The document discusses various types of drugs used to treat glaucoma, including beta-adrenergic blocking agents, prostaglandins, parasympathomimetic drugs, sympathomimetic drugs, carbonic anhydrase inhibitors, and hyperosmotic agents. It provides details on the mechanism of action, indications, contraindications, and side effects of representative drugs in each class, such as timolol for beta-blockers, latanoprost for prostaglandins, pilocarpine for parasympathomimetics, and glycerol for hyperosmotic agents. The document aims to comprehensively cover the major classes of antiglaucoma medications.

1. DOCTOR OF PHARMACY
II YEAR
GLAUCOMA
170101
CHAPTER-6
Opthomology
Dr. V. Chanukya (Pharm D)

2. 1
Introduction- Eye anatomy

3. Glaucoma
3
Aqueous humor dynamics

4. Glaucoma
Aqueous humor flow
4

5. Antiglaucoma drugs
A. β-Adrenergic blocking agents
B. Prostaglandins and Prostamides
C. Parasympathomimetic drugs (Miotics)
D. Sympathomimetic drugs (Adrenergic agonists)
E. Carbonic anhydrase inhibitors
F. Hyperosmotic agents
G. Calcium channel blockers

6. β-Adrenergic blocking agents
• These are, presently, the most frequently used antiglaucoma drugs.
• The 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 production.
The exact mechanism of action of betaxolol (cardioselective beta-blocker) is
unknown
• Betaxolol has 10 times more affinity for beta-1 than beta-2 receptors.

7. 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 glaucomas.
Contraindications
• These drugs should be used with caution or not at all, depending on the severity of the
systemic disease in patients with bronchial asthma, emphysema, S, 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 allergies.
Additive effects
• 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.

8. • 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. However, these are reported more
often than ocularside-effects.
These include
– Cardiovascular effects -which result from blockade of beta-1 receptors. These are
bradycardia, arrhythmias, heart failure and syncope.
– Respiratory reactions -These include bronchospasm and airway obstruction, especially
in asthmatics. These occur due to blockade of beta-2 receptors; and thus are not known
with betaxolol.
– Central nervous system effects- These include depression, anxiety, confusion,
drowsiness, disorientation, hallucinations, emotional lability, dysarthria and so on.
– Miscellaneous effects -are nausea, diarrhoea, decreased libido, skin rashes, alopecia and
exacerbation of myasthenia gravis.

9. Timolol
• Its action starts within 30 minutes, peak reaches in 2 hours and effects last up to 24 hours.
• The drug is very effective, however, the phenomenon of ‘short-term escape’ and ‘long term drift’
are well known.
Betaxolol
• It is a cardioselective beta1-blocker and thus can be used safely in patients prone to attack of
bronchial asthma; an advantage over timolol.
• It is slightly less effective than timolol in lowering the IOP

10. Ocular prostanoids: prostaglandin analogues
and prostamides
• The prostaglandin analogues, latanoprost, travoprost and tafluprost, are ester compounds
thought to achieve a fall in IOP primarily by increasing the uveoscleral outflow with no
significant effect on other parameters of aqueous humour dynamics, while the prostamide
bimatoprost is thought to increase outflow through both trabecular and uveoscleral
outflow pathways.
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 once daily.
• Its side effects include conjunctival hyperaemia, foreign body sensation and increased
pigmentation of the iris.

11. Bimatoprost (0.03%)
• It is a prostamide which decreases IOP by decreasing ocular outflow
resistance.
• It is used once a day (OD).
Travoprost (0.004%)
• It is a synthetic prostaglandin F2 analogue and decreases IOP by
increasing uveoscleral outflow of aqueous.
Unoprostive isopropyl (0.12%)
• It is a dolosanoid related in structure to prostaglandin F2-α. It lowers
IOP by increasing uveoscleral outflow of aqueous.
• Italso increases retinal blood flow.

