Papers - IKEDA Yasuhiro
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Genetic Risk Stratification of Primary Open-Angle Glaucoma in Japanese Individuals. Reviewed
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 2024.7
Language：English Publishing type：Research paper (scientific journal) Publisher：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.
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Specification of variant interpretation guidelines for inherited retinal dystrophy in Japan Reviewed
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 2024.7
Language：English Publishing type：Research paper (scientific journal) Publisher：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.
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Relationships between causative genes and epiretinal membrane formation in Japanese patients with retinitis pigmentosa. Reviewed
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 2024.6
Language：English Publishing type：Research paper (scientific journal)
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Genetic and Clinical Features of ABCA4-Associated Retinopathy in a Japanese Nationwide Cohort. Reviewed
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 2024.3
Language：English Publishing type：Research paper (scientific journal) Publisher：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.
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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
Authorship：Last author, Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：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.
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Funatsu Jun, Murakami Yusuke, Shimokawa Shotaro, Nakatake Shunji, Fujiwara Kohta, Okita Ayako, Fukushima Masatoshi, Shibata Kensuke, Yoshida Noriko, Koyanagi Yoshito, Akiyama Masato, Notomi Shoji, Nakao Shintaro, Hisatomi Toshio, Takeda Atsunobu, Paschalis Eleftherios I, Vavvas Demetrios G, Ikeda Yasuhiro, Sonoda Koh-Hei
PNAS Nexus 1 ( 1 ) 1 - 14 2022.3
Language：English Publishing type：Research paper (scientific journal)
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.
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Hisai T., Shimokawa S., Fukushima M., Fujiwara K., Koyanagi Y., Hirata A., Takada A., Miyahara F., Nakashima N., Kobayakawa Y., Mawatari G., Ishizu M., Toyama N., Kaida T., Miyata K., Ikeda Y., Sonoda K.H., Murakami Y.
Ophthalmology Science 6 ( 1 ) 100930 2026.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Ophthalmology Science
Purpose: To analyze the association between visual function and inflammatory markers in the baseline data of a prospective natural history registry of patients with typical retinitis pigmentosa (RP) (Retinitis Pigmentosa Progression and Inflammatory Marker Registry Study [RP-PRIMARY Study]). Design: A cross-sectional observational study using baseline data from the RP-PRIMARY study. Participants: A total of 67 patients with moderate-stage typical RP who were treated between October 2021 and October 2022 in 1 of 3 participating hospitals consented to participate and met the inclusion criteria. Methods: Visual functions were ETDRS best-corrected visual acuity (BCVA), Humphrey Field Analyzer 10-2 program (mean deviation value, and the mean sensitivity within the central 1° area [central 4 points, RS Cent 1’] and the 4° area [central 12 points, RS Cent 4’]), ellipsoid zone (EZ) length, central foveal thickness (CFT), hyper-autofluorescence (AF) ring area, and inflammatory markers were aqueous flare and blood test measurements. Main Outcome Measures: Association between visual function and inflammatory markers. Results: The median age of participants was 51 (interquartile range: 43–60) years. Spearman rank correlation coefficient demonstrated that aqueous flare values were negatively correlated with ETDRS BCVA (ρ = –0.35; P = 0.004), RS Cent 1’ (ρ = –0.32; P = 0.008), EZ length (ρ = –0.28; P = 0.023), and hyper-AF ring area (ρ = –0.31; P = 0.016). There was no significant correlation between systemic inflammatory markers and visual function. Eyes with intraocular lens (IOL) had significantly lower values of ETDRS BCVA (P = 0.004), RS Cent 1’ (P = 0.005), RS Cent 4’ (P = 0.010), CFT (P = 0.001), and EZ length (P = 0.011), in addition to higher values of aqueous flare (P < 0.001). Multiple linear regression analysis revealed that eyes with IOL (β = 0.262; P < 0.001) were significantly associated with aqueous flare. Conclusions: In the baseline data of the RP-PRIMARY study, aqueous flare, an ocular inflammatory marker, was negatively associated with visual function, and IOL implantation was most strongly associated with an increase in aqueous flare in patients with moderate-stage RP. The association between inflammatory markers and disease progression will be evaluated in the ongoing RP-PRIMARY study. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Clinical characteristics of EYS-associated retinal dystrophy in 291 Japanese patients. Reviewed
Koyanagi Y, Murakami Y, Kominami T, Fukushima M, Goto K, Yokota S, Mizobuchi K, Mawatari G, Torii K, Inoue Y, Ota J, Okuda D, Fujiwara K, Yamaga H, Hisai T, Endo M, Iijima H, Kaida T, Miyata K, Nakazaki S, Hayashi T, Hirami Y, Akiyama M, Terao C, Momozawa Y, Sonoda KH, Nishiguchi KM, Ikeda Y
NPJ genomic medicine 2025.12
Language：English Publishing type：Research paper (scientific journal)
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特集 遺伝性網膜疾患の最新情報 １ わが国の遺伝性網膜疾患の現状 Reviewed
池田 康博
眼科 67 ( 11 ) 1133 - 1137 2025.10
Publishing type：Research paper (scientific journal) Publisher：金原出版
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Castleman Disease Manifesting as an Orbital Tumor: A Case Report Reviewed
Kawano Motoyuki, Mitsutome Ikki, Tamura Chinami, Chuman Hideki, Ikeda Yasuhiro
Neuro-Ophthalmology Japan 42 ( 3 ) 334 - 339 2025.9
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Neuro-Ophthalmology Society
Castleman disease is a polyclonal lymphoproliferative disorder characterized by distinctive histopathological features. Lymph node involvement is predominant. However, orbital manifestations are rare, accounting for only 1% of all orbital tumors. We report a case of Castleman disease initially presenting as an orbital lesion. A 52-year-old man developed a right subcutaneous eyelid mass for which a biopsy was planned but was lost to follow-up. The patient was referred again four years later due to tumor enlargement and systemic symptoms including fever and vomiting. Blood tests revealed anemia, elevated inflammatory markers, and polyclonal hypergammaglobulinemia. Contrast-enhanced magnetic resonance imaging revealed a heterogeneous enhancing orbital mass, and positron emission tomography-computed tomography revealed multiple hypermetabolic lymphadenopathies, including those in the right cervical region. Partial biopsy of the orbital mass revealed histopathological findings of lymphoid follicular hyperplasia with plasma cell proliferation, leading to the diagnosis of Castleman disease. Treatment with an anti-IL-6 receptor antibody resulted in tumor shrinkage and improvement of systemic symptoms and laboratory findings. Castleman disease should be considered in the differential diagnosis of orbital tumors.
