This document provides information about glaucoma, including its etiology, pathophysiology, clinical manifestations, types, and treatment options. It begins with an introduction to glaucoma as a group of disorders characterized by optic nerve damage and vision loss associated with increased intraocular pressure. The document then discusses the etiology and pathophysiology of glaucoma, describing how increased pressure damages the optic nerve. It outlines the clinical signs and symptoms of various types of glaucoma and concludes by explaining non-pharmacological and pharmacological treatment approaches that aim to lower intraocular pressure and prevent further vision loss.

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s.no TOPIC Page no
1 Introduction of glaucoma 01
2 Etiology 02
3 Pathophysiology 03
4 Clinical manifestation 04
5 Types of glaucoma 05
6 Non pharmacological
treatment
09
7 Pharmacological treatment 10
8 References 19

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GLAUCOMA
Glaucoma is not a single disease process but a group of disorders
characterized by a progressive optic neuropathy resulting in a
characteristic appearance of optic disc & specific pattern of
irreversible visual field defects that are associated frequently but not
invariably with ↑IOP.
The normal eye pressure is 12-22mm Hg.
The word “glaucoma” is derived from Ancient Greek word glaukos
which means grey, blue or green eyes.
Glaucoma is the second leading cause of blindness globally after
cataracts.
The most common type is open-angle glaucoma with less common
types including closed-angle glaucoma and normal-tension
glaucoma. Open-angle glaucoma develops slowly over time and there
is no pain. Peripheral vision may begin to decrease followed by
central vision resulting in blindness if not treated. Closed-angle
glaucoma can present gradually or suddenly. The sudden presentation
may involve severe eye pain, blurred vision, mid-dilated pupil,
redness of the eye, and nausea. Vision loss from glaucoma, once it has
occurred, is permanent.

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ETIOLOGY
All types of glaucoma – progressive optic neuropathy due to the death
of retinal ganglion cells (RGCs).
• RGCs death is initiated by:
Block in transport of neurotrophins from brain to RGCs
Damaging cascade activity
Apoptosis of RGCs
• RGCs death – loss of retinal fibers – optic neuropathy & visual field
defects
Mechanical theory:
↑IOP – mechanical stretch of lamina cribtosa – axonal deformation
& altered capillary blood flow -- ↓neurotrophins to reach RGC`s
• Pressure independent factors:
1 Failure of autoregulation
2. Vasospasm
3. Systemic hypotension

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PATHOPHYSIOLOGY
The underlying cause of open-angle glaucoma remains unclear.
Several theories exist on its exact etiology. “However, the major risk
factor for most glaucomas and the focus of treatment is increased
intraocular pressure.” Intraocular pressure is a function of production
of liquid aqueous humor by the ciliary processes of the eye, and its
drainage through the trabecular meshwork. Aqueous humor flows
from the ciliary processes into the posterior chamber, bounded
posteriorly by the lens and the zonules of Zinn, and anteriorly by
the iris. It then flows through the pupil of the iris into the anterior
chamber, bounded posteriorly by the iris and anteriorly by the cornea.
From here, the trabecular meshwork drains aqueous humor via the
scleral venous sinus (Schlemm's canal) into scleral plexuses and
general blood circulation.
In open/wide-angle glaucoma, flow is reduced through the trabecular
meshwork, due to the degeneration and obstruction of the trabecular
meshwork, Loss of aqueous humor absorption leads to increased
resistance and thus a chronic, painless buildup of pressure in the eye.
In close/narrow-angle, the iridocorneal angle is completely closed
because of forward displacement of the final roll and root of the iris
against the cornea, resulting in the inability of the aqueous fluid to
flow from the posterior to the anterior chamber and then out of the
trabecular network. This accumulation of aqueous humor causes an
acute increase in pressure and pain.

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CLINICAL MANIFESTATION
 A- POAG: General
POAG is usually bilateral with asymmetric disease progression
1. Loss of peripheral vision.
2. Presence of scotomata (blind spots) in vision field.
3. .Large cup-to-disc ratio.
4. .Notching of the optic nerve head rim.
5. .Splinter hemorrhages (using a slit-lamp biomicroscope)
B- PACG: General
(Medical emergency due to high risk of vision loss)
Unilateral in presentation, the other eye is at risk
 Ocular pain & red eye
 Blurry vision.
 Nausea/vomiting.
 Headache / Diaphoresis.
 Cloudy cornea
 Pupil semidilated and fixed to light
 Eye will be harder on palpation.

