RESUMEN
INTRODUCTION: Primary uveal melanoma is the most common intraocular malignancy in adults. Almost 50% of patients die from metastatic disease despite successful local treatment. The objective was to estimate the incidence of metastasis and survival in patients with primary uveal melanoma. The second objective was to determine the independent predictors of metastasis. METHODS: A retrospective, observational, analytical study was carried out using an ambidirectional cohort design in patients from Buenos Aires City between January 2003 to January 2020. Patients with uveal melanoma and potential clinical predictors of metastasis were identified. The density of incidence of metastasis and mortality were determined, and survival curves were analyzed (Kaplan Meir) A univariate and multivariate analysis using Cox proportional hazard models was performed. RESULTS: 143 patients (mean age 57 SD 16) were included. The median thickness was 6.2 mm SD 3.4 mm, the mean tumor diameter was 12.6 mm (SD 3.8). 69.9% of the patients underwent conservative treatment with brachytherapy while 25.9% underwent enucleation. 19.6% presented metastasis, the median time to the event was 26.5 months. The specific mortality due to melanoma was 17.5%. Diameter greater than 12 mm and extension were predictor variables of metastasis in a multivariable model. CONCLUSION: Although the median time to the event (metastasis) is 26.5 moths, it could occur many years after local oncological effective treatment. An early diagnosis would allow finding smaller tumors and would improve the prognosis.
Introducción: El melanoma uveal primario es el tumor intraocular maligno más frecuente del adulto. Cerca del 50% de los pacientes fallecen de enfermedad metastásica, a pesar de un tratamiento local exitoso. El objetivo primario fue estimar la incidencia de metástasis y sobrevida en los pacientes con melanoma uveal primario. Como objetivo secundario se planteó determinar los predictores independientes de metástasis. Métodos: Se realizó un estudio analítico observacional, retrospectivo mediante un diseño de cohorte ambidireccional entre 2003 y 2020 en CABA, en pacientes con melanoma uveal primario y los potenciales factores clínicos predictores de metástasis. Se determinó la densidad de incidencia de metástasis, la mortalidad, y se analizaron las curvas de sobrevida (Kaplan-Meier). Se realizó un análisis uni y multivariado utilizando el modelo de riesgos proporcionales de Cox. Resultados: De los 143 pacientes (edad promedio 57, DS 16), la mediana del espesor fue de 6. 2 mm DS 3.4, la media del diámetro tumoral fue de 12.6 mm (DS 3.8). Un 69.9% realizó tratamiento conservador con braquiterapia, un 25.9% enucleación. Un 19.6% presentaron metástasis (mediana de tiempo al evento: 26.5 meses). La mortalidad específica por melanoma fue de 17.5%. El diámetro mayor a 12 mm y la extensión fueron variables predictoras de metástasis en el modelo multivariado. Conclusión: Si bien la mediana del tiempo al evento metástasis fue de 26.5 meses, puede presentarse muchos años después de un tratamiento local oncológicamente eficaz. Un diagnóstico precoz permitiría pesquisar tumores más pequeños y mejoraría el pronóstico.
