Late complications show vigilance still needed in IOL manufacturing, testing

Longer premarket evaluation period may be needed as late-onset opacifications are reported, IOL experts say.

Issue: November 1, 2001

Figure 1: Breakdown of PMMA optic material has been seen in lenses implanted 10 years ago and more.
Figure 2: Hydroxapatite calcification is seen in this explanted Hydroview IOL.
Figure 3: Complete opacity of the IOL optic is seen in this lens from MDR.
Figure 4: Opacity of the optic and haptic is seen in this IOL from OII.

ALL FIGURES COURTESY DAVID J. APPLE, MD, LILIANA WERNER, MD, PHD, AND SURESH K. PANDEY, MD.

CHARLESTON, S.C. — Longer premarket evaluation of IOLs may be called for in light of late-onset opacifications in several IOL designs that have been noted recently.

“The complications that are now surfacing are in general different from most that occurred during the early years of IOLs,” said David J. Apple, MD, and colleagues Liliana Werner, MD, PhD, and Suresh K. Pandey, MD, of the Storm Eye Institute here.

The three ophthalmologists and researchers, who have extensive experience in analysis of IOL explants and pseudophakic human eyes obtained postmortem, recently wrote an editorial on the subject that appeared in Archives of Ophthalmology.

The researchers said they have documented late complications and to date have studied 106 explants related to IOL biomaterial opacification from four and probably as many as eight different manufacturers, pending final and definitive pathological studies.

Their editorial in Archives focused on IOL models from three manufacturers. In this article they add a fourth.

“In the 1970s and 1980s, most complications were based on faulty IOL designs and manufacture. Those described here are opacifications that usually became evident clinically 1 or more years postoperatively. This raises the question of what quality controls should be required and what duration of premarket studies should be enforced in initial evaluations as IOLs are introduced,” the researchers told Ocular Surgery News. The routine success of cataract/IOL surgery may cause complacency and overconfidence among some surgeons, manufacturers and regulators, they said.

“As even better devices and techniques have evolved in the fields of cataract and refractive surgery, the vigilance and oversight regarding the basic cataract/IOL operation seem to have diminished,” they stated. “Attention has shifted in some instances to refractive devices and techniques as they are enthusiastically introduced, thus requiring increased resources for systematic evaluation.”

Based on their research in the field since 1983, “we would have hoped that potentially severe IOL-induced problems such as these we are now seeing would have been eradicated at least by the beginning of the 1990s,” the researchers said. “The continuous occurrences of such complications makes it clear that modern IOLs are not perfect.”

As they said in their earlier Archives editorial, “Complications such as optic opacification should not be occurring in the year 2001!”

Late PMMA surprise

The researchers recently described breakdown of PMMA optic material in IOLs implanted 10 years ago and more. Dr. Apple and colleagues are aware of at least 25 cases of this condition that they have designated “snowflake” IOL optic degeneration. Of these they have examined 13 in their laboratory at the Center for Research on Ocular Therapeutics and Biodevices at the Medical University of South Carolina. One-third of the lenses were manufactured by Ioptex Research in the 1980s and early 1990s.

The researchers said this is at least a partial vindication of skeptical ophthalmologists who in the 1970s and early 1980s warned about possible long-term complications, especially with untested IOL materials.

“To our knowledge, this is the first systemic clinico-pathological documentation of an in situ degradation of PMMA. PMMA has been and remains a tried-and-true material for fabrication of rigid IOLs since Harold Ridley’s first implant was performed in 1949-1950,” they said.

The first clinical observation of this type of PMMA lens opacification was brought to their attention by David Davis, MD, who submitted clinical photos to the researchers and published them in Ocular Surgery News, July 15, 1993, issue. The first explant of an affected IOL was sent to Dr. Apple’s lab by Jean Campbell, MD, of the Mayo Clinic.

“This process appears to be a breakdown of the of PMMA polymer chains within the substance of the PMMA optic biomaterial,” the researchers said. It is likely that several thousand of these PMMA IOL styles have been implanted over the past 20 years.

“It is therefore probable that this newly recognized material breakdown would be seen even more often, except for the fact that many patients who received these IOLs are probably now deceased,” they said.