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TYPES OF GLAUCOMA
Primary open angle glaucoma: This is the most common type of
glaucoma. It occurs when the trabecular meshwork becomes clogged.
As the fluid builds up, it causes pressure to build within the eye. High
pressure damages the optic nerve.
Symptoms: Most patients do not have any symptoms in the early
stages of the condition. However, if it is not treated early, gradual loss
of sight starting with peripheral vision will occur – before finally
resulting in permanent vision loss. In most cases of primary open
angle glaucoma, medications can control the condition if it is
diagnosed and treated in its early stage.

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Normal-tension glaucoma: Some patients develop glaucoma with
eye pressure below 22 mmHg. Important risk factors include:
o A family history of normal-tension glaucoma
o Being of Japanese descent
o Having a personal history of cardiovascular disease,
hemodynamic crisis, low blood pressure at night, abnormal
blood coagulation, migraines, or immune factors
Angle-closure glaucoma: This type of glaucoma is less common than
primary open angle glaucoma. It occurs when the iris bulges forward
to block the drainage angle formed by the cornea and iris. As a result,
fluid is unable to circulate through the eye and pressure increases.
Symptoms: In angle-closure glaucoma, the symptoms vary:
 angle-closure glaucoma: This is a considered a Acute medical
emergency due to the sudden extreme increase in eye pressure.
Symptoms include severe headache and eye pain, eye redness,

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watery eyes, sensitivity to light, blurred vision, halos around
lights, nausea and vomiting.
 Sub-acute angle-closure glaucoma: Symptoms are mild and
intermittent. Patients may only have a headache. It is difficult to
diagnose this form of glaucoma without an eye screening.
Chronic acute angle-closure glaucoma: Patients usually have no
symptoms in the early stage of this form of glaucoma, as it
develops very slowly.
Congenital glaucoma: This form of glaucoma is already present in
babies and children, as it can be inherited. While it is rare, the
symptoms are severe and hard to be controlled. Permanent vision loss
occurs if it is not treated in its early stage.
Secondary glaucoma: This type of glaucoma is caused by an eye
disease or underlying medical condition, including an eye injury, eye
inflammation, eye tumor, advanced cataract, diabetes, hyper tension
and the use of certain medications such as steroids. Treatments vary,
depending on the cause of the high eye pressure.
Glaucoma suspect: In some cases, patients have an optic nerve or
visual field that looks suspicious for glaucoma, requiring regular
medical attention.

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NON-PHARMACOLOGICAL TREATMENT
1. Eat healthy diet.
2. Maintain good health.
3. Avoid stress.
4. Go for aromatic therapy.
5. Avoid cigarette, caffeine & alcohol.
6. Avoid allergic foods.
7. Eat fruits and leafy vegetables (especially citrus fruits).

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PHARMACOLOGICAL TREATMENT
Ophthalmic Drugs for Glaucoma Lowering IOP by
1-REDUCING PRODUCTION OF AQUEOUS HUMOR:
a) β- adrenergic Blockers.
b) α2Adrenergic Agonists
c) Carbonic Anhydrase Inhibitors.
2-DECREASING THE RESISTANCE TO OUTFLOW OF
AQUEOUS HUMOR THROUGH TRABECULAR
MESHWORK:
Cholinergic and cholinesterase inhibitors.
3-IMPROVING THE OUTFLOW OF AQUEOUS HUMOR:
a) Prostaglandins (uveoscleral outflow)
b)sympathomimetics (trabecular meshwork and uveoscleral
outflow).

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A. TOPICAL β-ADRENERGIC BLOCKING DRUGS
Includes:
1. Non-selective: Timolol, Levobunolol, Metipranolol & Carteolol.
2. β1-Selective: Betaxolol.
TIMOLOL
-Mechanism of action: timolol blocks response to beta adrenergic
stimulation to β1 and β2 receptors of ciliary muscle and decreases the
production of aqueous muscle.
-Dosing: 1 drop BID
-Contraindicaions:
1- Bronchial asthma (COPD)
2- Heart block.
3- Sinus bradicardia.
4- 2nd
or 3rd
degree heart failure.
-Drug interactions:
1- Hypotensive effect may be antagonised by NSAIDs
2- Additive effect with other antihypertensive drugs.
-Side effects:
1- Bronchospasm.
2- Bradycardia.
3- Hypotension.
4- CHF exacerbation.
5- Mask hypoglycemia.
6- Tachyphylaxis (20% to 50% of pts)
. -Nasolacrimal occlusion is a technique to decrease amount of drug
absorbed systemically and decrease the incidence of side effects and
improve medication effectiveness.

