Radiation of eye AND ORBIT

1. RT in EYE and ORBIT
DR KIRAN

2. INDRODUCTION
• Tumors of the eye and orbit are rare.
• Male to female incidence is similar,
• Metastases, or secondary intraocular tumors, are more common than
primary tumors .
• Melanoma is mc intraoccular tumour in adults.
• Retinoblastoma mc in paediatric age group

3. Anatomy
• Eye-ball consists of anterior segment and posterior segment.
• Anterior cornea and sclera which are connected by the limbus.
• Pigmented iris, pupil, and lens which is held in place by suspensary
ligaments.
• Three coats ie covering of eye : outer sclera and cornea, middle
choroid layer ciliary body and iris, inner retina.

4. Clinical Anatomy
 The eye is composed of three layers.
 Outer fibrous layer formed by the sclera
posteriorly and the cornea anteriorly.
 Inner layer , sensory retina with vision
concentrated at the fovea which is
lateral to the optic nerve and directly
posterior to the lens.
 In between these vascular layer – the
uvea or choroid –which supplies the
retina. The iris is the outer continuation
of the vascular layer
 Lens sits just behind iris, suspended
from the ciliary body.
 No lymphatic drainage

5. Use of RT in Occular Diseases
Malignant Diseases:
Metastatic Carcinoma to Uvea
Malignant Melanoma of Uvea
Retinoblastoma
Optic Pathway Glioma
Primary Orbital Lymphoma
Sebaceous Ca of Eyelid
Orbital Rhabdomyosarcoma
• Beningn Diseases:
• Choroidal Hemangioma
• Capillary Hemangioma
• Orbital Psuedotumour
• Thyroid associated Orbitopathy

6. Administering of RT to eye
• Radiotherapy to the Eye can be administered in two ways:
-Plaque BrachyTherapy
-External Beam Radiation

7. Plaque Brachytherapy
• Used since 1930s
• Types of plaque :iodine-125, palladium-103 and ruthenium-106 , Cs-
131, Co-60, Sr-90.
• Ru-106 has a half life of 373.59 days and is beta emitter
• Ru-106 better tolerated, limited by lesser penetrating capacity,
recurrences vary from 3-4% - 11-16%.
• I-125 used for tumours till depth of 10mm, half life of 59.4 days

10. Complications
• Cataract formation is the most common complication and the 5-year probability
is 37%.
• vitreous hemorrhage
• Dry eye, keratitis,
• radiation-induced iris neovascularization,
• neovascular glaucoma,
• radiation-induced retinopathy,
• radiation-induced optic neuropathy,
• episcleral deposits, scleral necrosis and
• extraocular muscle alterations are the other ocular complications reported after
plaque brachytherapy.

11. Uveal Malignancy
• Uvea consists of – Iris, Choroid
and ciliary body.
• Plaque brachy therapy is main
stay at many centres.
• The general objective with all
plaques is to deliver 80 Gy to the
tumor apex by fixing the plaque
in the exact location of the
tumor.

12. Proton Therapy for Uveal Melanoma
• Used in uveal melanoma close to or contagious with optic disc-
parapapillary and peripapillary
• Large tumours and lesion of iris and ciliary body not suitable for
surgery
• Proton beam delivers a homogeneous dose to tumor and has a sharp edge, a high
tumor dose can be delivered with relative sparing of the optic nerve.

13. Proton Therapy
• Treatment planning ----- intraoperative examination by transillumination or
indirect ophthalmoscopy------edges of the tumor are delineated by four tantalum
rings sutured to the sclera.
• Patients receive a total dose of 70 CGE, which is delivered in 5 equal fractions
over 7 to 10 days (63.6 proton Gy × 1.1 relative biological effectiveness = 70 CGE)
• The most common complications were :
• radiation maculopathy and papillopathy.
• Anterior segment complications, such as rubeosis iridis and neovascular
glaucoma, are the most serious, but occur less frequently.

14. Stereotactic Radiotherapy
• Stereotactic radiation can be delivered by linear accelerator (LINAC)
or by specialized devices for focused radiation such as the Leksell
Gamma Knife.
• Gamma knife radiosurgery for uveal melanoma introduced in 1998.
• Nineteen patients with uveal melanoma were treated to a dose of 40
Gy prescribed to the 50% isodose line.
• Median follow-up was 40 months,
• 3- and 5-year overall survival rates were 86 and 55%.
• The 3- and 5-year tumor control rates were both 94%.