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臨床報告 硝子体手術により網膜血管腫を切除したvon Hippel Lindau病の1例 Reviewed
林 俊平, 石津 正崇, 杉田 直大, 日髙 貴子, 池田 康博
臨床眼科 79 ( 9 ) 1090 - 1097 2025.9
Publishing type：Research paper (scientific journal) Publisher：株式会社医学書院
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臨床報告 MOG抗体陽性視神経炎の再発率の検討 Reviewed
和田 英里香, 津村 諒, 中馬 秀樹, 池田 康博
臨床眼科 79 ( 9 ) 1098 - 1102 2025.9
Publishing type：Research paper (scientific journal) Publisher：株式会社医学書院
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Shiozawa A.L., Kobayashi M.H., Shiozawa Y., Ikeda Y., Miyagawa Y., Okamoto F., Sakai M., Okada T., Igarashi T.
Plos One 20 ( 9 September ) e0332446 2025.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Plos One
Purpose The rd6 mouse model, characterized by retinal degeneration due to an Mfrp mutation, has been widely studied. However, we identified a subset of rd6 mice that developed severe non-rhegmatogenous retinal detachment (rd6-RD), suggesting the presence of additional genetic factors. This study aimed to characterize the retinal phenotype of rd6-RD mice and identify potential causative genetic mutations. Methods We performed optical coherence tomography, fundus imaging, electroretinography, and histological analysis to compare retinal structures and functions between rd6, rd6-RD, and C57BL/6J mice. Whole-genome sequencing was conducted to identify potential mutations associated with the retinal detachment phenotype. Results Optical coherence tomography revealed retinal detachment in rd6-RD mice as early as 4 weeks old, with complete loss of the outer nuclear layer by 6 weeks. Fundus examination at 11 weeks showed pale fundi and narrowed, whitened retinal vessels in rd6-RD mice, distinct from rd6 mice. On electroretinography, rd6-RD mice displayed significantly diminished a- and b-wave amplitudes, with no detectable responses by 10 weeks. Histological analysis confirmed severe outer retinal degeneration and disappearance of the outer layers in rd6-RD mice. Whole-genome sequencing identified a missense R560C mutation in Pde6b, corresponding to the Pde6b<sup>rd10</sup> mutation, in rd6-RD mice. Conclusions A subset of rd6 mice exhibited severe retinal detachment and outer retinal degeneration, distinct from the previously characterized Mfrp-related phenotype. The identification of the Pde6b<sup>rd10</sup> mutation suggests that these mice possess a dual-mutant genotype (Mfrp<sup>rd6</sup> and Pde6b<sup>rd10</sup>), exacerbating retinal degeneration. These findings highlight the importance of genetic verification in commercially available mouse models and provide new insights into the genetic complexity of inherited retinal degenerations.
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Tsumura Ryo, Chuman Hideki, Ikeda Yasuhiro
Neuro-Ophthalmology Japan 42 ( 2 ) 201 - 206 2025.6
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Neuro-Ophthalmology Society
A 51-year-old man noted difficulty in following object movements. The patient was referred to our institution at day 24 after onset. Corrected visual acuities was 1.5 OU. The pupils were isocoric under dark and light conditions; the light reflex was prompt and completely OU, and the relative afferent pupillary defect was negative. The patient’s eyes were orthotropic. His eye movements were complete in all directions, bilaterally and unilaterally. His bilateral horizontal saccadic eye movements were impaired; however, vertical saccades remained intact. His pursuit eye movements were normal horizontally and vertically. The vestibulo-ocular reflex was warm-positive. Brain magnetic resonance imaging showed a discrete area in dorsomedial pontine tegments with hyperintensity on FLAIR. The patient was diagnosed with multiple sclerosis after close examination at the Neurology Department. The horizontal slow saccades improved after steroid treatment. This is a rare case in which the demyelinating lesion was located in the paramedian pontine reticular formation (PPRF), resulting in impairment of only bilateral horizontal SM. We believe this is a valuable clinical case demonstrating the involvement of the PPRF in horizontal SM.
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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 69 ( 3 ) 378 - 386 2025
Language：English Publishing type：Research paper (scientific journal) Publisher：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.
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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 ) 2024.12
Publishing type：Research paper (scientific journal) Publisher：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.
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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 2024.11
Language：English Publishing type：Research paper (scientific journal) Publisher：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.
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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 Invited
池田 康博
臨床眼科 78 ( 11 ) 220 - 226 2024.10
Authorship：Lead author, Corresponding author Language：Japanese Publishing type：Part of collection (book) Publisher：株式会社医学書院
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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 2024.9
Publishing type：Research paper (scientific journal) Publisher：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.
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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 2024.9
Language：English Publishing type：Research paper (scientific journal) Publisher：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.