Kazuno Negishi
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Kazuno Negishi has a total of 563 co-authors. Here are the top co-authors by number of shared publications:
Kazuo Tsubota
Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
82 shared publications- Kazuo Tsubota
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan; and
67 shared publications - Masahiko Ayaki
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan
53 shared publications - Toshihide Kurihara
Laboratory of Photobiology, Keio University School of Medicine, Tokyo, Japan
45 shared publications Hidemasa Torii
27 shared publicationsMegumi Saiki
27 shared publications
Latest Publications
- Open Access
- 5 November 2026
- Published by Elsevier in Ophthalmology Science
Full-Field Stimulus Test for Visual Function Assessment in Ultra-Low Vision with Retinitis Pigmentosa
- 5 November 2026
- Published by Elsevier in Ophthalmology Science
Open AccessFull-Field Stimulus Test for Visual Function Assessment in Ultra-Low Vision with Retinitis Pigmentosa
- Open Access
- 27 October 2026
- Published by Springer Nature in Japanese Journal of Ophthalmology
Clinical utility of pupil diameter cutoffs for detecting early presbyopia
Purpose: Little data exist on clinically relevant pupil diagnostic values for detecting early presbyopia (accommodative amplitude [AA]< 2.50D). This study aimed to determine the optimal cutoff value of pupil diameters for screening early presbyopia. Study design: Cross-sectional observational study Methods: 115 individuals aged ≥20 with visual acuity ≥20/25 who had attended one of two healthcare facilities in Japan between December 2020 and December 2021 were included. AA and near and distance pupillary diameters were measured by auto kerato-refractometer (ARK-1s; NIDEK Co.). Optimal cutoff values for early presbyopia were determined by receiver operating characteristic plots based on the Youden index. Results: Among the pupil-related parameters (near or distance alone, or the difference between these), the difference between near and distance pupil diameters of 0.95 mm yielded the best results, with 82.4% sensitivity and 82.9% specificity (AUC 0.87). Conclusion: A difference in pupil diameter of 0.95mm could be the optimal cutoff value for assessing early presbyopia. As pupil dynamics have been previously related to presbyopia, this study proposes threshold pupil diameter measurement values to provide an alternative practical way to clinically screen for and assess presbyopia.
- 27 October 2026
- Published by Springer Nature in Japanese Journal of Ophthalmology
Open AccessClinical utility of pupil diameter cutoffs for detecting early presbyopia
Purpose: Little data exist on clinically relevant pupil diagnostic values for detecting early presbyopia (accommodative amplitude [AA]< 2.50D). This study aimed to determine the optimal cutoff value of pupil diameters for screening early presbyopia. Study design: Cross-sectional observational study Methods: 115 individuals aged ≥20 with visual acuity ≥20/25 who had attended one of two healthcare facilities in Japan between December 2020 and December 2021 were included. AA and near and distance pupillary diameters were measured by auto kerato-refractometer (ARK-1s; NIDEK Co.). Optimal cutoff values for early presbyopia were determined by receiver operating characteristic plots based on the Youden index. Results: Among the pupil-related parameters (near or distance alone, or the difference between these), the difference between near and distance pupil diameters of 0.95 mm yielded the best results, with 82.4% sensitivity and 82.9% specificity (AUC 0.87). Conclusion: A difference in pupil diameter of 0.95mm could be the optimal cutoff value for assessing early presbyopia. As pupil dynamics have been previously related to presbyopia, this study proposes threshold pupil diameter measurement values to provide an alternative practical way to clinically screen for and assess presbyopia.
