This document provides an overview of glaucoma, including its anatomy, pathophysiology, classification, and pharmacological treatment. Glaucoma involves progressive optic neuropathy and vision loss due to increased intraocular pressure. It is classified into primary and secondary types. The main drugs used for treatment are prostaglandin analogues, beta blockers, alpha agonists, cholinergic agonists, and carbonic anhydrase inhibitors, which work to reduce aqueous humor production or increase outflow. Emerging therapies aim to provide neuroprotection to retinal ganglion cells. Surgery may also be used in some cases.

1. Pharmacotherapy of
. Glaucoma
Dr Manjuprasad
Moderator: Dr Vijayalaxmi M.K

2. Overview
• Introduction
• Anatomy
• Aqueous humour dynamics
• pathophysiology
• Drugs used in the treatment
• Recent advances
• Conclusion
2

3. Introduction
• Glaucoma – ancient greek
meaning clouded or blue- green hue
• In Hippocratic aphorisms
Glaucoma – blindness coming from advancing years
• Second leading cause of blindness
3

4. • 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
4

5. Anatomy of the eye
5

6. Aqueous humor
• Derived from the plasma
• 2.3µl/min
Production:
• Ultrafiltration
• Secretion
• Diffusion
6

7. Aqueous humor dynamics
7

8. Classification
• Congenital glaucoma
- Primary congenital glaucoma
- Developmental glaucoma
• Primary adult glaucoma
- Primary open angle glaucoma
- Primary angle closure glaucoma
- Primary mixed mechanism glaucoma
• Secondary glaucoma 8

9. Pathogenesis
• All types of glaucoma – progressive optic neuropathy due to the
death of retinal ganglion cells(RGCs)
• RGCs death is initiated – block in transport of neurotrophins
from brain to RGCs
damaging cascade activation
Apoptosis of RGCs
• RGCs death – loss of retinal fibers – optic neuropathy & visual
field defects 9

10. • Mechanical theory :
↑IOP – mechanical stretch of lamina cribrosa – axonal
deformation & altered capillary blood flow -- ↓neurotrophins
to reach RGC`s
• Pressure independent factors
- Failure of autoregulation
- Vasospasm
- Systemic hypotension
- Blood / fluid loss
• Excitotoxicity theory:
glutamate , oxygen free radicals, nitric oxide
10

11. Congenital glaucoma
• Seen in 1 in 10,000 births
• Pathology- mal development
of trabeculum
• True congenital glaucoma
• Infantile glaucoma
• Juvenile glaucoma
• Diagnosis – corneal diameter measurement
- ophthalmoscopic evaluation of disc
- gonioscopic examination 11

12. Primary open angle glaucoma
• No obvious cause
• Polygenic inheritence
• ↑incidence in smokers
• Blacks > whites
• Pathology:
- Age related thickening & sclerosis of trabeculae
- Absence of giant vacuoles in cell lining canal of schlemm
12

13. Primary angle closure glaucoma
• Increase in IOP – due to closure of angle of anterior chamber.
Acute & chronic
• Chronic PACG:- progress slowly with / without symptoms
• Acute PACG:-
-Is an emergency
-Severe eye pain
-Nausea, vomiting, prostration
-Redness, photophobia, lacrimation
-Rapid, progressive impairment of vision
13

14. Risk factors:
• Hypermetropic eye
• Small eye
• 5th decade
• Female > male
• > in rainy season and dim light
14

15. Secondary glaucomas
• Lens induced glaucoma
• Pigmentary glaucoma
• Neovascular glaucoma
• Glaucoma associated with intravascular tumor
• Traumatic glaucoma
• Steroid induced glaucoma
15

16. 16

17. Drugs used in the treatment
DRUGS THAT REDUCE AQUEOUS HUMOUR PRODUCTION
I. Beta-Blockers : levobunolol, timolol, carteolol,
betaxolol
II. Alpha-2 Adrenergic Agonists : apraclonidine,
brimonidine
III. Carbonic Anhydrase Inhibitors :acetazolamide,
dorzolamide 17

18. DRUGS THAT INCREASE AQUEOUS OUTFLOW
I. Nonspecific Adrenergic Agonists :epinephrine,
dipivefrin
II. Parasympathomimetics : pilocarpine, carbachol,
echothiophate
III. Prostaglandin Analogues : latanoprost
18

19. Cholinergic agonists
• Most commonly used – Pilocarpine
• Derived from shrub – pilocarpus jaborandi
MOA:-
• Acts on M3 receptors
– contraction
of sphincter pupillae
• Causes contraction of
longitudinal ciliary muscle →
trabecular outflow
19

