the most commonly prescribe treatment for glucoma is eye drops. These medicine decreases IOP to the level that prevents damage to the optic nerve by either decrease acqueous secretion from the ciliary body or facilitating acqueous drainage through the trabecular or uveoscleral outflow systems. This presentation outlines the principal eye medicine currently used in ophthalmic practice.

1. Medicines used for
Glaucoma management
Dr Gauri Sr Shrestha, IOM, TU

2. Principle summary of glaucoma treatment
1. Reduce
secretion of
aqueous humour
• Cells
responsible for
Aqueous
secretion: non-
pigmented
epithelium of
the ciliary body

3. Principle summary of glaucoma treatment
2. Promote
aqueous humour
drainage
• Trabecular
meshwork (90%)
• Uveoscleral flow
(10%)

4. Goals and plans of glaucoma treatment
• Goals
• Lower IOP at a level that
will stop or slow the
progression of optic nerve
damage and related loss
of visual functions
• The purpose of the
therapy is not glaucoma
cure but rather is its
control
• Plans
• Choose a drug with the lowest
concentration
• Use drugs with potentially
fewer side effects
• If IOP does not fall significantly
with monotherapy, select a
combination therapy.

5. Categories of anti-glaucoma medicines
Increase aqueous
outflow (primary)
1. Cholinergic drugs
(e.g., pilocarpine,
carbachol)
2. Cholinesterase
inhibitor (e.g.,
physostigmine,
echothiophate)
3. Prostaglandin
analogue (e.g
latanoprost,Bimatop
rost unoprostone,
travoprost)
Decrease production of aqueous humour (primary)
1. Non-selective β-adrenergic blocker (e.g., timolol,
levobunolol, metipranolol, carteolol)
2. Selective β-blocker (e.g., Betaxolol)
3. Non-selective α-adrenergic agonist (e.g.,
epinephrine, dipivefrin)
4. Selective α2-adrenergic agonist (e.g., clonidine,
apraclonidine, brimonidine)
5. Carbonic anhydrase inhibitor (e.g., dorzolamide,
brinzolaminde, acetazolaminde, methazolamide)
6. Hyperosmotic agents (e.g., oral glyceride, IV
mannitol, Urea)

6. Increase aqueous outflow (primary
action)
1. Cholinergic drugs (e.g., pilocarpine, carbachol)
2. Cholinesterase inhibitor (e.g., physostigmine, echothiophate)
3. Prostaglandin analogue (e.g latanoprost, unoprostone, travoprost)

7. 1. Cholinergic medicine (Pilocarpine 1%, 4%)
• Enhance aqueous outflow by contraction of the ciliary muscle in OAG
(not commonly used due to inherent side effects of cholinergic drugs)
• Release pupillary block (therapeutic management of ACG)
• Dose: TID – QID (increase dose in darkly pigmented eyes)
• Side effects
• Systemic: perspiration, stimulation of glands, contraction of smooth muscles,
pulmonary oedema.
• Ocular: ciliary muscle spasm, retinal detachment, vitreous haemorrhage, corneal
endothelial toxicity, cataract, band keratopathy, cicatricle pemphigoid,
hypersensitivity, and toxic reaction.
• Contraindication: age below 40 years (accommodative spasm), uveitis,
and neovascular glaucoma
ACG = angle closure glaucoma, OAG = open-angle glaucoma

8. 2. Cholinergic medicine (Carbachol 0.75 – 3%)
• A synthetic analogue of acetylcholine
• Poorly absorb across the cornea
• Alternative: pilocarpine (fails to control IOP)
• Dose: TID
• Side effects: ocular pain, impaired vision, pseudomyopia

9. 3. Prostaglandin (PG) analogue
• Mediators of inflammation (a product of cell membrane PLs by the
action of COX-related enzyme)
• PG receptors:
• ciliary muscles, iris sphincter, trabecular meshwork
• Reduce IOP by
1. Increase uveal-scleral outflow by relaxing ciliary muscles
2. Increase aqueous outflow through the trabecular meshwork
• Reduce IOP by 25%

