Ординатура / Офтальмология / Английские материалы / Biomaterials and regenerative medicine in ophthalmology_Chirila_2010

30 Biomaterials and regenerative medicine in ophthalmology

Although lens refilling holds significant potential, many problems remain to be solved. These include achieving emmetropia in the relaxed state, adequate accommodative response upon zonular relaxation, appropriate image quality throughout the full range of accommodation, and sustained functionality (Menapace et al., 2007). The most significant problem, however, remains the incidence of PCO. According to Menapace and coworkers (Menapace et al. 2007), the ideal material for lens refilling should be cytotoxic upon direct contact with the capsule to prevent PCO but should not release toxic substances to the surroundings or leak into the anterior chamber prior to polymerization. Combination materials or materials that are capable of delivery of drugs that disrupt the pathways necessary for cellular transformations in

PCO may be necessary to overcome these problems.

2.9Conclusions

Through a better understanding of the optical and biological properties, there have been numerous advances in IOL materials since the implantation of

PMMA in the eye in 1949. Through developments in lens design, lenses have a lower incidence of complications. Multifocal and even accommodative IOLs are now available. With a developing understanding of the biological processes that occur following lens implantation and the development of new materials, future generations of IOLs will have better optical properties and even fewer complications.

2.10References

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3

Opacification and degradation of implanted intraocular lenses

L. Werner, University of Utah, USA

Abstract: This chapter presents a summary of different causes of opacification/discoloration/degradation of intraocular lenses (IOLs) manufactured from different biomaterials and in different designs. The majority of the cases presented are based on the author’s own analyses, but a brief review of the literature is also provided. Different processes leading to IOL opacification/discoloration/degradation were identified and may include: formation of deposits/precipitates on the IOL surface or within the IOL substance, excess influx of water in hydrophobic materials, direct discoloration of the IOL by capsular dyes or medications, IOL coating

by substances such as ophthalmic ointment and silicone oil, and slowly progressing degradation of the lens biomaterial facilitated by long-term ultraviolet exposure.

Key words: intraocular lenses, poly(methyl methacrylate), silicone, hydrophilic acrylic, hydrogel, hydrophobic acrylic.

3.1Introduction

A significant number of intraocular lens (IOL) explantations performed in this past decade were prompted by a process related to lens opacification and/ or degradation. Based on a review of the literature, as well as on our own analyses, the types of processes identified included: formation of deposits/ precipitates on the IOL surface or within the IOL substance, IOL opacification by excess influx of water in hydrophobic materials, direct discoloration of the IOL by capsular dyes or medications, IOL coating by substances such as ophthalmic ointment and silicone oil, and slowly progressing degradation of the lens biomaterial.1 The inability to recognize a process of IOL opacification or discoloration may prompt surgeons to perform unnecessary surgical procedures, such as neodymium: yttrium–aluminum–garnet (Nd:YAG) posterior capsulotomies, or vitrectomies, in eyes where the opacification is actually in the IOL itself, and not at the level of the posterior capsule or the vitreous. This may jeopardize subsequent implantation of a new IOL in the capsular bag, among other complications. This chapter describes causes of opacification and discoloration of IOLs of different biomaterials and designs. The text is largely, but not exclusively based on analyses performed in our laboratories in Salt Lake City, Utah, USA and in Berlin, Germany. The causes of IOL opacification and discoloration are presented according to the

36 Biomaterials and regenerative medicine in ophthalmology

biomaterial used in the manufacture of the IOL: poly(methyl methacrylate) (PMMA), silicone, hydrophilic acrylic, and hydrophobic acrylic.

3.2Opacification and degradation of poly(methyl methacrylate) intraocular lenses

3.2.1Snowflake degeneration

PMMA was used as an optic biomaterial in Sir Harold Ridley’s original IOL, manufactured by Rayner Intraocular Lenses Ltd, London, UK and first implanted in 1949–1950. Since that time, as surgical techniques and IOL designs have improved, the overwhelming majority of lenses manufactured from PMMA have provided stellar results for visual rehabilitation after cataract removal. Although PMMA has largely been replaced in the industrialized world by foldable IOL biomaterials intended for small incision surgery, on a worldwide basis PMMA-optic IOLs are still commonly implanted, especially in the developing world.

