Abstract
Background
Individuals who have failed one or more full thickness penetrating keratoplasties may be offered repeat corneal surgery using an artificial or donor cornea. An artificial or prosthetic cornea is known as a keratoprosthesis. Both donor and artificial corneal transplantations involve removal of the diseased and opaque recipient cornea (or the previously failed cornea) and replacement with another donor or prosthetic cornea.
Objectives
To assess the effectiveness of artificial versus donor corneas in individuals who have had one or more failed donor corneal transplantations.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 11); Ovid MEDLINE; Ovid Embase; LILACS (Latin American and Caribbean Health Sciences Literature database); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 4 November 2019.
Selection criteria
Two review authors independently assessed reports from the electronic searches to identify randomized controlled trials or controlled clinical trials. Any discrepancies were resolved by discussion or consultation.
Data collection and analysis
We used standard methodological procedures expected by Cochrane. For discussion purposes, we summarized findings from relevant comparative case series. We performed no data synthesis.
Main results
We did not identify any randomized controlled trials or controlled clinical trials comparing artificial corneas with donor corneas for repeat corneal transplantations.
Authors' conclusions
The optimal management for those individuals who have failed a conventional corneal transplantation is unknown. Currently, in some centers, artificial corneal devices are routinely recommended after just one graft failure, while in other centers, they are not recommended until after multiple graft failures, or not at all. To date, there have been no controlled trials comparing the visual outcomes and complications of artificial corneal devices (particularly the Boston type 1 keratoprosthesis, which is the most commonly implanted artificial corneal device) with repeat donor corneal transplantation, in order to guide surgeons and their patients. Such a trial is needed and would offer significant benefit to an ever‐increasing pool of people with visual disability due to corneal opacification, most of whom are still in productive stages of their lives.
Plain language summary
Artificial corneal devices versus human donor corneas for people undergoing repeat corneal transplantation
What is the aim of the review? The aim of this Cochrane Review was to compare the effectiveness and safety of artificial corneal devices versus donor (human) corneas in people who had at least one donor cornea transplant that had failed.
Key messages The optimal management for people who have failed a donor corneal transplantation is unknown.
What was studied in the review? There are several types of corneal transplants. The type of transplantation is defined by how much of the cornea is removed and replaced. Removal and complete replacement of the entire cornea is known as a full thickness penetrating keratoplasty (PK). Removing part of the cornea with replacement of the same part from a donor is based on the parts transplanted (e.g. endothelial keratoplasty refers to transplantation of the inner or endothelial layers of the cornea). Corneal transplantation is one of the most successful transplantations. However, sometimes the transplantation fails and the donor tissue becomes cloudy. No current guidelines are available as to how many donor corneal transplants can be performed in an eye that has failed a previous donor corneal transplantation.
Corneal transplantation with either a donor cornea or an artificial cornea (known as a keratoprosthesis) involves removal of the cloudy cornea and replacement with a clear cornea or corneal device. Some examples of keratoprostheses (KPro) are the Boston KPro (Types I and II), AlphaCor, osteo‐odonto‐keratoprosthesis, and Fyodorov‐Zuev KPro.
What are the main results of the review? We found no randomized clinical trials or controlled clinical trials in this review. There is no high‐quality evidence to guide surgeons and patients as to the best treatment to use after failure of a donor transplant. A trial comparing the use of artificial versus human donor corneas after PK failure is therefore needed.
How up‐to‐date is this review? We searched for studies published up to 4 November 2019.
Background
Description of the condition
The cornea is the transparent layer of the anterior surface of the eye and functions to transmit light and provide most of the refractive power of the eye. Diseases affecting the cornea are a major cause of blindness worldwide. Globally, corneal opacity is the fourth‐leading cause of bilateral blindness after cataract, glaucoma, and age‐related macular degeneration, affecting some 4 to 8 million people, 90% of whom live in the low income countries (Murthy 2012; Whitcher 2001). Furthermore, unilateral corneal blindness, which also creates much disability, is not reflected in these statistics. Additionally, children and young adults are affected by corneal blindness proportionately more than by other major, age‐related blinding diseases such as macular degeneration and glaucoma.
There are currently no proven medical treatments available to restore clarity in diseased corneas. Surgery with donor corneal transplantation (keratoplasty) is the definitive treatment for corneal blindness. Although the majority of these transplants are successful, if the transplantation fails the first time for any reason, a repeat transplantation using an artificial or donor cornea may be considered.
Description of the intervention
Corneal transplantation is one of the most commonly performed transplant procedures in the low income countries. A total of 51,294 corneal transplantations were performed in the USA in 2018 (EBAA 2018). Successful transplantation occurs when the corneal graft is not rejected and it retains clarity and integrity. Several published studies have documented that the single most important factor affecting the success of corneal transplantation is the preoperative indication for the surgery (Thompson 2003; Wagoner 2009). Donor corneal transplantation achieves remarkable overall success rates, with approximately 90% of "low risk" patients having successful transplants (ACGR 1993; Thompson 2003; Wagoner 2009). Patients at "low risk" of corneal graft failure typically suffer vision loss from corneal shape problems (such as keratoconus) or from loss of clarity due to genetic problems of the endothelial layer of the cornea (such as Fuchs endothelial dystrophy), trauma, or infection. For example, although the five‐year survival probability is usually over 90% for keratoconus, this rate is less than 50% when the indication is corneal edema due to endothelial failure from intraocular surgery, and even lower when the eye is aphakic (without the natural lens) (ACGR 1993; Thompson 2003).
The likelihood of corneal graft survival drops markedly in the setting of previous corneal graft failure. Re‐graft (repeat donor corneal transplantation), presence of significant neovascularization of the host bed, history of glaucoma, and previous herpetic infection also decrease the likelihood of graft survival (ACGR 1993; Siganos 2010; Thompson 2003; Wagoner 2009). The overall risk of failure for re‐grafts is about 50% at five years (Ahmad 2016; Thompson 2003; Yildiz 2010); this percentage is likely an underestimate, as most surgeons tend to limit re‐grafting only to patients in whom they believe there is a reasonable chance of success for subsequent graft survival and improvement in visual acuity. Notably, re‐grafts are now the most common indication for penetrating keratoplasty (PK) in the USA, comprising 18% of all PKs (EBAA 2018).
In the USA, patients who have failed multiple corneal grafts may be offered an artificial cornea. An artificial or prosthetic cornea, known as a keratoprosthesis (KPro), is a corneal implant made of synthetic material, the most common of which is the Boston keratoprosthesis (Boston KPro). The Boston KPro is a two piece, collar‐button device made of polymethylmethacrylate (PMMA), a transparent thermoplastic, with a titanium locking ring. Although it is associated with complications including infection, extrusion, glaucoma, and retinal detachment, because it is made of artificial material it will not opacify (become cloudy). The AlphaCor device, made from poly‐2‐hydroxyethyl methacrylate, is made of a one‐piece flexible implant with a peripheral skirt and a transparent central region connected on a molecular level by an interpenetrating polymer network. It is implanted in the recipient eye via a two‐stage surgical procedure. Osteo‐odonto‐keratoprosthesis, which is reserved for individuals with severe ocular surface disorders, requires a complex, multistep surgical procedure and is therefore performed very infrequently. A lamina of the patient's tooth is grafted into the eye after having been transplanted elsewhere for biointegration and vascularization purposes. An artificial optic made of PMMA is then installed in the unit to allow vision. The Fyodorov–Zuev keratoprosthesis, commonly used in the former Soviet Union, is made of a titanium supporting plate with two large openings to allow aqueous humor to flow anteriorly. An optical cylinder is screwed into the center of the supporting plate, then the assembled device is implanted.