- Open Access
- 17 September 2026
- Published by Elsevier in SSRN Electronic Journal
Chimeric Gtacr2 Restores ON Responses Involving Hyperpolarization-Activated Channels In A Mouse Model Of Retinal Degeneration
Background: Optogenetic tools have been extensively investigated in basic and clinical research to restore vision in advanced retinal degeneration. Although microbial ion channel opsins, mammalian G protein-coupled receptor opsins, and chimeric opsins combining domains from different molecules have been reported, how these domain combinations affect opsin function and retinal responses remains poorly understood.Methods:We engineered a chimeric GtACR2 (chGtACR2) containing bovine rhodopsin cytoplasmic loops and delivered it to the retinas of rd1 mice. light-induced responses of GtACR2 and chGtACR2 in the cell line and retinas were compared by patch-clump and multielectrode array, respectively. Visual acuity and contrast sensitivity of chGtACR2-treated mice were examined by optomotor response test. Endogenous ion channels involved in the chGtACR2-induced light responses were tested by pharmacological blockade.Findings: Although patch-clamp recordings confirmed that chGtACR2 functioned as a light-gated chloride channel that induced membrane hyperpolarization, multielectrode array recordings revealed chGtACR2-induced ON-like responses in retinal ganglion cells across the tested stimulus intensities, with increases in the number of responsive units and their firing rates. Visual acuity and contrast sensitivity were improved in vivo. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity contributed to these ON-like responses.Interpretation:These findings suggest that endogenous HCN channel activity can influence retinal responses to an introduced optogenetic tool and highlight the potential of modifying cytoplasmic domains to alter the functional properties of microbial opsins.Funding: AMED-CRST (JP22gm1510007), JSPS KAKENHI (JP25K12842, JP26H00468, and JP24K12796), and SPRING(JPMJSP2123).
- 17 September 2026
- Published by Elsevier in SSRN Electronic Journal
Open AccessChimeric Gtacr2 Restores ON Responses Involving Hyperpolarization-Activated Channels In A Mouse Model Of Retinal Degeneration
Background: Optogenetic tools have been extensively investigated in basic and clinical research to restore vision in advanced retinal degeneration. Although microbial ion channel opsins, mammalian G protein-coupled receptor opsins, and chimeric opsins combining domains from different molecules have been reported, how these domain combinations affect opsin function and retinal responses remains poorly understood.Methods:We engineered a chimeric GtACR2 (chGtACR2) containing bovine rhodopsin cytoplasmic loops and delivered it to the retinas of rd1 mice. light-induced responses of GtACR2 and chGtACR2 in the cell line and retinas were compared by patch-clump and multielectrode array, respectively. Visual acuity and contrast sensitivity of chGtACR2-treated mice were examined by optomotor response test. Endogenous ion channels involved in the chGtACR2-induced light responses were tested by pharmacological blockade.Findings: Although patch-clamp recordings confirmed that chGtACR2 functioned as a light-gated chloride channel that induced membrane hyperpolarization, multielectrode array recordings revealed chGtACR2-induced ON-like responses in retinal ganglion cells across the tested stimulus intensities, with increases in the number of responsive units and their firing rates. Visual acuity and contrast sensitivity were improved in vivo. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity contributed to these ON-like responses.Interpretation:These findings suggest that endogenous HCN channel activity can influence retinal responses to an introduced optogenetic tool and highlight the potential of modifying cytoplasmic domains to alter the functional properties of microbial opsins.Funding: AMED-CRST (JP22gm1510007), JSPS KAKENHI (JP25K12842, JP26H00468, and JP24K12796), and SPRING(JPMJSP2123).
