OCT takes on increased role in glaucoma assessment

Use of ophthalmic imaging for detecting glaucoma is rising as use of visual field testing is declining. But it is too soon to fully make the switch in technology, experts say, because optical coherence tomography should be viewed as another tool in the kit instead of a replacement when it comes to assessing glaucomatous progression.

“For glaucoma detection, OCT is definitely ready for prime time,” OSN Glaucoma Board Member Joel S. Schuman, MD, FACS, one of the originators of the technology, said. “It is something that we can use to identify the presence or absence of disease. It is probably the most useful information of any single parameter as to whether or not glaucoma is present.”

But, he said, it is not yet proven to detect progression because it lacks normative databases and longitudinal studies that would confirm correspondence between what is seen on OCT and what is detected by visual fields, the current gold standard of care.

“OCT is extremely helpful in detecting the presence or absence of glaucoma,” Schuman said. “It can be very helpful in detecting progression of glaucoma. But for progression, at this time, we need other supporting evidence for progression to say that real change has occurred.”

Teresa C. Chen, MD, who is an associate professor of ophthalmology at Harvard Medical School and practices at the Massachusetts Eye and Ear Infirmary Glaucoma Service, said that the relative lack of longitudinal 3-D imaging data adds to the difficulty in deciding how to interpret spectral domain OCT findings. As a part of the Spectral Domain Optical Coherence Tomography in Glaucoma Study, her clinic is gathering data on more than 1,000 patients and seeking 5 years of follow-up on patients to address that point.

“In the next few years, we’ll have better data that can tell us how to use these newer 3-D imaging tests for the care of glaucoma patients,” Chen said. “There will be better guidelines in the future as we get better data from studies in glaucoma patients. [OCT is] a good supplemental tool that adds to the clinical exam and other test results.”

Growing use of OCT

Despite Schuman’s caveat, it seems that eye care clinicians are increasingly adopting imaging assessments over visual field exams.

“It may be OCT. It may be the confocal scanning laser ophthalmoscope, like the Heidelberg Retina Tomograph, or scanning laser polarimetry,” Schuman said. “But OCT is very broadly used and is continuing to be deployed at a rapid rate globally.”

From 2001 to 2009, ophthalmic imaging increased dramatically as visual field testing declined considerably, Stein and colleagues said in Ophthalmology. But the authors expressed concerns that imaging in lieu of visual field testing may hurt patients because imaging has not yet proven to be better than visual fields at detecting open-angle glaucoma or disease progression for all patients.

To assess trends in the use of ancillary diagnostic tests in the evaluation of patients with open-angle glaucoma and glaucoma suspects, the researchers conducted a retrospective, longitudinal cohort analysis of nearly 170,000 individuals with open-angle glaucoma and nearly 400,000 individuals with suspected glaucoma enrolled in a U.S. managed care network between 2001 and 2009.

Claims data showed the odds of patients with open-angle glaucoma undergoing visual field testing decreased by 36% from 2001 to 2005, by 12% from 2005 to 2009, and by 44% for the entire time span of 2001 to 2009. At the same time, the odds of having other ophthalmic imaging increased by 100% from 2001 to 2005, by 24% from 2005 to 2009, and by 147% for the entire time span of 2001 to 2009.

Among patients cared for exclusively by optometrists, visual field testing decreased from 66% in 2001 to 44% in 2009, compared with patients seen exclusively by ophthalmologists, for whom visual field testing decreased from 65% in 2001 to 51% in 2009. Other ophthalmic imaging increased from 26% in 2001 to 47% in 2009 for patients of optometrists and from 30% in 2001 to 46% in 2009 for patients of ophthalmologists.

A tipping point occurred in 2008, the researchers said, when patients with open-angle glaucoma receiving care exclusively by optometrists were more likely to undergo imaging than visual field testing.

Uncertainty of changes

David Huang, MD, PhD, was one of the original inventors of OCT as a graduate student at MIT. He built an early prototype and, with Schuman, did the first retinal imaging in the laboratory.

“OCT tends to be more sensitive in early glaucoma and visual fields more so in later stages of glaucoma,” Huang said. “But both are valuable. If you just have a few time points over a couple years, often you can catch change on one and on the other you don’t. But the longer the patient progresses, the more the two converge.”