In general, artificial corneal implantation requires long‐term topical and sometimes oral treatment to prevent or treat complications such as infections and glaucoma. Close postoperative follow‐up is required due to risk of complications, which can sometimes lead to permanent blindness, particularly due to retinal detachment and endophthalmitis. These complication rates have been well monitored by surveillance studies (Boston Type 1 KPro Study; Hicks 2006). The rates of vision‐threatening complications and visual outcomes on the other hand are less well studied in repeat donor corneal transplantation cases. However, the rates of corneal melting and infection are certainly expected to be lower with donor transplantation than with artificial devices.
How the intervention might work
Both donor and artificial corneal transplantations involve removal of the diseased and opaque portion of the recipient cornea, and replacement with clear cornea or corneal device. The surgical procedure using an artificial cornea is similar to full thickness corneal transplantation using a donor cornea (penetrating keratoplasty, PK) once the device has been assembled.
The Boston KPro, the most commonly implanted artificial corneal device, comes in two main types (Aquavella 2005; Ilhan‐Sarac 2005; Ma 2005). Type I is the most commonly used style in the USA and consists of two plastic parts: an anterior part that houses the refractive portion, and a removable perforated back plate. The device requires donor corneal tissue to be sandwiched between the two plates. The holes in the back plate are thought to enhance nutrition and rehydration of the clamped corneal stroma adjacent to the stem, which may help to prevent necrosis of the surrounding tissue. In addition, the device has a titanium locking c‐ring to secure the unit after its assembly and prevent unscrewing of the back plate. After assembly, the whole device is then sutured into the recipient eye in the same manner as with donor corneal transplantation. A newer‐generation type I KPro with a back plate made of titanium was recently cleared by the US Food and Drug Administration (FDA) (MEEI 2019). This model does not require a locking c‐ring (Todani 2011).
The type I Boston KPro is indicated in eyes with sufficient tear secretion and normal blinking. The longer type II device is similar to type I, except for an additional 2‐millimeter‐long anterior nub for through‐the‐lid implantation. The front plate is usually 5 mm in diameter, and the back plate is 8.5 mm in diameter. The back plate also has two rows of eight holes, each 1.5 mm in diameter. The type II Boston KPro is reserved for extreme dry eye conditions and end‐stage ocular surface diseases with significant cicatricial conjunctival changes, such as mucous membrane pemphigoid and Stevens‐Johnson syndrome, in which there is a lack of fornices to support a contact lens as recommended for the type I device. Both types are custom made to have a range of dioptric powers to match the axial length of the patient’s eye when aphakic (the natural lens, if present, is removed during surgery, and no additional intraocular lens needs to be implanted).
Other artifical corneas such as AlphaCor, osteo‐odonto‐keratoprosthesis, and Fyodorov–Zuev keratoprosthesis work in the same general manner, as substitutes for donor corneas.
Why it is important to do this review
There has been a renewed interest in artificial corneal implantation following FDA approval of the AlphaCor device in 2002. Although the Boston type I device was cleared by the FDA in 1992, prior to 2004, fewer than 100 had been implanted, most of which were performed at the Massachusetts Eye and Ear Infirmary (the distributor of the device) (Zerbe 2006). This renewed interest resulted in a wealth of studies evaluating artificial corneal devices. However, due to high complication rates associated with the AlphaCor device, it has been removed from the market, leaving the artificial corneal device arena mostly to the Boston KPro. Once considered as a last resort, the Boston KPro is now a frequently viable alternative for eyes with prior failure of traditional donor PK. There has furthermore been interest in expanding indications for KPro implantation as a primary procedure in patients with limbal stem cell failure from various causes (Michael 2008; Utine 2011).
As surgeons and centers have gained more experience with keratoprosthesis, it has become apparent that artificial corneal devices may be an alternative to repeat PK in a broader subset of patients than was previously considered. It has also been suggested that artificial corneal transplant surgery is comparable to PK surgery using donor corneas in terms of cost‐effectiveness (Ament 2010). The purpose of this review was to systematically compare the clinical performance of artificial corneas with the current standard of care, transplantation with donor corneas, as the use of keratoprostheses becomes more popular for repeat corneal replacement procedures.
Objectives
To assess the effectiveness of artificial versus donor corneas in individuals who have had one or more failed donor corneal transplantations.
Methods
Criteria for considering studies for this review
Types of studies
We planned to include randomized controlled trials (RCTs) and controlled clinical trials (CCTs). We also stated a priori that we would discuss findings from non‐RCTs, prospective and retrospective cohort studies, and interventional case series (Akpek 2012). The previous version of this review reported the findings of non‐comparative case series. Since then, retrospective comparative case series have been published, which we have summarized in the Discussion.
Types of participants
We planned to include studies of participants with corneal opacity who had failed one or more full thickness PKs. We excluded reports of primary keratoprosthesis cases only. We planned to include studies with adults (ages 18 years and older), but would not exclude studies that also included some participants less than 18 years of age. However, we excluded studies that reported results exclusively or mostly from pediatric patients. There was no restriction regarding whether participants were phakic, aphakic, or pseudophakic.
Types of interventions
Artificial corneas (keratoprostheses) of any type and full thickness, and penetrating human donor corneal transplantations.
Types of outcome measures
Primary outcomes
Proportion of participants with best‐corrected visual acuity (BCVA) of 20/100 or better, measured as Snellen equivalent, at two years after corneal replacement
Secondary outcomes
Proportion of participants with BCVA of 20/100 or better at one and five years after corneal replacement
Proportion of participants with worse vision than preoperative vision at one, two, and five years after corneal replacement
Mean change in BCVA at one, two, and five years after corneal replacement
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Proportion of participants with corneal graft failure at one, two, and five years after corneal replacement:
PK group: the proportion of participants with corneal allograft rejection or failure leading to opacity of the graft at one, two, and five years after corneal replacement;
KPro group: the proportion of participants with removal of KPro due to any cause at one, two, and five years after corneal replacement.
Proportion of participants with enucleation of the eyeball due to any cause at one, two, and five years after corneal replacement
When data are available in future updates, we will report the proportion of participants with failure who require another corneal surgery with a donor or artificial cornea, and the proportion of participants who have complications requiring other surgery, such as glaucoma and retinal detachment.
We planned to summarize adverse events reported by the individual studies including glaucoma, infection, retinal detachment, retroprosthetic membrane formation and further extrusion of the device. We planned to evaluate quality of life and economic outcomes.
Search methods for identification of studies
Electronic searches
The Cochrane Eyes and Vision Information Specialist searched the following electronic databases for RCTs and CCTs. There were no restrictions on language or year of publication. We last searched the electronic databases on 4 November 2019.
Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 11) (which contains the Cochrane Eyes and Vision Trials Register) in the Cochrane Library (searched 4 November 2019) (Appendix 1).
MEDLINE Ovid (1946 to 4 November 2019) (Appendix 2).
Embase Ovid (1980 to 4 November 2019) (Appendix 3).
LILACS (Latin American and Caribbean Health Sciences Literature database) (1982 to 4 November 2019) (Appendix 4).
ISRCTN registry (www.isrctn.com/editAdvancedSearch; searched 4 November 2019) (Appendix 5).
US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov; searched 4 November 2019) (Appendix 6).
World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp; searched 4 November 2019) (Appendix 7).
Searching other resources
We searched the reference lists of relevant studies for any additional studies not identified by the electronic searches. We planned to use the Science Citation Index to identify potentially relevant studies that cited included studies; however, since no RCTs or CCTs were included in the review, we did not use this database.
Data collection and analysis
Selection of studies
At least two review authors (MC, SA, or SMN) independently assessed the search results, classifying each record based on title and abstract as: (1) definitely relevant, (2) possibly relevant, or (3) definitely not relevant according to the Criteria for considering studies for this review. We obtained full‐text copies of all publications or other documents that were selected by at least one review author as either (1) definitely relevant or (2) possibly relevant. Two review authors (SA and SMN) independently reviewed the full‐text copies for eligibility and classified each as (a) include, (b) unclear, or (c) exclude. Studies excluded at this stage were documented and the reasons for exclusion noted. For studies classified as unclear, we contacted study authors for additional information to determine eligibility. Any discrepancies were resolved by consensus.
