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1.
Proc Natl Acad Sci U S A ; 119(28): e2206113119, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35867764

RESUMO

The Hippo signaling pathway acts as a brake on regeneration in many tissues. This cascade of kinases culminates in the phosphorylation of the transcriptional cofactors Yap and Taz, whose concentration in the nucleus consequently remains low. Various types of cellular signals can reduce phosphorylation, however, resulting in the accumulation of Yap and Taz in the nucleus and subsequently in mitosis. We earlier identified a small molecule, TRULI, that blocks the final kinases in the pathway, Lats1 and Lats2, and thus elicits proliferation of several cell types that are ordinarily postmitotic and aids regeneration in mammals. In the present study, we present the results of chemical modification of the original compound and demonstrate that a derivative, TDI-011536, is an effective blocker of Lats kinases in vitro at nanomolar concentrations. The compound fosters extensive proliferation in retinal organoids derived from human induced pluripotent stem cells. Intraperitoneal administration of the substance to mice suppresses Yap phosphorylation for several hours and induces transcriptional activation of Yap target genes in the heart, liver, and skin. Moreover, the compound initiates the proliferation of cardiomyocytes in adult mice following cardiac cryolesions. After further chemical refinement, related compounds might prove useful in protective and regenerative therapies.


Assuntos
Inibidores de Proteínas Quinases , Proteínas Serina-Treonina Quinases , Regeneração , Animais , Proliferação de Células/efeitos dos fármacos , Coração/fisiologia , Humanos , Células-Tronco Pluripotentes Induzidas , Regeneração Hepática/efeitos dos fármacos , Regeneração Hepática/genética , Regeneração Hepática/fisiologia , Camundongos , Organoides/fisiologia , Fosforilação , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Regeneração/efeitos dos fármacos , Regeneração/genética , Retina/fisiologia , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Fenômenos Fisiológicos da Pele/genética , Transcrição Gênica/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos , Proteínas de Sinalização YAP/metabolismo
2.
Development ; 148(23)2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34738615

RESUMO

The development of the first synapse of the visual system between photoreceptors and bipolar cells in the outer plexiform layer (OPL) of the human retina is crucial for visual processing but poorly understood. By studying the maturation state and spatial organization of photoreceptors, depolarizing bipolar cells and horizontal cells in the human fetal retina, we establish a pseudo-temporal staging system for OPL development that we term OPL-Stages 0 to 4. This was validated through quantification of increasingly precise subcellular localization of bassoon to the OPL with each stage (P<0.0001). By applying these OPL staging criteria to human retinal organoids (HROs) derived from human embryonic and induced pluripotent stem cells, we observed comparable maturation from OPL-Stage 0 at day 100 in culture up to OPL-Stage 3 by day 160. Quantification of presynaptic protein localization confirmed progression from OPL-Stage 0 to 3 (P<0.0001). Overall, this study defines stages of human OPL development through mid-gestation and establishes HROs as a model system that recapitulates key aspects of human photoreceptor-bipolar cell synaptogenesis in vitro.


Assuntos
Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Organoides/metabolismo , Retina/metabolismo , Linhagem Celular , Células-Tronco Embrionárias Humanas/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Organoides/citologia , Retina/citologia
3.
Exp Eye Res ; 244: 109947, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38815793

