*2.4. Patient-Specific Implant Design*

Reconstructing the orbit with a PSI is the ultimate step of individualization for orbital reconstruction. A PSI is virtually modelled from scratch, using information from the (advanced) diagnostics phase and exported virtual models. In dedicated design software, a prototype implant is generated. The prototype is imported into the virtual surgical planning and its fit is evaluated. The position of the prototype is not adjusted in the virtual surgical planning to improve the fit, but the design of the prototype is adjusted and the novel prototype is reimported. Even though the design of a PSI is not set in stone by protocols, various design considerations have been described in the literature. An overview of options is summarized in Table 1. This overview is not comprehensive, and novel design options are regularly introduced in the literature.

**Table 1.** List of different design considerations as reported in the literature.


Design considerations can be categorized based on their intended effect: stability, positioning ease, accuracy of implant positioning or alleviation of clinical symptoms. The size and shape of the implant are dependent on the extent of the defect. The defect should

be covered by the implant and its shape should reflect the intended reconstruction of the affected orbital walls. Support on existing bony structures is taken into account to ensure the stability of the reconstruction. Analogous to the preformed implants, support is most often found at three points in the orbit [22,38]. Fixation is recommended to ensure a stable position of the PSI [39,40]. Possible screw positions can be assessed in virtual planning, factoring in the patient's anatomy and local bone quality. The thickness of the implant and implementation of an atraumatic cord around the edge are considerations that affect both the stability of the implant and the positioning ease during surgery. Due to additive-manufactured titanium's rigidity, an implant thickness of 0.3 mm in combination with an atraumatic cord results in a good balance between rigidity and positioning ease.

The accuracy of implant positioning can be controlled by extensions over unaffected bony pillars. A compelling fit is created by the extension(s) of the implant over bony structures. An infraorbital rim extension limits rotation and translation in the anteroposterior direction [47]. Additional flanges to the posterior lateral wall may be implemented to prevent unwanted implant movement [43]. Screw positions from fixation material from a previous reconstruction can be re-used in secondary reconstruction to provide guidance and thus improve the accuracy of the implant positioning [54]. Another design option is to incorporate navigation markers and vectors, which can enhance the interpretation of feedback from the intraoperative navigation system.

The last category, clinical symptoms, deals with the correction of globe displacement. The orbital volume is corrected to alleviate globe displacement, but the volume may be overcorrected to counteract fat atrophy and the anticipated iatrogenic loss of soft tissue [57]. The amount of overcorrection might be subjectively determined during surgery, by inserting additional spacers [51], or it may be fully integrated into the design of the PSI, posterior to the equator of the bulbus [22,38,50]. On the other hand, hypoglobus is the result of caudal displacement of the infra-orbital rim. An anterior elevation corresponding to the amount of downward displacement of the orbital rim may alleviate hypoglobus (Figure 4). The grid of the PSI can be designed with different techniques: using a large horizontal pattern to maximize drainage [37,40,43], or a more porous arrangement [42,45,46]. The multitude of design options and manual design leads to a wide range of possible PSI shapes (Figure 5). *J. Pers. Med.* **2022**, *12*, 1366 8 of 17 posterior to the equator of the bulbus [22,38,50]. On the other hand, hypoglobus is the result of caudal displacement of the infra-orbital rim. An anterior elevation corresponding to the amount of downward displacement of the orbital rim may alleviate hypoglobus (Figure 4). The grid of the PSI can be designed with different techniques: using a large horizontal pattern to maximize drainage [37,40,43], or a more porous arrangement [42,45,46]. The multitude of design options and manual design leads to a wide range of possible PSI shapes (Figure 5).

**Figure 4.** Examples of two patient-specific implant designs with overcorrection (red contour) of the mirrored orbital volume (yellow contour). The first patient-specific implant is designed with an anterior elevation at the infra-orbital rim to compensate for the asymmetry in globe position (**A**,**B**). The second patient-specific implant is designed with a large overcorrection for an anophthalmic socket reconstruction (**C**,**D**). **Figure 4.** Examples of two patient-specific implant designs with overcorrection (red contour) of the mirrored orbital volume (yellow contour). The first patient-specific implant is designed with an anterior elevation at the infra-orbital rim to compensate for the asymmetry in globe position (**A**,**B**). The second patient-specific implant is designed with a large overcorrection for an anophthalmic socket reconstruction (**C**,**D**).