12. Tafluprost is the first of the prostanoids available in a preservative- free form.
• In terms of efficacy and safety, it has been shown to be equivalent to a preserved
preparation of tafluprost and useful in patients allergic to, or intolerant of,
benzalkonium chloride.
• Tafluprost as adjunctive therapy to timolol results in consistently greater
reductions in IOP compared with vehicle in patients with glaucoma or OHT that is
inadequately controlled with timolol monotherapy

13. Parasympathomimetic drugs (Miotics)
• Parasympathomimetics, also called as cholinergic drugs, either imitate or potentiate the
effects of acetylcholine.
Classification
Depending upon the mode of action, these can be lassified as follows:
1. Direct-acting or agonists e.g., pilocarpine.
2. Indirect-acting parasympathomimetics or cholinesterase inhibitors
As the name indicates these drugs act indirectly by destroying the enzyme cholinesterase; thereby
sparing the naturally acting acetylcholine for its actions. These drugs have been divided into two
subgroups, designated as reversible (e.g., physostigmine) and irreversible (e.g., echothiophate
iodide, demecarium and diisopropyl-fluoro-phosphate, DFP3) antic-holinesterases.
3. Dual-action parasympathomimetics
which act as both a muscarinic agonist as well as a weak cholinesterase inhibitor e.g., carbachol

14. Mechanism of action
In primary open-angle glaucoma the miotics reduce the
intraocular pressure (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 fibers of ciliary muscle.
2. In primary angle-closure glaucoma these 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 meshwork.

15. Side-effects
1. Systemic side-effects : bradycardia, increased sweating, diarrhoea,
excessive salivation
and anxiety.
2. Local side-effects are encountered more frequently with long-acting
miotics (i.e. irreversible cholinesterase inhibitors).
• These include problems due to miosis itself (e.g. reduced visual acuity in
the presence of polar cataracts, impairment of night vision and
generalized contraction of visual fields), spasm of accommodation which
may cause myopia and frontal headache, retinal detachment, lenticular
opacities, iris cyst formation, mild iritis, lacrimation and follicular
conjunctivitis.

16. Pilocarpine
It is a direct-acting parasympathomimetic drug. It is the most commonly used and the most extensively
studied miotic.
Indications:
(i) Primary open-angle glaucoma
(ii) Acute angle-closure glaucoma
(iii) Chronic synechial angle-closureglaucoma.
Contraindications: inflammatory glaucoma, malignant glaucoma and known allergy.
Available preparations and dosage
(a) Eyedrops are available in 1%, 2% and 4% strengths. In POAG, therapy is usually initiated with 1 percent
concentration.
(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 daytime medication.
Carbachol It is a dual-action (agonist as well as weak cholinesterase inhibitor) miotic. It is a very good
alternative to pilocarpine in resistant or intolerant cases.
Echothiophate iodide (Phospholine iodide) It is a long acting cholinesterase inhibitor. It is very
effective in POAG.

17. Demecarium bromide
It is similar to ecothiopate iodide and is used as 0.125
percent or 0.25 per- cent eyedrops.
Physostigmine (eserine)
It is a reversible (weak) cholinesterase inhibitor. It is
used as 0.5 percent ointment twice a day.

18. Sympathomimetic drugs
Sympathomimetics, also known as adrenergic agonists, act by
stimulation of alpha, beta or both the receptors.
Classification
Depending upon the mode of action, these can be classified as
follows:
1. Both alpha and beta-receptor stimulators e.g., epinephrine.
2. Direct alpha-adrenergic stimulators e.g., norepinephrine and
clonidine hydrochloride.
3. Indirect alpha-adrenergic stimulators e.g., pargyline.
4. Beta-adrenergic stimulator e.g., isoproterenol.

19. Mechanisms of action
• Increased aqueous outflow results by virtue of both alpha and beta-
receptor stimulation.
• Decreased aqueous humour production occurs due to stimulation of alpha-
receptors in the ciliary body.
Side-effects
• Systemic side-effects include hypertension, tachycardia, headache,
palpitation, tremors, nervousness and anxiety.
• Local side-effects are burning sensation, reactive hyperaemia of
conjunctiva, conjunctival pigmentation, allergic blepharo conjunctivitis,
mydriasis and cystoid macular oedema (in aphakics).

