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Mechanisms and Monitoring: New Thinking on Glaucoma
Measuring intraocular pressures alone may be less useful in some glaucoma suspects than evaluating their sensitivity to any pressure. As this notion grows stronger, the technologies for monitoring optic disc changes are gathering more attention.
Imaging technologies that can assess glaucomatous changes in the optic nerve have been available for 15 years. But as evidence of the instruments’ predictive powers continues to emerge, the new technologies are finding a home in the day-to-day practice of glaucoma management, as well as playing a role in the management of other optic neuropathies.
“A reasonable literature review now shows that instruments that image the retinal nerve fiber layer or optic disc can provide predictive data on which patients with high pressures will develop glaucoma and perhaps which patients with suspected glaucoma under the threshold of detection will go on to develop clinical disease,” said Christopher A. Girkin, MD, professor of ophthalmology and director of the glaucoma service at the University of Alabama at Birmingham.
The currently available instruments’ value in following progression of optic nerve damage over time is less clear. “These technologies are good at separating healthy eyes from eyes that are unhealthy and may have glaucoma,” said Robert N. Weinreb, MD, professor of ophthalmology and director of the Hamilton Glaucoma Center at the University of California, San Diego. “The challenge for all of them is to demonstrate and have validated their use in clinical practice for detecting progression.”
Progression software has been developed and validated for confocal scanning laser tomography (Heidelberg Retina Tomograph, or HRT) and is under development for scanning laser polarimetry with variable corneal compensation (GDx VCC) and optical coherence tomography (OCT).
Imaging for Today and Tomorrow
Joel S. Schuman, MD, professor and chairman of ophthalmology at the University of Pittsburgh, noted that the available devices measure different aspects of the ocular tissue but perform in a similar fashion. Each has high reproducibility.
Value beyond glaucoma. “I have access to all three instruments, and I longitudinally follow patients with forms of optic neuropathy other than glaucoma. I personally have found OCT to be quite a useful adjunct to the clinical exam and visual field testing,” said Larry P. Frohman, MD, professor of ophthalmology and neurosciences at the University of Medicine & Dentistry of New Jersey. “I have a sense that when we are following people over time it is fairly reproducible. It seems to be correlating with what we expect to see in terms of functional deficits in the patients. We are using it in conditions such as demyelinating disease, and compressive tumors such as meningiomas and pituitary adenomas,” Dr. Frohman added. “I think it might be a particularly helpful adjunct in cases of intrinsic optic nerve tumors that we need to follow over long periods, such as the optic nerve glioma—pilocytic astrocytoma—of neurofibromatosis I, using visual fields as our marker of early disease progression. We would like to see if this technology might point out progressive nerve fiber layer loss, which might make us consider instituting therapy before field loss is seen. And it is a useful technology for following optic neuropathy in those who cannot reliably peform visual fields,” said Dr. Frohman.
The next big thing. Ultrahigh-resolution OCT (UHR-OCT) is expected to be a significant advance in monitoring glaucoma progression. The instrument measures the wavelengths of light that are reflected back to the detector. This enables UHR-OCT to measure the tissue much more quickly—about 60 times faster—than conventional OCT. The high speed allows more data to be acquired much more quickly.
“This technology will allow us to create 3-D data sets, and that will enable us to know exactly where a particular OCT image is taken in the fundus,” Dr. Schuman said. “We’ll be able to precisely register the OCT from one visit to the next. We expect that this will improve our reproducibility and sensitivity and specificity of measurement, but that remains to be proven.”
For now, UHR-OCT is being used in only a few academic research centers, Dr. Weinreb noted, adding that he believes the technology offers “tremendous promise in diagnosing glaucoma as well as in detecting progression.”
Impact on Clinical Practice
The commercially available imaging technologies are being used primarily in a predictive fashion. The mounting evidence supporting their value in this regard appears to be bolstering physicians’ comfort level with the technology.