Data extraction and management
We did not identify any relevant trials for this update. For future updates, two review authors will independently extract data onto data extraction forms adapted from Cochrane Eyes and Vision forms. We will extract study characteristics for each included study including methods, participants, interventions, outcomes, and funding sources. One review author will enter the data into Review Manager 5 (Review Manager 2014), and a second review author will verify the data entry. Any discrepancies will be resolved by discussion. We will contact primary investigators to request missing data, allowing an eight‐week response time; if no reply is received, we will use the available data.
Assessment of risk of bias in included studies
We did not assess risk of bias because no eligible trials were identified. For future updates, two review authors will independently assess the sources of systematic bias in studies according to the methods described in Chapters 8 and 13 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2017; Reeves 2011). Any discrepancies will be resolved by discussion.
We planned to consider the following parameters when assessing risk of bias in RCTs and CCTs:
selection bias (random sequence generation, quality of allocation concealment);
detection bias (masking of outcome assessors and data analyzers);
attrition bias (completeness of follow‐up, intention‐to‐treat analysis);
reporting bias; and
other potential sources of bias (such as funding source).
We did not plan to assess masking (blinding) of study participants and personnel (performance bias) due to the differences in interventions and surgical procedures. We planned to assess each 'Risk of bias' domain as low risk of bias, high risk of bias, or unclear risk of bias (insufficient information to permit judgement of low or high risk).
Although we did not perform a formal assessment of risk of bias for observational studies, we considered the following parameters:
selection bias (similarity between groups, reporting of baseline characteristics, and potential confounders);
performance bias (objective measurements of exposures);
detection bias (masking of outcome assessors, objective measurements of outcomes, equal likelihood of detecting outcome for both groups);
attrition bias (low attrition rates, similar follow‐up between groups);
reporting bias; and
other potential sources of bias (such as funding source).
For non‐randomized, comparative trials, we will consider the following parameters:
selection bias (sequential enrollment, reporting of potential confounders);
performance bias (objective measurements of exposures);
detection bias (masking of outcome assessors, objective measurements outcomes, equal likelihood of detecting outcome for both groups);
attrition bias (low attrition rates, similar follow‐up between groups);
reporting bias; and
other potential sources of bias (such as funding source).
Measures of treatment effect
The primary outcome for this review was a dichotomous outcome. We planned to report the measure of effect as a risk ratio with 95% confidence intervals. We planned to report dichotomous secondary outcomes in the same manner.
We planned to report mean changes in BCVA as mean differences between groups with 95% confidence intervals. We also planned to report continuous data for quality of life outcomes or economic outcomes as mean differences with 95% confidence intervals.
Unit of analysis issues
The unit of analysis was the eye. In future updates, we will report whether or not adjustments for interperson correlation of outcomes are made for studies in which both eyes of a single participant are included.
Dealing with missing data
We included no RCTs or CCTs in the review and did not contact study authors of non‐randomized studies for additional information.
Assessment of heterogeneity
We planned to use the I² statistic to examine heterogeneity. We would have interpreted an I² value greater than 60% as indicating substantial statistical heterogeneity. If substantial statistical heterogeneity was present, we would not conduct meta‐analysis and would instead have reported the study results independently. We also planned to assess clinical heterogeneity based on the characteristics of participants in the included studies, including type of artificial cornea, lens status (phakic, aphakic, or pseudophakic), age, and underlying comorbidities such as retinal detachment, glaucoma, and ocular surface disease.
Assessment of reporting biases
We planned to examine the symmetry of funnel plots to assess reporting biases when more than 10 studies were included in a meta‐analysis.
Data synthesis
We did not perform quantitative data synthesis.
Subgroup analysis and investigation of heterogeneity
We did not perform subgroup analysis.
Sensitivity analysis
We did not perform sensitivity analysis.
Results
Description of studies
Results of the search
Detailed results of the search for the 2014 version of this review were published previously (Akpek 2014). In brief, we did not identify any relevant RCTs or CCTs from 853 unique records from our search as of 27 November 2013. We excluded 19 studies (41 reports) for which details are provided in Characteristics of excluded studies.
We performed an updated electronic search in November 2019, which yielded 748 unique records. After title and abstract screening, we retrieved 17 full‐text reports for further review. Of these, we excluded 14 trials (16 reports) with reasons provided, and listed one trial (one report) as awaiting classification.
We excluded a total of 33 trials (57 reports) and assessed one study as awaiting classification. A study flow diagram is shown in Figure 1.
1.
Study flow diagram.
Included studies
We did not find any completed RCTs or CCTs. One study comparing a bioengineered cornea with a donor human cornea is awaiting classification as it is unclear if the participants had a history of graft failure (NCT02424006).
Excluded studies
In the previous version of this review, we excluded 19 non‐randomized trials that evaluated keratoprosthesis in people undergoing repeat corneal transplantation. For this update, we excluded 14 studies after full‐text screening. We excluded nine studies because they were not RCTs or CCTs, of which one report compared donor corneal transplantation with the Boston type 1 KPro in participants who had failed one or more PKs (Akpek 2015). We excluded the remaining five studies because the interventions were not relevant to this review. Details of the reasons for exclusion are provided in Characteristics of excluded studies.
Risk of bias in included studies
We could not assess risk of bias since no RCTs were included in the review.
Effects of interventions
We identified no evidence comparing the effectiveness of artificial versus donor corneas for repeat corneal transplantation.
Discussion
Summary of main results
We included no relevant RCTs or CCTs in this review. We identified one potentially eligible study that we listed as awaiting classification due to lack of information regarding its participants.
To the best of our knowledge, and based on our comprehensive search strategy without using an RCT filter, we identified only one comparative case series that investigated artificial versus donor corneas in participants who had failed one or more PKs. This study compared 53 and 27 participants who had undergone PK and Boston type I KPro, respectively, between January 2008 and December 2010 at the Wilmer Eye Institute in the USA (Akpek 2015). Postoperatively, 17 (35%) participants in the PK group and 10 (48%) participants in the Boston KPro group attained best‐ever visual acuity of 20/70 or better, of which, 8 (47%) in the PK group and 4 (40%) in the Boston KPro group retained that level of vision at two years. The cumulative rate of graft failure, which was defined as loss of clarity for PK and removal or replacement for KPro, was likely to be higher in participants with PK at two years (hazard ratio 3.23, 95% confidence interval 1.12 to 9.28). The most common postoperative complication was worsening glaucoma necessitating surgery, which occurred in 12 (23%) participants in the PK cohort and 6 (22%) participants in the Boston KPro cohort.
Overall completeness and applicability of evidence
We aimed in this review aimed to gain information regarding the visual outcomes and complication rates of artificial corneal transplantation surgeries in comparison with repeat donor corneal transplantation in individuals with prior failed full thickness penetrating keratoplasty. No such RCTs or CCTs directly comparing the results of these interventions were identified based on extensive literature searches. Given the increasing popularity of Boston type I KPro, and a trend to expanding the indications for it even to patients who have not yet received donor transplantations, a head‐to‐head comparison is needed. The inclusion criteria used to enroll participants in such a study should be carefully considered. For instance, a non‐vascularized cornea in a phakic eye after a single episode of rejection may do very well with repeat donor grafting and probably would not be considered for KPro surgery. The situation is entirely different when there are additional risk factors for failure such as neovascularization, ocular surface diseases, or glaucoma. Future studies comparing these treatment methods should take into consideration the cause of prior graft failure, preoperative diagnosis, and presence of high‐risk factors for rejection when enrolling participants.
