Faculty Profiles - Koji Nishiguchi

眼科診断・治療のイノベーションゲノム医療による眼疾患の診断・治療のイノベーション

遺伝性網膜ジストロフィ2459例の次世代シークエンスから得られた遺伝的特徴

後藤健介, 小柳俊人, 秋山雅人, 村上祐介, 福嶋正俊, 藤原康太, 飯島花枝, 山口光代, 橋本和軌, 石津正崇, 平形寿彬, 溝渕圭, 高山理和, 佐治木愛, 小南太郎, 牛田宏昭, 藤田幸輔, 兼子裕規, 上野真治, 林孝彰, 寺尾知可史, 堀田喜裕, 村上晶, 和田裕子, 阿部俊明, 中澤徹, 池田康博, 桃沢幸秀, 園田康平, 西口康二

日本眼科学会雑誌 Vol. 127 ( 臨増 ) page： 199 - 199 2023.3

西口康二, 藤田幸輔, 小柳俊人, 佐治木愛, 川野健一, 山田和久, 川部満希, 奥田大志, 鈴村文那, 清水英幸, 牛田宏昭, 兼子裕規, 小松紘之, 臼井嘉彦, 後藤浩, 中澤徹, 加地秀

日本眼科学会雑誌 Vol. 127 ( 3 ) page： 402 - 422 2023.3

Language：Japanese Publisher：(公財)日本眼科学会

眼科領域でのゲノム医療のプレゼンスは現時点では限定的である.しかし,来るべきゲノム医療時代を見据え,ゲノム情報を用いた先端的な研究を牽引することは,臨床検体にアクセスのある眼科アカデミアの使命である.我々は,眼感染症のゲノム診断と網膜ジストロフィに対するゲノム編集遺伝子治療のトランスレーショナルリサーチを重点テーマとして定め,それらの開発に取り組んでいる.本稿では,これらの新しいゲノム診療プラットフォームの構築と臨床実装を目指した研究の最新の成果を紹介する.I.Nanopore長鎖シークエンシングの眼感染症診断への応用近年,感染症の領域では,培養するプロセスを経ることなく,検体中の微生物群のDNAやRNAを直接精製し,網羅的にシークエンシングする「メタゲノム解析」が研究に広く用いられている.我々は,簡便性・迅速性に優れた人工知能搭載の長鎖シークエンサーであるNanoporeを用いた眼感染症診断のための新しいメタゲノム解析プラットフォームの開発に取り組んでいる.Multiplexポリメラーゼ連鎖反応(mPCR)でヘルペス属ウイルスなどが検出され診断のついた症例の前房水・硝子体液を対象にNanoporeを用いてメタゲノム解析を行ったところ,多くの検体で診断どおりの病原体が確認された.しかし,一部の検体では病原体が検出されず,さらに,微生物ゲノムのコンタミネーションがあることも判明した.そこで,これらの問題を克服し,起炎微生物を網羅的に探索することを目的に,mPCR陰性症例と対照を複数例解析し,結果を両群で比較するメタゲノム関連解析を行った.しかし,解析により起炎微生物由来と推測されるゲノム断片は検出できたものの,それはChlamydia Trachomatisなど複数の微生物が共通に持つ配列であることが後に判明した.以上より,現時点では,メタゲノム関連解析で検出されたmPCR陰性ぶどう膜炎に関連するゲノムの正体は絞り切れていない.現在,検出されたゲノム断片の由来である病原体を特定するために,多面的なゲノム解析を実施中である.また,Nanoporeメタゲノム解析では一部のぶどう膜炎症例においてtorque teno virusが検出された.同ウイルスは,これまで免疫抑制状態との関連が報告されているが,眼科領域での報告は未だ少ない.そこで,ぶどう膜炎症例において,定量的PCR(qPCR)を用いて前房水中のtorque teno virusの有無を調べ,全身性の免疫能低下の病歴との関連を解析した.その結果,ベースに全身性の免疫能低下がある患者では同ウイルスの検出率が高いことが判明した.このことは,torque teno virusの眼内感染と眼内の免疫能低下の関連性を示唆している可能性がある.II.網膜疾患に対するゲノム編集遺伝子治療戦略現在行われている眼疾患に対する遺伝子治療の多くはadeno-associated virus(AAV)ベクターを用いた遺伝子補充療法である.この治療の基本コンセプトは,機能喪失型の変異を持つ病的細胞に正常コピーの全長遺伝子を導入することで,欠損遺伝子の機能を補完することである.しかし,AAV容量の制約により,遺伝子補充療法では小さい病因遺伝子しか治療できない.したがって,この方法で治療できる日本人の網膜色素変性患者は,現状で全体のわずか数%程度である.それに対して,ゲノム編集遺伝子治療ではゲノム局所を標的とするため,治療対象の遺伝子のサイズに依存せず,理論的にはほとんどの遺伝子変異の治療が可能である.しかし,ゲノム編集遺伝子治療の治療効率は低く,そのことが臨床応用を妨げている.我々は,臨床応用を念頭にAAVゲノム編集遺伝子治療の効率改善に取り組み,3つの異なるゲノム編集手法を開発した.最初に,汎用性の高いプラットフォームとして,変異を正常配列に置換可能な単一AAVゲノム編集遺伝子治療プラットフォームを開発し(変異置換ゲノム編集遺伝子治療),その有効性をマウスモデルで証明した.続いて,塩基の挿入や欠失によって生じるフレームシフト変異を対象とし,ずれたフレームを元に戻すことに主眼を置いたシンプルかつ治療効率の高いゲノム編集法(リフレームゲノム編集遺伝子治療)を開発した.この方法を用いて,日本人網膜色素変性患者の約12%が保有するeyes shut homolog(EYS)遺伝子のS1653Kfs変異を有する患者由来細胞株を対象に,その有効性を実証した.最後に,マイクロホモロジー媒介末端結合(MMEJ)とhomology-independent targeted integration(HITI)の異なる2つのゲノム修復法をコンパクトに組み合わせたMMEJ-Hゲノム編集遺伝子治療を新たに考案し,イントロンなどの非翻訳領域を主なターゲットとする治療の開発を進めている.今後も,幅広い眼疾患に対して,ゲノム関連技術の応用にフォーカスを当てた挑戦的なトランスレーショナルリサーチを展開し,眼科アカデミアとして,ゲノム医療の発展に貢献していきたい.(著者抄録)