Schuman noted that there is less certainty about OCT as a tool for definitively assessing glaucoma progression. Abnormalities seen with OCT “occur out of step with changes occurring on the visual field. So we’ll often see a change in the OCT prior to the occurrence of a visual field defect or a visual field change. But sometimes it’s the other way around,” he said.

His hypothesis and current research interests consider changes in the nerve fiber layer that occur sometime before the change in the visual field — perhaps a year or two, perhaps longer, he said.

“When you see those changes occurring asynchronously, what we’re really seeing is a prior effect of glaucoma damage that already is in these sectors affected, and changes showing up on the OCT will be future change on the visual field,” he hypothesized. “That is controversial. And it’s controversial because we don’t know for sure that one necessarily reflects the other.”

Larger studies over longer periods of time will determine whether this is true, Schuman said.

Pearls and pitfalls

When Schuman is deciding whether a patient has glaucoma, he considers the region of the defect. A pattern superiorly or inferior temporally suggests glaucoma, he said. If the ganglion cell complex is abnormal in a way that matches the nerve fiber layer, then that is an internal correspondence suggesting that the abnormality is real, even if there is no visual field defect. This is called pre-perimetric glaucoma.

“The clinician needs to be the most careful in diagnosing those patients,” Schuman said. “If they have other abnormalities that make you think that the patient might have glaucoma — that they have a history, that they have significant risk factors or high intraocular pressure — that’s going to sway you toward making the diagnosis in the presence of an OCT abnormality without a visual field abnormality.”

Clinicians need to make sure that the quality of the scan and analysis is adequate before accepting the OCT results.

“A poor-quality scan can give you bad or incorrect information,” Schuman said. “You’re dealing with a garbage-in, garbage-out problem.”

Huang noted that at the very low end of signal strength, the nerve fiber layer begins to look thinner. Depending upon the system, images with a loss of signal of 35 to 45 out of 100 are not as reliable.

“It’s common sense that you have to look at the images for the quality of the image processing that outlines the inner and outer borders of the nerve fiber layer,” Huang said. “You still want to look at the image to make sure the image is not cropped. Sometimes the top of the nerve fiber layer might be cut off because the position of the OCT system was a little cut off when the image was taken.”

Donald L. Budenz, MD, MPH, of the University of North Carolina in Chapel Hill, said that in some cases, a weak signal might produce false positive results.

“I always encourage clinicians to get at least three OCT scans when doing this sort of analysis, so they can take into account small variations that might lead to misdiagnosis,” he said.

The correspondence that clinicians think confirms a diagnosis might not be enough. If a clinician sees corresponding changes between the visual field exam and the OCT, then it is likely that the change is real, Schuman said.

“But it may be that the person who has corresponding change occurring on both OCT and visual field will actually go on to have stronger visual field loss in the corresponding area because the OCT may actually be predicting visual field damage as opposed to corresponding damage that is occurring today,” Schuman said.

Huang said that high IOP can affect nerve fiber layer measurements.

“It’s an elastic response,” he said. “If you have a balloon and you blow it up harder, the balloon is going to be a little bit bigger and the wall is going to be thinner by a small amount. When the pressure is higher, the layers look slightly thinner because the balloon is slightly larger.”

If longitudinally, the pressure is within a couple of mm Hg, it is not a significant effect. But, Huang said, “If someone’s nerve fiber layer looks thinner than a year ago but their pressure is 4 mm Hg higher, you may want to take that into account.”

Budenz laid out the importance of variability during a 2012 joint meeting of the American Glaucoma Society and the U.S. Food and Drug Administration: The smaller the variability, the less likelihood of mischaracterizing people as having glaucoma on a single examination and the more precision in diagnosing progression.

It is important to know test-retest variability rates for different OCT machines, he said. For example, if all a physician knew was that measurements changed from exam one to exam two by five units, the physician might believe that the patient has progressed with glaucoma. However, if the variability of the test between exams is 14 units, then a test change of 5 units between exams becomes insignificant, whereas if the variability is 4 units, 5 units starts to look like change.

“We might suspect that this is real change, rather than just the normal noise of the instrument,” Budenz said.

Next-generation devices

Current OCT systems run between 17 KHz and 40 KHz, faster than previous generations but not as fast as the next generation of machines, which could run between 70 KHz and 100 KHz, Huang said. The faster speeds offer the potential of new measurements.