Furthermore, the currently available studies reporting outcomes of both repeat donor PK as well as KPro surgeries are limited with regard to length of follow‐up. It is conceivable that the lifetime risks of complications and the possibility of permanent vision loss may differ significantly after either procedure. We were unable to address this issue in this review due to the very limited follow‐up of the available reports. A careful review of the literature of repeat PK outcomes might help to determine the best outcomes to assess in a head‐to‐head comparison. For example, incidence of endophthalmitis and vision loss due to glaucoma, which has been reported to be higher after implantation of Boston type I KPro compared with PK, would be important outcomes to study.
Quality of the evidence
We could not assess the quality of the evidence because no relevant completed trials were included in the review.
Potential biases in the review process
We followed the Cochrane Handbook for Systematic Reviews of Interventions and Methodological Expectations of Cochrane Intervention Reviews (MECIR) standards for the reporting of new Cochrane Intervention Reviews (editorial-unit.cochrane.org/mecir) in conducting this review (Higgins 2011). We conducted a highly sensitive search to identify trials comparing artificial corneal implants with human donor corneas for people needing repeat corneal transplantation. At least two review authors independently screened the search results. None of the authors has any financial conflicts of interest.
Agreements and disagreements with other studies or reviews
We did not identify any relevant trials in this review. Based on non‐randomized studies identified from our searches, different types of KPros are being used for individuals undergoing repeat corneal transplantation procedures. Historically, artificial corneas have been considered as 'salvage' procedures when no alternative exists. Consequently, the majority of participants in the published reports had been deemed 'ineligible' to receive another donor corneal transplantation, and hence were likely to have worse vision prior to the surgery as well as worse comorbidity than the participants who were considered for repeat corneal transplantation with donor corneas. Despite this trend, the high retention rates and good intermediate‐term visual outcomes reported with the Boston type I KPro have made this device an attractive alternative to repeat donor corneal transplantations (AAO PPP 2018; Boston Type 1 KPro Study). As surgeons and centers have gained more experience with KPro, particularly following advances in design and materials, the utilization of KPros has shown an increase since it was cleared by the FDA in 1992 (MEEI 2019).
Re‐grafts are now the most common indication for penetrating keratoplasty in the USA. According to the Eye Bank Association of America, repeat transplants constituted about 18.3% (3166 surgeries) of all those undergoing PK in 2018, which is a significant increase from 2011 (11.8%, 4271 surgeries) (EBAA 2011; EBAA 2018). Interestingly, individuals receiving a PK for keratoconus decreased from 20.3% in 2011 to 15.2% in 2018. This decrease may be partially due to the advent of cross‐linking and use of scleral lenses in patients with keratoconus and corneal opacities; these trends have been demonstrated in other countries as well (Godefrooij 2016; Koppen 2018; Sarezky 2017). With a higher percentage of PKs being performed for repeat grafts and fewer for keratoconus, it has become particularly important to examine the survival for these surgeries. The Autralian graft registry reported a 17% additional risk of failure for each subsequent failed graft (95% confidence interval (CI) 2% to 34%) (Williams 2008). A systematic review reported a pooled survival of repeat PK of 67% at 2 years (95% CI 59% to 75%) and 47% at 5 years (95% CI 40% to 53%) (Ahmad 2016). A recent single‐site study from Japan reported a 91% and 64% survival at one and five years, respectively (Kitazawa 2018).
Authors' conclusions
Implications for practice.
The optimal management for patients who have failed conventional corneal transplantation is unknown. Our review did not find any evidence with respect to artificial corneal devices versus donor corneas in participants who had failed one or more full thickness human corneal transplantations. There are no current guidelines regarding limits to the number of times donor corneal transplantation should be repeated. The corneal surgeons managing these patients are left to make recommendations based only on patient values, personal clinical experience, local culture, and non‐randomized studies. Considering that re‐grafts are now the most common indicator for penetrating keratoplasty in the USA, and that sicker eyes will be receiving penetrating keratoplasty in the future, the implications of this review become particularly relevant, especially in the context of our finding that few studies have directly compared these interventions. Both repeat grafts and the Boston KPro have a notable side effect profile that includes infection, glaucoma, and failure.
Implications for research.
Currently, in some centers, KPros are routinely are recommended after a single graft failure, while in other centers, they are not recommended until after multiple graft failures, or not at all. To date, there have been no controlled trials comparing the visual outcomes and complications of artificial corneal devices with repeat donor corneal transplantation to guide surgeons and their patients, despite wide use of the Boston type l KPro and other artificial corneal devices. Such a trial is needed and should be conducted before an approach is adopted without evidence of comparative effectiveness. The findings from a randomized controlled trial would offer significant benefit to an ever‐increasing pool of people with visual disability due to corneal opacification, most of whom are still in productive stages of their lives. It is important that future studies measure clinical and patient‐important outcomes at specified follow‐up time points and account for all study participants in the analyses. Of particular interest would be long‐term visual acuity outcomes and complications (e.g. two and five years post‐transplantation) to help inform the expected benefits and risks associated with each procedure over time. Cost comparison outcomes should also be considered to evaluate the applicability of these procedures, particularly in regions with few eye banking resources. Finally, considering the significant side effect profile of the devices to date, there may also be a role for a bio‐integrated device.
What's new
| Date | Event | Description |
|---|---|---|
| 4 November 2019 | New search has been performed | Issue 5 2020: Electronic searches updated on 04 November 2019. |
| 4 November 2019 | New citation required but conclusions have not changed | Issue 5 2020: No new studies were identified. |
History
Protocol first published: Issue 1, 2012 Review first published: Issue 11, 2014
Acknowledgements
We acknowledge Iris Gordon, Information Specialist for the Cochrane Eyes and Vision (CEV), for devising and running the electronic search strategies.
The 2020 review update was managed by CEV@US and was signed off for publication by Tianjing Li and Richard Wormald.