眼科診断・治療のイノベーションゲノム医療による眼疾患の診断・治療のイノベーション

日本眼科学会雑誌 Vol. 127 ( 3 ) page： 402 - 422 2023.3

Language：Japanese Publisher：(公財)日本眼科学会

LONG-TERM MORPHOLOGIC CHANGES IN MACULAR NEOVASCULARIZATION UNDER AFLIBERCEPT TREATMENT WITH A TREAT-AND-EXTEND REGIMEN

Nakano, Y; Takeuchi, J; Horiguchi, E; Ota, H; Taki, Y; Ito, Y; Terasaki, H; Nishiguchi, KM; Kataoka, K

RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Vol. 43 ( 3 ) page： 412 - 419 2023.3

Language：English Publisher：Retina

Purpose:To examine the morphologic changes in macular neovascularization (MNV) secondary to age-related macular degeneration after 2 years of aflibercept treatment under a treat-and-extend (T&E) regimen.Methods:This retrospective study analyzed the medical records for 26 eyes of 25 patients diagnosed with treatment-naive neovascular age-related macular degeneration and treated with aflibercept under a treat-and-extend regimen for 2 years. The areas of the MNV and vascular structures were assessed using swept-source optical coherence tomography angiography at baseline and after 2 years of treatment.Results:The mean MNV area increased significantly from 0.65 ± 0.42 mm2 at baseline to 0.78 ± 0.45 mm2 at 2 years. At 2 years, the mean change in the MNV area from baseline was 22% (interquartile range: 4%-60%). The baseline MNV area was negatively correlated with the change ratio of the MNV areas at 2 years and baseline (R = -0.68, P < 0.001). Nine of the 26 eyes (34.6%) showed newly formed mature vessels, and 7 eyes (26.9%) showed prominently developing preexisting mature vessels.Conclusion:Macular neovascularization expanded and showed vascular maturation under aflibercept treatment with a treat-and-extend regimen. The smaller the MNV at baseline, the greater is its expansion in 2 years.

