcript levels of monocyte chemoattractant protein 1, macrophage inflammatory protein 1β, Il- 1β, and Il-6 also increased in the retinas of Lamp2 KO mice. Furthermore, pretreatment with the macrophage-depleting agent clodronate prevented NaIO3-induced RPE degeneration and macrophage infiltration in Lamp2 KO mice. CONCLUSIONS. Lamp2 deficiency, when combined with oxidative stress, leads to RPE degeneration in vivo. Lysosomal dysfunction also promotes macrophage engraftment and triggers neurotoxic inflammation.

DOI： 10.1167/iovs.66.2.2

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PubMed

記述言語：英語   出版者・発行元：Plos One  

Background Acute retinal necrosis (ARN) is a rare but vision-threatening viral retinitis that can lead to severe visual impairment or blindness if not diagnosed and treated promptly. However, due to its rarity, there are limited large-scale data on the clinical characteristics, treatment approaches, and outcomes of ARN in Japan. A nationwide registry is needed to systematically collect data on ARN cases across Japan to improve understanding of this condition and optimize patient care. We have designed a national registry that collects data of patient characteristics, diagnosis, treatment, and visual outcome to generate evidence for the management of ARN. Methods and design This research is a combined retrospective and prospective, multicenter cohort study of ARN in Japan from 1 April 2014–31 March 2029 (UMIN000056246). The registry has received Japan-wide approval from a national human research ethics committee. The following data will be collected: patient demographics, visual function at the initial visit and 6, 12, 24, and 36 months later, image data, diagnostic methods, virus analysis, indications and timing of vitrectomy, and complications. Customized software and platforms have been designed to permit data collection for a single baseline and multiple follow-up forms. Discussion By analyzing the accumulated patient information, the results of this study will generate real-world evidence that will contribute to solve various important clinical issues in ARN. The results will be presented after data collection and analysis are completed.

DOI： 10.1371/journal.pone.0323822

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記述言語：英語   出版者・発行元：Clinical Ophthalmology  

Purpose: This study aimed to evaluate the outcomes of aflibercept treatment using a treat-and-extend (TAE) regimen over up to 5 years in Japanese patients with neovascular age-related macular degeneration (nAMD). Patients and Methods: This retrospective study included 126 consecutive treatment-naïve nAMD patients (126 eyes) who received at least three monthly intravitreal aflibercept (IVA) injections as a loading phase, followed by a treat-and-extend (TAE) regimen with follow-up for 5 years. Injection intervals were adjusted every 2 weeks and could be extended up to 16 weeks based on macular condition. Treatment was suspended if patients received 3 injections at 16-week intervals and the macula remained dry (defined as “monitoring”). Ophthalmic exams were conducted at each visit to assess disease activity. Results: The mean logarithm of the minimum angle of resolution (logMAR) best corrected visual acuity (BCVA) at baseline was 0.42 ± 0.036. Following loading injections, the mean BCVA exhibited a significant improvement. Although it subsequently declined, it sustained the initial visual acuity. The average macular thickness (CMT) was significantly reduced and maintained throughout the follow-up period. The number of aflibercept injections decreased significantly from the second year and gradually decreased during the follow-up period. Intravitreal aflibercept (IVA) treatment could be discontinued in 36 (44%) cases during the follow-up period. However, 12 of these eyes (33%) experienced recurrence. Notably, significant recurrence was observed in patients who received a higher total number of aflibercept injections. Macular atrophy was significantly more likely to occur in cases with occult macular neovascularization (MNV) with subretinal hemorrhage than in cases with other forms of nAMD. Conclusion: The long-term outcomes of IVA treatment utilizing TAE regimens for nAMD in real-world practice have demonstrated favorable results, including the maintenance of visual acuity and improvement in CMT over a 5-year period.

DOI： 10.2147/OPTH.S501953

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PubMed

出版者・発行元：Scientific Reports  

We investigated the impact of drainage retinotomy on the outcome of pars plana vitrectomy for repair of rhegmatogenous retinal detachment (RRD). This study was a retrospective observational multicenter study. All patients were registered with the Japan-Retinal Detachment Registry. We analyzed 1887 eyes with RRD that had undergone vitrectomy and were observed for 6 months between February 2016 and March 2017. We compared the baseline characteristics and postoperative outcomes between eyes with and without drainage retinectomy. We then performed propensity score matching using preoperative findings as covariates to adjust for relevant confounders. Of 3446 eyes, 1887 met the inclusion criteria. Among them, 559 eyes underwent vitrectomy with drainage retinotomy, and 1328 eyes underwent vitrectomy without drainage retinotomy. After propensity score matching, each group comprised 544 eyes. There was no significant difference between the two groups in BCVA at 6 months after vitrectomy (0.181 vs. 0.166, P = 0.23), the primary anatomical success rate (6.3% vs. 4.4%, P = 0.22), or the rate of secondary surgery for ERM within 6 months (1.5% vs. 1.3%, P = 1.0). Drainage retinectomy does not increase the risk of decreased postoperative BCVA, surgical failure, or secondary surgery for ERM within six months outcomes.

DOI： 10.1038/s41598-024-58453-5

Scopus

記述言語：英語   出版者・発行元：Ophthalmology Science  

Purpose: To compare the usefulness of microperimetry and static automated perimetry in patients with retinitis pigmentosa (RP), using macular anatomical metrics as a reference. Design: Prospective observational study. Participants: Forty-eight eyes of 48 patients with RP in Kyushu University Hospital who underwent microperimetry-3 (MP-3) and Humphrey Field Analyzer (HFA) 10-2 testing ≥3 times during ≥2 years were included. Methods: Macular anatomy (ellipsoid zone [EZ] length) was assessed by OCT, and macular function was assessed by MP-3 (mean retinal sensitivity at radii 2°, 4°, and 8°) and HFA10-2 program (mean retinal sensitivity at radii 2°, 4°, and 8°). Correlations between functional and anatomical parameters were analyzed cross sectionally at baseline and longitudinally by comparing the rate of progression. Main Outcome Measures: Correlation coefficients between anatomical and functional metrics. Results: The mean age at baseline was 50.1 ± 12.3 years, and the mean follow-up period was 2.8 ± 0.7 years. At baseline, EZ length was significantly correlated with MP-3 mean retinal sensitivity at radii 2°, 4°, and 8° (Spearman's ρ = 0.65, 0.84, 0.89; all P < 0.005) and HFA10-2 mean retinal sensitivity at radii 2°, 4°, and 8° (Spearman's ρ = 0.61, 0.73, 0.78; all P < 0.005). Longitudinal analysis showed that the slope of EZ length (−88.92 μm/year) was significantly correlated with the slope of MP-3 retinal sensitivity at 8° radius (−0.62 decibels [dB]/year; Spearman's ρ = 0.31, P=0.03) and the slope of HFA retinal sensitivity at 8° radius (−0.60 dB/year; Spearman's ρ = 0.43, P < 0.005). Conclusions: Both MP-3 and HFA values were cross sectionally well-correlated with EZ length in patients with patients; however, these associations became weaker in the longitudinal analysis. This highlights the need for researchers to explore additional or more sensitive parameters to better monitor RP progression. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

DOI： 10.1016/j.xops.2024.100582

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記述言語：英語   出版者・発行元：Biochemistry and Biophysics Reports  

Lysosome-associated membrane protein-2 (LAMP2) deficiency causes the human Danon disease and represents a lysosomal dysfunction because of its pivotal role in regulating autophagy and lysosome biogenesis. LAMP2-deficient mice exhibit a spectrum of phenotypes, including cardioskeletal myopathy, mental retardation, and retinopathy, similar to those observed in patients with Danon disease. Its pathology is thought to involve altered energy metabolism and lipid dysregulation; however, the lipidomic profiles of LAMP2-deficient animals have not been investigated. In this study, we investigated lipid alterations in LAMP2 KO mice tissues, including those of the liver, plasma, and retina, using liquid chromatography-mass spectrometry. Our results revealed significantly increased free fatty acid (FFA) levels and decreased in triglyceride (TG) levels in LAMP2 KO liver tissues at three and six months. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species significantly decreased in LAMP2 KO mice livers at six months. Similarly, plasma TG and PC/PE levels decreased in LAMP2 KO mice. In contrast, plasma FFA levels were significantly lower in LAMP2 KO mice. Retina FFA levels were elevated in LAMP2 KO mice, accompanied by a partial decrease in PC/PE at six months. In summary, FFA levels increased in several tissues but not in the LAMP2 KO mice plasma, suggesting the potential consumption of FFA as an energy source in the peripheral tissues. The depletion of TG and PC/PE accelerated with age, suggesting an underlying age-dependent energy crisis condition. Our findings underscore the dysregulated distribution of fatty acids in LAMP2-deficient animals and provide new mechanistic insights into the pathology of Danon disease.

DOI： 10.1016/j.bbrep.2024.101822

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出版者・発行元：金原出版  

DOI： 10.18888/ga.0000003939

CiNii Research

記述言語：英語   出版者・発行元：Graefe S Archive for Clinical and Experimental Ophthalmology  

Purpose: To investigate the relationships between macular complications and causative genes frequently found in Japanese patients with retinitis pigmentosa (RP). Methods: In the retrospective and observational study, we analyzed the data of 75 patients with RP (EYS-RP: 42 patients; USH2A-RP: 19 patients; RHO-RP: 14 patients) who were followed-up at Kyushu University Hospital and whose causative genes had been identified. Macular complications including epiretinal membrane (ERM), macular edema (ME), and macular hole (MH) were evaluated using optical coherence tomography and fundus photography. Main outcome was the proportion of macular complications. Results: The proportion of ERM was 35.7% in the EYS group, 10.5% in the USH2A group and 14.3% in the RHO group. The proportion of ME was 7.1% in the EYS group, 5.3% in the USH2A group and 14.3% in the RHO group, and that of MH was 2.4% in the EYS group, 5.3% in the USH2A group and 0% in the RHO group. In the EYS group, the proportion of ERM was relatively higher (p = 0.06), and the presence of EYS was significantly associated with a higher age- and sex-adjusted OR for ERM (OR = 5.67, 95% CI = 1.59–25.20). There was no significant difference in the proportion of MH or ME among causative genes. Conclusions: EYS causative gene may be associated with higher rate of ERM complication in RP.

DOI： 10.1007/s00417-024-06534-6

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記述言語：英語   出版者・発行元：Ophthalmology  

Purpose: To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals. Design: Cross-sectional analysis. Participants: Genetic risk scores (GRSs) were constructed based on a genome-wide association study (GWAS) of POAG in Japanese people. A total of 3625 Japanese individuals, including 1191 patients and 2434 controls (Japanese Tohoku), were used for the model selection. We also evaluated the discriminative accuracy of constructed GRSs in a dataset comprising 1034 patients and 1147 controls (the Japan Glaucoma Society Omics Group [JGS-OG] and the Genomic Research Committee of the Japanese Ophthalmological Society [GRC-JOS]) and 1900 participants from a population-based study (Hisayama Study). Methods: We evaluated 2 types of GRSs: polygenic risk scores using the pruning and thresholding procedure and a GRS using variants associated with POAG in the GWAS of the International Glaucoma Genetics Consortium (IGGC). We selected the model with the highest areas under the receiver operating characteristic curve (AUC). In the population-based study, we evaluated the correlations between GRS and ocular measurements. Main Outcome Measure: Proportion of patients with POAG after stratification according to the GRS. Results: We found that a GRS using 98 variants, which showed genome-wide significance in the IGGC, showed the best discriminative accuracy (AUC, 0.65). In the Japanese Tohoku, the proportion of patients with POAG in the top 10% individuals was significantly higher than that in the lowest 10% (odds ratio [OR], 6.15; 95% confidence interval [CI], 4.35–8.71). In the JGS-OG and GRC-JOS, we confirmed similar impact of POAG GRS (AUC, 0.64; OR [top vs. bottom decile], 5.81; 95% CI, 3.79–9.01). In the population-based study, POAG prevalence was significantly higher in the top 20% individuals of the GRS compared with the bottom 20% (9.2% vs. 5.0%). However, the discriminative accuracy was low (AUC, 0.56). The POAG GRS was correlated positively with intraocular pressure (r = 0.08: P = 4.0 × 10^–4) and vertical cup-to-disc ratio (r = 0.11; P = 4.0 × 10^–6). Conclusions: The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

DOI： 10.1016/j.ophtha.2024.05.026

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出版者・発行元：株式会社医学書院  

DOI： 10.11477/mf.1410215296

CiNii Research

記述言語：英語   出版者・発行元：Eye Basingstoke  

Background/Objective: Acute retinal necrosis (ARN) is a vision-threatening disease caused by herpesvirus infection. This study aimed to investigate the visual prognostic factors that could be determined at the initial visit. Subjects and Methods: This retrospective study included 34 patients with ARN. Logistic regression analysis was employed to evaluate the associations between poor final visual outcomes and various factors, including poor initial visual acuity, presence of retinal detachment at the initial visit, posterior extension of necrotizing retinitis, and circumferential extension of necrotizing retinitis. Posterior extension was evaluated with three zonings, from the periphery (zone 3), mid-periphery (zone 2), and macula (zone 1). Circumferential extension was evaluated according to the degree of necrotizing retinitis lesions using ultra-wide fundus imaging. Results: The mean logarithm of the minimum angle of resolution was 0.63 ± 0.68 at the initial visit and 0.83 ± 0.65 at 12 months after the initial visit. Seven patients had a retinal detachment. The distribution of posterior extension at the initial visit was 5 in zone 1, 20 in zone 2, and 9 in zone 3. The average of necrotizing retinitis lesion angle was 249 ± 115°. The logistic regression analysis revealed that participants with wide angles of necrotizing retinitis were associated with final poor vision, with an odds ratio of 1.28 per 30° increase (95%CI: 1.00–1.65, p = 0.03). Conclusions: Assessment of the widespread circumferential extension of white necrotizing retinal lesions at the initial visit is a crucial risk factor for the visual prognosis in ARN.

DOI： 10.1038/s41433-024-03207-w

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞目的:小児の涙道閉塞に対して術前に施行した涙道造影CTの検討。対象と方法:2020年4月～2023年2月に九州大学病院で涙道内視鏡下で涙管チューブ挿入術を試みた小児のうち術前にCTを施行した27例(32側)を対象に,解剖学的構造,涙道造影の可否,骨性異常の有無について検討した。結果:平均年齢(±標準偏差)は3.8±2.9歳,男児が14例(51.9%)であった。チューブ挿入術の成功率は93.8%(30/32側)であった。CTより軸位断での患側の鼻涙管の最小内腔径平均は3.0×4.1mm,矢状断での鼻涙管長平均は21.6±3.3mmであった。造影方法は点眼法が19例,注入法が4例であった。患側で造影できたのは点眼法,注入法ともに約50%と同程度だった。涙道閉塞の原因は,先天性鼻涙管閉塞24側(75.0%),後天性4側(12.5%),骨性異常3側(9.4%),鼻性1側(3.1%)であった。結論:CTは術前に鼻性や骨性異常などの解剖学的情報を得られる有用な評価方法であるが,被曝のリスクを考慮し,個々の症例で慎重に必要性を検討する必要がある。

記述言語：英語   出版者・発行元：Graefe S Archive for Clinical and Experimental Ophthalmology  

Purpose: This study aimed to evaluate the factors associated with retinal pigment epithelium (RPE) tear development in the early phase after anti-vascular endothelial growth factor (VEGF) drug initiation in eyes with neovascular age-related macular degeneration (nAMD) and retinal pigment epithelial detachment (PED). Methods: Treatment-naive eyes with nAMD and PED for which anti-VEGF drug injections had been initiated and followed up for at least 3 months after the 1st anti-VEGF drug injection, were retrospectively investigated. Baseline characteristics of the PEDs, including type, height, and area, were evaluated using fundus photographs, fluorescein angiography, and optical coherence tomography images. The association between patient age, sex, medical history, PED characteristics, and the development of RPE tears within 3 months of starting anti-VEGF therapy was examined. Results: This study included 244 eyes (230 patients; mean age 75.0 years, 159 males and 71 females). RPE tears occurred in 13 eyes (5.3%) within 3 months of the start of anti-VEGF therapy. Multivariate analysis showed an association of the development of RPE tears with PED height (every 100 µm, odds ratio [OR]: 1.50, 95% confidence interval [CI]: 1.07–2.12, p = 0.019), PED area (every 10 mm², OR: 3.02, CI: 1.22–7.46, p = 0.016), and the presence of fibrovascular PED (OR: 59.22, CI: 4.12–850.59, p = 0.002). Eyes with cleft (the hypo-reflective space beneath the fibrovascular PED) were more likely to develop an RPE tear (p = 0.01, χ-square test). Conclusions: Fibrovascular PED, large PED area, high PED height, and the cleft finding are independent risk factors for the development of RPE tears early after the administration of anti-VEGF drugs.

DOI： 10.1007/s00417-024-06503-z

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PubMed

記述言語：英語   出版者・発行元：Diabetologia  

Aims/hypothesis: Diabetic retinopathy is characterised by neuroinflammation that drives neuronal and vascular degenerative pathology, which in many individuals can lead to retinal ischaemia and neovascularisation. Infiltrating macrophages and activated retina-resident microglia have been implicated in the progression of diabetic retinopathy, although the distinct roles of these immune cells remain ill-defined. Our aim was to clarify the distinct roles of macrophages/microglia in the pathogenesis of proliferative ischaemic retinopathies. Methods: Murine oxygen-induced retinopathy is commonly used as a model of ischaemia-induced proliferative diabetic retinopathy (PDR). We evaluated the phenotype macrophages/microglia by immunostaining, quantitative real-time RT-PCR (qRT-PCR), flow cytometry and scRNA-seq analysis. In clinical imaging studies of diabetic retinopathy, we used optical coherence tomography (OCT) and OCT angiography. Results: Immunostaining, qRT-PCR and flow cytometry showed expression levels of M1-like macrophages/microglia markers (CD80, CD68 and nitric oxide synthase 2) and M2-like macrophages/microglia markers (CD206, CD163 and macrophage scavenger receptor 1) were upregulated in areas of retinal ischaemia and around neo-vessels, respectively. scRNA-seq analysis of the ischaemic retina revealed distinct ischaemia-related clusters of macrophages/microglia that express M1 markers as well as C-C chemokine receptor 2. Inhibition of Rho-kinase (ROCK) suppressed CCL2 expression and reduced CCR2-positive M1-like macrophages/microglia in areas of ischaemia. Furthermore, the area of retinal ischaemia was reduced by suppressing blood macrophage infiltration not only by ROCK inhibitor and monocyte chemoattractant protein-1 antibody but also by GdCl<inf>3</inf>. Clinical imaging studies of diabetic retinopathy using OCT indicated potential involvement of macrophages/microglia represented by hyperreflective foci in areas of reduced perfusion. Conclusions/interpretation: These results collectively indicated that heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation in retinal vascular diseases including diabetic retinopathy. This adds important new information that could provide a basis for a more targeted, cell-specific therapeutic approach to prevent progression to sight-threatening PDR. Graphical Abstract: (Figure presented.).

DOI： 10.1007/s00125-024-06215-3

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PubMed

記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP). Study design: Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial. Methods: Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated. Results: Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group. Conclusion: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.

DOI： 10.1007/s10384-024-01100-3

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記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: Extracellular Adenosine triphosphate (ATP) released by dying cells may cause a secondary cell death in neighboring cells in retinal degeneration. We investigated intraocular ATP kinetics to gain mechanical insights into the pathology in rhegmatogenous retinal detachment (RRD). Study design: Retrospective clinical study. Methods: Vitreous or subretinal fluids (SRF) were obtained from patients with RRD (n=75), macular hole (MH; n=20), and epiretinal membrane (ERM; n=35) during vitrectomy. ATP levels in those samples were measured by luciferase assay. Results: Mean ATP levels in the vitreous from RRD patients were significantly higher compared to those from MH and ERM patients (2.3 and 0.3 nM, respectively. P<0.01). Mean ATP levels in the SRF from RRD (11.7 nM) were higher than those in the vitreous from RRD (P<0.01). Mean ATP levels in the vitreous with short durations (1–8 days) of RRD were higher compared to those with long durations (>8 days) (3.2 and 1.4 nM, respectively. P<0.05). Similarly, ATP in SRF with short durations were higher than those with long durations (23.8 and 3.6 nM, respectively. P<0.05). Furthermore, the concentrations of ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1), a major ATP degradative enzyme, in the vitreous from RRD were higher than those from MH/ERM (1.2 and 0.2 ng/ml, respectively. P<0.01). ENTPD1 expression was localized in the cytoplasm of CD11b-positive infiltrating cells in the vitreous and retinal cells. Conclusion: ATP increased in the vitreous and SRF in RRD and decreased over time with an upregulation of ENTPD1. The kinetics indicate the pathological mechanism of the excessive extracellular ATP after RRD.

