Introduction
Background
Pseudophakic bullous keratopathy (PBK) and aphakic bullous keratopathy (ABK) refer to the development of irreversible corneal edema as a complication of cataract surgery.1 As corneal edema progresses and worsens, first stromal and then intercellular epithelial edema develops. Epithelial edema is associated with the development of bullae; hence, the name bullous keratopathy.
Pseudophakic bullous keratopathy. Large multiple bullae, such as depicted here, are associated with moderate to severe pain and discomfort.
The history of PBK parallels the history of the development of the intraocular lens. As surgical techniques and lens design have improved, the incidence of this complication has decreased dramatically. However, it still represents an important cause of visual disability following routine and complicated cataract surgery.
Pathophysiology
Corneal transparency is, in a large part, dependent on the ability of the cornea to remain in a dehydrated state. It is affected by several interdependent factors. The epithelium and the endothelium are both semipermeable membranes that create a barrier to the flow of water and other electrolytes into the cornea. Evaporation from the corneal tear film results in slightly hypertonic tears that tend to draw fluid out of the cornea. Intraocular pressure tends to drive fluid into the cornea. Osmotic forces and the electrolyte balance within the corneal stroma also tend to draw water into the cornea. However, the most important influence on corneal deturgescence is the presence of an active metabolic pump in the endothelium.The endothelium is a single layer of cells present on the back of the cornea. The site of the metabolic pump is within the lateral cell membrane; it is temperature dependent, it is associated with the enzyme Na+/K+ ATPase, and it is inhibited by ouabain. Endothelial cells produce a basement membrane (the Descemet membrane), and they are of neuroectodermal origin. Cell density at birth can be as high as 7500 cells/mm2, decreasing to an average of about 2500-2700 cells/mm2 in older adults.
Endothelial cells are not capable of significant mitotic activity. The normal rate of endothelial loss after age 20 years is approximately 0.5% per year. Surgical trauma, inflammation, and corneal dystrophies can accelerate this normal aging loss. The final common pathway in the development of bullous keratopathy is damage to the corneal endothelium; when the cell density reaches a critically low level of about 300-500 cells/mm2, corneal edema develops.2
Frequency
United States
The exact incidence of PBK is unknown; however, it is estimated that 0.1% of patients undergoing cataract surgery will develop this problem.
The US Food and Drug Administration (FDA) premarket approval studies for intraocular lenses performed from 1978-1982 found an incidence of postoperative corneal edema of 0.06% for posterior chamber lenses, 1.2% for anterior chamber lenses, and 1.5% for iris fixated lenses.3,4,5 Certain styles of intraocular lenses introduced in the mid 1980s were reported to have an incidence as high as 5% (eg, Leiske and Hessburg closed loop anterior chamber intraocular lenses, ORC Stableflex, Azar model 91Z).6,7
Pseudophakic bullous keratopathy. This patient has a closed-loop anterior chamber intraocular lens (Leiske model).
From 1984-1989, ABK and PBK accounted for most corneal transplants (about 33%) performed in the United States. Since then, the number of cases has decreased, despite an increase in the number of overall cataract surgeries performed. Keratoconus surpassed PBK in 1990 as the leading indication for corneal transplantation in some studies in the United States.8 This overall drop in the incidence of PBK reflects the rapid development and improvement of both intraocular lens design and cataract surgical technique.
International
Trends similar to that in the United States have been noted in Canada, United Kingdom, Australia, and Scandinavia.9,10,11,12
Race
No known association of PBK with race exists.
Patients of Northern European descent do have an increased incidence of Fuchs corneal dystrophy. This dystrophy does predispose to the development of corneal edema (see Pathophysiology, Causes, Histologic Findings).
Sex
No known association of PBK with sex exists.
Fuchs corneal dystrophy, a known predisposing factor in the development of postoperative corneal edema, occurs approximately 3 times more frequently in women than in men.
Age
Older patients who have less endothelial reserve are more prone to develop this problem.
Clinical
History
- Symptoms of bullous keratopathy include the following:
- Poor vision
- Haloes around point sources of light
- Pain
- Foreign body sensation
- Photophobia
- Poor vision and haloes are symptoms of corneal edema.