DOI： 10.1097/IAE.0000000000003676

Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis

Panneman, DM; Hitti-Malin, RJ; Holtes, LK; de Bruijn, SE; Reurink, J; Boonen, EGM; Khan, MI; Ali, M; Andréasson, S; De Baere, E; Banfi, S; Bauwens, M; Ben-Yosef, T; Bocquet, B; De Bruyne, M; de la Cerda, B; Coppieters, F; Farinelli, P; Guignard, T; Inglehearn, CF; Karali, M; Kjellström, U; Koenekoop, R; de Koning, B; Leroy, BP; McKibbin, M; Meunier, I; Nikopoulos, K; Nishiguchi, KM; Poulter, JA; Rivolta, C; de la Rua, ER; Saunders, P; Simonelli, F; Tatour, Y; Testa, F; Thiadens, AAHJ; Toomes, C; Tracewska, AM; Tran, HV; Ushida, H; Vaclavik, V; Verhoeven, VJM; van de Vorst, M; Gilissen, C; Hoischen, A; Cremers, FPM; Roosing, S

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY Vol. 11 page： 1112270 2023.2

Language：English Publisher：Frontiers in Cell and Developmental Biology

Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies. Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases. Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.

DOI： 10.3389/fcell.2023.1112270

特集日本の眼の難病-何がどこまでわかってきたのか? 網膜色素変性

小南太郎, 西口康二

臨床眼科 Vol. 77 ( 1 ) page： 27 - 36 2023.1

Dimethyl Fumarate Protects Retinal Pigment Epithelium from Blue Light-Induced Oxidative Damage via the Nrf2 Pathway Reviewed

hideyuki shimizu, Kei Takayama, Kazuhisa Yamada, Ayana Suzumura, Tomohito Sato, Yoshiaki Nishio, Masataka Ito, Hiroaki Ushida, Koji M Nishiguchi, Masaru Takeuchi, Hiroki Kaneko

Antioxidants Vol. 12 ( 1 ) 2023.1

EFFECTS OF HALF-DOSE PHOTODYNAMIC THERAPY ON CHRONIC CENTRAL SEROUS CHORIORETINOPATHY WITH OR WITHOUT MACULAR NEOVASCULARIZATION ASSESSED USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY

Nakamura, K; Takeuchi, J; Kataoka, K; Ota, H; Asai, K; Nakano, Y; Horiguchi, E; Taki, Y; Ito, Y; Terasaki, H; Nishiguchi, KM

RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Vol. 42 ( 12 ) page： 2346 - 2353 2022.12

Language：English Publisher：Retina

Purpose:To assess the effects of half-dose photodynamic therapy on subretinal fluid and macular neovascularization (MNV) using optical coherence tomography angiography in patients with chronic central serous chorioretinopathy.Methods:Clinical information on 168 patients (168 eyes) with chronic central serous chorioretinopathy obtained before and 6 months after treatment with half-dose photodynamic therapy was retrospectively analyzed. Patients were categorized into a success (145 eyes) or failure (23 eyes) group based on the absence or presence of subretinal fluid, respectively, and clinical data were compared between them. Macular neovascularization was studied in 147 cases with available optical coherence tomography angiography images. P < 0.05 indicated statistical significance.Results:The success group showed a younger patient age, better posttreatment best-corrected visual acuity, and thicker pretreatment central choroidal thickness (all, P < 0.047) than did the failure group. Regarding MNV analysis, nine, eight, and 130 eyes had definite, possible, and no MNV, respectively, at baseline; among them, 100.0%, 75.0%, and 2.3%, respectively, had MNV at 6 months posttreatment. Patients with definite MNV at baseline were less likely to show successful subretinal fluid resolution.Conclusion:Although half-dose photodynamic therapy is generally effective for the treatment of chronic central serous chorioretinopathy, coexisting MNV may compromise the outcome; thus, optical coherence tomography angiography-based assessment of chronic central serous chorioretinopathy is important.

