Anatomy of the optic nerve based on cadaveric dissections and its neurosurgical approaches: a comprehensive review

Vision is a complex sense that is widely represented in the cortex and involves multiple pathways that can be affected by conditions amenable to surgical treatment. From a neurosurgical point of view, the treatment of major lesions affecting the optic nerve, such as tumours, intracranial hypertension, trauma and aneurysms, can be approached depending on the segment to be worked on and the surrounding structures to be manipulated. Therefore, surgical manipulation of the visual pathway requires a detailed knowledge of functional neuroanatomy. The aim of this review is to present the functional and microsurgical anatomy of the second cranial nerve, through illustrations and cadaveric dissections, to support the choice of the best surgical approach and avoid iatrogenic injuries. For this purpose, a literature search was performed using the PubMed database. Additionally, cadaveric dissections were performed on adult cadaver heads fixed with formaldehyde and injected with coloured silicone.


HIGHLIGHTS КЛЮЧЕВЫЕ ПОЛОЖЕНИЯ
The optic nerve is an extension of the telencephalon in the form of tracts.
Iatrogenic optic nerve damage in neurosurgical procedures is avoidable with accurate knowledge of neuroanatomy.
Damage of the neurovascular structures surrounding the optic nerve can result in significant visual loss.
Cadaveric dissections are an invaluable tool for gaining knowledge of neurosurgical anatomy.
Ignorance of the anatomical variants of the optic nerve can lead to errors during the neurosurgical procedure.
The choice of neurosurgical approach depends on the segment of the optic nerve to be approached.
The vision is a complex sense that has a broad representation in the cortex. The optic nerve, like the olfactory nerve, is not a true peripheral nerve but an extension of the telencephalon in the form of tracts [1,2]. From a neurosurgical perspective, the leading lesions that affect the optic nerve and are susceptible to surgical treatment are tumours, intracranial hypertension, traumatic brain injury, hematomas and aneurysms [3]. A detailed knowledge of the microsurgical anatomy of this nerve and neighbouring structures in cadaveric models contributes to the success of surgical treatments and avoids post-operative visual deficits, by minimizing the risk of a direct surgical injury [4]. Below we present a brief review of the functional anatomy of the visual pathway, and a description of the surgical anatomy of the optic nerve, based on cadaveric dissections and histologic sections.

FUNCTIONAL ANATOMY OF THE OPTICAL PATHWAY
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].
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].

Optic nerve and chiasm
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].

Optic tract, lateral geniculate body, and optic radiations
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 FIG. 3. Sagittal view (a) and basal surface (b) of a white matter fibres dissection of the optic radiations. a. The fibres emerge from the thalamus lateral geniculate body laterally coursing in the roof of the temporal horn towards the primary visual cortex passing laterally to the atrium. b. Optic radiation fibres from the lower part of the geniculate body loop forward and downward, forming the Meyer's loop, then turn back to join the central and posterior groups until they reach the calcarine fissure. РИС. 3. Сагиттальный вид (а) и базальная поверхность (b) диссекции волокон белого вещества зрительной лучистости. a. Волокна выходят из латерального коленчатого тела таламуса латерально, идут в крыше височного рога к первичной зрительной коре, проходя латерально к предсердию. b. Волокна зрительной лучистости из нижней части коленчатого тела направляются вперед и вниз, образуя петлю Мейера, затем поворачивают назад, чтобы присоединиться к центральной и задней группам волокон, пока не достигнут калькариновой щели.  b. Sagittal view of the optic nerve in cadaveric dissection. The lateral and superior rectus muscles have been retracted and the periorbital fat removed to expose the intra-orbital, intracanalicular, and the first portion of the intracranial segments. Anatomical relationships of the optic nerve with neighbouring structures such as blood vessels and muscle are shown. The anterior clinoid has been partially removed and the annular tendon opened so that the origin of the ophthalmic artery from the internal carotid artery and its intra-orbital pathway can be seen, but the intracanalicular segment remains hidden as its short longitude is covered with the annular tendon surrounding the orbital end of the optic foramen. c. Schematic illustration of the vascular supply of the optic nerve and structures of the eye. d. Unroofed optic canal to show the intracanalicular segment of the optic nerve without the optic sheath to reflect it upwards and uncover the intradural type of the ophthalmic artery. e. Schematic illustration of the ophthalmic artery classification: intradural type (a), extradural supraoptic strut type (b) and extradural transoptic strut type (c). f. Upper view of the osseous relationships of the sphenoid bone and its foramens, including the optic canal. РИС. 4. Микрохирургическая анатомия внутриглазного, интраорбитального и интраканального сегментов зрительного нерва. 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].

MICROSURGICAL ANATOMY OF THE OPTIC NERVE
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].

Intraocular segment
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].

Intraorbital segment
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].

Intracanalicular segment
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].

Intracranial segment
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]. b. Sagittal view of the sellar region, suprasellar area and third ventricle. Above the sella the infundibulum and optic chiasma, and between the later and the lamina terminalis we find the suprachiasmatic recess of the third ventricle. c. Postfixed variation of the optic chiasma on a subfrontal approach. d. Normal variation of the optic chiasma on a pterional approach. РИС. 5. Внутричерепная траектория зрительного нерва. a. Корональный срез с видом на гипофиз и расположенные ниже зрительные нервы и хиазму. Глазная артерия проходит в дуральной оболочке зрительного нерва по его нижнему краю. b. Сагиттальный вид селлярной области, надселлярной области и третьего желудочка. Над турецким седлом находятся воронка гипофиза и зрительный перекрест, а между ними и терминальная пластинка -супрахиазматическое углубление третьего желудочка. c. Постфиксированная вариация зрительного перекреста при субфронтальном доступе. d. Нормальная вариация зрительного перекреста при птериональном доступе. 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].

Optic chiasm
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].
Note: OBZ -orbitozygomatic. Примечанме: ОЗД -орбитозигоматический доступ. 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].

NEUROSURGICAL APPROACHES TO THE OPTIC NERVE
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].

CONCLUSION
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.