Posibilidad de terapia génica en pacientes con enfermedades retinianas hereditarias / Possibility of genetic therapy for inherited retinal conditions

Objetivo Evaluar la posibilidad de terapia génica en pacientes con enfermedades oculares hereditarias con diagnóstico genético establecido. Los objetivos secundarios son revisar la tasa de diagnóstico genético y hacer una actualización de los genes para los cuales hay estudios clínicos o preclínicos en curso que pudieran permitir la terapia génica. Métodos Estudio observacional, retrospectivo y multicéntrico de 177 pacientes con enfermedades oculares hereditarias a quienes se realizó estudio genético.Resultados De 177 pacientes con estudio genético, se incluyeron 146. Se identificaron variantes causantes de enfermedad en 117 pacientes con lo que se obtuvo una tasa de detección de variantes del 80,1%. Se encontraron variantes patogénicas en 47 genes, siendo ABCA4 el gen más común (17,9%), seguido por CRB1 (11,9%). De los pacientes con diagnóstico genético, el 64,1% tienen una variante en un gen para el cual se ha estudiado terapia génica y solo el 40,1% presentan una variante en genes con estudios para su terapia génica en fase clínica. Conclusiones El estudio genético ha abierto nuevos horizontes en el manejo de pacientes con enfermedades oculares hereditarias. Cerca de dos tercios de los pacientes presentó variantes patogénicas en genes para los cuales se ha evaluado la posibilidad de terapia génica. Sin embargo, muchos estudios se encuentran en fase preclínica. Se debe adecuar las expectativas de los pacientes sometidos a estudio genético y sus familias (AU)

Objective To evaluate the possibility of gene therapy in patients with inherited ocular conditions and established genetic diagnosis. The secondary objectives were to determine the genetic diagnostic rate and to update the list of genes for which there are ongoing clinical trials or preclinical studies that could allow for gene therapy. Methods Observational, retrospective, multicentric study of 177 patients with inherited ocular conditions that underwent genetic testing. Results Of 177 patients with genetic testing, 146 were enrolled for this study. Disease-causing variants were identified in 117 patients (variant detection rate of 80.1%). Pathogenic variants were found in 47 genes, with ABCA4 being the most common gene (17.9%), followed by CRB1 (11.9%). 64.1% of patients with a genetic diagnosis have a variant in genes for which gene therapy has been studied and only 40.1% have a variant in genes with studies for gene therapy in clinical phase. Conclusions Genetic testing has opened new horizons in the management of patients with hereditary ocular diseases. About two-thirds of the patients had pathogenic variants in genes for which gene therapy has been evaluated. However, many studies are in the pre-clinical phase. The expectations of patients undergoing genetic study and their families should be managed accordingly (AU)

Possibility of genetic therapy for inherited retinal conditions.

OBJECTIVE: To evaluate the possibility of gene therapy in patients with inherited ocular conditions and established genetic diagnosis. The secondary objectives were to determine the genetic diagnostic rate and to update the list of genes for which there are ongoing clinical trials or preclinical studies that could allow for gene therapy. METHODS: Observational, retrospective, multicentric study of 177 patients with inherited ocular conditions that underwent genetic testing. RESULTS: Of 177 patients with genetic testing, 146 were enrolled for this study. Disease-causing variants were identified in 117 patients (variant detection rate of 80.1%). Pathogenic variants were found in 47 genes, with ABCA4 being the most common gene (17.9%), followed by CRB1 (11.9%). 64.1% of patients with a genetic diagnosis have a variant in genes for which gene therapy has been studied and only 40.1% have a variant in genes with studies for gene therapy in clinical phase. CONCLUSIONS: Genetic testing has opened new horizons in the management of patients with hereditary ocular diseases. About two-thirds of the patients had pathogenic variants in genes for which gene therapy has been evaluated. However, many studies are in the pre-clinical phase. The expectations of patients undergoing genetic study and their families should be managed accordingly.

Intra-arterial chemotherapy for retinoblastoma treatment in Chile: Experience and results 2013-2020.