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B. α2-ADRENERGIC AGONISTS
-Includes: Brimonidine(more selective) & Apraclonidine.
-Brimonidine: (Effective long-term monotherapy / adjunctive
therapy)
- Apraclonidine (Short-term use only due to high rate of
tachyphylaxis)
Used for prevention & ttt of postsurgical IOP elevations.
BRIMIDONE
-Mechanism of action: It is a α2 adrenergic agonist through the
activation of G protein coupled receptor inhibit activity of adenylate
cyclise. This reduces cAMP and hence aqueous humour production
by ciliary body. Vasoconstriction due to ↓ed in aqueous humor flow.
The increased uveoscleral outflow from prolonged use may be
explained by increased prostaglandin release due to α adrenergic
stimulation. This may lead to relaxed ciliary muscle and increased
uveoscleral outflow.
-Dosing: 1 drop BID to TID.
-Contraindication:
1. Hypersensitivity.
2. Patients receiving MOA inhibior therapy.
-Drug interactions:
1. Additive effect with CNS depressants.
2. If used with cardiac tonic it increases effect of cardiac tonics.
-Side effects:
1- Blepharoconjunctivitis.
2- Foreign body sensation.
3- Papillary mydrasis (Apraclonidine).
4- Eyelid retraction (Apraclonidine).
5- Mild systemic hypotension and lethargy.
( Brimonidine pass BBB ).

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C. CARBONIC ANHYDRASE INHIBITORS
1- Topical agents :
-Includes: Dorzolamide and Brinzolamide.
DORZOLAMIDE
-Mechanism of action: The mechanism of diuresis involves the
proximal tubule of the kidney. The enzyme carbonic anhydrase is
found here, allowing the reabsorption of bicarbonate, sodium, and
chloride. By inhibiting this enzyme, these ions are excreted, along
with excess water, lowering blood pressure, intracranial pressure, and
intraocular pressure. By excreting bicarbonate.
-Dosing: 1 drop BID with beta blockers or TID alone.
Combination of Timolol+Dorzolamide is commonly used
-Contraindications:
1. Patients with history of hypersensitivity to sulphonamides.
2. It reduces phenytoin excretion, hence increasing the potential for
toxicity.
2. It reduces plasma levels of primidone. Hence reducing
anticonvulsant effect.
-Drug interactions:
1-May increase adverse/toxic effects of other carbonic anhydrase
inhibitors.
2-May increase serum concentration of α/β agonist(indirect acting).
-Side effects:
1-Burning.
2-Stinging.
3-Itching.
4-Dry eyes.
5-Conjunctivitis

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2- Orally-administered CAIs:
-Includes: Acetazolamide , Dichlorphenamide, and Methazolamide.
ACETAZOLAMIDE
-Mechanism of action: It is a highly specific carbonic anhydrase II
(CA II) inhibitor, which is the main CA isoenzyme involved in
aqueous humor secretion. Inhibition of CA-II in ciliary processes of
the eye decreses aqueous humor secretions, presumably by slowing
the formation of bicarbonate ion with subsequent reduction in sodium
and fluid transport.
-Dosing: 250-1000mg daily , given in divided doses for amount over
250mg.
-Contraindications:
1-Hypokalemia.
2-Hyponatremia.
-Drug interactions:
1-Dorzolamide may increase the hypotensive activities of Acebutolol.
2-Atenolol may increase the hypotensive activities of Dorzolamide.
-Side effects:
1-Paresthesia of hands and feet.
2-Hypokalemia and hyponatremia.
3-Nephrolethiasis and renal failure.
4-Hepatic insufficiency.
5-Blooddyscrasias from bone marrow suppression

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D. CHOLINERGICS AND CHOLINESTERASE
INHIBITORS
1- Cholinergics:
-Includes: Pilocarpine and Carbachol.
PILOCARPINE.
Mechanism of action: Pilocarpine is a cholinergic
parasympathomimetic agent. It increase secretion by the exocrine
glands, and produces contraction of the iris sphincter muscle and
ciliary muscle (when given topically to the eyes) by mainly
stimulating muscarinic receptors.
-Dosing: 1–2 drops TID or QID.
-Used with caution for closed angle
-Contraindications:
1. Severe myopia to avoid detachment.
2. pregnancy
3. Severe myopia to avoid detachment
-Drug interactions:
1. concurrent use with β blockers may lead to toxicity.
2. concomitant admin. of 2 miotics may ↑es risk of toxic reactions.
-Side effects:(due to miosis) 1-Brow ache and headache.
2-Affect night vision.
3-Bradycardia at high conc.
4-Retinal detachment.