DOI： 10.1007/s10384-024-01087-x

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記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: To evaluate the clinical features and prognosis of conjunctival melanoma in Japanese patients. Study design: Retrospective observational case series. Methods: Twenty patients (8 men and 12 women) diagnosed with conjunctival melanoma at a singlehospital between 2003 and 2017 were analyzed. Data on clinical presentation, sex, age, the affected eye, tumor location, tumor origin, tumor stage according to the American Joint Committee on Cancer staging system (eighth edition), treatment, outcomes, local recurrence, metastasis, and survival were extracted from the patients’ medical records and reviewed. Results: The mean age at diagnosis was 64.2 ± 14.8 years. Tumor locations at the first examination included the bulbar conjunctiva (n = 19), plica (n = 13), and fornix (n = 12). The tumor stage was T1 in 5 cases (25%), T2 in 12 cases (60%), T3 in 3 cases (15%), and T4 in none. The mean follow-up duration was 91.7 ± 46.0 months. The local recurrence rates at 1, 5, and 10 years were 5.0%, 18.8%, and 31.5%, respectively, whilst the metastasis rates were 5.0%, 25.6%, and 32.4%, respectively. Four of the 6 patients who experienced metastasis died; duration from metastasis to death was 17.5 months (range, 7–25). The 5-year survival rate for conjunctival melanoma was 78.8%. Tumor thickness was significantly associated with survival duration on univariate Cox regression analyses. Conclusion: The mortality rate for conjunctival melanoma in the Japanese population was lower and higher than that reported in the Chinese and United States populations, respectively. Tumor thickness was a prognostic factor for survival in patients with conjunctival melanoma.

DOI： 10.1007/s10384-024-01085-z

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記述言語：英語   出版者・発行元：British Journal of Ophthalmology  

Aims To investigate the association between corneal hysteresis and the presence of glaucoma and its subtypes in a general Japanese population. Methods We analysed the data of 2338 Japanese community-dwellers aged ≥40 years (1059 men, 1279 women) who underwent an eye examination in 2018 as part of the population-based, cross-sectional Hisayama Study. Participants were divided into quartile levels of corneal hysteresis, which had been measured with an ocular response analyzer. Glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. We conducted a logistic regression analysis to determine the ORs and their 95% CIs for the presence of outcomes according to the corneal hysteresis quartiles. Results Glaucoma was diagnosed in 154 participants: primary open-angle glaucoma (POAG), n=115; primary angle-closure glaucoma, n=17; exfoliation glaucoma, n=21 and secondary glaucoma without exfoliation glaucoma, n=1. After adjustment for confounders, the OR for prevalent glaucoma was significantly increased in the participants in the first corneal-hysteresis quartile compared with those in the fourth quartile (OR: 1.80; 95% CI: 1.03 to 3.17). Regarding glaucoma subtypes, the first-quartile participants had significantly greater likelihoods of the presence of POAG (OR: 1.63; 95% CI: 1.02 to 2.61) and exfoliation glaucoma (OR: 6.49; 95% CI: 1.44 to 29.30) compared with those in the third and fourth quartiles after adjustment for potential confounders. Conclusions These results demonstrated a significant inverse association between corneal hysteresis and the likelihood of glaucoma, suggesting that the measurement of corneal hysteresis would provide useful information for elucidating the aetiology of glaucoma.

DOI： 10.1136/bjo-2023-323987

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出版者・発行元：金原出版  

DOI： 10.18888/ga.0000003730

CiNii Research

記述言語：英語   出版者・発行元：Translational Vision Science and Technology  

Purpose: Proliferative retinal changes may occur postsurgery for rhegmatogenous retinal detachment (RRD), possibly preceding recurrent detachment. This study aims to establish the groundwork for an imaging system capable of discerning changes in retinal vessel tortuosity after RRD repair, analyzing widefield optical coherence tomog-raphy angiography (WF-OCTA) images. Methods: Eighty-eight eyes of 86 patients with RRD who underwent surgical proce-dures and had repeated imaging with clear widefield optical coherence tomography (WF-OCT) and WF-OCTA on different postoperative days were enrolled in this retrospec-tive study. We compared WF-OCTA images over time to identify alterations in retinal vessel tortuosity and observed regional changes in retinal morphology. Results: After image processing, changes in retinal vessel tortuosity were detected in 66 quadrants. These changes, attributed to retinal traction from proliferative membranes, were observed in 56 quadrants, among which retinal thickness remained unchanged in seven sectors (12.5%) according to the WF-OCT map. In nine quadrants, changes in retinal vessel tortuosity were attributed to changes in subretinal fluid, aligning with observable variations in retinal thickness. Conclusions: Observation of vessel tortuosity changes using WF-OCTA can help detect early postoperative proliferative changes in eyes with RRD. Translational Relevance: Because WF-OCTA can detect minute vessel tortuosity changes, it can offer a noninvasive alternative for the detection of early postoperative proliferative changes.

DOI： 10.1167/tvst.13.8.13

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記述言語：英語   出版者・発行元：Translational Vision Science and Technology  

Purpose: To investigate the profiles and correlations between local and systemic inflammatory molecules in patients with retinitis pigmentosa (RP). Methods: The paired samples of aqueous humor and serum were collected from 36 eyes of 36 typical patients with RP and 25 eyes of age-matched patients with cataracts. The concentration of cytokines/chemokines was evaluated by a multiplexed immunoarray (Q-Plex). The correlations between ocular and serum inflammatory molecules and their association with visual function were analyzed. Results: The aqueous levels of IL-6, Eotaxin, GROα, I-309, IL-8, IP-10, MCP-1, MCP-2, RANTES, and TARC were significantly elevated in patients with RP compared to controls (all P < 0.05). The detection rate of aqueous IL-23 was higher in patients with RP (27.8%) compared with controls (0%). In patients with RP, Spearman correlation test demon-strated positive correlations for IL-23, I-309, IL-8, and RANTES between aqueous and serum expression levels (IL-23: ρ = 0.8604, P < 0.0001; I-309: ρ = 0.4172, P = 0.0113; IL-8: ρ = 0.3325, P = 0.0476; RANTES: ρ = 0.6685, P < 0.0001). In addition, higher aqueous IL-23 was associated with faster visual acuity loss in 10 patients with RP with detected aqueous IL-23 (ρ = 0.4119 and P = 0.0264). Multiple factor analysis confirmed that aqueous and serum IL-23 were associated with visual acuity loss in patients with RP. Conclusions: These findings suggest that ocular and systemic inflammatory responses have a close interaction in patients with RP. Further longitudinal studies with larger cohorts are needed to explore the correlation between specific inflammatory pathways and the progression of RP. Translational Relevance: This study demonstrates the local–systemic interaction of immune responses in patients with RP.

DOI： 10.1167/tvst.13.8.18

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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＞目的 甲状腺眼症のステロイド治療および放射線治療後の斜視残存の関連因子について検討する。対象および方法 2014年5月から2019年4月に九州大学病院眼科を受診し甲状腺眼症と診断され,ステロイド全身投与および放射線治療の前後で眼位,眼球運動,両眼単一視が評価可能であった24例を対象とした。消炎治療後複視が軽快したものを経過良好群(9例),複視が残存し斜視手術やA型ボツリヌス毒素療法,プリズム眼鏡等の追加治療が必要であったものを経過不良群(15例)とし,甲状腺疾患の罹患期間,複視出現から治療開始までの期間,甲状腺自己抗体値,初診時臨床活動スコア,罹患筋内訳,年齢,性別,基礎疾患,喫煙の有無を背景因子として抽出した。さらに治療前後のfunctional scoring method(FSM)を用いた両眼単一視,percentage of Hess area ratio(HAR%)の評価を行い両群間で比較した。結果 経過不良群においてFSMスコアが初診時から有意に低値であり,治療後も改善はみられなかった。また経過不良群では経過良好群と比較し初診時の垂直斜視角が有意に大きく,初診時の垂直斜視角が増加するほどFSMスコアが低値になる負の相関を認めた。結論 甲状腺眼症において初診時に垂直斜視角が大きく,FSMスコアが低値であると消炎治療後に複視残存のリスクがあると考えられた。

出版者・発行元：金原出版  

DOI： 10.18888/ga.0000003699

CiNii Research

記述言語：日本語   出版者・発行元：金原出版(株)  

＜文献概要＞結膜粘液腫は間葉由来のまれな良性腫瘍である。今回われわれは,結膜粘液腫の2例を経験したため報告する。症例1は48歳男性。左眼の結膜充血を主訴に近医を受診し,左眼の耳側結膜下に隆起性の病変を指摘された。炎症性疾患と考えられ,ステロイド点眼治療が行われるも改善がなく,精査のため九州大学眼科に紹介となった。切除生検を行ったところ,腫瘍は結膜や強膜との癒着はなく摘出は容易であった。病理所見では線維組織を伴う紡錘形の腫瘍細胞を認めた。免疫染色でCD34陽性,α-SMA,デスミン,S-100蛋白は陰性であり,粘液腫と診断した。切除後,20ヵ月間再発はなかった。症例2は49歳男性。右眼の結膜充血と腫瘍を主訴に近医を受診し,右眼の耳側結膜下に隆起性の病変を指摘され,嚢胞を疑われ穿刺を施行されるも内容物の排出はなく,精査のため九州大学眼科に紹介となった。切除生検を行ったところ,腫瘍は結膜や強膜との癒着はなく摘出は容易であった。病理所見では間質を伴う紡錘形の腫瘍細胞と星細胞を認めた。アルシアンブルー染色で陽性であり,免疫染色でCD34陽性,α-SMA,デスミン,S-100蛋白は陰性であり,粘液腫と診断した。切除後,21ヵ月経過した現在,再発なく経過している。結膜腫瘍では結膜粘液腫の可能性も念頭に置き診断と治療を進める必要がある。

記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

目的:フィラデルフィア染色体陽性急性リンパ性白血病(Ph+ALL)の眼内浸潤に対してメトトレキサート(MTX)の硝子体内投与が有効であった1例を経験したので報告する.症例:76歳,男性.20XX年1月に前医血液腫瘍内科でPh+ALLと診断され,分子標的薬を含めた全身化学療法が行われるも中枢神経浸潤を認めていた.同年8月に両眼の霧視を主訴に当科を紹介受診したところ,左眼の前房蓄膿と両眼の硝子体混濁を認めた.前房水の細胞診でリンパ球性の白血病細胞を認め,Ph+ALLの眼内浸潤と診断した.全身化学療法を継続したが,両眼の硝子体混濁が増悪し,視力低下を来したため,20XX+1年7月に眼底透見の改善を目的に両眼の硝子体手術を施行したところ,視神経と網膜血管に沿って白色の浸潤病変を認めた.計10回のMTX硝子体内投与を施行したところ,眼内の浸潤性病変の萎縮瘢痕化が得られた.結論:眼内に浸潤を来したPh+ALLに対してMTXの硝子体内投与が有効であった症例を経験した.Ph+ALLに対しては全身化学療法や硝子体手術を含めた集学的治療が必要であるが,MTX硝子体内投与は眼局所での腫瘍細胞抑制効果が期待でき,治療の選択肢となり得ることが示唆された.(著者抄録)

記述言語：英語   出版者・発行元：Journal of Medical Genetics  

Background As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP-allied diseases. Methods We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines. Results A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with EYS accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases. Conclusion A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.

DOI： 10.1136/jmg-2023-109750

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記述言語：英語   出版者・発行元：Journal of the Neurological Sciences  

Background: Recent developments in the retinal hyperspectral imaging method have indicated its potential in addressing challenges posed by neurodegenerative disorders, such as Alzheimer's disease. This human clinical study is the first to assess reflectance spectra obtained from this imaging as a tool for diagnosing patients with Parkinson's disease (PD). Methods: Retinal hyperspectral imaging was conducted on a total of 40 participants, including 20 patients with PD and 20 controls. Following preprocessing, retinal reflectance spectra were computed for the macular retina defined by four rectangular regions. Linear discriminant analysis classifiers underwent training to discern patients with PD from control participants. To assess the performance of the selected features, nested leave-one-out cross-validation was employed using machine learning. The indicated values include the area under the curve (AUC) and the corresponding 95% confidence interval (CI). Results: Retinal reflectance spectra of PD patients exhibited variations in the spectral regions, particularly at shorter wavelengths (superonasal retina, wavelength < 490 nm; inferonasal retina, wavelength < 510 nm) when compared to those of controls. Retinal reflectance spectra yielded an AUC of 0.60 (95% CI: 0.43–0.78) and 0.60 (95% CI: 0.43–0.78) for the superonasal and inferonasal retina, respectively, distinguishing individuals with and without PD. Conclusion: Reflectance spectra obtained from retinal hyperspectral imaging tended to decrease at shorter wavelengths across a broad spectral range in PD patients. Further investigations building upon these preliminary findings are imperative to focus on the retinal spectral signatures associated with PD pathological hallmarks, including α-synuclein.

DOI： 10.1016/j.jns.2024.123061

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記述言語：英語   出版者・発行元：Scientific Reports  

We investigated the association of retinopathy with the risk of dementia in a general older Japanese population. A total of 1709 population-based residents aged 60 years or older without dementia were followed prospectively for 10 years (2007–2017). They underwent color fundus photography in 2007. Retinopathy was graded according to the Modified Airlie House Classification. Main outcome was the Incidence of dementia. A Cox proportional hazards model was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for the risk of dementia by the presence of retinopathy. During the follow-up period, 374 participants developed all-cause dementia. The cumulative incidence of dementia was significantly higher in those with retinopathy than those without (p < 0.05). Individuals with retinopathy had significantly higher risk of developing dementia than those without after adjustment for potential confounding factors (HR 1.64, 95% CI 1.19–2.25). Regarding the components of retinopathy, the presence of microaneurysms was significantly associated with a higher multivariable-adjusted HR for incident dementia (HR 1.94, 95% CI 1.37–2.74). Our findings suggest that, in addition to systemic risk factors, retinal microvascular signs from fundus photography provide valuable information for estimating the risk of developing dementia.

DOI： 10.1038/s41598-024-62688-7

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記述言語：英語   出版者・発行元：Retinal Cases and Brief Reports  

Purpose:The aim of this study was to demonstrate the spatial pattern of retinal pigment epithelium (RPE) tear development and progression after antivascular endothelial growth factor therapy for neovascular age-related macular degeneration.Methods:We retrospectively reviewed six eyes with neovascular age-related macular degeneration that showed RPE tears after administration of intravitreal antivascular endothelial growth factor agents and were followed up for 12 months. The patterns of RPE tear development and progression were evaluated by analyzing positional relationships among the locations of the choroidal neovascularization membrane and pigment epithelial detachment (PED) area at baseline and the tear area using spectral-domain optical coherence tomography, color photography, fluorescein angiography, and fundus autofluorescence images.Results:Pretear OCT images revealed fibrovascular PED in all eyes, one of which showed complications of hemorrhagic PED after treatment. In five eyes, RPE tears developed at the PED edge located on the opposite side of the choroidal neovascularization membrane. In the eye showing hemorrhagic PED, the RPE tear developed along the wide area of the PED edge. The torn RPE monolayer contracted toward the side of the choroidal neovascularization membrane in all eyes, and RPE loss involved the fovea in five eyes that showed significantly worse visual acuity (VA) after 12 months in comparison with the baseline value before the tear (logMAR VA; 0.3 vs. 1.29; P < 0.02).Conclusion:The location of choroidal neovascularization membrane in PED determines the spatial pattern of RPE tear development and progression and helps to predict the visual outcome after RPE tears.

DOI： 10.1097/ICB.0000000000001386

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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:甲状腺眼症の上下斜視に対する下直筋後転術の手術成績,および手術時の患者背景について報告する.対象および方法:対象は2016～2022年に,九州大学病院で甲状腺眼症と診断し,下直筋後転術を施行した15例である.手術時のプレドニゾロン(PSL)内服量,磁気共鳴画像冠状断における下直筋断面積,術前後の遠見眼位,正面視での術後複視の有無を後ろ向きに検討した.結果:手術時のPSL内服量は1.67±3.4mg/day,下直筋面積は53.4±20.7mm2,矯正効果は4.8±1.5Δ/mmであった.下直筋面積が大きいほど術前斜視角も有意に大きく(p=0.04),術前斜視角が大きいほど1mmあたりの矯正効果も有意に大きくなった(p=0.02).術後,正面視での複視は全例で消失した.結論:術前の下直筋面積や斜視角が大きい症例では,予測よりも矯正効果が大きくなることが示唆された.(著者抄録)

記述言語：英語   出版者・発行元：Journal of Clinical Medicine  

Background: Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection for PNV using UWF swept-source optical coherence tomography. Methods: Seventeen eyes with PNV that underwent half-fluence PDT with an adjuvant single intravitreal aflibercept injection were analyzed. To compare choroidal thicknesses in the central and peripheral choroids, we set subfields <3, <9, and 9–18 mm from the fovea. The <9 and 9–18 mm subfields were divided into four quadrants. Results: Choroidal thickness in each subfield decreased significantly after half-fluence PDT (p < 0.001); this reduction was more pronounced in the central area. We also investigated the relationship between the dominant side of the deep choroidal veins that harbor choroidal vein efflux from the macula. When choroidal thickness in the supratemporal and infratemporal 9 mm subfields were evaluated, the ratio of choroidal thickness reduction was not significantly different between the dominant and non-dominant sides. The dominant side was not associated with the extent of choroidal thickness reduction in PNV. Conclusions: Half-fluence PDT caused thinning of the entire choroid, especially in the central area, in PNV.

DOI： 10.3390/jcm13061608

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記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: Removing transparent vitreous tissues, such as a residual vitreous cortex (VC) or proliferative membrane, without damaging the retina is often problematic in vitrectomy. We examined the feasibility of an injectable in situ cross-linking hyaluronan hydrogel (XL-HA) for vitrectomy. Study design: Experiments using ex vivo and in vivo animal models. Methods: HA-dibenzocyclooctyne and HA-azidoethylamine solutions were mixed to form XL-HA, which then gradually formed a hydrogel. We tested the function of XL-HA in ex vivo porcine eyes. We then examined the performance of XL-HA in in vivo rabbit models of posterior vitreous detachment, posterior VC removal, and proliferative vitreoretinopathy. Results: The ex vivo study showed that XL-HA rapidly embedded triamcinolone acetonide, mimicking VC attached to the retina, and became hard enough to be pinched with tweezers within 3 minutes, allowing us to remove only the triamcinolone acetonide without impairing the internal limiting membrane. In the in vivo rabbit models, XL-HA injection improved posterior vitreous detachment, and the thin and fragile posterior VC or fibrous proliferative membrane was readily peeled off without any damage to the underlying retina as compared with untreated controls. A short-term intraocular biocompatibility test demonstrated that the intraocular pressure remained normal with XL-HA injected into the eye. In addition, transmission electron microscopy showed no obvious abnormalities in the cornea or in the inner and outer retina. Conclusion: The results indicate that XL-HA is a potential adjunctive device to help make vitrectomy safe, effective, and successful.

