Medical Care
Medical therapy of PBK consists of attempting to minimize corneal edema and the associated symptoms of discomfort and poor vision. Patients with mild disease may benefit from the use of hypertonic agents, such as sodium chloride 2% and 5% solution and ointment. These agents work by creating a hypertonic tear film, thereby drawing water out of the cornea. Because evaporation from the tear film is minimal at night with the eyes closed (therefore, the tears are less hypertonic), corneal edema tends to be worse in the morning. Use of hypertonic sodium chloride 5% ointment at night applied to the conjunctival cul-de-sac may limit this build-up of edema. Use of hypertonic solutions in the morning also may help eliminate some of this nightly fluid accumulation. Some clinicians even recommend a gentle hair dryer to the cornea in the morning to accelerate corneal deturgescence and therefore improved vision.
The benefit of hyperosmolar eye drops is associated with increased duration and frequency of use. [51] Side effects such as burning, dryness, and redness are common with hyperosmolar eye drops.
One regimen for Muro 128 2-5% drops is to instill drops hourly in the affected eye until noon (4-5 times). As the day progresses, evaporation from the tear film begins to create relative hypertonicity of the tears, drawing fluid from the cornea. This accounts for the typical history of improving vision toward the end of the day. [52]
Other practical methods of limiting corneal edema in eyes with borderline endothelial function include treatment of both ocular inflammation and elevated intraocular pressure (see Pathophysiology, Causes) if present.
Bandage contact lenses may be useful as an adjunct to medical treatment for the temporary relief of corneal pain and discomfort. They act to shield the cornea and epithelium from the eyelid. In general, thin, high-water content lenses are tolerated best because they are more oxygen permeable. However, contact lens wear, especially overnight wear, can be associated with increased corneal edema due to improper fit (tight lens) and an increased risk for infection in an already compromised cornea. Patients for whom a bandage lens is prescribed should be treated with a broad-spectrum antibiotic (eg, Polytrim, moxifloxacin) 2-4 times a day. These patients require close follow-up care. Long-term use of a bandage lens for the treatment of this condition is not advised.
Patients who have poor visual potential and severe pain sometimes can benefit from anterior stromal puncture. [53] A 25-gauge needle is used to place multiple small superficial punctures in the affected area of the cornea. The depth of the puncture site is just at or below the Bowman layer. The epithelium subsequently scars firmly over the treated area. This often results in resolution of bullae and pain relief. A bandage lens should be placed over the cornea for 1-2 weeks to allow the epithelium to adhere to the underlying cornea. Excimer laser phototherapeutic keratectomy also has been used to achieve this effect, as has epithelial debridement or lamellar keratectomy.
Corneal cross linking has emerged as a tool in the management of PBK. It has been found to improve corneal transparency, corneal thickness, and ocular pain after surgery. The effect, however, is temporary and decreases with time. Case selection therefore is very important with more effect seen in patients with a thinner CCT (< 700 um) at presentation. [54, 55, 56]
Surgical Care
Definitive treatment of PBK and ABK is a corneal transplant. [57, 39] Corneal transplantation is indicated when vision is decreased significantly by corneal edema or when pain becomes intractable. Although a complete discussion of corneal transplantation is beyond the scope of this article, certain unique aspects of corneal transplantation in this setting should be emphasized. First, the size of the graft should be as large as practical without increasing the risk of placing the graft too close to the limbus, thereby increasing the risk for graft rejection. This generally means a donor graft size of 8.00-8.50 mm. Increasing the donor graft size means that more of the healthy endothelium is transplanted. In addition, grafts with higher initial cell counts, 2500-3000 cells/mm2, are desirable for the same reason.
Another important consideration is the management of a preexisting intraocular lens. [58, 59, 60, 61]
Closed-loop anterior chamber intraocular lenses and iris clip style lenses should be removed because of their high association with continued endothelial cell loss and the potential harm to the donor cornea. Special techniques have been devised to remove the often scarred and embedded haptics of closed-loop anterior chamber intraocular lenses with the goal of minimizing iris and angle trauma and associated bleeding.
