Advanced aniridic keratopathy with conjunctivalization of the entire corneal surface. A cortical cataract is also seen
What Treatment Options Would You Recommend?
Aniridic keratopathy develops from limbal stem cell deficiency. Early epitheliopathy and conjunctivalization of the corneal surface starts peripherally and advances centrally with development of subepithelial fibrosis and stromal scarring in later stages. Before the development of significant corneal opacity, keratolimbal allograft or other limbal transplantation procedures can be attempted alone without a penetrating procedure to reverse the keratopathy. However, if the patient has advanced aniridic keratopathy as in our case, a penetrating procedure will be required. In this patient, there are two options: limbal stem cell transplantation followed by corneal transplantation or keratoprosthesis placement.
What Are the Considerations for These Options?
Holland et al. evaluated the success of keratolimbal allograft (KLAL) in aniridia and found that 74.2% of eyes achieved a stable ocular surface and 70% of subsequent penetrating keratoplasties (PKP) remained clear during the study period (mean follow-up 35 months). Long-term immunosuppression was required to improve the odds of maintaining a stable ocular surface . The most likely cause of late failure is graft rejection which argues in favor of continuing immunosuppression beyond the first 2 years. Systemic immunosuppression with a combination of medications, often with cyclosporine/tacrolimus, azathioprine/mycophenolate, and oral prednisone, is required to reduce the risk of limbal graft rejection. Patients taking these medications should be monitored for toxicity, as discussed elsewhere in this book.
In recent years, the Boston keratoprosthesis has become an increasingly accepted option with the advantage of avoiding systemic immunosuppression and faster visual rehabilitation. Studies reporting outcomes of Boston KPro implantation in aniridics with follow-up of 17–28 months on average report visual improvement in 65–94% of patients. However, these patients need to be monitored for unique complications that can be seen after KPro implantation, including retroprosthetic membrane (RPM) formation, melting, worsening glaucoma, infectious keratitis, and device extrusion [2–4]. Although in traditional cases KPro implantation was considered after failure of prior grafts, in these patients KPro placement may be considered as the primary penetrating procedure in advanced keratopathy with or without prior failed KLAL.
Our approach to aniridic patients with limbal stem cell deficiency is as follows: In cases where the disease is limited to the epithelium and there is minimal to no stromal or endothelial disease, limbal transplantation, which is a non-penetrating procedure, is considered first-line treatment (assuming the patient is a good candidate for immunosuppression). Otherwise, when there is coexisting endothelial disease and/or history of previous graft failure, then KPro may be a preferred option given that the success rate with limbal transplant may be lower. If performing cataract surgery at the time of KPro in aniridic patients, we typically prefer to leave the patient aphakic and use an aphakic KPro given that these patients have a higher likelihood of having zonular instability.
After discussion with the patient, it was decided to proceed with Boston type 1 keratoprosthesis placement in the right eye. Her cataract was removed at the time of surgery and an aphakic KPro was placed. Postoperatively, she was treated with topical antibiotics (gatifloxacin) which was maintained at TID for prophylaxis. A 16.0 mm Kontur bandage contact lens was also placed (changed every 2 months). At postop week 2, she had 20/80 vision but at month 1 had started to develop an RPM with decrease in vision to 20/100 (Fig. 22.2). A YAG membranectomy was performed approximately 5 months postoperatively. The vision improved, but approximately 2 months later, the patient was noted to have circumferential melting around the KPro optic. It was noted that the holes of the KPro backplate were filled with RPM tissue although the optic remained clear.
(a) RPM formation after Boston type 1 KPro placement , with membrane behind the optic as well as filling the backplate holes. (b) Anterior segment OCT image showing the thickness of the RPM behind the optic and backplate
What Risk Factors Did This Patient Have for Corneal Melting?
It has been demonstrated that retro-backplate membranes may be a risk factor for corneal melting , possibly secondary to the impedance of aqueous providing nutritional support to the cornea. In a retrospective study, 100% of eyes that melted had evidence of retro-backplate membrane vs. 34% of eyes that did not melt. In addition, the retro-backplate membrane was thicker in the group that melted . To compound this, patients with aniridia are likely to have an unstable ocular surface that may exacerbate the problem. Although this patient did not have any conjunctival disease, patients with conjunctival deficiency (Stevens-Johnson syndrome and mucous membrane pemphigoid) also appear to have a significantly greater risk of developing a melt after KPro .
In our patient, the backplate was noted to be exposed in some areas, although there was no Seidel-positive leak, possibly due to the presence of a dense RPM. Due to this, it was decided to proceed with KPro replacement.
The patient recovered well postoperatively but was noted to develop recurrent RPM which required YAG membranectomy approximately 4 months later. She began to develop increased intraocular pressures and was referred to the glaucoma service. Ultimately her IOP was uncontrolled with drops and oral medication, and she had a pars plana Baerveldt shunt placement approximately 10 months following the KPro replacement. Throughout her clinical course, she had episodes of persistent inflammation postoperatively and intermittent episodes of episcleritis related to her Baerveldt plate (Fig. 22.3 ), which at times required frequent topical prednisolone or oral steroids. Approximately 2.5 years after KPro replacement, she was found to have recurrent melting around the KPro optic again associated with a very thick retro-backplate RPM.
