Implantation of a corneal graftkeratoprosthesis for severe corneal opacity in wet blinking eyes

# Recommendations
Current evidence on the efficacy of implantation of a corneal graftkeratoprosthesis for severe corneal opacity in wet blinking eyes is adequate in the short to medium term. Although the evidence on safety shows a high incidence of significant adverse effects, there are few options for patients with severe corneal opacity if standard corneal grafts have failed or are not appropriate. Therefore this procedure may be used with normal arrangements for clinical governance, consent and audit.
During the consent process, clinicians should ensure that patients clearly understand the balance of risks and benefits of this procedure, including: the need for longterm followup, which some patients find burdensome; the possibility that sight may not improve and may deteriorate; and the risk of serious complications. Patients should be provided with clear information in an appropriate format. In addition, the use of NICE's information for the public is recommended.
Implantation of a corneal graftkeratoprosthesis for severe corneal opacity in wet blinking eyes should only be done on carefully selected patients with corneal blindness, when standard treatments such as keratoplasty have failed or are not appropriate.
Implantation of a corneal graftkeratoprosthesis for severe corneal opacity in wet blinking eyes should only be done in specialist centres by surgeons experienced in the technique; longterm followup should be carried out by an experienced multidisciplinary team.# Indications and current treatments
Injury or disease of the cornea can make it opaque, stopping light from entering the eye and resulting in loss of vision. Some severe corneal diseases can also affect the eye's blink and tear mechanisms. Corneal injuries can be caused by direct trauma, including surgery, as well as chemical or thermal burns. Diseases that can cause corneal opacity include autoimmune diseases, bullous keratopathy, keratoconus, keratitis and corneal stromal dystrophies.
The standard treatment for significant corneal opacity is a corneal transplant (penetrating keratoplasty). Penetrating keratoplasty removes the opaque cornea using a trephine, replacing it with a donor cornea. Some patients cannot have a standard corneal transplant for reasons including: disease severity; severe involvement of the conjunctiva; a failed previous corneal transplant; or when measures needed to prevent graft rejection are contraindicated. For these patients, penetrating keratoplasty using an artificial cornea (keratoprosthesis) may be an option.# The procedure
A corneal graftkeratoprosthesis is an artificial clear central corneal window surrounded by a human donor cornea. Implantation is generally done if a standard corneal transplant has failed, or when it is inappropriate. The procedure is used to treat only the most severe corneal opacity.
A type I corneal graftkeratoprosthesis is the most commonly implanted artificial corneal device and is suitable for patients whose blink and tear mechanisms are reasonably intact (wet blinking eyes) and who have had multiple graft failures. The device is custommade to have a range of dioptric powers to match the axial length of the patient's aphakic eye. It is shaped like a collar button, with a refractive front and porous back plate and a titanium locking ring.
Implantation of the fully assembled corneal graftkeratoprosthesis is done under general or local anaesthesia. A human donor corneal graft with a central hole is positioned between the front and back plate, and held in place by the titanium ring. The central portion of the patient's opaque cornea is removed and if the natural lens is in place, it is also removed. The corneal graftkeratoprosthesis is then transferred to the patient's corneal opening and secured with multiple interrupted sutures. Finally, a soft bandage contact lens is placed on the surface of the eye.
Postoperatively, patients wear a soft contact lens and use prophylactic antibiotic drops for the rest of their lives. In addition, topical steroids are usually recommended and patients need frequent followup and monitoring for life.# Efficacy
This section describes efficacy outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
A case series of 150 patients (158 eyes) who had type I corneal graftkeratoprosthesis implantation reported that preoperatively only 9% of eyes had best corrected visual acuity (BCVA) of 20/200 or better. Postoperatively, 70% (97/138) of eyes had BCVA of 20/200 or better at a median followup of 6.3 months; 30% (41/138) of eyes did not have BCVA of 20/200 or better because of preexisting posterior segment conditions. The probability of maintaining the same vision at 7 years (n=97 eyes; estimated with KaplanMeier survival curves) was 50%.
The case series of 150 patients (158 eyes) reported an overall device retention rate of 84% at 2 years and 67% (89/133) at 7year followup.
The case series of 150 patients (158 eyes) reported device removal in 33% (44/133) of patients at 7year followup. In 25% (35/139) of eyes, the device was removed (30/139) or the eye was enucleated (5/139) as a result of devicerelated complications during followup.
