Revised April 2000

General Information / Anatomy / Function / Statistics


The eyes are the organs of vision, contained in a bony orbit at the front of the skull.
Also included with the eye are all the accessory structures such as the muscles, eyebrows, eyelids, conjunctiva muscles, lacrimal gland, lacrimal sac and drainage system, nerves, fat, vessels and the optic nerve.
Layers of the eye include:
• Outer sclera which continues arterially as the transparent cornea
• Middle vascular pigmented layer consisting of the choroid, ciliary body and the iris
• Inner nerve tissue is the retina

In general, cancer in this region can be divided into three categories as determined by the site in which the cancer originates. These locations are:
• the eyeball
• the orbit
• the eyelids and conjunctiva

Tumor involving the eye includes the globe or eyeball itself. Tumours of the orbit include the bone surrounding the orbital cavity, soft tissues and muscles that lie between the eyeball or globe and the bony cavity in which it sits. Tumours of the lid include all types of skin tumours.

Vision is made possible by the passage of rays of light from an object through the cornea, aqueous humor, the lens and vitreous humor to the retina. For normal vision, rays coming from an object will be brought to a focal point on the retina by the lens.

Table of Contents
I. Ocular Tumours
i. Retinoblastoma
ii.Ocular Melanoma
iii. Metastatic Tumours of the Eyeball
iv. Miscellaneous IntraocularTumours

II. Orbital Tumours
i. Optic Nerve
Meningioma
Glioma
Sphenoid Wing Meningiomas
ii. Lymphoma
iii. Secondary Tumours
iv. Soft Tissue Tumours
Rhabdomyosarcoma
Fibrous Histiocytoma
v. Vascular Tumours
Capillary Hemangiomas
Cavernous Hemangiomas
vi. Metastatic Tumours
vii. Lacrimal Tumours
Lymphomas
Epithelial Tumours
Carcinoma or Malignant Tumours

III. Cancer of the Eyelids
IV. Tumours of the Conjunctiva
Squamous Cell Carcinoma
Malignant Melanoma


I. Ocular Tumours

i. Retinoblastoma

General Information / Anatomy / Function / Statistics
• Cancer of the eyeball arising from the retina
• Most common eye malignancy in babies and children under the age of two. Incidence is 1/20,000 live births
• Disease may arise in several locations within the same eye, and in about 30% of patients both eyes will be affected
• This tumour is malignant but highly curable by radiation therapy, chemotherapy, and local measures alone or in combination if diagnosed at an early stage
• May go unnoticed in the early stages because the child is too young to complain about visual problems
• Inheritable form of the disease accounts for 30 to 35% of cases but a family history is evident in only 6% cases
• Formerly was often fatal but to date the overall cure rate is about 95%
• Following treatment child should be examined several times a year for four to six years to search for recurrence or development of cancer in the remaining eye
• Some patients with retinoblastoma have a D-Group chromosome deletion
• The genetic basis of this disorder is becoming much better understood

Symptoms / Signs
• Most common early signs are:
• Development of a squint (crossed eyes);
• Appearance of a white area in the center of the pupil, the part of the eye that normally looks back with a red reflex;
• Poor vision; and
• Rarely inflamed eyes or glaucoma (high pressure).

Etiology / Carcinogens / Risks
• Follows a well recognized hereditary pattern which strongly suggests that a cancer-causing gene may be the instigating factor.
• Few patients have a D-Group chromosome deletion.

Diagnosis / Screening / Staging / Grading / Types
• The tumours are staged according to size, position, extent and number of tumours
• Other tests may include:
• Fluorescein angiography;
• CT scanning and ultrasound examinations; and/or
• Biopsy using small needle aspiration method. This is rarely necessary.

Treatment
• Depends on the stage of the disease and the state of the other eye.
• Specialization is critical with ophthalmologist, pediatrician and surgeon skilled in cancer treatment .
• Small tumours or those that have not spread locally (generally <10mm) may be treated by local measures, including photocoagulation (light or laser treatment), cryotherapy (freezing), or local radiation with radioactive plaques.
• Larger or multiple tumours or those critically close to the visual centre may be:
o Pretreated with chemotherapy to shrink them and then treated using local measures;
o Treated with chemotherapy alone; or
o Irradiated by external beam radiation therapy.

