論文 - 池田 康博
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Koyanagi Y., Ueno S., Ito Y., Kominami T., Komori S., Akiyama M., Murakami Y., Ikeda Y., Sonoda K.H., Terasaki H.
Investigative Ophthalmology and Visual Science 61 ( 10 ) 6 2020年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Investigative Ophthalmology and Visual Science
Copyright 2020 The Authors. PURPOSE. To determine the relationship between the macular curvature and the causative genes of retinitis pigmentosa (RP). METHODS. We examined the medical records of the right eyes of 65 cases with RP (31 men and 34 women; average age, 47.6 years). There were 31 cases with the EYS variants, 11 cases with the USH2A variants, six cases with the RPGR variants, 13 cases with the RP1 variants, and four cases with the RP1L1 variants. The mean curvature of Bruch’s membrane was calculated within 6 mm of the fovea as the mean macular curvature index (MMCI, 1/μm). We used multiple linear regression analysis to determine the independence of the causative genes contributing to the MMCIs after adjustments for age, sex, axial length, and width of the ellipsoid zone. RESULTS. The median MMCI was -31.2 × 10-5/μm for the RPGR eyes, -16.5 × 10-5/μm for the RP1L1 eyes, -13.0 × 10-5/μm for the RP1 eyes, -9.8 × 10-5/μm for the EYS eyes, and -9.0 × 10-5/μm for the USH2A eyes. Compared with the EYS gene as the reference gene, the RPGR gene was significantly related to the MMCI values after adjusting for the other parameters (P = 5.30 × 10-6). In contrast, the effects of the other genes, USH2A, RP1, and RP1L1, were not significantly different from that of the EYS gene (P = 0.26, P = 0.49, and P = 0.92, respectively). CONCLUSIONS. The RPGR gene had a stronger effect on the steep macular curvature than the other ciliopathy-related genes.
DOI： 10.1167/IOVS.61.10.6
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Nishiguchi K.M., Kunikata H., Fujita K., Hashimoto K., Koyanagi Y., Akiyama M., Ikeda Y., Momozawa Y., Sonoda K.H., Murakami A., Wada Y., Nakazawa T.
Clinical and Experimental Ophthalmology 48 ( 5 ) 644 - 657 2020年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Clinical and Experimental Ophthalmology
© 2020 Royal Australian and New Zealand College of Ophthalmologists Importance: A framework for understanding the phenotypic features of CRX retinopathy was established. Background: To perform a phenotype-genotype correlation analysis in two groups of patients with heterozygous mutations in distinct locations of the CRX gene, encoding the cone-rod homeobox. Design: Multicentre retrospective study. Participants: Twenty-one Japanese patients from 14 families with a heterozygous CRX mutation. Methods: Retrospective data analysis. Main Outcome Measures: Clinical records on CRX mutation, symptoms, best-corrected visual acuity (BCVA), visual field, fundus photography, fundus auto-fluorescence, optical coherence tomography and electroretinograms (ERGs). Results: Six different CRX heterozygous mutations were identified in the subjects. Twelve patients from 9 families shared the p.R41W mutation and 1 patient had the p.R43C mutation, both of which affect the homeobox domain of CRX. These patients often displayed adult-onset retinal dystrophy with macular degeneration. In contrast, five patients with downstream mutations (p.S204fs, p.S213fs, p.G243X and p.L299F) displayed retinal degeneration or macular degeneration with bone-spicule pigmentation. Three asymptomatic carriers with different mutations (p.R41W, p.S213fs and p.G243X) were present in both groups. Nearly all patients and carriers had an electronegative ERG in response to a bright flash under dark adaptation. There was no cross-sectional association between patients' age and BCVA, despite progressive decline in BCVA. Conclusions and Relevance: Heterozygous mutations within or downstream of the homeobox domain in CRX relate to the difference associated retinal phenotypes, which was confounded by variable expressivity and electronegative ERGs. CRX mutations should be considered in patients with an electronegative ERG with minimal or no macular changes.
DOI： 10.1111/ceo.13743
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A founder Alu insertion in RP1 gene in Japanese patients with retinitis pigmentosa 査読あり
Nishiguchi K.M., Fujita K., Ikeda Y., Kunikata H., Koyanagi Y., Akiyama M., Abe T., Wada Y., Sonoda K.H., Nakazawa T.
