Safeguarding the Cornea

Keratoprosthesis can be a viable option

KPRo gives those with graft rejections a sighting chance.

By Peter Zloty, MD, Thomas John, MD, and Yichieh Shiuey, MD

Globally, 285 million people are visually impaired and 39 million are blind, and 82% of the blind individuals are 50 years or older.¹ Corneal blindness represents the fourth leading cause of global blindness (5.1%) after cataract, glaucoma and AMD.² Corneal decompensation and scarring can be a result of a wide spectrum of inflammatory and infectious diseases that can result in functional visual loss and possible blindness. According to the World Health Organization (WHO), 80% of all visual impairment can be prevented or cured.¹

Some of the major causes of corneal blindness, according to WHO, include trachoma (about 4.9 million), ocular trauma and corneal ulceration.³ About 1.5 million to 2 million new cases of unilateral blindness occur every year.³ Surgical intervention, namely corneal transplantation, is usually required to correct corneal blindness with normal posterior segment.

Corneal blindness can be surgically corrected by: penetrating keratoplasty (PKP); anterior lamellar keratoplasty (ALK), from superficial ALK to total ALK (John-Malbran classification)⁴; or posterior lamellar keratoplasty (PLK), such as Descemet’s stripping endothelial keratoplasty (DSEK) and Descemet’s membrane endothelial keratoplasty (DMEK), when the patient’s cornea is conducive to such procedures.^4-8 While more than 20,000 PKPs are performed in the United States annually, repeated graft rejections can occur in a subset of these patients. Success rates after more than three grafts reach around 50% (Figure 1).⁹

Figure 1. Graft rejection rate following penetrating keratoplasty.
*Collaborative Corneal Transplantation Studies

Restoring vision

However, a subset of patients exists whose corneal blindness requires an artificial cornea or keratoprosthesis for visual rehabilitation and vision restoration. Proper patient selection and counseling, along with appropriate surgical techniques, pre- and postoperative topical eyedrops (antibiotics and corticosteroid) and close follow-up are all required for a successful outcome and patient satisfaction.

Early prosthetic corneas were susceptible to tissue necrosis, corneal melt, extrusion, secondary glaucoma and infection problems. While still an issue to some degree, the integrated Boston keratoprosthesis (KPRo) has made the option of keratoprosthesis a viable one. The Boston Keratoprosthesis Type 1 (formerly known as the Dohlman or Doane-Dohlman) has emerged as a feasible solution to the problem of the multiple graft-rejection patient. Surgeons choose the KPro with increasing frequency for an expanded variety of indications, including congenital corneal opacification, congenital opacities with cataract and limbal stem cell failure, aniridia and the previously mentioned repeat corneal graft failure.¹⁰

Throughout the United States and internationally, what was once considered a heroic last chance effort at visual recovery is now being offered to patients at a rate of over 1,000 per year in the United States, and a slightly greater number of times internationally (Figure 2). While other types of keratoprosthesis exist, namely the OOKP device, and the AlphaCor, they usually require a staged approach over many months. They are complex procedures often requiring a multidisciplinary approach and tremendous technical ability. By contrast, an average corneal transplant surgeon can implant the Boston KPRo Type 1, in a standard operating room (OR), with usual PKP equipment, in a single OR session.

Figure 2. Boston KPRo usage in the United States and internationally.

In general, areas of focus for continued improvement of keratoprosthesis include: (1) tissue-prosthesis interface interactions, where late corneal melt and possible extrusion of the device can occur, and (2) secondary glaucoma management. The latter will be discussed in more detail.

Indications

Some patients have ocular pathology that makes a primary KPRo the procedure of choice; however, most KPRo surgeons reserve the device for patients who have had two or more conventional PKPs with graft rejection. Corneal neovascularization in two or more quadrants, indicating a high risk for rejection, is an indication even after one failed PKP. Stevens-Johnson syndrome and post-alkali burn are considered relative contraindications for a Boston KPRo. Ideally, the patient has well-functioning lids without lagophthalmos. Any lid abnormalities or fornix pathology should be fixed well before a KPRo is attempted. The surface needs to be wetable without keratinization. Patients with substantial limbal stem cell deficiency should probably not have a KPRo until some modification of the ocular surface is achieved with a limbal allograft.

There is another version of the Boston KPRo, namely, the Type 2 Boston KPRo. It is used much less frequently and is designed as a through-the-lid prosthesis for severe surface-disease indications. Patients with extensive corneal scarring and vascularization after trauma or acid injury may do better with a primary KPRo instead of a PKP, especially if the repair may include coincident vitreoretinal surgery with silicone oil. The KPRo device is made from medical grade polymethylmethacrylate (PMMA) and is therefore compatible with silicone oil.

