Cerebrovascular disease comprises conditions that affect the blood flow and the blood vessels of the brain. Pathologies that affect blood flow include narrowing of the blood vessels (stenosis), clot formation (thrombosis), blockage (embolism), ballooning and weakening of the arterial wall (aneurysms), cerebral arteriovenous fistula (AVF), transient ischemic attack (TIA), and arteriovenous malformations (AVM). In this review, various ophthalmology-related cerebral arterial circulation diseases are explained in detail, along with detailed 3D images.
The circle of Willis [Figure 1] is a ring of vessels that provides important colligative communications between the anterior and posterior circulations of the midbrain and hindbrain. It is named after Thomas Willis (1621–1675), an English physician. The circle of Willis plays an important role in defending against ischemia, by providing collateral arterial flow to the affected brain regions.[2,3,4]
Cerebral arterial circulation comprising the circle of Willis includes the following:
Anterior circulation is comprised of bilateral anterior cerebral artery (ACA), which is linked by the anterior communicating artery (AComA).
The posterior communicating artery (PComA) links the medial cerebral artery (MCA) with the posterior cerebral artery (PCA), to form the posterior-most aspect of the circle of Willis. Posterior circulation comprises the basilar artery (BA), superior cerebellar arteries, pontine arteries, anterior inferior cerebellar artery (AICA), bilateral vertebral artery (VA), posterior inferior cerebellar artery (PICA) and anterior spinal artery.
Anterior communicating artery aneurysms
The AComA aneurysms are the most common form of circle of Willis aneurysms accounting for about 25–38% of the total cerebral aneurysm cases. It can lead to visual field defects, visual deterioration and frontal lobe pathologies.[5,6,7]
AComA aneurysms generally cause visual symptoms based on the following three categories:
- Aneurysm causing bleeding in the fundus
- Aneurysm compressing the optic pathway
- Aneurysm causing poor blood circulation to the optic pathway.
Though the mechanism of post-rupture bleeding into the eyeball has not been fully explained, the most convincing mechanism is due to the sudden increase in venous pressure with the blockage of venous flow to the eyeball caused by increased intracranial pressure; small veins are ruptured and as a result, cause haemorrhage in the subhyaloid region and vitreous body [Figure 2].[8,9,10] Usually, patients presenting with sudden headache, mental changes and loss of light reflex show a bleeding tendency in the fundus. It can also manifest as Terson's syndrome, where visual symptoms are generated by intraglobe haemorrhage due to ruptured AComA aneurysm.
AComA aneurysms are more likely to rupture due to their anatomical and haemodynamic characteristics.[11,12] When the aneurysm is ruptured, the pressure from arterial blood flow is suspected to damage the optic nerve, as much as the presence of a hematoma compressing the optic nerve, which may cause visual symptoms. As the subarachnoid space is empty, haematoma which builds around the ruptured intracranial aneurysm may constrict the optic pathway. In cases where there is adhesion to the surrounding brain tissues caused by a small amount of primary bleeding, when re-bleeding occurs, a localized haematoma may form and can cause significant compression of the optic nerve.[13,14,15]
Generally, AComA aneurysms tend to rupture even when they are relatively small leading to visual symptoms. Hence, the presence of large AComA aneurysms are extremely rare. An unruptured giant aneurysm with headache and visual loss will always require a differential diagnosis of pituitary adenoma or meningioma that are often suspected in this area. Large intracranial aneurysms with visual impairment can be differentiated from a brain tumour by their pattern of improvement, which is repetitive and cyclic, along with the deterioration of symptoms and by performing cerebral angiography.
In the case of a giant intracranial aneurysm, visual symptoms [Figure 3] may be noticed unilaterally, such as a unilateral scotoma or blindness due to the pressure on the optic nerve. Bitemporal hemianopia can be caused by the pressure on the optic chiasma, or homonymous hemianopia can be caused due to compression on the optic tract due to the pressure from the aneurysm.[9,16,17] If the aneurysm increases in size, such symptoms can consistently progress with multiple cycles of improvement and deterioration. These multiple episodes are explained by the development and expansion of the thrombus in the intracranial aneurysm.
Visual symptoms due to poor blood circulation can be caused by large intracranial aneurysms by compressing the optic pathway as well as resulting from the pressure building upon the vessels running to the nerve as well. Haematoma may constrict microvessels in and around the optic pathway and leading to poor blood circulation. Visual symptoms due to poor blood circulation also can be developed by vasospasm following subarachnoid haemorrhage (SAH). Poor blood circulation due to vasospasm causes unilateral visual symptoms; this can help rule out the chance of a haematoma or cerebral aneurysm.[19,20,21,22,23]
Gold standard modalities for investigations are magnetic resonance angiography (MRA), computed tomography angiography (CTA), lumbar puncture (LP) and cerebral angiography.
- Treatment of the cerebral aneurysm causing visual symptoms is done by clipping the base of the aneurysm with a specially designed clip and removing the aneurysm sac or haematoma which may compress the optic pathway. In order not to damage the nerve, particular care must be taken during surgery.
- In most cases, clipping operation has shown good prognosis, even with poor fundus findings in the patients. Observation for up to two years is mandatory after clipping surgery.
- Recently, coiling of aneurysms are commonly considered, as they improve patients' visual symptoms by reducing thrombus size.[24,25,26]
Posterior communicating artery aneurysm
The PComA is the second most common location of intracranial aneurysm, approximately 25%. Aneurysms of the PComA are the third most common circle of Willis aneurysms and can cause oculomotor nerve palsy [Figure 4].[5,28] On emerging from the midbrain, the oculomotor nerve lies in the subarachnoid space, where it passes between the superior cerebral artery and PComA, and goes forward in the interpeduncular cistern along the lateral aspect of the PComA. Hence, oculomotor nerves are more prone to damage from PComA aneurysms.
The PComA aneurysm causes oculomotor nerve (third cranial nerve) palsy either by direct mass effect or by its rupture, leading to SAH-induced nerve irritation. The long-standing mass effect can cause ischemia leading to subsequent scarring associated with fibrosis. Similarly, in SAH there might be intraneural blood extravasation leading to intraneural fibrosis. An acute palsy of the third nerve involving the pupil is highly suspicious of an unstable aneurysm.
The patient presents with signs of ipsilateral ptosis, mydriasis with impaired light reflex, and ophthalmoplegia with the eye rotated outwards and downwards. The patient may either have partial or complete III nerve palsy.
In cases of complete III nerve palsy, the signs present in the following order:
- Pupillary dilatation [Figure 5a]
- Drooping of the eyelid [Figure 5b]
- Deficit of superior, inferior and medial recti muscles [Figure 6].
In the case of partial III nerve palsy, the patient will present with symptoms of partial drooping of eyelid with diplopia. 50–64% of patients present with sharp localized pain in the retro-orbital or forehead region preceding the palsy.[29,30,31] In long-standing cases, aberrant regeneration can occur, causing oculomotor synkinesis.
The following signs can be present in cases of aberrant regeneration.
- Pseudo-von Graefe's sign: There is retraction of the lid when the patient looks down due to innervation of the lid elevators by a few nerve fibres supplying the inferior rectus.
- Inverse Duane's syndrome: There is lid retraction on adduction of the eye as few nerve fibres supplying the medial rectus innervates the levator muscle.
- Pseudo-Argyll Robertson Pupil: Greater constriction of the pupil to convergence than to light and gaze-evoked pupillary constriction due to innervation of the sphincter pupillae by few medial rectus fibres.[32,33]
Gold standard modalities for investigations are MRA, CTA and digital subtraction angiography (DSA).
The prognosis of treatment depends on the time interval of the symptoms and management in view of intraneural fibrosis. Spontaneous recovery is a rare occurrence. Treatment modalities include surgical clipping via pterional approach and endovascular embolization with coil packing.[35,36] The minipterional approach, which is a modified approach, is more advantageous for the clipping of aneurysms.
Terson's syndrome (TS) is defined as the occurrence of intraocular haemorrhage, manifesting as subhyaloid, vitreous, intraretinal or subretinal bleeding, which typically occurs in a case of intracranial haemorrhage secondary to traumatic brain injury. Terson's syndrome was initially coined for vitreous haemorrhage associated with SAH post-trauma, but the definition has expanded since then.[37,38,39,40,41,42,43,44,45,46] A systemic review has shown the incidence of TS to be about 13%. This is a relatively underdiagnosed condition due to the nature of the disease, considering that the patient will be neurologically impaired, hindering them from voicing their complaints. Also, more urgent and primary interventions will be taking place, so an ocular examination may get deferred. A delay in diagnosis can render permanent visual damage in these conditions.
It has been recorded that patients with TS tend to have periods of raised intracranial pressure (ICP), which brings us to the three postulated theories for TS.
- An increase in ICP causes reflux of cerebrospinal fluid (CSF) or haemorrhage via the optic nerve sheath, which causes compression of the central retinal vein, obstructing the venous flow leading to rupture of smaller retinal venules.
- The acute elevation of ICP causes an increase in orbital venous pressure, hence causing a venous backflow leading to intraocular haemorrhage.
