Dr. Sridevi Rajeeve
Angle of anterior
Role in aqueous drainage.
Root of iris
Anterior-most part of ciliary body
flow chart depicting drainage of aqueous
definition & classification
Definition:- Group of disorders characterized by a progressive optic
neuropathy resulting in a characteristic appearance of the optic disc and a
specific pattern of irreversible visual field defects that are associated frequently
but not invariably with raised intraocular pressure (IOP)
Classification:- Clinico-etiologically glaucoma may be classified as
(A) Congenital and developmental glaucomas
1. Primary congenital glaucoma (without associated anomalies)
2. Developmental glaucoma (with associated anomalies).
(B) Primary adult glaucomas
1. Primary open angle glaucomas (POAG)
2. Primary angle closure glaucoma (PACG)
3. Primary mixed mechanism glaucoma
(C) Secondary glaucomas
etiology (in Brief)
A. Primary insults
1. Raised intraocular pressure (Mechanical theory)
2. Pressure independent factors (Vascular insufficiency theory)
i. Failure of auto-regulatory mechanism of blood flow
iii. Systemic hypotension
iv. Other factors (acute blood loss and abnormal coagulability
B. Secondary insults (Excito-toxicity theory)
glutamate (excitatory toxin),
oxygen free radicals, or nitric oxide which are released
when RGCs undergo death due to primary insults
Site of action of miotics in angle closure glaucoma:
Contraction of sphincter pupillae, removes pupillary
block and reverses obliteration of iridocorneal angle
Site of action of miotics in open angle glaucoma:
Contraction of ciliary muscle pulls on scleral spur
and improve trabecular patency
Site of alpha1 alpha2 agonist and beta blockers
Site of action of prostaglandins and possibly
adrenalin: Increase uveo-scleral outflow by altering
permeability and or pressure gradients
Site of action of Adrenaline: possibly increases
aqueous conductivity trabecular filtering cells (Beta
Depending upon the mode of action, these can be classified as follows:
1. Direct-acting or agonists e.g., Pilocarpine.
2. Indirect-acting parasympathomimetics or cholinesterase inhibitors:
Indirect destruction of the enzyme cholinesterase; spares the naturally
acting Acetylcholine for its actions. Types;
(i) Reversible (e.g., Physostigmine)
(ii) Irreversible (e.g., Echothiophate iodide, Demecarium and
3. Dual-action parasympathomimetics, i.e., which act as both a muscarinic
agonist as well as a weak cholinesterase inhibitor e.g., Carbachol.
Mechanism of action
1. In primary open-angle glaucoma: Miotics reduce IOP by
enhancing the aqueous outflow facility. This is achieved by
changes in the trabecular meshwork produced by a pull exerted
on the scleral spur by contraction of the longitudinal fibres of
2. In primary angle-closure glaucoma: Miotics reduce the IOP
due to their miotic effect by opening the angle. The mechanical
contraction of the pupil moves the iris away from the trabecular
1. Systemic side-effects:
Bradycardia, increased sweating, diarrhoea, excessive salivation and anxiety.
2. Local side-effects: Encountered more frequently with long-acting
Miotics (i.e. irreversible cholinesterase inhibitors).
Problems due to miosis itself (e.g. reduced visual acuity in the presence of polar cataract,
impairment of night vision and generalized contraction of visual fields)
Spasm of accommodation - Myopia and frontal headache, retinal detachment
Iris cyst formation
1. Pilocarpine. Direct-acting parasympathomimetic drug. Most commonly used.
Indications: (i) Primary open-angle glaucoma
(ii) Acute angle-closure glaucoma
(iii) Chronic synechial angle-closure glaucoma.
Contraindications: (i) Inflammatory glaucoma
(ii) Malignant glaucoma
(iii) Known allergy.
Available preparations and dosage are:
(a) Eyedrops are available in 1%, 2% and 4% strengths. In POAG, therapy is usually
initiated with 1 percent concentration. The onset of action occurs in 20 minutes,
peaks in 2 hours and duration of effect is 4-6 hours. Therefore, the eyedrops are
usually prescribed every 6 or 8 hourly.
(b) Ocuserts are available as pilo-20 and pilo-40. These are changed once in a week.