DOI： 10.1007/s10384-023-01039-x

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記述言語：英語   出版者・発行元：American Journal of Ophthalmology Case Reports  

Purpose: Primary orbital liposarcomas are rare. To the best of our knowledge, only four cases of primary dedifferentiated liposarcomas of the orbit have been reported. Furthermore, there have been no reports of primary orbital liposarcomas transitioning from a highly differentiated to a dedifferentiated form. Here, we report a case of primary orbital liposarcoma that was well-differentiated at the time of initial resection at our hospital but had dedifferentiated on recurrence 10 years after the initial resection. Observations: The patient was diagnosed with an inflammatory mass after an initial tumor resection by a previous physician at age 52. Thereafter, there were four recurrences (first to fourth recurrences), and the patient underwent five surgeries and radiotherapy. For the fifth recurrence, he first visited our hospital at age 64 and was diagnosed with a well-differentiated liposarcoma after undergoing tumor resection. When the tumor recurred 9 years later (the sixth recurrence), it was well-differentiated. When the tumor recurred (the seventh recurrence) six months after surgery at the age of 73 years, the patient underwent orbital exenteration because of rapid tumor growth, and pathological examination showed that the tissue had changed to a dedifferentiated liposarcoma. Conclusions and Importance: Primary well-differentiated orbital liposarcoma may transform to a dedifferentiated form over time. The risk of dedifferentiation at recurrence should be considered in developing a treatment plan, even if the initial pathology is a well-differentiated liposarcoma.

DOI： 10.1016/j.ajoc.2023.101983

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記述言語：英語   出版者・発行元：Frontiers in Immunology  

Mucosal-associated invariant T (MAIT) cells are a unique subset of T cells that recognizes metabolites derived from the vitamin B2 biosynthetic pathway. Since the identification of cognate antigens for MAIT cells, knowledge of the functions of MAIT cells in cancer, autoimmunity, and infectious diseases has been rapidly expanding. Recently, MAIT cells have been found to contribute to visual protection against autoimmunity in the eye. The protective functions of MAIT cells are induced by T-cell receptor (TCR)-mediated activation. However, the underlying mechanisms remain unclear. Thus, this mini-review aims to discuss our findings and the complexity of MAIT cell-mediated immune regulation in the eye.

DOI： 10.3389/fimmu.2024.1341180

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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】片眼の視力低下を初発自覚症状として慢性骨髄性白血病の診断に至った症例を報告する。【症例】20歳女性。全身既往歴なし。2021年X月、突然の右眼視力低下を主訴に当院救急科を受診し、同日、精査目的に当科紹介受診した。初診時、視力は右眼(0.1)、左眼(1.5)。右眼に内境界膜下出血、左眼にRoth斑を認めた。当院内科に即日入院し、全身精査で慢性骨髄性白血病と診断された。【結論】慢性骨髄性白血病は自覚症状に乏しく、眼症状のみを初発症状に診断されることは稀である。全身既往歴がなくとも、Roth斑を含む網膜出血を認めた場合は、鑑別として白血病を考慮し、早急に全身精査を行う必要がある。(著者抄録)

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】外斜視を伴うdouble elevator palsyに対しKnapp法および水平筋前後転術を施行した症例を報告する。【症例】19歳女性。左眼瞼下垂の手術目的で当科受診。初診眼位は30Δ外斜視、50Δ左下斜視で左眼上転障害と左眼瞼下垂がみられた。左Knapp法と右内直筋前転、右外直筋後転術を施行し、4ヵ月後左眼下直筋後転術、上眼瞼挙筋短縮術を施行。術後眼位は、10Δ左下斜視で、術後7年の眼位は4Δ内斜視、14Δ左上斜視と上下逆転がみられた。【結論】Knapp法による矯正効果は経過とともに増強し、上下偏位の逆転が生じる可能性があるため、治療効果判定に長期経過観察を要する。(著者抄録)

記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: To report the genotypes and clinical features of RHO-associated retinitis pigmentosa (RHO-RP) in the Kyushu region of Japan. Study Design: Retrospective, single-center study. Methods: Sixteen RP patients with pathogenic RHO variants seen at Kyushu University Hospital were investigated. Clinical data including age, best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (logMAR) units, visual field, fundus photography, and optical coherence tomography were retrospectively obtained. Visual outcomes were compared between classical and sector phenotypes and among genetic variants. Results: The mean age at the first visit was 54.0 ± 15.7 years, with a mean follow-up of 7.6 ± 4.0 years. Fourteen patients (87.5%) showed the classical RP phenotype, of whom four were associated with p.[Pro23Leu] and two had p.[Pro347Leu] variants. In addition, two patients with the sector phenotype harbored p.[Ala164Val] variants. Among the classical RHO-RP patients, the mean BCVA decreased from 0.60 to 1.08 logMAR over the follow-up period (7.4 ± 4.1 years) whereas BCVA was preserved at 0.04 logMAR in sector RHO-RP patients (9.0 ± 3.0 years). Genotype-to-phenotype analysis demonstrated that p.[Pro347Leu] was associated with severe vision loss at an earlier age. Macular complications such as epiretinal membrane and cystoid macular edema were observed in 5 classical RHO-RP patients. Conclusion: p.[Pro23Leu], but not p.[Pro23His], was a frequent variant causing RHO-RP in the Kyushu region of Japan. As reported in previous studies, patients with the p.[Pro347Leu] variant showed a more severe phenotype, and variants causing sector RHO-RP were associated with a good prognosis.

DOI： 10.1007/s10384-023-01036-0

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記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: To explore the clinical features of COVID-19-associated conjunctivitis with the objective of preventing the spread of infection. Study design: Retrospective cohort study. Methods: From March 2020 to March 2021, we retrospectively reviewed 26 (9.8%) consecutive COVID-19 patients with conjunctivitis among 282 COVID-19 cases admitted to our hospital. Clinical symptoms, onset date of conjunctivitis, time to patient recovery, and eye drop intervention were investigated. In addition, risk factors for developing conjunctivitis were statistically examined among 206 inpatients available for within 5 days of the onset. A multivariate analysis of conjunctivitis risk factors was performed. Results: Among the 282 COVID-19 patients, 4 (1.4%) had conjunctival hyperemia as the primary symptom. The median time of onset was 4 days after the COVID-19 onset. Hyperemia was observed in all cases, but other ocular symptoms were rare. The median duration of hyperemia was 3 days. A multiple logistic regression analysis revealed that a young age (p=0.005) and current smoking habit (p=0.027) were independent risk factors for conjunctivitis after COVID-19. Conclusions: COVID-19-associated conjunctivitis is rare in the elderly and strongly associated with a history of smoking. It often occurs in the early stages of infection, and while hyperemia is recognized as a clinical symptom, other ocular symptoms are rare or non-existent. Many cases recover within a short time.

DOI： 10.1007/s10384-023-01033-3

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記述言語：英語   出版者・発行元：Gastroenterology Report  

DOI： 10.1093/gastro/goad071

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記述言語：英語   出版者・発行元：Scientific Reports  

Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for diabetic macular edema (DME), but is less effective in some patients. We conducted a prospective study to determine whether laser combination therapy with anti-VEGF was more effective than Ranibizumab monotherapy in anti-VEGF-resistant DME patients. There was no significant difference in the improvement of the best-corrected visual acuity (BCVA) between the laser combination therapy and Ranibizumab monotherapy groups (3.2 letters and -7.5 letters, p = 0.165). BCVA did not significantly change between visits 1 and 7 (the laser combination group, 64.3 letters 70.3 letters, respectively, p = 0.537; the Ranibizumab monotherapy group, 72.3 letters and 64.8 letters, respectively, p = 0.554), with no significant improvements in central foveal retinal thickness (the laser combination therapy group, 9.3%: the Ranibizumab monotherapy groups, − 7.3%; p = 0.926). There was no significant difference in the number of Ranibizumab intravitreal therapy (IVT) sessions between the groups (laser combination therapy, 5.2; ranibizumab monotherapy, 6.0; p = 0.237). This study did not show that laser combination therapy was significantly more effective for anti-VEGF-resistant DME than anti-VEGF monotherapy alone. Therefore, for anti-VEGF-resistant DME, alternative therapeutic approaches beyond combined laser therapy may be considered.

DOI： 10.1038/s41598-023-48665-6

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記述言語：英語   出版者・発行元：Ophthalmology Science  

Purpose: To examine the association between choroidal thickness and myopic maculopathy in a general Japanese population. Design: Population-based cross-sectional study. Participants: A total of 2841 residents of a Japanese community aged ≥ 40 years, who consented to participate and had available data of choroidal thickness and fundus photographs, were enrolled in this study. Methods: The choroidal thickness was measured by swept-source OCT. Participants were divided into quartiles of choroidal thickness. Myopic maculopathy was defined according to the classification system of the Meta-analysis of Pathologic Myopia Study Group. Main outcome measures were odds ratios (ORs) of choroidal thickness for prevalent myopic maculopathy. The ORs and 95% confidence intervals (CIs) were estimated using a logistic regression model. Main Outcome Measures: Prevalent myopic maculopathy. Results: Eighty-one participants had myopic maculopathy (45 diffuse chorioretinal atrophy, 31 patchy chorioretinal atrophy, and 5 macular atrophy). Individuals in the lowest quartile of choroidal thickness had a significantly greater OR for the presence of myopic maculopathy than those in the highest quartile of choroidal thickness (OR: 4.78 [95% CI: 1.78–16.72]) after adjusting for confounders, including axial length. The sensitivity analysis among the 1176 myopic individuals with axial length of ≥ 24.0 mm also showed that thinner choroidal thickness was significantly associated with prevalent myopic maculopathy. Conclusions: The present study demonstrated the significant inverse association between choroidal thickness and the likelihood of myopic maculopathy, suggesting that the measurement of choroidal thickness in addition to axial length would be useful for assessing the risk of myopic maculopathy and elucidating its pathogenesis. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

DOI： 10.1016/j.xops.2023.100350

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記述言語：英語   出版者・発行元：Ocular Immunology and Inflammation  

Purpose: This study aimed to assess the clinical features of pediatric uveitis at a tertiary referral center in Western Japan. Methods: One hundred forty eyes of 80 patients aged <20 years at the time of uveitis onset, who visited Kyushu University Hospital between January 2010 and December 2019 were included in this study. Clinical records were retrospectively reviewed. Demographics, clinical findings, treatments, and visual prognoses were compared between the disease groups. Results: Of 80 patients, 32 were males and 48 were females. The average age of onset was 12.5 ± 4.8 (0–19) years. Tubulointerstitial nephritis and uveitis (TINU) and juvenile idiopathic arthritis (JIA) were the most frequent causes, accounting for 11.3% and 10% of cases, respectively, followed by sarcoidosis (5%), Behçet’s disease, acute anterior uveitis, Vogt-Koyanagi-Harada disease, and juvenile chronic iridocyclitis (3.8% each). Infectious uveitis accounted for 7.6% of the cases: cytomegalovirus was the most frequent agent. Of these cases, 43.8% were unclassified. Systemic therapies were administered to 87.5% of the patients with JIA, 33.3% of those with TINU, and 28.6% of the other diagnostic groups. In the unclassified group, 80% of the patients were followed up with only topical corticosteroids. LogMAR visual acuity of 0 or less accounted for more than 80% in the final examination. Conclusion: TINU and JIA were the most common causes of pediatric uveitis. Although each required systemic therapy, most unclassified cases of pediatric uveitis were managed by topical corticosteroids alone with good visual prognosis. Accurate diagnosis is important for pediatric uveitis management.

DOI： 10.1080/09273948.2023.2273363

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記述言語：英語   出版者・発行元：Journal of Materials Science Materials in Medicine  

Ophthalmologists have used hyaluronan (HA) products as adjuncts to ocular surgery since the 1970s. However, HA products are not always functional in surgeries of the posterior eye segment due to their lack of biomechanical strength. In this study, we developed an in situ crosslinked HA (XL-HA) and evaluated its potential as an adjunct to vitrectomy surgery in an in vitro model with a triamcinolone acetonide (TA) layer used as a pseudo residual vitreous cortex (RVC). Within a few minutes at concentrations over 0.9%, XL-HA, generated by the click chemistry of HA-dibenzocyclooctyne and HA-azidoethylamine, formed a hydrogel with the appropriate hardness for tweezers peeling. XL-HA (concentration, 0.76–1.73%) without dispersion successfully entered the TA layer and removed more than 45% of the total TA. Dynamic viscoelasticity helps to explain the rheological behavior of hydrogels, and the assessment results for XL-HA indicated that suitable concentrations were between 0.97% and 1.30%. For example, 1.30% XL-HA hydrogel reached sufficient hardness at 3 min for tweezers peeling, and the TA removal ability exceeded 70%. These results demonstrated that XL-HA was a potential adjunct to successful vitrectomy. Graphical Abstract: [Figure not available: see fulltext.]

DOI： 10.1007/s10856-023-06757-9

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出版者・発行元：Retina Today  

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記述言語：英語   出版者・発行元：Redox Biology  

Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer ⁵⁷Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.

DOI： 10.1016/j.redox.2023.102890

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記述言語：英語   出版者・発行元：Graefe S Archive for Clinical and Experimental Ophthalmology  

In the published online version of this article, the title and the text contained mistakes. The authors would like to correct “VEGF therapy” to “anti-VEGF therapy”. The correct title is shown below: Persistence of vascular empty sleeves in choroidal neovascularization after anti-VEGF therapy in both animal models and humans. The correct Purpose is shown below: This study investigated whether the proposed mechanism is involved in CNV during anti-VEGF therapy. The correct Introduction is shown below: In this study, we investigated whether the proposed mechanism of vascular regrowth is involved in CNV during anti-VEGF therapy using a mouse model and long-term clinical observations in optical coherence tomography angiography (OCTA).

DOI： 10.1007/s00417-023-06214-x

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記述言語：英語   出版者・発行元：Journal of Clinical Medicine  

Background: Although anti-vascular endothelial growth factor (anti-VEGF) therapy is the first choice of treatment for eyes with neovascular age-related macular degeneration (AMD), it sometimes results in retinal pigment epithelium (RPE) tears. This study presents the detailed clinical characteristics of RPE tears to help predict their occurrence before anti-VEGF therapy initiation. Methods: This study retrospectively analyzed neovascular age-related macular degeneration (nAMD) patients who visited the Kyushu University Hospital and started anti-VEGF therapy between April 2013 and June 2020. Using medical records, we collected the clinical data of patients with RPE tears, including age, sex, best-corrected visual acuity (BCVA), number of anti-VEGF drug injections and the type and size of pigment epithelial detachment (PED). Results: RPE tears occurred in 16 (1.50%) eyes of 16 patients in all 1068 nAMD eyes of 987 patients. The mean age of these patients with RPE tear was 81.7 ± 8.7 years. Fifteen eyes had typical AMD and one eye had polypoidal choroidal vasculopathy. The mean number of anti-VEGF drug injections before RPE tears was 5.0 ± 5.1. All patients experienced PED before the RPE tear (hemorrhagic, 4 eyes; serous vascular, 2 eyes; fibrovascular, 10 eyes). The average PED height and area were 615.7 ± 175.3 μm and 21.0 ± 7.2 mm², respectively. The sub-RPE cleft was observed in 10 eyes. The logMAR BCVA immediately after the RPE tear (0.73 ± 0.40) at 6 months (0.86 ± 0.51) and 12 months (0.84 ± 0.43) after the RPE tear were significantly worse than that before the RPE tear (0.58 ± 0.31; p < 0.05). The BCVA of patients with RPE tears that spread to the fovea was poorer than that of patients without RPE tears. Conclusions: In patients with nAMD, RPE tears tended to occur in typical AMD eyes with high or large PEDs, and sub-RPE clefts. The visual prognosis depended on whether the RPE tear included the fovea.

DOI： 10.3390/jcm12175496

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Journal of Clinical Medicine  

Age-related macular degeneration (AMD) causes visual impairment in individuals who are >50 years of age. However, no study has investigated AMD when using ultra-wide-field swept-source optical coherence tomography (UWF SS-OCT). We aimed to evaluate central and peripheral choroidal thicknesses using UWF SS-OCT, and to compare these across the AMD subtypes. We included 75 eyes of patients with typical AMD (tAMD), 56 with polypoidal choroidal vasculopathy (PCV), 29 with pachychoroid neovasculopathy (PNV), and 12 with retinal angiomatous proliferation (RAP). To compare choroidal thicknesses in the central and peripheral choroids, we established subfields of <3 mm, <9 mm, and 9–18 mm from the fovea. PNV patients were significantly younger than those with tAMD (p = 0.01). The choroidal thicknesses of PNV were significantly greater than that of tAMD in all subfields (p < 0.01), and choroidal thickness significantly correlated with age and axial length in all subfields (p < 0.05). Even after adjusting for age and axial length, the choroidal thickness in PNV was significantly greater than that in tAMD (p < 0.05). In addition, the ratio of the posterior <9 mm to a peripheral 9–18 mm choroidal thickness in PNV was significantly greater than that in tAMD (p < 0.01). A thickened choroid in PNV was more pronounced in the posterior choroid than in the periphery.

DOI： 10.3390/jcm12165364

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記述言語：英語   出版者・発行元：Graefe S Archive for Clinical and Experimental Ophthalmology  

Purpose: Choroidal neovascularization (CNV) often recurs during anti-vascular endothelial growth factor (VEGF) therapy; however, little is known about the mechanism of vascular regrowth. Vascular regrowth along the empty sleeves of basement membranes was proposed as a mechanism for recurrence after the reversal of VEGF inhibition in tumors. This study investigated whether the proposed mechanism is involved in CNV during VEGF therapy. Methods: We made two observations using a mice model, as well as patients with CNV. Laser-induced CNV mice were used to examine the vascular empty sleeves of the basement membrane and CNV with the immunohistochemistry of type IV collagen and CD31, respectively. A retrospective cohort study included 17 eyes from 17 patients with CNV treated with anti-VEGF treatment. Vascular regrowth during anti-VEGF treatment was assessed using optical coherence tomography angiography (OCTA). Results: In the CNV mouse model, the CD31⁺ vascular endothelium area was decreased during anti-VEGF treatment compared with the IgG control (33516.7 ± 10864.7 vs. 10745.9 ± 5755.9 μm², P < 0.05), whereas a significant difference was not observed in the area of type IV collagen⁺ vascular empty sleeve after the treatment compared with the control (29135.0 ± 7432.9 vs. 24592.0 ± 5935.3 μm², P = 0.7). The proportions of CD31⁺ to type IV collagen⁺ areas were significantly decreased after the treatment (38.7 ± 7.4% vs. 17.1 ± 5.4%, P < 0.05). In the OCTA observations, the follow-up period in the retrospective cohort study was 58.2 ± 23.4 months. CNV regrowth was observed in 682 neovessels of the 17 eyes. In group 1, CNV regression and regrowth are in the same form (129 neovessels, 18.9%). In group 2, CNV regression and regrowth are in a different form (170 neovessels, 24.9%). In group 3, CNV regrowth is with a different form without the regression (383 neovessels, 56.2%).[Figure not available: see fulltext.] Conclusions: Parts of CNV regrowth may occur along the vascular empty sleeve, which remain after anti-VEGF treatment.

DOI： 10.1007/s00417-023-06018-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   出版者・発行元：International Journal of Medical Robotics and Computer Assisted Surgery  

Background: Robotic ophthalmic endoscope holders allow surgeons to execute dual-hand operations in eye surgery. To prevent needle-like endoscopes from invading the retina when moving, surgeons expect visual and real-time information about the relative special relationship between the endoscope and fundus. Methods: This study develops a real-time fundus reconstruction method. First, using deep learning, the method estimates the distance between the fundus part corresponding to every pixel of the RGB endoscopic image and the endoscope. Then, by combining the estimated distance with the kinematics of a robotic holder, the point cloud representing the present fundus area is generated, and by which the size and position of the eyeball are estimated. Results: This method shows a real-time frequency of 10 Hz, which is robust to eyeball movement. The error of fundus reconstruction is about 0.5 mm, and the error of eyeball estimation is about 1 mm. Conclusion: Using this fundus reconstruction method can map the position of the endoscope inside the eyeball when using a robotic endoscope holder in eye surgery. The overall accuracy level meets the ophthalmologists' accuracy requirements of ophthalmologists.

