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Koh-Hei Sonoda Last modified date：2024.04.15

Professor / Surgery / Department of Clinical Medicine / Faculty of Medical Sciences


Papers
1. Nagata J, Shiose S, Ishikawa K, Fukui T, Kano K, Mori K, Nakama T, Notomi S, Sonoda KH, Clinical characteristics of neovascular age-related macular degeneration eyes with retinal pigment epithelium tears　, J Clin Med., 2023.08.
2. Fukuda Y, Notomi S, Shiose S, Kano K, Hashimoto S, Fujiwara K, Akiyama M, Ishikawa K, Hisatomi T, Sonoda KH, Differences in central and peripheral choroidal thickness among the subtypes of age-related macular degeneration in an Asian population　, J Clin Med., 2023.08.
3. Wada I, Nakao S, Fukuda Y, Shiose S, Takeda A, Kannan R, Sonoda KH, Persistence of vascular empty sleeves in choroidal neovascularization after VEGF therapy in both animal models and humans　, Graefes Arch Clin Exp Ophthalmol., 2023.08.
4. Ueda E, Yasuda M, Fujiwara K, Hashimoto S, Nakamura S, Honda T, Hata J, Ninomiya T, Sonoda KH;, Association between choroidal thickness and myopic maculopathy in a Japanese population: the Hisayama Study　, Ophthalmol Sci., 2023.06.
5. Akiyama M, Miyake M, Momozawa Y, Arakawa S, Maruyama-Inoue M, Endo M, Iwasaki Y, Ishigaki K, Matoba N, Okada Y, Yasuda M, Oshima Y, Yoshida S, Nakao S, Morino K, Mori Y, Kido A, Kato A, Yasukawa T, Obata R, Nagai Y, Takahashi K, Fujisawa K, Miki A, Nakamura M, Honda S, Ushida H, Yasuma T, Nishiguchi KM, Mori R, Tanaka K, Wakatsuki Y, Yamashiro K, Kadonosono K, Terao C, Ishibashi T, Tsujikawa A, Sonoda KH, Kubo M, Kamatani Y , Genome Wide Association Study of Age-Related Macular Degeneration Reveals Two New Loci Implying Shared Genetic Components with Central Serous Chorioretinopathy　, Ophthalmology. , 2023.04.
6. Yamana S, Hasegawa E, Takeda A, Yawata N, Sonoda KH, Long-term outcomes of infliximab in patients with Behçet's disease-associated uveitis　, International ophthalmology , 2023.03.
7. Hashimoto S, Yasuda M, Fujiwara K, Ueda E, Nakamura S, Hirakawa Y, Higashioka M, Hata J, Ninomiya T, Sonoda KH, Secular trends in the prevalence, incidence, and progression of diabetic retinopathy: the Hisayama Study, Graefes Arch Clin Exp Ophthalmol. , 2023.03.
8. Nakao S, Kaizu Y, Horie J, Wada I, Fukuda Y, Ishikawa K, Sonoda KH　, Volumetric Three-Dimensional Optical Coherence Tomography Angiography of Retinal Neovascularization in Proliferative Diabetic Retinopathy, Retin Cases Brief Rep. , 2023.03.
9. Fujii Y, Arima M, Murakami Y, Sonoda KH, Rhodopsin-positive cell production by intravitreal injection of small molecule compounds in mouse models of retinal degeneration　, PLoS One. , 2023.02.
10. Takeuchi M, Usui Y, Namba K, Keino H, Takeuchi M, Takase H, Kamoi K, Hase K, Ito T, Nakai K, Maruyama K, Kobayashi E, Mashimo H, Sato T, Ohguro N, Hori J, Okada AA, Sonoda KH, Mizuki N, Goto H , Ten-year follow-up of infliximab treatment for uveitis in Behçet disease patients: a multicenter retrospective study　

