Medical management of glaucoma

MEDICAL
MANAGEMENT
OF GLAUCOMA
Dr Kumar Siddharth

A.Making accurate clinical diagnosis
B.Assessing stage of the disease
C.Assessing risk factors for disease progression
D.Understanding patient’s access to healthcare and socioeconomic factors
E.Considering patient’s lifestyle, health status and life expectancy
F.Implementing treatment strategy on the basis of these factors and other
considerations

 Goal
 To manage all patients with glaucoma, preserving visual function while
maintaining best possible quality of life
 Achieving the goal
 By preventing or slowing the progression of glaucomatous damage by
lowering IOP to a level at which further damage is nil or minimal

 Elevated IOP, without
glaucomatous damage
 Evaluate risk factors
 Established glaucomatous damage
or dangerously high IOP
 Treat
Treat all if IOP > 28mmHg
Treat if IOP < 28mmHG, But elevat
• Disc suspect (haemorrhage)
• Retinal vascular occlusion
• Positive family history
• Other eye open angle glaucom
• Thin CCT < 500 micron
• Exfoliation
• OCT defect suspicious of glau
• Follow up doubtful
• One eyed patient
• Angle closure suspect
• Angle closure

NEW PATIENT
1. Chief complaints with medical and
ocular history
2. Visual acuity/refraction
3. Tonometry and pachymetry
4. External examination, pupil
5. Slit lamp and gonioscopy
6. Retina, optic nerve head with photo
7. Visual field
ESTABLISHED PATIENT
1. Adherence to treatment
2. Tolerance to treatment
3. IOP
4. Stability of optic nerve head and
visual function
5. Surgical site, if had surgical
intervention

1. Chronic open angle glaucoma
2. Normal tension glaucoma
3. Primary angle closure glaucoma after iridotomy
4. Secondary glaucoma
5. Acute angle closure attack

A.Establishing target IOP
B.Selecting initial medication

Sihota R, angmo D, ramaswamy D, dada T. Simplifying “target” intraocular pressure for different stages of primary
open-angle glaucoma and primary angle-closure glaucoma. Indian J ophthalmol 2018;66:495-505
 The European Glaucoma Society guidelines
define target IOP as “an estimate of the mean
IOP obtained with treatment that is expected to
prevent further glaucomatous damage”
 The American Academy of Ophthalmology
defines target IOP as “a range of IOP adequate to
stop progressive pressure-induced injury”
 The World Glaucoma Association defines it as
“an estimate of the mean IOP at which the risk
of decreased vision-related quality of life due to
glaucoma exceeds the risk of the treatment.”
What is target IOP??
The concept of target
IOP:
IOP that prevent
further progression of
glaucomatous visual
field loss, without
compromising patient’s
quality of life.

 Examination of optic nerve head
 Intraocular pressure
 Perimetry
 Age
 Additional risk factors

 Examination of the optic nerve
 Looking especially at the inferior and
superior poles
 Identify thinning/notching/pallor of the
neuroretinal rim
 retinal nerve fiber layer defects.
 This provides a measure of the amount of
structural damage to the nerve
 Cup: disc (C: D) ratio is more commonly
employed in clinical practice
 This is best assessed by a 90/78 D
examination for accurate delineation of
the neuroretinal rim
Staging of
glaucomatous
damage
C:D ratio
Early <0.65
Moderate 0.7-0.85
Severe >0.9

 At least three IOP measurements
 Taken at different times of the day
 Ideally with an applanation tonometer
 Helps 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.
 In PACG, it is important that the baseline IOP be recorded after iridotomy.
 On review, the IOP should be rechecked at the point of peak baseline IOP, if
available

 Reliable perimetry with reproducible VF
defects on at least two consecutive fields
 Allows staging of the functional visual loss in
each patient.
 Rate of progression on glaucoma progression
analysis of Humphrey field analyzer should
also be noted, as it will indicate the need of
aggression in therapy

