OBJECTIVE: To analyze the clinical manifestations and causative gene variants of the choroideremia patients, and to help the patients bedifferential diagnosed by whole exome sequencing and provide theoretical basis for their genetic counseling. METHODS: Clinical data of 3 families were collected and genomic DNA was extracted respectively from peripheral blood of patients and related subjects. Exome targeted sequencing was used to screen suspicious gene mutations. Sanger sequencing and quantitative PCR were used to verify the candidate mutations and investigate the mutation carrying status of other members of the family. The candidate mutations were searched through HGMD and PubMed databases for the pathogenicity reports, and the pathogenicity of candidate mutations was judged according to a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. RESULTS: The proband of family 1 is c.1584_1587del (p.Val529Hisfs*6) variant hemizygote, whose daughter carries c.1584_1587del (p.Val529Hisfs*6) heterozygous variation. The proband of family 2 is a hemizygote with deletion of exons 10 to 15 (E10-15del), and her mother and sister carry the E10-15del heterozygous variation. In family 3, the proband is c.544delT (p.Cys182Valfs*14) variant hemizygote, and his mother is c.544delT (p.Cys182Valfs*14) heterozygote, but the father do not detect this variant. All the 3 families were detected pathogenic gene variations of CHM, two of which were known pathogenic variation and one of which was novel CHM gene c.544delT (p.C182Vfs*14) in this study. The c.544delT frameshift mutation of CHM gene can lead to the premature termination of the product protein translation and nonfunctioning protein. It is a pathogenic mutation according to ACMG guidelines. CONCLUSION The findings of this study expand the gene variation spectrum of choroideremia.
Choroideremia/genetics* ; Female ; Heterozygote ; Humans ; Mutation ; Pedigree ; Whole Exome Sequencing

Moyamoya disease (MMD) is a progressive cerebrovascular disease with unknown etiology, characterized by bilateral stenoocclusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network formation at the base of the brain. MMD has an intrinsic nature to convert the vascular supply for the brain from internal carotid (IC) system to the external carotid (EC) system, as indicated by Suzuki’s angiographic staging. Insufficiency of this ‘IC-EC conversion system’ could result not only in cerebral ischemia, but also in intracranial hemorrhage from inadequate collateral anastomosis, both of which represent the clinical manifestation of MMD. Surgical revascularization prevents cerebral ischemic attack by improving cerebral blood flow, and recent evidence further suggests that extracranial-intracranial bypass could powerfully reduce the risk of re-bleeding in MMD patients with posterior hemorrhage, who were known to have extremely high re-bleeding risk. Although the exact mechanism underlying the hemorrhagic presentation in MMD is undetermined, most recent angiographic analysis revealed the characteristic angio-architecture related to high re-bleeding risk, such as the extension and dilatation of choroidal collaterals and posterior cerebral artery involvement. We sought to update the current management strategy for hemorrhagic MMD, including the outcome of surgical revascularization for hemorrhagic MMD in our institute. Further investigations will clarify the optimal surgical strategy to prevent hemorrhagic manifestation in patients with MMD.
Angiography ; Brain ; Brain Ischemia ; Carotid Artery, Internal ; Cerebrovascular Circulation ; Cerebrovascular Disorders ; Choroid ; Dilatation ; Hemorrhage ; Humans ; Intracranial Hemorrhages ; Moyamoya Disease ; Posterior Cerebral Artery

