RESUMEN
Conjunctival melanoma (CJM) is a rare but potentially lethal and highly-recurrent cancer of the eye. Similar to cutaneous melanoma (CM), it originates from melanocytes. Unlike CM, however, CJM is relatively poorly characterized from a genomic point of view. To fill this knowledge gap and gain insight into the genomic nature of CJM, we performed whole-exome (WES) or whole-genome sequencing (WGS) of tumor-normal tissue pairs in 14 affected individuals, as well as RNA sequencing in a subset of 11 tumor tissues. Our results show that, similarly to CM, CJM is also characterized by a very high mutation load, composed of approximately 500 somatic mutations in exonic regions. This, as well as the presence of a UV light-induced mutational signature, are clear signs of the role of sunlight in CJM tumorigenesis. In addition, the genomic classification of CM proposed by TCGA seems to be well-applicable to CJM, with the presence of four typical subclasses defined on the basis of the most frequently mutated genes: BRAF, NF1, RAS, and triple wild-type. In line with these results, transcriptomic analyses revealed similarities with CM as well, namely the presence of a transcriptomic subtype enriched for immune genes and a subtype enriched for genes associated with keratins and epithelial functions. Finally, in seven tumors we detected somatic mutations in ACSS3, a possible new candidate oncogene. Transfected conjunctival melanoma cells overexpressing mutant ACSS3 showed higher proliferative activity, supporting the direct involvement of this gene in the tumorigenesis of CJM. Altogether, our results provide the first unbiased and complete genomic and transcriptomic classification of CJM.
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Neoplasias de la Conjuntiva/genética , Variaciones en el Número de Copia de ADN , Melanoma/genética , Mutación , Transcriptoma , Línea Celular Tumoral , Neoplasias de la Conjuntiva/metabolismo , Femenino , Humanos , Masculino , Melanoma/metabolismo , Persona de Mediana Edad , Neurofibromina 1/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas ras/genéticaRESUMEN
PURPOSE: To evaluate 18 months' results of a strict anti-vascular endothelial growth factor protocol for radiation maculopathy following proton therapy in choroidal melanoma. METHODS: Retrospective, comparative, nonrandomized study of 74 radiation maculopathy patients presenting macular lipid deposits, hemorrhages, microaneurysms, cystoid edema, nerve layer infarction, telangiectasia, or capillary nonperfusion. The study group included 52 consecutive patients injected with intravitreal anti-vascular endothelial growth factors (bevacizumab/ranibizumab: 46/6) every two months for the first and every 3 months for the second year, with minimum 12 months' follow-up. The control group consisted of 22 patients having declined this treatment. Best-corrected visual acuity, spectral domain-optical coherence tomography and optical coherence tomography angiography were recorded at baseline, 6, 12, and 18 months. The foveal avascular zone and capillary density were measured at the superficial capillary plexus. RESULTS: Radiation maculopathy was diagnosed at 2 years (1.5-3.5) after proton therapy. Best-corrected visual acuity at baseline, 12 and 18 months improved in the study group from 0.45, 0.3 to 0.2 logarithm of the minimum angle of resolution, but decreased in the control group from 0.5, 0.9 to 1.0 logarithm of the minimum angle of resolution respectively (P < 0.001 at 12 months). Simultaneously, foveal avascular zone enlargement was less in the study (from 0.377, 0.665 to 0.744 mm2) than control group (from 0.436, 1.463 to 2.638 mm2) (P = 0.05 at 12 months). CMT (280 and 276 µm) and capillary density (37% and 38%, at baseline, respectively) did not evolve significantly different. CONCLUSION: Intravitreal anti-vascular endothelial growth factors, every 2 months for the first and every 3 months for the second year, slow down, over up to 18 months, vision loss and anatomical degradation in radiation maculopathy following proton therapy for choroidal melanoma.