**Figure 5.** Different shapes of the available preformed implants and patient-specific implants are illustrated. There is a wide variety in shapes in the patient-specific implants. From left to right the

The PSI design can be adapted to facilitate the reconstruction of multi-wall defects, for example, through the application of multiple PSIs (Figure 6). This enables a reconstruction that covers the entire defect while limiting the size of the PSI and, in turn, the required

rim extension is increased. From top to bottom the medial wall support is increased.

posterior to the equator of the bulbus [22,38,50]. On the other hand, hypoglobus is the result of caudal displacement of the infra-orbital rim. An anterior elevation corresponding to the amount of downward displacement of the orbital rim may alleviate hypoglobus (Figure 4). The grid of the PSI can be designed with different techniques: using a large horizontal pattern to maximize drainage [37,40,43], or a more porous arrangement [42,45,46]. The multitude of design options and manual design leads to a wide range of

**Figure 4.** Examples of two patient-specific implant designs with overcorrection (red contour) of the mirrored orbital volume (yellow contour). The first patient-specific implant is designed with an anterior elevation at the infra-orbital rim to compensate for the asymmetry in globe position (**A**,**B**). The second patient-specific implant is designed with a large overcorrection for an anophthalmic

possible PSI shapes (Figure 5).

socket reconstruction (**C**,**D**).

tioning [54].

*2.5. Intraoperative Feedback* 

physically in the OR.

sition.

**Figure 5.** Different shapes of the available preformed implants and patient-specific implants are illustrated. There is a wide variety in shapes in the patient-specific implants. From left to right the rim extension is increased. From top to bottom the medial wall support is increased. The PSI design can be adapted to facilitate the reconstruction of multi-wall defects, **Figure 5.** Different shapes of the available preformed implants and patient-specific implants are illustrated. There is a wide variety in shapes in the patient-specific implants. From left to right the rim extension is increased. From top to bottom the medial wall support is increased.

for example, through the application of multiple PSIs (Figure 6). This enables a reconstruction that covers the entire defect while limiting the size of the PSI and, in turn, the required The PSI design can be adapted to facilitate the reconstruction of multi-wall defects, for example, through the application of multiple PSIs (Figure 6). This enables a reconstruction that covers the entire defect while limiting the size of the PSI and, in turn, the required incision [46,55]. Depending on the connection used, it also provides the opportunity to create artificial support and relative feedback. A PSI that solely reconstructs the orbit will not suffice in cases with concomitant fractures of the surrounding bony structures. Repositioning the surrounding bone may be required in addition to the orbital reconstruction. Additional design options are available to gain feedback from PSIs on the subsequent reconstruction steps in these more extensive cases. An example of this is embedding the desired position of the zygomatic complex in the PSI design to facilitate correct repositioning [54]. *J. Pers. Med.* **2022**, *12*, 1366 9 of 17 incision [46,55]. Depending on the connection used, it also provides the opportunity to create artificial support and relative feedback. A PSI that solely reconstructs the orbit will not suffice in cases with concomitant fractures of the surrounding bony structures. Repositioning the surrounding bone may be required in addition to the orbital reconstruction. Additional design options are available to gain feedback from PSIs on the subsequent reconstruction steps in these more extensive cases. An example of this is embedding the desired position of the zygomatic complex in the PSI design to facilitate correct reposi-

**Figure 6.** Patient-specific implant design for multi-wall cases. (**A**) Ridges on the orbital floor implant provide relative feedback for the positioning of the lateral wall implant. (**B**) Patrix–matrix connection to connect a medial wall and orbital floor implant. (**C**) The orbital floor implant with medial wall extension is connected to a lateral wall implant dorsally with ridges and anteriorly with a puzzle connection. (**D**) Four-wall reconstruction with a hook-and-bar connection for additional support for the orbital floor implant. . **Figure 6.** Patient-specific implant design for multi-wall cases. (**A**) Ridges on the orbital floor implant provide relative feedback for the positioning of the lateral wall implant. (**B**) Patrix–matrix connection to connect a medial wall and orbital floor implant. (**C**) The orbital floor implant with medial wall extension is connected to a lateral wall implant dorsally with ridges and anteriorly with a puzzle connection. (**D**) Four-wall reconstruction with a hook-and-bar connection for additional support for the orbital floor implant.

