Takenori Inomata

Juntendo University · Department of Ophthalmology

To elucidate the role of perlecan (Hspg2), a large multidomain heparan sulfate proteoglycan expressed in the basement membrane, in the structure of the corneal epithelium. A previously developed perlecan-deficient (Hspg2⁻/⁻-Tg) mouse model was used. Histologic analysis of their corneas was performed by light and transmission electron microscopy. Th...

Corneal transplantation serves as a reproducible and simple surgical model to study mechanisms regulating immunity and angiogenesis. The simplicity of the model allows for systematic analysis of different mechanisms involved in immune and angiogenic privilege and their failures. This protocol describes how to induce neovessels and inflammation in a...

Background: Corneal allograft survival dramatically decreases in hosts with inflamed or vascularized recipient beds. We have previously shown that in rejected corneal allografts regulatory T cells (Treg) demonstrate diminished Foxp3 expression and immunoregulatory function. Treatment with low doses of IL-2 selectively expands Treg and has been pro...

Regulatory T cells (Tregs) are crucial for allograft survival. Tregs can be divided into thymus-derived natural Tregs (tTregs) and peripherally-derived induced Tregs (pTregs). Here, we determine whether the suppressive function of Treg subsets is hampered in hosts who are at high risk for rejecting their graft. To induce graft beds that promote hig...

Purpose: To delineate and compare the kinetics of corneal angiogenesis after high-risk (HR) versus low-risk (LR) corneal transplantation. Methods: In mice, intrastromal sutures were placed in the recipient graft bed 2 weeks before allogeneic transplantation to induce angiogenesis and amplify the risk of graft rejection. Control (LR) graft recipi...

Background Dry eye (DE) and hay fever (HF) show synergistic exacerbation of each other’s pathology through inflammatory pathways. Objective This study aimed to investigate the association between DE and HF comorbidity and the related risk factors. Methods A cross-sectional observational study was conducted using crowdsourced multidimensional data...

The coronavirus disease (COVID-19) pandemic has emphasized the paucity of non-contact and non-invasive methods for the objective evaluation of dry eye disease (DED). However, robust evidence to support the implementation of mHealth- and app-based biometrics for clinical use is lacking. This study aimed to evaluate the reliability and validity of ap...

Background: Using traditional patient-reported outcomes (PROs), such as paper-based questionnaires, is cumbersome in the era of web-based medical consultation and telemedicine. Electronic PROs may reduce the burden on patients if implemented widely. Considering promising reports of DryEyeRhythm, our in-house mHealth smartphone app for investigatin...

Medical interviews are expected to undergo a major transformation through the use of artificial intelligence. However, artificial intelligence-based systems that support medical interviews are not yet widespread in Japan, and their usefulness is unclear. A randomized, controlled trial to determine the usefulness of a commercial medical interview su...

Background: Hay fever is a common allergic disease, with an estimated worldwide prevalence of 14.4% and a variety of symptoms. This study assessed the minimal clinically important difference (MCID) of nasal symptom score (NSS), non-nasal symptom score (NNSS), and total symptoms score (TSS) for app-based hay-fever monitoring. Methods: MCIDs were...

Topic Numerous smartphone applications have been devised for diagnosis, treatment, and symptom management in ophthalmology. Despite the importance of systematic evaluation of the purpose, target disease, effectiveness, and utility of smartphone applications to their effective utilization, few studies have formally evaluated their validity, reliabil...

Background/objective: To test the feasibility of a dry eye disease (DED) symptom stratification algorithm previously established for the general population among patients visiting ophthalmologists. Subject/methods: This retrospective cross-sectional study was conducted between December 2015 and October 2021 at a university hospital in Japan; par...

Background: Dry eye disease (DED) is one of the most common ocular surface diseases. Numerous patients with DED remain undiagnosed and inadequately treated, experiencing various subjective symptoms and a decrease in quality of life and work productivity. A mobile health smartphone app, namely, the DEA01, has been developed as a noninvasive, noncon...

Unlabelled: Dry eye is a multifactorial and common age-related ocular surface disease. Dyslipidemia has been reported to be involved in meibomian gland dysfunction (MGD). However, it has not been clearly identified which lipid abnormality is responsible for MGD. In this systematic review and meta-analysis, we discuss how lipid profile changes with...

Background: Multidisciplinary efforts to prospectively collect and analyze symptoms of hay fever are limited. We aimed to identify the characteristics of nasal and ocular symptoms of hay fever, using the AllerSearch smartphone application. Methods: This mobile health-based prospective observational study using the AllerSearch smartphone applicat...