10. 3. Prostaglandin (PG) analogue
• Side effects:
• burning, blurred vision, itching, FB sensation, conjunctival hyperemia,
increase coronary blood flow, bronchoconstriction, CME in aphakia and
pseudophakia, increase iris pigmentation, hypertrichosis of eyelashes,
anterior uveitis
• Latanoprost 0.005% (Xalatan):
• acts on PG receptor 1 (predominant)
• Bimatoprost 0.01%, 0.03% (Lumigan):
• mimics PG-α2 receptor without acting on any PG receptor (both 1 and 2)
• Travoprost 0.004% (travatan)
• similar to latanoprost, stable at room temperature

11. Decrease production of aqueous
humour (primary action)
1. Non-selective β-adrenergic blocker (e.g., timolol, levobunolol, metipranolol, carteolol)
2. Selective β-blocker (e.g., Betaxolol)
3. Non-selective α-adrenergic agonist (e.g., epinephrine, dipivefrin)
4. Selective α2-adrenergic agonist (e.g., clonidine, apraclonidine, brimonidine)
5. Carbonic anhydrase inhibitor (e.g., dorzolamide, brinzolaminde, acetazolaminde,
methazolamide)
6. Hyperosmotic agents (e.g., oral glyceride, IV mannitol, Urea)

12. 1. Adrenergic receptors : β-blockers
• Reduce aqueous
secretion by
blocking beta-
receptors (reduce
Cl- ions)
• Receptors:
• β1: heart and
kidney
• β2: bronchi
(asthmatic
patients)

13. 1. Side effect and Contraindication of β-
blocker
• Side effects of β-blockers
• Bradycardia, systemic hypotension, bronchospasm, amnesia,
nausea
• Alopecia, hypoglycemia, dry eye, loss of corneal sensation, uveitis,
cataract
• Contraindications
• Asthama, COPD, Bradycardia, heart block, children, pregnancy

14. 1. Non-selective β-blockers
Timolol 0.25, 0.50
• A well-tolerated ophthalmic
solution
• Dose: BD
• Efficacy decline with long-term
use
• Side effect: cardiovascular and
respiratory complications
Levobunolol (betagon 0.5)
• Similar to timolol
Metipranolol 0.1, 0.3
• Similar to levobunolol
• Gives more stinging sensation
than levobunolol
Carteolol 1.0, 2.0
• Less potent than other drugs in
this group
Commonly used or available medicines

15. 2. Selective β-blocker
Betaxolol 0.25, 0.50
• Less bronchoconstriction than timolol because of its cardioselectivity
(effective more on β1 receptor than β2 receptor.
• Modest reduction in IOP.
• More effective in slowing the rate of VF deterioration.
Commonly used or available medicines

16. 3. Adrenergic receptors
• Decrease IOP in POAG, increase IOP
in ACG
• Causes pupil dilation
• Acts on two types
• α1-receptors
• arterioles, dilator pupillae, and muller
muscle
• Its stimulation causes hypotension,
mydriasis, and lid retraction
• α2-receptors
• are located in the ciliary epithelium and
presynaptic adrenergic nerve terminals.
• Its stimulation inhibits the aqueous
secretion

17. 3. Non-selective α-adrenergic agonist (e.g.,
epinephrine, dipivefrin)
Dipivefrin 0.1%
• Prodrug
• Less effective than timolol
• Side effects: reactive hyperemia, endothelial damage and follicular
conjunctivitis

18. 4. Selective α2-adrenergic agonist
Brimonidine 0.2% (alphagan)
• Highly selective for α2-adrenergic
receptors
• 1000 times more effective than α1-
adrenergic receptors
• No mydriasis and vasoconstriction
and little effect on the
cardiovascular system
• Decreases aqueous secretion and
enhances uveoscleral outflow.
• Safe in long-term treatment
• Has neuroprotective properties
Apraclonidine 0.5%, 1.0% (Iopidine)
• Reduce blood pressure and heart rate
by reducing sympathetic tone
• Significantly decrease IOP in post-
operative cataract cases
• No conjunctival hyperemia and
blanching
• Perceived contraindication: a narrow
filtration angle, cardiovascular
problems, peripheral vasospastic
conditions, Horner’s syndrome
Commonly used or available medicines

