Improvements in detecting and measuring glaucoma round out 2015

Reviewed by Robert Ritch, MD

As 2015 progressed, researchers reported better ways to detect glaucoma, measure the damage it is causing, and understand how that damage is affecting their patients’ lives. No single innovation revolutionized the profession, but a wide range of technologies became more available to clinicians.

Electrophysiology

One of the newest diagnostic measures becoming available to clinicians is the use of visual evoked potentials (VEP) and electroretinography (ERG). These two techniques, collectively known as electrophysiology, can help account for unexplained scores on visual field examinations in patients whose IOP is normal and whose retinal nerve fiber layer also appears normal.

VEP uses sensors placed on the patient’s head to track electrical activity from the retina to the visual cortex. The amplitude of the signal reveals the number of healthy retinal cells and the patient’s ability to discriminate between different-sized objects. In the clinic, low-contrast VEP protocol could help identify patients who have normal achromatic perimetry, but structural abnormalities consistent with glaucoma.

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ERG also detects the size and speed of the electrical signal, but through the retinal ganglion cells rather than the optic nerve. ERG results can detect early states of glaucoma before the onset of visual field defects and before retinal nerve fiber loss shows up on optical coherence tomography (OCT).

Researchers have used these techniques for a long time, but the size and expense of the equipment made it impractical for use in private practice. Now some manufacturers are bringing this technology to the clinic. Diopsys has led the pack with its Nova cart system. And in November, the company launched its Argos, intended to provide the same visual electrophysiology suite in a tabletop version. 

Contrast sensitivity

Contrast sensitivity, too, is making strides.  Researchers at Wills Eye Hospital at Jefferson Medical College in Philadelphia have developed the Spaeth/Richman contrast sensitivity test (SPARCS), which can be used through the internet making it available to patients at home.

In a study reported in January, these researchers showed the test could detect patients with glaucoma with 79% sensitivity and 93% specificity, which compares well to accuracy of the Pelli-Robson, a standard method of measuring contrast sensitivity. Because of its high reproducibility, the SPARCS could also measure disease progression in an individual patient.

Monitoring changes in IOP over the course of a day can also yield useful findings. The Sensimed Triggerfish uses a soft disposable silicone contact lens with an embedded micro-sensor to capture spontaneous circumferential changes at the corneoscleral area. In May, researchers reported that the system compared well to the pneumatonometer and may be practical for detecting sleep-induced IOP changes. 

Relative afferent pupillary defect

Relative afferent pupillary defect

Another way of measuring damage in glaucoma is the relative afferent papillary defect (RAPD). It is particularly important in detecting asymmetric damage and it is closely associated with visual field changes, ophthalmoscopically apparent disc damage, and reduction of retinal nerve fiber layer (RNFL) thickness. An RAPD may even precede visual field changes.

Traditionally, ophthalmologists have used the swinging flashlight method to detect a relative afferent papillary defect.

Konan Medica developed the RAPDx, which uses a digital, high-definition, infrared camera with eye-tracking and automated blink detection technology. The RAPDx presents light stimuli to the eye and plots the pupil response curve as a graph. It also provides values to compare the amplitude of maximum constriction and latency of constriction onset between the two eyes.

In a study published in June, researchers compared the swinging flashlight method, the magnified-assisted swinging flashlight method and the RAPDx. While the RAPDx had higher sensitivity, it had lower specificity in detecting mean deviation (MD), cup to disc ratio (CDR), disc damage likelihood scale (DDLS), and retinal nerve fiber layer (RNFL) asymmetry.

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Swept-source OCT

Though optical coherence tomography (OCT) is not new to 2015, researchers throughout the year reported new applications for it in glaucoma. Both Fourier-domain OCT (otherwise known as spectral-domain OCT) and the newer, more powerful, swept-source OCT are allowing them to analyze anatomy for early glaucoma warning signs.

In one study published in June, high correlations between FD-OCT retinal nerve fiber layer maps and photography in RNFL defects were reported, suggesting FD-OCT can detect localized glaucomatous RNFL damage.