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Inhibidores de la Angiogénesis/administración & dosificación , Neoplasias de la Coroides/radioterapia , Mácula Lútea/efectos de la radiación , Melanoma/radioterapia , Microcirculación/efectos de los fármacos , Terapia de Protones/efectos adversos , Enfermedades de la Retina/diagnóstico por imagen , Anciano , Bevacizumab/administración & dosificación , Femenino , Angiografía con Fluoresceína/métodos , Estudios de Seguimiento , Humanos , Inyecciones Intravítreas , Mácula Lútea/diagnóstico por imagen , Masculino , Microcirculación/fisiología , Persona de Mediana Edad , Ranibizumab/administración & dosificación , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/etiología , Estudios Retrospectivos , Factores de Tiempo , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza VisualRESUMEN
PURPOSE: To evaluate why small- and certain medium-sized parapapillary choroidal melanoma (pcM) patients treated with hypo-fractionated proton therapy (PT) retain excellent long-term visual acuity (VA) and assess the negative predictive factors for retaining good vision (≤ 0.2 logMAR (≥ 0.6 decimal) after 5 years. METHODS: This single-center, retrospective, comparative study recruited consecutive pcM patients that were treated with PT. Between 1984 and 2005, 609 patients received a total of 60 CGE, of whom 310 met the following inclusion criteria: posterior tumor border ≤ 2.5 mm from the optic disc, largest tumor diameter ≤ 17.9 mm, tumor thickness ≤ 5.2 mm and available follow-up data for at least 5 years. RESULTS: Mean follow-up was 120.8 ± 48.8 months (54.0-295.0). Out of 310 patients, 64 (21%) maintained a VA ≤ 0.2 logMAR (≥ 0.6 decimal) for at least 5 years following PT and were allocated to the "good visual outcome" (GVO) group, while the remaining 246 (79%) constituted the "poor visual outcome" (PVO) group, subdivided into 70 (22%) with a VA of 0.3-1.0 logMAR (0.1-0.5 decimal) and 157 (57%) patients with a VA > 1.0 logMAR (< 0.1 decimal). On multivariate analysis, older age (P = 0.04), tumor localization ≤ 0.5 mm to the fovea (P < 0.03), volume of the optic disc and macula receiving 50% of dose (30 CGE) (P = 0.02 and P < 0.001, respectively) were independent negative predictors of GVO. CONCLUSIONS: Of 310 small- to medium-sized pcM patients successfully treated with PT, 21% retained a VA ≤ 0.2 logMAR (≥ 0.6 decimal) for at least 5 years. Strongest negative predictive factor for retaining good long-term vision was the volume of the macula irradiated with at least 30 Gy.
Asunto(s)
Neoplasias de la Coroides , Melanoma , Terapia de Protones , Anciano , Neoplasias de la Coroides/radioterapia , Estudios de Seguimiento , Humanos , Melanoma/radioterapia , Dosificación Radioterapéutica , Estudios RetrospectivosRESUMEN
Purpose: The exact cellular types that form the human fovea remain a subject of debate, and few studies have been conducted on human macula to solve this question. The purpose of this study was to perform immunohistochemistry on fresh human samples to characterize the glial cells that form the human fovea. Methods: Immunohistochemistry was performed using antibodies against proteins expressed in astrocytes or in retinal Müller glial cells or both types of cells on six human macula obtained from eyes enucleated for peripheral intraocular tumors and on two postmortem eyes from healthy donors. The posterior poles of the enucleated eyes were cryosectioned and stained with antibodies against the glial proteins GFAP, vimentin, CRALBP, glutamine synthetase, and connexin 43. Results: A population of cells positive for GFAP and negative for glutamine synthetase and CRALBP that express connexin 43 were identified at the roof of the foveal pit. These cells are distinct from the Müller cone cells described by Yamada and Gass, suggesting that another type of foveal glial cells, most likely astrocytes, are present in the human fovea. Conclusions: This study showed that in humans, astrocytic glial cells cover the foveal pit. Their roles in macula homeostasis and mechanisms of macular diseases disease remain to be determined.
