Looking Migraine in the Eye

By Fred Schwaller | March 13, 2024 | Posted in

A non-invasive imaging tool reveals changes in the retinal microvasculature during migraine. The approach could help researchers better understand the pathophysiology of the condition and perhaps be of clinical use, too.

The eyes are the window to the soul, as the familiar saying goes. But the eyes can also offer a peek into the brain and what happens to it during migraine – this according to new research investigating the retinal microvasculature, which is the system of tiny blood vessels in the retina, in people with migraine.

Investigators from the University of California, Los Angeles, US, used a non-invasive imaging tool called optical coherence tomography angiography (OCTA) to reveal several changes in the retinal vasculature during a migraine attack and between attacks, in those having migraine with aura or migraine without aura, including alterations in the shape and blood supply of the retina.

“This study shows that blood vessels in the retina are affected in migraine patients with aura and migraine without aura. OCTA could be a very important tool for the future of understanding the migraine process,” said Kathleen Digre, University of Utah, Salt Lake City, US, a neuro-ophthalmology and headache expert who was not involved in the research.

In addition, the authors say that retinal vasculature “signatures” of the sort identified in the study could perhaps one day serve as biomarkers – objective, measurable indicators – of migraine.

The study appeared in the January 2024 issue of the journal Headache.

Using OCTA
With OCTA, the team aimed to capture different features of the retinal vasculature both during migraine attacks (known as the ictal phase) and between migraine attacks (the interictal phase). One of those features is blood perfusion, which the team assessed using the vessel flux index (VFI), a parameter based on the intensity of the OCTA signal.

“The VFI provides a sensitive measure for capturing changes in retinal vasculature during an attack, and while a few recent studies in neuro-ophthalmology have used this measure, it has not been used previously in headache research,” said Katherine Podraza, first author of the study and a headache specialist now at Hartford Healthcare Headache Center, Mystic, Connecticut, US, via email.

In addition to the VFI, the researchers considered a number of other vascular parameters. And, they examined structural features, too, including the shape and size of the foveal avascular zone (FAZ).

The FAZ is a region that surrounds the fovea and lacks blood vessels, and previous research had linked increased size of the FAZ to migraine with aura. (The fovea is a small depression in the macula, which is an area of the retina at the back of the eye that is needed for central vision, color vision, and seeing fine detail.)

Ultimately, the study would include 37 patients having migraine with aura (86% female, median age of 37); 30 patients having migraine without aura (77% female, median age of 37); and 20 healthy controls (50% female, median age of 35).

“Other groups have used OCTA, but the strength of this study is that the authors screened a large number of patients that could be statistically analyzed,” Digre told Migraine Science Collaborative.

Changes in structure and function
First directing their attention to the interictal phase, the researchers found differences in retinal structure and function depending on the migraine subtype study participants had.

“Interictally, we found differences in the shape of the foveal avascular zone as well as reduced foveal perfusion in participants with migraine with aura compared to migraine without aura,” Podraza told MSC.

The team next compared the ictal and interictal phases.

First, they found no differences in FAZ area or shape, or in the foveal vasculature, in the migraine groups compared to healthy controls.

However, there were differences depending on the migraine phase. Specifically, during a migraine attack, those having migraine with aura, as well as those without aura, had a reduction in blood perfusion in the parafoveal retina, compared to the interictal phase. (The parafovea is a part of the retina that surrounds the fovea.)

“The change we see of reduced parafoveal perfusion during migraine attacks is an interesting finding. It is unclear if this contributes to symptoms during a migraine attack. However, it is possible that it may be related to some visual symptoms we see during migraine attacks, including blurred vision, but this needs more research,” according to Podraza.

Unilateral headache
The team also looked at the interictal foveal microvasculature in 26 of the participants who experienced unilateral headache during their migraine attacks: 14 who had migraine with aura, and 12 without aura.

Here, the investigators found an asymmetry of retinal perfusion between eyes. Specifically, whether they had aura or not, those with unilateral headache showed increased vascular parameters in the eye on the side of the headache. These results showed that vascular changes in the eye are linked to the side of pain.

“The differences seen in those with unilateral headaches might be a response to pain or reflect fundamental migraine mechanisms involved in unilateral attacks,” said Podraza.

Future uses of OCTA
Digre said the study opens up new ways to study the pathophysiology of migraine. One area where OCTA could be particularly useful, she said, is to elucidate how autonomic features of migraine affect the retinal vasculature.

“This includes sympathetic and parasympathetic effects on retinal vasculature,” she said.

What’s more, Digre said OCTA could help advance understanding of spreading depression in the retina (which is similar to cortical spreading depression, a phenomenon thought to be the physiological correlate of aura.)

“I think that OCTA could tell us a lot about migraine and the vascular implications of migraine and spreading depression in the retina. Is spreading depression occurring in the retina? The retina has been shown to play a role in spreading depression in chicks, but has never been shown in humans. There are many open questions about vascular changes in migraine,” said Digre.

The authors say that their study also shows how OCTA could improve knowledge of the role of the retina in the visual symptoms of migraine, like light sensitivity and blurring.

“Our results raise the possibility that reduced retinal perfusion could play a role in visual symptoms that occur during a migraine attack. The long-term effects of these changes require further longitudinal studies. However, this may allow us to screen for patients who may have a higher risk of vascular complications,” said Podraza.

A new biomarker?
The authors say that a retinal vasculature signature – a unique pattern of changes in the retina of each particular person – could be a promising biomarker of migraine. The advantage of using OCTA to image that pattern is that this tool is non-invasive and could be highly sensitive in detecting clinically relevant differences in migraine pathophysiology, if future research bears that out.

“With further research, I do think a pattern of changes seen with OCTA could play a role as a biomarker in migraine. We are seeing significant differences in the vascular pattern, specifically in migraine with aura participants, and this may allow us to separate subgroups of migraine patients on the basis of their OCTA changes,” said Podraza.

Podraza added that long-term changes in vascular patterns could be useful for monitoring migraine treatment efficacy in patients over time.

Digre was more skeptical about the potential clinical uses of OCTA, at least for the time being.

The caution I have is that these are really subtle, microscopic changes [in retinal vasculature], and not major changes. They’re statistically significant, but are they clinically significant? Are we going to suggest all people with migraine should have OCTA of their macula? I don’t think we’re there yet.”

Digre was nevertheless enthusiastic about OCTA and the importance of the current study in demonstrating its potential.

“It’s a great research tool. I do believe that the eye is all connected with the migraine process because it’s a window to the brain and part of the brain. For instance, there’s a condition called retinal migraine, but we really don’t have a handle on what retinal migraine really is. Is it a spreading depression in the retina, or is it related to blood flow change? We just don’t know,” Digre told MSC.

Fred Schwaller, PhD, is a freelance science writer based in Germany. Follow him on Twitter @SchwallerFred

Image credit: 123RF Stock Photo.

Reference
Reduction in retinal microvascular perfusion during migraine attacks.
Podraza et al.
Headache. 2024 Jan;64(1):16-36.

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Fred Schwaller is a science writer and communicator based in Berlin, Germany. Fred spent a decade in pain research during his doctoral degree at University College London, UK, and his postdoc at the Max Delbrück Centre in Berlin, Germany. After transferring to science communication in 2020, he has been writing and podcasting about life sciences and medicine, specializing in somatosensation and pain. Follow him on Twitter @SchwallerFred.

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