Well-positioned and appropriately sized flexible haptic anterior chamber intraocular lenses can be left in the eye or exchanged for a posterior chamber intraocular lens. Modern posterior chamber intraocular lenses can be safely left in the eye. A complete discussion of the options for replacement (intraocular lens exchange) are beyond the scope of this article. However, current options include (1) using a modern flexible loop anterior chamber intraocular lens, (2) placing a three-piece posterior chamber lens in the ciliary sulcus, (3) suturing a posterior chamber lens to the iris, (4) suturing a posterior chamber lens in the sulcus with Gore-tex or other sutures, (5) externalizing the haptics of a posterior chamber intraocular lens, inserting them under scleral flap into a scleral tunnel and gluing the flap over the haptic as described by Agarwal et al [62] or (6) externalizing the haptics through transconjunctival sclerotomies, then anchoring them in the sclera by the flange created at the end of the haptics via low temperature cautery (Yamane technique). [63] Implantation techniques begin with careful removal of any anterior displaced vitreous and an equally careful lysis of iris synechiae.
Flexible haptic anterior chamber lenses should be reserved for those eyes with minimal anterior segment pathology, less than 90° of angle synechiae, and well-controlled intraocular pressure. [64, 65] Determining the correct width to implant is essential in preventing complications, such as iris tuck and ovaling (too large), as well as spinning or displacement of the lens (too small). Generally, the width chosen should correspond to a measurement of the horizontal white-to-white corneal diameter plus 1 mm. If inspection of the ciliary sulcus through gentle retraction of the iris reveals an intact and adequate capsular rim, then a posterior chamber intraocular lens can be inserted in the sulcus without suturing the lens in place. [66]
In iris fixation technique, a foldable, three-piece PCIOL is passed behind the iris and a 10-0 polypropylene suture is used to imbricate the haptics into the iris. This technique, however, can produce long-term complications of chronic inflammation including UGH syndrome and pigment dispersion from the iris rubbing on the implant. Prolene suture also breaks down over time with a rate as high at 20% in some studies requiring re-operation. [67] In the scleral fixated IOL technique, many surgeons are adopting the sutureless methods. The two most popular ways to secure the posterior chamber implant to the sclera without sutures are the glued IOL technique and the Yamane technique. In 2007 Agarwal et al first described the glued IOL technique where the haptics of a three-piece IOL were externalized after being passed through two sclerotomies spaced 180 degrees apart. They are secured by tucking each haptic end into a tunnel. Glue is then applied to the haptics and the flaps are replaced over them. In 2016, Yamane et al described a sutureless, flanged haptic technique that also externalizes the haptics of a three-piece IOL through two sclerotomies. The haptics then are secured by creating a flange with low-temperature cautery at the end of each haptic that prevents it from sliding back into the posterior chamber.
A meta-analysis by Lau et al in 2022 found that there was no significant difference in the mean corrected distance visual acuity at the final follow-up between scleral fixated IOL(SFIOL) and Iris fixated IOL (IFIOL) implantation. Although the incidence of vitreous hemorrhage was significantly higher and the final endothelial cell count ECD was significantly higher in the SF IOL group, there were no differences in visual acuity and refractive outcomes between SF IOL and IF IOL. A significantly greater proportion of patients also experienced pupil distortion following IFIOL relative to sutureless SFIOL implantation. [68]
Many different variations of these techniques have evolved along with micro-instrumentation and intraocular lenses. It is up to the individual practitioner to determine which of these lens implant options is most appropriate for a given patient; however, it is important to note that no study to date has clearly pointed to an advantage of one technique or style of intraocular lens replacement in terms of corneal transplant survival, vision, or development of secondary complications.