Surgical considerations

The patient must be either aphakic or pseudophakic to have a KPRo. The device can be ordered with a corneal dioptric power of 44 for pseudophakic patients, and with a variable dioptric power for aphakic patients. An axial length measurement is submitted when the aphakic version is ordered to customize the anterior curvature.

If the patient has a well-positioned IOL, it can be left in place. The surgery can proceed as a normal PKP except that the device is assembled prior to implantation . The assembly can be carried out on a sterile table along with the use of an operating microscope. The patient is positioned at the same height as the assembly table and the microscope is rotated over to the assembly area. The donor tissue is cut (typically 8.5 to 9.25 mm). A rim smaller than this makes suturing more difficult. Alternatively, a 7.0-mm back plate can be ordered (PMMA only for now) and the rim can be as small as 7.5 mm, ideal for pediatric patients .

Once the device is assembled it is stored in medium until needed. The assembly can usually be done in fewer than five minutes. Oversizing the graft by 0.5 mm usually affords enough room for the device without crowding the anterior chamber. For example, a 9.5-mm donor button would be placed into a 9.0-mm host-site incision. If the aphakic version is being used, it is often because there is no capsular support or because the lens was removed in a prior surgery. A generous open sky vitrectomy will facilitate placement of the device. If there is not a patent peripheral iridotomy, one should be made.

Suturing is performed in the usual fashion, with either 9-0 or 10-0 nylon suture. Usually, the surgeon uses 16, interrupted, 9-0 or 10-0 nylon sutures to hold the device in place while suturing the donor corneal periphery to the recipient peripheral corneal rim. During the surgical procedure, 0.1 cc of preservative-free dexamethasone is then injected into the anterior chamber.

Postoperative management

The postoperative management of the Boston KPRo has many similarities to PKP. The patient is directed to use a potent topical steroid four to six times daily. A topical fluoroquinolone antibiotic q.i.d. is also prescribed along with an aqueous suppressant. Since a high percentage of both community-acquired and hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) are often unaffected by fluoroquinolones, trimethoprim-polymyxin B ophthalmic solution, with its excellent MRSA coverage could also be used q.i.d. in appropriate cases. Also, unique to KPRo oral doxycycline (Vibramycin, Pfizer) 50 to 100 mg daily for its anticollagenolytic effect may be added to the treatment regimen as needed.

A bandage contact lens is placed after surgery. The patient keeps it in place for two to three months, depending on patient hygiene and protein deposition. It is usually replaced every two to four months with a fresh clean lens of a similar type, although any appropriate extended-wear contact lens can be substituted to achieve a proper fit. The potential risk for dellen formation, melt and extrusion of the prosthetic devise increases dramatically in the absence of a bandage contact lens.

After the initial postoperative period, the patient’s use of daily prophylactic antibiotics is necessary.¹¹ Between 1990 and 2011, 368 surgeons worldwide implanted 4729 B-KPros.¹² The current recommendation in the non-autoimmune patient is polymyxin B/trimethoprim once daily. Other options are a fourth-generation fluoroquinolone plus topical vancomycin 14 mg/mL. Chloramphenicol is not used in the United States due to its reported association with aplastic anemia. In an autoimmune or monocular patient the recommendation now is polymyxin B/trimethoprim plus vancomycin or a fourth-generation fluoroquinolone plus vancomycin. In areas endemic for fungus (deep south United States, China) periodic use of amphotericin B (0.15%) or natamycin twice daily for one week every three months is suggested. Fungal infection of the KPRo stem is a serious globe-threatening emergency that often necessitates KPRo explantation. The KPRo patient can undergo routine fundus photography, optic nerve OCT and routine threshold visual field testing through the device, but the fields are often constricted to 30 degrees. Peripheral retinal examination is problematic as well, but can be overcome with wide-angle fundus imaging.¹²

Finally, whereas steroids are typically tapered with PKP, KPRo patients may be encumbered with complications such as vitritis, retroprosthetic membrane formation, secondary angle closure and elevated IOP due to aqueous misdirection or neovascular glaucoma. Therefore, should IOP rise, reduction of the steroid, though intuitive, can have an opposite effect. Rather, additional glaucoma medication or surgery should be considered.¹³

Glaucoma management

KPRo patients are prone to elevated IOP.¹⁴ Digital palpation is currently the only way we can assess IOP, although work on implanted sensors is ongoing.¹⁵ Patients can be taught to monitor their IOP this way. This is crucial since a patient can go from a normal IOP to a hemorrhage-inducing IOP within a few weeks. This is frequently due to the sudden angle closure to which KPRo patients are prone. Both patient and physician must be vigilant about this since a great visually restorative result can be lost in a matter of weeks.