DOI： 10.1002/rcs.2496

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記述言語：英語   出版者・発行元：Retinal Cases and Brief Reports  

Purpose:To evaluate structural and angiographic neovascularization in patients with proliferative diabetic retinopathy using volumetric three-dimensional optical coherence tomography angiography (OCTA).Methods:This prospective, observational cross-sectional study included 29 eyes of 27 patients with proliferative diabetic retinopathy. The angiogenic structure, feeding vessel (epicenter), flow volume, and flow volume density of the neovasculatures were evaluated using three-dimensional OCTA imaging. The flow area and the flow area density were also measured using en face OCTA imaging.Results:Sites of neovascularization were imaged successfully in 17 of the 29 eyes (58.6%). Three proposed types of neovascularization were identified on the basis of structural features seen on the three-dimensional OCTA images. Neovascularization of the adhesion type (9 of 17, 52.9%) adhered to the retinal vasculature. Those of the traction type (5 of 17, 29.4%) were partially separated from the retinal vascular plexus. Those of the mushroom type (3 of 17, 17.6%) were connected to the retinal vasculature by several epicenters. There was a significant difference between highly leaky (active) and faintly leaky (inactive) neovascularization for flow volume density, but not for flow area, flow volume, or flow area density (P = 0.01, 0.9, 0.6, and 0.1, respectively).Conclusion:Volumetric three-dimensional OCTA revealed three types of neovascularization in proliferative diabetic retinopathy and may be useful for assessing neovascular activity and planning vitrectomies.

DOI： 10.1097/ICB.0000000000001183

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記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

目的:線維柱帯切開術眼外法(LOT-ext)とマイクロフックを用いた眼内法(LOT-int)の術後2年間の成績を比較した.対象および方法:2017年1月～2018年12月に九州大学病院においてLOT-extおよびLOT-intを白内障手術と同時に行った患者を後ろ向きに抽出し,術後1年以上経過観察できた39例39眼(LOT-ext:20眼,LOT-int:19眼)を対象とした.術後6,12,18,24ヵ月時点での術後眼圧値,および術後合併症の有無について両術式間で比較した.結果:術後の平均眼圧下降値および平均眼圧下降率は術式間で差はなかった.また,生存時間分析でも術後眼圧値は術式間で差はなかった.術後合併症は,LOT-extでニボーを伴う前房出血(p=0.001)および術後1ヵ月以内の眼圧スパイクが有意に多かった(p=0.002).結論:LOT-extとLOT-intの眼圧下降効果に違いはなかった.LOT-extは術後前房出血の頻度および術後眼圧スパイクがLOT-intより多くみられ,術後管理により注意を要する.(著者抄録)

出版者・発行元：株式会社医学書院  

DOI： 10.11477/mf.1410214765

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Ophthalmology  

Purpose: To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population. Design: Genome-wide association study (GWAS). Participants: Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses. Methods: We conducted a meta-analysis of 2 independent GWASs that included a total of 2663 patients with AMD and 9471 control participants using the imputation reference panel for genotype imputation specified for the Japanese population (n = 3541). A replication study was performed using an independent set of 1109 patients with AMD and 7299 control participants. Main Outcome Measures: Associations of genetic variants with AMD. Results: A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P < 5.0 × 10^–8). Of these loci, 4 were known to be associated with AMD (CFH, C2/FB, TNFRSF10A, and ARMS2), and 2 were novel (rs4147157 near WBP1L and rs76228488 near GATA5). The newly identified associations were confirmed in a replication study (P < 0.01). After the meta-analysis of all datasets, we observed strong associations in these loci (P = 1.88 × 10^–12 and P = 1.35 × 10^–9 for meta-analysis for rs4147157 and rs76228488, respectively). When we looked up the associations in the reported central serous chorioretinopathy (CSC) GWAS conducted in the Japanese population, both loci were associated significantly with CSC (P = 4.86 × 10^–3 and P = 4.28 × 10^–3 for rs4147157 and rs76228488, respectively). We performed a genetic colocalization analysis for these loci and estimated that the posterior probabilities of shared causal variants between AMD and CSC were 0.39 and 0.60 for WBP1L and GATA5, respectively. Genetic correlation analysis focusing on the epidemiologically suggested clinical risk factors implicated shared polygenic architecture between AMD and smoking cessation (r<inf>g</inf> [the measure of genetic correlation] = –0.33; P = 0.01; false discovery rate, 0.099). Conclusions: Our findings imply shared genetic components conferring the risk of both AMD and CSC. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

DOI： 10.1016/j.ophtha.2022.10.034

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞目的:ポリープ状脈絡膜血管症(PCV)に対する抗血管内皮増殖因子(VEGF)薬併用光線力学的療法(PDT)後2年における治療成績の検討。対象と方法:対象は2017年8月～2019年8月に九州大学病院眼科で未治療PCVに初回からPDTと抗VEGF薬導入期3回投与(1クール)を施行し,2年以上経過観察できた20例20眼。眼底写真での新たな出血,光干渉断層計で確認された滲出性変化,および蛍光眼底造影でのポリープを認めたものを再発と定義した。治療前患者背景,治療前病巣径(GLD),治療前,1,2年後の視力,中心窩網膜厚(CRT),中心窩脈絡膜厚(CCT),dry fovea率,2年間の治療回数,再発率について,診療録をもとに後ろ向きに検討した。結果:治療前平均logMAR視力(0.23)は,1年後0.12,2年後0.14と改善し,治療前CRT(333.3±21.2μm),CCT(264.6±17.8μm)は,1年後(CRT 231.9±10.7μm,CCT 220.3±17.0μm),2年後(CRT 237.7±9.56μm,CCT 234.9±18.4μm)に減少していた(p<0.05)。1年後80%,2年後70%でdry foveaが得られていた。1年目の抗VEGF薬投与回数は導入期の3回を含めて平均4.65回±0.47回/年,2年目1.9回±0.60回/年であった。2年後の視力不良との関連因子を検討したところ,治療前視力不良,治療前GLDが大きいこと,と有意に関連があった。15例(75%)が再発し,そのうち40%が1年未満に再発していた。それらの早期再発症例の治療前平均CCT(234.9μm)は,1年以上後で再発した症例の平均CCT(314.3μm)に比べ有意に薄くなっていた。結論:PCVに対するPDT併用抗VEGF薬治療は2年後の視力,網膜形態を改善したが,症例により再発し,追加治療が必要となることが示唆された。治療前CCTが薄いと再発までの期間が短い傾向があった。

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Graefe S Archive for Clinical and Experimental Ophthalmology  

Purpose: To examine the secular trends in the prevalence, incidence, and progression rates of diabetic retinopathy (DR) in a Japanese community. Methods: Community-dwelling Japanese residents aged ≥ 40 years with diabetes participated in comprehensive systemic and ophthalmological surveys, including an examination for DR, in 1998 (n = 220), 2007 (n = 511), 2012 (n = 515), and 2017 (n = 560). DR was assessed using colour fundus photographs after pupil dilation according to the modified Airlie House classification system. To compare the frequencies of newly developed or progressed DR between the studied decades, two eye cohorts were established (the 2000s cohort included 145 participants examined in 1998 and 2007; the 2010s cohort included 255 participants examined in 2007, 2012, and 2017). Trends in the prevalence, incidence, and progression rate of DR were tested by logistic regression analysis with a generalised estimating equation. Results: The age-adjusted prevalence of DR among individuals with diabetes decreased significantly with time from 1998 to 2017 (27.4% in 1998, 22.8% in 2007, 12.8% in 2012, and 6.4% in 2017; p for trend < 0.001). During this period, the prevalence of DR was decreasing in every haemoglobin A<inf>1c</inf> category, but it remained constant in the high systolic blood pressure category. In addition, the rates of new-onset of DR were significantly lower in the 2010s compared to the 2000s (p < 0.001). Conclusion: Our findings suggest that the prevalence and incidence of DR among diabetic people significantly decreased with time over the past two decades in a general Japanese population.

DOI： 10.1007/s00417-022-05839-8

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記述言語：英語   出版者・発行元：International Ophthalmology  

Objectives: To evaluate long-term outcomes of infliximab (IFX) treatment in patients with Behçet's disease (BD)-associated uveitis. Patients and methods: We retrospectively analyzed the cases of patients with BD-associated uveitis treated with IFX for > 5 years. We compared the numbers of ocular inflammatory attacks, ocular disease activities, and visual acuity before and after the initiation of IFX treatment. Results: The 24 patients were 20 men and 4 women. Their mean age at the initiation of IFX treatment was 37.3 ± 9.2 years. The mean term from the initiation of IFX treatment was 10.3 ± 2.4 years. The average number of ocular inflammatory attacks was 5.4 ± 2.1 per 12 months before the IFX treatment and significantly lower at 0.83 ± 0.96 per 12 months after the initiation of IFX treatment (p < 0.05). We used a scoring system for BD-associated uveitis named the Behçet's disease ocular attack score 24 (BOS24) to estimate the changes in ocular disease activities between before and after initiation of IFX treatment. The average score decreased significantly from 7.58 ± 2.77 to 2.55 ± 2.74 after the initiation of IFX treatment (p < 0.05). Even after > 5 years of the treatment, both the number of ocular attacks and the BOS24 score kept decreasing. The visual acuity in 42 of 48 eyes (24 patients) was improved or maintained. Conclusions: IFX was effective for controlling ocular inflammatory attacks and diminishing ocular disease activities in patients with BD-associated uveitis, and it maintained the patients' visual acuity.

DOI： 10.1007/s10792-022-02495-z

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記述言語：英語   出版者・発行元：Plos One  

We aimed to verify whether the intravitreal injection of small molecule compounds alone can create photoreceptor cells in mouse models of retinal degeneration. Primary cultured mouse Müller cells were stimulated in vitro with combinations of candidate compounds and the rhodopsin expression was measured on day 7 using polymerase chain reaction and immunostaining. We used 6-week-old N-methyl-N-nitrosourea-treated and 4-week-old rd10 mice as representative in vivo models of retinal degeneration. The optimal combination of compounds selected via in vitro screening was injected into the vitreous and the changes in rhodopsin expression were investigated on day 7 using polymerase chain reaction and immunostaining. The origin of rhodopsin-positive cells was also analyzed via lineage tracing and the recovery of retinal function was assessed using electroretinography. The in vitro mRNA expression of rhodopsin in Müller cells increased 30-fold, and 25% of the Müller cells expressed rhodopsin protein 7 days after stimulation with a combination of 4 compounds: transforming growth factor-β inhibitor, bone morphogenetic protein inhibitor, glycogen synthase kinase 3 inhibitor, and γ-secretase inhibitor. The in vivo rhodopsin mRNA expression and the number of rhodopsin-positive cells in the outer retina were significantly increased on day 7 after the intravitreal injection of these 4 compounds in both N-methyl-N-nitrosourea-treated and rd10 mice. Lineage tracing in td-Tomato mice treated with N-methyl-N-nitrosourea suggested that the rhodopsin-positive cells originated from endogenous Müller cells, accompanied with the recovery of the rhodopsin-derived scotopic function. It was suggested that rhodopsin-positive cells generated by compound stimulation contributes to the recovery of retinal function impaired by degeneration.

DOI： 10.1371/journal.pone.0282174

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

背景:肺癌患者にみられた硝子体混濁に対し硝子体生検を行ったが,硝子体由来標本から癌細胞が検出されず,CD8陽性T細胞の単クローン性増殖を認めた1例を報告する.症例:78歳,男性.前医内科で20XX-2年4月に肺扁平上皮癌(臨床病期T4N2M1,Stage IV),epidermal growth factor receptor(EGFR)遺伝子変異陽性と診断された.数ラインの化学療法が施行されたが,progressive diseaseであった.20XX年6月に左眼の霧視を主訴に近医眼科を受診したところ左眼の虹彩毛様体炎と診断され,副腎皮質ステロイド点眼治療を開始された.同年6月に左眼の硝子体混濁が出現し副腎皮質ステロイド内服治療が開始されたが,混濁が増悪したため同年9月に当科を初診した.転移性脈絡膜腫瘍を疑い,硝子体生検を行った.硝子体塗抹標本で核形不整のリンパ球が認められたが,肺癌細胞は検出されなかった.硝子体切除液から作製したセルブロック薄切標本からCD8陽性T細胞の浸潤を認めたが,肺癌細胞は検出されなかった.また,硝子体由来DNAからT細胞受容体の単クローン性遺伝子再構成が検出された.硝子体液中から肺扁平上皮癌マーカーである癌胎児性抗原(CEA),CYFRA21-1(シフラ)の検出はなかった.20XX+1年1月に脈絡膜に灰白色隆起病変が出現し,前房水中からシフラの上昇が検出された.腹部コンピュータ断層撮影の結果,副腎皮質への転移が見つかり,転移性脈絡膜腫瘍が考えられた.結論:本症例の硝子体混濁は肺癌の脈絡膜転移の後に生じ,腫瘍細胞に反応したCD8陽性T細胞の単クローン性増殖である可能性が最も考えられた.(著者抄録)

記述言語：日本語   出版者・発行元：(公財)鈴木謙三記念医科学応用研究財団  

記述言語：英語   出版者・発行元：Frontiers in Medicine  

Purpose: To evaluate 10-year outcome of infliximab (IFX) treatment for uveitis in Behçet disease (BD) patients using a standardized follow-up protocol. Design: Retrospective longitudinal cohort study. Participants: 140 BD uveitis patients treated with IFX enrolled in our previous study. Methods: Medical records were reviewed for demographic information, duration of IFX treatment, number of ocular attacks before IFX initiation, best corrected visual acuity (VA) at baseline and 1, 2, 3, 4, 5, and 10 years after IFX initiation, uveitis recurrence after IFX initiation and main anatomical site, concomitant therapies, and adverse events (AEs). Main outcome measures: 10-year IFX continuation rate and change in LogMAR VA. Results: Of 140 BD patients, 106 (75.7%) continued IFX treatment for 10 years. LogMAR VA improved gradually after initiation of IFX, and the improvement reached statistical significance from 2 years of treatment. Thereafter, significant improvement compared with baseline was maintained until 10 years, despite a slight deterioration of logMAR VA from 5 years. However, eyes with worse baseline decimal VA < 0.1 showed no significant improvement from baseline to 10 years. Uveitis recurred after IFX initiation in 50 patients (recurrence group) and did not recur in 56 (non-recurrence group). Ocular attacks/year before IFX initiation was significantly higher in the recurrence group (2.82 ± 3.81) than in the non-recurrence group (1.84 ± 1.78). In the recurrence group, uveitis recurred within 1 year in 58% and within 2 years in 74%. Seventeen patients (34%) had recurrent anterior uveitis, 17 (34%) had posterior uveitis, and 16 (32%) had panuveitis, with no significant difference in VA outcome. In addition, logMAR VA at 10 years did not differ between the recurrence and non-recurrence groups. AEs occurred among 43 patients (30.7%), and 24 (17.1%) resulted in IFX discontinuation before 10 years. Conclusions: Among BD patients with uveitis who initiated IFX, approximately 75% continued treatment for 10 years, and their VA improved significantly and was maintained for 10 years. Uveitis recurred in one-half of the patients, but visual acuity did not differ significantly from the patients without recurrence.

DOI： 10.3389/fmed.2023.1095423

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記述言語：英語   出版者・発行元：Frontiers in Immunology  

In the published article, there were errors. In the original article, there was an error in the description of the Reverse primer sequence in Materials and methods. A correction has been made to Materials and methods, “Deep amplicon sequencing of CMV-UL40 genomic DNA”. This sentence previously stated: “The following forward and reverse primers were used:Forward, 5′-TCGTCGGCAGCGTCAGATGTGTATAAGAGACAGCAACAGTCGGCAGAATGAAC-3′ and Reverse, 5′-GTCTCGTGGGCTCGGAGATGTGTATAAGAGACA GCTGGAACACGACGCATA-3’.”The corrected sentence appears below: “The following forward and reverse primers were used: Forward, 5′-TCGTCGGCAGCGTCAGATGTGTATAAGAGACAGCAACAGTCGGCAGAATGAAC-3′ and Reverse, 5′-GTCTCGTGGGCTCGGAGATGTGTATAAGAGAC AGCTGGAACACGAGCGGACATA-3’.”In the original article, there was another error in the description of the concentration of the anti-HLA-E antibody in Materials and methods. A correction has been made to Materials and methods, “Immunohistochemistry analysis”. This sentence previously stated: “After antigen retrieval with boiling citrate buffer (pH 6.0), the sections were incubated with 5% skim milk for 1 h at room temperature to prevent nonspecific binding and stained with 10 mL/mL anti-HLA-E antibody [MEM-E/02] (Abcam; Cambridge, UK) or IgG from mouse serum (Sigma-Aldrich) overnight at 4°C.” The corrected sentence appears below: “After antigen retrieval with boiling citrate buffer (pH 6.0), the sections were incubated with 5% skim milk for 1 h at room temperature to prevent nonspecific binding and stained with 10 mg/mL anti-HLA-E antibody [MEM-E/02] (Abcam; Cambridge, UK) or IgG from mouse serum (Sigma-Aldrich) overnight at 4°C.” The authors apologize for these errors and state that these do not change the scientific conclusions of the article in any way. The original article has been updated.

DOI： 10.3389/fimmu.2022.1124440

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: To report the characteristics of a case series of ocular inflammatory events following COVID-19 vaccination in Japan. Study design: Retrospective multicenter study Methods: In this retrospective multicenter survey, a questionnaire was sent to 16 Japanese hospitals that had uveitis specialty clinics. Information on patients who developed ocular inflammatory events within 14 days of COVID-19 vaccination between February 2021 and December 2021 was collected. Results: Thirty-seven patients were diagnosed with ocular inflammatory events following COVID-19 vaccination. The mean age was 53.4 ± 16.4 years (range, 26-86 years), and the mean time to onset after vaccination was 6.3 ± 4.2 days (range, 1-14 days). Vogt-Koyanagi-Harada disease (VKH) was the most common event (n = 17 patients, 46%), followed by anterior uveitis (n = 6), infectious uveitis (n = 3), acute zonal occult outer retinopathy (AZOOR) (n = 2), sarcoidosis-associated uveitis (n = 1), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1), optic neuritis (n = 1), multiple evanescent white dot syndrome (MEWDS) (n = 1), Posner-Schlossman syndrome (n = 1), and unclassified uveitis (n = 4). Twenty-eight cases occurred after BNT162b2 vaccination (Pfizer-BioNTech) and 8 after mRNA-1273 vaccination (Moderna), whilst 1 patient had no information about vaccine type. Conclusions: COVID-19 vaccination can be related to various types of ocular inflammatory events. When we encounter patients with ocular inflammatory disease, we should consider that it may be an adverse effect of COVID-19 vaccination.

DOI： 10.1007/s10384-022-00962-9

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記述言語：英語   出版者・発行元：Ophthalmic Research  

Introduction: Drusen and pigmentary abnormality are found as the hallmark to predict progression of age-related macular degeneration (AMD). In Asian populations, exudative AMD often appears in the absence of drusen but is rather accompanied by pigmentary abnormality. Recently, shallow irregular retinal pigment epithelium (RPE) elevations (SIRE) have been shown as a sign of subclinical nonexudative macular neovascularization. In this study, we aimed to investigate the characteristics of optical coherence tomography (OCT) findings including SIRE before the appearance of exudative AMD. Methods: We retrospectively reviewed 32 cases of exudative AMD that occurred in the fellow eye within the 5-year-observation period. Color fundus photography, OCT, and fluorescein/indocyanine-green angiography at the beginning of observation and at the time when exudative AMD appeared were examined to diagnose SIRE and the subtype of exudative AMD. Results: Exudative AMD was found in 19 eyes with large drusen and 13 eyes without large drusen. Mean sub-foveal choroidal thickness without large drusen was significantly thicker than that with large drusen (336 ± 109 and 220 ± 96 μm, respectively; mean ± SD). Six eyes with pachychoroid neovasculopathy, 4 eyes with type 1 macular neovascularization, and 3 eyes with PCV had occurred in the fellow eye without large drusen. Among those, 6 eyes had been accompanied by SIRE with a greatest transverse linear dimension of 1 mm or more at the beginning of observation period. Besides, small RPE elevations with a longest diameter of less than 1 mm had been observed in other 5 eyes. Three cases of polypoidal choroidal vasculopathy had originated from small RPE elevations. Moreover, pachyvessels, choriocapillaris thinning, or choroidal hyperpermeability were observed with SIRE or small RPE elevations. Conclusions: There is a non-drusen type of exudative AMD that originates from small RPE elevations as well as SIRE.