EARLY MODERATE SEVERE
AAO Optic disc cupping but no
visual field loss
Glaucomatous neuropathy
+
visual field loss not within 5
degrees of fixation
Visual field loss in both
hemispheres or within 5
degrees of fixation
CNADIAN
GUIDELINES
C:D ratio <0.65
or
Mild visual field defect
not within 10 degrees of
fixation
C:D ratio 0.7-0.85
or
Visual field defect not within
10 degrees of fixation or
Both
C:D ratio > 0.9
or
Visual field defect within 10
degrees of fixation
or
Both
INTERNATIONAL
CLASSIFICATION
OF DISEASES 10
Optic nerve
abnormalities consistent
with glaucoma
+
Normal fields
Optic nerve anomalies
consistent with glaucoma
+
One hemifield anomaly, not
within 5 degrees
Optic nerve abnormalities
consistent with glaucoma
+
Both hemifield abnormality
or within 5 degrees

 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.
 On analysis, AGIS also noted that an older patient was more likely to progress.
 Similar association with age has been seen in PACG eyes as well

 High initial IOP
 Family history
 Thin CCT (<500 micron)
 Exfoliation glaucoma
 History of PACG attack
 Steroid use
 Presence of co morbidities
 Cardiovascular diseases
 Sleep apnoea
 TIA
Pseudoexfoliation syndrome

POAG and PACG after an
iridotomy
•Mild glaucomatous
damage the 15 – 17
mmHg, modified after a
review with at least 6
monthly perimetric
evaluations
•Moderate glaucomatous
damage 12 – 15 mmHg
•Severe glaucomatous
damage 10 – 12 mmHg,
with minimal fluctuations
Ocular hypertension
•Upper limit should be less
than 18 mmHg in
patients (IOP >28 or high
risk patients)
Normal tension glaucoma
•A fall in IOP of 30% from
baseline

 The therapeutic goal is to use the least amount of medication that will accomplish
the desired therapeutic effect with fewest adverse reactions and affordable for the
patients
 Exceptions for glaucoma therapy with medications include
 Patients with very high IOP which pose immediate threat to vision
 History of medical therapy without success or intolerable side effects
 Problems with adherence to the therapy
 Angle closure glaucoma
 Childhood glaucoma

Cholinergic
agents
Pilocarpine
Carbachol
Adrenergic
agonists
Selective
1. Apraclonidine
2. Brimonidine
Non selective
1. Epinephrine
2. Dipivefrin
Beta blockers
Selective
Betaxolol
Non selective
1. Carteolol
2. Levobunolol
3. Metipranolol
4. Timolol
Carbonic
anhydrase
inhibitors
Topical
1. Brinzolamide
2. Dorzolamide
Systemic
1. Acetazolamide
2. Dichlorphenamide
3. Methazolamide
Prostaglandin
analogues
Bimatoprost
Latanoprost
Travoprost
Unoprostone

 Single topical drug
 Prostaglandin analogues and beta blockers being first choice
 High compliance
 Low side effects
 Low frequency
 Reasonable cost
 Systemic drugs can be added initially if IOP is very high (>30mm Hg) at presentation
 Uniocular trial
 Reverse uniocular trial
 If target not achieved with 3 drugs/intolerance – perform surgery

Prostaglandin analogues
Target IOP achieved Target IOP not achieved
Well tolerated Not tolerated
Continue
Switch within group
Not tolerated
Change group
Switch within group
Target IOP not achieved
IOP fall <15%
Change group
IOP fall >15%
Add drug

 Inability to maintain target IOP
 Progressive glaucomatous damage even on maximum medical therapy
 Inability of the patient to tolerate or adhere to the medical regimen

 If the IOP is dangerously high or one eyed patient, they should be evaluated
within days of the first visit
 For other cases, it is better to wait for a month or two to get a better sense of
long term benefit of the drug
 After acceptable IOP reduction, revaluated every 3-6 months
 After years of follow up one may consider to stop the drug in one eye to
determine if it is still contributing
 Patient adherence and general welfare