- The intraocular haemorrhages may be a direct extension of blood from the subarachnoid space via the optic nerve sheath.
The symptoms of TS primarily depend on the patient's neurological status and the location of the haemorrhage. In cases with neurological deficits, it depends on the primary physician to arrange for a prompt ophthalmic evaluation after stabilizing the patient. Those who can verbalize will report a sudden decrease in vision unilaterally or bilaterally, following an episode of severe headache or head trauma. TS usually develops within hours of the neurological event, though it can still occur after days or weeks as well.
TS is seen at higher incidence in patients who have an initially low Glasgow Coma Scale or those presenting with loss of consciousness. Fundus examination is the gold standard for diagnosing TS. Haemorrhages can be present in the vitreous, subhyaloid, intraretinal or subretinal space. When blood is present below the internal limiting membrane and posterior hyaloid, a double-ring sign is visualized. Loss of red reflex can be seen in those with dense haemorrhages. Secondary changes can include the development of macular holes, epiretinal membranes, retinal folds, proliferative vitreoretinopathy, retinal detachment and optic nerve sheath haemorrhage as early as one week after onset.
Imaging is utilized in cases of dense vitreous haemorrhage which obstructs the fundus view. B-scan ultrasonography is the imaging modality of choice. If B-scan is not possible, CT can also be done; but it has a comparatively lower sensitivity than B-scan.
The intraocular haemorrhages usually resolve within a few months. For non-resolving vitreous haemorrhages, vitrectomy will be needed. Early vitrectomy (within 3 months) has better visual outcomes. Early vitrectomy is indicated in bilateral haemorrhages, young individuals and dense haemorrhages.
Patients with TS have a notably poor prognosis. These patients were also found to have a five-time increase in their mortality rate. Thus, early detection of TS will have an impact on neurological rehabilitation efforts, along with preventing avoidable vision loss.
Posterior inferior cerebellar artery syndrome or lateral medullary syndrome
Lateral medullary syndrome (LMS) is seen in cases with vascular pathology of the lateral part of the medulla oblongata. It is also known as Wallenberg syndrome or posterior inferior cerebellar artery syndrome. Posterior circulation stroke contributes to about 20% of all ischemic strokes, and angiograms suggest that it is most probably a vertebral artery (VA) disease (67%) than a posterior inferior cerebellar artery (PICA) disease (10%). It was named after a Jewish neurologist, Adolf Wallenberg. He was the first to report LMS.
The following are the causes:
- Atherosclerotic disease leading to thromboembolism, hypertension, small vessel disease and cardiogenic embolus.
- Dissection of vertebral arteries, especially in young patients presenting as migraine.
- Individuals with Ehler–Danlos syndrome, Marfan syndrome and fibrovascular dysplasia have a risk of vertebral artery dissection.
- Hypoplastic vertebral artery in young patients.
- Moyamoya disease.
- Vertebrobasilar dolichoectasia.
- Other less common causes of ischemia with a predisposition for the posterior circulation include subclavian steal syndrome, Fabry disease, mitochondrial encephalopathy, lactic acidosis and migraines.[53,55,56,57,58,59]
The patient presents with symptoms of vertigo, dizziness, nystagmus, dysphagia, oscillopsia, ataxia, diplopia, nausea, headaches and vomiting. Signs include impairment of pain and thermal sensation over the contralateral side of the trunk and limbs, and the ipsilateral side of the face. There will be ipsilateral Horner's syndrome, ipsilateral limb ataxia, dysphagia, dysphonia, hiccups, ipsilateral hyperalgesia and rotatory nystagmus. One specific ophthalmic clinical sign of LMS is ipsipulsion. It is characterized by static eye deviation to the side of the lesion or saccadic lateropulsion where there are voluntary saccades towards the side of the lesion.
The following investigations are mandatory:
- Risk factors for stroke such as diabetes mellitus, hypertension, heart disease and history of smoking.
- Complete blood count (CBC)
- Electrocardiogram (EKG)
- Echocardiography (ECHO)
- Carotid Doppler
- Video-fluoroscopy and fibre-optic endoscopic examination for evaluating swallowing.
- Imaging: Computed tomography (CT) scan of the brain is typically done at first, but it gives suboptimal visualization of posterior fossa structures due to bony artefacts and can miss early ischemic changes. Magnetic resonance imaging (MRI) provides better visualization of the infarct. Fluid attenuation inversion recovery (FLAIR) sequences protocol is used for evaluation of the infarct. CTA and MRA provide a more precise location of the infarct.
A holistic multidisciplinary approach is the key to managing this condition.
- Patients will require intensive care unit (ICU) monitoring.
- Reperfusion is attempted by intravenous thrombolysis with IV recombinant tissue-plasminogen activator (IV-rt-PA) or by endovascular thrombectomy.
- Patient is started on antiplatelets, antihypertensives and statins.
- Enteral nutrition: Patients may need a nasogastric tube feeding.
- Dysphagia management: Dietary and/or posture changes are mandatory. If severe dysphagia is prolonged, conversion to percutaneous endoscopic gastrostomy (PEG) may be planned.
- Swallowing treatment: Swallowing musculatures are strengthened by active exercises. Botulinum toxin type-A injections have been used to treat severe dysphagia associated with trismus.
- Speech therapy assessment for hiccups: gabapentin can be used in the therapy of hiccups in cases of LMS, especially when they are persistent.
- Medullary infarction can cause autonomic abnormalities which can lead to acute heart failure. Hence, a pacemaker may be needed.
- Neurotrophic corneal ulcers can occur due to trigeminal neuropathy leading to loss of corneal sensitivity. This would require lubricating eye drops and ointments, 20% autologous serum eye drops and in extreme cases surgical interventions like punctal plugs, amniotic membrane graft or tarsorrhaphy.
- The lateral medullary syndrome can result in chronic facial pain which can be disabling. Gabapentin can be considered as therapy for those patients.
A carotid-cavernous fistula (CCF) occurs due to abnormal communication between the carotid artery and the cavernous sinus. It can be classified as direct or indirect CCF. Direct CCF is a connection between the ICA and the cavernous sinus. Indirect CCF is a connection between the cavernous sinus and one or more meningeal branches of the ICA, the external carotid artery (ECA) or both.
Classification of CCFs
In 1985, Barlow classified CCFs into four subtypes based on their vascular communications.
Type A: Communication between ICA and cavernous sinus.
Type B: Communication between dural branches of ICA and cavernous sinus.
Type C: Communication between dural branches of ECA and cavernous sinus.
Type D: Communication between dural branches of ICA and ECA to the cavernous sinus.
It can be anatomically classified as direct and indirect. It can be haemodynamically classified as high flow and low flow. Also, it can be etiologically classified as traumatic or spontaneous.
CCFs can either occur spontaneously or secondary to trauma. Traumatic CCFs can occur following closed head injury, penetrating head trauma, skull base fractures, rupture of cavernous ICA aneurysms or iatrogenically after craniotomies, endoscopic transsphenoidal sinus surgery, and endovascular procedures.[66,67,68] Traumatic CCFs contribute to the majority of the cases, and they typically correspond to Type A CCFs.
In CCFs, there is direct shunting of blood from a high-flow arterial system to a low-flow venous system without an intervening capillary bed. This leads to increased vascular pressure and resistance which hampers the venous flow, leading to congestion in the areas drained by the cavernous sinus, which in turn leads to ophthalmic manifestations especially in anterior draining CCFs.
- Type A or direct CCFs are the most common presentation, most of that is caused due to trauma. It is a high-flow variant that causes the retrograde flow of blood from the cavernous sinus into the superior ophthalmic vein (SOV) causing dilation of the SOV and other clinical signs.
- Types B, C and D are direct or indirect CCFs. These are low flow shunts that occur spontaneously in the majority of the cases. There are reported associations found with older age, female gender and hypertension. The incidence is high among pregnant women, in view of the hypercoagulable state.
Direct CCFs are acute in onset with a serious course, which often presents with the classical triad of pulsatile proptosis, conjunctival chemosis and a whooshing noise in the head. The indirect CCFs have a more gradual onset with a chronic course and typically present with engorgement of conjunctival vasculature.
- Vision loss may occur immediately after trauma due to optic nerve damage or ocular injury (in settings of trauma).
- Delayed visual loss can occur secondary to exposure keratopathy, secondary glaucoma, central retinal vein occlusion, anterior segment ischemia or ischemic optic neuropathy.
- Signs usually tend to occur ipsilateral to the fistula, but may be bilateral or sometimes even contralateral, because of midline connections between the cavernous sinuses.
- Marked epibulbar vascular dilatation is noted.
- Haemorrhagic chemosis is seen in the early stages.
- Pulsatile proptosis is associated with a bruit and thrill, which is abolished by compression of the ipsilateral carotid artery in the neck.
- Elevated episcleral venous pressure and orbital congestion lead to an increase in intraocular pressure (IOP) and rare cases of angle-closure glaucoma due to the development of the choroidal effusion secondary to partial thrombosis of the ipsilateral SOV and cavernous sinus.[72,73]
- Anterior segment ischemia may be noted, which is characterized by corneal epithelial oedema, aqueous cells and flare, and in severe cases iris atrophy, cataract and rubeosis iridis.