RESUMO

The non-canonical Wnt pathway is an evolutionarily conserved pathway essential for tissue patterning and development across species and tissues. In mammals, this pathway plays a role in neuronal migration, dendritogenesis, axon growth, and synapse formation. However, its role in development and synaptogenesis of the human retina remains less established. In order to address this knowledge gap, we analyzed publicly available single-cell RNA sequencing (scRNAseq) datasets for mouse retina, human retina, and human retinal organoids over multiple developmental time points during outer retinal maturation. We identified ligands, receptors, and mediator genes with a putative role in retinal development, including those with novel or species-specific expression, and validated this expression using fluorescence in situ hybridization (FISH). By quantifying outer nuclear layer (ONL) versus inner nuclear layer (INL) expression, we provide evidence for the differential expression of certain non-canonical Wnt signaling components in the developing mouse and human retina during outer plexiform layer (OPL) development. Importantly, we identified distinct expression patterns of mouse and human FZD3 and WNT10A, as well as previously undescribed expression, such as for mouse Wnt2b in Chat+ starburst amacrine cells. Human retinal organoids largely recapitulated the human non-canonical Wnt pathway expression. Together, this work provides the basis for further study of non-canonical Wnt signaling in mouse and human retinal development and synaptogenesis.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Retina , Via de Sinalização Wnt , Animais , Camundongos , Humanos , Retina/metabolismo , Retina/crescimento & desenvolvimento , Retina/embriologia , Via de Sinalização Wnt/fisiologia , Hibridização in Situ Fluorescente , Organoides/metabolismo , Camundongos Endogâmicos C57BL
4.
Genes Chromosomes Cancer ; 62(5): 275-289, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36550020

RESUMO

Retinoblastomas form in response to biallelic RB1 mutations or MYCN amplification and progress to more aggressive and therapy-resistant phenotypes through accumulation of secondary genomic changes. Progression-related changes include recurrent somatic copy number alterations and typically non-recurrent nucleotide variants, including synonymous and non-coding variants, whose significance has been unclear. To determine if nucleotide variants recurrently affect specific biological processes, we identified altered genes and over-represented variant gene ontologies in 168 exome or whole-genome-sequenced retinoblastomas and 12 tumor-matched cell lines. In addition to RB1 mutations, MYCN amplification, and established retinoblastoma somatic copy number alterations, the analyses revealed enrichment of variant genes related to diverse biological processes including histone monoubiquitination, mRNA processing (P) body assembly, and mitotic sister chromatid segregation and cytokinesis. Importantly, non-coding and synonymous variants increased the enrichment significance of each over-represented biological process term. To assess the effects of such mutations, we examined the consequences of a 3' UTR variant of PCGF3 (a BCOR-binding component of Polycomb repressive complex I), dual 3' UTR variants of CDC14B (a regulator of sister chromatid segregation), and a synonymous variant of DYNC1H1 (a regulator of P-body assembly). One PCGF3 and one of two CDC14B 3' UTR variants impaired gene expression whereas a base-edited DYNC1H1 synonymous variant altered protease sensitivity and stability. Retinoblastoma cell lines retained only ~50% of variants detected in tumors and enriched for new variants affecting p53 signaling. These findings reveal potentially important differences in retinoblastoma cell lines and tumors and implicate synonymous and non-coding variants, along with non-synonymous variants, in retinoblastoma oncogenesis.


Assuntos
Neoplasias da Retina , Retinoblastoma , Humanos , Retinoblastoma/genética , Nucleotídeos , Proteína Proto-Oncogênica N-Myc/genética , Regiões 3' não Traduzidas , Mutação , Neoplasias da Retina/genética , Genes do Retinoblastoma , Fosfatases de Especificidade Dupla
5.
Ophthalmology ; 130(7): 764-770, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36822437

RESUMO

PURPOSE: To analyze demographic and ophthalmic data in patients with and without chorioretinal atrophy after voretigene neparvovec-rzyl (VN) to identify possible causes for this phenomenon. DESIGN: Retrospective cohort study with longitudinal follow-up. PARTICIPANTS: A total of 71 eyes of 38 patients aged 2 to 44 years with RPE65-mediated retinal dystrophy treated with VN across 2 large gene therapy centers in the United States and Germany. METHODS: Patients treated with VN who developed atrophy were compared with those who did not. MAIN OUTCOME MEASURES: Gender, age, surgical center, spherical equivalent refraction, best-corrected visual acuity (BCVA), baseline full-field scotopic threshold testing (FST), and posttreatment change in FST. RESULTS: A total of 20 eyes of 12 patients developed atrophy after treatment with VN (28% of all eyes). There was no significant difference in gender, age, surgical center, or spherical equivalent refraction between the atrophy group and the no atrophy group. However, patients between school age and young adulthood were predominantly affected, whereas the youngest and the oldest patients did not develop atrophy. Baseline BCVA was better in patients who developed atrophy than those who did not (P = 0.006). The postoperative improvement in FST at 1 month was significantly higher in the atrophy group than in the no atrophy group (P = 0.0005), and this difference remained statistically significant at 1 year (P = 0.0001). There was no correlation to baseline FST, to inflammation, or to which eye was treated first. CONCLUSIONS: The degree of FST improvement after VN appears to be strongly correlated with the development of VN-related chorioretinal atrophy. This finding raises the possibility that atrophy may develop as a toxic or metabolic sequela of vector-mediated RPE65 expression. In light of the expanding number of retinal gene therapy clinical trials, this complication warrants further study because it may not be limited to VN. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.


