Brachytherapy has long been used to treat benign and, malignant ocular tumors as well as neovascular and fibrovascular, growths.1-24 Widespread acceptance of eye- and, vision-sparing plaque brachytherapy started with lowdose, rate (LDR) cobalt-60 eye plaques.1 Later, LDR, iodine-125 (125I) and then LDR palladium-103 (103Pd), seeds were affixed within high-Z gold, shielded plaque, seed carriers, and thus blocked the radiation posterior, and to the sides of the plaque (Table 21-1).25-28 Iodine-125, and 103Pd plaque brachytherapy diminished radiation, exposure to clinicians, improved the intraocular radiation, distribution, and allowed for outpatient, continuous,, multiday treatments (Mind Map 21-1).24, LDR ruthenium-106/rhodium-106 (106Ru/106Rh) and, high-dose rate (HDR) strontium-90/yttrium-90, (90Sr/90Y) beta-emitting radiation devices were commercialized, in England, Germany, and Russia.21,29-35 Of, these, Amersham’s legacy SIAQ 7321 (Amersham Corporation,, Amersham, UK) and Resutech (Moscow, Russia), HDR 90Sr/90Y sources are most like the currently available, LV Y-90 Disc (Liberty Vision Corp., Portsmouth,, NH, USA). However, unlike those prior 90Sr/90Y applicators, (which contain 2 radionuclides), the LV Y-90 Disc, is a single-source, disc-shaped device capable of being, assembled into clinical applicators (Fig. 21-1).36, For the purposes of this chapter, we will examine the, ocular use of beta-radiation-based brachytherapy for, ocular tumors and benign growths (Table 21-1). Beta-radiation, has been used to treat cancers such as choroidal, melanoma, RB, choroidal metastasis, conjunctival melanoma,, and conjunctival SCC.1,3,4,6,9,13,15,16,18,20-22,24,29,31,33-36, Beta-radiation has also been used to treat benign growths, such as uveal and retinal hemangioma (e.g., circumscribed, choroidal and retinal capillary angiomas) as, well as neovascular macular degeneration, eccentric, disciform degeneration, polypoidal choroidal vasculopathy,, pterygium, and as adjuvant for trabeculectomy, surgery.2,7,8,11,12,14,17-19,37-44, These reports include both LDR and HDR treatments., Of these, the most popularly known HDR 90Sr/90Y treatments, have been performed to prevent the recurrence, of pterygium.2,43,44 However, there also exists statistically, significant medical evidence that 90Sr/90Y has been used, as a tool to treat and prevent both the neovascularization, and fibrovascularization associated with failure of filtering, glaucoma surgery (e.g., trabeculectomy) in high-risk, patients compared to the antifibrotic drug 5-FU.8,13,14,42, Clearly, the literature shows that beta-radiation has been, effective for the treatment of both malignant ocular tumors, and benign growths., This chapter includes Liberty Vision’s experience creating, a new HDR 90Y beta-radiation brachytherapy system., It has been implemented by medical physics, radiation, oncology, and ophthalmology for the treatment of ocular, cancers.36 It is important to note that the 90Y radionuclide, has been previously used for the treatment of cancer in, the form of 90Y-laden glass or plastic microspheres arterially, perfused for radioembolization. Such 90Y treatments, have been directed toward hepatocellular carcinomas,, colon metastases, cholangiocarcinoma, and metastatic, choroidal melanoma. Such HDR 90Y brachytherapy offers, medical evidence of 90Y anticancer efficacy.45-50, Prior to bringing a new beta-radiation source to patient, care, Liberty Vision conducted preclinical studies examining, the dose distribution attributes of a variety of beta, sources. After choosing 90Y, Liberty Vision developed,, produced, and then obtained US Food and Drug Administration, (FDA) clearance for discrete 90Y disc sources to, be used in ophthalmic applicators.51 The clinical practice, parameters were then developed to implement this, new brachytherapy system. These included source calibration,, radiobiological dose derivation, sterilization,, assembly, radiation safety, and surgical techniques.36
Chapter Keyword: plaque
Scleral Toxicity and Repair
The sclera is the outermost coat of the eyeball and pro¬vides structural support and protection for intraocular structures. In contrast to the other coats, the sclera is hypovascular, hypocellular, and composed of dense con-nective tissue. Histologically, it consists of interwoven collagen fibrils and a dense extracellular matrix. Scleral rigidity is imparted by glycation-induced cross-linking of collagen fibrils.1 Despite a low metabolic activity, the sclera undergoes remodeling throughout life. For exam¬ple, fibroblastic activity and increased scleral thickness have been reported in response to thermal stimuli.2 Scle¬ral metabolism plays an integral role in emmetropization by precisely regulating the growth of the extracellu¬lar matrix, suggesting that the sclera is metabolically active.3 Although sparsely populated, scleral fibroblasts can be activated to proliferate after injury, pathology, or infection.4
Treatment of benign and malignant intraocular (e.g., uveal, retinal, neural) tumors as well as extraocular (e.g., ocular surface and orbital) often require episcle¬ral or trans-scleral modalities. Therefore, scleral toxicity can be an adverse effect, manifesting as scleral thinning or scleral melt. In addition, these tumors can directly invade and thus weaken the sclera in select cases. Result¬ant scleral thinning can lead to perforation and expulsion of intraocular contents. Early diagnosis and appropriate management can prevent the consequences of scleral toxicity.
