Pathological findings in enucleated eyes after intravitreal melphalan injection

The aim of this study is to evaluate the pathological findings of the eye after intravitreal melphalan for viable vitreous seeding from retinoblastoma. All enucleated eyes receiving an intravitreal injection of melphalan (10?50 μg in 0.05 cc) were evaluated for histological changes. Of 25 treated cases, 8 eyes needed enucleation because of phthisis, parent request, or new tumor development. One of the cases was excluded from the study because of a history of intra-arterial chemotherapy with melphalan. There was no case of needle-site scleral involvement by retinoblastoma cells. In two eyes receiving 50 μg melphalan, no viable retinoblastoma cell was detectable in the eye. Severe gliosis, vascular occlusion, retinal necrosis, hemorrhage and neovascularization were seen. Histologically, intravitreal melphalan for recalcitrant or recurrent vitreous seeds from retinoblastoma appears to provide acceptable vitreous seed control. It seems that higher doses could be destructive causing ischemic necrosis in the retina, severe gliosis and secondary neovascular changes as well as having a destructive effect on retinoblastoma cells.     

Porous orbital implant after enucleation in retinoblastoma patients: indications and complications

This study aims to identify risk factors associated with complications in retinoblastoma patients following primary and secondary enucleations with porous implant placement.

A retrospective case-control study was performed between 2010 and 2015. Data pertaining to subjects’ demographics, medical history, clinical, and pathological findings, implant characteristics and complications were collected.

The analysis included 103 eyes of 101 patients age 27.8 ± 21.9 months undergoing enucleation for retinoblastoma. Postoperatively, 19/103 (18%) eyes developed exposure, extrusion, or hematoma requiring subsequent surgery. Exposure was the most common postoperative complication (12/19, 63%). Age at enucleation 24 months or younger, Hispanic ethnicity, female gender, and intravenous chemotherapy prior to enucleation were associated with increased odds of implant complications. In contrast, patients who were given intravitreal melphalan (IM), subtenons carboplatin (SC), or external beam radiation therapy (EBRT) did not demonstrate an increased risk of complications.

In this cohort of retinoblastoma patients undergoing primary or secondary enucleation with porous implants, implant exposure was the most common postoperative complication. Our findings suggest that female gender, Hispanic ethnicity, age at enucleation 24 months or younger, and intravenous chemotherapy prior to enucleation may increase the risk of complications.     

Quimioterapia intraarterial para el tratamiento del retinoblastoma en Chile: experiencia y resultados,período 2013-2020

ObjectiveTo 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.MethodsRetrospective, interventional case series of 29 patients (35 eyes) with persistent or recurrent retinoblastoma.ResultsA 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.ConclusionIAC with melphalan and topotecan is a safe and effective treatment option for persistent or recurrent retinoblastoma, able to reduce enucleation rates.     

Intravitreal chemotherapy for vitreous seeding in retinoblastoma: Recent advances and perspectives

For decades intravitreal chemotherapy (IViC) remained virtually banished from the therapeutic armamentarium against retinoblastoma, except as a heroic attempt of salvage before enucleation in only eyes with refractory vitreous seeding. Very recently, we have initiated a reappraisal of this route of administration by (1) profiling eligibility criteria, (2) describing a safety-enhanced injection procedure, (3) adjusting the tumoricidal dose of melphalan, and (4) reporting an unprecedented efficacy in terms of tumor control of vitreous seeding. Since then, intravitreal chemotherapy is being progressively implemented worldwide with great success, but still awaits formal validation by the ongoing prospective phase II clinical trial. As far as preliminary results are concerned, IViC appears to achieve complete vitreous response in 100% of the 35 newly recruited patients irrespective of the previous treatment regimen, including external beam radiotherapy and/or intra-arterial melphalan. In other words, vitreous seeding, still considered as the major cause of primary and secondary enucleation, can now be controlled by IViC. However, sterilization of vitreous seeding does not necessarily translate into eye survival, unless the retinal source of the seeds receives concomitant therapy. In conclusion, IViC, an unsophisticated and cost-effective treatment, is about to revolutionize the eye survival prognosis of vitreous disease in advanced retinoblastoma.     