- Ophthalmoplegia and ptosis occur due to the oculomotor nerve damage from the initial trauma, intracavernous aneurysm or the fistula itself.
- Due to its free-floating location inside the cavernous sinus, the sixth cranial nerve is most frequently affected.
- The third and fourth nerves, situated in the lateral wall of the sinus, are less frequently involved.
- Patients can present with Horner's syndrome, commonly associated with sixth nerve palsy.
- Engorgement and swelling of extraocular muscles is another cause of ophthalmoplegia.
- Ocular fundus examination may reveal optic disc swelling, venous dilatation and intraretinal haemorrhages. Fundus changes are due to venous stasis and impaired retinal blood flow.
- Milder conjunctival injection is seen than the one seen with a direct CCF.
- Exaggerated ocular pulsations can be detected on slit lamp applanation tonometry.
- In later stages “corkscrew” epibulbar vessels can be seen.
- Bilateral raised IOP may be noted in these cases, with higher IOP on the side of the fistula.
- Proptosis and bruit if present, are mild.
- In marked cases there is swelling of extraocular muscles.
- Sixth nerve involvement may be present.
- Patient may have a normal fundus or develop moderate venous dilatation followed by tortuosity.
CT and MRI may demonstrate the prominence of the SOV and diffuse enlargement of the extraocular muscles. These structures may only be visible with a direct CCF. Orbital Doppler imaging can also be used to assess abnormal flow patterns, especially in the superior orbital vein. Definitive diagnosis may involve selective catheter DSA, especially in mild dural fistulae, though CTA and MRA can also be useful. DSA helps in identifying the location of the CCF, the flow rate, the arterial supply and the venous drainage. This helps classify the CCF and plan for endovascular management strategies.[75,76]
Asymptomatic patients, with incidentally discovered indirect CCF, can be observed and conservatively managed with routine follow-ups. Urgent intervention is required in cases of vision loss, progressive exophthalmos and paresis of extraocular muscles, bruit and intractable orbital pain.[64,77] Ocular complications may require specific measures in the form of topical medications, in addition to the treatment of the fistula itself. Even mild cases of CCF carry a high risk of stroke, so a neurologist's opinion should be sought at an early stage.
Most direct CCFs are not life-threatening; they still pose a major risk to the eye. Direct CCFs are unlikely to close spontaneously because of the high flow. Hence, the goal is to prevent this high flow into the cavernous sinus by reconstruction of the cavernous ICA. Endovascular approaches include coil embolization, coil embolization with stent assistance or balloon remodelling of the ICA.[78,79] Treatment is likely to consist of a combination of trans arterial and transvenous approaches. Occasionally, a craniotomy may be required for arterial repair.
Spontaneous closure or occluding thrombosis sometimes can occur in up to 50% of the cases. Intermittent carotid compression under specialist supervision will increase the chances of spontaneous closure. If required, treatment usually involves transvenous occlusion by catheterization of the cavernous sinus, either by the petrosal or pterygoid plexus, or via the transorbital route. Along with coil embolization, liquid embolic agents such as Onyx (ethylene vinyl alcohol copolymer, Medtronic, USA) and n-butyl cyanoacrylate glue (Trufill n-BCA, Cerenovus, USA) are used in the treatment of indirect CCFs. Radiosurgery is also an option for low-flow CCFs.[82,83]
The ocular manifestations that occur in patients with brainstem stroke due to vascular ischemia are given as followings:
- Oculomotor nerve palsy
- Trochlear nerve palsy
- Abducens nerve palsy
- Parinaud dorsal midbrain syndrome
- Skew deviation
- Horizontal gaze palsy
- Internuclear ophthalmoplegia.
OCULOMOTOR NERVE PALSY
The oculomotor nerve supplies the ipsilateral levator palpebrae superioris, medial rectus, inferior rectus, inferior oblique and contralateral superior rectus. The oculomotor nerve nuclear complex is present in the midbrain at the level of the superior colliculus, ventral to the Sylvian aqueduct. But unlike the other subnuclei, the levator subnucleus is unpaired and innervates both the levator muscles and the superior rectus subnuclei innervates the contralateral superior rectus. It supplies the pupillomotor parasympathetic fibres via the superficial layer of the nerve. Isolated third nerve palsies are rare; hence, it is important to evaluate other cranial nerves and the peripheral nervous system. Partial involvement of the third nerve will cause milder degrees of ophthalmoplegia [Figure 6] and partial ptosis. In the case of partial ptosis, when the eyelid is not covering the pupil, diplopia will be present. The eye is seen down and out in the primary position due to the unopposed action of the lateral rectus and superior oblique muscle. Normal abduction is present as the lateral rectus is intact. Limited adduction is noted due to medial rectus weakness. The limited elevation is observed due to the paresis of the superior rectus and inferior oblique muscles. It is also mandatory to examine the other cranial nerves and peripheral nervous system in these clinical scenarios.
There are various neurological manifestations depending on the location of the lesion. They are as follows:
- Nothnagel syndrome: Lesion at the level of superior cerebellar peduncle will produce ipsilateral third nerve palsy and cerebellar ataxia.
- Benedikt syndrome: Lesions at the level of the red nucleus will produce ipsilateral third nerve palsy and contralateral extrapyramidal signs.
- Weber syndrome: Lesion at the level of cerebral peduncle will produce ipsilateral third nerve palsy and contralateral hemiplegia.
- Claude syndrome: It is a combination of Nothnagel and Benedikt syndromes.
TROCHLEAR NERVE PALSY
The fourth nerve nucleus is present in the midbrain. In the midbrain, the nucleus is situated at the level of the inferior colliculus ventral to the Sylvian aqueduct. The contralateral superior oblique muscle is supplied by the fourth nerve nucleus. It has the longest intracranial course; it is the only cranial nerve to exit the brainstem in the dorsal aspect.
Common clinical manifestations include binocular diplopia which is vertical or torsional. The diplopia worsens on the downward and inward movements of the affected eye [Figure 7]. Patients may develop a head tilt and face turn to the opposite side to compensate for diplopia. The affected eye is in a misaligned position (hypertropia [Figure 8a] with excyclotorsion).
Parks–Bielschowsky three-step test [Figure 8] has been proposed to identify superior oblique palsy in such patients.
ABDUCENS NERVE PALSY
The sixth nerve nucleus is present at the midlevel of the pons, ventral to the floor of the fourth ventricle and in close relation to the facial nerve.
Abduction is restricted on the affected side leading to horizontal diplopia [Figure 9]. Esotropia is present due to the unopposed action of the medial rectus [Figure 9f]. A compensatory face turn will be adapted by the patient towards the side of paralyzed muscle.
Various neurological manifestations can occur depending on the location of the lesion. They are as follows:
- Foville syndrome: Lesion at the level of inferior medial aspect of the pons will involve the ipsilateral fifth, sixth, seventh and eighth cranial nerves, the central sympathetic fibres and the paramedian pontine reticular formation (PPRF). The patient will present with an inability to abduct the ipsilateral eye, horizontal gaze palsy towards the affected side, ipsilateral lower motor neuron (LMN) facial palsy, ipsilateral sensorineural hearing loss and ipsilateral loss of facial sensations [Figure 10a]. Sympathetic involvement will lead to Horner's syndrome.
- Millard–Gubler syndrome: Lesion is at the level of the ventral pons involving the fasciculus as it passes through the pyramidal tract. The patient will have ipsilateral sixth nerve palsy, contralateral hemiplegia and ipsilateral LMN facial palsy [Figure 10b].
- Raymond syndrome: Lesion is at the level of ventral medial pons. It can present as two subtypes (classical and common). Patients with classical subtype of Raymond syndrome present with clinical features of ipsilateral sixth nerve palsy, contralateral central facial paresis and contralateral hemiparesis. The common subtype presents with clinical features of ipsilateral lateral gaze paresis and contralateral hemiparesis [Figure 10c].
PARINAUD DORSAL MIDBRAIN SYNDROME
It was first described by a French ophthalmologist, Henri Parinaud in the late 1800s. It is caused by lesions involving the dorsal midbrain.
The clinical triad of dorsal midbrain syndrome is light-near dissociation, convergence retraction nystagmus and supranuclear upgaze palsy. Upgaze palsy occurs due to the damage to the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), the interstitial nucleus of Cajal (INC) and its connections [Figure 11]. Convergence retraction nystagmus occurs due to damage to the midbrain supranuclear fibres [Figure 12a] which have an inhibitory effect on the midbrain convergence neurons or divergence neurons. It is characterized by irregular, jerky nystagmus, associated with convergence, and retraction of both eyes on attempted upgaze. There is a poor pupillary reaction to light, but the pupil constricts with convergence. Light-near dissociation also happens due to damage to the pretectal nucleus (or its decussating fibres) and the Edinger–Westphal nucleus [Figure 12b, c & d]. Lid retraction in the primary position can occur due to damage to the posterior commissure. It is called the Collier sign.
