Hiroto Ishikawa

• M.D., Ph.D.
• Director at Mirai Eye and Skin Clinic

This retrospective observational multicentre cohort study compared the rate of postoperative cystoid macular oedema (CME) between two intraocular lens (IOL) scleral fixation (SFIOL) techniques: a flanged IOL fixation technique (Yamane technique) and a suture IOL transscleral fixation technique (conventional technique). The study included 207 eyes w...

To objectively assess visual function in Leber’s Hereditary Optic Neuropathy (LHON) patients; this study evaluated pre- and post-idebenone treatment changes in primary visual cortical (V1) responses using functional magnetic resonance imaging (fMRI), given the challenges in subjective testing due to central retinal ganglion cell damage. A descripti...

We investigated the impact of drainage retinotomy on the outcome of pars plana vitrectomy for repair of rhegmatogenous retinal detachment (RRD). This study was a retrospective observational multicenter study. All patients were registered with the Japan-Retinal Detachment Registry. We analyzed 1887 eyes with RRD that had undergone vitrectomy and wer...

PurposeTo investigate age-specific prevalence of disease subtypes and baseline best-corrected visual acuity (BCVA) in Japanese patients with treatment-naïve neovascular age-related macular degeneration (nAMD).Study designRetrospective multicenter case series.Methods We reviewed the records of patients with treatment-naïve nAMD who underwent initial...

Purpose We investigated potential risk factors for visual prognosis in Japanese patients with exogenous endophthalmitis. Methods In this retrospective observational multicenter cohort study, risk factors for legal blindness at 12 weeks after treatment initiation were evaluated based on patient characteristics, initial BCVA, causative events, patho...

Choroidal melanoma is the leading primary intraocular tumor with potentially fatal outcomes in adults. The coexistence of choroidal melanoma and a macular hole is extremely rare, and treatment strategies and information on the prognosis of associated complications are currently lacking. We report the first case of choroidal melanoma complicated wit...

Purpose We investigated potential predictive factors for visual prognosis in Japanese patients with endogenous endophthalmitis. Design Retrospective observational multicenter cohort study. Methods We examined the characteristics of 77 Japanese patients with endogenous endophthalmitis and performed statistical analyses of these real-world data. Th...

Background Leber hereditary optic neuropathy (LHON) is an acute or subacute optic neuropathy that mainly affects young males. The first nationwide epidemiological survey of LHON was conducted in 2014 in Japan, and LHON was officially designated as a rare intractable disease by the Japanese government in 2015. We conducted a second survey of the ann...

In the original publication [...]

Aims/introduction: In older patients, the management of diabetic macular edema (DME) would be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME. Materials and methods: This is a real-world clinical study including 1552 patients with treatment-naïv...

The aim of this study was to determine the prevalence and progression of diabetic retinopathy (DR) with hyperglycemic disorders during pregnancy (HDPs) in Japan between 2013 and 2018 using two cohorts. The patients with HDPs were classified as those with pre-existing DM (pexD), gestational DM (GDM), and overt DM (ODM). Cohort 1 was obtained from th...

Background: Conventional trabeculotomy (CT) is performed in an ab-externo manner with at most 120 degrees of incision area of Schlemm's canal (SC). Recently, gonioscopy-assisted transluminal trabeculotomy (GATT), which makes possible a 360-degree incision area of SC in an ab-interno manner, is introduced. The purpose of this study was to compare s...

Purpose: To determine the baseline characteristics of patients with central retinal vein occlusion (CRVO) that were significantly associated with the best-corrected visual acuity (BCVA) at the initial examination. Methods: This was a retrospective multicenter study using the medical records registered in 17 ophthalmological institutions in Japan...

This retrospective multicenter study was designed to determine the baseline characteristics of patients in Japan with central retinal vein occlusion (CRVO) that were significantly associated with best-corrected visual acuity (BCVA) at the initial examination. The patients’ baseline factors that were significantly associated with the BCVA at the ini...