15. Complications of EBRT
• Complications were exudative retinopathy (33.3%),
• Neovascular glaucoma (18.7%),
• Radiogenic retinopathy (13.5%)
• Vitreous hemorrhage (10.4%)
• Severe radiation retinopathy is dose dependent with respect
• to both total dose (>25 Gy) and dose per fraction (>2 Gy) major
disadvantage for single fractionization

16. Metastatic Carcinoma to Uvea
• Most common malignancy
• Choroid is mostly affected 88%
• Males primary is lung kidney genitourinary.
• Females breast followed by lungs.
• Multifocal and diffuse EBRT 20-40Gy used.
• Plaque brachy single lesions, dose 68.8Gy to apex and 235 Gy to base,
for 86 hours

17. Retinoblastoma
• Mid 18th century: 1st clinical report of RB was recognized
• 1920-“ Vernoff” coined the term retinoblastoma
• 2.5-4% of paediatric malignancies
• Most common intraocular malignancy of childhood
• 2nd most common primary intraocular malignancy in any age group
• Tumor is of neuroepithelial origin & arises from unidentified progenitor cell in
nucleated layers of one or both eyes
• Accounts for 1:17,000-34,000 live births worldwide

18. Genetics
• Deletion of long arm of chromosome 13, 13q14, which is a tumor suppressor gene termed as RB
gene.
• ‘Alfred Knudson’ hypothesis: 2 types
Hereditary Non-hereditary
Familial Sporadic
Germline mutations 2 hits
Bilateral, multifocal Unilateral, unifocal
Young age older age

20. Clinical features
• Family history: 10%
• Leukocoria (white pupillary reflex): 50% , commonest
• Strabismus [esotropia]: 20%
• Ocular inflammation: due to necrosis of tumor or tumor cells may
enter AC resembling hyphema [pseudohypopyon]
• Secondary glaucoma: angle-closure
• Loss of vision
• Proptosis: extra ocular invasion
• Trilateral retinoblastoma; bil RB+ pineoblastoma
• Distant metastases

23. Routes of spread
• Local spread; anteriorly- seeding of vitreous & aqueous; posteriorly, sub retinal space
and choroids
• May spread through optic nerve
• Along the central retinal vessels: tumor cells pass through the lamina cribrosa and
enter subarachnoid space
• Distant metastases: CNS, skull, bones, lymph nodes, spinal cord, bone marrow
• Orbital involvement

24. Diagnosis
• Clinical History
• Ophthalmoscopy
• CT / MRI.
• Anterior chamber para-centesis: to assay LDH. Elevated ratio of aqueous
LDH5/LDH1 iso-enzymes, elevated ratio of aqueous LDH/ serum LDH
• Fluorescein angiography: tumor blush
• CSF cytology
• Bone scan
• Lab tests: Hemogram, Blood chemistries, KFT, LFT

25. Treatment of Retinoblastoma
• Primary goal
• to ensure the survival of children.
• retention of eyes and vision.
• Avoidance of side effects- second malignancies, facial bony deformities, or other physical changes
that can affect functional well-being.
• Treatment approaches are guided by the presence of intraocular or extraocular
disease.
• 5 yr. DFS > 90% for intraocular disease pts., but < 10% for extra-ocular disease.

26. Treatment Modalities
Surgery
• enucleation, exenteration
Local therapy
• cryotherapy, photocoagulation, laser
hyperthermia, radioactive plaque applications
Radiotherapy • EBRT, radioactive plaque, Particle treatment
Chemotherapy
• Systemic Chemotherapy, intra-arterial

28. Iodine 125 plaques
• Plaque Brachytherapy
• Indications:
• Solitary lesion 2-16 mm
basal diameter
• Unifocal lesions
• Located greater than 3 mm
from optic nerve or fovea
• Thickness <10 mm
• Two lesions, small or close
enough to be covered by
one plaque
• Local recurrence (small)
following radiotherapy
[EBRT]

29. Plaque Brachytherapy
• Sources I-125 , Ir-192, Ru-106.
• Duration 2-4 days @ dose rate 0.7-1.0 Gy/hr
• The dose is prescribed at the tumor apex or extended to include overlying
localized vitreous seeds if present.
• Dose of 40 Gy to apex if I- 125 used, 50-70Gy if Ru 106 used.
• Scleral dose 120Gy for I -125 , 150-200Gy for Ru-106