, Frontiers in Medicine, 2023.01.
11. Zhou D, Takeyama H, Nakao S, Sonoda KH, Tadano K, Real-time fundus reconstruction and intraocular mapping using an ophthalmic endoscope　, International Journal of Medical Robotics and Computer Assisted Surgery, 2023.01.
12. Yamaguchi M, Nakao S, Wada I, Matoba T, Arima M, Kaizu Y, Shirane M, Ishikawa K, Nakama T, Murakami Y, Mizuochi M, Shiraishi W, Yamasaki R, Hisatomi T, Ishibashi T, Shibuya M, Stitt AW, Sonoda KH, Identifying Hyperreflective Foci in Diabetic Retinopathy via VEGF-induced Local Self-Renewal of CX3CR1+ Vitreous Resident Macrophages　, Diabetes, 2022.12.
13. Fukui T, Ishikawa K, Shiose S, Kano K, Mori K, Notomi S, Sonoda KH　 , Spatial pattern of retinal pigment epithelium tear development and progression after anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration　, Retin Cases Brief Rep., 2022.11.
14. Fujiwara K, Yasuda M, Hata J, Nakano S, Hashimoto S, Ueda E, Nakamura S, Murakami Y, Nakamuro T, Araie M, Tawara A, Kubota T, Yoshitomi T, Ninomiya T, Sonoda KH , Prevalence of glaucoma and its systemic risk factors in a general Japanese population: the Hisayama Study　, Transl Vis Sci Technol, 2022.11.
15. 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, Likely pathogenic structural variants in genetically unsolved patients with retinitis pigmentosa revealed by long-read sequencing, J Med Genet, 2022.11.
16. Fukuda Y, Nakao S, Kaizu Y, Arima M, Shimokawa S, Wada I, Yamaguchi M, Takeda A, Sonoda KH, Morphology and Fluorescein Leakage in Diabetic Retinal Microaneurysms: A Study Using Multiple En Face OCT Angiography Image Averaging, Graefes Arch Clin Exp Ophthalmol, 2022.11.
17. Shirane M, Yawata N, Motooka D, Shibata K, SS Khor , omae Y, Kaburaki T, Yanai R, Mashimo H, Yamana S, Ito T, Hayashida A, Mori Y, Numata A, Murakami Y, Fujiwara K, Ohguro N, Hosogai M, Akiyama M, Hasegawa E, M Paley , Takeda A, Maenaka K, Akashi K, WM Yokoyama, Tokunaga K, Yawata M, Sonoda KH, Intraocular human cytomegaloviruses of ocular diseases are distinct from those of viremia and are capable of innate and adaptive immune escape by exploiting HLA-E-mediated peripheral and central toler　, Front Immunol , 2022.10.
18. Wada I, Nakao S, Arima M, Ishikawa K, Yamaguchi M, Kaizu Y, Sekiryu H, Mori K, Kiyohara Kohei, Takeda A, Ishibashi T, Sadda SR, Sonoda KH, Hyperreflective Membrane at the Vitreoretinal Interface in Diabetic Macular Edema: A Finding in Ultra-High-Resolution Optical Coherence Tomography, Transl Vis Sci Technol, 11, 9, 21, 2022.09.
19. Takeda A, Sakoda T, Yawata Nobuyo, Kato K, Hasegawa E, Shima T, Hikita S, Yoshitomi K, Takenaka K, Oda Y, Akashi K, Sonoda KH, Panuveitis induced by donor-derived CD8+ T cells after allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia, Am J Ophthalmol Case Rep, 27, 101673, 2022.09.
20. Notomi S, Shiose S, Fukuda Y, Mori K, Hashimoto S, Kano K, Ishikawa K, Sonoda KH, Characteristics of retinal pigment epithelium elevations preceding exudative age-related macular degeneration in Japanese, Ophthalmic Research, doi.org/10.1159/000526445, 2022.08.
21. Murata C, Murakami Y, Fukui T, Shimokawa S, Sonoda KH, Fujisawa K, Serous retinal detachment without leakage on fluorescein/indocyanine angiography in MEK inhibitor-associated retinopathy, Case Rep Ophthalmol, 13, 2, 542-549, 2022.07.
22. Hongo T, Yamamoto H, Tanabe M, Yasumatsu R, Kuga R, Miyazaki Y, Jiromaru R, Hashimoto K, Tateishi Y, Sonoda KH, Nakagawa T, Oda Y, High-risk HPV-related Squamous Cell Carcinoma in the Conjunctiva and Lacrimal sac: Clinicopathologic Characteristics and Diagnostic Utility of p16 and Rb Immunohistochemistry, 46, 7, 977-987, 2022.07.
23. Mori K, Ishikawa K, Fukuda Y, Rui ji, Wada I, Kubo Y, Akiyama M, Notomi Shoji, Murakami Y, Nakao S, Arakawa S, Shiose Satomi, Hisatomi T, Yoshida S, Ram Kannan, Sonoda KH, TNFRSF10A downregulation induces retinal pigment epithelium degeneration during the pathogenesis of age-related macular degeneration and central serous chorioretinopathy, Hum Mol Genet, 31, 13, 2194-2206, 2022.07.
24. Kaizu Y, Nakao S, Soda T, Horie J, Wada I, Yamaguchi M, Takeda A, Sonoda KH, Longer Interscan Times in Optical Coherence Tomography Angiography Detect Slower Capillary Flow in Diabetic Retinopathy  , Ophthalmol Sci, , 2023.06.
25. Umazume A, Ohguro N, Okada A A, Namba K, Sonoda KH, Tsuruga H, Morita K, Goto H, Use of systemic corticosteroids in patients newly registered at a claims database with a diagnosis of non-infectious uveitis: results from a real-world claims database analysis, Jpn J Ophthalmol, 2022.06.
26. Notomi S, Shiose S, Kohno RI, Shimokawa S, Ishikawa K, Kano K, Mori K, Wada I, Fukuda Y, Nakatake S, Yamaguchi M, Sonoda KH, A case of bullous central serous chorioretinopathy treated with surgical removal of submacular fibrin and subsequent photodynamic therapy under silicone oil, Case Rep Ophthalmol, 13, 385-392, 2022.05.
27. Fukuda Y, Nakao S, Kohno RI, Ishikawa K, Shimokawa S, Shiose Satomi, Takeda A, Morizane Y, Sonoda KH, Postoperative follow‐up of submacular hemorrhage displacement treated with vitrectomy and subretinal injection of tissue plasminogen activator, Jpn J Ophthalmol, 66, 3, 264-270, 2022.05.
28. Nakamura S, Fujiwara K, Yoshida N, Murakami Y, Shimokawa S, Koyanagi Y, Ikeda Y, Sonoda KH, Long-term Outcomes of Cataract Surgery in Patients with Retinitis Pigmentosa, Ophthalmology Retina, 6, 4, 268-272, 2022.04.
29. Nakao S, Nishida T, Sonoda KH, Removal of MIRAgel Scleral Buckle Implants using Yankauer Suction Catheter with Adjusted Diameter, Am J Ophthalmol Case Rep, 26, 10140, 2022.03.
30. Funatsu J, Murakami Y, Shimokawa S, Nakatake S, Fujiwara K, Okita A, Fukushima Masatoshi, Shibata K, Yoshida N, Koyanagi Y, Akiyama M, Notomi S, Nakao S, Hisatomi T, Takeda A, Eleftherios I. Paschalis, Demetrios G. Vavvas, Ikeda Y, Sonoda KH, Circulating inflammatory monocytes oppose microglia and contribute to cone cell death in retinitis pigmentosa　, PNAS Nexus, 1, 1, 3, 2022.03.
31. Takeda A, Hasegawa E, Yawata N, Notomi S, Ishikawa K, Murakami Y, Hisatomi T, Kimura K, Sonoda KH, Increased vitreous levels of B cell activation factor (BAFF) and soluble interleukin-6 receptor in patients with macular edema due to uveitis related to Behçet’s disease and sarcoidosis, Graefes Arch Clin Exp Ophthalmol, 268, 2675-2686, 2022.03.
32. Yamana S, Shibata K, Hasegawa E, Arima M, Shimokawa S, Yawata N, Takeda A, Yamasaki S, Sonoda KH, Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity, Mucosal Immunol, 15, 2, 351-361, 2022.02.
33. Sakisaka S, Tanabe M, Imayama S, Zeze N, Yamana K, Yoshikawa H, Sonoda KH, Two Cases of Angiosarcoma with Persistent Unilateral Eyelid Swelling, Ocular Oncology and Pathology, 8, 1, 16-21, 2022.02.
34. Takase H, Goto H, Namba k, Mizuki N, Ohguro N, Sonoda KH, Tomita M, Keino H, Kezuka T, Kubono R, Mizuuchi K, Shibuya E, Takahashi H, Yanai R, Mochizuki M, Clinical characteristics, management, and factors associated with poor visual prognosis of acute retinal necrosis, Ocul Immunol Inflamm, 30, 1, 48-53, 2022.01.
35. Wada I, Shiose S, Ishikawa K, Kano K, Notomi S, Mori K, Akiyama M, Nakao S, Sonoda KH, One-year efficacy of “rescue-photodynamic therapy” for patients with typical age-related macular degeneration, polypoidal choroidal vasculopathy, and pachychoroid neovasculopathy refractory to anti-, Graefes Arch Clin Exp Ophthalmol, 260, 6, 2029-2036, 2022.01.
36. Nakamura S, Nakao S, Shiose S, Kohno RI, Hasegawa E, Sonoda KH; Eur J, Optical Coherence Tomography Angiography of Choroidal Neovascularization in Immune Choroiditis Following Acute Retinal Necrosis, Ophthalmol, 32, 1, 114-118, 2022.01.
37. Shimokawa S, Murakami Y, Fujiwara K, Funatsu J, Nakatake S, Koyanagi Y, Akiyama M, Yoshida N, Takeda A, Ikeda Y, Sonoda KH, Recurrence Rate of Cystoid Macular Edema with Topical Dorzolamide Treatment and its Risk Factors in Retinitis Pigmentosa, 42, 1, 168-173, 2022.01.
38. Murakami Y, Koyanagi Y, Fukushima M, Yoshimura M, Fujiwara K, Akiyama M, Momozawa Y, Ueno S, Terasaki H, Oishi A, Miyata M, Ikeda H, Tsujikawa A, Mizobuchi K, Hayashi T, Fujinami K, Tsunoda K, Park JY, Han J, Kim M, Lee CS, Kim SJ, Park TK, Joo K, Woo SJ, Ikeda Y, Sonoda KH, Genotype and Long-term Clinical Course of Bietti Crystalline Dystrophy in Korean and Japanese Patients, Ophthalmology Retina, 5, 12, 1269-1279, 2021.12.