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Astrocitos/metabolismo , Células Ependimogliales/metabolismo , Fóvea Central/citología , Fóvea Central/metabolismo , Neuroglía/metabolismo , Anciano , Astrocitos/citología , Proteínas Portadoras/metabolismo , Conexina 43/metabolismo , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Glutamato-Amoníaco Ligasa/metabolismo , Humanos , Inmunohistoquímica , Mácula Lútea/metabolismo , Masculino , Persona de Mediana Edad , Neuroglía/citología , Vimentina/metabolismoRESUMEN
Uveal melanoma (UM) is a rare intraocular tumor that, similar to cutaneous melanoma, originates from melanocytes. To gain insights into its genetics, we performed whole-genome sequencing at very deep coverage of tumor-control pairs in 33 samples (24 primary and 9 metastases). Genome-wide, the number of coding mutations was rather low (only 17 variants per tumor on average; range 7-28), thus radically different from cutaneous melanoma, where hundreds of exonic DNA insults are usually detected. Furthermore, no UV light-induced mutational signature was identified. Recurrent coding mutations were found in the known UM drivers GNAQ, GNA11, BAP1, EIF1AX, and SF3B1. Other genes, i.e., TP53BP1, CSMD1, TTC28, DLK2, and KTN1, were also found to harbor somatic mutations in more than one individual, possibly indicating a previously undescribed association with UM pathogenesis. De novo assembly of unmatched reads from non-coding DNA revealed peculiar copy-number variations defining specific UM subtypes, which in turn could be associated with metastatic transformation. Mutational-driven comparison with other tumor types showed that UM is very similar to pediatric tumors, characterized by very few somatic insults and, possibly, important epigenetic changes. Through the analysis of whole-genome sequencing data, our findings shed new light on the molecular genetics of uveal melanoma, delineating it as an atypical tumor of the adult for which somatic events other than mutations in exonic DNA shape its genetic landscape and define its metastatic potential.
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Estudio de Asociación del Genoma Completo , Melanoma/genética , Neoplasias de la Úvea/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Variaciones en el Número de Copia de ADN , Factor 1 Eucariótico de Iniciación/genética , Factor 1 Eucariótico de Iniciación/metabolismo , Exones , Femenino , Subunidades alfa de la Proteína de Unión al GTP/genética , Subunidades alfa de la Proteína de Unión al GTP/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Humanos , Masculino , Melanocitos/patología , Melanoma/diagnóstico , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Mutación , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismo , Neoplasias Cutáneas , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Proteína 1 de Unión al Supresor Tumoral P53/genética , Proteína 1 de Unión al Supresor Tumoral P53/metabolismo , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Neoplasias de la Úvea/diagnóstico , Melanoma Cutáneo MalignoRESUMEN
PURPOSE: To evaluate, in eyes with radiation maculopathy, the effect of 2-month-interval anti-vascular endothelial growth factor therapy on best-corrected visual acuity and foveal avascular zone (FAZ) enlargement using optical coherence tomography angiography. METHODS: Consecutive treatment-naive patients with radiation maculopathy after proton beam irradiation for choroidal melanoma were retrospectively included. Clinical and optical coherence tomography angiography data at baseline and the 6-month visit were recorded. Two independent observers measured FAZ area manually on 3 × 3-mm optical coherence tomography angiography images of the superficial capillary plexus and deep capillary plexus. Patients were encouraged to follow strictly a 2-month-interval intravitreal anti-vascular endothelial growth factor treatment by either bevacizumab or ranibizumab. Findings were analyzed based on the adherence to the treatment scheme. RESULTS: According to the adherence to the bimonthly anti-vascular endothelial growth factor treatment protocol, patients were categorized into 3 groups: treatment protocol (n = 19, strict adherence), variable intervals (n = 11, intervals other than 2 months), and no treatment (n = 11). The estimated radiation dose to the foveola in each group was 49 ± 16, 46 ± 17, and 46 ± 18 cobalt gray equivalent, respectively (P = 0.85). For the entire cohort, best-corrected visual acuity loss (P < 0.02) and FAZ enlargement (P < 0.0001) were observed over 6 months. Best-corrected visual acuity loss was significantly less pronounced in the treatment-protocol group than in the variable-interval and no-treatment groups (P = 0.007 and P = 0.004). The FAZ enlargement was lower in the treatment-protocol group compared with the variable-interval group for both superficial capillary plexus (P = 0.029) and deep capillary plexus (P = 0.03), and to the no-treatment group for the deep capillary plexus only (P = 0.016). CONCLUSION: Decrease in best-corrected visual acuity and FAZ enlargement on optical coherence tomography angiography occurred over 6 months in eyes with radiation maculopathy and were significantly reduced under 2-month-interval anti-vascular endothelial growth factor therapy.