1.About the disease
2.Why the medications
 Treatment will not improve the VA
 Potential side effects of medication
3. Therapeutic regimen
 Spacing if more than one drop is being
used
4. Administration of eye drops
 Nasolacrimal occlusion for 5 mins/gentle
eyelid closure for 5 mins
 No frequent blinking movements

Conjunctival cul-de-sac
• Degree to which the
drug saturates the
tear film
• Retention time in the
cul-de-sac
Corneal and
transconjunctival-
scleral penetration
• The drugs which can
exist in both water
soluble and lipid
soluble state are able
to penetrate the
intact cornea
• Endogenous enzymes
in corneal epithelium
Intraocular factors
influencing drug
bioavailability
• Local tissue binding
• Local tissue
metabolism
• Diffusion into
vascular system

1. Vehicle
• Affects
• Elimination
• Saturation in the
tear film
• Viscosity and
homogeneity
• Methyl cellulose or
polyvinyl alcohol
2. pH
• pH influences the
ratio of ionized and
non ionized
• Most of the
glaucoma drugs are
weak bases and are
absorbed at higher
Ph
3. Additives
• Most commonly
used preservative is
Benzalkonium
chloride
• It has bacteriostatic
activity
• Affects corneal
penetration by
affecting surface
tension of the drugs

 The study of impact of genetics on
drug response is known as
pharmacogenetics
 Predict the disease progression and
treatment outcome by studying drug
target genes, drug metabolizing
enzymes and disease genes
Example:
One gene variation in
Beta 2 adrenergic
receptor was
associated with 20%
greater IOP decrease
with use of topical
Timolol

 Adherence
 Pharmacokinetics
 Environmental factors
 Genetics
IOP response
Mean IOP before and after treatment
Change in IOP
Percentage change in IOP
Effect on diurnal IOP
Drug peak effect on IOP
Drug trough effect on IOP
Target IOP
Contralateral effect
Regression to the mean
Placebo effect

 Prostaglandins are eicosanoids, metabolic products of arachidonic
acid
 Prostaglandins that reach the systemic circulation are inactivated
by lung and liver
 Small doses (5mcg) lower the IOP

 Commercially used prostaglandin analogues
are modifications of PGF2alpha which acts on
FP receptor
 Increase in uveoscleral flow by two possible
mechanisms:
1. Relaxing the ciliary muscle
2. Matrix metalloproteinase induced remodelling of
extracellular matrix of the ciliary muscle
(reduction in collagen IV and myocilin)
• Prostaglandin
receptors have 4
subtypes EP, FP, IP,
TP
• FP receptors are G
protein coupled
receptors with
phospholipase C, and
inositol phosphate as
secondary messenger

Name Concentration Frequency
LATANOPROST 0.005% Once daily
UNOPROSTONE 0.15% Twice daily
TRAVOPROST 0.004% Once daily
BIMATOPROST 0.03% Once daily
TALFUPROST 0.0015% Once daily

Name Features
LATANOPROST • Latanoprost exhibits thermal and ultraviolet instability
• Latanoprost unopened bottles should be refrigerated, once opened can be stored at
room temperature of up to 25 degrees Celsius for 6 weeks
UNOPROSTONE • Low efficacy is due to increase in tissue matrix metalloproteinase inhibitors
• Storage - 2-25 degrees Celsius
TRAVOPROST • Storage - 2-25 degrees Celsius
BIMATOPROST • Hydrolysed by cornea to a lesser extent than other analogues
• Evidence that it also influences trabecular outflow
• Storage - 15-25 degrees Celsius
TAFLUPROST • Slightly less efficacious
• Better tolerated

