論文 - 池田 康博
-
Genetic Risk Stratification of Primary Open-Angle Glaucoma in Japanese Individuals. 査読あり
Akiyama M, Tamiya G, Fujiwara K, Shiga Y, Yokoyama Y, Hashimoto K, Sato M, Sato K, Narita A, Hashimoto S, Ueda E, Furuta Y, Hata J, Miyake M, Ikeda HO, Suda K, Numa S, Mori Y, Morino K, Murakami Y, Shimokawa S, Nakamura S, Yawata N, Fujisawa K, Yamana S, Mori K, Ikeda Y, Miyata K, Mori K, Ogino K, Koyanagi Y, Kamatani Y, Biobank Japan Project, Ninomiya T, Sonoda KH, Nakazawa T, Japan Glaucoma Society Omics Group, Genomic Research Committee of the Japanese Ophthalmological Society
Ophthalmology 131 ( 11 ) 1271 - 1280 2024年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 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.
-
Specification of variant interpretation guidelines for inherited retinal dystrophy in Japan 査読あり
Fujinami K., Nishiguchi K.M., Oishi A., Akiyama M., Ikeda Y., Hotta Y., Kondo H., Maeda A., Miyake M., Kondo M., Sakamoto T.
Japanese Journal of Ophthalmology 68 ( 4 ) 389 - 399 2024年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Ophthalmology
Accurate interpretation of sequence variants in inherited retinal dystrophy (IRD) is vital given the significant genetic heterogeneity observed in this disorder. To achieve consistent and accurate diagnoses, establishment of standardized guidelines for variant interpretation is essential. The American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for variant interpretation serve as the global “cross-disease” standard for classifying variants in Mendelian hereditary disorders. These guidelines propose a systematic approach for categorizing variants into 5 classes based on various types of evidence, such as population data, computational data, functional data, and segregation data. However, for clinical genetic diagnosis and to ensure standardized diagnosis and treatment criteria, additional specifications based on features associated with each disorder are necessary. In this context, we present a comprehensive framework outlining the newly specified ACMG/AMP rules tailored explicitly to IRD in the Japanese population on behalf of the Research Group on Rare and Intractable Diseases (Ministry of Health, Labour and Welfare of Japan). These guidelines consider disease frequencies, allele frequencies, and both the phenotypic and the genotypic characteristics unique to IRD in the Japanese population. Adjustments and modifications have been incorporated to reflect the specific requirements of the population. By incorporating these IRD-specific factors and refining the existing ACMG/AMP guidelines, we aim to enhance the accuracy and consistency of variant interpretation in IRD cases, particularly in the Japanese population. These guidelines serve as a valuable resource for ophthalmologists and clinical geneticists involved in the diagnosis and treatment of IRD, providing them with a standardized framework to assess and classify genetic variants.
-
Relationships between causative genes and epiretinal membrane formation in Japanese patients with retinitis pigmentosa. 査読あり
Nakamura S, Fujiwara K, Fukushima M, Shimokawa S, Shimokawa S, Koyanagi Y, Hisatomi T, Takeda A, Yasuhiro I, Murakami Y, Sonoda KH
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 262 ( 11 ) 3553 - 3558 2024年6月
-
Genetic and Clinical Features of ABCA4-Associated Retinopathy in a Japanese Nationwide Cohort. 査読あり
Mizobuchi K, Hayashi T, Tanaka K, Kuniyoshi K, Murakami Y, Nakamura N, Torii K, Mizota A, Sakai D, Maeda A, Kominami T, Ueno S, Kusaka S, Nishiguchi KM, Ikeda Y, Kondo M, Tsunoda K, Hotta Y, Nakano T
American journal of ophthalmology 264 36 - 43 2024年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Ophthalmology
Purpose: To clarify the genetic and clinical features of Japanese patients with ABCA4-associated retinopathy. Design: Retrospective, multicenter cohort study. Methods: Patients with retinal degeneration and biallelic ABCA4 variants were recruited from 13 different hospitals. Whole exome sequencing analysis was used for genetic testing. Comprehensive ophthalmic examinations were performed on matched patients. The primary outcome measure was identifying multimodal retinal imaging findings associated with disease progression. Results: This study included 63 patients: 19 with missense/missense, 23 with missense/truncation, and 21 with truncation/truncation genotypes. In total, 62 variants were identified, including 29 novel variants. Six patients had a mild phenotype characterized by foveal-sparing or preserved foveal structure, including 4 with missense/missense and 2 with missense/truncation genotypes. The p.Arg212His variant was the most frequent in patients with mild phenotypes (4/12 alleles). Clinical findings showed a disease duration-dependent worsening of the phenotypic stage. Patients with the truncation/truncation genotype exhibited rapid retinal degeneration within a few years and definite fundus autofluorescence imaging patterns, including hyper autofluorescence at the macula and few or no flecks. Conclusions: Our results indicate that missense/missense or missense/truncation genotypes, including the p.Arg212His variant, are associated with a relatively mild phenotype. In contrast, the truncation/truncation genotype causes rapid and severe retinal degeneration in Japanese patients with ABCA4-associated retinopathy. These data are vital in predicting patient prognosis, guiding genetic counseling, and stratifying patients for future clinical trials.
