FDA panel recommends Hyperion for approval

Approval recommended for diminishing correction in low hyperopes more than 40 years old with stable refraction.

ROCKVILLE, Md. — An advisory panel recommended approval for Sunrise Technologies’ (Fremont, Calif.) Hyperion laser for hyperopia, with a list of suggested conditions and labeling.

The Food and Drug Administration’s (FDA’s) Ophthalmic Devices Panel unanimously voted to recommend approval with conditions Jan. 13. Panelists recommended approval for the temporary correction of hyperopia between 0.75 D and 2.5 D with less than 0.75 D cylinder, where the magnitude of correction diminishes over time. Patients should have stable refraction for 6 months prior to surgery and be at least 40 years old.

Panelists also recommended that the FDA add labeling that there is not enough data to draw conclusions about the efficacy of re-treatments, which could be common because of the regression seen in hyperopic correction. The label also should include data on efficacy compared with the age of patients, who will be age stratified by decade. Older patients typically see more correction.

The FDA will review the Hyperion application and may adopt any or none of the panel’s recommendations.

Public comments

Many refractive surgeons and patients who underwent the procedure spoke about the need for a treatment for hyperopia during an open comment period, during which time the FDA accepts comments from the public.

Refractive surgeon Charles Casebeer, MD, said that while myopes usually can function without glasses, hyperopes cannot. Myopes may improve when they become presbyopic, but hyperopes lose what little uncorrected visual acuity they might have had.

“I’ve always identified the hyperope as a patient in need,” he told the panel.

While various hyperopic procedures all have been discontinued for safety concerns, they all have made the patients happy, he added. Dr. Casebeer leads a group of surgeons studying laser in situ keratomileusis (LASIK) for hyperopia, but he added that LASIK is not as good in applicable ranges as the Hyperion procedure.

Refractive surgeon Charles Kelman, MD, also spoke about his personal experience as a hyperope. He underwent the procedure last year under a special protocol to treat a +4 D refractive error, which is outside the range of correction the panel considered in January.

While contact lenses helped his vision, he said, they do not provide correction overnight, they could drop out of his eye, and they did not provide centration as his eyes converged. Also, he eventually became contact lens intolerant after his eyes dried out.

He added that his vision stabilized since undergoing the Hyperion procedure and that he has not experienced any glare, night vision or photophobia since treatment.

Reversal of fate

In July 1999, the panel unanimously voted not to recommend the Hyperion for approval, saying the effect was not stable. Sunrise changed its labeling request to state the effect diminished over time, and then tried to quantify exactly what that rate was in the labeling.

Douglas Koch, MD, medical monitor for Sunrise’s study, led off the presentation to support the approval.

Researchers reported data on a cohort of 612 eyes in 379 patients. Data included 592 eyes at 1 month postoperatively, which fell to 555 eyes at 6 months, 267 eyes at 18 months and 72 eyes at 24 months.

Dr. Koch said that the mean change in refraction at between 1 week and 1 month was a mean of 0.34 D. The mean change fell to 0.1 D between 3 months and 6 months.

“There’s a more rapid change and then it begins to slow,” he said to the panel. “What this curve signifies is that the rate of change is continuing to decrease throughout the period postoperatively. By 21 months, we’re down to 0.02 D per month of change.”

Researchers wanted to predict the long-range stability by hiring a statistician to create a linear regression model. The model predicted the correction would disappear by 46.2 months. However, Dr. Koch told the panel that the data deviate from the model at 24 months and the 30-month data deviate even more.

“The regression model substantially underestimates the longevity of effect,” Dr. Koch said. (See related article, “New data show LTK stability”.)

Dr. Koch also showed data to the panel to illustrate the near-absence of complications. The procedure incurred no corneal infiltrates or erosions, intraocular pressure (IOP) spikes, late onset of haze or retinal complications.

Patients reported pain in isolated cases. Foreign body sensation occurred in 1.9% of patients at 1 month but dropped below 1% afterward, he said.

The laser did not induce losses of best spectacle corrected visual acuity of more than two lines, and the rate of induced cylinder fell within the FDA’s safety requirement for myopia treatments, he added.

Panel review

The FDA and two primary panel reviewers also analyzed the company’s data and summarized results for the meeting.

According to panelist Walter Stark, MD, one of two primary reviewers, the mean spherical reduction of spherical equivalence was 2.37 D at 1 month. This decreased to 1.84 D at 3 months, 1.54 at 6 months, 1.12 D at 12 months, 0.97 D at 18 months and 0.79 D at 24 months. At 24 months, none of the patients were overcorrected.

