The Orbit 14
DAVID L. SCHWARTZ, STELLA K. KIM, AND K. KIAN ANG
ANATOMY BENIGN ORBITAL DISEASES
Graves Ophthalmopathy
RESPONSE OF NORMAL ORBITAL
STRUCTURES TO IRRADIATION Orbital Pseudotumor
Eyelashes and Eyelid Pterygium
Lacrimal Gland
MALIGNANT ORBITAL DISEASES
Cornea
Ocular Melanoma
Lens
Orbital Lymphomas
Sclera
Metastasis to the Orbit
Retina
Optic Nerve and Chiasm
The eye and surrounding orbit are subject to malignant and mean distance from the anterior surface of the superior
benign processes that exact steep tolls in quality of life, fre- eyelid to the posterior surface of the lens was 10.1 Ä… 1 mm
quently outpacing the accompanying risk to survival. For and that the mean distance from the posterior surface of
such conditions, radiation is used to treat for cure while the lens to the intercanthal line was 8.5 Ä… 2.6 mm. The
preserving orbital contents and function. Although orbital median sagittal globe diameter was 24.6 mm.
irradiation is typically safe, the chronic effects of treatment-
related morbidity can have drastic effects on visual func-
tion. For benign orbital diseases, radiation therapy typically
RESPONSE OF NORMAL ORBITAL
is used as an adjunct to surgery or is reserved for cases in
STRUCTURES TO IRRADIATION
which other treatments have failed. For malignant orbital
diseases, however, radiation therapy has emerged as the The various orbital tissues each respond differently to
initial treatment of choice given that surgical alternatives irradiation. In general, radiosensitivity decreases gradu-
range from partial excision to formal enucleation. Techni- ally from the anterior structures to the posterior struc-
cal advances in radiation delivery, such as particle beam tures. Rohrschneider, one of the first to address the topic,
treatment, hold promise for further improvements in safe reported that the most radiosensitive structures, in order
and effective treatment. In all cases, optimal outcomes re- of decreasing sensitivity, were the lens, conjunctiva, cornea,
quire careful patient selection. uvea, and retina and that the least radiosensitive structure
was the optic nerve.4 Later findings regarding the radio-
sensitivity of orbital structures5 confirm Rohrschneider s
ANATOMY
early findings.
The outer covering of the eyeball is composed of three
main tissue layers (Fig. 14-1).1 The external fibrous
coat consists of the sclera, cornea, and corneal limbus.
The middle vascular coat, the uvea, consists of the cho-
Lateral rectus
roid, ciliary body, and iris. The inner neural coat, the
muscle
Sclera
retina, is the sensory region. Within the outer covering of the
Schlemm s
Choroid
eyeball lie the crystalline lens, vitreous humor, and aqueous
canal
humor. The six extraocular muscles controlling eye move- Iris
Retina
Lens
ment insert into the sclera. The orbital contents that hold
Fovea
Pupil
the eyeball in place consist of the extraocular muscles, the centralis
Anterior
Central retinal
nerves and vessels that serve the globe, and in-filling fatty
chamber
vein and artery
tissues. The orbital contents reside in a protective cone con-
Cornea
Lamina
sisting of seven bones of the skull that together compose
Posterior cribrosa
the bony orbit (Figs. 14-2 and 14-3).2
chamber Optic nerve
In the treatment of orbital diseases, detailed knowledge
Ciliary body
of the spatial relationships between anatomic structures
Ora serrata
allows radiation oncologists to spare as much normal tissue
Medial rectus
muscle
as possible without compromising coverage of the target
volume. From topographic measurements of 66 patients
FIGURE 14-1. Horizontal section of the right eye. (From Saude
made from computed tomography (CT) scans with eye- T. The outer coats of the eye. In Saude T [ed]: Ocular Anatomy
lid markers, Karlsson and colleagues3 determined that the and Physiology. Oxford, UK: Blackwell Science, 1993, pp 11-25.)
309
310 PART 3 Head and Neck
Lesser wing Optic Supraorbital Superciliary
of sphenoid foramen notch ridge
Orbital plate of
Trochlear
great wing
fossa
of sphenoid
Anterior ethmoidal
Fossa for
foramen
lacrimal gland
Maxillary
Zygomatic process
process
Ethmoid
Superior orbital
fissure
Nasal bone
Zygomatic
tubercle
Lateral orbital
Lacrimal bone
tubercle
and fossa
Sutura notha
Zygomatic
foramen
Lacrimal
tubercle
Zygomaticofacial
Orbital plate
foramen
of maxilla
Zygomatic
Infraorbital
bone
suture
Inferior orbital Maxillary Infraorbital Infraorbital
fissure process groove foramen
FIGURE 14-2. The right orbit viewed along its axis. (From Bron AJ, Tripathi RC, Tripathi BJ. Wolff s Anatomy of the Eye and Orbit,
8th ed. London: Arnold, 1997.)
Frontal sinus
Frontoethmoidal
sinus
Trochlear
Anterior ethmoidal
fossa
foramen
Frontal
Ethmoid
Posterior ethmoidal
Lacrimal
foramen
Lacrimal fossa
Optic foramen
Frontal process
Sphenoid
Nasal bone
Pituitary
Orbital process
Infraorbital
of palatine
canal
Lacrimal bone
Foramen
rotundum
Uncinate process
Sphenoid process
of ethmoid
of palatine bone
Inferior Lateral pterygoid plate
concha
Pterygoid hamulus
Antrum
Vertical plate of palatine bone
FIGURE 14-3. The medial wall of the orbit. (From Bron AJ, Tripathi RC, Tripathi BJ. Wolff s Anatomy of the Eye and Orbit, 8th ed.
London: Arnold, 1997.)
Eyelashes and Eyelid
Irradiation of the eyelid produces observable effects
The eyelashes are end organs of touch and, on contact, ini- similar to those produced by irradiation of other skin and
tiate a blink reflex to protect the eye. Doses of 20 to 30 Gy mucosa in the body, and with commonly prescribed radia-
or more given in 2- to 3-Gy fractions cause alopecia of the tion doses, healing is typically complete. However, the skin
eyelashes and abolish this protective mechanism, result- and mucosa of the eyelid are among the more delicate tis-
ing in irritation of the conjunctiva and corneal surfaces.6 sues in the body, and side effects occurring in this region
Occasionally, regrowth of the lashes may produce trichiasis are more uncomfortable for the patient than those arising
and entropion requiring intervention.7 in other regions.
14 The Orbit 311
shielding during irradiation developed visual impairment.
Lacrimal Gland
In contrast, two of eight patients treated with lacrimal
Radiation treatment fields that include the lacrimal gland shielding only and two of 12 patients treated with cornea-
can cause atrophy and loss of glandular function, leading lens shielding only developed corneal injury. The incidence
to dry eye syndrome. Dry eye symptoms usually can be of visual impairment at 2 years was 81% to 88% with doses
sufficiently treated with artificial tears or lubricants. Chronic of 56 to 74.5 Gy to the lacrimal gland (corneal dose, 31
irritation of the cornea by the eyelid, however, may lead to to 41 Gy) with or without chemotherapy, compared with
a painful eye with visual loss because of corneal laceration 17% for doses of 42 to 45 Gy (corneal dose, 23 to 30 Gy)
and subsequent ulceration with infection, opacification, without chemotherapy. The overall treatment time ranged
or vascularization. Parsons and colleagues8 examined the from 29 to 52 days. The median time to manifestation of
dose-response relationship for dry eye complications using visual impairment was 9 months (range, 1 to 31 months).
data from the University of Florida and from the literature. If the cornea and conjunctiva are not at risk for harbor-
In that review, no complications occurred with doses up ing subclinical disease, a practical strategy for decreasing
to 30 Gy. The incidence of injury was 5% to 25% in the the incidence of corneal complications is to irradiate pa-
range of 30 to 40 Gy and increased steeply for doses above tients with their eyelids open for the anterior field such
40 Gy, reaching 100% for doses of 57 Gy or more. that the cornea and conjunctiva are located in the buildup
With doses of radiation in the curative range, stenosis or region of the megavoltage beams.
