Glaucoma and Brain Nerve Relation

Shuxin Jiang

1,† a

and Yuqi Wan

2,† b

Guangdong Experimental Highschool AP course, Guangzhou, Guangdong, China

Mounthouse School Alevel Barnet London, U.K.

†

These authors contributed equally

Keywords: Glaucoma, Retinal Ganglion Cell, White Matter, Cortex, Retinal, Central Nervous System, Optic Nerve

Neuropathy.

Abstract: Glaucoma is a common eye condition where optic nerve damage, this is not only the pathological changes in

the optic nerve its effect the brain nerve too, the human brain is a complex web of neurons and synapses,

however the eye correlated with the brain in a specific way, therefore when people study the diseases of the

eye the first thing that comes to mind is always the connection to the brain. Which means glaucoma lesions

are not limited to the retinal nerves, its damage reaches the white matter areas that are involved in the

processing and integration of visual information in the brain, which means that the damage caused by

glaucoma can reach the brain. We found researchers who used the VBM method to study whole brain

comparisons in glaucoma patients, to meticulously describing the effects of glaucoma lesions in the brain.

These two methods allow the comparison of multiple images of the brain with voxels to measure differences

in local concentrations of brain tissue, thus revealing intra cerebral differences between patients with

glaucoma and the general. It is also the relationship between glaucoma and the nerves in the brain that is at

the center of the title and exploration of this paper. The differences between the brains of glaucoma patients

and the general will be mentioned, as well as the pathogenesis of glaucoma, the treatment of the glaucoma

works through medical method and surgery are also be mentioned in this paper.

1 INTRODUCTION

Over 60 million people worldwide are diagnosed with

glaucomatous optic neuropathy, which is a disease

that could cause irreversible blindness. It is a leading

public health concern given the high prevalence. Are

large proportion of people with glaucoma still

remained undiagnosed, since the accurate decision of

glaucoma is challenging, particularly in early disease.

Patients with early glaucoma are typically unaware of

it, other patients with severer or more advanced

disease may see a shadow in their vision or a

reduction in their acuity of visual. There may be

difficulties when diagnosing glaucoma without

facilities to measure IOP and evaluate optic discs and

visual fields. A proportion of patients may experience

headache, ocular pain, nausea, vomiting, and blurred

vision if they are diagnosed as angle closure

glaucoma. Once diagnosed, glaucoma needs lifelong

https://orcid.org/0000-0001-9586-9021

https://orcid.org/0000-0001-7810-780X

monitoring, IOP is need to be monitored and

functional visual change is evaluated during the

visual field testing especially in the secondary care.

Glaucoma is referred to characteristic damage to the

optic nerve and patterns of visual field loss.

Degeneration of these nerves results in cupping, a

characteristic appearance of the optic disc and visual

loss. This results in the loss of Retinal ganglion

cells(RGCs) which carries the visual information

from the retina to the brain. After the damage, the

RGC undergo apoptosis resulting in visual loss.

Glaucoma can be classified into two broad categories:

Open angle glaucoma and angle closure glaucoma.

They can be classified by mechanism and appearance

of the anterior chamber angle. As shown in figure 1.

The dominant group of patients are diagnosed with

open angle glaucoma. While the others with severe

vision loss are diagnosed as angle closure glaucoma.

Both of the glaucoma can be primary diseases.

Jiang, S. and Wan, Y.

Glaucoma and Brain Nerve Relation.

DOI: 10.5220/0011245600003443

In Proceedings of the 4th International Conference on Biomedical Engineering and Bioinformatics (ICBEB 2022), pages 579-583

ISBN: 978-989-758-595-1

579

Secondary glaucoma can result from trauma or other

conditions such as pigment dispersion. The treatment

options for glaucoma are medical, laser, and surgical

options for them to lower IOP. Usually, patients starts

with glaucoma drop mono-therapy. However, if the

case is too difficult to control, extra drops will be

added as required. Furthermore, if the maximum

tolerant treatment is unsuccessful, a laser intervention

may be advised, in some cases, the patients may

proceed directly to surgery. Our goal is to identify the

connections between glaucoma and the brain, since

our visual function depends mostly on our nerves in

brain. Treatments for glaucoma and the nerves in our

brain which links our eyes and visions together will

be laid out.