- Stromal edema affects vision much less and causes less light scatter than epithelial edema; epithelial edema involves the corneal surface and disrupts the normally smooth and regular tear film. The development and subsequent rupture of corneal bullae on the densely innervated corneal surface cause pain and photophobia.
Physical
- Vision will be decreased in proportion to the development of central corneal edema. Slit lamp examination invariably reveals folds in the Descemet membrane and obvious overall thickening of the central and peripheral cornea.
- In the more advanced stages of PBK, vesicles and bullae can be seen on the corneal surface.
- In patients with predisposing corneal problems (eg, Fuchs dystrophy), cornea guttata may be seen. On slit lamp examination, guttate excrescences appear as golden-brown confluent endothelial lesions and give the posterior corneal surface a characteristic beaten metal appearance.
Causes
- Causes of corneal edema include the following:
- Congenital hereditary endothelial syndrome13
- Posterior polymorphous dystrophy14
- Chandler syndrome
- Acute narrow-angle glaucoma
- Herpetic disciform keratitis
- Corneal transplant rejection
- Surgical trauma at the time of cataract surgery can be associated with a marked reduction in endothelial cell counts.15,16,17,18,19
- Modern techniques of cataract extraction (eg, phacoemulsification) are associated with endothelial cell loss of about 4-10%; however, on any individual patient, wide variations in cell loss can occur. Diabetes is a risk factor for endothelial damage as well.20
- Endothelial cell loss has been correlated with cataract incision size and location, density of nucleus, total ultrasound energy used, and volume of fluid irrigated into the eye at the time of surgery. Individual surgeon techniques and skill vary widely, and, correspondingly, endothelial cell loss will vary.21,22
- Directly touching the endothelium during cataract surgery with instruments, nuclear fragments, or the intraocular lens should be avoided. Routine use of viscoelastic agents has resulted in a dramatic decrease in endothelial cell loss and offers a practical and effective means of protecting the cornea from inadvertent trauma during cataract surgery.23 Dispersive viscoelastics may offer more protection to the endothelium than cohesive viscoelastics, especially if the surgeon's technique is such that nuclear fragments are removed with phacoemulsification more anteriorly, above the iris plane.
- Older style intraocular lenses have been associated with accelerated endothelial cell loss following cataract surgery.
- In particular, closed-loop anterior chamber intraocular lenses (ie, Leiske, Hessburg style) have been implicated with this problem. The haptics with these lenses tended to be stiff and erode through uveal tissue, causing chronic low-grade inflammation and continued endothelial cell loss.
- This style of lens is thought to be partly responsible for the epidemic of PBK of the mid 1980s. These lenses are no longer implanted. Modern flexible open-loop anterior and posterior chamber intraocular lenses have proven to be much safer alternatives. Biocompatible materials (eg, polymethylmethacrylate, acrylic, silicone), excellent finish, and good flexibility characterize these lenses.
- Corneal dystrophies (eg, Fuchs endothelial dystrophy) sometimes are overlooked on the preoperative exam, where the finding of cornea guttata may be subtle.24
Fuchs endothelial dystrophy. The apparently empty spaces are occupied by guttate.
- Fuchs dystrophy is more common in women than in men and usually presents in older patients. The pattern of inheritance is not known with certainty, but it is thought to be autosomal dominant. Characteristics of this dystrophy include cornea guttata, which are droplike excrescences produced by the endothelium, a thicker than normal Descemet membrane, and a decreased number of endothelial pump sites.25
- An increased frequency of cornea guttata in the opposite unoperated eye in patients developing PBK has been noted. In one study, 67% of corneal buttons removed at the time of keratoplasty for bullous keratopathy from eyes with posterior chamber lenses (suggesting an intact posterior capsule and uncomplicated cataract surgery) were noted to have evidence of an endothelial dystrophy. This highlights the need for a careful preoperative slit lamp examination to help identify patients at risk for the development of postoperative corneal edema. If cornea guttata are noted on slit lamp examination, specular microscopy and ultrasound pachymetry should be performed to help quantify endothelial reserve and to aid in risk assessment. In such patients, the intraoperative use of balanced salt solution plus glutathione, bicarbonate, and adenosine (BSS plus) and dispersive viscoelastic agents may limit endothelial damage.