Biomarkers in retinoblastoma

AIM: To evaluate the efficacy and safety of combined intra-arterial chemotherapy (IAC) and intravitreal melphalan (IVM) for the treatment of advanced unilateral retinoblastoma. METHODS: This retrospective study involved 30 consecutive eyes from 30 Chinese patients with advanced unilateral retinoblastoma. All patients were initially treated with IAC combined with IVM. The clinical status and complications were recorded at each visit. RESULTS: The International Intraocular Retinoblastoma Classification groups were D in 23 eyes and E in 7 eyes. All eyes showed severe cloud vitreous seeds at the first visit. The mean number of IAC cycles and intravitreal injections was 3.2 (range, 3-4) and 6 (range, 1-14), respectively. The median follow-up time was 29 months (range, 7-36 months). Treatment success with regression of the retinal tumor and vitreous seeds was achieved in 29 of 30 eyes (96.7%). Globe salvage was attained in 93.3% (28/30) eyes, and enucleation (n=2) was performed due to neovascular glaucoma and persistent vitreous hemorrhage. Complications included retinal pigment epithelium (RPE) atrophy (n=13; 43%), mild lens opacity (n=7; 23%), vitreous hemorrhage (n=5; 17%) and rhegmatogenous retinal detachment (n=1; 3%). No extraocular tumor extension or metastasis occurred. CONCLUSION: Combined IAC and intravitreal melphalan is effective and safe for the treatment of advanced unilateral retinoblastoma.     

Persistence of retinal function after intravitreal melphalan injection for retinoblastoma

Background

The risk/benefit profile of intravitreal melphalan injection for treatment of active vitreous seeds in retinoblastoma remains uncertain. We report clinical and electroretinography results after 6 months of one patient who has shown a favorable initial clinical response to intravitreal melphalan injections for treatment of refractory vitreous seeds.

Methods

Clinical case report.

Patient

The patient presented at age 17 months with bilateral retinoblastoma [OD: International Classification (ICRB) group E, Reese-Ellsworth (R-E) class Vb; OS: ICRB D, R-E Vb] with no known prior family history. The right eye was enucleated primarily. The patient received systemic chemotherapy and extensive local treatment to the left eye. Ten months later, she presented with recurrent disease, including fine, diffuse vitreous seeds. Tumor control was established with intra-arterial chemotherapy and local treatment. Subsequent recurrence was treated with further intra-arterial chemotherapy, local treatment, and plaque radiotherapy with iodine-125. Persistent free-floating spherical vitreous seeds were treated with 4 cycles of intravitreal melphalan injection via the pars plana, with doses of 30, 30, 30, and 20 μg.

Results

After 6 months of follow-up, the left eye remained free of active tumor. Visual acuity was 20/40. Photopic ERGs amplitudes were unchanged compared with those recorded prior to the intravitreal injection treatments.

Conclusions

Intravitreal melphalan injection for refractory spherical vitreous seeds of retinoblastoma with favorable tumor response is compatible with good central visual acuity and preservation of retinal function as indicated by photopic ERG recordings.     

