Beyond retinal nerve fiber layer loss: What optical imaging can tell us

TAKE HOME

Taking a deeper look at several imaging technology which have advanced optical imaging.

Dr. KupersmithBy Michelle Dalton, ELS; Reviewed by Mark J. Kupersmith, MD

New York-These days, it’s commonplace to use optical coherence tomography (OCT) to measure retinal nerve fiber layer (RNFL) thinning with optic nerve injury, due to glaucoma, optic neuritis, ischemic optic neuropathy, and to determine disease progression and the effects of therapy.

At the 2014 American Academy of Ophthalmology meeting, Mark J. Kupersmith, MD, delivered the 2014 Hoyt Lecture, concentrating on some of his earlier findings in optical imaging studies. Dr. Kupersmith discussed his interest in neuro-ophthalmology, and how far imaging has come since his resident days.

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Other methods of optical imaging, polarimetry and applied optics, are either less commonly used or in development.

These and other techniques “can show injury to peripapillary retinal axons and ganglion cells before the RNFL is thinned and can be used to increase the intensity of therapy or serve as an objective outcome or biomarker in treatment trials,” said Dr. Kupersmith, director of neuro-ophthalmology, Institute of Neurology and Neurosurgery, at Mount Sinai, New York, and the chief of service of neuro-ophthalmology at New York Eye and Ear. “Like most neuro-ophthalmologists and glaucoma specialists, I am always interested in identifying changes in the optic nerve that can be used to monitor the effects of treatment, so-called biomarkers, or those that might suggest permanent injury that would not improve with an intensive or invasive therapy.

Dr. Kupersmith, through his work with many collaborators, looked at diseases that cause optic nerve injury, including optic neuritis related to multiple sclerosis, or ischemic optic neuropathy, or optic nerve damage from chronic papilledema, among others.

“All of those disorders result in either one-time or progressive visual loss,” Dr. Kupersmith said. “We're looking at therapies to try to prevent the subsequent vision loss when someone presents, or try to reverse the visual loss.”

To date, no neuroprotective drug has been proven efficacious in humans. “But when they are available, the question is, how are you going to study it?” he asked, and answers, “Imaging.”

Optic neuritis

As early as 1972, studies (red free photography) showed axonal loss in the RNFL despite visual recovery in optic neuritis, Dr. Kupersmith said.

“What would be predictive of having a bad outcome at presentation? We looked at the original optic neuritis treatment trial data, and we found there was nothing in the baseline vision studies that could distinguish those eyes that would recover from those that would to do poorly,” he said. Optical imaging results confirmed the evidence provided by vision studies, that the 1 month time frame was crucial, as the amount of visual or residual vision loss or loss of RNFL at 1 month was predictive of the propensity for recovery.

But by the end of that first month, “sometimes it seemed to be too late,” he said; axonal loss may not be recognized early due to RNFL swelling.

“We realize now that if we look at optical coherence tomography (OCT) of the ganglion cell layer in the macula at baseline, it may look okay but by 2 weeks we can start to see the loss of ganglion cells in optic neuritis,” Dr. Kupersmith said. Spectral-domain OCT helped confirm the early loss in optic neuritis and his group found “a similar, but more profound loss, in ischemic optic neuropathy.”

Scanning laser polarimetry

Scanning laser polarimetry (SLP) is based on a different type of bio-physics than OCT, Dr. Kupersmith said. “It's based on the fact that the nerve fiber layer is polarized, due to having intact neural filaments.”

If a pathological process, such as ischemia, causes irreversible injury to a group of axons, “the peripapillary RNFL and affected retina could lose neural filaments acutely and, lo and behold, at presentation patients with anterior ischemic optic neuropathy show a loss of birefringence in the areas that are most affected,” he said.

But, he laments, the SLP technology is somewhat outdated and hasn’t been updated because most clinicians, groups and departments will only purchase one new imaging device and the flexibility of the OCT outweighs the SLP, he said.

“SLP only looks at the nerve fiber layer, so it’s limited to use in glaucoma and other optic neuropathies, and has fallen out of favor because favor. Thus the business decision is not to put money into furthering that technology,” he said. Ideally, using this type of technology to notice a change in birefringence in optic neuritis or neuromyelitis optica would be helpful, but it is currently not possible with today’s “crude technology.”

Idiopathic intracranial hypertension (IIH)

Although an uncommon illness, “it’s associated being a woman and obesity,” Dr. Kupersmith said, and after making “all kinds of adjustments on the imaging programs we use” on OCT, his group found a dynamic shape changes of the neural canal that occurs in “the optic nerve that no one ever suspected was possible. Prior work in glaucoma suggested the increased pressure in the eye resulted in shape change of the optic nerve head only after patients lost a tremendous amount of neural and lamina tissue,” he said. But with IIH, observing pressure arising from outside the eye, “it turns out the optic nerve head shape changes tremendously and quickly.” His group quickly developed some hypotheses on the relationship between the shape of the optic nerve head and how that reflects changes in intracranial pressure.

“There’s a complex relationship between the pressure in the subarachnoid space behind the eye and the intraocular pressure that has implications for the changes in the optic nerve relative to glaucoma,” he said.

A new study will evaluate if patients with IIH and visual field loss will have early ganglion cell loss and if that relates to later visual loss or poor recovery.

“Our study will investigate patients with moderate to severe loss due to papilledema in a randomized trial comparing surgeries and medication,” he said.

“I’m not a tech person. I’m not an OCT expert,” Dr. Kupersmith said. “I'm a clinician, and I have questions that relate to current and future patient care. I have to find the best way I can to answer them and optical imaging may provide some of the needed tools.”

Mark J. Kupersmith, MD

E: mkuper@chpnet.org

Dr. Kupersmith did not indicate a proprietary interest in the subject matter.