Japanese Journal of Ophthalmology 64 ( 4 ) 346 - 350 2020年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Ophthalmology
© 2020, Japanese Ophthalmological Society. Purpose: To screen for the 328 bp Alu insertion (c.4052_4053ins328, p.Tyr1352Alafs) in RP1 in a group of retinitis pigmentosa (RP) patients who had been previously identified with a heterozygous deleterious mutation in the gene. Study design: Prospective, clinical and experimental study. Methods: The Alu insertion in RP1 was screened with an optimized PCR-based method in 26 RP patients with a heterozygous deleterious mutation (nonsense or frameshift) in RP1 that had been identified in a preceding genetic study. The genetic location of the previously identified mutation and its inheritance pattern were assessed. Results: Out of 26 RP patients with a heterozygous deleterious mutation in RP1, 5 (19.2%) were found to carry an additional heterozygous Alu insertion, presumably resulting in a compound heterozygous state. This included 3 patients who had been previously diagnosed as autosomal dominant RP based on genetic findings. They were re-diagnosed as having an autosomal recessive disease following our new findings. In all patients identified with the Alu insertion, the other mutations found in the preceding study were outside the defined region in exon 4 (encoding amino acids 677 to 917) in which truncation mutations have been suggested to exert a dominant negative effect. Conclusion: The founder Alu insertion in RP1 is an important cause of autosomal recessive RP in Japanese patients and can be missed in standard targeted resequencing. Screening optimized for this mutation is warranted, particularly in patients with a heterozygous deleterious mutation outside the defined region in exon 4 of RP1.
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Aqueous flare and progression of visual field loss in patients with retinitis pigmentosa 査読あり
Fujiwara K., Ikeda Y., Murakami Y., Tachibana T., Funatsu J., Koyanagi Y., Nakatake S., Shimokawa S., Yoshida N., Nakao S., Hisatomi T., Ishibashi T., Sonoda K.H.
Investigative Ophthalmology and Visual Science 61 ( 8 ) 26 2020年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Investigative Ophthalmology and Visual Science
© 2020 The Authors. 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 < 0.05). These associations remained unchanged after adjustment for age, sex, and posterior subcapsular cataract, and epiretinal membrane. CONCLUSIONS. Elevation of aqueous flare is a risk factor for the decline of central visual function in RP. Aqueous flare may be a useful marker for disease progression in RP.
DOI： 10.1167/IOVS.61.8.26
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Shimokawa S., Nakao S., Murakami Y., Ikeda Y., Sonoda K.H.
American Journal of Ophthalmology Case Reports 18 100682 2020年6月
記述言語：日本語 掲載種別：症例報告 出版者・発行元：American Journal of Ophthalmology Case Reports
Purpose: Two diabetic case reports of serous retinal detachment (SRD) accompanied by pachychoroid in hypotony maculopathy after trabeculectomy for neovascular glaucoma (NVG). Observations: Case 1: A 66-year-old female with stage 3 NVG and decreased vision acuity in the left eye. After trabeculectomy, postoperative laser suture lysis (LSL) resulted in development of hypotony maculopathy, followed by pachychoroid and SRD. Injection of C3F8 gas in the anterior chamber was unsuccessful and transconjunctival scleral re-suturing was performed. Intraocular pressure (IOP) consequently increased and SRD improved. Case 2: A 60-year-old man with stage 2 NVG and decreased vision acuity in the right eye. Trabeculectomy was uneventful, but postoperative LSL also resulted in development of hypotony maculopathy followed by pachychroid and SRD. Intravitreal bevacizumab injection had no effect and transconjunctival flap re-suturing was performed. IOP consequently increased and SRD improved. Conclusions: SRD accompanied by pachychoroid was observed in hypotony maculopathy in diabetic cases. VEGF-independent exudative change in hypotony maculopathy may be due to hydrostatic pressure elevation in choroidal blood vessels based on Starling's hypothesis with the consequent breakdown of retinal pigment epithelium barrier in diabetic patients.
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Serous retinal detachment accompanied by pachychoroid in hypotony maculopathy after trabeculectomy for diabetic neovascular glaucoma. 査読あり
Shimokawa S, Nakao S, Murakami Y, Ikeda Y, Sonoda KH.