-
Mawatari G., Hiwatashi S., Motani T., Nagatomo S., Ando E., Kuwahata T., Ishizu M., Ikeda Y.
Japanese Journal of Ophthalmology 68 ( 4 ) 321 - 326 2024年
担当区分：最終著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Ophthalmology
Purpose: To investigate the efficacy of our wearable night-vision aid in patients with concentric peripheral visual field loss. Study Design: Prospective, single blind, three-group, and three-period crossover clinical study. Methods: The study included patients with concentric peripheral visual field loss, a best-corrected visual acuity (decimal visual acuity) of 0.1 or higher in the better eye, and the presence of a central visual field. HOYA MW10 HiKARI® (HOYA Corporation), our original wearable night-vision aid, was used as the test device with three types of camera lenses (standard-, middle-, and wide-angle lenses). Under both bright and dark conditions, the angle of the horizontal visual field was measured using each of the three lens types for each group. The baseline angle was measured when each participant wore the night-vision aid (powered off). Results: The study included 21 participants. Under bright condition, the perceived horizontal visual field was significantly wider than the baseline setup when using the standard-angle lens (“the standard lens”); the middle-angle lens (“the middle lens”) was significantly wider than both the baseline setup and the standard lens; and the wide-angle lens (“the wide lens”) was significantly wider than the other lenses. Under dark condition, the perceived horizontal visual field was again significantly wider when using the middle lens than the baseline setup and the standard lens, and when using the wide lens, the perceived horizontal visual field was again wider than when using the other lenses. The control in the bright condition was significantly wider (p < 0.001) than when used in the dark condition, while the standard-angle lens in the dark condition was significantly wider (p = 0.05) than when used in the bright condition. In regards to the middle and wide lenses, there was no statistically significant result emerging from either of the illumination conditions. Conclusion: Our wearable night-vision aid with a middle-angle or wide-angle lens appears to provide wider visual field images in patients with concentric peripheral visual field loss, regardless of whether the illumination conditions are bright or dark.
-
Funatsu J, Murakami Y, Shimokawa S, Nakatake S, Fujiwara K, Okita A, Fukushima M, Shibata K, Yoshida N, Koyanagi Y, Akiyama M, Notomi S, Nakao S, Hisatomi T, Takeda A, Paschalis EI, Vavvas DG, Ikeda Y, Sonoda KH
PNAS nexus 1 ( 1 ) 1 - 14 2022年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 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.
-
Murakami Y., Hisai T., Shimokawa S., Fukushima M., Fujiwara K., Hirata A., Takada A., Miyahara F., Nakashima N., Kobayakawa Y., Arima M., Mawatari G., Ishizu M., Kaida T., Miyata K., Ikeda Y., Sonoda K.H.
Japanese Journal of Ophthalmology 2025年
記述言語：英語 掲載種別：研究論文（学術雑誌） 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.