Asunto(s)
Melanoma , Neoplasias de la Úvea , Humanos , Melanoma/mortalidad , Melanoma/patología , Melanoma/secundario , Neoplasias de la Úvea/mortalidad , Neoplasias de la Úvea/patología , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Incidencia , Anciano , Adulto , Metástasis de la Neoplasia , Argentina/epidemiología , Braquiterapia , Modelos de Riesgos Proporcionales , Anciano de 80 o más Años , Estimación de Kaplan-Meier , Tasa de SupervivenciaRESUMEN
Importance: Multi-institutional collaborative studies that include large patient populations for the management of retinoblastoma with histopathological risk factors could provide important information for patient management. Objective: To evaluate the implementation of a strategy for the management of nonmetastatic unilateral retinoblastoma in children based on standardized diagnostic and treatment criteria. Design, Setting, and Participants: This single-arm prospective study applied a strategy based on a single-center experience. The setting was a multicenter study in Latin America (Grupo de America Latina de Oncologia Pediatrica [GALOP]). Participants were children with nonmetastatic unilateral retinoblastoma (staged with the International Retinoblastoma Staging System). The study opened on July 1, 2008, and closed on December 31, 2014. Follow-up was updated until June 30, 2017. Interventions: Stage 0 patients (without enucleation) were given conservative therapy without a protocol. Stage I patients (with enucleation and no residual tumor) were divided into a high-risk group (retrolaminar invasion and/or scleral invasion) and a low-risk group (all remaining patients). High-risk children received adjuvant chemotherapy with 4 alternating cycles of regimen 1 (cyclophosphamide [65 mg/kg/d] [plus sodium-2-mercaptoethane sulfonate], idarubicin hydrochloride [10 mg/m2/d], and vincristine sulfate [0.05 mg/kg/d]) and 4 cycles of regimen 2 (carboplatin [500 mg/m2/d, days 1 and 2] and etoposide [100 mg/m2/d, days 1-3]). Low-risk children did not receive adjuvant therapy. Children with buphthalmia received neoadjuvant and adjuvant chemotherapy for a total of 8 cycles. Main Outcomes and Measures: Probability of event-free survival (extraocular relapse and death from any cause were considered events). Results: Among 187 children registered in the study, 175 were evaluable (92 [52.5%] female; median age, 22 months; age range, 3-100 months). Forty-two were stage 0 children, 84 were stage I low-risk children, and 42 were stage I high-risk children; there were 7 children in the buphthalmia group. With a median follow-up of 46 months, the 3-year probability of event-free survival was 0.97 (95% CI, 0.94-0.99), and the probability of overall survival was 0.98 (95% CI, 0.94-1.00). Stage 0 patients had no events, stage I low-risk patients had 1 event (orbital relapse treated with second-line therapy), stage I high-risk patients had 2 events (1 central nervous system relapse and 1 death from sepsis), and the buphthalmia group had 1 event (orbital relapse, followed by central nervous relapse and death). Conclusions and Relevance: Adjuvant therapy may be effective for high-risk unilateral retinoblastoma but is toxic, and neoadjuvant chemotherapy for buphthalmus appears feasible.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Retina/tratamiento farmacológico , Retinoblastoma/tratamiento farmacológico , Carboplatino/administración & dosificación , Niño , Preescolar , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Enucleación del Ojo , Femenino , Humanos , Hidroftalmía/complicaciones , Idarrubicina/administración & dosificación , Lactante , Masculino , Mesna/administración & dosificación , Metástasis de la Neoplasia , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias de la Retina/mortalidad , Neoplasias de la Retina/patología , Retinoblastoma/mortalidad , Retinoblastoma/patología , Tasa de Supervivencia , Vincristina/administración & dosificaciónRESUMEN
PURPOSE: The objective is to analyze the antiangiogenic mechanism of suramab, a pharmaceutical compound of bevacizumab and suramin, in a rabbit model of corneal angiogenesis. MATERIAL AND METHODS: Corneal neovascularization was induced in four groups of six New Zealand White rabbits by applying a filter paper disk soaked in 1 M Na (OH) on the central cornea. Group one was treated after injury with intravenous suramab at a dose equivalent to 3 mg/kg of bevacizumab and 10 mg/kg of suramin. Group two was treated with intravenous bevacizumab (5 mg/kg). Group three was treated with 10 mg/kg of suramin while the control group received no treatment. Digital photographs were taken at days 9, 15, 21, and 35. Neovessel formation was quantified giving a 0-4 score to each quadrant according to the centripetal growth of the longest vessel (neovessel index, NVI). Animals were sacrificed at day 35. Corneas were processed for histology, immunohistochemistry, and Western-blot using primary antibodies against P2X2, basic fibroblast growth factor (bFGF), LYVE-1, PECAM-1, and vascular endothelial growth factor-A (VEGF-A). RESULTS: Suramab significantly reduced neovessel growth (mean NVI: 4.2) compared to bevacizumab (8.4), suramin (7.22), and control animals (12.2) at 35 days post-injury (p < 0.01). A lower protein expression of P2X2, bFGF, LYVE-1, PECAM-1, and VEGF-A was found in the cornea of suramab animals than in the other groups of animals. CONCLUSIONS: Joint downregulation of bFGF, P2X2, bFGF, and LYVE-1 constitutes a mechanism that induces greater and longer inhibition of corneal angiogenesis. Results might be relevant to ophthalmic care. Ocular administration of suramab is currently being investigated.
