January 16, 2015
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Complications possible during learning curve for PDEK

The complications are generally manageable, and the risk decreases as the surgeon gains experience.

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Various endothelial keratoplasty techniques have evolved over the last 2 decades and have been shown to aid in the provision of potential vision through endothelial transplantation. Although endothelial keratoplasties avoid the major complications of penetrating keratoplasty, such as suture inflammation, irregular astigmatism and keratitis, they are not free of complications.

Pre-Descemet’s endothelial keratoplasty (PDEK), a recent modification of endothelial keratoplasty, involves the transplantation of the pre-Descemet’s layer (Dua’s layer) along with the Descemet’s membrane with endothelium. PDEK has many potential advantages over procedures such as Descemet’s membrane endothelial keratoplasty or Descemet’s stripping endothelial keratoplasty; however, in the learning curve, complications are inevitable. These complications are generally manageable, and the risk tends to decline as a surgeon gains experience with the new surgical technique. In this column, we discuss the complications of PDEK and the methods of management.

Intraoperative complications:
Failure to form type 1 bubble

Type 1 bubble formation is the preliminary step in PDEK surgery for obtaining the donor graft. Failure to form a type 1 bubble can happen intraoperatively, when the correct plane of dissection is not reached. In that case, a small peripheral type 2 bubble or a small type 1 bubble is formed. When a small type 1 bubble is formed (Figure 1), it is enhanced by air or viscoelastic injection in a controlled fashion. However, when a type 2 bubble is formed, a conversion is made to DMEK surgery (Figure 2). Double bubble formation (Figure 3) is sometimes also noted.

Figure 1. Donor graft preparation. Small type 1 bubble formed (a). Type 1 bubble enhanced with air (b).

Figure 2. Donor graft preparation. Type 2 bubble formed (a). PDEK converted to DMEK surgery (b).

Images: Agarwal A

Bubble burst during pneumatic dissection

When the bubble bursts early during pneumatic dissection, the size can be enhanced by slow viscoelastic injection via the ostium. Bubble burst usually happens when the surgeon pushes too much air into a small space and the intrabubble pressure raises exponentially faster (Figure 4). Once the bubble bursts after reaching maximum size, Vannas scissors can be used to excise the graft uniformly along its margin.

Figure 3. Donor graft preparation. Both type 1 and type 2 bubble formed (a and b).

Figure 4. Small type 1 bubble formed (a). Bubble bursts when the surgeon pushes too much air into a small space (b).

Small graft

Similar to any endothelial keratoplasty, the size of the graft is vital in PDEK. A small graft is obtained due to the formation of a small type 1 bubble. Whenever a bubble less than 4 mm is seen after pneumatic dissection, viscoelastic can be injected into the bubble to enhance the size. However, too much intrabubble pressure should be avoided because it can lead to another bubble burst. The preferred graft size in PDEK is 7.5 mm to 8 mm. Grafts smaller than 6.5 mm run the risk of failure later. However, a small 6.5-mm graft with a good endothelial count and morphology has shown good results (Figure 5).

Figure 5. Small donor graft about 6.5 mm shows good corneal clearance.

Reverse graft unfolding

An endothelial graft always scrolls with the endothelium to the outside. A PDEK graft curling away from the host cornea indicates that the graft is inverted (Figure 6). This is managed by reinversion with saline in the anterior chamber. Intraoperative optical coherence tomography can also be a guide in visualizing the orientation of the graft. Care should be taken to prevent too much manipulation on the endothelium while reinverting.

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Immediate postoperative complications:
Graft detachment

Due to improper air injection or a leaking wound, the pressure inside the chamber may not be sufficient for graft adhesion. Prolonged graft hydration, which induces a change in IOP, is known to affect the immediate graft attachment. The initial 30 minutes after air injection is crucial in maintaining the graft.

In a short series of 12 PDEK eyes, we noted graft detachment in four eyes. Graft detachment was classified similar to DMEK grafts as grade 1 when there was a minimal peripheral edge detachment with the remainder of the graft being well attached; grade 2 when there was a graft detachment less than one-third of the graft surface area not affecting the visual axis; grade 3 when there was a graft detachment affecting more than one-third of the graft surface area; and grade 4 when there was a completely detached graft. Out of four eyes with graft detachment, two were in group 1, one in group 2 and one in group 3. In group 1, detached grafts and shallow peripheral detachment inferiorly and nasally were observed. Both the group 1 and 2 detachments did not require any further intervention. One eye with grade 3 detachment underwent air injection on day 1 postoperative, and the graft was noted to be apposed after air injection. However, there was redetachment on day 12 (Figure 7) in the same eye, and re-bubbling was successfully done.