During the 5th Science, Technology, and Innovation Basic Plan, the Japanese government proposed a novel societal concept -Society 5.0- that promoted a healthcare system characterized by its capability to provide unintrusive, predictive, longitudinal care through the integration of cyber and physical space. The role of Society 5.0 in managing our qu...

Background: Corneal transplantation outcomes are generally less favorable in young children compared with adults. The purpose of this study was to determine the immunological mechanisms underlying this difference. Methods: A murine model of allogeneic corneal transplantation was used in the study, and graft survival was determined by evaluating...

BACKGROUND Dry eye disease (DED) is one of the most common ocular surface diseases. Numerous patients with DED remain undiagnosed and inadequately treated, experiencing various subjective symptoms and a decrease in quality of life and work productivity. A mobile health smartphone app, namely, the DEA01, has been developed as a noninvasive, nonconta...

We investigated and characterized the prevalence of dry eye disease (DED) in Parkinson’s disease (PD). PubMed and EMBASE databases were searched for relevant studies between January 1, 1979 and March 10, 2022. Quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Study-specific estimates were combined using the DerSim...

Background/aims This study aimed to assess the efficacy and sterility of stored platelet-rich plasma (PRP) eye-drops for corneal epithelial wound healing compared with those of autologous serum (AS) eye-drops. Methods At our single institution, PRP and AS eye-drops were prepared using peripheral blood obtained from six healthy volunteers and store...

BACKGROUND Using traditional patient-reported outcomes (PROs), such as paper-based questionnaires, is cumbersome in the era of web-based medical consultation and telemedicine. Electronic PROs may reduce the burden on patients if implemented widely. Considering promising reports of DryEyeRhythm, our in-house mHealth smartphone app for investigating...

Background: Smartphones are being increasingly used for research owing to their multifunctionality and flexibility, and crowdsourced research using smartphone applications (apps) is effective in the early detection and management of chronic diseases. We developed the AllerSearch app to gather real-world data on individual subjective symptoms and l...

Background Hay fever is a highly prevalent, heterogenous, and multifactorial disease. Patients may benefit from longitudinal assessments using mobile health (mHealth) principles. We have previously attempted to establish an effective mHealth platform for patients with hay fever through AllerSearch, our in-house smartphone app that assesses electron...

This study aimed to determine the characteristics and clinical ocular manifestations of acute corneal graft rejection after coronavirus disease 2019 (COVID-19) vaccination. We conducted an online search of the PubMed and EMBASE databases. Data on recipients’ characteristics, corneal transplantation types, interval between vaccination and allograft...

This systematic review aimed to determine the comorbid dry eye (DE) and allergic conjunctivitis (AC) prevalence. We searched PubMed and EMBASE for articles published until 22 March 2022, combining the terms "(dry eye OR keratoconjunctivitis sicca) AND allergic conjunctivitis." Study-specific estimates (DE and AC incidence rates among patients with...

Purpose: Dry eye disease (DED) is a common age-related ocular surface disease. However, it is unknown how aging influences the ocular surface microenvironment. This systematic review aims to investigate how the aging process changes the ocular surface microenvironment and impacts the development of DED. Methods: An article search was performed i...

Dry eye disease (DED) after cataract surgery is associated with various risk factors, while causing a wide range of heterogeneous symptoms including decreased quality of vision. This systematic review and meta-analysis aimed to determine the prevalence and characteristics of DED after cataract surgery. We searched PubMed and EMBASE and included stu...

BACKGROUND Dry eye (DE) and hay fever (HF) show synergistic exacerbation of each other’s pathology through inflammatory pathways. OBJECTIVE This study aimed to investigate the association between DE and HF comorbidity and the related risk factors. METHODS A cross-sectional observational study was conducted using crowdsourced multidimensional data...

Purpose Undiagnosed or inadequately treated dry eye disease (DED) decreases the quality of life. We aimed to investigate the reliability, validity, and feasibility of the DryEyeRhythm smartphone application (app) for the diagnosis assistance of DED. Methods This prospective, cross-sectional, observational, single-center study recruited 82 particip...

We investigated the effects of anti-CD80/86 antibodies in a murine high-risk corneal transplantation rejection model. A mixed lymphocyte reaction (MLR) assay was conducted with anti-CD80/86 antibodies. Inflammatory cytokine levels in the culture supernatant were measured using an enzyme-linked immunosorbent assay. Interferon (IFN)-γ-producing CD4+...