Appendices
Appendix 1. CENTRAL search strategy
#1 keratoprostheses or keratoprosthesis #2 Kpro or Kpros or K‐Pro #3 AlphaCor #4 KeraKlear #5 Osteo near/1 Odonto near/1 Keratoprosthesis* #6 Osteo near/1 odontokeratoprosthesis #7 osteo near/1 odonto near/1 kerato near/1 prosthesis #8 osteo near/1 keratoprosthesis #9 OOKP or OKP or MOOKP #10 cornea* near/2 prosthesis #11 Dohlman‐Doane #12 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11
Appendix 2. MEDLINE Ovid search strategy
1. exp animals/ 2. exp humans/ 3. 1 not (1 and 2) 4. (keratoprostheses or keratoprosthesis).tw. 5. (Kpro or Kpros or K‐Pro).tw. 6. AlphaCor.tw. 7. KeraKlear.tw. 8. (Osteo adj1 Odonto adj1 Keratoprosthesis$).tw. 9. (Osteo adj1 odontokeratoprosthesis).tw. 10. (osteo adj1 odonto adj1 kerato adj1 prosthesis).tw. 11. (osteo adj1 keratoprosthesis).tw. 12. (OOKP or OKP or MOOKP).tw. 13. (cornea$ adj2 prosthesis).tw. 14. Dohlman‐Doane.tw. 15. or/4‐14 16. 15 not 3
Appendix 3. Embase Ovid search strategy
1. exp animals/ 2. exp humans/ 3. 1 not (1 and 2) 4. keratoprosthesis/ 5. (keratoprostheses or keratoprosthesis).tw. 6. (Kpro or Kpros or K‐Pro).tw. 7. AlphaCor.tw. 8. KeraKlear.tw. 9. (Osteo adj1 Odonto adj1 Keratoprosthesis$).tw. 10. (Osteo adj1 odontokeratoprosthesis).tw. 11. (osteo adj1 odonto adj1 kerato adj1 prosthesis).tw. 12. (osteo adj1 keratoprosthesis).tw. 13. (OOKP or OKP or MOOKP).tw. 14. (cornea$ adj2 prosthesis).tw. 15. Dohlman‐Doane.tw. 16. or/4‐15 17. 16 not 3
Appendix 4. LILACS search strategy
keratoprostheses or keratoprosthesis or Kpro or AlphaCor or KeraKlear or odontokeratoprosthesis or OOKP or OKP or MOOKP
Appendix 5. ISRCTN search strategy
keratoprostheses or keratoprosthesis or Kpro or AlphaCor or KeraKlear or odontokeratoprosthesis or OOKP or OKP or MOOKP
Appendix 6. ClinicalTrials.gov search strategy
keratoprostheses OR keratoprosthesis OR Kpro OR AlphaCor OR KeraKlear OR odontokeratoprosthesis OR OOKP OR OKP OR MOOKP
Appendix 7. WHO ICTRP search strategy
keratoprostheses or keratoprosthesis or Kpro or AlphaCor or KeraKlear or odontokeratoprosthesis or OOKP or OKP or MOOKP
Characteristics of studies
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Akpek 2015 | Retrospective case series comparing donor corneal transplantation with Boston type I keratoprosthesis |
| Al‐Arfai 2015 | Retrospective case series of penetrating keratoplasty, deep lamellar keratoplasty, triple procedures, Descemet stripping automated endothelial keratoplasty, and Boston keratoprosthesis implantations |
| Aldave 2012a | Retrospective case series of Boston keratoprosthesis |
| Aldave 2012b | Retrospective case series of Boston keratoprosthesis; international cohort compared with cohort from Aldave 2012a |
| Aquavella 2005 | Retrospective case series of Boston keratoprosthesis (Dohlman‐Doane model) |
| Avadhanam 2019 | Review article when there was no tooth for the osteo‐odonto‐keratoprosthesis |
| Baratz 2017 | Retrospective observational study of keratoprosthesis only and keratoprosthesis plus glaucoma drainage device |
| Boston Type 1 KPro Study | Multicenter prospective and retrospective case series of Boston keratoprosthesis |
| Chew 2009 | Retrospective case series of Boston keratoprosthesis |
| Dunlap 2010 | Retrospective case series of Boston keratoprosthesis |
| Ghaffariyeh 2011 | Retrospective case series of Fyodorov‐Zuev keratoprosthesis |
| Gonzalez‐Andrades 2017 | Randomized controlled trial comparing bioengineered human allogeneic nanostructured anterior cornea with amniotic membrane |
| Greiner 2011 | Retrospective case series of Boston keratoprosthesis |
| Guell 2011 | Retrospective case series of Boston keratoprosthesis |
| Harissi‐Dagher 2007 | Retrospective case series of Boston keratoprosthesis (Dohlman‐Doane model) |
| Hassan 2017 | Retrospective comparative case series of Boston keratoprosthesis, traditional keratolimbal allograft, and traditional keratolimbal allograft followed by Boston keratoprosthesis |
| Hicks 2006 | Multicenter prospective and retrospective surveillance study of AlphaCor |
| Hille 2006 | Retrospective case series of osteo‐odonto‐keratoprosthesis |
| Jiraskova 2011 | Retrospective case series of AlphaCor |
| Kamyar 2012 | Retrospective case series of Boston keratoprosthesis |
| Koller 2012 | Retrospective case series of Boston keratoprosthesis |
| Muzychuk 2017 | Not interventions of interest: fresh vs frozen corneal graft carrier |
| NCT01582880 | Case report of riboflavin cross‐linked donor cornea |
| NCT01950598 | Not intervention of interest: fresh vs frozen graft in Boston keratoprosthesis type I |
| NCT02863809 | Not intervention of interest: de‐epithelialized corneas cross‐linked with vs without ultraviolet A light |
| NCT03041883 | Not intervention of interest: cross‐linking with riboflavin of the corneal graft support vs de‐epithelization of the corneal graft support with instillation of riboflavin |
| NCT03126903 | Case series of KeraKlear non‐penetrating keratoprosthesis |
| NCT03812341 | Case report of KeraKlear non‐penetrating keratoprosthesis |
| Patel 2012 | Retrospective case series of Boston keratoprosthesis |
| Plattner 2017 | Retrospective case series of osteo‐odonto‐keratoprosthesis |
| Shihadeh 2012 | Retrospective case series of Boston keratoprosthesis |
| Talajic 2012 | Retrospective case series of Boston keratoprosthesis |
| Trichet 2013 | Retrospective case series of AlphaCor |
Characteristics of studies awaiting classification [ordered by study ID]
NCT02424006.
| Methods | Randomized, parallel‐group controlled trial |
| Participants | Inclusion criteria:
Exclusion criteria:
|
| Interventions |
|
| Outcomes |
|
| Notes | clinicaltrials.gov/ct2/show/NCT02424006 |
RHCIII‐MPC: recombinant human collagen type III and 2‐methacryloyloxyethyl phosphorylcholine
Differences between protocol and review
None.
Contributions of authors
Conceiving and designing the review: EKA
Data collection for the review
Designing electronic search strategies: Iris Gordon at the CEV editorial base
Screening search results: MC, SMN, SA
Organizing retrieval of papers: SMN
Interpretation of data
Providing a methodological perspective: SMN
Providing a clinical perspective: MC, EKA, SA
Providing a policy perspective: MC, EKA, SA
Providing a consumer perspective: MC, EKA, SA
Writing the review: MC, SMN, EKA, SA
Providing general advice on the review: MC, EKA, SMN, SA
ESK, MA (Majed Alkharashi), FSH (Frank S Hwang), SMN, and KL (Kristina Lindsley) performed previous work which was the foundation of the current review (Akpek 2012; Akpek 2014).
Sources of support
Internal sources
No sources of support supplied
External sources
Grant 1 U01 EY020522, National Eye Institute, National Institutes of Health, USA
-
National Institute for Health Research (NIHR), UK
Richard Wormald, Co‐ordinating Editor for the Cochrane Eyes and Vision (CEV), acknowledges financial support for his CEV research sessions from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology.
The NIHR also funds the CEV Editorial Base in London.
The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS, or the Department of Health.
Declarations of interest
Masako Chen: None known. Sueko M Ng: None known. Esen K Akpek: None known. Sumayya Ahmad: None known.
