Chapter 16: Introduction to Part II
Intraocular tumors make up a broad spectrum of benign and malignant lesions that can lead to loss of vision and/or loss of life. Effective management of these lesions depends on accurate diagnosis. In most cases, experienced ophthalmologists diagnose intraocular neoplasms via clinical examination and ancillary diagnostic tests. When evaluating a patient with a tumor, the ophthalmologist should have sufficient knowledge to make an accurate diagnosis or at least to develop a differential diagnosis. In addition, there should be a low threshold for referral to a specialist when the diagnosis is not clear or treatment involves complex therapies and/or a multispecialty approach.
In the past 4 decades, significant advances have been made in understanding the biology of intraocular tumors and in managing these lesions. The Collaborative Ocular Melanoma Study (COMS) gathered important information concerning the most common primary intraocular malignant tumor in adults, choroidal melanoma. The study incorporated both randomized clinical trials for patients with medium and large choroidal melanomas and an observational study for patients with small choroidal melanomas. The COMS reported outcomes for enucleation versus brachytherapy for the treatment of medium-sized tumors and for enucleation alone versus enucleation preceded by external beam radiotherapy for large melanomas. In addition to the study’s primary objectives, which were to evaluate the mortality outcomes after enucleation and globe-sparing radiotherapy for uveal melanoma, the COMS provided data regarding local tumor failure rates and visual acuity outcomes after iodine 125 brachytherapy. The results confirmed that eye-sparing plaque brachytherapy for well-selected patients does not adversely affect melanoma-related morbidity or mortality. The most common form of treatment for uveal melanoma is now eye-sparing radiation.
In recent years, there have been several other advances in the understanding and management of choroidal melanoma. Researchers have identified key cytogenetic aberrations that are associated with metastatic disease, including monosomy of chromosome 3, especially with gains in chromosome 8. Gene expression profile testing, another molecular technique, is highly predictive for late metastasis in uveal melanoma. Both forms of prognostic testing require tumor sampling obtained through fine-needle aspiration biopsy (FNAB) of the tumor or evaluation of paraffin-embedded tissue. Information gained from FNAB is useful for tumor prognostication and identification of patients at high risk for distant metastasis.
Retinoblastoma, the most common primary intraocular cancer in children, is most often caused by a mutation in the tumor suppressor gene RB1, which was isolated, cloned, and sequenced in the 1980s (the first tumor suppressor gene ever sequenced). As with choroidal melanoma, treatment of retinoblastoma has transitioned toward globe-conserving therapy with chemotherapy and local treatments, including laser therapy and cryotherapy. The trend away from external beam radiotherapy and toward chemotherapy has been fueled, in part, by growing recognition of the former’s potential risk for increasing the incidence of second nonocular malignancies in children who harbor a germline mutation in the retinoblastoma gene. Advances in understanding the molecular genetics of retinoblastoma continue to enhance clinicians’ ability not only to screen for this tumor in families with retinoblastoma, but also to provide appropriate counseling (see Chapter 19).
In the United States and Europe, most malignancies are staged using the classification system developed by the American Joint Committee on Cancer (AJCC). The AJCC system stages cancer in patients based on tumor size, lymph node status, and distant metastasis. Both clinical and pathologic data may be used to clinically stage a tumor. It is an important distinction that patients—not just a single organ, such as the eye—are staged. For certain tumors, such as retinoblastoma, other systems are used to stratify the level of disease within the eye and the risk of loss of the eye.
As with many other pathologic conditions of the eye, intraocular tumors may result in irreversible vision loss. Patient education and, if appropriate, referral for vision rehabilitation can be considered before loss of function and independence occur. The American Academy of Ophthalmology’s Initiative in Vision Rehabilitation page on the ONE Network (www.aao.org/low-vision-and-vision-rehab) provides resources for low vision management, including patient handouts, and information about additional vision rehabilitation opportunities beyond those provided by the ophthalmologist.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.