Background Adrenaline is the first-line medication for managing anaphylaxis. A better understanding of prescription trends for adrenaline auto-injectors (AAIs) is important to improving patient care as well as information on health education interventions and medical guidelines. However, it has been difficult to gather comprehensive data in a susta...

Different pathophysiologic mechanisms are involved in the initiation, development, and outcome of dry eye disease (DED). Animal models have proven valuable and efficient in establishing ocular surface microenvironments that mimic humans, thus enabling better understanding of the pathogenesis. Several dry eye animal models, including lacrimal secret...

Introduction: The number of cataract surgeries, the most common ophthalmic surgery, is expected to increase due to ageing populations. Dry eye disease (DED) is a frequent side effect of cataract surgery, contributing to lower postoperative patient satisfaction and suboptimal quality of vision. It is unclear which eye-drops commonly used in these p...

Background The prevalence of hay fever, a multifactorial allergic disease, is increasing. Identifying individual characteristics and associated factors of hay fever is essential for predictive, preventive, personalized, and participatory (P4) medicine. This study aimed to identify individual characteristics and associated factors of hay fever using...

Multidimensional integrative data analysis of digital phenotyping is crucial for elucidating the pathologies of multifactorial and heterogeneous diseases, such as the dry eye (DE). This crowdsourced cross-sectional study explored a novel smartphone-based digital phenotyping strategy to stratify and visualize the heterogenous DE symptoms into distin...

We systematically reviewed published research on dry eye disease and its association with higher order aberrations (HOAs). The purpose of this review was to first determine if an association between tear film metrics and HOAs exists and second to determine if the treatment of dry eyes can improve tear film metrics and HOAs together. A search was co...

Society 5.0, a visionary human-centered societal model, fuels economic development and resolves long-standing social problems. The model establishes a technological foundation and social contract to integrate cyberspace into the physical (real) space fully. The medical infrastructure outlined by the model envisions a healthcare paradigm that revolv...

Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure. Both innate and adaptive immunity play a significant role in allograft tolerance. Therefore, immune cells, cytokines, and signal-transduction pathways are critical therapeutic targets...

Background: Dry eye syndrome (DES) is strictly connected to systemic and topical sex hormones. Breast cancer treatment, the subsequent hormonal therapy, the subsequent hyperandrogenism and the early sudden menopause, may be responsible for ocular surface system failure and its clinical manifestation as dry eye disease. This local dryness is part o...

Purpose: To investigate the effects of ex vivo-induced bone marrow myeloid-derived suppressor cells (BM-MDSCs) on allogeneic immune responses in corneal transplantation. Methods: Bone marrow cells from C57BL/6J (B6) mice were cultured with IL-6 and GM-CSF for four days. The ex vivo induction of the BM-MDSCs was assessed using flow cytometry, ind...

Background Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are attractive immune cells to induce immune tolerance. To explore a strategy for improving the efficacy of MDSC therapies, we examined the impact of adoptive transfer of several types of MDSCs on graft rejection in a murine heart transplantation model. Methods We a...

Corneal neovascularization (CNV) causes higher-order aberrations, corneal edema, ocular inflammation, and corneal transplant rejection, thereby decreasing visual acuity. In this study, we investigated the effects of topical administration of the kappa opioid receptor agonist nalfurafine (TRK-820) on CNV. To induce CNV, intrastromal corneal sutures...

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health problem. Although the respiratory system is the main impaired organ, conjunctivitis is one of its common findings. However, it is not yet understood if SARS-CoV-2 can infect the eye and if the ocular surface can be a potential route of SARS-CoV-2 transmissions. Our...

Purpose: To determine eye drop type and usage frequency and investigate risk factors for no eye drop use in individuals with symptomatic dry eye (DE) in Japan. Study design: Crowdsourced observational study. Methods: This study was conducted using the DryEyeRhythm smartphone application between November 2016 and September 2019. Data collected...

Purpose : This study implemented patient and public involvement (PPl) with the iPhone application for hay fever research, AllerSearch®, by adopting novel and diverse perspectives to establish a robust foundation for interactive research. Material & Methods : PPI members were recruited from November 2019 to January 2020 through a dedicated website....

Corneal neovascularization (CNV) causes higher-order aberrations, corneal edema, ocular inflammation, and corneal transplant rejection, thereby decreasing visual acuity. Here, we investigated the effects of topical administration of the kappa opioid receptor agonist nalfurafine (TRK-820) on CNV. To induce CNV, intrastromal corneal sutures were plac...