even obstruction of the nasolacrimal duct may occur. The
Lens
main symptom is epiphora, which may be remedied with
recanalization of the duct. The lens is the most radiosensitive organ in the body. The
lens itself consists largely of fiber cells covered anteriorly by
Cornea
an epithelium and is enclosed in a capsule.15 Cell division
It is difficult to distinguish direct radiation injury to the cor- in the lens continues throughout a person s lifetime. With
nea from indirect injury resulting from dry eye syndrome radiation injury to the dividing cells, the resulting abnormal
because in most reported series, the entire eye is included fibers migrate toward the posterior pole, where they consti-
in the treatment volume.9-11 Radiation-induced keratitis tute the beginning of a cataract.
with various amounts of tearing may develop during treat- Definitive studies from Merriam and colleagues9
ment but may also manifest a few weeks or months after shed light on the dose-response relationship for cata-
treatment.9 Radiation-induced corneal injury manifests as racts. The investigators analyzed the available dose esti-
multiple, tiny ulcers in the corneal epithelium seen under mates to the lens in 233 patients who received radiation
fluorescein staining. This type of injury typically occurs therapy to the eye. Radiation cataracts developed in 128
after doses of 30 to 50 Gy given over 4 to 5 weeks12,13 patients. The minimum cataractogenic doses were 2 Gy
and gradually resolves over 4 to 6 weeks with conserva- for single-dose radiation, 4 Gy for multiple doses given
tive treatment without sequelae. Larger corneal ulcerations over a period ranging from 3 weeks to 3 months, and 5.5
may occur with doses greater than 50 Gy in 4 to 5 weeks. Gy for multiple doses given over a period longer than 3
Merriam and colleagues9 reported three severe corneal months. Higher doses decreased the latent period and
ulcerations in 25 patients treated for rhabdomyosarcoma of increased the severity of the cataracts. In patients who
the orbit with 60 Gy (22.5 MeV) given over 5 to 6 weeks. received 2.5 to 6.5 Gy, the latent period was 8 years and
The cornea received the full dose, and perforation in two 7 months, and one third of the patients developed pro-
patients necessitated enucleation. Chan and Shukovsky10 gressive cataracts. For patients who received 6.51 to 11.5
reported that with a follow-up time of 2 years, corneal le- Gy, the latent period was 4 years and 4 months, and two
sions occurred in 15% of patients treated with 60 Gy over 6 thirds of the patients developed progressive cataracts.
weeks to the entire eye for nasal cavity and paranasal sinus
Sclera
tumors. When intra-arterial fluorouracil was given along
with radiation, all patients developed corneal lesions. Bes- The sclera is extremely radioresistant, as illustrated by its
sell and colleagues11 reported corneal ulceration in 2 of 13 tolerance of the high doses of radiation used for the treat-
patients treated with 40 to 49 Gy over 3 or 4 weeks for ment of ocular melanomas. However, doses in the range of
orbital lymphoma. However, both patients also had tear 200 to 300 Gy may cause atrophy after a latency period of
film instability, which most likely contributed to the ul- several years.9
cerative process. In both cases, the corneal ulcer eventually
Retina
healed.
Corneal stromal edema may be seen with doses of 40 to Radiation damage to the retina is primarily seen in the
50 Gy in 2 to 3 weeks.9 The edema is typically self-limiting, endothelium of the retinal capillaries.16 Ophthalmoscop-
resolving over 2 to 4 weeks, and can be adequately treated ic findings include retinal hemorrhages, microaneurysms,
with topical antibiotics and steroids. Prolonged edema of hard exudates, cotton-wool spots, and telangiectases.17 In
the stroma is uncommon but is more likely with doses the M. D. Anderson Cancer Center series from Jiang and
greater than 50 Gy usually on the order of 70 to 80 Gy. colleagues,14 the onset of visual impairment caused by reti-
Reporting on a series of patients treated at The University nopathy occurred 5 to 30 months (median, 11 months)
of Texas M. D. Anderson Cancer Center, Jiang and col- after radiation treatment. With doses of 50 to 60 Gy
leagues14 suggested that visual impairment from corneal given over 29 to 62 days, the overall actuarial incidence
injury most likely resulted from a combination of lacrimal of retinopathy was 20%.14 However, this was most likely
gland injury and direct effects of radiation on the cornea. an underestimation because not all patients underwent
In that series, no patients who had lacrimal and corneal systematic ophthalmologic evaluation.
312 PART 3 Head and Neck
Published findings on the dose-response relationship for the development of antibodies against specific antigens
radiation retinopathy are limited. Parsons and colleagues18 in the extraocular muscles. In most patients, the dis-
reported no retinopathy in 33 eyes treated with doses less ease has a benign course that does not follow the course
than 45 Gy. For higher doses, the incidences of retinopa- of the hyperthyroidism. More severe cases of Graves
thy were as follows: 50% (6 of 12) for doses of 45 to 55 ophthalmopathy require medical intervention. The first
Gy; 83% (10 of 12) for doses of 55 to 65 Gy, and 100% line of treatment is high-dose steroids (e.g., 100 to 120
(11 of 11) for doses above 65 Gy. Several anecdotal reports mg of prednisone per day). Surgical decompression of the
have suggested that patients with diabetes mellitus are at orbit can be performed to relieve severe proptosis or acute
increased risk of developing radiation retinopathy.19-21 In compression of the optic nerve and to reduce pain. Surgi-
our practice, we prefer to limit the retinal dose to 50 Gy cal correction of the eye muscles can diminish diplopia,
when possible to minimize complications. and correction of the eyelids can improve the function of
the distorted edematous lids to lessen corneal damage.
Optic Nerve and Chiasm
Orbital irradiation in the treatment of Graves ophthal-
In an M. D. Anderson series, Jiang and colleagues14 repor- mopathy is generally reserved for symptoms that are re-
ted that visual impairment caused by damage to the op- fractory to steroids or for patients in whom steroids are
tic nerve and chiasm occurred 7 to 50 months (median, contraindicated (e.g., those with severe corneal abrasion or
27 months) after radiation therapy. Optic neuropathy was optic neuropathy). Because radiation effects can take up
not observed after doses of less than 56 Gy, and the inci- to several weeks to manifest and may transiently worsen
dence of this complication remained low (< 5% at 10 years) local inflammation, steroid therapy can be continued for
with doses up to 60 Gy in fractions not exceeding 2.5 Gy. several weeks. Bilateral irradiation is preferred because of
However, with doses higher than 60 Gy, the incidence of the high incidence of contralateral involvement detect-
optic neuropathy increased considerably, up to 34% at able by diagnostic imaging, even in patients with minimal
10 years. In a University of Florida series from Parsons and symptoms and signs.24 Moreover, when a one-sided lateral
colleagues,22 optic neuropathy was not observed in 106 photon portal is used, subsequent treatment of the con-
optic nerves that received a total dose of less than 60 Gy. tralateral eye is problematic because of the relatively high
With doses of 60 Gy or more, the incidence of optic neu- exit dose received (approximately 60%).25 Opposed lateral
ropathy increased, with the suggestion that the incidence fields with half-beam technique have been advocated.24,25
depended on dose per fraction. With doses of 60 Gy or With this technique, the dose to the lens can be limited
more, the 15-year actuarial risk of optic neuropathy was to only 4% of the prescribed dose by placing the anterior
11% with fractions of less than 1.9 Gy and 47% with frac- border at the lateral fleshy canthus. For more severe cases,
tions of 1.9 Gy or greater. however, the anterior border should be adjusted according
Optic chiasm injury resulting in bilateral blindness is one to the degree of exophthalmos.
of the most devastating complications of radiation therapy. Evidence of the efficacy of radiation therapy for Graves
In the series reported by Jiang and colleagues,14 none of 32 ophthalmopathy largely comes from reports of institutional
patients who received total doses of less than 50 Gy and experiences with patients receiving radiation as second-line
only 4 of 110 patients (8% actuarial rate at 10 years) who treatment.24,29,30 With the recommended treatment course
received doses of 50 to 60 Gy in fractions of 2.6 Gy or less of 20 Gy in 10 fractions, steroid therapy can be discontin-
developed optic chiasm injury. Total doses of 61 to 76 Gy ued after irradiation in 76% to 90% of patients.
were associated with a higher complication rate (24% at Two small, randomized studies comparing the com-
10 years). For treatment planning, we prefer to limit the bination of radiation therapy and systemic steroids with
dose to the optic nerve and chiasm to 54 Gy. When gross steroids alone or radiation therapy alone showed the com-
tumor is close and requires higher doses, we limit the dose bined treatment to be beneficial.28,31 Two randomized,
to the optic nerve and chiasm to 60 Gy, and we ensure that double-blind trials directly compared sham irradiation
the patient understands that the risk of blindness with this with 20 Gy of irradiation. In one of these studies, Mourits
treatment approaches approximately 10%. and others32 enrolled a total of 60 patients with moder-
ately severe ophthalmopathy; in the other, Prummel and
colleagues33 studied 88 patients with milder problems.