Skew deviation is a supranuclear motility disorder that presents in brainstem or cerebellar stroke [Figure 13a]. There is vertical deviation of eyes, which is often associated with cyclotorsional disturbances. It has three variable presentations. They are as follows:
- Both eyes deviate upwards [Figure 13b] (or)
- One eye is hypertropic [Figure 13c] (or)
- One eye is hypotropic [Figure 13d].
The deviation is relatively comitant in nature. It is associated with binocular torsion and head tilt, known as the ocular tilt reaction.
HORIZONTAL GAZE PALSY
A lesion of the horizontal gaze centre in the PPRF manifests as ipsilateral horizontal gaze palsy, with an inability to look in the direction of the lesion [Figure 14].[63,96] On the contrary, damage to the frontal eye field (FEF) will produce a conjugate gaze towards the lesion [Figure 15].
The medial longitudinal fasciculus (MLF) is supplied by the branches of the basilar artery (BA). Ischemia in the vertebrobasilar system can produce an ischemic internuclear ophthalmoplegia (INO).
Unilateral INO clinically manifests with defective adduction of the eye on the side of the lesion and nystagmus of the contralateral eye on abduction will be noted [Figure 16]. As the eyes are orthotropic in the primary position, the patient won't have diplopia.[98,99] Convergence is usually normal. Bilateral INO will present as adduction defect of the left eye and abduction nystagmus of the right eye on the right gaze, and adduction defects of the right eye and abduction nystagmus of the left eye on the left gaze [Figure 17].
There are various variants of INO [Figure 18].
WALL-EYED BILATERAL INTERNUCLEAR OPHTHALMOPLEGIA
Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) starts when there is bilateral damage to the MLF [Figure 19a]. There is bilateral exotropia (XT) [Figure 19b] in the primary position, and the eyes appear to be looking at the opposite wall, thus the term wall-eyed was coined. However, exotropia need not be present in all cases of bilateral INO. The most common aetiology of WEBINO is infarction at the level of the midbrain.
WALL-EYED MONOCULAR INTERNUCLEAR OPHTHALMOPLEGIA
There is another less common variant of INO called wall-eyed monocular internuclear ophthalmoplegia (WEMINO). In WEMINO, patients will have a unilateral MLF lesion with primary position XT [Figure 20].
When the lesion involves the MLF and the PPRF, or the sixth cranial nerve nucleus on the same side, it results in an INO in one eye and ipsilateral horizontal gaze palsy [Figure 21]. Only the abduction of the contralateral eye will be retained which will be associated with abduction nystagmus. This condition is termed as one-and-a-half syndrome.
The lesion in the dorsal tegmentum of the caudal pons may cause eight-and-a-half syndrome [Figure 22]. It is characterized by having one-and-a-half syndrome and facial fascicular nerve palsy. The ipsilateral facial nerve fascicle is affected as it goes around the abducens nucleus. The patient will present with conjugate horizontal gaze palsy on looking to one side and INO on looking to the opposite side, along with ipsilateral LMN facial nerve weakness. This condition is termed as eight-and-a-half syndrome.
It is a very rare syndrome that consists of unilateral INO, combined with an ipsilateral sixth nerve fascicular involvement with sparing of the sixth nerve nucleus. Thus, there is half of the ipsilateral gaze (abduction deficit from CN VI fascicular palsy) plus 'half' of a horizontal gaze palsy (INO) [Figure 23]. This condition is defined as half-and-half syndrome.
POSTERIOR INO OF LUTZ
This syndrome is a rare ophthalmoplegia. It presents either bilateral or unilateral. It exhibits contralateral adducting eye nystagmus (rather than abducting eye nystagmus) with abduction restriction. It is the reverse of a typical INO. Lesions interrupting the tracts connecting the pontine centre for conjugate horizontal gaze and the ipsilateral abducens nucleus can lead to posterior INO of Lutz. This syndrome can be differentiated from abducens nerve palsy as the eyes will be orthotropic in the primary position.
The first step in diagnosis is to rule out haemorrhagic stroke, which can be accomplished through a non-contrast CT. For posterior circulation strokes, MRI with diffusion-weighted imaging (DWI) might be required. Along with imaging, a thorough history and physical examination will also help in localizing the region of the stroke. It is recommended to do a complete eye examination that includes visual acuity determination, pupillary exam, fundoscopy and visual field testing.
Initial management would involve securing the airway and circulation stabilization. Intravenous tissue-type plasminogen activator (tPA) can be administered within the window period (4.5 hours of the onset of symptoms). Acute endovascular therapy involving intra-arterial mechanical clot retrieval or lysis can also be considered in basilar occlusion. However, benefits as compared with tPA are still unclear.
PRINCIPLES OF THERAPY
The ocular misalignment associated with brainstem stroke might resolve on its own over a period of time. So initially to overcome diplopia, temporary press-on prisms or botulinum toxin injections can be given. In cases where diplopia does not resolve, strabismus surgery could be done after 6–12 months.
THIRD NERVE PALSY TREATMENT
In pupil-sparing third nerve palsies, surgical treatment is advised after a minimum of 6 months of observation. Strabismus surgery should always be performed before correcting ptosis. In the case of complete third nerve palsy, patients will require resection of the medial rectus and recession of the lateral rectus for correction of horizontal deviation component followed by superior oblique tendon transposition if required. Partial third nerve palsy patients may require surgery based on the extent of the extraocular muscle involvement.[109,110]
FOURTH NERVE PALSY TREATMENT
For correcting vertical diplopia in superior oblique palsy, initially, inferior oblique muscle is weakened either by removing a segment of the muscle or by recession. If diplopia persists, superior oblique strengthening by superior oblique tuck or Harada-Ito procedure (where just the front fibres of the tendon are utilized) can be considered.
SIXTH NERVE PALSY TREATMENT
In sixth nerve palsies, botulinum toxin is injected into the medial rectus muscle to prevent contracture. In mild sixth nerve palsy cases, medial rectus weakening with lateral rectus strengthening can be considered. In severe sixth nerve palsy cases, vertical rectus transposition can be performed. The vertical rectus transposition can be done by the Hummelsheim procedure, where the vertical recti are split and their temporal component is transposed, or the Jensen's procedure where the vertical rectus muscle bellies along with the lateral rectus muscle belly are split, and then adjacent muscle bellies are tied together.[111,112,113,114]
PARINAUD SYNDROME TREATMENT
Persistent symptoms of Parinaud syndrome are first managed conservatively. If conservative treatment fails, surgical correction may be planned. Preferred surgical methods include bilateral inferior rectus resection or superior transposition of the medial and lateral rectus insertions. Both these methods help in the improvement of upgaze palsy and convergence retraction nystagmus.[94,115]
SKEW DEVIATION TREATMENT
In cases of persistent skew deviation, vertical rectus muscle recession has been found to be effective for treating vertical diplopia. Correction of head tilt will require surgically augmenting the torsional deviation in the direction of the head tilt. This surgical cyclorotation of the eyes would serve to counter-rotate the visual world in the opposite direction and thereby eliminating the need for a compensatory head tilt.[116,117,118]
INOs usually recover on their own. However, patients with WEBINO or WEMINO may require patching, prisms or surgery to correct XT in the primary position.
Owing to the rich blood supply of the optic chiasma by the circle of Willis, it is very rare to experience chiasmal strokes. Chiasmal strokes usually present as bitemporal hemianopia [Figure 24]. Anterior chiasmal strokes can present as a central scotoma in one eye and temporal field defects in the other eye [Figure 24].[120,121] ICA aneurysms can also cause an asymmetrical chiasmal syndrome, associated with optic nerve compression on the side of the aneurysm. Optic nerve lesion on the affected side may cause central vision loss, decreased visual acuity, relative afferent pupillary defect (RAPD) and dyschromatopsia.
Post chiasmal strokes
Lesions of the optic tract and lateral geniculate body (LGB) [Figure 25] will produce incongruous contralateral homonymous hemianopia [Figure 24]. The ocular examination will reveal sectoral optic atrophy and contralateral wedge-shaped pallor.
Optic tract stroke
Ischaemic lesions of the optic tract are very rare and usually result from infarction of the anterior choroidal artery. Lesions usually produce contralateral incongruous homonymous hemianopia associated with optic tract syndrome [Figure 24]. Bow-tie or band-optic atrophy in the contralateral eye is noted, as it involves fibres nasal to the macula, constituting the papillomacular fibres and the nasal radiating fibres. On the ipsilateral side, atrophy involves the arcuate temporal fibres. There will be mild RAPD in the contralateral eye, as the optic tract contains more crossed than uncrossed pupillary fibres.
Lateral geniculate body stroke
The watershed location of the LGB makes it more susceptible to ischaemia during hypoperfusion. In the case of extensive LGB injury, it will manifest as complete homonymous hemianopia [Figure 26]. However, visual disturbances rarely occur with LGB lesions.[125,126,127]
Medial LGB lesions manifest as wedge-shaped homonymous hemianopia [Figure 26], where only the lateral posterior choroidal artery is occluded. Whereas in anterior choroidal artery occlusion, upper and lower homonymous hemianopia [Figure 26] with preservation of the horizontal wedge is documented. Occlusion of both the lateral posterior choroidal artery and the anterior choroidal artery will produce complete homonymous hemianopia [Figure 26]. Bilateral LGB lesions are very rare, and patients present with incongruous bitemporal and binasal visual field defects [Figure 26].