Assuntos
Refração Ocular , Distrofias Retinianas , Humanos , Adulto Jovem , Adulto , Acuidade Visual , Estudos Retrospectivos , Distrofias Retinianas/genética , Distrofias Retinianas/terapia , Retina
6.
Ophthalmology ; 130(3): 265-273, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36270406

RESUMO

PURPOSE: To report the clinical and imaging findings of 4 patients with benign intraretinal tumors, 2 of which were associated with retinal pigment epithelium (RPE) hypertrophy. To our knowledge, this condition has not been described previously and should be distinguished from retinoblastoma and other malignant retinal neoplasms. DESIGN: Retrospective case series. PARTICIPANTS: Four patients from 3 institutions. METHODS: Four patients with intraretinal tumors of the inner nuclear layer (INL) underwent a combination of ophthalmic examination, fundus photography, fluorescein angiography, OCT, OCT angiography, and whole exome sequencing. MAIN OUTCOME MEASURES: Description of multimodal imaging findings and systemic findings from 4 patients with benign intraretinal tumors and whole exome studies from 3 patients. RESULTS: Six eyes of 4 patients 5, 13, 32, and 27 years of age were found to have white intraretinal tumors that remained stable over the follow-up period (range, 9 months-4 years). The tumors were unilateral in 2 patients and bilateral in 2 patients. The tumors were white, centered on the posterior pole, and multifocal, with some consisting of multiple lobules with arching extensions that extended beyond the central tumor mass. OCT demonstrated these lesions to be centered within the INL at the border of the inner plexiform layer. In addition, 2 patients demonstrated congenital hypertrophy of the RPE (CHRPE) lesions. Three of 4 patients underwent whole exome sequencing of the blood that revealed no candidate variants that plausibly could account for the phenotype. CONCLUSIONS: We characterize a novel benign tumor of the INL that, in 2 patients, was associated with separate CHRPE lesions. We propose the term benign lobular inner nuclear layer proliferation to describe these lesions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.


Assuntos
Doenças Retinianas , Neoplasias da Retina , Humanos , Epitélio Pigmentado da Retina/patologia , Estudos Retrospectivos , Retina/patologia , Doenças Retinianas/diagnóstico , Neoplasias da Retina/patologia , Angiofluoresceinografia , Tomografia de Coerência Óptica/métodos , Hipertrofia/congênito , Hipertrofia/patologia
7.
Retina ; 42(10): 1829-1835, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35858274

RESUMO

PURPOSE: To provide a concise review of induced pluripotent stem cells (iPSCs) and retinal organoids as models for human retinal diseases and their role in gene discovery and treatment of inherited retinal diseases (IRDs). METHODS: A PubMed literature review was performed for models of human retinal disease, including animal models and human pluripotent stem cell-derived models. RESULTS: There is a growing body of research on retinal disease using human pluripotent stem cells. This is a significant change from just a decade ago when most research was performed on animal models. The advent of induced pluripotent stem cells has permitted not only the generation of two-dimensional human cell cultures such as RPE but also more recently the generation of three-dimensional retinal organoids that better reflect the multicellular laminar architecture of the human retina. CONCLUSION: Modern stem cell techniques are improving our ability to model human retinal disease in vitro, especially with the use of patient-derived induced pluripotent stem cells. In the future, a personalized approach may be used in which the individual's unique genotype can be modeled in two-dimensional culture or three-dimensional organoids and then rescued with an optimized therapy before treating the patient.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Doenças Retinianas , Animais , Diferenciação Celular , Humanos , Organoides , Doenças Retinianas/terapia
8.
Int J Mol Sci ; 23(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36362148