BENIGN ORBITAL DISEASES
Although both series demonstrated an approximate dou-
Graves Ophthalmopathy
bling of response rates in irradiated patients (52% to 60%
Graves disease is an autoimmune disorder with three ma- in the Mourits study versus 27% to 31% in the Prummel
jor manifestations: hyperthyroidism, ophthalmopathy, and study), investigators in both series observed that these
dermopathy. Graves ophthalmopathy is an inflammatory differences were mostly caused by improvements in eye
process involving extraocular muscles and orbital tissues; motility rather improvements in proptosis, eyelid swell-
occurring in 20% to 40% of patients with Graves disease, it ing, or overall quality of life. Nonetheless, radiation did
manifests as exophthalmos with ophthalmoplegia and con- seem to reduce the need for strabismus surgery and long-
gestive oculopathy characterized by chemosis, conjuncti- term follow-up and provided effective relief of symp-
vitis, periorbital swelling, and the potential complications tomatic diplopia.
of corneal ulceration, optic nerve compression, and optic Fortunately, long-term morbidity after irradiation for
atrophy.23 Pathologic examination reveals an inflammatory Graves ophthalmopathy is quite limited; nevertheless,
infiltrate of the orbital contents and enlargement of the ex- the risk of secondary retinopathy after treatment may be
traocular muscles. higher in patients with diabetes.34 No secondary radiation-
Although the pathogenesis of Graves ophthalmopathy related orbital malignancies in patients with Graves
is still not fully understood, one proposed mechanism is ophthalmopathy have been reported, although some
14 The Orbit 313
investigators have estimated a theoretical risk of tumor in- in one fraction to 24 to 60 Gy given in weekly fractions
duction of 0.3% to 1.2%.35,36 of 8 to 10 Gy. With the addition of adjuvant radiation
therapy to surgery, the control rate is excellent: the
Orbital Pseudotumor
recurrence rate is less than 5%. The main concern with
Orbital pseudotumor (idiopathic orbital inflammatory radiation therapy is the risk of late scleral necrosis and
disease) is a nongranulomatous, acute or subacute inflam- the attendant risks of corneoscleral ulceration and infec-
matory disease that usually occurs in the anterior orbit or tion. However, with fractionated radiation therapy, the
midorbit and often involves the lacrimal gland.37 This con- late complication rate is usually less than 1%.51,53,54,56
dition is idiopathic by definition, and neoplastic, infectious, Higher complication rates have been associated with
and systemic inflammatory or immunologic causes must be the use of large single fractions.49,57,58 To minimize late
excluded.38 Contrast-enhanced magnetic resonance imag- complications, plaques must be carefully calibrated to
ing (MRI) is usually the most helpful modality for gauging ensure an accurate dose rate, because measured rates can
the extent of disease. The disease usually is unilateral, al- be 30% to 57% higher than the dose rates provided by
though it can be bilateral in some cases. the manufacturer.59,60
Clinical symptoms consist of abrupt pain, conjunctival Paryani and colleagues53 from the North Florida Pte-
redness, chemosis, lid edema, exophthalmos, and restric- rygium Study Group reported outcomes from the largest
tion of eye movement. Pathologic examination reveals a series of patients in North America treated with scleral
gray, rubbery mass composed of a polymorphic infiltrate plaques after surgery. Adjuvant beta-ray therapy was given
of lymphocytes, eosinophils, plasma cells, and polymorpho- within 24 hours after complete surgical excision of pri-
nuclear leukocytes.39 The clinical course varies, and spon- mary or recurrent pterygia in 690 patients. The source was
taneous regression may occur in a few patients. In severe calibrated by the National Bureau of Standards, and the
cases, mass effects can cause secondary optic nerve atrophy, regimen was 60 Gy in 6 weekly fractions of 10 Gy. At a me-
disc edema, and complete visual loss. dian follow-up time of more than 8 years, the recurrence
Treatment is nonsurgical, with resection reserved only rate was 1.7%, with most of the recurrences occurring in
for cases that do not respond to medical management and patients who received fewer than five of the prescribed
radiation. First-line treatment consists of steroids, which fractions. No major late complications were reported with
produce dramatic responses in 30% to 60% of patients this regimen.
within 2 to 3 days.38,40 In refractory cases, radiation therapy Primary radiation therapy can be considered for reduc-
is highly effective, yielding control rates of 65% to 75% ing the size of pterygia and preventing the future growth
after doses of 10 to 30 Gy, with or without systemic ther- of symptomatic lesions. Pajic and colleagues55 reported a
apy.38,40-45 For anterior lesions, Donaldson and Findley46 small series of 54 primary pterygia in 43 patients treated
described an electron beam technique with lens shield- exclusively with 90Sr/90Y beta irradiation to a total dose of
ing that uses a centrally placed lead eye shield suspended 50 Gy in 4 weekly fractions. Reduction in size occurred in
1 cm above the lens. The field size should be at least all lesions. No patients developed recurrent growth, and no
4 × 4 cm to reduce dose inhomogeneity. The investigators late side effects were reported.
recommend 9- to 16-MeV beams for superficial lesions. At
M. D. Anderson, we prefer to mount the block on a contact
MALIGNANT ORBITAL DISEASES
lens to place the shield directly over the lens and cornea
(see  Orbital Lymphomas ). Treatment planning should Basal and squamous cell carcinoma and melanoma of the
be individualized with the aid of three-dimensional CT eyelids have a natural history similar to that of their coun-
guidance. terparts in other skin locations. These neoplasms are dis-
cussed in Chapter 6.
Pterygium
Ocular Melanoma
A pterygium is a conjunctival growth over the sclera and
onto the cornea; it occurs most often on the nasal side in The most common primary malignant tumor of the eye is
the palpebral fissure area.47 Chronic exposure to ultraviolet melanoma. Like its cutaneous counterpart, ocular melano-
light or dust may be causative.47 Treatment is indicat- ma originates from melanocytes derived from neural crest
ed when pterygia cause visual or cosmetic impairment. tissue. However, ocular melanomas are not related to sun
First-line therapy is surgical excision of the pterygium. exposure.61 Melanomas of the uveal tract (iris, ciliary body,
However, because the incidence of recurrence after exci- and choroid) are 20 to 40 times more common than those
sion alone is relatively high (20% to 39%,48,49 with most of the conjunctiva.