30. External beam radiotherapy
• Indications
• Multi-focal retinoblastoma
• RB close to macula or optic nerve
• Large tumor with vitreous seeding
• Positioning
• Proper immobilization is important
• thermoplastic or Perspex shell with the patient supine and
the chin in a neutral position
• Treatment is done under anesthesia: Ketamine
• Energy: Co-60 or 4-6 MV photons

31. Technique
Lateral field technique
• Started in 1930’s
• D – shaped lateral field with anterior border kept at bony orbit
• Disadvantage: tumor recurrence at or near ora serrata
Modified lateral beam technique
• Two lateral opposed D-shaped fields are used

32. Direct anterior field [Hungerford et al ]
• Whole eye is treated
• Disadvantage:
• Cataract formation
• Dose exits through brain
• Lacrimal gland irradiation-impaired tear production
• Advantages:
• Simple, easy to setup
• Reproducible
• Homogenously irradiates entire retina
Anterior lens sparing technique (ALD) [Abramson et al ]
• Lateral D-shaped field: Day1-Day 4 by photons
• Anterior electron beam field with central circular contact lens as lens shaped shield: on Day 5

33. • Unilateral disease:
• one lateral field or
• 2 oblique portals [superior and inferior]
• Bilateral disease:
• parallel opposed lateral fields
The anterior beam edge is placed at the bony canthus and the
beam is angled 1.5 degrees posteriorly if the contralateral eye
remains in place.

34. Dose
• Ideal: 40-45 Gy, 1.8-2 Gy per fraction, 5 days a week
• For large tumor /vitreous seeding: 48-50 Gy
• Palliative radiotherapy:
• Extra-ocular involvement: 20-25 Gy
• Metastatic disease: CNS, bones: 5 Gy/1#, 15 Gy/3#
• Unilateral : single lateral field
• With anterior extension: anterior field + lateral field tilted 5-15° posteriorly
• Bilateral disease: parallel opposed lateral fields

35. 3D conformal radiotherapy
technique
Based on 3D CT scan planning
In unilateral RB, 4 non-coplanar fields are used.
All fields are anterior oblique: superior, inferior, medial,
and lateral.
0.5-cm bolus can be used.
entire retina should be treated, including 5 to 8 mm of
the proximal optic nerve.
critical structures such as the opposite eye, optic
chiasm, pituitary gland, brainstem, posterior most
upper teeth, and upper cervical spine.
the tumor volume is treated to the 98% or 95%
line,with the aforementioned organs and tissues
receiving significantly less dose.

36. • bilateral disease, six noncoplanar fields
are used:
• two lateral opposing, and
• two anterior oblique fields to each eye
following the same criteria described
previously.
3D CT scan reconstruction image showing beam arrangement for unilateral RB : anterior medial and lateral fields (A), anterior superior and inferior
fields (B), sagittal view of composite isodose distribution (C), and axial transverse view of isodose distribution (D)

37. Side effects of RT
• Cataract formation: lens
• Lacrimal gland: decreased tear film production
• Vascular: retinal vasculitis → hemorrhage, and vitreous opacity
• Bone & soft tissue: temporal bone hypoplasia, molar tooth abnormalities
• Mid-facial hypoplasia: hypotelorism, enophthalmos, atrophy of temporalis muscle,
narrow and deep orbits, depressed nasion.
• Second malignancies: overall incidence: 3-5%
• Most common are osteosarcoma, fibrosarcoma, other spindle cell sarcomas

38. Primary Intraoccular Lymphoma
• Uncommon manifestation of NHL.
• Seen in fifth and sixth decade of life
• chronic, relapsing, and steroidresistant uveitis and vitritis.
• Radiation therapy has been used with durable control after 35 to 45
Gy given exclusively to both eyes.
• Methotrexate and cytosine arabinoside are most commonly used,
given their ability to cross the

39. Optic Pathway Glioma
• Contagiuos involment of hypothalamus.
• 90% of tumour presentation in first 2 decades
• Radiation therapy has resulted in 10-year survival rates ranging from
40% to 93%,
• Side effects includes severe long-term sequelae, including endocrine
problems, neurodevelopmental disorders, and second malignancy.
•

40. Optic Glioma contd
• Indication of radiation is progression of disease
• Doses is 45-60Gy in 1.8-2.0 Gy/fraction
• Hypothalamic deficiency seen in children less than 10 yrs
• Other Treatment options include Fractionated Stereotactic RT, IMRT
and proton therapy

41. Sebaceous Carcinoma Eyelid
• Occurs in periorbital region of eyelid.
• Aggressive disease, occurs in elderly persons
• Assoc with Muir Torre syndrome.
• Orbital exenteration folowed with adjuvant topical chemotherapy and
cryotherapy.
• RT upto dose of 60Gy when regional lymphnode are present or in
recurrence.

