5. Objectives
Identify risk factors for the development of primary open-angle
glaucoma (POAG) and acute angleclosure glaucoma.
Recommend a frequency for glaucoma screening based on patient-
specific risk factors.
Compare and contrast the pathophysiologic mechanisms responsible
for open-angle glaucoma and acute angle-closure glaucoma.
Compare and contrast the clinical presentation of chronic open-
angle glaucoma and acute angleclosure glaucoma.
2/20/2023 5
6. Objectives ...,
List the goals of treatment for patients with POAG suspect, POAG, and
acute angle-closure glaucoma.
Choose the most appropriate therapy based on patient-specific data for
open-angle glaucoma, glaucoma suspect, and acute angle-closure
glaucoma.
Develop a monitoring plan for patients on specific pharmacologic
regimens.
Counsel patients about glaucoma, drug therapy options, ophthalmic
administration techniques, and the importance of adherence to the
prescribed regimen.
2/20/2023 6
7. Introduction
Glaucoma, a leading cause of blindnessworldwide,
Is a nonspecific term used for a group of diseases that can irreversibly
damage the optic nerve, resulting in visual field loss.
Glaucoma refers to a spectrum of ophthalmic disorders characterized
by neuropathy of the optic nerve and loss of retinal ganglion cells,
Which typically leads to permanent deterioration of the visual field
(peripheral vision) initially and potentially total vision loss (including
central vision).
It is often, but not always, eye pressure related.
2/20/2023 7
8. Introduction...,
Primary open-angle glaucoma (POAG) and primary
angleclosure glaucoma (PACG) represent the most common
types of glaucoma
A common presentation of PACG is acute angle-closure crisis
(AACC).
AACC is the sudden obstruction of the trabecular meshwork,
which leads to rapid increases in IOP resulting in
pressureinduced optic neuropathy if untreated.
Patients with POAG typically have a slow, insidious loss of
vision.
This is contrasted by the course of AACC, which can lead to
rapid vision loss that develops over hours to days.
2/20/2023 8
9. EPIDEMIOLOGY AND ETIOLOGY
It is estimated that almost 65 million people had glaucoma in 2013,
making it the second leading cause of blindness after cataracts
In 2010, glaucoma was the second leading cause of blindness
worldwide
The prevalence varies with race and ethnicity, increases with age and
is rarely seen in patients younger than 40 years
The prevalence of angle closure glaucoma is lower than POAG and
varies significantly by race and ethnicity
PACG is also more prevalent with increasing age and among females
2/20/2023 9
14. PATHOPHYSIOLOGY...,
The pathophysiology of glaucomatous neurodegeneration
has not been completely elucidated but
Appears to be caused by both IOP-dependent and IOP-
independent factors.
Elevated IOP is clearly associated with damage and eventual
death of optic nerves;
However, optic neuropathy still occurs in patients without
elevated IOP which indicates the presence of independent
factors that contribute to ganglion cell death
2/20/2023 14
15. Pathophysiology of Open Angle
Retinal Ganglion cells
The underlying pathology of glaucoma is lies in the apoptosis of
retinal ganglion cells.
RGCs form functional microcircuits with rods, cones, amacrine cells,
and bipolar cells that help transmit both image forming and non-
image forming information to the brain.
Regardless of whether intraocular pressure is elevated, normal, or
decreased- it is the death of RGCs that underlies the pathology of
glaucoma.
16. Pathophysiology of Open Angle...,
Lamina Cribrosa
The lamina cribrosa is a sieve-like fenestration at the back of
the sclera that allows for a conglomeration of retinal axons
and blood vessels to exit the posterior of the eye.
Changes in the three-dimensional structure of the lamina
cribrosa have been implicated in the pathogenesis of
glaucomatous optic atrophy.
17. It is thought that mechanical damage to axons and the prevention
of essential trophic factors, such as
Brain-derived neurotrophic factor (BDNF) being appropriately
delivered is conducive to the disease process.
Elevated Intraocular Pressure
High IOP is an important risk factor for the progression of
glaucoma.
Of the risk factors causing open-angle glaucoma, the most studied
risk factor had been elevated IOP, as it is modifiable.
