Definition

The main intraocular tumors are melanoma and choroidal metastases in adults, and retinoblastoma in children. Major conjunctival tumors, typical of adults, include squamous cell carcinoma and conjunctival melanoma. The most frequent orbital tumors include, in turn, angioma (benign, of the child and of the adult), rhabdomyosarcoma (malignant, of the child), lymphoma and metastases (malignant, mainly of the adult).

Choroidal melanoma represents the most frequent primary intraocular tumor in adults, with an incidence of 6 cases per million people/year. Conservative radiation therapy (brachytherapy or accelerated protons) is now able to treat more than 95 percent of cases locally satisfactorily. For too large lesions, enucleation of the eyeball is still used. Despite favorable results in the local treatment of neoplasia, choroidal melanoma remains a life-threatening disease with a 10-year metastasis risk of about 50 percent.

Choroidal metastases are considered the most frequent malignant intraocular tumor, although their clinical finding is quite rare because they generally affect patients at an advanced stage of systemic disease, in which the eye examination is often omitted. The diagnosis is mainly ophthalmoscopic, although it must be supported by an ultrasound, tomographic and, possibly, angiographic study. The ophthalmoscopic aspect is that of single, but more often multiple and/or bilateral, hypopigmented, subretinal lesions, located mainly at the posterior pole, near the optic nerve and macula. The treatment of choroidal metastases is multidisciplinary, based on systemic chemotherapy and, possibly, radiotherapy (standard or brachytherapy) or other focal treatments (photodynamic therapy).

Retinoblastoma is the most frequent malignant intraocular tumor in pediatric age. Depending on the case, it may affect one or both eyes and may or may not be hereditary. To date, retinoblastoma is a cancer that has a very high 5-year survival rate (> 95 percent). The most common sign of onset is Leukocoria (white pupillary reflex), which unfortunately remains a late sign. The standard therapy for retinoblastoma is chemoreduction (systemic chemotherapy aimed at reducing the size of eye lesions) associated with focal consolidation therapies (thermotherapy, cryotherapy, brachytherapy) or more recently intra-arterial chemotherapy and thermochemotherapy. Enucleation of the eyeball remains a curative therapy in cases with locally advanced neoplasia.

Choroidal hemangioma is the most common primary vascular tumor of the choroid. The tumor remains generally unknown until it becomes symptomatic. Symptoms, such as decreased visual acuity and/or metamorphopsia, usually occur in the third or fourth decade of life. Choroid hemangioma is a benign tumor and therefore treatment is not aimed at destroying the tumor but at maintaining the best visual acuity for as long as possible. If the patient has no symptoms or decreased visual acuity, treatment is not necessary, and the patient will need to be checked over time. If a lift of the neuroepithelium results in a decrease in visual acuity, treatment should be considered. The most used treatment today is photodynamic therapy.

Ocular Surface Squamous Neoplasia
Ocular Surface Squamous Neoplasia includes clinical pictures ranging from simple epithelial dysplasia to frankly invasive squamous carcinoma. Standard therapy is extensive surgical excision associated with surgical cryotherapy and conjunctiva reconstruction. The use of topical antimetabolites (chemotherapy in drops) has recently been introduced, and is now increasingly used, in the integrated treatment of this pathology, both in combination with surgery and as a single therapy.

Conjunctival melanoma is a very rare tumor of the conjunctiva, (less than 2 percent of all ocular tumors). The therapeutic approach depends on the size and location of the melanoma. In small melanomas located in favorable locations (bulbar conjunctiva and perilimbal) a wide surgical resection is sufficient, possibly associated with topical chemotherapy and brachytherapy of the surgical bed. In cases they are in unfavorable locations (palpebral conjunctiva, fornix, caruncle and eyelid margin) or in large locations, surgical excision may not be sufficient even if associated with topical chemotherapy or radiation therapy. In unresponsive, very extensive, and orbit-infiltrating cases, the orbital exenteration, a radical surgical technique in which all orbital content is removed, is still used. The use of topical antimetabolites is now increasingly used, mainly in the treatment of premalignant lesions (primary acquired melanosis).

Diagnostics

The diagnostic approach includes an accurate family history, investigating the presence of neoplastic or hereditary-family diseases in the family. The systematic investigation proceeds with a complete ophthalmological evaluation (visual acuity, biomicroscopic examination of the anterior and posterior segment, ophthalmoscopy, intraocular pressure), extended to all those second-level investigations deemed useful for the specific case, such as: ocular ultrasound, optical coherence tomography (OCT) examination of the visual field, study of retinal function and optical pathway. The lesions found – both on the anterior and posterior segment of the eye – must always be documented photographically: this investigation is essential to objectively evaluate the natural history or the effect of any therapy over time. Other important investigations in ocular oncology include retinal and choroidal angiography, Optical Coherence Tomography (OCT) Angiography, fundus autofluorescence, and confocal microscopy of the ocular surface. In selected cases, specific neuroradiological investigations (CT and MRI) may also be useful. If these methods are not correct, minimally diagnostic methods, such as diagnostic cytology, or invasive methods, such as incisional or excisional surgical biopsies (partial or total removal of the lesion) will be used.

Therapy

Therapy in ocular and orbital oncology is based on an oncology team planning and it is up to the ocular oncologist to coordinate this activity. Currently the approach to eye tumors is as conservative as possible, meaning by that the need to destroy the neoplastic lesion but always preserving the eye and its visual function. When the preservation of the eyeball affected by the neoplasm (malignancy) can be life-threatening for the patient, the eye must be enucleated. Radiation therapy is the main and most effective method of treating malignant and benign tumors of the eye. Radiation therapy is mainly applied by contact (episcleral plaques loaded with radioactive isotopes), or with external sources (linear accelerator or heavy-particle accelerator). Other treatments performed are: transpupillary thermotherapy that finds indication, associated with chemotherapy, in the treatment of retinoblastoma, as well as cryotherapy, surgery, systemic and topical chemotherapy, photodynamic therapy, super selective chemotherapy with ophthalmic artery cannulation, intraocular injection of antineoplastic drugs and immunotherapy.