Purpose We investigated 10-year changes in baseline best-corrected visual acuity (BCVA), as well as functional and anatomical changes at 1 and 2 years after initial treatment, in eyes with treatment-naïve neovascular age-related macular degeneration (nAMD). Methods This retrospective, multicenter, case series reviewed patients with treatment-naïve...

Purpose To investigate the effects of cataract surgery in Japanese patients with neovascular age-related macular degeneration (nAMD). Methods The primary endpoint in this prospective, observational study was patient satisfaction at 6 months after cataract surgery in patients with nAMD. Secondary endpoints comprised changes in best-corrected visual...

Bacterial endophthalmitis is an intraocular infection that causes rapid vison loss. Pathogens can infect the intraocular space directly (exogenous endophthalmitis (ExE)) or indirectly (endogenous endophthalmitis (EnE)). To identify predictive factors for the visual prognosis of Japanese patients with bacterial endophthalmitis, we retrospectively ex...

Purpose: Leber’s hereditary optic neuropathy (LHON) is a mitochondrial neuropathy that causes acute vision loss. Idebenone, a short-chain ubiquinone analog that preserves mitochondrial function is thought to suppress disease progression in early-onset LHON patients. We investigated the effects of idebenone in Japanese LHON patients. Study design: P...

Purpose: Leber’s hereditary optic neuropathy (LHON) is a mitochondrial neuropathy that causes acute vision loss. Idebenone, a short-chain ubiquinone analog that preserves mitochondrial function is thought to suppress disease progression in early-onset LHON patients. We investigated the effects of idebenone in Japanese LHON patients. Study design: P...

Ten-year changes in visual acuity at baseline and at 2 years after treatment in a Japanese population with age-related macular degeneration J-CREST (Japan Clinical Retinal Study Team) Study Group, Japan 1 2 3 Your article is protected by copyright and all rights are held exclusively by Springer-Verlag GmbH Germany, part of Springer Nature. This e-o...

This is the first report to mention the association between visual outcome and mechanism of injury in patients with an OGI with NLP at first examination.

Purpose: The sunset glow fundus (SGF) appearance in Vogt-Koyanagi-Harada (VKH) disease was evaluated by means of adaptive binarization of patients' fundus photographs. Methods: Twenty-nine Japanese patients with acute VKH were enrolled in this study. We evaluated one eye of each patient, and thereby divided the patients into two groups; SGF+ and...

This study investigated postoperative changes in metamorphopsia and aniseikonia in eyes that underwent vitrectomy for epiretinal membrane (ERM), macular hole (MH), or rhegmatogenous retinal detachment (RRD). In total, 166 eyes were included from 166 patients with ERM, MH, or RRD who underwent primary vitrectomy. Metamorphopsia and aniseikonia were...

Purpose To report the case of a Japanese girl with a perforating ocular injury caused by a cat scratch, resulting in Pasteurella multocida-induced endophthalmitis. Observations A 10-year-old girl presented with a red eye, eye pain, and blurred vision in her right eye immediately after receiving a cat scratch. We performed lensectomy and vitrectomy...

Background/aims To investigate the yearly change of real-world outcomes for best corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve diabetic macular oedema (DMO). Methods Retrospective analysis of aggregated, longitudinal medical records obtained from 27 retina specialised institutions in Japan from Survey of Tre...

Purpose: The Glaucoma Module Premium Edition (GMPE) software for the SPECTRALIS® OCT is able to automatically track the anatomical centers of both the fovea and the optic disc. We investigated the efficacy of the OCT in measuring the ocular torsion angle before and after strabismus surgery. Methods: Between June 2017 and December 2018, 40 patients...

Purpose: To investigate the clinical characteristics and visual outcomes of patients with work-related open globe injuries (OGIs) and compare them with patients with non-work-related OGIs. Design: Retrospective, observational, multicentre, case-control study. Methods: A total of 374 patients with work-related OGIs and 170 patients with non-wor...