Am J Ophthalmol Case Rep 2020年3月
記述言語：英語 掲載種別：研究論文（その他学術会議資料等）
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Sakamoto T., Kawano S., Kawasaki R., Hirakata A., Yamashita H., Yamamoto S., Ishibashi T., Sato E., Kitahashi M., Tatsumi T., Miura G., Niizawa T., Yamakiri K., Yamashita T., Otsuka H., Sameshima S., Yoshinaga N., Sonoda S., Koto T., Inoue M., Hirota K., Itoh Y., Orihara T., Emoto Y., Sano M., Takahashi H., Tokizawa R., 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., Sonoda K.H., Ikeda Y., Kohno R., Ishikawa K., Kondo M., Kozawa M., Kitaoka T., Tsuiki E., Ogura Y., Yoshida M., Morita H., Kato A., Hirano Y., Sugitani K., Terasaki H., Iwase T., Ito Y., Ueno S., Kaneko H., Nonobe N., Kominami T., Azuma N., Yokoi T., Shimada H., Nakashizuka H., Hattori T., Shinojima A., Kutagawa Y., Shiraga F., Morizane Y., Kimura S., Ikeda T., Kida T., Sato T., Fukumoto M., Emi K., Nakashima H., Ohji M., Kakinoki M.
Japanese Journal of Ophthalmology 64 ( 1 ) 1 - 12 2020年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Ophthalmology
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<0.05, Steel-Dwass test). The proportion of complex cases was significantly higher in the 10-year, 70-year, and 80+ year age groups than in the 40 and 50-year age groups (P<0.05, Steel-Dwass test). The size of RD was significantly associated with the male sex (odds ratio, 1.29; 95% confidence interval [CI], 1.07 to 1.56; P=0.0085) and the interval from onset to surgery (odds ratio, 1.03 95% CI, 1.01 to 1.04; P=0.0014). Low IOPs in eyes with RD were significantly associated with an older age (-0.24 mmHg/10 years, 95% CI, -0.32 to -0.16], P<0.0001) and larger RD area (-0.91 mmHg/quadrant, 95% CI, [-1.06 to -0.76], P <0.0001). Conclusion: Profile and clinical characteristics of patients with a primary RD were not exactly the same as previous reports. A preoperative low IOP was associated with several ocular factors while the area of RD was associated not only with ocular but with social factors as well.
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Direct comparison of retinal structure and function in retinitis pigmentosa by co-registering microperimetry and optical coherence tomography. 査読あり
Funatsu J, Murakami Y, Nakatake S, Akiyama M, Fujiwara K, Shimokawa S, Tachibana T, Hisatomi T, Koyanagi Y, Momozawa Y, Sonoda KH, Ikeda Y.
PLoS One. 2019年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Nikopoulos K., Cisarova K., Quinodoz M., Koskiniemi-Kuendig H., Miyake N., Farinelli P., Rehman A., Khan M., Prunotto A., Akiyama M., Kamatani Y., Terao C., Miya F., Ikeda Y., Ueno S., Fuse N., Murakami A., Wada Y., Terasaki H., Sonoda K., Ishibashi T., Kubo M., Cremers F., Kutalik Z., Matsumoto N., Nishiguchi K., Nakazawa T., Rivolta C.
Nature Communications 10 ( 1 ) 2019年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Nature Communications
© 2019, The Author(s). 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.
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Kaizu Y., Nakao S., Arima M., Hayami T., Wada I., Yamaguchi M., Sekiryu H., Ishikawa K., Ikeda Y., Sonoda K.
Scientific Reports 9 ( 1 ) 2019年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
© 2019, The Author(s). 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 < 0.05), including discriminating between eyes without DR and with early DR (P < 0.01). Prediction using this particular AUC was also significantly better than that by FAZ area and HbA1c (P < 0.001 and <0.001, respectively). Area-divided FD in OCTA may be valuable for diagnosing retinopathy in diabetic patients.
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Notomi S, Ishihara K, Efstathiou NE, Lee JJ, Hisatomi T, Tachibana T, Konstantinou EK, Ueta T, Murakami Y, Maidana DE, Ikeda Y, Kume S, Terasaki H, Sonoda S, Blanz J, Young L, Sakamoto T, Sonoda KH, Saftig P, Ishibashi T, Miller JW, Kroemer G, Vavvas DG.