42. Orbital rhabdomyosarcoma
• Orbit 9%,
• Asymptomatic mass, proptosis, ophthalmoplegia.
• Favourable prognosis.
• Embryonal histology.
• Chemotherapy VAC , RT with dose of 45Gy used.

43. Benign Diseases-Pterygium
• Benign growth of fibrovascular tissue on the conjunctiva that can
cause irritation, erythema of the cornea, and obstructed vision in
advanced cases.
• Historically beta irradiation was used. Sr 90
• Severe complications
• Now surgery and conjuctival autografting used.

44. Choroidal Hemangioma
• benign vascular tumors of the choroid.
• Congenital, assoc with Struge Webber Synd.
• Most circumscribed choroidal hemangiomas are first noted when
they produce visual symptoms caused by accumulation of serous
subretinal fluid, degenerative changes in the macular retina, or both.
• Treatment alternatives include laser photocoagulation,
chermotherapy, photodynamic therapy, and radiotherapy.

45. Choroidal hemangioma contd.
• Low to moderate dose radiation using lens-sparing external beam
photon irradiation
• episcleral plaque therapy,
• proton beam therapy,
• stereotactic radiotherapy
• Total doses of 18 to 30 Gy delivered in 10 to 18 fractions of external
beam photon radiation therapy can result in partial flattening of the
hemangioma, resorption of subretinal fluid, and reattachment of the
retina within 6 to 12 months

46. Radiation Tolerance of Occular Structure
• Eyelid: 20Gy madarosis, xerophthalmia at 24-26Gy.
• Conjuctiva : >30Gy acute conjuctivitis and super added infection.
• Cornea: most acute corneal toxicity results from loss of the tear film
with secondary keratitis sicca. Punctate epithelial erosions are
common after conventionally fractionated RT doses of 30 to 50 Gy.
corneal edema (40–50 Gy) or perforation (60 Gy)

47. • Iris : acute iriditis is rare, iris is relatively radioresistant.
sysmptoms include pain, reddeness , blurred vision.
Usually seen in hypofraction regimen 30-40Gy and dose > 70Gy .
Neovascular glaucoma : late complication ,
Symptoms include headache, blurred vision, reddness , photo
phobia.
• Risk factors : higher radiation dose, diabetes, vitreous hemorrhage, and
retinal detachment.
•

48. Lens
• Age at time of treatment, total dose, and fractionation contribute to cataract
formation.
• Hall et al estimated an increased risk of approximately 50% for 1-Gy exposure to
the lens during childhood.
• In adults, higher doses are associated with cataract: after 2.5 to 6.5 Gy, the latent
period is 8 years with a 33% of progressive cataract,
• For 6.5 to 11.5 Gy, the latent period is 4 years, with a 66% risk.
• Cataract risk can be reduced by using customized lens shields and lens-sparing
techniques or by using fully fractionated RT schedules. IMRT may be used to
reduce cataract risk by reducing overall lens dose and relative fraction size.
• The definitive treatment for RT-induced cataract is surgery.

49. Retina
• Radiation retinopathy is a late effect seen 6 months to 3 years after treatment.
• Asymptomatic or may complain of floaters or reduced visual acuity,
• Clinical signs include microaneurysms, telangiectasia, hard exudates, cotton wool
spots, and neovascularization.
• The threshold dose for retinal damage is usually considered to be 30 to 35 Gy.
• The risk of retinopathy increases dramatically when doses exceed 50 Gy using
standard fractionation.
• Risk factors include coexistenting diabetic retinopathy, hypertension, collagen
vascular disease, simultaneous chemotherapy, and pregnancy.
• Photocoagulation may improve symptoms
• intravitreal bevacizumab.

50. Optic Nerve
• Radiation induced optic neuritis.
• Rare < 55Gy, the risk of RION increases from 3% to 7% at 55 to 60 Gy
and is substantial (>7% to 20%) at doses >60 Gy.
• Fraction size was of primary importance; in cases where >60 Gy was
received, fraction size was more important than total dose in
producing RION

51. • THANK YOU