Optic radiation stroke
Lesions of the anterior optic radiation will cause incongruous visual field defects [Figure 27]. The field defects are predominantly incongruous contralateral homonymous hemianopia or quadrantanopia with sloping borders, associated with hemiparesis. The more posterior the lesion, the more congruous the field defect will be.
Temporal lobe stroke
Contralateral homonymous superior quadrantanopia ('pie-in-the-sky' defect) is seen in temporal lobe infarction [Figure 27]. It involves Meyer's loop comprising the inferior visual fibres. Damage to the temporal lobe anterior to the Meyer loop does not cause any visual field defect. Temporal lobe lesions often produce gustatory and olfactory hallucinations. They can also trigger complex, formed hallucinations in either the ipsilateral or contralateral visual field. It will probably be associated with symptoms of seizures, receptive aphasia and memory deficits.
Parietal lobe stroke
Parietal lobe stroke causes a variety of symptoms based on its location.
RIGHT SIDE PARIETAL LOBE STROKES
Right-sided parietal lobe stroke may present with the following features:
- Left-sided hemiparesis with paraesthesia on the left side of the body
- Contralateral homonymous inferior quadrantanopia (pie-on-the-floor defect) [Figure 27]
- Spatial disorientation along with problems with depth perception and movements
- Hemiagnosia (i.e., inability to recognize objects to the left side of the space)
- Alien hand syndrome – inability to recognize the left side of one's own body
- Loss of proprioception leading to misjudgement in movement and balance
- Hemispatial neglect (i.e., lack of awareness or concern about the left-sided impairment)
- Damaged pursuit pathway with impaired optokinetic nystagmus (OKN) response towards the side of the lesion
LEFT-SIDE PARIETAL LOBE STROKES
Left-sided parietal lobe stroke may present with the following features:
- Right-sided weakness and paraesthesia on the right side of the body with contralateral homonymous inferior quadrantanopia [Figure 27].
- Aphasia (i.e., difficulty with reading, writing, speaking, language comprehension and learning new information)
- Anosognosia (i.e., lack of awareness that a stroke had even occurred).
BOTH PARIETAL LOBE STROKES
A stroke involving both parietal lobes may result in depression, chronic fatigue, memory problems and astereognosis. Astereognosis is a sensory disorder with an inability to recognize an object by touch. Astereognosis occurs if the back end of the parietal lobe is damaged.
Gerstmann syndrome is a rare disorder that occurs due to damage or impaired blood flow to the upper sides of the parietal lobe. It is characterized by the impairment of four specific neurological functions. It occurs when the dominant parietal lobe is affected. The patient develops the inability to write (agraphia), inability to do math (acalculia), inability to identify fingers (finger agnosia) and right-left disorientation.
Occipital lobe stroke
Occipital lobe lesions occur due to stroke at the level of the PCA. The only clinical manifestation is vision loss with no neurological deficits. It can produce a varied presentation of visual field defects. They are as follows:
- Strokes involving the primary visual cortex supplied by the PCA will produce contralateral congruous homonymous hemianopia with macula-sparing [Figure 27]. This happens because the tip of the occipital lobe receives a dual blood supply from the MCA and the PCA.
- Stroke involving the most anterior portion of the occipital lobe will produce monocular temporal crescent defect [Figure 27] in the far periphery between 60°–90° of the visual field.
- Anton syndrome is a characteristic feature of bilateral occipital infarctions. Patients have cortical blindness but they deny any visual problems. They hallucinate and confabulate visual images, thus claiming the ability to see. Patients will have intact pupillary reflexes and normal ocular examination.
- Riddoch phenomenon, also known as statokinetic dissociation, is a phenomenon in which the person can perceive visual motion in a blind hemifield. This can be seen in the anterior visual pathway or occipital lobe lesions.
- In bilateral occipital lobe ischemia, a complete whiteout of vision may occur.
- Prosopagnosia can occur with bilateral inferior occipitotemporal lobe damage but may also occur with right inferior occipital lobe damage. It is a form of visual disconnection with the inability to recognize familiar faces. It is frequently accompanied with superior homonymous visual field defects.
- Balint syndrome is a rare syndrome that results from occipitotemporal lesions. It consists of a triad of simultanagnosia, optic ataxia and ocular motor apraxia. Simultanagnosia is the inability to identify more than one object at a time. Optic ataxia is the disconnection between visual input and the motor system. Acquired ocular motor apraxia is the acquired loss of voluntary movement of the eyes while fixating on a target.
It is important to combat vision loss as it plays a major role in the quality of life. So, it is mandatory to provide visual rehabilitation to enhance residual visual function. Low vision aids should be considered for treating visual impairment. Optical devices in the form of mirrors and prisms can be used to enhance the patient's residual visual field. Additionally, it is important to provide strategies to the patients to compensate and adapt to their current scenario.
- Periodic radiographic imaging is recommended at regular intervals for monitoring the size and/or growth of the aneurysm to avoid severe life-threatening as well as vision-threatening outcomes.
- It is mandatory to provide cardiac monitoring, airway and ventilatory support in managing haemorrhagic and ischaemic strokes.
- Recovery period of six months should be given for ocular muscle recovery following which the residual misalignment should be corrected via strabismus surgery. During the recovery period, temporary treatment in the form of prisms and botulinum injection can be used.
- The primary goal of visual rehabilitation is to increase the independency and adaptability of the patient.
- The orthoptist plays an important role in managing these cases pertaining to eye movements.
Ophthalmology-related cerebral arterial circulation diseases are complex and difficult to understand by a neophyte resident.[137,138,139,140,141,142,143,144,145] In this review, we have used 3D images for an easy understanding of the aetiopathogenesis of this ophthalmology-related cerebrovascular disease.
Declaration of patient consent
In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the chapter. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
1. Uston C. NEUROwords Dr. Thomas Willis' famous eponym: The circle of Willis J Hist Neurosci. 2005;14:16–21
2. Menshawi K, Mohr JP, Gutierrez J. A functional perspective on the embryology and anatomy of the cerebral blood supply J Stroke
3. Rosner J, Reddy V, Lui F. Neuroanatomy, Circle of Willis StatPearls [Internet]. 2021Last accessed on 2021 Dec 25 Treasure Island, FL StatPearls Publishing Available from: http://www.ncbi.nlm.nih.gov/books/NBK534861/
4. Circle of Willis. Kenhub.Last accessed on 2021 Dec 25 Available from: https://www.kenhub.com/en/library/anatomy/circle-of-willis
5. Beck J, Rohde S, Berkefeld J, Seifert V, Raabe A. Size and location of ruptured and unruptured intracranial aneurysms
measured by 3-dimensional rotational angiography Surg Neurol. 2006;65:18–25 discussion 25-7.
6. Aoki N. Partially thrombosed aneurysm presenting as the sudden onset of bitemporal hemianopsia Neurosurgery. 1988;22:564–6
7. Johnson MK, O'Connor M, Cantor J. Confabulation, memory deficits, and frontal dysfunction Brain Cogn. 1997;34:189–206
8. McCarron MO, Alberts MJ, McCarron P. A systematic review of Terson's syndrome; frequency and prognosis after subarachnoid haemorrhage J Neurol Neurosurg Psychiatry. 2004;75:491–3
9. Pfausler B, Belcl R, Metzler R, Mohsenipour I, Schmutzhard E. Terson's syndrome in spontaneous subarachnoid haemorrhage a prospective study in 60 consecutive patients J Neurosurg. 1996;85:392–4
10. Resnick SJ, Rabinstein AA. Neurological picture. Terson's syndrome in subarachnoid haemorrhage J Neurol Neurosurg Psychiatry. 2006;77:287
11. Wong H, Banfield J, Hughes N, Shankar JJS. Are anterior communicating aneurysms
truly anterior communicating aneurysms
? An observational study World Neurosurg. 2019;125:E1089–92
12. Matsukawa H, Uemura A, Fujii M, Kamo M, Takahashi O, Sumiyoshi S. Morphological and clinical risk factors for the rupture of anterior communicating artery aneurysms
clinical article J Neurosurg. 2013;118:978–83
13. Chan JW, Hoyt WF, Ellis WG, Gress D. Pathogenesis of acute monocular blindness from leaking anterior communicating artery aneurysms
; report of six cases Neurology. 1997;48:680–3
14. Chong CT, Chin KJ, Yip LW, Singh K. Case series: Monocular visual loss associated with subarachnoid haemorrhage secondary to ruptured intracranial aneurysms
Can J Anaesth. 2006;53:684–9
15. Claes C, Milea D, Bodaghi B, Tran TH, LeHoang P, Blanc R. Acute retrobulbar optic neuropathy due to rupture of anterior communication artery aneurysm Acta Ophthalmol Scand. 2006;84:145–6
16. Højer-Pedersen E, Haase J. Giant anterior communicating aneurysm with bitemporal hemianopsia: Case report Neurosurgery. 1981;8:703–6
17. Craenen G, Brown SM, Freedman KA, Windisch TR, Corona J. Rapid, painless unilateral vision loss in an 37-year-old healthy woman Surv Ophthalmol. 2004;49:343–8
18. Thygesen J, Rosenørn J. Transient bilateral blindness in relation to subarachnoid haemorrhage caused by spastic ischemic changes in retina and optic nerve Acta Ophthalmol (Copenh). 1982;60:325–31
19. Kassell NF, Sasaki T, Colohan AR, Nazar G. Cerebral vasospasm following aneurysmal subarachnoid haemorrhage Stroke
20. Hara N, Mukuno K, Ohtaka H, Shimizu K. Ischemic optic neuropathy associated with subarachnoid haemorrhage after rupture of anterior communicating artery aneurysm Ophthalmologica. 2003;217:79–84
21. Lee Ag, Brazis PW, Miller NR. Posterior ischemic optic neuropathy associated with migrane Headache. 1996;36:506–10
22. Portney GL, Roth AM. Optic cupping caused by an intracranial aneurysm Am J Ophthalmol. 1977;84:98–103
23. Sadda SR, Nee M, Miller NR, Biousse V, Newman NJ, Kouzis A. Clinical spectrum of posterior ischemic optic neuropathy Am J Ophthalmol. 2001;132:743–50
24. Debrun GM, Aletich VA, Kehrli P, Misra M, Ausman JI, Charbel F. Selection of cerebral aneurysm for treatment using Guglielmi detachable coils: The preliminary university of Illinois at Chicago experience Neurosurgery. 1998;43:1281–95 discussion 1296-7.