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Inhibidores de la Angiogénesis/uso terapéutico , Terapia de Protones/efectos adversos , Traumatismos por Radiación/tratamiento farmacológico , Retina/efectos de la radiación , Enfermedades de la Retina/tratamiento farmacológico , Trastornos de la Visión/tratamiento farmacológico , Anciano , Bevacizumab/uso terapéutico , Neoplasias de la Coroides/radioterapia , Femenino , Angiografía con Fluoresceína , Fóvea Central/irrigación sanguínea , Humanos , Inyecciones Intravítreas , Masculino , Melanoma/radioterapia , Persona de Mediana Edad , Proyectos Piloto , Traumatismos por Radiación/etiología , Traumatismos por Radiación/fisiopatología , Dosificación Radioterapéutica , Ranibizumab/uso terapéutico , Enfermedades de la Retina/etiología , Enfermedades de la Retina/fisiopatología , Vasos Retinianos/fisiopatología , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Trastornos de la Visión/etiología , Trastornos de la Visión/fisiopatología , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. DESIGN: Retrospective, multicenter observational study. PARTICIPANTS: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. METHODS: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. MAIN OUTCOME MEASURES: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. RESULTS: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. CONCLUSIONS: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.
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Neoplasias de la Coroides/epidemiología , Cuerpo Ciliar/patología , Melanoma/epidemiología , Neoplasias de la Úvea/epidemiología , Adolescente , Niño , Preescolar , Neoplasias de la Coroides/mortalidad , Neoplasias de la Coroides/terapia , Europa (Continente)/epidemiología , Enucleación del Ojo , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Oncología Médica/organización & administración , Melanoma/mortalidad , Melanoma/terapia , Recurrencia Local de Neoplasia/diagnóstico , Procedimientos Quirúrgicos Oftalmológicos , Oftalmología/organización & administración , Fotoquimioterapia , Radioterapia , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias de la Úvea/mortalidad , Neoplasias de la Úvea/terapia , Adulto JovenRESUMEN
PURPOSE: To examine the metastatic and survival rates, eye retention probability, and the visual outcomes of juvenile patients after proton beam radiotherapy (PBRT) for uveal melanoma (UM). DESIGN: Retrospective case-factor matched control study. PARTICIPANTS AND CONTROLS: Forty-three patients younger than 21 years treated with PBRT for UM were compared with 129 matched adult control patients. METHODS: Information on patient demographics and clinical characteristics were recorded before and after treatment from patients' files. The control group was composed of adult patients (>21 years) matched for tumor size (largest tumor diameter, ±2 mm; height, ±2 mm) and anterior margin location (iris, ciliary body, pre-equatorial or postequatorial choroid). For each juvenile patient, 3 adults were selected. MAIN OUTCOME MEASURES: Comparing outcomes of juvenile and adult patients in terms of metastatic and eye retention rates using the log-rank statistic, relative survival using the Hakulinen method, as well as their visual outcomes. RESULTS: Forty-three juvenile and 129 control cases were reviewed. The metastatic rate at 10 years was significantly lower in juvenile UM patients than in adult controls (11% vs. 34%; P <0.01), with an associated relative survival rate of 93% versus 65% (P = 0.02). Six juvenile patients (14%) demonstrated metastases. One patient underwent enucleation because of a presumed local tumor recurrence and 4 additional patients underwent enucleation because of complications (9.3%). In the adult control group, 27% (n = 35) of matched patients demonstrated metastases, there were 2 cases of local recurrence, and 16% (n = 21) underwent enucleation because of complications. A visual acuity of more than 0.10 was maintained in most cases, without any significant differences before or after treatment observed between both groups. CONCLUSIONS: After PBRT, metastatic and survival rates are significantly better for juvenile than for adult patients with UM. Clinically, juvenile and adult eyes react similarly to PBRT, with patients having a comparable eye retention probability and maintaining a useful level of vision in most cases. This is the largest case-control study of proton therapy in juvenile eyes to date and further validates PBRT as an appropriate conservative treatment for UM in patients younger than 21 years.
