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

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

PURPOSE: To report a case of choroidal neovascularization in a Best disease patient treated with intravitreal bevacizumab injection and followed up with optical coherence tomography angiography (OCTA). CASE SUMMARY: A 20-year-old female visited our clinic with decreased visual acuity of the left eye for 6 months. On optical coherence tomography (OCT), subretinal fluid and hyperreflective subretinal clumps were observed in the macula of the right eye. Subretinal hemorrhage and subretinal fluid were observed in the left eye. Choroidal neovascularization in the left eye was observed using OCTA, fluorescein angiography, and indocyanine green angiography. A full-field electroretinogram was normal in both eyes, but an electrooculogram revealed that the Arden ratio was 1.564 in the right eye and 1.081 in the left eye. Intravitreal bevacizumab injection was performed in the left eye. At 6 months after the intravitreal injection, the best-corrected visual acuity of the left eye had recovered to 20/20. OCT revealed that subretinal fluid reduced and choroidal neovascularization was stable. After 12 months, visual acuity of the left eye was maintained at 20/20, but OCTA revealed that choroidal neovascularization had increased. CONCLUSIONS: Choroidal neovascularization associated with Best disease can improve by intravitreal bevacizumab injection, and the changes in choroidal neovascularization can be followed using OCTA.
Angiography ; Bevacizumab ; Choroid ; Choroidal Neovascularization ; Electrooculography ; Female ; Fluorescein Angiography ; Hemorrhage ; Humans ; Indocyanine Green ; Intravitreal Injections ; Subretinal Fluid ; Tomography, Optical Coherence ; Visual Acuity ; Vitelliform Macular Dystrophy ; Young Adult

PURPOSE: To report a case of fulminant toxoplasmic chorioretinitis following intravitreal dexamethasone implantation monotherapy in a stabilized toxoplasmic chorioretinitis patient with initial treatment. CASE SUMMARY: A 60-year-old healthy female presented with decreased visual acuity in the left eye. On fundus examination, focal chorioretinitis and yellow-white infiltration were observed. Laboratory work-up, including blood chemistry, complete blood count, and serum serology, was negative; however, toxoplasmic chorioretinitis could not be ruled out. The primary lesion improved with antibiotics and prednisolone treatment. However, the patient did not come in for her follow-up visit, as she had already received an intravitreal dexamethasone implant for recurrent vitreous inflammation elsewhere. On her return, she presented with necrotic retinitis with extensive infiltration. She underwent diagnostic vitrectomy and implant removal. A diagnosis of toxoplasma antigen was confirmed by polymerase chain reaction analysis; the lesions stabilized after anti-toxoplasmic therapy. CONCLUSIONS: Intravitreal dexamethasone implant monotherapy with stabilized toxoplasmic chorioretinitis without systemic antibiotics can lead to fulminant toxoplasmic chorioretinitis and should be used with caution.
Anti-Bacterial Agents ; Blood Cell Count ; Chemistry ; Chorioretinitis ; Dexamethasone ; Diagnosis ; Female ; Follow-Up Studies ; Humans ; Inflammation ; Intravitreal Injections ; Middle Aged ; Polymerase Chain Reaction ; Prednisolone ; Retinitis ; Toxoplasma ; Toxoplasmosis ; Visual Acuity ; Vitrectomy

PURPOSE: To report a case of extensive choroidal effusion following the Valsalva maneuver under consecutive general anesthesia. CASE SUMMARY: A 41-year-old man who underwent panretinal photocoagulation with proliferative diabetic retinopathy had pars plana vitrectomy and endolaser photocoagulation under general anesthesia due to vitreous hemorrhage. Urology cooperated as the patient had hematuria; the day after the operation, he was transferred to the urology department. Two days after vitrectomy, the patient had an urgent transurethral bladder tumor resection under general anesthesia with suspicion of bladder tumor. At 6 days postoperatively, extensive choroidal effusion was observed from 8 to 10 o'clock on fundus examination and ultrasonography. On day 23 after urological surgery, the choroidal effusion had disappeared without treatment. CONCLUSIONS: Consecutive general anesthesia requires caution, as it is not only burdensome to the body as a whole but may also cause choroidal effusion in the eye.
Adult ; Anesthesia, General ; Choroid ; Diabetic Retinopathy ; Hematuria ; Humans ; Light Coagulation ; Ultrasonography ; Urinary Bladder Neoplasms ; Urology ; Valsalva Maneuver ; Vitrectomy ; Vitreous Hemorrhage

PURPOSE: To report a rare case of Sjögren's reticular retinal dystrophy. CASE SUMMARY: A 54-year-old male presented with blurred vision and metamorphopsia in both eyes since a few years prior to his initial visit. There was a bilateral reticular network of yellow deposits throughout the posterior pole on fundus examination, which was hyperautofluorescent in fundus autofluorescence photographs. The pigment alterations were more visible with fluorescein angiography, which showed hypofluorescent lesions with hyperfluorescent borders. Spectral-domain optical coherence tomography showed elevations of the outer retina associated with the presence of subretinal hyperreflective material. Based on the conclusive correlation with clinical features, we diagnosed Sjögren's reticular retinal dystrophy. CONCLUSIONS: Sjögren's reticular retinal dystrophy is characterized by its specific pigment changes at the level of clinical manifestations and the retinal pigment epithelium. In cases of Sjögren's reticular retinal dystrophy, close monitoring is required because it has a lifetime risk of choroidal neovascularization.
Choroidal Neovascularization ; Fluorescein Angiography ; Humans ; Macular Degeneration ; Male ; Middle Aged ; Retina ; Retinal Dystrophies ; Retinal Pigment Epithelium ; Retinaldehyde ; Tomography, Optical Coherence ; Vision Disorders