“We are now able to look at the nerve fiber layer as a map over a wider area,” Huang said. “As the analysis of that improves, there will be an improvement in diagnostic accuracy and the ability to track small changes over the long run.”

Faster processors and 3-D scans over a wider area will improve the ability to detect focal changes, Huang said. Measuring changes over a small area is more difficult, but newer technology will offer better sampling and better position tracking.

This year, Huang will finish the Advanced Imaging for Glaucoma Study, which is sponsored by the National Eye Institute. He hopes to publish results for mapping the ganglion cell complex, which may help catch more cases of glaucoma earlier.

In addition, Huang has been taking advantage of faster scanning speeds to look at optic nerve head blood flow using OCT angiography and to look at total retinal blood flow with Doppler OCT. He has found that these perfusion measurements correlate better with visual field function than with nerve fiber layer thickness and other structural measurements. Thus, the new functional OCT technology has the potential to further improve glaucoma diagnosis and tracking. – by Ryan DuBosar

What are the public health implications for OCT screening for glaucoma?

OCT needs to meet screening criteria

OCT has to meet certain criteria to have a role in widespread glaucoma screening.

There are well-known criteria for mass screening. The disease should be common and serious, as we know glaucoma is. The screening test should be highly accurate. The natural history needs to be understood, there needs to be acceptable resources for treatment, and the treatment should favorably influence outcomes.

One of the problems that we have had with glaucoma is that it is not very prevalent in the general population in the U.S.; it is around 2%.

Sensitivity and specificity are very important for looking at the validity of the test, and it is the positive predictive value — the probability that a label of “positive” is actually a true case — that determines whether the screening program will be cost effective.

The Agency for Healthcare Research and Quality Screening for Glaucoma: Comparative Effectiveness report issued in 2012 said that there really is no one test or group of tests that would be suitable for screening for glaucoma, including OCT.

Considerations for screening with any device include not only how good the device is, but also whether the device is transportable and durable. You do not want it falling apart when you put it in a van and take it out for mass screenings in the general population.

In addition, you want it to be usable with a standard wall outlet. You want it to be rapid. You want to have few poor quality scans. You want it to be relatively inexpensive so that community groups can afford it and use it. You want those lay people to be able to understand what the results mean and then refer those patients who fail borderline tests to appropriate clinical offices for evaluation.

Anne L. Coleman, MD, PhD, is the Fran and Ray Stark Professor of Ophthalmology and Epidemiology at the University of California-Los Angeles Jules Stein Eye Institute. Disclosure: Coleman has no relevant financial disclosures.

Reference:
http://effectivehealthcare.ahrq.gov/ehc/products/182/1025/CER59_GlaucomaScreening_executive
summary.pdf.

Questions arise as imaging devices are integrated

As ocular imaging devices have been integrated into clinical practices, public health considerations have emerged: Do these devices have adequate sensitivity and specificity? How valuable are these tests at identifying patients with glaucoma? Do patients from minority racial–ethnic groups have access to these technological innovations?

From a public health perspective, mischaracterizing patients as having glaucoma when they do not can result in unnecessary patient fear and anxiety, interventions, treatments, side effects and costs. Likewise, mischaracterizing patients as being disease-free when they do have glaucoma can result in the patient’s false sense of security, making follow-up care less likely until damage has occurred.

In the future, I hope to see the normative databases for ocular imaging devices expanded, with inclusion of larger numbers and improved diversity of patients. It is also important for device companies to fully disclose the number and characteristics of patients in their normative databases.

There needs to be improved compatibility between OCT devices and models so patients can be longitudinally monitored for glaucoma progression, even when using different equipment. It is essential that the output from devices be open source so providers can extract individual data elements and integrate them into electronic health records.

All patients should have access to technological innovations, regardless of their race or ethnicity, education level, socioeconomic status and geographic location. And providers need to be educated on the strengths and limitations of ocular imaging devices — how they can be an excellent adjunct to, but not a replacement for, some of the more traditional tests for glaucoma.

Joshua D. Stein, MD, MS, an Assistant Professor of Ophthalmology and Visual Sciences, specializes in glaucoma at the University of Michigan W.K. Kellogg Eye Center. Disclosure: Stein has no relevant financial disclosures.