Intraocular lens opacification: What have we learned so far

"Wisdom is not a product of schooling but of the lifelong attempt to acquire it." —Albert Einstein Cataract surgery, the most commonly performed surgical procedure, has had an interesting and illustrious history. The earliest reference to "cataract surgery" in the form of couching dates back 3000 years to the ancient Indian text of Mahābhārata. However, the major development in surgical techniques and intraocular lenses (IOLs) have taken place only in the last 60 years. On November 29, 1949, Harold Ridley implanted the first IOL. This lens was made of ICI's Transpex I, a high-quality version of poly(methyl methacrylate) (PMMA), manufactured by Rayner Intraocular Lenses Ltd.1 However, Ridley was uncertain that the lens implantation was stable and so removed the IOL and reinserted it definitively, as a secondary procedure on February 8, 1950, when the eye had healed and become quiet.2 This marked the beginning of a major change in the practice of ophthalmology. By the late 1970s IOLs and implantation procedures had undergone many improvements, and Ridley's invention had become an accepted option for the optical correction of aphakia. While PMMA was the material of choice for the earlier generation of IOLs, it had its disadvantages in that being a rigid material (water content <1%) it required a large incision for the lens implantation. Also, one of the major drivers for progress in IOL materials and technology was the introduction of small-incision cataract surgery and phacoemulsification by Charles Kelman in 1967. Foldable IOLs were designed and introduced in the 1980s and 1990s with the introduction of silicone and acrylic polymers. Acrylic IOLs are manufactured from a wide variety of co-polymers that vary in their refractive indexes, water content, glass-transition temperatures, and surface properties. Hydrophobic acrylic IOLs have very low water content (<1%) compared with the hydrophilic or hydrogel IOLs whose water content varies from 18% to 38%.3 Although the first silicone IOL implantation in human eyes was reported in 1983,4 the U.S. Food and Drug Administration granted regulatory approval for a 3-piece silicone IOL in 1990.5 One of the earliest reports of IOL discolouration dates to 1991 when Milauskas reported brown discoloration and central haze in silicone IOLs.6 As it was considered clinically insignificant IOL explantation was not performed. It was speculated that the brown haze was due to light scatter from water vapour that may have diffused into the silicone optic when immersed in an aqueous medium.7 Since then opacification of silicone IOLs has been associated with systemic medications like amiadorone8 and rifanbutin,9 ocular conditions like the use of silicone oil for retinal surgery,10 and the presence of asteroid hyalosis.11 In subsequent studies the team from Intermountain Ocular Research Center (Salt Lake City, Utah, USA) have elegantly demonstrated that the opacification of silicone IOLs is caused by the deposition of calcium and phosphate on the posterior aspect of the silicone optic and that the presence of asteroid hyalosis is a potential risk factor.12,13 Improvements in material chemistry saw the introduction of foldable acrylic IOLs in the 1980s. By substituting the side chains on the PMMA molecule with hydroxyethyl or polyethyl groups the manufacturers were able to create a flexible clear acrylic IOL that could be folded or injected into the eye. Depending on the side chain chemistry the water content of these IOLs varies from <1% (hydrophobic) to about 38% (hydrophilic). However, reports on surface precipitates on hydrogel (hydrophilic) IOLs began to emerge in the early 1990s.14,15 Bucher et al. in 1995 reported the first late opacification of a hydrogel IOL. 16 With X-ray microanalysis they confirmed that the opacification was due to the deposition of calcium phosphate salts on the optic.16 Between 2000 and 2006 there were several reports of opacification of hydrophilic IOLs manufactured in the U.S. that required explantation. These included Hydroview (Bausch & Lomb, Inc.), MemoryLens (Ciba Vision), SC60B-OUV (Medical Developmental Research), and Aqua-Sense (Ophthalmic Innovations International, Inc.).17–20 Dorey et al., using transmission electron microscopy X-ray spectroscopy, very elegantly demonstrated that the calcium deposition in the Hydroview IOL was associated with silicon, which was presumably derived from the silicone gasket in the Surefold packaging system (Bausch & Lomb, Inc.) manufactured specifically for this IOL.21 There have also been reports of hydrophilic IOL opacification from IOL manufacturers in Europe.22,23 In this issue, Gurabardhi et al. (page 1326) report on serial IOL opacification with different designs of IOLs from the same manufacturer based in Europe. They demonstrated localized to generalized calcification of the IOL not only involving the optic but the optic haptic junction as well. They were unable to demonstrate any ocular causes for this opacification and suspected manufacturing issues. To streamline our understanding of calcification of IOLs Neuhann et al. proposed a new classification system.24 They suggested defining primary calcification as that inherent to the IOL or related to polymer composition, fabrication techniques, or the packaging process. They suggested the term secondary calcification for that caused by ocular environmental factors. We as clinicians should collaborate more often with researchers and regulatory authorities in reaching a common ground on quality standards for and surveillance of new IOL materials and injectors and the production process. To this effect the European Union in April 2017 introduced a new regulation, the Medical Devices Regulation (MDR), which replaced the previous Medical Device Directives.A The new MDR requires increased post-market surveillance of medical devices; specifically, it calls for more proactive post-market surveillance and data collection to analyse the ongoing risk management and clinical evaluation processes throughout a device's life cycle. I am hopeful that these new regulations will benefit clinicians, industry, and the general public.