2 GLAUCOMA

2.1 Profile of Glaucoma

Glaucoma is one of the major causes of irreversible

blindness over the world and is associated with

damages to the optic nerves and degeneration of the

retinal ganglion cell (RGC). The major risk factor is

Intraocular pressure (IOP) inside the eye. Over 60

million people worldwide are estimated with

glaucomatous optic neuropathy, in which about 8.5

million are blind (Review and MetaAnalysis). The

definition of clinical glaucoma could be defined as a

various multifactorial ocular disorders, combined

with clinically characteristic optic neuropathy, which

the optic nerve head (ONH) has potentially

progressive and clinically visible changes, including

focal or generalized neuroretinal rim thinning,

enlargement and excavation of the optic cups. This

represents the neurodegeneration of retinal ganglion

cell axons and the deformation of the lamina cribrosa;

in the early stage of glaucoma, corresponding diffuse

and localized nerve-fiber-bundle pattern visual field

loss might not be able to be detectable; while visual

acuity is initially spared, progression can lead to

complete loss of vision; The collection of clinical

features is diagnostic (Foster, Buhrmann, Quigley,

Johnson 2002).

Open-angle or angle-closure are the two subtypes

of glaucoma, where angle closure refers to the

presence of appositional or synechial iridotrabecular

contact leading to the obstruction of trabecular

meshwork and elevated IOP(Foster, Buhrmann,

Quigley, Johnson 2002).

2.2 The Human Visual Pathways

There are two parts in the human visual pathways; the

anterior visual pathway is composed of the retina,

optic nerve, and chasm and lateral geniculate nucleus

(LGN), while the optic radiations and visual cortex

are comprised in the posterior visual pathway. Over

90% of RGC axons in human project to the LGN, a

relay station which in turn projects its axons to the

visual cortex cia the optic radiation. The other 10%

of RGCs project to brain structures, including the

superior colliculus, which commands the movement

of the eye, pretectal area (pupillary reflex) and the

accessory optic system nuclei, that is the optokinetic

nystagmus (Goebel, Muckli LARS, Kim DS 2004).

Figure 1: Overview of the human visual pathway. a

Diagrammatic representation of the human visual pathway.

b Overview of the structure of the lateral geniculate nucleus

illustrating the organization of magnocellular (M-cells),

parvocellular (P-cell), and Koniocellular cells (K-cells)

2.3 Visually Relates Imaginary

Structure

Most visual functions are controlled by the occipital

lobe, a small section of the brain near the back of the

skull. However, processing eyesight is a complicated

work, the other parts of the brain will also need to be

involved. The occipital lobe is responsible for

receiving the data from our visions. Thus, injuries or

illnesses which could affect the occipital lobe can

cause detrimental effects such as visual disturbances

or even blindness.

The connections throughout the eye and the brain

utilizes a structure in brain called the pons. It is

shaped as a horse-shoe composed of transversed

nerve fibres, lying above medulla oblongata and

bellow cerebellum. It controls the movements of the

eye, sending signals which helps the eye respond to

the correct stimulus of light. The lights reflects into

our eyes strikes photo-receptor cells in the retina

called rods and cones. Rod cells only respond when

the surrounding area is in a dim condition thus it is

responsible for our peripheral vision and night vision,

while cone cells react to brighter light, giving us

ICBEB 2022 - The International Conference on Biomedical Engineering and Bioinformatics

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When light hits its corresponding rod or cone, the cell

activates, then it transmits a nerve impulse through

the optic nerve. This impulse ends up at the occipital

lobe, where it ’s processed and perceived as a visible

image. Occasionally, occipital lobe sends this visual

information to the hippocampus in the temporal lobe,

stored as a memory.

3 GLAUCOMA EXPERIMENT

3.1 Glaucoma Neuropathy

Glaucoma neuropathy is not limited to retinal

ganglion cells, it can affect the entire visual system.

In a series of studies conducted by Dr. Carlo Nucci, a

full professor of ophthalmology at the University of

Tower Vergara in Rome, and his colleagues observed

that in patients with early glaucoma, the optic nerve

damage is mainly located at the proximal end of the

eyeball, while in patients with advanced glaucoma in

the middle, the optic nerve damage is at the far back

of the eyeball. They also found that glaucoma damage

reaches the white matter areas, which are involved in

the processing and integration of visual information

in the brain. Because the retinal ganglion cell axon is

extended from the retina through the optic nerve to

the brain, the cells in its immediate vicinity can also

be damaged by glaucoma. (Gupta, Neeru,. Yücel

2007)

