Intravitreal chemotherapy in the management of retinoblastoma in a resource-limited setting

Intravitreal chemotherapy (IVitC) in the management of retinoblastoma has increased the rate of globe salvage, specifically in patients with recurrent disease and associated vitreous seeds. A significant number of children with retinoblastoma in developing countries present late, resulting in higher intraocular tumour-stage at presentation. Treatment requirements for such tumours usually include intravenous chemotherapy (IVC) and/or intra-arterial chemotherapy (IAC). While IVC has a long usage track record and a good efficacy, it has been reported to be associated with higher recurrence rates in a significant number of patients. Intra-arterial chemotherapy has the advantage of lower recurrence rates but requires personnel with advanced interventional radiology skills and has limited efficacy in treating intravitreal seeds. Intravitreal chemotherapy has gained popularity recently, largely because of its superior efficacy in the management of vitreous seeds, subretinal seeds and recurrent retinal tumour. An 8-month-old male infant initially presented with bilateral retinoblastoma, International Classification System for Intraocular Retinoblastoma (ICRB) Group E in the right eye and Group B on the left eye. The right eye was enucleated and currently has a prosthesis. The left eye had tumours that initially responded to brachytherapy and transpupillary thermotherapy (TTT). Approximately two years later his tumours recurred with vitreous seeds and were successfully managed with the use of cryotherapy and intravitreal chemotherapy. The simplicity of the technique of IVitC and its efficacy in controlling vitreous seeds and recurrent retinal tumours makes this route of regional chemotherapy a viable one in areas with limited expertise and resources such as South Africa.

Combination of brachytherapy and intravitreal chemotherapy in the treatment of retinoblastoma with vitreous seeding

Purpose: To report the efficacy of combined intravitreal chemotherapy (IVC) and ruthenium-106 brachytherapy in retinoblastoma, either as first line or second line treatment following systemic chemoreduction or intraarterial chemotherapy. Methods: Retrospective data collection of 18 eyes from 18 patients treated with IVC and brachytherapy from August 2014 to December 2019. Results: The method described was our first line therapy in 6 patients, whereas it was used as second line treatment after chemoreduction in the remaining 12 patients. The eyes showed the following classification at initial presentation: 2 group B eyes, 3 group C eyes and 13 group D eyes. The mean follow-up was 19.5 months (range 2 – 53 months). Mean patient age at brachytherapy was 34.0 months (range 15 – 83 months). Median prescribed dose at the tumour base and apex was 574.5 ± 306.7Gy and 88.5 ± 12.2Gy, respectively. The ocular retention rate was 66.7%. Six eyes had to be enucleated due to uncontrollable subretinal and recurrent vitreous seeding, tumour relapse, recurrence of a solid tumour elsewhere in the eye and persistent vitreous bleeding with loss of tumour control. The mean number of intravitreal injections of Melphalan was 5.0. Two patients received a simultaneous injection of Topotecan for insufficient therapeutic response. With regard to radiogenic complications, we could observe temporary retinal and vitreous bleeding (27.8%), serous retinal detachment (44.4%) and radiogenic maculopathy and retinopathy (11.1%). None of the children showed metastatic disease during follow up. Conclusion: Ruthenium-106 plaque therapy in combination with intravitreal chemotherapy is an effective local therapy with good tumour control rates even in advanced eyes. Overall, the analysed therapeutic approach shows an acceptable side effect profile, especially when considering that EBRT and systemic polychemotherapy, or at least the number of cycles needed, with their increased incidence of adverse events can thus be avoided.

Changes in Treatment Patterns and Globe Salvage Rate of Advanced Retinoblastoma in Korea: Efficacy of Intra-Arterial Chemotherapy

(1) Background: To analyze changes in treatment patterns for advanced retinoblastoma over time and differences in globe salvage rates; (2) Methods: Retrospective, observational case-control study of 97 eyes of 91 patients with advanced retinoblastoma (Group D and E).; (3) Results: Patients were divided into two groups based on whether they were treated before or after intraarterial chemotherapy (IAC) was introduced in our center in 2010. Before 2010, primary treatment pattern was enucleation, which was performed in 57.6% of cases, whereas primary treatment pattern after 2010 was IAC combined with intravenous chemotherapy (IVC), which was performed in 78.1%. Intravitreal chemotherapy (IVitC) has been performed to treat vitreous and subretinal seeding since 2015. The 5-year globe salvage rate of IVC alone was 24.0% for Group D and 0% for Group E, whereas that of IVC–IAC was 50.4% for Group D and 49.7% for Group E. Whether IVitC was performed or not did not significantly contribute to globe salvage rate. There was one metastatic death in the IVC alone group.; (4) Conclusions: Primary treatment pattern changed from enucleation to IAC-based treatment, which can now save nearly half of eyes with advanced retinoblastoma with excellent safety profile and survival rate.

