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Preventing posterior capsule opacification: What have we learned?

2011; Lippincott Williams & Wilkins; Volume: 37; Issue: 4 Linguagem: Inglês

10.1016/j.jcrs.2011.02.021

1873-4502

Thomas Kohnen,

Connective tissue disorders research

Even today’s high-quality cataract surgery with intraocular lens (IOL) implantation in the capsular bag does not prevent posterior capsule opacification (PCO) as the most frequent long-term complication. Lens epithelial cells (LECs) remaining in the capsular bag after any type of extracapsular cataract surgery are primarily responsible for PCO development. Proliferation, migration, epithelial-to-mesenchymal transition, collagen deposition, and lens fiber regeneration of LECs are the main causes of opacification, as described by Awasthi et al.1 Cataract surgery appears to induce a wound-healing response in the lens and residual LECs proliferate and migrate across the posterior capsule and undergo lens fiber regeneration and epithelial-to-mesenchymal transition. Two morphological types of PCO can be differentiated: fibrotic and regenerative or pearl. The fibrotic type is caused by the proliferation and migration of LECs, which undergo the epithelial-to-mesenchymal transition, resulting in fibrous metaplasia and leading to significant visual loss by producing wrinkles and folds in the posterior capsule. The pearl type is caused by the LECs located at the equatorial lens region. They induce regeneration of crystallin-expressing lenticular fibers that form Elschnig pearls and Soemmerring ring. These are responsible for most cases of PCO-related visual loss. The histological features of PCO are now well established, but to date the molecular mechanisms influencing the behavior of residual LECs after cataract surgery are not completely understood. In vitro studies and animal models of PCO suggest that several cytokines and growth factors play a major role in the pathogenesis of PCO because they influence the behavior of the LECs that remain after cataract surgery. Several reasons for eradicating PCO exist: (1) It remains the most common complication of cataract surgery. (2) The rate in children is particularly high (>40%; sometimes 100%). (3) A neodymium:YAG laser capsulotomy, which is the common currently available treatment for PCO, has several significant complications (intraocular pressure rise, laser IOL cracks, IOL dislocation, cystoid macular edema, retinal detachment or floaters due to remaining posterior capsule pieces). (4) The treatment of PCO is a high cost factor in every health-care system. Therefore, investigators are constantly working to advance a safe and effective way to reduce, eventually eradicate, PCO. The following factors in PCO treatment have been identified: surgical technique, IOL design and material, and therapeutic agents. SURGICAL TECHNIQUES Several surgical techniques for removing LECs at the time of lens extraction have been evaluated. They include aspiration of the anterior capsule using extensive irrigation/aspiration or manual polishing of the anterior and/or posterior capsule during cataract surgery and pharmacological dispersion and aspiration of the anterior capsule. Vacuuming or polishing the capsule may delay the onset of PCO, but the long-term benefit is limited. Equatorial capsule vacuuming has been associated with additional surgery time and risk for capsule tears. Hydrodissection is an effective, practical, and inexpensive method for cortex removal, but alone it does not completely eliminate LECs. The advantages of a closed endocapsular ring to prevent PCO have been reported, and recently, a sealed-capsule irrigation device that allows selective irrigation of the capsular bag with a pharmacological agent without damaging surrounding tissues was introduced.2,3 Finally, primary capsulorhexis with anterior vitrectomy or posterior optic capture has been suggested as an effective procedure to lower PCO rates in children.4 INTRAOCULAR LENS DESIGN AND MATERIAL Several clinical and experimental studies have demonstrated the role of IOL materials in reducing the incidence of PCO. Although it is well recognized that a hydrophilic acrylic material is biocompatible, IOLs made of this material have been shown to support LEC adhesion, migration, and proliferation and thus an increased rate of PCO development compared with an IOL made of hydrophobic acrylic or silicone.5 Modification of the IOL surface, which can inhibit cell and protein adhesion, has been suggested as one of the most tolerable methods for preventing PCO. Many advances in IOL designs have reduced PCO incidence. A high PCO inhibitory effect has been observed with IOLs that provide a mechanical barrier effect (sharp-edged optic [Maddula et al., pages 740–748] and the formation of a capsular bend) on the posterior lens capsule. Adhesion of the IOL material with the lens capsule also plays a role in PCO prevention by creating a sharp bend in the capsule. With the growing interest in treating presbyopia by restoring the eye’s ability to accommodate, another problem arises. The potential anteroposterior movement of an accommodating IOL might have an effect on PCO, either by dynamic differences in the tension or possible changes in the distance of the IOL from the posterior capsular bag. While accommodating dual optics, such as the Synchrony IOL, appear to be almost free of PCO, single-optic models have shown an increased incidence. Experimental options for the restoration of accommodation, such as refilling the capsular bag with a refractive viscous substance, will be even more affected by PCO development. However, sharp-edged designs are difficult to implement. Only therapeutic agents within the refilling material likely provide some PCO prevention. THERAPEUTIC AGENTS Intraocular application of pharmacological agents to prevent PCO has been investigated, and the commonly used methods for this application are direct injection into the anterior chamber, addition to the irrigating solution, and impregnation of the IOL. Pharmacological agents such as thermosetting plastic, methotrexate, mitomycin, daunomycin, and fluorouracil have been effective in preventing PCO in vitro, but in vivo studies have shown their toxicity to corneal endothelial cells, iris, ciliary body, and retina.1 In this issue, Yao et al. (pages 733–739) describe a promising method that combines diclofenac sodium with nuclear rotation in hydrodissection to prevent PCO. Studies have tested cytotoxic and therapeutic agents, including diclofenac sodium, saporin, thapsigargin, salmosin, minoxidil (a matrix metalloproteinase inhibitor), and cyclooxygenase (2 inhibitors). The studies showed promise in finding medical treatment of PCO by targeting the survival, adhesion, proliferation, migration, and transdifferentiation of residual LECs, but the risk for toxic effects to surrounding intraocular tissues has restricted clinical use of the agents. Researchers and laboratories worldwide attempting to eliminate PCO development are focusing on several strategies, including improving surgical techniques, IOL materials, and designs, use of therapeutic agents, and combination therapy. The recent changes in surgery have mainly delayed the onset of PCO rather than eliminated the problem. To do this, further research is need.