During surgery, the surgeon aims to position the implant as closely as possible to the

Surgical navigation may be utilized to provide dynamic feedback on the implant position. During the registration for surgical navigation, the patient's position in the operating room (OR) is linked to the preoperative imaging data in the virtual surgical planning. Several registration methods are available: soft-tissue registration, bone-anchored fiducials, and surgical splints [56,58]. Splint registration methods used to require repeated radiographic imaging with the fiducial splint in place, but the fusion of intraoral scan data in the advanced diagnostics phase allows the fabrication of a registration splint without additional radiologic imaging [59]. The splint is designed on the individual patient's dentition and carries fiducials that can be indicated virtually in the planning software and

After registration, the navigation pointer's position in the patient is visualized in the virtual surgical planning on the navigation system's screen. This provides the surgeon with feedback on the position of the pointer, representing the position of the indicated location (a specific spot on the implant's surface). The quality and interpretability of the feedback may be enhanced through navigation markers embedded in the design [39,52]. The markers are indicated in the VSP as navigation landmarks and used as a reference in

of feedback are available to aid in the accurate positioning of the implant (summarized in Table 2). The design options relating to implant positioning ensure static feedback through the unique and compelling fit of the PSI (Figure 7). In secondary cases, the re-use of screw positions from the primary reconstruction will also help to find the planned po-

#### *2.5. Intraoperative Feedback*

During surgery, the surgeon aims to position the implant as closely as possible to the ideal position that was established in the VSP. The availability of the VSP provides intraoperative feedback that improves the result of the reconstruction [35]. Additional types of feedback are available to aid in the accurate positioning of the implant (summarized in Table 2). The design options relating to implant positioning ensure static feedback through the unique and compelling fit of the PSI (Figure 7). In secondary cases, the re-use of screw positions from the primary reconstruction will also help to find the planned position. *J. Pers. Med.* **2022**, *12*, 1366 10 of 17 the OR. If the surgeon positions the pointer in the navigation marker on the implant, visual and quantitative feedback about the pointer's position compared to the landmark is provided.

> **Table 2.** Different feedback methods available in the operation room. **Table 2.** Different feedback methods available in the operation room.


**Figure 7.** Illustration of the different feedback methods.). Markers and vectors are visualized in (**A**) and (**B**). Compelling fit of the patient-specific implant design is indicated with red arrows (**A**–**C**) Segmentation of screw holes of the previous reconstruction are illustrated in red (**D**) and the previous implant in dark grey. **Figure 7.** Illustration of the different feedback methods.). Markers and vectors are visualized in (**A**) and (**B**). Compelling fit of the patient-specific implant design is indicated with red arrows (**A**–**C**) Segmentation of screw holes of the previous reconstruction are illustrated in red (**D**) and the previous implant in dark grey.

*2.6. Evaluation*  Intraoperative imaging of the patient after implant positioning is highly recommended, since the realized implant position can be qualitatively evaluated. If the surgeon is not satisfied with the position, the implant can be repositioned in the same surgical setting, preventing a revision surgery. For a complete quantitative evaluation of the surgical result, the scan can be reconstructed and fused with the VSP. The planned position of the implant can be compared to the achieved position of the implant to enable an objective assessment (Figure 8). Differences between planned and realized position can be quantified in three dimensions and expressed as rotations (roll, pitch and yaw) and translations (x, y and z) [60]. Additionally, the volumetric difference between the reconstructed Surgical navigation may be utilized to provide dynamic feedback on the implant position. During the registration for surgical navigation, the patient's position in the operating room (OR) is linked to the preoperative imaging data in the virtual surgical planning. Several registration methods are available: soft-tissue registration, bone-anchored fiducials, and surgical splints [56,58]. Splint registration methods used to require repeated radiographic imaging with the fiducial splint in place, but the fusion of intraoral scan data in the advanced diagnostics phase allows the fabrication of a registration splint without additional radiologic imaging [59]. The splint is designed on the individual patient's dentition and carries fiducials that can be indicated virtually in the planning software and physically in the OR.

and unaffected or planned orbit may be assessed. Post-operative CT-scans are indicated if intra-operative CT is not acquired (or offered incomplete information), or if clinical considerations in the follow-up period necessitate additional imaging. After registration, the navigation pointer's position in the patient is visualized in the virtual surgical planning on the navigation system's screen. This provides the surgeon with feedback on the position of the pointer, representing the position of the indicated location (a specific spot on the implant's surface). The quality and interpretability of the feedback may be enhanced through navigation markers embedded in the design [39,52]. The markers are indicated in the VSP as navigation landmarks and used as a reference in the OR. If the surgeon positions the pointer in the navigation marker on the implant, visual and quantitative feedback about the pointer's position compared to the landmark is provided.

