Papers - IKEDA Yasuhiro
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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 Reviewed
山添 早織, 中馬 秀樹, 池田 康博
臨床眼科 78 ( 7 ) 823 - 827 2024.7
Publishing type：Research paper (scientific journal) Publisher：株式会社医学書院
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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 2024.6
Language：English Publishing type：Research paper (scientific journal) Publisher：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.
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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 2024.6
Publishing type：Research paper (scientific journal) Publisher：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.
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Genotypes and clinical features of RHO-associated retinitis pigmentosa in a Japanese population. Reviewed
Tsutsui S, Murakami Y, Fujiwara K, Koyanagi Y, Akiyama M, Takeda A, Ikeda Y, Sonoda KH
Japanese journal of ophthalmology 68 ( 1 ) 1 - 11 2024.1
Language：English Publishing type：Research paper (scientific journal) Publisher：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.
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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 2024.1
Authorship：Last author, Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：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.
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A Case of Junctional Scotoma Caused by Idiopathic Optic Chiasmitis at the Macular Fiber Chiasm Reviewed
Tamura Chinami, Nagatomo Saori, Chuman Hideki, Ikeda Yasuhiro
Neuro-Ophthalmology Japan 40 ( 3 ) 248 - 253 2023.9
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Neuro-Ophthalmology Society
A 37-year-old man experienced blurry vision in his left eye. His corrected visual acuity was 1.2 OD and 0.6 OS. The relative afferent pupillary defect was negative. Humphrey visual field test indicated bitemporal hemianopia within 10º of visual field and diminished sensitivity in the central nasal field of the left eye. Brain gadolinium-enhanced magnetic resonance imaging (MRI) revealed an enhanced small lesion slightly to the left posterior part within the center of the optic chiasma. The patientʼs visual acuity recovered to 1.0 without treatment, and his visual field defect disappeared. A repeated brain MRI showed no enhanced lesion in the optic chiasma. We speculate that this patient had inflammation, specifically of the crossed macular fibers and uncrossed fibers towards the left of the chiasma. Consequently, this case supports the anatomical evidence indicating the existence of macular fiber chiasma within the optic chiasm. Moreover, such cases could be misdiagnosed as a nonorganized visual disturbance, especially without appropriate selection of the visual field program.
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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 2023.7
Publishing type：Research paper (scientific journal) Publisher：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.
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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 2023.5
Publishing type：Research paper (scientific journal) Publisher：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.
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第5土曜特集 mRNAワクチンやゲノム編集で注目が集まる遺伝子治療 遺伝子治療技術を用いた疾患治療 眼科疾患に対する遺伝子治療 Invited
池田 康博
医学のあゆみ 285 ( 5 ) 414 - 419 2023.4
Authorship：Lead author, Corresponding author Language：Japanese Publishing type：Part of collection (book) Publisher：医歯薬出版
DOI： 10.32118/ayu28505414
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特集 日本の眼の難病-何がどこまでわかってきたのか? 網膜色素変性の疾患レジストリ Reviewed
池田 康博
臨床眼科 77 ( 1 ) 37 - 40 2023.1
Publishing type：Research paper (scientific journal) Publisher：株式会社医学書院
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Drinking hydrogen water improves photoreceptor structure and function in retinal degeneration 6 mice Reviewed
Igarashi T., Ohsawa I., Kobayashi M., Miyazaki K., Igarashi T., Kameya S., Shiozawa A.L., Ikeda Y., Miyagawa Y., Sakai M., Okada T., Sakane I., Takahashi H.
Scientific Reports 12 ( 1 ) 13610 2022.12
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Scientific Reports
Retinitis pigmentosa (RP) is a genetically heterogeneous group of inherited retinal disorders involving the progressive dysfunction of photoreceptors and the retinal pigment epithelium, for which there is currently no treatment. The rd6 mouse is a natural model of autosomal recessive retinal degeneration. Given the known contributions of oxidative stress caused by reactive oxygen species (ROS) and selective inhibition of potent ROS peroxynitrite and OH·by H2 gas we have previously demonstrated, we hypothesized that ingestion of H2 water may delay the progression of photoreceptor death in rd6 mice. H2 mice showed significantly higher retinal thickness as compared to controls on optical coherence tomography. Histopathological and morphometric analyses revealed higher thickness of the outer nuclear layer for H2 mice than controls, as well as higher counts of opsin red/green-positive cells. RNA sequencing (RNA-seq) analysis of differentially expressed genes in the H2 group versus control group revealed 1996 genes with significantly different expressions. Gene and pathway ontology analysis showed substantial upregulation of genes responsible for phototransduction in H2 mice. Our results show that drinking water high in H2 (1.2–1.6 ppm) had neuroprotective effects and inhibited photoreceptor death in mice, and suggest the potential of H2 for the treatment of RP.
