RESUMEN
BACKGROUND: Solid evidence of the safety and effectiveness of retinoblastoma (RB) conservative treatment using thermotherapy and systemic chemotherapy with long-term follow-up is scarce, especially in low-resource countries. AIMS: This study examined the outcomes of this treatment and associated predictors in Vietnam to strengthen the current RB treatment protocol focusing on preserving eye and vision in low-resource settings. METHODS AND RESULTS: A prospective cohort study was conducted at Ho Chi Minh City Eye Hospital in Vietnam from 2005 to 2019. All eligible patients with bilateral RB (one eye already removed and another eye classified as group A or B) and without previous treatment were recruited. All patients received thermotherapy and six cycles of systemic three-agent chemotherapy repeated every 4 weeks. A standardized questionnaire was used to collect information on study participants' age, symptoms, tumor characteristics, treatment, and outcomes. Among 50 eyes of all 50 patients with a median age of 9 (4-20) months, 34 eyes were in group B (68%). The median follow-up time was 60 (60-84) months. All 139 preserved tumors regressed mostly to type 4 (70.4%) and type 3 (23.7%) scars. Kaplan-Meier analysis found the overall globe-salvage rate at 5 years of 91.9% (95% CI: 80.1%-97.7%). Most eyes (41/50, 82%, 95% CI: 69.2%-90.2%) had a final visual acuity ≥0.1. The visual acuity is higher when tumors regressed to a type 4 scar (p = .007, AOR = 8.098, 95% CI: 1.79-36.53) which also shows less enucleation than a type 3 scar (p = .002, AOR = 0.06, 95% CI: 0.01-0.37%). Gender effect on visual acuity after treatment was significant and may be due to discrimination. No major complications were recorded. CONCLUSION: Conservative treatment of early-stage RB is safe and effective. Long-term, thorough follow-ups of patients post-treatment are needed. The regression patterns of scars could be a useful indicator of treatment failure.
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Neoplasias de la Retina , Retinoblastoma , Humanos , Lactante , Retinoblastoma/diagnóstico , Retinoblastoma/tratamiento farmacológico , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/tratamiento farmacológico , Cicatriz/patología , Tratamiento Conservador , Estudios Prospectivos , Rayos LáserRESUMEN
With an average incidence of 1 in every 18,000 live births, retinoblastoma is a rare type of intraocular tumour found to affect patients during their early childhood. It is curable if diagnosed at earlier stages but can become life-threateningly malignant if not treated timely. With no racial or gender predisposition, or even environmental factors known to have been involved in the incidence of the disease, retinoblastoma is often considered a clinical success story in pediatric oncology. The survival rate in highly developed countries is higher than 95% and they have achieved this because of the advancement in the development of diagnostics and treatment techniques. This includes developing the already existing techniques like chemotherapy and embarking on new strategies like enucleation, thermotherapy, cryotherapy, etc. Early diagnosis, studies on the etiopathogenesis and genetics of the disease are the need of the hour for improving the survival rates. According to the Knudson hypothesis, also known as the two hit hypothesis, two hits on the retinoblastoma susceptibility (RB) gene is often considered as the initiating event in the development of the disease. Studies on the molecular basis of the disease have also led to deciphering the downstream events and thus in the discovery of biomarkers and related targeted therapies. Furthermore, improvements in molecular biology techniques enhanced the development of efficient methods for early diagnosis, genetic counseling, and prevention of the disease. In this review, we discuss the genetic and molecular features of retinoblastoma with a special emphasis on the mutation leading to the dysregulation of key signaling pathways involved in cell proliferation, DNA repair, and cellular plasticity. Also, we describe the classification, clinical and epidemiological relevance of the disease, with an emphasis on both the traditional and innovative treatments to tackle retinoblastoma. Video Abstract.