**Figure 8.** Illustration of an evaluation. (**A**) Three-dimensional model of the planned patient-specific implant (red) and the realized patient-specific implant (green) viewed from different perspectives. (**B**–**D**) Axial, sagittal, and coronal view of the postoperative computed tomography scan with the

#### *2.6. Evaluation 2.6. Evaluation*

ous implant in dark grey.

provided.

Intraoperative imaging of the patient after implant positioning is highly recommended, since the realized implant position can be qualitatively evaluated. If the surgeon is not satisfied with the position, the implant can be repositioned in the same surgical setting, preventing a revision surgery. For a complete quantitative evaluation of the surgical result, the scan can be reconstructed and fused with the VSP. The planned position of the implant can be compared to the achieved position of the implant to enable an objective assessment (Figure 8). Differences between planned and realized position can be quantified in three dimensions and expressed as rotations (roll, pitch and yaw) and translations (x, y and z) [60]. Additionally, the volumetric difference between the reconstructed and unaffected or planned orbit may be assessed. Post-operative CT-scans are indicated if intra-operative CT is not acquired (or offered incomplete information), or if clinical considerations in the follow-up period necessitate additional imaging. Intraoperative imaging of the patient after implant positioning is highly recommended, since the realized implant position can be qualitatively evaluated. If the surgeon is not satisfied with the position, the implant can be repositioned in the same surgical setting, preventing a revision surgery. For a complete quantitative evaluation of the surgical result, the scan can be reconstructed and fused with the VSP. The planned position of the implant can be compared to the achieved position of the implant to enable an objective assessment (Figure 8). Differences between planned and realized position can be quantified in three dimensions and expressed as rotations (roll, pitch and yaw) and translations (x, y and z) [60]. Additionally, the volumetric difference between the reconstructed and unaffected or planned orbit may be assessed. Post-operative CT-scans are indicated if intra-operative CT is not acquired (or offered incomplete information), or if clinical considerations in the follow-up period necessitate additional imaging.

**Figure 7.** Illustration of the different feedback methods.). Markers and vectors are visualized in (**A**) and (**B**). Compelling fit of the patient-specific implant design is indicated with red arrows (**A**–**C**) Segmentation of screw holes of the previous reconstruction are illustrated in red (**D**) and the previ-

*J. Pers. Med.* **2022**, *12*, 1366 10 of 17

**Table 2.** Different feedback methods available in the operation room.

the OR. If the surgeon positions the pointer in the navigation marker on the implant, visual and quantitative feedback about the pointer's position compared to the landmark is

**Feedback Method Static/Dynamic** 

Fixation re-use Static Navigation Dynamic Markers and vectors Dynamic Intraoperative imaging Static

Virtual surgical planning Static

Compelling fit patient-specific implant Static

**Figure 8.** Illustration of an evaluation. (**A**) Three-dimensional model of the planned patient-specific implant (red) and the realized patient-specific implant (green) viewed from different perspectives. (**B**–**D**) Axial, sagittal, and coronal view of the postoperative computed tomography scan with the planned contour of the patient-specific implant in red. **Figure 8.** Illustration of an evaluation. (**A**) Three-dimensional model of the planned patient-specific implant (red) and the realized patient-specific implant (green) viewed from different perspectives. (**B**–**D**) Axial, sagittal, and coronal view of the postoperative computed tomography scan with the planned contour of the patient-specific implant in red.

An optimally positioned orbital implant is no guarantee for a perfect clinical outcome. Restoration of the globe position can be relatively well achieved with a PSI, even in secondary reconstructions [22]. It is more complex to treat diplopia, as it involves the mechanical mobility of the eye, combined visual perception, and processing in the visual cortex. Visual processing may (partially) adapt over time. At discharge, the patient is informed that double vision will be experienced for the first 10–14 days, possibly longer. Ocular motility can be improved by training the extraocular muscles to prevent scarring and anticipate fibrosis [61]. Instructions are provided to mobilize the eye as much as possible: monocular orthoptic exercises six times per day for 6–12 weeks to prevent adhesions and stimulate a reduction in orbital soft tissue swelling, especially for the extraocular muscles. This protocol positively affects clinical improvement in both primary and secondary cases [13,22,47].

