Rana Khalil1
1 Royal College of Surgeons, Dublin, Ireland
Introduction
Glaucoma is the second leading cause of graft failure after graft rejection (1). Sustained elevations in intraocular pressure (IOP) can lead to corneal endothelial decompensation, graft failure and vision loss (2). Causes of glaucoma post-keratoplasty include steroid response, pupillary block, retained viscoelastic material, distortion of the trabecular meshwork or Schlemm’s canal, haemorrhage, lens protein leakage, secondary angle-closure from peripheral anterior synechiae, and pre-existing glaucoma (3, 4). Close monitoring, coupled with prompt diagnosis and appropriate treatment of post-keratoplasty glaucoma are vital to the preservation of optic nerve function and a successful graft outcome (5).
Penetrating keratoplasty (PK) has been the gold standard of corneal transplantation for over a century, having also been the first successful allograft ever performed. However, in the last twenty years, other less invasive techniques have become popularised. These include the posterior lamellar keratoplasties Descemet’s membrane endothelial keratoplasty (DMEK), Descemet’s stripping endothelial keratoplasty/ Descemet’s stripping automated endothelial keratoplasty (DSEK/DSAEK), and deep lamellar endothelial keratoplasty (DLEK). These techniques benefit from more rapid restoration of vision, as well as lower rates of graft rejection, infection and wound related complications, such that nowadays PK is rarely the keratoplasty of choice for corneal endothelial disease (6-8).
Post-PK glaucoma occurs in 9-31% of patients in the early postoperative period and 18-35% of patients in the late postoperative period (1, 2, 9, 10). It is important to differentiate between true post-keratoplasty glaucoma and ocular hypertension (OHT) secondary to a reversible steroid response. Importantly, 18-36% of the population are ‘steroid responders’ (11).
Medical Treatment
Steroid-induced ocular hypertension can occur up to six months after surgery, usually peaking at 3 months (12-14). In a detailed study of serial IOP trends post-DSAEK, Kaleem et al found the peak incidence of IOP elevation to be at 1 month and decreasing thereafter, suggesting that mechanisms other than steroid response may be at play, potentially involving corneal biomechanics and air migration intraoperatively (15). Early reduction of steroid therapy confers a significant risk of immunogenic graft rejection and must be approached with caution.
This risk is mitigated with DMEK, as the overall reduced risk of immune-mediated graft rejection post-DMEK warrants a shorter course of topical steroids. Current practice in post-keratoplasty OHT suspects involves a combination of topical steroid reduction with initiation of antiglaucoma, which involves a combination of one or more of topical prostaglandin analogues, beta blockers, alpha agonists, carbonic anhydrase inhibitors, pilocarpine or systemic agents. Before the initiation of antiglaucoma therapy, however, it is prudent to consider any potentially adverse effect this may have on subsequent trabeculectomy outcomes. Specifically, the use of IOP-lowering drops (regardless of type) for three or more years has been associated with significant subclinical conjunctival inflammation, with the three-agent group conferring the worst outcomes (16, 17).
Interestingly, the choice of steroid drops also appears to have differential effects on postoperative IOP. In a study involving de novo OHT post-PK, a switch from prednisolone acetate 1% to rimexolone 1% or fluorometholone 0.1% alone achieved normalisation of IOP in 32.5% of eyes (P <0.01) (18). Similarly, topical prednisolone acetate 1% was found to confer an over 2-fold risk of IOP elevation post-DSAEK when compared to loteprednol etabonate 0.5% gel (P=0.016) (19).
Intraoperative treatment
In the early phase, post-DMEK ocular hypertension is usually secondary to pupillary block. This is easily prevented intraoperatively through peripheral iridectomy or incomplete tamponade. Other options include keeping the patient supine and inducing pupillary dilation alongside medical therapy (dorzolamide 2%/timolol 0.5%, brimonidine tartrate 0.15% drops and oral acetazolamide). Cases of pupillary block and significant iridocorneal adhesions post-DSEK have raised the question as to the ideal amount of air needed for graft retention while protecting against acute IOP rises. Despite interventions ranging from air removal, viscodissection and peripheral iridotomy, more than 70% of grafts may fail at 6 months (20). Several authors have attempted to address this; Lee et al employ a technique of completely filling the anterior chamber with an air bubble which was left for 10 minutes and subsequently reduced in size to 75% of the donor tissue size (20). Other DSEK/DSAEK studies advocate leaving an air bubble ranging from 3 to 8 mm in diameter at the end of the surgery (21-23). In DLEK, the retained air bubble size ranged from 75% of graft diameter to nearly all air removed (24, 25). Certainly, these are challenging complications which are difficult to manage in the context of graft preservation.
Surgical treatment
As any increase in IOP post-keratoplasty can significantly compromise an already low reserve of endothelial cells, the surgical challenge lies in ensuring the intervention is as minimally invasive as possible (26). One minimally invasive technique is laser trabeculoplasty, which has been shown to achieve a mean IOP reduction of 29.7% in post-PK patients with uncontrolled glaucoma (27). Cyclodestructive procedures, including cryotherapy and Nd:YAG or diode cyclophotocoagulation, are generally reserved for cases of advanced refractory glaucoma where visual function is significantly compromised. This is because they often need to be repeated and may precipitate phthisis bulbi (28). Ayyala et al, in a landmark systematic review, reported that in 78% (range 64-85%) of post-keratoplasty glaucoma patients, cyclodestructive procedures achieved adequate IOP control. Deep sclerectomy is useful when the angle is open and there are no peripheral anterior synechiae. They have been associated with a higher graft survival as compared to trabeculectomy with MMC (29).
Trabeculectomy has been the gold standard for surgical treatment of glaucoma for many years. In post-PK glaucoma, Ayyala reported success rates of conventional trabeculectomy in controlling IOP to be 40-50% (2). The addition of MMC further accelerates this, with 66- 89.5% of post-PK glaucoma eyes achieving adequate IOP control (16, 56, 57). Further to this, Boey et al conducted a retrospective case-control study comparing outcomes of trabeculectomy with MMC after DSAEK and PK, in patients without prior glaucoma who go on to develop glaucoma (16). They reported that mean IOP reduction at 12 months was higher in the DSAEK group (70.1%) compared to the PK group (55.6%) (P=0.04), particularly in the proportion of patients achieving IOP ≤12 mm Hg (80% in DSAEK vs 43.9% in PK, P=0.03). In terms of visual outcomes post trabeculectomy, however, no statistically significant difference was observed between both groups.
Other options include a glaucoma drainage device such as the Ahmed glaucoma valve, which has been found to successfully control post-PK glaucoma in 74-92% of cases at 1 year (30-33). It should be noted that ocular hypertension following Ahmed valve implantation has been reported to be more common than Molteno or Baerveldt implants, likely due to the smaller surface area of the former (26). The cause of increased graft failure following glaucoma drainage device implantation compared to traeculectomy is multifactorial; it may be due to mechanical damage from tube-corneal contact resulting in endothelial decompensation and graft rejection, particularly in a shallow anterior chamber (34). In a comparative study performed by Ayyala et al which compared trabeculectomy with MMC, glaucoma drainage device, and laser cyclophotocoagulation in managing post-PK glaucoma, IOP control as well as the rate of graft failure was observed to be the same for all 3 groups (28).
In conclusion, glaucoma is the second leading cause of corneal graft failure after graft rejection. Sustained elevations in intraocular pressure can lead to endothelial cell loss and corneal decompensation, graft failure and sight loss. The management of post-keratoplasty glaucoma is a true ophthalmic challenge and may require a combination of medical and surgical interventions to achieve adequate resolution of IOP.
References
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