Once True. Now, Maybe Not So Much. Toppling Myths in Ophthalmology | AAO 2024

The best strategy for treatting optics neuritis, the importance of complete elimination of subretinal fluid and many other long-held beliefs in ophthalmology were challenged during a session Saturday focused on breaking down myths at the annual meeting of the American Academy of Ophthalmology (AAO) in Chicago.

The moderator of the session, Sruthi Arepalli, M.D., noted that new research findings can chip away at cherished notions about diagnosis and treatment that were once held firmly as true.

“Things change with time as more data comes,” said Arepalli, an assistant professor in the Department of Ophthalmology at the Emory School of Medicine in Atlanta.

Optic neuritis: To treat (and test) or not to treat (and not to test)

John J. Chen, M.D., Ph.D., a neuro-ophthalmologist at the Mayo Clinic, said the belief that optic neuritis tends to get better on its own stemmed from a landmark study published in the New England Journal of Medicine in 1992. Findings from that study established that high-dose intravenous methylprednisolone can speed recovery but, ultimately, it does not change visual acuity.

John J. Chen, M.D., Ph.D.

But Chen told AAO audience that “not all cases of optic neuritis will improve without intervention, and understanding the underlying pathology is essential for effective management.” Testing for specific antibodies is crucial, he said, because it can significantly influence prognosis and guide treatment choices.

Although some cases will optic neuritis resolve, Chen said, but others may get much worse. Neuromyelitis optica, for example, can lead to blindness and needs to be treated, he noted. It is important to uncover the underlying pathology of optic neuritis, Chen continued, and specifically whether it is related to multiple sclerosis or myelin oligodendrocyte glycoprotein, both of which could dramatically alter the approach to treatment.

Testing for AQP4 and MOG antibodies is crucial to differentiating between the types of optic neuritis and making treatment choices, said Chen.

To further illustrate that treatment is often needed, Chen shared a case scenario wherein there was testing and antibody detection followed by intervention and another with no testing. The outcomes were vastly different because the testing identified AQP4-positive neuromyelitis optica spectrum disorder, leading to early intervention with Uplizna (inebilizumab) and avoidance of paralysis.

Macular degeneration: Can dry be too dry?

Treating the macula till it is “dry” and the excess fluid removed is often seen as the goal of macular degeneration treatment. Yasha S Modi, M.D., a vitreoretinal surgeon at Tisch Hospital in New York and an associate professor at NYU Grossman School of Medicine, said answers to two main questions could poke a hole in that idea: Does all fluid need to be treated? And should a perfectly dry retina always be the goal?

Modi told the AAO audience that clinical evidence shows that not all fluid is the result of neovascularization. Subretinal fluid alone may occur in specific situations, such as pigment epithelial detachment (PED), and in many cases doesn’t require treatment, he said.

“Not all fluid is necessarily neovascular ... and in rare cases, even with neovascularization, we can observe closely, if asymptotic and with excellent visual acuity," said Modi. The only challenge, he noted, was that these cases were very difficult to identify.

Yasha S. Modi,M.D.

In fact, some research has shown that having a fully dry retina may be less than ideal, Modi said, referencing a post-hoc analysis of the phase 3 HARBOR trial of ranibizumab. The study participants with some residual subretinal fluid at 12 and 24 months were found to have better best-corrected visual acuity than those with complete resolution of fluid.

Modi emphasized the importance of individualized treatment. Striving for a completely dry retina is not always achievable or necessary, he said, and in some cases persistent subretinal fluid may be protective. “Persistent subretinal fluid may paradoxically be associated with better vision. Perhaps it plays a protective role in preserving photoreceptor health," he said.

Thyroid eye disease: Straightening out the thinking about Rundle’s curve

Rundle's curve is used to define the natural history of thyroid eye disease (TED). Many studies since Francis Felix Rundle’s publication of research in 1945 that became the basis for the eponymous curve have cast doubts on its accuracy, and several anecdotal patient case reports do not align with its timelines, said Amina I. Malik, M.D., chief of ophthalmic plastic and reconstructive surgery at Houston Methodist Hospital.

Amina I.Malik, M.D.

“I think 80 years later, it’s time to set the record straight on Rundle’s curve,” she said. “Not every patient is going to follow this oversimplified biphasic curve ... it’s time we really focus on their symptoms and quality of life.”

The biggest deviation from the curve is that TED often persists beyond the “inactive” phase, Malik said. This is noted by ongoing inflammation at the cellular level, she said. Although the levels of insulinlike growth factor expression were not as high in those with"noninflammatory" TED, the levels in this group were still much higher than in control arms. This was observed in studies of Tepessa (teprotumumab) for patients with noninflammatory TED.

"There is still persistence of this upregulation and overexpression of growth factor receptors telling us that even if we don't see the external signs of inflammation, there is still some ongoing inflammation happening," said Malik. "It's a complex heterogeneous inflammatory disease."

The good news with uncovering this new complexity is that several therapies are currently in development, she said. Treatment strategies should focus on the patient rather than on Rundle’s curve, Malik said.