Figure 6. An inverted PDEK graft in OCT. Note the graft curling away from the host cornea (above) and reattached graft (below).

Figure 7. Grade 3 graft detachment after PDEK. Before (above) and after (below) air injection.

Lenticule drop

When graft attachment is hindered or when the chamber pressure is not sufficient to maintain graft apposition, lenticule drop can happen. Especially in eyes with complicated surgery, such as posterior capsular rupture or deficient capsule, there is always difficulty in maintaining the air in the anterior chamber. In such eyes, one can implant a transscleral-fixated IOL and do a pupilloplasty if the pupil is large. Strict supine positioning and following the above surgical steps can prevent lenticule drop. By combining the glued IOL procedure with PDEK in eyes with deficient capsules, the posterior chamber IOL aids in maintaining the air in place as compared with an aphakic eye.

Descemet’s folds

A smooth concave configuration of posterior cornea should be obtained in all eyes with good graft adherence. Descemet’s fold can occur when there is excess tissue manipulation intraoperatively (Figure 8). Avoiding too much endothelial handling and following the “no-touch” technique would reduce this complication in the immediate postoperative period. Descemet’s fold usually resolves with medical management, and no additional treatment is required except for the maintenance of the supine position for the next 24 hours.

Loss of air bubble

We expect 80% of the anterior chamber to be filled with the air bubble in the immediate postoperative period. When the surgeon has injected enough air at the end of the procedure but notices less air on day 1, there could be two reasons. Air has the tendency to move or shift depending on the pressure gradient (either the ocular or the atmosphere). In ocular causes, such as large pupil, posterior capsular rupture, decentered scleral-fixated IOL or previous iridectomy, the air enters the posterior chamber or the vitreous. In leaky wound or loose sutures, the air escapes into the atmosphere (Figure 9). In both cases, there is less air in the anterior chamber to aid graft adherence. This can lead to spontaneous graft detachment, and therefore it is recommended to inject air in cases in which there is less or no air on the immediate postoperative day 1 and there is associated detachment.

Figure 8. Day 1 postoperative image showing clear cornea and Descemet’s folds after PDEK.

Figure 9. Post-PDEK patient with loss of air due to wound leak (a) and shallow detachment (b).

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Ocular hypertension

Raised IOP recorded for the first time after PDEK on day 1 postoperative in an eye without any preoperative clinical signs of glaucoma is termed ocular hypertension due to surgery. The common cause is the high bubble pressure due to the 100% air bubble filling the anterior chamber. In this case, anti-osmotic medications, both topical and systemic, should be given. If the IOP is not controlled by medications, the anterior chamber can be decompressed surgically by reducing the air bubble size.

Hyphema

Postoperative hyphema is seen in eyes with intraoperative iris tissue manipulation and combined surgeries. Usually it is mild and resolves spontaneously. Rarely, it can affect graft attachment.

Sterile hypopyon or fibrin

Sterile hypopyon or fibrin is seen in eyes with prolonged surgeries, especially in eyes with combined procedures such as pupilloplasty or in eyes predisposed to uveitis. It is always sterile and resolves with intense topical steroids and rarely oral steroids. Non-resolving fibrin in the anterior chamber can induce traction and affect graft adherence. Hence, it is essential to quickly treat these eyes. Subconjunctival steroids along with hyaluronidase can help in some cases; topical cycloplegic is required in all eyes.

Late postoperative complications:
Graft rejection

Graft rejection is identified by the formation of acute onset endothelial keratic precipitates, Khodadoust line and sudden anterior chamber reaction with corneal edema. The incidence of rejection in PDEK is expected to be similar to DMEK. However, this needs to be evaluated and confirmed by further study in the future. When endothelial rejection is diagnosed, immediate, intense topical steroids (1% prednisolone acetate hourly) and systemic steroids (oral prednisolone 1 mg/kg for the first week followed by tapering dose) are recommended. A topical immunosuppressant such as 2% cyclosporine three times daily can also be added. Regular follow-up with good compliance of medication is required to prevent rejection in some cases.

Graft failure

Graft failure is a rare complication after endothelial keratoplasty and is seen in eyes in which donor endothelium was less than 2,500 cells/mm2 or donors were older than 60 years. Because PDEK is done with both young and adult donor corneas, the risk of primary graft failure due to donor age is less. Non-resolving corneal edema after endothelial keratoplasty with recurrence of bullous keratopathy is a sign of graft failure. Incidence of graft failure and the factors determining it will be similar to other endothelial keratoplasty procedures.

