Management of Glaucoma in Eyes with Boston Keratoprosthesis
Advances in keratoprosthesis implant design along with improvements in postoperative management have led to a decline in complications associated with keratoprosthesis. However, while the incidence of implant extrusion, corneal necrosis, and infectious endophthalmitis have decreased, glaucoma remains a primary threat to visual prognosis in patients with a keratoprosthesis . The Boston Keratoprosthesis (Kpro) is an artificial corneal transplant composed of polymethyl methacrylate (PMMA). It is available in two types; Type I Kpro is the most widely used and Type II Kpro is reserved for more severe ocular surface disease. Most of the available literature pertains to glaucoma management in eyes with Boston Type I Kpro.
Incidence of Glaucoma prior to Kpro Surgery
Outcome studies have found a pre-existing diagnosis of glaucoma in 36-76% of patients receiving Kpro and many had undergone prior glaucoma surgery. In some cases, the underlying ocular conditions that contributed to corneal decompensation necessitating a Kpro also confer an increased risk of glaucoma. In addition to a multitude of corneal and anterior segment complications, herpes simplex virus (HSV) infection is associated with trabeculitis and increased intraocular pressure. One cohort study of 17 eyes with KPro following HSV keratitis found that 66% had glaucoma preoperatively. Stevens Johnson Syndrome (SJS) is also associated with increased glaucoma risk. Sayegh et al found glaucoma preoperatively in 75% of KPro eyes with severe anterior segment inflammation and scarring from SJS. Cade et al report preoperative glaucoma in 75% of eyes with KPro caused by chemical burns. Alkali burns in particular are associated with severe glaucoma. Alkaline material penetrates deeper into the eye than other substances and damages angle structures, which leads to scarring and outflow obstruction. Harissi-Dagher et al. found that eyes with alkaline injuries may continue to have progressive optic nerve damage despite adequate intraocular pressure control with glaucoma drainage devices (GDD). Finally, prior failed penetrating keratoplasty (PKP) transplant, which is common in many KPro recipients, is a risk factor for glaucoma because PKP may cause synechiae formation and chronic angle closure.
Incidence of Glaucoma Following Kpro Surgery
Glaucoma in Kpro eyes is often advanced at the time of keratoprosthesis implantation and demonstrates a more aggressive course with disease progression exacerbated by perioperative inflammation. Following KPro surgery, 14-28% of patients have elevated IOP. Glaucomatous damage progresses in 7-14% of patients after KPro. Development of glaucoma de novo following Kpro placement has been reported in 2-28% of KPro recipients. Crnej et al found a rate of cup to disc ratio (C/D) progression of 0.075 per year in glaucomatous KPro eyes, which is approximately 7 times faster than the rate of C/D progression in patients with primary open angle glaucoma. Some studies have found an increase in number of glaucoma medications used to control IOP following KPro implantation while others have reported a decrease.
A number of mechanisms for glaucoma development and progression in KPro eyes have been proposed. As noted by Crnej et al, eyes undergoing Kpro implantation often have pre-existing anterior segment damage due to an aggressive inflammatory process or traumatic event. It remains unclear if the Kpro surgery itself confers a unique glaucoma risk or if glaucoma simply develops as a consequence of further surgical trauma to already diseased eyes.
Chronic angle closure (CACG) results from peripheral anterior synechiae formation caused by chronic inflammation or following surgery, especially amongst patients who have failed one or more prior PKP surgeries. Netland et al used ultrasound biomicroscopy (UBM) to visualize posterior anterior synechiae following Kpro placement in eyes with glaucomatous optic neuropathy due to chronic angle closure. Larger implant backplates clamp surgical wounds and reduce PAS formation. However, larger implant backplates cause more congestion in the anterior chamber, which may impede aqueous outflow.