- Open Access
- 14 September 2026
- Published by Elsevier in AJO International
- Vol. 3 (4)
Layer-specific retinal remodeling after epiretinal membrane surgery assessed with ultra-widefield optical coherence tomography
- 14 September 2026
- Published by Elsevier in AJO International
- Vol. 3 (4)
Open AccessLayer-specific retinal remodeling after epiretinal membrane surgery assessed with ultra-widefield optical coherence tomography
- Open Access
- 6 August 2026
- Published by Springer Nature in Scientific Reports
- Vol. 16 (1)
Association between outdoor activity and peripapillary choroidal thickness in school-aged children: a 1-year observational study
This study investigated the relationship between changes in choroidal thickness (CT) and environmental factors, given that CT alterations may predict myopia progression in school-aged children. Tokyo-based elementary schoolchildren were assessed from July 2023 to July 2024. Students who transferred, received atropine treatment, or required a lid speculum were excluded. Measurements included the spherical equivalent, axial length, and CT in foveal-centered regions—central (C0), inner (C1), and outer (C2)—and ocular total higher order aberrations (THOAs) (φ = 4 mm). Multiple regression analyses examined the associations between C0CT, C1CT, and C2CT and sex, body mass index, outdoor time, time spent on near work, reading distance, parental myopia, and ocular THOAs. Greater baseline CT was associated with greater thinning in all regions ( p < 0.001). Longer outdoor time was associated with increased CT in the nasal quadrant of C1 and the superior quadrant of C2 ( p < 0.05). Elevated THOAs were associated with greater CT thinning in all regions of C1 except the temporal region and the temporal quadrants of C2 ( p < 0.05). The findings from this 1-year observational study suggested that outdoor activity contributes to regional changes in the CT, particularly in the peripapillary area between the optic disc and macula.
- 6 August 2026
- Published by Springer Nature in Scientific Reports
- Vol. 16 (1)
Open AccessAssociation between outdoor activity and peripapillary choroidal thickness in school-aged children: a 1-year observational study
This study investigated the relationship between changes in choroidal thickness (CT) and environmental factors, given that CT alterations may predict myopia progression in school-aged children. Tokyo-based elementary schoolchildren were assessed from July 2023 to July 2024. Students who transferred, received atropine treatment, or required a lid speculum were excluded. Measurements included the spherical equivalent, axial length, and CT in foveal-centered regions—central (C0), inner (C1), and outer (C2)—and ocular total higher order aberrations (THOAs) (φ = 4 mm). Multiple regression analyses examined the associations between C0CT, C1CT, and C2CT and sex, body mass index, outdoor time, time spent on near work, reading distance, parental myopia, and ocular THOAs. Greater baseline CT was associated with greater thinning in all regions ( p < 0.001). Longer outdoor time was associated with increased CT in the nasal quadrant of C1 and the superior quadrant of C2 ( p < 0.05). Elevated THOAs were associated with greater CT thinning in all regions of C1 except the temporal region and the temporal quadrants of C2 ( p < 0.05). The findings from this 1-year observational study suggested that outdoor activity contributes to regional changes in the CT, particularly in the peripapillary area between the optic disc and macula.
- Open Access
- 24 July 2026
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 21 (7) , e0354452
Fundus image analysis of retinitis pigmentosa using artificial intelligence
Retinitis pigmentosa (RP) is a group of inherited retinal diseases that are caused by genetic defects that lead to progressive photoreceptor loss and eventual blindness. Early diagnosis would be helpful for effective management of the disease; however, many patients stay unaware of early symptoms. Meanwhile, fundus images are widely obtained during routine medical checkups but are underused for detecting RP. This study explores the effectiveness of finetuning deep learning models, pre-trained for general visual tasks, to identify RP from color fundus images. The dataset comprised 321 color fundus images from 201 Japanese subjects at Keio University Hospital, including 200 images from 107 patients with retinitis pigmentosa and 121 images from 94 non-retinitis pigmentosa subjects. Multiple images were available for some subjects. Using transfer learning, pretrained convolutional neural network models -VGG16, Resnet50, and InceptionV3- were finetuned to detect RP. As a result, Inception V3 achieved the best accuracy of 96.97%, which matches the average diagnostic accuracy of ophthalmologists. Gradient-weighted Class Activation Mapping (Grad-CAM) suggested that the model attended to clinically relevant fundus regions, including the peripheral retina and posterior pole, which may reflect features such as peripheral degenerative changes and retinal vascular attenuation. These findings support the potential interpretability of the finetuned model and suggest that deep learning may assist ophthalmologists in RP screening as a supportive tool.