RESUMO

Signal peptide (SP) mutations are an infrequent cause of inherited retinal diseases (IRDs). We report the genes currently associated with an IRD that possess an SP sequence and assess the prevalence of these variants in a multi-institutional retrospective review of clinical genetic testing records. The online databases, RetNet and UniProt, were used to determine which IRD genes possess a SP. A multicenter retrospective review was performed to retrieve cases of patients with a confirmed diagnosis of an IRD and a concurrent SP variant. In silico evaluations were performed with MutPred, MutationTaster, and the signal peptide prediction tool, SignalP 6.0. SignalP 6.0 was further used to determine the locations of the three SP regions in each gene: the N-terminal region, hydrophobic core, and C-terminal region. Fifty-six (56) genes currently associated with an IRD possess a SP sequence. Based on the records review, a total of 505 variants were present in the 56 SP-possessing genes. Six (1.18%) of these variants were within the SP sequence and likely associated with the patients' disease based on in silico predictions and clinical correlation. These six SP variants were in the CRB1 (early-onset retinal dystrophy), NDP (familial exudative vitreoretinopathy) (FEVR), FZD4 (FEVR), EYS (retinitis pigmentosa), and RS1 (X-linked juvenile retinoschisis) genes. It is important to be aware of SP mutations as an exceedingly rare cause of IRDs. Future studies will help refine our understanding of their role in each disease process and assess therapeutic approaches.


Assuntos
Doenças Retinianas , Distrofias Retinianas , Retinose Pigmentar , Humanos , Sinais Direcionadores de Proteínas/genética , Doenças Retinianas/genética , Distrofias Retinianas/genética , Distrofias Retinianas/diagnóstico , Retina , Retinose Pigmentar/genética , Testes Genéticos , Mutação , Linhagem , Análise Mutacional de DNA , Proteínas do Olho/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Receptores Frizzled/genética
9.
Ophthalmology ; 127(11): 1567-1577, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32507351

RESUMO

PURPOSE: To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course. DESIGN: Multicenter retrospective observational case series. PARTICIPANTS: Sixty-three patients with SIC in 1 eye. METHODS: Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography. MAIN OUTCOME MEASURES: Standardized grading of imaging features. RESULTS: Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 µm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution. CONCLUSIONS: In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.


Assuntos
Corioide/patologia , Corioidite/diagnóstico , Angiofluoresceinografia/métodos , Esclera/patologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Seguimentos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
Retina ; 40(11): 2083-2090, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32091489

RESUMO

PURPOSE: To report on the indications, outcomes, and complications of endoscopic vitrectomy in a large cohort of pediatric vitreoretinal patients. METHODS: This is a retrospective interventional case series consisting of 244 eyes of 211 patients aged 18 years or younger undergoing a total of 326 endoscopic vitrectomies from 2008 to 2017. A 23-gauge vitrectomy was performed with use of a 19-gauge endoscope. RESULTS: Two hundred and eleven patients with a mean age of 7.5 years (range: 0-18 years) and median follow-up since last surgery of 28 months (range: 3 months-8.7 years) were included. The most common indication for endoscopic vitrectomy was retinal detachment (234/326; 72%) with proliferative vitreoretinopathy (162/234; 69%). Other diagnoses included trauma (25%), retinopathy of prematurity (15%), and glaucoma (9%). Twenty-five percent of surgeries (80/326) were performed on eyes with significant corneal opacities. Retinal reattachment was achieved in 67% of eyes with retinal detachment (119/178). Visual acuity improved in 26% of retinal detachment eyes versus 53% of nonretinal detachment eyes (P = 0.005). Surgical complications included band keratopathy (15%), hypotony (8%), cataract (7%), and elevated intraocular pressure (3%). CONCLUSION: In this large series of pediatric endoscopic vitreoretinal surgeries, anatomic outcomes and complication rates were comparable with previous studies.


