Eye Cancer Retinoblastoma & Ocular Melanoma

The most common first sign is leukocoria — a white or grayish pupillary reflex ('cat's eye') that may be visible in photographs taken in dim light or with flash. It is caused by light reflecting off the tumor behind the lens. Strabismus (crossed or wandering eyes) is the second most common presenting sign. Any child with these findings requires urgent ophthalmologic evaluation, as retinoblastoma is highly treatable when caught before it spreads beyond the eye.

Approximately 40% of retinoblastoma cases are caused by a germline (inherited) mutation in the RB1 tumor suppressor gene. Children with germline RB1 mutations frequently develop bilateral disease (both eyes) at a younger age. These children, their siblings, and parents may benefit from genetic testing and screening. Retinoblastoma survivors with germline RB1 mutations also have an elevated lifelong risk of developing other cancers (such as osteosarcoma) and require long-term specialist surveillance. Genetic counseling is an important part of care for hereditary retinoblastoma families.

Uveal melanoma arises from melanocytes within the uveal tract of the eye (choroid, ciliary body, or iris). While it shares a cell of origin with cutaneous (skin) melanoma, it is a biologically distinct disease with a very different mutational landscape — driven by GNAQ or GNA11 mutations rather than BRAF mutations. This means that BRAF-targeted therapies effective in cutaneous melanoma do not work for uveal melanoma. Uveal melanoma also behaves differently: it primarily metastasizes to the liver rather than the lungs or lymph nodes, and it responds poorly to the checkpoint immunotherapies that have transformed cutaneous melanoma treatment.

Modern treatment approaches have dramatically improved eye salvage rates. For intraocular retinoblastoma, techniques including intra-arterial chemotherapy (IAC), systemic chemotherapy with local consolidation, intravitreal chemotherapy, laser photocoagulation, cryotherapy, and plaque radiotherapy can often preserve the eye and functional vision — particularly for Groups A through D. Enucleation (eye removal) remains the recommended approach for Group E disease (the most advanced intraocular extent), when globe-salvaging is not feasible, or when there is extraocular spread. The decision should be made in consultation with a specialist retinoblastoma center with experience in all available approaches.

Intra-arterial chemotherapy (IAC) is a minimally invasive procedure in which a microcatheter is guided through a blood vessel in the groin up to the ophthalmic artery supplying the eye. Chemotherapy (usually melphalan, sometimes carboplatin or topotecan) is delivered directly into the blood supply of the eye, achieving very high local drug concentrations while minimizing systemic exposure. IAC has greatly improved eye salvage rates for advanced intraocular retinoblastoma and is now a primary globe-preserving treatment at experienced retinoblastoma centers.

Despite successful local treatment of the primary uveal tumor (with plaque brachytherapy or proton therapy achieving excellent local control), a significant proportion of patients with high-risk uveal melanoma develop distant metastases — most commonly to the liver. The risk of metastasis is stratified by molecular features including monosomy 3, BAP1 inactivation, and gene expression class (Class 1A/1B/2). All uveal melanoma patients should undergo regular hepatic surveillance — typically liver MRI or ultrasound every 6 months — after definitive local treatment, as early detection of liver-limited disease may enable targeted liver-directed therapies.

Yes. Tebentafusp (Kimmtrak) is a first-in-class bispecific gp100 peptide-HLA-directed T-cell engager approved for adults with HLA-A*02:01-positive unresectable or metastatic uveal melanoma. It was the first systemic therapy to demonstrate improved overall survival in this setting compared to investigator's choice. Eligibility requires HLA typing, as only HLA-A*02:01-positive patients — approximately half of Caucasian adults but a lower proportion in other populations — can receive this treatment. Multiple other trials evaluating novel combinations are actively enrolling.

Retinoblastoma survivors require long-term follow-up tailored to their risk profile. All survivors need regular ophthalmologic assessments to monitor for local tumor recurrence and treatment-related ocular complications. Survivors with germline RB1 mutations require lifelong surveillance for second cancers — including osteosarcoma, soft tissue sarcoma, and other RB1-associated tumors. Psychosocial support, educational monitoring (for children with visual impairment), and genetic counseling for family planning are also important components of survivorship care.

Yes. CancerFax supports families and patients facing eye cancer diagnoses by facilitating expert ocular oncology report review, coordinating second opinions — particularly for decisions between vision-preserving approaches and enucleation in retinoblastoma, or between brachytherapy, proton therapy, and observation in uveal melanoma. For metastatic uveal melanoma, CancerFax can help patients identify HLA testing, access tebentafusp-eligible treatment programs, and identify enrollment opportunities in clinical trials of combination systemic therapies. We also coordinate referrals to specialist retinoblastoma centers and proton therapy facilities internationally.