Pilo-20 is generally used in patients controlled with 2 percent or less concentration
of eyedrops; and pilo-40 in those requiring higher concentration of eyedrops.
(c) Pilocarpine gel (4%) is a bedtime adjunct to the sridevirajeeve_oph dthaalymtoilmogye medication. 14
2. Carbachol. It is a dual-action (agonist as well as weak cholinesterase
Indications. It is a very good alternative to pilocarpine in resistant or
Preparations. It is available as 0.75 percent and 3 percent eyedrops.
Dosage: The action ensues in 40 minutes and lasts for about 12 hours.
Therefore, the drops are instilled 2 or 3 times a day.
3. Echothiophate iodide (Phospholine iodide). It is a long acting
Indications: It is very effective in POAG.
Preparations: Available as 0.03, 0.06 and 0.125 percent eye- drops.
Dosage: The onset of action occurs within 2 hours and lasts up to 24 hours.
Therefore, it is instilled once or twice daily.
4. Demecarium bromide. It is similar to ecothiopate iodide and is used as
0.125 percent or 0.25 per- cent eyedrops.
5. Physostigmine (eserine). It is a reversible (weak) cholinesterase
inhibitor. It is used as 0.5 percent ointment twice a day.
B. symPAthomimetic drugs
Depending upon the mode of action;
1. Both Alpha and Beta-receptor Stimulators e.g. Epinephrine.
2. Direct Alpha-Adrenergic Stimulators e.g. Norepinephrine
3. Indirect Alpha-Adrenergic Stimulators e.g. Pargyline.
4. Beta-Adrenergic Stimulator e.g. Isoproterenol.
Mechanisms of action
1. Increased aqueous outflow results by virtue of both alpha and beta-receptor
2. Decreased aqueous humour production occurs due to stimulation of alpha-receptors
in the ciliary body.
1. Systemic side-effects:
Hypertension, tachycardia, headache, palpitation, tremors, nervousness and
2. Local side-effects:
Burning sensation, reactive hyperaemia of conjunctiva, conjunctival
pigmentation, allergic blepharo conjunctivitis, mydriasis and cystoid macular
oedema (in aphakics).
1.Epinephrine. Direct-acting sympathomimetic drug stimulates both alpha
and beta- adrenergic receptors.
Indications: (i) POAG - DoC
(ii) Secondary glaucomas.
Preparations: It is available as 0.5 percent, 1 percent and 2 percent eyedrops.
Dosage: The action starts within 1 hour and lasts up to 12-24 hours.
Therefore, it is instilled twice daily.
2. Dipivefrine (Propine or dipivalylepinephrine): Prodrug which is converted
into epinephrine after its absorption into the eye. More lipophilic than
epinephrine and thus its corneal penetration is increased by 17 times.
Preparations: It is available as 0.1 percent eyedrops
Dosage : Action and efficacy is similar to 1 percent epinephrine.
Instilled twice daily.
3. Clonidine hydrochloride. It is a centrally-acting systemic antihypertensive
agent, which has been shown to lower the IOP by decreasing aqueous
humour production by stimulation of alpha-receptors in the ciliary body.
Preparations and dosage. It is used as 0.125 percent and 0.25 percent eye
drops, twice daily.
4. Brimonidine (0.2%). Selective alpha-2 adrenergic agonist. Lowers IOP by
decreasing aqueous production and enhancing uveoscleral outflow.
Additive effect to betablockers.
Dosage: It has a peak effect of 2 hours and action lasts for 12 hours; so it is
administered twice daily.
Prophylactically for prevention of IOP elevation following laser
trabeculoplasty, YAG laser iridotomyand sridevirajeevpe_oopshtteharlmioolrog cyapsulotomy 19
C. . Beta-adrenergiC BloCker
The most frequently used antiglaucoma drugs.
Commonly used preparations are Timolol and Betaxolol. Other available
preparations include Levobunolol, Carteolol and Metipranolol.
Mechanism of action. Timolol and levobunolol are non-selective beta-
1 (Cardiac) and beta-2 (smooth muscle, pulmonary) receptor blocking
agents. The drugs timolol and levobunolol lower IOP by blockade of beta-2
receptors in the ciliary processes, resulting in decreased aqueous
Indications. Beta adrenergic blockers are useful in all types of glaucomas,
viz., developmental, primary and secondary; narrow as well as open angle.
