From the Outside Looking In: Sophisticated Imaging Helps Detect Glaucoma

BrightFocus Grants Have Advanced New Imaging Techniques

This research was supported by BrightFocus

In recent years there have been major improvements in imaging technologies that can help lead to an earlier detection of glaucoma.

To diagnose and monitor vision problems, clinicians often rely on a mixture of self-report data from the patient, such as mentions of eye discomfort and vision disturbances, as well as measurements of visual acuity and field using standards tests like the visual field exam and the eye chart. That’s the view from the inside looking out.

However, they also look inside your eye to gauge the health and integrity of its tissue and the health of eye structures like the cornea, lens, retina, and optic nerve. That’s the view from outside looking in. Traditionally, it’s done with a dilated eye exam, where drops are used to numb and dilate your eyes, and then instruments with magnification are used to look deep inside.

In recent years, there have been major advances in eye imaging technologies that offer the promise of improvement over manual methods. Optical coherence tomography (OCT), magnetic resonance imaging (MRI), and other techniques are improving our ability to look deep inside the eye. These techniques have some benefits over traditional methods, in that they can be done in a relatively brief period of time, without an uncomfortable dilated exam, and they capture high-resolution images which can be studied, compared with healthy eyes, and tracked over time to detect and monitor any abnormalities.

As a further benefit, researches and engineers are working on ways to downsize eye imaging technologies so they are mobile and can be used remotely from anywhere around the globe. That will greatly extend our ability to screen for and manage vision diseases.

Advanced imaging is especially helpful for glaucoma, the “silent thief of sight,” which often doesn’t announce itself with pain or telltale signs that are visible to the clinician’s eye (even with magnification). However, there are physiologic changes resulting from sustained pressure elevations that can be detected at the earliest stages—before vision loss occurs—using imaging techniques. This can be done by visualizing the rate and volume of fluid outflow from the eye; and by measuring a reduction in optic nerve fibers, indicating damage or loss of axons which carry visual signals from the retina to the brain.

Thanks to National Glaucoma Research funding, BrightFocus researchers are among those who have advanced new imaging methods, taking them from experimental stages to their new threshold, where they wait to become standard as clinical tools. One leader in this area is Joel Schuman, MD, of the University of Pittsburgh, who used his 2010-12 BrightFocus grant to develop spectral domain OCT Doppler, which detects glaucoma by measuring aqueous outflow. Schuman currently serves as mentor and co-PI on a 2013-15 BrightFocus grant to Kevin Chan, PhD, who is developing ways of using MRI to measure and track the impact of pressure elevations on visual brain structures apart from the eye in glaucoma’s earliest stages. Along with Schuman, bioengineer Wolfgang Drexler, PhD, of the Medical University of Vienna (Austria), helped develop OCT. Now he is co-PI on a 2011-13 grant to Julie Albon, PhD, of Cardiff University, Wales, who applied OCT to detecting and quantifying signs of very early optic nerve damage, before nerve fibers and vision are destroyed.

And that’s just a few of the many NGR grants that have focused on new imaging techniques for glaucoma.

Schuman and Drexler were featured in Ocular Surgery News on October 23. Here are highlights from that review of OCT applications that can be used to detect and manage glaucoma.

• For diagnosis and management of glaucoma, Schuman cited benefits, of OCT over visual field testing that include less discomfort for patients and significantly lower variability than visual fields. However, “that does not mean that visual fields do not have a place [in glaucoma diagnosis and management],” he cautioned.
• He predicted OCT will be able to detect glaucomatous abnormalities prior to current state-of-the-art visual field measurements (called “perimetry”), “and the earlier in the disease that you can detect damage or progression, the more likely it is you are able to prevent further progression with less intensive intervention,” Schuman said.
• The most established use of OCT so far has been for measuring retinal nerve fiber layer (RNFL) thickness, and here Schuman  identified a “tipping point,” or threshold of utility for OCT from 75 micromillimeters, where there is a good correlation between structural thinning of the RNFL and functional loss, down to about 50 or 55 micromillimeters, at which point “OCT is no longer able to measure change in the RNFL thinning, but visual field can be used to measure the progression of glaucoma.”
• “You need to lose about 17% to 20% of nerve tissue before an abnormality is likely to be present on a standard achromatic visual field,” Schuman said, and right now, OCT has achieved that capability. “Pre-perimetric glaucoma can be identified by OCT RNFL thickness with the detectable visual field loss first appearing with RNFL approximately 17% below that expected for healthy eyes,” he and colleagues reported recently in the British Journal of Ophthalmology.
• Drexler pointed to additional benefits gained from the increased speed and sensitivity of OCT. “For glaucoma, that means you can have all the retinal layers properly segmented. You can have access to the choroid. You can visualize the optic disc better, especially in myopic long eyes. You can see the lamina cribrosa properly. You might use this also as a biomarker of early glaucoma changes.”
• Compromised blood flow is believed to be another hallmark of glaucoma. The retina, as one of the most blood- and oxygen-rich tissues in the body, draws blood from its own circulatory system and that of the underlying choroid. Doppler OCT is under investigation as a new method for measuring choroidal blood flow, so far found effective only in larger vessels.
• Other uses envisioned for OCT include “adaptive optics (AO)” that enable real-time, three-dimensional in vivo images of cellular complexes in additional structures of the eye, including photoreceptors, retinal pigment epithelial cells, choriocapillaris, and nerve fiber bundles.  AO OCT can be used for diagnosis, monitoring treatment, and as a surrogate marker of treatment effect in clinical trials through in vivo detection of retinal ganglion cell death (or “apoptosis”), according to Francesca Cordeiro, MD, PhD, of the University of Pittsburgh, another expert interviewed for the article.
• Regarding diagnosis, “The gold standard for glaucoma now is when a [visual field] defect develops, and we know that this could be as much as after 50% of retinal ganglion cells have died. There is a delay of about 10 years between when the disease starts and when it is detected. Hopefully DARC [detection of apoptosing retinal cells] will allow us to pick up the disease 10 years earlier than it is currently possible,” Cordeiro said.

BrightFocus-funded research is part of these exciting developments. Stay tuned for more information.