Imaging Eyes Before Damage Becomes Irreversible

Laird Harrison

October 17, 2019

SAN FRANCISCO — A new imaging technique can detect stress in mitochondria, allowing physicians to catch eye diseases and test treatments years before other signs or symptoms appear.

With a modification to a fundus camera, clinicians can measure the fluorescence of flavoproteins, which increases before the irreversible cell damage seen in patients with glaucoma, macular degeneration, and many other eye diseases, said Richard Rosen, MD, from the Icahn School of Medicine at Mount Sinai in New York City.

"It's a noninvasive way of monitoring the health of tissue," he told Medscape Medical News.

Flavorprotein fluorescence analysis differs from other imaging systems, such as optical coherence tomography (OCT), because it shows what is happening inside cells before damage becomes irreversible.

"It's substructural information, which makes it very exciting," Rosen said here at the American Academy of Ophthalmology 2019 Annual Meeting, where he presented studies on the technique. "OCT is just starting to show us glimmers of things inside the cell."

OcuMet, a startup headquartered in Ann Arbor, Michigan, is working to commercialize a camera that can measure this fluorescence. Development of the technology began after it was determined that certain pressures — such as hyperglycemia, aging, environmental factors, and increased intraocular pressure — cause oxidative stress on mitochondria.

It's a noninvasive way of monitoring the health of tissue.

Stress on the mitochondria affects the entire cell; eventually, cell membranes decompensate, causing apoptosis. When mitochondrial flavoproteins are oxidized, their enzymes become electron-poor and susceptible to excitation by blue light. After exposure to blue light, the electrons fall back to their original state, emitting green fluorescence.

Researchers have measured increases in retinal and optic nerve flavoprotein fluorescence in patients with diabetes, diabetic retinopathy, central serous retinopathy, age-related macular degeneration, idiopathic intercranial hypertension, and glaucoma.

"It's an indication of whether the tissue is under attack, so we may be able to use this as a very early marker," Rosen said.

To test this theory, Rosen and his colleagues conducted a study in which they measured the fluorescence of the full retinal thickness in 38 eyes with various stages of primary open-angle glaucoma, 16 eyes with ocular hypertension, and 32 control eyes.

They used OCT to measure the thickness of the retinal ganglion cell-plus (RGC+) layer.

In patients with ocular hypertension, macular flavoprotein fluorescence was significantly elevated (P < .05) and there was an increase in the ratio of flavoprotein fluorescence to RGC+ thickness (< .01).

Macular flavoprotein fluorescence was not significantly higher in patients with glaucoma than in control subjects (= .24), but the ratio of this fluorescence to macular RGC+ thickness was significantly higher (< .001). In addition, an increase in flavoprotein fluorescence was correlated with age and with disease stage in the eyes of glaucoma patients.

In a study presented last year at the American Geriatrics Society Annual Scientific Meeting, Rosen and his team tested whether a combination of over-the-counter nutritional supplements could reverse this sign of mitochondrial damage. They assigned seven patients to a combination of curcumin, Ginkgo biloba extract, citicoline, coenzyme Q10, N-acetylcysteine, alpha-lipoic acid, grape-seed extract, and green-tea extract (GlaucoHealth, Guardion Health Sciences), and seven patients to placebo.

After a month, flavoprotein fluorescence dropped a significant 38.78% in the supplement group (P = .003), but only 15.54% in the placebo group (P = 0.47).

In a study of eight patients with diabetic retinopathy and diabetic macular edema, a correlation was shown between a decrease in flavoprotein fluorescence and improvement in best-corrected visual acuity after treatment with vascular endothelial growth-factor (VEGF) inhibitors

The technology is "potentially really interesting," said Sunir Garg, MD, from the Wills Eye Hospital in Philadelphia.

He said he could also envision using it to check for early warning signs of retinal damage related to hydroxychloroquine, a drug used to treat rheumatoid arthritis and lupus.

"This technology would be ideal for macular degeneration," he told Medscape Medical News. "But it's maybe not that useful right now because the image quality is not as good or reliable as you might hope."

American Academy of Ophthalmology (AAO) 2019 Annual Meeting. Presented October 12, 2019.

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