Guía de recomendaciones para el manejo de brolucizumab / Guidance on brolucizumab management recommendations

Objetivo: Brolucizumab, un anti-VEGF de nueva generación, ha demostrado su eficacia y seguridad en la degeneración macular asociada a la edad neovascular exudativa (DMAEn) en los ensayos pivotales HAWK y HARRIER. Tras su comercialización, se han reportado eventos adversos relacionados con la inflamación intraocular no detectados previamente. Una revisión post hoc independiente de los ensayos pivotales cifra la tasa de inflamación intraocular (IIO) en el 4,6%. El objetivo de este trabajo es proponer una serie de recomendaciones para implementar el manejo de brolucizumab en la práctica clínica. Método: Las recomendaciones realizadas por los autores se han basado en su experiencia clínica y en la revisión crítica de: 1)los ensayos pivotales; 2)el análisis post hoc del Comité de Revisión de Seguridad, y 3)la literatura publicada. Resultados: En los ensayos pivotales, brolucizumab mostró ganancias funcionales sostenidas, resultados anatómicos superiores con intervalos entre inyecciones potencialmente más prolongados y un perfil de seguridad global bien tolerado. Los eventos adversos reportados tras la comercialización incluyen vasculitis retiniana y la oclusión vascular retiniana. De acuerdo con la información disponible, los expertos recomiendan: 1)descartar los perfiles de pacientes no recomendados (historial previo de IIO); 2)explorar al paciente antes de cada inyección para descartar la presencia de IIO activa; 3)monitorizar al paciente para detectar precozmente los signos de alerta, y 4)tratar de inmediato en el caso de que se desarrolle algún evento adverso. ConclusionesLos : eventos adversos reportados son poco frecuentes, pero pueden estar asociados con una pérdida severa e irreversible de agudeza visual. Las recomendaciones realizadas pretenden facilitar el manejo de brolucizumab en la práctica habitual de los retinólogos, garantizar la seguridad del paciente y, en caso de que se produzca alguno de los eventos adversos, minimizar su impacto sobre la visión. (AU)

Purpose: Brolucizumab, a new generation anti-VEGF, has demonstrated efficacy and safety in AMD in the pivotal HAWK and HARRIER trials. Post-marketing, previously undetected adverse events related to intraocular inflammation have been reported. An independent post hoc review of the pivotal trials puts the rate of intraocular inflammation (IOI) at 4.6%. The aim of this paper is to propose a set of recommendations for implementing the management of brolucizumab in clinical practice. Method: The recommendations made by the authors are based on their clinical experience and critical review of (i)the pivotal trials; (ii)the post-hoc analysis of the Safety Review Committee, and (iii)the published literature. Results: In the pivotal trials, brolucizumab showed sustained functional gains, superior anatomical outcomes with potentially longer intervals between injections and a well-tolerated overall safety profile. Adverse events reported post-marketing include retinal vasculitis and retinal vascular occlusion. Based on the available information, experts recommend (i)ruling out non-recommended patient profiles (prior history of ORI); (ii)screening the patient prior to each injection to rule out active IOI; (iii)monitoring the patient for early warning signs, and (iv)treating immediately should any adverse events develop. Conclusions: The adverse events reported are rare, but may be associated with severe and irreversible loss of visual acuity. The recommendations made are intended to facilitate the management of brolucizumab in the routine practice of retinologists, to ensure patient safety and, should any adverse events occur, to minimise their impact on vision. (AU)

Guidance on brolucizumab management recommendations.

PURPOSE: Brolucizumab, a new generation anti-VEGF, has demonstrated efficacy and safety in AMD in the pivotal HAWK and HARRIER trials. Post-marketing, previously undetected adverse events related to intraocular inflammation have been reported. An independent post hoc review of the pivotal trials puts the rate of IOI at 4.6%. The aim of this paper is to propose a set of recommendations for implementing the management of brolucizumab in clinical practice. METHODS: The recommendations made by the authors are based on their clinical experience, critical review of (i) the pivotal trials, the post-hoc analysis of the Safety Review Committee, (ii), and (iii) the published literature. RESULTS: In the pivotal trials, brolucizumab showed sustained functional gains, superior anatomical outcomes with potentially longer intervals between injections and a well-tolerated overall safety profile. Adverse events reported post-marketing include retinal vasculitis and retinal vascular occlusion. Based on the available information, experts recommend (i) ruling out non-recommended patient profiles (prior history of ORI), (ii) screening the patient prior to each injection to rule out active ORI, (iii) monitoring the patient for early warning signs, and (iv) treating immediately should any adverse events develop. CONCLUSIONS: The adverse events reported are rare, but may be associated with severe and irreversible loss of visual acuity. The recommendations made are intended to facilitate the management of brolucizumab in the routine practice of retinologists, to ensure patient safety and, should any adverse events occur, to minimise their impact on vision.