-
Fukuyama H., Ishikawa H., Gomi F., Yamamoto S., Baba T., Sato E., Kitahashi M., Tatsumi T., Miura G., Niizawa T., Sakamoto T., Yamakiri K., Yamashita T., Otsuka H., Sameshima S., Yoshinaga N., Sonoda S., Hirakata A., Koto T., Inoue M., Hirota K., Itoh Y., Orihara T., Emoto Y., Sano M., Takahashi H., Tokizawa R., Yamashita H., Nishitsuka K., Kaneko Y., Nishi K., Yoshida A., Ono S., Hirokawa H., Sogawa K., Omae T., Ishibazawa A., Kishi S., Akiyama H., Matsu-moto H., Mukai R., Morimoto M., Nakazawa M., Suzuki Y., Kudo T., Adachi K., Ishida S., Noda K., Kase S., Mori S., Ando R., Saito M., Suzuki T., Takahashi K., Nagai Y., Nakauchi T., Yamada H., Kusaka S., Tsujioka D., Tsujikawa A., Suzuma K., Ishibashi T., Sonoda K.H., Ikeda Y., Kohno R., Ishikawa K., Kondo M., Kozawa M., Kitaoka T., Tsuiki E., Ogura Y., Yoshida M., Morita H., Kato A., Hirano Y., Sugitani K., Terasaki H., Iwase T., Ito Y., Ueno S., Kaneko H., Nonobe N., Kominami T., Azuma N., Yokoi T., Shimada H., Nakashizuka H., Hattori T., Shinojima A., Kutagawa Y., Shiraga F., Morizane Y., Kimura S., Ikeda T., Kida T., Sato T., Fukumoto M., Emi K., Nakashima H., Ohji M.
Scientific Reports 14 ( 1 ) 2024年12月
掲載種別：研究論文（学術雑誌） 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.
-
Fukushima M., Tao Y., Shimokawa S., Zhao H., Shimokawa S., Funatsu J., Hisai T., Okita A., Fujiwara K., Hisatomi T., Takeda A., Ikeda Y., Sonoda K.H., Murakami Y.
Ophthalmology Science 4 ( 6 ) 100582 2024年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 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.
-
増刊号 6年前の常識は現在の非常識!-AI時代へ向かう今日の眼科医へ Ⅷ.網膜 遺伝子治療 招待あり
池田 康博
臨床眼科 78 ( 11 ) 220 - 226 2024年10月
担当区分：筆頭著者, 責任著者 記述言語：日本語 掲載種別：論文集(書籍)内論文 出版者・発行元：株式会社医学書院
-
Tachibana T., Notomi S., Funatsu J., Fujiwara K., Nakatake S., Murakami Y., Nakao S., Kanamoto T., Ikeda Y., Ishibashi T., Sonoda K.H., Hisatomi T.
Japanese Journal of Ophthalmology 68 ( 5 ) 500 - 510 2024年9月
掲載種別：研究論文（学術雑誌） 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.
-
Arima M., Inoue H., Misumi A., Tsukamoto S., Matsushita I., Araki S., Ohta M., Takahashi K., Imazato M., Goto T., Aoki Y., Tagawa K., Hirose M., Fujita Y., Yoshida N., Nakao S., Kondo H., Kusuhara K., Kimura K., Hasegawa S., Ikeda Y., Kodama Y., Moritake H., Ochiai M., Ohga S., Kishimoto J., Todaka K., Ieiri I., Sonoda K.H.
Japanese Journal of Ophthalmology 68 ( 5 ) 490 - 499 2024年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 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.
-
特集 第77回日本臨床眼科学会講演集[5] 原著 抗アクアポリン4抗体陽性視神経炎の視力の経過 査読あり
山添 早織, 中馬 秀樹, 池田 康博
臨床眼科 78 ( 7 ) 823 - 827 2024年7月
-
Goto K, Koyanagi Y, Akiyama M, Murakami Y, Fukushima M, Fujiwara K, Iijima H, Yamaguchi M, Endo M, Hashimoto K, Ishizu M, Hirakata T, Mizobuchi K, Takayama M, Ota J, Sajiki AF, Kominami T, Ushida H, Fujita K, Kaneko H, Ueno S, Hayashi T, Terao C, Hotta Y, Murakami A, Kuniyoshi K, Kusaka S, Wada Y, Abe T, Nakazawa T, Ikeda Y, Momozawa Y, Sonoda KH, Nishiguchi KM
Journal of medical genetics 61 ( 7 ) 613 - 620 2024年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 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.