The high fluctuation of IOP may also lead to glaucoma
progression.
Pathophysiology...........,
18. Aqueous Outflow
The two main proposed mechanisms by which an elevated
IOP is thought to contribute to glaucomatous damage includes
Vascular dysfunction resulting in ischemia to the optic nerve, and
Mechanical dysfunction as a result of compression of the axons.
When open-angle glaucoma in a patient is attributed to
elevated IOP, the cause of this increase in IOP is commonly
thought occur
Due to dysfunction in aqueous outflow through the
trabecular meshwork of the eye.
Pathophysiology...........,
19. Finally, it has been proposed that certain individuals may
have a genetic predisposition to cell death of individual
axons in the eye, resulting in
The release of potentially cytotoxic substances such as
Glutamate, calcium, nitric oxide, and free radicals, as
well as apoptosis of neighboring cells.
Pathophysiology...........,
20. Pathophysiology of Angle-Closure
Glaucoma
PACG can be separated into three categories:
Acute primary angle closure, subacute primary angle closure, and
chronic primary angle closure.
Acute PACG is the sudden obstruction of the trabecular meshwork which
leads to rapid increases in IOP resulting in pressure-induced optic
neuropathy if left untreated.
Acute PACG is a medical emergency and requires laser or surgical
intervention.
Subacute PACG is characterized by self-limiting angle closure that
resolves spontaneously.
2/20/2023 20
21. Pathophysiology of Angle-Closure
Glaucoma
Chronic PACG is characterized by the presence of peripheral anterior
synechia that partially obstruct the flow of aqueous humor through the
trabecular meshwork resulting in an elevated IOP that is similar to what it is
seen in POAG.
PACG involves a mechanical obstruction of aqueous humor outflow
through the trabecular meshwork by the peripheral iris.
Two major mechanisms of trabecular meshwork obstruction by the
peripheral iris include:
Pupillary block and
An abnormality of the iris called iris plateau.
2/20/2023 21
22. Pathophysiology of Angle-Closure
Glaucoma...,
Pupillary block is the more common mechanism of obstruction
and results from
A complete or functional apposition of the central iris to the
anterior lens and is associated with mid-dilation of the pupil.
The trapped aqueous humor in the posterior chamber increases
pressure behind the iris, causing the peripheral iris to bow
forward and obstruct the trabecular meshwork.
23. Pathophysiology of Angle-Closure
Glaucoma....,
Plateau iris refers to an anterior displacement of the peripheral iris
caused by anteriorly positioned ciliary processes.
In this configuration, the peripheral iris bunches as the eye dilates.
Both of these mechanisms result in the occlusion of aqueous humor
outflow, causing IOP elevation at extreme levels that can lead to
vision loss in hours to days.
The degree of iridotrabecular contact (angle closure) can be assessed
by
Visualizing the anatomy of the iridocorneal angle by an examination
technique called gonioscopy.
24. Clinical Presentation
Patients with ocular hypertension or POAG typically have a slow,
insidious loss of vision.
This is contrasted by the course of acute PACG which can lead to rapid
vision loss that develops over hours to days.
For POAG, only 4% to 8% of patients may progress to legal blindness.
It may take 13 to 16 years for a patient to go blind from glaucoma.
Vision loss does not occur until there has been significant loss of the
retinal ganglion cells.
2/20/2023 24
25. Peripheral vision is the most susceptible to glaucomatous damage,with
central vision being preserved until advanced disease progression has
occurred.
Visual field abnormalities include paracentral scotoma, nasal scotoma, and
arcuate scotoma.
Patients may also have problems with depth perception and contrast
sensitivity.
Peripheral vision may worsen until the patient has tunnel vision and
ultimately total field loss.
Visual fields can be measured by perimetry and can detect defects in the
visual field before a patient may notice.
2/20/2023 25
Clinical Presentation.....,
28. TREATMENT
Primary Open-Angle Glaucoma
Desired Outcomes and Goals
The goals of therapy are to
Prevent further loss of visual function;
Minimize adverse effects of therapy and its impact on the
patient’s vision, general health, and quality of life;
Maintain IOP at or below a pressure at which further optic
nerve damage is unlikely to occur; and educate and involve the
patient in the management of their disease.