Corneal allograft survival is mediated by the variety of immunological reactions and wound healing process. Our aim was to explore the effects of topical administration of ripasudil, a selective Rho-associated coiled-coil protein kinase inhibitor, on corneal allograft survival. Ripasudil was administered to mice thrice a day after allogeneic cornea...

Dry eye disease (DED) is a chronic, multifactorial ocular surface disorder with multiple etiologies that results in tear film instability. Globally, the prevalence of DED is expected to increase with an aging society and daily use of digital devices. Unfortunately, the medical field is currently unprepared to meet the medical needs of patients with...

Various symptoms of the dry eye disease (DED) interfere with the quality of life and reduce work productivity. Therefore, screening, prevention, and treatment of DED are important. We aimed to investigate the potential diagnostic ability of the maximum blink interval (MBI) (the length of time participants could keep their eyes open) with disease-sp...

Purpose: This systematic review aimed to determine currently reported clinical and prodromal ocular symptoms in patients with coronavirus disease 2019 (COVID-19). Methods: An online article search was performed in PubMed and EMBASE. Altogether 15 studies (retrospective, prospective, or case studies) involving 1533 patients with COVID-19, reporti...

Dry eye disease (DED) is among the most common eye diseases and is becoming increasingly prevalent. Its symptoms cause a long-term decline in patients’ health-related quality of life (HRQL). Inconsistencies often occur between the clinical findings and the subjective symptoms of DED. Therefore, a holistic, balanced, and quantitative evaluation of t...

Allergic conjunctivitis affects approximately 15–20% of the global population and can permanently deteriorate one's quality of life (QoL) and work productivity, leading to societal work force costs. Although not fully understood, allergic conjunctivitis is a multifactorial disease with a complex network of environmental, lifestyle, and host contrib...

Background Discontinuation of contact lens use is mainly caused by contact lens–associated dry eye. It is crucial to delineate contact lens–associated dry eye's multifaceted nature to tailor treatment to each patient’s individual needs for future personalized medicine. Objective This paper aims to quantify and stratify individual subjective sympto...

Das Trockene Auge (dry eye syndrome, DES) gehört zu den häufigsten Augenkrankheiten und betrifft Millionen von Menschen weltweit. Die Erkrankung ist jedoch noch nicht vollständig erforscht und bleibt nicht vollumfänglich behandelt. Multidisziplinäre Ansätze, darunter immunmetabolische Untersuchungen, Mikrobiomanalysen und biotechnologische Verfahre...

The aim of this study was to compare patient-reported symptoms of dry eye disease (DED) between the Japanese version of the Ocular Surface Disease Index (J-OSDI) and the Dry Eye-Related Quality-of-Life Score (DEQS). A total of 169 participants were enrolled between September 2017 and May 2018. Patients were administered the J-OSDI and DEQS question...

BACKGROUND Discontinuation of contact lens use is mainly caused by contact lens–associated dry eye. It is crucial to delineate contact lens–associated dry eye's multifaceted nature to tailor treatment to each patient’s individual needs for future personalized medicine. OBJECTIVE This paper aims to quantify and stratify individual subjective sympto...

Corneal grafts interact with their hosts via complex immunobiological processes that sometimes lead to graft failure. Prediction of graft failure is often a tedious task due to the genetic and nongenetic heterogeneity of patients. As in other areas of medicine, a reliable prediction method would impact therapeutic decision-making in corneal transpl...

The purpose of this study was to compare central corneal thickness, thinnest corneal thickness, and the thinnest point of the cornea between Pentacam and anterior segment optical coherence tomography (ASOCT) in patients with dry eye disease (DED). This cross-sectional study included 195 participants between November 2015–June 2017. DED was diagnose...

Purpose Dry eye (DE) disease and depression are increasing in modern times. We investigated the association between DE and depressive symptoms using the iPhone application, DryEyeRhythm. Methods This large-scale crowdsourced observational study was conducted within iPhone users in Japan who downloaded DryEyeRhythm. Participants with a Zung Self-ra...

Importance The incidence of dry eye disease has increased; the potential for crowdsource data to help identify undiagnosed dry eye in symptomatic individuals remains unknown. Objective To assess the characteristics and risk factors associated with diagnosed and undiagnosed symptomatic dry eye using the smartphone app DryEyeRhythm. Design, Setting...