39. Wada I, Nakao S, Yamaguchi M, Kaizu Y, Arima M, Shinichiro Sawa, Sonoda KH, Retinal VEGF-A Overexpression Is Not Sufficient to Induce Lymphangiogenesis Regardless of VEGF-C Upregulation and Lyve1+ Macrophage Infiltration, Invest Ophthalmol Vis Sci, 62, 13, 17, 2021.10.
40. Mori Y, Arima M, Ueda E, Fujiwara K, Seki E, Nakama T, Tsukamoto S, Akiyama M, Sonoda KH, Risk factors for myopia at 1-year corrected age following laser photocoagulation for retinopathy of prematurity, Eye, 35, 10, 2820-2825, 2021.10.
41. Uchi SH, Yanai R, Tsuneoka H, Otsuyama KI, Sonoda KH, Kimura K, A case of cat scratch disease diagnosed by Indirect fluorescent antibody assay of igm specific for a Japanese strain of Bartonella henselae, Retin Cases Brief Rep, 15, 5, 571-574, 2021.09.
42. Umazume A, Ohguro N, Okada A, Namba K, Sonoda KH, Tsuruga H, Morita K, Prevalence and incidence rates and treatment patterns of non-infectious uveitis in Japan: real-world data using a claims database, Jpn J Ophthalmol, 65, 5, 657-665, 2021.09.
43. Ishikawa K, Akiyama M, Mori K, Nakama T, Notomi S, Nakao S, Kohno RI, Takeda A, Sonoda KH, Drainage retinotomy confers risk of epiretinal membrane formation following vitrectomy for rhegmatogenous retinal detachment repair, Am J Ophthalmol, 234, 20-27, 2021.07.
44. Notomi S, Shiose S, Ishikawa K, Fukuda Y, Kano K, Mori K, Wada I, Kaizu Y, Matsumoto H, Akiyama M, Sonoda KH, Drusen and pigment abnormality predict the development of neovascular age-related macular degeneration in Japanese patients, PLoS One, 16, 7, e0255213, 2021.07.
45. Arima M, Inoue H, Nakao S, Misumi A, Suzuki M, Matsushita I, Araki S, Yamashiro C, Takahashi M, Ochiai M, Yoshida N, Hirose M, Kishimoto J, Todaka K, Hasegawa S, Kimura K, Kusuhara K, Kondo H, Ohga S, Sonoda KH, Study protocol for a multi-center, open-label, single-arm phase I/II trial to evaluate the safety and efficacy of ripasudil 0.4% eye drops for retinopathy of prematurity, BMJ Open, 11, 7, e047003, 2021.07.
46. Nakao S, Kaizu Y, Horie J, Wada I, Fukuda Y, Ishikawa K, Sonoda KH, Volumetric Three-Dimensional Optical Coherence Tomography Angiography of Retinal Neovascularization in Proliferative Diabetic Retinopathy, Retin Cases Brief Rep, 2021.07.
47. Tanabe M, Yoshikawa H, Yamada Y, Oda Y, Sonoda KH, A case of primary orbital solitary fibrous tumor with lung metastases 41 years after initial treatment, Orbit, 10, 1-5, 2021.07.
48. Terada Y, Kaburaki T, Takase H, Goto H, Nakano S, Inoue Y, Maruyama K, Miyata K, Namba K, Sonoda KH, Kaneko Y, Numaga J, Fukushima M, Horiguchi N, Ide M, Ehara F, Miyazaki D, Hasegawa E, Mochizuki M, Distinguishing Features of Anterior Uveitis Caused by Herpes Simplex Virus, Varicella-Zoster Virus and Cytomegalovirus, Am J Ophthalmol, 227, 191-200, 2021.07.
49. Takeda A, Hasegawa E, Notomi S, Ishikawa K, Arima M, Murakami Y, Nakao S, Hisatomi T, Sonoda KH, Surgical outcomes of cataract surgery for contrast sensitivity and visual acuity in uveitis-associated cataract, Clin Ophthalmol, 15, 2665-2673, 2021.06.
50. Asano M, Sonoda KH, Tsukamoto S, Kondo H, Revesz syndrome with bilateral retinal detachments successfully treated by pars plana vitrectomy, Am J Ophthalmol Case Rep, 23, 101137, 2021.06.
51. Sasaki M, Miyake M, Fujiwara K, Namba H, Akiyama M, Yanagi Y, Harada S, Tabara Y, Yasuda M, Yamashita H, Kayama T, Tsubota K, Matsuda F, Hashimoto S, Ueda E, Ninomiya T, Takebayashi T, Tsujikawa A, Sonoda KH, Kawasaki R, Cohort Profile: the Ganka-Ekigaku Network (GEN), a network of Japanese ophthalmological epidemiology studies, Ophthalmic Epidemiol, 28, 3, 237-243, 2021.06.
52. Yawata N, Shirane M, Woon K, Lim X, Tanaka H, Kawano YI, Yawata M, Chee SP, Siak J, Sonoda KH, Molecular Signatures of Natural Killer Cells in CMV-Associated Anterior Uveitis, A New Type of CMV-Induced Disease in Immunocompetent Individuals, Int J Mol Sci, 22, 7, 3623, 2021.03.
53. Sonoda KH, Hasegawa E, Namba K, Okada A, Ohguro N, Goto H, Epidemiology of uveitis in Japan: a 2016 retrospective nationwide survey, Jpn J Ophthalmol, 65, 184-190, 2021.03.
54. Arima M, Nakao S, Kaizu Y, Wada I, Yamaguchi M, Fujiwara K, Akiyama M, Stitt AW, Sonoda KH, Diabetic vascular hyperpermeability: optical coherence tomography angiography and functional loss assessments of relationships among retinal vasculature changes, Sci Rep, 11, 1, 4185, 2021.02.
55. Oshima Y, Ishibashi Y, Umeda N, Nagata T, Yoshida S, Uchio Eiichi, Kondo H, Sonoda KH, Ishibashi T, Correlation between Improvement in Visual Acuity and QOL after Ranibizumab Treatment for Age-Related Macular Degeneration Patients: QUATRO study, BMC Ophthalmol, 21, 58, 2021.01.
56. Yuki Kubo, Keijiro Ishikawa, Kenichiro Mori, Yoshiyuki Kobayashi, Takahito Nakama, Mitsuru Arima, Shintaro Nakao, Toshio Hisatomi, Masatoshi Haruta, Koh Hei Sonoda, Shigeo Yoshida, Periostin and tenascin-C interaction promotes angiogenesis in ischemic proliferative retinopathy, Scientific reports, 10.1038/s41598-020-66278-1, 10, 1, 2020.06, Ischemic proliferative retinopathy (IPR), such as proliferative diabetic retinopathy (PDR), retinal vein occlusion and retinopathy of prematurity is a major cause of vision loss. Our previous studies demonstrated that periostin (PN) and tenascin-C (TNC) are involved in the pathogenesis of IPR. However, the interactive role of PN and TNC in angiogenesis associated with IPR remain unknown. We found significant correlation between concentrations of PN and TNC in PDR vitreous humor. mRNA and protein expression of PN and TNC were found in pre-retinal fibrovascular membranes excised from PDR patients. Interleukin-13 (IL-13) promoted mRNA and protein expression of PN and TNC, and co-immunoprecipitation assay revealed binding between PN and TNC in human microvascular endothelial cells (HRECs). IL-13 promoted angiogenic functions of HRECs. Single inhibition of PN or TNC and their dual inhibition by siRNA suppressed the up-regulated angiogenic functions. Pathological pre-retinal neovessels of oxygen-induced retinopathy (OIR) mice were attenuated in PN knock-out, TNC knock-out and dual knock-out mice compared to wild-type mice. Both in vitro and in vivo, PN inhibition had a stronger inhibitory effect on angiogenesis compared to TNC inhibition, and had a similar effect to dual inhibition of PN and TNC. Furthermore, PN knock-out mice showed scant TNC expression in pre-retinal neovessels of OIR retinas. Our findings suggest that interaction of PN and TNC facilitates pre-retinal angiogenesis, and PN is an effective therapeutic target for IPR such as PDR..
57. Mori Y, Arima M, Ueda E, Fujiwara K, Seki E, Nakama T, Tsukamoto S, Akiyama M, Sonoda KH, Risk factors for myopia at 1-year corrected age following laser photocoagulation for retinopathy of prematurity, Eye, 10.1038/s41433-020-01321-z, 2020.11.
58. Nakamura S, Nakao S, Shiose S, Kohno RI, Hasegawa E, Sonoda KH, Optical Coherence Tomography Angiography of Choroidal Neovascularization in Immune Choroiditis Following Acute Retinal Necrosis, 10.1177/1120672120977349, 2020.11.
59. Shotaro Shimokawa, Kohta Fujiwara, Yusuke Murakami, Jun Funatsu, Shunji Nakatake, Noriko Yoshida, Koh Hei Sonoda, Yasuhiro Ikeda, Effect of Topical Dorzolamide on Cystoid Macular Edema in Retinitis Pigmentosa, Ophthalmology Retina, 10.1016/j.oret.2020.05.012, 4, 10, 1036-1039, 2020.10.
60. Nakao S, Sonoda KH, Gas Bubbles in The Anterior Chambe, 138, 11, e202049, 2020.10.
61. Mori K, Ishikawa K, Wada I, Kubo Y, Kobayashi Y, Nakama T, Masatoshi Haruta, Akiyama M, Nakao S, Yoshida S, Sonoda KH, Changes in metamorphopsia after the treat-and-extend regimen of anti-VEGF therapy for macular edema associated with branch retinal vein occlusion , PLoS One, org/10.1371/journal.pone.0241343, 2020.10, This study aims to investigate the changes in metamorphopsia after administering the treat-
and-extend regimen of anti-vascular endothelial growth factor therapy for branch retinal vein
occlusion-associated macular edema. We retrospectively examined 27 patients (27 eyes) with macula