Assuntos
Endoscopia/métodos , Retina/anatomia & histologia , Acuidade Visual/fisiologia , Vitrectomia/métodos , Cirurgia Vitreorretiniana , Adolescente , Criança , Pré-Escolar , Traumatismos Oculares/cirurgia , Feminino , Glaucoma/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Descolamento Retiniano/cirurgia , Retinopatia da Prematuridade/cirurgia , Estudos Retrospectivos , Vitreorretinopatia Proliferativa/cirurgia
11.
Retina ; 38(4): 748-754, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28368975

RESUMO

PURPOSE: To study the use of ultra-widefield fluorescein angiography (UWF FA) in the detection and management of retinal capillary hemangioblastomas in patients with von Hippel-Lindau disease. METHODS: This is a retrospective study of patients with von Hippel-Lindau disease who underwent UWF FA using the Optos camera at a single center from June 2009 to May 2015. The clinical use of UWF FA was reviewed, and the number of hemangioblastomas identified on UWF FA was compared with ophthalmoscopy and a simulated seven standard field (7SF) FA montage. RESULTS: Twenty eyes of 10 patients were identified. Only 33% of lesions seen on UWF FA were also found on ophthalmoscopy, and 88% of lesions visualized on UWF FA were located outside the 7SF overlay. In 5 eyes that had gaze steering, 18% of lesions could be visualized only on gaze-steered images. For the 14 eyes with data available, 6 had procedures recommended and 8 eyes observed based on data from UWF FA. One of 20 eyes had a lesion on ophthalmoscopy that was missed by imaging. CONCLUSION: Ultra-widefield FA using the Optos camera is helpful for the evaluation and management of patients with von Hippel-Lindau disease. The UWF FA with gaze steering appears to detect more hemangioblastomas than ophthalmoscopy and conventional angiography.


Assuntos
Técnicas de Diagnóstico Oftalmológico , Angiofluoresceinografia/métodos , Hemangioblastoma/diagnóstico por imagem , Neoplasias da Retina/diagnóstico por imagem , Doença de von Hippel-Lindau/complicações , Adolescente , Adulto , Criança , Diagnóstico Precoce , Feminino , Hemangioblastoma/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Retina/etiologia , Estudos Retrospectivos , Adulto Jovem
12.
Retina ; 38(9): 1652-1667, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29135799

RESUMO

PURPOSE: To describe the features of peripapillary pachychoroid syndrome (PPS), a novel pachychoroid disease spectrum (PDS) entity. METHODS: Medical records of 31 eyes (16 patients) with choroidal thickening associated with intraretinal and/or subretinal fluid in the nasal macula extending from the disk were reviewed (patients with PPS). Choroidal thickness was compared with 2 age-matched cohorts: typical PDS (17 eyes with central serous chorioretinopathy or pachychoroid neovasculopathy) and 19 normal eyes. RESULTS: The patients with PPS were 81% men aged 71 ± 7 years. Peripapillary pachychoroid syndrome eyes displayed thicker nasal versus temporal macular choroids, unlike PDS eyes with thicker temporal macular choroids (P < 0.0001). Peripapillary intraretinal and/or subretinal fluid was often overlying dilated Haller layer vessels (pachyvessels). Fundus autofluorescence and fluorescein angiography illustrated peripapillary pigmentary mottling without focal leakage. Most PPS eyes (70%) exhibited other PDS findings including serous pigment epithelial detachment or gravitational tracks. Indocyanine green angiography illustrated dilated peripapillary pachyvessels and choroidal hyperpermeability. The disk was usually crowded, with edema noted in 4/31 (13%) eyes and mild late fluorescein disk leakage identified in half of the cases. Choroidal folds (77%), short axial lengths (39% less than 23 mm), and hyperopia (86%) were common. CONCLUSION: Peripapillary pachychoroid syndrome is a distinct PDS variant, in which peripapillary choroidal thickening is associated with nasal macular intraretinal and/or subretinal fluid and occasional disk edema. Recognition of PPS is important to distinguish it from disorders with overlapping features such as posterior uveitis and neuro-ophthalmologic conditions.


