Current and Future Effects of Radiation Therapy on the Eyes

Abstract

Radiation therapy is a kind of therapy where high-energy particles are used to destroy or damage cancer cells. This type of therapy involves the use of x-rays, protons, electron beams, and gamma rays. Radiation therapy has different side effects that depend on various factors including the location of cancer, radiation dosage, and health of an individual receiving treatment. This assignment examined the various effects of radiation therapy, both current and future effects. Evidently, special attention is needed when applying radiation therapy on eyes, because effects always manifest even with very small doses. Some of the effects of radiation therapy include loss of eyelashes, glaucoma, dry eye syndrome, blocked nasal drainage, ulceration of the anterior epithelium of the cornea, edema, scleral thinning and perforation, disruption of membrane channel proteins, and retinal ischemia. Other effects include poor prosthetic fitting, telangiectasis, shortened fornices, as well as hemorrhage.

Introduction

Radiation therapy, also known as radiotherapy, irradiation, or x-ray therapy, is a kind of therapy that involves the use of high-energy waves or particles, including x-rays, electron beams, gamma rays, or protons, to destroy or damage cancer cells (American Cancer Society, n.d.). It remains one of the common methods that are used in the treatment of cancer. Radiation may be given alone or in a mixture of other treatments, such as chemotherapy or surgery. There are radio-sensitizers that can increase the sensitivity of cancer cells to radiation; therefore, enhancing the killing of cancer cells in the process of radiation (American Cancer Society, n.d.). Like other forms of treatment, radiation therapy also has side effects, which are often different for various categories of people, depending on a cancer’s type and its location, the dose of radiation therapy, as well as general health of a person receiving the therapy. This assignment discusses both the current and future effects of radiation therapy on the eyes.

Overview of Side Effects of Radiation Therapy

Side effects occur when radiation therapy damages healthy cells or tissues that are near the treatment area (Cancer.Net, 2016). However, there have been notable advancements in radiation technology that have made radiation therapy more precise, resulting in fewer adverse effects. For certain individuals, there may not be many side effects. Others individuals also have none at all, while some may go through severe effects. Reactions occur two or three weeks after the treatment process and may last for many weeks even after the final treatment (Cancer.Net, 2016). Even though there can be general side effects, there are also specific side effects depending on the type of radiation or location of radiation. Some of the locations might be head, neck, chest, stomach, abdomen, and pelvis.

Short-term and Long-term Effects of Radiation Therapy on the Eyes

Healthy eyes require special attention, because radiation effects on the lens of the eyes occur even with much lower doses. Acute effects of radiation in children may result in conjunctivitis, corneal ulceration, keratitis, as well as retinal edema. On the other hand, in the long-term, the effects could entail tissue necrosis and less production of tear. There can also be melting of sclera, cornea neovascularization, cases of cataracts or cancer, telangiectasia, and radiation retinopathy.

The Effects of Radiation Therapy

Loss of Eyelashes

The eyelashes are the end organs of touch; therefore, whenever they come into contact with tiny particles, the eyes blink for protection. Irritation causes epilation of the lash, which then abolishes protective reflexes. Radiation affects hair follicles; therefore, people are likely to lose their eyelashes if they are treated using proton beam radiation therapy. Radiation therapy doses of 28 Gy every fortnight with orthovoltage of about 100 kVp may cause permanent depilation. Loss of eyelashes or eyebrows is also known as madarosis. Toxic alopecia often occurs following the disruption of hair growth during the anagen phase. The lost eyelashes may grow after treatment, but that will depend on radiation dose that a patient receives. Hair loss becomes permanent when radiation dose is between 50 and 60 Gy. The eyelashes may take some time to grow, but there are also instances when hair loss can be permanent (Arepalli et al., 2014). The eyebrows can also be affected, particularly, when the orbit of the eye is under treatment. The eyelids allow rapid and effortless movement of the lids. Therefore, any inflammatory process decreases the flexibility of the lids. Inducing radiation changes to the eyelid causes skin erythema, telangiectasia, trichiasis, and eyelid closure punctae. Deformity to the margins of the eyelid can cause corneal irritation, which may result in severe damage over time. Changes that occur in the upper lid are often more serious due to the tarsus. Permanent alterations become rare when doses of less than 45 Gy are applied with conventional fractionation. Besides, both eyelashes and eyebrows have a cosmetic function, therefore, they contribute to an individual’s self-esteem. Just like hair in other parts of the body, an epilated lash can regrow with a different color, and the newly grown hair may be short and sparse.

Glaucoma

Radiation therapy can also cause pressure in the eyes. Usually, two types of glaucoma occur, namely open-angle glaucoma and closed angle glaucoma. Closed-angle glaucoma often occurs quickly. Glaucoma occurs when there is damage to the optic nerve due to increased pressure in the eye. There is always a special fluid, which surrounds the eyes and makes them stay healthy and remain in shape. The fluid found in the aqueous humor flows to eyes chambers before draining out. However, the fluid may build up in case of a problem with the drainage system of the eyes. The problem may occur suddenly, and if not treated properly, the pressure created on the optic nerve can lead to irreversible blindness.