Current therapy is directed at altering the flow of aqueous
humor, which is the major determinant of IOP.
2/20/2023 28
29. TREATMENT.....,
General Approach
Since POAG is a chronic, often asymptomatic condition, the decision
of when and how to treat patients is difficult since the treatment
modalities are often expensive and have potential adverse effects or
complications.
The clinician should evaluate the potential effectiveness, toxicity,
and the likelihood of patient adherence for each therapeutic modality.
The ideal therapeutic regimen should have maximal effectiveness
and patient tolerance to achieve the desired therapeutic response.
2/20/2023 29
30. TREATMENT.....,
The AAO recommends an initial target IOP to be set at 20%
lower than the patient’s baseline IOP.
The target IOP can be set lower (30% to 50% of baseline IOP)
for patients that already have severe disease or have normal-
tension glaucoma
Initial IOP control can be achieved by medical, laser, surgical,
or a combination of these therapies.
2/20/2023 30
31. TREATMENT OF CLOSED-ANGLE GLAUCOMA
Acute ACG with high IOP requires rapid reduction in IOP.
Iridectomy is the definitive treatment producing a hole in the iris that
permits aqueous humor flow to move directly from the posterior to the
anterior chamber.
Drug therapy of an acute attack typically consists of a miotic (eg,
pilocarpine), secretory inhibitor (eg, β-blocker, α2-agonist, latanoprost, or
CAI), or prostaglandin agonist.
Osmotic agents are used to rapidly decrease IOP. Examples include oral
glycerin, 1 to 2 g/kg, and mannitol, 1 to 2 g/kg IV.
Topical corticosteroids can be used to reduce ocular inflammation and
synechiae.
2/20/2023 31
32. Treatment of suspected glaucoma and
ocular hypertension
Ocular hypertension is when patient IOP >22 mm Hg [>2.9 kPa
Risk factors which must be taken into consideration when deciding which
individuals need treatment
Family history of glaucoma
Black ethnicity,
Severe myopia, and
Patients with only one
Patients without risk factors typically are not treated and are monitored for the
development of glaucomatous changes.
2/20/2023 32
33. The goal of therapy
Lower the IOP to a level associated with a decreased risk of optic nerve
damage
Greater decreases may be required in high-risk patients or those with
higher initial IOPs.
Pharmacological treatment for patient who have risk factor
Topical agent depending on individual patient characteristics
Prostaglandin analog or β-blocking agent.
Brimonidine or a topical carbonicanhydrase inhibitor also as alternative drug
Therapy is initiated in one eye to assess efficacy and tolerance
34. Second- or third-line agents
Pilocarpine or dipivefrin when first-line agents fail to reduce IOP
depends on the risk-to-benefit assessment of each patient.
Monitoring drug therapy
Measurement of IOP
Examination of the optic disk,
Assessment of the visual fields, and
Evaluation of the patient for drug adverse effects
Patients who are unresponsive to or intolerant of a drug should be
switched to an alternative agent
35. Primary Angle-Closure Glaucoma
Desired Outcomes and Goals
Therapeutic modalities for PACG are targeted at decreasing
IOP.
The goals of therapy are to
Preserve visual function by controlling the elevation in IOP,
Manage an acute attack of angle closure,
Reverse or prevent angle closure using a laser and/or surgical
intervention, and
Educate and involve the patient in the management of the disease
2/20/2023 35
36. General Approach
The treatment of choice for PACG is laser iridotomy.
Medical therapy is used to lower IOP, reduce pain, and reverse corneal
edema prior to the iridotomy.
IOP should first be lowered with
Topical β-blockers,
Topical α-agonists,
Prostaglandin F2α analogs,
Systemic carbonic anhydrase inhibitors, or
Hyperosmotic agents.
2/20/2023 36
37. Non pharmacologic Therapy
Laser iridotomy
Uses laser energy to cut a hole in the iris to alleviate the aqueous humor
build-up behind the iris, resulting in reversal of appositional angle
closure.
