Eye Cancer: Types, Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Eye cancer encompasses a range of malignancies affecting the uveal tract (choroid, ciliary body, iris), retina, conjunctiva, eyelid, and orbital structures. Uveal melanoma is the most common primary intraocular malignancy in adults, with approximately 2,500 new US cases annually and an incidence of approximately 5 per million per year. It arises from uveal melanocytes and is biologically distinct from cutaneous melanoma — it does not harbor BRAF V600E mutations and does not respond to BRAF inhibitors. The choroid is the most frequent primary site (85% of uveal melanoma cases), followed by the ciliary body (5–10%) and iris (3–5%). Retinoblastoma is the most common primary eye cancer in children (approximately 300 US cases per year), caused by inactivating mutations of the RB1 tumor suppressor gene. Conjunctival melanoma and ocular surface squamous neoplasia are less common external eye cancers. The unique anatomy of the eye and the high blood flow through the choroidal vasculature make uveal melanoma prone to hematogenous metastasis, predominantly to the liver.

Risk factors for uveal melanoma include fair skin and light eye color (blue, gray, or green iris), predisposing light complexion, cumulative UV and infrared radiation exposure (outdoor occupation, welding arc exposure without protective eyewear), the presence of choroidal or uveal nevi (the direct precursor lesion, present in approximately 5% of the white population), and ocular melanocytosis (oculodermal melanocytosis, nevus of Ota), which confers a lifetime risk of approximately 1 in 400. BAP1 germline mutations cause the BAP1 tumor predisposition syndrome, elevating risk of uveal melanoma, mesothelioma, clear cell renal carcinoma, and cutaneous melanoma; affected families warrant coordinated surveillance. Retinoblastoma is caused by biallelic inactivation of RB1 — hereditary cases (40%) carry one germline mutation and require only one somatic hit; non-hereditary sporadic cases (60%) require two somatic hits in the same retinal cell.

Many uveal melanomas — particularly small choroidal tumors — are asymptomatic and discovered incidentally during routine dilated fundus examination by an optometrist or ophthalmologist. Symptomatic tumors cause blurred or distorted central or peripheral vision, photopsia (flashing lights), new floaters from vitreous hemorrhage, or a visual field defect due to secondary exudative retinal detachment adjacent to the tumor. Iris melanomas may present as a visible dark pigmented lesion on the iris surface, heterochromia (different iris colors), or pupil distortion causing cosmetic concern. Large posterior choroidal or ciliary body tumors may cause pain from secondary glaucoma. Retinoblastoma in children classically presents with leukocoria (white pupillary reflex replacing the normal red reflex) and strabismus, detected during routine child health screening or by parents noticing the abnormal eye reflex in photographs.

Diagnosis of uveal melanoma is predominantly clinical in experienced ocular oncology centers: indirect ophthalmoscopy reveals an orange-brown dome-shaped choroidal mass with lipofuscin surface deposits (orange pigment). A/B-scan ultrasonography is diagnostic, showing acoustic hollowness and intrinsic vascularity, and measures tumor thickness and basal diameter for AJCC T-staging. MRI of the orbit confirms intraocular location and extent. Fluorescein angiography characterizes the double circulation pattern. Fine-needle aspiration biopsy (FNAB) provides tissue for gene expression profiling (GEP: Class 1A, 1B, or 2) and chromosome 3 status — Class 2 and monosomy 3 predict high metastatic risk. AJCC 8th edition T-staging is based on basal diameter and thickness, correlating with metastatic risk. Retinoblastoma is staged using the International Classification (Group A–E) for intraocular disease and AJCC TNM for extraocular spread.

Episcleral plaque brachytherapy with iodine-125 seeds is the gold-standard eye-conserving treatment for uveal melanoma tumors up to 10 mm thick and 16 mm in basal diameter, delivering 80–100 Gy to the tumor apex. Proton beam irradiation (60–70 CGE in 4–5 fractions) treats larger and anteriorly situated tumors with excellent local control exceeding 95%. Transpupillary thermotherapy (TTT) with infrared diode laser controls very small tumors and is used as adjunct to plaque brachytherapy. Enucleation (surgical eye removal) is reserved for very large tumors (thickness greater than 18 mm), blind painful eyes, or when vision-sparing treatment fails. Fine needle biopsy at time of plaque placement allows GEP testing for prognostic stratification and enrollment in systemic surveillance programs. For metastatic uveal melanoma in HLA-A*02:01-positive patients, tebentafusp (IMCgp100, a bispecific gp100/CD3 T-cell engager) is approved based on the IMCgp100-202 phase 3 trial showing improved OS (21.7 vs 16.0 months). Retinoblastoma: intra-arterial ophthalmic artery chemotherapy (melphalan), intravitreous chemotherapy (melphalan), systemic chemotherapy (carboplatin, etoposide, vincristine), and external beam radiation or enucleation.

Local tumor control with plaque brachytherapy exceeds 90% at 5 years. Despite excellent local control, approximately 50% of uveal melanoma patients develop metastatic disease (predominantly liver) within 10–15 years of treatment due to hematogenous dissemination. Metastatic risk stratification by GEP: Class 1A greater than 95% 5-year metastasis-free survival; Class 1B approximately 70%; Class 2 approximately 25%. Overall 5-year survival for localized uveal melanoma is approximately 80%, dropping below 15% with distant metastases. Tebentafusp extends median OS to 21.7 months in eligible metastatic patients. Retinoblastoma: 5-year survival exceeds 95% in high-income countries. The prognosis for Eye Cancer: Types, Causes, Symptoms, Diagnosis and Treatment varies depending on severity at diagnosis, the patient's overall health, and how promptly treatment is initiated. With early diagnosis and appropriate management, many patients achieve good outcomes and maintain quality of life. Regular follow-up with healthcare providers is essential to monitor progress, adjust treatment as needed, and detect any complications early. Adherence to prescribed treatments and lifestyle modifications significantly improves long-term prognosis.

UV-protective wrap-around sunglasses with UV400 certification may reduce cumulative ocular UV and infrared radiation exposure. Patients with BAP1 germline mutations should be enrolled in a structured multidisciplinary surveillance program including annual dilated eye examination by an ocular oncologist, full-body skin examination, annual chest CT or abdominal MRI, and renal ultrasound. Individuals with choroidal nevi (the uveal melanoma precursor lesion) require annual fundus photography and OCT monitoring by a retinal specialist to detect growth or suspicious features (greater than 2 mm thickness, subretinal fluid, orange pigment, visual symptoms) indicating malignant transformation. No chemoprevention has proven effective. Retinoblastoma: all children with a positive family history of retinoblastoma or a known RB1 germline mutation require dilated fundus examination under anesthesia from birth with frequent monitoring during infancy.

Seek urgent ophthalmology evaluation for any sudden onset of new floaters, flashing lights, or a shadow or curtain obscuring part of the visual field — these may indicate retinal detachment adjacent to a choroidal tumor. A new dark spot on the iris, change in iris color, or visible lump on the surface of the eye requires prompt evaluation by an ophthalmologist. Blurred vision that is not correctable with eyeglasses, particularly when affecting one eye asymmetrically, needs ophthalmic assessment. Parents who notice a white or absent red reflex in a child's eye in a photograph, or a squint in a child under 5, should seek immediate pediatric ophthalmology evaluation, as these are warning signs of retinoblastoma. All adults with risk factors for uveal melanoma (light eye color, choroidal nevi, BAP1 syndrome) should have annual dilated fundus examinations. Any known uveal melanoma patient who develops new right upper quadrant discomfort, jaundice, or unexplained weight loss should be evaluated urgently for liver metastases.