論文 - 栗原　俊英

Recurrent Spontaneous Closure of a Full-Thickness Macular Hole Following IOL Scleral Fixation: A Case Report

Ogawa M, Tomita Y†, Ota Y, Ban N, Kunimi H, Hayashi I, Jiang X, Kurihara T, Shinoda H, Negishi K

Am J Ophthalmol Case Rep. （Elsevier BV）  42   102573 - 102573 2026年03月

査読有り,  ISSN  2451-9936

　概要を見る

Purpose To report a rare case of a full-thickness macular hole (FTMH) that underwent spontaneous closure on two separate occasions following vitrectomy and intraocular lens (IOL) scleral fixation. Observations A 58-year-old man, who had undergone IOL scleral fixation and vitrectomy for a dislocated IOL, developed an FTMH (minimum diameter: 21 μm) in the left eye approximately one year post-surgery. While awaiting surgical intervention, the macular hole closed spontaneously two months after its discovery. Two years and nine months later, the FTMH recurred (minimum diameter: 180 μm) and closed spontaneously again within four weeks. Optical coherence tomography (OCT) confirmed the presence of epiretinal proliferation (EP) at the macular surface during both occurrences. Conclusions and Importance Small-diameter FTMHs that form after vitrectomy, particularly those with associated EP, may have the potential for spontaneous closure. This case indicates that short-term observation may be a reasonable management option for select cases of small post-vitrectomy macular holes before proceeding with further surgery.

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Near work affects ocular higher order aberrations in children—a longitudinal study before and after COVID-19: The Tokyo Myopia Study

Shimizu Y*, Yotsukura E*, Ogawa M, Hanyuda A, Tsubota K, Kurihara T, Torii H*†, Negishi K†

Sci Rep. （Springer Science and Business Media LLC）  2026年03月

査読有り

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The impact of introducing a low vision care hub on visitor satisfaction at a university hospital

Sakagami T, Shinojima A, Fukuda K, Yamamoto S, Katada Y, Hanyuda A, Kanai M, Kiyono H, Horie T, KuriharaT†, Negishi K

Jpn J Ophthalmol. 2026年03月

責任著者, 査読有り,  ISSN  00215155

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Purpose: Although Japan has an established welfare system for individuals with visual impairments, medical-welfare coordination remains limited. To address this gap, the Low Vision Care Hub (LVCH) was established within a university hospital. We evaluated the impact of LVCH on visitor satisfaction before and after consultation Study design: A single-center, one-group pre–post study Methods: Individuals with self-reported functional vision difficulties who visited LVCH between July 1 and December 20, 2024 were included. Consultation was provided based on seven domains of low vision care outlined by the Japan Society for Low-Vision Research and Rehabilitation. Satisfaction was measured on a custom 6-point ordinal scale (0–5) pre/post consultation. Changes in satisfaction scores were analyzed using the Wilcoxon signed-rank test. Multivariable logistic regression adjusted for potential confounders Results: Ninety-three participants were included. Satisfaction scores significantly increased after consultation (p <.001) and improvements were consistent across sex, age groups, and visual impairment classification using the International Council of Ophthalmology (ICO) criteria (all p <.001). Notably, participants not meeting the ICO-defined low vision criteria also improved (p <.001). On multivariable logistic regression, only older age (≥ 60 years) remained significantly associated with a markedly improved satisfaction score (OR = 2.98, 95% CI 1.10–8.05, p =.03) Conclusion: Consultations provided at LVCH significantly improved visitor satisfaction, including those who did not meet the ICO low vision criteria. Consultation may be particularly effective in individuals aged over 60 years. Overall, early-stage intervention through structured consultation may benefit individuals with functional vision difficulties

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Photobiomodulation Therapy: The Dawn of Myopia Control