20. Epinephrine
This direct-acting sympathomimetic drug stimulates both alpha and
beta- adrenergic receptors.
Indications
It is one of the standard drugs used for the management of POAG.
It is also useful in most of the secondary glaucomas
Dipivefrine(Propine or dipivalylepinephrine)
It is a prodrug which is converted into epinephrine after its
absorption into the eye. It is more lipophilic than epinephrine and thus
its corneal penetration is increased by 17 time

21. Brimonidine (0.2%)
• It is a selective alpha-2 adrenergic agonist and lowers IOP by decreasing aqueous
production and enhancing uveoscleral outflow.
• It has an additive effect to betablockers
Apraclonidine (0.5%, 1%)
• It is also alpha-2 adrenergic agonist like brimonidine. It is an extremely potent ocular
hypotensive drug and is commonly used prophylactically for prevention of IOP elevation
following laser trabeculoplasty, YAG laser iridotomy and posterior capsulotomy. It is of
limited use for long-term administration because of the high rate of ocular side-effects

22. Carbonic anhydrase inhibitors (CAIs)
• These are potent and most commonly used systemic antiglaucoma drugs.
These include acetazolamide (most frequently used), methazolamide,
dichlorphenamide and ethoxzolamide.
Mechanism of action
• As the name indicates 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 treatments fail.

23. Side-effects
Unfortunately, 40-50 percent of patients are unable to tolerate CAIs for long term because of various disabling side-
effects.
These include:
1. Paresthesias of the fingers, toes, hands, feet and around the mouth are experienced by most of the
patients.
2. Urinary frequency may also be complained of by most patients due to the diuretic effect.
3. Serum electrolyte imbalances may occur with higher doses of CAIs. These may be in the form of
(i) Bicarbonate depletion leading to metabolic acidosis. This is associated with ‘malaise symptom
complex’,
which includes: malaise, fatigue, depression, loss of libido, anorexia and weight loss.
(ii) Potassium depletion. It may occur in some patients, especially those simultaneously getting
corticosteroids, aspirin or thiazide diuretics.
(iii) Serum sodium and chloride may be transiently reduced; more commonly with dichlorphenamide.

24. 4. Gastrointestinal symptom complex. It is also very common. It is not related to
the malaise symptom complex caused by biochemical changes in the serum.
Its features include—vague abdominal discomfort, gastric irritation, nausea, peculiar
metallic taste and diarrhoea.
5. Sulfonamide related side-effects of CAIs, seen rarely, include renal calculi, blood
dyscrasias, Stevens-Johnson syndrome, transient myopia, hypertensive nephropathy
and teratogenic effects

25. 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.
2. Dichlorphenamide. It is available as 50 mg tablets. Its recommended dose is 25 to 100 mg three
times a day. It causes less metabolic acidosis but has a sustained diuretic effect.
3. Methazolamide. It is also available as 50 mg tablets.
It has a longer duration of action than acetazolamide. Its dose is 50-100 mg, 2 or 3 times a day.
4. Ethoxzolamide. It is given in a dosage of 125 mg every 6 hours and is similar to acetazolamide in
all aspects.
5. Dorzolamide (2%). It is a topical carbonic anhydrase inhibitor. It is water soluble, stable in solution
and has excellent corneal penetration. It decreases IOP by 22% and has got additive effect with timolol.
It is administered thrice daily. Its side effects include burning sensation and local allergic reaction.
6. Brinzolamide (1%). It is also a topical CAI which decreases IOP by decreasing aqueous
production. It is administered twice daily (BD).