Results of cataract surgery in children with retinoblastoma

Purpose. To present results of cataract surgery in children with retinoblastoma. Material and methods. Within the period from 2012 to 2020, cataract surgery was performed in 21 children (22 eyes) with retinoblastoma aged 28 to 155 months (average – 65 months). Tumors of group B occurred in 2 cases, group C – in 4, group D – in 14, group E – in 1. In 8 cases, cataract occurred in a single eye. Posterior capsular cataract was observed in 18 patients, total – in 3. In all cases, the presence of cataract impeded the control of the tumor. Before cataract surgery all children underwent systemic chemotherapy, some of them also underwent intra-arterial and/or intravitreal chemotherapy, external beam radiotherapy, Gamma Knife stereotactic radiosurgery and local treatment modalities (episcleral plaque brachytherapy, thermotherapy, cryotherapy). There were no signs of tumor progression in all cases at the time of cataract surgery. The mean interval between complete tumor regression and cataract surgery was 23 months (range 6–75 months). Results. Full transparency of optical media was achieved in all eyes after surgery. No intraoperative and postoperative complications occurred. The final visual acuity was improved in 12 eyes, in the rest visual acuity could not be determined due to age. There were no signs of tumor recurrence or metastases in mean follow-up after surgery of 29 months (range 3–60). Conclusion. Our experience of cataract surgery in children with complete regression of retinoblastoma was proved to be a safe and effective way to improve visual functions and achieve transparency of optical media. Key words: retinoblastoma, cataract surgery, ophtalmooncology, functional results

Vitreoretinal Lymphoma

Vitreoretinal lymphoma (VRL) is a rare variant of primary central nervous system lymphoma (PCNSL), mostly of diffuse large B cell lymphoma, which affects the retina and/or the vitreous with or without optic nerve involvement. The disease course is aggressive. Up to 90% of the patients develop central nervous system lymphoma within one year. The diagnosis of VRL is challenging due to nonspecific chronic and relapsing uveitis and is made by anterior chamber tab or vitreous aspirate biopsy. There is no established treatment protocol for VRL patients with bilateral involvement without CNS involvement. There are suggestions to use only intravitreal chemotherapy with methotrexate and/or rituximab. Alternatively, systemic high-dose MTX treatment or external beam radiotherapy is used. Further studies are needed to prove and confirm the prophylactic systemic therapy in preventing CNS involvement in limited VRL.

Safety and Efficacy of Intravitreal Chemotherapy (Melphalan) to Treat Vitreous Seeds in Retinoblastoma

Background: Active vitreous seeds in eyes with retinoblastoma (Rb) adversely affects the treatment outcome. This study aimed to investigate the safety and efficacy of intravitreal melphalan chemotherapy (IViC) as a treatment for recurrent and refractory vitreous seeds in patients with Rb.Methods: We used a retrospective non-comparative study of patients with intraocular Rb who had vitreous seeds and were treated by IViC (20–30 μg of melphalan) using the safety-enhanced anti-reflux technique. Tumor response, ocular toxicity, demographics, clinical features, and survival were analyzed.Results: In total, 27 eyes were treated with 108 injections for recurrent (16 eyes) or refractory (11 eyes) vitreous seeds after failed systemic chemotherapy. A total of 15 (56%) were males, and 20 (74%) had bilateral disease. At diagnosis, the majority (n = 21) of the injected eyes were group D, and n = 6 were group C. Vitreous seeds showed complete regression in 21 (78%) eyes; 100% (n = 10) for eyes with focal seeds; 65% (n = 11/17 eyes) for eyes with diffuse seeds (p = 0.04); 7 (64%) eyes with refractory seeds; and 14 (87%) eyes with recurrent seeds showed complete response (p = 0.37). In total, 16 (59%) eyes developed side effects: retinal toxicity (48%), pupillary synechiae (15%), cataracts (30%), iris atrophy (7%), and retinal and optic atrophy (4%). Only one child was lost to follow-up whose family refused enucleation and none developed orbital tumor recurrence or distant metastasis.Conclusion: IViC with melphalan is effective (more for focal than diffuse seeding) and a relatively safe treatment modality for Rb that can improve the outcomes of eye salvage procedures. However, unexpected toxicity can occur even with the standard dose of 20–30 μg.