Gettinger K*, Huang Y*, Tsubota K, Negishi K, Kurihara T†

Cells （MDPI AG）  15 （ 6 ） 526 - 526 2026年03月

最終著者, 責任著者, 査読有り

　概要を見る

Highlights: What are the main findings? Light exposure potentially influences myopia development through a variety of proposed mechanisms, although a full understanding of the mechanisms is still lacking. Recent research into the role of nonvisual opsins and spectrum-specific influences on myopia development has highlighted the complexity of these potential pathways. What are the implications of the main findings? Future myopia prevention strategies may utilize promising findings featuring both red, blue, and violet light exposure as a means to control axial growth and refractive changes. While there is still much to be explored, recent findings have suggested several potential mechanisms through which light influences myopia development. As the prevalence of myopia, or near-sightedness, continues to rise globally, it becomes imperative to determine the mechanisms driving myopia so that appropriate interventions to mitigate it can be developed. Light appears to be critical for normal ocular development, and over the past several decades research has explored the connection between light exposure and myopia development. This review explores the growing field of photobiomodulation, or the use of light to modulate biological processes, to prevent myopia development. To complete this review, relevant texts published from January 1990 to December 2025 were retrieved from the PubMed database using a combination of search terms covering myopia and ocular development, light exposure conditions related to myopia, myopia development in relation to circadian and diurnal regulation, nonvisual opsins and myopia, and light-induced ocular damage. Through this review, we see that photobiomodulation offers a potential intervention to control myopia progression, but the mechanisms behind light’s influence on ocular development remain complex and incompletely understood. This review aims to summarize what is currently known to serve as a basis for future research and to delineate important findings.

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Light and myopia: a focus on the expanding role of non-visual opsins

Gettinger K, Tsubota K, Negishi K, Kurihara T†

Eye Vis. （Springer Science and Business Media LLC）  13 （ 1 ） 6 2026年01月

最終著者, 責任著者, 査読有り

　概要を見る

Myopia, or near-sightedness, is a growing global concern as its incidence rate continues to dramatically rise. It has been linked to significant ocular morbidity and reduced quality of life. Despite this, much is still largely unknown about the development of and the mechanisms driving the pathogenesis of myopia. As such, myopia prevention and myopia mitigation treatment strategies are occasionally ineffective, can be difficult to adhere to, and have diminishing returns over time. Recently, non-visual opsins (OPN3, OPN4, and OPN5) have emerged as potentially impacting myopia regulation. This narrative review aims to summarize the current understanding of the non-visual opsins and how they might influence myopia. In addition, this review explores how utilizing this knowledge can help develop promising future treatment strategies to reduce the incidence and severity of myopia.

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Ocular siderosis caused by a subretinal iron foreign body masquerading as a blood clot: a case report

Lin JS, Nagamoto T, Ban N†, Moriya M, Jiang X, Kunimi H, Tomita Y, Kurihara T, Shinoda H, Negishi K

Am J Ophthalmol Case Rep. 41 2026年01月

査読有り,  ISSN  24519936

　概要を見る

Purpose We report a case of ocular siderosis caused by a subretinal iron foreign body. Observations A 30-year-old male construction worker injured by a small piece of shrapnel while working visited an eye clinic for decreased vision in left eye on day X, and was subsequently referred to our hospital with a diagnosis of vitreous hemorrhage on day X+1. Although a penetrating foreign body was suspected, no obvious wound or intraocular foreign body was found even after the hemorrhage subsided. On X+3 months, a rhegmatogenous retinal detachment was found and a lens-sparing vitrectomy was performed. A black elevated subretinal lesion was noted intraoperatively but not removed because it was considered to be a blood clot. The postoperative course was stable with best corrected visual acuity (BCVA) recovering to 20/16. However, the BCVA decreased to 20/30 on X+11 months with the subretinal lesion turning reddish brown. The electroretinogram also showed a significant attenuation of all stimuli. Siderosis was considered to have developed due to the subretinal foreign body. On X+14 months, we performed a combined phaco-vitrectomy to remove the foreign body. Analysis revealed iron as the main component of the foreign body. However, the postoperative electroretinogram remained unchanged, and the BCVA was 20/63 without improvement. Conclusions and importance We experienced a case of a subretinal iron foreign body being mistaken for a blood clot. Even if the vision stays stable, ocular siderosis may occur over the long term if a subretinal iron foreign body remains. Therefore, surgical removal should be actively considered when a subretinal iron foreign body is suspected.

