Techniques for delivering chemotherapeutic agents for intraocular tumors have evolved. In addition to the traditional intravenous chemotherapy, more localized intra-arterial, periocular, and intravitreal chemotherapy (IVC) techniques place chemotherapeutic agents into the eye. Ocular chemotherapy achieves maximum local drug concentrations, improves efficacy, and minimizes adverse effects.
RB and vitreoretinal lymphoma are 2 intraocular tumors where periocular and intraocular chemotherapy are widely used. This chapter focuses on the medications and techniques of ocular chemotherapy.
Chapter Publication Title: Finger’s Essential Ophthalmic Oncology
Foreword by Tero T. Kivelä
Systemic Treatment of Uveal Melanoma: Insights and Emerging Strategies
Uveal melanoma (UM) is a relatively rare cancer, but is the most common primary intraocular malignancy (see Chapter 25) and comprises 5% of all melanoma diagnoses in the United States.1,2 UM arises from melanocytes within the capillary-rich uveal tract, with the most frequent locations being the choroid (90%), ciliary body (6%), and iris (4%).3 Although UM occurs with an incidence of ~2,000 cases per year, it is an aggressive cancer.4,5 Screening with periodic, abdominal radiographic imaging, 25%–30% of patients are diagnosed with metastatic UM within 5 years (see Chapter 27). Exiting the eye by hematogenous spread, commonly reported metastatic sites include the liver (89%), lung (29%), and bone (17%).6 The latency between the treatment of the primary tumor and the emergence of metastases ranges from months to decades, underscoring the likelihood of early dissemination from the primary site and variable metastatic growth rates.7 Unfortunately, there is no standardized consensus and known effective treatment for advanced UM in the adjuvant or metastatic settings. The prognosis is poor once metastasis develops, with a median overall survival of 10.2 months.8 Long-term sur-vival is unusual except in rare patients with isolated liver metastases amenable to surgical resection. When available and clinically appropriate, treatment within a clinical trial is recommended.
Although UM differs from cutaneous melanoma both clinically and biologically, treatment options for advanced stages have largely been adopted with much lower resultant response rates.9 Similarly, in that UM metastases are less responsive than cutaneous melanoma to both chemotherapy and immune checkpoint inhibitors, several treatment modalities have been evaluated, including systemic chemotherapy, immunotherapy, and molecularly targeted agents for the MAPK pathway. As the most common initial site of metastasis is the liver, palliative management includes liver-directed therapies such as bland embolization, chemoembolization, radioembolization, immunoembolization, and hepatic arterial infusion of chemotherapy. In this chapter, we review the molecular pathogenesis of UM, its prognosis, and advances in the management of metastatic UM (Mind map 14-1).
About the Editors
Enucleation and Exenteration
Eye removal is done for managing cancers, infections, inflammatory disorders, and intractable eye pain. It involves the removal of the eye by evisceration, enucleation, or orbital exenteration (Fig. 15-1). Evisceration involves removing the intraocular contents while preserving the outer scleral ocular coat and its orbital attachments. Enucleation consists of removing the entire eyeball; thus, the muscles and optic nerve must be detached. Orbital exenteration consists of removing all the orbit’s contents to bone (including periosteum).
Evisceration is rarely used in ocular oncology due to risks related to seeding the orbit with the tumor, recur-rence, and metastatic spread.1 In ophthalmic oncology, enucleation is most commonly used for advanced uveal melanoma and RB, whereas orbital exenteration is most commonly required for managing
About the Authors
List of Abbreviations
Functional Ophthalmic Oncology Anatomy
Anatomic and tumor-specific factors play dominant roles in clinical decision-making. Select examples include eyelid tumor position directing the postresection method of repair (see Chapter 37), orbital optic nerve sheath obstruction requiring slotted plaques (see Chapter 18) to completely cover juxtapapillary intraocular tumors, and the shape of the orbit affecting the orbitotomy approach. In consideration of the basic anatomy of the eyeball, the adnexa, and the orbit, this chapter highlights select salient anatomical features that affect tumor growth, metastasis (regional or distant), diagnosis, and management.
Overview of Ophthalmic Clinical Examination
The breadth of pathology within the scope of ocular oncology spans all ocular, orbital, and adnexal structures. As such, the clinical assessment of patients must be accordingly comprehensive and tailored for the detection and surveillance of neoplastic processes. While the essential modalities of standard ophthalmic examination are utilized in the practice of ocular oncology, a nuanced perspective is necessary to optimize management for this subset of patients. In this chapter, we present the systematic approach to clinical examination employed at The New York Eye Cancer Center as a basis for the assessment of patients in ophthalmic oncology practice.
Multimodality Imaging of Intraocular Tumors
Ophthalmology and ophthalmic oncology are blessed with excellent intraocular imaging modalities.1-4 Traditionally, we had slit-lamp examination, gonioscopy, and direct and indirect ophthalmoscopy (see Chapter 3). However, these techniques did not provide a recorded image and thus required both observational and recol-lection skills utilized over relatively short observational periods. Clearly, what we observe and recollect is processed to determine the diagnosis and condition of the eye. It is no wonder that ophthalmology quickly added photographic imaging to anterior and posterior segment examinations.
Photography not only provided a “snapshot” of the patient’s condition at a specific time but also allowed specialists to take more time to observe the ocular condition without the previously required cooperation of the patient. Such “snapshot” photographic images document the patient’s condition at one specific time, allowing for side-by-side comparisons with future or past images to assess change. For example, in ophthalmic oncology, we may use side-by-side imaging to monitor for tumor growth, increased SRF, or the presence of radiation side effects. Then, more complex ophthalmic imaging systems evolved. Angiographic (e.g., fluorescein [FA], indocyanine green [ICGA]) imaging is utilized to assess differences in tumor circulation, patterns of regression, and treatment-related side effects.5,6 Ultrasound imaging allows eye specialists to “see” within eyes with opaque media, evaluate mass lesions for internal reflectivity, and measure tumors prior to treatment. In addition, ultrasonography offers a method to measure intraocular neoplasms as well as reveal their internal reflectivity and interstitial extent. Three-dimensional ultrasound made a brief appearance in ophthalmology and offered interactive computerized reconstructions also like computerized radiographic imaging (e.g., MRI and CT). More recently, optical coherence tomography (OCT) with and without angiography uses laser-based imaging to create 2-D slices and 3-D reconstructions such as those previously limited to computerized radiographic imaging.7
However, multimodality imaging is what eye cancer specialists use to achieve a clinical diagnosis so accurate it is often used instead of pathology. For example, it is the low-lying, yellow tumor with scalloped edges combined with slow fluorescein uptake and internal acoustic reflectivity so high that it shadows the orbit which makes the clinical diagnosis of choroidal osteoma. Herein, we describe the use of ophthalmic imaging techniques to diagnose intraocular tumors. The process of diagnosis is dependent upon visible tumor characteristics as well as those that can only be uncovered with multiple ophthalmic imaging techniques (Mind map 4-1 and 4-2).