A late Day 4 session at AAO 2024 in Chicago saw experts from the ocular oncology world give practical pearls for general ophthalmologists in identifying and managing sight- and life-threatening ocular cancers.
When a patient with a suspicious ocular lesion or mass enters the clinic of a comprehensive ophthalmologist, time can be a luxury in tragically short supply. And considering the wide and complex range of potential maladies—and the many pitfalls involved in early oncological decision making—deciding quickly on the correct course of action can be a nightmare for the nonspecialist.
Fortunately an instructive Day 4 session at the 128th Annual Meeting of the American Academy of Ophthalmology (AAO 2024) on practical oncology targeted at general ophthalmologists has your back.
In its 12th year running, this session saw oncology experts like Dr. Prithvi Mruthyunjaya, Dr. Dan Gombos and more give their top tips for navigating an ocular oncology patient. We run down the top tips here.
Prognosis of uveal melanoma (Dr. Zelia Correra; Bascom Palmer Eye Institute, University of Miami)
- 15-GEP associated with PRAME expression status should be the go to for uveal melanoma prognosis.
Dr. Carrera’s presentation reviewed the literature, including some work of her own, on the latest methodology for uveal melanoma prognostication, but the tried and true GEP-PRAME expression methodology still reigns.
“Uveal melanoma-associated mutations are of clinical value but cannot replace the GEP-PRAME prognostication,” she said. “This has been shown to be the most robust and predictable method…and this is the way to go as far as our clinical care.”
Diagnosing choroidal melanoma (Dr. Prithvi Mruthyunjaya; Byers Eye Institute, Stanford University)
- When in doubt, don’t forget about DOCTOR GASS
Though the mnemonic device DOCTOR GASS is 43 years old, Dr. Mruthyunjaya championed its enduring relevance in distinguishing a nevus from a malignant growth. DOCTOR GASS stands for the following: Drusen, Overlying retinal degeneration, Chronic RPE changes, Thickness, Orange pigment, Reflectivity, Growth, Angiographic hot spots, Subretinal fluid, Symptoms.
Dr. Mruthyunjaya also pointed to another, more recent checklist that can also help guide decision making with smaller melanomas: thickness <2mm, fluid, symptoms, orange pigment, distance to the optic nerve, acoustic hollowness, absence of halo nevus and absence of drusen.
In the end, though, Dr. Mruthyunjaya believes that it is most important to not rely on one single factor. Fast growth, he said, might seem to indicate a melanoma over a nevus, but it cannot be considered in isolation.
“The tip is that there’s no one magic risk factor,” he said. “Not all growth is malignant, and a nevus can grow—we just have to watch it for other signs to be sure.”
- A picture is worth a thousand words
Making sure that evidence is clearly documented is another critical consideration. “A picture is worth a thousand words,” Dr. Mruthyunjaya said. “Use your clinical exams and imaging to help give you multiple layers of evidence.”
Clear and rigorous documentation can not only help you revisit an assessment with fresh eyes, but it can also help when it comes time to an all-important consultation with a specialist. “Always feel free to discuss your case, share pictures or refer your patient to an ocular tumor specialist,” he said at the conclusion of his talk.
Vitreoretinal Lymphomas (Dr. J. William Harbour, UT Southwestern Medical Center)
- When taking a biopsy, use a slow vitrector cut rate
Taking a vitreous biopsy is a key part of diagnosis, but the success rate of taking such a biopsy hinges on a slow (~300/min) vitrector cutter speed so as not to damage the sample.
“If this is done by a vitreoretinal surgeon not familiar with the disease and they use a very high cut rate, they can just rupture all of these highly friable tumor cells,” Dr. Harbour explained. “I go down to a 300-cut rate when I’m doing the primary vitrectomy, and we use manual aspiration into a TB syringe for the first couple of passes.”
- There’s increasing support for liquid biopsy and looking for the MYD88 mutation
One of the more recent developments in identifying vitreoretinal lymphomas has come with the identification of the MYD88 mutation, and Dr. Harbour suggested considering a liquid biopsy in order to look for just that.
A liquid biopsy, where intact cells are not as critical, affords many advantages, including the ability to identify the MYD88 mutation. This can even be identified in the office from the aqueous, adding to its appeal.
“MYD 88 is present in about 70-90% of vitreoretinal lymphomas, so when it’s present you can be just about sure that this is what you have,” Dr. Harbour said—though he did caution against dismissing a vitreoretinal lymphoma diagnosis if MYD88 is not present.
Retinoblastoma (Dr. Brian Marr; Harkness Eye Institute, Columbia University)
- It’s not always leukocoria
One of Dr. Marr’s biggest pieces of advice was not to rely on leukocoria as the end-all be-all of retinoblastoma signs. Though it is indeed the most common symptom, assuming that no leukocoria means no retinoblastoma could be a deadly error.
“Something that the primary care team should know is that sometimes you have inflammation or pseudocellulitis,” Dr. Marr said.
“If you have an uncomfortable kid with pseudocellulitis, you have to open that eye and take a look in because the third-most common presentation of retinoblastoma is cellulitis. That’s a key pearl, and all primary or pediatric ophthalmologists should know that,” he concluded.
- Liquid biopsy is emerging for retinoblastoma
Liquid biopsy is emerging as a critical tool for many ocular oncology pathologies, and retinoblastoma is no different. Dr. Marr pointed to its utility in detecting tumor characteristics and disease status, and helping to identify genetic characteristics to predict treatment response.
“We can take a small sample of the anterior chamber, look at the DNA in there, and reflect how it’s representing the retinoblastoma and the treatment of the eye,” Dr. Marr said. “There’s new and exciting research going on, so everyone should be aware of this new process.”
- Retinoblastoma is an emergency!
During the Q+A session, a doctor in a rural area asked about the referral process and timeline for retinoblastoma. The panelists, including chair Dr. Miguel A. Materin and Dr. Mruthyunjaya, were unequivocal: treat retinoblastoma as an emergency, and push a specialist to see the child immediately.
The main reason is that sight, and potentially life, is at stake and time is of the essence. But there is another factor that could spell disaster. “These parents’ anxiety levels are through the roof,” said Dr. Mruthyunjaya. “They’ll look something up on Google and then go into the emergency room, and this can actually delay quality treatment by putting the child into the wrong hands,” he explained.
Toxicities of Cancer Therapeutics (Dr. Dan Gombos, MD Anderson Cancer Center)
- Chemotherapy, immune and targeted therapies and antibody drug conjugates are the ‘big three’ to watch out for
Patients on these three classes of oncology therapeutics should always be monitored for ocular complications, said Dr. Gombos.
Among others, key things to watch out for include keratitis and cataract with chemotherapy (and steroids); uveitis and serous retinopathy (and especially MEK retinopathy on patients taking mitogen-activated protein kinase [MEK] inhibitors) for patients on immune and targeted therapies; and corneal microcysts with antibody drug conjugates.
- When in doubt, call it out (to your medical oncologist)
Throwing up the white flag and calling a specialist or another member of a patient’s care team was a theme that echoed the words of almost every other doctor in the symposium.
Ocular pathologies are complicated, stressed members of the panel, and there are highly qualified specialists there to help share the burden. Not everyone knows everything, and while these tips can certainly make a difference in the lives of patients, there is no substitute for calling in the heavies!
“If you’re seeing these patients, don’t just say ‘Oh, I’ll get in touch later’”, said Dr. Gombos. “Pick up the phone.”
Editor’s Note: Reporting for this story took place during the 128th Annual Meeting of the American Academy of Ophthalmology (AAO 2024) from 18-21 October in Chicago, Illinois, USA.
