This document provides information on glaucoma medications. It discusses how most glaucoma medications are administered topically but can still be systemically absorbed. It recommends measures to minimize absorption like closing the eyes after instillation. It also categorizes different classes of glaucoma medications and discusses their common side effects. Prostaglandin agonists are highlighted as first-line treatment options but warnings are provided about potential side effects like pigmentation changes. The document aims to guide practitioners on appropriate treatment and management of glaucoma patients.

1. GLAUCOMA MEDICATION
DR. ALSHYMAA MOUSTAFA
OPTHALMOLOGIST

2. CONTENTS
INTRODUCTION
GENERAL
CONSIDERATION
TARGET IOP
MEDICATION
1
2
3
4

3. 01
INTRODUCTION

4. • Most glaucoma medications are administered
topically, but significant systemic absorption
can still occur, with resultant systemic adverse
effects.
• Systemic absorption may be minimized by
lacrimal occlusion following instillation:
1. Closing the eyes for 3 minutes will reduce
systemic absorption by about 50% and this can
be enhanced.
2. Digital pressure over the lacrimal sac –
these measures also prolong eye–drug

5. • Effects on the periocular skin may be reduced by
blotting overflow from the eyelids with a clean dry
tissue immediately after instillation.
• Glaucoma medications should be avoided in
pregnancy if possible, with systemic carbonic
anhydrase inhibitors perhaps carrying the
greatest risk due to teratogenicity concerns.

6. 02
GENERAL
CONSIDERATION

7. WHO TO TREAT?
1. Is the glaucomatous process
present?
2. Is the glaucomatous process
active?
3. Is the glaucomatous process likely
to cause disability?

8. 1. Is the glaucomatous process
present?
• Glaucomatous damage is likely if any of the following are
present:
presence of thin or notched optic nerve rim
characteristic visual field loss.
retinal nerve fiber layer damage.
DDLS score is >5.
• Treatment should be considered in the absence of manifest
damage if IOP is higher than 30 mm Hg, and/or IOP
asymmetry is more than 10 mm Hg.

9. Disc damage likelihood scale (DDLS)

10. 2. Is the glaucomatous process
active?
• Determine the rate of damage progression by
careful follow up.
• Certain causes of optic nerve rim loss may be
static (e.g., prior steroid response).
• Disc hemorrhages suggest active disease.

11. 3. Is the glaucomatous process likely to
cause disability?
Consider :
1. The patient’s age,
2. Overall physical and social health,
3. Estimation of his or her life expectancy.

12. WHAT IS THE
TREATMENT GOAL?
• Enhance or maintain the patient’s health by halting optic
nerve damage while avoiding undue side effects of treatment.
• The only proven method of stopping or slowing
optic nerve damage is reducing IOP.
• Reduction of IOP by at least 30% appears to have the best
chance of preventing further optic nerve damage.
• If damage is severe, greater reduction in IOP may be
necessary.

13. HOW TO TREAT?
• The TTT modalities of glaucoma are:
1. Medications
2. laser trabeculoplasty (LT): (selective [SLT] more commonly
than argon [ALT]).
3. Glaucoma surgery.
• Medications or LT are appropriate initial therapies.
• LT may be especially suitable in patients at risk for poor
compliance, with medication side effects, and who have
significant trabecular meshwork (TM) pigmentation.

14. • Surgery may be appropriate initial treatment if damage is
advanced in the setting of a rapid rate of progression or
difficult follow up. Options include glaucoma filtering
surgery (e.g., trabeculectomy, tube shunt), minimally
invasive glaucoma surgery (MIGS), laser
cyclophotocoagulation of the ciliary body (e.g., with diode
laser or endolaser), and cyclocryotherapy.
• Surgery should always be considered for any patient with
advanced/progressive disease or IOP uncontrolled by other
methods.

15. 03
TARGET IOP

16. 1. What is “normal” IOP?
2. The concept of “target” IOP
3. Parameters that influence
progression and hence target
IOP.
4. Staging of Glaucomatous
Damage.
5. Suggested methods to
determine “target” IOP
6. Limitations of using “target”
IOP
7. Reassessing “target” IOP
over time.