Proc Natl Acad Sci U S A. 116 ( 47 ) 23724 - 23734 2019年11月
記述言語：英語 掲載種別：研究論文（学術雑誌）
© 2019 National Academy of Sciences. All rights reserved. The early stages of age-related macular degeneration (AMD) are characterized by the accumulation of basal laminar deposits (BLamDs). The mechanism for BLamDs accumulating between the retinal pigment epithelium (RPE) and its basal lamina remains elusive. Here we examined the role in AMD of lysosome-associated membrane protein-2 (LAMP2), a glycoprotein that plays a critical role in lysosomal biogenesis and maturation of autophagosomes/ phagosomes. LAMP2 was preferentially expressed by RPE cells, and its expression declined with age. Deletion of the Lamp2 gene in mice resulted in age-dependent autofluorescence abnormalities of the fundus, thickening of Bruch’s membrane, and the formation of BLamDs, resembling histopathological changes occurring in AMD. Moreover, LAMP2-deficient mice developed molecular signatures similar to those found in human AMD—namely, the accumulation of APOE, APOA1, clusterin, and vitronectin—adjacent to BLamDs. In contrast, collagen 4, laminin, and fibronectin, which are extracellular matrix proteins constituting RPE basal lamina and Bruch’s membrane were reduced in Lamp2 knockout (KO) mice. Mechanistically, retarded phagocytic degradation of photoreceptor outer segments compromised lysosomal degradation and increased exocytosis in LAMP2-deficient RPE cells. The accumulation of BLamDs observed in LAMP2-deficient mice was eventually followed by loss of the RPE and photoreceptors. Finally, we observed loss of LAMP2 expression along with ultramicroscopic features of abnormal phagocytosis and exocytosis in eyes from AMD patients but not from control individuals. Taken together, these results indicate an important role for LAMP2 in RPE function in health and disease, suggesting that LAMP2 reduction may contribute to the formation of BLamDs in AMD.
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Ishizu M., Murakami Y., Fujiwara K., Funatsu J., Shimokawa S., Nakatake S., Tachibana T., Hisatomi T., Koyanagi Y., Akiyama M., Momozawa Y., Ishibashi T., Sonoda K.H., Ikeda Y.
Investigative Ophthalmology and Visual Science 60 ( 13 ) 4462 - 4468 2019年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Investigative Ophthalmology and Visual Science
Copyright 2019 The Authors PURPOSE. To investigate the serum changes of antioxidant/oxidant markers and the relationship between these factors and visual function in patients with retinitis pigmentosa (RP). METHODS. Fifty-two RP patients <40 years old and 25 controls were included. Serum samples were analyzed for superoxide dismutase 3 (SOD3) activity, glutathione peroxidase (GPx), potential antioxidant (PAO), and hexanoyl-lysine (HEL). The relationships between these markers and visual parameters, including best-corrected visual acuity (BCVA), mean deviation (MD), and average retinal sensitivity of 4 or 12 central points on static perimetry tests (Humphrey Field Analyzer, the central 10–2 program) were examined in the RP patients. RESULTS. Although there was no significant difference in the serum SOD3 activity between RP patients and controls, serum SOD3 activity in the severe degeneration group with macular involvement (16.3 6 11.3 U/mL) was significantly lower compared with those in the mild degeneration group (those with midperipheral scotomas; 28.5 6 16.6 U/mL, P ¼ 0.0459). SOD3 was significantly related to visual acuity (r ¼ -0.3701, P ¼ 0.0069) and the average retinal sensitivity of four central points (r ¼ 0.3463, P ¼ 0.0137) in RP patients. The linear trends of these two parameters across SOD3 levels were also significant (P ¼ 0.0264 and 0.0172, respectively). There was no consistent correlation between other serum antioxidant/ oxidant markers and visual parameters. CONCLUSIONS. Lower serum SOD3 activity was associated with the severe retinal degeneration in RP patients. Our results suggest that serum SOD3 activity may be related to disease severity in RP.
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Ishizu M, Murakami Y, Fujiwara K, Funatsu J, Shimokawa S, Nakatake S, Tachibana T, Hisatomi T, Koyanagi Y, Akiyama M, Momozawa Y, Ishibashi T, Sonoda KH, Ikeda Y.
