INTRODUCTION

The orbits are bilateral bony cavities in the facial skeleton housing numerous canals and foramina, which form connections with other neighbouring cavities of the skull. Oftentimes, these osteological structures are used as surgical landmarks by ophthalmic surgeons to define operating margins and locate nearby vulnerable neurovascular structures [28].

The cranio-orbital foramen (COF) is an ostial opening in the lateral wall of the orbit, adjacent to the superior orbital fissure. The COF is known by different names, such as the meningo-orbital foramen, lacrimal foramen, foramen of Hyrtl, spheno-frontal foramen, sinus canal foramen, and anastomotic foramen [9, 27, 30]. The foramen is said to contain an arterial anastomosis between the orbital branch of the middle meningeal artery and the lacrimal artery [31]. Its prevalence, which has been widely discussed in the available literature and across all studies, ranges from 28% to 82.9% [9]. Moreover, the morphometrical aspects of this osseous opening have also been a topic of discussion. These parameters include the distance between the supraorbital notch/foramen and the COF [1, 5, 21]. Furthermore, many studies have reported double or even triple accessory cranio-orbital foramina in cadaveric specimens [5, 21].

Knowledge about the prevalence and morphometrical aspects of the COF may be of great importance for ophthalmic surgeons involved in orbital reconstructions, anterior skull base procedures, orbital tumour resection, and decompression surgery for thyroid eye disease [1, 12]. During deep dissection of the lateral orbital wall, unexpected haemorrhage may complicate surgery if the COF is present.

Therefore, the goal of the present study was to provide accurate data on the prevalence and morphometrical aspects of the COF, which can surely be of use by surgeons performing procedures on the lateral orbit. Furthermore, the embryology and the clinical significance of this osseous structure were thoroughly discussed.

MATERIALS AND METHODS

Search strategy

Major online medical databases such as PubMed, Scopus, Embase, Web of Science, and Google Scholar were searched to find all relevant studies regarding COF. The search was conducted in July 2022. The following search terms were used: ‘cranio-orbital’ OR ‘cranio orbital’ OR ‘meningo-orbital’ OR ‘meningo orbital’ OR ‘lacrimal foramen’ OR ‘Hyrtl foramen’ OR ‘spheno-frontal foramen’ OR ‘sinus canal foramen’ OR ‘anastomotic foramen’. The search terms were adjusted to each of the databases in order to maximise the number of results. No dates, language, article type, and/or text availability conditions were applied. Subsequently, an additional search was carried out for references from the screened studies. During this study, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. In addition, the Critical Assessment Tool for Anatomical Meta-analysis (CATAM) was used to provide the highest quality findings [7].

Eligibility assessment

The database search and the manual search identified a total of 3621 studies and were initially evaluated by two independent reviewers. After removing duplicates and irrelevant records, a total of 956 articles were qualified for full-text evaluation. To minimise potential bias and maintain an accurate statistical methodology, articles such as case reports, case series, conference reports, reviews, letters to the editors, and studies that provided incomplete or irrelevant data were excluded. The inclusion criteria involved original studies with extractable numerical data on the prevalence, morphology, and anatomical relations of the COF. Finally, a total of 25 studies were included in this meta-analysis. The AQUA Tool, which was specifically designed for anatomical meta-analyses, was used to minimise the potential bias of included studies [13]. The flow chart presenting the study inclusion process is shown in Figure 1.

Figure 1. Flow-chart presenting the inclusion process in this meta-analysis.

Data extraction

Data from qualified studies were extracted by two independent reviewers. Qualitative data, such as year of publication, country, and continent, were gathered. Quantitative data, such as sample size, numerical data regarding the prevalence of the COF, its morphology, and the distances between the COF and other anatomical structures, were gathered. Studies containing mean results but without standard deviation or interquartile range or unclear or unspecified variations were excluded. Any discrepancies between the studies identified by the two reviewers were resolved by contacting the authors of the original studies wherever possible or by consensus with a third reviewer.

