Advice
Clinical and technical evidence
Clinical and technical evidence
A literature search was carried out for this briefing in accordance with the published process and methods statement. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting mibs@nice.org.uk.
Published evidence
Evidence published on the efficacy and safety of the device before January 2015 is included in the NICE interventional procedures guidance on implantation of a corneal graft–keratoprosthesis for severe corneal opacity in wet blinking eyes and so has not been included in this briefing. Nine studies (2 prospective and 7 retrospective) including a total of 1,162 patients (1,202 eyes) were selected for inclusion and are summarised in this briefing.
Of the 2 prospective studies, 1 reported visual acuity improvement after implantation with the Boston KPro Type I (Boston KPro 1; Rudnisky et al. 2016), and the other reported a higher incidence of bacterial microbiota colonising the ocular surface of patients' eyes with Boston KPro I implantation compared with the patients' untreated eyes (Jassim et al. 2015).
Of the 7 retrospective studies, Akpek et al. (2015) and Ahmad et al. (2016) reported greater visual improvement, and greater likelihood of maintaining the visual improvement, with Boston KPro I compared with repeat penetrating keratoplasty (PK). Additionally, Akpek et al. reported less frequent graft failure for the Boston KPro I. Fadous et al. (2015) reported better visual acuity for people who had Boston KPro I as a primary penetrating corneal surgery compared with the Boston KPro I as a secondary procedure (after a failed PK), with similar complication rates. In a non‑comparative study, Goins et al. (2016) reported that although Boston KPro I implantation was associated with satisfactory visual acuity outcomes and device retention, serious postoperative complications were common.
Two studies compared visual acuity and complications in patients with and without Stevens–Johnson syndrome (Alexander et al. 2015) and in eyes with and without limbal stem cell deficiency (Aravena et al. 2016). The studies found that Boston KPro I was an effective means to restore vision in individuals in people with these co-morbidities. However, Chan et al. (2016) reported a higher incidence of KPro-corneal melt-related complications in patients with severe ocular surface disease than in those without.
Strengths and limitations of the evidence
Seven of the studies were weakened because they were retrospective in design. All but 3 (Akpek et al. 2015; Fadous et al. 2015; Ahmed et al. 2016) were non‑comparative studies that evaluated the Boston KPro I without a control group. The rest of the studies compared outcomes on the same eye before and after the implantation of the Boston KPro I. Although the lack of a control is a limitation of the evidence base, the intended use of Boston KPro I is as a secondary treatment option after PK has failed, and this reduces the opportunity for comparative studies in this field. Instead, the patient becomes their own historical control.
Two studies, Alexander et al. (2015) and Aravena et al. (2016), were done in the same centre, so there could be some overlap in the populations. In their analysis, Aravena et al. included 10 patients with limbal stem cell deficiency who also had Stevens–Johnson syndrome, but because of different recruitment periods it is unclear whether the same patients were also included in the study by Alexander et al.
None of the 9 studies were done in the UK, which may affect their generalisability to the NHS because standard care may differ. It is unclear which version of the Boston KPro I has been used in any of the studies other than in Fadous et al. (2015). The description of the procedure was also generally poor. The studies had long recruitment periods, covering different versions of the technology with most being done before 2014. Most of the studies reported visual acuity or graft survival outcomes with up to 2 years of follow-up for all patients. Longer follow-up periods would have been more informative on the long-term outcomes of this procedure.
The study by Akpek et al. (2015) was a comparative study but participants were not randomised. People having Boston KPro I implantation tended to have a more complicated ocular history. Also, the study was done in a single tertiary care practice, which could lead to selection bias towards including patients with more complex eye conditions and possibly lower visual potential and higher chances of failure with successive donor PK than in previously reported series. However, it is noted that patients with more complex eye conditions may be the most appropriate population to have the Boston KPro I. Post-operative care was not standardised in either group but was instead designed to suit each patient, leading to potential performance bias.
Although the Aravena et al. (2016) study compared the outcomes of Boston KPro I implantation in eyes with limbal stem cell deficiency with those without the condition, it would have been more relevant to compare it with other procedures for managing limbal stem cell deficiency.
The study by Rudnisky et al. (2016) was sponsored (but not funded) by the manufacturer, which could be a source of bias.
Table 1 summarises the clinical evidence for the device as well as its strengths and limitations.
