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Genetics, objective perimetry on the horizon for early glaucoma diagnosis
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Most practitioners are familiar with the laser-based retinal imaging systems that are now frequently used when attempting to diagnose glaucoma. However, these techniques all share a common limitation, said Charles M. Wormington, PhD, OD, FAAO, associate professor of biophysics and optometry at the Pennsylvania College of Optometry. The normal variations of the optic disc and retinal nerve fiber layer parameters make it difficult to diagnose a glaucomatous eye in the early stages.
“There’s a large variation among normals in terms of the size and shape of the disc and in the numbers of the ganglion cell fibers,” Dr. Wormington told Primary Care Optometry News. “Because of that, it’s going to be hard for any of these techniques to definitively and sensitively identify glaucoma early on. You can have a patient who has a fairly large number of fibers, on the high side of normal, and if he or she lost one third of those, you wouldn’t necessarily be able to detect it because it’s still in the normal range. If you had taken the measurement earlier, when the patient was seemingly normal, and followed him or her, then you could probably catch it because most of these techniques have a significantly high probability of being useful for progression analysis as opposed to early detection.”
Now, cutting-edge new technologies that are a far cry from the standard visual field test are currently in the research stages and are preparing to take glaucoma testing to an entirely new level.
DNA gene chips
With reports indicating that three genes associated with causing glaucoma have been identified, genetics is on its way to becoming a front-runner in the early detection of normal-tension, primary open-angle and primary congenital glaucoma. “Once you identify the gene, you can identify who in the population has a mutation in that particular gene,” Dr. Wormington said. “The emerging technology to come into our offices in the future will be DNA microarrays or DNA gene chips.”
A small sample of blood, such as a finger prick, will be tested by the chip to see if a patient possesses any of the gene mutations that would make him or her more susceptible to glaucoma, he said. “Eventually, that will assist in the early detection of primary open-angle glaucoma,” Dr. Wormington said. “The gene chips can also then help determine how you’re going to manage patients. If patients have a susceptibility gene, then you’ll see them more often than you would see a normal patient who does not exhibit a mutation in that gene. New genes, as they are discovered, will lead researchers to new drugs. Drug discovery, which will also be aided by the gene chips, will progress faster because of the identification of those genes.”
While some commercially available DNA gene chips are already used in ophthalmic disease, chips for glaucoma detection will soon be available and will be in practitioners’ offices within the next 10 years, Dr. Wormington said.
“Right now, if you suspected that a patient had a susceptibility gene, you’d have to draw the blood and then have it sent to one of the university labs,” he noted. “As each gene and its associated mutations are found, it will be feasible to begin to screen the population for various genes. It’s not common practice now, but it is the wave of the future for assessing patients.”
Researchers are on the verge of identifying another five genes that have been located on the chromosomes, Dr. Wormington said.
Machine learning classifiers
Machine learning classifiers are another advancement on the horizon. These are a neural network analysis of visual field data in which a special program installed into an existing perimeter can identify glaucomatous types of visual fields. According to Dr. Wormington, the GDx (Laser Diagnostic Technologies, San Diego) already has this type of analysis incorporated into it.
Multifocal objective perimetry
While most perimeters require patients to inform the practitioner when they see a flash of light during the visual field test, multifocal objective perimetry records patients’ neurological recognition of light flashes. Using electrodes attached to the back of the head and the ear, for example, the practitioner then shines a light in the patient’s eye at various positions on the retina, and the perimeter can assess visual fields and identify glaucomatous visual field defects.
“So you’re performing perimetry in that sense, but the patient doesn’t have to click a button saying he or she saw a light,” Dr. Wormington said. “You’re measuring the visual-evoked response from the occipital lobe, and by doing that, you can then see how certain areas of the visual field respond objectively.”
Dr. Wormington said that a number of papers have discussed this technique’s potential for early identification of defects, including contrast sensitivity using these multifocal visual-evoked responses. The procedure, which is still evolving in the research stages, is fairly quick and causes no discomfort to the patient — with the possible exception of attaching the electrodes, which results in mild abrasion of the skin.
Comparing new technologies
Just as it is difficult to compare existing glaucoma diagnosis technologies, Dr. Wormington said it is equally difficult to speculate on which of the new technologies is the most promising. He is hopeful about the potential role of DNA gene chips in early diagnosis, which is crucial in preventing the development and subsequent progression of the disease.
“With some genes, a mutation will always result in development of the disease,” he said. “In most cases, though, the patient may have a mutation and never develop the disease. So it relates more to risk or susceptibility for developing the disease, which relates to how closely you’re going to follow patients. If they have a susceptibility gene for glaucoma, you decide that you’re going to see them every 6 months as opposed to every year or two.”
Dr. Wormington said that multifocal objective perimetry will require additional labs to confirm that it can help detect glaucoma earlier than conventional perimetry, in order to expand the knowledge base. Machine learning classifiers, as well, will benefit from more research before other companies will follow suit and use the system in their current perimeters.
“All of these machines and technologies are providing doctors with risk factors; most of them cannot definitively indicate that a particular person has glaucoma,” he said. “There is such promise with the measurement techniques, because it seems clear that there can be damage to the optic nerve and retinal nerve fiber layer earlier than the visual field data can indicate damage.”
For Your Information:
- Charles M. Wormington, PhD, OD, FAAO, is associate professor of biophysics and optometry at the Pennsylvania College of Optometry. He may be reached at 8360 Old York Rd., Elkins Park, PA 19027; (215) 780-1371; fax: (215) 780-1254; e-mail: cwormington@pco.edu. Dr. Wormington has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.