Current treatment of retinoblastoma

Chemotherapy has recently achieved a major role in the primary management of intraocular retinoblastoma. Tumor reduction by first-line chemotherapy (chemoreduction) followed by local treatments is now accepted as treatment strategy for intraocular retinoblastoma with the goal of avoiding external beam radiotherapy (EBRT) or enucleation. Although efficient in reducing tumor volume, chemotherapy cannot cure retinoblastoma. Different chemoreduction protocols are used to shrink the tumor, making it treatable with cryotherapy, laser photocoagulation, thermotherapy, and plaque radiotherapy. Systemic chemotherapy used with local ophthalmic therapies during or after the chemotherapy can eliminate the need for enucleation or external beam radiotherapy in Reese-Ellsworth group 1, 2, or 3 retinoblastoma. This combination is not sufficient to obtain tumor control in most eyes with large tumors and diffuse vitreous and subretinal seeds (Reese-Ellsworth group 4 and 5 tumors), and EBRT or enucleation is eventually required. The resultant visual acuity after globe-conserving therapies in those eyes with Reese-Ellsworth group 4 and 5 tumors is often poor. Preliminary results of a phase I/II study of subconjunctival carboplatin injection are encouraging. Enucleation is still recommended in situations such as eyes containing large tumors, long standing retinal detachment, neovascular glaucoma, pars plana tumor seeding, anterior chamber involvement or choroid, optic nerve or orbital tumor extension, and no expectation for useful vision. Chemoprophylaxis is necessary for patients with tumor extending to the surgical margin of the optic nerve and is likely beneficial in preventing metastases in patients with tumor extending beyond the lamina cribrosa. Intensified chemotherapy with autologous stem cell rescue appears effective for patients with metastatic retinoblastoma.     

Unilateral retinoblastoma; natural history and an age-based protocol in 248 patients

ObjectivesWe aimed to study the clinical state and prognosis of patients with unilateral retinoblastoma who were being treated at a paediatric comprehensive cancer centre in a limited-resource country, to assess the different phases of treatment and the success of different, more complex real-life models.SubjectsIn this retrospective study, we created a snapshot of our retinoblastoma database for the period between 2007 and 2015. Patients whose data were included in the study were followed up until 2016. Out of a total of 744 screened patients, we included data of 248 patients who had been diagnosed with unilateral retinoblastoma.ResultsAs classified as per the International Retinoblastoma Classification, 1 patient presented with group A, 21 with group B, 39 with group C, 104 with group D and 83 with group E retinoblastoma. Chemotherapy was the initial line of treatment in 115 patients and enucleation in 133 others. Later, 141 patients (56.9%) required further management. Patients had a mean ocular survival time of 20.8 months. Nine patients developed extraocular disease at a later stage of management: five after upfront enucleation and four after neoadjuvant chemotherapy. Mean overall survival time stood at 90.2 months. Four and three deaths were recorded in groups D and E, respectively. A single patient died in the initial chemotherapy arm, while six passed away in the initial enucleation arm.ConclusionOur study highlights the importance of initial chemotherapy and close follow-up after enucleation of classes D and E affected eyes even in absence of germline mutations.Subject terms: Paediatrics, Retinal diseases     

视网膜母细胞瘤综合治疗后临床组织病理学特点及VEGF和Ki-67蛋白表达研究

目的 探讨视网膜母细胞瘤(RB)综合治疗后组织病理学和临床特点,以及综合治疗后RB的血管内皮细胞生长因子(VEGF)、Ki-67蛋白的表达情况。方法 对9例综合治疗后行眼球摘除术的病例的组织病理学和临床资料进行回顾性分析。使用免疫组织化学和实时多聚合酶链反应方法测量VEGF的表达,用免疫组织化学法测Ki-67的表达。结果 在9例眼球中,6例为RB国际分期D期的肿瘤,3例为E期。眼球摘除的原因为：肿瘤广泛玻璃体种植8例,肿瘤复发3例,大量视网膜下积液,肿瘤视网膜下种植3例,玻璃体出血2例,完全的牵引性视网膜脱离3例。在综合治疗期间肿瘤都表现为缩小,基底部宽度平均缩小43.7％,厚度平均缩小57.9％。3例表现为奶酪-芝士状消退模式,1例表现为鱼肉状消退模式,5例表现为混合型消退模式。计划性眼球摘除病例的VEGF表达低于复发性RB。结论 综合治疗后眼球摘除的最主要原因为广泛玻璃体种植。混合型消退模式是较常见的消退模式。综合治疗过程中行计划性眼球摘除病例VEGF表达降低。VEGF表达增高在综合治疗后RB的复发中可能起到一定的作用。     

Intravitreal HDAC Inhibitor Belinostat Effectively Eradicates Vitreous Seeds Without Retinal Toxicity In Vivo in a Rabbit Retinoblastoma Model