Table 1 Summary of selected studies
|
Study size, design and location |
Intervention and comparators |
Outcomes |
Strengths and limitations |
|
174 eyes of 165 patients Retrospective case series Multicentre US |
Boston KPro I initial implantation (n=112). Boston KPro I (n=36) repeat implantation. Follow-up period: 2 years. |
Visual acuity improved in two-thirds of eyes after the repeat KPro 1 implantation. The probability of maintaining visual acuity was significantly better for the first implantation compared with repeat implantation. Better vision before explantation and immediately after repeat KPro 1 implantation were significant predictors of the ability to maintain vision of 20/200 or more. |
Small sample size for repeat KPro 1 implantation. Follow-up periods to assess maintenance of visual acuity differed between the 2 comparisons. Unclear which version or model of Boston KPro I was used. |
|
149 eyes of 149 patients Retrospective cohort study Single-centre US |
Boston KPro I (n=149). No comparator intervention. Treated eyes were compared with non‑treated eyes. Follow-up period: 5 years. |
A significantly greater percentage of eyes with corneal LSCD had improved visual acuity at each of the first 5 years after surgery. Persistent corneal epithelial defect was the only postoperative complication more common in eyes with LSCD compared with eyes without LSCD. Retention failure rates in eyes with and without LSCD were similar. |
Unclear which version or model of Boston KPro I was used. The study was carried out at the same location as the Alexander et al. (2015) study and there may be some overlap in the populations. |
|
128 eyes of 110 patients Retrospective cohort study Single-centre US |
Boston KPro I (n=128). No comparator intervention. Mean follow-up period: 29 months. |
Patients in the cohort with severe ocular surface disease who had Boston KPro I implantation experienced more corneal melts, leaks, and extrusions than those without severe ocular surface disease. |
This was a large cohort with a long follow-up (29 months on average). Unclear which version or model of Boston KPro I was used. |
|
75 eyes of 75 patients Retrospective cohort study Single-centre US |
Boston KPro I (n=75). No comparator. Mean follow-up period: 41.4 months. |
Improved vision was recorded in more eyes than full functional vision. The first device was retained in most eyes with Kaplan–Meier retention probability decreasing between 6 months and 5 years. One or more sight-threatening complications occurred in more than half of the eyes. |
Unclear which version or model of Boston KPro I was used. |
|
300 eyes of 300 patients Prospective cohort study Multicentre US |
Boston KPro I (n=300). No comparator. Mean follow-up period: 8.5 months. |
After Boston KPro I implantation:
|
This was a prospective but non‑comparative cohort study. Unclear which version or model of the Boston KPro I was used. |
|
80 eyes of 80 patients Retrospective, non-randomised case series Single-centre US |
Boston KPro I (n=27). Repeat PK (n=53). Mean follow up: 19.5 months in the PK group and 16.5 months in the KPro group. |
In the post-operative period, a greater percentage of eyes with the Boston KPro I attained visual acuity than eyes having PK, but a greater percentage of eyes with PK kept this visual acuity for longer. The 2‑year cumulative rate of graft failure was higher for eyes with PK. Post-operative complications were similar for both groups. |
Non-randomised case series, with a short follow-up period. Unclear which version of the technology was used. |
|
209 eyes of 209 patients Retrospective comparative case series Multicentre (US, India, Philippines) |
Boston KPro I (n=209). No comparator intervention. Follow-up period: patients with SJS (17.6±16.2 months), patients without SJS (29.3±22.8 months. |
A significantly greater percentage of patients with SJS had a corrected distance visual acuity 12 months after surgery compared with those without SJS. Postoperative complications were more common in patients with SJS, which led to a higher retention failure rate and secondary surgical procedures. But, after repeat implantation, eyes in patients with SJS were no less likely to retain a keratoprosthesis than those of patients without SJS. |
Unclear which version of the technology was used. |
|
70 eyes of 70 patients Retrospective comparative study Single-centre Canada |
Boston KPro I as a primary penetrating corneal surgery (n=30). Boston KPro I as a secondary penetrating corneal surgery (n=40). Follow-up period: 12 months. |
Throughout the follow-up period, visual acuity was significantly better in patients who had KPro I as a primary procedure. At 12 months, more eyes had a best-corrected visual acuity in this group than in the group having the device as secondary treatment. The complication and retention rates were similar in the 2 groups. |
The threadless 'Snap-on' KPro I with a PMMA backplate and 16 holes was used for all patients. |
|
43 eyes of 26 patients Prospective cohort study Single-centre US |
Boston KPro I (n=27). Untreated eyes as the control group (n=16). Follow-up period: over 6 months. |
There were more cultures with bacterial microbiota from eyes with the KPro I than from control eyes (healthy eyes from the same patients). |
This was a prospective study with a small sample size. Unclear which version or model of the Boston KPro I was used. |
|
Abbreviations: Boston KPro I, Boston Keratoprosthesis Type I; LSCD, limbal stem cell deficiency; PK, penetrating keratoplasty; SJS, Stevens–Johnson syndrome. |
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Recent and ongoing studies
One ongoing trial using Boston KPro I was identified.
NCT01950598: a prospective, single-blind, randomised controlled trial to determine the safety and efficacy of using frozen corneas as carriers with the Boston KPro I compared with fresh corneas over long-term follow-up. The estimated completion date is January 2020.