Introduction
Orbital fractures are commonplace in craniomaxillofacial trauma, accounting for approximately 10–25% of injuries to the region [
1,
2]. Management of these injuries is inherently challenging as clinical sequelae, both functional and aesthetic, may not always be immediately obvious. Thus, a period of observation may be sensible in the acute setting. Inappropriate management, however, may result in reduced visual acuity, persistent enophthalmos, ocular motility deficits, diplopia, and sensory disturbance [
3]. Operative management to repair the defect may be warranted either immediately (such as for trapdoor fractures with entrapment in paediatric patients or in the case of a profound oculocardiac reflex with the possibility of haemodynamic instability) or delayed, according to persistence or progression of symptoms post-trauma [
4,
5]. Indeed, indications quoted for delayed operative management, ideally within 2 weeks of the inciting trauma, include enophthalmos (> 2 mm); ocular dysmotility; persistent diplopia; computed tomography (CT) findings of extraocular muscle entrapment; progressive infraorbital nerve (ION) hypoaesthesia; and abnormal forced duction testing [
6].
Orbital reconstruction following trauma is complicated by the limited operative view and the complexity of the anatomical region with the presence of vital neurovasculature in close proximity [
7]. The procedure involves mobilisation of entrapped soft tissues and the restoration of the orbit to its correct anatomical position and volume by replacing the bony defect and providing stable fixation using an implant [
8,
9]. The decision on which implant material to use is influenced by surgeon experience, fracture severity, patient characteristics, and cost; traditionally, conventional implants have taken the form of either prefabricated (i.e. mass-produced) alloplastic plates, such as titanium, or autologous bone grafts [
10]. Conventional reconstruction methods afford the advantages of availability and biostability allows intra-operative contouring as well as cost-effectiveness. The emergence and widespread availability of computer-assisted surgery (CAS), including computer-aided design and computer-aided manufacturing (CAD/CAM) processes, has precipitated the development of individualised implants. These may take one of two forms: either entirely bespoke implants which are usually manufactured externally following provision of a CT scan–derived mirror-image overlay (MIO) from the contralateral, uninjured orbit (hereafter termed patient-specific implants (PSI)); or conventional implants that are manipulated and contoured pre-operatively on patient-specific, three-dimensional (3D) models created through stereolithography from CT imaging (hereafter termed hybrid-PSI) [
11]. The perceived hypothetical benefits of using PSI or hybrid-PSI in orbital reconstruction are apparent and include reduced operative time (through avoiding the need for intra-operative contouring) and more precise reconstitution of the patient’s pre-morbid orbital architecture to optimise restoration of both function and form. Nonetheless, despite the promise of patient-specific implants, there is limited comparative data in the literature supporting their benefit over conventional implants. Previous systematic reviews on their use in orbital reconstruction have either included heterogeneous datasets (such as defects secondary to neoplasia and resection, thereby precluding a formal quantitative comparison of key outcomes) or featured incomplete search strategies, such that key comparative studies were not included [
12]. Moreover, although comprehensive reviews have been conducted on the use of computer-assisted, technology-augmented surgery in post-traumatic orbital reconstruction, no study to the authors’ knowledge has thus far provided a quantitative evaluation of relevant clinical outcomes between conventional reconstruction methods and PSI [
8]. The purpose of the current systematic review and meta-analysis was, therefore, to synthesise the currently available data from comparative studies on patient-specific (hereafter encompassing both PSI and hybrid-PSI) implants vs. conventional reconstruction methods with respect to operative time, enophthalmos, diplopia, and orbital volume reconstitution.
Materials and methods
This study was completed in keeping with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Institutional review board (IRB) approval was not required for the current study.
Research question (according to the PICO framework)
Do patient-specific implants, manufactured or designed using computer-assisted technology, improve outcomes (orbital volume change, enophthalmos, diplopia, and operative duration) compared to conventional methods in orbital reconstruction following traumatic orbital injury in the adult patient population?