PurposeCurrent melphalan-based regimens for intravitreal chemotherapy for retinoblastoma vitreous seeds are effective but toxic to the retina. Thus, alternative agents are needed. Based on the known biology of histone deacetylases (HDACs) in the retinoblastoma pathway, we systematically studied whether the HDAC inhibitor belinostat is a viable, molecularly targeted alternative agent for intravitreal delivery that might provide comparable efficacy, without toxicity.MethodsIn vivo pharmacokinetic experiments in rabbits and in vitro cytotoxicity experiments were performed to determine the 90% inhibitory concentration (IC₉₀). Functional toxicity by electroretinography and structural toxicity by optical coherence tomography (OCT), OCT angiography, and histopathology were evaluated in rabbits following three injections of belinostat 350 µg (2× IC₉₀) or 700 µg (4× IC₉₀), compared with melphalan 12.5 µg (rabbit equivalent of the human dose). The relative efficacy of intravitreal belinostat versus melphalan to treat WERI-Rb1 human cell xenografts in rabbit eyes was directly quantified. RNA sequencing was used to assess belinostat-induced changes in RB cell gene expression.ResultsThe maximum nontoxic dose of belinostat was 350 µg, which caused no reductions in electroretinography parameters, retinal microvascular loss on OCT angiography, or retinal degeneration. Melphalan caused severe retinal structural and functional toxicity. Belinostat 350 µg (equivalent to 700 µg in the larger human eye) was equally effective at eradicating vitreous seeds in the rabbit xenograft model compared with melphalan (95.5% reduction for belinostat, P < 0.001; 89.4% reduction for melphalan, P < 0.001; belinostat vs. melphalan, P = 0.10). Even 700 µg belinostat (equivalent to 1400 µg in humans) caused only minimal toxicity. Widespread changes in gene expression resulted.ConclusionsMolecularly targeted inhibition of HDACs with intravitreal belinostat was equally effective as standard-of-care melphalan but without retinal toxicity. Belinostat may therefore be an attractive agent to pursue clinically for intravitreal treatment of retinoblastoma.     

Clinical audit of retinoblastoma management: a retrospective single-institution study

ObjectiveThe primary aim of this study was to identify the frequency of death, metastasis, enucleation, and use of external beam radiation therapy (EBRT) among retinoblastoma patients. The secondary aim was to determine whether any events were associated with suboptimal clinical management to identify areas for clinical care improvement.MethodsPatients diagnosed with retinoblastoma between January 1, 2000, and December 31, 2015, at The Hospital for Sick Children were included. Medical records of eligible patients underwent a comprehensive 2-part review. First, a chart review collected diagnostic details, treatment course, and occurrence of 4 events: death, metastasis, use of EBRT, and enucleation. Next, events were reviewed in detail, and a multidisciplinary committee reached consensus on cases managed suboptimally.ResultsThe study included 209 patients (292 eyes). There were 8 deaths, 11 metastases, 177 enucleations (143 primary, 34 secondary), and 8 uses of EBRT. Thirteen patients were reviewed by the multidisciplinary committee, which confirmed that 5 of these patients had events associated with suboptimal clinical management. Three patients developed metastases leading to death (misdiagnosis and mismanagement of trilateral retinoblastoma [1], parental refusal of enucleation [1], and inaccurate histopathology after primary enucleation [1]). One patient developed extraocular extension related to scleral invasion following aggressive focal therapy. One patient underwent secondary enucleation for a Group B eye related to mismanagement of a treatment complication.DiscussionDeaths, metastases, and enucleations with documented instances of suboptimal care highlighted a need to enhance medical team and patient communication, histopathology interpretation, laser treatment guidelines, and trilateral retinoblastoma management. Routine clinical audit of retinoblastoma management can identify areas for clinical practice change.     

The clinical outcomes of proton beam radiation therapy for retinoblastomas that were resistant to chemotherapy and focal treatment

Purpose

To evaluate the clinical results of proton beam radiation therapy (PBRT) for treatment of retinoblastoma.