recurrences happening in the first year after excision50),
Uveal Melanoma
surgery is usually accompanied by adjuvant treatment in an
attempt to prevent recurrence. Nonirradiation treatment Although melanoma is the most common primary
options include mitomycin C, thiotepa, fluorouracil, and malignant tumor of the eye, the overall incidence of uveal
conjunctival autotransplantation. melanoma is only five to seven cases per million people per
Extensive experience has been reported for treatment year.61 The average age at diagnosis is 55 years.62 Tumors
of pterygia with strontium 90/yttrium 90 (90Sr/90Y) beta- of the posterior uvea account for more than 90% of cases,
ray surface applicators.49,51-55 The maximum surface with most being choroidal melanomas. In the past, the
dose and rapid dose fall-off make beta-rays ideally suited misdiagnosis rate was high because of the difficulties in
for superficial disease coverage. The first application is obtaining biopsy material. With the emergence of ancil-
typically given 12 to 24 hours after surgery. A variety of lary imaging techniques such as fluorescein angiography,
radiation schedules have been used, ranging from 20 Gy sonography, color Doppler imaging, phosphorus 32 uptake
314 PART 3 Head and Neck
BOX 14-1. American Joint Committee on Cancer Tumor Staging System for Melanomas of the Ciliary
Body and Choroid
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1* Tumor 10 mm or less in greatest diameter and 2.5 mm or less in greatest height (thickness)
T1a Tumor 10 mm or less in greatest diameter and 2.5 mm or less in greatest height (thickness) without
microscopic extraocular extension
T1b Tumor 10 mm or less in greatest diameter and 2.5 mm or less in greatest height (thickness) with
microscopic extraocular extension
T1c Tumor 10 mm or less in greatest diameter and 2.5 mm or less in greatest height (thickness) with
macroscopic extraocular extension
T2* Tumor greater than 10 mm but not more than 16 mm in greatest basal diameter and between 2.5
and 10 mm in maximum height (thickness)
T2a Tumor 10 mm to 16 mm in greatest basal diameter and between 2.5 and 10 mm in maximum height
(thickness) without microscopic extraocular extension
T2b Tumor 10 mm to 16 mm in greatest basal diameter and between 2.5 and 10 mm in maximum height
(thickness) with microscopic extraocular extension
T2c Tumor 10 mm to 16 mm in greatest basal diameter and between 2.5 and 10 mm in maximum height
(thickness) with macroscopic extraocular extension
T3* Tumor more than 16 mm in greatest diameter and/or greater than 10 mm in maximum height
(thickness) without extraocular extension
T4 Tumor more than 16 mm in greatest diameter and/or greater than 10 mm in maximum height
(thickness) with extraocular extension
Stage Grouping
Stage I T1 N0 M0
T1a N0 M0
T1b N0 M0
T1c N0 M0
Stage II T2 N0 M0
T2a N0 M0
T2b N0 M0
T2c N0 M0
Stage III T3 N0 M0
T4 N0 M0
Stage IV Any T N1 M0
Any T Any N M1
*In clinical practice, the tumor base may be estimated in optic disc diameters (dd) (average: 1 dd = 1.5 mm). The elevation may be
estimated in diopters (average: 3 diopters = 1 mm). Other techniques used, such as ultrasonography and computed stereometry, may
provide a more accurate measurement.
From Greene FL, Page DL, Fleming ID, et al (eds). AJCC Cancer Staging Manual, 6th ed. New York: Springer, 2002, pp 365-370.
testing, CT, and MRI, the error rate has been reduced to infiltration into orbital soft tissues. Anterior choroidal and
less than 1%, as reported by the multicenter Collaborative ciliary body tumors may involve the lens and seed the
Ocular Melanoma Study (COMS).63 Combined positron posterior chamber.6,67,68
emission tomography/CT may eventually be useful in the Because the uvea has no lymphatic drainage, metasta-
pretreatment assessment of uveal melanoma.64 Prognostic sis occurs hematogenously. The overall metastasis rate is
factors include age, cell type, tumor size, tumor location, approximately 50%, and metastases have a particular pre-
integrity of Bruch s membrane (the lamina between the dilection for the liver. Doubling times range from a few
choriocapillaris and the pigmented layer of the retina), months to several years. Sato and colleagues69 reported
scleral invasion, and pigmentation.65 As reflected by the that the median time from treatment to systemic metasta-
American Joint Committee on Cancer staging system sis was 20 months for the group with the most unfavorable
(Box 14-1),66 tumor size seems to be the most impor- prognosis (i.e., age > 60 years, male sex, and tumor diam-
tant prognostic factor, with tumors measuring more than eter > 10 mm), in contrast with 76 months for the group
10 mm conferring a poor prognosis. with the most favorable prognosis (i.e., age d" 60, female
For many years, all uveal melanomas were treated by sex, and diameter d" 10 mm).
enucleation, and little is known about the natural histo- The traditional practice of enucleation of the involved
ry of this disease. Most tumors arise from the pigmented eye was questioned in the 1970s by Zimmerman and col-
cells in the choroid. Tumor spread is mainly local. With leagues,70,71 who suggested that enucleation may worsen
inward growth, the tumor may displace the retina or rup- prognosis by promoting metastasis through the dissemi-
ture Bruch s membrane and spread over the retinal surface. nation of tumor cells during the surgical procedure. Al-
Outward growth of the tumor may lead to extrascleral though this theory has been questioned by others,72-74
14 The Orbit 315
the trend at many centers has shifted toward preserving for both treatment groups, actuarial 5-year overall survival
vision whenever possible. Shields and Shields75 advocate rates were 56% for those who underwent enucleation only
reserving enucleation for large melanomas (those that are and 61% for those who had pre-enucleation radiation ther-
> 10 mm thick and > 15 mm in diameter), treatment of apy. Serious complications were uncommon and were not
which with radiation therapy would be expected to cause increased by presurgical radiation.82 Given these findings,
considerable visual morbidity. However, if the melanoma routine preoperative irradiation probably has no role in the
is located in the patient s only useful eye, it is reasonable treatment of large uveal melanomas.
to attempt control with radiation therapy despite the ex- Particle Beam Therapy. During the past 3 decades,
pected poor visual outcome. particle beam therapy has emerged as an effective al-
Brachytherapy. A variety of radiation therapy tech- ternative to brachytherapy. By taking advantage of the
niques are used for conservative management of uveal Bragg peak effect (described in Chapters 1 and 40), par-
melanoma, including plaque therapy with radon 222 ticle beam therapy can deposit radiation in the target
(222Rn), gold 198 (198Au), cobalt 60 (60Co), iridium 192 while limiting the fall-off dose to adjacent noninvolved
(192Ir), tantalum 182 (182Ta), iodine 125 (125I), and ru- structures. Brachytherapy is effective and has potentially
thenium 106 (106Ru). In the United States, 125I has be- less associated morbidity for directly accessible lesions
come widely used because its lower energy allows less anterior to the equator of the globe, but particle beam
shielding of normal tissues and medical personnel with- therapy can be used to treat posterior lesions more ho-
out compromising the dose distribution in the target mogeneously and completely, especially those approxi-
volume.76 mating the optic disc. Several series have demonstrated
The continued controversy regarding the relative in- equivalent outcomes for brachytherapy and particle
dications for enucleation and radiation therapy led to the beam therapy, although these findings remain somewhat
launch of a multicenter COMS77 in the United States limited at this time.83-85
and Canada in 1986. In that trial, 1317 patients with Helium ions86 and protons have been investigated for
medium-sized tumors (2.5 to 10 mm in apical height and uveal melanoma, but most of the work has been done with
d" 16 mm in basal diameter) were randomly assigned over a protons. Clinical results have been promising. Investiga-
12-year accrual period to treatment with 125I brachyther- tors from the Curie Institut-Orsay Proton Therapy Center
apy or enucleation. The COMS trial used 125I plaques, published a review of their 20-year experience treating
the size of which was chosen to cover the tumor base 1406 patients with protons.87 Patients were managed uni-
(defined to include all pigmented areas) plus a margin formly with 60Co Gy equivalent (CGE) in four consecutive
of 2 to 3 mm. Tumors contiguous with the optic disc once-daily fractions. At a median follow-up time of just
were excluded because vision would be compromised over 6 years, the actuarial 5-year local disease control rate
because of radiation damage to the optic nerve. A dose was 96%, the metastasis-free survival rate was 81%, and
of 100 Gy was delivered at a rate of 0.5 to 1.25 Gy/hr. the overall survival rate was 79%. These results echo data
Accrual ended in July 1998, and follow-up was expected from previous smaller series88-92; retrospective compari-
to continue for up to an additional 10 years.78 Initial sons of protons with enucleation have not shown proton
clinical outcomes were reported in 2001, when 81% of beam therapy to compromise survival.93,94 Complication
patients had been followed up for at least 5 years.79 No rates were relatively low and mirrored published experi-
significant differences in unadjusted or adjusted mortal- ences. The enucleation rate for treatment-related toxicity
ity rates could be demonstrated between the two groups (most often neovascular glaucoma and its attendant pain)
at that time. Five-year cumulative mortality rates were was 7.7%. The risk of toxicity-related enucleation was
19% for the enucleation group and 18% for the brachy- associated with tumor thickness and the volume of lens
therapy group. The risk of treatment failure at 5 years receiving more than 30 CGE. Future efforts to reduce
after brachytherapy was only 10.3%; however, visual toxicity will focus on prospective trials of dose and treat-
acuity was 20/200 or worse in 43% of treated eyes. In ment margin reduction strategies.