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Neoplasias de la Retina , Retinoblastoma , Preescolar , Niño , Humanos , Retinoblastoma/diagnóstico , Retinoblastoma/genética , Retinoblastoma/terapia , Proliferación Celular , Reparación del ADN , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/genética , Neoplasias de la Retina/terapiaRESUMEN
BACKGROUND: Retinal retinoblastoma growth phenotypes can be endophytic, exophytic, diffuse infiltrating or anterior diffuse. Herein, we describe a novel tumor growth pattern in two patients. MATERIAL AND METHODS: Imaging with spectral-domain optical coherence tomography (SD-OCT). RESULTS: Both cases were diagnosed with unilateral group D retinoblastoma treated with first-line or bridge intra-arterial chemotherapy (IAC). Case 1 had a new intravitreal/epiretinal relapse 3 months after brachytherapy and intravitreal chemotherapy. SD-OCT showed a disruption of the inner limiting membrane (INL) underneath a parapapillary epiretinal seed. The intravitreal/epiretinal disease completely regressed with intravitreal melphalan. Three months later, an isolated intraretinal growth was documented on SD-OCT at the site of previously INL disruption, which was treated by thermotherapy. He remained disease-free at 1-year follow-up with 0.6 visual acuity. Case 2 was seen 2 months after treatment interruption due to the COVID-19 pandemic. Fundus examination showed a massive intravitreal/epipapillary invasion completely obscuring the papilla. Salvage treatment of this seeing eye consisted of combined intra-arterial and intravitreal melphalan and topotecan injections. An infraclinical papillary regrowth 4 months later was treated with additional IAC. Six months later, enucleation was performed due to an infraclinical papillary relapse with suspicion of intralaminar invasion. Histopathology showed retrolaminar optic nerve invasion with tumor-free surgical section. The child received four cycles of adjuvant chemotherapy and remained disease-free at 1-year follow-up. CONCLUSION: Epiretinal/epipapillary vitreous seeding can be the source of a secondary intraretinal/optic nerve head relapse. SD-OCT is instrumental to follow such cases. Enucleation remains the safest option if secondary optic nerve invasion is suspected.
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Braquiterapia , COVID-19 , Neoplasias de la Retina , Retinoblastoma , Masculino , Humanos , Retinoblastoma/diagnóstico , Neoplasias de la Retina/diagnóstico , Tomografía de Coherencia Óptica , Melfalán/uso terapéutico , Braquiterapia/métodos , Pandemias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/patología , Nervio Óptico , Estudios Retrospectivos , Inyecciones IntravítreasRESUMEN
A preschool child presented with white reflex in left eye since 2 months. Examination under anaesthesia revealed left eye retinoblastoma group D as per international classification of retinoblastoma. In collaboration with medical oncologist, systemic chemotherapy was started. After two cycles of systemic chemotherapy, tumour ruptured into the vitreous cavity suspending the tumour cells in the vitreous jelly. After a combination of systemic and intravitreal chemotherapy with adjuvant transpupillary thermotherapy of the residual retinal tumour, retinoblastoma regressed completely with corresponding flat scar.
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Neoplasias de la Retina , Retinoblastoma , Preescolar , Humanos , Lactante , Retina/patología , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/terapia , Retinoblastoma/diagnóstico , Retinoblastoma/terapia , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate the risk factors leading to recurrence and new tumor (NT) development in patients with retinoblastoma after intravenous chemotherapy (IVC) and to review the treatment outcomes. MATERIALS AND METHODS: The records of 166 retinoblastoma cases (having 246 affected eyes) who underwent six-cycle IVC (vincristine, etoposide, and carboplatin) as primary treatment between October 1999 and August 2020 were reviewed retrospectively. RESULTS: The mean ages at presentation were 9.0 (median: 8.0) and 9.2 (median: 8.5) months in cases with recurrence and NTs respectively. Recurrence was detected in 40 (16.3%) eyes, NTs in 29 (11.8%), and both recurrence/NTs in 24 (9.8%). The mean time elapsed till recurrence and NT was 10.7 months. Multivariable analysis showed that the factors predictive of recurrence were largest tumor base diameter (LTBD) >12 mm (p = 0.039) and presence of subretinal seeds at diagnosis (p = 0.043). Multivariable risk factors for the development of NTs were bilateral familial retinoblastoma (p = 0.001) and presence of subretinal seeds at diagnosis (p = 0.010). Mean follow-up was 80.1 (median: 72.5) months. By Kaplan-Meier analysis, the 1-, 3-, and 6-year recurrence and NT rates were 21.2%, 28.1%, and 28.7% and 14.9%, 22.6%, and 23.9% respectively. The most common treatment methods used for recurrent and/or NTs included cryotherapy, transpupillary thermotherapy, and intra-arterial chemotherapy. Enucleation was eventually required in 24/93 (25.8%) eyes. No patient developed metastasis. DISCUSSION: Development of recurrence and/or NT after IVC was noted in 38% of all retinoblastoma eyes. Bilateral familial disease, LTBD >12 mm, and presence of subretinal seeds at baseline were risk factors for recurrence and NTs in this study.