Incisional iridectomy
Is the surgical removal of a small portion of the iris to allow drainage of
aqueous humor trapped in the posterior chamber.
Surgical iridectomy
Is reserved for when laser iridotomy is not possible or indicated.
2/20/2023 37
38. FIGURE. Algorithm for the pharmacotherapy,of open-angle glaucoma. aFourth-line agents not
commonly used any longer. bMost clinicians believe laser procedure should be performed earlier
(e.g., after three-drug maximum, poorly adherent patient). CAI, carbonic anhydrase inhibitor.
2/20/2023 38
39. Pharmacologic Therapy
1. Beta-Adrenergic Antagonists
Topical β-adrenergic antagonists (β-blockers) are generally considered first-
line agents for the treatment of POAG unless contraindications are present.
Topical β-blockers decrease IOP by
Reducing the formation of aqueous humor made by the ciliary body, which
results in a 20% to 35% reduction in IOP.
Timolol, levobunolol, metipranolol, and carteolol
Are non-selective for β1- and β2-adrenergic receptors, while betaxolol has β1-
selective properties.
All of the topical β-blockers have similar efficacy and adverse-effect profiles.
2/20/2023 39
40. Topical β-blockers are typically administered twice daily.
A gel-forming solution of timolol (Timoptic-XE) can be administered
once daily.
Adverse effects
Bronchospasm
Pulmonary edema, status asthmaticus, and respiratory arrest
Cardiovascular effects include bradycardia, hypotension, and congestive heart
failure exacerbation
Topical β-blockers are generally contraindicated
In patients with asthma, chronic obstructive pulmonary disease, sinus
bradycardia, second- or third-degree heart block, cardiac failure, and
hypersensitivity to the product
2/20/2023 40
41. 2. Ocular Hypotensive Lipids
The ocular hypotensive lipids in typical ophthalmology
practice are considered first-line alternatives to topical β-
blockers
Because of their superior efficacy and safety profiles.
Latanoprost is currently the only ocular hypotensive lipid
drug that has a Food and Drug Administration (FDA)
indication for first-line therapy.
Bimatoprost and travoprost are indicated by the FDA for
patients who are intolerant of other IOP-lowering therapy or
2/20/2023 41
42. 2. Ocular Hypotensive Lipids....,
Latanoprost and travoprost are analogs of prostaglandin F2α and
are agonists of the prostanoid FP receptor,
Which appears to lower IOP by increasing aqueous humor outflow
through the uveoscleral pathway.
Bimatoprost is a prostamide analog and appears to lower IOP by
Activating prostamide receptors in the uveoscleral pathway and
possibly through increasing outflow through the trabecular
meshwork.
2/20/2023 42
43. 2. Ocular Hypotensive Lipids.....,
Latanoprost, travoprost, and bimatoprost are administered
once daily at bedtime and should not be increased to twice daily,
as this may decrease effectiveness.
The ocular hypotensive lipids are well tolerated and rarely cause
systemic side effects (though headache has been reported).
Local effects include conjunctival
Hyperemia, stinging on instillation, an increase in iris pigmentation,
hypertrichosis, and darkening of the eyelashes.
2/20/2023 43
44. 3. Alpha2-Adrenergic Agonists
Brimonidine and apraclonidine are α2-adrenergic agonists that
decrease IOP by reducing aqueous humor production.
Brimonidine has a higher selectivity to the α2 receptor than
apraclonidine and has a dual mechanism of action by increasing
uveosceral outflow.
Apraclonidine is often used for the prevention and treatment of
post-surgical IOP elevations and no longer commonly used for
long-term treatment of POAG because of tachyphylaxis and a
high rate of blepharoconjunctivitis.
2/20/2023 44
45. 3. Alpha2-Adrenergic
Agonists...,
Apraclonidine and brimonidine cause both local and systemic
effects.
Local effects of apraclonidine include
Blepharoconjunctivitis, foreign body sensation, pupillary
mydrasis, and eyelid retraction.
The brimonidine- purite solution has a lower incidence of ocular
allergy.
Systemic effects of both agents include headache, dry mouth, and
fatigue.