edema due to branch retinal vein occlusion who received intravitreal injections of anti-vascular
endothelial growth factor agents using the treat-and-extend regimen for
�18 months. We evaluated best-corrected visual acuity, central macular thickness, macular edema
recurrence, and amount of metamorphopsia quantified by M-CHARTS. The best- corrected visual acuity
(logarithm of minimum angle of resolution) and central macular thick- ness significantly improved
at 18 months compared to baseline, the median value (inter- quartile range [IQR]), 0.30 (0.15–0.52)
and 459 (373–542) μm at baseline, and 0 (-0.08– 0.16) and 267 (232–306) μm at 18 months. The
M-CHARTS score (the mean of vertical and horizontal scores) significantly decreased at 1, 6, and 12
months compared to baseline, but worsened at 18 month, the median value (IQR), 0.45 (0.250–0.925),
0.4 (0.15–0.70), 0.4
(0.150–0.625), 0.4 (0.225–0.550) and 0.45 (0.225–0.750) at baseline, 1 month, 6 months, 12 months
and 18 months, respectively. The median cumulative number of macular edema recurrences was 2 (IQR,
0.5–3.0) at 18 months. Simple linear regression and multivariate analyses revealed that the change
in the mean M-CHARTS score at 18 months was signifi- cantly correlated with the baseline score and
the cumulative number of macular edema recurrences. Anti-vascular endothelial growth factor therapy
using the treat-and-extend regi- men improved metamorphopsia in branch retinal vein
occlusion-related macular edema in the short to mid-term follow-up period, but not in the long
term. Macular edema recurrence
may be associated with persistent metamorphopsia.
.
62. Shinji Ueno, Yoshito Koyanagi, Taro Kominami, Yasuki Ito, Kenichi Kawano, Koji M. Nishiguchi, Carlo Rivolta, Toru Nakazawa, Koh Hei Sonoda, Hiroko Terasaki, Clinical characteristics and high resolution retinal imaging of retinitis pigmentosa caused by RP1 gene variants, Japanese Journal of Ophthalmology, 10.1007/s10384-020-00752-1, 64, 5, 485-496, 2020.09, Purpose: To report the clinical course and high resolution images of autosomal recessive retinitis pigmentosa (RP) associated with a variant of the RP1 gene (c.4052_4053ins328/p.Tyr1352Alafs*9; m1), a high frequency founder variant in Japanese RP patients. Study design: Retrospective case series. Methods: Nine patients from 5 unrelated Japanese families were studied. Five patients had the m1 variant homozygously, and 4 patients had the m1 variant compound heterozygously with another frameshift variant (c.4196delG/p.Cys1399Leufs*5). Ophthalmic examinations including adaptive optics (AO) fundus imaging were performed periodically. Results: The fundus photographs, fundus autofluorescence (FAF) images, and optical coherence tomographic (OCT) images indicated severe retinal degeneration in all the patients involving the macula even at a young age (20 s). The areas of surviving photoreceptors in the central macula were seen as hyper-autofluorescent regions in the FAF images and preserved outer retinal structure in the OCT images; they were identifiable in the AO fundus images in 8 eyes. The borders of the surviving photoreceptor areas were surrounded by hyporeflective clumps, presumably containing melanin, and the size of these areas decreased progressively during the 4-year follow-up period. The disappearance of the surviving photoreceptor areas was associated with complete blindness. Conclusion: Patients with RP associated with the m1 variant have a progressive and severe retinal degeneration that begins at an early age. Monitoring the surviving photoreceptor areas by AO fundus imaging can provide a more precise pathological record of retinal degeneration..
63. Toshio Hisatomi, Hiroshi Enaida, Shigeo Yoshida, Akito Hirakata, Masahito Ohji, Kohji Nishida, Toshiaki Kubota, Nahoko Ogata, Takaaki Matsui, Kazuhiro Kimura, Koh Hei Sonoda, Makiko Uchiyama, Junji Kishimoto, Koji Todaka, Yoichi Nakanishi, Tatsuro Ishibashi, Safety and efficacy of brilliant blue g250 (BBG) for lens capsular staining
a phase III physician-initiated multicenter clinical trial, Japanese Journal of Ophthalmology, 10.1007/s10384-020-00763-y, 64, 5, 455-461, 2020.09, Purpose: To evaluate the safety and efficacy of BBG (Brilliant Blue G250) for lens capsular staining during cataract surgery with continuous curvilinear capsulorhexis. Study design: Prospective clinical study. Methods: This clinical trial enrolled 30 eyes of 30 patients who underwent cataract surgery with BBG (0.25 mg/mL Brilliant Blue G250) for capsular staining. Visualization of the lens capsule and the ease of capsulorhexis with BBG staining were evaluated in five grades (grade 0 to 4) by the Independent Data Monitoring Committee and the surgeons. The safety of BBG was also evaluated in terms of ocular and systemic tolerance for 7 days after surgery. Results: The use of BBG improved visualization of the lens capsule and complete capsulorhexis was performed in all patients. The major endpoint (Independent Data Monitoring Committee evaluation) showed that use of BBG improved visualization of the lens capsule and the ease of capsulorhexis (grades 2 to 4); the committee’s grading results were similar to those of the surgeons. Frequent complications observed in more than two eyes were conjunctival injection, corneal edema and intraocular pressure elevation. No severe complications were observed in ocular and systemic evaluations. Conclusion: BBG staining contributed to improved visualization of the lens capsule and aided in the completion of capsulorhexis during cataract surgery. The use of BBG for capsular staining also exhibited favorable safety results..
64. Takeda A, Hasegawa E, Nakao S, Ishikawa K, Murakami Y, Hisatomi T, Arima M, Yawata N, Oda Y, Kimura K, Yoshikawa H, Sonoda KH, Vitreous levels of interleukin-35 as a prognostic factor in B-cell vitreoretinal lymphoma　, 10.1038/s41598-020-72962-z , 10, 1, 15715, 2020.09, Vitreoretinal lymphoma (VRL) is a rare disease of B-cell origin with poor prognosis. Regulatory cytokines promote tumor development by suppressing antitumor immunity in several cancer types, including B-cell malignancies. To identify the regulatory cytokines associated with poor prognosis in patients with B-cell VRL, we determined the regulatory cytokines profiles in the vitreous humor of patients with VRL. This retrospective study included 22 patients with VRL, 24 with non-infectious uveitis (NIU), and 20 with idiopathic epiretinal membrane (control). Vitreous concentrations of regulatory cytokines were assessed using a cytometric beads assay and association with clinical data was examined. IL-35 and soluble IL-2 receptor α levels were significantly higher in patients with VRL and NIU than those in the control group. The 5-year overall survival (OS) rates for the group with high intravitreal IL-35 was significantly poorer than those for the group with low intravitreal IL-35, who were diagnosed with VRL at the onset (P = 0.024, log-rank test). The 5-year OS rates with intravitreal IL-35 levels above and below the median were 40.0% and 83.3%, respectively. Our results suggest that high intravitreal IL-35 levels indicate poor prognosis for patients diagnosed with B-cell VRL at the onset. .
65. Sasaki M, Miyake M, Fujiwara K, Namba H, Akiyama M, Yanagi Y, Harada S, Tabara Y, Yasuda M, Yamashita H, Kayama T, Tsubota K, Matsuda F, Hashimoto S, Ueda E, Ninomiya T, Takebayashi T, Tsujikawa A, Sonoda KH, Kawasaki R, Cohort Profile: the Ganka-Ekigaku Network (GEN), a network of Japanese ophthalmological epidemiology studies, 10.1080/09286586.2020.1815803 , 28, 3, 237-243, 2020.09,
Purpose: Japan has been known as a super-aged society, and ageing is a well-known risk factor for blinding eye diseases. However, epidemiological studies in ophthalmology are still scarce in Japan, and the sizes of the cohorts are relatively small. "Ganka-Ekigaku Network" (GEN, an acronym for the epidemiological network in ophthalmology in Japanese) is established to develop a capacity to boost each epidemiological study and enrich a potential inter-study collaboration to identify risk factors of visual impairment in aged society.