26. Hyperosmotic agents
• These are the second class of compounds, which are administered systemically to
lower the IOP.
• These include: glycerol, mannitol, isosorbide and urea.
Mechanism of action
• Hyperosmotic 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.
Indications
These are used as additive therapy for rapidly lowering the IOP in emergency
situations, such as acute angle-closure glaucoma or secondary glaucomas with very
high IOP.
They are also used as a prophylactic measure prior to intraocular surgery.

27. 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 metabolized to glucose in the body. Thus, its repeated use in
diabetics is not recommended.
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.

28. 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.
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.

29. 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 ciliary epithelium.
Preparations.
Verapamil has been tried as 0.125 percent and 0.25 percent eye drops
twice a day.

30. Indications
• Though the IOP lowering effect of verapamil is not
superior than the standard 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.

31. Antiglaucoma drugs:Mechanism of lowering IOP
Drugs which increase trabecular outflow
• Miotics (e.g., pilocarpine)
• Epinephrine, Dipivefrine
• Bimatoprost
Drugs which increase uveoscleral outflow
• Prostaglandins (latanoprost)
• Epinephrine, Dipivefrine
• Brimonidine
• Apraclonidine
Drugs which decrease aqueous production
• Carbonic anhydrase inhibitors (e.g., acetazolamide,dorzolamide)
• Alpha receptor stimulators in ciliary process (e.g., epinephrine, dipivefrine, clonidine, brimonidine,
apraclonidine).
• Beta blockers (e.g., timolol, betaxolol, levobunolol)
Hyperosmotic agents (e.g., glycerol, mannitol, urea)

32. Sites of action of ocular hypotensive drugs
1. Site of action of miotics in angle closure
glaucoma: contraction of sphincter pupillae
removes pupillary block and reverses obliteration
of iridocorneal angle
2. Site of action of miotics in open angle glaucoma:
contraction of ciliary muscle pulls on scleral spur
and improves trabecular patency.
3. Site of action of (a) β blockers (b) α1 agonists (c)
α2 agonists (d) carbonic anhydrase inhibitors: all
reduce aqueous secretion by ciliary body
4. Site of action of prostaglandins and possibly
adrenaline: increase uveoscleral outflow by
altering permeability and/or pressure gradients.
5. Site of action of adrenaline: possibly increases
aqueous conductivity of trabecular filtering cells
(β2 action)

33. • Location of α1, α2 and β2 adrenergic receptors and of carbonic anhydrase enzyme
(molecules which are targets of drug action for reducing aqueous formation) in the
processes of the ciliary body
• α1 adrenoceptors constrict ciliary vessels and reduce aqueous production
• α2 adrenoceptors located on ciliary epithelium reduce aqueous secretion.
• β2 adrenoceptors located on ciliary epithelium enhance aqueous secretion via
increased cAMP. Their blockade reduces secretion.
• Carbonic anhydrase present within ciliary epithelial cells generates HCO3¯ ion
which is secreted into aqueous humor

34. POAG Treatment
Therapeutic choices include:
• Medical therapy,
• Argon or diode laser trabeculoplasty
• Filteration surgery

35. Basic principles of medical therapy of POAG
Identification of target pressure.
• From the baseline evaluation data a ‘target pressure’ (below which glaucomatous
damage is not likely to progress) should be identified for each patient.
• The target pressure is identified taking into account the severity of existing
damage, the level of IOP, age, and general health of the patient.
• Although it is not possible to predict the safe level of IOP, however, progression is
uncommon if IOP is maintained at less than 16 to 18 mm of Hg in patients having
mild to maderate damage.
• Lower target pressures (12-14 mmHg) are required in patients with severe damage.

36. Single drug therapy.
• One topically instilled antiglaucoma drug should be
chosen after due consideration to the patient’s personal
and medical factors.
• If the initial drug chosen is ineffective or intolerable, it
should be replaced by the drug of second choice.
Combination therapy
• If one drug is not sufficient to control IOP then a
combination therapy with two or more drugs should be
tried.