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Neoplasias de la Retina , Retinoblastoma , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/uso terapéutico , Etopósido/uso terapéutico , Humanos , Lactante , Neoplasias de la Retina/diagnóstico , Retinoblastoma/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Purpose: Enucleation performed in children with retinoblastoma is associated with severe postoperative pain. The use of opioids for the pain is associated with numerous complications which demand careful monitoring. Subtenon infiltration and peribulbar block are useful in ameliorating pain perioperatively following various ophthalmic surgeries which are yet to be evaluated in enucleation. Therefore, we designed this study to compare the effects of peribulbar block and subtenon infiltration on postoperative pain with opioids in pediatric enucleation surgeries. Methods: 60 children of American Society of Anesthesiologists grade I and II, age ranging from 6 months to 6 years with retinoblastoma undergoing enucleation surgery were included in the study. Group A (n = 20): received peribulbar block (peribulbar group); Group B (n = 20): received subtenon local infiltration (subtenon group); and Group C (n = 20): no block was given. Results: The postoperative fentanyl consumption was lowest with Group B compared to Group A and Group C (P value 0.001). However, the total fentanyl consumption was comparable between groups A and B, while it was significantly higher in the control group. The mean pain score face, legs, activity, cry, consolability (FLACC) scale and mean time to discharge from post anesthesia care unit were lowest in Group B followed by Group A, while Group C had the highest. There was no statistically significant difference among the 3 groups with regards to side effects. Conclusion: Subtenon infiltration showed significantly better outcomes when compared to peribulbar block and intravenous opioids alone without any untoward adverse effects.
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Bloqueo Nervioso , Neoplasias de la Retina , Retinoblastoma , Anestesia Local , Anestésicos Locales , Niño , Humanos , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/cirugía , Retinoblastoma/diagnóstico , Retinoblastoma/cirugíaRESUMEN
PURPOSE: To determine prospectively the efficacy and to assess potential side effects of melphalan selective ophthalmic artery chemotherapy (SOAC) as first-line treatment for unilateral retinoblastoma. DESIGN: Phase 2 nonrandomized, prospective study. PARTICIPANTS: Patients with unilateral retinoblastoma group B, C, or D of the International Classification for Intraocular Retinoblastoma (IRC). Group D eyes with massive vitreous seeding were not eligible. METHODS: Melphalan SOAC associated with diode laser thermotherapy, cryotherapy, or both at 4-week intervals (3-6 cycles). For persistent vitreous seeding, intravitreal melphalan chemotherapy also was used. MAIN OUTCOME MEASURES: The primary outcome was globe preservation rate. Secondary outcomes were tumor relapse rate, occurrence of ocular or systemic adverse events, and measurement of the dose area product (DAP). RESULTS: Between 2012 and 2017, 39 patients (39 eyes) with unilateral retinoblastoma were included prospectively. Three included patients did not receive SOAC (2 catheterization failures and 1 case of viral syndrome) and were considered failures. At diagnosis, IRC groups for the 36 treated patients were: B, n = 4 (11%); C, n = 13 (36%); and D, n = 19 (53%); median age was 21.5 months (range, 3.2-61.6 months). Median number of SOAC cycles was 3.9 (range, 1-6 cycles), and median melphalan dose was 4.9 mg/procedure. The median DAP was 1.24 Gy.cm2/procedure. Median follow-up was 63 months (range, 34-93 months). SOAC was associated with local treatments for 31 patients (86%): diode laser thermotherapy for all of them and cryotherapy or intravitreal chemotherapy for 10 (32%) and 9 patients (25%), respectively. SOAC treatment was interrupted in 5 patients because of severe ophthalmic (ptosis, n = 2; retinal ischemia, n = 2) or systemic (hypotension, n = 1) adverse events. At the cutoff date analysis, all patients were alive without metastasis. The 18-month eye preservation rate was 80% (range, 68.6%-94.6%). After a follow-up of at least 30 months, the ocular preservation rate was 69% (n = 24 preservations). CONCLUSIONS: This first prospective trial demonstrated that SOAC with melphalan alone as first-line treatment for retinoblastoma is efficient and well tolerated with no metastatic events, although ocular ischemic complications were observed.
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Manejo de la Enfermedad , Melfalán/administración & dosificación , Neoplasias de la Retina/terapia , Retinoblastoma/terapia , Antineoplásicos Alquilantes/administración & dosificación , Niño , Preescolar , Terapia Combinada , Crioterapia/métodos , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intraarteriales , Imagen por Resonancia Magnética , Masculino , Estadificación de Neoplasias/métodos , Arteria Oftálmica , Estudios Prospectivos , Neoplasias de la Retina/diagnóstico , Retinoblastoma/diagnóstico , Factores de Tiempo , Resultado del TratamientoRESUMEN
Retinoblastoma management remains complex, requiring individualized treatment based on International Classification of Retinoblastoma (ICRB) staging, germline mutation status, family psychosocial factors and cultural beliefs, and available institutional resources. For this 2020 retinoblastoma review, PubMed was searched for articles dated as early as 1931, with an emphasis on articles from 1990 to the present day, using keywords of retinoblastoma, chemotherapy, intravenous chemotherapy, chemoreduction, intra-arterial chemotherapy, ophthalmic artery chemosurgery, intravitreal chemotherapy, intracameral chemotherapy, cryotherapy, transpupillary thermotherapy, laser, radiation, external beam radiotherapy, plaque radiotherapy, brachytherapy, and enucleation. We discuss current treatment modalities as used in the year 2020, including intravenous chemotherapy (IVC), intra-arterial chemotherapy (IAC), intravitreal chemotherapy (IvitC), intracameral chemotherapy (IcamC), consolidation therapies (cryotherapy and transpupillary thermotherapy [TTT]), radiation-based therapies (external beam radiotherapy [EBRT] and plaque radiotherapy), and enucleation. Additionally, we present a consensus treatment algorithm based on the agreement of three North American retinoblastoma treatment centers, and encourage further collaboration amongst the world's most expert retinoblastoma treatment centers in order to develop consensus management plans and continue advancement in the identification and treatment of this childhood cancer.