SIDE EFFECTS
PROSTAGLANDIN
ANALOGUES
• Conjunctival hyperaemia
[Travoprost >Bimatoprost >Unoprostone>latanoprost]
• Upregulation of conjunctival fibroblasts
• Reactivation of herpes simplex keratitis (except Unoprostone)
• Irreversible pigmentation of iris (stromal)
• Reversible pigmentation of periocular area
• Hypertrichosis, stimulating growth phase in the hair cycle
• Superficial epithelial lesion with long term
• Allergic contact dermatitis
• Iris cyst
• Anterior uveitis and CME has been

Additive effect Fixed dose combination
Beta blockers Additional IOP
reduction
• Bimatoprost 0.03% + Timolol 0.5%, OD
• Latanoprost 0.005% + Timolol 0.5%, OD
• Travoprost 0.004% + timolol 0.5%, OD
Alpha agonists Additional IOP
reduction
Not available
Carbonic anhydrase
inhibitors (oral/
Additional IOP
reduction
Not available
Cholinergics Additional IOP
reduction
Not available

 Beta adrenergic receptor antagonists
 Alpha adrenergic antagonists
 Not used for long term treatment of glaucoma

 Reduces aqueous humour production by acting on beta 2 subtype adrenergic
receptor on the ciliary body
 It causes inhibition of catecholamine induced CAMP in the sympathetic nervous
system
 No effect on outflow
 Long term use in primates showed degeneration and rarefaction of trabecular meshwork
 It is not clear whether beta blockers influence the ocular blood flow and its impact
on IOP and visual field damage
 Does not reduce IOP during sleep
 They do not affect blood aqueous barrier

TIMOLOL MALEATE
[Non selective]
0.5% • Twice daily
• Gel form once daily
BETAXOLOL HYDROCHLORIDE
[Cardio selective]
0.25% Twice daily
LEVOBUNOLOL HYDROCHLORIDE
[Non selective]
• 0.5%
• 0.25%
• Once daily
• Twice daily
CARTEOLOL HYDROCHLORIDE
[Non selective]
1% Twice daily
METIPRANOLOL HYDROCHLORIDE
[Non selective]
0.3% Twice daily

CONCETRATION
• O.25% and 0.5% timolol are
equally efficacious, but 0.5%
timolol provided longer duration
of action
• People with darker iris required
higher concentration of timolol
FREQUENCY
• IOP lowering effect peaks at
2 hrs, with effect lasting for 24
hrs
• Timolol gel provided greater
efficacy compared to the solution
• After long term use, even after
stopping the IOP does not
increase until 14th day, because of
slow release from the pigmented
ocular tissue
• IOP lowering effect on treating and non treating eye via systemic
circulation

 In long term the pressure responsiveness to timolol decreases with continued
administration
 This happens in 2 phases
1.Short term escape
2.Long term drift

 Dramatic lowering of IOP after initiating the therapy, after which pressure rises
to reach a maintenance level
 The number of beta receptors increase after initiating the therapy
 Therefore it is prudent to wait for at least a month after initiating the therapy to
determine the efficacy

 Some patients show decline in pressure response to timolol, usually after 3
months to 1 year
 Aqueous production was more in most patients after 1 year of therapy compared
to after 1 week of therapy
 In a study patients were divided in 2 groups after continued timolol therapy
 In the 30 day timolol holiday period half of them received Dipivefrin and other half tear
substitute
 After the reinstitution of timolol the group that received dipivefrin during the timolol
holiday showed mean IOP reduction of 8.2mmHg, compared to IOP reduction of
3.9mmHg in group with tear substitute
 Based on this observation concept of pulsatile therapy came into the picture

Betaxolol • IOP reduction less than timolol
• Retinal protection better than timolol
• Lower plasma level compared to timolol and double the
aqueous concentration
Levobunolol /
Metipranolol
• IOP reduction and side effects were comparable to timolol
Carteolol • Intrinsic sympathomimetic action (early transient adrenergic
agonist action)
• Less ocular irritation than timolol
• IOP reduction comparable to timolol