-
Wong T.Y., Haskova Z., Asik K., Baumal C.R., Csaky K.G., Eter N., Ives J.A., Jaffe G.J., Korobelnik J.F., Lin H., Murata T., Ruamviboonsuk P., Schlottmann P.G., Seres A.I., Silverman D., Sun X., Tang Y., Wells J.A., Yoon Y.H., Wykoff C.C., Aaberg T., Abbey A., Abdulaeva E., Abengoechea S., Abraham P., Ach T., Adams S., Adan Civera A., Adrean S., Agostini H., Alam S., Alezzandrini A., Alfaro V., Aliseda D., Almony A., Amat P., Amini P., Antoszyk A., Arias L., Asaria R., Avila M., Awh C.C., Bafalluy J., Baker C., Bandello F., Barakat M., Barraza K., Bator G., Belfort R., Bergstrom C., Bertolucci G., Bochow T., Bolz M., Borcz E., Bordon A., Boyer D., Bratko G., Brent M., Brown J., Brown D.M., Budzinskaya M., Buffet S., Burgess S., Burton B., Busquets M., Cabrera F., Cagini C., Calzada J., Campochiaro P., Carlson J., Castellarin A., Cava C., Chaikitmongkol V., Chan C., Chang E., Chang J., Chang A., Charles S., Chaudhry N., Chee C., Chen J., Chen F., Chen S.J., Cheong-Leen R., Chiang A., Chittum M., Chow D., Connolly B., Cornut P.L., Danzig C., Das A., Daskalov V., Desco C., Dessouki A., Dickinson J., Do B., Dollin M., Dugel P.
Ophthalmology 131 ( 6 ) 708 - 723 2024年6月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Ophthalmology
Purpose: To evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2 and vascular endothelial growth factor (VEGF) A pathway inhibition with intravitreal faricimab according to a personalized treat-and-extend (T&E)-based regimen with up to every-16-week dosing in the YOSEMITE and RHINE (ClinicalTrials.gov identifiers, NCT03622580 and NCT03622593, respectively) phase 3 trials of diabetic macular edema (DME). Design: Randomized, double-masked, noninferiority phase 3 trials. Participants: Adults with visual acuity loss (best-corrected visual acuity [BCVA] of 25–73 letters) due to center-involving DME. Methods: Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg every 8 weeks. The T&E up to every-16-week dosing regimen was based on central subfield thickness (CST) and BCVA change. Main Outcome Measures: Included changes from baseline in BCVA and CST, number of injections, durability, absence of fluid, and safety through week 100. Results: In YOSEMITE and RHINE (n = 940 and 951, respectively), noninferior year 1 visual acuity gains were maintained through year 2; mean BCVA change from baseline at 2 years (weeks 92, 96, and 100 average) with faricimab every 8 weeks (YOSEMITE and RHINE, +10.7 letters and +10.9 letters, respectively) or T&E (+10.7 letters and +10.1 letters, respectively) were comparable with aflibercept every 8 weeks (+11.4 letters and +9.4 letters, respectively). The median number of study drug injections was lower with faricimab T&E (YOSEMITE and RHINE, 10 and 11 injections, respectively) versus faricimab every 8 weeks (15 injections) and aflibercept every 8 weeks (14 injections) across both trials during the entire study. In the faricimab T&E arms, durability was improved further during year 2, with > 60% of patients receiving every-16-week dosing and approximately 80% receiving every-12-week or longer dosing at week 96. Almost 80% of patients who achieved every-16-week dosing at week 52 maintained every-16-week dosing without an interval reduction through week 96. Mean CST reductions were greater (YOSEMITE/RHINE weeks 92/96/100 average: faricimab every 8 weeks –216.0/–202.6 µm, faricimab T&E –204.5/–197.1 µm, aflibercept every 8 weeks –196.3/–185.6 µm), and more patients achieved absence of DME (CST < 325 μm; YOSEMITE/RHINE weeks 92–100: faricimab every 8 weeks 87%–92%/88%–93%, faricimab T&E 78%–86%/85%–88%, aflibercept every 8 weeks 77%–81%/80%–84%) and absence of intraretinal fluid (YOSEMITE/RHINE weeks 92–100: faricimab every 8 weeks 59%–63%/56%–62%, faricimab T&E 43%–48%/45%–52%, aflibercept every 8 weeks 33%–38%/39%–45%) with faricimab every 8 weeks or T&E versus aflibercept every 8 weeks through year 2. Overall, faricimab was well tolerated, with a safety profile comparable with that of aflibercept. Conclusions: Clinically meaningful visual acuity gains from baseline, anatomic improvements, and extended durability with intravitreal faricimab up to every 16 weeks were maintained through year 2. Faricimab given as a personalized T&E-based dosing regimen supports the role of dual angiopoietin-2 and VEGF-A inhibition to promote vascular stability and to provide durable efficacy for patients with DME. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
-
Genotypes and clinical features of RHO-associated retinitis pigmentosa in a Japanese population. 査読あり
Tsutsui S, Murakami Y, Fujiwara K, Koyanagi Y, Akiyama M, Takeda A, Ikeda Y, Sonoda KH
Japanese journal of ophthalmology 68 ( 1 ) 1 - 11 2024年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 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.
-
Hidaka T, Chuman H, Ikeda Y
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 262 ( 1 ) 161 - 169 2024年1月
担当区分：最終著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Graefe's Archive for Clinical and Experimental Ophthalmology
Purpose: To investigate the objective function of the inner retinal layer in each stage of primary open angle glaucoma (POAG) using the photopic negative response (PhNR) measured by RETeval full-field electroretinography (ERG), and to identify which PhNR parameter is the most useful. Methods: Ninety eyes of 90 patients with POAG (30 with mild POAG (mean deviation (MD) ≥ -6 dB) and 60 with moderate-to-advanced POAG (MD < -6 dB)) and 76 eyes of 76 control cases were examined. We investigated six PhNR parameters and their relationships with the results of the Humphrey 30–2 visual field test and the thickness of the circumpapillary retinal nerve fiber layer (cpRNFL) obtained from optical coherence tomography. The following PhNR parameters were assessed: base-to-trough (BT), peak-to-trough (PT), 72msPhNR, the W-ratio, P-ratio, implicit time (IT), and a-wave and b-wave amplitudes on ERG. Results: All PhNR parameters other than IT significantly differed between the all POAG (all stages) and control groups and between the moderate-to-advanced POAG and control groups. BT and 72msPhNR in the mild POAG group, significantly differed from those in the control group. Regarding the relationships between PhNR parameters and the visual field and between these parameters and cpRNFL thickness, correlations were observed between all PhNR parameters, except PT and IT, and both the visual field and cpRNFL thickness in the all and moderate-to-advanced POAG groups. 72msPhNR correlated with cpRNFL thickness in the mild POAG group. The area under the receiver operating characteristic curve was greater for BT than for the other PhNR parameters in both the mild and moderate-to-advanced POAG groups. The discriminant linear function for examining the presence or absence of POAG and the threshold for diagnosis were quantitatively obtained as follows. Regarding BT: discriminant = 0.505 × BT + 2.017; threshold = positive for POAG, negative for no POAG; correct answer rate = 80.7%. Concerning 72msPhNR: discriminant = 0.533 × 72msPhNR + 1.553; threshold = positive for POAG and negative for no POAG; correct answer rate = 77.1%. Conclusion: RETeval-measured PhNR parameters were useful for an objective evaluation of visual function in moderate-to-advanced POAG. BT appeared to be the most diagnostically useful parameter.