• Tumours that have damaged the eye irreparably require enucleation (eye removal).
• Tumours that extend beyond the eye may require radiotherapy and chemotherapy.
• Metastatic tumours are treated with chemotherapy.

ii. Ocular Melanoma

General Information / Anatomy / Function / Statistics
• Disease of adults, but may affect all ages.
• Originates in the pigment producing cells (melanocytes), choroids, iris, ciliary body, conjunctiva, sclera (rare).
• Melanoma of the eye differs in behaviour and management from melanoma arising from skin or mucous membranes.
• Most common site is the choroid (or uvea), which is located between the sclera (whitish fibrous tissue of the outside of the eye) and retina (innermost layer of the eye). It contains blood vessels and pigment. Less frequently involves the ciliary body, iris, and sclera.
• Incidence in Europe and US is 5 to 7.5 per million per year
• Over 50 years old the incidence rate is 21 per million per year
• Malignant melanomas of the iris appear to be quite different from melanomas arising elsewhere in the eye or body. This tumour is very slow growing and death rate from it is very low (1 - 4%)
• Melanoma of the choroid is much more serious
• About 60% are alive five years after diagnosis
• Patients often die from metastases to the liver
Symptoms / Signs
• Melanoma of the choroid, if situated near the macula (central part of the retina and the point of maximal visual acuity) usually produces a decline in vision
• In other areas melanoma produces no symptoms in the early stages
• Any changes in vision or the appearance of the eye should be checked by a doctor, particularly sudden development of photopsia (sparks or flashes) or black spots
• May be found during routine eye examination

Etiology / Carcinogens / Risks
• Only known risk factors are light complexion and light colored eyes.

Prevention
• Dark glasses completely blocking ultraviolet rays should be worn by blue-eyed people when out in bright sunlight.

Diagnosis / Staging / Grading / Types
Diagnosis
• Diagnostic tests may include:
• Clinical examination using routine and special ophthalmic instruments that allow a full field, three dimensional view of the back of the eye.
• Examination of anterior portion of the globe is done using a biomicroscope, which can be used with special lenses to examine the posterior part of the globe.
• Fluorescein angiography, a diagnostic test in which a dye is injected into the blood stream, can be used to visualize that blood vessels of the eye or of the tumour thus helping to visualize the blood vessels of the eye or of the tumour thus helping to visualize and characterize an ocular tumour.
• Ocular fundus color photography allows visualization and documentation of tumours.
• Ophthalmic A and B ultrasound may be used to characterize the size, tissue features and extent of an ocular melanoma.
• Magnetic resonance imaging (MRI) may also help to identify an ocular tumour and define its extent.
• Needle biopsies, in which a small amount of tissue is removed by a hollow aspiration needle, are possible for tumours of the eye.

Staging
• Small tumors are less than 10 mm
• Medium tumors are 10-16 mm
• Large melanomas are more than 16 mm

Types
• The more benign types of eye melanomas are composed of spindle-shaped cells
• More malignant type is composed of epithelioid (plump, round) cells or consist of a mixture of spindle and epithelioid cells

Treatment
Systemic evaluation
• All patients with suspected malignant melanoma of the uveal tract should have a complete medical examination to assess the presence of distant metastatic disease
• Small tumors are usually closely observed by an ocular oncologist and documented on a regular basis to identify growth

Choroidal
• When of an appropriate size, choroidal tumours may be treated with radioactive plaque therapy, proton beam therapy or local excision
• Plaques of iodine 125 or radioactive gold are sewn on the outside of the eye (to the sclera) so that the required amount of radiation therapy can be delivered to the tumour. These are removed one or two weeks later
• Proton therapy, given at TRIUMF on the UBC campus utilizes a narrow proton beam of radiation to destroy the tumour
• All forms of radiation therapy result in the disappearance or shrinkage of the tumour one or two years after treatment
• Location of the tumour is a major factor in determining whether there will be radiation side effects to the retina, lens or the optic nerve.