The case series of 150 patients (158 eyes) reported that 12% (5/42) of eyes had repeated keratoprosthesis implantation because of recurrent corneal melts with device extrusion.
A case series of 24 patients who had corneal graftkeratoprosthesis implantation (type I in 23 patients) reported significant improvement in postoperative visionrelated quality of life (assessed using the National Eye Institute Visual Functioning Questionnaire ) at 3month followup when compared with baseline scores (patientreported visual function overall score: 43.1 at baseline versus 70.0 at 3 months ). Subscale scores within the NEI VFQ25 showed significant improvement in general vision, near and distance activities, social functioning, mental health, role difficulties, dependency, colour vision and peripheral vision (p<0.05). The improvement was also seen when comparing baseline scores with postoperative scores at an average followup of 16 months.
The specialist advisers listed key efficacy outcomes as improvement in visual acuity, adequate management of glaucoma and device retention.# Safety
This section describes safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
Retroprosthetic membrane formation was reported in 54% (22/41) of eyes in a case series of 37 patients who had type I corneal graftkeratoprosthesis implantation at a mean followup of 22 months. Fourteen patients needed treatment with yttriumaluminiumgarnet (YAG) laser (3 of them needed additional surgical membranectomy) and 8 patients did not need any treatment. In 6 patients, retroprosthetic membrane formation was secondary to concomitant surgical procedures. Epiretinal membrane formation was reported in 1 patient in a case series of 40 patients (42 eyes) at 1year followup (further details were not reported).
Corneal melting was reported in 24% (10/42) of eyes in the case series of 40 patients at a mean followup of 64 months. This occurred in patients with StevensJohnson syndrome and the melt led to further morbidity, infection and implant extrusion.
Chorioretinal adhesion problems (retinal detachment with or without choroidal detachment or retinoschisis) were reported in 27% (11/41) of eyes in the case series of 37 patients at a mean followup of 22 months. Six patients needed surgery: 5 had vitrectomy and 1 had transscleral cyclophotocoagulation.
Glaucoma or increased intraocular pressure was reported in 81% (34/42) of eyes (in 5 eyes of people with, and 29 eyes of people without, StevensJohnson syndrome) in the case series of 40 patients at a mean followup of 64 months. Increased intraocular pressure was noted in 19% (8/42) of eyes, glaucoma was newly diagnosed in 30% (13/42) of eyes and 30% (13/42) of eyes with preoperative glaucoma had disease progression. All were treated with antiglaucoma drugs (mean 2.7 drugs per eye), but 12 needed surgical interventions at a mean followup of 22.1 months, corresponding to a glaucoma surgery rate of 0.062/eye year.
Infectious endophthalmitis was reported in 16% (20/133) of patients in a case series of 150 patients (158 eyes) at 7year followup (further details were not reported). Infectious keratitis was reported in 21% (9/42) of eyes (3 eyes of people with autoimmune disease and 6 eyes of people with nonautoimmune disease) in the case series of 40 patients at a mean followup of 64 months (further details were not reported).
Sterile corneal necrosis was reported in 20% (26/133) of patients in the case series of 150 patients (158 eyes) at 7year followup (further details were not reported).
Sterile vitritis was reported in 4% (4/101) of eyes in an international series and 11% (10/94) of eyes in a US series in a retrospective case series of 194 patients at a mean followup of 14.2 and 24.1 months (further details were not reported).
Cystoid macular oedema was reported in 10% (13/133) of patients in the case series of 150 patients (158 eyes) at 7year followup (further details were not reported).
Persistent epithelial defects were reported in 10% (10/101) of eyes in the international series and 36% (34/94) of eyes in the US series in the retrospective case series of 194 patients at a mean followup of 14.2 and 24.1 months (further details were not reported).
Vitreous haemorrhage was reported in 10% (4/42) of eyes in the case series of 40 patients at 1year followup (further details were not reported). Choroidal haemorrhage was reported in 3% (4/122) of patients in a case series of 122 patients (126 eyes) at 6month followup (further details were not reported).
Device leaks at the keratoprosthesis stem (through the corneaanterior front plate interface of the device) were reported in 3 eyes (at a mean of 13.7 months) after type I corneal graftkeratoprosthesis implantation in a case report of 3 patients. In 1 patient, the leak was not evident; in the second patient, a repeat keratoprosthesis implantation was needed to stop the persistent leak; in the third patient the persistent leak was repaired with glue.