Asunto(s)
Bevacizumab/farmacología , Córnea/patología , Neovascularización de la Córnea/tratamiento farmacológico , Regulación hacia Abajo/efectos de los fármacos , Factor 2 de Crecimiento de Fibroblastos/biosíntesis , Receptores Purinérgicos P2X2/biosíntesis , Suramina/farmacología , Animales , Western Blotting , Córnea/metabolismo , Neovascularización de la Córnea/metabolismo , Neovascularización de la Córnea/patología , Modelos Animales de Enfermedad , Combinación de Medicamentos , Inmunohistoquímica , ConejosRESUMEN
BACKGROUND: Radial optic neurotomy (RON) has been proposed as a treatment for central retinal vein occlusion. However, it is still under debate whether RON would be an adequate treatment or a dangerous procedure, and persuasive animal studies are lacking. The aim of this study was to analyze the early histologic and functional outcomes of RON in normal rat eyes. METHODS: Radial optic neurotomy was performed by cutting into the optic nerve edge at the nasal hemisphere, while the contralateral eye underwent a sham procedure. The retinal function was assessed by scotopic electroretinography, and the visual pathway was assessed by flash visual evoked potentials. Intraocular pressure was assessed with a tonometer, the pupillary light reflex was measured after exposing eyes to a 30-second light flash, whereas the optic nerve head structure was examined by histologic analysis. RESULTS: In normal rat eyes, RON provoked minor histologic alterations at the optic nerve head level and a transient decrease in the electroretinography. No changes in visual evoked potentials, intraocular pressure, and pupillary light reflex were observed in rat eyes submitted to RON. CONCLUSION: To our knowledge, this is the first study describing the early histopathologic and functional consequences of RON in normal rat eyes.
Asunto(s)
Potenciales Evocados Visuales/fisiología , Procedimientos Quirúrgicos Oftalmológicos , Disco Óptico/cirugía , Nervio Óptico/cirugía , Retina/fisiología , Animales , Descompresión Quirúrgica , Electrorretinografía , Presión Intraocular/fisiología , Masculino , Disco Óptico/irrigación sanguínea , Nervio Óptico/irrigación sanguínea , Estimulación Luminosa , Ratas , Ratas Wistar , Reflejo Pupilar/fisiología , Vías Visuales/fisiologíaRESUMEN
PURPOSE: Oncological and ophthalmological diseases are increasingly treated with antiangiogenic agents. These agents have different intensities and duration of effects that should be considered to choose the most suitable therapy. Our purpose was to evaluate the synergistic effect of two drugs, jointly administered as a pharmaceutical compound, in two animal models. METHODS: Corneal neovascularization was induced in three groups of nine white New Zealand rabbits, applying a filter paper disk soaked in 1 M NaOH on the central cornea (Ormerod et al., Invest Ophthalmol Vis Sci 30:2148-2153, 1989). Group one was treated immediately after injury with intravenous Suramab, compound of Bevacizumab + Suramin, and group two with intravenous Bevacizumab. A third group of non-treated rabbits was included as control group. Digital photographs were taken at days 9, 15, 21, and 35. Neovessel index (NVI) was calculated using the Image J Program. Neovessels formation was quantified and given a score from 0 to 4 to each quadrant according to the centripetal growth of the longest vessel. Colorectal animal model: 6- to 8-week-old male BALB/c mice were inoculated with cancer cells. Seven days after tumor inoculation, four groups of BALB/c mice were treated with intravenous Bevacizumab (n = 9); intravenous Suramin (n = 10); intravenous Suramab (n = 10); and intravenous saline solution (n = 4). Tumor growth was assessed twice weekly by caliper measurement. RESULTS: The NVI was remarkably inferior in the group of rabbits treated with intravenous Suramab compared with controls after 35 days of follow-up. A greater inhibitory effect was obtained with Suramab compared to that obtained with Bevacizumab. Suramab significantly reduced tumor volume and prolonged survival of mice compared to controls. CONCLUSIONS: Suramab strongly reduced neovascularization in a rabbit model of corneal angiogenesis and induced a potent antitumoral effect in mice.