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Melanoma/radioterapia , Terapia de Protones , Neoplasias de la Úvea/radioterapia , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Supervivencia sin Enfermedad , Enucleación del Ojo , Femenino , Estudios de Seguimiento , Humanos , Lactante , Neoplasias Hepáticas/secundario , Masculino , Melanoma/mortalidad , Melanoma/patología , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Neoplasias de la Úvea/mortalidad , Neoplasias de la Úvea/patología , Agudeza Visual/fisiología , Adulto JovenRESUMEN
PURPOSE: The aim of our study was to describe the clinical presentation of an unusual evanescent, exudative, choroidal pseudo-tumor with acute painful onset, and propose a pathogenesis. METHODS: We carried out a retrospective, observational study using the case series of three patients presenting with an evanescent, exudative, choroidal pseudo-tumor with acute painful onset. Ultra-widefield fluorescein and indocyanine green angiography (ICGA) using the Heidelberg Retina Angiograph and the Staurenghi 230 SLO Retina Lens were used to propose a pathogenesis of this unusual entity. RESULTS: In all three cases, acute ocular pain led to discovery of an exudative, partially hemorrhagic choroidal mass (thickness 2.4 mm-4.1 mm on ultrasound) that quickly regressed within weeks. In the subacute phase, all patients showed choroidal circulation abnormalities on dynamic wide-field ICGA in the affected quadrant, with delayed arterio-venous filling in two patients, and a poorly-defined vortex vein in the third. The choroidal circulation abnormalities resolved within 8-12 weeks, simultaneously with the spontaneous resolution of the choroidal pseudo-tumor. The findings evoked a self-resolving vortex vein occlusion in the corresponding quadrants with acute, painful choroidal exudation. CONCLUSIONS: An evanescent, exudative, hemorragic choroidal pseudo-tumor with acute painful onset may be caused by a vortex vein occlusion. Future patients need to be studied with ICGA in the acute phase to confirm this hypothesis.
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Hemorragia de la Coroides/etiología , Neoplasias de la Coroides/etiología , Coroides/irrigación sanguínea , Dolor Ocular/etiología , Trombosis de la Vena/complicaciones , Enfermedad Aguda , Adulto , Anciano , Circulación Sanguínea , Hemorragia de la Coroides/diagnóstico , Neoplasias de la Coroides/diagnóstico , Colorantes , Exudados y Transudados , Dolor Ocular/diagnóstico , Angiografía con Fluoresceína , Humanos , Verde de Indocianina , Presión Intraocular , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trombosis de la Vena/diagnósticoRESUMEN
PURPOSE: To assess the role of vitreoretinal surgery in maximizing treatment outcome following complications after proton therapy for uveal melanoma and to evaluate its safety. METHODS: Retrospective chart study on 21 patients (2% of a total of 1,005 treated by proton therapy between January 2003 and August 2007) who had developed a complication requiring vitreoretinal surgery. Mean/median total follow-up after irradiation was 43/43 months (range, 12-70 months). RESULTS: Indications for surgery included vitreous hemorrhage (n = 13), epimacular membrane (n = 5), rhegmatogenous retinal detachment (n = 1), combined vitreous hemorrhage with total serous retinal detachment (n = 1), and vitritis (n = 1). Mean/median interval for vitreoretinal surgery after irradiation was 21/20 months (range, 4-45 months), and mean/median follow-up after pars plana vitrectomy was 22/23 months (range, 2-56 months). Pars plana vitrectomy was combined with retinal photocoagulation (n = 5), air/gas (n = 5), or silicone oil tamponade (n = 1). Mean Snellen visual acuity was 20/200 (0-20/40) before and 20/100 (0-20/25) after pars plana vitrectomy. A transient postoperative rise in intraocular pressure was measured in seven patients. Four patients developed phthisis bulbi. CONCLUSION: Vitreoretinal surgery was efficient in maximizing treatment outcome after proton therapy, as it allowed a better oncologic follow-up. Pars plana vitrectomy permitted panretinal photocoagulation to avoid neovascular glaucoma or retinal detachment repair. Macular surgery improved visual acuity, especially in anterior melanoma, whereas repeated surgery may increase the risk of enucleation.