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Neoplasias de la Retina , Retinoblastoma , Protocolos de Quimioterapia Combinada Antineoplásica , Niño , Terapia Combinada , Crioterapia , Enucleación del Ojo , Humanos , Lactante , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/epidemiología , Neoplasias de la Retina/terapia , Retinoblastoma/diagnóstico , Retinoblastoma/epidemiología , Retinoblastoma/terapiaRESUMEN
PURPOSE: To identify risk factors for retinoblastoma recurrence following chemoreduction. METHODS: This was a retrospective review of patients with retinoblastoma treated from 1994 to 2019 using chemoreduction with analysis for recurrence using Kaplan-Meier, Cox regression, and logistic regression. RESULTS: There were 869 eyes of 551 patients with retinoblastoma treated with chemoreduction. Follow-up in 556 eyes revealed main solid tumor recurrence (n = 355, 64%), subretinal seed recurrence (n = 244, 44%), vitreous seed recurrence (n = 162, 29%), and/or new tumor (n = 118, 21%) requiring management with focal therapy (transpupillary thermotherapy, cryotherapy) (n = 294, 53%), intra-arterial chemotherapy (n = 125, 22%), intravitreal chemotherapy (n = 36, 6%), plaque radiotherapy (n = 120, 22%), external beam radiotherapy (n = 57, 10%), and/or enucleation (n = 49, 9%). Of all recurrences, 62% were detected by 1 year, 86% by 2 years, 94% by 3 years, 98% by 5 years, 99% by 10 years, and 100% by 15 years. Risk factors for recurrence on multivariate analysis included younger patient age at presentation (odds ratio [OR] = 1.02 [1.00 to 1.04] per 1 month decrease, P = .02), greater International Classification of Retinoblastoma group (OR = 1.24 [1.05 to 1.47] per 1 more advanced group, P = .01), shorter tumor distance to optic disc (OR = 1.11 [1.01 to 1.21] per 1 mm decrease, P = .03), and presence of subretinal seeds (OR = 1.66 [1.09 to 2.53], P = .02). CONCLUSIONS: Retinoblastoma recurrence after chemoreduction is usually detected within the first 3 years following treatment. Younger patients with more advanced, posteriorly located tumors and subretinal seeds at presentation are at increased risk, but recurrence can often be managed with globe-sparing therapy. [J Pediatr Ophthalmol Strabismus. 2020;57(4):224-234.].
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/epidemiología , Neoplasias de la Retina/epidemiología , Retinoblastoma/epidemiología , Carboplatino/uso terapéutico , Niño , Preescolar , Terapia Combinada , Crioterapia , Etopósido/uso terapéutico , Femenino , Angiografía con Fluoresceína , Humanos , Hipertermia Inducida , Lactante , Recién Nacido , Infusiones Intravenosas , Masculino , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/tratamiento farmacológico , Retinoblastoma/diagnóstico , Retinoblastoma/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Tomografía de Coherencia Óptica , Ultrasonografía , Vincristina/uso terapéuticoRESUMEN
BACKGROUND/AIMS: To report conservative therapy in diffuse infiltrating retinoblastoma (DIR) and describe specific optic coherence tomography (OCT) features of the tumour. METHODS: Retrospective review of all DIR cases treated conservatively between 1998 and 2012. RESULTS: Three patients (three eyes) were included, cases 1 and 3 with previous enucleation of the contralateral eye and case 2 with unilateral retinoblastoma referred after prior pars plana vitrectomy with silicone oil. Mean age at diagnosis was 7 years (range 14 months-14 years). Globe and vision preservation (Snellen visual acuity of 12.5/10) was achieved in case 3 with a recurrence-free follow-up of 33 months after first-line thermotherapy followed by salvage intra-arterial chemotherapy (IAC) plus focal treatments. Cases 1 and 2 were enucleated for progressive disease, case 1 after first-line intravenous chemotherapy (IVC) consolidated by focal therapies and salvage treatments given over 8 years of partial remission and case 2 after IAC, brachytherapy and intracameral chemotherapy. Neither showed any high-risk histopathological features, and no adjuvant chemotherapy was necessary. Both patients are alive without metastasis (mean follow-up of >10 years). Pathognomonic features of the tumour were revealed by OCT in all cases, showing infiltration of the ganglion cell layer and horizontal growth over the inner plexiform layer. Complete restoration of the retinal microanatomy was documented after retraction of the tumour following IVC in case 2 and IAC in case 3. CONCLUSION: This is the first report of successful conservative management in DIR. OCT enabled diagnosis, delimitation of the tumour margins and monitoring of the treatment response in this context.