37. Monitoring of therapy
Monitoring by disc changes and field changes and
tonometry is most essential on regular follow-up.
In the event of progress of glaucomatous damage
the target pressure is reset at a lower level.

38. Medical therapy
• The initial therapy of POAG is still medical, with
surgery as the last option.

39. Single drug therapy
Topical beta-blockers are being recommended as the first drug of choice for medical therapy of POAG in
poors and average income patients. These lower IOP by reducing the aqueous secretion due to their effect
on beta - receptors in the ciliary processes.
Preparations. In terms of effectiveness, there is little difference between various beta-blockers.
However, each offers a slight advantage over the other, which may help in choosing the particular
medication as follows:
Timolol maleate (0.25, 0.5% : 1-2 times/day) is most popular as initial therapy. However, it should not be
used in patients having associated bronchial asthma and/or heart blocks.
Betaxolol (0.25% : 2 times/day). Being a selective beta-1 blocker it is preferred as initial therapy in
patients with cardiopulmonary problems.
Levobunolol (0.25, 0.5% : 1-2 times/day). Its action lasts the longest and so is more reliable for once a
day use than timolol.
Carteolol (1%: 1-2 times/day). It raises triglycerides and lowers high density lipoproteins the least.
Therefore, it is the best choice in patients with POAG having associated hyperlipidemias or atherosclerotic
cardiovascular disease.

40. Pilocarpine (1, 2, 4%: 3-4 times/day).
• It is a very effective drug and had remained as the sheet anchor in the medical
management of POAG for a long time.
• However, presently it is not being preferred as the first drug of choice or even as
second choice because of its adverse effects in young people but tolerated well in
old patients.
• Therefore, presently pilocarpine is being considered only as an adjunctive therapy
where other combinations fail and as second choice in poor patients.
Mechanism of action.
• Pilocarpine contracts longitudinal muscle of ciliary body and opens spaces in
trabecular meshwork, thereby mechanically increasing aqueous outflow.

41. Latanoprost (0.005%: once daily)
• It is a prostaglandin by nature and decreases the IOP by
increasing the uveo-scleral outflow of aqueous.
• Presently, it is being considered the drug of first choice for the
treatment of POAG (provided patient can afford to buy it).
• Therefore, it is a very good adjunctive drug to beta-blockers,
dorzolamide and even pilocarpine when additional therapy is
indicated.

42. Adrenergic drugs
1. Epinephrine hydrochloride (0.5, 1, 2%: 1-2 times/day)
2. Dipivefrine hydrochloride (0.1%: 1-2 times/day)
These drugs lower the IOP by increasing aqueous outflow by stimulating beta
receptors in the aqueous outflow system.
• These are characterized by a high allergic reaction rate.
• For these reasons, epinephrine compounds are no longer being used as first
line or second line drug.
• However, dipivefrine may be combined with beta-blockers in patients
where other drugs are contraindicated.

43. 3. Brimonidine (0.2% : 2 times/day)
• It is a selective alpha-2-adrenergic agonist and
lowers IOP by decreasing aqueous production.
• Because of increased allergic reactions and
tachyphylaxis rates it is not considered the
drug of first choice in POAG.
• It is used as second drug of choice and also for
combination therapy with other drugs.

44. Dorzolamide (2%: 2-3 times/day)
• It is a recently introduced topical carbonic
anhydrase inhibitor which lowers IOP by
decreasing aqueous secretion.
• It has replaced pilocarpine as the second line
of drug and even as an adjunct drug.

45. 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 increase aqueous outflow (latanoprost or pilocarpine) may be used.
• Combination of timolol 0.5% and dorzolamide 2% (Cosopt®) was the first topical ocular
hypotensive combination to be marketed. It is indicated in the treatment of elevated IOP in
patients with open-angle glaucoma or pseudoexfoliative glaucoma when topical β-blocker
monotherapy is not sufficient.
• Combination of timolol 0.5% and latanoprost 0.005%, marketed as Xalacom®, was first
launched in the UK in 2001, shortly before the launch of travoprost and bimatoprost.
• Xalacom® is indicated for the reduction of IOP in patients with open-angle glaucoma and
OHT who are insufficiently responsive to topical beta-blockers or prostaglandin analogues.