17. What is “normal” IOP?
• It is important to know the IOP in people without
glaucoma in a population, both for better diagnosis and
also better management of glaucoma patients from that
population, as there are racial differences.
• Mean applanation IOP to be 15.9 mmHg in males and
16.6 mmHg in females.
• An IOP of < 21 mmHg should not be taken an
appropriate “target” IOP or as normal.

19. The concept of “target”
IOP
• That of an IOP that prevent further progression of
glaucomatous visual field (VF) loss, without
compromising a patient's quality of life.
• Quality of life would be significantly and
permanently affected by progression of VF loss
and stabilization of the VF is therefore the major
goal.

20. Parameters that influence
progression and hence target
IOP
Certain important risk factors need to be
assessed before an objective plan to
prevent/stabilize glaucoma progression in
POAG and PACG can be formulated.

21. 1. Examination of the optic nerve
head
• looking especially at the inferior and superior poles as
pointed out by Chandler, helps identify
thinning/notching/pallor of the neuroretinal rim and
associated retinal nerve fiber layer defects.
• This provides a measure of the amount of structural damage to
the nerve.

22. 2. IOP
• At least three IOP measurements, taken at different times
of the day, ideally with an applanation tonometer, help
determine baseline IOP, the pressure at which optic nerve
damage can be taken to have occurred.
• Any single IOP measurement taken between 7 am and 9 pm
has a > 75% chance of missing the highest point of a
diurnal curve.

23. 3. Perimetry
• Reliable perimetry with reproducible VF defects on at least
two consecutive fields allows staging of the functional
visual loss in each patient.
• The speed of progression of VF loss over time; rate of
progression on glaucoma progression analysis of Humphrey
field analyzer should also be noted, as it will indicate the need
for a more or less aggressive therapy.

24. 4. Age
• Collaborative Initial Glaucoma Treatment Study (CIGTS) found
that patients who were a decade older had a 40% risk of
perimetric loss.
• Early Manifest Glaucoma Trial (EMGT) reported that those >
68 years old were more likely to progress.

25. 5. Additional risk factors
① Family history of glaucoma.
② Thinner central pachymetry
③ Pseudoexfoliation
④ History of an acute PACG attack,
⑤ Cardiovascular disease,
⑥ Patient's life expectancy,
⑦ Steroid use,
⑧ Transient ischemic attacks (TIAs),
⑨ Other systemic problems should be recorded.

26. Staging of Glaucomatous
Damage
Unfortunately, there is no universally
accepted staging of either optic nerve
head abnormalities or VF changes, with
regard to their relevance to progression.

28. 1. ONH staging
• Staging glaucoma by a careful examination of the
neuroretinal rim.
• Rim loss generally starts inferiorly, and then superiorly,
finally extending around the disc.
• The inner edge of the neuroretinal rim should be
identified by the bending of the blood vessels onto
the surface of the neuroretinal rim.

30. 2.Perimetric Staging
• There are many suggested classifications of the
severity of glaucomatous damage:
1. Hodapp Parrish Anderson,
2. Glaucoma Severity Staging system (GSS)
3. Enhanced GSS.etc.
• They are based on the extent of damage and
proximity to fixation, using global indices and
number/percentage of significantly depressed loci,
with multiple and varied stages.

32. Methods of Determining
Target Intraocular Pressure
• Various approaches for setting a target IOP include as follows:
1. Threshold/absolute cut off value
2. Percentage reduction
3. Formula-based values.
4. 3 step process AGIS.

33. 1.Threshold/absolute cut off value
• In general
1. Mild < 18 mmmHg
2. Moderate 15 mmHg
3. Severe 12 mmHg.

34. 2.Percentage reduction in intraocular
pressure
• OHT 20%
• Early glaucoma 25%
• Moderate Glaucoma, LTG 30% - 35%
• Sever Glaucoma > 35%

36. 3.Formulas for setting a “target”
intraocular pressure
•TP = IP × [1 – IP/100]
•TP = ( IP × [1 – IP/100] − Z ± 2)
• Jampel first calculated target IOP by taking into
account several attributes of the patient
1. Initial pretreatment IOP
2. Z score (an indicator of disease severity)

37. 4. AGIS 3 Step process
• First: IOP reduced by its own percent.
• Secend: further reduce by MD percent.
• Third: aditional reduction by 10% :15% (risk factirs).

