Precision medicine: Tracking glaucoma progression

Measures of structure and function change can help ophthalmologists individualize treatment of glaucoma patients, according to Robert Chang, MD, assistant professor of ophthalmology, Stanford University.

Since glaucoma progresses faster in some patients than others, optical coherence tomography (OCT) and visual field progression analysis can be more useful than IOP in guiding treatment decisions, said Dr. Chang during the Glaucoma Symposium CME at the 2016 Glaucoma 360 meeting. 

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“I use structure and function glaucoma progression analysis to really customize therapy over a lifetime,” he said. “That’s my method of precision medicine in treating glaucoma patients today.”

Concept of precision medicine has gotten attention in recent years, he said, citing the Precision Medicine Initiative presented by President Barack Obama in his 2015 State of the Union address. The initiative calls on health care providers to take into consideration genetic, lifestyle, and environmental factors to tailor treatments to individual patients.

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“How are we going to apply precision medicine when we don’t have much genetic data and we don’t know what the patient’s environmental effects are?” Dr. Chang asked. “Maybe there aren’t any specifically for glaucoma.”

Considerations

The answer to treating glaucoma starts with preserving ganglion cells as long as the patient lives, he said. Clinicians must take into consideration the rate that the disease is progressing in each patient in order to choose a treatment that strikes the right balance between probable efficacy and the risk of adverse reactions.

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“We need something quantitative,” he said, “not just looking at the nerve or asking them how their vision is doing.”

OCT-guided progression analysis in early stages of glaucoma and visual field progression analysis in later stages can provide the data to monitor progression, he said. OCT is highly repeatable, so clinicians can compare a patient’s status to baseline measurements. And visual field index can be calculated against the patient’s age.

For example, he said, the Zeiss Forum Glaucoma Workplace (Carl Zeiss Meditec) displays visual field baselines against current visual fields, highlighting event-based analysis and trends.

Useful information

“Everyone should know that there is no age-related loss progression correction on these OCT calculations,” Dr. Chang said. “On average, age-related loss is about 2-3 µm every decade or 0.2 µm per year,” he said.

In some patients, the disease may progress very slowly, he said. He cited the Canadian Glaucoma Study (Arch Ophthalmol. 2010;128(10):1249-1255), in which 216 patients were followed up at 4-month intervals with perimetry and were monitored for progression.

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The patients who reached an end point based on total deviation analysis underwent 20% or greater reduction in IOP. The researchers found that median mean deviation rate in progressing patients prior to the first end point was − 0.35dB/y.

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Dr. Chang recalled a patient he had followed for about 5 years and was “very noncompliant.” At baseline, the patient’s untreated IOP was a maximum of 32 mm Hg, he said. The patient refused surgery, so Dr. Chang was “almost just documenting the natural course of disease.” Interestingly the patient’s right eye did not progress as fast as the right, despite high pressure in both.

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The structural changes generally precede the functional changes, he said. But eventually if a patient loses a certain amount of nerve fiber layer, the patient will experience a visual field defect.

How can clinicians make use of this information? Dr. Chang pointed out that more glaucoma treatments are available than in the past. Ophthalmologists have to decide whether to prescribe medications, perform conventional surgery, or implant a minimally invasive glaucoma surgery (MIGS) device.

Peronsalized progression

“While we have a lot of studies, major trials that give us the target range pressures, it may not be the absolute value of the pressure that you should reach for in every single patient,” said Dr. Chang. “But instead, start looking at what their individualized rates of progressions are over time.”

He pointed out that glaucoma doesn’t change overnight. It might be worthwhile to “sacrifice a few neurons” to avoid subjecting patients to a treatment that may cause side effects, he said. “What we’re really getting at here is their personalized rate of progression.”

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He uses a grid to figure out what treatment might work best, and to present it to the patient. On the left column is “high-efficacy, but high side-effects” treatments, like filtering surgery. On the right is “watchful waiting.” In between are treatments with medium efficacy and medium risk. The faster the patient’s disease is progressing, the farther the left the patient belongs, and vice versa.

Dr. Chang still sets initial target pressures, and he lowers the patient’s pressure if he thinks the patient’s condition is deteriorating. “That’s what I’m focusing on, using visual fields maximally… to know are they getting a little bit worse therefore I’m going to think about all the new treatments available.”

Robert Chang, MD

Dr. Chang disclosed that he does research for Carl Zeiss Meditec.