- 24 July 2026
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 21 (7) , e0354452
Open AccessFundus image analysis of retinitis pigmentosa using artificial intelligence
Retinitis pigmentosa (RP) is a group of inherited retinal diseases that are caused by genetic defects that lead to progressive photoreceptor loss and eventual blindness. Early diagnosis would be helpful for effective management of the disease; however, many patients stay unaware of early symptoms. Meanwhile, fundus images are widely obtained during routine medical checkups but are underused for detecting RP. This study explores the effectiveness of finetuning deep learning models, pre-trained for general visual tasks, to identify RP from color fundus images. The dataset comprised 321 color fundus images from 201 Japanese subjects at Keio University Hospital, including 200 images from 107 patients with retinitis pigmentosa and 121 images from 94 non-retinitis pigmentosa subjects. Multiple images were available for some subjects. Using transfer learning, pretrained convolutional neural network models -VGG16, Resnet50, and InceptionV3- were finetuned to detect RP. As a result, Inception V3 achieved the best accuracy of 96.97%, which matches the average diagnostic accuracy of ophthalmologists. Gradient-weighted Class Activation Mapping (Grad-CAM) suggested that the model attended to clinically relevant fundus regions, including the peripheral retina and posterior pole, which may reflect features such as peripheral degenerative changes and retinal vascular attenuation. These findings support the potential interpretability of the finetuned model and suggest that deep learning may assist ophthalmologists in RP screening as a supportive tool.
- 24 July 2026
- Published by Elsevier in American Journal of Ophthalmology
- Vol. 291, 416-421
Cultured Human Corneal Endothelial Cell Injection Therapy in Phakic Eyes with Bullous Keratopathy
- 24 July 2026
- Published by Elsevier in American Journal of Ophthalmology
- Vol. 291, 416-421
Cultured Human Corneal Endothelial Cell Injection Therapy in Phakic Eyes with Bullous Keratopathy
- Open Access
- 17 July 2026
- Published by MDPI AG in Bioengineering
- Vol. 13 (7) , 824
Development of a Deep Learning Model to Estimate Anemia from Palpebral Conjunctiva Taken with a Portable Slit-Lamp Microscope
Background: Anemia is a common systemic condition associated with adverse maternal, perioperative, and cardiovascular outcomes. Although timely screening is clinically important, diagnosis still relies on invasive blood testing. Palpebral conjunctival pallor has traditionally been used as a noninvasive indicator of anemia, but its diagnostic accuracy remains limited. This study aimed to develop and validate a deep learning system to estimate hemoglobin (Hb) concentration and screen for anemia using palpebral conjunctiva images captured with a smartphone-compatible slit-lamp microscope. Methods: In this prospective observational study, 225 Japanese participants (20–92 years) underwent conjunctival imaging and blood testing. Palpebral conjunctiva videos were obtained using the Smart Eye Camera. Video frames were processed using automated anterior-segment segmentation and conjunctiva extraction. A ConvNeXt-based regression model was trained to predict Hb values. Anemia was defined using sex-specific Hb thresholds. Results: From 225 videos, 53,776 frames were extracted, yielding 9903 quality-filtered conjunctiva images (training: 8082; test: 1821). Video-level predicted Hb values moderately correlated with measured Hb (r = 0.42). For anemia screening, frame-level analysis achieved an AUC of 0.75, with accuracy of 0.76, sensitivity of 0.71, and specificity of 0.79. Video-level aggregation achieved 69% accuracy. Conclusions: Deep learning analysis of palpebral conjunctiva images acquired with a portable slit-lamp microscope demonstrated the feasibility of non-invasive hemoglobin estimation and anemia screening. Although the proposed approach achieved moderate performance, further improvements in model accuracy and prospective multi-center validation are required before clinical implementation.