PURPOSE: To investigate the short-term efficacy and safety of ranibizumab in the routine clinical setting in patients with neovascular age-related macular degeneration and to analyze the associated factors for visual outcome. METHODS: This was a post-hoc analysis of a ranibizumab regulatory post-marketing surveillance study in which 4,136 patients were enrolled and followed for 12 weeks. Change in best-corrected visual acuity (BCVA), size of choroidal neovascularization, and the presence of hemorrhage and exudate were analyzed and the association between BCVA change and baseline characteristics were investigated. Data on ocular and systemic adverse events were collected. RESULTS: Mean BCVA improved significantly and mean BCVA change was the logarithm of the minimal angle of resolution 0.13 ± 0.01 (p < 0.001). A lower baseline BCVA and younger age were significant predictive factors for visual improvement or maintenance (≥0 lines). For greater visual acuity gain (≥3 lines), no treatment history, lower baseline BCVA, younger age, and classic-type choroidal neovascularization were significant predictive factors. No new safety signals were found. CONCLUSIONS: In this study, conducted in real-world clinical practice with a large number of neovascular age-related macular degeneration patients, visual and anatomical outcomes improved significantly after three monthly ranibizumab treatments. Treatment-naive patients had a higher chance of greater visual gain (≥3 lines) than non-naive patients.
Choroidal Neovascularization ; Exudates and Transudates ; Hemorrhage ; Humans ; Macular Degeneration ; Ranibizumab ; Visual Acuity

PURPOSE: To evaluate the influence of axial length on the recurrence of wet age-related macular degeneration (AMD) after anti-vascular endothelial growth factor therapy. METHODS: A retrospective review of the medical records for 45 eyes of 45 patients, who were diagnosed with neovascular AMD and treated with three ranibizumab injections per month, was performed. Axial length was compared between eyes with (recurrence group) and without (no recurrence group) recurrence of fluid during a 12-month follow-up period. In eyes with recurrence, the association between axial length and the time between the third injection and the first recurrence was also evaluated. RESULTS: The axial length was measured at a mean of 20.6 ± 10.1 months after the diagnosis of neovascular AMD. The mean axial length at that time was 23.33 ± 0.90 mm. The mean axial length was 23.29 ± 0.96 mm in the recurrence group (n = 30) and 23.40 ± 0.79 mm in the no-recurrence group (n = 15). There was no difference in the axial length between the two groups (p = 0.709). In the recurrence group, the period between the third injection and the first recurrence was not associated with axial length (p =0.582). CONCLUSIONS: There was no significant difference in axial length between eyes with and without recurrence after initial treatment for wet AMD. In addition, the time to first recurrence was not significantly associated with axial length. Because the present study was retrospective and the sample size was small, further prospective studies with a better design are needed to more accurately assess the influence of axial length.
Choroidal Neovascularization ; Diagnosis ; Endothelial Growth Factors ; Follow-Up Studies ; Humans ; Macular Degeneration ; Medical Records ; Prospective Studies ; Ranibizumab ; Recurrence ; Retrospective Studies ; Sample Size

Choroid plexus tumors are uncommon brain tumors that primarily occur in children. Most of these tumors originate from the intraventricular area, and the most common clinicalpresentation is increased intracranial pressure. Dissemination through the cerebrospinal fluid space is the inevitable natural course of the disease. Here, we present 2 rare cases of adult choroid plexus carcinoma (CPC), each with distinct clinical presentation and progression. The first case was a 40-year-old male who presented with multiple intraventricular masses. After surgical biopsy, radiation and intrathecal chemotherapy failed to elicit any response. The patient progressed with spinal cord dissemination and expired 1 year later. The second case presented with visual disturbance, and brain MRI revealed a large ovoid juxtaventricular mass with peritumoral edema. This 49-year-old female patient underwent craniotomy for what was thought to be a high-grade glioma; however, the mass was connected to the choroid plexus at the operative field. Her pathology specimen was diagnosed as CPC, and adjuvant systemic chemotherapy was administered. She has now been free of recurrence for 10 months. The description of the presentation and progression of these rare adult-onset CPC provides insight for the diagnosis and treatment of other rare instances of choroid plexus tumors.
Adult ; Biopsy ; Brain ; Brain Neoplasms ; Cerebrospinal Fluid ; Child ; Choroid Plexus Neoplasms ; Choroid Plexus ; Choroid ; Craniotomy ; Diagnosis ; Drug Therapy ; Edema ; Female ; Fourth Ventricle ; Glioma ; Humans ; Intracranial Pressure ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pathology ; Recurrence ; Spinal Cord

Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, β-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.
Actins ; Animals ; Capillary Permeability ; Choroid ; Choroidal Neovascularization ; Claudin-5 ; Endothelial Cells ; Endothelium ; Humans ; Macular Degeneration ; Mice ; Nitric Oxide Synthase Type III ; Permeability ; Phosphorylation ; Receptors, Vascular Endothelial Growth Factor ; Retinaldehyde ; Vascular Endothelial Growth Factor A

A 35-year-old female visited emergency department for a sudden onset of headache with vomiting after management for abortion at local department. Neurological examination revealed drowsy mentality without focal neurological deficits. CT showed 3.2×3.4 cm hyperdense intraventricular mass with intraventricular hemorrhage. The intraventricular hemorrhage was found in lateral, 3rd, and 4th ventricles. MRI showed well enhancing intraventricular mass abutting choroid plexus in the trigone of the right lateral ventricle. CT angiography showed tortuous prominent arteries from choroidal artery in tumor. Her neurological status deteriorated to stupor and contralateral hemiparesis during planned preoperative workup. Urgent transtemporal and transcortical approach with decompressive craniectomy for removal of intraventricular meningioma with hemorrhage was done. Grossly total removal of ventricular mass was achieved. Pathological finding was meningotheliomatous meningioma of World Health Organization (WHO) grade I. The patient recovered to alert mentality and no motor deficit after intensive care for increased intracranial pressure. However, visual field defect was developed due to posterior cerebral artery territory infarction. The visual deficit did not resolve during follow up period. Lateral ventricular meningioma with spontaneous intraventricular hemorrhage in pregnant woman is very uncommon. We report a surgical case of lateral ventricular meningioma with rapid neurological deterioration for intraventricular hemorrhage.
Adult ; Angiography ; Arteries ; Choroid ; Choroid Plexus ; Critical Care ; Decompressive Craniectomy ; Emergency Service, Hospital ; Female ; Follow-Up Studies ; Fourth Ventricle ; Headache ; Hemorrhage ; Humans ; Infarction ; Intracranial Pressure ; Lateral Ventricles ; Magnetic Resonance Imaging ; Meningioma ; Neurologic Examination ; Paresis ; Posterior Cerebral Artery ; Pregnancy ; Pregnant Women ; Stupor ; Visual Fields ; Vomiting ; World Health Organization

BACKGROUND: Because of genetically and phenotypically heterogenous features, identification of causative genes for inherited retinal diseases (IRD) is essential for diagnosis and treatment in coming gene therapy era. To date, there are no large-scale data of the genes responsible for IRD in Korea. The aim of this study was to identify the distribution of genetic defects in IRD patients in Korea. METHODS: Medical records and DNA samples from 86 clinically diagnosed IRD patients were consecutively collected between July 2011 and May 2015. We applied the next-generation sequencing strategy (gene panel) for screening 204 known pathogenic genes associated with IRD. RESULTS: Molecular diagnoses were made in 38/86 (44.2%) IRD patients: 18/44 (40.9%) retinitis pigmentosa (RP), 8/22 (36.4%) cone dystrophy, 6/7 (85.7%) Stargardt disease, 1/1 (100%) Best disease, 1/1 (100%) Bardet-Biedl syndrome, 1/1 (100%) congenital stationary night blindness, 1/1 (100%) choroideremia, and 2/8 (25%) other macular dystrophies. ABCA4 was the most common causative gene associated with IRD and was responsible for causing Stargardt disease (n = 6), RP (n = 1), and cone dystrophy (n = 1). In particular, mutations in EYS were found in 4 of 14 autosomal recessive RP (29%). All cases of Stargardt disease had a mutation in the ABCA4 gene with an autosomal recessive trait. CONCLUSION: This study provided the distribution of genetic mutations responsible for causing IRD in the Korean patients. This data will serve as a reference for future genetic screening and treatment for Korean IRD patients.
Bardet-Biedl Syndrome ; Choroideremia ; Diagnosis ; DNA ; Genetic Testing ; Genetic Therapy ; Humans ; Korea ; Macular Degeneration ; Mass Screening ; Medical Records ; Night Blindness ; Retinal Diseases ; Retinaldehyde ; Retinitis Pigmentosa ; Vitelliform Macular Dystrophy