Nitric oxide and vascular endothelial growth factor concentrations are increased but not related in vitreous fluid of patients with proliferative diabetic retinopathy.

AIMS: Several reports have implicated nitric oxide (NO) in the angiogenic process. The assessment of NO stable end products, nitrite and nitrate (NOx), is commonly used as a measure of NO production in biological fluids. The aims of the study were to investigate NOx concentrations in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and to evaluate the relationship between NOx and vascular endothelial growth factor (VEGF). PATIENTS AND METHODS: Serum and vitreous fluid samples were obtained simultaneously at the time of vitreoretinal surgery from 23 patients with PDR, and 17 control non-diabetic patients with non-proliferative ocular disease. NOx was determined by using the Griess reaction and VEGF levels were assessed by ELISA. RESULTS: The intravitreous concentration of NOx was significantly elevated in patients with PDR in comparison with the control group (31.6 +/- 2.96 micromol/l vs. 18 +/- 2.46 micromol/l; P = 0.01). However, we did not detect any differences between NOx serum concentrations. We observed a correlation between serum and vitreous levels of NOx in diabetic patients (r = 0.79; P < 0.001), but not in the control group. Intravitreous levels of VEGF in patients with PDR were higher than those obtained in serum (1.42 ng/ml (0.12-7.62) vs. 0.12 ng/ml (0.03-0.42); P < 0.01). Vitreal levels of VEGF were strikingly higher in patients with PDR than in the control subjects (1.42 ng/ml (0.12-7.62) vs. 0.009 ng/ml (0.009-0.04); P < 0.001). No correlation between vitreal concentrations of NOx and VEGF was observed, either in diabetic patients or in the control group. CONCLUSIONS: NOx and VEGF are increased but not related in the vitreous fluid of diabetic patients with PDR. Our results suggest that serum diffusion could play a significant role in explaining the increase of NOx. By contrast, intraocular production seems to be the main factor responsible for the intravitreous enhancement of VEGF.

Vitreoretinal surgery and endoresection in high posterior choroidal melanomas.

PURPOSE: Eyes with posterior choroidal melanomas more than 9 mm in thickness frequently are enucleated because of the potential complications of radiotherapy. The aim of this study was to evaluate the safety and efficacy of internal resection of these tumors. METHODS: Twenty-five consecutive patients with high posterior choroidal melanomas with a diameter less than 15 mm and a thickness greater than 9 mm were treated. If the retina was not invaded by the tumor, a vitrectomy was performed, followed by posterior hyaloid dissection, 120 degrees anterior retinotomy, endophotocoagulation 2 mm past the tumor margin, melanoma removal with the vitrectomy probe, retinal reattachment with liquid perfluorocarbon and air, and silicone oil exchange. If the tumor invaded the retina, the laser was applied through the retina, and the retina and tumor were removed together. RESULTS: The mean patient age was 46.6 years. The tumor thicknesses ranged from 9.1 to 12.8 mm, and the tumor diameter ranged from 8.9 to 14.8 mm. The mean preoperative visual acuity was 20/60. In 11 patients, the tumor had invaded the retina. We removed the entire tumor from all 25 eyes. The main postoperative complications were cataract (40%), retinal detachment (16%), macular traction (16%), and epiretinal macular proliferation (8%). The mean postoperative visual acuity was 20/100. No tumors recurred, and there was no evidence of metastasis. The follow-up ranged from 12 to 72 months. CONCLUSIONS: These data suggest that internal resection of high posterior melanomas may conserve ocular and functional vision and does not seem to increase the risk of metastatic disease. Longer follow-up is necessary to establish the safety of the procedure.

[Subretinal neovascularization and hemorrhages in angioid streaks]. / Neovascularización y hemorragias subretinianas asociadas a estrías angioides.

PURPOSE: To study the development of subretinal neovascularization and/or subretinal hemorrhages in patients with angioid streaks. METHODS: Fifty two eyes from twenty six patients with angioid streaks were included in our study. The diagnosis of angioid streaks was established by ophthalmoscopic and florescein angiographic features. All the patients underwent a complete ophthalmological study that included an examination of the ocular fundus and a retinography every six months. RESULTS: Subretinial neovascularization was found in 38% in this group of patients. Subretinal hemorrhages, either with or without neovascularization, were found in 59%. CONCLUSIONS: There is no known treatment capable of preventing these conditions from appearing, however the patients should be informed about the risk of subretinal hemorrhages after relatively minor ocular trauma. These results may be helpful in the evaluation, prognosis and surgical planning for patients with angioid streaks.