- 17 July 2026
- Published by MDPI AG in Bioengineering
- Vol. 13 (7) , 824
Open AccessDevelopment of a Deep Learning Model to Estimate Anemia from Palpebral Conjunctiva Taken with a Portable Slit-Lamp Microscope
Background: Anemia is a common systemic condition associated with adverse maternal, perioperative, and cardiovascular outcomes. Although timely screening is clinically important, diagnosis still relies on invasive blood testing. Palpebral conjunctival pallor has traditionally been used as a noninvasive indicator of anemia, but its diagnostic accuracy remains limited. This study aimed to develop and validate a deep learning system to estimate hemoglobin (Hb) concentration and screen for anemia using palpebral conjunctiva images captured with a smartphone-compatible slit-lamp microscope. Methods: In this prospective observational study, 225 Japanese participants (20–92 years) underwent conjunctival imaging and blood testing. Palpebral conjunctiva videos were obtained using the Smart Eye Camera. Video frames were processed using automated anterior-segment segmentation and conjunctiva extraction. A ConvNeXt-based regression model was trained to predict Hb values. Anemia was defined using sex-specific Hb thresholds. Results: From 225 videos, 53,776 frames were extracted, yielding 9903 quality-filtered conjunctiva images (training: 8082; test: 1821). Video-level predicted Hb values moderately correlated with measured Hb (r = 0.42). For anemia screening, frame-level analysis achieved an AUC of 0.75, with accuracy of 0.76, sensitivity of 0.71, and specificity of 0.79. Video-level aggregation achieved 69% accuracy. Conclusions: Deep learning analysis of palpebral conjunctiva images acquired with a portable slit-lamp microscope demonstrated the feasibility of non-invasive hemoglobin estimation and anemia screening. Although the proposed approach achieved moderate performance, further improvements in model accuracy and prospective multi-center validation are required before clinical implementation.
- Open Access
- 1 July 2026
- Published by Taylor & Francis in Clinical Optometry
- Vol. ume 18, 1-9
Presbyopic Glaucoma Patients Exhibit Greater Contact Lens Under-Correction Than Non-Glaucomatous Subjects
Objective: Previous studies have suggested that presbyopia may progress faster in patients with glaucoma. This study aimed to compare glaucoma patients and controls to assess the severity of presbyopia in terms of the preference for contact lens (CL) correction. Methods: We compared 457 glaucoma patients and 500 controls aged 40– 69 years, assessing near add power, CL-corrected visual acuity, under-correction with CL (CL power- full correction power), and glaucoma and dry eye-related parameters. Regression analyses were used to evaluate the relationship between the near-add power and ocular parameters. Kaplan-Meier survival analysis estimated the age at which the near add power reached +3.00 D. Results: The mean near add power was 2.27 ± 0.84 D in the control group and 2.47 ± 0.71 D in the glaucoma group (p < 0.01). The CL-corrected visual acuity (LogMAR) was 0.02 ± 0.10 and 0.04 ± 0.11 (p < 0.01), and the under-correction was 0.28 ± 0.69 D and 0.43 ± 0.94 D (p < 0.01), respectively. The glaucoma group showed poorer dry eye-related parameters, and under-correction was associated with myopia, anisometropia, near-add power, lower Schirmer test values, and superficial punctate keratopathy. Kaplan-Meier analysis revealed that glaucoma patients reached +3.00 D near add power significantly earlier than the controls (P< 0.01). Conclusion: Patients with glaucoma preferred more under-corrected CLs than controls. Our results further confirmed the presence of severe presbyopia in individuals with glaucoma.