25. Halbach VV, Higashida RT, Dowd CF, Barnwell SL, Fraser KW, Smith TP, et al The efficacy of endosaccular aneurysm occlusion in alleviating neurological deficits produced by mass effect J Neurosurg. 1994;80:659–66
26. Malisch TW, Guglielmi G, Viñuela F, Duckwiler G, Gobin YP, Martin NA, et al Unruptured aneurysms
presenting with mass effect symptoms; response to endosaccular treatment with Guglielmi detachable coils. Part I. Symptoms of cranial nerve dysfunction J Nurosurg. 1998;89:956–61
27. Golshani K, Ferrell A, Zomorodi A, Smith TP, Britz GW. A review of the management of posterior communicating artery aneurysms
in the modern era Surg Neurol Int. 2010;1:88
28. Dimopoulos VG, Fountas KN, Feltes CH, Robinson JS, Grigorian AA. Literature review regarding the methodology of assessing third nerve paresis associated with non-ruptured posterior communicating artery aneurysms
Neurosurg Rev. 2005;28:256–60
29. Giombini S, Ferraresi S, Pluchino F. Reversal of oculomotor disorders after intracranial aneurysm surgery Acta Neurochir. 1991;112:19–24
30. Haider AS, Gottlich C, Sumdani H, Layton KF, Doughty K. Acute oculomotor nerve palsy caused by compression from an aberrant posterior communicating artery Cureus. 2019Last accessed on 2021 Oct 20 Available from: https://www.cureus.com/articles/16585-acute-oculomotor-nerve-palsy-caused-by-compression-from-an-aberrant-posterior-communicating-artery
31. Soni SR. Aneurysms
of the posterior communicating artery and oculomotor paresis J Neurol Neurosurg Psychiatry. 1974;37:475–84
32. Shrestha UD, Adhikari S. Aberrant regeneration of the third cranial nerve Nepal J Ophthalmol. 2012;4:176–8
33. Weber ED, Newman SA. Aberrant regeneration of the oculomotor nerve: Implications for neurosurgeons Neurosurg Focus. 2007;23:E14
34. Botterell EH, Lloyd LA, Hoffman HJ. Oculomotor palsy due to supraclinoid internal carotid artery berry aneurysm. A long-term study of the results of surgical treatments on the recovery of third-nerve function Am J Ophthalmol. 1962;54:609–16
35. Tian L, Fu Q. Recovery of posterior communicating artery aneurysm induced oculomotor nerve palsy: A comparison between surgical clipping and endovascular embolization BMC Neurol. 2020;20:351
36. Alkhalili KA, Hannallah JR, Alshyal GH, Nageeb MM, Aziz KMA. The minipterional approach for ruptured and unruptured anterior circulation aneurysms
: Our initial experience Asian J Neurosurg. 2017;12:466–74
37. . Terson Syndrome: Don't Let It Go Unrecognized American Academy of Ophthalmology. 2018Last accessed on 2021 Oct 21 Available from: https://www.aao.org/eyenet/article/terson-syndrome-dont-let-it-go-unrecognized
38. Am G, Ir D, Da N, Ar C, S B. Terson's syndrome: A reversible cause of blindness following subarachnoid haemorrhage J Neurosurg. 1992;76:766–71
39. McCarron MO. A systematic review of Terson's syndrome: Frequency and prognosis after subarachnoid haemorrhage J Neurol Neurosurg Psychiatry. 2004;75:491–3
40. Ramesh SV, Ramesh PV, Ramesh MK, Ramesh R. Acute traumatic maculopathy Kerala J Ophthalmol. 2021;33:123–5
41. Ramesh SV, Ramesh PV, Ray P, Balamurugan A, Madhanagopalan VG. Photo quiz answers TNOA J Ophthalmic Sci Res. 2021;59:230
42. Ramesh SV, Ramesh PV, Ray P, Balamurugan A, Madhanagopalan VG. Photo Quiz: Holistic integrative ophthalmology with multiplex imaging- Part II TNOA J Ophthalmic Sci. 2021;59:228–9
43. Ramesh SV, Ramesh PV, Ramesh MK, Ramesh R. Optical coherence tomography findings of photoreceptor retinal pigment epithelium complex in acute traumatic maculopathy Delhi J Ophthalmol. 2020;31:96
44. Ramesh SV, Ramesh PV, Ramesh MK, Ramesh R. A rare presentation of bilateral subclinical macular commotio retinae TNOA J Ophthalmic Sci Res. 2020;58:318–9
45. Ramesh SV, Ramesh SV. Photo quiz: Holistic integrative ophthalmology with multiplex imaging TNOA J Ophthalmic Sci Res. 2020;58:334–5
46. Ramesh SV, Ramesh SV. Photo quiz answers TNOA J Ophthalmic Sci Res.. 2020;58:336
47. Manschot WA. Subarachnoid haemorrhage; intraocular symptoms and their pathogenesis Am J Ophthalmol. 1954;38:501–5
48. Weingeist TA, Goldman EJ, Folk JC, Packer AJ, Ossoinig KC. Terson's syndrome. Clinicopathologic correlations Ophthalmology. 1986;93:1435–42
49. Gress DR, Wintermark M, Gean AD. A case of Terson syndrome and its mechanism of bleeding J Neuroradiol. 2013;40:312–4
50. Czorlich P, Skevas C, Knospe V, Vettorazzi E, Richard G, Wagenfeld L, et al Terson syndrome in subarachnoid haemorrhage, intracerebral haemorrhage, and traumatic brain injury Neurosurg Rev. 2015;38:129–36
51. Terson Syndrome. 2020Last accessed on 2021 Oct 222020th ed. Thieme Verlag Available from: https://www.thieme-connect.de/products/ebooks/lookinside/10.1055/b-0040-174266
52. Gnanaraj L, Tyagi AK, Cottrell DG, Fetherston TJ, Richardson J, Stannard KP, et al Referral delay and ocular surgical outcome in Terson syndrome Retina. 2000;20:374–7
53. Kim JS. Pure lateral medullary infarction: Clinical-radiological correlation of 130 acute, consecutive patients Brain. 2003;126:1864–72
54. Saleem F, Das J. Lateral Medullary Syndrome StatPearls. 2021Last accessed on 2021 Dec 04 Treasure Island (FL) StatPearls Publishing Available from: http://www.ncbi.nlm.nih.gov/books/NBK551670/
55. Kumar N, Garg RK, Malhotra HS, Lal V, Uniyal R, Pandey S, et al Spontaneous vertebral artery dissection and thrombosis presenting as lateral medullary syndrome J Neurosci Rural Pract. 2019;10:502–3
56. Giannopoulos S, Markoula S, Kosmidou M, Pelidou S-H, Kyritsis AP. Lateral medullary ischemic events in young adults with hypoplastic vertebral artery J Neurol Neurosurg Psychiatry. 2007;78:987–9
57. Shetty SR, Anusha R, Thomas PS, Babu SG. Wallenberg's syndrome J Neurosci Rural Pract. 2012;3:100–2
58. Ischemic Posterior Circulation Stroke
: A Review of Anatomy, Clinical Presentations, Diagnosis, and Current Management.Last accessed on 2021 Oct 28 Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985033/
59. Ramesh SV, Ramesh PV, Rajasekaran R, Ramesh MK, Ray PA. Tale of hypertensive retinopathy with choroidopathy and neuropathy in a young patient: A sign of end stage renal disease Delhi J Opthalmol. 2021;31:106–7
60. Paliwal VK, Kumar S, Gupta DK, Neyaz Z. Ipsipulsion: A forgotten sign of lateral medullary syndrome Ann Indian Acad Neurol. 2015;18:284–5
61. Battel I, Koch I, Biddau F, Carollo C, Piccione F, Meneghello F, et al Efficacy of botulinum toxin type-A and swallowing treatment for oropharyngeal dysphagia recovery in a patient with lateral medullary syndrome Eur J Phys Rehabil Med. 2017;53:798–801
62. Unilateral Punctate Keratitis Secondary to Wallenberg Syndrome.Last accessed on 2021 Oct 28 Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038737/
63. Bowling B, Kanski JJ Kanski's clinical ophthalmology: a systematic approach. 2016Last accessed on 2022 Dec 23;917Eighth edition Edinburgh Elsevier (Expertconsult). Available from: http://medlib.med.miami.edu/login?url=https://www.clinicalkey.com/dura/browse/bookChapter/3-s2.0-C20120072808