A New Rapidly Growing Dome-Shaped Choroidal Lesion in an Eye with Treated Retinoblastoma

Background. To describe an extensive untreatable choroidal metastasis by retinoblastoma in the treated patient which was clinically indistinguishable from regular tumor recurrence. Methods. A 24-month-old girl without a family history of retinoblastoma (RB) was discovered to have group C RB in her right eye and group D in her left eye. The patient received 12 cycles of intravenous chemotherapy, intra-arterial chemotherapy (IAC), and intravitreal chemotherapy for the left eye and focal adjuvant therapy (laser thermotherapy and cryotherapy) for both eyes. Six months after the last treatment, fundus examination showed a regressed tumor in both eyes. Ten months after the last treatment, except for in addition to tumor recurrence, rising intraocular pressure was noticed in the left eye. While doing IAC for the left eye, a very rapid growing yellowish dome-shaped mass was found which had doubled in size in two weeks. Enucleation was considered for her. Results. Pathology evaluation of the enucleated eye revealed a very massive dome-shaped choroidal metastasis invasion with poorly differentiated RB tumor. Prophylactic systemic chemotherapy was performed for the patient. Conclusion. Choroidal metastasis in RB patients is often diagnosed based on pathology reports, but it may rarely be seen in clinical examinations especially if the pattern of tumor recurrence and growth is abnormal.

Management of cataracts secondary to intravitreal chemotherapy injections for retinoblastoma seeding

Purpose: To report our experience in the management of cataracts presumably due to intravitreal chemotherapy administration in eyes with vitreous disease associated with retinoblastoma. Methods: This retrospective study consisted of a cohort of five eyes of five retinoblastoma patients who developed cataracts secondary to intravitreal chemotherapy administration and who then underwent cataract surgery. All patients underwent lensectomy and anterior vitrectomy with/without intraocular lens implantation via clear corneal approach. All cases were administered intraoperative intravitreal melphalan (35–40 mcg) and topotecan (10–20 mcg) at the end of cataract surgery as a preventive measure against retinoblastoma spread. Injections were repeated as needed in monthly follow-ups. Main outcome measures were enucleation rate and disease-free survival time. Results: The age at surgery ranged between 5 and 10 years. Follow-up time varied from 12 to 16 months. Treatment-free period before surgery ranged between 3 and 20 months. Time from last injection to cataract detection was: 2, 2, 10, 6, and 7 months; and time from last injection to cataract surgery was: 8, 3, 20, 7, and 15 months in cases 1–5, respectively. None of the eyes required enucleation. Tumor control was achieved in all patients at the end of follow-up. Conclusions: Injection of melphalan and topotecan into anterior parts of the vitreous may lead to cataract formation. This can be safely managed with lensectomy and anterior vitrectomy and the use of intravitreal administration of melphalan and topotecan at the conclusion of the surgery as a precautionary measure against the potential risk of extraocular spread.

Peripapillary Neuroendocrine Carcinoma Metastasis: A Novel Approach to Treatment

Peripapillary and circumpapillary retinal intraocular metastases are rare and present a treatment challenge for ophthalmologists because of the high risk of iatrogenic injury to the optic nerve. There are no clear guidelines on the management of these lesions, and many clinicians will initially observe for improvement of the metastases with systemic chemotherapy before considering local therapy with external beam radiation. Radiation to the optic disc carries a significant risk of injuring the optic nerve, leading to worsening of vision. Alternative treatment approaches are needed. We present a patient with large-cell neuroendocrine carcinoma with metastasis to the peripapillary retina who was treated with intravitreal topotecan and with intravitreal aflibercept. Serial fundus photos, ultrasound, and optical coherence tomography demonstrated a reduction in size of the lesion and a decrease in subretinal fluid with intravitreal topotecan and aflibercept. In addition, visual acuity was stabilized during treatment. Intravitreal chemotherapy for intraocular metastases in vision-sensitive areas such as the peripapillary retina may be a viable alternative for patients who seek to preserve their vision and maintain their quality of life.