Lacrimal Apparatus

Tears are made up of secretions derived from glands such as the major lachrymal gland, accessory lachrymal glands, superior conjunctival fornices, and Sebaceous glands found on both eyelids. The tear film is made up of the superficial lipid, the middle aqueous, and the major and deep mucinous layers. Therefore, the absence of any of the three layers causes the tear film to become unstable and lead to the dry eye disease. Those who suffer from the disease do possess red eyes with the characteristics of sensation from foreign bodies as well as photophobia. Most of the patients, who develop dry eye, become symptomatic within a period of one month, following their completion of radiation therapy (Arepalli et al., 2014). However, neovascularization as well as opacification occurs after nine or ten months of therapy. Severe dry eye causes rapid deterioration of vision, and the whole eye becomes more predisposed to infections by bacteria. Fractionated dose of between 32-45 Gy that is directed to the lachrymal glands may cause slow changes with patients eventually losing their eyes.

Blocking of the Nasolacrimal Drainage

Applying radiation doses of more than 50 Gy to the nasal segment of the eyelids causes blockage of the nasolacrimal drainage system due to epiphora. The blockage is usually due to desquamation of the ducts that are within epithelium, with resulting inflammation that may cause stenosis or fibrosis. The blockage can manifest faster in patients that had prior surgery, which may have changed the strength of their nasolacrimal drainage system.

Cornea

The cornea is usually the refractive component of the eye; therefore, whenever there is a decrease in the clarity of the cornea, vision diminishes. Changes induced by radiation are not dependent on vascular damage; instead, they are associated with alteration of mitotic activity that occurs in connective tissues and epithelium. The five layers in the epithelium include the epithelium, corneal storm, Bowman’s membrane, endothelium, and Descemet’s membrane. Usually, the anterior epithelium gets thin when exposed to radiation therapy and may become ulcerated with doses of between 30 and 50 Gy. For instance, keratitis may occur by the time that radiation therapy is coming to an end, or immediately after and may last for between four and six weeks. Besides, patients may develop increased blinking, photophobia, as well as lacrimation. However, appropriate ophthalmologic care prevents tiny ulcers from coalescing, but it can still occur when corneal ulcer is developing. Patients become more predisposed to corneal ulceration when radiation doses increase from 60 Gy. Besides, corneal edema may occur in the corneal stroma when radiation doses of between 30 and 50 Gy are applied, but this is often transient and diminishes within a period of one month. However, edema may become more permanent when high doses of about 80 Gy are applied.

Uvea and Sclera

The sclera is fairly radioresistant. Therefore, the major effects of x-ray therapy can be explained by episcleral plaques that are used in treating choroidal melanoma (Arepalli et al., 2014). X-ray therapy causes scleral thinning, scleral perforation, and loss of episcleral vessels. Scleral thinning is treated to help restore and preserve the function of globe. On the other hand, irradiation of uveal structures with cancerous doses can cause vascular changes including rubeosis iridis, neovascularization, as well as iridociclitis, which may cause an imbalance in the production and absorption of aqueous with the end result being glaucoma. Patients with neovascular glaucoma may suffer rapid vision loss, headache, and severe pain. It is also possible for the condition to advance to blindness.

Lens

The lens is a refractive structure that is located behind the pupil. The germinal epithelium found at the equator is a part that is always most sensitive to radiation, due to the lens epithelial cells that actively proliferates. Consequently, damages caused to the germinative zone of the lens epithelial by radiation therapy can lead to post-treatment cataracts. In addition, DNA damage due to radiation therapy can cause serious cytoplasmic effects such as abnormalities in ion pump as well as disruption of membrane channel proteins. The abnormalities are responsible for the progression of post-radiation cataract. In older patients, cataracts may develop sooner due to pre-existing damages that had occurred in DNA. Moreover, patients treated with helium that covers less than 25% of the lens field may suffer from cataract. In children, cataracts may cause amblyopia before surgery is performed. In addition, cataracts can occur when radiation therapy causes secondary metabolic damage to the anterior epithelium where lens nutrients often pass.

Retina

The neurosensorial retina comprises an extensive network of vascular and neural glial elements. Retinopathy induced by radiation is as a result of retinal injury following high doses of radiation. Notably, certain people with radiation retinopathy have had the inner parts of their iris being vasoproliferative. It is hypoxia and the retinal ischemia that triggers the development of diffusible vasoproliferative factor. The factor, in turn, triggers neovascularization of both optic and retinal nerves. The development of the factor causes retinal ischemia, capillary dilatation, microaneurysm, telangiectasia, and hemorrhage.