DOI： 10.1159/000526445

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   出版者・発行元：(公社)日本視能訓練士協会  

【背景】視神経炎との鑑別に苦慮した視神経管内神経鞘腫の1例を経験したので報告する。【症例】25歳女性。3ヵ月前より左眼視力低下あり、ステロイドパルス3クール行うも効果なく、当科紹介受診。初診時左視力(0.04)、MRIで左視神経に径5×5mmの結節状病変を認めた。前医を含めた4回のステロイドパルスで視機能改善はなく、放射線治療にも病変の縮小が見られず腫瘍性疾患と考えた。初診後1年7ヵ月左眼光覚消失に至った。初診後3年4ヵ月腫瘍は10×7mmまで増大し、腫瘍摘出術を施行した。切除組織から腫瘍は神経鞘腫と確定診断した。【結果】急速に視機能低下を呈する疾患の鑑別診断として神経鞘腫を考慮すべきである。(著者抄録)

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】急性帯状潜在性網膜外層症(AZOOR)として長期経過観察された急性梅毒性後部脈絡網膜炎の症例を報告する。【症例】39歳男性。2019年X月左眼光視症を主訴に前医を受診し、AZOORとして経過観察された。13ヵ月後、確定診断目的に当科紹介受診した。初診時、左眼の眼底に黄斑反射の低下と視神経乳頭発赤を認め、OCTでellipsoid zoneの不整、造影検査で視神経乳頭の蛍光漏出と多発性の蛍光貯留を認めた。血液検査で、梅毒性ぶどう膜炎と診断された。【結論】眼梅毒は特徴的な臨床所見が乏しく、診断と治療の開始が遅れてしまうことが多い。診断に苦慮する症例では梅毒を鑑別診断に考慮する必要がある。(著者抄録)

記述言語：日本語   出版者・発行元：眼科臨床紀要会  

目的:九州大学病院における2007～2012年までの5年間の緑内障手術の術式別の成績,および5年生存率と関連する予後因子について検討した.対象:2007年1月～2012年12月にかけて施行され,12ヵ月以上経過観察可能であった原発開放隅角緑内障(POAG)と落屑緑内障(EXG)の115例153眼を対象とし,線維柱帯切開術(LOT)と線維柱帯切除術(LEC)の術後成績,合併症,予後因子を調査した.結果:対象者115名の平均年齢は70.5±10.1歳,男女の割合は97:56であった.眼圧21mmHg以下の5年生存率はLOT群88%,LEC群84%であった.術後成績の予後因子解析においてLOT群は水晶体再建術併施が有意な防御因子となり,LEC群は術前眼圧高値(30mmHg以上)が有意な危険因子となった.結論:LOT群は水晶体再建術併施で術後成績は良好,LEC群は術前眼圧が高値で術後成績不良であった.(著者抄録)

記述言語：英語   出版者・発行元：Diabetes  

Intraretinal hyperreflective foci (HRF) are significant biomarkers for diabetic macular edema. However, HRF at the vitreoretinal interface (VRI) have not been exam-ined in diabetic retinopathy (DR). A prospective observational clinical study with 162 consecutive eyes using OCT imaging showed significantly increased HRF at the VRI during DR progression (P < 0.01), which was reversed by anti-vascular endothelial growth factor (VEGF) therapy. F4/80⁺ macrophages increased significantly at the VRI in Kimba (vegfa^+/+) or Akimba (Akita × Kimba) mice (both P < 0.01), but not in diabetic Akita (Ins2^+/2) mice, indicat-ing macrophage activation was modulated by elevated VEGF rather than the diabetic milieu. Macrophage depletion significantly reduced HRF at the VRI (P < 0.01). Fur-thermore, BrdU administration in Ccr2^rfp/+Cx3cr1^gfp/+ vegfa^+/2 mice identified a significant contribution of M2-like tissue-resident macrophages (TRMs) at the VRI. Ki-67⁺ and CD11b⁺ cells were observed in preretinal tissues of DR patients, while exposure of vitreal macrophages to vitreous derived from PDR patients induced a significant proliferation response in vitro (P < 0.01). Taken to-gether, the evidence suggests that VEGF drives a local proliferation of vitreous resident macrophages (VRMs) at the VRI during DR. This phenomenon helps to explain the derivation and disease-relevance of the HRF lesions observed through OCT imaging in patients.

DOI： 10.2337/db21-0247

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出版者・発行元：金原出版  

DOI： 10.18888/ga.0000002857

CiNii Research

記述言語：英語   出版者・発行元：Orbit London  

Here, we report a case of an orbital solitary fibrous tumor (SFT) with multiple local recurrences, even after orbital exenteration, and lung metastases after 41 years. The report discusses the clinical and histopathological findings of this case. A 34-year-old female patient with an orbital SFT was treated with orbital exenteration after local resection failed to prevent a recurrence. Ten years later, the patient underwent radiation therapy, followed by two rounds of gamma knife treatment, leading to remission. Forty-one years after the first treatment, the patient, at the age of 75 years, was found to have lung metastases along with orbital recurrence for the eighth time. The patient underwent radiation therapy but died from radiation pneumonitis. Our case emphasizes the need for long-term follow-up of patients with orbital tumors, even after orbital exenteration, to monitor for metastasis.

DOI： 10.1080/01676830.2021.1954665

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Graefe S Archive for Clinical and Experimental Ophthalmology  

Purpose: To investigate the relevance of microaneurysm morphology in optical coherence tomography angiography (OCTA) image averaging and fluorescein leakage in diabetic retinopathy (DR). Methods: In 38 consecutive patients with DR, ten consecutive 3- × 3-mm fovea-centered OCTA (HS100, Canon Inc., Tokyo, Japan) and fluorescein angiography (FA) were performed, and averaged OCTA images were created based on the 10 images. After detecting all microaneurysms in FA images, the morphology was classified into four types (focal bulge, saccular/pedunculated, fusiform, and mixed) using averaged OCTA images. The correlation between microaneurysm leakage in FA, retinopathy stage, and microaneurysm morphology was estimated. Results: Thirty-eight eyes (50.0%) of the 33 patients were available for analysis, and 370 (63.5%) of the 583 FA-detected microaneurysms were morphologically classifiable (focal bulge, 46; saccular/pedunculated, 143; fusiform, 29; and mixed, 152) in OCTA. There was a significant correlation between stage and percentage of microaneurysm morphology and between morphology and the presence of leakage (P < 0.0001 and P < 0.01, respectively). The proportion of focal bulges decreased with stage progression, while the other three types increased with stage progression. The percentage of FA leakage for focal bulge, saccular/pedunculated, fusiform, and mixed was 41.3%, 66.4%, 82.8%, and 66.4%, respectively, and the fusiform type showed significant FA leakage. Conclusion: Microaneurysm morphology is correlated with the DR stage and FA leakage. Microaneurysm morphology recognition using OCTA image averaging may be useful for the clinical evaluation of DR. [Figure not available: see fulltext.]

DOI： 10.1007/s00417-022-05713-7

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記述言語：英語   出版者・発行元：Journal of Medical Genetics  

Despite the successful identification of causative genes and genetic variants of retinitis pigmentosa (RP), many patients have not been molecularly diagnosed. Our recent study using targeted short-read sequencing showed that the proportion of carriers of pathogenic variants in EYS, the cause of autosomal recessive RP, was unexpectedly high in Japanese patients with unsolved RP. This result suggested that causative genetic variants, which are difficult to detect by short-read sequencing, exist in such patients. Using long-read sequencing technology (Oxford Nanopore), we analysed the whole genomes of 15 patients with RP with one heterozygous pathogenic variant in EYS detected in our previous study along with structural variants (SVs) in EYS and another 88 RP-associated genes. Two large exon-overlapping deletions involving six exons were identified in EYS in two patients with unsolved RP. An analysis of an independent patient set (n=1189) suggested that these two deletions are not founder mutations. Our results suggest that searching for SVs by long-read sequencing in genetically unsolved cases benefits the molecular diagnosis of RP.

DOI： 10.1136/jmedgenet-2022-108428

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記述言語：英語   出版者・発行元：Frontiers in Immunology  

Human cytomegalovirus (HCMV) infections develop into CMV diseases that result in various forms of manifestations in local organs. CMV-retinitis is a form of CMV disease that develops in immunocompromised hosts with CMV-viremia after viruses in the peripheral circulation have entered the eye. In the HCMV genome, extensive diversification of the UL40 gene has produced peptide sequences that modulate NK cell effector functions when loaded onto HLA-E and are subsequently recognized by the NKG2A and NKG2C receptors. Notably, some HCMV strains carry UL40 genes that encode peptide sequences identical to the signal peptide sequences of specific HLA-A and HLA-C allotypes, which enables these CMV strains to escape HLA-E-restricted CD8⁺T cell responses. Variations in UL40 sequences have been studied mainly in the peripheral blood of CMV-viremia cases. In this study, we sought to investigate how ocular CMV disease develops from CMV infections. CMV gene sequences were compared between the intraocular fluids and peripheral blood of 77 clinical cases. UL40 signal peptide sequences were more diverse, and multiple sequences were typically present in CMV-viremia blood compared to intraocular fluid. Significantly stronger NK cell suppression was induced by UL40-derived peptides from intraocular HCMV compared to those identified only in peripheral blood. HCMV present in intraocular fluids were limited to those carrying a UL40 peptide sequence corresponding to the leader peptide sequence of the host’s HLA class I, while UL40-derived peptides from HCMV found only in the peripheral blood were disparate from any HLA class I allotype. Overall, our analyses of CMV-retinitis inferred that specific HCMV strains with UL40 signal sequences matching the host’s HLA signal peptide sequences were those that crossed the blood–ocular barrier to enter the intraocular space. UL40 peptide repertoires were the same in the intraocular fluids of all ocular CMV diseases, regardless of host immune status, implying that virus type is likely to be a common determinant in ocular CMV disease development. We thus propose a mechanism for ocular CMV disease development, in which particular HCMV types in the blood exploit peripheral and central HLA-E-mediated tolerance mechanisms and, thus, escape the antivirus responses of both innate and adaptive immunity.

DOI： 10.3389/fimmu.2022.1008220

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

背景:炎症性筋線維芽細胞性腫瘍(IMT)は筋線維芽細胞の増殖と炎症細胞浸潤を特徴とする中間悪性腫瘍であり,肺,腹腔骨盤内,後腹膜に好発し,眼窩に発生することはまれである.今回,眼窩に発生したIMTの1例を経験したので報告する.症例:46歳,女性.複視を主訴に近医眼科を受診し,眼窩に腫瘍を指摘され九州大学病院眼科を紹介受診した.初診時に右眼球結膜下の赤色調腫瘤および画像診断で右眼窩内下方に35×20×15mmの紡錘形腫瘤を認め,眼球運動障害を来していた.結膜下の腫瘤を生検したところ,炎症細胞浸潤を伴った紡錘形細胞の増殖を認めた.免疫染色の結果,増殖細胞はanaplastic lymphoma kinase(ALK),α-平滑筋アクチン(α-SMA),desmin陽性であり,IMTと診断した.結膜切開および鼻内視鏡下にアプローチして全摘出し,術後24ヵ月の現在,再発は認めていない.結論:眼窩腫瘍で非上皮性腫瘍を疑う際はIMTの可能性も検討する必要がある.(著者抄録)

記述言語：英語  

記述言語：英語  

記述言語：英語   出版者・発行元：Translational Vision Science and Technology  

Purpose: Detecting subtle vitreoretinal interface (VRI) findings, such as a posterior hyaloid membrane, is difficult with conventional retinal imaging. We compared ultra-high-resolution spectral domain optical coherence tomography (UHR-SD-OCT) with standard-resolution OCT (SD-OCT) for the imaging of VRI abnormalities in diabetic retinopathy (DR). Methods: This prospective cross-sectional study included 113 consecutive patients (91 patients with diabetes and 22 healthy controls). The VRI was evaluated, and the results were compared between the conventional SD-OCT and UHR-SD-OCT images. VRI findings were also investigated before and after internal limiting membrane peeling during vitrectomy for proliferative DR. Results: A total of 159 eyes (87.4%) of 91 patients with diabetes were analyzed. UHR-SD-OCT could detect a hyperreflective layer at the VRI, in which en face OCT showed a membrane-like structure, termed the hyperreflective membrane (HRMe). The preop-erative HRMe could not be detected in all patients with proliferative DR who under-went internal limiting membrane peeling during vitrectomy. Although the HRMe did not correlate with the DR stage, eyes with diabetic macular edema (DME) (64.5%) showed a significant HRMe with UHR-SD-OCT more frequently than those without DME (35.8%) (P = 0.005). Conclusions: UHR-SD-OCT can detect the HRMe at the VRI in DR eyes, particularly in eyes with DME. The HRMe may present a thickened posterior hyaloid membrane that contributes to DME development. Translational Relevance: UHR-SD-OCT detects slight changes in the VRI in DR eyes. In the future, it may help to elucidate the mechanism of DME formation.

DOI： 10.1167/tvst.11.9.21

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記述言語：英語   出版者・発行元：American Journal of Ophthalmology Case Reports  

Purpose: This article presents a case of panuveitis that occurred after unrelated allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a patient with lymphoma-type human T-cell leukemia virus type-1 (HTLV-1)-associated adult T-cell leukemia (ATL). Observations: A 45-year-old man developed unilateral panuveitis 18 months after undergoing allo-HSCT. He underwent vitrectomy, and depositions of grey-white granules localized on the retinal artery were observed in the eye. Cytological examination of the vitreous aspirates showed that the atypical lymphoid cells stained positive for CD3 and CD8, but negative for CD4, B-cell markers, and cytomegalovirus antigen. Interphase fluorescence in situ hybridization using X‐ and Y‐chromosome probes revealed complete donor chimerism in CD8⁺ T cells in the vitreous aspirates. Conclusions and importance: Donor-derived CD8⁺ T lymphocytes can induce panuveitis like HTLV-1-assiciated uveitis after allo-HSCT in patients with ATL. Pathological diagnosis of vitreous infiltration by vitrectomy is helpful in patients with ATL. Donor-derived CD8⁺ T lymphocytes-induced panuveitis is recurrent but susceptible to regional corticosteroid treatment.

DOI： 10.1016/j.ajoc.2022.101673

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記述言語：英語   出版者・発行元：Ophthalmology Science  

Purpose: To investigate the detection of slower retinal capillary blood flow using commercial OCT angiography (OCTA) with a longer interscan time in diabetic retinopathy (DR). Design: Observational, prospective, cross-sectional study. Participants: A total of 62 eyes from 39 subjects with diabetes mellitus and 10 eyes from 9 healthy subjects. Methods: Commercial spectral domain-OCT was used to obtain 3 × 3-mm fovea-centered OCTA images of all eyes with 3 different interscan times (4.3, 5.7, and 8.6 ms). For each interscan time, OCTA imaging was performed 5 consecutive times, and a ×5 averaged image was obtained. Capillary flow density and visualization of retinal capillaries in the superficial and deep capillary plexuses (SCPs and DCPs, respectively) were compared between the 3 averaged images from the 3 different interscan times. Main Outcome Measures: Capillary flow density and visualization of foveal capillaries in 3 images with different interscan times. Results: Forty-five eyes of 34 patients were analyzed. There was no significant difference in the flow density of the SCP and DCP between the 3 images with different interscan times in all the DR stages. Some capillaries including microaneurysms that could not be observed at 4.3 ms could be observed at 5.7 or 8.6 ms. There were significantly more capillaries with difference points between the 3 images in the group with DR than in the group without DR (P < 0.01). The morphology of some microaneurysms also changed with longer interscan times. Conclusions: OCTA with longer interscan times revealed slower flow points in capillaries and more accurate visualization and morphology of microaneurysms in DR.

DOI： 10.1016/j.xops.2022.100181

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記述言語：英語  

DOI： doi.org/10.1159/000526445

記述言語：英語   出版者・発行元：Graefe S Archive for Clinical and Experimental Ophthalmology  

Purpose: Uveitis accounts for 10–15% of all cases of blindness in the developed world. Uveitic macular edema (UME) is a primary cause of permanent visual impairment in patients with uveitis. Because proinflammatory mediators elicit inflammation and lead to UME, we determined the profiles of proinflammatory mediators associated with complications, such as ME, in the vitreous humor of patients with panuveitis related to Behçet’s disease (BD) and sarcoidosis. Methods: In this retrospective study, we enrolled 21 patients with uveitis, including 6 with BD and 15 with sarcoidosis, and 15 patients with idiopathic epiretinal membrane (iERM) at the Department of Ophthalmology, Kyushu University Hospital, between January 2008 and April 2016. Vitreous concentrations of 32 proinflammatory mediators, including cytokines and soluble receptors of tumor necrosis factor (TNF) and interleukin (IL)-6 families, were assessed using a bead-based multiplex assay and their association with clinical data was examined. Results: The levels of proinflammatory mediators, including a proliferation-inducing ligand (APRIL), B cell activating factor belonging to the TNF family (BAFF), soluble cluster of differentiation 30 (sCD30), soluble TNF receptor-1 (sTNFR1), sTNFR2, TNF-α, IL-6, and soluble IL-6 receptor-α (sIL-6Rα), were significantly higher in patients with uveitis. With regard to clinical parameters in patients with uveitis, vitreous levels of BAFF and sIL-6Rα were prominently elevated in patients with UME compared to in those without UME (P < 0.01, respectively). Conclusions: Our results suggest that elevated vitreous levels of BAFF and sIL-6Rα are associated with the pathogenesis of UME in patients with panuveitis related to BD and sarcoidosis. [Figure not available: see fulltext.]

DOI： 10.1007/s00417-022-05600-1

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記述言語：英語   出版者・発行元：Human Molecular Genetics  

Age-related macular degeneration (AMD) and central serous chorioretinopathy (CSC) are common diseases that can cause vision loss in older and younger populations. These diseases share pathophysiological conditions derived from retinal pigment epithelium (RPE) dysfunction. Tumor necrosis factor receptor superfamily 10A (TNFRSF10A)-LOC389641 with the same lead single-nucleotide polymorphism (SNP) (rs13278062) is the only overlapped susceptibility locus found in both AMD and CSC through genome-wide association studies. This lead SNP has been reported to alter the transcriptional activity of TNFRSF10A. This study aimed to elucidate the function of TNFRSF10A in RPE degeneration using human primary RPE cells and Tnfrsf10 knockout (Tnfrsf10-/-) mice. TNFRSF10A was found to be localized in human RPE. In vitro assays revealed that a T allele of rs13278062, the risk allele for AMD and CSC, downregulated TNFRSF10A transcription in RPE, leading to decreased cell viability and increased apoptosis through protein kinase C-α (PKCA) downregulation. Treatment with phorbol 12-myristate 13-Acetate, a PKC activator, rescued the cell viability. Morphological RPE abnormality was found in the retina of Tnfrsf10-/- mice. Our data suggest that downregulation of TNFRSF10A expression inactivates PKCA signaling and causes cellular vulnerability of the RPE, which may contribute to the pathogenesis of AMD and CSC.