Hydroview and hydroxyapatite

Bausch & Lomb has undertaken a diligent search for the cause of hydroxapatite calcification that Dr. Apple’s group and others have noted in a small number of its Hydroview IOLs. (See related article, "Researchers: source of Hydroview IOL calcification found".)

Dr. Werner and colleagues published the first clinico-pathological analysis of this complication, verifying the nature of the surface calcium depositions. The first clinical report of this calcification was published in the same issue of Archives that contains the editorial by Dr. Apple and coworkers.

Silicone from a sealing gasket in the IOL packaging has been suggested by the manufacturer as a likely cause of the lens calcification. The lens manufacturer now believes the problem is resolved. However, “final verification will require a careful 1- to 2-year clinical study,” the researchers noted.

The Hydroview has been approved by several regulatory agencies and implanted extensively outside the United States. Of approximately 400,000 lenses implanted worldwide, the calcification has been reported in only 301 cases.

In the cases reported to date, opacification appeared at 1 to 2 years postoperatively. In advanced stages it obscured the posterior capsule and fundus, the researchers said.

“The opacifications described in these reports have an entirely different appearance than classic posterior capsular opacification or anterior lens epithelial cell proliferation,” the authors stated. The calcification is resistant to Nd:YAG lasering, unlike classic posterior capsular opacification, they noted.

The evidence to date indicates that only specific lots of these IOLs were affected, thus suggesting a manufacturing alternative.

Two hydrophilic designs

“There are two other IOL models that have been distributed widely outside the United States that have been shown to demonstrate a severe opacification within the optic material,” said Dr. Apple and colleagues. “In some cases the opacity progressed to a degree that we have not previously seen in more than 9,000 explanted IOLs accessioned in our laboratory over the course of 17 years. In some cases, the entire optical component (and occasionally the haptics) are completely opaque,” they said.

These lenses include the SC60B-OUV model manufactured by Medical Developmental Research (MDR) and the Aqua-Sense design manufactured by Ophthalmic Innovations International (OII).

Dr. Apple and coworkers are aware of several hundred cases of lens opacification in the MDR IOL and have tested 40 of these explants.

“Calcium deposits within the substance of the IOL biomaterial and possible degeneration of the UV filtration material are characteristic of the problem,” they said. They have accessioned only four of the OII lens, but are aware of “many other” clinical cases, the researchers said. The pathological alteration appears to be identical with both lenses, they said.

“It is possible that a problem may have occurred in the polymer manufacture, but we were not in a position to evaluate that,” they said.

It is not possible to elucidate the exact pathogenesis of the calcification process in each of the three foldable IOL models described here, the researchers said, but they did not observe any specific problem with the IOL manufacturing technique. The polymer biomaterial for the MDR IOLs was manufactured by Vista Optics of London. The manufacturer has found a new source for the polymer. One to 2 years of clinical testing will be required to confirm that the problem has been resolved, the researchers said.

For Your Information:
David J. Apple, MD, Liliana Werner, MD, and Suresh K. Pandey, MD, can be reached at the Storm Eye Institute, 167 Ashley Ave, Charlleston, SC 29425; (843) 792-2760; fax: (843) 792-7920.
References:
Apple DJ, Werner L. Newly recognized complications of posterior chamber intraocular lenses. Arch Ophthalmol. 2001;119:581-582.

Yu AKF. Shek TWH. Hydroxyapatite formation on implanted hydrogel intraocular lenses. Arch Ophthalmol. 2001;119:611-614.
Werner L, Apple DJ, et al. Postoperative deposition of calcium on the surfaces of a hydrogel intraocular lens. Ophthalmology. 2000;107:2179-2185.
Frohn A, Dick HB, et al. Eintrubungen bei Acryllinsen Typ SC60B-OUV der Firma MDR. Ophthalmo-Chirurge. 2000;12:173-175.
Werner L, Apple DJ, et al. Dense opacification of the optical component of a hydrophilic acrylic intraocular lens: a clinicopathological analysis of 9 explanted lenses. J Cataract Refract Surg. 2001; 27:1485-1492.
Apple DJ, Werner L, et al. Deposits on the optical surfaces of Hydroview intraocular lenses (letter). J Cataract Refract Surg. 2000;26:796-797.