Removal of the tumour
• Selected melanomas of the iris and ciliary body may require excision when of significant size or when they demonstrate significant growth
• Eye wall resections may be carried out to remove some of the posterior tumours

Enucleation
• Removal of the eye may be recommended for large tumors that have caused detachment of the retina and a significant disorganization of the eye structure. This is performed gently to avoid spreading the cancer cells in the bloodstream. Very rarely, radiation therapy may be administered to the eyeball prior to surgery.
• Tumours that have extended beyond the eye into the local tissues may require removal of adjacent tissues to control local recurrence.

iii. Metastatic Tumours of the Eyeball

General information / Anatomy / Function / Statistics
• Metastatic tumours of the eyeball are the second most common intraocular tumours of the adult
• They usually metastasize to the choroid at the back of the eye and rarely to the iris
• The most common sites of origin is from breast, lung cancer and gastrointestinal sites

Symptoms
• Usually present with a decrease in vision, spots of flashing lights (photopsias)
• May be discovered on routine follow up examination of patients with unknown cancer

Diagnosis / Screening / Staging / Grading / Types
• Diagnosis is usually made by direct ophthalmic observation, fluorescein angiography, ultrasound examination, CT scan or MRI

Treatment
• If the tumour is solitary local radiotherapy is usually effective in shrinking the metastasis
• Chemotherapy may also be used in particular chemo-sensitive tumours

iv. Miscellaneous Intraocular Tumours
• There are a number of intraocular tumours that may originate from various tissues within the eye, most of which are in a benign category and require expert ocular oncology consultation.
• They affect visual function.
• Many can be treated by excision or local measures.


II. Orbital Tumours
General Information / Anatomy / Function / Statistics
Tumors of the orbit are in order of frequency:
• Neurogenic including meningiomas of the optic nerve, gliomas of the optic nerve, and meningiomas that arise from the lining of the brain (meningiomas behind the orbit)
• Lymphoma
• Secondary tumours of the orbit including tumours from the adjacent tissues that have invaded the orbit, such as sinus, eyelids, or bones
• Tumours of the soft tissues (i.e.: tumours that have originated from other sites)
• Vascular tumours, the most common in childhood being capillary hemangiomas and cavernous hemangiomas in adults
• Lacrimal tumors (i.e.: tumours originating from the tear gland)

Symptoms / Signs
The most common symptoms of orbital tumours are in order of frequency:
• Forward bulging (proptosis) or displacement downward / upward / outward
• Squinting
• Pain and double vision
• Drooping eyelid with or without a palpable mass
• Loss of vision or distortion of vision

Diagnosis / Screening / Staging / Grading / Types
Diagnostic tests include:
• Ultrasound scanning primarily for tissue typing of more anterior tumours;
• CT scanning;
• MRI (Magnetic Resonance Imaging); and
• Biopsy (either by fine needle aspiration when the tumour is soft or by direct, open surgical methods).

Treatment
General Principles
• Isolated mass - for any orbital tumour that is well defined, isolated and causing dysfunction of the eye, total excision of the tumour by open surgical techniques with or without the use of laser surgery is recommended.
• For tumours that invade the tissues of the orbit, biopsy is recommended in order to define the appropriate treatment.
Neurogenic

i. Optic Nerve
a. Meningioma
Generally, optic nerve meningiomas present with decrease of vision with or without proptosis. They are usually treated by observation alone if there is minimal dysfunction. If progressive, radiotherapy may be used to stop progression. If large or extending intracranially, these lesions are excised.

b. Glioma
Glioma of the optic nerve usually occurs in children and may be associated with a hereditary syndrome (neurofibromatosis). The hereditary gliomas have a good visual prognosis and are usually observed. If they progress and interrupt visual function, radiotherapy or chemotherapy may be used. In gliomas that are large and localized, combined neurosurgical-orbital excision may be performed.