PURPOSE: To evaluate the long-term treatment outcomes of bevacizumab therapy in patients with myopic choroidal neovascularization (CNV). METHODS: A retrospective review was performed of medical records regarding 43 eyes with myopic CNV that were treated with intravitreal bevacizumab injection. Visual acuity at diagnosis was compared with that measured at the final follow-up; the incidence and timing of re-activation were evaluated. In addition, factors associated with final follow-up were analyzed. RESULTS: Mean patient age was 39.3 ± 12.9 years and mean spherical equivalent (SE) was −11.9 ± 4.4 diopters. Patients were followed-up at a mean of 42.1 ± 17.0 months. Re-activation of the lesion was noted in 17 eyes (39.5%). The mean time to first re-activation was 19.5 ± 15.4 months from the time that resolution of subretinal fluid/retinal fluid was confirmed after initial treatment. The mean visual acuity (the logarithm of the minimal angle of resolution) was 0.40 ± 0.25 at diagnosis and 0.26 ± 0.31 at the final follow-up. Visual acuity at the final follow-up was significantly improved when compared with the baseline value (p = 0.005). Patient age (p < 0.001), SE (p = 0.003), and visual acuity at diagnosis (p < 0.001) were significantly associated with visual acuity at the final follow-up. CONCLUSIONS: Bevacizumab therapy was a useful method for long-term treatment of myopic CNV. The observation of relatively late re-activation after the initial treatment suggests a need for continuous long-term follow-up.
Bevacizumab ; Choroid ; Choroidal Neovascularization ; Diagnosis ; Follow-Up Studies ; Humans ; Incidence ; Medical Records ; Methods ; Myopia ; Retrospective Studies ; Visual Acuity

PURPOSE: To evaluate the clinical presentations of focal choroidal excavation and to report long-term outcomes of cases without retinal disorders at the initial presentation. METHODS: A retrospective review of medical records was performed for patients diagnosed with focal choroidal excavation. Concomitant retinal disorders at the initial presentation were identified. In cases without retinal disorders, the development of retinal disorders during follow-up was also evaluated. RESULTS: Forty-five eyes in 45 patients were examined in this study. Focal choroidal excavation was accompanied with retinal disorders in 16 eyes (35.6%). In the remaining 29 eyes, only focal choroidal excavation was noted without any accompanying retinal disorders. The accompanying retinal disorders included choroidal neovascularization (n = 8), central serous chorioretinopathy (n = 4), epiretinal membrane (n = 1), macular hole (n = 1), branch retinal vein occlusion (n = 1), and uveitis (n = 1). Of the 29 eyes without retinal disorders, 22 were followed up for a mean period of 33.5 ± 18.2 months. Consequently, choroidal neovascularization was found to have developed in one eye at 59 months, and subretinal fluid had developed in two eyes at 17 and 28 months, respectively. CONCLUSIONS: Focal choroidal excavation was accompanied by retinal disorders in 35.6% of the included patients. In patients without retinal disorders, the development of a retinal disorder was noted in some eyes, suggesting the need for long-term regular follow-up in patients diagnosed with focal choroidal excavation.
Central Serous Chorioretinopathy ; Choroid ; Choroidal Neovascularization ; Epiretinal Membrane ; Follow-Up Studies ; Humans ; Medical Records ; Retinal Perforations ; Retinal Vein Occlusion ; Retinaldehyde ; Retrospective Studies ; Subretinal Fluid ; Uveitis