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Melanoma/radioterapia , Terapia de Protones/efectos adversos , Traumatismos por Radiación/cirugía , Enfermedades de la Retina/cirugía , Neoplasias de la Úvea/radioterapia , Cirugía Vitreorretiniana/métodos , Adulto , Anciano , Terapia Combinada , Endotaponamiento/métodos , Femenino , Humanos , Presión Intraocular/fisiología , Coagulación con Láser/métodos , Masculino , Persona de Mediana Edad , Traumatismos por Radiación/etiología , Enfermedades de la Retina/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza Visual/fisiología , Vitrectomía/métodos , Adulto JovenAsunto(s)
Enfermedades de la Conjuntiva , Cuerpos Extraños en el Ojo , Conjuntiva/lesiones , Enfermedades de la Conjuntiva/diagnóstico , Cuerpos Extraños en el Ojo/diagnóstico , Cuerpos Extraños en el Ojo/cirugía , Femenino , Humanos , Persona de Mediana Edad , Procedimientos Quirúrgicos Oftalmológicos/métodosRESUMEN
PURPOSE: To describe a unique unilateral association between an iris stromal tumor and a macular focal choroidal excavation. CASE DESCRIPTION: A 40-year old patient presented with a small iris tumor associated with a unilateral macular lesion disclosed during a routine ophthalmologic examination. The patient was asymptomatic and visual function was not affected. After clinical and instrumental evaluation, a diagnosis of nonmelanocytic undefined stromal tumor of the iris associated with macular focal choroidal excavation was made. The size and shape of the two lesions remained stable during a 7-year follow-up and the patient did not develop other signs. CONCLUSION: The concurrent presence of a stromal iris tumor associated with focal choroidal excavation has never been reported. Further reports of this association are required in order to understand its exact pathogenesis.
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Enfermedades de la Coroides , Neoplasias del Iris , Humanos , Adulto , Enfermedades de la Coroides/diagnóstico , Neoplasias del Iris/complicaciones , Neoplasias del Iris/diagnóstico , Neoplasias del Iris/patología , Tomografía de Coherencia Óptica , Angiografía con Fluoresceína , Coroides/patologíaRESUMEN
OBJECTIVE: The aim of this study was to compare the clinical outcomes of adolescents and young adults (AYAs) with those of elder adult patients treated with proton therapy (PT) for uveal melanoma (UM). MATERIAL AND METHODS: A retrospective, comparative study was conducted in UM patients who underwent PT at the Ocular Oncology Unit of the Jules-Gonin Eye Hospital (University of Lausanne, Lausanne, Switzerland) and the Paul Scherrer Institute (PSI); (Villigen, Switzerland) between January 1997 and December 2007. Propensity score matching (PSM) was used to select for each AYA (between 15-39 years old) an elder adult patient (≥40 years) with similar characteristics. We assessed ocular follow-up, local tumor control, metastasis incidence, and overall and relative survival (OS and RS). Non-terminal outcomes were then compared between the two groups using competing risk survival analysis. RESULTS: Out of a total of 2261 consecutive UM patients, after excluding 4 children (<15 years) and 6 patients who were metastatic at presentation, we identified 272 AYA patients and matched 270 of them with 270 elder adult patients. Before PSM, the AYA patients had a higher incidence of primary iris melanoma (4.0% vs. 1.4%; p = 0.005), while the elder patients were more likely to have other neoplastic diseases at presentation (9% vs. 3.7%; p = 0.004). Ocular outcomes and local tumor control were similar in both groups. Cumulative metastasis incidence for the AYA and elder adult groups was 13% and 7.9% at 5 years and 19.7% and 12.7% at 10 years, respectively, which was not significantly different between the groups (p = 0.214). The OS was similar in the two groups (p = 0.602), with estimates in the AYA and elder adult groups of 95.5% and 96.6% at 5 years and 94.6% and 91.4% at 10 years, respectively. However, the relative survival (RS) estimation was worse in the AYA group than the elder group (p = 0.036). CONCLUSION: While AYAs treated with PT for UM have similar ocular outcomes and present the same metastasis incidence and OS as elder adults, their RS is worse than that in elder adults, when compared with the population in general.