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Clinical implications of systolic blood pressure for diabetic retinopathy across HbA1c levels in a Japanese population

Sasaki M*†, Ofuji Y*, Hanyuda A, Kurihara T, Tomita Y, Mori K, Ozawa N, Ozawa Y, Yamagishi K†, Yuki K, Sawada N, Tsubota K, Negishi K, Tsugane S, Iso H

Sci Rep. 16 （ 1 ）  2026年01月

査読有り

　概要を見る

This study evaluated the association between systolic blood pressure (SBP) and diabetic retinopathy (DR) across different glycemic levels in a Japanese population. We analyzed data from 1,049 residents aged ≥ 40 years with diabetes who underwent ophthalmic screening in Chikusei City. Participants were stratified into four groups by glycated hemoglobin (HbA1c) level (< 7% or ≥ 7%) and SBP (< 140 or ≥ 140 mmHg). Logistic regression was used to examine associations between SBP and prevalent DR within HbA1c strata. DR was present in 136 participants (13.0%), including 82 (7.8%) with mild-to-moderate nonproliferative DR (NPDR) and 54 (5.1%) with severe NPDR or proliferative DR (PDR). Among participants with lower HbA1c levels, higher SBP was significantly associated with greater odds of DR (odds ratio, 2.21; 95% confidence interval, 1.16–4.23). A similar association was observed among those with mild-to-moderate NPDR, but not among participants with higher HbA1c levels. SBP was not significantly associated with severe NPDR or PDR in any group. These findings suggest that elevated SBP may contribute to the development of early-stage DR even in individuals with well-controlled blood glucose levels, underscoring the importance of blood pressure management in DR prevention strategies.

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Violet light-transmitting intraocular lens increases choroidal thickness: 1-year prospective, randomised controlled trial

Yotsukura E*, Torii H*†, Hayashi K, Hayashi S, Ohnuma K, Mori K, Ogawa M, Hanyuda A, Kurihara T†, Tsubota K†, Negishi K

BMJ Open Ophthalmol. （BMJ）  10 （ 1 ） e002441 - e002441 2025年12月

責任著者, 査読有り

　概要を見る

Aims To compare the changes in ocular parameters after implantation of two types of intraocular lenses (IOLs) following cataract surgery. One IOL transmits violet light (VL), and the other does not. Methods A total of 402 patients were randomly assigned to receive either a VL-non-transmitting IOL or a VL-transmitting IOL. Ocular parameters were measured preoperatively and postoperatively, and participants completed a lifestyle questionnaire. The choroidal thickness (CT) was measured using the PLEX Elite 9000 (Carl Zeiss Meditec). The associations between changes in CT and age, sex, type of IOL, preoperative CT, time spent outdoors, time spent using a smartphone or tablet and time spent reading were examined using stepwise multiple regression analysis (SPSS V.28.0 for Windows, IBM-SPSS). Results The baseline mean spherical equivalents were −4.00±5.97 D and −2.19±4.73 D, the axial lengths were 24.84±1.82 mm and 24.19±1.65 mm, and the CTs were 213.78±102.93 μm and 239.20±104.98 μm for the VL-non-transmitting and VL-transmitting IOL groups, respectively. The mean changes in the CT from 3 to 12 months postoperatively were −0.30±18.32 μm for the VL-non-transmitting IOLs and 3.48±16.46 μm for the VL-transmitting IOLs (p=0.012). Multiple regression analysis identified significant choroidal thickening associated with female sex (p=0.004), VL-transmitting IOL implantation (p=0.049) and increased outdoor exposure (p=0.008). Conclusion The choroidal thickening after cataract surgery was associated with the VL-transmitting IOL and longer time spent outdoors with exposure to abundant VL. Despite these findings, this study has several limitations, including a relatively short follow-up period, and it did not assess postoperative lifestyle, VL exposure or actual peripheral defocus in the patients. Trial registration number UMIN000038961.