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Tratamiento Conservador/métodos , Diagnóstico por Computador/métodos , Neoplasias de la Retina/terapia , Retinoblastoma/terapia , Tomografía de Coherencia Óptica/métodos , Adolescente , Antineoplásicos/administración & dosificación , Braquiterapia/métodos , Niño , Preescolar , Vías de Administración de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Hipertermia Inducida/métodos , Lactante , Masculino , Neoplasias de la Retina/diagnóstico , Retinoblastoma/diagnóstico , Estudios Retrospectivos , Agudeza VisualRESUMEN
OBJETIVOS: El número de enucleaciones y secuelas visuales por retinoblastoma es elevado. El objetivo del estudio fue evaluar diferentes aspectos diagnósticos y plantear estrategias que ayuden a mejorar el manejo clínico del retinoblastoma. Método: Estudio retrospectivo de 38 pacientes con retinoblastoma estudiados genéticamente (29 unilaterales, 9 bilaterales). Se evaluaron la edad de inicio, los signos clínicos y el tiempo de evolución, el número de enucleaciones, el momento de realización y la supervivencia a 5 años. Resultados: La leucocoria fue el signo clínico fundamental (presente en el 90% de los casos). El retraso diagnóstico medio fue de 3,2 meses. Entre los casos unilaterales se enuclearon el 76% de los ojos y en las formas bilaterales el 55%. Solo se encontró un fallecimiento entre los 25 pacientes seguidos durante al menos 5 años. Conclusiones: Las estrategias de diagnóstico y tratamiento del retinoblastoma necesitan ser actualizadas. Para ello, una buena coordinación entre pediatras y oftalmólogos es esencial. El manejo en centros de referencia, que dispongan de la tecnología y experiencia necesarias, debería contribuir a aumentar la tasa de preservación de órganos
OBJETIVOS: The number of enucleations and visual sequels due to retinoblastoma is high. The aim of this study was to evaluate the different diagnostic aspects and propose strategies that might improve the clinical management of this condition. Method: A retrospective study was conducted on 38 patients with retinoblastoma studied genetically (29 unilateral, 9 bilateral). The evaluation included: age of onset, clinical signs, and time since onset, number of enucleations, time to diagnosis, and survival at 5 years. Results: Leukocoria was the main clinical sign (present in 90% of cases). The mean diagnostic delay was 3.2 months. Among the unilateral cases, the eyes were enucleated in 76%, and 55% in the bilateral forms. Only one death was found among the 25 patients followed-up for at least 5 years. Conclusions: Retinoblastoma diagnostic and treatment strategies need to be updated. Good coordination between paediatricians and ophthalmologists is essential for this. Its management in reference centres, which have the necessary technology and experience, should contribute to increase the rate of organ preservation
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Humanos , Masculino , Femenino , Lactante , Preescolar , Retinoblastoma/diagnóstico , Diagnóstico Precoz , Estrabismo/diagnóstico , Retinoblastoma/tratamiento farmacológico , Quimioterapia , Enucleación del Ojo/métodos , Estudios Retrospectivos , Estadificación de Neoplasias , Retinoblastoma/clasificación , Crioterapia , Braquiterapia , Hipertermia InducidaRESUMEN
Over recent years, hand-held optical coherence tomography (HH-OCT) has become critical for retinoblastoma diagnosis and management. We report precise HH-OCT findings in a case of sub-millimeter retinoblastoma treated with foveal-sparing indocyanine green-enhanced transpupillary thermotherapy (ICG-TTT). A 2-month-old Caucasian female with bilateral Group B retinoblastoma showed two recurrent macular tumors in the right eye, demonstrating 88 µm and 37 µm of growth to 344 µm and 413 µm in thickness, respectively, on HH-OCT. Each was treated with additional intravenous chemotherapy and foveal-sparing ICG-TTT. Tumor regression to 154 µm and 224 µm was documented on HH-OCT and maintained on follow-up. HH-OCT is vital in confirming clinical findings and influencing management decisions in retinoblastoma. In this case, HH-OCT precisely documented submillimeter retinoblastoma recurrence and treatment response.