the absence of mature prospective data, Augsburger and Other reports suggest that proton therapy can be useful
colleagues80 published a matched-pair analysis of 448 for carefully selected, large melanomas of the uvea (i.e.,
patients (from an original group of 734 patients). The 15- tumors at least 10 mm thick or 20 mm in diameter and tu-
year survival rates were 57% for the enucleation group mors located within 3 mm of the optic nerve that are at least
and 62% for the plaque-radiation-therapy group.80 The 8 mm thick or 16 mm in diameter)95 or melanomas of
15-year local relapse rate in the plaque-radiation group the iris.96
was 18.9%. Although this study did not have sufficient
Conjunctival Melanoma
power to reveal small differences in survival, a large
difference in survival between the treatment groups Conjunctival melanomas are rare, accounting for 2% of
would be unlikely. ocular melanomas. These tumors are treated with local ex-
A second COMS randomized trial81 compared results cision or cryotherapy. The role of radiation therapy in this
after enucleation, preceded or not preceded by preopera- disease is unclear.97
tive external beam radiation therapy (20 Gy in 5 daily frac-
Orbital Lymphomas
tions) for patients with large tumors (i.e., > 10 mm in apical
height or > 16 mm in basal diameter). Mortality findings Primary non-Hodgkin lymphoma of the orbit is a rare
were published in 2004.81 With 10-year results known for disease, accounting for 1% of cases of non-Hodgkin
75% of enrolled patients, pre-enucleation radiation thera- lymphoma98 and 10% of all orbital tumors.99 Primary
py did not yield a statistically significant improvement in non-Hodgkin lymphomas of the orbit are distinct from
survival. At a median survival time of approximately 7 years intraocular lymphomas involving the vitreous humor, retina,
316 PART 3 Head and Neck
or choroid, which have a high rate of central nervous system dose-response relationship for follicular lymphoma of
involvement.100 Usually arising from the conjunctiva, non- the ocular adnexa; all cases were controlled with doses
Hodgkin lymphomas of the orbit manifest as smooth, shiny, in the mid-20-Gy range. However, MALT-type lympho-
salmon-colored swellings that often are asymptomatic.98 mas seemed to require at least 30 Gy (30.6 to 32.4 Gy in
Retrobulbar lesions restrict extraocular movement and 1.8-Gy fractions was recommended) to achieve 100% lo-
cause exophthalmos, diplopia, edema, chemosis, and pain. cal control. Several other series support this finding,105-107
Vision is usually preserved. In addition to CT or MRI to although doses between 25 and 30 Gy may also be effec-
evaluate the extent of local disease, diagnostic evaluation tive.108,109 In a series from M. D. Anderson, none of the pa-
should include the ancillary evaluations typically done for tients with low-grade lymphomas treated with 30 Gy given
lymphoma (e.g., bone marrow biopsies and CT scanning in 20 fractions had a local relapse.110 For high-grade lesions,
of the chest, abdomen, and pelvis) to evaluate the extent we recommend initial chemotherapy followed by 30 Gy
of systemic disease. Although any subtype of non-Hodgkin in 20 fractions for those tumors that show a complete re-
lymphoma can affect the orbital adnexa, marginal zone B- sponse to chemotherapy or 36.0 to 39.6 Gy in 20 to 22
cell mucosa-associated lymphoid tissue (MALT) type and fractions if the tumor shows a partial response. The limited
follicular histologies are the most common. published experience with observation only after biopsy
The selection of treatment depends on the pathologic of MALT-type orbital lymphoma111,112 suggests that this
subtype and disease stage. Radiation therapy alone is an approach requires careful patient selection and counseling
accepted treatment for low-grade lymphomas confined to and cannot be considered the standard of care given the
the orbit. Because high-grade lymphomas are associated expected efficacy and low morbidity of radiation.
with high distant relapse rates (60%),101,102 treatment usu- Electron beam therapy, typically 6 to 9 MeV with a 0.5-
ally consists of initial chemotherapy followed by consolida- to 1.0-cm bolus, is adequate for anterior lesions involving
tive irradiation. Series published in the late 1980s reported the eyelid or conjunctiva. A lens or eye shield can be used
excellent local control rates with radiation doses of 25 to if its use does not compromise tumor coverage. For eyelid
40 Gy given in the 1.5- to 2.0-Gy fractions typical for lym- tumors, commercial lead eye shields, 1.7 mm thick, pro-
phoma (90% to 100%).101-103 Fung and others from Mas- vide inadequate protection for electron beam energies of
sachusetts General Hospital104 reported a lack of radiation 6 MeV or greater, with 50% dose transmission on the sur-
face (cornea) and 27% dose transmission at a depth of
6 mm (lens).113 In place of lead, we use a tungsten eye
9-MeV Electron beam
shield, 3 mm thick, which reduces the transmission dose
to the cornea and lens to less than 5% for 6- to 9-MeV
electrons (Fig. 14-4).114 Conjunctival tumors require irra-
diation of the palpebral and bulbar conjunctivae. In these
cases, the lens may be protected by using a suspended lead
eye bar, as outlined under  Orbital Pseudotumor. With this
technique, it is essential that the patient fix his or her gaze
0.0
on the block while the treatment beam is on. However,
we prefer to mount the block on a contact lens so that the
shielding is placed directly over the lens and cornea (Fig.
14-5). The dose to the cornea with this technique has been
1.0
calculated to be approximately 5% of the total dose. Poste-
rior lesions usually require treatment with photon beams
to achieve sufficiently deep dose distribution.
3
2.0
5
10
3.0
20
4.0
40 40
27
27
20
5.0
10
5
3
6.0
Long axis
FIGURE 14-4. Isodose distribution beneath a tungsten eye FIGURE 14-5. Field setup for an anteriorly located orbital lym-
shield for a 9-MeV electron beam from a linear accelerator. phoma treated with an electron beam with shielding of the lens
(Modified from Block R, Gartner S. The incidence of ocular meta- and cornea through the use of a brass shield mounted on a
static carcinoma. Arch Ophthalmol 1971;85:673-675.) contact lens.
Depth (cm)
14 The Orbit 317
7. Brady L, Shields J, Augusburger J, et al. Complications from
Metastasis to the Orbit radiation therapy to the eye. Front Radiat Ther Oncol 1989;
23:238-250.
Although metastasis to the orbit is uncommon, metastat-
8. Parsons J, Bova FJ, Fitzgerald CR, et al. Severe dry-eye syndrome
ic tumors are the most common intraocular malignancy.
following external beam irradiation. Int J Radiat Oncol Biol Phys
Metastases to the orbit most often originate from primary
1994;30:775-780.
breast carcinoma or lung cancer.113,115-117 Given the in- 9. Merriam G, Szechter A, Focht E. The effects of ionizing
radiations on the eye. In Vaeth JM (ed): Radiation Effect and
creasing survival times of cancer patients, the incidence of
Tolerance, Normal Tissue. Baltimore: University Park Press,
orbital metastasis can be expected to increase. Metastases
1972, pp 346-385.
to the eye can involve any orbital structure. Intraocular
10. Chan R, Shukovsky L. Effects of irradiation on the eye. Radiology
metastases are typically located in the choroid. Presenting
1976;120:673-675.
symptoms include decreased vision, exophthalmos, pain,
11. Bessell E, Henk JM, Whitelocke RA, et al. Ocular morbidity
heaviness, and double vision. Ophthalmoscopic examina-
after radiotherapy of orbital and conjunctival lymphoma. Eye
tion often reveals retinal detachment.117 CT or MRI delin- 1987;1:90-96.