New search for studies and content updated (no change to conclusions)
References
References to studies excluded from this review
Akpek 2015 {published data only}
- Akpek EK, Cassard SD, Dunlap K, Hahn S, Ramulu PY. Donor corneal transplantation vs Boston type 1 keratoprosthesis in patients with previous graft failures: a retrospective single center study (an American Ophthalmological Society thesis). Transactions of the American Ophthalmological Society 2015;113:T3. [PMC free article] [PubMed] [Google Scholar]
Al‐Arfai 2015 {published data only}
- Al-Arfai KM, Yassin SA, Al-Beshri AS, Al-Jindan MY, Al-Tamimi ER. Indications and techniques employed for keratoplasty in the Eastern province of Saudi Arabia: 6 years of experience. Annals of Saudi Medicine 2015;35(5):387-93. [DOI] [PMC free article] [PubMed] [Google Scholar]
Aldave 2012a {published data only}
- Aldave AJ, Kamal KM, Vo RC, Yu F. The Boston type I keratoprosthesis: improving outcomes and expanding indications. Ophthalmology 2009;116(4):640-51. [DOI] [PubMed] [Google Scholar]
- Aldave AJ, Sangwan VS, Basu S, Basak SK, Hovakimyan A, Gevorgyan O, et al. International results with the Boston type I keratoprosthesis. Ophthalmology 2012;119(8):1530-8. [DOI] [PubMed] [Google Scholar]
- Goldman DR, Hubschman JP, Aldave AJ, Chiang A, Huang JS, Bourges JL, et al. Postoperative posterior segment complications in eyes treated with the Boston type I keratoprosthesis. Retina 2013;33(3):532-41. [DOI] [PubMed] [Google Scholar]
- Kim MJ, Yu F, Aldave AJ. Microbial keratitis after Boston type I keratoprosthesis implantation: incidence, organisms, risk factors, and outcomes. Ophthalmology 2013;120(11):2209-16. [DOI] [PubMed] [Google Scholar]
- Sejpal K, Yu F, Aldave AJ. The Boston keratoprosthesis in the management of corneal limbal stem cell deficiency. Cornea 2011;30(11):1187-94. [DOI] [PubMed] [Google Scholar]
Aldave 2012b {published data only}
- Aldave AJ, Sangwan VS, Basu S, Basak SK, Hovakimyan A, Gevorgyan O, et al. International results with the Boston type I keratoprosthesis. Ophthalmology 2012;119(8):1530-8. [DOI] [PubMed] [Google Scholar]
Aquavella 2005 {published data only}
- Aquavella JV, Qian Y, McCormick GJ, Palakuru JR. Keratoprosthesis: current techniques. Cornea 2006;25(6):656-62. [DOI] [PubMed] [Google Scholar]
- Aquavella JV, Qian Y, McCormick GJ, Palakuru JR. Keratoprosthesis: the Dohlman-Doane device. American Journal of Ophthalmology 2005;140(6):1032-8. [DOI] [PubMed] [Google Scholar]
Avadhanam 2019 {published data only}
Baratz 2017 {published data only}
Boston Type 1 KPro Study {published data only}
- Ament JD, Stryjewski TP, Ciolino JB, Todani A, Chodosh J, Dohlman CH. Cost-effectiveness of the Boston keratoprosthesis. American Journal of Ophthalmology 2010;149(2):221-8. [DOI] [PubMed] [Google Scholar]
- Ciolino JB, Belin MW, Todani A, Al-Arfaj K, Rudnisky CJ, Boston Type 1 Keratoprosthesis Study Group. Retention of the Boston keratoprosthesis type 1: multicenter study results. Ophthalmology 2013;120(6):1195-200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rudnisky CJ, Belin MW, Todani A, Al-Arfaj K, Ament JD, Zerbe BJ, et al. Risk factors for the development of retroprosthetic membranes with Boston keratoprosthesis type 1: multicenter study results. Ophthalmology 2012;119(5):951-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zerbe BL, Belin MW, Ciolino JB, Boston Type 1 Keratoprosthesis Study Group. Results from the multicenter Boston Type 1 Keratoprosthesis Study. Ophthalmology 2006;113(10):1779.e1-7. [DOI] [PubMed] [Google Scholar]
Chew 2009 {published data only}
- Chew HF, Ayres BD, Hammersmith KM, Rapuano CJ, Laibson PR, Myers JS, et al. Boston keratoprosthesis outcomes and complications. Cornea 2009;28(9):989-96. [DOI] [PubMed] [Google Scholar]
Dunlap 2010 {published data only}
- Akpek EK, Harissi-Dagher M, Petrarca R, Butrus SI, Pineda R 2nd, Aquavella JV, et al. Outcomes of Boston keratoprosthesis in aniridia: a retrospective multicenter study. American Journal of Ophthalmology 2007;144(2):227-31. [DOI] [PubMed] [Google Scholar]
- Dunlap K, Chak G, Aquavella JV, Myrowitz E, Utine CA, Akpek E. Short-term visual outcomes of Boston type 1 keratoprosthesis implantation. Ophthalmology 2010;117(4):687-92. [DOI] [PubMed] [Google Scholar]
- Khan BF, Harissi-Dagher M, Pavan-Langston D, Aquavella JV, Dohlman CH. The Boston keratoprosthesis in herpetic keratitis. Archives of Ophthalmology 2007;125(6):745-9. [DOI] [PubMed] [Google Scholar]
Ghaffariyeh 2011 {published data only}
- Ghaffariyeh A, Honarpisheh N, Karkhaneh A, Abudi R, Moroz ZI, Peyman A, et al. Fyodorov-Zuev keratoprosthesis implantation: long-term results in patients with multiple failed corneal grafts. Graefes Archive for Clinical and Experimental Ophthalmology 2011;249(1):93-101. [DOI] [PubMed] [Google Scholar]
Gonzalez‐Andrades 2017 {published data only}
- EUCTR2010-024290-40-ES. Multicenter clinical trial to evaluate the safety and feasibility of allogeneic tissue engineered product (human nanostructured artificial cornea) in patients with advanced corneal trophic ulcers refractory to (ophthalmic) conventional treatment. www.clinicaltrialsregister.eu/ctr-search/trial/2010-024290-40/ES (first received 9 March 2012).
- Gonzalez AM, Martinez-Atienza J, Campos A, Arias-Santiago S, Gonzalez GC, Mataix B, et al. Preliminary results of a multicenter randomized clinical trial evaluating the safety and feasibility of an allogeneic nanostructured artificial anterior human cornea. Cytotherapy 2017;19(5):S26. [Google Scholar]
- Gonzalez-Andrades M, Mata R, Gonzalez-Gallardo MDC, Medialdea S, Arias-Santiago S, Martinez-Atienza J, et al. A study protocol for a multicentre randomised clinical trial evaluating the safety and feasibility of a bioengineered human allogeneic nanostructured anterior cornea in patients with advanced corneal trophic ulcers refractory to conventional treatment. BMJ Open 2017;7(9):e016487. [DOI] [PMC free article] [PubMed] [Google Scholar]
Greiner 2011 {published data only}
- Bradley JC, Hernandez EG, Schwab IR, Mannis MJ. Boston type 1 keratoprosthesis: the University of California Davis experience. Cornea 2009;28(3):321-7. [DOI] [PubMed] [Google Scholar]
- Greiner MA, Li JY, Mannis MJ. Longer-term vision outcomes and complications with the Boston type 1 keratoprosthesis at the University of California, Davis. Ophthalmology 2011;118(8):1543-50. [DOI] [PubMed] [Google Scholar]
- Shapiro BL, Cortes DE, Chin EK, Li JY, Werner JS, Redenbo E, et al. High-resolution spectral domain anterior segment optical coherence tomography in type 1 Boston keratoprosthesis. Cornea 2013;32(7):951-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
Guell 2011 {published data only}
- Guell JL, Arcos E, Gris O, Aristizabal D, Pacheco M, Sanchez CL, et al. Outcomes with the Boston Type 1 Keratoprosthesis at Instituto de Microcirugia Ocular IMO. Saudi Journal of Ophthalmology 2011;25(3):281-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Verdejo-Gomez L, Pelaez N, Gris O, Guell JL. The Boston Type I keratoprosthesis: an assessment of its efficacy and safety. Ophthalmic Surgery, Lasers and Imaging 2011;42(6):446-52. [DOI] [PubMed] [Google Scholar]
Harissi‐Dagher 2007 {published data only}
- Harissi-Dagher M, Dohlman CH. The Boston keratoprosthesis in severe ocular trauma. Canadian Journal of Ophthalmology 2008;43(2):165-9. [DOI] [PubMed] [Google Scholar]