Statistical analysis

To perform statistical analysis, STATISTICA version 13.1 software (StatSoft Inc., Tulsa, OK, USA), MetaXL version 5.3 software (EpiGear International Pty Ltd, Wilston, Queensland, Australia), and Comprehensive Meta-analysis version 3.0 software (Biostat Inc., Englewood, NJ, USA) were used. A random-effects model was performed in all analyses. The chi-square test and I-square statistics were used to assess heterogeneity among the studies [14]. A p-value and confidence intervals were used to determine statistical significance between studies. A p-value less than 0.05 was considered statistically significant. In the case of overlapping confidence intervals, differences were considered statistically insignificant. The statistics of squares were interpreted as follows: values of 0–40% were considered ‘may not be important’, values of 30–60% were considered ‘may indicate moderate heterogeneity’, values of 50–90% were considered ‘may indicate substantial heterogeneity’, and values of 75% to 100% were considered ‘may indicate substantial heterogeneity’.

RESULTS

Eventually, a total of 25 studies that matched the required criteria and contained complete and relevant data were included in this meta-analysis [1–3, 5, 6, 9–11, 17–24, 26, 29, 31–33, 35, 37, 38, 40]. The characteristics of each study submitted are shown in Table 1.

The pooled prevalence of COF (n = 5649) was found to be 48.37% (95% confidence interval [CI]: 41.67–55.10%). The occurrence of the COF unilaterally (n = 926) was set to be 73.92% (95% CI: 41.87–96.97%). The occurrence of the COF bilaterally (n = 926) was set at 26.08% (95% CI: 3.03–58.13%).

The pooled prevalence of COF in men (n = 1061) was found to be 50.52% (95% CI: 40.38–60.64%). The pooled prevalence of COF in women (n = 1061) was 51.91% (95% CI 28.75–74.68%). Overall, there are no statistically significant differences in the occurrence of COF between men and women (p = 0.93).

The pooled prevalence of the COF on the left side (n = 773) was found to be 51.42% (95% CI: 34.85–67.83%), as on the right side (n = 773) it was established at 47.63% (95% CI: 28.11–67.51%).

The pooled prevalence of the accessory COF (n = 257) was set to 16.72% (95% CI: 11.09–23.22%). All the results mentioned above and the more detailed ones can be found in Table 2.

The mean maximal diameter (n = 944) of the COF was set at 0.969 mm (standard error [SE] = 0.140). For more detailed results, see Table 3.

The mean distance between the COF and the frontozygomatic suture (n = 1347) was set to 26.89 mm (SE = 0.62). The mean distance between the COF and the supraorbital notch (n = 1347) was established at 34.95 mm (SE = 0.74). The mean distance between the COF and the Whitnall tubercle (n = 1347) was established to be 27.56 mm (SE = 0.62). The mean distance between the COF and the lateral angle (n = 1347) was established at 7.18 mm (SE = 0.76). For more detailed results and the analysis of distances on the sex and side of the patients, see Table 4.

DISCUSSION

Numerous anatomical studies have discussed the location, prevalence, and morphometric properties of the COF (Figs. 2–4) [1, 6, 17]. O’Brien and McDonald [31] conducted an anatomical study on the prevalence and the location of the COFs. In the study, the prevalence of this foramen was stated to be 73%. However, the location of the COF varied significantly, being found predominately where the frontosphenoidal suture had fused. This raised the question of whether the COF could create connections with the frontal rather than the middle cranial fossa. This communication was proved to exist in the aforementioned study, where 2 out of 16 specimens contained this connection. Pankaj et al. [32] reported a significantly lower prevalence of this structure (36.02%) in their cadaveric study. However, they also reported an orbit-anterior cranial fossa communication. Our results show that the COF is present in 48.37% of the cases and occurs more frequently unilaterally (73.92%), than bilaterally (26.08%). Furthermore, the location of the COF within the orbit was proven to be quite variable. The COF was located most frequently in the greater wing of the sphenoid bone (26.28%) and the orbital surface of the frontal bone (25.69%). Other intraorbital locations of the COF were within the frontosphenoidal suture (15.06%) and where the frontosphenoidal suture had fused (18.87%). Interestingly, no statistically significant differences in prevalence were observed with respect to the sex of the subject.

Figure 2. Scheme illustrating the cranio-orbital foramen and its anatomical area; A — cranio-orbital foramen; B — frontozygomatic suture; C — superior orbital fissure; D — supraorbital notch; E — inferior orbital fissure; F — Whitnall’s tubercle.

Figure 3. A photograph depicting the right orbit; A — cranio-orbital foramen; B — frontozygomatic suture; C — superior orbital fissure; D — supraorbital notch.

Figure 4. A photograph depicting the left orbit; A — cranio-orbital foramen; B — frontozygomatic suture; C — superior orbital fissure; D — supraorbital notch.