-
視交叉内の黄斑線維走行部に限局する 接合部障害と思われた特発性視交叉炎の一例 査読あり
田村 千奈見, 長友 さおり, 中馬 秀樹, 池田 康博
神経眼科 40 ( 3 ) 248 - 253 2023年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：日本神経眼科学会
37歳の男性が左眼の霧視を自覚した．矯正視力は右1.2 左0.6．相対的瞳孔求心路障害（relative afferent pupillary defect: RAPD）は陰性であった．周辺視野欠損は明らかでなく，ハンフリー静的視野10-2プログラムを用いた中心視野に両耳側半盲と左眼の中心感度の低下を認めた．頭部磁気共鳴画像（MRI）にて視交叉内部後方やや左側よりに造影される病変を認めた．視交叉炎と診断し原因検索を行い，明らかな全身性炎症性疾患は認められなかった．その後自然軽快し，左矯正視力は1.0まで回復，両耳側半盲は消失し，左眼の中心感度も正常化した．頭部MRIの造影効果も消失した．本症例は，視交叉内の黄斑線維走行部に限局した接合部障害をきたした特発性視交叉炎で，組織学的研究を臨床的に証明する，まれでかつ貴重な症例であると思われた．またこのような症例は，適切な視野プログラムを選択しないと病変を見逃す可能性があり，注意を要すると思われた．
-
Obata S., Sawada O., Kakinoki M., Matsumoto R., Saishin Y., Ohji M., Yamamoto S., Baba T., Sato E., Kitahashi M., Tatsumi T., Miura G., Nizawa T., Sakamoto T., Yamakiri K., Yamashita T., Otsuka H., Sameshima S., Yoshinaga N., Sonoda S., Hirakata A., Koto T., Inoue M., Hirota K., Itoh Y., Orihara T., Emoto Y., Sano M., Takahashi H., Tokizawa R., Yamashita H., Nishitsuka K., Kaneko Y., Nishi K., Yoshida A., Ono S., Hirokawa H., Sogawa K., Omae T., Ishibazawa A., Kishi S., Akiyama H., Matsumoto H., Mukai R., Morimoto M., Nakazawa M., Suzuki Y., Kudo T., Adachi K., Ishida S., Noda K., Kase S., Mori S., Ando R., Saito M., Suzuki T., Takahashi K., Nagai Y., Nakauchi T., Yamada H., Kusaka S., Tsujioka D., Tsujikawa A., Suzuma K., Ishibashi T., Sonoda K.H., Ikeda Y., Kohno R., Ishikawa K., Kondo M., Kozawa M., Kitaoka T., Tsuiki E., Ogura Y., Yoshida M., Morita H., Kato A., Hirano Y., Sugitani K., Terasaki H., Iwase T., Ito Y., Ueno S., Kaneko H., Nonobe N., Kominami T., Azuma N., Yokoi T., Shimada H., Nakashizuka H., Hattori T., Shinojima A., Kitagawa Y., Shiraga F., Morizane Y., Kimura S., Ikeda T., Kida T., Sato T., Fukumoto M.
Japanese Journal of Ophthalmology 67 ( 4 ) 417 - 423 2023年7月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Ophthalmology
Purpose: To investigate the effects of internal limiting membrane (ILM) peeling on retinal attachment after a single surgery, and on postoperative visual acuity (VA) at 6 months, in eyes with macula-off rhegmatogenous retinal detachment (RRD) complicated by proliferative vitreoretinopathy (PVR). Study design: Nationwide, multicenter retrospective cohort study. Methods: The Japan-RD Registry database was used for analysis of patients who had undergone vitrectomy for macula-off RRD complicated by PVR. Multivariate analysis was performed to detect prognostic factors for retinal attachment after a single surgery and for VA at 6 months postoperatively. Retinal attachment after a single surgery or VA at 6 months postoperatively was the objective variable; ILM peeling, preoperative VA, PVR grade, age, and intraocular pressure were explanatory variables. Results: Eighty-nine eyes met the inclusion criteria; ILM peeling was performed in 25 eyes (28%). Preoperative VA was significantly associated with retinal attachment, but ILM peeling did not (odds ratios = 2.1 and 1.3, respectively; p = 0.009 and 0.67, respectively). Poor preoperative VA and younger patient age were significantly associated with poor postoperative VA, but ILM peeling was not (β-values = 0.37, −0.008, and 0.15, respectively; p < 0.001, p = 0.02, and p = 0.15, respectively. Conclusions: Preoperative VA was a risk factor associated with retinal attachment. Preoperative VA and patient age were risk factors associated with postoperative poor VA. In eyes with macula-off RRD complicated by PVR, ILM peeling did not have a clear beneficial effect on anatomical and functional outcomes, suggesting that it may be unnecessary for eyes with this condition.