Unless contraindicated due to systemic diseases,
betablockers are frequently used as the first
choice drug in POAG and all secondary
Use with caution in patients with Bronchial Asthma, Emphysema, COPD, Heart blocks,
Congestive Heart Failure or Cardiomyopathy. Betaxolol is the beta blocker, of choice in
patients at risk for pulmonary diseases. The other contraindication includes known drug
Beta-blockers have very good synergistic effect when combined with Miotics; and are
thus often used in combination in patients with POAG, unresponsive to the single drug.
Ocular side-effects are not frequent. These include burning and conjunctival
hyperaemia, superficial punctate keratopathy and corneal anaesthesia.
Systemic side-effects are also unusually low.
(i) Cardiovascular effects which result from blockade of beta-1 receptors. These
are bradycardia, arrhythmias, heart failure and syncope.
(ii) Respiratory reactions: bronchospasm and airway obstruction, especially in
asthmatics. These occur due to blockade of beta-2 receptors; and thus are not
known with betaxolol.
(iii) Central nervous system effects. Depression, anxiety, confusion, drowsiness,
disorientation, hallucinations, emotional lability, dysarthria and so on.
3. Miscellaneous effects are nausea, diarrhoea, decreased libido, skin rashes, alopecia
and exacerbation of myasthenia gravis.
1. Timolol. It is a non-selective beta-1 and beta-2 blocker. It is available as
0.25 per cent and 0.5 percent eye drops. The salt used is timolol maleate.
Its action starts within 30 minutes, peak reaches in 2 hours and effects last
up to 24 hours.
2. Betaxolol: It is a cardioselective beta-blocker and thus can be used safely
in patients prone to attack of bronchial asthma.
3. Levobunolol: 0.5%
4. Carteolol :1-2%
5. Metipranolol : 0.1, 0.3, 0.6%
d .CarBoniC anhydrase
Potent and most commonly used Systemic Anti-Glaucoma drugs. These
include Acetazolamide (most frequently used), Methazolamide,
Dichlorphenamide and Ethoxzolamide.
Mechanism of action. CAIs inhibit the enzyme carbonic anhydrase which is
related to the process of aqueous humour production. Thus, CAIs lower
the IOP by reducing the aqueous humour formation.
Indications. These are used as additive therapy for short term in the
management of all types of acute and chronic glaucomas. Their long-term
use is reserved for patients with high risk of visual loss, where all other
1. Paresthesias of the fingers, toes, hands, feet and around the mouth.
2. Urinary frequency
3. Serum electrolyte imbalance
4. GI symptoms
Preparations and doses
1. Acetazolamide (diamox). It is available as tablets,
capsules and injection for intravenous use. The acetazolamide 250 mg
tablet is used 6 hourly. Its action starts within 1 hour, peak is reached in
4 hours and the effect lasts for 6-8 hours.
e. hyperosmotiC agents
Mechanism of action:
Hyper-osmotic agents increase the plasma tonicity. Thus, the osmotic
pressure gradient created between the blood and vitreous draws sufficient
water out of the eyeball, thereby significantly lowering the IOP.
These are used as additive therapy for rapidly lowering the IOP in emergency
situations - Acute Angle-Closure Glaucoma or Secondary Glaucomas with very
high IOP. They are also used as a prophylactic measure prior to intraocular
Preparations and doses
1. Glycerol. It is a frequently used oral hyperosmotic agent. Its recommended dose is 1-1.5
gm/kg body weight. It is used as a 50 percent solution. So, glycerol (50 to 80 ml in adults) is
mixed with equal amount of lemon juice (preferably) or water before administering orally. Its
action starts in 10 minutes, peaks in 30 minutes and lasts for about 5-6 hours. It can be given
repeatedly. It is metabolised to glucose in the body. Thus, its repeated use in diabetics is not
2. Mannitol. It is the most widely used intravenous hyperosmotic agent. It is indicated when
the oral agents are felt to be insufficient or when they cannot be taken for reasons such as
nausea. Its recommended dose is 1-2 gm/kg body weight. It is used as a 20 percent solution.