46. • A combination of timolol 0.5% with brimonidine 0.2% is marketed as Combigan® and is
indicated for the reduction of IOP in patients with COAG or OHT who are insufficiently
responsive to topical beta-blockers.
• A fixed combination of travoprost 0.004% and timolol 0.5% (DuoTrav®) has been
shown to be more effective than either of its components. The fixed combination of
travoprost and timolol is indicated to decrease IOP in patients with open angle glaucoma or
OHT who are insufficiently responsive to topical β-blockers or prostaglandin analogues.
• A fixed combination of bimatoprost 0.03% and timolol 0.5% (Ganfort®) is available for
the reduction of IOP in patients with open-angle glaucoma or OHT who are insufficiently
responsive to topical β-blockers or prostaglandin analogues
• A fixed combination of brinzolamide 1% and timolol 0.5% (Azarga®) is a recently
launched combination topical ocular hypotensive presentation. The combination is indicated
to reduce IOP in adult patients with open-angle glaucoma or OHT for whom monotherapy
has produced insufficient IOP reduction.

47. Role of oral carbonic anhydrase
inhibitors in POAG
• Acetazolamide and methazolamide are not
recommended for long-term use because of
their side effects.
• However, these may be added to control IOP
for short term.

50. Argon or diode laser trabeculoplasty (ALT or DLT)
• It should be considered in patients where IOP is uncontrolled despite maximal
tolerated medical therapy. It can also be considered as primary therapy where there
is non-compliance to medical therapy.
Technique and role of ALT in POAG
• It has an additive effect to medical therapy. Its hypotensive effect is caused by
increasing outflow facility, possibly by producing collagen shrinkage on the inner
aspect of the trabecular meshwork and opening the intratrabecular spaces.
• The treatment regimen usually employed consists of 50 spots on the anterior half
of the trabecular meshwork over 180°.

51. Argon or diode laser trabeculoplasty (ALT or
DLT)
Complications
• These include transient acute rise of IOP, which can be prevented by pretreatment with
pilocarpine and/or acetazolamide; and inflammation which can be lessened by use of topical
steroids for 3-4 days. Less commonly haemorrhage, uveitis, peripheral anterior synechiae and
reduced accommodation may occur

52. Surgical therapy
Indications
1. Uncontrolled glaucoma despite maximal medical therapy and laser
trabeculoplasty.
2. Non-compliance of medical therapy and non availability of ALT.
3. Failure with medical therapy and unsuitable for ALT either due to
lack of cooperation or inability to visualize the trabeculum.
4. Eyes with advanced disease i.e., having very high IOP, advanced
cupping and advanced field loss should be treated with filtration
surgery as primary line of management.

53. Types of surgery
• Surgical treatment of POAG primarily consists of a fistulizing (filtration)
surgery which provides a new channel for aqueous outflow and successfully
controls the IOP (below 21 mm of Hg).
• Trabeculectomy is the most frequently performed filtration surgery now-a-
days.

54. FILTERING OPERATIONS
Filtering operations provide a new channel for aqueous
outflow and successfully control the IOP
(below 21 mm of Hg).
Fistulizing operations can be divided into three groups :
1. Free-filtering operations (Full thickness fistula).
• These are no longer performed now-a-days, because of high
rate of postoperative complications. Their names are
mentioned only for historical interest.

55. 2. Guarded filtering surgery (Partial thickness fistula e.g., trabeculectomy).
3. Non-penetrating filtration surgery e.g., deep sclerectomy and
viscocanalostomy.
Trabeculectomy
Trabeculectomy, first described by Carain in 1980 is the most frequently performed partial
thickness filtering surgery till date.
Indications
1. Primary angle-closure glaucoma with peripheral anterior synechial involving more than
half of the angle.
2. Primary open-angle glaucoma not controlled with medical treatment.
3. Congenital and developmental glaucomas where trabeculotomy and goniotomy fail.
4. Secondary glaucomas where medical therapy is not effective.