Purpose To investigate the characteristics of tear abnormalities with benign essential blepharospasm (BEB) and the effect of botulinum toxin type A (BTX-A) treatment. Study Design Prospective and clinical study. Methods Forty eyes of 40 patients (12 men and 28 women, ages 63.5 ±12.9) with BEB and tear abnormalities were enrolled. Results The ave...

Purpose To evaluate real-world evidence for intraocular pressure (IOP) elevation after subtenon triamcinolone acetonide injection (STTA) in 1252 Japanese patients (1406 eyes) in the Japan Clinical REtina STudy group (J-CREST). Methods This was a multicentre retrospective study of the medical records of 1252 patients (676 men (758 eyes); mean age:...

Background/Aims To investigate real-world outcomes for best-corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve, centr-involving diabetic macular oedema (DME). Methods Retrospective analysis of longitudinal medical records obtained from 27 institutions specialising in retinal diseases in Japan. A total of 2049 eye...

Purpose: Intraocular lens (IOL) fixation using a sutureless 27-gauge needle intrascleral IOL implantation technique requires six surgical wounds. We developed a modified technique using two 27-gauge trocars for vitrectomy and indwelling flanged IOL haptics to reduce the number of surgical wounds. Setting: Department of Ophthalmology, Hyogo Colle...

Demyelination and remyelination play pivotal roles in the pathological process of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a well-established animal model of MS. Although increasing evidence shows that various stimuli can promote the activation/induction of endogenous neural stem/progenitor cells (NSPCs) in the c...

Rodents display “empathy” defined as perceived physical pain or psychological stress by cagemates when co-experiencing socially distinct traumatic events. The present study tested the hypothesis that empathy occurs in adult rats subjected to an experimental neurological disorder, by allowing co-experience of stroke with cagemates. Psychological str...

Purpose: To compare United States and international drug pricing for commonly prescribed intravitreal and topical ophthalmic medications. Design: Cross-sectional observational study. Methods: For 25 commonly used ophthalmic medications (3 intravitreal, 22 topical), we obtained 2017 third quarter United States average wholesale price (AWP), dru...

We investigated the rates of the use of steroids in Japanese central serous chorioretinopathy (CSC) cases and differences in the characteristics of CSC with and without steroids. A total of 538 eyes of 477 patients diagnosed with CSC, with 3 months or more of follow-up between April 2013 and June 2017 at 8 institutions. Patients with CSC with more...

Original data used in this article are included. (PDF)

We aimed to investigate the possible causes of metamorphopsia for rhegmatogenous retinal detachment (RRD) based on findings of enface optical coherence tomography (OCT). The study was a retrospective, consecutive case series of 33 eyes with macula-off RRD. Metamorphopsia was measured by M-CHARTS and enface OCT images covering a macular area of 6 ×...

Purpose To describe the epidemiology and clinical outcomes of open globe injuries (OGIs) in Japan over 10 years, and examine preoperative factors influencing the visual prognosis after surgery. Study Design Retrospective, observational, multicenter case-series study. Methods Patients’ data were entered into a computerized database for review and...

Objective To determine the current clinical preferences of anti‐vascular endothelial growth factor (VEGF) treatment protocols for diabetic macular edema (DME) in Japan. Research Design and Methods This was a descriptive cross‐sectional study. Answers to a questionnaire consisting of 16 questions were obtained from 176 of 278 (63.3%) surveyed ophth...

Purpose: To investigate the clinical characteristics and visual outcomes in patients with fall-related open globe injuries and to evaluate differences between fall-related and non-fall-related open globe injuries in Japan. Methods: A retrospective review of patients with open globe injury who presented to Japan-Clinical Research of Study (J-CRES...

Purpose To elucidate the factors that affect the visibility of polypoidal lesions on OCT angiography (OCTA) based on indocyanine green angiography (ICGA) findings in eyes with polypoidal choroidal vasculopathy (PCV). Design Retrospective, consecutive case series. Participants Thirty-one eyes of 31 patients with PCV diagnosed on ICGA. Methods We...

