Last year, European regulatory agencies pulled several models of angle-supported phakic intraocular lenses from the market in response to reports of unreasonable amounts of endothelial cell loss. This move gave surgeons everywhere pause, and caused them to take a hard look at the phakic lenses they were using. To help inform you about the safety profile of the phakic lenses we currently use in the United States, as well as a new lens we may be using in the next year or so, here's a look at what the prospective studies have to say.

 

Europe Pulls AS-IOLs

Corneal endothelial cell density is one of the issues that the U.S. Food and Drug Administration watches carefully with these lenses, and has been a problem with some devices, such as the phakic anterior chamber angle-supported IOLs.

The concerns began after the release of a 2006 Ophthalmology article that retrospectively analyzed 100 eyes of 66 angle-supported phakic IOL patients who had to have their lenses explanted at the practice of the article's first author, Jorge Alio, of Alicante, Spain. He found 64 of them (64 percent) were removed due to cataract formation, but that 24 (24 percent) had to be explanted as a result of endothelial cell loss.1 Most of the cell loss occurred with the Baikoff ZB5M IOL. Though cataract is, of course, a problem, the cell loss was perhaps even more serious, since our ability to treat it isn't as simple as performing phaco and can lead to a more significant loss of vision that can't be easily recovered. This data was compounded by a subsequent study published in February 2007 that outlined problems with the ZB5M lens. The article found a 10.6-percent reduction of endothelial cell density in the first year following implantation, with a mean loss of 1.78 percent per year thereafter, and that the losses continued over 12 years of follow-up.2

Phakic lenses that are approved in the United States, such as the AMO Verisyse (above), have shown a trend toward stable endothelial cell counts.

In response to this, the European regulatory authorities, with France acting first, ordered the withdrawal of angle-supported phakic lenses pending further investigation of these continuous cell losses. A retrospective study was subsequently performed in several centers in France that confirmed the high incidence of endothelial complications two to three years postop. In the study, of 2,300 implants, 27 (1 percent) were removed due to significant loss, emphasizing the need for long-term monitoring of angle-supported phakic lenses, since most of the losses occurred at three to four years postop.

 

Current and Future Lenses

In all of the clinical trials for the phakic lenses currently available in the United States, the posterior chamber Visian (Staar) and the iris-fixated Verisyse (AMO) have shown excellent efficacy in terms of visual acuity, gain in best-corrected vision, predictability and other visual measurements. Since these lenses are much more similar than they are different in terms of efficacy, safety becomes a key issue when deciding which lens is best for a particular patient. Central to this safety question is the idea that there's a "time in service" risk, meaning the length of time these lenses remain in the eye may have some bearing on the cumulative risk of complications over time, such as cataract formation and endothelial damage.

The Staar Visian sits in the posterior chamber, and, if the location of the implant in relation to the cornea is related to mechanical cell loss, one might presume the Visian's location helps avoid endothelial damage.

After three years of follow-up, cumulative cell loss with the Visian is just under 9 percent, and seems to be hitting a plateau at 12.5 percent between four and five years. So, there does appear to be cell loss associated with the actual surgical implantation, but whether or not this loss progresses is a question we can't definitively answer yet. However, we remain optimistic about the endothelial health post-Visian implantation, and will continue to monitor it going forward.

The iris-fixated Verisyse lens sits in an intermediate position between the angle and the posterior chamber. It's not in direct apposition to the angle or the peripheral cornea, therefore, simply based on location alone, it presumably may have a risk profile between that of an angle-supported lens and a posterior-chamber IOL.

Based on data from Mainz, Germany's H. Burkhard Dick, MD, that was used as part of the U.S. FDA clinical trial for the Verisyse, there is a cumulative cell loss that's virtually identical to that posted by the Visian. After three years, it was 9.6 percent, with a continuous loss of 1.7 percent between two and three years.

Overall, though it appears there's a trend toward stabilization in endothelial cell density over time with these two lenses, the numbers currently aren't large enough to prove anything at a statistically significant level. Therefore, we'll continue to watch these cells carefully. Many of us feel these lenses remain a reasonable alternative for certain patients. In fact, they continue to show increased use, demonstrating surgeons' confidence.

Finally, there is yet another version of angle-supported lens in the pipeline, the Alcon AcrySof anterior chamber angle-supported phakic lens, of which I am an investigator in the United States. The AcrySof phakic lens has completed U.S. Phase III trials, and has also been studied in Europe. Alcon is now in the process of analyzing its data and deciding how to proceed with the regulatory process.

The cell densities with the AcrySof lens have been quite good. The data reported in both the two- and three-year studies from Europe and early results from the United States suggest that the endothelial cell loss is quite low and doesn't appear to be problematic. In a pooled data set of the European and Canadian Phase III and the United States Phase II studies, at six months the AcrySof angle-supported lens shows an acute loss of 3.48 ±8.38 percent in the central endothelial cell density (n=318) and a 2.98 ±8.49-percent loss in peripheral cell density (n=314). These losses are most likely attributable to the implantation of the lenses. From six months to two years, the Phase II multicenter U.S. trial shows an annual average gain of 1.33 percent in central endothelial cell density per year (n=45), and an average gain of 0.8 percent in peripheral cell density per year (n=45). These counts are encouraging, though we'll continue to watch them.

What all of this means, in light of the trend toward implanting more of these lenses, is that continuous monitoring of endothelial cell density is now a must. We'll remain cautiously optimistic about the future of these IOLs, and will pass on what we learn about them to patients so they can make the most informed decision about their potential surgeries. 

 

Dr. Vukich is director of the Davis Duehr Dean Center for Refractive Surgery in Madison.

 

1. Alió JL, Abdelrahman AM, Javaloy J, et al. Angle-supported anterior chamber phakic intraocular lens explantation causes and outcome. Ophthalmology 2006;113:12:2213-20.

2. Javaloy J, Alió JL, Iradier MT, et al. Outcomes of ZB5M angle-supported anterior chamber phakic intraocular lenses at 12 years. J Refract Surg 2007;23:2:147-58.