Methods

Children with retinoblastoma who were treated with chemotherapy and focal treatment such as brachytherapy and thermotherapy but showed no response or developed recurrences later received PBRT. The PBRT strategy was designed to concentrate the radiation energy to the retinoblastoma and spare the surrounding healthy tissue or organs.

Results

There were three patients who received PBRT. The first patient received PBRT because of an initial lack of tumor regression with chemotherapy and brachytherapy. This patient showed regression after PBRT. The second patient who developed recurrence of retinoblastoma as diffuse infiltrating subretinal seeding was taken PBRT. After complete regression, there was recurrence of tumor and the eye was enucleated. The third patient had unilateral extensively advanced retinoblastoma. Initial chemotherapy failed and tumor recurred. The tumor responded to PBRT and regressed significantly. However, the eye developed sudden multiple recurrences, so we had to perform enucleation.

Conclusions

PBRT for retinoblastoma was effective in cases of showing no response to other treatment modalities. However, it should be carefully applied when there was recurrence of diffuse infiltrating subretinal seeding or extensively advanced retinoblastoma initially.     

Role of chemotherapy alone or in combination with hyperthermia in the primary treatment of intraocular retinoblastoma: preliminary results

BACKGROUND—The efficacy of the etoposide-carboplatin combination in extraocular retinoblastoma is well known. This drug combination is therefore used in intraocular retinoblastoma, as primary reduction chemotherapy, before local treatment. The use of carboplatin in combination with diode laser hyperthermia as local treatment (thermochemotherapy) has been recently described as a conservative approach avoiding external beam radiotherapy in posterior pole tumours.
METHODS—All patients were reviewed, who were treated for retinoblastoma at the Institut Curie between June 1994 and October 1995, in whom treatment included either reduction chemotherapy or thermochemotherapy or both modalities successively. 23 patients presenting with unilateral (three) or bilateral (20) intraocular retinoblastoma received neoadjuvant chemotherapy consisting of two courses of etoposide 150 mg/m²/day and carboplatin 200 mg/m²/day for 3 days. 15 patients (17 eyes), eight of whom had already received neoadjuvant chemotherapy, were treated by thermochemotherapy.
RESULTS—Neoadjuvant chemotherapy: overall, seven eyes in seven patients could be treated conservatively, avoiding external beam irradiation, with a median follow up of 14 months. Thermochemotherapy: external beam irradiation was avoided for 14 of the 17 eyes treated.
CONCLUSION—Integration of neoadjuvant chemotherapy and combined treatment with carboplatin and diode laser, into the therapeutic armamentarium for retinoblastoma allows use of more aggressive treatments such as enucleation and external beam radiation.

Keywords: retinoblastoma; chemotherapy; thermochemotherapy     

Enucleation for retinoblastoma: the experience of a single center in Jordan

Despite multiple advances in the management of retinoblastoma, enucleation remains an essential therapeutic modality. We studied patients who underwent enucleation at the King Hussein Cancer Center in Jordan. We retrospectively reviewed medical records of children with retinoblastoma who were treated at our center from June 2002 to February 2008. Twenty-eight eyes from 27 patients were enucleated. Median age at diagnosis was 1.1 years (range, 0.3–6.3 years). Twenty-six eyes (93%) had advanced disease (RE groups IV and V). Seventeen patients (61%) had unilateral retinoblastoma, and 11 (39%) had bilateral retinoblastoma. The median time from diagnosis to enucleation was 0.45 months (range, 0–45 months; mean, 4.4 months) and was longer for patients with bilateral retinoblastoma (median, 2.2 vs. 0.2 months; P = 0.034). Twenty enucleated eyes (71%) did not show high-risk pathologic features. Seventeen eyes with advanced intraocular disease were enucleated at the time of presentation, whereas chemoreduction was attempted for the other 19 eyes with advanced intraocular disease. Enucleation was then recommended for nine (47%) of those eyes. Enucleation at the time of diagnosis was feasible for most patients with advanced disease. Attempted salvage of eyes with advanced disease is justified, particularly in patients with bilateral disease. We were able to salvage almost half of these eyes. We hope our study provides new insights for counseling patients.     

