麻豆传媒

STOCKHOLM -- A form of low-level light to stimulate cellular energy production achieved durable improvement in visual acuity in early-intermediate geographic atrophy (GA), a multicenter, sham-control study showed.

Patients randomized to photobiomodulation (PBM) had a five- to six-letter improvement in best corrected visual acuity (BCVA) at 12 and 24 months. Most patients in the control group had a decrease in BCVA, and twice as many had developed GA at 2 years.

The difference between the two groups translated into a 53% reduction in the hazard ratio for a >5-letter loss, reported Eleonora Lad, MD, PhD, of Duke University in Durham, North Carolina, at the American Society of Retina Specialists meeting.

"What I like is that 18.7% of the photobiomodulation eyes responded with more than a 10-letter gain, with a mean of 13.4," said Lad. "More patients lost BCVA in the sham group compared with photobiomodulation at both timepoints...Cox proportional analysis showed a significant reduction in the hazard ratio for BCVA vision loss and onset of new GA with photobiomodulation. The study accomplished a favorable safety profile. There were no signs of phototoxicity or deterioration."

A phase IIIb open-label trial of PBM has already begun and will have findings through 13 months of follow-up, she added.

During a discussion that followed the talk, co-moderator Raj Maturi, MD, of the Midwest Eye Institute in Indianapolis, called the results impressive and expressed surprise in the vision gain in intermediate-risk GA. "Did the patients with intermediate AMD [age-related macular degeneration] have significant loss of vision [prior to treatment]?"

Eligibility criteria included a Snellen equivalent of 20/32 to 20/100, and the treatment has a "ceiling effect," said Lad, "so that patients with better vision did not improve that much because they don't have the opportunity to do so."

"We understand that in intermediate AMD, the photoreceptors change," she continued. "Some of these patients have extensive EZ [ellipsoid zone] loss overlaying large drusen. I think this is where there's an opportunity to intervene therapeutically."

Deval Joshi, MD, of the Joshi Eye Institute in Boynton Beach, Florida, asked about the scope-of-practice and business implications of PBM. "There have been some pretty aggressive maneuvers in the U.S. with regard to use of light by optometrists. Is this something that is planned to be broadly marketed when it comes to the U.S., as far as treatment for dry AMD?"

Lad replied, "We're assuming this could have broad penetrance in the intermediate dry AMD population. I think a lot of patients would be interested. The business model is still to be determined in the United States. It works well in Europe, where people can easily walk into the retina specialist's office and get this done, but it does involve frequent treatments. We have to figure out how to apply this in the U.S., perhaps even home use. The jury's still out."

Several speakers noted that GA is almost always vision loss. Joshi quipped, "I think I had to pinch myself when I saw an increase in visual acuity for dry AMD."

Maturi asked whether Lad already uses PBM in clinical practice. She said some of her own patients have asked when PBM will be FDA approved and where can they find PBM treatment. The technology currently is in Europe and approved in South America.

PBM is the application of low-level light wavelengths to a specific area of tissue to . Specifically, the mechanism of action involves absorption of photons by cytochrome C oxidase in the mitochondria of the target tissue. PBM also induces sustained cellular changes by activating transcription factors. Wavelengths are selected on the basis of the cellular targets and their relative importance in AMD, said Lad.

Investigators in the trial enrolled patients ages ≥50 with BCVA between 20/32 and 20/100 and randomized them 2:1 to PBM or sham, which consisted of a modified light application. Patients attended nine treatment sessions every 3 to 5 weeks for 20 months, with follow-up at 24 months.

Data analysis included 100 patients and 144 treated eyes. The primary outcome was the difference in BCVA between the PBM and sham control group. The 13-month results were reported previously, and Lad presented the final 24-month findings.

The results showed that the PBM arm achieved statistically significant superiority over the control group during the first month (P<0.05) and reached a maximal difference at 9 months (P<0.001), which was maintained throughout 24 months. The hazard ratio for >5-letter vision loss showed a significant advantage for PBM at the end of the study (P=0.02).

By month 24, 58.2% of PBM-treated eyes had a >5-letter gain in BCVA and a mean of 8.5, 18.7% had a >10-letter improvement and 13.4-letter mean, and 5.5% of patients had a >15-letter gain and mean of 16.6 letters.

New-onset GA occurred in five of 50 sham-treated eyes versus one of 87 eyes treated with PBM at 13 months (P=0.024). By 24 months, the sham group had 12 (24.0%) new cases of GA as compared with six (6.8%) in the PBM arm (P=0.007).

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