20. • Onset of action – rapid
peak effect – 30min
lasts for 4 – 6hrs
• S/E:-
• LOCAL:- Superficial punctate keratitis , brow ache,
induced myopia, increased risk of retinal
detachment & iritis
• SYSTEMIC – rare
• Available as 0.5 to 10 % eye drops
20

21. • Pilocarpine gel (pilocarpine HCl 4%) HS
• Membrane controlled delivery system:-
-Insert placed in cul-de-sac that gradually release drug
at rate of 20mcg/hr
-Effective for 7 days
• Pilocarpine soaked contact lens
• Liposomal pilocarpine
21

22. ADRENERGIC AGONISTS
Includes:
• Non selective – epinephrine & dipivefrin
• Selective alpha2 agonists- Apraclonidine, Brimonidine
22

23. • EPINEPHRINE:-
• Directly acting sympathomimetic
• MOA:
• Reduced aqueous production due to alpha action
• trabecular outflow via Beta receptor stimulation
• Due to its CVS s/e , allergic reaction – no longer used
• DIPIVEFRIN:-
• Is a prodrug
• Formed by di-esterification of epinephrine –
lipophilicity– increased penetration to anterior
chamber .
23

24. • Onset of action-30min, peak effect – 1hr
• Used as an adjuvant therapy
• Available as 0.1% solution , dosage BD
A/E :
• Less compared to epinephrine
• Follicular conjunctivitis, blurring of vision, stinging
24

25. ALPHA2 AGONISTS
MOA:-
• Decrease aqueous humour production by alpha2
action on ciliary epithelium.
APRACLONIDINE:
• Also known as para amino clonidine
• Available as 0.5 – 1 % , dosage BD
• Short term use – Post op rise in IOP & adjuvant in
POAG
25

26. BRIMONIDINE:-
• 30 times more selective α2 agonist than apraclonidine
• Additional neuroprotective effect
• Available as 0.2 - 0.5% , applied BD
• Uses:- in patients with contraindications to beta
blockers,
-short term use in post op raise in IOP
26

27. BETA BLOCKERS
• Introduced in 1979
• Considered to be 1st line therapy for all types of glaucoma
• Good efficacy
• Minimal S/E
MOA:
• Decreases aqueous humour production by blocking
beta2 receptors on ciliary epithelium.
27

28. TIMOLOL:
• Introduced 1978 as 1st approved beta blocker for
glaucoma
• Most widely used ocular hypotensive agent
• Due to its non selective beta action – cautious in
COPD, asthma & heart failure
• Available as 0.5 % solution & gel
• S/E:-
• Systemic
• Local:- superficial punctate keratitis, corneal
anesthesia
CARTEOLOL:
• Available as 1% solution
28

29. • LEVOBUNOLOL
• Available as 0.5 – 1% solution, applied BD /OD
• Metabolized to di- hydrolevobunolol
• BETAXOLOL
• Introduced in 1980s as 1st topical β1 blocker used in
glaucoma
• Clinical trials – lesser efficacy in reducing IOP
compared to timolol
• Additional neuroprotective effect.
29

30. CARBONIC ANHYDRASE INHIBITORS
2 types:-
• Systemic CA inhibitors:-
• Acetazolamide, Methazolamide
• Topical CA inhibitors:-
• Dorzolamide, Brinzolamide
MOA:-
• Blocks CA enzyme reversibly in ciliary body – reduces
aqueous humour production
30

31. SYSTEMIC CARBONIC ANHYDRASE INHIBITORS
DOSAGE:-
• Acetazolamide 125mg, 250mg p.o TID or QID
• Methazolamide 25mg, 50mg p.o BD or TID
SIDE EFFECTS:-
• High risk of systemic S/Es.
• Paraesthesias, Kidney stones, aplastic anaemia,
depression
31

32. TOPICAL CARBONIC ANHYDRASE INHIBITOR
• DORZOLAMIDE:-
• 1st topical CA inhibitor launched in market
• Advantage – not absorbed systemically
• Available as 2 % solution- applied TID
• S/E:- systemic is minimal
- local S/E includes corneal edema, allergic reaction,
burning & stinging sensation
• BRINZOLAMIDE
• Available as 1% solution
• Better tolerated than dorzolamide – its pH is 7.4 32

33. PROSTAGLANDIN ANALOGUES
• Includes latanoprost, unoprostone, bimatoprost,
travoprost.
• MOA:-
• Decreases IOP by increasing uveoscleral
outflow
33