Neovascularización y hemorragias subretinianas asociadas a estrías angioides / Subretinal neovascularization and hemorrhages in angioid streaks

Objetivo: Estudiar el desarrollo de neovascularización subretiniana y/o hemorragias subretinianas en pacientes afectos de estrías angioides. Métodos: 52 ojos, de 26 pacientes, fueron incluidos en nuestro estudio. El diagnóstico de las estrías angioides se estableció mediante oftalmoscopia y angiografía fluoresceínica. Todos los pacientes fueron sometidos, cada seis meses:, a un estudio oftalmológico completo, incluyendo un examen de fondo de ojo y retinografía. Resultados: En ese grupo de pacientes encontramos neovascularización subretiniana en un 38 por ciento. El hallazgo de hemorragias subretinianas, con o sin neovascularización, fue del 59 por ciento. Conclusiones: No se conoce ningún tratamiento capaz de prevenir la aparición de estas complicaciones, pero los pacientes deben ser informados del riesgo de hemorragias subretinianas ante mínimos traumatismos oculares. Estos resultados pueden ser útiles para la evaluación, pronóstico y planificación quirúrgica de los pacientes afectos de estrías angioides. (AU)

Therapeutic options for capillary papillary hemangiomas.

PURPOSE: To describe the results and therapeutic complications of treatment of papillary capillary hemangiomas over the last 13 years. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Five cases of unilateral capillary papillary hemangiomas were reviewed. Three patients had von Hippel-Lindau disease, and two had no associated familial or systemic disease. METHODS: Two patients were treated with argon green laser, one patient received argon green and diode photocoagulation, and two patients underwent argon green photocoagulation and diode transpupillary thermotherapy (TTT); two eyes also underwent vitreoretinal surgery. Follow-up ranged from 1 to 13 years. MAIN OUTCOME MEASURES: The presence of exudative retinal detachment associated with the activity of the hemangioma and the visual acuity were the two main parameters. RESULTS: Prompt argon green laser treatment was the most effective therapy; -II was ineffective. Vitreoretinal surgery, transscleral drainage, and argon endolaser photocoagulation in one case resolved bullous retinal detachment secondary to tumor exudation. Pretreatment visual acuity (VA) levels ranged from 20/25 to counting fingers; posttreatment VA levels ranged from 20/25 to light perception. CONCLUSIONS: If left untreated, papillary hemangiomas may evolve to exudative retinal detachment and marked VA decreases. Although we have not established an ideal therapy, we recommend appropriate treatment on diagnosis. Close follow-up and multiple treatments with argon laser are likely the best therapeutic course.

The role of vitreoretinal surgery in the treatment of posttraumatic macular hole.

PURPOSE: To determine if vitreoretinal surgery is successful in closing traumatic macular holes and subsequently improving visual acuity. Blunt trauma may result in a macular hole when it causes traumatic separation of the vitreous from the retina, contusion necrosis, or subfoveal hemorrhage. Like idiopathic macular holes, traumatic macular holes are surrounded by a ring of subretinal fluid and result in severely diminished visual acuity. METHODS: Fourteen eyes with full-thickness posttraumatic macular holes were treated. The patients ages ranged from 15 years to 36 years (mean, 22 years). Preoperative best corrected visual acuity ranged from 20/200 to 20/50 (mean, 20/80). A pars plana vitrectomy and posterior hyaloid dissection were performed, followed by complete fluid-gas exchange and instillation of 0.1 mL of platelet concentrate just over the macular hole. A final flushing with 25% sulfur hexafluoride was done. The postoperative follow-up period ranged from 6 months to 28 months (average, 13 months). RESULTS: Successful anatomic macular hole closure was achieved 6 months after surgery in 13 years (92.86%). Visual acuity improved four or more lines on the Snellen chart within 6 weeks after surgery in every eye with a closed hole; a final visual acuity of 20/20 was achieved in two eyes (15.3%). The mean postoperative visual acuity was 20/30. No intraoperative or postoperative complications were noted, and the lens remained clear in all eyes during the follow up period. CONCLUSION: Our results suggest that intraoperative application of platelet concentrate in combination with vitrectomy may be useful in managing posttraumatic full-thickness macular holes, thus improving anatomic and visual outcomes. The greater recovery of visual acuity obtained in this study compared with that obtained in other series of idiopathic macular holes could be related to the young age of the patients with traumatic macular holes and the early diagnosis and treatment.