- Harissi-Dagher M, Khan BF, Schaumberg DA, Dohlman CH. Importance of nutrition to corneal grafts when used as a carrier of the Boston keratoprosthesis. Cornea 2007;26(5):564-8. [DOI] [PubMed] [Google Scholar]
- Nouri M, Terada H, Alfonso EC, Foster CS, Durand ML, Dohlman CH. Endophthalmitis after keratoprosthesis: incidence, bacterial causes, and risk factors. Archives of Ophthalmology 2001;119(4):484-9. [DOI] [PubMed] [Google Scholar]
- Sayegh RR, Ang LP, Foster CS, Dohlman CH. The Boston keratoprosthesis in Stevens-Johnson syndrome. American Journal of Ophthalmology 2008;145(3):438-44. [DOI] [PubMed] [Google Scholar]
- Yaghouti F, Nouri M, Abad JC, Power WJ, Doane MG, Dohlman CH. Keratoprosthesis: preoperative prognostic categories. Cornea 2001;20(1):19-23. [DOI] [PubMed] [Google Scholar]
Hassan 2017 {published data only}
- Hassan O, Djalilian AR, Cortina MS. Keratolimbal allograft and Boston keratoprosthesis in management of aniridic keratopathy. Investigative Ophthalmology and Visual Science 2017;58(8):ARVO E-abstract 2602. [Google Scholar]
Hicks 2006 {published data only}
- Crawford GJ, Hicks CR, Lou X, Vijayasekaran S, Tan D, Mulholland B, et al. The Chirila keratoprosthesis: phase I human clinical trial. Ophthalmology 2002;109(5):883-9. [DOI] [PubMed] [Google Scholar]
- Hicks CR, Crawford GJ, Dart JK, Grabner G, Holland EJ, Stulting RD, et al. AlphaCor: clinical outcomes. Cornea 2006;25(9):1034-42. [DOI] [PubMed] [Google Scholar]
- Hicks CR, Crawford GJ, Lou X, Tan DT, Snibson GR, Sutton G, et al. Corneal replacement using a synthetic hydrogel cornea, AlphaCor: device, preliminary outcomes and complications. Eye 2003;17(3):385-92. [DOI] [PubMed] [Google Scholar]
- Hicks CR, Crawford GJ, Tan DT, Snibson GR, Sutton GL, Gondhowiardjo TD, et al. Outcomes of implantation of an artificial cornea, AlphaCor: effects of prior ocular herpes simplex infection. Cornea 2002;21(7):685-90. [DOI] [PubMed] [Google Scholar]
- Hicks CR, Macvie O, Crawford GJ, Constable IJ. A risk score as part of an evidence-based approach to the selection of corneal replacement surgery. Cornea 2005;24(5):523-30. [DOI] [PubMed] [Google Scholar]
Hille 2006 {published data only}
- Hille K, Hille A, Ruprecht KW. Medium term results in keratoprostheses with biocompatible and biological haptic. Graefes Archive for Clinical and Experimental Ophthalmology 2006;244(6):696-704. [DOI] [PubMed] [Google Scholar]
Jiraskova 2011 {published data only}
- Jiraskova N, Rozsival P, Burova M, Kalfertova M. AlphaCor artificial cornea: clinical outcome. Eye 2011;25(9):1138-46. [DOI] [PMC free article] [PubMed] [Google Scholar]
Kamyar 2012 {published data only}
- Kamyar R, Weizer JS, Paula FH, Stein JD, Moroi SE, John D, et al. Glaucoma associated with Boston type I keratoprosthesis. Cornea 2012;31(2):134-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
Koller 2012 {published data only}
- Koller B, Neuhann T, Neuhann I. Results with the Boston keratoprosthesis. Ophthalmologe 2012;109(5):454-61. [DOI] [PubMed] [Google Scholar]
Muzychuk 2017 {published data only}
- Muzychuk AK, Robert MC, Dao S, Harissi-Dagher M. Boston keratoprosthesis type 1: a randomized controlled trial of fresh versus frozen corneal donor carriers with long-term follow-up. Ophthalmology 2017;124(1):20-6. [DOI] [PubMed] [Google Scholar]
NCT01582880 {published data only}
- NCT01582880. Use of cross-linked donor corneas as carriers for the Boston keratoprosthesis [The use of riboflavin/ultraviolet a cross-linked human donor corneas as carriers for the Boston keratoprosthesis]. clinicaltrials.gov/ct2/show/NCT01582880 (first received 23 April 2012).
NCT01950598 {published data only}
- NCT01950598. Frozen versus fresh corneal carriers for the Boston KPro type I donor carriers. clinicaltrials.gov/ct2/show/NCT01950598 (first received 25 September 2013).
NCT02863809 {published data only}
- NCT02863809. Vision restoration with a collagen crosslinked Boston keratoprosthesis unit [A Phase I/II prospective, randomized, multicenter, double-masked, vehicle-controlled clinical trial to evaluate the safety and efficacy of corneal collagen cross-linking of keratoprosthesis carrier tissue in high-risk keratoprosthesis implantation]. clinicaltrials.gov/ct2/show/NCT02863809 (first received 11 August 2016).
NCT03041883 {published data only}
- NCT03041883. Corneal collagen crosslinking to increase the resistance of the support graft of the Kpro type I against corneal melting. clinicaltrials.gov/ct2/show/NCT03041883 (first received 3 February 2017).
NCT03126903 {published data only}
- NCT03126903. A clinical study to evaluate the KeraKlear keratoprosthesis in patients with corneal opacity [A prospective, multicenter clinical trial designed to evaluate the safety and probable benefit of the KeraKlear non-penetrating keratoprosthesis in subjects with corneal opacity with poor prognosis for corneal transplant]. clinicaltrials.gov/ct2/show/NCT03126903 (first received 25 April 2017).
NCT03812341 {published data only}
- NCT03812341. Single patient expanded access of a prospective, multicenter clinical trial designed to evaluate the safety and probable benefit of the KeraKlear non-penetrating keratoprosthesis in subjects with corneal opacity with poor prognosis for corneal transplant. clinicaltrials.gov/ct2/show/NCT03812341 (first received 23 January 2019).
Patel 2012 {published data only}
- Patel AP, Wu EI, Ritterband DC, Seedor JA. Boston type 1 keratoprosthesis: the New York Eye and Ear experience. Eye 2012;26(3):418-25. [DOI] [PMC free article] [PubMed] [Google Scholar]
Plattner 2017 {published data only}
- Plattner K, Goldblum D, Halter J, Kunz C, Koeppl R, Gerber-Hollbach N. Osteo-Odonto-Keratoprosthesis in severe ocular graft versus host disease [Osteo-Odonto-Keratoprothese bei schwerer okularer graft-versus-host-reaktion]. Klinische Monatsblatter fur Augenheilkunde 2017;234(4):455-6. [DOI] [PubMed] [Google Scholar]
Shihadeh 2012 {published data only}
- Shihadeh WA, Mohidat HM. Outcomes of the Boston keratoprosthesis in Jordan. Middle East African Journal of Ophthalmology 2012;19(1):97-100. [DOI] [PMC free article] [PubMed] [Google Scholar]
Talajic 2012 {published data only}
- Robert MC, Biernacki K, Harissi-Dagher M. Boston keratoprosthesis type 1 surgery: use of frozen versus fresh corneal donor carriers. Cornea 2012;31(4):339-45. [DOI] [PubMed] [Google Scholar]
- Robert MC, Harissi-Dagher M. Boston type 1 keratoprosthesis: the CHUM experience. Canadian Journal of Ophthalmology 2011;46(2):164-8. [DOI] [PubMed] [Google Scholar]
- Talajic JC, Agoumi Y, Gagne S, Moussally K, Harissi-Dagher M. Prevalence, progression, and impact of glaucoma on vision after Boston type 1 keratoprosthesis surgery. American Journal of Ophthalmology 2012;153(2):267-74. [DOI] [PubMed] [Google Scholar]
Trichet 2013 {published data only}
- Trichet E, Carles G, Matonti F, Proust H, Ridings B, Conrath J, et al. Alphacor keratoprosthesis: device, surgical technique and clinical outcomes. Journal Francais d'Opthalmologie 2013;36(5):393-401. [DOI] [PubMed] [Google Scholar]
References to studies awaiting assessment
NCT02424006 {published data only}
- NCT02424006. Safety and effectiveness of the RHCIII-MPC biosynthetic cornea in patients requiring anterior lamellar keratoplasty [A prospective, randomized, open label clinical trial to evaluate the safety and effectiveness of the RHCIII-MPC biosynthetic cornea compared to human cornea in patients requiring anterior lamellar keratoplasty]. clinicaltrials.gov/ct2/show/NCT02424006 (first received 22 April 2015).