DOI： 10.1093/hmg/ddac020

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記述言語：日本語  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：日本語   出版者・発行元：眼科臨床紀要会  

背景:クリスタリン網膜症はCYP4V2を原因遺伝子とする遺伝性網膜変性疾患で、常染色体劣性遺伝形式をとるが、近親婚家系で親子発症する場合もある。症例:症例1は59歳の女性。初診時の矯正視力は右0.9、左0.7で、眼底にクリスタリン顆粒と網脈絡膜萎縮を認めた。15年の経過中に網脈絡膜萎縮が拡大し、最終受診時には視力が右0.4、左0.1に低下した。症例2は39歳の男性で、症例1の子。初診時の黄斑部網膜変性は軽微で、矯正視力両眼1.5と良好であった。8年の経過中に網脈絡膜萎縮が進行し、視力は右0.9、左0.6と低下した。家系内に複数の近親婚歴があり、両者にCYP4V2 c.G1020A(p.W340X)ホモ接合型変異を認めた。結論:近親婚家系に生じたクリスタリン網膜症の親子症例を経験した。長期経過で網脈絡膜変性が進行し、中高年で高度の視力障害をきたした。(著者抄録)

記述言語：英語   出版者・発行元：American Journal of Surgical Pathology  

High-risk human papillomavirus (HPV) infection in conjunctival and lacrimal sac squamous cell carcinomas (SCCs) has been sporadically reported; however, its prevalence, clinicopathologic significance and surrogate markers have not been fully elucidated. Here, we attempted to clarify these questions in Japanese patients with conjunctiva and lacrimal sac SCCs. We retrospectively collected 51 conjunctival SCC and 7 lacrimal sac SCC samples and analyzed them for (1) transcriptionally active high-risk HPV infection using messenger RNA in situ hybridization and (2) protein expressions of p16 and Rb using immunohistochemistry (IHC). Among a total of 58 cases, 25 (43.1%) and 16 (27.6%) tumors were positive for p16-IHC and HPV in situ hybridization, respectively. Ten (19.6%) of the 51 conjunctival SCCs, especially in the palpebral conjunctiva, and 6 (85.7%) of the 7 lacrimal sac SCCs were positive for high-risk HPV. High-risk HPV infection was significantly associated with younger patients, nonkeratinizing SCC histology, p16-positivity and partial loss of Rb expression, but not with recurrence risk. Notably, p16-IHC was not a perfect surrogate marker for high-risk HPV infection; only 64% (16/25) of p16-positive tumors were positive for high-risk HPV. In contrast, the p16+/Rb partial loss pattern was exclusively correlated with high-risk HPV-positivity. The results suggest that the combination of p16 and Rb expression patterns by IHC could be a useful method to predict high-risk HPV infection in conjunctival and lacrimal sac SCCs. HPV infection may be of less prognostic value in this field of cancers.

DOI： 10.1097/PAS.0000000000001857

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記述言語：英語   出版者・発行元：Frontiers in Neuroscience  

Necroptosis mediates the chronic inflammatory phenotype in neurodegeneration. Receptor-interacting protein kinase (RIPK) plays a pivotal role in the induction of necroptosis in various cell types, including microglia, and it is implicated in diverse neurodegenerative diseases in the central nervous system and the retina. Targeting RIPK has been proven beneficial for alleviating both neuroinflammation and degeneration in basic/preclinical studies. In this review, we discuss the role of necroptosis in retinal degeneration, including (1) the molecular pathways involving RIPK, (2) RIPK-dependent microglial activation and necroptosis, and (3) the interactions between necroptosis and retinal neuroinflammation/degeneration. This review will contribute to a renewed focus on neuroinflammation induced by necroptosis and to the development of anti-RIPK drugs against retinal degeneration.

DOI： 10.3389/fnins.2022.911430

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記述言語：英語  

DOI： 10.1016/j.xops.2022.100157

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記述言語：英語  

DOI： 10.1016/j.ajoc.2022.101470

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記述言語：英語   出版者・発行元：Graefe S Archive for Clinical and Experimental Ophthalmology  

Purpose: This study aimed to evaluate the one-year outcomes of photodynamic therapy (PDT) as a rescue treatment for age-related macular degeneration (AMD) refractory to anti-vascular endothelial growth factor (VEGF) therapy. Methods: Patients with AMD refractory to anti-VEGF therapy, treated with “rescue-PDT” were retrospectively investigated. The time of PDT was defined as the baseline value. Baseline characteristics including sex, age, best-corrected visual acuity (BCVA), central macular thickness (CMT), and foveal choroidal thickness (FCT) were examined. The changes in BCVA, CMT, and recurrence were also assessed at the 1-year follow-up. The logMAR VA change of 0.3 or more was defined as “improved” or “declined.” Results: Twenty-three consecutive eyes (typical AMD: 10 eyes, polypoidal choroidal vasculopathy: 10 eyes, and pachychoroid neovasculopathy: 3 eyes), which underwent “rescue-PDT,” were analyzed in this study. The BCVA was improved in three patients and maintained in 20 patients at 12 months after PDT (mean BCVA change: 0.11 ± 0.19). The CMT improved in 19 patients (82.6%), and the mean CMT changed from 318.5 ± 93.7 μm to 225.9 ± 51.6 μm (p < 0.01) 12 months after PDT. “Retreatment” of anti-VEGF drug injections was considered if the retinal fluid or retinal hemorrhage recurred after PDT. The baseline FCT of the “retreatment group (15 eyes)” was significantly lower than that of the “no retreatment group (8 eyes)” (206.3 ± 50.7 μm vs 293.9 ± 85.7 μm: p = 0.033). Conclusions: PDT could be an effective treatment option for anti-VEGF refractory AMD to maintain visual acuity and control retinal fluid for up to 12 months.

DOI： 10.1007/s00417-022-05553-5

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出版者・発行元：Ophthalmology Science  

Purpose: To assess the association of inner retinal thickness with prevalent dementia and regional brain atrophy in a general older population of Japanese. Design: Population-based, cross-sectional study. Participants: A total of 1078 residents aged 65 years or older who participated in an eye examination, a comprehensive survey of dementia, and brain magnetic resonance imaging scanning in 2017. Methods: The thicknesses of the inner retinal layers, namely, the ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL)—were measured by swept-source OCT (SS-OCT). The association of these retinal thicknesses with the risk of the presence of dementia was estimated using restricted cubic splines and logistic regression models. Regional brain volumes were estimated separately by applying 2 different methods: voxel-based morphometry (VBM) and analysis by FreeSurfer software. The associations of GC-IPL and RNFL thickness with each brain regional volume were analyzed using multiple regression analysis. Main Outcome Measure: Prevalent dementia and regional brain atrophy. Results: Among the study participants, 61 participants (5.7%) were diagnosed with dementia. The likelihood of the presence of dementia significantly increased with lower GC-IPL thickness after adjusting for potential confounders (odds ratio, 1.62 [95% confidence interval, 1.30–2.01] per 1 standard deviation decrement in the GC-IPL thickness), but no significant association was observed with RNFL thickness. In the VBM analyses with the multivariable adjustment, lower GC-IPL thickness was significantly associated with lower volume of known brain regions related to cognitive functions (i.e., the hippocampus, amygdala, entorhinal area, and parahippocampal gyrus) and visual functions (i.e., the cuneus, lingual gyrus, and thalamus). Meanwhile, the volume of the thalamus significantly decreased with lower RNFL thickness, but none of the brain regions related to cognitive function exhibited a volume change in association with RNFL thickness. The sensitivity analysis using FreeSurfer analysis also showed that lower GC-IPL thickness was significantly associated with lower regional brain volume/intracranial volume of the hippocampus, amygdala, cuneus, lingual gyrus, and thalamus. Conclusions: Our findings suggest that the measurement of GC-IPL thickness by SS-OCT, which is a noninvasive, convenient, and reproducible method, might be useful for identifying high-risk individuals with dementia.

DOI： 10.1016/j.xops.2022.100157

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記述言語：英語  

記述言語：英語  

記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: To investigate the utility of Optos ultrawide-field fundus autofluorescence (UWF-FAF) imaging for postoperative follow-up of gas-filled eyes after vitrectomy with subretinal tissue-plasminogen activator (t-PA) injection for subretinal hemorrhage (SRH) displacement. Study design: Retrospective consecutive case series. Methods: This study included 24 eyes with SRH. Vitrectomy with subretinal t-PA injection was performed, followed by postoperative prone positioning. FAF images acquired using Optos California were examined and the SRH occupancy in the macula was calculated. The main outcome measures were displacement rate and direction of SRH for 3 days postoperatively, and postoperative best-corrected visual acuity (BCVA). Results: The postoperative BCVA ranged from improvement (23 eyes; 95.8%) to no change (one eye; 4.2%). Analysis was done using postoperative Optos FAF images for 20 eyes (83.3%). Postoperative SRH occupancy was significantly reduced, by 27.4%, compared with the preoperative occupancy (P = 0.03). A statistically significant reduction was found between the preoperative and postoperative day (POD)1 (P = 0.04), but not between POD1 and POD2 (P = 0.7), or between POD2 and POD3 (P = 1.0). Conclusion: UWF-FAF imaging is useful for postoperative follow-up of gas-filled eyes after vitrectomy with subretinal t-PA injection for SRH displacement.

DOI： 10.1007/s10384-022-00910-7

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記述言語：英語  

記述言語：英語   出版者・発行元：Ophthalmology Retina  

Purpose: To investigate the long-term outcomes of cataract surgery in patients with retinitis pigmentosa (RP). Design: Retrospective, observational study. Participants: Sixty-four patients with typical RP (22 men, 42 women; average age, 62.8 ± 10.1 years) who underwent cataract surgery at Kyushu University Hospital between May 2007 and October 2015 and were followed up for ≥3 years after the surgery. Methods: Differences between presurgery and postsurgery visual function, including best-corrected visual acuity (BCVA) and parameters in the Humphrey field analyzer (HFA) examination using the central 10-2 program, were investigated. The presurgery conditions of the foveal ellipsoid zone (EZ) were classified into 3 grades (grade 1: invisible; grade 2: abnormal; grade 3: normal) based on OCT findings. Main Outcome Measures: BCVA, the retinal sensitivity in the HFA 10-2 test. Results: Cataract surgery was performed in 96 eyes, with an average follow-up period of 5.8 ± 2.4 years. The mean presurgery BCVA was 0.64 ± 0.52 logarithm of the minimum angle of resolution (logMAR), and the final postsurgery BCVA was 0.61 ± 0.67 logMAR (P = 0.57). Significant improvement in the postsurgery BCVA was observed only in eyes with preserved foveal EZ (grade 3) (P < 0.01). In 62 eyes of 45 patients who underwent the HFA 10-2 test, the mean values of deviation, macular sensitivity, and foveal sensitivity at the final visit were significantly decreased compared with preoperative values (P < 0.01), whereas those in grade 3 eyes did not change significantly after the surgery (P = 0.13). Conclusions: In the long-term course after cataract surgery in patients with RP, many patients experienced vision loss with progression of the disease. The preoperative finding of preserved foveal EZ was associated with a better visual prognosis, suggesting that EZ evaluation is useful for predicting the long-term visual outcome of cataract surgery in patients with RP.

DOI： 10.1016/j.oret.2021.12.010

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PubMed

記述言語：英語   出版者・発行元：Gynecologic Oncology  

Objective: Sentinel node biopsy alone (SNB) reduces the postoperative complications of pelvic lymphadenectomy, such as lymphedema and lymphangitis; however, the long-term prognosis after SNB is unclear. The objective of this study was to evaluate the long-term outcome and complications of patients with early-stage cervical cancer who underwent SNB for hysterectomy or trachelectomy. Methods: We performed SNB for cervical cancer using a radioisotope method in 181 patients between 2009 and 2017. If the intraoperative sentinel lymph node evaluation was negative for metastasis, no further lymph nodes were removed. Results: The median age of the patients was 34 years (range, 21–73 years). The International Federation of Gynecology and Obstetrics 2008 stage was IA1 in 6 patients, IA2 in 18, IB1 in 154, and IIA1 in 3. Of the 181 patients (44 with hysterectomy, 137 with trachelectomy), 8 did not undergo pelvic lymphadenectomy because of a false-negative intraoperative diagnosis, 20 received adjuvant therapy after surgery, and 4 (2.2%) experienced recurrence over a median follow-up period of 83.5 months (range, 25–145 months). In the four recurrent cases, recurrence occurred in the pelvis, lung, and bone in one patient each, while the remaining patient developed pelvic and para-aortic lymph node metastases. Of these four patients, one died, and the remaining three are alive without disease after multidisciplinary therapy. The 5-year progression-free and overall survival rates were 98.8% and 99.4%, respectively. Postoperative complications, such as lymphedema, were very low rate. Conclusions: SNB for early-stage cervical cancer might be safe and effective, with no increase in the recurrence and postoperative complications rate.

DOI： 10.1016/j.ygyno.2022.01.031

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PubMed

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：英語   出版者・発行元：Pnas Nexus  

Retinitis pigmentosa (RP) is an intractable inherited disease that primarily affects the rods through gene mutations followed by secondary cone degeneration. This cone-related dysfunction can lead to impairment of daily life activities, and ultimately blindness in patients with RP. Paradoxically, microglial neuroinflammation contributes to both protection against and progression of RP, but it is unclear which population(s)— tissue-resident microglia and/or peripheral monocyte-derived macrophages (mϕ)— are implicated in the progression of the disease. Here, we show that circulating blood inflammatory monocytes (IMo) are key effector cells that mediate cone cell death in RP. Attenuation of IMo and peripherally engrafted mϕ by Ccl2 deficiency or immune modulation via intravenous nanoparticle treatment suppressed cone cell death in rd10 mice, an animal model of RP. In contrast, the depletion of resident microglia by a colony-stimulating factor 1 receptor inhibitor exacerbated cone cell death in the same model. In human patients with RP, IMo was increased and correlated with disease progression. These results suggest that peripheral IMo is a potential target to delay cone cell death and prevent blindness in RP.

DOI： 10.1093/pnasnexus/pgac003

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記述言語：英語  

記述言語：英語  

記述言語：英語   出版者・発行元：Ocular Oncology and Pathology  

Angiosarcoma is a widely known neoplasm with one of the poorest prognoses; however, such cases are rarely observed by the ophthalmologists in clinical practice. The tumor commonly develops on the face and scalp and may cause eyelid swelling. We present 2 such cases. Case 1 was an 82-year-old woman who presented with indulated swelling of the right eyelid that extended to the upper forehead. Biopsy revealed a poorly circumscribed tumor infiltrated throughout the dermis and fat tissue, exhibiting both angiomatous and solid patterns. Immunohistochemistry showed CD31(-) and D2-40/podoplanin(+), suggesting angiosarcoma. The patient had multiple lung metastases and died 14 months later. Case 2 was a 77-year-old man who presented with swelling of the left eyelid, and erythema on the left temporal skin developed ulcerated nodules. Biopsy showed proliferated tumor cells in a sheet form, extensively throughout the dermis. Angiosarcoma was preferred based on immunohistochemistry: CD31(+), CD34(+), and D2-40(-). The patient was treated with electron beam therapy and chemotherapy and died after 13 months. It would be difficult for an ophthalmologist to suspect such a rare neoplasm only from swelling of the eyelids. However, angiosarcoma should be considered if the swelling spreads steadily from a head rash with a nodule or ulcer nearby.

DOI： 10.1159/000520293

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PubMed

記述言語：英語   出版者・発行元：Mucosal Immunology  

Autoimmune uveitis is a sight-threatening disease induced by pathogenic T cells that recognize retinal antigens; it is observed in disorders including Vogt–Koyanagi–Harada disease (VKH). The roles of specific T cell subsets and their therapeutic potential against autoimmune uveitis are not fully understood. Here we conducted multi-parametric single-cell protein quantification which shows that the frequency of CD161^highTRAV1-2⁺ mucosal-associated invariant T (MAIT) cells that recognize vitamin B2 metabolite-based antigens is decreased in relapsing VKH patients compared to individuals without active ocular inflammation. An experimental autoimmune uveitis (EAU) mouse model revealed that genetic depletion of MAIT cells reduced the expression of interleukin (Il) 22 and exacerbated retinal pathology. Reduced IL-22 levels were commonly observed in patients with relapsing VKH compared to individuals without active ocular inflammation. Both mouse and human MAIT cells produced IL-22 upon stimulation with their antigenic metabolite in vitro. An intravitreal administration of the antigenic metabolite into EAU mice induced retinal MAIT cell expansion and enhanced the expressions of Il22, as well as its downstream genes related to anti-inflammatory and neuroprotective effects, leading to an improvement in both retinal pathology and visual function. Taken together, we demonstrate that a metabolite-driven approach targeting MAIT cells has therapeutic potential against autoimmune uveitis.

DOI： 10.1038/s41385-021-00469-5

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PubMed

記述言語：英語   出版者・発行元：American Journal of Ophthalmology  

Purpose: To describe the factors associated with epiretinal membrane (ERM) formation in eyes treated with pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). Design: Nationwide, multicenter, clinical cohort study based on registry data. Methods: We reviewed 2239 cases treated with PPV for RRD repair registered in the Japan-Retinal Detachment Registry between February 2016 and March 2017. Associations of 13 baseline characteristics and 8 surgical procedures with ERM formation were evaluated using univariate analysis. We conducted a propensity score–matched analysis for the significantly associated clinical factor(s). The primary outcome measure was ERM formation after 6 months of vitrectomy. Results: ERM had developed in 104 cases (4.6%) by 6 months. We found that drainage retinotomy was significantly associated with ERM after multiple testing correction (odds ratio [OR] 2.22 [95% confidence interval {CI} 1.50-3.31]; P < .001). In the propensity score–matched analysis (n = 492 in each group), we confirmed a significant difference in the incidence of ERM after 6 months of vitrectomy (8.3% and 2.6% in cases with and without drainage retinotomy, respectively; OR 3.35 [95% CI 1.77-6.33]; P < .001). Conclusions: Eyes treated with PPV combined with drainage retinotomy are more likely to develop ERM postoperatively.

DOI： 10.1016/j.ajo.2021.07.028

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PubMed

出版者・発行元：株式会社医学書院  

DOI： 10.11477/mf.1410214260

CiNii Research

記述言語：英語   出版者・発行元：Biology Methods and Protocols  

With the advent of new molecular diagnostic techniques, retrieving DNA from the formalin-fixed paraffin-embedded (FFPE) tissues has become an essential yet challenging step for efficient downstream processes. Owing to low quality and quantity of DNA retrieved from the FFPE sections, the process is often impractical and needs significant improvements. Here, we established an efficient method for the purification of DNA from FFPE specimens by optimizing incubation temperature, incubation time, and the concentration of a formalin scavenger tris(hydroxymethyl)aminomethane (Tris) for reverse-crosslinking. The optimized method, named "Highly concentrated Tris-mediated DNA extraction"(HiTE), yielded three times the DNA yield per tissue slice compared with a representative DNA extraction kit. Moreover, the use of HiTE-extracted DNA increased the yield of the sequencing library three times and accordingly yielded a log higher and more reproducible sequencing library compared with that obtained using the commonly used commercial kit. The sequencing library prepared from HiTE-extracted FFPE-DNA had longer inserts and produced reads that evenly covered the reference genome. Successful application of HiTE-extracted FFPE-DNA for whole-genome and targeted gene panel sequencing indicates its practical usability.

DOI： 10.1093/biomethods/bpac014

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記述言語：英語   出版者・発行元：Ocular Immunology and Inflammation  

Purpose: To identify the clinical characteristics of acute retinal necrosis (ARN) and clarify factors associated with poor visual prognosis. Methods: a nationwide multi-center retrospective chart review study was performed in Japan using data from the medical records of 149 consecutive ARN patients. Demographics, ocular signs, virologic testing of intraocular fluids, and treatment were examined. Factors associated with poor visual prognosis were investigated by regression analysis. Results: At initial presentation, anterior chamber cells or mutton-fat keratic precipitates (97%), unilaterality (93%), and yellow-white retinal lesions (86%) were recognized. In the clinical course, rapid circumferential expansion of retinal lesions (39%), development of retinal break or retinal detachment (55%), and optic atrophy (43%) were recorded. Four variables were identified as associated with poor visual prognosis. Conclusions: The present study identified clinical characteristics and factors associated with poor visual prognosis of ARN.