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Hipertermia Inducida/métodos , Verde de Indocianina/farmacología , Neoplasias de la Retina/diagnóstico , Retinoblastoma/diagnóstico , Tomografía de Coherencia Óptica/instrumentación , Colorantes/farmacología , Diseño de Equipo , Femenino , Humanos , Lactante , Pupila , Neoplasias de la Retina/terapia , Retinoblastoma/terapiaRESUMEN
Retinoblastoma represents 3% of all childhood cancers, and is the most common intraocular malignancy of childhood. It is fatal, if untreated. White eye reflex, also known as leukocoria, is the commonest sign, followed by strabismus. The pediatricians have a very important role to play in the diagnosis of this relatively rare, but easily detectable tumor. Early diagnosis yields better results. The management of retinoblastoma has gradually evolved over the past few decades, with an aim to not only preserve life and eye, but also optimize residual vision. The treatment of retinoblastoma is multimodal, with chemotherapy, focal treatment including trans-pupillary thermotherapy, cryotherapy and laser photocoagulation, radiation therapy and surgery, all playing a vital role. Intravenous chemotherapy has been the mainstay of treatment for the past two decades, and still continues to be the most extensively used eye-saving modality of treatment. Periocular and intravitreal chemotherapy have specific indications in the management of retinoblastoma. Intra-arterial chemotherapy has emerged as a promising alternative for advanced and refractory retinoblastoma, both as a primary and secondary therapy. Recent advances in genetics of retinoblastoma have also helped in improving the overall clinical management of this malignancy.
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Neoplasias de la Retina , Retinoblastoma , Terapia Combinada , Diagnóstico Diferencial , Detección Precoz del Cáncer , Humanos , Recién Nacido , Estadificación de Neoplasias , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/epidemiología , Neoplasias de la Retina/genética , Neoplasias de la Retina/terapia , Retinoblastoma/diagnóstico , Retinoblastoma/epidemiología , Retinoblastoma/genética , Retinoblastoma/terapiaRESUMEN
PURPOSE: To analyze the long-term visual acuity, strabismus, and nystagmus outcomes in Group D retinoblastoma following multimodality treatments in a national retinoblastoma referral center. DESIGN: Retrospective interventional case series. METHODS: A 13-year retrospective chart review of Group D eyes treated initially with intravenous chemotherapy (IVC) and followed up for at least 1 year from last treatment. Risk factors for final visual acuity (VA) were analyzed, and rate of strabismus and nystagmus at last follow-up visit were calculated. RESULTS: One hundred and four Group D eyes (92 patients) presented to our center during the study period, of which 32 (27 patients) met the inclusion criteria. Following IVC (vincristine, etoposide, and carboplatin), adjuvant treatments included intraophthalmic artery chemotherapy in 5 (16%) eyes, plaque brachytherapy in 5 (16%), transpupillary thermotherapy (TTT) in 18 (56%), and cryotherapy in 24 (75%) eyes. On last examination, 64.41 ± 6.76 months from presentation, mean final VA was 20/283 (logMAR equivalent of 1.15 ± 0.15). On univariate analysis, presentation age, foveal retinoblastoma (at initial examination), use of TTT, and tumor-foveola distance (at last visit) were found to be significant risk factors for worse VA (P < .026). On multivariate analysis, however, only TTT was found to be significant (P = .010). At last visit, 6 of 27 (22%) patients had nystagmus and 12 of 20 (60%) bilaterally salvaged patients had strabismus (n = 10 exotropia and n = 2 esotropia). CONCLUSIONS: After multimodality treatments initiated with IVC, 50% of salvaged Group D retinoblastoma eyes had <20/200 vision, with TTT being a risk factor for worse vision; 60% had strabismus; and 22% had nystagmus.
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Movimientos Oculares/fisiología , Predicción , Nistagmo Patológico/etiología , Neoplasias de la Retina/terapia , Retinoblastoma/terapia , Estrabismo/etiología , Agudeza Visual , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Estadificación de Neoplasias , Nistagmo Patológico/diagnóstico , Nistagmo Patológico/fisiopatología , Neoplasias de la Retina/complicaciones , Neoplasias de la Retina/diagnóstico , Retinoblastoma/complicaciones , Retinoblastoma/diagnóstico , Estudios Retrospectivos , Estrabismo/diagnóstico , Estrabismo/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: Reports on retinoblastoma relapse at the optic nerve head (ONH) are anecdotal and include only treatments by external beam radiotherapy (EBRT) or enucleation. We aimed to describe such cases, termed secondary epipapillary retinoblastoma, diagnosed and monitored with the assistance of hand-held spectral domain optical coherence tomography (HHSD-OCT) and treated with intraophthalmic artery chemotherapy (IAC) and/or intravitreous chemotherapy (IViC). METHODS: A retrospective analysis of secondary epipapillary retinoblastoma cases treated conservatively. RESULTS: Four males and two females were included, diagnosed with secondary epipapillary retinoblastoma at a median time of 8.6â months (mean 24.0) from initial retinoblastoma diagnosis. HHSD-OCT was used in all cases for accurate diagnosis; in 2/6, the epipapillary relapse was detected only by means of HHSD-OCT. Treatments for secondary epipapillary retinoblastoma included IAC and IViC (n=4), IAC alone (n=1) and IViC alone (n=1). HHSD-OCT demonstrated complete epipapillary tumour regression in all cases, achieved in a median time of 1.6â months (mean 1.8). The median time from secondary epipapillary retinoblastoma resolution to last visit was 29.2â months (mean 27.5). At last visit, all eyes were tumour-free and no cases of metastasis recorded. CONCLUSIONS: Cases of retinoblastoma relapse at the ONH show common clinical features and represent specific diagnostic and therapeutic challenge; hence, we propose to consider this condition as a subset of retinoblastoma, termed secondary epipapillary retinoblastoma. HHSD-OCT is an invaluable diagnostic tool in the initial diagnosis as well as in monitoring these lesions, and IAC and IViC are efficient modalities for this clinical scenario, obviating the need for EBRT or enucleation.