2/20/2023 45
46. 4. Carbonic Anhydrase Inhibitors
Carbonic anhydrase inhibitors decrease aqueous humor
production
By inhibition of the carbonic anhydrase isoenzyme II located
in the ciliary body.
In the eye, carbonic anhydrase catalyzes the conversion of water
and carbon dioxide to bicarbonate and hydrogen ion, which is a
significant step in aqueous humor production.
Carbonic anhydrase inhibitors are available in systemic and
topical preparations.
2/20/2023 46
47. 4. Carbonic Anhydrase Inhibitors.....,
Topical Carbonic Anhydrase Inhibitors
Dorzolamide and brinzolamide are the only topical carbonic
anhydrase inhibitors available and lower IOP by 15% to 24%.
Both medications are administered every 8 hours and are use as
adjunctive therapy or as monotherapy for patients that cannot tolerate
first-line agents.
Nasolacrimal occlusion may allow for dosing every 12 hours.
Local side effects include burning, stinging, itching, foreign body
sensation, dry eyes, and conjunctivitis.
2/20/2023 47
48. 4. Carbonic Anhydrase Inhibitors....,
Both topical carbonic anhydrase inhibitors are sulfonamides
and are contraindicated in patients with history of sulfonamide
hypersensitivity.
A combination product of timolol (0.5%) and dorzolamide
(2%) (Cosopt™) is available and
Can be administered twice daily and provides an additive
reduction in IOP
2/20/2023 48
49. 4. Carbonic Anhydrase Inhibitors.....,
Systemic Carbonic Anhydrase Inhibitors
There are three systemic carbonic anhydrase inhibitors: acetazolamide,
dichlorphenamide, and methazolamide.
These agents effectively lower IOP by 20% to 30% but are reserved as
third-line agents because of their significant adverse effects.
They are typically used as bridge therapy from maximal medical therapy to
laser or surgical intervention.
The systemic carbonic anhydrase inhibitors can also be used to lower IOP in
acute angle-closure glaucoma.
Acetazolamide has an intravenous formulation that can be utilized in
patients having nausea due to the angle-closure attack.
2/20/2023 49
50. 4. Carbonic Anhydrase Inhibitors.....,
Acetazolamide and methazolamide are the best tolerated of the three agents.
The systemic carbonic anhydrase inhibitors are associated with
significant adverse effects which include paresthesias of the hands
and feet, nausea, vomiting, and weight loss.
Patients can develop systemic acidosis, hypokalemia, hyponatremia,
and nephrolithiasis due to the inhibition of renal carbonic anhydrase.
Sulfonamide allergy, renal failure, hepatic insufficiency, chronic
obstructive pulmonary disease, and decreased serum potassium and
sodium levels are all contraindications of systemic carbonic
anhydrase inhibitor therapy.
2/20/2023 50
51. 5. Cholinergic Agents
Cholinergic agents (also called parasympathomimetics or miotics) were the
first class of agents used to treat glaucoma.
The class can be divided into
Direct-acting cholinergic agents and indirect-acting cholinergic agents
Direct-Acting Cholinergic Agents
Pilocarpine directly stimulates the muscarinic (M3) receptors of the ciliary
body which causes contraction of the ciliary muscle.
This results in widening of the spaces in the trabecular meshwork,
Which causes an increase in aqueous humor outflow and reduces IOP by 20%
to 30%.
2/20/2023 51
52. 5. Cholinergic Agents....,
Pilocarpine requires administration four times daily, since the
IOP-lowering effect lasts only 6 hours.
A pilocarpine 4% gel is available and allows for once-daily
dosing at bedtime
The adverse effects of pilocarpine are caused by the induction
of miosis.
2/20/2023 52
53. 5. Cholinergic Agents.....,
Indirect-Acting Cholinergic Agents
Ecothiophate iodide and denecarium bromide inhibit
acetylcholinesterase.
Inhibition of this enzyme increases the availability of
acetylcholine at the nerve junction,
Thus increasing the stimulation of the muscarinic (M3) receptors of
the ciliary body.
These products are given twice daily and have similar efficacy to
pilocarpine in the degree of IOP reduction.
