4. What is Glaucoma
The anterior chamber contains the ciliary body 1, the site of aqueous humor
production. The aqueous humor percolates around the lens 4 and the iris 3 to
drain (white lines 2) from the posterior chamber into the anterior chamber
through the pupil 5. The anterior chamber angle is located between the
peripheral cornea 6 and the peripheral iris, and it contains the trabecular
meshwork (TM 7 red arrow) and Schlemmās canal 8. The aqueous humor leaves
the eye through the trabecular meshwork and Schlemmās canal, and through the
uveo-scleral outflow pathway in the ciliary muscle 9. Modified from Jonas et al,
2017.
5.
6.
7. What is Glaucoma
The glaucoma's are a group of ocular
disorders that lead to an optic neuropathy
characterized by changes in the optic
nerve head (optic disk) that is associated
with loss of visual sensitivity and field.
8. Aqueous Humor and IOP
ā¢ Aqueous humor is formed in the ciliary body and its
epithelium through both filtration and secretion.
ā¢ Osmotic gradients produced by active secretion of sodium
and bicarbonate, and possibly other solutes such as
ascorbate from the ciliary body epithelial cells into the
aqueous humor, result in movement of water from the pool
of ciliary stromal ultrafiltrate into the posterior chamber,
forming aqueous humour.
9. Aqueous Humor and IOP
The pressure in the posterior chamber produced by the constant inflow pushes the
aqueous humor between the iris and lens and through the pupil into the anterior
chamber of the eye.
Aqueous humor in the anterior chamber leaves the eye by two routes:
1. Filtration through the trabecular meshwork (conventional outflow) to
Schlemmās canal (80% to 85%) and
2. Through the ciliary body and the suprachoroidal space (uveoscleral outflow or
unconventional outflow).
10. Aqueous Humor and IOP
ā¢ Carbonic anhydrase, Ī±- and Ī²-adrenergic
receptors, and sodium- and potassium-
activated ATPases are found on the ciliary
epithelium and appear to be involved in this
secretion of the solute's sodium and
bicarbonate.
11. Aqeous Humor and IOP
ā¢ Pharmacologic studies suggest that Ī²-adrenergic
agents increase inflow, whereas Ī±2-adrenergic-
blocking,Ī±-adrenergic-blocking, Ī²-adrenergic-
blocking, dopamine-blocking, carbonic anhydraseā
inhibiting, and adenylate cyclaseāstimulating
agents decrease aqueous inflow.
12. Aqueous Humor and IOP
ā¢ Cholinergic agents such as pilocarpine increase outflow
by physically opening the meshwork pores secondary to
ciliary muscle contraction.
ā¢ The uveoscleral outflow of aqueous humor is also
increased by prostaglandin analogs, and Ī²- and Ī±2-
adrenergic agonists.
13. Aqueous Humor and IOP
Glaucoma medications that provide maximal reduction of
IOP over 24 hours and have minimal influence on blood
pressure may be advantageous in treating glaucoma
patients.
14. Open-Angle Glaucoma
Open-angle glaucoma is a type of chronic eye disease
characterized by progressive damage to the optic
nerve.
In open-angle glaucoma, the drainage channels in the
eye, known as the trabecular meshwork, are not
blocked but instead are unable to drain fluid effectively,
15. Open-Angle Glaucoma
The open angle in open-angle glaucoma may
appear normal, but the drainage of aqueous
humor is disrupted due to a buildup of the fluid,
resulting in elevated intraocular pressure.
16.
17. Open-Angle Glaucoma
It is called "open-angle" because the term refers to the
appearance of the anterior chamber angle, which is the
part of the eye where the iris meets the cornea, and the
aqueous humor drains out.
In open-angle glaucoma, the angle is open and
unobstructed, allowing the aqueous humor to circulate
18.
19. Open-Angle Glaucoma-
Pathophysiology
Aqueous humor production: The rate of
aqueous humor production must be balanced
by an equal rate of outflow through the
trabecular meshwork, in order to maintain a
stable IOP.
21. Open-Angle Glaucoma-
Pathophysiology
Optic nerve damage:
Elevated IOP places pressure on the optic nerve,
causing damage to the nerve fibers over time.
This can lead to vision loss, starting with peripheral
vision and eventually affecting central vision if left
untreated.
22. Open-Angle Glaucoma- Clinical
Presentation
ā¢ The presence of characteristic disk changes and
visual field loss with or without increased IOP
confirms the diagnosis of glaucoma.
