Unlike other sensitive neural pathways such as smell, touch or hearing, which use a single neuronal relay to send the signal directly to the central structures, the visual path requires two further steps to connect to the cortex (three synaptic relays) [5]. The first three neurons are found in the retina, the fourth relay is at the lateral geniculate body and projects to the primary visual cortex (calcarine cortex) in the occipital lobe. In both, the lateral geniculate body and the calcarine cortex, retinal distribution of the stimuli is preserved with high accuracy, creating a retinotopic map that allows the visual information of both eyes to be integrated [6].

The retina is a light-sensitive layered tissue that coats the eyeball-inner-posterior surface. It originates from the embryonic diencephalon and contains different kinds of neurons: photoreceptors (cones and rods), ganglion, bipolar, amacrine and horizontal neurons. It also contains neuroglia, such as Müller’s (radial glial) cells, astrocytes, and microglia. Müller’s cells contribute to the formation of inner and outer retinal limiting barriers, and, during embryonic development, they guide the cellular stratification of the retina [7]. Astrocytes provide metabolic support to the other retinal components, regulate blood flow in the optic nerve and are major contributors to the blood-retinal barrier. Microglia participate in the local innate immune response [8].

Three of the retinal layers are made up of somas from retinal cells (ganglion cell layer, inner nuclear layer, and outer nuclear layer) and two layers are made up of the synapses between these cells (inner and outer plexiform layers) [7]. Light passes through the five inner layers to reach and stimulate the photoreceptors (outer nuclear layer). The average human retina is comprised of 92 million rods and 4.6 million cones. Rods are responsible for dim-light vision because they can detect single-photons [9], while cones are for colour vision due to a better sensitivity to red, green and blue colours [7]. Pigmentary epithelium and choroid are beyond the cytoplasmic projections of photoreceptors (Fig. 1) [5].

The retina varies in structure in different regions. The macula is a specialized area, 5-6mm in diameter, located on the temporal side. In this area, the stratum of ganglion cells has several layers of thickness. The fovea, (within the macula,) a small depression in the surface of approximately 1–1.5 mm, specializes in high-definition visual acuity. While rods are more abundant in the periphery of the retina, cones are particularly plentiful in the macula, specifically in the fovea, which contributes to increased visual acuity [10].

The optic nerve is the first segment of the optic tract running from the eyeball to the optic chiasm (Fig. 2). Each optic nerve is composed of around 0.8–1.2 millions of axons from ganglion cells, a number which decreases with age [11]. The axons originate from both the medial (nasal) portion and the lateral (temporal) portion of the retina to form each optic nerve [1)], and are then fused together to form the optic chiasm [12][13].

The optic chiasm is the anatomical structure where fibres from both nasal parts of the retina intersect and are joined to the temporal tracts. The number of fibres which cross is greater than those which do not; this is vital for binocular vision as chiasmal decussation combines information from the halves of each retina of the same visual field [13].

From the optic chiasm, the axons continue through the optic tract, but a specific type of retinal ganglion cell axon, which characteristically contain a photo-sensitive pigment called melanopsin, leave the chiasm and project toward the suprachiasmatic nucleus [14]. This establishes the retinohypothalamic pathway (Fig. 2) which contributes to controlling the circadian cycle [15].

Following chiasmatic decussation, the set of axons which comes from the ipsilateral temporal retina and the contralateral nasal retina compose each optic tract. Their primary target is the thalamus, where they establish a synaptic relay and then move on to the visual cortex or other central structures [6].

A small number of fibres are sent towards the dorsal midbrain and synapse with neurons in the superior colliculi, relevant for eye and head movements (saccade) in response to visual stimuli [16]. Another set of fibres project to the pretectal area to innervate the pretectal olivary nucleus (Fig. 2 and 3) that send axons to both Edinger-Westphal nuclei. Parasympathetic neuronal relays are then directed to the ciliary ganglion and innervate the ciliary muscle, integrating the circuit for light reflex in both pupils [17].