2/20/2023 53
54. 6. Hyperosmotics
Glycerin, isosorbide, and mannitol are hyperosmotic agents which
increase the osmolality of blood.
These agents create an osmotic gradient that draws water from the vitreous
humor, thus decreasing IOP.
The resulting dehydration of the vitreous humor may cause posterior
movement of the lens, which then causes the anterior chamber to deepen,
thus opening the anterior angle.
If the patient is not vomiting, glycerin (1 to 1.5 g/kg of a 50%) solution and
isosorbide (1.5 to 2 g/kg) can be given orally.
Isosorbide is preferred in patients with diabetes since it is not metabolized
into glucose.
2/20/2023 54
55. 6. Hyperosmotics.....,
If the patient has nausea or vomiting, mannitol (20%) can be
given intravenously at a dose of 1 to 2 g/kg over 45 minutes.
The hyperosmotic agents are rapid acting, reaching peak effect in
30 to 60 minutes.
Headache and thirst are common complaints.
Patients that are already dehydrated are at risk of developing
central nervous system dehydration which can lead to coma.
These agents should be used with caution in patients with renal or
cardiovascular disease, as extracellular water is increased.
2/20/2023 55
56. Drug Induced glaucoma
Medications have the potential to cause or exacerbate both
POAG and PACG; however,
PACG is more likely to be exacerbated by medications than
POAG.
PACG patients who have been treated with laser iridotomy can
usually use these agents without causing an exacerbation.
Patients with open or closed anterior angles can experience
elevated IOP from these drugs.
59. EVALUATION OF THERAPEUTIC OUTCOMES
Successful outcomes require identifying an effective, well-tolerated
regimen; closely monitoring therapy; and patient adherence..
Monitoring therapy for POAG should be individualized.
Assess IOP response every 4 to 6 weeks initially, every 3 to 4 months after
IOPs become acceptable, and more frequently if therapy is changed.
Visual field and disc changes are monitored annually, unless glaucoma is
unstable or worsening.
Monitor patients for loss of control of IOP (tachyphylaxis), especially with
β- blockers or apraclonidine.
Treatment can be temporarily discontinued to monitor benefit.
2/20/2023 59
60. There is no specific target IOP because the correlation between IOP and
optic nerve damage is poor.
Typically, a reduction of 25% to 30% is desired.
The target IOP also depends on disease severity and is generally less than 21
mm Hg (2.8 kPa) for early visual field loss or optic disc changes, with
progressively lower targets for greater levels of glaucomatous damage.
Targets as low as less than 10 mm Hg (1.3 kPa) are desired for very
advanced disease, continued damage at higher IOPs, normal-tension
glaucoma, and pretreatment pressures in the low to middle teens.
Monitor medication adherence because it is commonly inadequate and a
cause of therapy failure.
2/20/2023 60
61. Reference
1. Pharmacotherapy-Principles and Practice Chisholm (
PDFDrive )
2. Joseph_T_DiPiro,_Gary_C_Yee,_L_Michael_Posey_edi
tors_Pharmacotherapy
3. Barbara G. Wells_ Joseph T. DiPiro_ Terry L.
Schwinghammer_ Cecily DiPiro - Pharmacotherapy
Handbook, Tenth Edition (2017, McGraw-Hill
Education _ Medical)
2/20/2023 61
If laser iridotomy cannot be performed, incisional
iridectomy is used. A topical corticosteroid may be employed
to decrease inflammation. The fellow eye is at high risk of having
an acute attack and should receive prophylactic iridotomy.
Patients with chronic angle closure should also receive laser iridotomy.
Acute and chronic angle-closure patients may require
chronic medical therapy if the patient has PACG superimposed
on preexisting POAG, or synechia formation causes continued
increases in IOP
If laser iridotomy cannot be performed, incisional iridectomy is used.
A topical corticosteroid may be employed to decrease inflammation.
The fellow eye is at high risk of having an acute attack and should receive prophylactic iridotomy.
Patients with chronic angle closure should also receive laser iridotomy.
Acute and chronic angle-closure patients may require chronic medical therapy if the patient has PACG superimposed on preexisting POAG, or synechia formation causes continued increases in IOP