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Yamakiri K., Sakamoto T., Koriyama C., Kawasaki R., Baba T., Nishitsuka K., Koto T., Terasaki H., Yamamoto S., Baba T., Sato E., Kitahashi M., Tatsumi T., Miura G., Niizawa T., 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., 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.
Scientific Reports 12 ( 1 ) 2022.12
Publishing type：Research paper (scientific journal) Publisher：Scientific Reports
The purpose of this study was to investigate the effects of surgeon-related factors on the surgical outcome of pars plana vitrectomy (PPV) and scleral buckling (SB) surgery on eyes with a rhegmatogenous retinal detachment (RRD). This was a nationwide, multicenter, observational study of the data in the Japan-RD Registry. Registered cases that had undergone surgery for a RRD by 128 accredited surgeons in 26 institutions were studied. The surgeon-related factors that significantly affected surgical success and visual outcomes of simple RRD treated by PPV or SB at 6 months postoperatively were analyzed and compared. Among 3446 registered cases, 2533 cases met the inclusion criteria with 1896 in the PPV group and 637 cases in the SB group. The median total number of lifetime cases was 150 and the rate of surgeries/year was 22. Multivariate regression analyses showed that the number and rate of surgeries/year were not significantly associated with the surgical outcome in the PPV group. However, surgeons with a higher average annual number of surgeries had significantly better surgical outcomes in the SB group (P = 0.038). Analyses of a nationwide registry showed that SB but not PPV surgeries require sufficient experience and case numbers to acquire and maintain skills to treat RRDs successfully.
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Takano F, Ueda K, Godefrooij DA, Yamagami A, Ishikawa H, Chuman H, Ishikawa H, Ikeda Y, Sakamoto T, Nakamura M
Orphanet journal of rare diseases 17 ( 1 ) 319 2022.8
Language：English Publishing type：Research paper (scientific journal) Publisher：Orphanet Journal of Rare Diseases
Background: Leber hereditary optic neuropathy (LHON) is an acute or subacute optic neuropathy that mainly affects young males. The first nationwide epidemiological survey of LHON was conducted in 2014 in Japan, and LHON was officially designated as a rare intractable disease by the Japanese government in 2015. We conducted a second survey of the annual incidence of LHON in 2019, and estimated the total number of patients with LHON in Japan. Results: A questionnaire was sent to 997 facilities accredited by the Japanese Ophthalmological Society and/or affiliated with the councilors of the Japanese Neuro-Ophthalmology Society. Responses were received from 791 facilities, with a response rate of 79%. Fifty-five newly diagnosed cases (49 males and 6 females) of LHON were reported from 35 institutions in 2019, with a median age of 28.5 for males and 49.5 years for females. The total number of newly diagnosed cases was calculated as 69 (62 were males and 7 were females, 95% confidence interval 55–83), and the total number of patients was estimated to be 2491 (95% confidence interval: 1996–2986), suggesting a prevalence of LHON in Japan of 1:50,000. Conclusion: The incidence of LHON in 2019 was lower than the estimate in 2014, whereas its prevalence may be similar to that reported in other countries. The accurate estimation of the incidence and prevalence of patients with LHON requires prospective registration.
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Sano Y, Koyanagi Y, Wong JH, Murakami Y, Fujiwara K, Endo M, Aoi T, Hashimoto K, Nakazawa T, Wada Y, Ueno S, Gao D, Murakami A, Hotta Y, Ikeda Y, Nishiguchi KM, Momozawa Y, Sonoda KH, Akiyama M, Fujimoto A
Journal of medical genetics 2022.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Medical Genetics
Despite the successful identification of causative genes and genetic variants of retinitis pigmentosa (RP), many patients have not been molecularly diagnosed. Our recent study using targeted short-read sequencing showed that the proportion of carriers of pathogenic variants in EYS, the cause of autosomal recessive RP, was unexpectedly high in Japanese patients with unsolved RP. This result suggested that causative genetic variants, which are difficult to detect by short-read sequencing, exist in such patients. Using long-read sequencing technology (Oxford Nanopore), we analysed the whole genomes of 15 patients with RP with one heterozygous pathogenic variant in EYS detected in our previous study along with structural variants (SVs) in EYS and another 88 RP-associated genes. Two large exon-overlapping deletions involving six exons were identified in EYS in two patients with unsolved RP. An analysis of an independent patient set (n=1189) suggested that these two deletions are not founder mutations. Our results suggest that searching for SVs by long-read sequencing in genetically unsolved cases benefits the molecular diagnosis of RP.