12. Merriam G. Late effects of beta radiation on the eye. Arch Oph-
eates the extent of the metastatic deposit.
thalmol 1955;53:708.
In most cases, a history of prior malignancy, multiple
13. Merriam G. The effects of ²-radiation on the eye. Radiology
lesions in one eye, or bilateral tumors establishes the di-
1956;66:240.
agnosis. In other cases, metastatic choroid tumors can be
14. Jiang G, Tucker SL, Guttenberger R, et al. Radiation-induced
distinguished from other tumors mainly choroidal mela-
injury to the visual pathway. Radiother Oncol 1994;30:17-25.
nomas, benign lesions such as hemangiomas, and inflamma- 15. Hall EJ. Radiation cataractogenesis. In Hall EJ (ed): Radiobi-
ology for the Radiologist. Philadelphia: JB Lippincott, 1994,
tory granulomas118 by using ancillary studies as described
pp 379-384.
earlier under  Uveal Melanoma. Bilateral involvement is
16. Archer D. Doyne lecture: responses of retinal and choroidal ves-
found in 20% to 25% of cases.116,117 The initial evaluation
sels to ionizing radiation. Eye 1993;7:1-13.
should include MRI of the brain because of the possibility
17. Brown G, Shields JA, Sanborn G, et al. Radiation retinopathy.
of synchronous brain metastases.
Ophthalmology 1982;89:1494-1501.
Unilateral radiation therapy with a lateral electron por- 18. Parsons J, Bova FJ, Fitzgerald CR, et al. Radiation retinopathy
after external-beam irradiation: analysis of time-dose factors. Int
tal of sufficient energy is adequate to treat most ocular me-
J Radiat Oncol Biol Phys 1994;30:765-773.
tastases. The anterior border should be placed just behind
19. Dhir S, Joshi A, Banerjee A. Radiation retinopathy in diabetes
the anterior chamber of the eye, and a posterior tilt should
mellitus. Acta Radiol Oncol 1982;21:111-113.
be placed to avoid the lens. For bilateral metastases, poste-
20. Mewis L, Tang R, Salmonsen P. Radiation retinopathy after
riorly tilted opposing photon fields can be used.
 safe levels of irradiation. Invest Ophthalmol Vis Sci 1982;
Radiation therapy is quite effective in relieving symp-
22:222.
toms and controlling tumor growth. With doses of at least 21. Viebahn M, Barricks M, Osterloh M. Synergism between
diabetic and radiation retinopathy: case report and review. Br
30 Gy in daily fractions of 2 to 3 Gy, symptomatic im-
J Ophthalmol 1991;75:629-632.
provement and tumor control are seen in approximately
22. Parsons J, Bova FJ, Fitzgerald CR, et al. Radiation optic neuropathy
90% of patients.117,119 Doses less than 30 Gy may be less
after megavoltage external-beam irradiation: analysis of time-
effective. In a report by Maor and colleagues,119 none of
dose factors. Int J Radiat Oncol Biol Phys 1994;30:755-763.
the nine patients who received 30 Gy in 10 fractions had
23. Wartofsky L. Diseases of the thyroid. In Isselbacher KJ, Braun-
tumor regrowth after therapy, but 2 of 10 patients treated wald E, Wilson JD, et al (eds): Harrison s Principles of Internal
Medicine, 13th ed. New York: McGraw-Hill, 1994, pp 1930-
with 25 Gy in 10 fractions had tumor regrowth. In a series
1953.
reported by Reddy and colleagues,116 30% of tumors did
24. Olivotto I, Ludgate CM, Allen LH, et al. Supervoltage radio-
not respond to treatment with doses of 21 to 30 Gy. The
therapy for Graves ophthalmopathy: CCABC technique and
median survival time after detection of choroidal metasta-
results. Int J Radiat Oncol Biol Phys 1985;11:2085-2090.
ses is 8.5 to 12 months, and for most patients, the benefit in
25. Donaldson S, McDougall I, Kriss J. Grave s disease. In Alberti
vision produced by radiation therapy lasts for the remain-
WE, Sagerman RH (eds): Medical Radiology: Radiotherapy of
Intraocular and Orbital Tumors. Berlin: Springer-Verlag, 1993,
der of their lives.
pp 192-197.
26. Palmer D, Greenberg P, Cornell P, et al. Radiation therapy for
REFERENCES Graves ophthalmopathy: a retrospective analysis. Int J Radiat
Oncol Biol Phys 1987;13:1815-1820.
1. Saude T. The outer coats of the eye. In Saude T (ed): Ocular
27. Petersen I, Kriss JP, McDougall IR, et al. Prognostic factors in
Anatomy and Physiology. Oxford, UK: Blackwell Science, 1993,
the radiotherapy of Graves ophthalmopathy. Int J Radiat Oncol
pp 11-25.
Biol Phys 1990;19:259-264.
2. Bron AJ, Tripathi RC, Tripathi BJ. Wolff s Anatomy of the Eye
28. Marcocci C, Bartalena L, Bogazzi F, et al. Orbital radiotherapy
and Orbit, 8th ed. London: Arnold Publishers, 1997.
combined with high dose systemic glucocorticoids for Graves
3. Karlsson U, Kirby T, Orrison W, et al. Ocular globe topography
ophthalmopathy is more effective than radiotherapy alone:
in radiotherapy. Int J Radiat Oncol Biol Phys 1995;33:705-712.
results of a prospective randomized study. J Endocrinol Invest
4. Rohrschneider W. Experimentelle Untersuchungen uber die Ve-
1991;14:853-860.
randerungen normaler Augengewebe nach Rontgenbestrahlung.
29. Pitz S, Kahaly G, Rosler HP, et al. Retrobulbar irradiation for
III. Mitteilung. Beranderungen der Linse der Netzhaut und des
Graves ophthalmopathy long-term results [in German]. Klin
Sehnerven nach Rontgenbestrahlung. Graefes Arch Ophthal
Monatsbl Augenheilkd 2002;219:876-882.
1929;122:282.
30. Kulig G, Kazmierczyk-Puchalska A, Krzyzanowska-Swiniarska B,
5. Fajardo LF, Berthrong M, Anderson RE. Eye and its adnexa. In:
et al. Effectiveness of treatment for thyroid orbitopathy in
Radiation Pathology. New York: Oxford University Press, 2001,
patients hospitalized at the Endocrinology Department of
pp 399-408.
Pomeranian Medical University [in Polish]. Przegl Lek 2004;
6. Hungerford J. Current management of choroidal malignant
61:852-854.
melanoma. Br J Hosp Med 1985:34:287-293.
318 PART 3 Head and Neck
31. Bartalena L, Marcocci C, Chiovato L, et al. Orbital cobalt 57. MacKenzie F, Hirst LW, Kynaston B, et al. Recurrence rate and
irradiation combined with systemic corticosteroids for Graves complications after beta irradiation for pterygia. Ophthalmol-
ophthalmopathy: comparison with systemic corticosteroids ogy 1991;8:1776-1781.
alone. J Clin Endocrinol Metab 1983;56:1139-1144. 58. Moriarty A, Crawford GJ, McAllister IL, et al. Severe corneo-
32. Mourits MP, van Kempen-Harteveld ML, Garcia MB, et al. scleral infection. A complication of beta irradiation scleral necro-
Radiotherapy for Graves orbitopathy: randomised placebo- sis following pterygium necrosis. Arch Ophthalmol 1993;111:
controlled study. Lancet 2000;355:1505-1509. 947-951.
