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Late Effects



Radiation Therapy (RT) related Orbital injury

For general discussion see overview


Tolerance of Orbital structures:

Current COG rhabdomyosarcoma studies have dose recommendations which are aimed to reduce the risk of damage to critical orbital structures. 

Different orbital tissues have different “tolerances” or amounts of RT they can tolerate before there is a significant risk of RT induced toxicity:

This table specifies the maximum dose that these organs should receive when a child is receiving high dose RT for a head and neck rhabdomyosarcoma:


Volume (Maximum % of organ recommended to be in RT field)

Maximum Dose in Gy

Optic nerve







Lachrymal gland



Optic chiasm





RT related skin changes around eye:

  • Scarring and fibrosis of the eyelid occurs with RT (eyelid skin is very thin)38
  • Acute erythema (typically 2-4 weeks after starting treatment)7
  • Dry and moist desquamation (more likely to occur after doses of 50 - 60 Gy over 5-6 weeks)7
  • Cicatricial scarring can result in entropion or ectropion of eyelids7
  • Slow progressive skin changes such as thinning of skin, depigmentation and telangiectasia9
  • Eyelash loss may be complete (dose of 30 Gy) or incomplete (dose of 10 Gy) depending on dose and dose rate7
  • Greater than 50 Gy can cause permanent alopecia with trichiasis and secondary corneal disease9



  • RT induced  damage to the lachrymal gland can produce irreversible corneal changes7
  • Degeneration and necrosis of acinar cells of the major and accessory lacrimal glands occurs which eventually progresses to a loss of Meibomian glands and ducts38
  • Childhood Cancer Survivor Study found that eye RT doses of greater than 500 cGy were associated with statistically significant increased risk of dry eyes compared to those with no eye radiation1
  • Previous research showed that doses in the range of 30-40 Gy could be delivered to the entire orbit without long term keratitis sicca7
  • Factors that affect the incidence of RT related dry eye10:
    • Volume/number of lacrimal glands within the targeted RT volume
    • RT total dose
    • RT dose rate
    • Tear function prior to RT
    • Progressive age related loss of tear production



  • Late effects of RT to the conjunctiva include:
    • Prolonged Injection (redness)
    • Telangiectasia
    • Symblepharon (adhesions between the bulbar and the palpebral conjunctiva)
    • Subconjunctival hemorrhage
    • Shortening of the fornices
    • Keratinization
    • Ulcer
  • Exposure to 30 - 50 Gy leads to prolonged conjunctival injection (after 1 - 2 years), followed by telangiectasia (after 3 - 6 years)
  • The fragile telangiectatic vessels rupture easily causing subconjunctival hemorrhage
  • Chronic ulceration may occur after 60 Gy



RT damage to the cornea:

  • Damage from delayed neovascularization of the limbus38
  • Direct corneal injury, such as cornea erosion and ulcerations, can result from fractionated high dose RT above 40 Gy39
  • Most acute corneal toxicity results from a loss of the tear film with secondary keratitis sicca11

Dry Eye Syndrome



  • The lens is the most sensitive structure in the eye, generally total fractionated doses under 500 cGy have not produced significant lens opacities39
  • Cataracts are common in patients who have RT to the orbit or adjacent structures (such as the brain)
  • Radiation cataracts seem to occur from DNA mediated damaged to the germinal cells of the lens epithelium as well as cytoplasmic effects that cause the disruption of membrane channels38
  • Posterior migration of epithelial cells may possibly cause the initial opacity of the lens38
  • Pediatric retinoblastoma patients are particularly at risk due to the direct radiation exposure to the eye and are almost certain to develop cataracts12
  • Cataracts are treated easily by very straightforward surgery    
Clinical Tip: Assessment of the red reflex with a direct ophthalmoscope is the most sensitive way of appreciating a cataract. Steroid induced cataracts are often located posteriorly in the lens (so called posterior subcapsular) and can be seen a central irregularity in the red reflex.



  • Iritis has been reported with a single dose of 10-20 Gy
  • Severe anterior uveitis has been observed with doses of 30 - 40 Gy (in 10 Gy fractions) and after 70 – 80 Gy (over 6-8 weeks)9
  • RT can cause:
    • Iris neovascularization
      • Rubeosis iritis
      • Abnormal vessels grow into the trabecular meshwork and cause acute angle glaucoma15
      • Result is a painful, red blind eye that cannot be saved and requires enucleation
    • Posterior synechiae (adhesions between the iris and the lens)
    • Iris atrophy



  • The sclera is particularly radiation resistant13 and no scleral RT damage has been reported after external beam radiation doses of 60 Gy9
  • Radiation tolerance of the sclera may be be as high as 150 Gy39
  • Scleral thinning and necrosis if it does occur, results from very high dose radiation exposure as this area is largely avascular38
  • Beta emitting strontium 90 and ruthenium 106 episcleral applicators are more likely to deliver greater sclera-thinning doses as compared with low energy iodine-125 or palladium-103 during plaque radiation therapy of intraocular tumors14



  • Retinal rods seem to be damaged first as they are the most sensitive to radiation38
  • Retinal vascular changes, thickening of the arteriole walls and hemorrhage of the vitreous area can occur38
  • Optic nerve damage seems to occur secondary to ischemia causing both demyelination and loss of nerve fibers38
  • RT-related choroid and retinal vascular changes have previously been associated with RT doses in the range of 45 – 60 Gy7
  • RT doses as low as 18 Gy can induce radiation retinopathy in patients with compromised chorioretinal circulation (i.e. diabetes) and those treated with chemotherapy16
  • 50 Gy is generally regarded as the threshold dose of RT required to induce retinopathy in patients without pre-existing health conditions.
  • Total dose and dose rate play a key role in the risk for RT retinopathy17
  • Radiation retinopathy looks very much like diabetic retinopathy and is characterized on examination by:
    • Micro-aneurysms
    • Hard exudates
    • Microinfarctions of the retina (cotton wool spots)
    • Optic disc swelling
    • Vascular occlusion
    • Intra-retinal hemorrhages
    • Neovascularization9
  • Radiation retinopathy in macula places patients at an increased risk for vision loss and blindness7
  • Radiation retinopathy can also cause closure of blood vessels within optic nerve itself18


ORBITAL BONE and soft tissues

Bone development is likely to be affected after in orbital RT in irradiation children.  This leads to hypoplasia and orbital asymmetry9

The younger the child is then the more severe this effect is likely to be.

Any child who has received radiation therapy is at risk in the long term for the development of a radiation induced second neoplasm. For most patients this risk is small, but children who receive orbital radiotherapy for bilateral retinoblastoma have a very high risk of developing a radiation induced sarcoma within the previous treatment field.


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