#### **3. Discussion**

Surgical complexity and the fact that an inappropriate reconstruction potentially leads to an adverse outcome have led to the parallel incorporation of computer-assisted surgery and personalized medicine in the orbital reconstruction workflow. Although both concepts aim to optimize treatment outcome, their rationale differs. CAS centralizes medical technology to improve the predictability and accuracy of all treatment stages, but various steps have been standardized and can be considered independent of the patient. CAS has catalyzed the incorporation of personalized medicine in orbital reconstruction: virtual surgical planning technology enables surgical preparation, implant selection, and the simulation of the desired implant position based on the individual's characteristics. The concepts are considerably intertwined in PSI reconstruction, and mutual interactions can be discerned. Personalization of the implant design is directly affected by information gathered in the preoperative CAS stage, and tailoring the implant to the patient's anatomy provides feedback on positioning during the intraoperative stage. Intraoperative CAS technology supports the accurate positioning of the PSI, which is a prerequisite for achieving the intended treatment effect of the personalized implant. In light of this symbiosis, surgical

reconstruction with a PSI can be considered the pinnacle of both CAS and personalized medicine in orbital reconstruction.

Several larger comparative studies have demonstrated the beneficial effects of (components of) CAS on the accuracy of volumetric reconstruction [62], clinical outcome [36], and need for revision surgery [63]. In practice, a combination of several CAS building stones is often utilized. This yields heterogeneity in surgical approaches, which makes it difficult to compare outcomes between studies. Differences in indication, patient and fracture characteristics, or implant materials used further complicate comparison [64]. Isolating the effect of individual CAS techniques on patient outcome is hampered by an overlap of techniques within study populations. The individual effects of CAS techniques have been assessed in a one-to-one comparison in a cadaver series [65]. Despite limitations associated with the cadaver model and an inability to assess clinical outcome parameters, positive effects of virtual planning, intraoperative imaging, and surgical navigation on reconstruction accuracy were established.

Several indications for PSI in orbital reconstruction have been advocated, relating to defect size, location, or timing of reconstruction [22,47,49,50,66–69]. The common denominator between extensive defect size, the lack of bone support in the posterior third of the orbit, or secondary reconstruction after inadequate primary reconstruction is that the difficulty of reconstruction has been significantly increased. The possibility to perfectly tailor the shape of the implant to the patient's anatomy makes a PSI better suited for these complex reconstructions compared to implants that lack these options. Other advantages of PSIs are improved ease of use and precise, accurate fit, which leads to accurate implant positioning and a decreased surgery time [41,43,45,49,50,70–72]. Iatrogenic soft-tissue damage is prevented as much as possible since the number of try-ins necessary to correctly position the implant is reduced, and no sharp edges are present around the implant's circumference [37,72–74]. These factors lead to the high predictability of functional and aesthetic outcomes, fewer complications during or after surgery, and a lower revision rate than other implant types [37,45,54,62,67].

The list provided in Table 1 stipulates an ever-increasing armamentarium of design features to improve (ease of) positioning or alleviate clinical symptoms. The positioningrelated characteristics guarantee adequate implant support and a unique, compelling fit for the implant. It is vital to evaluate the surgical accuracy of the PSI reconstruction and the added value of the positioning features [72]. Several studies have used a comparison between unaffected and reconstructed orbital volume or angulation between the floor and medial to measure surgical accuracy [37,75–77]. These outcome parameters may conceal incorrect implant positioning. In contrast, a direct comparison between planned and acquired implant positions will reveal all surgical errors qualitatively and quantitatively [60]. Assessing individual degrees of freedom is even feasible with this approach. The evaluation phase is an indispensable component of the CAS workflow and should be performed for each orbital reconstruction. A direct comparison between planned and acquired implant positions is advocated to maximize the potential of the evaluation phase.