In a transgenic mouse line hK14mIL33tg, with the expression of interleukin-33 (IL-33) driven by a keratin 14 promoter, keratoconjunctivitis developed spontaneously between 18 and 22 weeks of age under specific-pathogen-free conditions. These mice showed blepharitis and corneal impairments, and the histology revealed epithelial thickening in the con...

Purpose: To evaluate the clinical characteristics and visual outcomes of patients with traffic accident-related open globe injuries, and to examine preoperative factors influencing the visual prognosis after pars plana vitrectomy, as compared with common open globe injuries. Methods: Patients with open globe injuries, who underwent pars plana vi...

Purpose: To report 2 cases of corneal disorder after cancer treatment with nab paclitaxel. Methods: Retrospective review of 2 cases. Case presentation: Case 1 was a 55-year-old female who presented with blurred vision. She underwent cancer treatment in the form of combination therapy with nab-paclitaxel, trastuzumab and pertuzumab for breast cancer...

Objective: We describe a technique for the in toto extraction of spontaneous conjunctival cysts without incision under slit-lamp microscopic view. Design: Interventional case series. Participants: Eleven eyes of 11 patients. Methods: This was a multicentre study. Selection criterion was symptomatic conjunctival spontaneous cysts. Topical ana...

Background/aimsTo evaluate the effects of botulinum toxin type A (BTX-A) treatment in patients with benign essential blepharospasm (BEB) by monitoring the ocular surface and ocular higher-order aberrations (HOAs) before and after treatment. Methods The present study reports a prospective case series of 38 patients (76 eyes, 11 men and 27 women; mea...

Purpose Periodic alternating nystagmus (PAN) is a spontaneous horizontal nystagmus observed in disorders of the central nervous system. Patients with congenital PAN complain of oscillating vision at high rates. Medication is the first-choice treatment for PAN; however, clinicians still seek better therapy. The aim of this study was to evaluate outc...

Stem cells exert therapeutic effects for central nervous system (CNS) trauma. Accumulating evidence reveals that stem cell-based therapies for CNS trauma can be achieved via transplantation of exogenous stem cells or stimulation of endogenous stem cells from the neurogenic niches of subventricular zone and subgranular zone, or recruited from the bo...

Modified mesenchymal stromal cells (MSCs) display a unique mechanism of action during the repair phase of traumatic brain injury by exhibiting the ability to build a biobridge between the neurogenic niche and the site of injury. Immunohistochemistry and laser capture assay have visualized this biobridge in the area between the neurogenic subventric...

Traumatic brain injury (TBI) is associated with neuro-inflammation, debilitating sensory-motor deficits, and learning and memory impairments. Cell-based therapies are currently being investigated in treating neurotrauma due to their ability to secrete neurotrophic factors and anti-inflammatory cytokines that can regulate the hostile milieu associat...

Traumatic brain injury (TBI) survivors exhibit motor and cognitive symptoms from the primary injury that can become aggravated over time because of secondary cell death. In the present in vivo study, we examined the beneficial effects of human adipose-derived stem cells (hADSCs) in a controlled cortical impact model of mild TBI using young (6 month...

Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cel...

Refractive change can be caused by systemic illnesses such as Lupus erythematosus, thyroid deficiency, and diabetes mellitus. However, refractive change after pituitary tumor removal has so far not been reported. A 62-year-old woman presented with blurred near vision 10 days after trans-sphenoidal surgery (TSS) for a pituitary tumor. Around the sam...

Despite the reported functional recovery in transplanted stroke models and patients, the mechanism of action underlying stem cell therapy remains not well understood. Here, we examined the role of stem cell-mediated vascular repair in stroke. Adult rats were exposed to transient occlusion of the middle cerebral artery and 3 hours later randomly ste...

Ischemic stroke is a leading cause of mortality and morbidity in the world and may be associated with cardiac myocyte vulnerability. However, it remains uncertain how an ischemic brain contributes to cardiac alternations. Here, we used experimental stroke models to reveal the pathological effects of the ischemic brain on the heart. For the in vitro...

Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zon...

The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neuro...

Stem cell-based therapies for stroke have expanded substantially over the last decade. The diversity of embryonic and adult tissue sources provides researchers with the ability to harvest an ample supply of stem cells. However, the optimal conditions of stem cell use are still being determined. Along this line of the need for optimization studies,...

Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB) competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB inte...

Stem cells exert therapeutic effects against ischemic stroke via transplantation of exogenous stem cells or stimulation of endogenous stem cells within the neurogenic niches of subventricular zone and subgranular zone, or recruited from the bone marrow through peripheral circulation. In this paper, we review the different sources of stem cells that...

Stroke remains a significant unmet condition in the USA and throughout the world. To date, only approximately 3% of the population suffering an ischemic stroke benefit from the thrombolytic drug tissue plasminogen activator, largely due to the drug's narrow therapeutic window. The last decade has witnessed extensive laboratory studies suggesting th...

Our understanding of biological mechanisms and treatment options for traumatic brain injury (TBI) is limited. Here, we employed quantitative real-time PCR (QRT-PCR) and immunohistochemical analyses to determine the dynamic expression of cell proliferation and apoptosis in an effort to provide insights into the therapeutic window for developing rege...

Cell therapy has been established as an important field of research with considerable progress in the last years. At the same time, the progressive aging of the population has highlighted the importance of discovering therapeutic alternatives for diseases of high incidence and disability, such as stroke. Menstrual blood is a recently discovered sou...

In considering ways that physics has helped advance biology and medicine, what typically comes to mind are the various tools used by researchers and clinicians. We think of the optics put to work in microscopes, endoscopes, and lasers; the advanced diagnostics permitted through magnetic, x-ray, and ultrasound imaging; and even the nanotools, that a...

We examined the availability of human bone marrow stromal cells (MSCs) as a source of transplantation therapy in nerve injury. Human MSCs were subjected to a series of treatments with a reducing agent, retinoic acid and a combination of trophic factors. Morphologically and immunocytochemically, such treated cells differentiated into Schwann cell ch...

We investigated if bone marrow stromal cells (BMSCs) transplanted into the vitreous body of a glaucoma model eye could be integrated in the host retina and also whether they could rescue the retinal ganglion cells (RGCs) from death induced by the elevated intraocular pressure. Glaucoma was induced in the right eye of adult Wistar rats by ligating t...

Cell transplantation is a promising strategy for the treatment of neurodegenerative and muscle degenerative diseases. Many kinds of cells, including embryonic stem cells and tissue stem cells, have been considered as candidates for transplantation therapy. Bone marrow stromal cells (MSCs) have great potential as therapeutic agents since they are ea...

Bone marrow stromal cells (MSCs) have great potential as therapeutic agents. We report a method for inducing skeletal muscle lineage cells from human and rat general adherent MSCs with an efficiency of 89%. Induced cells differentiated into muscle fibers upon transplantation into degenerated muscles of rats and mdx-nude mice. The induced population...

We developed an in vivo electroporation method to introduce foreign genes into retinal ganglion cells (RGCs). After the intravitreous injection of the plasmid gene (20 mug), five electric pulses (6 V/cm, 100 ms duration) were each delivered twice with 5 min interval to the rat eye using a contact lens-type electrode (cathodal) attached to the corne...

Bone marrow stromal cells (MSCs) have the capability under specific conditions of differentiating into various cell types such as osteocytes, chondrocytes, and adipocytes. Here we demonstrate a highly efficient and specific induction of cells with neuronal characteristics, without glial differentiation, from both rat and human MSCs using gene trans...

In the present study, we studied drug effects of Ca(2+) antagonists on the retinal degeneration of rd mouse to evaluate their efficacy. Several kinds of Ca(2+) antagonists, diltiazem, nicardipine, nilvadipine or nifedipine were administrated intraperitoneally and thereafter retinal morphology and functions were analyzed. In addition, we performed D...