Pseudophakic Bullous Keratopathy

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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 occurs when the corneal endothelium becomes damaged and, as a result, the cornea swells. The inner cell layer of the cornea, the endothelium, is responsible for maintaining the cornea in a relatively dehydrated state. 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, and their pump functions begin to fail.

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 with higher pressures leading to more edema. 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.

Epithelial edema manifests as fluid accumulation between the basal epithelial cells. With increased fluid accumulation, blisters and then bullae develop. Epithelial edema may result from anterior movement of aqueous and fluid in the stroma driven by intraocular pressure. With a small amount of epithelial edema, environmental factors (eg, temperature, humidity) may affect evaporation of tears with blinking. At night with the eye closed, epithelial edema typically worsens due to a lack of tear evaporation. This results in symptoms that are generally worse in the morning hours.

Patients with bullous keratopathy demonstrate decreased visual acuity and can have symptoms of pain or discomfort. Decreased visual acuity is related to the inability of the stroma to maintain its 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. 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.

Epidemiology

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.

History

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

Physical

The cornea consists of 5 layers, as follows:

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.

Hydration of the cornea is kept in balance by multiple opposing forces. The epithelium and the endothelium restrict rapid fluid movements. Both the corneal epithelium and endothelium are now known to be permeable to solutes and act as imperfect semipermeable barriers. The resistance to electrolytes in the epithelium is about 100 times higher than in the endothelium. The tendency of the stroma to swell is termed the swelling pressure, which tends to pull fluid into the cornea. The swelling pressure is counteracted by the intraocular pressure, which tends to flatten the cornea and thus decreases the imbibition of fluid into the cornea. The endothelial pump secretes sodium and bicarbonate into the aqueous humor, providing the osmotic pressure to pull water out of the corneal stroma. This is counterbalanced by the swelling pressure, which tends to pull water into the cornea.

When the endothelium is compromised, as in the case of pseudophakic bullous keratopathy, the ability of the endothelium to maintain osmotic pressure begins to fail. As the corneal stroma imbibes fluid, it begins to thicken, causing folds to develop in the Descemet membrane. The corneal epithelium can also become edematous. Corneal epithelial edema appears to be a function of intraocular pressure. In cases of high intraocular pressure, epithelial edema can develop with little or no stromal edema, as in the case of angle-closure glaucoma.

Alternatively, in an eye with hypotony and advanced pseudophakic bullous keratopathy, there can be no epithelial edema even though there is extensive stromal edema. It appears that intraocular pressure causes the edema to advance to more superficial layers. Clinically, epithelial edema is characterized by fluid-filled cysts or bullae between epithelial cells. Epithelial edema is typically seen in more advanced cases of pseudophakic bullous keratopathy, and these bullae frequently cause pain.

Causes

Procedures

A number of studies can be helpful in confirming the diagnosis and in offering a reasonable prognosis for the patient.

In the final analysis, visual acuity and the patient's level of functional capacity determine the prognosis. Quite often, corneal edema, while progressive, can afford reasonable levels of visual acuity for many years. Consequently, surgical intervention should be based more upon the patient's needs than upon the degree of corneal decompensation.

Medical Care

Therapy for pseudophakic bullous keratopathy (PBK) and aphakic bullous keratopathy (ABK) is performed to reduce discomfort and/or to improve visual acuity. The corneal edema associated with bullous keratopathy is chronic and usually noninflammatory. A number of treatment options are available.

Surgical Care

Surgical treatments for bullous keratopathy include enucleation or evisceration, retrobulbar alcohol injection, conjunctival flap, cauterization of the Bowman layer, anterior stromal micropuncture, excimer laser phototherapeutic keratectomy (PTK), annular keratotomy, penetrating keratoplasty, and Descemet stripping automated endothelial keratoplasty (DSAEK).

Medication Summary

The goal of medical treatment is to improve visual acuity by deturgescence of the edematous corneal epithelium.

5% Sodium chloride (Muro 128, Adsorbonac, SalineX, Ak-NaCl)

Clinical Context:  Dehydrates the cornea.

Class Summary

Hypertonic saline solution dehydrates the epithelium and tends to improve acuity.

Further Outpatient Care

In cases of ruptured bullae, patients should receive follow-up care every 24-48 hours until the epithelial defect heals; otherwise, follow-up care should be scheduled every 1-6 months, depending on symptoms.

Inpatient & Outpatient Medications

Complications

With a deteriorating condition, corneal transplant may be necessary.

Prognosis

Significant corneal edema that persists for 3 months after cataract surgery is unlikely to resolve on its own.

Author

James V Aquavella, MD, Professor of Ophthalmology, Department of Ophthalmology, University of Rochester School of Medicine, University of Rochester Eye Institute

Disclosure: Nothing to disclose.

Coauthor(s)

Gregory J McCormick, MD, Consulting Staff, Corneal and Refractive Surgery, Vermont Laser Vision at Timber Lane and Ophthalmic Consultants of Vermont

Disclosure: Nothing to disclose.

Holly Hindman, MD, Assistant Professor, Cornea and External Disease, Department of Ophthalmology, University of Rochester Eye Institute

Disclosure: Nothing to disclose.

R Marshall Ford, MD, Cornea Fellowship, Flaum Eye Institute at University of Rochester School of Medicine and Dentistry

Disclosure: Nothing to disclose.

Zoe R Williams, MD, Assistant Professor, Department of Ophthalmology, University of Rochester School of Medicine, Strong Memorial Hospital

Disclosure: Nothing to disclose.

Specialty Editors

Fernando H Murillo-Lopez, MD, Senior Surgeon, Unidad Privada de Oftalmologia CEMES

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital

Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; RPS Ownership interest Other; Bausch & Lomb Honoraria Speaking and teaching; Bausch & Lomb Consulting fee Consulting; Tear Science Consulting fee Consulting; Nicox Consulting; Bio-Tissue Honoraria Speaking and teaching

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Disclosure: Nothing to disclose.

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