Search strategy
A systematic literature search was performed on 24 January 2022 using the following databases: ClinicalTrials.gov; Cochrane CENTRAL; EMBASE via OVID; MEDLINE via OVID; PubMed; Scopus; Web of Science Core Collection; and World Health Organization International Clinical Trials Registry Platform. The detailed search strategy is appended in the Supplementary Material
S1. References of identified records were iteratively searched for further suitable records.
Selection criteria
Inclusion criteria:
1.
Computer-assisted technology in the prefabrication or design process of implants for use in orbital reconstruction following orbital fracture.
2.
Implants were patient-specific, achieved either through bespoke fabrication based on CAD/CAM technologies (PSI) or through pre-operative bending of plates using patient-specific 3D modelling (hybrid-PSI).
3.
Performed primary and/or secondary reconstruction of orbital fractures.
4.
Provided details on at least one of the following outcomes: orbital volume change; enophthalmos; diplopia; hypoglobus; restricted ocular motility; ION hypoaesthesia; or procedure-related complications.
Exclusion criteria:
1.
Computer-assisted technologies were used only for diagnostic, pre-operative planning, or intra-operative navigation purposes.
2.
Observational studies only, including a single, non-comparative treatment arm.
3.
Insufficient description of post-operative outcomes.
4.
Orbital reconstruction performed for non-traumatic indications.
Data collection
Titles, abstracts, and full texts were independently assessed by two reviewers (AF and SK). Discrepancies were resolved by consensus following discussion between reviewers to minimise selection bias. In addition to the exclusion criteria above, the following identified studies were excluded: case reports; review articles; recommendations and guidelines; expert opinions; full texts not available in English; cadaveric studies; animal studies; surveys; and shared data. A custom data collection form was used to extract the following data: study title; authors; year of publication; the nature of the study; randomisation method; patient demographics; mechanism of injury; time from injury to surgery; sample size of both patient-specific and conventional cohorts; implant type; manufacturing process; presence or absence of intra-operative navigation; fracture characteristics; surgical approach; whether reconstruction was primary or secondary; and follow-up duration. Outcomes measured were as follows: operative duration; enophthalmos (as measured using an exophthalmometer); diplopia; orbital volume change; hypoglobus; restriction of ocular motility; ION hypoaesthesia; and procedure-related complications. Where multiple follow-up periods were reported, data were extracted from the most recent follow-up.
Assessment of bias
Risk of bias for the relevant studies was evaluated using two tools: the Newcastle–Ottawa Scale (NOS) was utilised for non-randomised studies and the Revised Cochrane Risk-of-Bias Tool for randomised trials (RoB2), both of which are recommended by the Cochrane Collaboration. Studies were not excluded on the grounds of bias. Instead, bias was acknowledged and highlighted. Non-randomised studies assessed using the NOS were classified as either high (score 0–3), moderate (score 4–6), or low risk of bias (score 7–9) based on evaluations of three domains [
13]. Randomised studies assessed using RoB2 were given an overall ranking of low risk of bias, some concerns, or high risk of bias based on evaluations of five domains [
14]. Discrepancies in scoring were resolved through consensus.
Statistical analysis
Continuous outcomes and baseline characteristics, where available, were reported as weighted combined means using formulae provided by the Cochrane Collaboration [
15]. Means and standard deviations were approximated according to Wan et al. (2014) where not otherwise provided [
8]. Study heterogeneity was assessed using the Cochrane Q-statistics chi-square test and Higgins
I2 statistic.
I2 was interpreted as follows: 0–40% as low heterogeneity; 30–60% as moderate heterogeneity; 50–90% as substantial heterogeneity; and > 75% as considerable heterogeneity [
15]. A Cochrane Q statistic
p-value < 0.10 was considered significant. Meta-analysis of binary outcomes (complication vs. no complication, for example) was achieved using the Mantel–Haenszel approach as part of a random-effects model. Results are reported as risk ratios (RR) with 95% confidence intervals. For continuous outcomes (such as enophthalmos), Hedges’
g was used as the measure of standardised mean difference (SMD), and a random-effects model was performed using the Hartung-Knapp adjustment. For descriptive summary statistics, where significance between groups was not reported in identified studies, Welch’s two-tailed independent samples
t-test was employed based on estimated means and standard deviations for continuous data and Fisher’s exact test for categorical data, where appropriate. Statistical analysis was performed using R Statistical Software version 4.0.0.