Asunto(s)
Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/terapia , Retinoblastoma/diagnóstico , Retinoblastoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia/métodos , Carboplatino/administración & dosificación , Preescolar , Crioterapia/métodos , Femenino , Humanos , Hipertermia Inducida/métodos , Lactante , Infusiones Intraarteriales , Masculino , Melfalán/administración & dosificación , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Topotecan/administración & dosificaciónRESUMEN
PURPOSE: To prospectively study the clinical outcome and regression patterns of early retinoblastoma (Groups A and B) after systemic chemotherapy and focal consolidation in Indian children. MATERIALS AND METHODS: Group A eyes were treated with focal therapy (transpupillary thermotherapy/cryotherapy) and Group B with systemic chemoreduction and focal therapy. Outcome measures were efficacy and safety of treatment, risk factors for treatment failure, regression patterns, and factors predictive of regression patterns. RESULTS: Of 119 eyes (216 tumors), 14 (11.8%) were Group A and 105 (88.2%) were Group B eyes. The mean follow-up was 22.6 months. Tumor control was achieved in 111/119 eyes (93.3% overall, 100% Group A, 92.4% Group B). Eight Group B eyes (6.7%) had treatment failure. No serious systemic side-effects were noted. Risk factors for failure included larger tumors (P = 0.001) and proximity to posterior pole (P = 0.014). Regression patterns were Type 4 (50.2%), Type 3 (31.7%), Type 1 (11.1%), and Type 2 (7%). Factors predictive of Type 4 regression were smaller tumors, anterior location, younger age; Type 3 regression was associated with larger tumors, macular location, and older age. CONCLUSIONS: Systemic chemoreduction and focal therapy provided effective tumor control in Indian children. Factors predictive of regression patterns included age, tumor size and its location, and the modality of treatment.
Asunto(s)
Antineoplásicos/uso terapéutico , Crioterapia/métodos , Hipertermia Inducida/métodos , Neoplasias de la Retina/terapia , Retinoblastoma/terapia , Preescolar , Terapia Combinada , Femenino , Humanos , Lactante , Masculino , Oftalmoscopía , Estudios Prospectivos , Neoplasias de la Retina/diagnóstico , Retinoblastoma/diagnóstico , Resultado del Tratamiento , UltrasonografíaRESUMEN
BACKGROUND: Retinoblastoma is the most common intraocular malignancy of childhood. There is a paucity of genetic testing and prenatal genetic diagnosis from India, which has the highest incidence worldwide. MATERIALS AND METHODS: RB1 gene screening of an 8-month-old female child with bilateral retinoblastoma was accomplished using next generation sequencing. The results were used for prenatal testing in this family. RESULTS: A heterozygous germline mutation (chr13: 48951119delA; c.1281delA) was detected, which resulted in premature termination of a protein product (p.Glu428Argfs*29). Prenatal testing in maternal DNA revealed carrier status of the mother. Further clinical examination in the family members revealed retinocytomas in both eyes of the mother and maternal grandmother. Prenatal genetic testing of the developing fetus showed positivity for the mutation. As the family preferred to continue the pregnancy, serial 3-D ultrasounds were carried out every 2 weeks in the third trimester. Ten days after delivery, small extrafoveal tumors developed in both eyes, which were then treated successfully with transpupillary thermotherapy. CONCLUSION: We report the significance of genetic testing in the early detection and management of retinoblastoma from India.