This chapter discusses the various mechanisms of scleral toxicity, scleral complications of cancer therapy, indica¬tions, and techniques of scleral repair.
Overview of Ophthalmic Radiation Therapy
Radiation therapy is widely used for the treatment of intraocular and orbital tumors as well as inflammatory ocular diseases.1-3 Both implant brachytherapy and EBRT techniques are widely employed. For example, linear accelerator (LINAC)-based EBRT is widely used to treat metastatic uveal, orbital, and sinus tumors as it involves directing an external radiation beam source to the eye, eyelids, sinuses, and orbit. Should one or both eyes need be irradiated, LINAC-based EBRT can be delivered using an anterior unilateral approach as seen in Figure 1, or as 2 apposing, bilateral confrontational fields.4 In con¬trast, most patients with uveal melanoma are commonly treated with ophthalmic plaque brachytherapy. Here, disc-shaped radioactive devices are affixed to the sclera beneath the tumor volume within the eye (Fig. 17-2).
Orbital disease is most commonly treated with LIN¬AC-derived EBRT, and less frequently with proton beam, stereotactic radiosurgery (SRS) and Gamma Knife®, and intensity-modulated radiation therapy (IMRT).2 Radiation can be used alone, after surgery, and with chemother¬apy. In contrast, orbital brachytherapy involves surgical placement of radiation sources next to a tumor or within a targeted orbital volume. Typically considered the most conformal form of radiotherapy, brachytherapy relatively increases the radiation dose within the targeted volume while decreasing exposure to most normal tissues.
At The New York Eye Cancer Center, orbital high-dose rate brachytherapy is used to treat the resected tumor bed followed by an overlay of lower-dose EBRT to the entire orbit (Fig. 17-3).5-7 Called “brachy-boost”, this technique increases the dose to a targeted portion of the orbit.
This chapter explores the unique challenges associated with irradiation of the eye, lids, and orbit. It includes basic radiobiology, doses, indications, and results of treatment. We discuss the tolerances of normal ocular and orbital tissues. Herein, we review the literature to offer a unique perspective of the world’s experience with ocular and orbital radiation therapy.
Ocular and orbital anatomy, as well as tissue radiosen¬sitivity, provide unique challenges for radiation-based patient care. By definition, the eye globe is bounded by the sclera and cornea, within which there exist tissues that contain melanocytes, retinal, and epithelial cells, amongst others. Each gives rise to unique tumors with different radiosensitivities. Most orbital tumors occur between the eyeball and bony orbital walls, within which there exist even more varieties of progenitor cells and their related tumors. Orbital tumors may also extend either into or from the eye, orbit orbital bone, brain, and sinuses. As a result, radiation delivery systems (teletherapy or brachytherapy)—each with unique char¬acteristics—are carefully selected to deliver tailored dose distributions within the eye and orbit. To better under¬stand the differences between these radiation modalities, this chapter reviews their inherent differences and why each is typically selected.