Joel Schuman, MD, chairman of ophthalmology at the University of Pittsburgh, believes one of the most promising applications is to examine the lamina cribrosa because it is where injury is initiated in glaucoma.

“You can quantify the relevant parameters using this noninvasive noncontact quick technique,” he said. “You can look not only at the shape of the lamina but also its microstructure.”

By raising the pressure of the lamina cribosa, researchers hope to learn about the health of the optic nerve, Dr. Schuman said. “Is this patient likely to be a fast progresser or a slow progresser? The lamina cribrosa is where we believe injury is initiated in glaucoma.”

Links to other diseases

Links to other diseases

These powerful imaging techniques are also allowing researchers to examine the intriguing links between glaucoma and other neurological disorders. A review published in September found that the average RNFL thickness loss is 11 μm in Alzheimer’s disease, and 7 μm in multiple sclerosis patients.

“I see glaucoma as a brain disease, not an eye disease,” said Robert Ritch, MD, surgeon director emeritus and chief of Glaucoma Services at The New York Eye and Ear Infirmary of Mount Sinai in New York.

One of the connections he is investigating is the relationship of cerebrospinal fluid pressure. In a study published in May, he and his colleagues outlined evidence that cerebrospinal fluid pressure could be associated with glaucomatous optic neuropathy in normal-pressure glaucoma. But not enough is known yet about measuring cerebral spinal fluid pressure, particularly noninvasively, to make it useful in diagnosis, he said.

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He is also heavily involved in working out the mechanisms and new approaches to treatment of exfoliation syndrome, the most common identifiable cause of open angle glaucoma worldwide. For the past 3 years, the annual Optic Nerve Rescue and Regeneration Think Tank of The Glaucoma Foundation has focused on exfoliation syndrome, as has its pilot grant program, resulting in a quadrupling of the number of people involved in research on exfoliation syndrome, which is a disorder with numerous systemic associations.

Working groups have been established in genomics, animal models, cellular mechanisms of production, and biomarkers. Two genes involved in the disease, LOXL1 and CACNA1A have been described and more are being sought. Lysosomal dysfunction and impaired autophagy have been implicated as a disease process.

Researchers do not believe these genetic defects cause glaucoma directly, but they may combine with environmental factors to bring it about. If researchers can pin these relationships, Dr. Ritch said, clinicians of the future may not only be able to catch the disease early but prevent, reverse, or even cure it.

Performance Centered Portable Test

Performance Centered Portable Test

After diagnosis of glaucoma, clinicians must help patients figure out the extent functional vision loss is affecting their ability to carry out the tasks of daily living. Clinicians have long relied on standard automated perimetry (SAP) to measure visual function loss, but the technique requires trained technicians. Its cost, complexity, and lack of portability make it hard to use in primary care settings or in underserved populations.

As an alternative, researchers at the University of California, San Diego, designed an application for the Apple iPad tablet, the PERCEPT.  For a study published in October, the screen displayed a small orange dot with a black rim in the center of the screen, followed by a central tumbling E and a peripheral Gabor patch in eight different locations, which occurred simultaneously and for the same duration of time but were independent of each other.

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The researchers asked the subjects to identify the orientation of the tumbling E and the location of the Gabor patch using the touch screen. More tests followed with decreasing presentation time. The researchers also collected driving records for the subjects, and asked them to fill out a questionnaire about their driving habits and the number of times they had fallen over the past year.

The PERCEPT results correlated well with SAP results and with patients’ history of vehicle crashes and falls. The correlation was stronger than the Useful Field of View test (UFOV, Visual Awareness), which has been used to assess visual processing speed in different conditions, the authors reported. 

Robert Ritch, MD

e: ritchmd@earthlink.net

Dr. Ritch reported financial relationships with the following: Aeon Astron, iSonic Medical, Ocular Instruments Inc., Sensimed, Diopsys Inc., GLIA LLC, Guardion Health Sciences, and Mobius Therapeutics.

Joel Schuman, MD

e: schumanis@upmc.edu

Dr. Schuman did not indicate any financial interest relevant to the subject matter.