OBJECTIVE: To establish the success rate of salvage intra-arterial chemotherapy (IAC), defined as the percentage of eyes that achieved tumoral remission and avoided enucleation. The second objective was the clinical characterization, catheterization results, and associated local and systemic complications. METHODS: Retrospective, interventional case series of 29 patients (35 eyes) with persistent or recurrent retinoblastoma. RESULTS: A total of 73 salvage IAC procedures with topotecan and melphalan were carried out. Success rate was 77% at a mean follow-up of 41.4 months. All patients with only one remaining eye avoided enucleation (10 cases). Catheterization was successful in 98.6% of cases. The types of catheterizations were as follows: 71.2% supraselective ophthalmic artery, 12.3% occlusion pump assisted supraselective ophthalmic artery, 16.4% selective external carotid with retrograde flow. 14% of patients suffered local adverse effects: 1 (2.8%) transitory ptosis, 1 (2.8%) transitory oculomotor nerve palsy, 2 (5.7%) aseptic cellulitis and 1 (2.8%) periorbitary pigmentation. 4.1% (3 cases) suffered neutropenia due to medullar chemosuppression. There were no cases of severe anemia or thrombocytopenia. There were no cerebral ischemic events or mortality associated to the procedure. CONCLUSION: IAC with melphalan and topotecan is a safe and effective treatment option for persistent or recurrent retinoblastoma, able to reduce enucleation rates.

Quimioterapia intraarterial para el tratamiento del retinoblastoma en Chile: experiencia y resultados, período 2013-2020 / Intra-arterial chemotherapy for retinoblastoma treatment in Chile: experience and results 2013-2020

Objetivo Establecer la tasa de éxito de la quimioterapia intraarterial (QIA) en modalidad de rescate expresada en el porcentaje de ojos que lograron remisión tumoral y evitaron la enucleación. El segundo objetivo fue analizar la caracterización clínica, resultados del cateterismo, complicaciones locales y sistémicas asociadas. Métodos Estudio retrospectivo de serie de casos intervencional de 29 pacientes (35 ojos) con retinoblastoma intraocular persistente o recidivado. Resultados Se realizaron un total de 73 procedimientos de QIA con topotecán y melfalán en modalidad de rescate. La tasa de éxito de la QIA fue del 77% en un seguimiento promedio de 41,4 meses. Todos los casos con ojo único evitaron la enucleación de su ojo residual (10 casos). El cateterismo fue exitoso en un 98,6%. Los tipos de cateterización logrados fueron los siguientes: supraselectiva por arteria oftálmica (71,2%), supraselectiva por arteria oftálmica asistida con balón de oclusión en carótida externa (12,3%), selectiva por rama de carótida externa con flujo retrógrado (16,4%). Se reportaron efectos adversos locales en el 14% de los pacientes: una (2,8%) ptosis palpebral transitoria, una (2,8%) parálisis del sexto par transitoria, 2 (5,7%) celulitis aséptica y una (2,8%) pigmentación de región periorbitaria. La frecuencia de neutropenia por quimiosupresión medular fue del 4,1% (3 casos). No hubo casos de anemia ni trombocitopenia severas. No hubo eventos isquémicos cerebrales ni mortalidad asociada al procedimiento. Conclusión La QIA con melfalán y topotecán es una alternativa segura y efectiva para el tratamiento del retinoblastoma persistente o recidivado, permitiendo reducir las tasas de enucleación (AU)

Objective To establish the success rate of salvage intra-arterial chemotherapy (IAC), defined as the percentage of eyes that achieved tumoral remission and avoided enucleation. The second objective was the clinical characterization, catheterization results, and associated local and systemic complications. Methods Retrospective, interventional case series of 29 patients (35 eyes) with persistent or recurrent retinoblastoma. Results A total of 73 salvage IAC procedures with topotecan and melphalan were carried out. Success rate was 77% at a mean follow-up of 41.4 months. All patients with only one remaining eye avoided enucleation (10 cases). Catheterization was successful in 98.6% of cases. The types of catheterizations were as follows: 71.2% supraselective ophthalmic artery, 12.3% occlusion pump assisted supraselective ophthalmic artery, 16.4% selective external carotid with retrograde flow. 14% of patients suffered local adverse effects: 1 (2.8%) transitory ptosis, 1 (2.8%) transitory oculomotor nerve palsy, 2 (5.7%) aseptic cellulitis and 1 (2.8%) periorbitary pigmentation. 4.1% (3 cases) suffered neutropenia due to medullar chemosuppression. There were no cases of severe anemia or thrombocytopenia. There were no cerebral ischemic events or mortality associated to the procedure. Conclusion IAC with melphalan and topotecan is a safe and effective treatment option for persistent or recurrent retinoblastoma, able to reduce enucleation rates (AU)