c. Sphenoid Wing Meningiomas
Common ocular symptoms of sphenoid wing meningioma are decrease in vision or proptosis. When they interfere with function, surgical resection with or without radiotherapy may be performed.

ii. Lymphoma
Lymphomas of the orbit are the second most common orbital tumour and are increasing in frequency as they are elsewhere in the body. They usually present as soft tissue masses without much interference with function. They may appear as fleshy surface masses. Management is by biopsy then treatment by local radiation therapy unless there is evidence of lymphoma elsewhere, in which case chemotherapy would be used.

iii. Secondary Tumours
Secondary tumours originate from the adjacent sinuses, intracranial cavity, or the face. Therapy is usually radiotherapy and/or chemotherapy. Surgical excision may be carried out with or without combined radiotherapy and chemotherapy.

iv. Soft tissue tumours
This category includes a large variety of soft tissue tumours, the most important ones being rhabdomyosarcoma and fibrous histiocytoma.

a. Rhabdomyosarcoma
This cancer originates from embryonic muscle cells. Most frequently, it occurs in children under the age of 10 and can grow quite rapidly, leading to protrusion of the eyeball and swelling of the lid. Diagnosis is made by biopsy. Treatment is with a combination of radiation therapy plus multiple chemotherapy. Prognosis for an orbital rhabdomyosarcoma is excellent for local cure. Radiation therapy may result in damage to the eyeball, tear gland, and adjacent tissues. (See also childhood cancers).

b. Fibrous Histiocytoma (Solitary Fibrous Tumour)
Fibrous histiocytoma is a tumour that arises from the connective tissues cells of the orbit. These are usually moderately large, rounded well-defined tumours in the socket. Best treatment is wide local excision of the tumour performed by exposing it through a window made in the bone of the socket with preservation of vision. More aggressive subtypes that can recur may require radical exenteration of soft tissues of the orbit.

v. Vascular Tumours
The two major vascular tumours of the orbit are capillary hemangiomas in childhood and cavernous hemangiomas in adults.

a. Capillary Hemangiomas
Capillary hemangiomas usually go through a phase of growth followed by involution within one to five years of onset. They are benign and can be treated by simple observation if there is no threat to vision. In the instance of a threat to vision in young children (amblyopia), treatment may be with oral, intravenous, or intratumour cortisone. When localized causing visual dysfunction, these tumours can be excised by expert surgeons in order to provide a clear visual pathway.

b. Cavernous Hemangiomas
Cavernous hemangiomas usually present in adults during midlife and are associated with proptosis or distortion of vision. These lesions vary in size, have smooth contours, and are non-invasive. When interfering with visual function, complete surgical excision is recommended and usually successful.

vi. Metastatic Tumours
The common childhood metastatic tumour of the orbit is neuroblastoma (see childhood cancers). In adults, these include tumours originating from the lung, breast or gastrointestinal tract. Melanoma of the skin may metastasize to the extraocular muscles. Orbital metastases usually present as proptosis or double vision and rarely as enophthalmos (inward pulling of the eye). Treatment is usually by local radiotherapy with or without chemotherapy.

vii. Lacrimal Tumours
Lacrimal gland tumours arise from the tear gland and represent a special category of orbital cancer. There are three categories.

a. Lymphomas
These are best managed through biopsy characterization with the use of low-dose orbital radiation if localized. When part of a systemic lymphoma, chemotherapy is the treatment of choice. Recommended treatment is managed by a group of experts in lymphoma and involves generalized assessment and work up.

b. Epithelial Tumours (benign)
There are number of tumours which originate from the lacrimal gland, in particular the benign mixed tumours which are safe to remove. These localized tumours require total removal using a lateral orbital approach with careful techniques.

c. Carcinoma or Malignant Tumours
Carcinomas of the lacrimal gland have a tendency to invade the adjacent tissues and nerves. The recommended method of management includes debulking of the tumour, either by local or en bloc methods, complemented by orbital radiation depending on the specific tumour type.