DOI： 10.1080/09273948.2020.1789179

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記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：英語   出版者・発行元：Translational Vision Science and Technology  

Purpose: To estimate the prevalence of glaucoma and its risk factors in a Japanese community. Methods: This study included 3405 Japanese community dwellers who were ≥40 years of age and enrolled in the Hisayama Study. This population-based, cross-sectional study was conducted from 2017 to 2018. A glaucoma screening test was performed using stereo fundus images and swept-source optical coherence tomography. Glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. Results: The prevalence of glaucoma was 7.6% (95% confidence interval [CI], 6.7–8.6) overall. The prevalence of primary open-angle glaucoma (POAG) was 5.8% (95% CI, 5.0– 6.6); that of primary angle-closure glaucoma (PACG) was 0.7% (95% CI, 0.5–1.1); and that of exfoliation glaucoma was 1.1% (95% CI, 0.7–1.4). In addition to aging, lower estimated glomerular filtration rate (eGFR) (odds ratio [OR] = 1.15; 95% CI, 1.02–1.33), higher intraocular pressure (OR = 1.06; 95% CI, 1.01–1.12), longer axial length (OR = 1.44; 95% CI, 1.31–1.59), and thinner central corneal thickness (CCT) (OR = 1.09; 95% CI, 1.04–1.15) were significant risk factors for POAG. Diabetes (OR = 2.81; 95% CI, 1.19– 6.62) was a significant risk factor for PACG, and diabetes (OR = 2.15; 95% CI, 1.03–4.47) and thinner CCT (OR = 1.14; 95% CI, 1.02–1.28) were significant risk factors for exfoliation glaucoma. Conclusions: The prevalence of glaucoma was approximately 8%, probably due to the increase in the Japanese aging population. Not only ocular factors but also lower eGFR for POAG and diabetes for PACG and exfoliation glaucoma were risk factors in a general Japanese population. Translational Relevance: Systemic factors such as eGFR and diabetes must also be considered when implementing preventive measures against glaucoma.

DOI： 10.1167/tvst.11.11.11

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PubMed

記述言語：日本語   出版者・発行元：公益社団法人 日本視能訓練士協会  

<p> <b>【背景】</b>視神経炎との鑑別に苦慮した視神経管内神経鞘腫の1例を経験したので報告する。</p><p> <b>【症例】</b>25歳女性。3ヶ月前より左眼視力低下あり、ステロイドパルス3クール行うも効果なく、当科紹介受診。初診時左視力（0.04）、MRIで左視神経に径5×5mmの結節状病変を認めた。前医を含めた4回のステロイドパルスで視機能改善はなく、放射線治療にも病変の縮小が見られず腫瘍性疾患と考えた。初診後1年7ヶ月左眼光覚消失に至った。初診後3年4ヶ月腫瘍は10×7mmまで増大し、腫瘍摘出術を施行した。切除組織から腫瘍は神経鞘腫と確定診断した。</p><p> <b>【結果】</b>急速に視機能低下を呈する疾患の鑑別診断として神経鞘腫を考慮すべきである。</p>

DOI： 10.4263/jorthoptic.52f114

CiNii Research

記述言語：英語   出版者・発行元：Case Reports in Ophthalmology  

The aim of this paper was to report the cases of 3 consecutive patients with mitogen-activated protein kinase kinase inhibitor (MEKi)-associated retinopathy with characteristic multiple serous retinal detachments (SRDs). A functional analysis of the retinal pigment epithelium was performed in 2 patients by electro-oculography (EOG). In all 3 patients, SRD lesions were observed in the posterior pole including the fovea of both eyes. Interestingly, neither obvious leakage in fluorescein/indocyanine angiography nor abnormal fundus autofluorescence was associated. SRDs and associated cystoid macular edema in one case rapidly resolved with the cessation of MEKi but recurred quickly after treatment resumption. In EOG tests, three of four eyes with multiple SRDs showed a marked decrease in the light-peak-to-dark-trough ratio (LP:DT ratio). The LP:DT ratio in EOG reflects the transepithelial potential of the retinal pigment epithelium, suggesting the involvement of disrupted tight junctions and impaired active transport of fluid/ions in MEKi-associated retinopathy. The latter may be the major cause of SRDs as we observed that fluid leakage in angiography was absent in the areas of the patients' SRDs.

DOI： 10.1159/000524558

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記述言語：英語   出版者・発行元：Case Reports in Ophthalmology  

Bullous retinal detachment is a rare complication in the chronic phase of central serous chorioretinopathy (CSC). Only a small subset of eyes with chronic CSC develops into the bullous variant of CSC (bCSC). In patients with bCSC, the elevated concentration of fibrin in the subretinal space leads to persistent retinal detachment and eventually, severe vision loss. We experienced a case of unilateral bCSC with a massive accumulation of subretinal fibrin. Multiple leakage points and dilated choroidal veins were also observed. The patient underwent surgical removal of subretinal fibrin and silicone oil injection followed by photodynamic therapy (PDT). After this treatment, the retina was successfully reattached, and the affected eye was free from recurrent exudative changes for more than 18 months. Massive subretinal fibrin could be surgically removed to prevent the formation of subretinal fibrosis and retinal fold, and PDT under silicone oil can control the underlying exudative changes in bCSC.

DOI： 10.1159/000524515

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記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：英語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語   掲載種別：研究論文（大学，研究機関等紀要）  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：European Journal of Ophthalmology  

Purpose: To report optical coherence tomography angiography (OCTA) findings in a case of immune choroiditis following contralateral acute retinal necrosis (ARN) with choroidal neovascularization (CNV) during anti-vascular endothelial growth factor (VEGF) therapy. Case report: A 64-year-old woman with immune choroiditis following contralateral ARN and secondary CNV presented with decreased visual acuity. Fundus examination revealed macular and peripheral yellowish lesions in the right eye. Inflammatory cells were observed in the anterior chamber and the vitreous. OCT revealed retinal exudative changes and subretinal lesions suggestive of CNV. OCTA detected an abnormal vascular net in the outer retina as well as choriocapillaris, corresponding to type 2 CNV, that reduced following intravitreous anti-VEGF therapy. Two weeks after treatment, OCTA showed re-dilated choroidal neovasculature at the outer retina despite no exudative recurrence in OCT. Six weeks after treatment, OCT detected exudative changes around the neovascular lesion. Conclusion: This case discusses the use of OCTA detection of CNV in a case of immune choroiditis following contralateral ARN. During anti-VEGF therapy for inflammatory CNV-related diseases, OCTA may be useful not only for CNV detection but also for the follow-up of CNV activity.

DOI： 10.1177/1120672120977349

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41433-020-01321-z

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.oret.2020.05.012

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study aims to investigate the changes in metamorphopsia after administering the treat-
and-extend regimen of anti-vascular endothelial growth factor therapy for branch retinal vein
occlusion-associated macular edema. We retrospectively examined 27 patients (27 eyes) with macula
edema due to branch retinal vein occlusion who received intravitreal injections of anti-vascular
endothelial growth factor agents using the treat-and-extend regimen for
�18 months. We evaluated best-corrected visual acuity, central macular thickness, macular edema
recurrence, and amount of metamorphopsia quantified by M-CHARTS. The best- corrected visual acuity
(logarithm of minimum angle of resolution) and central macular thick- ness significantly improved
at 18 months compared to baseline, the median value (inter- quartile range [IQR]), 0.30 (0.15–0.52)
and 459 (373–542) μm at baseline, and 0 (-0.08– 0.16) and 267 (232–306) μm at 18 months. The
M-CHARTS score (the mean of vertical and horizontal scores) significantly decreased at 1, 6, and 12
months compared to baseline, but worsened at 18 month, the median value (IQR), 0.45 (0.250–0.925),
0.4 (0.15–0.70), 0.4
(0.150–0.625), 0.4 (0.225–0.550) and 0.45 (0.225–0.750) at baseline, 1 month, 6 months, 12 months
and 18 months, respectively. The median cumulative number of macular edema recurrences was 2 (IQR,
0.5–3.0) at 18 months. Simple linear regression and multivariate analyses revealed that the change
in the mean M-CHARTS score at 18 months was signifi- cantly correlated with the baseline score and
the cumulative number of macular edema recurrences. Anti-vascular endothelial growth factor therapy
using the treat-and-extend regi- men improved metamorphopsia in branch retinal vein
occlusion-related macular edema in the short to mid-term follow-up period, but not in the long
term. Macular edema recurrence
may be associated with persistent metamorphopsia.

DOI： org/10.1371/journal.pone.0241343

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To report the clinical course and high resolution images of autosomal recessive retinitis pigmentosa (RP) associated with a variant of the RP1 gene (c.4052_4053ins328/p.Tyr1352Alafs*9; m1), a high frequency founder variant in Japanese RP patients. Study design: Retrospective case series. Methods: Nine patients from 5 unrelated Japanese families were studied. Five patients had the m1 variant homozygously, and 4 patients had the m1 variant compound heterozygously with another frameshift variant (c.4196delG/p.Cys1399Leufs*5). Ophthalmic examinations including adaptive optics (AO) fundus imaging were performed periodically. Results: The fundus photographs, fundus autofluorescence (FAF) images, and optical coherence tomographic (OCT) images indicated severe retinal degeneration in all the patients involving the macula even at a young age (20 s). The areas of surviving photoreceptors in the central macula were seen as hyper-autofluorescent regions in the FAF images and preserved outer retinal structure in the OCT images; they were identifiable in the AO fundus images in 8 eyes. The borders of the surviving photoreceptor areas were surrounded by hyporeflective clumps, presumably containing melanin, and the size of these areas decreased progressively during the 4-year follow-up period. The disappearance of the surviving photoreceptor areas was associated with complete blindness. Conclusion: Patients with RP associated with the m1 variant have a progressive and severe retinal degeneration that begins at an early age. Monitoring the surviving photoreceptor areas by AO fundus imaging can provide a more precise pathological record of retinal degeneration.

DOI： 10.1007/s10384-020-00752-1

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To report the clinical course and high resolution images of autosomal recessive retinitis pigmentosa (RP) associated with a variant of the RP1 gene (c.4052_4053ins328/p.Tyr1352Alafs*9; m1), a high frequency founder variant in Japanese RP patients.

Study design: Retrospective case series.

Methods: Nine patients from 5 unrelated Japanese families were studied. Five patients had the m1 variant homozygously, and 4 patients had the m1 variant compound heterozygously with another frameshift variant (c.4196delG/p.Cys1399Leufs*5). Ophthalmic examinations including adaptive optics (AO) fundus imaging were performed periodically.

Results: The fundus photographs, fundus autofluorescence (FAF) images, and optical coherence tomographic (OCT) images indicated severe retinal degeneration in all the patients involving the macula even at a young age (20 s). The areas of surviving photoreceptors in the central macula were seen as hyper-autofluorescent regions in the FAF images and preserved outer retinal structure in the OCT images; they were identifiable in the AO fundus images in 8 eyes. The borders of the surviving photoreceptor areas were surrounded by hyporeflective clumps, presumably containing melanin, and the size of these areas decreased progressively during the 4-year follow-up period. The disappearance of the surviving photoreceptor areas was associated with complete blindness.

Conclusion: Patients with RP associated with the m1 variant have a progressive and severe retinal degeneration that begins at an early age. Monitoring the surviving photoreceptor areas by AO fundus imaging can provide a more precise pathological record of retinal degeneration.

Keywords: Adaptive optics images; Autosomal recessive retinitis pigmentosa; Fundus autofluorescence; RP1.

DOI： 10.1007/s10384-020-00752-1

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: Japan has been known as a super-aged society, and ageing is a well-known risk factor for blinding eye diseases. However, epidemiological studies in ophthalmology are still scarce in Japan, and the sizes of the cohorts are relatively small. "Ganka-Ekigaku Network" (GEN, an acronym for the epidemiological network in ophthalmology in Japanese) is established to develop a capacity to boost each epidemiological study and enrich a potential inter-study collaboration to identify risk factors of visual impairment in aged society.

Methods: We reviewed cohort studies in Japan with the inclusion criteria as: (1) at least n = 1000 at baseline, (2) multiple modalities of ophthalmic data, and (3) diagnosis reviewed by ophthalmologist(s), and (4) ophthalmologists are involved in the investigators group. As of January 2020, GEN includes 4 individual Japanese epidemiological studies namely, Hisayama study, Yamagata Study (Funagata), Tsuruoka Metabolomics Cohort study, and the Nagahama Prospective Genome Cohort for Comprehensive Human Bioscience.

Results: GEN includes approximately 25,000 Japanese participants. The baseline surveys started from 1998 to 2012, and since then the data has been prospectively collected approximately every 5 years. A variety of ophthalmic measurements and other factors have been collected in each study in GEN: ophthalmic measurements (fundus photography, optical coherence tomography, etc.), systemic conditions (laboratory data, etc.), and others (DNA, etc.).

Conclusion: GEN is an open platform for observational ophthalmic epidemiological studies to share standardized methodologies. While each study in GEN pursues specific and original research questions, standardization of the methods will enable us to conduct reliable meta-analysis/pooled data analyses.

Keywords: cohort study; consortium; meta-analysis; pooled data analysis; risk factor.

DOI： 10.1080/09286586.2020.1815803

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Vitreoretinal lymphoma (VRL) is a rare disease of B-cell origin with poor prognosis. Regulatory cytokines promote tumor development by suppressing antitumor immunity in several cancer types, including B-cell malignancies. To identify the regulatory cytokines associated with poor prognosis in patients with B-cell VRL, we determined the regulatory cytokines profiles in the vitreous humor of patients with VRL. This retrospective study included 22 patients with VRL, 24 with non-infectious uveitis (NIU), and 20 with idiopathic epiretinal membrane (control). Vitreous concentrations of regulatory cytokines were assessed using a cytometric beads assay and association with clinical data was examined. IL-35 and soluble IL-2 receptor α levels were significantly higher in patients with VRL and NIU than those in the control group. The 5-year overall survival (OS) rates for the group with high intravitreal IL-35 was significantly poorer than those for the group with low intravitreal IL-35, who were diagnosed with VRL at the onset (P = 0.024, log-rank test). The 5-year OS rates with intravitreal IL-35 levels above and below the median were 40.0% and 83.3%, respectively. Our results suggest that high intravitreal IL-35 levels indicate poor prognosis for patients diagnosed with B-cell VRL at the onset.

DOI： 10.1038/s41598-020-72962-z

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To evaluate the safety and efficacy of BBG (Brilliant Blue G250) for lens capsular staining during cataract surgery with continuous curvilinear capsulorhexis. Study design: Prospective clinical study. Methods: This clinical trial enrolled 30 eyes of 30 patients who underwent cataract surgery with BBG (0.25 mg/mL Brilliant Blue G250) for capsular staining. Visualization of the lens capsule and the ease of capsulorhexis with BBG staining were evaluated in five grades (grade 0 to 4) by the Independent Data Monitoring Committee and the surgeons. The safety of BBG was also evaluated in terms of ocular and systemic tolerance for 7 days after surgery. Results: The use of BBG improved visualization of the lens capsule and complete capsulorhexis was performed in all patients. The major endpoint (Independent Data Monitoring Committee evaluation) showed that use of BBG improved visualization of the lens capsule and the ease of capsulorhexis (grades 2 to 4); the committee’s grading results were similar to those of the surgeons. Frequent complications observed in more than two eyes were conjunctival injection, corneal edema and intraocular pressure elevation. No severe complications were observed in ocular and systemic evaluations. Conclusion: BBG staining contributed to improved visualization of the lens capsule and aided in the completion of capsulorhexis during cataract surgery. The use of BBG for capsular staining also exhibited favorable safety results.

DOI： 10.1007/s10384-020-00763-y

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: Retinal degeneration involves neuroinflammation, and pro-inflammatory cytokines/chemokines are markedly increased in the eyes of patients with retinitis pigmentosa (RP). In this study, we investigated the changes of serum cytokines/chemokines in RP, and their relationships with visual parameters.

Methods: Forty-five consecutive patients with typical RP aged 20 to -39 years and 28 age-matched and gender-matched controls were included. Fifteen cytokines (interleukin [IL]-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, 1L-15, IL-17, IL-23, interferon [IFN]-γ, and tumor necrosis factor [TNF]-α, TNF-β) and 9 chemokines (eotaxin, growth-related oncogene [GRO]-α, I-309, IL-8, IFN-γ-inducible protein [IP]-10, monocyte chemotactic protein [MCP]-1, MCP-2, regulated activation normal T-cell expressed and secreted [RANTES], and thymus and activated regulated chemokine [TARC]) in the serum were simultaneously measured by a multiplexed immunoarray (Q-Plex). Relationships between these cytokines/chemokines and indices of central vision, such as visual acuity (VA), the values of static perimetry tests (Humphrey Field analyzer, the central 10-2 program), and optical coherence tomography measures were analyzed in the patients with RP.

Results: Among the 15 cytokines and 9 chemokines, serum IL-8 and RANTES levels were significantly increased in patients with RP compared with controls (IL-8: P < 0.0001; RANTES: P < 0.0001). Among the elevated cytokines/chemokines, the levels of IL-8 were negatively correlated with VA (ρ = 0.3596 and P = 0.0165), and the average retinal sensitivity of four central points (ρ = -0.3691 and P = 0.0291), and 12 central points (ρ = -0.3491 and P = 0.0398), as well as the central subfield thickness (ρ = -0.3961 and P = 0.0094), and ellipsoid zone width (ρ = -0.3841 and P = 0.0120).

Conclusions: Peripheral inflammatory response may be activated and serum IL-8 levels are associated with central vision in patients with RP.

DOI： 10.1167/iovs.61.11.30

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Importance: Myopic maculopathy is a leading cause of irreversible visual impairment worldwide. Moreover, the burden of myopic maculopathy has been expected to increase owing to the rising prevalence of myopia globally. However, there is limited epidemiologic evidence regarding the incidence of and risk factors for myopic maculopathy. This study from Japan, with a relatively high prevalence of myopia, could provide valuable information related to these issues.

Objective: To estimate the incidence of myopic maculopathy and its risk factors in Hisayama in southwestern Japan.

Design, setting, and participants: A population-based prospective cohort study in a Japanese community in Hisayama, Japan. The study included a total of 2164 residents 40 years or older who had no myopic maculopathy at the baseline eye examination in 2012 and underwent follow-up eye examinations in 2017.

Main outcomes and measures: Incidence of myopic maculopathy. The grades of myopic maculopathy were categorized based on the criteria of the Meta-analysis of Pathologic Myopia Study Group classification system.

Results: The mean (SD) age of the study participants was 62.4 (10.9) years, and the proportion of men was 42.5% (920 participants). In the follow-up examination in 2017, 24 patients developed myopic maculopathy. The 5-year cumulative incidence of myopic maculopathy was 1.1% (95% CI, 0.6-1.5) overall, 1.4% (95% CI, 0.6-2.2) for men, and 0.9% (95% CI, 0.4-1.4) for women. Multiple logistic regression analysis showed that older age (per 1 year; odds ratio [OR], 1.06; 95% CI, 1.01-1.11) and longer axial length (per 1 mm; OR, 2.94; 95% CI, 2.19-3.95) were associated with incident myopic maculopathy.

Conclusions and relevance: Twenty-four study participants (1%) developed myopic maculopathy during the 5-year study period, which is much higher than the rate in a previous study on a Chinese population. We also confirmed that aging and longer axial length were independent and significant risk factors for myopic maculopathy. These findings should be reviewed among various populations in other parts of the world.

DOI： 10.1001/jamaophthalmol.2020.2211

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1167/iovs.61.10.6

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In the twentieth century, a conspicuous lack of effective treatment strategies existed for managing several retinal disorders, including age-related macular degeneration; diabetic retinopathy (DR); retinopathy of prematurity (ROP); retinitis pigmentosa (RP); uveitis, including Behçet's disease; and vitreoretinal lymphoma (VRL). However, in the first decade of this century, advances in biomedicine have provided new treatment strategies in the field of ophthalmology, particularly biologics that target vascular endothelial growth factor or tumor necrosis factor (TNF)-α. Furthermore, clinical trials on gene therapy specifically for patients with autosomal recessive or X-linked RP have commenced. The overall survival rates of patients with VRL have improved, owing to earlier diagnoses and better treatment strategies. However, some unresolved problems remain such as primary or secondary non-response to biologics or chemotherapy, and the lack of adequate strategies for treating most RP patients. In this review, we provide an overview of the immunological mechanisms of the eye under normal conditions and in several retinal disorders, including uveitis, DR, ROP, RP, and VRL. In addition, we discuss recent studies that describe the inflammatory responses that occur during the course of these retinal disorders to provide new insights into their diagnosis and treatment.