The main target of the optic tract in the posterior thalamus is the lateral geniculate body, a six-layered structure localized lateral and caudal to the pulvinar, which comprises the first relay between retinal cells and the cerebral cortex [18]. The fourth-order neurons from each lateral geniculate body project ipsilaterally to the primary visual cortex (Brodmann area 17 or striate cortex) of the occipital lobe forming the geniculocalcarine tract [6][19].

Based on microsurgical anatomical studies [19][20] and in diffusion tensor imaging technology [6], the trajectory and anatomical relationships of optical radiations have been detailed. Three bundles have been described in this tract (Fig. 2 and 3): anterior, central and posterior [6]. The anterior bundle carries visual information from the lower retina (lower contralateral visual quadrant), runs through the temporal lobe (Meyer´s loop) and terminates at the lingual gyrus. The posterior bundle represents the superior retina (upper contralateral visual quadrant), goes through the parietal lobe, and ends at the cuneus gyrus. The central bundle transmits macular information [6, 19, 20].

According to Bernstein et al. (2016), the optic nerve is 43 to 47 mm long from globe to chiasm [21]. For its study, it is divided into four segments (Fig. 4a and 4b): intraocular, intraorbital, intra-canalicular, and intracranial [22].

Also known as the optic disc or optic nerve head, it is located inside the sclera and measures 0.91–2.91 mm long at its largest diameter, with the horizontal diameter usually smaller than the vertical [23]. The chorioscleral canal, shaped like a cone and found at the level of Bruch’s membrane, determines the shape and dimension of the vertical diameter, which generally measures 1.5–1.9 mm [1][23]. Four regions, front to back, can be identified in this portion (Fig. 4a): 1) superficial nerve fibre layer; 2) prelaminar region; 3) lamina cribrosa region; and 4) retrolaminar region [24].

The most anterior region is the superficial nerve fibre layer, composed mainly of ganglion cell axons, and separated from the vitreous by the (Elsching’s) inner limiting membrane, which in turn is continuous with the inner limiting barrier of the retina. The prelaminar region behind the latter is composed of astrocytes and a superficial capillary network as well as tributaries of the retinal vessels immersed in supporting connective tissue, maintaining the viability of this first segment of the nerve [24][25]. The prelaminar region is where pathological changes such as optic disc ooedema, glaucoma or anterior ischemic optic neuropathy can be detected [1].

The lamina cribrosa region, known as the scleral segment, has fibres similar to those in the prelaminar region, surrounded by concentric connective tissue fibres (elastin and collagen) forming pores through which the nerve fibres pass [26]. In the retrolaminar region, axons follow a parallel course to each other and are surrounded by astrocytic processes [24][25]. The presence of oligodendrocytes documented in this layer coincides with the onset of the myelinated portion of the nerve, 400 to 500 um beyond the laminar region limit [27]. Intraretinal myelination of ganglion cell axons is present in 1% of the human population [28].

The retinal vascular supply comes from the retinal artery. The retinal and choroid circulation supply the prelaminar region; the laminar region is supplied by the posterior ciliary short arteries (branches of the ophthalmic artery) and the retrolaminar region by the pial arteries (Fig. 4c). Its venous drainage is provided by the central vein of the retina [29].

This segment constitutes the area from the eyeball to the optical canal, with an approximate length of 25–30 mm and a larger diameter than the intraocular (3 to 4 mm) because of the myelin [1]. From the retrolaminar region, once it emerges from the eyeball, it is coated by the typical meningeal layers: the pia mater and arachnoid membranes continuations of the choroid; and by the dura mater from the connective tissue of the sclera (Fig. 4b). A subarachnoid space is therefore generated which continues to the intracranial segment and central structures. This anatomical condition explains optic disc oedema as a consequence of intracranial hypertension [30].

This segment is in relation with the muscles of the orbit initially separated by fat but as it approaches the entry point into the optic canal, its sheath binds to the tendon fibres of the upper oblique, medial straight and upper rectus muscles. The ciliary ganglion is found between the rectus lateralis muscle and the lateral wall of the optic nerve [31]. In this portion, the optic nerve is medial to the annular tendon and below the elevator muscles of the eyelid and superior rectus muscles (Fig. 4b). The surrounding dura mater of the optic nerve is attached to the annular tendon [31].