According to Dr. Girkin, the instruments are helping to redefine glaucoma suspects and ocular hypertensives. “In the Zangwill study1 using OHTS baseline data, there was a much higher chance that a patient with a glaucomatous-appearing HRT using Moorfields Regression Analysis would develop visual field defects,” Dr. Girkin said. “The study showed a really strong negative predictive value, and as the data go out longer, it should just get better. It’s becoming more and more valid to add HRT into the calculation of risk in ocular hypertensives.”
Dr. Girkin remarked that even a year ago he just used photos and relied very little on imaging instruments. “The instruments have been out for more than 10 years, but there have been no data on them,” he said. “It’s only in the last few years that enough predictive data have emerged that will allow you to know what a finding means. So that’s actually a big change.”
Finding the right tool for the job. With a glaucoma suspect, he takes simultaneous stereophotos and obtains SITA (Swedish interacting thresholding algorithm) standard visual fields if the photos are normal. Depending on his level of suspicion, he may order one of the specialized functional tests like short wavelength automated perimetry (SWAP). “If the nerve fiber layer is really crisp and visible, and the patient has cupping and a larger disc, I just leave it at a visual field test,” Dr. Girkin said. “But if I can’t see the nerve fiber layer well, I might get an OCT or GDx or both. It depends on the patient and what I can’t see in that patient.”
Does having these quantitative tests change the threshold for treatment? Dr. Schuman said the imaging technologies do help guide therapy, and they can help the clinician cinch a diagnosis without having to repeat the visual function tests multiple times. “If I see a very subtle abnormality on a visual field test––maybe even one that isn’t outside normal limits—and I find a correspondence with the ocular structure, such as thinning of the neural retinal rim or thinning of the retinal nerve fiber layer, I will often treat that patient.”
Like all instrumentation, these monitoring devices are only as good as the individuals who perform and interpret the tests. Drs. Schuman and Weinreb pointed out several potential pitfalls. “It’s not unusual to see patients who were referred to us because they have had a change in one of the instrument-based measures, but their clinical exam has not changed,” Dr. Weinreb said. “In some cases, the instruments are detecting disease or progression of disease at an earlier stage than is possible with the clinical exam. But more often the interpretation of the measurements is incorrect, or errors were made in acquiring the images.”
Artifact in, artifact out. These errors can lead to untimely treatment. “When you obtain an imaging study on a patient, you need to be certain that the quality of that study is adequate to be analyzed and that the analysis is performed properly before drawing any clinical conclusions,” Dr. Schuman said. “The user has to evaluate the test, and there are a variety of quality indices for the different tests.” On HRT, he said, the standard deviation should be less than 30. GDx has a quality number, which should be 8 or greater. With OCT, it’s signal strength, which should be 6 or higher.
“Look at the images,” Dr. Schuman continued. “If the GDx is an atypical scan, the data should not be accepted. If an HRT shows movement artifact, for example, don’t trust the data on that scan. In an OCT image that shows areas of signal dropout or regions where the analysis algorithm has failed, the images should not be trusted.” Dr. Schuman and colleagues recently published a handbook called Everyday OCT,2 which educates the user on how to obtain high-quality images and how to evaluate the images for clinical use.
Still no match for clinical skill. It’s easy to become enamored of technology, but clinical skill and low-tech exams remain important. “At the current time, I use the imaging technologies as an adjunct to my clinical examination of the optic nerve,” Dr. Weinreb said.
According to Dr. Schuman, “Physicians should always use the technology to bring them back to the patient. If the imaging test reveals an area of abnormality, I encourage physicians to go back to the clinical exam and try to see the indicated abnormality in the patient’s eye. You can almost always see it once it has been pointed out on the test. The imaging findings should never be accepted in a vacuum. The physician should use the imaging information together with the functional testing results to evaluate structure-function correspondence, which is also important.”
2 Schuman, J. S. et al. Everyday OCT: A Handbook for Clinicians and Technicians (Thorofare, N.J.: Slack Inc., 2007).