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Anticuerpos Monoclonales/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neovascularización de la Córnea/tratamiento farmacológico , Suramina/farmacología , Inhibidores de la Angiogénesis/administración & dosificación , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Bevacizumab , Neoplasias Colorrectales/patología , Neovascularización de la Córnea/patología , Modelos Animales de Enfermedad , Combinación de Medicamentos , Sinergismo Farmacológico , Inyecciones , Masculino , Ratones , Ratones Endogámicos BALB C , Conejos , Suramina/administración & dosificación , Sobrevida , Factores de TiempoRESUMEN
PURPOSE: To evaluate the short- and long-term sequential histological changes of the cornea in vivo after corneal collagen cross-linking (CXL) in patients with keratoconus. METHODS: Eighteen patients with keratoconus (Amsler-Krumeich classification: stages I, II, and III) underwent CXL with riboflavin/ultraviolet A (UVA) in one eye. The corneas were examined preoperatively and within 5 hours, 7 and 14 days, and 1, 3, 6, 9, 12, 18, 24, and 36 months after the procedure using in vivo confocal microscopy. RESULTS: Early changes included edema, superficial nerve loss, cellular modifications, and isolated endothelial damage. At intermediate time points, there was nerve fiber regeneration, increased reflectivity of the extracellular matrix, enlarged keratocytes and extracellular deposits, and remodeling of the endothelial layer (two eyes). At later time points, loss of keratocytes and remodeling of the extracellular deposits were noted. CONCLUSIONS: Although the cornea has no significant tissue modifications clinically after CXL, this study has shown that corneal wounding by riboflavin/UVA collagen CXL induces cellular wound-healing mechanisms and alters the normal structure and cellularity of the cornea for up to 36 months.
Asunto(s)
Córnea/patología , Queratocono/tratamiento farmacológico , Queratocono/patología , Fotoquimioterapia , Fármacos Fotosensibilizantes/uso terapéutico , Cicatrización de Heridas , Adolescente , Adulto , Colágeno/metabolismo , Sustancia Propia/metabolismo , Reactivos de Enlaces Cruzados , Femenino , Humanos , Queratocono/metabolismo , Masculino , Microscopía Confocal , Persona de Mediana Edad , Riboflavina/uso terapéutico , Rayos Ultravioleta , Adulto JovenRESUMEN
Purpose. Intravenous or periocular topotecan has been proposed as new treatment modality for patients with advanced intraocular retinoblastoma, but systemic topotecan lactone exposure induced by both approaches may cause toxicity. The purpose of this study was to develop a topotecan-loaded ocular delivery system to minimize systemic exposure and achieve selective transscleral penetration. Methods. Biocompatible polymer implants containing low (0.3 mg) or high (2.3 mg) topotecan load were manufactured and characterized in vitro. Adrenaline (500 mug) was coloaded to induce local vasoconstriction in vivo in 2 of 4 animal groups. Implants were inserted into the episclera of rabbits, and topotecan (lactone and total) concentrations in ocular tissues and plasma were determined over a period of 48 hours. Results. In vitro, implants released 30% to 50% of the loaded drug within 48 hours and 45% to 70% by day 10. In vivo, topotecan lactone was highly accumulated in locally exposed ocular tissues (ranging from 10(5) to 10(6) ng/g in sclera and choroid and 10(2) to10(3) ng/g in retina) over 48 hours with all the formulations studied. Low vitreous topotecan lactone levels (approximately 5 ng/mL) were found in animals receiving concomitant local vasoconstriction and high load implants. Topotecan lactone concentrations in plasma and in contralateral eyes were minimal or undetectable as a marker of tissue selectivity of the proposed strategy. Conclusions. These studies may contribute to improving the efficacy and safety of chemotherapy treatments for retinoblastoma and may support the role of the local vasculature and tissues promoting drug clearance and local accumulation during transscleral drug delivery.