In this segment, irrigation is dependent on the ophthalmic artery (Fig. 4c and 4d). Anatomical studies report that in 75% of specimens its origin is in the anteromedial or superomedial faces of the supraclinoid segment of the internal carotid artery (Fig. 4d and 4e) [30][32][33]. Other reported origins are in the intradural segment [34], the middle meningeal artery [35] and even the anterior cerebral artery [35]. The optic canal is the entrance site of the ophthalmic artery to the cranial cavity (Fig. 4f), usually inferolateral in relation to the optic nerve [36, 37]. On its intraorbital trajectory, the artery travels immersed in the dural covering of the optic nerve usually on its inferolateral edge for the first third of the path to the eyeball (Fig. 4d). It is then angulated to cross either over (in 83% of cases) or under (17%) the optic nerve, adjacent to the superior rectus muscle (Fig. 4e), as observed by S.S. Hayreh in 61 specimens [36]. The final segment runs medial to the optic nerve to finish at the superomedial angle of the orbit (Fig. 4b) [38].

The ophthalmic artery branches to the central retinal artery or, less commonly, can arise from the posterior ciliary or a muscular branch [39]. This artery penetrates the dural sheath and the nerve inferomedially (mainly) or inferolaterally, approximately 11 mm from the sclera, to run centrally through the nerve, along with the central vein until reaching the retina [39]. The ophthalmic artery also gives rise to short and long ciliary arteries that emit multiple small branches that penetrate the nerve and form the pial plexus, which is in turn anastomosed by branches of the central artery of the retina to irrigate the intraorbital segment of the optic nerve (Fig. 4b and 4c). The ciliary arteries also irrigate the structures of the eyeball [40].

This corresponds to the segment that runs through the optic canal (Fig. 4b), with an approximate length of 5 to 10 mm, and is attached to the Zinn’s ring making it the segment that is most susceptible to compression [41]. On its canalicular pathway, the nerve is covered medially by a small layer of bone in relation to the sphenoidal recess and ethmoid cells, and between these are sphenoethmoid or Onodi cells [41][42]. According to K. Fujii et al., 4% of the population does not have this layer of bone, so the nerve is in direct contact with the sphenoidal sinus and 8% of the population has no bone covering of the carotid artery in the sphenoidal sinus [43]. Due to its trajectory, an impression is made on the sphenoidal sinus and, depending on the protuberance, it can be divided into four types: type 1 nerves course adjacent to the sphenoid sinus with no indentation of the wall; type 2 nerves course adjacent to the sphenoidal sinus, causing indentation of the sinus wall; type 3 nerves course through the sphenoid sinus; type 4 nerves course immediately adjacent to the sphenoidal sinus and the posterior ethmoidal air cell. These variants are also called non-impression, impression, semi-canal and canal, respectively [44].

The optic canal is composed of four walls (Fig. 4f): 1) The optical abutment or the posterior root of the sphenoid (inferior wall); 2) the body of the sphenoid (medial wall); 3) the anterior or superior root of the lesser sphenoid wing (superior wall); and 4) the anterior clinoid process (lateral wall) [42]. If a straight line is drawn from the frontozygomatic suture in the medial direction, the optical canal is at approximately 13 mm [37].

With a width of 4 to 5mm and a length of approximately 10mm, the canal becomes thinner as it approaches the eyeball, although the subarachnoid space surrounding the intracranial segment of the optic nerve is continuous with the intracranial portion [37]. Once in the optical canal, the dura mater fuses to form the periorbital connective tissue [37][41][45]. It is in the optic canal where the optic nerve is closely related to the ophthalmic artery, from which it receives its major irrigation, found in an inferolateral situation going to inferomedial in the next segment [37].

This segment is only 10mm long [46]; the nerve rests on the sellar diaphragm, and more dorsally is in relation to the cavernous sinus, covered only by the pia mater in all its trajectory at this level up to the entry of the optic canal [1][40]. The irrigation of this segment is provided by branches of the anterior cerebral artery, internal carotid artery, and anterior communicating artery (Fig. 5a and 5b) [40].