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Effect of Anti-VEGF Therapy on Wide-Field Retinal and Choroidal Thickness in Macular Edema Secondary to Retinal Vein Occlusion

Araki R, Tomita Y†, Yuda T, Jiang X, Ban N, Kunimi H, Uchida A, Kurihara T, Shinoda H, Negishi K

AJO Int. （Elsevier BV）  3 （ 1 ） 100207 2025年12月

査読有り,  ISSN  2950-2535

　概要を見る

Objective or Purpose: To investigate the effect of anti-VEGF therapy on wide-field retinal and choroidal thickness in patients with macular edema secondary to RVO, and to identify how these effects vary based on clinical characteristics such as occlusion location and patient sex. Design: Retrospective observational study. Subjects, Participants, and/or Controls: Thirty-eight patients (38 eyes) with RVO treated at Keio University Hospital (26 males, 12 females; mean age, 67.7 ± 8.5 years). Seventeen fellow eyes without injection served as internal controls. Methods, Intervention, or Testing: We analyzed 38 eyes with RVO who received intravitreal injections of aflibercept (n = 31) or ranibizumab (n = 7). Wide-field optical coherence tomography (OCT) was performed at baseline (within 7 days before the injection) and at the follow-up visit (30 ± 14 days after the injection). Changes in retinal and choroidal thickness were analyzed across nine predefined regions: a central 5-mm subfield (C0) and eight surrounding peripheral sectors: temporal (L1), superior-temporal (L2), superior (L3), superior-nasal (L4), nasal (L5), inferior-nasal (L6), inferior (L7), and inferior-temporal (L8). Statistical analysis was performed using the Wilcoxon signed-rank test and Bonferroni correction for nine regions. Main Outcome Measures: Changes in regional retinal and choroidal thickness Results: Post-injection, retinal thickness significantly decreased in all regions except L4 and L6 (p < 0.0056). Choroidal thickness showed a significant reduction in L2, L5, and L8 (p < 0.0056). Subgroup analyses revealed no significant changes in choroidal thickness in either the superior RVO group (n = 9) or the inferior RVO group (n = 17). A clear sex-based difference was also observed: male patients (n = 26) exhibited choroidal thinning in L4, L5, L6, and L8 (p < 0.0056), whereas female patients (n = 12) showed no significant changes in any region. Conclusion: Anti-VEGF therapy reduced retinal and choroidal thickness in specific regions in eyes with RVO. No significant differences were observed between eyes with superior and inferior occlusions. In male patients, significant thinning was observed in multiple peripheral regions, whereas no significant changes were noted in female patients. These findings suggest that the choroidal response to anti-VEGF therapy is complex and warrants further investigation.

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Polarized Light Microscopy-Based Quantification of Scleral Collagen Fiber Bundle Remodeling in the Lens-Induced Myopia Mouse Model

Yang Y*, Ikeda SI*, Kang L, Ma Z, Negishi K, Tsubota K, Tomita Y, Gettinger K, Kurihara T†

Life. 15 （ 11 ） 1743 2025年11月

最終著者, 責任著者, 査読有り

　概要を見る

Scleral remodeling plays a crucial role in myopia development. Although ultrastructural collagen changes have been described, quantitative assessment at the fiber bundle level remains limited. This study quantitatively evaluated scleral collagen remodeling in a lens-induced myopia (LIM) mouse model using polarized light microscopy (PLM) combined with picrosirius red (PSR) staining. LIM was induced in C57BL/6J male mice by applying a monocular −30 D lens from postnatal week 3 to 6. Eyes wearing −30 D lenses showed myopic shifts in refraction (−8.42 ± 3.87 D vs. 4.42 ± 4.45 D; p = 0.002) and axial elongation (0.21 ± 0.04 mm vs. 0.18 ± 0.05 mm; p = 0.020) compared with contralateral controls. PLM revealed looser, more disorganized collagen bundles in myopic sclera. Quantitative analysis showed reduced bundle proportion (40.91 ± 6.58% vs. 48.36 ± 6.47%; p = 0.040) and mean size (147.11 ± 59.38 µm² vs. 281.45 ± 101.00 µm²; p = 0.002). These results indicate that myopia development involves structural remodeling of the sclera and that PLM with PSR staining provides a practical approach for quantitative wide-field evaluation of collagen architecture in experimental myopia.

