Retinoblastoma is the most common primary malignant intraocular tumor in children. Seeding, specifically the dispersion of the tumor into the adjacent compartments, represents a major parameter determining the degree of retinoblastoma according to the International Classification of Retinoblastoma. In this article we focused on vitreous seeding, one of the main limiting factors in the successful \"eye preservation treatment\" of retinoblastoma. This article presents an overview of the history of vitreous seeding of retinoblastoma, established treatment procedures and new-research modalities. The introduction of systemic chemotherapy in the treatment of retinoblastoma at the end of the 1990s represented a significant breakthrough, which enabled the progressive abandonment of radiotherapy with its attendant side effects. However, the attained concentrations of chemotherapeutics in the vitreous space during systemic chemotherapy are not sufficient for the treatment of vitreous seeding, and the toxic effects of systemic chemotherapy are not negligible. A significant change came with the advent of chemotherapy in situ, with the targeted administration of chemotherapeutic drugs, namely intra-arterial and intravitreal injections, contributing to the definitive eradication of external radiotherapy and a reduction of systemic chemotherapy. Although vitreous seeding remains the most common reason for the failure of intra-arterial chemotherapy, this technique has significantly influenced the original treatment regimen of children with retinoblastoma. However, intravitreal chemotherapy has made the greatest contribution to increasing the probability of preservation of the eyeball and visual functions in patients with advanced findings. Novel local drug delivery modalities, gene therapy, oncolytic viruses and immunotherapy from several ongoing preclinical and clinical trials may represent promising approaches in the treatment of vitreous retinoblastoma seeding, though no clinical trials have yet been completed for routine use.

Retinoblastoma is the most common primary malignant intraocular tumor in children. Seeding, specifically the dispersion of the tumor into the adjacent compartments, represents a  major parameter determining the degree of retinoblastoma according to the International Classification of Retinoblastoma. In this article we focused on vitreous seeding, one of the main limiting factors in the successful \"eye preservation treatment\" of retinoblastoma. This article presents an overview of the history of vitreous seeding of retinoblastoma, established treatment procedures and new-research modalities. The introduction of systemic chemotherapy in the treatment of retinoblastoma at the end of the 1990s represented a  significant breakthrough, which enabled the progressive abandonment of radiotherapy with its attendant side effects. However, the attained concentrations of chemotherapeutics in the vitreous space during systemic chemotherapy are not sufficient for the treatment of vitreous seeding, and the toxic effects of systemic chemotherapy are not negligible. A significant change came with the advent of chemotherapy in situ, with the targeted administration of chemotherapeutic drugs, namely intra-arterial and intravitreal injections, contributing to the definitive eradication of external radiotherapy and a reduction of systemic chemotherapy. Although vitreous seeding remains the most common reason for the failure of intra-arterial chemotherapy, this technique has significantly influenced the original treatment regimen of children with retinoblastoma. However, intravitreal chemotherapy has made the greatest contribution to increasing the probability of preservation of the eyeball and visual functions in patients with advanced findings. Novel local drug delivery modalities, gene therapy, oncolytic viruses and immunotherapy from several ongoing preclinical and clinical trials may represent promising approaches in the treatment of vitreous retinoblastoma seeding, though no clinical trials have yet been completed for routine use.

Aim: To report an exceptionally rare case of malignant choroidal melanoma with vitreous seeding, supported by histopathological and field emission scanning electron microscopic (FESEM) studies. Case report: A 58-year-old male with painless diminution of vision in his left eye for past 1 month was found to have a brown retrolental mass lesion on slit lamp examination in the left eye. Detailed fundus examination revealed choroidal melanoma in the left eye with pigmented seeds extending into the vitreous cavity and associated exudative retinal detachment. Ocular imaging was consistent with the diagnosis. Results: The eyeball was enucleated and the tumor was considered as stage IIB (AJCC 8th edition classification). Metastatic workup of the patient was negative. One half of the eyeball was subjected to field emission scanning electron microscopy to further study the nature and appearance of vitreous seeds. Discussion: Vitreous seeding in choroidal melanoma has been reported only in a handful of cases in literature. Histopathological confirmation of vitreous seeds was done in our case and morphological detailing was performed using FESEM study. Conclusions: Treatment naïve choroidal melanoma can very rarely have vitreous seeds. Early enucleation in such cases carries a favorable prognosis.