64. Barrow DL, Spector RH, Braun IF, Landman JA, Tindall SC, Tindall GT. Classification and treatment of spontaneous carotid-cavernous sinus fistulas J Neurosurg. 1985;62:248–56
65. Ellis JA, Goldstein H, Connolly ES, Meyers PM. Carotid-cavernous fistulas Neurosurg Focus. 2012;32:E9
66. Chaudhry IA, Elkhamry SM, Al-Rashed W, Bosley TM. Carotid cavernous fistula: Ophthalmological implications Middle East Afr J Ophthalmol. 2009;16:57–63
67. Chang C-M, Cheng C-S. Late intracranial haemorrhage and subsequent carotid-cavernous sinus fistula after fracture of the facial bones Br J Oral Maxillofac Surg. 2013;51:e296–298
68. Ono K, Oishi H, Tanoue S, Hasegawa H, Yoshida K, Yamamoto M, et al Direct carotid-cavernous fistulas occurring during neurointerventional procedures Interv Neuroradiol. 2016;22:91–6
69. Fattahi TT, Brandt MT, Jenkins WS, Steinberg B. Traumatic carotid-cavernous fistula: Pathophysiology and treatment J Craniofac Surg. 2003;14:240–6
70. Yeung SW, Suen SSH, Yu SCH, Lao TT, Leung TY, Lau TK. Spontaneous carotid cavernous fistula complicating pregnancy Hong Kong Med J. 2013;19:258–61
71. Bhatti MT, Peters KR. A red eye and then a really red eye Surv Ophthalmol. 2003;48:224–9
72. Ishijima K, Kashiwagi K, Nakano K, Shibuya T, Tsumura T, Tsukahara S. Ocular manifestations and prognosis of secondary glaucoma in patients with carotid-cavernous fistula Jpn J Ophthalmol. 2003;47:603–8
73. Talks SJ, Salmon JF, Elston JS, Bron AJ. Cavernous-dural fistula with secondary angle-closure glaucoma Am J Ophthalmol. 1997;124:851–3
74. Jindal G, Miller T, Raghavan P, Gandhi D. Imaging evaluation and treatment of vascular lesions at the skull base Radiol Clin North Am. 2017;55:151–66
75. Williams ZR. Carotid-cavernous fistulae: A review of clinical presentation, therapeutic options, and visual prognosis Int Ophthalmol Clin. 2018;58:271–94
76. Meyers PM, Halbach VV, Dowd CF, Lempert TE, Malek AM, Phatouros CC, et al Dural carotid cavernous fistula: Definitive endovascular management and long-term follow-up Am J Ophthalmol. 2002;134:85–92
77. Gupta AK, Purkayastha S, Krishnamoorthy T, Bodhey NK, Kapilamoorthy TR, Kesavadas C, et al Endovascular treatment of direct carotid cavernous fistulae: A pictorial review Neuroradiology. 2006;48:831–9
78. Ducruet AF, Albuquerque FC, Crowley RW, McDougall CG. The evolution of endovascular treatment of carotid cavernous fistulas: A single-center experience World Neurosurg. 2013;80:538–48
79. Balloon-Assisted Coiling of the Cavernous Sinus to Treat Direct Carotid Cavernous Fistula.Last accessed on 2021 Oct 28 Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3806010/
80. Nossek E, Zumofen D, Nelson E, Raz E, Potts MB, Desousa KG, et al Use of Pipeline Embolization Devices for treatment of a direct carotid-cavernous fistula Acta Neurochir (Wien). 2015;157:1125–9 discussion 1130.
81. Kai Y, Hamada J, Morioka M, Yano S, Kuratsu J. Treatment of cavernous sinus dural arteriovenous fistulae by external manual carotid compression Neurosurgery. 2007;60:253–7 discussion 257-8.
82. Morton RP, Tariq F, Levitt MR, Nerva JD, Mossa-Basha M, Sekhar LN, et al Radiographic and clinical outcomes in cavernous carotid fistula with special focus on alternative transvenous access techniques J Clin Neurosci. 2015;22:859–64
83. Chalouhi N, Dumont AS, Tjoumakaris S, Gonzalez LF, Bilyk JR, Randazzo C, et al The superior ophthalmic vein approach for the treatment of carotid-cavernous fistulas: A novel technique using Onyx Neurosurg Focus. 2012;32:E13
84. Modi P, Arsiwalla T. Cranial Nerve III Palsy StatPearls. 2021Last accessed on 2021 Nov 18 Treasure Island (FL) StatPearls Publishing Available from: http://www.ncbi.nlm.nih.gov/books/NBK526112/
85. Aizawa H, Morita K, Yamaguchi S, Sasaki N, Tobise K, Makita Y. [A case of Nothnagel syndrome] Rinsho Shinkeigaku. 1996;36:889–91 Japanese.
86. Burr P, Mandalaneni K. Benedikt Syndrome StatPearls. 2021Last accessed on 2021 Nov 11 Treasure Island (FL) StatPearls Publishing Available from: http://www.ncbi.nlm.nih.gov/books/NBK560509/
87. Munakomi S, Das J. Weber Syndrome StatPearls. 2021Last accessed on 2021 Nov 11 Treasure Island (FL) StatPearls Publishing Available from: http://www.ncbi.nlm.nih.gov/books/NBK559158/
88. Khanam S, Sood G. Trochlear Nerve Palsy StatPearls. 2021Last accessed on 2021 Nov 11 Treasure Island (FL) StatPearls Publishing Available from: http://www.ncbi.nlm.nih.gov/books/NBK565850/
89. Graham C, Mohseni M. Abducens Nerve Palsy StatPearls. 2021Last accessed on 2021 Nov 11 Treasure Island (FL) StatPearls Publishing Available from: http://www.ncbi.nlm.nih.gov/books/NBK482177/
90. Khazaal O, Marquez DL, Naqvi IA. Foville Syndrome StatPearls. 2021Last accessed on 2021 Nov 12 Treasure Island (FL) StatPearls Publishing Available from: http://www.ncbi.nlm.nih.gov/books/NBK544268/
91. Sakuru R, Elnahry AG, Bollu PC. Millard Gubler Syndrome StatPearls. 2021Last accessed on 2021 Nov 12 Treasure Island (FL) StatPearls Publishing Available from: http://www.ncbi.nlm.nih.gov/books/NBK532907/
92. Zaorsky NG, Luo JJ. A case of classic Raymond syndrome Case Rep Neurol Med. 2012;2012:583123
93. Feroze KB, Patel BC. Parinaud Syndrome StatPearls. 2021Last accessed on 2021 Nov 12 Treasure Island (FL) StatPearls Publishing Available from: http://www.ncbi.nlm.nih.gov/books/NBK441892/
94. Shields M, Sinkar S, Chan W, Crompton J. Parinaud syndrome: A 25-year (1991-2016) review of 40 consecutive adult cases Acta Ophthalmol. 2017;95:e792–3
95. Rabinovitch HE, Sharpe JA, Sylvester TO. The ocular tilt reaction. A paroxysmal dyskinesia associated with elliptical nystagmus Arch Ophthalmol. 1977;95:1395–8
97. Kim JS. Internuclear ophthalmoplegia as an isolated or predominant symptom of brainstem infarction Neurology. 2004;62:1491–6
98. Feroze KB, Wang J. Internuclear Ophthalmoplegia StatPearls. 2021Last accessed on 2021 Nov 15 Treasure Island (FL) StatPearls Publishing Available from: http://www.ncbi.nlm.nih.gov/books/NBK441970/
99. Stroud MH, Newman NM, Keltner JL, Gay AJ. Abducting nystagmus in the medial longitudinal fasciculus (MLF) syndrome- internuclear ophthalmoplegia (INO) Arch Ophthalmol. 1974;92:2–5
100. Shinoda K, Matsushita T, Furuta K, Isobe N, Yonekawa T, Ohyagi Y, et al Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome in a patient with neuromyelitis optica spectrum disorder and anti-aquaporin-4 antibody Mult Scler. 2011;17:885–7
101. Jeon SB, Chung SJ, Ahn H, Lee J-H, Jung JM, Lee MC. Wall-Eyed Monocular Internuclear Ophthalmoplegia (WEMINO) with contraversive ocular tilt reaction J Clin Neurol. 2005;1:101–3
102. Xue F, Zhang L, Zhang L, Ying Z, Sha O, Ding Y. One-and-a-half syndrome with its spectrum disorders Quant Imaging Med Surg. 2017;7:691–7
103. Mesina BVQ, Sosuan GMN, Reyes KB. Eight-and-a-half syndrome: A rare potentially life-threatening disease GMS Ophthalmol Cases. 2018;8:Doc04
104. Gómez Iglesias P, Sanesteban Beceiro E, Gómez Ruíz MN, Matías Guiu JA. Half and half syndrome as a presentation of multiple sclerosis Neurologia. 2021;36:246–8
105. Topilow HW. Posterior internuclear ophthalmoplegia of Lutz Ann Ophthalmol. 1981;13:221–5