RESUMEN
PURPOSE: To report the first case of choroidal schwannoma in a patient affected by PTEN hamartoma tumor syndrome (PHTS) and investigate the molecular involvement of the phosphatase and tensin homolog (PTEN) and neurofibromin 2 (NF2) genes in this rare intraocular tumor. DESIGN: Observational case report. PARTICIPANT: A 10-year-old girl diagnosed with PHTS. METHODS: The enucleated specimen underwent histologic, immunohistochemical, and transmission electronic microscopy. The expression of PTEN and NF2 and their protein products were evaluated by reverse transcription-polymerase chain reaction and immunohistochemistry. Somatic mutations of PTEN and NF2, as well as allelic loss, were investigated by direct sequencing of DNA extracted from the tumor. PTEN epigenetic silencing was investigated by pyrosequencing. MAIN OUTCOME MEASURES: Histopathologic and molecular characterization of a choroidal pigmented schwannoma. RESULTS: Histopathologic, immunohistochemical, and electron microscopic analysis demonstrated features consistent with a pigmented cellular schwannoma of the choroid. We found no loss of heterozygosity at the genomic level for the PTEN germline mutation and no promoter hypermethylation or other somatic intragenic mutations. However, we observed an approximate 40% reduction of PTEN expression at both the mRNA and the protein level, indicating that the tumor was nonetheless functionally deficient for PTEN. Although DNA sequencing of NF2 failed to identify any pathologic variants, its expression was abolished within the tumor. CONCLUSIONS: We report the first description of a pigmented choroidal schwannoma in the context of a PHTS. This rare tumor showed a unique combination of reduction of PTEN and absence of NF2 expression.
Asunto(s)
Neoplasias de la Coroides/genética , Síndrome de Hamartoma Múltiple/genética , Neurilemoma/genética , Neurofibromina 2/genética , Fosfohidrolasa PTEN/genética , Niño , Neoplasias de la Coroides/diagnóstico por imagen , Neoplasias de la Coroides/patología , Metilación de ADN , Análisis Mutacional de ADN , ADN de Neoplasias/genética , Enucleación del Ojo , Femenino , Síndrome de Hamartoma Múltiple/diagnóstico por imagen , Síndrome de Hamartoma Múltiple/patología , Humanos , Inmunohistoquímica , Neurilemoma/diagnóstico por imagen , Neurilemoma/patología , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ultrasonografía , Agudeza VisualAsunto(s)
Neoplasias de la Conjuntiva/genética , Melanoma/genética , Luz Solar/efectos adversos , Anciano , Neoplasias de la Conjuntiva/etiología , Neoplasias de la Conjuntiva/patología , Daño del ADN/genética , Daño del ADN/efectos de la radiación , Femenino , Humanos , Melanoma/etiología , Melanoma/fisiopatología , Persona de Mediana Edad , Piel/fisiopatología , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversosRESUMEN
Complete achromatopsia is a rare autosomal recessive disease associated with CNGA3, CNGB3, GNAT2 and PDE6C mutations. This retinal disorder is characterized by complete loss of color discrimination due to the absence or alteration of the cones function. The purpose of the present study was the clinical and the genetic characterization of achromatopsia in a large consanguineous Tunisian family. Ophthalmic evaluation included a full clinical examination, color vision testing and electroretinography. Linkage analysis using microsatellite markers flanking CNGA3, CNGB3, GNAT2 and PDE6C genes was performed. Mutations were screened by direct sequencing. A total of 12 individuals were diagnosed with congenital complete achromatopsia. They are members of six nuclear consanguineous families belonging to the same large consanguineous family. Linkage analysis revealed linkage to GNAT2. Mutational screening of GNAT2 revealed three intronic variations c.119-69G>C, c.161+66A>T and c.875-31G>C that co-segregated with a novel mutation p.R313X. An identical GNAT2 haplotype segregating with this mutation was identified, indicating a founder mutation. All patients were homozygous for the p.R313X mutation. This is the first report of the clinical and genetic investigation of complete achromatopsia in North Africa and the largest family with recessive achromatopsia involving GNAT2; thus, providing a unique opportunity for genotype-phenotype correlation for this extremely rare condition.