Assuntos
Doenças da Coroide/diagnóstico , Corioide/patologia , Angiofluoresceinografia/métodos , Macula Lutea/patologia , Disco Óptico/patologia , Tomografia de Coerência Óptica/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome
13.
Retina ; 37(7): 1377-1382, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28486310

RESUMO

PURPOSE: Fine-needle aspiration biopsy of small choroidal melanomas 2 mm or less in thickness may be associated with a low biopsy yield. This report describes our center's experience using the 27-gauge vitreous cutter to perform tumor sampling in these small melanomas. METHODS: This was a retrospective analysis of all patients who underwent a 27-gauge vitreous cutter biopsy for molecular prognostication at the time of iodine-125 plaque placement for local treatment of choroidal melanoma ≤2.0 mm in height. RESULTS: Seventeen consecutive patients with a mean baseline tumor height of 1.67 mm (range, 1.31-2.03 mm) and median follow-up time of 7.0 months (range, 3.3-19.5 months) were included. The 27-gauge cutter biopsy yielded sufficient material for multiplex-ligation probe amplification (MLPA) or gene expression profiling (GEP) in 17/17 (100%) patients. Complications were limited to focal vitreous hemorrhage in 13/17 patients and diffuse vitreous hemorrhage in 1/17 patients, with no instance of retinal detachment or nonclearing vitreous hemorrhage. CONCLUSION: Tumor sampling of small choroidal melanoma with a 27-gauge vitreous cutter is safe and offers excellent biopsy yield for molecular prognostication when cancer prognosis is desired by patients.


Assuntos
Biópsia por Agulha Fina/métodos , Neoplasias da Coroide/cirurgia , Melanoma/cirurgia , Microcirurgia/métodos , Cirurgia Assistida por Computador/métodos , Vitrectomia/instrumentação , Corpo Vítreo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Coroide/diagnóstico , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Corpo Vítreo/cirurgia , Adulto Jovem
15.
Retina ; 36(4): 660-78, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27014860

RESUMO

PURPOSE: To review the basic principles of ultra-widefield fundus imaging and discuss its clinical utility for a variety of retinal and choroidal disorders. METHODS: A systematic review of the PubMed database was performed using the search terms Optos, optomap, panoramic, ultra-widefield, wide-angle, and ellipsoid mirror. This yielded 158 publications of which 128 were selected based on content and relevance. RESULTS: A total of 128 articles pertaining to ultra-widefield imaging were cited in this review. CONCLUSION: Optos ultra-widefield imaging has become an essential tool for the identification of peripheral retinal and vascular pathology. The high resolution and multimodal capabilities of this device are also providing new insights into a variety of disorders, even those that primarily involve the posterior pole. Although the presence of artifact and the need for clinical validation are significant hurdles to more widespread use, ultra-widefield is evolving to become the standard-of-care imaging modality for many diseases and is finding new clinical and research applications such as for screening and telemedicine.


Assuntos
Doenças da Coroide/diagnóstico , Diagnóstico por Imagem/tendências , Técnicas de Diagnóstico Oftalmológico , Doenças Retinianas/diagnóstico , Técnicas de Diagnóstico Oftalmológico/tendências , Humanos
17.
Retina ; 35(4): 638-47, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25650713