DOI： 10.1097/IAE.0000000000003604

Likely pathogenic structural variants in genetically unsolved patients with retinitis pigmentosa revealed by long-read sequencing. International journal

Yusuke Sano, Yoshito Koyanagi, Jing Hao Wong, Yusuke Murakami, Kohta Fujiwara, Mikiko Endo, Tomomi Aoi, Kazuki Hashimoto, Toru Nakazawa, Yuko Wada, Shinji Ueno, Dan Gao, Akira Murakami, Yoshihiro Hotta, Yasuhiro Ikeda, Koji M Nishiguchi, Yukihide Momozawa, Koh-Hei Sonoda, Masato Akiyama, Akihiro Fujimoto

Journal of medical genetics Vol. 59 ( 11 ) page： 1133 - 1138 2022.11

Language：English Publishing type：Research paper (scientific journal)

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

ASSESSMENTS OF MACULAR FUNCTION BY FOCAL MACULAR ELECTRORETINOGRAPHY AND STATIC PERIMETRY IN EYES WITH RETINITIS PIGMENTOSA

Okado, S; Koyanagi, Y; Inooka, T; Kominami, T; Terasaki, H; Nishiguchi, KM; Ueno, S

RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Vol. 42 ( 11 ) page： 2184 - 2193 2022.11

Language：English Publisher：Retina

Purpose:To assess the macular function by focal macular electroretinography and static perimetry in eyes with retinitis pigmentosa.Methods:Eighty-eight eyes of 88 retinitis pigmentosa patients were analyzed. The relationships between the focal macular electroretinography components and the mean deviations (MDs) of the Humphrey Field Analyzer 10-2 were determined. Spectral-domain optical coherence tomography was used to determine the integrity of the ellipsoid zone (EZ) and the interdigitation zone.Results:Forward-backward stepwise regression analyses showed that the amplitudes (r = 0.45, P < 0.01) and implicit times (r = -0.29, P < 0.01) of the b-waves were significantly correlated with the MDs. Some of the eyes had reduced b-wave amplitudes (<1.0 µV) and disrupted interdigitation zone, despite having a better MD (≥ -10.0 dB) and intact EZ. Subgroup analyses of eyes with better MD (≥ -10.0 dB) showed that the EZ width was correlated with the MDs but not with the b-wave amplitude. The thickness of the EZ-retinal pigment epithelium as an alternative indicator of interdigitation zone was correlated with the b-wave amplitude (r = 0.32, P = 0.04) but not with the MDs (r = -0.10, P = 0.53).Conclusion:The fact that the focal macular electroretinography amplitudes are reduced before the shortening of the EZ in the early stage of retinitis pigmentosa indicates that the focal macular electroretinography amplitudes are an earlier indicator of macular dysfunction than the Humphrey Field Analyzer 10-2 findings.

DOI： 10.1097/IAE.0000000000003589

Choroidal hemodynamics in central serous chorioretinopathy after half-dose photodynamic therapy and the effects of smoking. International journal

Etsuyo Horiguchi, Jun Takeuchi, Ryo Tomita, Keiko Asai, Yuyako Nakano, Hikaru Ota, Yosuke Taki, Yasuki Ito, Hiroko Terasaki, Koji M Nishiguchi, Keiko Kataoka

Scientific reports Vol. 12 ( 1 ) page： 17032 - 17032 2022.10

Language：English Publishing type：Research paper (scientific journal)