3.2 Use VBM to Compare

In the retina, other cells, such as anapestic cells,

regenerate and rejoin their connections after the

retinal ganglion cells are lost.Recently, researchers

have shown that glaucoma is not simply an eye

disease, but may be a disease of the central nervous

system. The central nervous system in glaucoma may

have similar or dissimilar pathogenesis to other

cranio-cerebral disorders. (Li, et al 2012) They are

using the VBM method to study whole brain

comparisons in glaucoma patients. When comparing

patients with glaucoma to those with normal

glaucoma, there were no differences in whole brain

grey matter, white matter, or brain parenchyma

volumes in patients with glaucoma. However in the

left middle frontal gyrus, right superior frontal gyrus,

right precuneus, and right angular gyrus, the volume

of the grey matter area decreased and the grey matter-

free area increased. While the volume of the white

matter area in the right middle occipital gyrus

decreased and the volume of the white matter area in

the right precentral gyrus increased, the areas of local

volume changes in brain structures in the NTG group

all correlated with GSS staging, this suggests that

glaucoma does not cause changes in the volume of

grey matter, white matter and brain parenchyma in

the whole brain, but the change have probability to

displayed and the analysis was generally based on

reduction. changes in brain structures in the NTG

group were mainly concentrated in frontal lobe (left

middle frontal gyrus, right superior frontal gyrus and

right precentral gyrus), occipital lobe (right

precuneus, right middle occipital gyrus) and parietal

lobe (right angular gyrus). The frontal lobe is not only

the processing and adjustment center for higher

cognitive functions, but is also responsible for

initiating, monitoring and modifying emotions. It has

a specific role in emotional decision-making and

emotional self-regulation and response inhibition.

(Iau, Ptc, et al. 2004) Numerous studies agree that

patients with glaucoma have varying degrees of

deficits in emotion regulation, which may be

associated with structural damage and dysfunction in

brain regions. Another study found a close

relationship between glaucoma and various

degenerative diseases of the central nervous system,

mainly manifesting as widespread brain atrophy. The

processing of visual information has extensive

connections with other brain regions and plays an

important role in the integration of visual information

with other sensory systems. Several studies have

shown a reduction in the volume of the right middle

gyrus of the group occipital lobe to support the NTG

In patients, there is indeed localized atrophy of the

occipital lobe, which is sufficient to suggest that

glaucoma damage extends beyond the visual cortex

and also affects the wider central nervous system. (

Iau, Ptc , et al. 2004)

3.3 The Pathogenesis of Glaucoma

The pathogenesis of glaucoma can be grouped into

two main categories: the mechanical theory and the

vascular theory. The mechanical theory emphasizes

the role of IOP and suggests that elevated IOP causes

deformation and displacement of the layers of the

sieve plate, resulting in shear forces that block the

axoplasmic flow of optic nerve cells in the sieve plate

area and reduced production and transport of axonal

proteins, leading to impaired cellular

metabolism.(Garaci, Francesco, et al., 2009) In

contrast, the vascular theory suggests that due to

various causes of impaired microcirculation in the

optic nerve papilla, the supply of nutrients to the optic

papilla and its surrounding tissues is reduced, causing

the tissue there to become stunted or damaged, and

Glaucoma and Brain Nerve Relation

581

damage to the optic nerve fibers occurs due to

ischemia and hypoxia and loss of protection from

surrounding tissues. A one-sided emphasis on the role

of mechanical or vascular theories in the pathogenesis

of glaucoma is biased. The mechanical theory does

not fully explain the occurrence of normal Intraocular

pressure glaucoma and signs of high Intraocular

pressure, while the vascular theory does not exclude

an important role for Intraocular pressure in the

pathogenesis of glaucoma. Therefore, it is generally

accepted that the pathogenesis of glaucoma is a

multifactorial and integrated process. ''Glaucoma is

an optic neuropathy with characteristic optic nerve

damage and corresponding impairment of visual

function". (Gupta, Neeru, Yücel. 2001)This suggests

that progressive damage to the optic nerve head is the

essential feature of glaucoma and can therefore be

divided into factors that cause damage to the optic

nerve head and factors that resist damage to the optic

nerve head according to the role of various factors in

the pathogenesis of glaucoma Normal people are able

to achieve a paradoxical balance between factors that

cause damage to the optic nerve head and factors that

resist damage to the optic nerve head making The

optic nerve head is protected from damage. In

patients with glaucoma, the balance is disturbed when

the optic nerve head damaging factor is enhanced or

the anti-optic nerve head damaging factor is

weakened for some reason unilaterally, resulting in

progressive damage to the optic nerve head.(Garaci,

Francesco, et al. 2009)

4 MEDICAL TREATMENT FOR

GLAUCOMA

4.1 Glaucoma Drops

The goal of treating glaucoma is to slow down the

disease's progression and preserve the quality of life.