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Graft-host interface

Graft-host interface is examined for the presence of haze or opacification. It can be seen clinically with the slit lamp and confirmed by OCT. In our series, 11 out of 12 eyes had smooth graft-host interface. One eye had minimal interface haze (Figure 10) by postoperative 1 month. After a course of intense steroid treatment, the graft-host interface haze decreased in the final follow-up.

Epithelial change

Central corneal epithelial defect on postoperative day 1 is often seen due to the intraoperative removal of epithelium. Epithelial healing is completed in all eyes by 48 hours. In our short series, mean epithelial thickness of 44.4 ± 9.8 µm on day 7 was reduced to 37.5 ± 6.2 µm by day 90. There was no significant change in the thickness over the time period. There was no difference in the central and peripheral epithelium.

Chronic epithelial haze can happen in eyes with too many topical medications with preservatives. In such situations, reduce the frequency of medication or change to an alternative medication without a preservative. Copious ocular lubricants in the form of drops and gels are recommended for further prevention of symptoms. In some cases, autologous serum may be required for a short period.

Figure 10. Spectral-domain OCT showing graft interface opacification (above, arrows) and resolution after treatment with intense steroids (below, arrow).

Figure 11. Clinical photograph showing IOL opacification after PDEK. Note the clear cornea after PDEK with vision of 20/30.

IOL opacification

IOL opacification after endothelial keratoplasty has been reported. Intracameral expansible gases such as C3F8 or SF6 have been noted to be the etiology in some cases. Although this is a rare complication (Figure 11), it can happen after PDEK in those eyes that required repeat gas injection.

Infection

Infections are rare after endothelial keratoplasty because there are no sutures or open sky manipulation as in conventional keratoplasty. However, these patients are on prolonged steroid therapy, and the risk of keratitis cannot be excluded. Hence, regular follow-up and monitoring of symptoms in patients on steroids with or without antibiotics are necessary.

Graft attachment is vital

Graft adherence is an important factor for better functional outcomes after successful endothelial keratoplasty. Graft detachment has been described as a common complication after endothelial keratoplasty techniques such as DMEK and DSAEK. Although thinner grafts are more susceptible to incomplete graft adhesion after primary positioning, early and possibly better visual recovery may be possible only with a thin graft. PDEK has the advantage of thinner grafts, similar to DMEK, which can aid in easy intraoperative manipulation, better postoperative adherence and fewer complications.

References:
Agarwal A, et al. Br J Ophthalmol. 2014;doi:10.1136/bjophthalmol-2013-304639.
Anshu A, et al. Ophthalmology. 2012;doi:10.1016/j.ophtha.2011.09.019.
Dirisamer M, et al. Arch Ophthalmol. 2012;doi:10.1001/archophthalmol.2011.343.
Dua HS, et al. Ophthalmology. 2013;doi:10.1016/j.ophtha.2013.01.018.
Guerra FP, et al. Ophthalmology. 2011;doi:10.1016/j.ophtha.2011.06.002.
Kumar DA, et al. Postoperative spectral domain optical coherence tomography evaluation of pre-Descemet’s endothelial keratoplasty (PDEK) grafts. J Cataract Refract Surg. 2014. Accepted.
Nanavaty MA, et al. Cochrane Database Syst Rev. 2014;doi:10.1002/14651858.CD008420.pub3.
Shih CY, et al. Am J Ophthalmol. 2009;doi:10.1016/j.ajo.2009.06.034.
Suh LH, et al. Ophthalmology. 2008;doi:10.1016/j.ophtha.2008.01.024.
Yeh RY, et al. Ophthalmology. 2013;doi:10.1016/j.ophtha.2012.08.011.

For more information:
Amar Agarwal, MS, FRCS, FRCOphth, is director of Dr. Agarwal’s Eye Hospital and Eye Research Centre. Agarwal is the author of several books published by SLACK Incorporated, publisher of Ocular Surgery News, including Phaco Nightmares: Conquering Cataract Catastrophes, Bimanual Phaco: Mastering the Phakonit/MICS Technique, Dry Eye: A Practical Guide to Ocular Surface Disorders and Stem Cell Surgery and Presbyopia: A Surgical Textbook. He can be reached at 19 Cathedral Road, Chennai 600 086, India; email: dragarwal@vsnl.com; website: www.dragarwal.com.
Disclosure: No products or companies that would require financial disclosure are mentioned in this article.