Discussion
Despite the prevalence of post-traumatic orbital injuries, there is still a lack of consensus in the literature as to the optimal management pathway for this cohort of patients. This divergence encompasses not only the timing of surgery (i.e. how soon post-injury elective orbital reconstruction should take place), but also the operative approach and the implant-type employed in reconstruction of the orbital architecture [
27,
28]. A variety of implant materials and types have been used, including both alloplastic and autologous implants, and resorbable and non-resorbable implants. The choice of implant is influenced by various factors, including fracture complexity and location, operator familiarity and preference, as well as resource availability [
29]. The emergence of CAS has accompanied advancements in surgery in a number of ways, from both a pre-operative planning perspective and intra-operative surgical approach. This includes the implementation of stereolithography in creating 3D models of patient anatomy and real-time operative navigation and guidance [
30,
31]. Specifically, CAD/CAM processes have enabled an increasing degree of customisation to be afforded to individual patients. With regard to orbital reconstruction, the ability to generate fully customised PSI to accurately replicate the complex and elaborate anatomy of the orbital region is one way in which improvements to pre-existing surgical methods have been attempted. The ability to implement the use of hybrid-PSI, whereby conventional, mass-produced implants are manipulated pre-operatively based on stereolithographically engineered patient models from CT imaging data, represents another potential method of optimising patient outcomes [
32]. The hypothetical advantages conferred by PSI (both PSI and hybrid-PSI) include not only the potential for reduced injury-associated complications (diplopia, enophthalmos, reduced visual acuity, etc.) and reduced intra-operative complications, but also the possibility of reduced operating time, obviating the need to manipulate the implant intra-operatively [
33].
The purpose of the current study, comprising a total of 628 patients across 11 studies, was to collate relevant comparative data in order to elucidate whether there are any differences in outcomes in patients undergoing orbital reconstruction post-trauma, specifically with regard to patient-specific versus conventional implants. From an epidemiological perspective, the demographic domains of age (mean 39 years) and sex (approximately 2:1 male to female ratio) of the patients were generally similar to data elsewhere in the literature [
34]. Likewise, the three most prevalent aetiological reasons for trauma, interpersonal violence, road traffic collisions, and falls, are consistent with the mechanisms of injury most widely reported in the literature [
34‐
36]. Insufficient data were available, however, to determine whether the baseline characteristics between treatment groups were similar between studies.
The benefits of reduced operating time have been described in the literature. It has been suggested that operations of shorter duration are associated with improved clinical outcomes, such as reduced estimated blood loss, and reduced overall length of hospital admission [
33]. Moreover, efficient operating can have subsequent ramifications on an organisation’s overall productivity [
37]. Although not supported by meta-analysis, 3 of the 6 reporting studies independently identified significantly shorter operative duration in the group of patients undergoing reconstruction with PSI, supporting the notion of more rapid implant placement.
Similarly to operative duration, weighted post-operative mean difference in orbital volume between the post-operative orbit and contra-lateral unaffected orbit was smaller in the patient-specific group, indicating better reconstitution of pre-operative orbital anatomy. Despite non-significance on meta-analysis, it is telling that 3 of the 4 studies reporting on changes in orbital volume identified significantly better outcomes with the use of PSI, whether by virtue of a reduction in the orbital volume difference between affected and unaffected orbits, or as a result of the degree of precision in the reconstruction. Three of the 8 reporting studies also found a statistically significant benefit of PSI in improving post-operative enophthalmos, though a commensurate improvement was apparently not translated to diplopia (Fig.
3).