Endothelial keratoplasty (EK) options include Descemet membrane endothelial keratoplasty (DMEK) and DSAEK (Descemet Stripping Automated Endothelial Keratoplasty). The choice of whether to perform DMEK or DSAEK may depend upon surgeon preference and patient characteristics including anterior segment disease, intraocular lens status and location, iris defects, history of vitrectomy, and prior glaucoma surgery. The method of insertion of DMEK and DSAEK grafts can damage the donor corneal endothelium, and there are different techniques for insertion. [69]
DSAEK (Descemet Stripping Automated Endothelial Keratoplasty) begins by stripping off and removing the patient's central endothelium and Descemet’s membrane (Descemet stripping). A posterior lamellar disc is prepared by placing a donor cornea in an artificial anterior chamber and cutting it with a microkeratome. Eye banks can provide surgeons with precut corneal tissue for DSAEK surgery. The thickness of DSAEK grafts has decreased over time and many surgeons now use ultra-thin (50-100 microns) or nano-thin (less 50 microns) tissue. The donor graft is folded and inserted into the eye, where it is subsequently unfolded and elevated up against the patient's cornea with an air bubble. The bubble then is partially removed at the end of surgery. [70] The patient lies flat in the supine position after surgery to allow the donor disc to attach to the host cornea.
A newer modification of endothelial keratoplasty is called Descemet membrane endothelial keratoplasty (DMEK). In this procedure, an ultra-thin graft consisting of only Descemet’s membrane and endothelium from a donor is used to replace the recipient endothelium. Eye banks can prepare DMEK grafts for surgeons. The donor graft in DMEK is inserted into the eye and unfolded. Air or gas is used to elevate the graft and attach it to the host cornea. The patient lies flat in the supine position after surgery to allow the graft to attach to the host cornea. DMEK has been adopted by many corneal surgeons, and newer techniques have helped flatten the learning curve and overcome the technical difficulties of manipulating and unfolding the donor graft. [71, 72]
Compared with traditional DSAEK surgery, DMEK offers more rapid visual recovery, better visual acuity outcomes, and a decreased risk for rejection. In a first series of 50 DMEK surgeries performed for Fuchs endothelial dystrophy, 95% had a best-corrected visual acuity of 20/40 or better (≥0.5) and at 6 months 75% reached 20/25 or better. [73] However, many surgeons now use thinner DSAEK grafts. The Descemet Endothelial Thickness Comparison Trial (DETECT), which was a randomized, masked study that compared DMEK and ultra-thin DSAEK, found that DMEK patients had better visual acuity 24 months after surgery but may have had higher endothelial cell loss and more complications than ultra-thin DSAEK patients. [73] A larger, multicenter DETECT study will determine if differences exist in visual acuity, graft survival, complications, and endothelial cell loss after DMEK versus ultra-thin DSAEK.
In terms of graft rejection, the risk for an immunologic rejection episode is significantly lower with EK than PK. EK rejection episodes also are milder and less likely to progress to graft failure than PK rejection episodes. [74] A study found that at 2 years, the cumulative rejection risk was 2% with DMEK, 12% with DSEK, and 18% with PK when performed for similar indications. [74] Another comparative study found that at 5 years the reported cumulative graft rejection rates of 1.7% with DMEK, 5% with DSEK, and 14% with PK performed for similar indications. [75]
In the absence of other corneal disease or opacity, full-thickness penetrating keratoplasty (PK) no longer is performed for PBK and ABK. The advantages of endothelial keratoplasty techniques (DMEK, DSAEK) include quicker visual recovery, better visual outcomes, decreased risk for rejection, preservation of the natural topography and prolate corneal contour, and a much smaller incision, with improved wound strength, comparable to that seen with small-incision cataract surgery. The patient's own corneal curvature is preserved, with less induction of astigmatism.
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Pseudophakic bullous keratopathy. Large multiple bullae, such as depicted here, are associated with moderate to severe pain and discomfort.
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Pseudophakic bullous keratopathy in a patient with a Binkhorst style iris-fixated lens.
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Pseudophakic bullous keratopathy. This patient has a closed-loop anterior chamber intraocular lens (Leiske model).
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Specular microscopy of a normal cornea. Note the compact, uniform hexagonal appearance of the endothelial cells.
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Specular microscopy illustrating moderate polymegathism and polymorphism. This is thought to be evidence of endothelial physiologic stress.
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Fuchs endothelial dystrophy. The apparently empty spaces are occupied by guttate.