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Choroidal Mast Cells and Their Degranulation Are a Pivotal Trigger for Myopia Development.

Shi J*, Ikeda SI*, Fukuchi*., Chen J, Gettinger K, Imanishi S, Negishi K, Tsubota K, Kurihara T†

Invest Ophthalmol Vis Sci. 66 （ 14 ） 22 2025年11月

最終著者, 責任著者, 査読有り,  ISSN  01460404

　概要を見る

PURPOSE. Mast cells (MCs), key immune regulators, contribute to inflammatory responses through their degranulation. Choroidal thinning is a hallmark of myopia, and MC degranulation has been shown to induce choroidal thinning in a rat model of geographical atrophy. However, the role of choroidal MCs in myopia remains poorly understood. This study aimed to demonstrate that an increased number and proportion of degranulated MCs in the choroid are important determinants of choroidal thinning and myopia development. METHODS. Lens-induced myopia (LIM) was induced by monocular −30 diopter (D) lens wearing in C57BL/6 mice, MC-deficient mice (Mcpt5/Cma1^DTR/⁺), and MC-deficient mice receiving suprachoroidal injection of peritoneal MCs (PMCs). Cromolyn sodium (cromolyn) and pemirolast potassium (pemirolast), reagents that inhibit degranulation by stabilizing MC membranes, were topically applied in LIM mice. Ocular parameters including refraction, axial length, and choroidal thickness were measured before and after LIM. Choroidal MC degranulation was evaluated by choroidal flatmount staining. RESULTS. LIM was successfully induced in wild-type mice but was significantly suppressed in MC-deficient mice. Suprachoroidal injection of PMCs into MC-deficient mice restored myopia progression, as evidenced by axial elongation and choroidal thinning. MC degranulation was significantly increased by −30 D lens wearing, whereas topical administration of cromolyn and pemirolast effectively inhibited both MC degranulation and myopia progression. CONCLUSIONS. Choroidal MC degranulation plays a critical role in LIM by promoting choroidal thinning and axial elongation. These findings enhance our understanding of the role of choroidal MC degranulation in myopia, suggesting a potential therapeutic target for myopia treatment.

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Validation of phiC31-mediated expression and functional knockout of Opn3 in the Opn3-phiC31o knock-in mouse

Kwok RKY, Ikuta H*, Iba C*, Nakano Y*, Ma Z*, Chuai Y, Hiraoka Y, Sayanagi T, Kurihara T, Moritoh S†, Tanaka KF