106. Merwick Á, Werring D. Posterior circulation ischemic stroke
107. Pollak L, Zehavi-Dorin T, Eyal A, Milo R, Huna-Baron R. Parinaud syndrome: Any clinicoradiological correlation? Acta Neurol Scand. 2017;136:721–6
108. Padget DHDandy WE. The circle of Willis: Its embryology and anatomy Intracranial Arterial Aneurysms
, Chapter III. 1948 New York Comstock Publishing:67–90
109. Kattleman B, Flanders M, Wise J. Supramaximal horizontal rectus surgery in the management of third and sixth nerve palsy Can J Ophthalmol. 1986;21:227–30
110. Singh A, Bahuguna C, Nagpal R, Kumar B. Surgical management of third nerve palsy Oman J Ophthalmol. 2016;9:80–6
111. . Superior Oblique Palsy: Surgery American Academy of Ophthalmology. 2015Last accessed on 2021 Nov 18 Available from: https://www.aao.org/basic-skills/superior-oblique-palsy-surgery
112. . Lateral Rectus Palsy: Surgery American Academy of Ophthalmology. 2015Last accessed on 2021 Nov 17 Available from: https://www.aao.org/basic-skills/lateral-rectus-palsy-surgery
113. Jensen CD. Rectus muscle union: A new operation for paralysis of the rectus muscles Trans Pac Coast Otoophthalmol Soc Annu Meet. 1964;45:359–87
114. Hummelsheim E. Weitere Erfahrungen mit partieller Sehnenu ber-Pflanzung an den Augen-muskeln Arch Augenheilkd. 1908;62:71–4
115. Buckley EG, Holgado S. Surgical treatment of upgaze palsy in Parinaud's syndrome J AAPOS. 2004;8:249–53
116. Brodsky MC, Donahue SP, Vaphiades M, Brandt T. Skew deviation revisited Surv Ophthalmol. 2006;51:105–28
117. Newman NJ, Lambert SR. Botulinum toxin treatment of supranuclear ocular motility disorders Neurology. 1992;42:1391–3
118. Rajasekaran R, Kumari RM, Balagopal A, Ramesh PV, Mohan K. Prevalence of various types of strabismus among patients attending a tertiary eye care hospital at Tiruchirappalli J Evolution Med Dent Sci. 2018;7:5484–7
119. Murthy R, Dawson E, Khan S, Adams GG, Lee J. Botulinum toxin in the management of internuclear ophthalmoplegia J AAPOS. 2007;11:456–9
120. Shelton JB, Digre KB, Katz BJ, Warner JEA, Quigley EP. Chiasmal stroke
in patient with atrial fibrillation and complete occlusion of right internal carotid artery J Neuroophthalmol. 2012;32:189
121. Fabian ID, Greenberg G, Huna-Baron R. Chiasmal stroke
following open-heart surgery J Neuroophthalmol. 2010;30:219–21
122. Savino PJ, Paris M, Schatz NJ, Orr LS, Corbett JJ. Optic tract syndrome. A review of 21 patients Arch Ophthalmol. 1978;96:656–63
123. Kardon R, Kawasaki A, Miller NR. Origin of the relative afferent pupillary defect in optic tract lesions Ophthalmology. 2006;113:1345–53
124. Silva RR, Penna ER, Fusão EF, Faria EC, Pinho RS, Pereira Vilanova LC, et al An unusual cause of blindness: Infarction in the bilateral lateral geniculate bodies J Stroke
Cerebrovasc Dis. 2014;23:1736–7
125. De Vries TM, Aries MJH, De Groot JC, Bonte GJ, de Jong BM. A grid-like hemi-field defect following a lacunar infarct in the lateral geniculate nucleus Clin Neurol Neurosurg. 2012;114:278–80
126. Tsuda H, Yoshizawa T. Localized Infarction of the Lateral Geniculate Body Intern Med. 2014;53:1891–2
127. Huang M, Ilsen PF. Sectoranopia: A stroke
in the lateral geniculate nucleus or optic radiations? Optometry. 2007;78:356–64
128. Pula JH, Yuen CA. Eyes and stroke
: The visual aspects of cerebrovascular disease Stroke
Vasc Neurol. 2017;2:210–20
129. Glisson CC. Visual loss due to optic chiasm and retrochiasmal visual pathway lesions Continuum (Minneap Minn). 2014;20:907–21
130. Cheng B, Forkert ND, Zavaglia M, Hilgetag CC, Golsari A, Siemonsen S, et al Influence of stroke
infarct location on functional outcome measured by the modified rankin scale Stroke
131. Cureus | Posterior Alien Hand Syndrome from Acute Ischemic Left Parietal Lobe Infarction.Last accessed on 2021 Nov 16 Available from: https://www.cureus.com/articles/23447-posterior-alien-hand-syndrome-from-acute-ischemic-left-parietal-lobe-infarction
132. Cognitive Alterations in Motor Imagery Process after Left Hemispheric Ischemic Stroke
.Last accessed on 2021 Nov 16 Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042922
133. Chen T-Y, Chen C-Y, Yen C-H, Kuo S-C, Yeh Y-W, Chang S, et al Acute parietal lobe infarction presenting as Gerstmann's syndrome and cognitive decline mimicking senile dementia Neuropsychiatr Dis Treat. 2013;9:937–40
134. Hayashi R, Yamaguchi S, Narimatsu T, Miyata H, Katsumata Y, Mimura M. Statokinetic dissociation (Riddoch Phenomenon) in a patient with homonymous hemianopsia as the first sign of posterior cortical atrophy Case Rep Neurol. 2017;9:256–60
135. Schmidt D. Neuro-ophthalmological findings in patients with acquired prosopagnosia Graefes Arch Clin Exp Ophthalmol. 2015;253:333–4
136. Amalnath SD, Kumar S, Deepanjali S, Dutta TK. Balint syndrome Ann Indian Acad Neurol. 2014;17:10–1
137. Ramesh PV, Aji K, Joshua T, Ramesh SV, Ray P, Raj PM, et al Immersive photoreal new-age innovative gameful pedagogy for e-ophthalmology with 3D augmented reality Indian J Ophthalmol. 2022;70:275–80
138. Ramesh PV, Ramesh SV, Ray P, Devadas AK, Surendran A, Joshua T, et al Going Green in Ophthalmological Practice. 2022Last accessed on 2022 Oct 14 IntechOpen
139. Ramesh PV, Joshua T, Ray P, Devadas AK, Raj PM, Ramesh SV, et al Holographic elysium of a 4D ophthalmic anatomical and pathological metaverse with extended reality/mixed reality Indian Journal of Ophthalmology. 2022;70:3116–21
140. Ramesh PV, Devadas AK, Joshua T, Ray P, Ramesh SV, Raj PM, et al Eye MG 3D Application - A comprehensive ocular anatomy and pathophysiology 3D atlas with real-time true color confocal images to enhance ophthalmology education and e-Counseling Indian Journal of Ophthalmology. 2022;70:1388
141. Ramesh PV, Devadas AK, Joshua T, Ray P, Ramesh SV, Ramesh MK, et al 3D printing ophthalmology related models for enhancing learning through the concept of puzzle assembly - A comprehensive self-learning tactile tool kit Indian Journal of Ophthalmology.. 2022;70:1384
142. Ramesh PV, Ramesh SV, Ray P, Devadas AK, Joshua T, Balamurugan A, et al The holistic spectrum of thrombotic ocular complications: Recent advances with diagnosis, prevention, and management guidelines [Internet] Art and challenges involved in the treatment of ischaemic damage. 2022Last accessed on 2023 Jan 21 IntechOpen
143. Ramesh PV, Ramesh SV, Ray P, Devadas AK, Joshua T, Balamurugan A, et al Diagnosis and treatment of ophthalmology related cerebral arterial circulation
diseases: A 3D animated encyclopedia Cerebral circulation - updates on models, diagnostics and treatments of related diseases. 2022Last accessed on 2023 Jan 21 IntechOpen
144. Ramesh PV, Ray P, Ramesh SV, Devadas AK, Joshua T, Balamurugan A, et al Cerebral arterial circulation
: 3D augmented reality models and 3D printed puzzle models. 2022Last accessed on 2022 Mar 3 IntechOpen
145. Ramesh PV, Ramesh SV, Devadas AK, Ray P, Verghese S, Shipra S, et al Photo quiz: Holistic integrative ophthalmology with multiplex imaging part IV TNOA J Ophthalmic Sci Res. 2022;60:338–40