Posterior capsule opacification
Posterior Capsule Opacification
Posterior capsule opacification (PCO) is the most common complication of cataract surgery. PCO can cause significant visual symptoms and is effectively treated with laser capsulotomy. Evolving understanding of the underlying pathophysiology has led to modifications in surgical techniques and intraocular lens designs with the potential to decrease the incidence of PCO.
Posterior capsule opacification
Posterior capsule opacification (PCO), often referred to as “secondary cataract,” is the most common postoperative complication of cataract extraction. In PCO, the posterior capsule undergoes secondary opacification due to the migration, proliferation, and differentiation of lens epithelial cells (LECs). PCO can cause significant visual symptoms, particularly when it involves the central visual axis. Despite advances in surgical techniques, intraocular lens (IOL) design, and development of therapeutic agents to inhibit PCO, this condition continues to impose a significant burden on patients and the health care system.
PCO occurs in 20-50% of patients within 2 to 5 years of cataract surgery. Although the incidence of PCO is reported to have declined in recent years, there is no definitive data, and the reported decrease may represent only a later onset of PCO. Children and infants have a significantly higher incidence and earlier onset of PCO, along with the potential for associated amblyopia. In children, reported rates of PCO reach 100% .
Younger age is a significant risk factor for PCO Other potential risk factors include the presence of conditions such as diabetes, uveitis, myotonic dystrophy, retinitis pigmentosa, and traumatic cataract.
Etiology and Pathophysiology
The pathophysiology of PCO is multifactorial. During routine phacoemulsification surgery, the surgeon excises a portion of the anterior capsule (capsulorrhexis), removes the cataractous lens material, and then implants a synthetic lens into the intact capsular bag. PCO occurs when residual LECs on the residual anterior capsule undergo three phenomena: proliferation, migration toward the posterior capsule, and normal and abnormal differentiation. The accumulated LECs result in opacification of the intact posterior lens capsule, with resultant negative effects on vision.
Multiple cytokines and growth factors, including transforming growth factor β (TGF-β), fibroblast growth factor 2 (FGF-2), and hepatocyte growth factor (HFG), and matrix metalloproteinases (MMOs) have been implicated in the pathogenesis of PCO. Exogenous hyaluronic acid (HA), a component of some viscoelastic substances used during cataract surgery, may result in increased rates of ex vivo PCO.
PCO has two forms, fibrous and pearl (also referred to as proliferative). Fibrous PCO occurs due to abnormal proliferation of LECs, and presents as wrinkles and folds on the posterior capsule at the site of fusion of the anterior and posterior capsules. Histological examination reveals extracellular matrix (ECM) accumulation and elongated fibroblast cells. Pearl PCO is responsible for the majority of PCO-related visual loss. Pearl PCO is composed of normally differentiated LECs that line the equatorial lens region. Examination shows clusters of swollen, opacified, and differentiated LECs called bladder or Wedl cells.
The onset of blurry vision or visual acuity decline after cataract extraction should prompt the examiner to look for signs of PCO. The diagnosis of PCO is clinical, based on history and slit lamp examination of the eye.
History and Symptoms
Most patients present between months up to several years following uneventful cataract extraction. Patients may complain of decreased vision, blurred vision, glare, light sensitivity, impaired contrast sensitivity, halos around lights, or difficulty reading.
If PCO involves the visual axis, patients typically present with decreased visual acuity. Slit lamp examination reveals a semi-opaque membrane with variable levels of fibrosis forming on the posterior capsule. Other notable signs include:
- Elschnig’s pearls: seen in pearl-type PCO, in which clusters of residual LECs appear as round, clear “pearls” that shine on retro-illumination. If these accumulate on the visual axis, they can cause decreased visual acuity.
- Soemmering rings: rings of residual LECs and cortical fibers that form between the posterior capsule and the edges of the anterior capsule remnant. These are often too peripheral to cause visual symptoms, but they can cause glare and visual loss if severe.
- Capsular wrinkling
PCO causing visual disturbance is most commonly treated in older children and adults with neodymium:YAG (Nd:YAG) laser capsulotomy. Rarely, it is treated with surgical capsulotomy. Although non-invasive, quick, and effective, Nd:YAG capsulotomy is not without significant risk and expense, and may not be available in large parts of the developing world. Complications are uncommon but may include retinal detachment, IOL damage, cystoid macular edema, increased intraocular pressure, iris hemorrhage, corneal edema, IOL subluxation, iritis, macular hole, corneal endothelial cell loss, and exacerbation of localized endophthalmitis. Rarely, patients may develop re-opacification and require a second laser treatment . The estimated annual cost of Nd:YAG capsulotomy in the United States alone has been estimated at $250 million (for 1 million patients with PCO).
Various pharmacological and immunological methods to treat PCO are under investigation, but in vivo studies have not yet shown conclusive efficacy or safety of these modalities.
Despite the ability to effectively treat PCO with Nd:YAG laser capsulotomy, the potential complications and significant cost of treatment makes PCO prevention an important goal. Additionally, as new, accommodating IOLs that rely on flexible and intact posterior capsules become available, the prevention of PCO formation will gain further importance. Many studies have attempted to identify interventions that delay or inhibit PCO formation. These interventions include surgical techniques, IOL design and material, and pharmacological interventions.
- Thorough cortical clean-up with irrigation, aspiration, and/or manual polishing of the capsule. This in an attempt to remove all LECs remaining in the capsule bag, and in some studies has been shown to have a significant effect on the development of PCO.
- Hydrodissection-enhanced cortical clean-up. Hydrodissection is a technique that weakens capsular-cortical connections in order to enhance cortical clean-up.
- In-the-bag capsular fixation of the optic and haptic. This enhances the barrier effect of the IOL optic.
- Continuous circular capsulorhexis diameter slightly smaller than the IOL optic. Capsulorhexis edge on the IOL surface. This technique creates a “shrink-wrap” effect of the anterior capsule over the IOL optic. This sequesters the optic from the aqueous humor surrounding the capsule, preventing the potentially harmful effect of macromolecules and inflammatory mediators within the aqueous.
- Broad adhesion of the IOL to the posterior capsule. This is another form of the “shrink-wrap effect” in order to minimize LEC migration by creating a tight fit of the posterior capsule against the back of the IOL optic.
Intraocular lens design and material
A square, truncated optic edge IOL design has demonstrated decreased PCO rates and improved visual outcomes compared to a soft, round optic edge IOL design. This is thought to be due to a mechanical barrier effect of the optic edge, preventing LEC growth over the posterior capsule. At this time, it is unclear whether differences in the IOL loops (haptics) design play a role in PCO development.
Widely used IOL materials include high water content hydrophilic acrylic, low water content hydrophobic acrylic, and hydrophobic silicone hydrogel. Although some studies have suggested that the use of hydrophobic IOL material decreases PCO formation, meta-analysis has not demonstrated such an effect.
Pharmacologic methods are currently under study with the goal of either depleting or inhibiting the regeneration of remaining LECs without exerting toxic side effects on surrounding intraocular tissues. These methods include antimetabolites, anti-inflammatory agents, hypo-osmolar drugs, and immunological agents. With the exception of two studies that observed lower rates of PCO with the use of immunotoxin MDX-A, there is no evidence for a significant effect of any other drug on PCO development.
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