Episcleritis associated with Baerveldt plate
What Options Can Be Considered at This Time?
This patient has recurrent RPM formation, ocular surface inflammation, and most problematic, recurrent corneal melting likely stemming from these issues. Aniridia has been found to be an independent risk factor for RPM formation , although whether this is due to chronic inflammation or another mechanism remains unclear . To our knowledge there is no literature regarding systemic immunosuppression in KPro patients ; however, due to this patient’s propensity to developing RPM and episodes of ocular inflammation, it was felt that decreasing inflammation could stabilize her ocular surface and perhaps prevent RPM formation. There is some data suggesting that systemic immunosuppression is useful and well tolerated in patients with multiple traditional grafts [8–10]. In addition, a replacement KPro was needed given the amount of melting around the KPro optic.
She was placed on oral mycophenolate (1000 mg bid), and the KPro was replaced. At last follow-up 21 months after her second KPro replacement, she was doing well with 20/70 vision and clear optic.
Patients with aniridia should be monitored carefully after KPro placement , and complications managed promptly. Although melting and device extrusion increases morbidity, prompt treatment including replacement of KPro if necessary usually results in return to baseline vision.
E.H. is a 41-year-old male who presented approximately 1 month after a chemical burn. He had sustained a workplace accident of anhydrous ammonia to both eyes, right greater than left. His eyes were flushed immediately afterward. While the left eye had mostly recovered, the right eye continued to have decreased vision, pain, and light sensitivity. On examination, he was counting fingers at 3–4 feet in the right eye and 20/25 in the left eye. He was noted to have superior and temporal ischemia, an epithelial defect covering most of the cornea as well as surrounding conjunctiva, edematous cornea, and cataract (Fig. 22.4 ). The left eye appeared normal. On presentation he was on ciprofloxacin four times a day, atropine once a day, and prednisolone acetate 1% every 2 h, all in the right eye. Over the next 9 months, he was managed with topical corticosteroids, oral corticosteroids, oral vitamin C, punctal plugs, amniotic membrane, and bandage contact lenses. Scleral lenses were attempted but with poor fit. He continued to have a persistent epithelial defect with decrease in vision to light perception. In addition, his intraocular pressure increased 4 months after presentation, necessitating maximal medical therapy and diode cyclophotocoagulation to achieve IOP control. Nine months following presentation, the patient had still a nearly complete epithelial defect of his cornea despite multiple treatment strategies attempted.
(a) Chemical injury with limbal ischemia, diffuse corneal opacification and edema, cataract, and (b) limbus-to-limbus epithelial defect highlighted with fluorescein
What Are Management Options for the Patient at This Point?
This patient has severe limbal stem cell deficiency from his chemical injury and is unable to heal his corneal surface 10 months after injury despite intensive therapy. At this point a strategy for stabilization of the ocular surface and visual rehabilitation should be considered. Severe limbal/corneal injuries usually result in irreversible corneal opacity that requires limbal transplantation with subsequent penetrating keratoplasty. Patients with less severe ocular surface injury may do well after these procedures; however, patients with severe injuries are prone to failure even after these measures are taken with a reported 50–60% or less of patients maintaining a clear cornea [11, 12].
KPro placement for chemical injuries has been reported to be a viable option. Most patients experienced significant improvements in vision, although complications included epithelial defects with sterile melting, likely related to an unstable ocular surface with limbal stem cell deficiency [13, 14]. Efforts to stabilize the ocular surface prior to KPro implantation should be undertaken as much as possible. One study showed that patients with chemical burn had relatively good visual outcome compared to other indications for KPro placement . In addition, in our series of patients who received a primary KPro, that is, without a prior penetrating corneal procedure, we report good outcomes with 100% retention of the KPro in patients whose indication was chemical injury .
Keratolimbal allograft vs. keratoprosthesis placement was discussed with the patient, and given the unilateral nature of the disease, it was decided to proceed with Boston type 1 keratoprosthesis placement, lensectomy, amniotic membrane, and permanent lateral tarsorrhaphy. The patient’s vision improved to counting fingers following surgery. Postoperatively, he was maintained on vancomycin 15 mg/mL bid. However, he was still noted to have a persistent epithelial defect; therefore, conjunctival flaps over the corneal portion of the graft, amniotic membrane, and a more aggressive tarsorrhaphy were performed 2 months after the initial surgery. Unfortunately, the conjunctiva retracted and the patient’s epithelial defect persisted.
A recent study found that in patients with the Boston type 1 keratoprosthesis who required mucosal rehabilitation, free grafting and simple advancement flaps resulted in graft retraction in all cases, whereas vascularized pedicles and bucket handle flaps were stable 50% of the time . Therefore, although these techniques may be effective in patients with cicatrizing conjunctivitis or chemical injury, after keratoprosthesis placement, the ocular environment may not be conducive to survival of these grafts.