Invest Ophthalmol Vis Sci. 60 ( 13 ) 4462 - 4468 2019年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
Copyright 2019 The Authors PURPOSE. To investigate the serum changes of antioxidant/oxidant markers and the relationship between these factors and visual function in patients with retinitis pigmentosa (RP). METHODS. Fifty-two RP patients <40 years old and 25 controls were included. Serum samples were analyzed for superoxide dismutase 3 (SOD3) activity, glutathione peroxidase (GPx), potential antioxidant (PAO), and hexanoyl-lysine (HEL). The relationships between these markers and visual parameters, including best-corrected visual acuity (BCVA), mean deviation (MD), and average retinal sensitivity of 4 or 12 central points on static perimetry tests (Humphrey Field Analyzer, the central 10–2 program) were examined in the RP patients. RESULTS. Although there was no significant difference in the serum SOD3 activity between RP patients and controls, serum SOD3 activity in the severe degeneration group with macular involvement (16.3 6 11.3 U/mL) was significantly lower compared with those in the mild degeneration group (those with midperipheral scotomas; 28.5 6 16.6 U/mL, P ¼ 0.0459). SOD3 was significantly related to visual acuity (r ¼ -0.3701, P ¼ 0.0069) and the average retinal sensitivity of four central points (r ¼ 0.3463, P ¼ 0.0137) in RP patients. The linear trends of these two parameters across SOD3 levels were also significant (P ¼ 0.0264 and 0.0172, respectively). There was no consistent correlation between other serum antioxidant/ oxidant markers and visual parameters. CONCLUSIONS. Lower serum SOD3 activity was associated with the severe retinal degeneration in RP patients. Our results suggest that serum SOD3 activity may be related to disease severity in RP.
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Kaizu Y., Nakao S., Arima M., Wada I., Yamaguchi M., Sekiryu H., Hayami T., Ishikawa K., Ikeda Y., Sonoda K.
Acta Ophthalmologica 97 ( 5 ) e811 - e812 2019年8月
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Capillary Dropout is Dominant in Deep Capillary Plexus in Early Diabetic Retinopathy in Optical Coherence Tomography Angiography 査読あり
Kaizu Y, Nakao S, Arima M, Wada I, Yamaguchi M, Sekiryu H, Hayami T, Ishikawa K, Ikeda Y, Sonoda KH
Acta Ophthalmol 2019年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1111/aos.14041
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Capillary Dropout is Dominant in Deep Capillary Plexus in Early Diabetic Retinopathy in Optical Coherence Tomography Angiography. 査読あり
Kaizu Y, Nakao S, Arima M, Wada I, Yamaguchi M, Sekiryu H, Hayami T, Ishikawa K, Ikeda Y, Sonoda KH
Acta Ophthalmol 2019年8月
記述言語：英語 掲載種別：研究論文（その他学術会議資料等）
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Nakatake S., Murakami Y., Funatsu J., Koyanagi Y., Akiyama M., Momozawa Y., Ishibashi T., Sonoda K., Ikeda Y.
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 257 ( 6 ) 1169 - 1181 2019年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
PURPOSE: The purpose of the study was to investigate the characteristics of the parafoveal cone density changes in patients with retinitis pigmentosa (RP) using adaptive optics scanning laser ophthalmoscopy (AO-SLO). METHODS: A total of 14 eyes of RP patients and 10 eyes of control subjects were examined. High-resolution images of cone photoreceptor cells were obtained with a Canon AO-SLO system in the four retinal regions of the superior, inferior, temporal, and nasal areas located 1.0 mm from the central fovea. The relationships of cone density with optical coherence tomography (OCT) findings and the visual sensitivity of the static perimetry tests were analyzed in RP patients. RESULTS: The averaged cone densities in RP patients were decreased at 1.0 mm eccentricity from the fovea (11,899 cells/mm2) compared with those in control subjects (16,647 cells/mm2; P < 0.01). The cone density was substantially decreased even in RP patients with an intact interdigitation zone at the examined area (12,865 cells/mm2; P < 0.01 vs. controls) and preserved visual sensitivity with > 35 dB (13,019 cells/mm2; P < 0.001 vs. controls). CONCLUSIONS: In RP, cone photoreceptor cell loss occurred in the parafoveal region with a preserved EZ/IZ or visual sensitivity. AO-SLO may be a useful modality to detect early changes of cone photoreceptor cells in RP patients.
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Night-vision aid using see-through display for patients with retinitis pigmentosa 査読あり
Ikeda Y., Nakatake S., Funatsu J., Fujiwara K., Tachibana T., Murakami Y., Hisatomi T., Yoshida S., Enaida H., Ishibashi T., Sonoda K.
Japanese Journal of Ophthalmology 63 ( 2 ) 181 - 185 2019年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Japanese Journal of Ophthalmology
© 2019, Japanese Ophthalmological Society. Purpose: From an early stage, retinitis pigmentosa (RP) patients suffer from night blindness which causes nocturnal mobility difficulties. We created a wearable visual aid that uses a high-performance see-through display, and added a high-sensitivity camera with a complementary metal-oxide-semiconductor sensor. Here, we evaluate the device’s efficacy for helping night-blindness sufferers walk in the dark. Study design: Prospective clinical study. Methods: Twenty-eight subjects underwent binocular visual acuity testing in the dark without (power off) and with (power on) the device. The test was carried out in a darkened room. We recorded the number of trial errors and the time it took each subject to arrive at the goal both with and without the aid of our device. Results: Our device effectively assists walking in RP patients with mobility problems in the dark. Conclusion: Binocular visual acuity in the dark was significantly improved with the aid of our device. In the walking test, the number of errors decreased greatly with the device, and the travel time was significantly shortened.