- 1 July 2026
- Published by Taylor & Francis in Clinical Optometry
- Vol. ume 18, 1-9
Open AccessPresbyopic Glaucoma Patients Exhibit Greater Contact Lens Under-Correction Than Non-Glaucomatous Subjects
Objective: Previous studies have suggested that presbyopia may progress faster in patients with glaucoma. This study aimed to compare glaucoma patients and controls to assess the severity of presbyopia in terms of the preference for contact lens (CL) correction. Methods: We compared 457 glaucoma patients and 500 controls aged 40– 69 years, assessing near add power, CL-corrected visual acuity, under-correction with CL (CL power- full correction power), and glaucoma and dry eye-related parameters. Regression analyses were used to evaluate the relationship between the near-add power and ocular parameters. Kaplan-Meier survival analysis estimated the age at which the near add power reached +3.00 D. Results: The mean near add power was 2.27 ± 0.84 D in the control group and 2.47 ± 0.71 D in the glaucoma group (p < 0.01). The CL-corrected visual acuity (LogMAR) was 0.02 ± 0.10 and 0.04 ± 0.11 (p < 0.01), and the under-correction was 0.28 ± 0.69 D and 0.43 ± 0.94 D (p < 0.01), respectively. The glaucoma group showed poorer dry eye-related parameters, and under-correction was associated with myopia, anisometropia, near-add power, lower Schirmer test values, and superficial punctate keratopathy. Kaplan-Meier analysis revealed that glaucoma patients reached +3.00 D near add power significantly earlier than the controls (P< 0.01). Conclusion: Patients with glaucoma preferred more under-corrected CLs than controls. Our results further confirmed the presence of severe presbyopia in individuals with glaucoma.
- Open Access
- 24 June 2026
- Published by Springer Nature in Scientific Reports
Comparison of eyes with shallow vs. non-shallow anterior chambers undergoing cataract surgery: a multicenter study
This study investigated preoperative biometric measurements and perioperative complications of cataract surgery in eyes with shallow and non-shallow anterior chambers. This multicenter retrospective study included 1423 eyes of 1053 patients who underwent cataract surgery at five Japanese institutions between April 2016 and July 2023. Eyes with an anterior chamber depth (ACD) of ≤ 2.5 mm were classified as the shallow group; those with an ACD > 2.5 mm were categorized as the non-shallow group. The shallow group included older patients, more women, and better best-corrected visual acuity. Preoperative comorbidities, including retinitis pigmentosa, pseudoexfoliation syndrome, and a history of laser iridotomy or peripheral iridectomy, were more frequent in the shallow group. Intraoperatively, the eyes in the shallow group had higher rates of zonular dehiscence (ZD) (odds ratio [OR] 3.04; 95% confidence interval [CI] 1.32-6.94), use of a capsular tension ring (OR 3.52; 95% CI 1.54-8.07) or pupil expansion device (OR 2.17; 95% CI 1.20-3.85), and a higher incidence of postoperative corneal edema. In the shallow group, eyes with ZD had a smaller anterior lens radius of curvature and larger posterior lens radii of curvature. Lens curvature measurements may predict zonular instability in eyes with shallow anterior chambers.
- 24 June 2026
- Published by Springer Nature in Scientific Reports
Open AccessComparison of eyes with shallow vs. non-shallow anterior chambers undergoing cataract surgery: a multicenter study
This study investigated preoperative biometric measurements and perioperative complications of cataract surgery in eyes with shallow and non-shallow anterior chambers. This multicenter retrospective study included 1423 eyes of 1053 patients who underwent cataract surgery at five Japanese institutions between April 2016 and July 2023. Eyes with an anterior chamber depth (ACD) of ≤ 2.5 mm were classified as the shallow group; those with an ACD > 2.5 mm were categorized as the non-shallow group. The shallow group included older patients, more women, and better best-corrected visual acuity. Preoperative comorbidities, including retinitis pigmentosa, pseudoexfoliation syndrome, and a history of laser iridotomy or peripheral iridectomy, were more frequent in the shallow group. Intraoperatively, the eyes in the shallow group had higher rates of zonular dehiscence (ZD) (odds ratio [OR] 3.04; 95% confidence interval [CI] 1.32-6.94), use of a capsular tension ring (OR 3.52; 95% CI 1.54-8.07) or pupil expansion device (OR 2.17; 95% CI 1.20-3.85), and a higher incidence of postoperative corneal edema. In the shallow group, eyes with ZD had a smaller anterior lens radius of curvature and larger posterior lens radii of curvature. Lens curvature measurements may predict zonular instability in eyes with shallow anterior chambers.