34. LATANOPROST:-
• Introduced in 1996
• An ester prodrug analogue of PGF2α
• Available as 0.0005% solution, OD (evening)
• Requires refrigeration & protection from sunlight
• S/E – conjunctival hyperemia ( initially), Iris
pigmentation, cystoid macular odema
34

35. UNOPROSTONE:-
• Available as 0.15% solution, BD
• Additional neuroprotective effect – increasing
microcirculation in optic nerve head.
BIMATOPROST:
• A synthetic prostamide analogue
• Available as 0.03% solution , OD
• Does not require refrigeration
35

36. TRAVAPROST
• Synthetic PGF2α analogue
• Available as 0.004% solution, OD at evening
• Does not require refrigeration/ protection from
sunlight
36

37. Surgical procedures
37
• Trabeculoplasty
• Iridotomy
• Iridectomy
• Filtering procedures
• Canaloplasty
• Goniotomy
• Goniocurettage
• Cyclodialysis
• Ciliarotomy

38. Other treatment modalities
ALPHA LIPOIC ACID:-
• Powerful antioxidant
• Useful in glaucoma by decrease in nerve cell damage
due to oxidative stress
VITAMIN C :-
• Said to increase aqueous outflow by reducing viscosity
of hyaluronic acid in trabecular meshwork
SALVIA MILTIORRHIZA:-
• Chinese herb, given i.v said to improve
microcirculation of RGCs 38

39. CANNABINOIDS
• Believed to improve uveoscleral outflow
• Not yet available for this purpose
39

40. Herbal products
• Boerhavia Diffusa
• Emblica Officinalis
• Terminalia Chebulia
• Commiphora Mukul
• Curcuma Longa
40

41. FUTURE GLAUCOMA THERAPY
• NMDA receptor antagonist:-
• Provides neuroprotection by blocking glutamate
mediated death of RGCs
• Includes memantine & eliprodil
• Riluzole:-
• Is a presynaptic glutamate release inhibitor
• Neuroprotective nature
• Neuroprotective vaccines:- R16
41

42. Erythropoetin:-
• Neuroprotective by inhibiting RGCs apoptosis
• In animal studies – intravitreal injection enhances
RGC survival
Caspase inhibitors:-
• Inhibits apoptosis of RGCs
• Promising approach in terms of Rx of glaucoma
iNOS inhibitors:-
• Increased level of NO – neuronal damage via
apoptosis
42

43. DRUG ELUTING MICRO STENTS
• Microstents were coated with a polymer-drug compound
and is implanted in the angle of iris and cornea
• Diffusion controlled
release of paclitaxel or
mitomycin is used to
avoid blocking of stent
43

44. Acute angle closure glaucoma
• IOP – 40-70 mmHg
• Systemic hyperosmotic agent- IV mannitol 1mg/kg
• Actazolamide 500mg IV followed by 250mg TID
• Analgesics and Antiemetics
• Corticosteroids e/d like dexamethasone 3-4/day to reduce
inflammation
• Sx- periferal iridotomy
filteration surgery
44

45. BIBLIOGRAPHY
• Pharmacological aspects of therapeutics – Goodman and Gilman – 12th edition
• Principles of pharmacology Sharma and sharma 2nd edition
• Textbook of medical pharmacology – Dr.PadmajaUdaykumar – third edition
• Essentials of medical pharmacology – K.D.Tripathi
• A. K. Khurana - comprehensive ophthalmology
• Quigley HA, Broman AT. The number of people with glaucoma worldwide in
2010 and 2020. Br J Ophthalmol. 2006;90:262–7
• Killer HE, Miller NR, Flammer J, Meyer P, Weinreb RN, Remonda L, Jaggi GP.
Cerebrospinal fluid exchange in the optic nerve in normal-tension glaucoma.
Br J Ophthalmol. 2012;96:544–8.
• Collaborative Normal-Tension Glaucoma Study Group. The effectiveness of
intraocular pressure reduction in the treatment of normal-tension glaucoma.
Am J Ophthalmol. 1998;126:498–505
• . Bergeå B, Bodin L, Svedbergh B. Impact of intraocular pressure regulation on
visual fields in open-angle glaucoma. Ophthalmology. 1999;106:997–1004
• Rao HL, Addepalli UK, Jonnadula GB, Kumbar T, Senthil S, Garudadri CS.
Relationship between intraocular pressure and rate of visual field progression
in treated glaucoma. J Glaucoma. 2012 In press.
45

46. 46