How phase-OCT could transform glaucoma care

The trabecular meshwork opens and closes like the feathered brow of a wise owl.

The video could be from outer space – a semaphore from a galaxy far, far away. But it is in fact an insight into a much smaller world – capturing the flow of tides within the eye, a shore only a handful of microns across.

Professor Murray Johnstone spent more than three decades grappling with the mechanics of the eye in order to bring this hidden landscape into focus.

After many failures and false turns, Johnstone described viewing the trabecular meshwork in motion for the first time.

“It truly was a feeling of amazement,” he said.

“No one had any idea that this beautiful apparatus is present within the eye,” Johnstone highlighted.

The ocular pulse is not dissimilar to what causes the pulse within the heart. There are two chambers, two valves and a pumping action.

No one had any idea that this beautiful apparatus is present within the eye

Johnstone will sometimes tell people that everything he learned about the outflow system came from a single textbook on cardiovascular biomechanics.

“I don't pretend to understand the mathematics, but the person who wrote a book had a very good narrative capability, explaining all the phenomena that occur within the cardiovascular system. All of this is fully mirrored in the outflow system,” he said.

So, what course of events transformed a Harvard ophthalmology resident into someone who discovered the body’s most intricate plumbing?

Johnstone explained that 37 years of clinical practice – caring for a large number of glaucoma patients over this time – has fuelled his drive.

“My whole motivation has been to try and find some improved understanding of how the outflow system works. Before a disease can be adequately treated, we have to understand how it works,” he said.

As part of his training, Johnstone carried out a residency at the Massachusetts Eye and Ear Infirmary and completed research under the supervision of eminent glaucoma scholar, Professor W Morton Grant.

The first minimally invasive glaucoma surgery was carried out at the Massachusetts Eye and Ear Infirmary during his time there.

“It was a time of tremendous excitement and the reason I chose glaucoma as a field of interest,” Johnstone shared.

After his residency, he initiated the first systemic study of outflow biomechanics as part of a post doctorate with Morton Grant.

The researchers were able to show that the trabecular meshwork motion was tightly linked to the force induced by intraocular pressure.

“The structures had always been thought of as unmoving, so it was regarded as a major breakthrough in understanding at the time,” Johnstone said.

“The concept now underpins much of our conceptual framework of what goes wrong in glaucoma,” he highlighted.

When asked about the challenges of studying the motion of the trabecular meshwork, Johnstone highlighted the size of the structure.

“It's about 300 microns thick. And most of the motion occurs in the micron and nanometer range. So, it required a number of years to develop the techniques needed to establish the functional features we now see in the video,” he said.

He added that blood refluxed into the Schlemm's canal used in the initial discovery of the valves also makes it difficult to see the structures within the canal.

It was not until the development of viscoelastics in 2002, that Johnstone had the tools needed to gain an unobstructed view.

“We discovered that viscoelastic could be used to create a widely dilated canal, which could then be washed out and reveal the structures within,” he said.

“It was a tremendous breakthrough because it permitted the study of features inside the canal without the confusing and obscuring presence of blood,” Johnstone shared.

We're at the inception of a new era

Since this development, a broad range of imaging technology has been used to gain a closer view of the outflow system – including transmission electron microscopy, confocal microscopy and fluorescent tracer studies.

However, Johnstone highlighted that the most valuable tool has been high-resolution optical coherence tomography (OCT) for fine structural details.

The development of phase-based OCT by Professor Ruikang Wang has been another step-change in the research – by measuring nanometer-level motion and synchronising the images with the ocular pulse using a digital pulsimeter.

Researchers have found that the trabecular meshwork stiffens in glaucoma. When the trabecular meshwork collapses into Schlemm's canal, the outflow is halted.

“Pulsatile flow is present in normal patients, reduced in those with mild glaucoma and absent in those with severe glaucoma,” Johnstone explained.

He believes that in time, phase-OCT could be used to monitor the health of the eye in the same way that an electrocardiogram guides cardiac care.

“You can interrogate the whole outflow system and watch whether these structures are undergoing normal motion,” he shared.

In order to keep costs down, Johnstone envisages the development of an add-on device that can be fully integrated into commercially available systems.

“I'm going to take an aspirational approach and suggest that we'll be living in a very different world using phase-OCT for diagnosis, monitoring and surgical decisions 10 years from now,” he observed.

“Technology is moving extremely rapidly. We're just at the beginning of what it can accomplish. We're at the inception of a new era,” Johnstone concluded.