Many studies have also reported the presence of accessory COFs [9, 31, 32, 38]. The present study shows that the prevalence of any accessory COFs is 16.72%. However, Abed et al. [1] stated that these accessory cranio-orbital foramina are unlikely to be a source of significant haemorrhage because of their small calibre. However, bleeding at these locations can serve as a warning that a potential COF may be present, with a significantly larger vessel passing through it.

Georgiou and Cassell [11] presented a study about the relationship between the COF and the development of the ophthalmic artery. They described that the initial vascular supply of the orbit arises from the internal carotid artery and then by the supraorbital division of the stapedial artery, which is an embryonic artery that disappears during the 10th week in utero and is the precursor of some orbital, dural, and maxillary branches [4]. Furthermore, they describe the formation of an anastomosis between the ophthalmic artery and the supraorbital branch of the stapedial artery which forms a “ring” around the optic nerve. The stapedial artery is represented as the orbital branch of the middle meningeal artery in adulthood. It is thought that the COF represents the point at which the supraorbital division of the stapedial artery passes through the greater wing of the sphenoid bone which has not been ossified yet [1, 11].

The orbital branch of the middle meningeal artery (OB) enters the orbit through the superior orbital fissure or the COF and it forms an anastomosis with the lacrimal artery [8]. The anatomic features of the COF and the course of the OB were thoroughly described by Erturk et al. [9] in a cadaveric study. In the study, the OB was most frequently observed to pass through the COF (43.2%). However, the vessel was also running through the superior orbital fissure in 16.2% of the cases. Shimada et al. [36] presented similar results, with the OB coursing most commonly through the COF rather than the superior orbital fissure. This vessel is said to contribute to the arterial supply of the anterior part of the dura of the middle cranial fossa and form anastomoses between the ophthalmic artery and middle meningeal artery. Furthermore, Stiernberg et al. [39] and Price et al. [34] showed that the aforementioned branch might provide accessory blood supply to the orbital contents. Therefore, great care has to be taken by the surgeon performing reconstructions of the anterior base of the skull and the orbit because the OB can get damaged and a large part of the blood supply to the orbital contents may be lost [9].

In order to provide an effective method for surgeons to localize the COF, morphometric values from the frontozygomatic suture and the supraorbital notch to the foramen have been measured and reported by previous studies [1, 15, 25]. The results of the present meta-analysis show that the average distance between the COF and the frontozygomatic suture and the supraorbital notch is 26.89 mm and 34.95 mm, respectively. McQueen et al. [25] presented a method of defining a safe operating zone with respect to the COF, where the shortest aforementioned measurements were subtracted by 5 mm. When using this method and taking advantage of the frontozygomatic suture and the supraorbital notch as surgical landmarks, operating beyond a distance of 29.95 mm and 21.89 mm from the COF, respectively, may increase the risk of damaging the contents of the foramen [1].

Other landmarks may also be used by the ophthalmic surgeon in order to establish a safe zone for the COF. These include the Whitnall’s tubercle and the lateral angle, and the mean distance between these landmarks and the COF was set as 27.56 mm and 7.18 mm, respectively. All of the aforementioned measurements give the ophthalmic surgeon flexibility in choosing the technique of locating the COF in the orbit.

Limitations of the study

This study is not without limitations. It may be burdened with potential bias, as the results of this meta-analysis are limited by the accuracy of the studies submitted. The authors of the present study were unable to perform some of the morphological analyses due to the lack of consistent data in the literature. Additionally, most of the evaluated studies come from Asia, therefore, the results of this study may be burdened, as they may reflect the anatomical features of Asian people rather than the global population.

CONCLUSIONS

In conclusion, we believe that this is the most accurate and up-to-date study regarding the anatomy of the COF. The COF is prevalent in 48.37% of the cases, and it is most frequently unilateral (73.92%). Furthermore, the prevalence of accessory COFs was found to be 16.72%. The presence of these foramina may represent a source of haemorrhage that ophthalmic surgeons should be aware of when performing procedures in the lateral part of the orbit.

Acknowledgements

The authors are indebted to Mr. Jacenty Urbaniak for the technical support. “The authors sincerely thank those who donated their bodies to science so that anatomical research could be performed. Results from such research can potentially increase mankind’s overall knowledge that can then improve patient care. Therefore, these donors and their families deserve our highest gratitude” [16].

Conflict of interest: None declared