eMedicine Specialties > Ophthalmology > Cornea

Keratopathy, Pseudophakic Bullous

Author: James V Aquavella, MD, Professor of Ophthalmology, Department of Ophthalmology, University of Rochester School of Medicine, University of Rochester Eye Institute
Coauthor(s): Zoe R Williams, MD, Staff Physician, Department of Ophthalmology, University of Rochester School of Medicine, Strong Memorial Hospital; Gregory J McCormick, MD, Consulting Staff, Corneal and Refractive Surgery, Vermont Laser Vision at Timber Lane and Ophthalmic Consultants of Vermont; Diane E Singer, MD, Clinical Senior Instructor, Department of Ophthalmology, University of Rochester Medical Center
Contributor Information and Disclosures

Updated: Feb 19, 2008

Introduction

Background

Corneal edema occurs for many reasons, but it is often a sequela of intraocular surgery. Corneal edema resulting from cataract extraction is called either pseudophakic bullous keratopathy (PBK) or aphakic bullous keratopathy (ABK). Knowledge of the structure of the cornea and the proper functioning of its layers is fundamental to understanding corneal edema.

Pathophysiology

Bullous keratopathy is caused by changes in the corneal endothelium, which allow the cornea to be in an abnormal state of hydration. As endothelial cells are damaged, the remaining cells rearrange themselves to cover the posterior corneal surface. The remaining endothelial cells become irregularly shaped and enlarged. Any pathologic process that affects the endothelial cells results in cornea guttata due to overproduction of the Descemet membrane.

As the endothelium becomes increasingly unable to act as a pump to deturgesce the cornea, the stroma begins to swell, especially in the central cornea. As the stroma swells, the cornea thickens and folds are seen in the Descemet membrane. The edema may fluctuate in response to changing intraocular pressure. At this point, maintenance of intraocular pressure at a low level is important. The combination of variable endothelial function and variable intraocular pressure determines the extent of corneal edema.

Patients with bullous keratopathy demonstrate decreased visual acuity and pain or discomfort. Decreased visual acuity is related to inability of the stroma to maintain deturgescence, which often is followed by epithelial edema. Epithelial edema can be responsible for great changes in visual acuity due to irregularity in the corneal refractive surface. Examination with contact lens over refraction may be the best way to confirm the status of the posterior segment.

Pain associated with bullous keratopathy can be due to swelling of the epithelium with resultant stretching of corneal nerves or rupture of bullae with exposure of corneal nerve endings to an often noxious environment. As the edema progresses, bullae rupture results in pain, photophobia, and epiphora. Subsequent epithelial defects predispose the cornea to infection and can contribute to the development of anterior uveitis.

Frequency

United States

Prior to implantation of intraocular lenses, in the era of intracapsular cataract extraction and postoperative aphakia, the rate of ABK was reported to be less than 1% in uncomplicated cases without vitreous loss. Early results with implantation of anterior chamber intraocular lenses by Barraquer in the 1950s, while initially promising, ultimately resulted in corneal decompensation in half of the postoperative eyes. As intraocular lenses have evolved, these rates have steadily dropped. In the modern era, numerous closed loop anterior chamber intraocular lenses have consistently resulted in an elevated risk of PBK relative to flexible open loop anterior chamber and posterior chamber intraocular lenses. Despite improved surgical techniques, PBK remains a leading indication for penetrating keratoplasty because of the high volume of cataract surgery performed.

Several studies in the 1980s demonstrated rates of corneal decompensation after uncomplicated extracapsular cataract extraction with posterior chamber intraocular lens placement to be 0.1-0.5%. In the setting of vitreous loss, the rate of corneal edema 4 years postoperatively has been reported to increase to 2.4%.

Mortality/Morbidity

Corneal bullae may cause pain.

Age

Most cataract surgery is performed after age 65 years; thus, this condition is more frequent in elderly persons.

Clinical

History

By definition, this condition occurs after cataract extraction. The edema may be present immediately after cataract surgery or may occur years later.

• Typical symptoms include poor vision and discomfort or pain.
  • Mild stromal edema alone does not cause severe visual loss. However, mild epithelial edema can cause a significant drop in vision.
  • Stromal edema alone does not cause much, if any, discomfort. Mild epithelial edema causes some discomfort, while epithelial bullae and especially ruptured bullae can cause moderate to severe pain.

Physical

• The cornea consists of 5 layers, as follows:  
  • The first layer is a multilayered epithelial sheet of superficial nonkeratinized stratified squamous epithelium, covering 2-3 layers of closely packed transitional cells, and a basal layer of columnar cells anchored to the underlying basement membrane.
  • The second layer, called the Bowman layer, is made of collagen fibrils.
  • The third layer is the stroma, which is made of collagen producing fibroblasts, ground substance, and collagen lamellae. This layer accounts for 90% of the corneal thickness.
  • The fourth layer is the Descemet membrane, which is the basement layer of the corneal endothelium. Part of it is formed in utero, while part is laid down by the corneal endothelium throughout life.
  • The fifth layer is the endothelium, which is a single layer of hexagonal cells that face the anterior chamber with their basal surfaces against the Descemet membrane.
• Physiology
  • The endothelium is responsible for maintaining deturgescence of the corneal stroma. Endothelial cells do not divide. Thus, the number of endothelial cells is maximal at birth and decreases naturally as the body ages. As the number of endothelial cells decreases, the degree of pleomorphism and polymegathism increases. The remaining endothelial cells spread and thin out over the inner corneal surface. Although cell density decreases due to cataract extraction, intraocular lens implantation, clear corneal transplants, increased intraocular pressure, and ocular inflammation, it is not solely the decrease in endothelial cells that determines corneal swelling.
  • A damaged endothelial cell responds by producing a new Descemet membrane, which differs qualitatively from the cornea's original Descemet membrane. Irregularities in the density and surface characteristics of this new substance are referred to as cornea guttata. On slit lamp examination, these irregularities give a characteristic beaten silver appearance to the thickened Descemet membrane.
  • The endothelium also acts as a barrier, separating the stroma from the aqueous humor. Its prime function is to transfer, by way of a sodium/bicarbonate pump, water from the stroma into the aqueous humor, an energy dependent process that derives oxygen from the aqueous humor.