Asunto(s)
Genes de Retinoblastoma , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Diagnóstico Prenatal , Neoplasias de la Retina/genética , Proteínas de Unión a Retinoblastoma/genética , Retinoblastoma/genética , Ubiquitina-Proteína Ligasas/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Análisis Mutacional de ADN , Etopósido/uso terapéutico , Exones/genética , Femenino , Pruebas Genéticas , Humanos , India , Lactante , Linaje , Terapia de Protones , Neoplasias de la Retina/diagnóstico , Retinoblastoma/diagnóstico , Vincristina/uso terapéuticoRESUMEN
The paper presents clinical and morphological case analysis of primary intraocular malignant medulloepitelioma (medulloblastoma) of rare localization (central part of the retina with optic nerve involvement) that simulated retinoblastoma in a 2-year-old child. Histological features of the tumor are given in details (tubular and mesh structures of the tumor, rosettes, ribbons, cells with hyperchromic nuclei, and cellular polymorphism). An experience of creating a primary intraocular malignant medulloepitelioma cell culture, as yet exclusive in the Russian Federation, is described. Culture sensitivity for particular drugs (oxaliplatin, irinotecan, ifosfamide, and ascorbic acid at different concentrations) was evaluated by MTT-assay. Of the four products, IC50 (3.3 mg/ml) was obtained only for ascorbic acid. Despite the relative rarity of primary intraocular malignant medulloepitelioma, its differential diagnosis should be carried out, with retinoblastoma in mind in the first place. The obtained data on the effectiveness of ascorbic acid against intraocular malignant medulloepitelioma cells can be used to supplement the existing chemotherapeutic protocols in pediatric ocular and neuro-oncology.
Asunto(s)
Enucleación del Ojo/métodos , Tumores Neuroectodérmicos Primitivos , Retinoblastoma/diagnóstico , Biopsia/métodos , Preescolar , Diagnóstico Diferencial , Neoplasias del Ojo/diagnóstico , Neoplasias del Ojo/patología , Neoplasias del Ojo/cirugía , Humanos , Masculino , Estadificación de Neoplasias , Tumores Neuroectodérmicos Primitivos/diagnóstico , Tumores Neuroectodérmicos Primitivos/patología , Tumores Neuroectodérmicos Primitivos/cirugía , Retina/diagnóstico por imagen , Ultrasonografía/métodosRESUMEN
CASO CLÍNICO: Un lactante de 10 meses fue remitido para estudio de leucocoria izquierda de un mes de evolución. En la exploración se detectó un retinoblastoma que ocupaba el área macular. Fue tratado con quimioterapia intraarterial con 6 mg de melfalán, sin requirir posteriores intervenciones para el control de la enfermedad. DISCUSIÓN: El melfalán es un agente quimioterápico muy efectivo, con uso limitado por la toxicidad sistémica que genera. La quimioterapia intraarterial permite la liberación selectiva en la arteria oftálmica, lo que limita la toxicidad sistémica. Esta combinación de eficacia, seguridad y precisión la hacen una alterativa terapéutica atractiva para el manejo del retinoblastoma
CASE REPORT: A 10-month old infant was referred for the study of a leukocoria of the left eye of one month onset. On examination, a retinoblastoma occupying the macular area was detected. Treatment with intra-arterial chemotherapy (melphalan 6 mg) was performed, with no further intervention required for disease control. DISCUSSION: Melphalan is an effective chemotherapeutic agent. However, its use is limited by the systemic toxicity that may occur. Intra-arterial chemotherapy allows the selective release of melphalan into the ophthalmic artery, thus limiting its systemic toxicity. This combination of efficiency, safety and accuracy makes it an attractive therapeutic alternative for the management of retinoblastoma
Asunto(s)
Humanos , Lactante , Masculino , Retinoblastoma/complicaciones , Retinoblastoma/diagnóstico , Retinoblastoma/terapia , Melfalán/uso terapéutico , Quimioterapia/tendencias , Quimioterapia , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/prevención & control , RetinoblastomaRESUMEN
Retinoblastoma is the most common intraocular eye tumor of the pediatric age. It develops on account of a mutation on chromosome 13 in the 13q14 locus. New studies additionally demonstrated changes in the expression of other genes classified as oncogenes and suppressor genes. The tumor occurs in two forms--heritable (genetic) and non-heritable (non-genetic, sporadic). The most common clinical features of retinoblastoma are leucocoria and strabismus, however, they are not that specific because may also occur in several other eye diseases, such as Coats disease and toxocarosis. The diagnosis of retinoblastoma requires an indirect ophthalmoscopic examination. In addition, imaging techniques such as ultrasonography (USG), magnetic resonance imaging (MRI) and, less commonly, computer tomography (CT) are used. Biopsy is contraindicated because of the risk of spreading cancer cells to the adjacent tissues and possibility of a metastasis development. Currently, the stage of the disease and the therapy prognosis are classified by the International Intraocular Retinoblastoma Classification. At present, chemotherapy is the standard treatment of retinoblastoma. During the last decades new therapies have been introduced, such as transpupillary thermotherapy (TTT), cryotherapy, brachytherapy, limiting the use of teletherapy and the number of performed enucleations. Patients with therapy-induced remission of retinoblastoma should undergo routine examinations because of the increased risk of subsequent neoplasms and other possible complications.