Asunto(s)
Antineoplásicos/administración & dosificación , Coroides/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Retina/efectos de los fármacos , Esclerótica , Topotecan/administración & dosificación , Animales , Antineoplásicos/farmacocinética , Coroides/metabolismo , Implantes de Medicamentos , Epinefrina/administración & dosificación , Poliésteres , Conejos , Retina/metabolismo , Distribución Tisular , Topotecan/farmacocinéticaRESUMEN
PURPOSE: To evaluate the usefulness of epithelial corneal sheets mounted on platelet poor plasma (PPP) for allograft transplantation of rabbits with total limbal stem cell deficiency (LSCD) and to prove its efficacy at 1 year after surgery. METHODS: LSCD was induced in 21 female rabbits by mechanical keratectomy. To configure the grafts, limbal biopsies were taken from male rabbits and cells were cultured on a fibroblast feeder layer grown on clotted autologous PPP. After keratectomy, grafts were sutured over the stroma. Control groups consisted of no implant or an implant of clotted PPP. Rabbits were euthanized at 3 and 12 months. Corneas and cultured sheets were processed for histopathology and immunohistochemistry (K3/12 and K19). Gender analysis was performed at 4 and 7 months. RESULTS: One rabbit had endophthalmitis, and another died of no apparent cause. The rest of the animals treated had no inflammation, showed a stratified epithelium, keratin 3/12 expression, and no expression of keratin 19. At 1 year, seven of eight rabbits showed no LSCD or corneal rejection signs. Y chromosomes were detected at 4 and 7 months postoperatively. All controls showed LSCD signs, erratic epithelium, and minimal cell differentiation; they revealed a slight expression of K3/12 and an expression of K19 in patchy patterns. CONCLUSIONS: Allografts contributed to restoring a healthy eye surface without signs of graft rejection. This technique seems to be a promising procedure for bilateral ocular surface diseases and may be useful for new therapeutic strategies.
Asunto(s)
Plaquetas/metabolismo , Epitelio Corneal/trasplante , Animales , Enfermedades de la Córnea/patología , Enfermedades de la Córnea/cirugía , Epitelio Corneal/patología , Femenino , Técnica del Anticuerpo Fluorescente , Estudios de Seguimiento , Masculino , Neovascularización Patológica/terapia , Conejos , Trasplante HomólogoRESUMEN
PURPOSE: To evaluate the efficacy of autologous corneal epithelial sheet implantation in restoring transparency of rabbit corneas severely injured by alkaline and the effect of photocoagulation in arresting corneal neovessel ingrowth. SETTING: Ophthalmology Department, School of Biomedical Sciences, Universidad Austral, Buenos Aires, Argentina. METHODS: Limbal stem-cell deficiency (LSCD) was induced in 14 rabbits by alkali burns. A limbal cell biopsy was done in the contralateral eye, and the cells were cultured on a fibroblast feeder layer grown on autologous clotted platelet-poor plasma or commercial fibrin for 21 days. Anterior keratectomy was followed by suturing corneal cell sheets over the stroma. If regrowth of vessels occurred, argon laser photocoagulation was applied to them. Rabbits were killed at 30, 60, 90, 180, and 360 days and the corneas processed for histopathology and inmunohistochemistry. RESULTS: A small (2.5 mm(2)) limbal biopsy achieved stem-cell replication in vitro. Corneal clarity and epithelial defects evolved with a trend toward improvement. There was a significant reduction in corneal neovascularization. Histology showed a multilayered stratified epithelium including several epithelial-like cells with clear cytoplasm in the deepest part. There were no signs of intraepithelial mucin cells on the implanted corneas. Immunohistochemical results showed expression of cytokeratins 3 and 12 in the central corneal epithelium and an absence of cytokeratin 19. CONCLUSIONS: Autologous limbal epithelial cell transplantation improved the corneal surface in eyes with LSCD. Photocoagulation of neovessel ingrowth was effective over the 1-year follow-up. Results may facilitate the application of this technique in patients.