At the opening of the optic canal, there is a fold of dura mater known as the falciform process which lies over it, covering it by several millimetres medially following the anterior clinoid processes [37][45]. As each nerve emerges from the optic canal they adopt an angle of 45 degrees and, after a short path, fuse to the contralateral nerve to form the optic chiasm, taking a medial position to the internal carotid and lower frontal lobe (Fig. 5a and 5b) [12].

The optic chiasm, covered with arachnoid and pia mater has an anteroposterior diameter of 4 to 13mm, a width of 3 to 5 mm, and a transverse diameter of 4 to 13 mm [12]. The incisura of tentorium is crossed by the anterior part of the optic tract, chiasm and optic nerves [12][47].

The chiasm (Fig. 5c and 5d) is located in the suprasellar cistern, below the hypothalamus, 10mm above the pituitary gland and sellar diaphragm, in front of the pituitary stem [12]. In front of the chiasm, we find the continuation of the subarachnoid space, through which the intracranial portion continues, with third ventricle behind and above [48]. The anterior cerebral artery and the anterior communicating artery run above the optic chiasm [40].

Although uncommon, there are anatomical variants where the intracranial portion of the optic nerve may be so long or so short that the chiasm is not found in relation to the sellar diaphragm or the pituitary gland [49]. The two variants are: prefixed (Fig. 5d) which lays more anteriorly in relation to the tuberculum sellae, and postfixed (Fig. 5c) found over the dorsum sellae [12, 48]. The importance of identifying them is that a prefixed chiasm or a protruding tuberculum will limit access to the sellar and suprasellar region in a transcranial approach [31][47].

Depending on the segment to be approached, we suggest an algorithm to choose the most suitable and effective surgical approach for the optic nerve (Fig. 6). For the intraorbital segment, the orbital bones are taken as reference, dividing the nerve in a lower, upper, lateral, and medial face. The lesions that most commonly affect this area and are surgically treatable are neoplasms derived from glia and the optic nerve sheath [31]. The intracanalicular segment is, as explained before, the site of surgical decompression, with either an extracranial or transcranial approach [50]. There are several open extracranial approaches as well as minimally invasive endoscopic ones, but these only release the Zinn’s ring and not the falciform ligament. This only being possible via a transcranial approach as required in trauma or tumours [42]. Finally, in the intracranial segment affected by tumoral lesions such as sellar or clinoid tubercular meningiomas, a working angle for removal of the lesion allowing decompression of the respective nerves or infiltrated ones is required [51].

When a surgery which involves the optic nerve is planned, the surgeon must have knowledge of both the functional and microsurgical anatomy to preserve the important neurovascular structures surrounding the nerve. While it is true that most postoperative complications are resolved without sequelae, others involving the vascular structures can result in significant visual loss, forever changing the lifestyle of the patient. Therefore, surgical approaches to the optic nerve use intracranial and extracranial nerve location as criteria to consider the structures we must manipulate in each segment. Understanding and using this knowledge provides the foundation to choose and perform successful neurosurgical approaches without increasing such morbility.

AUTHOR CONTRIBUTIONS

R. López-Elizalde: project development, cadaveric dissection and photography, manuscript writing. M. Godínez-Rubí: project development, manuscript writing, photography. Y. Lemus-Rodríguez: project development, literature search, manuscript writing. E. Mercado-Rojas: literature search, manuscript writing.T. Sánchez-Delgadillo: literature search, manuscript writing. D. Sánchez-Delgadillo: literature search, manuscript writing. Á. Campero: cadaveric dissection, critical review of the manuscript. R.G. Párraga: cadaveric dissection. All authors participated in the discussion and editing of the work. All authors approved the final version of the publication.

Conflict of interests. The authors declare that there is no conflict of interests.

Financial support. The study was not sponsored (own resources).

Acknowledgments. The authors gratefully acknowledge those who donated their bodies to medical research and their families. The authors also thank Carlos Alberto García for the significant contributions made to this work through his illustrations. Author MGR acknowledges the support of the University of Guadalajara and the PRODEP program (Programa para el Desarrollo Profesional Docente, para el Tipo Superior)1.

1. Programa para el Desarrollo Profesional Docente (PRODEP): https://dgesui.ses.sep.gob.mx/programas/programa-para-el-desarrollo-profesional-docente-para-el-tipo-superior-prodep