Keratopathy, Pseudophakic Bullous Clinical Presentation

By definition, bullous keratopathy occurs after cataract extraction. The edema may be present immediately after cataract surgery, or it 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.

• The cornea consists of 5 layers, as follows:

  • The first or outermost 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 or innermost 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 the deturgescence of the corneal stroma. Endothelial cells do not divide well. 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 (cells of different shapes) and polymegathism (cells of different sizes) 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.
  • 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 requires oxygen from the aqueous humor.

• 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.
  • Patients with Fuchs' endothelial corneal dystrophy which characterized by corneal guttata on histopathologic examination have a higher incidence of 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 prompt the surgeon to take additional measure 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% povidone-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 causes of PBK.
  • 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 subsequent explantation.