Anatomy and Physiology of Glaucoma

Elevated intraocular pressure (IOP) is a hallmark of glaucoma, a complex eye disease that

can eventually lead to vision loss. There are primary and secondary kinds of this eye ailment and

open-angle and closed-angle variations. Primary open-angle glaucoma (POAG), angle-closure

glaucoma, and secondary open and angle-closure glaucoma are all considered forms of adult

glaucoma, with particular attention paid to POAG, the most common variety (Dietze et al.,

2024).

The sclera is a strong white coating covering most of the eye's exterior. The sclera is

covered by a thin layer known as the conjunctiva cover. The cornea, a transparent surface

resembling a window at the front of the eye, shields the pupil and the iris behind it. The colored

portion of the eye that contracts and expands to allow light into the eye is called the iris, a

muscle. Light enters the eye through the pupil, a hole in the middle of the iris shielded by the

transparent cornea. This light is focused onto the retina, the back of the eye, by the lens inside

our eye. The nerve cells and fibers in the retina transform the light images into electrical signals,

which are then transmitted to the brain via the optic nerve. The region of the retina, known as the

optic disc, is where all nerve fibers converge to form the optic nerve, which emerges from the

eye and connects to the brain.

The ciliary body produces the clear fluid known as aqueous humor, which fills the front

portion of the eye. The pupil allows the fluid to exit. It then makes its way to the eye's drainage

system, which consists of a network of canals and the trabecular meshwork. The balance

between the amount of fluid produced and the amount that drains from the eye determines the

eye's intraocular pressure, or "IOP," interior pressure. The necessary amount of fluid will be

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created if your eye's fluid system functions correctly. Similarly, fluid can freely drain out of your

eye to avoid pressure buildup if the drainage system functions properly. The eye's health depends

on proper drainage, an ongoing, dynamic process that helps maintain appropriate eye pressure.

The optic nerve comprises millions of nerve fibers that run from your retina to the optic disc,

where they meet. In most cases of glaucoma, the eye's drainage system becomes clogged,

preventing the intraocular fluid from draining. As the fluid accumulates, pressure builds inside

the eye, which can damage these sensitive nerve fibers and cause vision loss. As the fibers are

lost and damaged, the optic disc starts to hollow out and takes on a cupped shape, visible to

doctors during examinations.

The typical range for intraocular pressure (IOP) is 12 to 22 mmHg ("millimeters of

mercury," a measurement of pressure). If the IOP stays too high for an extended period, the extra

strain on the delicate optic disc may cause irreversible vision loss. High intraocular pressure is

undoubtedly a risk factor for glaucoma. Still, since glaucoma can cause vision loss in people

with normal IOP, we also know that additional variables are at play. The goal of the current study

is to identify these extra elements. Although elevated eye pressure often starts in one eye,

glaucoma typically affects both eyes. Over several years, this damage may result in progressive

visual changes and blindness. You might not notice the difference in your eyesight because it

usually affects your peripheral (side) vision first. Your center vision may eventually be impacted

as well. It is impossible to recover vision lost due to glaucoma. Nonetheless, vision loss can be

avoided, and residual vision can be preserved with early detection and treatment (Eye Anatomy -

Glaucoma Research Foundation. 2024)

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 Disease Process

Eyes makes a fluid called aqueous humor to keep it healthy. This fluid flows in and out of

eye. As new fluid enters, the same amount should drain out through a special area in the eye

called the drainage angle. This keeps the pressure inside the eye stable, but if the drainage angle

gets blocked, the fluid can’t leave the eye properly. This causes the pressure inside the eye to go

up, which can hurt the optic nerve.

The optic nerve is like a cable made of tiny wires that carry signals from the eye to the

brain. When the pressure is too high, it can damage these tiny wires. As more of these wires are

damaged, this can result to loss vision. The first thing to notice is small blind spots, but if the

damage gets worse, it can lose all the vision.

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 Sign & Symptoms

Pharmacological Management

The pharmacological management of glaucoma is primarily aimed at lowering intraocular

pressure (IOP) to prevent optic nerve damage and preserve vision. Different classes of eye drops

targeting specific mechanisms are used in this process. Prostaglandins, including latanoprost and

travoprost, increase the outflow of aqueous humor and can be administered once daily. Beta-

blockers, such as timolol and betaxolol, decrease aqueous humor production and can be

administered once or twice daily. Alpha-adrenergic agonists, such as brimonidine, decrease fluid

production while enhancing outflow and are generally dosed twice to thrice daily. Carbonic

anhydrase inhibitors, such as dorzolamide, decrease aqueous humor production and are typically

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dosed two to three times daily. Rho kinase inhibitors, like netarsudil, inhibit enzymes that

contribute to increased fluid levels and are applied once daily. Finally, miotic agents, such as

pilocarpine, which increase fluid outflow, are used less frequently because of side effects and the

need for frequent application. Patients are instructed to close their eyes and massage the tear duct

lightly for 1–2 minutes after receiving drops and to wait for at least five minutes before receiving

different medications. Patients should be instructed on proper adherence for effective

management of glaucoma.

Mode of Action of each Medication

Prostaglandin Analogs:

 Mechanism of Action: These medications increase the outflow of aqueous humor from

the eye, which lowers Intra Occular Pressure (IOP).

Common Drugs:

 Latanoprost (Xalatan)

Side Effects:

 Eye irritation, redness, or itching.

Beta-Blockers:

 Mechanism of Action: These medications reduce aqueous humor production in the eye,

thus lowering IOP.

Common Drugs:

 Timolol (Timoptic)

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Side Effects:

 Fatigue, dizziness, or lightheadedness (due to systemic absorption)

Alpha Agonists:

 Mechanism of Action: These drugs reduce aqueous humor production and increase its

outflow.

Common Drugs:

 Apraclonidine (Iopidine)

Side Effects:

 Drowsiness, fatigue, or dizziness.

Carbonic Anhydrase Inhibitors (CAIs):

 Mechanism of Action: These medications reduce the production of aqueous humor by

inhibiting the enzyme carbonic anhydrase.

Common Drugs:

 Dorzolamide (Trusopt) — topical

 Acetazolamide (Diamox) — oral (used more in acute situations or when other

medications are ineffective)

Rhopressa (Netarsudil):

 Mechanism of Action: Netarsudil works by increasing the outflow of aqueous humor via

the trabecular meshwork and decreasing the production of aqueous humor.

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Common Drugs:

 Netarsudil (Rhopressa)

Side Effects:

 Eye redness (conjunctival hyperemia).

 Eye discomfort or irritation.

Combination Medications: Sometimes, combinations of medications from different classes are

used to enhance IOP-lowering effects. These combinations can improve patient compliance by

reducing the number of drops required.

 Common Combination Drugs:

Cosopt (Dorzolamide + Timolol)

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