In recent years, new treatment strategies and more effective therapeutic agents have significantly changed the field of ocular oncology, Timothy G. Murray, MD, MBA, said during a session titled “What Has Changed in the World of Retina,” which kicked off Friday’s Retina Subspecialty Day at the American Academy of Ophthalmology’s 2024 meeting in Chicago.
Enucleation, once the most common treatment for both ocular melanoma and retinoblastoma, is now very rarely employed and almost never as a primary therapy, Dr. Murray said. Instead, new options like intra-arterial chemotherapy and intravitreal chemotherapy have become so effective that enucleation is now done only after eyes are unresponsive to treatment. “That’s taken the enucleation rates from over 30% to less than 5%, with a particular decline over the last decade as we’ve gone to these advanced chemotherapy agents,” said Dr. Murray. “That’s exciting because it means the treatment cure rate maintains a really high level without having to remove the eye in the vast majority of patients, including children.”
Treatment changes were driven, in part, by the results of the Collaborative Ocular Melanoma Study (1985-2000), which compared radiation treatment to enucleation to determine the best management for melanomas. Two multicenter randomized clinical trials conducted as part of the study showed that survival outcomes were identical with either treatment. “Over time, we’ve evolved away from enucleation and toward plaque brachytherapy or charged particle radiotherapy with proton beam,” said Dr. Murray. “It turns out those are equally effective — and you keep the patient’s eye.”
In the September issue of Retinal Physician, Yehonatan Weinberger, MD, and Arun D. Singh, MD, discuss 3 treatments currently being tested to prevent or mitigate the effects of radiation. Read more here.
Other factors that have led to improved outcomes are earlier diagnoses, thanks to genetic testing and improved imaging modalities like optical coherence tomography angiography (OCT-A), which allows earlier treatment, and the use of anti-VEGF therapy to mitigate complications from radiation, such as retinopathy or radiation-related secondary neovascular glaucoma. “So, it’s not just that we're keeping the eye — you’re actually going to have an eye that has function,” said Dr. Murray. More data will eventually be available on anti-VEGF treatment, as results of the DRCR Network’s randomized clinical trial for radiation retinopathy (NCT05844982) become available, he added.
The increased use of genetic testing has contributed to the earlier diagnosis of ocular melanoma. “I use gene expression profiling (GEP), which is a micro-RNA analysis,” explained Dr. Murray. “You only need about 10 tumor cells to be able to get an accurate gene profile. We’ve found that even in very, very small tumors, we were able to get the gene expression profiling in 99% of patients.” GEP is important because it is a prognostic indicator for survival, with tumors defined as class 1 (low risk) or class 2 (high risk). These are stratified into a and b levels to further define risk. With new adjunctive systemic therapies now available, the high-risk class 2 patients can be treated earlier, which reduces the metastatic incidence (Figure 1).
Figure 1. Timothy G. Murray, MD, speaks on the outcomes of uveal melanomas as classified by gene expression profiling. Earlier treatment reduces the risk of metastasis, he said.
Artificial intelligence (AI) is going to play a role in ocular oncology, as it will in all of health care, Dr. Murray says. “As we've built [patient image] databases, people are getting interested in whether AI can look at images and give us better prognostic information as to whether a patient is going to have a melanoma,” he said. “That’s kind of exciting for the future. Those studies are still very preliminary, I think AI is going to touch pretty much every part of imaging for ophthalmology, retina, and specifically ocular oncology.” RP