Additive effect Fixed dose combination
PG analogues Additional IOP reduction • Bimatoprost 0.03% + Timolol 0.5%, OD
• Latanoprost 0.005% + Timolol 0.5%, OD
• Travoprost 0.004% + timolol 0.5%, OD
Alpha agonists Additional IOP reduction Brimonidine tartrate 0.2% + Timolol 0.5%, BD
Carbonic anhydrase
inhibitors
• Additional IOP reduction
• Timolol more effective with
oral CAIs than topical
• Dorzolamide 2% + timolol 0.5%, BD
• Brinzolamide 1% + timolol 0.5%, BD
Cholinergics Additional IOP reduction Not available

Side effects
Beta blockers • Affects mucous layer of tear film
• Punctate keratopathy and corneal anaesthesia
• Cicatricial pemphigoid
Betaxolol • CME
• Periocular cutaneous pigmentary changes
Metipranolol • Granulomatous anterior uveitis

 Measurable plasma level is present within 8 minutes or less of topical application
Cardiovascular
•Slows pulse rate
and weakens
muscular
contractility
•Associated with
arrhythmias,
heart failure
and syncope
•Profound when
combined with
calcium channel
blockers
Respiratory
effects
•Contraction of
bronchial
smooth muscles
Central nervous
system
•Vague
behavioural
symptoms
Effect on
cholesterol levels
•Decrease
plasma HDL,
increase the
risk of coronary
artery disease
Other systemic
reactions
•Nausea,
diarrhoea
•Alopecia, rash
•Worsening of
myasthenia
gravis
•Masked
symptoms of
hypoglycemia

 Thymoxamine
 Produces miosis, without shallowing of the anterior chamber or ciliary spasm
 Role in angle closure glaucoma
 Miosis without cyclotropia prevents against pigment dispersion
 Causes substantial narrowing of the palpebral fissure, useful in thyroid
ophthalmopathy
 Reversal of mydriasis
 Dipiprazole
 Commercially available for reversal of mydriasis

 Reduce IOP by reducing aqueous production acting on alpha 2 receptors on
ciliary epithelium
 No effect on blood aqueous permeability
 Increase uveoscleral outflow
 Apraclonidine
 Reduce episcleral venous pressure

Apraclonidine hydrochloride
[ALPFA 2 AGONIST]
• 1%
• 0.5%
Thrice daily
Brimonidine tartrate
[ALPFA 2 AGONIST]
• 0.2% Thrice daily
Dipivefrin and epinephrine
[NON SELECTIVE ALPHA AGONIST]
• 0.1% Twice daily

Apraclonidine • Apraclonidine 1% can be used for short term therapy (post laser)
• Reduces IOP during sleep also
• Tachyphylaxis
Brimonidine • Useful to control IOP in post laser
• Prevents optic nerve head damage, neuroprotective (not confirmed in
humans)
Dipivefrin • Dipivefrin is a modification of epinephrine which makes it lipophilic
and increases its penetration 17 folds

Ocular toxicity
Ocular side effects Systemic side effects
Apraclonidine • Follicular conjunctivitis
• Contact dermatitis
• Alpha receptor cross reactivity
• Eyelid retraction
• Mydriasis
• Conjunctival blanching
Brimonidine • Lesser allergic side effects • Oral dryness
• Sedation/ drowsiness/ headache/ fatigue
• Pronounced CNS depression in children
(NOT GIVEN IN LESS THAN 5 YEARS)
Dipivefrin • Reactive hyperaemia
• Dark deposits in various ocular
structures (adrenochrome)
• CME (aphakic eyes)
• Fewer systemic sympathetic side effects
compared to epinephrine since it converts to
epinephrine after it enters in the eye

PG Analogues Additive Not available
Beta blockers Additive Brimonidine 0.2% + Timolol 0.5%, BD
Carbonic anhydrase inhibitors Additive Brinzolamide 1% + brimonidine 0.2%, TID
Pilocarpine Additive Not available

 Sulphonamide class of drugs
 Systemic and topical preparations available
 Decrease aqueous humour flow by inhibition of carbonic anhydrase in ciliary
epithelium

