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.

[Treatment of non infectious ocular inflammatory disease with low doses of cyclosporin A]. / Tratamiento con dosis bajas de ciclosporina A en pacientes con enfermedad ocular inflamatoria de etiología no infecciosa.

BACKGROUND: Cyclosporin A has an adequate immunosuppressive capacity and can be useful in the treatment of non infectious ocular inflammatory diseases. AIM: To describe the clinical effect of cyclosporin A treatment in low doses, along with corticosteroids, in the treatment of refractory ocular inflammatory diseases. PATIENTS AND METHODS: Twenty patients (13 female), aged 17 to 74 years old with severe and refractory ocular inflammatory diseases were studied. All except one, received variable doses of prednisone (10 to 60 mg/kg/day) and all received cyclosporin in doses that started in 2.5 mg/day and were increased to 5 mg/kg/day, according to clinical response. Patients were followed from 8 to 24 months, with monthly assessments of ocular inflammation (using a four point score), visual acuity and adverse effects of treatment. RESULTS: A two points or more reduction in the ocular inflammation score was observed in 52% of patients. Visual acuity improved in 10 subjects, stabilized in 8 and worsened in 2. Prednisone doses were reduced in most patients. Observed adverse effects were hypertension in 2 patients, creatinine elevation in 2, gastrointestinal disturbances in 3 and hypertrichosis in 12. A reduction of cyclosporin dose was required in these cases, but it was discontinued only in one patient with a vascular purpura. CONCLUSIONS: Low cyclosporin doses, associated to prednisone, are useful to reduce inflammation and improve visual acuity in patients with non infectious ocular inflammatory diseases, refractory to other treatment methods.

Surgical treatment for chronic hypotony and anterior proliferative vitreoretinopathy.

PURPOSE: To determine whether vitreoretinal surgery to release anterior traction in eyes with chronic hypotony and attached posterior retinas increases the intraocular pressure and prevents atrophia bulbi. METHODS: In this prospective study, we operated on and followed-up postoperatively 17 eyes of 17 consecutive patients with previous vitreoretinal surgeries for retinal detachments and severe proliferative vitreoretinopathy. These eyes had developed chronic hypotony (intraocular pressure < or = 5 mm Hg for at least one month) and anterior proliferative vitreoretinopathy. RESULTS: After a minimum of six months of postoperative follow-up (mean, 10.6 months), mean intraocular pressure had increased significantly after surgery from 1.7 to 7.2 mm Hg (P < .001), and ten (59%) of the 17 eyes had a final intraocular pressure greater than 5 mm Hg. Visual acuity did not change significantly after surgery (P = .25). In 13 (76%) of the 17 eyes, visual acuity improved or remained the same. Factors associated with higher postoperative intraocular pressure included hypotony of less than three months' duration (P = .007), preoperative visual acuity of 2/200 or more (P = .02), extent of anterior proliferative vitreoretinopathy of less than 90 degrees (P = .003), absence of tissue over the pars plicata (P = .001), and no anterior reproliferation after surgery (P = .04). CONCLUSIONS: Early surgery to release traction over the anterior retina and uveal tissue in eyes with chronic hypotony and anterior proliferative vitreoretinopathy can increase intraocular pressure and stabilize visual acuity.

[Treatment of ocular inflammatory disease with glucocorticoids and cyclophosphamide pulses]. / Tratamiento de la enfermedad ocular inflamatoria con glucocorticoides y pulsos de ciclofosfamida.

UNLABELLED: The effectiveness, toxicity and prognostic factors influencing responses to cyclophosphamide (CP) iv pulses plus oral glucocorticosteroids (GC) in patients with GC-resistant ocular inflammatory diseases (OID) was evaluated in a cohort of 15 consecutive patients suffering from active, non-infectious OID refractory to oral GC. All patients underwent monthly evaluations with clinical, hematological, hepatic, renal and ophthalmologic tests. These included checking visual acuity and both anterior chamber and posterior segment inflammation. The overall effect evaluated by repeated measurements ANOVA demonstrated that after an average of 5 CP pulses 1-10, the group showed significant improvement regarding of visual acuity and inflammation (p < 0.000001). Amelioration was not sustained over time in patients with granulomatous uveitis. Patients with retinal vasculitis experienced rapid and sustained recovery. By the end of the follow-up period, 53% of the patients had improved, 20% remained stationary and 26% suffered visual acuity deterioration as compared with the baseline. No serious side effects were detected during treatment and follow-up. CONCLUSIONS: A combination of oral GC and iv CP pulses appears to be an effective way to treat patients suffering from noninfectious, non-granulomatous, GC-resistant OID.

[New concepts on the pathogenesis of uveitis]. / Nuevos conceptos en la patogenia de la uveitis.

The pathogenesis of uveitis is not entirely clear. Diverse clinical and experimental findings support the participation of immunologic mechanisms. In fact, uveitis may appear along with many immunologic systemic diseases. In this article, possible etiologic agents of uveitis are described and experimental models discussed. The immunologic mechanisms are analyzed and a unifying hypothesis is presented.