While any radiation modality can sterilize a cancer, the location and intensity of side effects or normal tis¬sue tolerances typically govern the physician’s choice of method. However, individual tissue tolerances and
thus the incidence of radiation side effects are variable. For example, the sclera, cornea, bones, ocular muscles, optic nerve, and orbital fat can tolerate relatively high doses, whereas the lens, eyelashes, retina, and lacrimal system are more radiosensitive.2 Therefore, side effects of ocular and orbital irradiation commonly include dry eye, eyelash loss, cataracts, neovascular glaucoma, radia¬tion retinopathy (see Chapter 22), and optic neuropathy as opposed to osteonecrosis, strabismus, or enophthal¬mos.1,2 Depending on the tissue and its function, each ophthalmic side effect results in either cosmetic or func¬tional morbidities. In practice, modality selection and treatment plans are typically created to avoid the retina, lacrimal system, and natural lens.2,8-10 In addition, there exists an oncogenic risk associated with ionizing radia¬tion as most commonly seen in children.11-16
It is important to note that the incidence of side effects is proportional to the volume of irradiated tissue. There¬fore, any technique that reduces the irradiated volume, conforms to the tumor, and reduces organ dose will be beneficial. Despite the risks of side effects, radiation therapy has become an essential tool used by eye cancer specialists to provide local control of benign and malig¬nant ocular and orbital diseases. The clinical benefits of improving survival and preserving vision have clearly outweighed the radiation risks. Herein, we review how radiotherapy has played an integral role in the treatment of benign and malignant ocular tumors.
Finger’s Methods for Ophthalmic Plaque Surgery
Plaque surgical techniques are rarely described in the literature. 1-6 When available, they are typically found in the methods sections of papers describing a new radiation source or plaque position verification technique.3,7-14 This understates their importance in that our surgical methods affect the incidence of secondary radiation complications, local control, and thus metastasis.1,15-17 Plaque modality, construction, and medical physics calculations are critical foundational elements of treatment success.4,18-20 Significant research indicates that failure of local control is associated with a 6.3x hazard for metastatic disease.15,21 My techniques have been refined over the last 35 years, leading to a current local control rate greater than 99% as measured by doctor-reported outcomes.22,23 Herein, I offer my thoughts, methods, and experience with surgical ophthalmic plaque radiation therapy. The lack of consensus guidance is related to the complexity of plaque therapy. For example, there exist a variety of radiation plaque modalities: palladium-103 (103Pd), iodine-125 (125I), ruthenium-106 (106Ru), strontium-90 (90Sr), and most recently yttrium-90 (90Y).24-28 In addition, ophthalmic plaques come in different shapes and sizes.18,20 Although the American Brachytherapy Society (ABS) together with the American Association of Physicists in Medicine (AAPM) have published guidelines for ophthalmic plaque brachytherapy for choroidal melanoma and RB, there exist nuances that were beyond the scope of that multicenter, international effort.18,29 Intraocular tumors also occur at different intraocular locations.30 Clearly, epicorneal plaque positioning differs from that on the posterior pole, particularly due to optic nerve sheath obstruction.6,17,31,32 However, there are commonalities and differences that need be described to improve ophthalmic plaque surgery.
A Review of Ophthalmic Plaque Brachytherapy Consensus Guidelines
Brachytherapy involves the application of a radioactive, source inside or close to a tumor or benign growth.1 During, application, this radiation is delivered continuously, but over a fixed amount of time. Therefore, in radiation, oncology there exist short-term (temporary) implants, and long-term (even permanent) implants. Temporary, brachytherapy implants can be either low-dose rate, (LDR) or high-dose rate (HDR), requiring days or minutes, of application respectively. In radiation oncology,, brachytherapy is used because it is conformal, allowing, irradiation of targeted tissue volume with limited radiation, to nearby healthy tissues.1-3, As early as 1911, Dr. Albert Terson used radium to prevent, pterygium recurrence.4 Since that time, a number of, beta and gamma applicators have been important tools, for delivering radiation within the eye and orbit.2,3 Given, the small size of the eye and proximity of visually significant, structures, precise calculation of the radiation, dose to these vital structures is essential.5,6 However,, there exists scant clinical research comparing the efficacy, of various methods and brachytherapy types. The, closest research includes a 2012 American Association, of Physicists in Medicine (AAPM) comparison of, iodine-125 (125I) versus palladium-103 (103Pd) sources, used in eye plaques which included a review of ophthalmic, brachytherapy.7 Then, in 2014 the American, Brachytherapy Society (ABS) OOTF together with the, AAPM published a 47-person consensus, multicenter,, international OOTF guideline for plaque brachytherapy, of choroidal melanoma and RB.8 We suggest that all, eye cancer specialists obtain these open-access publications, and integrate their recommendations into clinical, practice. Lessons learned from these 2 publications are, presented in this chapter.