This retrospective study aimed to evaluate choroidal hemodynamics after half-dose photodynamic therapy (PDT) for central serous chorioretinopathy (CSC) and the effects of smoking using laser speckle flowgraphy. This study included 29 eyes of 29 patients treated with half-dose PDT for CSC, who were followed-up for at least 6 months. The mean blur rate (MBR) in the PDT irradiation area (whole area), the pachyvessel (PV) area, non-PV (NPV) area, and filling delay (FD) area were assessed at baseline and 1, 3, and 6 months post-PDT, respectively. The MBR was also assessed by smoking status. The MBR significantly decreased from baseline in the whole, PV, NPV, and FD areas at all time points (P < 0.001). Of the 29 patients, 6 were never smokers, 13 were past smokers, and 10 were current smokers. At baseline, no significant difference was found in the MBR in the whole, PV, NPV, and FD areas among never, past, and current smokers. The MBR changes showed a significantly smaller decrease in current smokers than in never smokers in the whole (P = 0.021), PV (P = 0.009), and NPV (P = 0.034) areas, but not in the FD area (P = 0.172). Half-dose PDT for CSC reduced choroidal blood flow in the PDT-irradiated area, which was blunted by current smoking status.

DOI： 10.1038/s41598-022-21584-8

Switching from aflibercept to brolucizumab for the treatment of refractory neovascular age-related macular degeneration.

今月の表紙サルコイドーシス

平田泰介, 山本素士, 西口康二

臨床眼科 Vol. 76 ( 9 ) page： 1191 - 1191 2022.9

第1土曜特集五感を科学する--感覚器研究の最前線視覚難治性眼疾患に対するin vivo遺伝子治療の最前線

西口康二

医学のあゆみ Vol. 282 ( 6 ) page： 634 - 640 2022.8

綜説網膜ジストロフィに対する遺伝子治療の進歩

西口康二

眼科 Vol. 64 ( 7 ) page： 647 - 652 2022.7

今月の表紙アトピー性白内障

坂本正明, 髙橋次郎, 西口康二

臨床眼科 Vol. 76 ( 6 ) page： 722 - 722 2022.6

Hikaru Ota, Jun Takeuchi, Yuyako Nakano, Etsuyo Horiguchi, Yosuke Taki, Yasuki Ito, Hiroko Terasaki, Koji M Nishiguchi, Keiko Kataoka

Japanese journal of ophthalmology Vol. 66 ( 3 ) page： 278 - 284 2022.5

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To examine the 16-week outcomes of switching to brolucizumab in eyes with neovascular age-related macular degeneration (nAMD) refractory to aflibercept. STUDY DESIGN: Retrospective observational study. METHODS: Data of eyes with nAMD who switched to brolucizumab because of resistance to aflibercept were collected. The best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status on optical coherence tomography were analyzed. RESULTS: A total of 48 eyes of 48 patients were reviewed. At 4 to 7 weeks after switching, BCVA changed from 0.26 ± 0.19 to 0.25 ± 0.21 (not significant; P = 0.95), but CRT significantly decreased from 298.9 ± 108.4 µm to 241.9 ± 92.5 µm (P < 0.001) and CCT from 182.6 ± 89.3 µm to 169.7 ± 82.6 µm (P < 0.001). Of the 23 eyes refractory to monthly aflibercept injections, 12 (52.2%) achieved a dry macula, and 8 (34.8%) reduced exudative changes at 1 month. At 16 weeks, 31 eyes (64.6%) achieved the treatment interval ≥ 8 weeks. Two patients (4.2%) dropped out, 7 eyes (14.6%) developed intraocular inflammation (IOI), and 8 eyes (16.7%) switched back to aflibercept because of the failure to extend the treatment interval ≥ 8 weeks. CONCLUSION: Switching to brolucizumab in eyes refractory to aflibercept conferred favorable outcomes in controlling exudative changes. However, IOI and the regulation of the treatment interval to at least 8 weeks during the maintenance phase disrupted the continuation of brolucizumab treatment.