By the late 1980s, most surgeons and researchers had not only concluded that PMMA was a safe biomaterial, they also had confidence in the various manufacturing techniques required for lens fabrication. However, we analyzed in our laboratory different PMMA lenses explanted because of optic opacification, characterized by a gradual and sometimes progressive late-postoperative alteration of PMMA optic biomaterial. Based on both the clinical appearance as well as the macroscopic, pathologic morphology of the affected IOL optics, we termed this a ‘snowflake’ degeneration of the PMMA polymer. The broad constellation of clinical findings that ensues, ranging from glare and other types of visual aberration to clinically significant decrease in visual acuity represents a distinct clinical syndrome.2,3

The cases were generally related to three-piece posterior-chamber IOLs with rigid PMMA optical components and blue polypropylene or extruded PMMA haptics. Most had been implanted in the 1980s to early 1990s and the clinical symptoms occurred late postoperatively, sometimes more than a decade after the implantation. A correlation of the clinical, gross, and light and electron microscopic profiles of all cases showed a distinct pattern and revealed almost identical findings. The recurrent and interconnecting finding in all cases was the presence of the roughly spherical snowflake lesion, which we interpreted as foci of degenerated PMMA biomaterial. These varied only in the number and density of the lesions, which, in general, reflected also the severity and probably the duration of the opacification. Most examiners described the white-brown opacities within the IOL optics as ‘crystalline deposits’ (Fig. 3.1).

Views of the cut edges of the bisected optic specimens prepared for scanning electron microscopy (SEM) confirmed that the snowflake lesions

38 Biomaterials and regenerative medicine in ophthalmology

generally less involved or free of opacification. The lesions were usually focal and discrete, with intervening clear areas, but some did appear to coalesce. Viewed in sagittal sections, the lesions generally involved the anterior third of the optic’s substance. All histochemical and energy dispersive x-ray spectroscopy (EDS) analyses were negative indicating that the materials involved in the snowflake lesions are non-proteinaceous and are composed of elements common to PMMA (carbon, oxygen).

We suggested that manufacturing variations in some lenses fabricated in the 1980s to early 1990s may be responsible. It is possible that the late change in the PMMA material process is facilitated by long-term ultraviolet (UV, solar) exposure. This is supported by two pathologic observations. First, many opacities have been clustered in the central zone of the optic, extending to the mid-peripheral portion but often leaving the distal peripheral rim free of the opacities. This observation would support the hypothesis that the slow and sometimes progressive lesion formation might relate to the fact that the IOL’s central optic is exposed to UV radiation over an extended period, whereas the peripheral optic may be protected by the iris. Furthermore, the opacities are present most commonly and intensely within the anterior third of the optic’s substance. Since the anterior strata of the optic are the first to encounter the UV light, this might explain why the opacities are seen more frequently in this zone. The manufacturing process of PMMA utilizes many different polymerization techniques, and various components such as UV absorbers and initiators. Therefore, various impurity profiles are possible. A frequently used initiator is azo-bis-isobutyryl nitrile (AIBN). It is possible that UV radiation is a contributing factor; however, the exact pathogenesis can as of now only be hypothesized. Potential causes of a snowflake lesion include: (a) insufficient post-annealing of the cured PMMA polymer; (b) excessive thermal energy during the curing process leaving voids in the polymer matrix; (c) non-homogeneous distribution of the UV chromophore and/or thermal initiator into the polymer chain; (d) poor filtration of the pre-cured monomeric components (MMA, UV blocker, thermal initiator). Another possible pathogenic factor could be an inadvertent use of excessive initiator substance during the polymerization process that may facilitate the formation of the snowflake lesions. The N==N bond of the AIBN initiator may be disrupted by gradual UV exposure with a release of nitrogen gas (N2). Such gas formation can be caused by either heat or UV light exposure. Indeed the normal polymerization process for PMMA synthesis consists in part of a heat-induced N2 formation as a byproduct. During normal polymerization the N2 escapes from the mixture. However, in cases where there is excessive initiator, more than the fractional amount required, unwanted initiator may be entrapped in the PMMA substance. Slow release of gaseous N2 within the PMMA substance trigged by long-term UV exposure would explain the formation of the cavitations within the snowflake lesions. Additional