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

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

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

Keywords: cohort study; consortium; meta-analysis; pooled data analysis; risk factor.
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66. Okita A, Murakami Y, Shimokawa S, Funatsu J, Fujiwara K, Nakatake S, Koyanagi Y, Akiyama M, Takeda A, Hisatomi T, Ikeda Y, Sonoda KH, Clinical Characteristics and High Resolution Retinal Imaging of Retinitis Pigmentosa Caused by RP1 Gene Variants　, 10.1007/s10384-020-00752-1, 64, 5, 485-496, 2020.09, Purpose: To report the clinical course and high resolution images of autosomal recessive retinitis pigmentosa (RP) associated with a variant of the RP1 gene (c.4052_4053ins328/p.Tyr1352Alafs*9; m1), a high frequency founder variant in Japanese RP patients.

Study design: Retrospective case series.

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

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

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

Keywords: Adaptive optics images; Autosomal recessive retinitis pigmentosa; Fundus autofluorescence; RP1..
67. Okita A, Murakami Y, Shimokawa S, Funatsu J, Fujiwara K, Nakatake S, Koyanagi Y, Akiyama M, Takeda A, Hisatomi T, Ikeda Y, Sonoda KH, Changes of Serum Inflammatory Molecules and Their Relationships with Visual Function in Retinitis Pigmentosa, 10.1167/iovs.61.11.30, 61, 11, 30-30, 2020.08, Purpose: Retinal degeneration involves neuroinflammation, and pro-inflammatory cytokines/chemokines are markedly increased in the eyes of patients with retinitis pigmentosa (RP). In this study, we investigated the changes of serum cytokines/chemokines in RP, and their relationships with visual parameters.

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

Results: Among the 15 cytokines and 9 chemokines, serum IL-8 and RANTES levels were significantly increased in patients with RP compared with controls (IL-8: P
Conclusions: Peripheral inflammatory response may be activated and serum IL-8 levels are associated with central vision in patients with RP..
68. Koyanagi Y, Ueno S, Ito Y, Kominami T, Komori S, Akiyama M, Murakami Y, Ikeda Y, Sonoda KH, Terasaki H, Relationship between macular curvature and common causative genes of retinitis pigmentosa in Japanese patients　, 10.1167/iovs.61.10.6, 61, 10, 6-6, 2020.08.
69. Ueda E, Yasuda M, Fujiwara K, Hashimoto S, Ohno-Matsui K, Hata J, Ishibashi T, Ninomiya T, Sonoda KH, The 5-year incidence of myopic maculopathy in a general Japanese population: the Hisayama Study　, 10.1001/jamaophthalmol.2020.2211 , 138, 8, 887-893, 2020.08, Importance: Myopic maculopathy is a leading cause of irreversible visual impairment worldwide. Moreover, the burden of myopic maculopathy has been expected to increase owing to the rising prevalence of myopia globally. However, there is limited epidemiologic evidence regarding the incidence of and risk factors for myopic maculopathy. This study from Japan, with a relatively high prevalence of myopia, could provide valuable information related to these issues.