RESUMO

PURPOSE: To demonstrate the evolution and treatment response of Type 3 neovascularization using spectral domain optical coherence tomography. METHODS: We retrospectively analyzed 40 eyes treated with intravitreal anti-vascular endothelial growth factor therapy for Type 3 neovascularization over a variable follow-up period. RESULTS: In 17 eyes, spectral domain optical coherence tomography captured the development of Type 3 neovascularization from punctate hyperreflective foci that preceded any outer retinal defect. The more mature Type 3 lesions were associated with outer retinal disruption and adjacent cystoid macular edema. In addition, 37 of 40 Type 3 lesions (93%) were associated with an underlying pigment epithelial detachment, of which 26 (70%) were drusenoid, 6 (16%) serous, and 5 (14%) mixed. Type 3 vessels appeared to leak fluid into the pigment epithelial detachment cavity, creating serous pigment epithelial detachments as large as 925 µm in maximal height. Treatment with anti-vascular endothelial growth factor agents led to prompt involution of the lesion and resorption of the intraretinal and subretinal pigment epithelium fluid after one or two injections (median = 1). CONCLUSION: In some eyes with age-related macular degeneration, the earliest sign of Type 3 neovascularization is punctate hyperreflective foci above the external limiting membrane. The mature Type 3 lesions and associated serous pigment epithelial detachments are highly responsive to anti-vascular endothelial growth factor therapy.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Papiledema/diagnóstico , Descolamento Retiniano/diagnóstico , Neovascularização Retiniana/diagnóstico , Epitélio Pigmentado da Retina/patologia , Degeneração Macular Exsudativa/patologia , Idoso , Idoso de 80 Anos ou mais , Corantes , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Verde de Indocianina , Injeções Intravítreas , Masculino , Papiledema/tratamento farmacológico , Descolamento Retiniano/tratamento farmacológico , Neovascularização Retiniana/classificação , Neovascularização Retiniana/tratamento farmacológico , Estudos Retrospectivos , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/tratamento farmacológico
18.
Ophthalmic Plast Reconstr Surg ; 31(6): e145-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24833448

RESUMO

Mucormycosis is a rare fungal infection typically limited to immunocompromised patients or patients with diabetes., Clinical manifestation varies, with rhino-orbital-cerebral mucormycosis as the most common presentation. The authors present here a 56-year-old man who complained of isolated OD pain with no evidence of cerebral or sinus inflammation on imaging. Enucleation was eventually performed, and histopathology of the globe demonstrated characteristics of zygomycetes infection. Intraocular mucormycosis is rare and when reported is related to contiguous spread of disease or surgical inoculation. After thorough literature review, the authors believe this to be the first reported case of isolated intraocular mucormycosis in a patient with no prior history of ocular surgery.


Assuntos
Endoftalmite/microbiologia , Infecções Oculares Fúngicas/microbiologia , Mucorales/isolamento & purificação , Mucormicose/microbiologia , Biópsia , Diabetes Mellitus Tipo 2/complicações , Endoftalmite/diagnóstico por imagem , Endoftalmite/cirurgia , Enucleação Ocular , Infecções Oculares Fúngicas/diagnóstico por imagem , Infecções Oculares Fúngicas/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mucormicose/diagnóstico por imagem , Mucormicose/cirurgia , Tomografia Computadorizada por Raios X
19.
Retina ; 39(1): e4, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30418390

Assuntos
Retina
20.
Retin Cases Brief Rep ; 18(1): 6-10, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36007194

RESUMO

PURPOSE: We report two siblings with genetically confirmed Walker-Warburg syndrome (WWS), studied with multimodal imaging, who presented with different retinal manifestations. METHODS: This is a retrospective report of two WWS cases with ultra-widefield fundus photography, fluorescein angiography, and ultrasound. Molecular diagnosis was achieved using panel testing and targeted variant testing. RESULTS: Two siblings, one male and one female, born 17 months apart with a diagnosis of WWS underwent retinal examination with imaging. The 3-month-old female infant exhibited microphthalmia, persistent hyaloidal arteries, and retrolental membranes with total tractional retinal detachments on ultrasound in both eyes. The 22-day-old male newborn exhibited persistent hyaloidal arteries and extensive peripheral avascular retina on angiography in both eyes. Both were found to be positive for the same two pathogenic variants in the RXYLT1/TMEM5 gene, which accounts for approximately 9% of cases of genetically confirmed WWS. CONCLUSION: Siblings with genetically confirmed WWS can have variable presentations despite identical genotype. This highlights the phenotypic disease spectrum of WWS, which may be similar to that seen in familial exudative vitreoretinopathy.


Assuntos
Síndrome de Walker-Warburg , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Angiofluoresceinografia , Imagem Multimodal , Mutação , Retina , Estudos Retrospectivos , Irmãos , Síndrome de Walker-Warburg/diagnóstico , Síndrome de Walker-Warburg/genética , Proteínas de Membrana/genética , Pentosiltransferases/genética
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