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March 2011

 
Clinical Update: Retina
Collateral Retinopathy From Treatment With Radiation, Part One
By Barbara Boughton, Contributing Writer
Interviewing James J. Augsburger, MD, Paul T. Finger, MD, and Tara Mccannel, MD, PHD
 
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The tremendous benefits, and dangers, of radiation therapy have been known since at least the 1930s, when radiation became a cornerstone of cancer treatment. Marie Curie, in fact, the revered physicist who conducted the world’s first studies of radioactive isotopes to treat cancer, died in 1934 of aplastic anemia, her demise widely attributed to unshielded work with radiation. Henry Stallard, who pioneered cobalt plaque therapy for pediatric ocular tumors, died of cancer as well.

For ocular cancer patients, the effects of radiation secondary to the desired therapeutic ones include cataract, glaucoma and vitreous hemorrhage, as well as radiation retinopathy and maculopathy. The last two are the most common causes of irreversible radiation-related vision loss.1

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Wonderful Benefits vs. Terrible Costs

The use of radiation to treat ocular cancers has brought welcome benefits, often increasing survival while avoiding enucleation. It is also useful for managing other ophthalmic conditions, such as Graves ophthalmopathy. But radiation-induced retinopathy is an alarming hazard; by some estimates, 50 percent of patients treated with radiation for choroidal melanoma are left with less than 20/200 vision after five years.1

Iatrogenic retinopathy is seen most commonly after treatment for choroidal or uveal melanoma, although it has also been reported in cases where radiation was used for metastatic disease. “Because we’re concerned about the side effects of radiation in metastatic cancer that has spread to the eye, often the treatment of these cases uses lower radiation dosages than for primary choroidal melanoma, and retinopathy is less likely to occur,” said Tara McCannel, MD, PhD, assistant professor of ophthalmology and director of ophthalmic oncology at the University of California, Los Angeles.

Saving a life takes priority. When treating patients with choroidal melanoma, the first priority is to battle the cancer, Dr. McCannel said. Yet loss of vision from radiation retinopathy can be devastating. Most of the ocular damage from radiation is delayed—becoming evident from six months to five or more years after treatment, she said. Symptoms generally start with changes in central vision and progress to significantly decreased visual acuity.

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Poorly Defined and Classified

The challenge for physicians confronted with radiation retinopathy has been the incomplete agreement on a staging system or consensus definition for the presenting complication, said James J. Augsburger, MD, professor and chairman of ophthalmology at the University of Cincinnati.

Building a definition. Dr. Augsburger said that radiation retinopathy was originally understood to be a problem of retinal circulation related to inadvertent inclusion of the eye in the radiation field. And that really should remain the basis for a definition, he said.

Any damage outside the intended treated area of the tumor plus 1.5 to 2 mm on each margin should be considered radiation retinopathy. “For those areas of the eye that get the full intended therapeutic dose of radiation, we would expect to see profound progressive blockage of the vascular system. The vessels are obliterated; they are not just leaky,” he said.

One ocular oncologist who stepped up to the challenge of classifying radiation-induced pathologies is Paul T. Finger, MD, clinical professor of ophthalmology at New York University and director of the ocular tumor service at The New York Eye and Ear Infirmary. Dr. Finger proposed a classification in 2005 that was published in the British Journal of Ophthalmology.1

But over the years, the definition of radiation retinopathy expanded to include any vascular damage to the retina and optic nerve after radiation treatment to the eye, Dr. Augsburger said, even though the damage can vary widely—depending on:

  • the quality of vision before treatment of the tumor,
     
  • whether a tumor originated in the eye or metastasized from another site,
     
  • the location and size of the tumor,
     
  • the dosage of radiation used and volume of tissue treated,
     
  • how the type of radiation used—plaque vs. proton beam, for instance—affects surrounding tissue.