Eye Vis. （Springer Science and Business Media LLC）  12 （ 1 ） 41 2025年10月

査読有り

　概要を見る

Background: Opn3 is a non-visual blue light-sensitive opsin that has recently been reported to have an expansive repertoire of biological functions. To investigate the function of Opn3-expressing cells, we aimed to generate a system in which Opn3-expressing cells can be targeted by site-specific gene recombination. Methods: Opn3-phiC31o knock-in (KI) mice were generated using the CRISPR-Cas9 method. The phiC31o-poly(A) cassette was inserted into the translation start site in exon 1. Opn3 mRNA and phiC31o mRNA were visualized by in situ hybridization (ISH). 5' rapid amplification of cDNA end (5' RACE) analysis was performed using RNAs from wild-type mouse cerebral cortex and cerebellum to identify the transcription start site of Chml, predicted to be shared with the transcription start site of Opn3. Cold-induced decrease in body temperature was monitored with a telemetric probe to confirm the phenotype of Opn3 knockout. To examine the phiC31o integrase-mediated recombination, Opn3-phiC31o mice were crossed with the ROSA26 ^{MultiFPsΔPuro} reporter and cyan fluorescent protein, mCerulean, expression was labeled by immunohistochemistry. Results: The expression pattern of phiC31o mRNA was consistent with that of Opn3 mRNA in Opn3-phiC31o heterozygous mouse brains, indicating that phiC31o mRNA is expressed under the control of the Opn3 promoter. Based on the public database, the transcription start site of exon 1 of Opn3 is identical to that of Chml, suggesting that phiC31o KI disrupts Chml expression. However, Opn3-phiC31o homozygous mice sustained Chml expression, and the transcription start site of Chml was confirmed to be located 112 bp upstream of the predicted second exon. Opn3-phiC31o homozygous mice showed a larger decrease in body temperature under cold exposure compared to wild-type controls. In addition, these mice also exhibited a refractive myopia phenotype. These findings confirmed the functional knockout of Opn3. Double transgenic mice of Opn3-phiC31o and ROSA26 ^{MultiFPsΔPuro} reporter showed mCerulean expression mainly in the olfactory bulb, cerebral cortex, thalamus, and cerebellum. The recombination efficiency was 30% to 44% in the cerebellum. Conclusions: Opn3-phiC31o KI mice were successfully generated. We can generate Opn3 null mice that does not disrupt Chml by preparing homozygotes of Opn3-phiC31o. We have deposited the sequences including the newly found transcription start site of Chml.

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Diabetic Retinopathy, a Comprehensive Overview on Pathophysiology and Relevant Experimental Models

Gettinger K, Lee D, Tomita Y, Negishi K, Kurihara T†

Int J Mol Sci. （MDPI AG）  26 （ 20 ） 9882 - 9882 2025年10月

最終著者, 責任著者, 査読有り,  ISSN  16616596

　概要を見る

Diabetic retinopathy (DR) is a serious complication of diabetes, leading to vision loss worldwide. The prevalence of DR has increased in recent decades. To understand the pathophysiology of DR, various experimental models have been developed and used. In this review article, we first outline what is currently known of the general pathology of DR, including the mechanisms involved in hyperglycemia, vascular dysfunction, retinal ischemia, retinal inflammation, and retinal degeneration. We next summarize various pathologies detected in experimental models in vivo, such as in chemically and genetically induced murine, rat, and monkey models, surgical methods in larger animals like cats, and a novel murine DR model using occlusion of the carotid artery under early diabetic conditions. A general overview of the in vitro models, including cell monocultures, co-cultures, and 3D models, is also provided. This current summary enables further research to obtain a more thorough understanding of DR pathogenesis and develop appropriate treatment measures.

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An analysis of light that reaches the eye surface in an outdoor environment

Jiang X*, Kondo S*, Otsuka N, Kaneda D, Torii H, Negishi K, Kurihara T†, Tsubota K†

Sci Rep. （Springer Science and Business Media LLC）  15 （ 1 ） 34319 2025年10月

責任著者, 査読有り

　概要を見る

The global pandemic of myopia has become an urgent public health concern in recent years. Although the mechanism remains largely unclear, the importance of outdoor light exposure on myopia prevention is widely recognized. Outdoor light is more intense and has a different spectral composition compared to indoor lighting, which are believed to contribute to the suppression of myopia. However, due to modern lifestyles, even children find it difficult to spend time outdoors. To receive outdoor light efficiently is important, yet previous reports showed inconsistent findings on optimal thresholds for outdoor light exposure. One reason may be the lack of a standardized protocol for measuring light reaching the eye surface. In this study, we developed a novel measurement device using a 3D-printed mannequin head with a light sensor probe embedded at the eye position to mimic the human eye. We assessed the proportion of light that reached the mannequin’s eye surface from different directions at various time points on a sunny day and evaluated the influence of different eyeglasses and lenses.