56. 56
Angle – closure Glaucoma
(Acute Glaucoma)

57. Management
• It is essentially surgical.
• However, medical therapy is instituted as an emergency and
temporary measure before the eye is ready for operation.
• The goal of initial therapy for acute CAG with high IOP is rapid
reduction of the IOP to preserve vision and to avoid surgical or laser
iridectomy on a hypertensive, congested eye.
• Iridectomy (laser or surgical) is the definitive treatment of CAG;
it produces a hole in the iris that permits aqueous humor flow to
move directly from the posterior chamber to the anterior chamber,
opening up the block at the trabecular meshwork.

58. • Drug therapy of an acute attack typically involves
administration of
1. Hyperosmotic agents
2. Topical or systemic CAI)
3. Pilocarpine
4. β-blockers
5. α2-agonist
6. Prostaglandin F2α analog,
7. Corticosteroid eye drops

59. Medical therapy
• Hyperosmotic agent Oral glycerin 1 to 2 g/kg can be used if an oral agent is
tolerated or else intravenous mannitol (1 gm/kg body weight) should be given
initially to lower IOP.
• Acetazolamide (a carbonic anhydrase inhibitor) 500 mg intravenous
injection followed by 250 mg tablet should be given 3 times a day. Analgesics and
anti-emetics as required.
• Pilocarpine eyedrops should be started after the IOP is bit lowered by
hyperosomtic agents. At higher pressureiris sphincter is ischaemic and unresponsive
to pilocarpine. Initially 2 percent pilocarpine should be administered every 30
minutes for 1-2 hours and then 6 hourly.

60. Angle closure glaucoma and its reversal by
Pilocarpine
A. Mydriasis occurs in an eye with narrow iridocorneal angle and iris makes contact
with lens blocking passage of aqueous from posterior to anterior chamber.
B. Pressure builds up behind iris which bulges forward and closes the iridocorneal
angle thus blocking aqueous outflow.
C. Miotic makes the iris thin and pulls it away from the lens removing the pupillary
block and restoring aqueous drainage

61. • 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.
• Corticosteroid eye drops like dexamethasone
or betamethasone should be administered 3-4
times a day to reduce the inflammation.
• In classic CAG, once the IOP is controlled,
pilocarpine may be given every 6 hours until
iridectomy is performed.

62. • These drugs are among the first-line agents in the short-term
treatment of CAG or other forms of acute very high IOP
elevations.
• Topical corticosteroids often are used to reduce the ocular
inflammation.
• In classic CAG, once the IOP is controlled, pilocarpine may be
given every 6 hours until iridectomy is performed.
• Patients failing therapy altogether will require an emergency
iridectomy.

63. Surgical treatment
Peripheral iridotomy.
• It is indicated when peripheral anterior synechiae are formed in less than 50 percent of the
angle of anterior chamber and as prophylaxis in the other eye. Peripheral iridotomy re-
establishes communication between posterior and anterior chamber, so it bypasses the
pupillary block and thus helps in control of PACG.
• Laser iridotomy
• It is a non-invasive procedure, is a good alternative to surgical iridectomy.
Filtration surgery
• It should be performed in cases where IOP is not controlled with the best medical therapy
following an attack of acute congestive glaucoma and also when peripheral anterior
synechiae are formed in more than 50 percent of the angle of the anterior chamber.

64. • Mechanism: Filtration surgery provides an alternative
to the angle for drainage of aqueous from anterior
chamber into subconjunctival space.For surgical
technique, see page 238.
Prophylactic treatment in the normal
fellow eye
• Prophylactic laser iridotomy (preferably) or surgical
peripheral iridectomy should be performed on the
fellow asymptomatic eye.