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Ishikawa S., Yoshinaga Y., Kantake D., Nakamura D., Yoshida N., Hisatomi T., Ikeda Y., Ishibashi T., Enaida H.
Graefe's Archive for Clinical and Experimental Ophthalmology 257 ( 3 ) 557 - 565 2019年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Graefe's Archive for Clinical and Experimental Ophthalmology
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: This study was conducted in order to develop a novel noninvasive system for measurement and imaging of the arterial oxygen density ratio (ODR) in the retinal microcirculation. Methods: We developed a system composed of two digital cameras with two different filters, which were attached to a fundus camera capable of simultaneously obtaining two images. Actual measurements were performed on healthy volunteer eyes (n = 61). A new algorithm for ODR measurement and pixel-level imaging of erythrocytes was constructed from these data. The algorithm was based on the morphological closing operation and the line convergence index filter. For system calibration, we compared and verified the ODR values in arterioles and venules that were specified in advance for 56 eyes with reproducibility. In 10 additional volunteers, ODR measurements and imaging of the arterial phase in the retinal microcirculation corresponding to changes in oxygen saturation of the peripheral arteries at normal breathing and breath holding were performed. Results: Estimation of incident light to erythrocytes and pixel-level ODR calculation were achieved using the algorithm. The mean ODR values of arterioles and venules were 0.77 ± 0.060 and 1.02 ± 0.067, respectively. It was possible to separate these regions, calibrate at the pixel level, and estimate the arterial phase. In each of the 10 volunteers, changes in the arterial phase ODR corresponding to changes in oxygen saturation of the peripheral arteries were observed before and after breath holding on ODR images. The mean ODR in 10 volunteers was increased by breath holding (p < 0.05). Conclusions: We developed a basic system for arterial phase ODR measurement and imaging of the retinal microcirculation. With further validation and development, this may provide a useful tool for evaluating retinal oxygen metabolism in the retinal microcirculation.
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Verbakel S., Van Huet R., Den Hollander A., Geerlings M., Kersten E., Klevering B., Klaver C., Plomp A., Wesseling N., Bergen A., Nikopoulos K., Rivolta C., Ikeda Y., Sonoda K., Wada Y., Boon C., Nakazawa T., Hoyng C., Nishiguchi K.
Investigative Ophthalmology and Visual Science 60 ( 4 ) 1192 - 1203 2019年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Investigative Ophthalmology and Visual Science
© 2019 The Authors. PURPOSE. To describe the clinical and genetic spectrum of RP1-associated retinal dystrophies. METHODS. In this multicenter case series, we included 22 patients with RP1-associated retinal dystrophies from 19 families from The Netherlands and Japan. Data on clinical characteristics, visual acuity, visual field, ERG, and retinal imaging were extracted from medical records over a mean follow-up of 8.1 years. RESULTS. Eleven patients were diagnosed with autosomal recessive macular dystrophy (arMD) or autosomal recessive cone-rod dystrophy (arCRD), five with autosomal recessive retinitis pigmentosa (arRP), and six with autosomal dominant RP (adRP). The mean age of onset was 40.3 years (range 14–56) in the patients with arMD/arCRD, 26.2 years (range 18–40) in adRP, and 8.8 years (range 5–12) in arRP patients. All patients with arMD/arCRD carried either the hypomorphic p.Arg1933* variant positioned close to the C-terminus (8 of 11 patients) or a missense variant in exon 2 (3 of 11 patients), compound heterozygous with a likely deleterious frameshift or nonsense mutation, or the p.Gln1916* variant. In contrast, all mutations identified in adRPand arRP patients were frame shift and/or nonsense variants located far fromthe C -terminus. CONCLUSIONS. Mutations in the RP1 gene are associated with a broad spectrum of progressive retinal dystrophies. In addition to adRP and arRP, our study provides further evidence that arCRD and arMD are RP1-associated phenotypes as well. The macular involvement in patients with the hypomorphic RP1 variant suggests that macular function may remain compromised if expression levels of RP1 do not reach adequate levels after gene augmentation therapy.