RESUMEN
OBJECTIVE: Intravitreal chemotherapy has emerged as an important modality for treating vitreous seeding in retinoblastoma. A classification system has been described as predictive of response to intravitreal melphalan (IVM) in patients treated predominantly with primary intra-arterial chemotherapy. The objective of this study is to evaluate the outcomes of retinoblastoma treated with intravenous chemotherapy and IVM as salvage for vitreous seeding, and further to determine whether vitreous seed classification (dust, spheres, cloud) is predictive of the total number and dose of IVM injections required for treatment in this cohort. DESIGN: A nonrandomized retrospective review. PARTICIPANTS: Retinoblastoma patients treated at a single center with intravenous chemotherapy and IVM. METHODS: Retrospective review of patients with vitreous seeding from retinoblastoma treated with intravenous chemotherapy and IVM from 2012 to 2016. MAIN OUTCOME MEASURES: Primary outcome measure was eradication of seeds and globe salvage. Secondary measures included IVM-associated toxicity and complications. RESULTS: Overall, 28 eyes of 25 patients were included, with a total of 110 IVM injections. By seed classification, eyes with dust (n = 15) required a median of 3 injections, spheres (n = 8) required 4 injections, and clouds (n = 5) required 6 injections. Spherical seeds were only seen in recurrent vitreous seeding. Of the 28 treated eyes, 9 were enucleated, 6 for recurrent retinal disease, resulting in an overall globe salvage rate of 68%. The salvage rate secondary to active retinoblastoma was 79%. Dust classification was the most prevalent seeding type of the 9 enucleated eyes. There was 100% regression of vitreous seeds after intravitreal injection and no eye was treated with radiation or enucleated for seeding. Twelve eyes demonstrated grade 3 or greater IVM-associated retinal or anterior segment toxicity post injection. Mean follow-up was 33 months (range, 9-51 months). CONCLUSIONS: IVM is an effective treatment for vitreous seeding after intravenous chemotherapy for retinoblastoma. As with eyes treated with intra-arterial chemotherapy, seed classification is predictive of the total number and dose of IVM injections in eyes treated with intravenous chemotherapy. Eyes with clouds required significantly more injections than eyes with dust or spheres.
Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Melfalán/administración & dosificación , Siembra Neoplásica , Neoplasias de la Retina/tratamiento farmacológico , Retinoblastoma/tratamiento farmacológico , Cuerpo Vítreo/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Niño , Preescolar , Crioterapia , Etopósido/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Lactante , Infusiones Intravenosas , Inyecciones Intravítreas , Coagulación con Láser , Masculino , Neoplasias de la Retina/patología , Retinoblastoma/patología , Estudios Retrospectivos , Terapia Recuperativa , Vincristina/uso terapéutico , Cuerpo Vítreo/patologíaRESUMEN
BACKGROUND: To evaluate outcomes of Group D retinoblastoma (Rb) eyes during the intravitreal melphalan era. PROCEDURE: Retrospective chart review of patients diagnosed with Group D Rb from 2011 to 2016 was done. Overall, 76 Group D eyes of 68 patients were included; salvage therapy included systemic chemoreduction with vincristine, etoposide, and carboplatin with local consolidation, followed by intravitreal injection of melphalan for recurrent or persistent seeding. External beam radiation was not used as a treatment modality. Primary outcome measurement was globe salvage. RESULTS: Of 76 Group D eyes, 24 were enucleated primarily and 52 were treated with intent to salvage the globe. Systemic chemoreduction salvaged 25 of 52 eyes (48%). Tumor recurrences were diagnosed in 27 eyes (52%); five with massive retinal recurrences underwent enucleation and 22 were treated with intravitreal melphalan injection. Of the 22 injected eyes, 14 (64%) were salvaged and eight required enucleation primarily for retinal recurrences. Success in eradicating vitreous seeds was 100%. The Kaplan-Meier 3-year survival estimate for treated eyes is 76.5% (95% CI: 61.4-86.3). Median follow-up for the group of 76 Group D eyes was 29.5 months (SD 17.9 months). CONCLUSION: During a 6-year period that included the initiation of intravitreal melphalan at our institution, the salvage rate of treated Group D eyes was 75% (39/52 eyes). Intravitreal melphalan was utilized for ocular salvage in 42% (22/52 eyes). Systemic chemoreduction combined with intravitreal melphalan for seeding demonstrated a high overall salvage rate for Group D eyes in this cohort.
Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Melfalán/administración & dosificación , Neoplasias de la Retina/tratamiento farmacológico , Retinoblastoma/tratamiento farmacológico , Niño , Preescolar , Femenino , Humanos , Lactante , Inyecciones Intravítreas , Masculino , Neoplasias de la Retina/clasificación , Retinoblastoma/clasificación , Estudios Retrospectivos , Terapia Recuperativa , Resultado del TratamientoRESUMEN
Germline partial chromosomal deletions of the entire RB1 gene (13q deletions), account for 6% of the RB1 mutational spectrum. The authors report the rare case of one patient with suspected bilateral iris heterochromia who actually had iris hypoplasia (often masquerading as heterochromia) and bilateral retinoblastoma, due to 13q deletion syndrome. [J Pediatr Ophthalmol. 2018;55:e10-e13.].
Asunto(s)
Trastornos de los Cromosomas/complicaciones , Enfermedades del Iris/patología , Iris/patología , Mutación , Trastornos de la Pigmentación/diagnóstico , Proteínas de Unión a Retinoblastoma/genética , Retinoblastoma/diagnóstico , Ubiquitina-Proteína Ligasas/genética , Deleción Cromosómica , Trastornos de los Cromosomas/diagnóstico , Trastornos de los Cromosomas/genética , Cromosomas Humanos Par 13/genética , Análisis Mutacional de ADN , ADN de Neoplasias/genética , Diagnóstico Diferencial , Femenino , Angiografía con Fluoresceína , Fondo de Ojo , Humanos , Lactante , Enfermedades del Iris/diagnóstico , Enfermedades del Iris/etiología , Imagen por Resonancia Magnética , Proteínas de Unión a Retinoblastoma/metabolismo , Tomografía de Coherencia Óptica , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Cathepsin S (CTSS) activity is elevated in Sjögren's Syndrome (SS) patient tears. Here we tested whether protease inhibition and cystatin C (Cys C) levels are reduced in SS tears, which could lead to enhanced CTSS-driven degradation of tear proteins. CTSS activity against Cys C, LF and sIgA was tested in SS or healthy control tears. Tears from 156 female subjects (33, SS; 33, rheumatoid arthritis; 31, other autoimmune diseases; 35, non-autoimmune dry eye (DE); 24, healthy controls) were analyzed for CTSS activity and Cys C, LF, and sIgA levels. Cys C and LF showed enhanced degradation in SS tears supplemented with recombinant CTSS, but not supplemented healthy control tears. CTSS activity was significantly increased, while Cys C, LF and sIgA levels were significantly decreased, in SS tears compared to other groups. While tear CTSS activity remained the strongest discriminator of SS in autoimmune populations, combining LF and CTSS improved discrimination of SS beyond CTSS in DE patients. Reductions in Cys C and other endogenous proteases may enhance CTSS activity in SS tears. Tear CTSS activity is reconfirmed as a putative biomarker of SS in an independent patient cohort while combined LF and CTSS measurements may distinguish SS from DE patients.