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Kawano S., Imai T., Sakamoto T., 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., 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., Keijiro Ishikawa , 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.
Japanese Journal of Ophthalmology 66 ( 3 ) 271 - 277 2022.5
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Ophthalmology
Purpose: To investigate the characteristics of retinal detachment (RD) and compare the outcomes of surgical interventions, such as scleral buckling (SB), pars plana vitrectomy (PPV), or PPV combined with SB, conducted on holidays and on workdays to determine the optimal surgical timing for primary RD treatment in clinical practice. Study design: Retrospective cohort study. Methods: The cohort included 3178 patients with primary RD registered in the Japan Retinal Detachment Registry between February 2016 and March 2017. Surgery data were divided into holiday and workday groups. A descriptive analysis of primary RD characteristics was performed, and the outcomes for each surgical intervention were assessed. The primary outcome was anatomical failure at 6 months post-surgery classified as follows: level 1, inoperable state; level 2, anatomical recovery with silicone-oil use; and level 3, additional surgery required for RD repair. Results: The holiday group comprised 108 and the workday, 3070 cases of primary RD. Compared with those in the workday group, surgery in the holiday group took longer (PPV, P < 0.0001; SB, P = 0.047) and was performed by less experienced surgeons (P = 0.014). However, there were no statistically significant differences in surgical failure 6 months post-surgery between the workday and holiday groups. Conclusion: Although surgery conducted on holidays and workdays was not significantly different in terms of outcome, some surgery should be postponed with proper preoperative interim measures to limit RD progress until it can be conducted on workdays by a well-prepared team.
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Long-term Outcomes of Cataract Surgery in Patients with Retinitis Pigmentosa Reviewed
Nakamura S., Fujiwara K., Yoshida N., Murakami Y., Shimokawa S., Koyanagi Y., Ikeda Y., Sonoda K.H.
Ophthalmology Retina 6 ( 4 ) 268 - 272 2022.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Ophthalmology Retina
Purpose: To investigate the long-term outcomes of cataract surgery in patients with retinitis pigmentosa (RP). Design: Retrospective, observational study. Participants: Sixty-four patients with typical RP (22 men, 42 women; average age, 62.8 ± 10.1 years) who underwent cataract surgery at Kyushu University Hospital between May 2007 and October 2015 and were followed up for ≥3 years after the surgery. Methods: Differences between presurgery and postsurgery visual function, including best-corrected visual acuity (BCVA) and parameters in the Humphrey field analyzer (HFA) examination using the central 10-2 program, were investigated. The presurgery conditions of the foveal ellipsoid zone (EZ) were classified into 3 grades (grade 1: invisible; grade 2: abnormal; grade 3: normal) based on OCT findings. Main Outcome Measures: BCVA, the retinal sensitivity in the HFA 10-2 test. Results: Cataract surgery was performed in 96 eyes, with an average follow-up period of 5.8 ± 2.4 years. The mean presurgery BCVA was 0.64 ± 0.52 logarithm of the minimum angle of resolution (logMAR), and the final postsurgery BCVA was 0.61 ± 0.67 logMAR (P = 0.57). Significant improvement in the postsurgery BCVA was observed only in eyes with preserved foveal EZ (grade 3) (P < 0.01). In 62 eyes of 45 patients who underwent the HFA 10-2 test, the mean values of deviation, macular sensitivity, and foveal sensitivity at the final visit were significantly decreased compared with preoperative values (P < 0.01), whereas those in grade 3 eyes did not change significantly after the surgery (P = 0.13). Conclusions: In the long-term course after cataract surgery in patients with RP, many patients experienced vision loss with progression of the disease. The preoperative finding of preserved foveal EZ was associated with a better visual prognosis, suggesting that EZ evaluation is useful for predicting the long-term visual outcome of cataract surgery in patients with RP.