33. Prummel MF, Terwee CB, Gerding MN, et al. A randomized 59. Dusenbery K, Alul IH, Holland EJ, et al. ²-Irradiation of recur-
controlled trial of orbital radiotherapy versus sham irradiation in rent pterygia: results and complications. Int J Radiat Oncol Biol
patients with mild Graves ophthalmopathy. J Clin Endocrinol Phys 1992;24:315-320.
Metab 2004;89:15-20. 60. Goetsch S. Strontium-90 ophthalmic applicators: use with
34. Wakelkamp IM, Tan H, Saeed P, et al. Orbital irradiation for caution [letter]. Ophthalmic Surg 1988;19:827-828.
Graves ophthalmopathy: is it safe? A long-term follow-up 61. Scotto J, Fraumeni JJ, Lee J. Melanomas of the eye and non-
study. Ophthalmology 2004;111:1557-1562. cutaneous sites: epidemiologic aspects. J Natl Cancer Inst
35. Snijders-Keilholz A, De Keizer RJ, Goslings BM, et al. Prob- 1976;56:489-491.
able risk of tumour induction after retro-orbital irradiation for 62. Egan K, Seddon JM, Glynn RJ, et al. Epidemiological aspects of
Graves ophthalmopathy. Radiother Oncol 1996;38:67-71. uveal melanoma. Surv Ophthalmol 1988;32:239-251.
36. Blank L, Barendsen GW, Prummel MF, et al. Probable risk of 63. Collaborative Ocular Melanoma Study Group. Accuracy of
tumour induction after retro-orbital irradiation for Graves diagnosis of choroidal melanoma in the Collaborative Ocular
ophthalmopathy [letter]. Radiother Oncol 1996;40:187-188. Melanoma Study: COMS report no. 1. Arch Ophthalmol
37. Dutton J. Orbital diseases. In Yanoff M, Duker JS (eds): Oph- 1990;108:1268-1273.
thalmology London: Mosby, 1999, pp 7.14.1-7.14.18. 64. Reddy S, Kurli M, Tena LB, et al. PET/CT imaging: detection of
38. Char D, Miller T. Orbital pseudotumor. Fine needle aspiration choroidal melanoma. Br J Ophthalmol 2005;89:1265-1269.
biopsy and response to therapy. Ophthalmology 1993;100:1702- 65. Shammas H, Blodi F. Prognostic factors in choroidal and ciliary
1710. body melanomas. Arch Ophthalmol 1977;95:63-69.
39. Kennerdell J, Dresner S. The nonspecific orbital inflammatory 66. Greene FL, Page DL, Fleming ID, et al (eds): AJCC Cancer Stag-
syndromes. Surv Ophthalmol 1984;29:93-103. ing Manual. 6th ed. New York: Springer, 2002, pp 365-370.
40. Leone C, Lloyd W. Treatment protocol for orbital inflammatory 67. Moss W. The orbit. In Cox JD (ed): Moss Radiation Oncol-
disease. Ophthalmology 1985;92:1325-1331. ogy: Rationale, Technique, Results, 7th ed. St Louis: CV Mosby,
41. Sergott R, Glaser J, Charyulu K. Radiotherapy for idiopathic 1994, pp 246-259.
inflammatory orbital pseudotumor. Arch Ophthalmol 1981; 68. Sahel J, Earle J, Albert D. Intraocular melanomas. In DeVita
99:853-856. VT Jr, Hellman S, Rosenberg SA (eds): Cancer: Principles and
42. Orcutt J, Garner A, Henk JM, et al. Treatment of idiopathic in- Practice of Oncology, 4th ed. Philadelphia: JB Lippincott, 1993,
flammatory orbital pseudotumours by radiotherapy. Br J Oph- pp 1662.
thalmol 1983;67:570-574. 69. Sato T, Babazono A, Shields JA, et al. Time to systemic metas-
43. Gunalp I, Gunduz K, Yazar Z. Idiopathic orbital inflammatory tases in patients with posterior uveal melanoma. Cancer Invest
disease. Acta Ophthalmol Scand 1996;74:191-193. 1997;15:98-105.
44. Lanciano R, Fowble B, Sergott RC, et al. The results of radio- 70. Zimmerman L, McLean I. Changing concepts concerning
therapy for orbital pseudotumor. Int J Radiat Oncol Biol Phys the malignancy of ocular tumors. Arch Ophthalmol 1975;78:
1990;18:407-411. 487-494.
45. Jacobs D, Galetta S. Diagnosis and management of orbital pseu- 71. Zimmerman L, McLean I, Foster W. Does enucleation of the
dotumor. Curr Opin Ophthalmol 2002;13:347-351. eye containing a malignant melanoma prevent or accelerate
46. Donaldson S, Findley D. Treatment of orbital lymphoid tumors the dissemination of tumour cells? Br J Ophthalmol 1978;62:
with electron beams. Front Radiat Ther Oncol 1991;25:187- 420-425.
200. 72. Seigel D, Myers M, Ferris F, et al. Survival rates after enucleation
47. Sugar A. Conjunctival and corneal degenerations. In Yanoff M, of eyes with malignant melanoma. Am J Ophthalmol
Duker JS, (eds): Ophthalmology London: Mosby, 1999, pp 1979;87:761-765.
5.6.1-5.6.8. 73. Manschot W, van Peperzeel H. Choroidal melanoma: enucleation
48. Cameron M. Pterygium Throughout the World. Springfield, IL: or observation? A new approach. Arch Ophthalmol 1980;
Charles C Thomas, 1965. 98:71-77.
49. Bahrassa F, Datta R. Postoperative beta radiation treatment of 74. Manschot W, Van Strik R. Is irradiation a justifiable treatment
pterygium. Int J Radiat Oncol Biol Phys 1983;9:679-684. of choroidal melanoma? Analysis of published results. Br J Oph-
50. Hirst L, Sebban A, Chant D. Pterygium recurrence time. Oph- thalmol 1987;71:348-352.
thalmology 1994;101:755-758. 75. Shields J, Shields C. Management of posterior uveal melanoma.
51. Van Den Brenk H. Results of prophylactic postoperative ir- In Shields JA, Shields CL (eds): Intraocular Tumors: A Textbook
radiation in 1,300 cases of pterygium. AJR Am J Roentgenol and Atlas. Philadelphia: WB Saunders, 1992, pp 171-205.
1968;103:723-733. 76. Earle J, Kline R, Robertson D. Selection of iodine 125 for the
52. Wilder R, Buatti JM, Kittelson JM, et al. Pterygium treated with Collaborative Ocular Melanoma Study. Arch Ophthalmol
excision and postoperative beta irradiation. Int J Radiat Oncol 1987;105:763-764.
Biol Phys 1992;23:533-537. 77. Collaborative Ocular Melanoma Study Group. COMS Manual
53. Paryani S, Scott WP, Wells JW, et al. Management of pterygium of Procedures. Springfield, VA: National Technical Information
with surgery and radiation therapy. Int J Radiat Oncol Biol Phys Service, 1995.
1994;28:101-103. 78. Earle JD. Results from the Collaborative Ocular Melanoma
54. Monteiro-Grillo I, Gaspar L, Monteiro-Grillo M, et al. Postop- Study (COMS) of enucleation versus preoperative radiation
erative irradiation of primary or recurrent pterygium: results and therapy in the management of large ocular melanomas. Int J Ra-
sequelae. Int J Radiat Oncol Biol Phys 2000;48:865-869. diat Oncol Biol Phys 1999;43:1168-1169.
55. Pajic B, Greiner RH. Long term results of non-surgical, exclusive 79. Diener-West M, Earle JD, Fine SL, et al. The COMS randomized
strontium-/yttrium-90 beta-irradiation of pterygia. Radiother trial of iodine 125 brachytherapy for choroidal melanoma. III.
Oncol 2005;74:25-29. initial mortality findings. COMS report no. 18. Arch Ophthal-
56. Alaniz-Camino F. The use of postoperative beta radiation in mol 2001;119:969-982.
the treatment of pterygia. Ophthalmic Surg 1982;13:1022-
1025.