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We report a case of retinal atrophy and progressive preretinal fibrosis in an eye previously treated with intravenous and intra-arterial chemotherapy (IAC), which evolved immediately after treatment with intravitreal injection of melphalan. The atrophy and fibrosis progressed later to proliferative retinopathy with dystrophic ossification. The patient was originally diagnosed with bilateral retinoblastoma at 4 months of age and was treated with systemic chemotherapy followed by IAC. New vitreous seeds developed and required treatment with intravitreal chemotherapy. There was resolution of vitreous seeding after 2 doses of intravitreal melphalan, but clinically the eye developed new, widespread retinal atrophy and fibrosis within 1 month of the second injection. This was followed by phthisis and late proliferative retinopathy nearly 1 year later. Retinoblastoma specialists should be aware of this potential complication of combined chemotherapy treatments.

Melanocytoma is a locally invasive intraocular tumor usually located in the optic nerve head, iris, ciliary body and choroid. Melanocytoma can undergo necrosis and lead to pigment dispersion. We report a case of melanocytoma of the ciliary body with vitreous seeds filling the vitreous cavity. A sub conjunctival pigmented lesion was seen due to extra scleral extension of the tumor. The diagnosis of melanocytoma was confirmed by biopsy of the sub conjunctival lesion. Pars plana vitrectomy was performed to clear the vitreous cavity with good visual recovery.

OBJECTIVE: The aim of this study was to assess morphological risk factors associated with optic nerve invasion of choroidal melanoma and to identify possible mechanisms of optic nerve invasion.
METHODS: Medical charts and histology slides of patients with primary choroidal melanoma who were treated by enucleation/exenteration and whose pathology showed optic nerve invasion were reviewed.
RESULTS: Twenty-one patients (mean age: 65.67 ± 14.72 years) with primary uveal melanoma arising from the choroid were included in this analysis. A peripapillary location was present in 86% of the cases. Four types of optic nerve invasion were identified: transvitreal invasion (10%); retinal invasion (23%); direct peripapillary invasion (57%); and a combined mechanism (10%). Optic nerve invasion was prelaminar in 67%, laminar in 10%, and retrolaminar in 23% of the cases. Significantly higher largest basal diameter (p = 0.021) and tumor thickness values (p = 0.017) and higher rates of vortex vein (p = 0.022) and retinal invasion (p = 0.007) were observed in the transvitreal/retinal invasion groups when compared to the direct peripapillary invasion group.
CONCLUSIONS: A peripapillary tumor location was the most common mechanism of optic nerve invasion of choroidal melanoma. In 43% of the cases, other mechanisms including transvitreal and retinal invasion resulted in optic nerve invasion.

OBJECTIVE: To report the occurrence of acute hemorrhagic retinopathy following intravitreal melphalan injection for retinoblastoma.
METHODS: This is a retrospective case series of 2 patients with retinoblastoma treated with intravitreal melphalan for vitreous seeding who developed acute hemorrhagic retinopathy.
RESULTS: Patient 1 is a 6-month-old female with bilateral retinoblastoma (Group D right eye and Group B left eye) treated with 4 cycles of systemic chemotherapy and 2 intravitreal melphalan injections in each eye. Patient 2 is a 10-month-old male with unilateral Group D retinoblastoma treated with 6 cycles of systemic chemotherapy and 2 injections of intravitreal melphalan. At the 1-week follow-up after the second injection, both patients had an acute hemorrhagic retinopathy that resulted in chorioretinal toxicity with a sharp demarcation line between the normal and abnormal retina. At the last follow-up (22 and 12 months, respectively), there was total tumor control and resolution of vitreous seeding in both patients.
CONCLUSIONS: Although intravitreal melphalan injection is effective for vitreous seeding in eyes with retinoblastoma, acute hemorrhagic retinopathy and diffuse chorioretinal atrophy is a possible complication of this treatment modality. Given the clinical findings observed in these patients, the development of this retinal toxicity most likely results from a retrohyaloid overdose. Consequently we suggest preventive measures aimed at limiting the risk of retrohyaloid injection.

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.