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Flanged intrascleral intraocular lens fixation using 31 needles

Nagamoto T, Kurihara T, Negishi K, Ban N†

Retin Cases Brief Rep. （Ovid Technologies (Wolters Kluwer Health)）  2025年10月

査読有り,  ISSN  1935-1089

　概要を見る

Purpose:

To demonstrate the novel use of a 31-gauge needle for flanged intrascleral intraocular lens (IOL) fixation using the double-needle technique.

Methods:

Flanged intrascleral IOL fixation was performed using the ZELOSTAT 31G (ASTI, Shizuoka, Japan) needle in a 73-year-old male with right IOL subluxation.

Results:

The IOL was successfully fixated with smooth intraoperative handling, excellent postoperative outcomes, no complications, and minimal refractive error.

Conclusion:

The 31-gauge needle has a larger inner diameter compared to the conventional 30-gauge thin-wall needle, which may facilitate intrascleral IOL fixation procedures.

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Impact of Extended Lens-Induced Myopia on Retinal Structure and Function in Mice

Yang Y*, Tomita Y*, Lee D, Ikeda SI, Jiang X, Negishi K, Tsubota K†, Kurihara T†

Curr Eye Res. 51 （ 2 ） doi.org/10.1080/02713683.2025.2557590 - 197 2025年09月

最終著者, 責任著者, 査読有り,  ISSN  02713683

　概要を見る

Purpose: To investigate time-dependent structural and functional retinal alterations in a mouse model of prolonged lens-induced myopia. Methods: Myopia was induced in male C57BL/6J mice by fitting −30 D lenses on both eyes starting at postnatal week 3. Mice were assigned to either a long-term induction group (3–9 weeks of age) or a short-term induction group (3–6 weeks of age). Separate groups fitted with 0 D lenses served as controls. Ocular parameters, including refraction, axial length, choroidal thickness, and retinal thickness were measured at weeks 3, 6, and 9 using an infrared photorefractor and spectral-domain optical coherence tomography. Retinal function was assessed by dark-adapted electroretinography at week 9 for the long-term group and at week 6 for the short-term group. Statistical analyses included two-way repeated-measures ANOVA followed by Bonferroni’s post hoc test for comparisons across groups and time points, and two-tailed unpaired t-test or one-way ANOVA with Fisher’s LSD post hoc test for group comparisons at individual time points. Results: After 6 weeks of myopia induction, the long-term myopia group exhibited significant reduction in refraction, axial length elongation, and choroidal thickness thinning. Inner retinal thickness was markedly reduced, and electroretinography revealed attenuated amplitudes and delayed implicit times of the oscillatory potentials. Conclusion: Prolonged lens-induced myopia in mice induces time-dependent structural and functional retinal alterations, particularly in the inner layers. This model underscores the significance of early retinal monitoring under long-term myopic conditions and serves as a platform for investigating retinal vulnerability and developing preservation strategies over time.

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Digital health as a scalable strategy for equitable myopia management in East Asia

Chen J*, Lee D*, Negishi K, Tsubota K, Kurihara T†

Asia Pac J Ophthalmol. （Elsevier BV）  14 （ 6 ） 100241 2025年08月

最終著者, 責任著者, 査読有り,  ISSN  2162-0989

　概要を見る

East Asia is facing a growing burden of myopia, with pronounced disparities in access to eye care between urban and rural populations. Digital health technologies present a scalable and cost-effective alternative to traditional myopia interventions that enhance early detection, risk stratification, behavioral modification, and public education. Artificial intelligence-assisted screening tools, wearable monitors, and mHealth initiatives, such as the World Health Organization-International Telecommunication Union MyopiaEd program, have demonstrated effectiveness in improving myopia prevention and health education accessibility. However, achieving a sustained impact requires rigorous validation, robust data governance, infrastructure investment, and integration with established clinical strategies. East Asia could be well-positioned to pioneer a comprehensive digital model for equitable myopia control.