38. Limitations of using “target”
IOP
• To date, there are inadequate data available to show
that if an individual patient exceeds this target, he/she
will progress, and there are not enough evidence-based
studies to determine absolute IOP levels in each
individual.
• It is also difficult to definitively diagnose early
progression by perimetry or objective monitoring so
that resetting target IOP may be delayed, allowing some
loss of VF.

39. Reassessing “Target”
Intraocular Pressure over
Time
• There is no single, safe level of IOP that is
appropriate for all patients at all times, and in spite of
achieving target IOP, a few patients show progression of the
disease, probably because of other pathological factors.
• “Target” IOP requires further lowering when the patient
continues to progress or develops systemic diseases such as a
TIA.
• Conversely, in the event of a very elderly or sick patient with
stable nerve and VF over time, the target IOP could be
raised and medications reduced.

40. 04
MEDICATION

41. CLASSIFICATION
Miotics
Combined preparations
New topical
medications
Systemic carbonic
anhydrase inhibitors
Osmotic agents
Prostaglandin
derivatives
Beta-blockers
Alpha-2 agonists
Topical carbonic
anhydrase inhibitors

44. SIDE EFFECTS OF TOPICAL
MEDICATION
(A) Lengthening
and hyperpigmentation of lashes with
prostaglandin analogue treatment.
(B) monocular prostaglandin analogue treatment
darkening of left iris and eyelid skin.
(C) periocular atrophy on the left.

45. (D)
blepharoconjunctivitis
due to topical carbonic
anhydrase inhibitors.
(E) allergic
conjunctivitis due to
brimonidine.
(F) iritis secondary to
brimonidine, showing keratic
precipitates.

46. PROSTAGLANDIN AGONISTS
• latanoprost 0.005%, bimatoprost 0.01% or 0.03%,
travoprost 0.004% tafluprost 0.0015% [preservative free]
—> once daily.
• PGS are to be used with caution in patients with active uveitis
or (CME) and are contraindicated in pregnant women or in
women wishing to become pregnant.
• Inform patients of potential pigment changes in iris and
periorbital skin, as well as hypertrichosis of eyelashes.
• Irreversible iris pigment changes rarely occur in blue or dark
brown eyes; those at highest risk for iris hyperpigmentation
have hazel, gray irides.

48. BETA-BLOCKERS
• levobunolol or timolol 0.25% to 0.5% .
• ED —> twice daily ,Gel —> once daily .
• Carteolol—> oCuloselective, safe in Cardiac
• Metipranolol—> Uveitis
• BetaXolol—> Ca blocker ,Cardioselective (not in cardiac )
and is safe in Bronchial asthma.

49. ALPHA-2 AGONISTS
• Selective α2-receptor agonists
• Brimonidine 0.1%, 0.15%, or 0.2% b.i.d. to t.i.d.) ,
Contraindicate in patients taking monoamine oxidase inhibitors
(risk of hypertensive crisis) and relatively contraindicated in
children under the age of 5 (risk for cardiorespiratory and CNS
depression).
• Apraclonidine 0.5% or 1% is rarely used due to
tachyphylaxis and high allergy rate but may be used for
shortterm therapy (3 months).

50. TOPICAL CARBONIC
ANHYDRASE INHIBITORS
• Dorzolamide 2% or Brinzolamide 1% b.i.d. to t.i.d.
• Should be avoided, but are not contraindicated, in patients with
sulfa allergy.
• Systemic symptoms from topical CAIs are extremely rare, but
occurs.
• Corneal endothelial dysfunction may be exacerbated with
topical CAIs; these medications should be used cautiously in
patients with Fuchs corneal dystrophy and post keratoplasty.

51. MIOTICS
• Pilocarpine q.i.d. are usually used in low strengths initially
(e.g., 1% to 2%) and then built up to higher strengths (e.g., 4%).
• Commonly not tolerated in patients <40 years because of
accommodative spasm.
• Miotics are usually contraindicated in patients with retinal holes
and should be used cautiously in patients at risk for retinal
detachment (e.g., high myopes and aphakes).