Some have suggested removal of lens or iris to decrease complications from retroprosthetic membrane growth or PAS formation. Netland et al. removed iris tissue during Kpro placement in an attempt to decrease PAS and CACG. However, 21 of 36 eyes (58%) still developed glaucoma postoperatively in this series. Others suggest that removal of iris may distort the angle and lead to collapse of the trabecular meshwork with resultant outflow obstruction. Furthermore, a residual iris stump after resection may cause angle closure, similar to the mechanism for glaucoma observed in patients with congenital aniridia.
Inflammatory debris or vitreous material may obstruct the trabecular meshwork. Perioperative inflammation stimulates release of cytokines, which can cause direct damage to and/or cause apoptosis of retinal ganglion cells. This theory is supported by the presence of optic disc pallor in many Kpro patients.
Talajic et al propose that the Kpro implant causes surrounding tissue disruption and affects scleral rigidity. Alternation of scleral integrity can cause biomechanical damage to the optic nerve at the level of the lamina cribrosa. This may help explain progression of optic neuropathy despite adequate IOP control in Kpro patients.
Finally, following Kpro implantation there is decreased ocular surface area which results in decreased absorption and reduced effectiveness of IOP-lowering medications. Perioperative steroids can influence glaucoma development or progression due to steroid-induced ocular hypertension.
Diagnosis and Monitoring
Intraocular Pressure Measurement
Detection and monitoring of glaucoma after implantation of a Kpro poses many challenges, particularly when attempting to assess intraocular pressure. Applanation and handheld tonometers are inaccurate when applied over the Kpro. Handheld tonometer readings recorded from the limbus may be an alternative and comparison with limbus measurements from the fellow eye is recommended for interpretation of readings.
IOP estimation by finger tension or palpation, while being careful to avoid palpation over a GDD plate, is a commonly used method. The examiner should consider that GDD placement may alter scleral dynamics and complicate IOP estimation via palpation. Some studies report that amongst experienced practitioners digital palpation can accurately detect IOP greater than 30 mmHg and within a margin of error of 5 mmHg. Baum et al, however, report that digital palpation is generally inaccurate but useful for detection of markedly elevated IOP. They found little correlation between digital palpation and Goldmann tonometry readings. Netland et al. reported that pneumotonometer and handheld tonometer use on sclera in Kpro patients overestimated IOP and digital palpation was the preferred method of IOP assessment in their study. However, Kuo et al. found that although scleral pneumatonometry averaged 9 mmHg higher than corneal pneumatonometry, there was a linear correlation between the two over serial measurements. Kapamajian et al. extrapolated an equation for corneal pneumatonometry (IOPk) from scleral pneumatonometry (IOPs) where IOPk = 11.9 + 0.32(IOPs) – 0.05(Age), which may allow scleral pneumatonometry to be used as an adequate alternative when corneal measurements are unreliable. Finally, Estrovich et al. found that the Schiotz tonometer, when used on the temporal sclera or corneoscleral limbus, had higher accuracy than handheld tonometry or digital manometry.
Anterior segment optical coherence tomography (OCT) can be employed to evaluate angle structures in Kpro eyes. Garcia et al found that anterior segment OCT was superior to UBM for visualizing angle structures but inferior to UBM in assessment of GDD positioning in the sulcus. As with other forms of glaucoma, serial optic nerve head (ONH) OCT and optic disc photos are recommended to evaluate for disease progression. Posterior segment and macular OCT may detect cystoid macular edema (CME), a frequent complication in this patient population.
The clear optic of the keratoprosthesis implant allows direct visualization of the optic nerve and fundus for assessment of optic nerve health and C/D ratio changes. Preoperative visualization of optic nerve is often limited by corneal of intraocular media opacity.
The maximum Goldmann visual field in one series of Kpro patients was 90-95 degrees. Functional testing with visual fields was found to be more reliable than structural testing with Heidelberg Retinal Tomography.
Because of the reduced ocular surface available for absorption following Kpro placement, topical IOP-lowering medications are less effective. Netland et al report preferred use of systemic carbonic anhydrase inhibitors when medical therapy is required for IOP control.