Asunto(s)
Codón sin Sentido , Defectos de la Visión Cromática/diagnóstico , Defectos de la Visión Cromática/genética , Proteínas del Ojo/genética , Adolescente , Adulto , Niño , Codón sin Sentido/fisiología , Defectos de la Visión Cromática/fisiopatología , Análisis Mutacional de ADN , Familia , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Linaje , Polimorfismo de Nucleótido Simple/fisiología , Transducina/genética , Túnez , Adulto JovenRESUMEN
PURPOSE: To describe a patient with metastatic choroidal paraganglioma that was locally controlled with radiotherapy. DESIGN: Interventional clinicopathologic case report. PARTICIPANT: One patient with metastatic choroidal paraganglioma. METHODS: Interventional clinicopathologic case report and systematic search of the literature. MAIN OUTCOME MEASURES: Description of clinicopathologic features, treatment methods, and outcome. RESULTS: A 50-year-old man had a nonpigmented atypical choroidal mass with secondary retinal detachment in the left eye. After incisional biopsy, the diagnosis of paraganglioma was established. Metastatic work-up revealed vertebral, mediastinal, and pulmonary metastases of a nonsecretory, malignant paraganglioma without tracer uptake. The primary tumor was not identified. The ocular tumor regressed after stereotaxic radiotherapy. Two years later, recurrent lesions developed in the contralateral eye, which also was irradiated. CONCLUSIONS: Malignant paraganglioma can metastasize in the choroid and should be included in the differential diagnosis of a nonpigmented choroidal mass. Stereotaxic radiation therapy is an effective treatment method. To the authors' knowledge, this is the first report of a patient with choroidal paraganglioma. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Asunto(s)
Neoplasias de la Coroides/secundario , Neoplasias Pulmonares/secundario , Neoplasias del Mediastino/secundario , Paraganglioma/secundario , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Coroides/diagnóstico por imagen , Neoplasias de la Coroides/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Paraganglioma/diagnóstico por imagen , Paraganglioma/radioterapia , Ultrasonografía , Agudeza Visual/fisiologíaRESUMEN
BACKGROUND: Choriocarcinoma is a very rare cause of ocular metastasis. Only 18 male patients have been reported on, 4 of whom survived, but with significant loss of vision. CASE PRESENTATION: A 26-year-old Caucasian man, suffering from testicular choriocarcinoma with pulmonary, cerebral, renal, hepatic and osseous metastases, underwent left radical orchiectomy. While being treated with chemotherapy, he presented with loss of vision in the left eye. Ophthalmoscopy revealed bilateral non-pigmented, hemorrhagic choroidal tumours, compatible with secondary lesions. Continued chemotherapy and stereotactic radiotherapy of the skull and spine lead to full remission with excellent vision, after more than 4 years of follow up. CONCLUSION: Testicular choriocarcinoma is an exceptional cause of choroidal metastasis, potentially asymptomatic and with specific clinical features. Radiotherapy can complement radical orchiectomy and chemotherapy, to achieve full remission and maintain good vision.
Asunto(s)
Quimioradioterapia/métodos , Coriocarcinoma/terapia , Neoplasias de la Coroides/terapia , Neoplasias Testiculares/terapia , Adulto , Coriocarcinoma/diagnóstico , Neoplasias de la Coroides/diagnóstico , Humanos , Masculino , Resultado del TratamientoRESUMEN
PURPOSE: To report the case of a small pigmented tumor in the macular region investigated using optical coherence tomography angiography (OCT-A) in the context of a multimodal approach. METHODS: Case report. RESULTS: A 24-year-old man was referred for evaluation of an asymptomatic unilateral round comma-shaped pigmented tumor located in the macular region of his right eye. Spectral-domain OCT revealed an irregular hyperreflective mass within the retina, with a thickened hyaloid membrane and abrupt margins, and a complete posterior shadowing effect. On fluorescein angiography, early hyperfluorescence without leakage in the middle and late phases and a subtle halo of hyperfluorescence in the late phase were observed. OCT-A revealed the presence of intrinsic vascularization at the level of the inner capillary plexus, with signal intensity present at the level of the outer capillary plexus. In the superficial scans, the retinal vessels were oriented radially to the lesion and were in continuity with the vascular network within the tumor mass. No choroidal vessels could be identified. CONCLUSION: We report the case of a congenital simple hamartoma of the retinal pigment epithelium investigated using OCT-A as part of multimodal imaging. OCT-A provided a new insight in the assessment of the lesion, differential diagnosis, and follow-up of the patient. This imaging modality could be an important non-invasive tool in the management of congenital hamartomas of the retinal pigment epithelium.