Nonpigmented conjunctival tumors constitute a broad, spectrum of ocular conditions, spanning benign to malignant, entities.1 Diagnosis of these tumors often hinges, on their clinical characteristics, and in many instances,, cytologic or histopathologic evaluation becomes indispensable, (see Chapters 5 and 6).2 The management, approach frequently depends on both the diagnosis and, the extent of invasion., While most conjunctival tumors have epithelial or melanocytic, origins, they also originate from vascular,, fibrous, neural, histiocytic, myogenic, myxoid, lipomatous,, and lymphoid components (Mind map 38-1). The, most commonly diagnosed malignant conjunctival cancers, are squamous carcinoma, malignant melanoma, and, lymphoma (Fig. 38-1)., Further, conjunctival tumors are also classified into, 3 categories: benign, premalignant, and malignant., It is noteworthy that the 8th edition of the AJCC Cancer, Staging System discourages the use of premalignant, classifications for both melanocytic and squamous, intraepithelial neoplasia, now classified as stage Tis (in, situ, see Chapter 8).3 Such complexities necessitate a, thorough and thoughtful chapter dedicated to the diagnosis, and management of nonpigmented conjunctival, tumors.
Chapter Keyword: chemotherapy
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.
Treatment of Retinoblastoma
The aims of RB treatment in order of priority are to save, life, the eye, and vision. Early detection, prompt treatment,, and advanced treatment modalities have improved, survival leading to increased interest in globe salvage., All patients should be initially staged using the 8th edition, AJCC TNMH staging of RB as shown in Table 33-1.1, Many centers use the International Intraocular RB Classification, (IIRC) in addition to the AJCC.2 Staging can help, determine the type of treatment required and has been, shown to accurately predict both mortality from metastatic, disease and globe salvage rates.3,4 Table 33-1 includes, a column showing how the IIRC classification compares, to AJCC staging, as many studies discussed in this chapter, use the older, less robust classification. In contrast to IIRC, and other RB classification systems, the 8th edition AJCC, RB staging system is the only comprehensive classification, that addresses intraocular, orbital, and metastatic RB,, predicts metastatic death and local treatment outcomes,, accounts for sporadic and germline RB, and has been periodically, updated with new medical evidence.3,4, Treatment modalities have evolved from external radiation, in the 1960s, to systemic chemotherapy with sequentially, aggressive local treatments (SALT) in the 1990s.5 The, last decade has witnessed a growing interest in therapies, where treatment is delivered through regional arteries or, directly into the globe. In high resource countries, where, patients present early and more treatment options are readily, available, there exists a 3%–5% risk of metastasis-related, mortality.6-8 In contrast, children with RB from middle- and, lower-resource countries have a 10.3-fold and 9.3 to 10-fold, higher risk of metastasis-related mortality, respectively.9
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 mel¬anocytes 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 can¬cer.4,5 Screening with periodic, abdominal radiographic imaging, 25%–30% of patients are diagnosed with met¬astatic UM within 5 years (see Chapter 27). Exiting the eye by hematogenous spread, commonly reported met¬astatic 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 varia¬ble 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 availa¬ble 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 inhibi¬tors, 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 thera¬pies such as bland embolization, chemoembolization, radioembolization, immunoembolization, and hepatic arterial infusion of chemotherapy. In this chapter, we review the molecular pathogenesis of UM, its progno¬sis, and advances in the management of metastatic UM (Mind map 14-1).