Topical glaucoma medications are useful to maintain IOP in the absence of angle closure. However, the surface area of the cornea is decreased by the PMMA optic, so absorption could be hindered. If a closed angle does form, the surgeon must use a Seton device. Placement in the pars plana precludes the possibility of late closure of the angle on the tube but does necessitate a vitrectomy.

The recommendation of a glaucoma filtering tube or Seton has been controversial. The initial recommendation was that all KPRo patients have a Seton placed before or during the surgery. Presurgery was often problematic because the corneal opacity often precluded visualization and therefore tube placement. Placement during surgery often required two surgeons present in the operating theater, and the two procedures don’t lend themselves well to sequential performance. Manipulating the globe during Seton plate placement often collapsed the globe if the KPRo was performed first. Additionally, tube placement can often be incorrect if done first. Placement of tube in the pars plana was often considered a better choice especially when dealing with a scarred anterior chamber.

With the use of a Seton, various approaches have been considered. One such choice was to place the Seton under tenons but not to insert the tube into the eye, unless or until the pressure was determined to be elevated in the postoperative period. If there was hypotony or a normal IOP was maintained, tube insertion could be avoided indefinitely.

Since it appears that the majority of the post-KPRo glaucoma is secondary to late angle closure, it usually is necessary to place the tube in the pars plana after a core vitrectomy. Therefore many surgeons now place the tube after the KPRo, rather than before.

Foldable keratoprosthesis

The KeraKlear keratoprosthesis (KeraMed Inc.) is a foldable keratoprosthesis that is not FDA-approved; it does have its CE mark. It comprises a 4.0-mm central optic and an overall diameter of 7.0 mm. Unlike other artificial corneas, the KeraKlear is implanted using a nonpenetrating technique and does not require donor corneal tissue for implantation, according to its developer Yichieh Shiuey, MD. The KeraKlear is implanted into the cornea by using a femtosecond laser to create a uniform lamellar pocket within the cornea and to create a trephination incision. After preparation of the cornea, the KeraKlear is inserted into the corneal pocket through the anterior opening in the cornea using non-toothed forceps. The rim of the device is then tucked into the pocket recesses. Optionally, four sutures can be placed in each quadrant. This procedure requires removal of only 5% of the corneal tissue volume to implant.

In a recent unpublished study that included 19 patients with corneal blindness (Snellen acuity < 20/200), each received treatment with the KeraKlear. This population had a wide range of diagnoses including failed corneal transplants, limbal stem cell deficiency, corneal scars, corneal dystrophies and keratoconus. All patients improved in their visual acuity, with an average improvement of 4.2 lines of vision at the last follow-up visit. Larger patient populations with longer follow-up periods will provide useful long-term data of the overall usefulness of this unique foldable model of keratoprosthesis.

Conclusion

While scheduling Boston KPRo surgery, it is important to inform patients of the difference between KPRo surgery and a routine PKP. For instance, the surgeon must emphasize the necessity of wearing a bandage contact lens, postsurgery, and using prophylactic antibiotic drops each day for the rest of their lives. Postoperatively, we can only check the patient’s IOP by palpating the globe through the lids. While some patients embrace the new technology, others fear it. It is also important to show prospective patients clinical photos of what the keratoprosthesis looks like after placement; it is usually very good and acceptable to patients. Further, patients need to know that it is a reversible procedure and that a PKP can be performed at any time should the device fail. This often can bring comfort to the patient and the surgeon.

Use of modern-day keratoprosthesis is a viable surgical option in reversing corneal blindness, resulting in an acceptable cosmetic appearance and overall happy patient. OM

REFERENCES

About the Authors
	Peter Zloty, MD, is director, corneal and external diseases, Southern Eye Network; consulting physician, University of South Alabama Medical Center, Mobile; visiting professor, Liaoning University, Shenyang, China. E-mail: zman36@aol.com. No financial disclosures.
	Thomas “TJ” John, MD is on the editorial board of Ophthalmology Management; clinical associate professor at Loyola University at Chicago; and in private practice in Oak Brook, Tinley Park and Oak Lawn, Illinois. Phone: 708-429-2223; e-mail: tjcornea@gmail.com. Disclosure: No financial interests in any aspect of this article.
	Yichieh Shiuey, MD, practices at Palo Alto Medical Foundation in Sunnyvale, Calif. He can be reached at shiuey@yahoo.com. Disclosure: Dr. Shiuey is the inventor of the KeraKlear and has a financial interest in the product.