Modern treatment of retinoblastoma: A 2020 review

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.     

Retinopathy in young retinoblastoma patients receiving a chemotherapy treatment: clinical trials and morphometric analysis

ABSTRACT

Background: This research is to evaluate patients with retinoblastoma, who receive chemotherapy, with enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT) to compare the signs of retinopathy.

Materials and Methods: A prospective non-randomized trial included 125 eyes of 74 patients at the age of 24 ± 1.6 months with retinoblastoma. All patients underwent an ophthalmoscopic examination and EDI-OCT before therapeutic treatment. The test group consisted of 55 patients, who underwent a course of chemotherapy. Patients were divided into two groups depending on the type of chemotherapy. Group #1 patients received six cycles of systemic intravenous chemotherapy treatment, ophthalmoscopic examination, and EDI-OCT occurred after third cycle and sixth cycle. Group #2 underwent three cycles of IVC chemotherapy treatment, and then local chemotherapy – three cycles of super-selective intra-arterial chemotherapy for exophytic retinoblastoma and 9 procedures of intravitreal (IVT) for endophytic retinoblastoma. Eyes in the control group were affected by eccentric neoplasms but macula and the optic nerve were not damaged.

Results: After six cycles of IVC chemotherapy treatment, Group #1 history expanded with atrophy-induced peripapillary nerve fiber layer thinning (33.9%). At three cycle of super-selective intra-arterial chemotherapy, OCT imaging in Group #2 revealed more related symptoms like retinal vascular distention in peritumoral area. After systemic and intravitreal chemotherapy, macular puckers and small hyperreflective dotted foci in the inner retina were tracked. In Group #3 affected by peripheral tumors, the topographic anatomy of the macula was normal prior to therapy.

Conclusion: Profound morphometric disturbances that come with combined chemotherapy call for a more careful treatment with methods selected in terms of OCT findings and specific chemotherapy contraindications.     

Vasculopatía coroidea oclusiva tras quimioterapia intraarterial: hallazgos en la RMN

PurposeTo evaluate magnetic resonance imaging (MRI) findings in patients suffering choroidal occlusive vasculopathy (COV) after intra-arterial chemotherapy (IAC) for retinoblastoma.MethodsA retrospective study of 37 eyes of 34 patients receiving IAQ between 2016 to 2021 as primary or secondary treatment for retinoblastoma was conducted. Twenty-two patients received systemic chemotherapy with carboplatin, vincristine and etoposide. The rest received IAC as primary treatment. The drugs administered were melphalan (3-4 mg), carboplatin (40 mg) plus topotecan (20 mg). The patients were examined under general anaesthesia every month to observe tumor regression and possible complications of the treatment. For the patients with COV an MRI was obtained to analyse the choroidal thickness and axial ocular length.ResultsA COV was observed in 5 of the 37 eyes receiving IAC (13,51%), all of them with a complete sectorial choroidopathy not sparing the fovea (grade 2). In 4 of the 5 patients the choroidal thickness was decreased and in three cases the size of the eye which presented COV was clearly smaller than the contralateral eye. Tumor control was archived in all 5 patients.ConclusionIn our cases COV was associated with reduction of thinning of choroid and eye length in the MRI. A new classification maybe needed to correlate better with the severity of the complication affecting the fovea. Although early results generally are favorable to the use of IAC, longer follow up and scrupulous documentation of side effects will be necessary to know the true role of IAC for retinoblastoma.     

No ocular motility complications after subtenon topotecan with fibrin sealant for retinoblastoma

Objective

To report our long-term experience with the local toxicity profile and ocular motility changes after treatment of intraocular retinoblastoma with subtenon topotecan chemotherapy.

Design

Cross-sectional study.

Participants

Ten eyes in 8 patients with retinoblastoma treated with subtenon topotecan.

Methods

We assessed potential complications in ocular motility in eyes with retinoblastoma treated with subtenon topotecan using forced duction testing under general anaesthesia. Eyes subsequently enucleated because of treatment failure were examined histologically.

