October 2008




Innovative autofluorescence test lights the way

by Maxine Lipner Senior EyeWorld Contributing Editor



A new spectral biomarker indicates when eyes are under stress

A subtle flash of fluorescent light in the eye may be all that it takes to alert practitioners that patients are in the earliest stages of ocular disease, according to Howard R. Petty, Ph.D., professor of ophthalmology, microbiology, and immunology, Kellogg Eye Center, University of Michigan Medical School, Ann Arbor. In a recent study published in the February 2008 issue of Archives of Ophthalmology, investigators showed an increase in flavoprotein autofluorescence values in patients diagnosed with early pseudotumor cerebri. “There’s autofluorescence that comes off from the eye,” Dr. Petty said. “What we’re doing is we’re looking at a narrow band that corresponds to the emissions characteristics of molecules in the eye that are involved in the electron transport chain.” He deems this band of fluorescence a “spectral-biomarker,” not unlike genetic biomarkers with which practitioners already have familiarity. Investigators here built a special device to measure the autofluorescence. Then, to evaluate how accurately the device could detect vision loss when compared to standard vision tests, they selected patients with very early eye disease who would not have other mitigating factors. While patients with pseudotumor cerebri were used here, these were just test cases, Dr. Petty said. He hopes that the fluorescence seen might point the way to a variety of early eye diseases.

This study evolved out of Dr. Petty’s long-time interest in metabolic autoflorescence together with fellow investigator Victor M. Elner’s, M.D., Ph.D., professor of ophthalmology, University of Michigan Health System, Ann Arbor, interest in apoptosis and its metabolic regulation. In an attempt to see if they could detect any changes in autofluorescence in-vivo, the two chose the relatively pristine eyes of patients with early pseudotumor cerebri. “I was sort of pushing to do glaucoma patients who were pretty far along thinking that we’re going to get some really significant changes,” he said. “But these patients frequently have a lot of other complicating factors.” By contrast, patients with early pseudotumor cerebri were easy to study. “The advantage of these patients is that they’re really pristine from an academic point of view,” Dr. Petty said. “They were really clean because they’re young and they were all females. We just didn’t have that many variables and we were still able to obtain a very robust response.”

Eyes under stress

Patients here had already been seen by another clinician. “Before they were actually treated they came into the clinic and we were doing some photography as an adjunct to their own clinical work up,” Dr. Petty said. While traditional visual field tests indicated either subtle abnormalities or none at all, fluorescent imaging gave a clear picture of eyes under stress. Investigators determined that all of the patients with PTC had higher autofluorescence values in their more severely affected eyes. “We found a reduction in the metabolic activity which was due to cell stress in the retina,” Dr. Petty said. Investigators found that in the more affected eyes, autofluorescence values averaged 60% greater than in the fellow eye. Meanwhile, a healthy control group showed no significant difference in autofluorescence values for either eye. Based upon the autofluorescence data, investigators were also more accurately able to describe the degree of disease in each eye than they could with standard vision tests such as visual fields, visual acuity, and pupillary light response.

Putting practitioners on alert

Dr. Petty is hopeful that this autofluorescence response will foretell any number of eye diseases. “I think that there would be a number of diseases where one would have this sort of metabolic stress in the retina that we’re then able to detect in this way,” he said. “So we hope that it will be useful as a screening device.” He sees the device as likely sounding a very early warning. “In the case of these [pseudotumor cerebri] patients, we were able to detect fairly subtle changes,” he said. “What we hope is that we can detect eye disease very early on, which is not really done that well in ophthalmology.”

Akin to cancer where early detection is stressed for attaining best results, Dr. Petty hopes that the same can prove true for eye disease. “With glaucoma a patient can lose vision before he or she knows there’s an underlying disease,” he said. “I think this might be able to help bring early detection and early intervention into ophthalmology as an important tool.” The autofluorescence test is a general one that would alert ophthalmologists that something is amiss in the eye. “It’s specific for some ongoing underlying disease,” Dr. Petty said. “It could be glaucoma, it could be diabetic retinopathy, we don’t know.” As a screening device it could potentially be used to flag patients with problems and alert practitioners to continue to monitor them. “If nothing else you could make sure to catch the disease at a very early stage,” Dr. Petty said. “Once you’ve lost retinal ganglion cells, you’re not going to get them back.”

Overall, Dr. Petty sees biomarkers such as autofluorescence as playing an important role in the future. “My belief is that biomarkers are going to become more important over time, and I think this will find other applications clinically,” Dr. Petty said. “We’re testing a broad spectrum of diseases now, and hopefully we’ll have a few more papers coming out.”

Editors’ note: Dr. Petty is in discussions with the University of Michigan about forming a company to commercialize this.

Contact information

Petty: 734-647-0384, hpetty@med.umich.edu

Innovative autofluorescence test lights the way Innovative autofluorescence test lights the way
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