-
Shimura M., Kitano S., Ogata N., Mitamura Y., Oh H., Ochi H., Ohsawa S., Hirakata A., Bolz M., Findl O., Pollreisz A., Weger M., Daskalov V., Misheva A., Petkova I., Guneva D.T., Vassileva P., Cornut P.L., Korobelnik J.F., Lebreton O., Tadayoni R., Eter N., Feltgen N., Framme C., Lorenz K., Spital G., Bator G., Seres A., Szalczer L., Toth-Molnar E., Vajas A., Varsanyi B., Goldstein M., Levy J., Morori-Katz H., Rosenblatt I., Yoreh B., Bandello F., Cagini C., Mastropasqua L., Nicolo M., Parravano M.C., Viola F., Fukutomi A., Hayashi K., Hirakata A., Honda S., Ikeda Y., Ito Y., Kawasaki T., Kimura K., Kishino G., Kitano S., Maeno T., Murakami T., Noda K., Obana A., Oh H., Sawada O., Shimouchi A., Sugimoto M., Sugita I., Takagi H., Takayama K., Tanabe T., Yasukawa T., Yoshida S., Garcia R., Rechy D.L., Canton V.M., Estudillo J.R., Barraza K., Fernandez C., Guzman M., Lujan S., Gawecki M., Herba E., Michalska-Malecka K., Muzyka-Wozniak M., Nester-Ostrowska K., Oleksy P., Wowra B., Wylęgała E., Budzinskaya M., Kulikov A., Morugova T., Hurcikova M., Kacerík M., Lipkova B., Abengoechea S., Civera A.A., Amat P., Cabrera F., Cava C., Garcia-Layana A., Ulla F.G., Moreno J.M.R.
Japanese Journal of Ophthalmology 67 ( 3 ) 264 - 279 2023年5月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Ophthalmology
Purpose: To evaluate efficacy, durability, and safety of faricimab in Japanese patients with diabetic macular edema (DME). Study design: Subgroup analysis of 2 global, multicenter, randomized, double-masked, active-comparator–controlled, phase 3 trials (YOSEMITE, NCT03622580; RHINE, NCT03622593). Methods: Patients with DME were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W), faricimab 6.0 mg per personalized treatment interval (PTI), or aflibercept 2.0 mg Q8W through week 100. Primary endpoint was best-corrected visual acuity (BCVA) change from baseline at 1 year, averaged over weeks 48, 52, and 56. This is the first time 1-year outcomes between Japanese patients (only enrolled into YOSEMITE) and the pooled YOSEMITE/RHINE cohort (N = 1891) have been compared. Results: The YOSEMITE Japan subgroup included 60 patients randomized to faricimab Q8W (n = 21), faricimab PTI (n = 19), or aflibercept Q8W (n = 20). Consistent with global results, the adjusted mean (95.04% confidence interval) BCVA change at 1 year in the Japan subgroup was comparable with faricimab Q8W (+11.1 [7.6–14.6] letters), faricimab PTI (+8.1 [4.4–11.7] letters), and aflibercept Q8W (+6.9 [3.3–10.5] letters). At week 52, 13 (72%) patients in the faricimab PTI arm achieved ≥ Q12W dosing, including 7 (39%) patients receiving Q16W dosing. Anatomic improvements with faricimab were generally consistent between the Japan subgroup and pooled YOSEMITE/RHINE cohort. Faricimab was well tolerated; no new or unexpected safety signals were identified. Conclusion: Consistent with global results, faricimab up to Q16W offered durable vision gains and improved anatomic and disease-specific outcomes among Japanese patients with DME.