2016 Thomson & Chambers - Editorial Good Ideas Gone Bad: The MIRAgel Saga

Het Editorial van Thompson en Chambers in hun ‘Good Ideas Gone Bad: The MIRAgel Saga’ haakt in op het artikel van Crama en Klevering 2016. De auteurs vermelden wat er precies aan de hand is geweest en waar het fout is gegaan: MIRAgel is te kort getest en te gretig op de markt gebracht.

The article by Crama and Klevering (see p. 32) makes important observations about significant long-term complications of hydrogel episcleral implants (MIRAgel; MIRA, Inc., Waltham, MA) used as scleral buckles in 467 eyes. This is the largest series reported of the complications of MIRAgel implants and illustrates how these implants swell slowly, eventually creating orbital masses, extraocular motility disorders, buckle exposure, and intraocular complications. The enlargement of the MIRAgel scleral buckle increased progressively, so patients did not experience problems until 5 to 10 years after their retinal detachment repair. The story of MIRAgel implants illustrates the limitations of establishing the safety of any new drug or device because long-term studies are usually unavailable at the time the product is first proposed for marketing. Hydrogel scleral buckles were marketed first in the 1980s and were developed to try to improve on prior scleral buckle materials. Initial studies claimed long-term safety of the implants with follow-up of 2 years.1 Before the introduction of MIRAgel devices, scleral buckles were composed of silicone sponges or silicone rubber designed to be sutured to the external sclera or within the sclera. MIRAgel instead is a sponge-like material. These sponge-like buckles were promising because the pores in the sponge were hydrophilic and could store an antiinfective agent if soaked in the anti-infective solution before implantation. It was believed that this could help reduce the incidence of scleral buckle infections. It was known that the buckle would swell a little after surgery, and thus increase the buckling effect, which was believed to be desirable because theoretically it helped keep the retina reattached. MIRAgel scleral buckles are part of a group of products that were allowed to be marketed in the 1980s because they were considered to be substantially equivalent to products on the market before the enactment of the Food Drug and Cosmetic Act’s Device Amendments. Many of these devices were implanted in the late 1980s, but reports of problems with MIRAgel implants generally were not recognized until 5 years or more after their implantation. Numerous additional adverse event reports of progressive swelling of MIRAgel implants were received by the Food and Drug Administration in 1995 and 1996. In 1996, MIRA changed the material used for their buckles. The MIRAgel buckles are not the only example of what seemed like promising ophthalmic devices creating unrecognized late complications. Other examples of this problem, although never approved, were the use of an epikeratophakia lens and the iris clip lens.
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Food and Drug Administration regulators continually face this challenge. Longer studies can provide additional safety and efficacy information, but longer studies are more costly and delay the availability of promising new therapies. Carefully controlled studies can be designed to limit potential injuries to a small number of patients who have received informed consent; but the relatively small number of patients in a clinical trial makes it impossible to identify rare events.5 When approval occurs, approval of a product permits wider access to the therapy, but puts more patients at risk of injury. Ultimately, a balance must be struck that permits a product to be approved, but with a margin of risk.
It is important for ophthalmologists who pride themselves on being on the cutting edge of new technology to ask some important questions whenever a new drug, device, or procedure is available. First, is the new treatment truly superior to existing treatments? If existing treatments have a high success rate with low complications, ophthalmologists should be more wary of the new products until long-term results are available. The experiences with MIRAgel scleral buckles, epikeratophakia, iris clip IOLs, and other products also emphasize the importance of extended postmarket surveillance for new products. The approval process for surgical devices and drugs by the Food and Drug Administration in the United States and regulatory bodies in other parts of the world typically rest on the results of clinical trials lasting 1 to 2 years. If a new product results in complications that do not appear for several years, it is essential for ophthalmologists to report these complications to the manufacturer, in the scientific literature, and to regulatory agencies. These reports of complications can be collated to obtain a more accurate picture of the safety and efficacy profile of the new products. Diligent reporting of long-term complications should help identify when good ideas go bad and to promote the use of the most effective and safe products to our patients.