19. 5. Carbonic anhydrase inhibitor
• Enzyme carbonic anhydrase
produces HCO3
- ions from CO2
and H2O.
• The HCO3
- ions move to the
posterior chamber along with
Na+ through trans-epithelial
movement of bicarbonate ions
in the ciliary epithelium.
• CAI competes with bicarbonate
ions and block HCO3
- ion
formation from CO2.
• Dorzolamide 2.0%, Brinxolamide
1.0%
• Dose: BD – TID
• Effect similar to Betaxolol (a selective
β blocker)
• Adjunct therapy: B-blockers (dose BD)
• Acetazolamide
• Has poor ocular penetration, and is
not effective topically
• Oral dose: 250 – 500 mg BD
Commonly used or available medicines

20. 5. Side effects and contraindications of
Carbonic anhydrase inhibitor
Contraindications
Hypersensitivity,
impaired renal function,
COPD, a patient using
potassium-depleting
drugs, neovascular
glaucoma
Side effects

21. 6. Hyperosmotic agents (e.g., Oral glyceride,
IV Mannitol)
• Vitreous shrinkage leads to an osmotic
gradient b/w blood and ocular tissue
which drain fluids from the eyes.
• Side effects
• Major: nausea, vomiting, diuresis
• Others: headache, backache,
giddiness, diarrhea, confusion,
disorientation, cardiovascular
overload, intra-cranial
haemorrhage, pulmonary oedema,
acidemia, and renal insufficiency
• Glycerol
• Dose: 1 – 1.5 mg/kg
body weight (50%
solution)
• IV mannitol (20%)
• Dose: 1 – 2 gm/kg
body weight in 30
mins

22. Rationale for combination therapy
• Do not use drugs of the same group
• Select two drugs combination
• The first-line treatment has no effect or more adverse effect, change
this drug than using combination therapy.
• No results with combination therapy, change drug than increasing
doses.

23. Sample combination therapy
(feel free to update this table)
Primary Additional Medicine examples (if available in combination)
Alpha-1 agonist • β - blocker
Beta blocker • α - agonist Combigan, Brimolol (Brimonidine Tartarate 0.2% W/V + Timolol Malate
0.5%W/V),
• Cholinergic
• Prostaglandin Xalacom (timolol 0.5% and Latanoprost 0005%), DuoTrav (Timolol 0.5%
and Travoprost 0.004%), Ganfort (Timolol 0.5% and Bimatoprost 0.03%)
• Topical CAIs Cosopt (dorzolamide 2%-timolol 0.5%)
Cholinergic • Beta-blocker
• Topical CAIs
Prostaglandins • Beta-blocker
• Topical CAIs
Topical CAIs • Alpha 2 agonist Simbrinza (brinzolamide 1%-brimonidine 0.2%)
• Beta-blocker
• Prostaglandins

24. Choice of drug
• Betaxolol (Selective β-blocker): NTG, COPD
• Common combination therapy:
• timolol (Non-selective β – blocker) + latanoprost (Prostaglandin analogue)
• timilol (Non-selective β – blocker) + dorxolamide (Carbonic anhydrase
inhibitor)
• Pregnancy: Brimonidine (Selective α2-adrenergic agonist)
NTG = norma tension glaucoma
COPD = chronic obstructive pulmonary disease

25. Thank you

26. Efficacy of anti-glaucoma medicine
• Efficacy of monotherapy versus combination-therapy
• Efficacy, recommendation and dose of prostaglandin analogue (e.g
latanoprost and/or travoprost)
• Comparison of selective (e.g., betaxolol) and non-selective beta-
blockers (e.g., timolol and/or levobunolol)
• β-blockers (e.g., timolol and/or levobunolol/ betaxolol) versus
prostaglandin analogues (e.g latanoprost and/or travoprost)
• β-blockers (e.g., timolol and/or levobunolol/ betaxolol) versus α-
adrenergic agonist (e.g., apraclonidine, brimonidine)