DOI： 10.3389/fimmu.2020.01431

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE. To investigate the association between aqueous flare and progression of visual field loss using the Humphrey Field Analyzer in patients with retinitis pigmentosa (RP). METHODS. We examined a total of 101 eyes of 101 patients who were diagnosed with typical RP. Sixty-one percent of the patients were female, and the mean age of the total group was 47.4 years. Aqueous flare, visual field (by an Humphrey Field Analyzer, the central 10-2 SITA-Standard program), and optical coherence tomography measurements were obtained for all patients. The slope, which was derived from serial values of mean deviation, macular sensitivity, or foveal sensitivity for each eye with univariate linear regression, was used for analysis. RESULTS. Aqueous flare values were significantly correlated with the mean deviation slope (r =-0.20, P = 0.046), macular sensitivity slope (r =-0.28, P = 0.005) and foveal sensitivity slope (r =-0.20, P = 0.047). The values of the retinal sensitivity slope significantly decreased as the aqueous flare level increased (all P < 0.05). These associations remained unchanged after adjustment for age, sex, and posterior subcapsular cataract, and epiretinal membrane. CONCLUSIONS. Elevation of aqueous flare is a risk factor for the decline of central visual function in RP. Aqueous flare may be a useful marker for disease progression in RP.

DOI： 10.1167/IOVS.61.8.26

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ischemic proliferative retinopathy (IPR), such as proliferative diabetic retinopathy (PDR), retinal vein occlusion and retinopathy of prematurity is a major cause of vision loss. Our previous studies demonstrated that periostin (PN) and tenascin-C (TNC) are involved in the pathogenesis of IPR. However, the interactive role of PN and TNC in angiogenesis associated with IPR remain unknown. We found significant correlation between concentrations of PN and TNC in PDR vitreous humor. mRNA and protein expression of PN and TNC were found in pre-retinal fibrovascular membranes excised from PDR patients. Interleukin-13 (IL-13) promoted mRNA and protein expression of PN and TNC, and co-immunoprecipitation assay revealed binding between PN and TNC in human microvascular endothelial cells (HRECs). IL-13 promoted angiogenic functions of HRECs. Single inhibition of PN or TNC and their dual inhibition by siRNA suppressed the up-regulated angiogenic functions. Pathological pre-retinal neovessels of oxygen-induced retinopathy (OIR) mice were attenuated in PN knock-out, TNC knock-out and dual knock-out mice compared to wild-type mice. Both in vitro and in vivo, PN inhibition had a stronger inhibitory effect on angiogenesis compared to TNC inhibition, and had a similar effect to dual inhibition of PN and TNC. Furthermore, PN knock-out mice showed scant TNC expression in pre-retinal neovessels of OIR retinas. Our findings suggest that interaction of PN and TNC facilitates pre-retinal angiogenesis, and PN is an effective therapeutic target for IPR such as PDR.

DOI： 10.1038/s41598-020-66278-1

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: Although vitrectomy has been reported to be effective for the treatment of macular retinoschisis associated with glaucoma in a few case series, the surgical techniques have yet to be established. This article aimed to describe the cases of two patients with macular retinoschisis who underwent vitrectomy with peripapillary internal limiting membrane peeling around the defective area of the retinal nerve fiber layer. Observations: Both patients had been diagnosed with normal tension glaucoma and treated with eye drops to stabilize intraocular pressure. Progression of macular retinoschisis and accompanied vision loss were observed in both cases. Twelve months after the surgery, both patients had resolution of the retinoschisis and improvement in best corrected visual acuity. Conclusions and importance: Our surgical technique may be effective for the resolution of macular retinoschisis in eyes with normal tension glaucoma.

DOI： 10.1016/j.ajoc.2020.100663

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: In diabetic retinopathy (DR), OCT angiography (OCTA) could not image all fluorescein angiography (FA)-detected microaneurysms. We investigated whether multiple image averaging could enhance the microaneurysm detection capability of OCTA in patients with DR.

Design: Prospective and cross-sectional observational study.

Participants: Consecutive 31 patients (n = 62 eyes) with DR.

Methods: All eyes underwent FA and 3 × 3 mm fovea-centered OCTA images were obtained using 2 devices: RTVue XR Avanti (Optovue Inc, Fremont, CA) and OCT HS-100 (Canon Inc, Toyko, Japan). OCTA imaging (HS-100) was performed 10 consecutive times. Microaneurysm detection capability was compared among 5 OCTA images (single image, ×3, ×5, and ×10 averaged images and single scan image with the RTVue XR Avanti device).

Main outcome measures: Microaneurysm detection capability and the correlation between microaneurysm clinical characteristics or morphology and the extent of image averaging required for OCTA detection.

Results: A total of 415 microaneurysms could be analyzed in 31 eyes from 25 patients. Microaneurysms detected on single image, ×3, ×5, and ×10 averaged OCTA images were 144 (34.7%), 227 (54.7%), 285 (68.7%), and 306 (73.7%), respectively. Microaneurysm detection capability was significantly increased with increased image averaging. Microaneurysm detection with OCTA was not correlated with retinal thickness, FA leakiness, and indocyanine green angiogram detection or the number of averaged images, whereas there was significant correlation between microaneurysm morphology and microaneurysm visibility by the image-averaging process for 4 morphologies, particular the focal bulge types (P < 0.01).

Conclusions: In DR, multiple image averaging is useful for increasing the microaneurysm detection capability of OCTA, especially for focal bulge-type microaneurysms

DOI： 10.1016/j.oret.2019.09.010

記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To report the demographics and clinical characteristics of patients with a primary retinal detachment (RD). Design: Prospective cohort study by a registry design. Participants: Patients with RD treated at vitreoretinal sub-specialty institutions in Japan from February 2016 to March 2017. Methods: Descriptive statistics for the primary RD, and multivariable ordered logistic regression and multiple linear regression analyses were performed. Results: 3178 eyes of 3178 cases were analyzed. The interval from onset to surgery was significantly shorter in patients in the 40-year age group than in other age groups except for the 50-year age group (P<0.05, Steel-Dwass test). The proportion of complex cases was significantly higher in the 10-year, 70-year, and 80+ year age groups than in the 40 and 50-year age groups (P<0.05, Steel-Dwass test). The size of RD was significantly associated with the male sex (odds ratio, 1.29; 95% confidence interval [CI], 1.07 to 1.56; P=0.0085) and the interval from onset to surgery (odds ratio, 1.03 95% CI, 1.01 to 1.04; P=0.0014). Low IOPs in eyes with RD were significantly associated with an older age (-0.24 mmHg/10 years, 95% CI, -0.32 to -0.16], P<0.0001) and larger RD area (-0.91 mmHg/quadrant, 95% CI, [-1.06 to -0.76], P <0.0001). Conclusion: Profile and clinical characteristics of patients with a primary RD were not exactly the same as previous reports. A preoperative low IOP was associated with several ocular factors while the area of RD was associated not only with ocular but with social factors as well.

DOI： 10.1007/s10384-019-00702-6

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Innate immune cells such as neutrophils, monocyte-macrophages and microglial cells are pivotal for the health and disease of the retina. For the maintenance of retinal homeostasis, these cells and immunosuppressive molecules in the eye actively regulate the induction and the expression of inflammation in order to prevent excessive activation and subsequent tissue damage. In the disease context, these regulatory mechanisms are modulated genetically and/or by environmental stimuli such as damage-associated molecular patterns (DAMPs), and a chronic innate immune response regulates or contributes to the formation of diverse retinal disorders such as uveitis, retinitis pigmentosa, retinal vascular diseases and retinal fibrosis. Here we summarize the recent knowledge regarding the innate immune response in both ocular immune regulation and inflammatory retinal diseases, and we describe the potential of the innate immune response as a biomarker and therapeutic target.

DOI： 10.1016/j.preteyeres.2019.100778

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Optical coherence tomography angiography has a function to visualize the blood flow of multi-layered retinal capillary plexus by layer. OCTA signals would be more utilized if they are associated with blood flow dynamics of each layer. In this study, morphological top-hat transform was applied for OCTA en face retinal images of superficial and deep layers obtained from patients of diabetic retinopathy and controls to quantify the caliber-specific flow path length. As a result, the total length of the thick flow paths in deep layer more strongly reflected the progress of retinopathy than that in superficial layer. Supposing the thick flow paths observed in deep layer OCTA as a superposition of multiple capillaries, this trend seemed to be a possible expression of partial clogs of the capillary network.

DOI： 10.1541/ieejsmas.140.70

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Importance: Myopic maculopathy is a leading cause of irreversible visual impairment worldwide. Moreover, the burden of myopic maculopathy has been expected to increase owing to the rising prevalence of myopia globally. However, there is limited epidemiologic evidence regarding the incidence of and risk factors for myopic maculopathy. This study from Japan, with a relatively high prevalence of myopia, could provide valuable information related to these issues. Objective: To estimate the incidence of myopic maculopathy and its risk factors in Hisayama in southwestern Japan. Design, Setting, and Participants: A population-based prospective cohort study in a Japanese community in Hisayama, Japan. The study included a total of 2164 residents 40 years or older who had no myopic maculopathy at the baseline eye examination in 2012 and underwent follow-up eye examinations in 2017. Main Outcomes and Measures: Incidence of myopic maculopathy. The grades of myopic maculopathy were categorized based on the criteria of the Meta-analysis of Pathologic Myopia Study Group classification system. Results: The mean (SD) age of the study participants was 62.4 (10.9) years, and the proportion of men was 42.5% (920 participants). In the follow-up examination in 2017, 24 patients developed myopic maculopathy. The 5-year cumulative incidence of myopic maculopathy was 1.1% (95% CI, 0.6-1.5) overall, 1.4% (95% CI, 0.6-2.2) for men, and 0.9% (95% CI, 0.4-1.4) for women. Multiple logistic regression analysis showed that older age (per 1 year; odds ratio [OR], 1.06; 95% CI, 1.01-1.11) and longer axial length (per 1 mm; OR, 2.94; 95% CI, 2.19-3.95) were associated with incident myopic maculopathy. Conclusions and Relevance: Twenty-four study participants (1%) developed myopic maculopathy during the 5-year study period, which is much higher than the rate in a previous study on a Chinese population. We also confirmed that aging and longer axial length were independent and significant risk factors for myopic maculopathy. These findings should be reviewed among various populations in other parts of the world..

DOI： 10.1001/jamaophthalmol.2020.2211

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The eighth author’s name is spelled incorrectly. The correct name is: Kazuhiro Tokuda.

DOI： 10.1371/journal.pone.0231277

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To report 2 cases of oncocytoma in the lacrimal gland or near the lacrimal caruncle. Cases: One was a 67-year-old female and the other was a 65-year-old male. The first case had developed swelling of the left upper eyelid associated with swollen lacrimal gland. The circlating blood showed slightly elevated value of TRAb or antibody to TSH receptor. She was diagnosed with lacrimal adenitis associated with Basedow disease. The lesion subsided after systemic treatment with cystemic corticosterodi. Similar episodes recurred three times during the following 9 years. The lacrimal tumor was totally excised after MRI showed enlarged tumor in the lacrimal gland. The lesion showed proliferation of oxyphilic cells with round nuclei in addition to eosinophilic granular cytoplasm. The second case showed a tumor in the right caruncle. The lesion was excised and was diagnosed as oncocytoma with similar findings. No recurrence had developed in both cases during one year of follow-up. Conclusion: Oncocytoma in the eyelids, including ones involving the lacrimal gland, has to considered in the differential diagnosis of ocular adnexal tumors.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Our study evaluated the diagnostic capability of flow density (FD) in OCT angiography (OCTA) for diabetic retinopathy (DR) detection in diabetic patients. We studied 93 eyes of 68 diabetic patients who underwent OCTA (36 and 57 eyes without and with DR, respectively). Retinal capillary FD of a 2.6 × 2.6 mm² area and four divided areas at the superficial (SCP) and deep capillary plexus (DCP) were measured. Predictions were evaluated using the area under the receiver operating characteristic curve (AUC). The diagnostic capabilities of the FDs in discriminating between eyes without DR and eyes with total or early DR were compared. Furthermore, predictions with foveal avascular zone (FAZ) area, hemoglobin A1c (HbA1c), and DM duration were also compared with FD. Prediction using FD AUC in the temporal side in the DCP (0.83) was the highest and significantly better than all other AUCs examined (P < 0.05), including discriminating between eyes without DR and with early DR (P < 0.01). Prediction using this particular AUC was also significantly better than that by FAZ area and HbA1c (P < 0.001 and <0.001, respectively). Area-divided FD in OCTA may be valuable for diagnosing retinopathy in diabetic patients.

DOI： 10.1038/s41598-019-45194-z

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose To evaluate the retinal structure-function relationships in the macula of retinitis pigmentosa (RP) patients by comparing microperimetry-3 (MP-3) images with co-registered optical coherence tomography (OCT) images. Methods Thirty patients with typical RP were recruited from our hospital. The maculae of patients were examined with MP-3 and OCT. The retinal sensitivity was measured by MP-3 at 40 testing points arranged concentrically in a 16∘ diameter of the central retina, and we divided the 40 points into four zones according to degree from the fovea (2∘, 4∘, 6∘, and 8∘). We analyzed the correlation coefficients between the retinal sensitivity and the total retinal thickness (TRT), the length from the inner limiting membrane to the retinal pigment epithelium (RPE), and between the retinal sensitivity and the outer retinal thickness (ORT), the length from the outer plexiform layer to the RPE at each stimulus point. Results TRT showed moderate correlations with the retinal sensitivity at 2∘ (median ρ = 0.59 interquartile range (IQR) [0.38–0.72]), 4∘ (ρ = 0.59 [0.55–0.68]) and 6∘ (ρ = 0.60 [0.54–0.63]), and TRT was weakly-to-moderately related to the retinal sensitivity at 8∘ (ρ = 0.27 [0.19–0.48]). ORT exhibited strong correlations at 2∘ (ρ = 0.72 [0.60–0.81]), 4∘ (ρ = 0.71 [0.75–0.67]) and 6∘ (ρ = 0.70 [0.54–0.74]), and a weak-to-moderate correlations at 8∘ (ρ = 0.34 [0.29–0.53]). ORT was more strongly correlated with the retinal sensitivity compared to TRT (p = 0.018). Conclusion ORT, rather than TRT, within 6∘ eccentricity was strongly correlated with the retinal sensitivity, suggesting that measuring ORT in those areas will help evaluate the macular status and progression in RP.

DOI： 10.1371/journal.pone.0226097

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hereditary retinal degenerations (HRDs) are Mendelian diseases characterized by progressive blindness and caused by ultra-rare mutations. In a genomic screen of 331 unrelated Japanese patients, we identify a disruptive Alu insertion and a nonsense variant (p.Arg1933*) in the ciliary gene RP1, neither of which are rare alleles in Japan. p.Arg1933* is almost polymorphic (frequency = 0.6%, amongst 12,000 individuals), does not cause disease in homozygosis or heterozygosis, and yet is significantly enriched in HRD patients (frequency = 2.1%, i.e., a 3.5-fold enrichment; p-value = 9.2 × 10⁻⁵). Familial co-segregation and association analyses show that p.Arg1933* can act as a Mendelian mutation in trans with the Alu insertion, but might also associate with disease in combination with two alleles in the EYS gene in a non-Mendelian pattern of heredity. Our results suggest that rare conditions such as HRDs can be paradoxically determined by relatively common variants, following a quasi-Mendelian model linking monogenic and complex inheritance.

DOI： 10.1038/s41467-019-10746-4

記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To present phenotypic features of 22 patients with S-antigen (SAG) mutations. Design: Retrospective cohort study. Participants: Twenty-one Japanese patients from 16 families with a homozygous c.924delA mutation and 1 patient with a homozygous c.636delT mutation in the SAG gene. Methods: Clinical records on symptoms; best-corrected visual acuity; and Goldmann perimetry, fundus photography, fundus autofluorescence (FAF), OCT, and electroretinography results were reviewed. Main Outcome Measures: Best-corrected visual acuity, Goldmann perimetry results, imaging findings, and electroretinography results. Results: Ten patients had Oguchi disease and 12 had retinitis pigmentosa (RP) with mean follow-up periods of 13.8 and 10.2 years, respectively. Retinitis pigmentosa patients were older (mean age, 56.0 years) than those with Oguchi disease (mean age, 22.1 years; P < 0.001) at the initial visit. Night blindness noted in childhood was the most common initial symptom for both Oguchi disease (80.0%) and RP (91.7%) patients. Best-corrected visual acuity in the logarithm of the minimum angle of resolution (logMAR) was well preserved in Oguchi disease patients (mean, 0.02 logMAR in both eyes) but reduced in most RP patients (mean, 1.32 logMAR [right eye] and 1.35 logMAR [left eye]). Similarly, the visual field in the retinal area was preserved in Oguchi disease patients (mean, 677 mm² right eye and 667 mm² left eye) and reduced in RP patients (mean, 369 mm² right eye and 294 mm² left eye). Fundus images revealed a characteristic golden sheen with no retinal degeneration in Oguchi disease patients, excluding 2 with macular degeneration detected by FAF, OCT, or both and 1 with mild retinal degeneration confirmed by OCT and fluorescein angiography. Pigmentary retinal degeneration most evident posteriorly was observed in RP patients, accompanied by a characteristic golden sheen in 12 of 14 patients undergoing ultra-widefield fundus imaging. OCT showed disrupted macular structure, and FAF revealed variable hypofluorescence. Electroretinography identified absent rod responses in both diseases, along with relative preservation of cone responses in Oguchi disease patients. Three patients showed progressive loss of the golden sheen based on fundus images, including 1 who demonstrated RP 26 years after the initial diagnosis of Oguchi disease. Conclusions: Retinitis pigmentosa with SAG mutations often shows a characteristic golden sheen surrounding posterior pigmentary retinal degeneration. Oguchi disease can show progressive degeneration in adulthood, rarely resulting in RP.

DOI： 10.1016/j.ophtha.2019.05.027

記述言語：日本語  

担当ページ：プラクティス 8:122-123, 2023/03/31   記述言語：日本語  

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担当ページ：日本医事新報 5057:45   記述言語：日本語  

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担当ページ：今日の診断指針　第8版 1:1650－1652   記述言語：日本語  

担当ページ：臨床眼科 73:1128-1131   記述言語：日本語  

開催年月日： 2020年11月

記述言語：日本語  

開催地：福岡   国名：日本国  

開催年月日： 2020年11月

記述言語：日本語  

開催地：福岡県   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2020年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：石川県   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：石川県   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語   会議種別：口頭発表（一般）  

国名：日本国  

開催年月日： 2020年10月 - 2021年6月

記述言語：日本語  

開催地：東京都   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京都   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語  

開催地：東京都   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語  

開催地：東京都   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語  

開催地：東京都   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語  

開催地：東京都   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京都   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語  

開催地：web   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語  

国名：日本国  

開催年月日： 2020年10月

記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

開催地：大分県   国名：日本国  

開催年月日： 2020年10月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2020年5月

記述言語：日本語  

開催地：大分県   国名：日本国  

開催年月日： 2020年5月

記述言語：日本語  

開催地：福岡県   国名：日本国  

開催年月日： 2020年5月

記述言語：日本語  

開催地：福岡県   国名：日本国  

開催年月日： 2020年5月

記述言語：日本語  

開催地：福岡県   国名：日本国  

開催年月日： 2020年5月

記述言語：日本語  

開催地：福岡県   国名：日本国  

開催年月日： 2020年4月

記述言語：日本語  

国名：日本国  

開催年月日： 2020年2月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：大分県   国名：日本国  

開催年月日： 2020年2月 - 2021年2月

記述言語：日本語  

開催地：福岡県   国名：日本国  

開催年月日： 2020年2月

記述言語：日本語  

開催地：福岡県   国名：日本国  

開催地：Suzhou   国名：中華人民共和国