Two of the 11 papers eligible for inclusion reported on patient randomisation between treatment arms; however, the method of randomisation was not made explicit [
18,
21]. Failure to account for baseline differences in patient characteristics between groups using a robust process of randomisation will introduce bias. Moreover, outcome measurements on post-operative imaging were not blinded. Although this is not feasible where the control group implant is obviously distinct from the PSI (in the case of autologous bone, for example), blinding may be possible, at least to the individual interpreting post-operative imaging and to the patient, with the use of conventional versus hybrid-patient-specific plates. Baseline characteristics that might introduce heterogeneity include the fracture characteristics (severity or complexity, pattern, location); implant types used (alloplastic and autologous implants in the conventional groups); implant materials used (titanium and porous polyethylene in the conventional groups), degree of customisation employed (PSI or hybrid-PSI); operative approach to reconstruction; time to surgery from injury; and type of reconstruction (one study evaluated secondary reconstruction whilst the remainder examined primary reconstruction). Moreover, important clinical outcomes, such as hypoglobus, ION hypoaesthesia, ocular motility restriction, and procedure-related complications, could not be included in the current study due to insufficient reporting. A recent systematic review assessing patient-specific vs. conventional titanium mesh implants in post-traumatic orbital reconstruction, Hartmann et al. (2021), drew similar conclusions to the present study with generally positive outcomes across a range of clinical domains being attributed to the patient-specific group [
12]. Nevertheless, Hartmann et al. also reported encountering significant heterogeneity for various reasons including study design, materials, and non-standardised reporting. The present study expands on the results of this previous review, identifying a further 9 comparative studies that assess outcomes directly between patient-specific and conventional implants for traumatic orbital reconstruction.
A potential limitation of the current study is the pooling of patient-specific and hybrid-patient-specific plates as a single comparator group encompassing PSI. Despite the similarities between these two subgroups, the authors acknowledge that there are intrinsic differences relating to the different manufacturing processes, namely that hybrid-patient-specific plates (by virtue of modification and manipulation from conventional, mass-produced plates) will likely have sharper edges than plates of the patient-specific cohort and assumed less accurate adaptation to the printed 3D model relative to patient-specific plates. Moreover, in three of the included studies, manipulation of hybrid-patient-specific plates was performed intra-operatively, thereby negating any potential advantage on operative duration of pre-operatively contoured PSI [
16,
24,
26]. Collectively, these differences may have a discernible impact on intra-operative placement and post-operative complications. Nonetheless, there are several parallels between these two subgroups: both methods not only utilise CAM/CAM technology and MIO for virtual reconstruction, but also employ stereolithography at some point in the manufacturing process. Fundamentally, both patient-specific and hybrid-patient-specific manufacturing methods result in the application of an individualised implant at the time of surgery.
A further consideration with patient-individualised therapies, irrespective of disciplines, is that they are initially expensive. A study on cost-effectiveness of patient-specific versus conventional implants is beyond the scope of the current review. However, a previous review on costs of conventional implants in orbital reconstruction found that the mean cost of the implant itself ranged from $70.25 to $7718.00, with a mean total cost of care per patient of $35,585,57, the majority of which was attributable to theatre running costs, inpatient stay, and clinical review [
38]. The manufacturer cost of PSI involving the use of CAD/CAM is undoubtedly higher than that of conventional implants. Given the potential for shorter operative duration, shorter inpatient admission, and fewer post-operative complications, however, this unit cost deficit may well be offset.
Conclusion
Although some individual studies reported a potential advantage of patient-specific implants for reducing operative time, improved orbital volume recapitulation, and better outcomes with respect to post-operative enophthalmos, statistically significant results were not demonstrated on meta-analysis to reflect this. There are several potential reasons for this, which likely relate to the retrospective nature of the identified observational cohort studies with accompanying lack of randomisation. Inevitably there will be differences in fracture complexity, operator experience and technique, as well as patient baseline demographics between groups, which may limit the magnitude of detectable outcome differences attributable to treatment effects. The use of CAD/CAM is still a relatively emergent technology within the oral and maxillofacial surgery domain. As these technologies become more widely adopted within the community, it is the authors’ opinion that the benefits of this technology will be fully realised. Based on the results of this study, the choice of implant used should, thus, be left to the discretion of the surgeon.
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