Intraocular pressure reduction is the only proven

method to achieve this objective. Several multicenter

trials have shown that this procedure can prevent the

development and slow the disease's progression. The

initial target pressure should be decreased gradually

over time to a level that is considered ideal for

patients. It should also be adjusted depending on the

evolution of the condition. For instance, even though

the target pressure has been set, it may still need to be

lowered due to disease progression. Several classes of

pressure-lowering drugs are available. They can be

used with or without a schedule of events. The choice

of medication can be influenced by the cost, safety,

and efficacy of the drug.(Weinreb, Aung , Medeiros

2014) Glaucoma drops have the ability to lower the

IOP by changing the production or the out flow of

outflow of aqueous humour from the eye. Primary

treatments are usually Prostagladin analogues since

they possess the greatest ability to lower the IOP,

furthermore, profiles showcased that they also have

the smallest side effects. These side effects from

using the drops often causes blurring and transient

stinging, some may also cause discomfort in eyes,

redness or stimulating the growth of eyelashes.

Adherence to glaucoma drops is variable and difficult

to evaluate. (Kass, Gordon, Meltzer 1986) This

causes it to be hard to evaluate whether if the effects

of therapeutic is not enough or if the patients fail to

use the drops properly. If the IOP have not been

controlled, once the amount of drops a patient can

have exceeds, laser or surgical invention may be

needed.

4.2 Laser Treatment

Laser trabeculoplasty could be considered as as a

primary selection for the patients. It lowers the IOP

for open angle glaucoma by increasing the out flow.

This procedure of Laser trabeculoplasty is clinically

based.A recent systematic review of laser

trabeculoplasty highlighted the lack of data

comparing the effectiveness of this procedure with

modern medical and surgical options. (Rolim de

Moura, Paranhos, Wormald, 2007) The process of

which it opens the drainage tube, allowing more fluid

to drain from the eye, therefore reducing the pressure.

Another laser treatment could be cyclodiode laser

treatment, which it destruct some of the tissues with

in the eye that produces the liquid that is causing

pressure.

4.3 Surgery

This option is often suggested when the formal

treatments cannot succeed in lowering the IOP. Yet,

it could be used earlier if the patient have difficulties

in using the drops or whose presenting with advanced

glaucoma. The standard operation of glaucoma

creates aguarded fistula into the wall of the eye

(sclera), which allows a slow egression of aqueous

humour from the anterior chamber into the

subconjunctival space. (Wong, Husain, Ang,

Gazzard, Foster, Htoon, et al 2013) Trabeculectomy

is the commonest surgical method of reducing eye

pressure. It involves debridement of a small portion

of the trabecular meshwork, or adjacent corneal and

scleral tissue, to provide a drainage pathway for water

ICBEB 2022 - The International Conference on Biomedical Engineering and Bioinformatics

582

to drain from the eye into the conjunctiva and be

absorbed under the conjunctiva. Anti-scarring drugs

are often used at the surgical site to reduce the fibrotic

response and improve the success of the procedure,

but may increase the incidence of complications such

as infection and very low intraocular pressure

damage. A recent meta-analysis comparing

trabeculectomy with non-penetrating procedures

(deep sclerectomy, mucosal ostomy and catheter

angioplasty) concluded that although trabeculectomy

was more effective in reducing blood pressure, the

risk of complications was higher. ( Weinreb, Aung,

Medeiros 2014)

5 CONCLUSIONS

Glaucoma is not limited to retinal ganglion cells, it

can affect the entire visual system. Damage reaches

the white matter areas involved in processing and

integration of visual information in the brain. we

integrated the studies of VBM and Dartel methods of

whole brain comparisons in patients. Which suggest

that glaucoma damage extends beyond the visual

cortex and also affects the wider central nervous

system. Glaucoma damage is complex and

widespread. What we need to do in the future is to

pay more attention to the effects of glaucoma on the

central nervous system, and to study and compare the

differences between patients In order to better

understand the central nervous system glaucoma in

different disease stages, more methods are needed to

treat eye diseases. Strategies to prevent the

progression of glaucoma disease should also take into

account the degeneration of the central nervous

system other than wisdom and optic nerve head.

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