It should be administered very rapidly over 20-30 minutes. Its action peaks in 30 minutes and
lasts for about 6 hours. It does not enter the glucose metabolism and thus is safe in diabetics.
However, it should be used cautiously in hypertensive patients.
3. Urea. When administered intravenously it also lowers the IOP. However, because of lower
efficacy and more side-effects than mannitol, it is not recommended for routine use.
4. Isosorbide. It is an oral hyperosmotic agent, similar to glycerol in action and doses.
However metabolically it is inert and thus can be used repeatedly in diabetics.
F. Prostaglandin analogues
1. Latanoprost (0.005%)It is a synthetic drug which is an ester analogue of
prostaglandin F2-α. It is acts by increasing uveoscleral outflow and by causing
reduction in episcleral venous pressure. It is as effective as timolol. It has additive effect
with pilocarpine and timolol. Its duration of action is 24 hours and is, thus, administered
Side-effects: include Conjunctival hyperaemia, foreign body sensation and increased
pigmentation of the iris.
2. Bimatoprost (0.03%). It is a prostamide which decreases IOP by decreasing
ocular outflow resistance. It is used once a day (OD).
3. Travoprost (0.004%). It is a synthetic prostaglandin F2 analogue and
decreases IOP by increasing uveoscleral outflow of aqueous.
4. Unoprostive isopropyl (0.12%). It is a dolosanoid related in structure to
prostaglandin F2-α. It lowers IOP by increasing uveoscleral outflow of aqueous. It also
increases retinal blood flow.
g. CalCium Channel bloCkers
Calcium channel blockers such as Nifedipine, Diltiazem and Verapamil are
commonly used antihypertensive drugs. Recently, some of these have been
used as anti-glaucoma drugs.
Mechanism of action:
The exact mechanism of lowering IOP of topically used calcium channel
blockers remains to be elucidated. It might be due to its effects on secretory
Verapamil has been tried as 0.125 percent and 0.25 percent eyedrops twice a
Though the IOP lowering effect of verapamil is not superior than the
topical antiglaucoma drugs, it has a place in the mangement of patients with
POAG, where miotics, beta-blockers and sympathomimetics are all
contraindicated e.g., in patients suffering simultaneously from axial cataract,
bronchial asthma and raised blood pressure. It can also be used for additive
effect with pilocarpine and timolol. sridevirajeeve_ophthalmology 29
management in a nutshell…
I] PRIMARY OPEN ANGLE GLAUCOMA
(a) Single Drug Therapy
1. Topical beta-blockers: DoC, 1st line
Timolol maleate, Betaxolol, Levobunolol, Carteolol
2. Latanoprost: 1st line
3. Dorzolamide: 2nd line
4. Pilocarpine: 2nd line
5. Adrenergic drugs: Dipivefrine hydrochloride (combined with beta-blockers
in patients where other drugs are contraindicated)
(b) Combination topical therapy
If one drug is not effective, then a combination of two drugs—one drug
which decreases aqueous production (timolol or other betablocker, or
brimonidine or dorzolamide) and other drug which increases aqueous outflow
(latanoprost or brimonidine or pilocarpine) may be used.
II] ACUTE PRIMARY ANGLE-CLOSURE GLAUCOMA
Medical therapy is instituted as an emergency and temporary measure before
the eye is ready for operation;
1. Systemic hyperosmotic agent intravenous mannitol (1 gm/kg body weight)
2. Acetazolamide 500 mg intravenous injection followed by 250 mg tablet
should be given 3 times a day.
3. Analgesics and anti-emetics
4. Pilocarpine eyedrops 2 percentpilocarpine should be administered every 30
minutes for 1-2 hours and then 6 hourly
5. Beta blocker eyedrops like 0.5 percent timolol maleate or 0.5 percent
betaxolol should also be administered twice a day to reduce the IOP.
6. Corticosteroid eyedrops like dexamethasone or betamethasone should be
administered 3-4 times a day to reduce the inflammation
III] ABSOLUTE PRIMARY ANGLE-CLOSURE
Retrobulbar alcohol injection: It may be given to relieve pain. First, 1 ml of 2
percent xylocaine is injected followed after about 5-10 minutes by
1 ml of 80 percent alcohol. It destroys the ciliary ganglion.