Approximately 13% of patients required surgical treatment for glaucoma following Kpro placement. Crnej et al found that when glaucoma surgery was performed prior to or concurrently with Kpro implantation there were significantly slower rates of C/D progression compared to eyes that received delayed surgical glaucoma treatment. Lenis et al. found that, when compared to Kpro surgery alone, Kpro surgery combined with GDD placement resulted in improved IOP at 1 year. Therefore, concurrent placement of GDD with Kpro surgery should be considered for eyes at increased risk of glaucomatous progression.
Valved GDD (Ahmed tube shunt) is the most commonly used drainage device amongst Kpro patients requiring surgical treatment for glaucoma. Non-valved GDD can have more substantial IOP-lowering effect than valved GDD, but carry greater risk of hypotony from overfiltration. Non-valved GDD also require several weeks of hypertensive phase to prevent hypotony, which may allow for interval glaucoma progression. The delay in IOP-lowering with non-valved GDD is especially troublesome because topical medications are less effective in Kpro eyes, which can lead to marked ocular hypertension postoperatively. Trabeculectomies are less effective because of tissue scarring adjacent to keratoprostheses. Use of Ahmed GDD is generally recommended in all Kpro patients with glaucoma except in cases of primary open angle glaucoma or with normalized IOP not requiring medications. GDD placement 3-6 months prior to the Kpro implantation is sufficient to allow maturation of the GDD. If iris tissue or lens is removed during implantation of a Kpro, a pars plana vitrectomy should be performed and a GDD should be placed (9). For intact iris tissue it is recommended to perform a peripheral iridectomy concurrently. Following Kpro surgery, Cade et al favor placement of GDD for digital palpation IOP estimates near 20 mmHg. Netland et al report that GDD placement in Kpro patients successfully decreased IOP in nearly all cases.
Some surgeons recommend tube placement in the sulcus to prevent anterior chamber crowding. The GDD may be placed with a long tube in a radial orientation so that the tip may be visible in the sulcus. Netland et al report that tube occlusion was the most common complication, observed in 11% of this cohort. GDD placement in the sulcus decreases risk of tube exposure due to reduced contact with the implant backplate. Risk of tube exposure can be decreased further with use of a patch graft. If the GDD is placed in the anterior chamber, Kamyar et al suggest use of posterior chamber intraocular lens to protect against tube occlusion from anterior migration of the vitreous.
Other complications include formation of a fibrous capsule surrounding the GDD, which decreases effectiveness of the tube. This is observed more commonly in cicatrizing conjunctival disease. Alternate epithelium lined drainage locations including the lacrimal sac and the maxillary and ethmoid sinuses have been suggested on the basis of a theoretical benefit of decreased fibrosis surrounding the drainage plate, but no significant IOP reduction has been demonstrated.
Cyclophotocoagulation (CPC) uses a diode laser to ablate the ciliary process, decrease aqueous production, and lower IOP. This can be accomplished transsclerally or endoscopically under direct visualization. Transscleral illumination with a fiberoptic light can be used to help guide location choice for transscleral CPC, but excessive scar tissue on the ocular surface may limit the utility of this technique. Both endoscopic and transscleral forms of CPC are effective. Semchyshyn et al found that transscleral CPC lowered IOP by approximately 60%. A single transscleral CPC treatment resulted in normalized IOP at 48 months from treatment in 12 of 18 patients in one study by Rivier et al.
Compared to GDD, CPC has the benefit of no permanent hardware, and therefore no implant exposure and less risk of endophthalmitis. Talajic et al propose endoscopic CPC as an alternative first line glaucoma treatment in Kpro eyes because of fewer complications compared to surgery. Disadvantages to CPC include difficult titration requiring multiple procedures for adequate IOP control. Excessive ciliary body damage from CPC can result in hypotony and, rarely, phthisis bulbi, though hypotony and phthisis may also occur as a result of GDD overfiltration.
CPC is a good therapeutic option for type II keratoprothesis in which the conjunctiva has been resected and filtration surgery is not possible or in cases of type I keratoprosthesis if the conjunctiva is sufficiently scarred.
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