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

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

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

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

Conclusions and relevance: Twenty-four study participants (1%) developed myopic maculopathy during the 5-year study period, which is much higher than the rate in a previous study on a Chinese population. We also confirmed that aging and longer axial length were independent and significant risk factors for myopic maculopathy. These findings should be reviewed among various populations in other parts of the world.
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70. Kohta Fujiwara, Yasuhiro Ikeda, Yusuke Murakami, Takashi Tachibana, Jun Funatsu, Yoshito Koyanagi, Shunji Nakatake, Shotaro Shimokawa, Noriko Yoshida, Shintaro Nakao, Toshio Hisatomi, Tatsuro Ishibashi, Koh Hei Sonoda, Aqueous flare and progression of visual field loss in patients with retinitis pigmentosa, Investigative Ophthalmology and Visual Science, 10.1167/IOVS.61.8.26, 61, 8, 2020.07, PURPOSE. To investigate the association between aqueous flare and progression of visual field loss using the Humphrey Field Analyzer in patients with retinitis pigmentosa (RP). METHODS. We examined a total of 101 eyes of 101 patients who were diagnosed with typical RP. Sixty-one percent of the patients were female, and the mean age of the total group was 47.4 years. Aqueous flare, visual field (by an Humphrey Field Analyzer, the central 10-2 SITA-Standard program), and optical coherence tomography measurements were obtained for all patients. The slope, which was derived from serial values of mean deviation, macular sensitivity, or foveal sensitivity for each eye with univariate linear regression, was used for analysis. RESULTS. Aqueous flare values were significantly correlated with the mean deviation slope (r =-0.20, P = 0.046), macular sensitivity slope (r =-0.28, P = 0.005) and foveal sensitivity slope (r =-0.20, P = 0.047). The values of the retinal sensitivity slope significantly decreased as the aqueous flare level increased (all P
71. Atsunobu Takeda, Ryoji Yanai, Yusuke Murakami, Mitsuru Arima, Koh Hei Sonoda, New Insights Into Immunological Therapy for Retinal Disorders, Frontiers in Immunology, 10.3389/fimmu.2020.01431, 11, 2020.07, In the twentieth century, a conspicuous lack of effective treatment strategies existed for managing several retinal disorders, including age-related macular degeneration; diabetic retinopathy (DR); retinopathy of prematurity (ROP); retinitis pigmentosa (RP); uveitis, including Behçet's disease; and vitreoretinal lymphoma (VRL). However, in the first decade of this century, advances in biomedicine have provided new treatment strategies in the field of ophthalmology, particularly biologics that target vascular endothelial growth factor or tumor necrosis factor (TNF)-α. Furthermore, clinical trials on gene therapy specifically for patients with autosomal recessive or X-linked RP have commenced. The overall survival rates of patients with VRL have improved, owing to earlier diagnoses and better treatment strategies. However, some unresolved problems remain such as primary or secondary non-response to biologics or chemotherapy, and the lack of adequate strategies for treating most RP patients. In this review, we provide an overview of the immunological mechanisms of the eye under normal conditions and in several retinal disorders, including uveitis, DR, ROP, RP, and VRL. In addition, we discuss recent studies that describe the inflammatory responses that occur during the course of these retinal disorders to provide new insights into their diagnosis and treatment..
72. Keijiro Ishikawa, Takuma Fukui, Shintaro Nakao, Satomi Shiose, Koh Hei Sonoda, Vitrectomy with peripapillary internal limiting membrane peeling for macular retinoschisis associated with normal-tension glaucoma, American Journal of Ophthalmology Case Reports, 10.1016/j.ajoc.2020.100663, 18, 2020.03, Purpose: Although vitrectomy has been reported to be effective for the treatment of macular retinoschisis associated with glaucoma in a few case series, the surgical techniques have yet to be established. This article aimed to describe the cases of two patients with macular retinoschisis who underwent vitrectomy with peripapillary internal limiting membrane peeling around the defective area of the retinal nerve fiber layer. Observations: Both patients had been diagnosed with normal tension glaucoma and treated with eye drops to stabilize intraocular pressure. Progression of macular retinoschisis and accompanied vision loss were observed in both cases. Twelve months after the surgery, both patients had resolution of the retinoschisis and improvement in best corrected visual acuity. Conclusions and importance: Our surgical technique may be effective for the resolution of macular retinoschisis in eyes with normal tension glaucoma..
73. Kaizu Y, Nakao S, Wada I, Arima M, Yamaguchi M, Ishikawa K, Akiyama M, Kishimoto J, Hisatomi T, Sonoda KH, Microaneurysm Imaging using Multiple En Face Optical Coherence Tomography Angiography Image Averaging: Morphology and Visualization, 10.1016/j.oret.2019.09.010 , 4, 2, 175-186, 2020.02, Purpose: In diabetic retinopathy (DR), OCT angiography (OCTA) could not image all fluorescein angiography (FA)-detected microaneurysms. We investigated whether multiple image averaging could enhance the microaneurysm detection capability of OCTA in patients with DR.

Design: Prospective and cross-sectional observational study.