14 The Orbit 319
80. Augsburger J, Schneider S, Freire J, et al. Survival following 98. Fitzpatrick P, Macko S. Lymphoreticular tumors of the orbit. Int
enucleation versus plaque radiotherapy in statistically matched J Radiat Oncol Biol Phys 1984;10:33-340.
subgroups of patients with choroidal melanomas: results in pa- 99. Reese A. Orbital neoplasms and lesions simulating them. In
tients treated between 1980 and 1987. Graefes Arch Clin Exp Hoeber PB (ed): Tumours of the Eye. New York: Harper & Row,
Ophthalmol 1999;237:558-567. 1976, pp 434-440.
81. Hawkins BS. The Collaborative Ocular Melanoma Study 100. Char D, Ljung BM, Miller T, et al. Primary intraocular lympho-
(COMS) randomized trial of pre-enucleation radiation of ma (ocular reticulum cell sarcoma) diagnosis and management.
large choroidal melanoma. IV. Ten-year mortality findings and Ophthalmology 1988;95:625-630.
prognostic factors. COMS report no. 24. Am J Ophthalmol 101. Bessell E, Henk JM, Wright JE, et al. Orbital and conjunc-
2004;138:936-951. tival lymphoma treatment and prognosis. Radiother Oncol
82. Collaborative Ocular Melanoma Study Group. The Collabora- 1988;13:237-244.
tive Ocular Melanoma Study (COMS) randomized trial of pre- 102. Bolek T, Moyses HM, Marcus RB, et al. Radiotherapy in the
enucleation radiation of large choroidal melanoma. III. Local management of orbital lymphoma. Int J Radiat Oncol Biol Phys
complications and observations following enucleation. COMS 1999;44:31-36.
report no. 11. Am J Ophthalmol 1998;126:362-372.
103. Smitt M, Donaldson S. Radiotherapy is successful treatment for
83. Wilson MW, Hungerford JL. Comparison of episcleral plaque orbital lymphoma. Int J Radiat Oncol Biol Phys 1993;26:59-66.
and proton beam radiation therapy for the treatment of choroi- 104. Fung CY, Tarbell NJ, Lucarelli MJ, et al. Ocular adnexal lym-
dal melanoma. Ophthalmology 1999;106:1579-1587. phoma: clinical behavior of distinct World Health Organization
84. Char DH, Quivey JM, Castro JR, et al. Helium ions versus iodine classification subtypes. Int J Radiat Oncol Biol Phys 2003;57:1382-
125 brachytherapy in the management of uveal melanoma. 1391.
A prospective, randomized, dynamically balanced trial. 105. Le QT, Eulau SM, George TI, et al. Primary radiotherapy for
Ophthalmology 1993;100:1547-1554. localized orbital MALT lymphoma. Int J Radiat Oncol Biol Phys
85. Desjardins L, Lumbroso L, Levy C, et al. [Treatment of uveal 2002;52:657-663.
melanoma with iodine 125 plaques or proton beam therapy: 106. Tsang RW, Gospodarowicz MK, Pintilie M, et al. Localized
indications and comparison of local recurrence rates]. J Fr mucosa-associated lymphoid tissue lymphoma treated with
Ophtalmol 2003;26:269-276. radiation therapy has excellent clinical outcome. J Clin Oncol
86. Char DH, Kroll SM, Castro J. Ten-year follow-up of helium 2003;21:4157-4164.
ion therapy for uveal melanoma. Am J Ophthalmol 1998;125: 107. Uno T, Isobe K, Shikama N, et al. Radiotherapy for extranodal,
81-89. marginal zone, B-cell lymphoma of mucosa-associated lymphoid
87. Dendale R, Lumbroso-Le Rouic L, Noel G, et al. Proton beam tissue originating in the ocular adnexa: a multiinstitutional, ret-
radiotherapy for uveal melanoma: results of Curie Institut- rospective review of 50 patients. Cancer 2003;98:865-871.
Orsay proton therapy center (ICPO). Int J Radiat Oncol Biol 108. Zhou P, Ng AK, Silver B, et al. Radiation therapy for orbital
Phys 2006;65:780-787. lymphoma. Int J Radiat Oncol Biol Phys 2005;63:866-871.
88. Munzenrider J. Proton therapy for uveal melanomas and other 109. Suh CO, Shim SJ, Lee SW, et al. Orbital marginal zone B-cell
eye lesions. Strahlenther Onkol 1999;175(Suppl 2):68-73. lymphoma of MALT: radiotherapy results and clinical behavior.
89. Egger E, Schalenbourg A, Zografos L, et al. Maximizing local Int J Radiat Oncol Biol Phys 2006;65:228-233.
tumor control and survival after proton beam radiotherapy 110. Pelloski CE, Wilder RB, Ha CS, et al. Clinical stage IEA-IIEA
of uveal melanoma. Int J Radiat Oncol Biol Phys 2001;51: orbital lymphomas: outcomes in the era of modern staging and
138-147. treatment. Radiother Oncol 2001;59:145-151.
90. Fuss M, Loredo LN, Blacharski PA, et al. Proton radiation ther- 111. Matsuo T, Yoshino T. Long-term follow-up results of observa-
apy for medium and large choroidal melanoma: preservation tion or radiation for conjunctival malignant lymphoma. Oph-
of the eye and its functionality. Int J Radiat Oncol Biol Phys thalmology 2004;111:1233-1237.
2001;49:1053-1059.
112. Tanimoto K, Kaneko A, Suzuki S, et al. Long-term follow-up re-
91. Courdi A, Caujolle JP, Grange JD, et al. Results of proton sults of no initial therapy for ocular adnexal MALT lymphoma.
therapy of uveal melanomas treated in Nice. Int J Radiat Oncol Ann Oncol 2006;17:135-140.
Biol Phys 1999;45:5-11.
113. Shiu A, Tung SS, Gastorf RJ, et al. Dosimetric evaluation of lead
92. Hocht S, Bechrakis NE, Nausner M, et al. Proton therapy of and tungsten eye shields in electron beam treatment. Int J Ra-
uveal melanomas in Berlin: 5 years of experience at the Hahn- diat Oncol Biol Phys 1996;35:599-604.
Meitner Institute. Strahlenther Onkol 2004;180:419-424.
114. Block R, Gartner S. The incidence of ocular metastatic carci-
93. Seddon J, Gragoudas ES, Albert DM, et al. Comparison of noma. Arch Ophthalmol 1971;85:673-675.
survival rates for patients with uveal melanoma after treatment 115. Ferry A, Font R. Carcinoma metastatic to the eye and orbit.
with proton beam irradiation or enucleation. Am J Ophthalmol I. A clinicopathologic study of 227 cases. Arch Ophthalmol
1985;99:282-290. 1974;92:276-286.
94. Seddon J, Gragoudas ES, Egan KM, et al. Relative survival rates 116. Reddy S, Saxena VS, Hendrickson F, et al. Malignant metastatic
after alternative therapies for uveal melanoma. Ophthalmology disease of the eye: management of an uncommon complication.
1990;97:769-777. Cancer 1981;47:810-812.
95. Conway RM, Poothullil AM, Daftari IK, et al. Estimates of ocular 117. Glassburn J, Klionsky M, Brady L. Radiation therapy for meta-
and visual retention following treatment of extra-large uveal static disease involving the orbit. Am J Clin Oncol 1984;7:145-
melanomas by proton beam radiotherapy. Arch Ophthalmol 148.
2006;124:838-843.
118. Gragoudas E. Current treatment of metastatic choroidal tumors.
96. Damato B, Kacperek A, Chopra M, et al. Proton beam radio- Oncology 1989;3:103-110.
therapy of iris melanoma. Int J Radiat Oncol Biol Phys 2005;63: 119. Maor M, Chan R, Yound S. Radiotherapy of choroidal metastases.
109-115. Cancer 1977;40:2081-2086.
97. Rennie I. Diagnosis and treatment of ocular melanomas. Br
J Hosp Med 1991;46:144-156.