Results

Ten eyes in 8 patients with retinoblastoma treated with 1 to 4 injections of subtenon topotecan were examined repeatedly, with a mean follow-up period of 37 months. Ocular motility remained normal in all eyes by forced duction, with no observed persistent conjunctival congestion, abnormal ocular motility, or enophthalmos in retained eyes 3 years after last injection. Histopathologic examination of the 2 enucleated eyes did not reveal signs of orbital tissue necrosis or fibrosis.

Conclusions

Unlike subtenon carboplatin, subtenon topotecan therapy is not associated with long-term toxicity affecting ocular muscles or orbital soft tissue. No effect on ocular motility was observed.     

Successful conservative treatment of massive choroidal relapse in 2 retinoblastoma patients monitored by ultrasound biomicroscopy and/or spectral domain optic coherence tomography

Purpose: To report the occurrence and management of secondary choroidal infiltration in two retinoblastoma (rb) patients.

Methods: Fundus examination and imaging with spectral domain optical coherence tomography (SD-OCT), B-scan ultrasonography (B-scan), and ultrasound biomicroscopy (UBM).

Results: Case 1: A 19-month-old girl with multifocal unilateral group B rb pretreated with intravenous chemotherapy (IVC) was referred for further management. At 3.5 years of age, routine 3-Tesla magnetic resonance imaging (3T-MRI) revealed an asymptomatic pinealoblastoma that underwent resection and adjuvant intensive IVC. Concomitant ophthalmic follow-up revealed a recurrence 8.3 × 2.8 mm at the posterior pole nasally to the optic disc on B-scan, localized within the choroid on SD-OCT and 3T-MRI. With high dose IVC ongoing, total regression of the choroidal mass was confirmed on SD-OCT already after 3 weeks. At 6-month follow-up, choroidal and pineal tumors were in complete remission. Sadly, the child died of intravascular disseminated coagulation-like disease after the 5th IVC.

Case 2: A heavily pretreated 20-month-old girl with bilateral rb was referred for persistent vitreous seeding in her remaining eye (OD). Three months after intravitreal chemotherapy and chemothermotherapy, a hemorrhagic mass was observed inferior to the primary tumor. Two weeks later, an underlying peripheral choroidal mass 16 × 6 mm was documented by UBM and confirmed by 3T-MRI. Complete resolution was achieved 3 weeks after combined intra-arterial chemotherapy (IAC) of melphalan-topotecan. No recurrence or metastasis was observed at 34-month follow-up.

Conclusion: Isolated massive choroidal invasion can be treated conservatively with IVC or IAC in selected cases. SD-OCT, UBM, and B-scan ultrasonography are instrumental in the detection and follow-up of choroidal lesions.     

Development of New Solitary Retinoblastoma Tumors during and after Chemotherapy

PurposeTo review the occurrence of new solitary tumors during and after intravenous chemotherapy against retinoblastoma.MethodsFrom 115 eyes of 78 patients with a diagnosis of intraocular retinoblastoma who underwent intravenous chemotherapy and focal treatment without prior treatment, patient demographics, age at diagnosis, laterality, classification (Reese-Ellsworth and International Classification of Retinoblastoma), and treatment options were recorded. In addition, the occurrence of small tumors during and after chemotherapy was documented with a detailed review of medical records and fundus photographs.ResultsOf a total of 115 eyes of 78 consecutive patients, new solitary tumors were observed in 50 eyes (50 / 115, 43%) of 40 patients (40 / 78, 51%). Multinominal logistic regression analyses showed that age at diagnosis (before 1 year) and vitreal seeding at diagnosis were linked to the development of isolated and miliary tumors, respectively. Kaplan-Meier analyses demonstrated that all small tumors developed with 20 months from the start of chemotherapy. Twenty-eight eyes (28 / 34, 82%) were salvaged with additional focal treatment in 34 eyes with isolated tumors.ConclusionsSmall tumors were observed during and after chemotherapy against retinoblastoma in patients who underwent intravenous chemotherapy and focal treatment. It is necessary to promptly identify and address small tumors for the preservation of eyeball and vision.