ā¢ Normal tension glaucoma: Typical disk changes
and field loss occurring at an IOP of less than 21
mm Hg account for 20% to 30% of patients
23. Open-Angle Glaucoma- Clinical
Presentation
ā¢ Ocular Hypertension: Elevated IOP (>21 mm Hg)
without disk changes or visual field loss is observed in
5% to 7% of individuals (known as glaucoma
suspects)
ā¢ Secondary open-angle glaucoma has many causes,
including systemic diseases, trauma, surgery,
rubeosis, lens changes, ocular inflammatory
24. Pharmacotherapeutic Approach
Medications most used to treat glaucoma are the
1. nonselective Ī²-blockers,
2. the prostaglandin analogs (latanoprost, travoprost, and
bimatoprost),
3. brimonidine (an Ī±2-agonist), and
4. the fixed combination product of timolol and dorzolamide
25. Pharmacotherapeutic Approach
The prostaglandin analogs, brimonidine, and topical CAIs, are
also considered suitable first-line therapy or alternative initial
therapy in patients with contraindications to Ī²-blockers
Pilocarpine and epinephrine are used commonly as third-line
therapies because of their increased frequency of adverse
effects or reduced efficacy
26. Ī²-blockers
The choice of a specific Ī²-blocking
agent generally is based on
1. differences in adverse-effect
potential,
2. individual patient response, and
3. cost.
27. Ī²-blockers
ā¢ Ī²-Blockers lower IOP by 20% to 30% with a
minimum of local ocular adverse effects.
ā¢ These are commonly the agents of first choice in
treating POAG if no contraindications exist.
ā¢ The Ī²-blocking agents produce ocular
hypotensive effects by decreasing the production
of aqueous humor by the ciliary body.
28. Ī²-blockers
ā¢ Five ophthalmic Ī²-blockers are presently
available: timolol, levobunolol, metipranolol,
carteolol, and betaxolol.
ā¢ Timolol, levobunolol, and metipranolol are
nonspecific Ī²-blocking agents,
ā¢ Betaxolol is a relatively Ī²1-selective agent.
29. Ī²-blockers
All ophthalmic Ī²-blockers should be used with
caution in patients with CONTRAINDICATIONS-
pulmonary diseases, sinus bradycardia, second-
or third-degree heart block, congestive heart
failure, atherosclerosis, diabetes, and myasthenia
gravis, as well as in patients receiving oral Ī²-
blocker therapy.
30. Ī²-blockers
ā¢ Levobunolol may be more effective than timolol and
betaxolol in reducing postācataract surgery IOP
increases
ā¢ Levobunolol solution is more effective in controlling
IOP than other agents when given as aqueous
solutions on a once-daily schedule (up to 70% of
patients).
31. Ī²-blockers
Timolol in the form of a gel-forming solution
(Timoptic-XE) provides equivalent IOP control
with once-daily administration when compared
with the same concentration of the aqueous
solution administered twice daily.
33. Ī²-blockers
Switching from one agent to another or
switching the type of formulation may
improve tolerance in patients
experiencing local adverse effects.
34. Ī²-blockers
ā¢ Systemic effects are the most important adverse
effects of Ī²-blockers.
ā¢ Drug absorbed systematically may produce
decreased heart rate, reduced blood pressure,
negative inotropic effects, conduction defects,
bronchospasm, central nervous system effects,
and alteration of serum lipids, and may block the
symptoms of hypoglycemia.
35. Ī²-blockers
The Ī²1-specific agents betaxolol and possibly carteolol are less
likely to produce the systemic adverse effects caused by Ī²-
adrenergic blockade, such as the cardiac effects and
bronchospasm, but a real risk still exists.
The use of timolol as a gel-forming liquid or betaxolol as a
suspension allows for administration of less drug per day, and
therefore reduces the chance for systemic adverse effects
compared with the aqueous solutions.
36. Ī²-blockers
Use of nasolacrimal occlusion
technique during administration
reduces the risk or severity
of systemic adverse effects as well as
optimizes response
37. Ī²-blockers
In patients failing or having an inadequate
response to single-drug therapy with a Ī²-
blocking agent, the addition of a CAI,
parasympathomimetic agent,
prostaglandin analog, or an Ī±2-
adrenergic receptor agonist usually will
result in additional IOP reduction.
38.
39.
40.
41. Ī±2-ADRENERGIC AGONISTS
Brimonidine is considered a first-line
or adjunctive agent in the therapy of
POAG, and apraclonidine is seen as a
second-line or adjunctive therapy.
42. Ī±2-ADRENERGIC AGONISTS
Use of apraclonidine has fallen
dramatically because of a high incidence
of loss of control of IOP (tachyphylaxis)
and a more severe and prevalent ocular
allergy rate.
44. Ī±2-ADRENERGIC AGONISTS
Use of brimonidine 0.2% every 8 to 12 hours appears to provide
maximum IOP-lowering effects in long-term use.