Incorporating clinical considerations in the design is currently not as clear as the positioning-related features. Since the early introduction of PSI reconstruction, the overcorrection of resulting orbital volume has been suggested several times, and its use has been described (see Table 1). Still, guidelines to the amount of overcorrection are arbitrary and subjective, and not substantiated by evidence. Information about the location and shape of the overcorrection is lacking. The overcorrection may even be introduced through different pathways: it may be embedded in the PSI design or added afterwards through titanium blocks [51]. While the second option provides some freedom to the surgeon intraoperatively, the judgment is subjective and hampered by the soft-tissue reaction to the surgery (and the trauma in a primary setting). Trial and error positioning leads to the increased manipulation of orbital tissue, and any dislocation of the blocks may warrant a second procedure [78,79]. Embedding overcorrection in the design is suggested to be

the best solution for achieving an optimal result [78] and could be precisely tailored to the individual patient in the future, provided the abovementioned knowledge gaps are filled.

Cost, lead time, and logistic demands are drawbacks of using a PSI [37,71,73,79]. Pricing may vary based on geography, but the process usually costs EUR 1500-6000 [57,72,80,81]. Manufacturing of the implant takes approximately 3–5 working days; this does not include sterilization, or the time needed for virtual surgical planning and design. Korn et al. described a mean communication time between the surgeon and the PSI company technician during virtual surgical planning of almost nine days for isolated wall fractures and 16 days for multi-wall fractures [82]. An adjustment to the initial design that the technician proposed was necessary in nearly three-quarters of cases, but implants from technicians with previous in-house training required fewer adjustments. Improved communication and mutual understanding are suggested to be the reasons for the efficiency improvement. Complete in-house planning and design by a dedicated, on-site technician may ameliorate planning efficiency, ultimately greatly reducing the lead time (provided the surgeon and technician are experienced and have cooperated on previous cases). In-house design is suggested to reduce costs, since commercial partners are only relied upon for fabrication [81]. These benefits of in-house design may be why surgeons who use in-house planning feel less hindered by the drawbacks of using a PSI [71].

Although this paper focuses on post-traumatic orbital reconstruction, other PSI applications relating to the orbit have also been described. In zygomatic reconstruction after trauma, ablative surgery, or congenital malformation, PSIs were found to precisely restore the anatomy without the need for additional bone grafts [83]. In secondary post-traumatic reconstruction of the orbit and zygoma, PSIs enable a one-stage surgical procedure in which the surgical order is reversed: by operating the orbit first, the functional result of the orbital reconstruction is independent of repositioning the zygomatic complex [54]. PSIs may also be used to create an artificial orbital rim and floor for globe support after maxillectomy [84,85]. The most extensive orbital PSI reconstructions have been described after the resection of a spheno-orbital meningioma or neurofibroma [55,86]. In these cases, the reconstruction of all four orbital walls with multiple PSIs enabled a predictable reconstruction of the internal orbit in the same surgical setting as the resection. The PSI design in the abovementioned cases could differ greatly from the design in the post-traumatic reconstruction of solitary orbital fractures. Still, the rationale behind using a PSI is the same: freedom of design to adapt the PSI to the patient's anatomy and a predictable and accurate final result.

#### **4. Conclusions**

An overview of the CAS workflow for post-traumatic orbital reconstruction has been presented, with an in-depth description of the techniques embedded in the workflow and a special focus on PSI. It has been demonstrated how the conventional workflow can be complemented by both CAS and personalized medicine in order to optimize the clinical outcome of post-traumatic orbital reconstruction. CAS technology has catalyzed the incorporation of personalized medicine in orbital reconstruction. The reconstruction of the orbit with a PSI can be considered the pinnacle of CAS and personalized medicine. There are no strict guidelines for the design of patient-specific implants, but several design considerations can be implemented to improve the positioning or alleviation of clinical symptoms. Because of the high predictability of aesthetic and functional outcomes, the use of PSIs has been advocated especially in difficult reconstructions. Cost, lead time, and logistical demands are known drawbacks, although they may be alleviated by inhouse design.

**Author Contributions:** Conceptualization, J.F.S., R.S., A.G.B., L.D.; literature search, J.F.S., R.S.; visualization, J.F.S., L.D.; writing—original draft preparation, J.F.S., R.S., L.D.; writing—review and editing, H.E., A.G.B. All authors have read and agreed to the published version of the manuscript.

**Funding:** Funding for this research was received by KLS Martin and Brainlab AG. None of the funding parties had any involvement in the contents or decision to submit the manuscript.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Conflicts of Interest:** The authors declare no conflict of interest.

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