Additional references
AAO PPP 2018
- American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern® Guidelines. Corneal edema and opacification. www.aao.org/ppp (accessed 26 January 2020).
ACGR 1993
- The Australian Corneal Graft Registry. 1990 to 1992 report. Australian and New Zealand Journal of Ophthalmology 1993;21(2 Suppl):1-48. [PubMed] [Google Scholar]
Ahmad 2016
- Ahmad S, Mathews PM, Lindsley K, Alkharashi M, Hwang FS, Ng SM, et al. Boston Type 1 Keratoprosthesis versus repeat donor keratoplasty for corneal graft failure: a systematic review and meta-analysis. Ophthalmology 2016;123(1):165-77. [DOI] [PubMed] [Google Scholar]
Ament 2010
- Ament JD, Stryjewski TP, Ciolino JB, Todani A, Chodosh J, Dohlman CH. Cost-effectiveness of the Boston keratoprosthesis. American Journal of Ophthalmology 2010;149(2):221-8. [DOI] [PubMed] [Google Scholar]
EBAA 2011
- Eye Bank Association of America. 2011 Eye banking statistical report. restoresight.org/wp-content/uploads/2013/04/2012_Statistical_Report_FINAL-reduced-size-4-10.pdf.
EBAA 2018
- Eye Bank Association of America. 2018 Eye banking statistical report. restoresight.org/what-we-do/publications/statistical-report/ (accessed 4 February 2020).
Godefrooij 2016
- Godefrooij DA, Gans R, Imhof SM, Wisse RP. Nationwide reduction in the number of corneal transplantations for keratoconus following the implementation of cross-linking. Acta Ophthalmologica 2016;94(7):675-8. [DOI] [PubMed] [Google Scholar]
Higgins 2011
- Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Higgins 2017
- Higgins JPT, Altman DG, Sterne JAC, editor(s). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Churchill R, Chandler J, Cumpston MS, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017). Cochrane, 2017. Available from www.training.cochrane.org/handbook.
Ilhan‐Sarac 2005
- Ilhan-Sarac O, Akpek EK. Current concepts and techniques in keratoprosthesis. Current Opinion in Ophthalmology 2005;16(4):246-50. [DOI] [PubMed] [Google Scholar]
Kitazawa 2018
- Kitazawa K, Wakimasu K, Kayukawa K, Yokota I, Inatomi T, Hieda O, et al. Moderately long-term safety and efficacy of repeat penetrating keratoplasty. Cornea 2018;37(10):1255-9. [DOI] [PubMed] [Google Scholar]
Koppen 2018
- Koppen C, Kreps EO, Anthonissen L, Van Hoey M, Dhubhghaill SN, Vermeulen L. Scleral lenses reduce the need for corneal transplants in severe keratoconus. American Journal of Ophthalmology 2018;185:43-7. [DOI] [PubMed] [Google Scholar]
Ma 2005
- Ma JJ, Graney JM, Dohlman CH. Repeat penetrating keratoplasty versus the Boston keratoprosthesis in graft failure. International Ophthalmology Clinics 2005;45(4):49-59. [DOI] [PubMed] [Google Scholar]
MEEI 2019
- Massachusettes Eye and Ear Infirmary. Boston KPro Newsletter XIV: 2019. eye.hms.harvard.edu/files/eye/files/kpro_2019_newsletterfinalweb.pdf.
Michael 2008
- Michael R, Charoenrook V, la Paz MF, Hitzl W, Temprano J, Barraquer RI. Long-term functional and anatomical results of osteo- and osteoodonto-keratoprosthesis. Graefes Archive for Clinical and Experimental Ophthalmology 2008;246(8):1133-7. [DOI] [PubMed] [Google Scholar]
Murthy 2012
- Murthy GVS, Johnson GJ. Chapter 1: Prevalence, incidence and distribution of visual impairment. In: Johnson GJ, Minassian DC, Weale RA, West SK, editors(s). The Epidemiology of Eye Disease. 3rd edition. Imperial College Press, 2012. [Google Scholar]
Reeves 2011
- Reeves BC, Deeks JJ, Higgins JPT, Wells GA. Chapter 13: Including non-randomized studies. In: Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Review Manager 2014 [Computer program]
- Nordic Cochrane Centre, The Cochrane Collaboration Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Sarezky 2017
- Sarezky D, Orlin SE, Pan W, VanderBeek BL. Trends in corneal transplantation in keratoconus. Cornea 2017;36(2):131-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
Siganos 2010
- Siganos CS, Tsiklis NS, Miltsakakis DG, Georgiadis NS, Georgiadou IN, Kymionis GD, et al. Changing indications for penetrating keratoplasty in Greece, 1982-2006: a multicenter study. Cornea 2010;29(4):372-4. [DOI] [PubMed] [Google Scholar]
Thompson 2003
- Thompson RW Jr, Price MO, Bowers PJ, Price FW Jr. Long-term graft survival after penetrating keratoplasty. Ophthalmology 2003;110(7):1396-402. [DOI] [PubMed] [Google Scholar]
Todani 2011
- Todani A, Ciolino JB, Ament JD, Colby KA, Pineda R, Belin MW, et al. Titanium back plate for a PMMA keratoprosthesis: clinical outcomes. Graefes Archive for Clinical and Experimental Ophthalmology 2011;249(10):1515-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
Utine 2011
- Utine CA, Tzu J, Dunlap K, Akpek EK. Visual and clinical outcomes of explantation versus preservation of the intraocular lens during keratoprosthesis implantation. Journal of Cataract and Refractive Surgery 2011;37(9):1615-22. [DOI] [PubMed] [Google Scholar]
Wagoner 2009
- Wagoner MD, Gonnah ES, Al-Towerki AE, King Khaled Eye Specialist Hospital Cornea Transplant Study Group. Outcome of primary adult penetrating keratoplasty in a Saudi Arabian population. Cornea 2009;28(8):882-90. [DOI] [PubMed] [Google Scholar]
Whitcher 2001
- Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness: a global perspective. Bulletin of the World Health Organization 2001;79(3):214-21. [PMC free article] [PubMed] [Google Scholar]
Williams 2008
- Williams KA, Lowe M, Bartlett C, Kelly TL, Coster DJ. Risk factors for human corneal graft failure within the Australian corneal graft registry. Transplantation 2008;86(12):1720-4. [DOI] [PubMed] [Google Scholar]
Yildiz 2010
- Yildiz EH, Hoskins E, Fram N, Rapuano CJ, Hammersmith KM, Laibson PR, et al. Third or greater penetrating keratoplasties: indications, survival, and visual outcomes. Cornea 2010;29(3):254-9. [DOI] [PubMed] [Google Scholar]
Zerbe 2006
- Zerbe BL, Belin MW, Ciolino JB, Boston Type 1 Keratoprosthesis Study Group. Results from the multicenter Boston Type 1 Keratoprosthesis Study. Ophthalmology 2006;113(10):1779. [DOI] [PubMed] [Google Scholar]
References to other published versions of this review
Akpek 2012
- Akpek EK, Alkharashi M, Lindsley K. Artificial corneas versus donor corneas for repeat corneal transplants. Cochrane Database of Systematic Reviews 2012, Issue 1. [DOI: 10.1002/14651858.CD009561] [DOI] [PMC free article] [PubMed] [Google Scholar]
Akpek 2014
- Akpek EK, Alkharashi M, Hwang FS, Ng SM, Lindsley K. Artificial corneas versus donor corneas for repeat corneal transplants. Cochrane Database of Systematic Reviews 2014, Issue 11. [DOI: 10.1002/14651858.CD009561.pub2] [DOI] [PMC free article] [PubMed] [Google Scholar]