Asunto(s)
Quemaduras Químicas/cirugía , Epitelio Corneal/citología , Quemaduras Oculares/inducido químicamente , Limbo de la Córnea/citología , Trasplante de Células Madre , Animales , Biopsia , Células Cultivadas , Técnicas de Cocultivo , Neovascularización de la Córnea/cirugía , Modelos Animales de Enfermedad , Epitelio Corneal/metabolismo , Inmunohistoquímica , Queratina-12/metabolismo , Queratina-19/metabolismo , Queratina-3/metabolismo , Coagulación con Láser , Conejos , Hidróxido de Sodio , Trasplante AutólogoRESUMEN
This report makes reference to the refractive surgery and the corneal cicatrization. Previous description of the corneal structure, details the corneal cicatrizative process. Special attention was dedicated to the visual corrective effects following corneal surgery(AU)
Asunto(s)
Humanos , Extracción de Catarata , Miopía/cirugía , Hiperopía/cirugía , Astigmatismo/cirugía , Homeostasis , Córnea , Cicatrización de Heridas , Queratectomía Fotorrefractiva , Láseres de Excímeros , Miopía/diagnóstico , Hiperopía/diagnóstico , Astigmatismo/diagnósticoRESUMEN
This report makes reference to the refractive surgery and the corneal cicatrization. Previous description of the corneal structure, details the corneal cicatrizative process. Special attention was dedicated to the visual corrective effects following corneal surgery
Asunto(s)
Humanos , Astigmatismo , Extracción de Catarata , Córnea , Homeostasis , Hiperopía , Láseres de Excímeros , Miopía , Queratectomía Fotorrefractiva , Cicatrización de Heridas , Astigmatismo , Hiperopía , MiopíaRESUMEN
We used an Orbscan II topography system (Bausch & Lomb) to study anterior and posterior surface abnormalities, keratometry, and topographic pachymetry in a patient with circumscribed posterior keratoconus. This system clearly showed a marked localized paracentral annular elevation in the posterior corneal surface that corresponded to an abrupt decrease in thickness and a slightly localized anterior surface bulge in the anterior float.
Asunto(s)
Topografía de la Córnea/métodos , Endotelio Corneal/patología , Queratocono/diagnóstico , Dilatación Patológica , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To report a patient with a cystadenocarcinoma of the lacrimal gland, a tumor not previously described in the ophthalmic literature. Salivary gland cystadenocarcinomas constitute a distinct group of epithelial malignancies characterized by an invasive, predominantly cystic pattern of growth that have an indolent behavior and a low incidence of metastases and recurrences. DESIGN: Single interventional case report. METHODS: The clinical findings, results of imaging studies, and pathologic findings are presented. RESULTS: A 67-year-old man presented with a 5-year history of ptosis in the right upper eyelid. A lacrimal fossa tumor was found. The tumor was excised with an intact capsule, and the histopathologic diagnosis was primary cystadenocarcinoma of the lacrimal gland. The patient received no other form of treatment and has been observed for 1 year without evidence of recurrence or metastatic disease. CONCLUSIONS: Until recently, primary adenocarcinomas of the lacrimal gland were not further subclassified. Current knowledge gained from salivary gland tumors indicates that primary adenocarcinoma encompasses a group of tumors with separate morphologic features and varied biologic behavior.