Causes

• Preoperative risk factors  
  • Preoperative clinical specular microscopy is used to examine the quality and quantity of endothelial cells. In using this tool, no correlation has been found between the preoperative endothelial cell density or degree of postoperative cell loss and the subsequent development of corneal edema. Significant correlation has been found between variation in cell shape and size and the development of postoperative corneal edema.
  • Endothelium with a greater degree of pleomorphism reacts more adversely to intraocular surgery and requires a longer time for corneal deturgescence. As corneal deturgescence is maintained by the metabolic pump of endothelial cells and by tight cellular junctions, cells with greater variation in size may not fit together as well, leaving gaps and compromising the endothelial structural barrier.
  • An increased incidence of cornea guttata or Fuchs endothelial corneal dystrophy is seen on histopathologic examination of host corneal buttons removed during penetrating keratoplasty for PBK.
  • Pseudoexfoliation syndrome has been associated with an increased incidence of PBK.
• Intraoperative risk factors
  • Surgical trauma, most commonly during cataract extraction, can damage the endothelium, causing a period of postoperative edema that resolves in most cases. Knowledge of the preoperative status of corneal endothelium may help to reduce this complication.
  • The type of cataract surgery also has an impact on how much trauma occurs to the endothelium and the resultant pseudophakic or aphakic corneal edema (see Frequency).
  • Lenses made of polymethylmethacrylate adhere instantaneously to the endothelial surface when contact upon lens insertion occurs. With subsequent separation of the 2 surfaces, the anterior membranes of the endothelial cells are torn off.
  • Viscoelastics can be used to reduce touch between the cornea and the intraocular lens during lens insertion. By initially deepening the anterior chamber, the risk of endothelial damage in the event of chamber shallowing is minimized. Reusable cannulas with viscoelastic can result in toxic residues being introduced into the eye; therefore, disposable cannulas should be used whenever possible. A comparison of viscoelastic substances showed that no difference occurred in endothelial cell count, iritis, or corneal edema after cataract surgery with polymethylmethacrylate intraocular lens placement using either polyacrylamide or sodium hyaluronate. It has also been found that methylcellulose does not protect the corneal endothelium as effectively as sodium hyaluronate during phacoemulsification. The protective benefit of sodium hyaluronate is improved further when used in combination with chondroitin sulfate (making Viscoat).
  • While mechanical trauma to the endothelium during surgery is considered to be the most significant factor influencing postoperative corneal edema, other factors can adversely affect the endothelium. Toxic substances used to disinfect instruments may inadvertently be introduced into the eye, if inadequate rinsing of instruments allows some of the substances to remain in the small lumens of the instruments. Water, not saline, should be used to rinse the instruments.
  • Intraocular irrigation solutions must be appropriate; otherwise, endothelial injury and corneal edema will occur. Increasingly, topical and intracameral anesthesia have gained popularity and must be used appropriately. Up to 0.5 mL of 1% preservative-free lidocaine has been shown to result in no change of endothelial cell count at 3 months postoperatively, while numerous other preparations of lidocaine and other anesthetics have resulted in significant endothelial cell loss and corneal toxicity.
  • Intraocular medications that have resulted in corneal toxicity include epinephrine (now available preservative free), benzalkonium chloride-preserved viscoelastic, vancomycin at doses greater than 1 mg/mL, and inadvertent exposure of the endothelium to 5% povidine-iodine.
  • Detachment of the Descemet membrane, possibly more common with clear corneal incisions, will result in postoperative corneal edema.
• Postoperative causes
  • Routine uncomplicated phacoemulsification surgery has been reported to result in 9% endothelial cell loss at 1 year postoperatively.
  • Regardless of what surgery type was used and whether an intraocular lens is implanted, continuing endothelial loss of greater than the usual 1% per year occurs in patients who have undergone cataract extraction. Corneal edema usually develops within 1 year after the endothelial cell density falls below 500 cells/mm, but no absolute lower limit to the number of cells has been found to be associated with stromal edema.
• The type of lens implanted is also significant in determining the amount of endothelial cell loss over time.
  • Persistent low-grade inflammation and intermittent contact of the implant with the corneal endothelium may be primary causes.
  • Iris supported lenses may cause greater endothelial loss as high-speed photographic evaluation of them indicates that they can contact the endothelium during ocular saccades.
  • Anterior chamber lenses of the closed loop design have been responsible for a large amount of corneal pathology, while open loop design lenses have been shown to have a significantly lower rate of complications and need for subsequent explantation.

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