DOI： 10.1007/s10384-022-00908-1

Ablation of Ctrp9, Ligand of AdipoR1, and Lower Number of Cone Photoreceptors in Mouse Retina. International journal

Daiki Inooka, Yoshihiro Omori, Noriyuki Ouchi, Koji Ohashi, Yuto Kawakami, Yoshito Koyanagi, Chieko Koike, Hiroko Terasaki, Koji M Nishiguchi, Shinji Ueno

Investigative ophthalmology & visual science Vol. 63 ( 5 ) page： 14 - 14 2022.5

Language：English Publishing type：Research paper (scientific journal)

Purpose: C1q/TNF-related protein (CTRP) 9 is one of the adiponectin paralogs, and a genetic ablation of its receptor, AdipoR1, is known to cause retinal degeneration. The purpose of this study was to determine the role played by CTRP9 in the retina. Methods: The retinas of Ctrp9 gene knockout (KO) and wild type (WT) mice were examined by electroretinography (ERG), histology, RNA sequencing, and quantitative real-time PCR. Results: The amplitude of the photopic ERG elicited by the maximum stimulus intensity was smaller by 40% in the Ctrp9 KO mice than in WT mice at 8 weeks of age. However, the photopic ERGs was not reduced from 8 weeks to 6 months of age. The amplitudes of the scotopic ERGs were not reduced in the Ctrp9 KO mice at 8 weeks and 6 months of age. No distinct histological abnormalities were found in the retinal sections but the density of peanut agglutinin-stained cells in the retinal flat mount of KO mice was reduced to about 70% of that of WT mice. Genomewide RNA sequencing of the retina revealed the absence of the expression of CTRP9 in both KO and WT mice. RNA sequencing and quantitative real-time PCR analysis showed that the expressions of the transcripts of genes expressed in cones, Opn1sw, Opn1mw, Gnat2, and Cnga3, were reduced in the KO mice retina, however, the degree of expression of the transcripts in rods was not significantly reduced. Conclusions: CTRP9 is released ectopically from other tissues, and it regulates the number of cones in the mouse retinas.

DOI： 10.1167/iovs.63.5.14

Clinical findings in eyes with BEST1-related retinopathy complicated by choroidal neovascularization. International journal

Mai Miyagi, Jun Takeuchi, Yoshito Koyanagi, Kei Mizobuchi, Takaaki Hayashi, Yasuki Ito, Hiroko Terasaki, Koji M Nishiguchi, Shinji Ueno

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie Vol. 260 ( 4 ) page： 1125 - 1137 2022.4

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To determine the characteristics of eyes diagnosed with Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB) complicated by choroidal neovascularization (CNV). METHODS: This was a retrospective, multicenter observational case series. Fourteen genetically confirmed BVMD patients and 9 ARB patients who had been examined in 2 ophthalmological institutions in Japan were studied. The findings in a series of ophthalmic examinations including B-scan optical coherence tomography (OCT) and OCT angiography (OCTA) were reviewed. RESULTS: CNV was identified in 5 eyes (17.9%) of BVMD patients and in 2 eyes (11.1%) of ARB patients. Three of 5 eyes with BVMD were classified as being at the vitelliruptive stage and 2 eyes at the atrophic stage. The CNV in 2 BVMD eyes were diagnosed as exudative because of acute visual acuity reduction, retinal hemorrhage, and intraretinal fluid, while the CNV in 3 BVMD eyes and 2 ARB eyes were diagnosed as non-exudative. The visual acuity of the two eyes with exudative CNV did not improve despite anti-VEGF treatments. None of the eyes with non-exudative CNV had a reduction of their visual acuity for at least 4 years. All of the CNV were located within hyperreflective materials which were detected in 16 eyes (57.1%) of the BVMD eyes and in 7 eyes (38.9%) of the ARB eyes. CONCLUSIONS: CNV is a relatively common complication in BEST1-related retinopathy in Asian population as well. The prognosis of eyes with exudative CNV is not always good, and OCTA can detect CNV in eyes possessing hyperreflective materials.

DOI： 10.1007/s00417-021-05447-y