 In the eye there are 4 variants of
carbonic anhydrase
 The main therapeutic target is the
CAII form
 They alter the ion transport and pH
which affect aqueous humour secretion
 Acetazolamide creates local acidic
environment, it inhibits chloride flux
across the ciliary epithelium
 It also creates metabolic acidosis which
influences the production of aqueous
humour
 To achieve therapeutic
effect 90% of carbonic
anhydrase activity
needs to be inhibited
 Increases blood flow
velocities in retinal
circulation, central
retinal and short
posterior ciliary
arteries but not in
ophthalmic artery

Acetazolamide • Traditional dose is 250mg QID/ 500mg BD
• Children 5-10mg/kg body weight every 4-6 hours
• IV – 250mg stat, followed by 250 mg tabs
• Tablet - Peak at 2 hrs, lasts 6 hrs
• Capsule - Peak 8 hrs, lasts 12 hrs
Methazolamide 25 mg BD to 100 mg TDS
Dorzolamide 2% Thrice daily
Brinzolamide 1% Thrice daily

Oral
 ADDITIVE THERAPY OF TIMOLOL and
Acetazolamide Acetazolamide is highly protein bound, needed in higher dose
compared to methazolamide
Methazolamide Methazolamide Longer half life and lower protein binding
Dorzolamide Dorzolamide was most effective and best tolerated in childhood
glaucoma
Brinzolamide Efficacy same as Dorzolamide

Carbonic
anhydrase
inhibitors
 Transient shallowing of AC due to ciliary body oedema, can lead to angle closure
 Irritation, transient blurred vision occasional hypersensitivity reactions
(Dorzolamide>brinzolamide due to lower pH)
 Periorbital dermatitis
 Increased mean corneal thickness
 Potential effect on CAII on corneal endothelium, loss of transparency
Dorzolamide  Thrombocytopenia
 Erythema multiforme
 Bitter taste
Brinzolamide  Bitter taste

 Paraesthesia around fingers, toes and mouth is common
 Increased urinary frequency
 Metabolic acidosis
 Aspirin combined with CAIs can cause salicylate toxicity
 Potassium depletion (specially combined with other hypokalaemic drugs)
 Renal calculi
 Blood dyscrasias (neutropenia, aplastic anaemia)are rare
 Maculopapular, urticarial type skin eruptions, SJS
 TERATOGENIC EFFECTS

Prostaglandin analogue Additional IOP lowering Not available
Beta blockers Additional IOP lowering Dorzolamide 2% + timolol 0.5%, BD
Brinzolamide 1% + timolol 0.5%, BD
Alpha agonist Additional IOP lowering Brinzolamide 1% + brimonidine 0.2%, TID
Cholinergics Additional IOP lowering Not available

 Indicated for all forms of open angle glaucoma
 Stimulate m3 muscarinic cholinergic receptors expressed in human ciliary
muscles and iris sphincters (either direct or by acetylcholinesterase action)
 They lower IOP by increasing facility of aqueous outflow
 Ciliary muscle contraction which causes traction on scleral spur and alters the
configuration of trabecular meshwork and Schlemm canal
 Minimal stimulation of aqueous humour formation
 Decreases uveoscleral outflow

Molecules Concentration Frequency
Pilocarpine • 0.5-4%
• 4% in high
viscosity acrylic
vehicle
• QID
• OD Bedtime
Carbachol 1.5% TDS

Pilocarpine • The miotic effect of pilocarpine by action on sphincter pupillae short term management
of angle closure glaucoma resulting from pupillary block
Carbachol • Direct and indirect cholinergic action (blocks acetylcholinesterase enzyme)
• Poor corneal penetration (needs adjuvant such as benzalkonium chloride)
• Intracameral carbachol/ acetylcholine for post cataract IOP control
Echothiophate
iodide
• Acetylcholinesterase inhibitors
• Very rarely used
• Prolonged duration of action