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Wykoff C.C., Abreu F., Adamis A.P., Basu K., Eichenbaum D.A., Haskova Z., Lin H., Loewenstein A., Mohan S., Pearce I.A., Sakamoto T., Schlottmann P.G., Silverman D., Sun J.K., Wells J.A., Willis J.R., Tadayoni R., 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., Baumal C., 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., Csaky K., Danzig C., Das A., Daskalov V., Desco C., Dessouki A., Dickinson J., Do B., Dollin M., Dugel P., Dusova J., Eldem B.
The Lancet 399 ( 10326 ) 741 - 755 2022.2
Publishing type：Research paper (scientific journal) Publisher：The Lancet
Background: To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody. Methods: YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593). Findings: 3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference −0·2 ETDRS letters [−2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [−0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [−1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [−1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]). Interpretation: Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema. Funding: F Hoffmann-La Roche.
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特集 今知っておきたいゲノム医療と遺伝子治療-基礎から臨床まで 各論 遺伝子治療 遺伝性網膜疾患に対する遺伝子治療 Reviewed
池田 康博
小児内科 54 ( 2 ) 349 - 353 2022.2
Publishing type：Research paper (scientific journal) Publisher：東京医学社
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Shimokawa S., Murakami Y., Fujiwara K., Funatsu J., Nakatake S., Koyanagi Y., Akiyama M., Yoshida N., Takeda A., Ikeda Y., Sonoda K.H.
Retina 42 ( 1 ) 168 - 173 2022.1
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Retina
Purpose: To investigate the rate of the recurrence of cystoid macular edema (CME) secondary to retinitis pigmentosa (RP) after the initiation of topical dorzolamide and the recurrence risk factors. Methods: We retrospectively analyzed the data of RP patients at Kyushu University Hospital. We included patients who showed a treatment response to 1.0% topical dorzolamide. The day of treatment initiation was set as the baseline. Topical dorzolamide treatment was continued during the follow-up. The recurrence of CME (defined as a .20% increase in central subfield thickness compared to previous visit, or a central subfield thickness value that exceed baseline value) was evaluated at each follow-up visit. Risk factors for RP-CME recurrence were analyzed by Cox proportional hazards modeling. A Kaplan–Meier survival analysis was used to evaluate the time to recurrent RP-CME. Results: Forty RP-CME patients showed a treatment response to topical dorzolamide. During the mean 3.9-year follow-up, 14 patients exhibited recurrence; its rate was 15.6%, 34.7%, and 48.7% at 1, 3, and 5 years, respectively. A high baseline central subfield thickness was significantly associated with recurrent (hazard ratio 1.11, 95% CI: 1.05–1.18, P = 0.0004). Conclusion: The recurrence rate of RP-CME increased with time. A high baseline central subfield thickness value was a risk factor for recurrence.
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Regional and sex differences in retinal detachment surgery: Japan-retinal detachment registry report Reviewed
Funatsu R., Terasaki H., Sakamoto T., Yamamoto S., Baba T., Sato E., Kitahashi M., Tatsumi T., Miura G., Niizawa 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., Emi K., Nakashima H., Ohji M.
Scientific Reports 11 ( 1 ) 2021.12
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Scientific Reports
It is known that social factors affect the choice of treatments, and special attention has been paid to sex differences. The purpose of this study was to determine whether regional and sex differences exist in the treatment of rhegmatogenous retinal detachment (RD). We used Japan-RD Registry database of 2523 patients aged ≥ 40 years between February 2016 and March 2017 in 5 Japanese regions. Regional differences of patients’ perioperative factors were analyzed. The factors affecting the proportion of patients who underwent surgery within one week of the onset, defined as early-surgery, were examined by logistic regression. We observed regional differences in perioperative factors, especially in the use of phacovitrectomy, general anesthesia, and air-tamponade, which was higher in certain regions. (Fisher’s exact test, all P = 0.012) The proportion of early-surgery was significantly higher among men in Kyushu region (Odds ratio (OR) 1.83; 95% confidence interval (CI) 1.08–3.12; P = 0.02), and it was also significantly higher after adjusting for covariates (OR 1.89; 95% CI 1.06–3.42; P = 0.02). Regional and sex differences exist in the treatment of RD in Japan. Although there was no significant differences in the anatomical outcomes, women in certain regions of Japan are less likely to receive early surgical intervention for RD.