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

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

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

Results: A total of 415 microaneurysms could be analyzed in 31 eyes from 25 patients. Microaneurysms detected on single image, ×3, ×5, and ×10 averaged OCTA images were 144 (34.7%), 227 (54.7%), 285 (68.7%), and 306 (73.7%), respectively. Microaneurysm detection capability was significantly increased with increased image averaging. Microaneurysm detection with OCTA was not correlated with retinal thickness, FA leakiness, and indocyanine green angiogram detection or the number of averaged images, whereas there was significant correlation between microaneurysm morphology and microaneurysm visibility by the image-averaging process for 4 morphologies, particular the focal bulge types (P
Conclusions: In DR, multiple image averaging is useful for increasing the microaneurysm detection capability of OCTA, especially for focal bulge-type microaneurysms
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74. Yusuke Murakami, Keijiro Ishikawa, Shintaro Nakao, Koh Hei Sonoda, Innate immune response in retinal homeostasis and inflammatory disorders, Progress in Retinal and Eye Research, 10.1016/j.preteyeres.2019.100778, 74, 2020.01, Innate immune cells such as neutrophils, monocyte-macrophages and microglial cells are pivotal for the health and disease of the retina. For the maintenance of retinal homeostasis, these cells and immunosuppressive molecules in the eye actively regulate the induction and the expression of inflammation in order to prevent excessive activation and subsequent tissue damage. In the disease context, these regulatory mechanisms are modulated genetically and/or by environmental stimuli such as damage-associated molecular patterns (DAMPs), and a chronic innate immune response regulates or contributes to the formation of diverse retinal disorders such as uveitis, retinitis pigmentosa, retinal vascular diseases and retinal fibrosis. Here we summarize the recent knowledge regarding the innate immune response in both ocular immune regulation and inflammatory retinal diseases, and we describe the potential of the innate immune response as a biomarker and therapeutic target..
75. , Taiji Sakamoto, Sumihiro Kawano, Ryo Kawasaki, Akito Hirakata, Hidetoshi Yamashita, Shuichi Yamamoto, Tatsuro Ishibashi, Eiju Sato, Masayasu Kitahashi, Tomoaki Tatsumi, Gen Miura, Tomohiro Niizawa, Taiji Sakamoto, Keita Yamakiri, Toshifumi Yamashita, Hiroki Otsuka, Seiji Sameshima, Narimasa Yoshinaga, Shozo Sonoda, Takashi Koto, Makoto Inoue, Kazunari Hirota, Yuji Itoh, Tadashi Orihara, Yoshinobu Emoto, Masahiko Sano, Hiroyuki Takahashi, Ryo Tokizawa, Koichi Nishitsuka, Yutaka Kaneko, Katsuhiro Nishi, Akitoshi Yoshida, Shinji Ono, Hiroyuki Hirokawa, Kenji Sogawa, Tsuneaki Omae, Akihiro Ishibazawa, Shoji Kishi, Hideo Akiyama, Hidetaka Matsumoto, Ryo Mukai, Masahiro Morimoto, Mitsuru Nakazawa, Yukihiko Suzuki, Takashi Kudo, Kobu Adachi, Susumu Ishida, Kousuke Noda, Koh Hei Sonoda, Keijiro Ishikawa, Japan-Retinal Detachment Registry Report I
preoperative findings in eyes with primary retinal detachment, Japanese Journal of Ophthalmology, 10.1007/s10384-019-00702-6, 64, 1, 2020.01, Purpose: To report the demographics and clinical characteristics of patients with a primary retinal detachment (RD). Design: Prospective cohort study by a registry design. Participants: Patients with RD treated at vitreoretinal sub-specialty institutions in Japan from February 2016 to March 2017. Methods: Descriptive statistics for the primary RD, and multivariable ordered logistic regression and multiple linear regression analyses were performed. Results: 3178 eyes of 3178 cases were analyzed. The interval from onset to surgery was significantly shorter in patients in the 40-year age group than in other age groups except for the 50-year age group (P
76. Takehito Hayami, Shintaro Nakao, Yoshihiro Kaizu, Koh Hei Sonoda, An analysis of caliber-specific blood flow path length in optical coherence tomography angiography using morphological top-hat transform, IEEJ Transactions on Sensors and Micromachines, 10.1541/ieejsmas.140.70, 140, 3, 70-71, 2020, Optical coherence tomography angiography has a function to visualize the blood flow of multi-layered retinal capillary plexus by layer. OCTA signals would be more utilized if they are associated with blood flow dynamics of each layer. In this study, morphological top-hat transform was applied for OCTA en face retinal images of superficial and deep layers obtained from patients of diabetic retinopathy and controls to quantify the caliber-specific flow path length. As a result, the total length of the thick flow paths in deep layer more strongly reflected the progress of retinopathy than that in superficial layer. Supposing the thick flow paths observed in deep layer OCTA as a superposition of multiple capillaries, this trend seemed to be a possible expression of partial clogs of the capillary network..
77. Sho Hei Uchi, Ryoji Yanai, Masaaki Kobayashi, Makoto Hatano, Yuka Kobayashi, Chiemi Yamashiro, Tomohiko Nagai, Kazuhiro Tokuda, Kip M. Connor, Koh Hei Sonoda, Kazuhiro Kimura, Erratum
Dendritic cells mediate the anti-inflammatory action of omega-3 long-chain polyunsaturated fatty acids in experimental autoimmune uveitis (PLOS ONE (2019 14:7 (e0219405) DOI: 10.1371/journal.pone.0219405), PloS one, 10.1371/journal.pone.0231277, 15, 3, 2020, The eighth author’s name is spelled incorrectly. The correct name is: Kazuhiro Tokuda..
78. Emi Ueda, Miho Yasuda, Kohta Fujiwara, Sawako Hashimoto, Kyoko Ohno-Matsui, Jun Hata, Tatsuro Ishibashi, Toshiharu Ninomiya, Koh Hei Sonoda, Five-Year Incidence of Myopic Maculopathy in a General Japanese Population
The Hisayama Study, JAMA Ophthalmology, 10.1001/jamaophthalmol.2020.2211, 2020, Importance: Myopic maculopathy is a leading cause of irreversible visual impairment worldwide. Moreover, the burden of myopic maculopathy has been expected to increase owing to the rising prevalence of myopia globally. However, there is limited epidemiologic evidence regarding the incidence of and risk factors for myopic maculopathy. This study from Japan, with a relatively high prevalence of myopia, could provide valuable information related to these issues. Objective: To estimate the incidence of myopic maculopathy and its risk factors in Hisayama in southwestern Japan. Design, Setting, and Participants: A population-based prospective cohort study in a Japanese community in Hisayama, Japan. The study included a total of 2164 residents 40 years or older who had no myopic maculopathy at the baseline eye examination in 2012 and underwent follow-up eye examinations in 2017. Main Outcomes and Measures: Incidence of myopic maculopathy. The grades of myopic maculopathy were categorized based on the criteria of the Meta-analysis of Pathologic Myopia Study Group classification system. Results: The mean (SD) age of the study participants was 62.4 (10.9) years, and the proportion of men was 42.5% (920 participants). In the follow-up examination in 2017, 24 patients developed myopic maculopathy. The 5-year cumulative incidence of myopic maculopathy was 1.1% (95% CI, 0.6-1.5) overall, 1.4% (95% CI, 0.6-2.2) for men, and 0.9% (95% CI, 0.4-1.4) for women. Multiple logistic regression analysis showed that older age (per 1 year; odds ratio [OR], 1.06; 95% CI, 1.01-1.11) and longer axial length (per 1 mm; OR, 2.94; 95% CI, 2.19-3.95) were associated with incident myopic maculopathy. Conclusions and Relevance: Twenty-four study participants (1%) developed myopic maculopathy during the 5-year study period, which is much higher than the rate in a previous study on a Chinese population. We also confirmed that aging and longer axial length were independent and significant risk factors for myopic maculopathy. These findings should be reviewed among various populations in other parts of the world...
79. Konstantinos Nikopoulos, Katarina Cisarova, Mathieu Quinodoz, Hanna Koskiniemi-Kuendig, Noriko Miyake, Pietro Farinelli, Atta Ur Rehman, Muhammad Imran Khan, Andrea Prunotto, Masato Akiyama, Yoichiro Kamatani, Chikashi Terao, Fuyuki Miya, Yasuhiro Ikeda, Shinji Ueno, Nobuo Fuse, Akira Murakami, Yuko Wada, Hiroko Terasaki, Koh Hei Sonoda, Tatsuro Ishibashi, Michiaki Kubo, Frans P.M. Cremers, Zoltán Kutalik, Naomichi Matsumoto, Koji M. Nishiguchi, Toru Nakazawa, Carlo Rivolta, A frequent variant in the Japanese population determines quasi-Mendelian inheritance of rare retinal ciliopathy, Nature communications, 10.1038/s41467-019-10746-4, 10, 1, 2019.12, Hereditary retinal degenerations (HRDs) are Mendelian diseases characterized by progressive blindness and caused by ultra-rare mutations. In a genomic screen of 331 unrelated Japanese patients, we identify a disruptive Alu insertion and a nonsense variant (p.Arg1933*) in the ciliary gene RP1, neither of which are rare alleles in Japan. p.Arg1933* is almost polymorphic (frequency = 0.6%, amongst 12,000 individuals), does not cause disease in homozygosis or heterozygosis, and yet is significantly enriched in HRD patients (frequency = 2.1%, i.e., a 3.5-fold enrichment; p-value = 9.2 × 10−5). Familial co-segregation and association analyses show that p.Arg1933* can act as a Mendelian mutation in trans with the Alu insertion, but might also associate with disease in combination with two alleles in the EYS gene in a non-Mendelian pattern of heredity. Our results suggest that rare conditions such as HRDs can be paradoxically determined by relatively common variants, following a quasi-Mendelian model linking monogenic and complex inheritance..