Traumatic wound rupture (at the grafthost junction) at an average of 4.2 months after type I corneal graftkeratoprosthesis implantation was reported in 3% (4/136) of eyes in the case series of 122 patients. In 2 eyes, the device was extruded and therapeutic penetrating keratoplasties were performed, but vision deteriorated. In 2 eyes with wound rupture, suturing of the wound was done. Vision improved in 1 eye and in the other it was stable.
Occlusive vasculopathy (peripheral occlusive vasculitis and ischaemia of the entire retina) was reported in 5% (2/41) of eyes in the case series of 37 patients at a mean followup of 22 months (further details were not reported).
Corneal infiltrate was reported in 12% (12/101) of eyes in the international series and 10% (9/94) of eyes in the US series in the retrospective case series of 194 patients at a mean followup of 14.2 and 24.1 months (further details were not reported).
Scleritis was reported in 1 patient in the case series of 122 patients (126 eyes) at 6month followup (further details were not reported).
Chronic hypotony was reported in 9% (6/67) of patients in a case series of 68 patients at a median followup of 18.5 months after type I corneal graftkeratoprosthesis implantation. The incidence of chronic hypotony was 3.7% at 1 year (95% confidence interval  0.9% to 14%) and 13.3% at 2 years (95% CI 5.5% to 30%). All eyes had retroprosthetic membranes and decreased visual acuity and 5 eyes had previous history of glaucoma or ocular hypertension. Four patients had pars plana vitrectomy and silicone oil injection and reported increased vision ranging from 'hand motion' to 20/400. One patient with 1 affected eye deferred treatment and the eye progressed to phthisis bulbi needing enucleation. One eye had prephthisis and no surgery was needed.
Posterior capsular tear was reported in 1 patient during the surgery in the case series of 40 patients (further details were not reported).
Sterile corneal ulceration at the graftoptic junction was reported in 22% (2/9) of eyes (1 after 52 months and 1 at 10 months), in a case series of 9 patients (9 eyes) with failed interventions for chemical and thermal injury. Both devices were removed and replaced, 1 also had a concomitant retinal detachment repair. Vision deteriorated in 1 eye and the other eye developed endophthalmitis and became blind and painful, and was enucleated.
Horizontal diplopia after type I corneal graftkeratoprosthesis implantation was reported in a patient with a history of trauma and a series of failed corneal transplants. Strabismus surgery restored binocular vision.
Pigmented deposit on the keratoprosthesis (a large central black deposit on the bandage contact lens on the front plate of the device) associated with the use of topical ibopamine as a treatment for chronic hypotony was reported in a patient implanted with a type I device. Postoperatively, vision improved to a best corrected visual acuity (BCVA) of 20/200, but after 3 months, vision deteriorated because of the pigmented deposit. This was treated by removing the bandage contact lens and changing to a daily disposable contact lens and regular cleaning of the front plate with diluted baby shampoo and surgical sponges.
In addition to safety outcomes reported in the literature, specialist advisers are asked about anecdotal adverse events (events which they have heard about) and about theoretical adverse events (events which they think might possibly occur, even if they have never done so). For this procedure, specialist advisers reported no anecdotal or theoretical adverse events.# Further information
For related NICE guidance, see the NICE website.

# Information for patients
NICE has produced information on this procedure for patients and carers (information for the public). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance
NICE interventional procedures guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS.
This guidance was developed using the NICE interventional procedures guidance process.
We have produced information for the public explaining this guidance. Information about the evidence the guidance is based on is also available.
NICE produces guidance, standards and information on commissioning and providing high-quality healthcare, social care, and public health services. We have agreements to provide certain NICE services to Wales, Scotland and Northern Ireland. Decisions on how NICE guidance and other products apply in those countries are made by ministers in the Welsh government, Scottish government, and Northern Ireland Executive. NICE guidance or other products may include references to organisations or people responsible for commissioning or providing care that may be relevant only to England.
Your responsibility
    This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.
Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to have due regard to the need to eliminate unlawful discrimination, advance equality of opportunity and foster good relations. Nothing in this guidance should be interpreted in a way that would be inconsistent with compliance with those duties.
Copyright
     National Institute for Health and Care Excellence 2015. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.
ISBN: 978-1-4731-1537-8