Use of NLO may improve response and allow the longer dosing
frequency (i.e., every 12 hours).
Combinations of Ī±2-agonists with Ī²-blockers, prostaglandin
analogs, or CAIs produce additional IOP reduction.
45. Ī±2-ADRENERGIC AGONISTS- CI
Ī±2-Agonists should be used with caution in patients
with cardiovascular diseases, renal compromise,
cerebrovascular disease, and diabetes, as well as in
those taking antihypertensives and other
cardiovascular drugs, monoamine oxidase inhibitors,
and tricyclic antidepressants.
46. Ī±2-ADRENERGIC AGONISTS- CI
Brimonidine is also contraindicated in infants because of apneic
spells and hypotensive reactions.
In terms of overall efficacy and tolerability, brimonidine
approximates that achieved with Ī²-blockers
Brimonidine-purite 0.15% is a formulation of brimonidine in a lower
concentration than the original product, and it contains a less toxic
preservative than the most employed benzalkonium chloride.
47. Prostaglandin Analogues
The prostaglandin analogs, including
latanoprost, travoprost, Bimatoprost,
and unoprostone, reduce IOP by increasing
the uveoscleral and to a lesser extent
trabecular outflow of aqueous humor
48. Prostaglandin Analogues
Reduction in IOP with once-daily doses of
prostaglandin F2Ī± analogs (a 25% to 35%
reduction) is often greater than that seen
with timolol 0.5% twice daily.
In addition, nocturnal control of IOP is improved
compared with timolol.
50. Prostaglandin Analogues
Unoprostone 0.15% reduces IOP somewhat less than
prostaglandin analogs and requires twice-daily
administration.
Prostaglandin analogs are well tolerated and produce
fewer systemic adverse effects than timolol.
Local ocular tolerance generally is good, but ocular
reactions do occur.
51. Prostaglandin Analogues
With prostaglandin analogs, altered iris
pigmentation occurs in 15% to 30% of patients,
particularly those with mixed-color irises
which become browner in color over 3 to 12
months.
The change in iris pigmentation will often
appear within 2 years
52. Prostaglandin Analogues
Given their excellent efficacy and side effect
profile, prostaglandin analogs provide
effective monotherapy or adjunctive therapy in
patients not responding to or tolerating
other agents.
53. Carbonic Anhydrase Inhibitors- Topical
Agents
CAIs appear to inhibit aqueous production by blocking active
secretion of sodium and bicarbonate ions from the ciliary
body to the aqueous humor
Topical CAIs such as dorzolamide and brinzolamide are well
tolerated and are indicated for monotherapy or adjunctive
therapy of open-angle glaucoma and ocular hypertension.
54. Carbonic Anhydrase Inhibitors- Topical
Agents
Relatively specific inhibitors of carbonic anhydrase enzyme II
such as dorzolamide and brinzolamide reduce IOP by 15% to 26%.
Because of their favorable adverse-effect profile, topical CAIs
provide a useful alternative agent for monotherapy or adjunctive
therapy in patients with inadequate response to or who are
unable to use other agents.
55. Carbonic Anhydrase Inhibitors- Topical
Agents
The usual dose of a topical CAI is one drop every
8 to 12 hours.
Administration every 12 hours produces somewhat
less IOP reduction than administration every 8
hours.
56. Carbonic Anhydrase Inhibitors-
Systemic Agents
Oral CAIs reduce aqueous humor inflow by 40% to 60% and IOP by 25%
to 40%.
The available systemic CAIs produce equivalent IOP reduction but differ
in potency, adverse effects, dosage forms, and duration of action.
Despite their excellent effects on elevated IOP of any etiology, the
systemic CAIs frequently produce intolerable adverse effects.
57. Carbonic Anhydrase Inhibitors-
Systemic Agents
Elderly patients do not tolerate CAIs as well as younger patients.
Acetazolamide (standard or sustained-release capsules) and
methazolamide are considered the best-tolerated CAIs.
CAIs should be used with caution in patients with sulfa allergies
(all CAIs, topical or systemic, contain sulfonamide moieties).
58. Carbonic Anhydrase Inhibitors-
Systemic Agents
Concurrent use of a CAI and a diuretic may rapidly
produce hypokalaemia.
High-dose salicylate therapy may increase the
acidosis produced by CAIs
The acidosis produced by CAIs may increase the
toxicity of salicylates
Editor's Notes
Carbonic anhydrase is an enzyme that catalyzes the reversible reaction between carbon dioxide (CO2) and water to form carbonic acid (H2CO3), which quickly dissociates to bicarbonate (HCO3-) and hydrogen ions (H+).