80. Jun Funatsu, Yusuke Murakami, Shunji Nakatake, Masato Akiyama, Kohta Fujiwara, Shotaro Shimokawa, Takashi Tachibana, Toshio Hisatomi, Yoshito Koyanagi, Yukihide Momozawa, Koh Hei Sonoda, Yasuhiro Ikeda, Direct comparison of retinal structure and function in retinitis pigmentosa by co-registering microperimetry and optical coherence tomography, PloS one, 10.1371/journal.pone.0226097, 14, 12, 2019.12, Purpose To evaluate the retinal structure-function relationships in the macula of retinitis pigmentosa (RP) patients by comparing microperimetry-3 (MP-3) images with co-registered optical coherence tomography (OCT) images. Methods Thirty patients with typical RP were recruited from our hospital. The maculae of patients were examined with MP-3 and OCT. The retinal sensitivity was measured by MP-3 at 40 testing points arranged concentrically in a 16∘ diameter of the central retina, and we divided the 40 points into four zones according to degree from the fovea (2∘, 4∘, 6∘, and 8∘). We analyzed the correlation coefficients between the retinal sensitivity and the total retinal thickness (TRT), the length from the inner limiting membrane to the retinal pigment epithelium (RPE), and between the retinal sensitivity and the outer retinal thickness (ORT), the length from the outer plexiform layer to the RPE at each stimulus point. Results TRT showed moderate correlations with the retinal sensitivity at 2∘ (median ρ = 0.59 interquartile range (IQR) [0.38–0.72]), 4∘ (ρ = 0.59 [0.55–0.68]) and 6∘ (ρ = 0.60 [0.54–0.63]), and TRT was weakly-to-moderately related to the retinal sensitivity at 8∘ (ρ = 0.27 [0.19–0.48]). ORT exhibited strong correlations at 2∘ (ρ = 0.72 [0.60–0.81]), 4∘ (ρ = 0.71 [0.75–0.67]) and 6∘ (ρ = 0.70 [0.54–0.74]), and a weak-to-moderate correlations at 8∘ (ρ = 0.34 [0.29–0.53]). ORT was more strongly correlated with the retinal sensitivity compared to TRT (p = 0.018). Conclusion ORT, rather than TRT, within 6∘ eccentricity was strongly correlated with the retinal sensitivity, suggesting that measuring ORT in those areas will help evaluate the macular status and progression in RP..
81. Yoshihiro Kaizu, Shintaro Nakao, Mitsuru Arima, Takehito Hayami, Iori Wada, Muneo Yamaguchi, Haruka Sekiryu, Keijiro Ishikawa, Yasuhiro Ikeda, Koh Hei Sonoda, Flow Density in Optical Coherence Tomography Angiography is Useful for Retinopathy Diagnosis in Diabetic Patients, Scientific reports, 10.1038/s41598-019-45194-z, 9, 1, 2019.12, Our study evaluated the diagnostic capability of flow density (FD) in OCT angiography (OCTA) for diabetic retinopathy (DR) detection in diabetic patients. We studied 93 eyes of 68 diabetic patients who underwent OCTA (36 and 57 eyes without and with DR, respectively). Retinal capillary FD of a 2.6 × 2.6 mm2 area and four divided areas at the superficial (SCP) and deep capillary plexus (DCP) were measured. Predictions were evaluated using the area under the receiver operating characteristic curve (AUC). The diagnostic capabilities of the FDs in discriminating between eyes without DR and eyes with total or early DR were compared. Furthermore, predictions with foveal avascular zone (FAZ) area, hemoglobin A1c (HbA1c), and DM duration were also compared with FD. Prediction using FD AUC in the temporal side in the DCP (0.83) was the highest and significantly better than all other AUCs examined (P
82. Akira Hayashida, Mika Tanabe, Hiroshi Yoshikawa, Ken Ichi Takaki, Kanako Yamana, Satoshi Yamana, Koh Hei Sonoda, Two cases of oncocytoma in or near the lacrimal gland, Japanese Journal of Clinical Ophthalmology, 73, 13, 1565-1570, 2019.12, Purpose: To report 2 cases of oncocytoma in the lacrimal gland or near the lacrimal caruncle. Cases: One was a 67-year-old female and the other was a 65-year-old male. The first case had developed swelling of the left upper eyelid associated with swollen lacrimal gland. The circlating blood showed slightly elevated value of TRAb or antibody to TSH receptor. She was diagnosed with lacrimal adenitis associated with Basedow disease. The lesion subsided after systemic treatment with cystemic corticosterodi. Similar episodes recurred three times during the following 9 years. The lacrimal tumor was totally excised after MRI showed enlarged tumor in the lacrimal gland. The lesion showed proliferation of oxyphilic cells with round nuclei in addition to eosinophilic granular cytoplasm. The second case showed a tumor in the right caruncle. The lesion was excised and was diagnosed as oncocytoma with similar findings. No recurrence had developed in both cases during one year of follow-up. Conclusion: Oncocytoma in the eyelids, including ones involving the lacrimal gland, has to considered in the differential diagnosis of ocular adnexal tumors..
83. Koji M. Nishiguchi, Yasuhiro Ikeda, Kosuke Fujita, Hiroshi Kunikata, Makoto Akiho, Kazuki Hashimoto, Katsuhiro Hosono, Kentaro Kurata, Yoshito Koyanagi, Masato Akiyama, Takefumi Suzuki, Ryo Kawasaki, Yuko Wada, Yoshihiro Hotta, Koh Hei Sonoda, Akira Murakami, Mitsuru Nakazawa, Toru Nakazawa, Toshiaki Abe, Phenotypic Features of Oguchi Disease and Retinitis Pigmentosa in Patients with S-Antigen Mutations
A Long-Term Follow-up Study, Ophthalmology, 10.1016/j.ophtha.2019.05.027, 126, 11, 1557-1566, 2019.06, Purpose: To present phenotypic features of 22 patients with S-antigen (SAG) mutations. Design: Retrospective cohort study. Participants: Twenty-one Japanese patients from 16 families with a homozygous c.924delA mutation and 1 patient with a homozygous c.636delT mutation in the SAG gene. Methods: Clinical records on symptoms; best-corrected visual acuity; and Goldmann perimetry, fundus photography, fundus autofluorescence (FAF), OCT, and electroretinography results were reviewed. Main Outcome Measures: Best-corrected visual acuity, Goldmann perimetry results, imaging findings, and electroretinography results. Results: Ten patients had Oguchi disease and 12 had retinitis pigmentosa (RP) with mean follow-up periods of 13.8 and 10.2 years, respectively. Retinitis pigmentosa patients were older (mean age, 56.0 years) than those with Oguchi disease (mean age, 22.1 years; P 2 right eye and 667 mm2 left eye) and reduced in RP patients (mean, 369 mm2 right eye and 294 mm2 left eye). Fundus images revealed a characteristic golden sheen with no retinal degeneration in Oguchi disease patients, excluding 2 with macular degeneration detected by FAF, OCT, or both and 1 with mild retinal degeneration confirmed by OCT and fluorescein angiography. Pigmentary retinal degeneration most evident posteriorly was observed in RP patients, accompanied by a characteristic golden sheen in 12 of 14 patients undergoing ultra-widefield fundus imaging. OCT showed disrupted macular structure, and FAF revealed variable hypofluorescence. Electroretinography identified absent rod responses in both diseases, along with relative preservation of cone responses in Oguchi disease patients. Three patients showed progressive loss of the golden sheen based on fundus images, including 1 who demonstrated RP 26 years after the initial diagnosis of Oguchi disease. Conclusions: Retinitis pigmentosa with SAG mutations often shows a characteristic golden sheen surrounding posterior pigmentary retinal degeneration. Oguchi disease can show progressive degeneration in adulthood, rarely resulting in RP..
84. Nakao S, Yoshimitsu M, Kaizu Y, Wada I, Yamaguchi M, Sonoda KH, Branch Retinal Artery Occlusion in The Untreated Contralateral Eye Following Aflibercept Injections during Heparin Treatment: Possible Contribution of a Heparin-induced Thrombocytopenia-like Condition, Am J Ophthalmol Case Rep., 16, 100549, 2019.08.
85. Tokuda K, Baron B, Yamashiro C, Kuramitsu Y, Kitagawa T, Kobayashi M, Sonoda KH, Kimura K, Up-regulation of the pentose phosphate pathway and HIF-1α expression during neural progenitor cell induction following glutamate treatment in rat ex vivo retina., Cell Biol Int., 44, 137-144, 2020.01.


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