52. COMBINED PREPARATIONS
• Combined preparations with similar ocular hypotensive effects
to the sum of the individual components improve convenience
and patient adherence.
• They are also more cost effective.
Cosopt®: timolol and dorzolamide, administered twice daily.
Xalacom®: timolol and latanoprost once daily.
TimPilo®: timolol and pilocarpine twice daily.
Combigan®: timolol and brimonidine twice daily.

53. DuoTrav®: timolol and travoprost once daily.
Ganfort®: timolol and bimatoprost once daily.
Taptiqom®: timolol and tafluprost once daily.
Azarga®: timolol and brinzolamide twice daily.
•Simbrinza®: brimonidine and brinzolamide
a new combination (the only combination that does not contain
the betablocker timolol) administered twice daily.

54. NEW TOPICAL MEDICATIONS
Latanoprostene bunod 0.024%
(Vyzulta®) :
• is a new FDAapproved topical medication that reduces IOP
significantly.
• It has a dual mechanism of action: the latanoprost
component increases outflow through the uveoscleral route and
the butanediol mononitrate component undergoes further
metabolism in the anterior chamber to produce nitric oxide,
which has an effect on the trabecular meshwork leading to
enhanced aqueous outflow. It is used once daily and

55. Rho-kinase (ROCK) inhibitors :
• A novel class of topical medication that increase outflow of
aqueous through the trabecular meshwork. The drops are
instilled once daily and are effective in combination with
latanoprost (Roclatan®).
• Rhokinase inhibitors are slightly more effective than
latanoprost in reducing the IOP.

56. SYSTEMIC CAIS
• Methazolamide 25 to 50 mg p.o. b.i.d. to t.i.d.,
Acetazolamid 125 to 250 mg p.o. b.i.d. to q.i.d., or
Acetazolamide 500 mg sequel p.o. b.i.d.)
• Relatively contraindicated in patients with renal failure.
• Potassium levels must be monitored if the patient is taking
other diuretic agents or digitalis.
• Side effects such as fatigue, nausea, confusion, and
paresthesias are common.
• Rare, but severe, hematologic side effects (e.g., aplastic
anemia) and Stevens–Johnson syndrome have occurred.

57. • Allergy to sulfa drugs is not an absolute contraindication to the
use of systemic CAIs, but extra caution should be exercised in
monitoring for an allergic reaction.
• Intravenous forms of systemic CAIs (e.g.,acetazolamide 250
to 500 mg i.v.) may be utilized if IOP decrease is urgent or if
IOP is refractory to topical therapy.
• Consider checking baseline creatinine in patients with
suspected or confirmed renal disease.

58. OSMOTIC AGENTS
• Osmotic agents lower IOP by creating an osmotic gradient so that water
is ‘drawn out’ from the vitreous into the blood.
• They are employed when a short-term reduction in IOP is
required that cannot be achieved by other means, such as in resistant
acute angle-closure glaucoma or when the IOP is very high prior to
intraocular surgery.
• They are of limited value in inflammatory glaucoma, in which
the integrity of the blood–aqueous barrier is compromised.
• Side effects include cardiovascular overload as a result of increased
extracellular volume (caution in patients with cardiac or renal disease),
urinary retention (especially elderly men), headache, backache, nausea
and confusion.

59. •Mannitol is given intravenously (1 g/kg body weight or 5 ml/kg
body weight of a 20% solution in water) over 30–60 minutes, with a
peak action within 30 minutes.
•Glycerol is an oral agent (1 g/kg body weight or 2 ml/kg body
weight of a 50% solution) with a sweet and sickly taste and can be given
with lemon (not orange) juice to avoid nausea. Peak action occurs within 1
hour.
• Glycerol is metabolized to glucose and careful monitoring with insulin
cover may be required if administered to a (well-controlled only) diabetic
patient.
•Isosorbide is a metabolically inert oral agent with a minty taste, using
the same dose as glycerol. It may be safer for diabetic patients.