- The choice of intraocular irrigating fluid can have a profound affect on postoperative corneal edema.
- Under experimental conditions, normal saline induces more corneal swelling than Ringer's lactate solution, while BSS causes the least amount of swelling. BSS contains an electrolyte balance very similar to aqueous humor. BSS plus is probably the best solution for use in compromised corneas and when long case times are anticipated (vitrectomies).26,27
- Glutathione is a free radical scavenger and antioxidant, and its use with BSS has been shown to result in the least amount of corneal edema compared to any other intraocular irrigating solution.
- The use of intraocular solutions for specific purposes (eg, intracameral lidocaine for topical cataract anesthesia, Miochol and Miostat for pupillary miosis, epinephrine combined with BSS to maintain mydriasis during cataract surgery) has generally proven to be safe in terms of endothelial cell loss and toxicity.28 However, the use of such solutions should be limited, and the principal of the least amount of solution irrigated into the eye to accomplish the stated purpose should be followed.
- A recent outbreak of toxic anterior segment syndrome (TASS) brought the issue of the safety of irrigating solutions used in the eye to the forefront. An excellent review of toxic anterior segment syndrome can also be found in References.29
- Inflammation, specifically iritis and uveitis, can profoundly affect endothelial function.
- Classic examples include corneal transplant rejection and herpetic disciform keratitis. In both of these examples, the endothelial cells are the targets of the inflammatory response. However, even nonspecific inflammation, such as that occurring in postoperative and traumatic iritis and other causes of uveitis, can be associated with compromised endothelial function.
- Judicious use of topical steroids (eg, prednisolone acetate) can have a beneficial effect on corneal edema. This beneficial effect must always be balanced against the possible adverse effects of glaucoma and local immunosuppression.
- Intraocular pressure has an important effect on the state of corneal hydration.
- High intraocular pressure, such as that occurring in attacks of narrow-angle glaucoma, drives fluid into the cornea and is associated with the acute onset of corneal edema, even when the corneal endothelium is otherwise healthy. Conversely, prephthisical eyes with low intraocular pressure often have clear corneas, regardless of endothelial cell count and function.
- Lowering intraocular pressure can decrease corneal edema and thickness in the postoperative setting, even if the intraocular pressure is normal or only mildly elevated. Beta-blockers (eg, Timoptic, Betagan) and alpha-agonists (eg, Iopidine, Alphagan) are the first line of therapy for this purpose. Prostaglandin analogs (eg, Xalatan) and miotics (eg, pilocarpine) should be avoided because both drugs may adversely affect intraocular inflammation. Articles have suggested that topical carbonic anhydrase inhibitors should be avoided in this instance because some question as to their endothelial toxicity in compromised corneas exists.
- Postoperative factors that can be associated with endothelial cell loss include vitreous touch and flat anterior chamber with intraocular lens touch.
- If the posterior capsule is ruptured at the time of cataract surgery, vitreous may bulge forward into the anterior chamber. Careful vitrectomy at the time of surgery usually prevents prolonged contact of vitreous with the endothelial surface.30 However, if vitreous is noted to be in contact with the posterior cornea in the early postoperative period, serial pachymetry and specular microscopy can aid in determining if a vitrectomy is necessary.
- Removal of the vitreous via a pars plana approach may be beneficial in preventing progressive endothelial cell loss. Similarly, a flat anterior chamber in which the intraocular lens shifts forward and touches the endothelium should be addressed by reforming the anterior chamber as soon as practical. Such a situation may arise if a wound leak or choroidal effusion is present.
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Further Reading
Keywords
postoperative corneal edema, pseudophakic bullous keratopathy, PBK, aphakic bullous keratopathy, ABK, pseudophakic corneal edema, aphakic corneal edema, corneal edema, bullous keratopathy, cataract surgery
