Ophthalmologists Called to Catch Cancers Earlier

Laird Harrison

July 17, 2020

Significant advances in the management of eye cancer mean that early referrals to subspecialists are crucial when ophthalmologists suspect disease in their patients, two leaders in the field say.

"Don't be afraid or embarrassed to contact an ocular oncologist," said Carol Shields, MD, from Wills Eye Hospital in Philadelphia.

Improvements in prognosis and treatment are saving the eyes and lives of patients with uveal melanoma and retinoblastoma, said Timothy Murray, MD, from Ocular Oncology and Retina in Miami.

Because these cancers are so rare, there have been very few randomized clinical trials. Uveal melanoma, the most common primary eye cancer in adults, affects about 3000 Americans each year, and retinoblastoma, the most common eye cancer in children, affects about 300.

This means there is currently no consensus on standard of care. But ocular oncologists have helped each other move rapidly forward by tracking their own patients and sharing data with each other, said Murray, who will speak about advances in the field of ocular oncology at the virtual American Society of Retina Specialists (ASRS) 2020 Annual Meeting.

There was a time when enucleation was the only option for patients with uveal melanoma, but a transition to radiotherapy began in the late 1980s. Two forms — brachytherapy and charged-particle therapy — are now in use. And alternatives are being developed that allow ocular oncologists treat smaller and smaller tumors.

Imaging and genetic analyses can now help clinicians identify which cancers are most likely to metastasize.

"We're moving to treat patients earlier and earlier and earlier," Murray told Medscape Medical News.

Early Identification Key

Shields recommends a mnemonic — To Find Small Ocular Melanoma Doing Imaging — as a reminder of what to look for when imaging patients with suspected uveal melanoma: Thickness (greater than 2 mm), Fluid subretinal, Symptoms of visual acuity loss, Orange pigment, Melanoma hollow, DIameter (greater than 5 mm).

When genetic analyses indicate that patients are at risk for metastases, "we put them on neoadjuvant therapy to protect them from metastatic disease," she told Medscape Medical News.

Catching the tumor early is more important than categorizing it, said Murray.

"When I started, we believed that if you had a class 2 tumor, you were essentially going to die," he reported. "Now we know that if we can get you early and you have a class 2 tumor, that may not be the case. That was a really big finding."

Radiotherapy can cause radiation retinopathy, radiation optic neuropathy, and neovascular glaucoma, so Murray said he has moved to treatment with surgical ablation. In fact, he was a pioneer in the use of microincision vitrectomy surgery and endolaser photocoagulation.

"In the surgical ablation approach, you have almost 99% tumor control," he said. "Patients maintain visual acuity and function. The mortality rate is zero."

There have been concerns about scotomas in microincision vitrectomy surgery, but Shields said she has been impressed with Murray's short-term results with this form of surgical ablation and looks forward to longer-term data.

Meanwhile, she has been pleased with the effectiveness of prophylactic therapy, in which VEGF inhibitors are used to reduce the risk for adverse reactions to brachytherapy.

And she is involved in the development of AU-011 (Aura Biosciences), which consists of viral-like particle bioconjugates that bind selectively to receptors on cancer cells. The particles, activated with an ophthalmic laser, disrupt the membrane of tumor cells but spare key eye structures; no surgery is required.

Data from the ongoing phase 1b/2 clinical trial of AU-011 in the treatment of choroidal melanoma — the predominant form of uveal melanoma — will be presented at the ASRS meeting.

"Wild Ride" in Ocular Oncology

The management of retinoblastoma has gone through a similar progression.

Murray said his gold-standard treatment changed from enucleation to external-beam radiotherapy in the late 1980s. Then, in the mid-1990s, when it became clear that radiotherapy was leading to secondary malignancies, his gold standard became systemic chemotherapy. But this, too, led to adverse effects, so in the early 2010s, he switched to intra-arterial chemotherapy.

Shields said her practice has followed a similar progression, and she now uses intravenous, periocular, intravitreal, and intra-arterial routes for chemotherapy, depending on the tumor laterality and staging.

Thanks to these innovations, retinoblastoma is the most successfully treated of all pediatric cancers, Shields said.

But catching retinoblastoma earlier could further improve prognoses. "One of the things people have talked about is screening children in the NICU, which we do routinely now for retinopathy of prematurity," said Murray. "Maybe we could extend that screening to the well-baby nursery."

The two experts agree that the fast pace of these developments — almost without support from randomized clinical trials — is breathtaking.

"Boy, has it been a wild ride in the field of ocular oncology," Shields said. "It's wilder than any roller coaster you can ever imagine."

Shields reports a relationship with Aura Biosciences. Murray reports financial relationships with Regeneron and Alcon Surgical.

American Society of Retina Specialists (ASRS) 2020 Annual Meeting. To be presented July 25, 2020.

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