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Mechanisms Underlying Myopia Progression from Visual Signaling to Metabolic Remodeling in Retina

Yang Y, Lee D, Gettinger K, Tsubota K, Negishi K, Kurihara T, Tomita Y†

JMA J. （Japan Medical Association）  8 （ 4 ） DOI: 10.31662/jmaj.2025-0268 2025年08月

査読有り,  ISSN  2433-328X

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Dose-dependent myopia-suppressing effect of 4-phenlybutyric acid eye drops in a mouse myopia model under masked condition

Ikeda SI, Sone K, Takai Y, Miyano T, Negishi K, Tsubota K, Kurihara T†

BMC Ophthalmol. 25 （ 1 ） 383 2025年07月

最終著者, 責任著者, 査読有り

　概要を見る

Background: Myopia, characterized by excessive axial elongation of the eyeball, has become a significant global public health issue, particularly in Asia. Severe myopia increases the risk of ocular complications, including retinal degeneration and glaucoma. Recent studies have identified the role of scleral extracellular matrix remodeling and endoplasmic reticulum (ER) stress in myopia pathogenesis. Our previous study identified scleral ER stress as a critical factor in myopia development. This study aimed to investigate the therapeutic potential of 4-phenylbutyric acid (4-PBA), a chemical chaperone, in mitigating scleral ER stress and its effects on myopia progression in a mouse myopia model under masked condition. Methods: A lens-induced myopia (LIM) mouse model was utilized to evaluate the effects of 4-PBA administered as eye drops. Mice received varying concentrations of 4-PBA or phosphate-buffered saline (PBS) as a control. Changes in refractive error and axial length were measured to assess myopia progression. In addition, further experiments were also conducted under masked conditions, where the experimenter was unaware of the treatment was being applied, for the three conditions of 2%, 0.5% 4-PBA eye drops or vehicle treatment of LIM mice. Results: Administration of 4-PBA at concentrations of 0.5% and higher significantly suppressed the myopic shift in refraction and axial elongation associated with myopia compared to mice in the PBS control group. In a blinded, masked experiment, 2% and 0.5% 4-PBA eye drops also suppressed the progression of myopia in a dose-dependent manner. Conclusions: This study demonstrated that 4-PBA effectively mitigated myopia progression in a mouse model by targeting scleral ER stress. The dose-dependent suppression of myopic shifts and axial elongation under masked experimental condtion highlights the potential of 4-PBA as a therapeutic agent for managing myopia. These findings pave the way for further research and potential clinical applications in myopia treatment.

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Antibiotics-Induced Gut Microbiome Dysbiosis Affects Susceptibility to Minus Lens-Induced Myopia in Mice

Ikeda SI, Lee D, Chen J, Fukuda S, Negishi K, Tsubota K†, Kurihara T†

Invest Ophthal Vis Sci. （Association for Research in Vision and Ophthalmology (ARVO)）  66 （ 6 ） 76 2025年06月

最終著者, 責任著者, 査読有り,  ISSN  1552-5783

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PURPOSE. The prevalence of myopia has increased worldwide in recent decades, shifting the focus in research from genetic to environmental factors. The roles of diet in the development of myopia may be directly associated with gut microbiota composition. Therefore this study evaluated the effects of antibiotic-induced gut dysbiosis on the development of negative lens-induced myopia. METHODS. We administered several antibiotics (ampicillin, vancomycin, neomycin, or a mixture) to induce gut dysbiosis in male C57BL/6J mice with negative lens-induced myopia. Gut microbiome profiles were analyzed by 16 S rRNA gene sequencing. RESULTS. Mice administered vancomycin, neomycin, and a mixture of three antibiotics exhibited resistance to lens-induced myopia, unlike control or ampicillin-administered mice. Further analyses revealed no specific trend in the gut microbiota composition and diversity related to myopia resistance, except for an increase in the abundance of Clostridiaceae. CONCLUSIONS. These findings demonstrate the potential role of the gut microbiome, particularly Clostridiaceae family, in myopia susceptibility. This study offers new insights into the preventive strategies and therapeutic interventions to mitigate myopia development.

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