Overall, 19% of the patients had 20/40 or better vision preoperatively. This increased to 65% of patients at 1 month postoperatively and 68% of patients at 24 months, Dr. Stark said. By that endpoint, 70% of the cohort had improved by two lines or more of uncorrected visual acuity (UCVA). At 24 months, 55% of patients improved by three lines or more, 46% improved by four lines, and 19% improved by five lines or more.

Treatment effect regressed 0.3 D between postoperative months 1 and 3, by 0.1 D between months 3 and 6 and by 0.02 D between months 18 and 24.

“There does appear to be a progression in the treatment effect of the overall rate of change per month,” he said. “The device appears to be safe and temporarily effective at 24 months.”

The only complication that exceeded the 1% level was foreign body sensation, with 1.9% reported at 1 month.

Safe and effective

At 6 months, 64% of the cohort were within 0.5 D and 87.5% were within 1 D of emmetropia. At 24 months, one-third of eyes still had a reduction of hyperopia greater than or equal to 1 D, and 69% of eyes improved by two or more lines of visual acuity.

“The major concern is that the treatment causes a temporary reduction in hyperopia, with a progressive loss of effectiveness over time,” Dr. Stark said. “With only 72 eyes at 24 months and none beyond that, we do not know when the regression stops or if treatment will regress back to the pretreatment levels. This represents more a labeling issue than a safety issue, unless the patient decides to have another form of treatment, such as hyperopic laser in situ keratomileusis or hyperopic photorefractive keratectomy during the time the cornea is regressing.”

He added that proper labeling will be crucial to ensure the physician and patient realize the reduction of hyperopia is temporary.

“This will be acceptable for some patients, especially those who do not wish to have a surgical procedure in the central aspect of the cornea,” he said.

Regression and accuracy

The second panel reviewer, Joel Sugar, MD, added that because of regression, “The potential for re-treatment becomes of very great significance.”

A table should be included in the labeling so patients can judge the effect based on data. He said that the benefits of LTK were real but limited.

Accuracy measurements showed that 33.3% were within 0.5 D and 62.5% were within 1 D of intended correction. However, Dr. Sugar added, FDA guidelines designed for myopia suggested 50% of patients to be within 0.5 D and 75% within 1 D at stability.

“There’s no point at which stability was established, so it’s hard to assess these. But they certainly do not meet the [myopia] guidelines,” Dr. Sugar said. The FDA currently has no such guidelines for hyperopia.

What is in a word?

Panelists then debated over how the labeling should reflect that advice, and most agreed that the word “temporary” should play a significant role in the labeling.

Panelist Mark A. Bullimore, MCOptom, PhD, said, “I’d like to see ‘temporary’ in there, and I’d like to see it as the first or second word.”

Non-voting panelist and consumer representative Lynn Morris said that the loss of effect over time “is a huge implication on a patient whether to have a procedure.”

However, panelists also agreed that the word temporary could be construed to mean that all patients lose the effect of LTK over time. Panelist Michael G. Harris, OD, JD, said that some effect of LTK was retained by some patients throughout the follow-up period.

Dr. Sugar voiced the opinion of panel members who were concerned about calling LTK temporary.

“The use of the word temporary is a bit strong for the data presented,” he said.

Final arguments

Dr. Koch used the time allotted to his final arguments to respond to the characterization that the effect was “temporary.”

He said that evaluations at the 5-year point showed persistent corneal changes and that the effect was not temporary. “There is a distinction that we’d like to put forth,” he said.

Sunrise investigator R. Doyle Stulting, MD, PhD, added that the word temporary, “implies the effect disappears completely in all cases.”

Unoperated patients more than 40 years old also experience hyperopic changes as they age, he added.

“All procedures regress, and to single out this one as temporary is misleading,” he said.

Sunrise president and chief executive officer C. Russell Trenary III conducted an impromptu press conference at the FDA building immediately after the panel meeting. He said he welcomed the challenge of marketing the procedure as having a “temporary” effect.

“We may have difficulty supporting the notion with data that it’s a temporary treatment if people believe that the word ‘temporary’ means that the entire effect goes away,” he said.

However, the panel tried to quantify the rate of regression, he added.

“We are completely in favor of patients having a complete understanding of what all the options are for the treatment of whatever their refraction is. We eagerly look forward to competing in that environment,” he said.

All laser refractive treatments regress, and hyperopia treatments regress more than myopia.

“If the doctor and the patient have a complete ability to balance the risks of all of the procedures versus the benefits of all of the procedures, we believe we have the premier option for the treatment of hyperopia,” Mr. Trenary said.