Optic Nerve

A frequent cause of vision loss, optic neuropathy, due to radiation is a result of vascular ischemic activity that is caused by the occlusive disease. Besides, patients that have pre-existing vessel disease are at high risk for complication. The neuropathy occurs as a painless loss of vision, which happens suddenly, even though transient incidences of blurring may be witnessed. It is always important to determine the dose per fraction when evaluating optic neuropathy (Arepalli et al., 2014). The optic nerve tolerates neuropathy less compared with other cranial nerves. For instance, a single radiation of 7 Gy can cause blindness. However, radiation dose that the optic nerve tolerates is 8 Gy. In fractionated radiotherapy, optic neurotherapies have been recorded in radiation therapy doses of 50 Gy only in patients with pituitary tumors.

Orbit

The bony cavity that is located in the skull and contains the globe, intraorbital portion, extraocular muscles, as well as the orbital fat is known as the orbit (Chundury, Weber, & Perry, 2016). Side effects occur in the orbit when radiation therapy, particularly x-ray beam is applied to the growing facial bones of children, for instance, when treating rhabdomyosarcoma or retinoblastoma. Usually, radiation therapy arrests the growing bones in the orbit causing hypoplasia or changes in the atrophic soft tissues (Chundury et al., 2016). The level of hypoplasia has an inverse proportion to a patient’s age, when radiation therapy was being applied. Whenever the orbit becomes hypoplastic, there is constantly decreased orbital diameter (Dolman & Rath, 2012). Furthermore, radiation therapy results in flattened nasal bridge that increases the nasal angle. Besides, the frontal bone becomes unreasonably prominent. Midfacial hypoplasia can be less common when megavoltage irradiation is applied than when orthovoltage irradiation is applied (Dolman & Rath, 2012). Furthermore, fat atrophy or fibrosis can cause enophthalmos. Usually, contraction of mucous membrane due to irradiation may result in forth-shortening of symblepharon and fornices. Besides, when enucleation occurs followed by radiation therapy, the an ophthalmic socket may become exacerbated. Atrophy induced by X-ray therapy as well as contraction of soft tissues in the socket can cause poor prosthetic fitting or total destruction of the fornices (Dolman & Rath, 2012).

Radiation Therapy and Conjunctivitis

The conjunctiva is a mucous membrane that contains the lacrimal glands. It also contains a stratified non-keratinized epithelium, which overlies the substantia propia. The conjunctiva is a physical barrier, and it also hosts immune cells and colonizing bacteria. On the other hand, conjunctival inflammation, also known as conjunctivitis exhibits, has a vascular injection that is characterized by mucoid or clear discharge that occurs one to three weeks after the inception of radiation therapy (Stannard, Sauerwein, Maree, & Lecuona, 2013). Chemosis, also known as edema of conjunctiva, may occur immediately and last for a few days. Usually, the affected may have ulcerations, which increase the possibility of infection with the duration of symptoms likely to prolong where radiation therapy doses are over 30 Gy (Arepalli et al., 2014). Some of the late effects of radiation therapy to the conjunctiva include telangiectasis, prolonged injection, symblepharon, shortened fornices, subconjunctival hemorrhage, necrosis, keratinization as well as loss of goblet cells. Whenever people are exposed to radiation, therapy of between 30 and 50 Gy can cause prolonged conjunctival injection that can develop after one or two years, then followed by telangiectatic vessels that occur three or more years afterward (Arepalli et al., 2014). The fragile vessels often rupture accompanied by minor trauma, which results in subconjunctival hemorrhage.

Similarly, chronic ulceration of the conjunctiva may occur whenever there is a radiation therapy of 60 Gy. This kind of radiation can lead to the symblepharon, which can cause shortening of fornices, eyelid malpositioning, and trichiasis. Goblet cells can be lost at radiation doses that are relatively low of 50 Gy (Arepalli et al., 2014). The loss of goblet cell can cause tear films to become unstable and symptoms of dry eye to manifest. At doses of more than 50 Gy, keratinization of the conjunctiva may occur (Stannard et al., 2013). The keratin plaques formed continually cause irritation of adjacent cornea, resulting in scarring or visual loss. In fact, necrosis may occur for retinoblastoma patients receiving radioactive plaque therapy where doses are between 90 and 300 Gy (Arepalli et al., 2014).

Conclusion

As much as radiation therapy affects patients, not all are affected. Notably, the effects of radiation will be dependent on how big or small the area that is being treated is, the total dose applied, the specific area that is being treated, the treatment schedule, as well as the type of radiation therapy that a patient is receiving. Radiation therapy often destroys cancer cells; however, healthy cells may be destroyed as well. The current side effects occur immediately or a few days after therapy, but most of the effects will subside when the treatment ends. On the other hand, future side effects occur many months or years after treatment. Importantly, the effects may be permanent or temporary. Among the effects of radiation therapy, one can name cataracts, retinopathy, conjunctivitis, loss of eyelashes and eyelids, dry eyes, corneal injury, damage of optic nerve, and glaucoma.