“It’s difficult to consider all the factors that affect radiation retinopathy in a single unified way,” Dr. Augsburger said, because any classification system must take into account the intended obliterative effect of radiation as well as unintended damage. If a tumor is far away from the optic disc and macula, for example, and these areas received low doses of radiation, the damage will largely consist of retinal thickening and leakage of some of the components of serum from blood vessels. “Any worthwhile classification system for radiation fundopathy should account for all of the potentially confounding, competing and correlated clinical features,” Dr. Augsburger said. (See “Fundopathy: A Better Descriptor?”)
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1 Finger, P. T. and M. Kurli. Br J Ophthalmol 2005;89:730–738.
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NEXT MONTH: Treatments for radiation collateral retinopathy will be explored.

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FUNDOPATHY: A Better Descriptor?

Dr. Augsburger now considers radiation retinopathy to be just one manifestation of what he calls “radiation fundopathy.” This umbrella term, he said, reflects the fact that ionizing radiation can induce four subsets of ocular injury. Following, in Dr. Augsburger’s words, are elaborations of these:

“Radiation retinopathy is characterized by features that are often considered ‘background radiation retinopathy’—retinal cotton-wool spots, linear and dot-blot intraretinal hemorrhages, retinal capillary dropout, intraretinal edema and exudates, accumulation of exudative subretinal fluid and retinal arteriolar and venular occlusions— as well as those features comprising ‘proliferative radiation retinopathy’— intraretinal and preretinal neovascularization and vitreous hemorrhages.

“Radiation optic neuropathy is further broken down by anatomical geography. If the effects become evident at the optic disc, we refer to this as radiation optic papillopathy. If the effects are only retrobulbar, we refer to this, logically, as retrobulbar optic neuropathy. Radiation optic papillopathy in its acute phase is characterized by ischemic whitening of the retinal nerve fibers entering the optic disc, edematous optic disc swelling, circumpapillary exudative subretinal fluid and retinal edema, and linear hemorrhages on and around the optic disc. Visual acuity tends to dim abruptly in the eye. In most cases, the acute effects subside after a few weeks or months and are replaced by variable degrees of optic disc pallor associated with persistent visual loss (radiation-induced optic atrophy).

“Radiation choroidopathy is characterized by depigmentation of the RPE, obliteration of the choriocapillaris, accumulation of exudative subretinal fluid related to breakdown of the outer blood-retina barrier at the RPE level and sometimes obliteration of some medium-size choroidal arteries and veins. Because radiation retinopathy is frequently superimposed on radiation choroidopathy, the extent of the choroidal abnormalities is not always appreciated. The choroidal vascular features of this disorder are demonstrated best by indocyanine green angiography.

“Radiation intraocular tumor vasculopathy is the profound effect of ionizing radiation on an intraocular tumor following some method of irradiation intended to be focally obliterative. It is characterized in its acute phase by necrotizing cells of the tumor and its blood vessels, intravitreal or subretinal bleeding from the surface and margins of the tumor, and accumulation of intraretinal and subretinal exudates, blood and exudative subretinal fluid over and/or around the tumor. The principal obliterative-necrotizing effects of the intense focal radiation to the tumor (such as that delivered by episcleral plaque brachytherapy, proton beam irradiation or gamma knife-stereotactic radiation therapy) are confined to the target area of treatment, which includes the tumor and, typically, 1.5 to 2 mm or more around the margins of the clinically evident tumor. During the acute phase, an exudative retinal detachment can become subtotal or total in extent and bullous in height (sometimes displacing the retina anteriorly up to the back surface of the crystalline lens). This phase is usually accompanied by concurrent radiation retinopathy and choroidopathy around the treated tumor and is frequently accompanied by radiation optic papillopathy (if the tumor was located relatively close to the optic disc). As time passes, the exudative-hemorrhagic features of the obliterative-necrotizing ionizing radiation frequently subside, but when they do they leave behind organized subretinal blood and exudates and extensive disruption and clumping of the retinal pigment epithelium throughout the fundus. This phase is frequently associated with radiation-induced optic disc atrophy and proliferative radiation retinopathy. Radiation intraocular tumor vasculopathy is most commonly associated with larger choroidal and ciliochoroidal melanomas treated by focal obliterative radiation. It is infrequently associated with other types of tumors, such as retinoblastoma or nonophthalmic primary carcinoma metastatic to the choroid because these tumors are much more radioresponsive than choroidal melanomas and therefore require substantially lower radiation doses.”

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