III. Cancers of the Eyelids
General information / Anatomy / Function / Statistics
In order of general frequency, the common cancers of the eyelid are basal cell carcinoma, squamous cell carcinoma, sebaceous (or meibomian i.e., fat gland) carcinoma, and melanoma of the skin of the eyelid.
• Basal Cell cancers arise within the skin that covers the eyelid. These occur mostly in older people and in the lower lid. They occur more commonly in pale-skinned individuals and are directly related to sun exposure. They display similar behavior to basal cell carcinomas that develop in other locations (see Skin Cancer). Growth is slow but can invade the deeper layers of the lid while appearing relatively small on the surface.
• Squamous cell cancers of the lid are rare but more serious than basal cell carcinomas, since they may spread to adjacent and regional tissues more readily.
• Cancer may arise in the meibomian gland (the structure on the eyelid that produces sebum or oily secretion). Meibomian cancers grow slowly but are potentially aggressive. They tend to be recognized earlier in the lower lid, and may present as chronic inflammation of the eyelid.
• Melanoma of the eyelid is extremely rare and behaves similar to melanoma of the skin (see Melanoma Skin). These may be malignant and spread to distant organs and usually present as an abnormal pigmented mass, which may spread or ulcerate.

Symptoms
• Swelling of the eyelid
• Alteration in appearance of the skin of the eyelid
• Ulceration that does not heal
• Chronic infection and thickening of the lid
• Melanoma present as a spreading, pigmented mass

Diagnosis / Screening / Staging / Grading / Types
• Ophthalmological examination
• Biopsy
• MRI may be used to define the extent of some lesions

Treatment

Basal Cell Carcinomas
• Can be treated surgically with careful microscopic examination of the margins using frozen sections
• Extensive surgery can result in scarring & deformity of the eyelid and also result in problems with the tear ducts (i.e.. constant tearing or dry eyes)
• Radiation therapy is also used, particularly for recurrence or for tumour located in the inner corner of the eye. The globe would be protected during therapy as is the lacrimal system
• Mohs' surgery may be recommended for extensive or recurring disease. This is the technique of microscopic serial excision of skin cancer tissue, which may be carried out under local anaesthesia and followed by reconstruction
• Almost all basal cell cancers are curable

Squamous Cell Carcinomas
• These require meticulous treatment either by surgery, radiation therapy, or a combination of the two to prevent spread

Meibomian gland Carcinoma
• Meibomian gland cancers are usually treated surgically with microscopic margins.
• *When they have spread along the surface of the conjunctiva, they may be treated with cryotherapy to the margins and conjunctiva.
• More extensive lesions may be treated with radiotherapy and chemotherapy
• Cures are possible in the majority of cases

Malignant Melanomas of the Eyelid
• Focal excision with or without resection of lymphatics and the regional lymph nodes is the recommended form of therapy.


IV. Tumours of the Conjunctiva
The two major conjunctival tumours are squamous cell carcinomas and malignant melanomas:

Squamous Cell Carcinoma
These tumours usually occur in the open part of the eye (interpalpebral fissure) as small fleshy masses, which lead to eye irritation. The overwhelming majority can be removed by microscopic excision. Some may be treated with local radiotherapy using strontium 90, cryotherapy or local chemotherapy.

Malignant Melanoma
The majority of melanomas of the conjunctiva arise from spontaneously occurring, adult on-set, pigmented lesions. These precancerous lesions may grow at an extremely slow rate and can be managed by staging biopsy, resection of local nodular lesions, local cryotherapy, and strontium 90 application. Diffuse involvement (i.e., non-invasive) can be treated by local methods to prevent transformation to a more malignant state. When these precancerous lesions become malignant, more radical, local or regional measures become necessary. De novo nodular melanomas of the conjunctiva can be treated by wide local resection and cryotherapy. Overall the prognosis for metastatic disease in melanoma of the conjunctiva relates most closely to the thickness of the tumours. Tumours >3mm have a worse prognosis than those < 3 mm.