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2- Cholinesterase inhibitors:
-Includes: Echothiophate iodide &Demecarium bromide.
-Irreversible AchE inhibitors e’ long durations of action.
-Stop at least 1 week before general surgical procedure.
ECHOTHIOPHATE IODIDE
-Mechanism of action: Echothiophate Iodide is a long-acting
cholinesterase inhibitor for topical use which enhances the effect of
endogenously liberated acetylcholine in iris, ciliary muscle, and other
parasympathetically innervated structures of the eye. Echothiophate
iodide binds irreversibly to cholinesterase, and is long acting due to
the slow rate of hydrolysis by cholinesterase. It causes miosis,
increase in facility of outflow of aqueous humor, fall in intraocular
pressure, and potentiation of accommodation.
- Dosing: 1 drop BID.
-Contraindications:
 Parkinson Symptoms
 Detachment of the Retina of the Eye
 high blood pressure
 heart attack within the last 30 days
 asthma
 seizures
-Drug interactions:
1. The therapeutic efficacy of Echothiophate can be decreased
when used in combination with Dipyridamole
2. Echothiophate may increase the neuromuscular blocking
activities of Succinylcholine..
-Side effects:
1- Depletion of systemic cholinesterase and pseudocholinesterase.
2- Cataracts: occur in 30–50% of elderly patients using these drugs
for at least 6 months

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E. PROSTAGLANDINS
Includes: Latanoprost, Bimatoprost, Travoprost.
-First-line alternatives to topical β-blockers.
-Patients required to lower IOP by greater than 25%.
-Lower IOP by 25% to 35% (Lower nocturnal IOP).
LATANOPROST
Mechanism of action: latanoprost is an ester prodrug that is
activated to the free acid in the cornea. Also like the related drugs,
latanoprost acid is an analogue of prostaglandin F2α that acts as a
selective agonist at the prostaglandin F receptor. Prostaglandins
increase the sclera's permeability to aqueous fluid. So, an increase in
prostaglandin activity increases outflow of aqueous fluid thus
lowering intraocular pressure.
Dosing: 1 drop once a day at bedtime
Containdications
1-pregnancy
2-close angle glaucoma
3-ocular trauma or surgery
4-Hepatic or renal failure
Drug interaction:
 The concomitant use of latanoprost and bimatoprost or other
prostaglandins may result in increased intraocular pressure.
 Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce or
increase the effect of latanoprost.[9][10]
Side effects:
1- Conjunctival hyperemia.
2- Stinging on instillation
3- Inc. in iris pigmentation.
4- Hypertrichosis.
5- Eyelashes darkening.

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F. SYMPATHOMIMETICS
Includes: dipivefrin hcl , epinephrine.
-IOP is reduced by 20–25%.
-Last line agents due to their systemic S.E. Profile.
EPINEPHRINE
Mechanism of action: It is a direct acting sympathomimetic amine
and it acts by decreasing aqueous humor formation in the early phase
presumably due to its α-adrenergic effect. It also increases trabecular
outflow probably by stimulating β2 -adrenergic receptors in the
trabecular meshwork.
Dosing:1 drop BID.
Intolerance to ocular adverse effects leads to discontinuation of
epinephrine in 80% of patients.
Contraindications:
1-In narrow angle glaucoma
2 – may worsening of symptoms in patient with parkinsons
3- patients with heart problems
Drug interactions:
1 –Epinephrine and dopamine both decreses sedation.
2 – doxepin increases effect of epinephrine.
Side effects:
1 -Burning, tearing.
2-Reactive conjunctival hyperemia.
3-Allergic blepharoconjunctivitis.
4-Mydriasis → Blurring of vision.

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REFERENCES
 Clinical pharmacy and therapeutics – Roger and walker.
 Pharmacotherapy: A pathological approach – Joseph T. Dipiro
et al. Appleton & Lange.
 Pathologic basis of disease – Robins SL.
 Internet and wikipedia.