R adiation retinopathy is a common and devastating visual side effect of radiation therapy for uveal melanoma and other ocular cancers. While the Collaborative Ocular Melanoma Study demonstrated that plaque brachytherapy is a great alternative for treatment of ocular cancers, many patients develop a visual acuity of 20/200, or worse, with rare improvement after observation of disease. This poor vision emerges from radiation scatter, which can cause damage to the retina and the optic nerve with

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... ymptoms similar to other retinal vascular diseases, such as diabetic retinopathy and neovascular age-related macular degeneration. Disease symptoms can develop between 6 months and 3 years post-treatment. Several treatment options have been explored to slow or stop the progression of this retinopathy, including laser, surgical, and pharmacological treatments. Nevertheless, despite the significant visual loss caused by radiation retinopathy, there are currently no US Food and Drug Administration-approved treatments for the disease. This article will review the history of radiation retinopathy treatment and discuss recent prospective studies in anti-vascular endothelial growth factor treatment. Radiation retinopathy is a common and slowly progressive visual side effect of radiation therapy, such as brachytherapy, external beam radiotherapy, proton beam radiation, helium ion radiotherapy, and gamma knife radiotherapy for uveal melanoma and other intraocular or orbital cancers. 1-6 Patients treated with radiation therapy for cancers of the head and neck can also develop radiation-related retinopathy. 7 Although the lens normally functions to prevent damaging wavelengths of light and radiation from reaching the retina, therapeutic doses with scatter to the retinal vasculature can cause radiation retinopathy with onset typically occurring between 6-months and 3-years post-radiation therapy, with devastating visual outcomes. 8 Following the Collaborative Ocular Melanoma Study (COMS), which reported similar mortality rates after radiotherapy and enucleation for choroidal melanoma, 9-11 radiotherapy became the primary treatment for ocular cancers. While radiotherapy offers an eye-sparing alternative for patients and allows them to maintain some level of visual acuity, COMS also reported that at 3 years post-treatment, nearly 50% of patients had a visual acuity of 20/200 or worse. 12 Improvement in visual acuity was rare after observation of poor vision. Radiation retinopathy is a broad term that can refer to both non-proliferative and proliferative radiation retinopathy as well as radiation maculopathy. It includes all retinal vascular changes caused by radiation therapy which can lead to variable clinical findings. In addition, while several treatment options have been explored with both retrospective studies and prospective trials, there is no widespread standard for the treatment of radiation retinopathy. Due to its similarities with other retinal vascular diseases, such as diabetic retinopathy and neovascular age-related macular degeneration, several recent prospective studies have utilized anti-vascular endothelial growth factor (VEGF) injections for radiation retinopathy treatment. However, the challenge for this group of patients is to establish the best practice patterns for the frequency and duration of injections needed in order to maintain visual acuity in the long term. This article comprises a review of the history of radiation retinopathy treatment and the current strategies being studied by investigators. Etiology and clinical features Radiation therapy, such as local plaque brachytherapy treats a variety of cancers by directly damaging the DNA of rapidly dividing tumor cells, and by the indirect creation of free radicals that cause extensive damage to cellular structures. However, this damage, both direct and indirect, affects not only tumor cells, but surrounding healthy tissue as well. In the case of ocular cancers, or those in nearby areas, radiation therapy can result in retinal vascular endothelial cell loss and inflammation. 13 This leads to a catastrophic domino effect on the retinal vasculature. 1,14 Over time, the damaged capillaries close, inducing retinal ischemia and neovascularization. Eventually, closure of large retinal vessels can also be seen on fluorescein angiography. 15,16