 Ciliary muscle spasm, causing browache
 Transient myopia, axial thickening and forward displacement of the lens (15 mins
to 2 hrs after dosing)
 Retinal detachment suspected, due to vitreoretinal traction
 Cataractogenic effect has been suggested
 Corneal haze
 Increase blood aqueous permeability, increases inflammation, contraindicated in
uveitis or anterior segment neovascularisation
 Cicatricial pemphigoid
 Hypersensitivity reaction

 Diaphoresis/ increased secretions
 Nausea vomiting diarrhoea
 Smooth muscle contraction – bronchospasm, abdominal pain, genitourinary effects
 Av block
 Cognitive dysfunctions
 Antidote – Atropine

 Additive effects
 Pilocarpine + timolol
 Pilocarpine + PGA
 Pilocarpine + adrenergic agonists
 Pilocarpine + CAI
 Fixed dose combinations not available

 Reduction in vitreous volume due to change in osmotic gradient between blood
and ocular tissues
 Used as an emergency method of lowering IOP
 Can be used preoperatively to minimise the pressure effect of the vitreous in
supine position

 Mannitol If crystals are present, it should be warmed to 60-80 degrees and cooled
to room temperature before administration
 Glycerine is safer than mannitol, since it gets metabolised
Glycerine Mannitol
Dose Orally 1-1.5g/kg body weight
(50%solution)
• IV over 30 mins
• 1-2 g/kg body weight 25% solution
Action Effect peaks at 30 mins, lasts for 5
hours
Onset of action is 20-60 mins, duration 2-
6 hours

 Diuresis, acidaemia, anaphylactic reaction
 Fluid overload
 Chills, fever
 Confusion, stroke
 Renal insufficiency
 Increase post operative inflammation
 Nausea vomiting due to sweet taste, serve with ice and tart flavouring
 High caloric content can cause dehydration

Pregnancy Lactation and paediatric age group
• Category A (Proven no risk)
• None
• Category B (Proven risk in animals, none
in humans)
• Brimonidine
• Category C (risk in animals but benefit in
humans outweigh)
• Beta blockers
• Carbonic anhydrase inhibitors
• Cholinergic agents
• Prostaglandin analogues
• Hyperosmotic agents
• Category D (proven human foetal risk)
• None
• Brimonidine
• Crosses blood brain barriers
• CNS depression
• Not given <10 years
• Cholinergics and adrenergics have
systemic side effects and are almost never
used in children
• Oral carbonic anhydrase can cause
acidosis and growth retardation with long
term use
• Timolol and dorzolamide are the drug of
choice

Anecortave • Angiostatic steroid without glucocorticoid activity
• Therapeutic potential for ARMD and glaucoma
Cannabinoids • Smoking marijuana lowers IOP (tetrahydrocannabinol)
• No effect of topical application in humans
• Decreases aqueous production
Cellular cytoskeletal modulators • Ethacrynic acid
• Changes actin, alpha-actinin, vinculin and vimentin in trabecular meshwork
• Side effects – corneal and trabecular toxicity
• Latrunculins Toxins produced by marine sponge
• Disrupts actin cytoskeleton
Cellular signalling pathways • Olmesartan (angiotensin II receptor antagonists)
• Lomerizine (calcium channel blocker)
• Nivaldipine (calcium channel blocker)
• Nerve growth factors
Memantine • NMDA receptor antagonists
• NMDA receptor excitotoxicity causes inner retinal layer damage
Nitric oxide • Role in aqueous humour dynamics, blood flow, retinal and optic nerve function
Rho kinase inhibitors • Rho kinases regulate smooth muscle contractions in calcium independent manner
• Rho kinase inhibitors increase trabecular outflow

Rho kinases regulate smooth muscle contractions in calcium
independent manner
Ripasudil 0.4% twice daily
Netrasudil
Mechanism
 Increase trabecular outflow
 Increases matrix metalloproteinase expression
 Increase intraocular blood flow

 Immunomodulation
 Gene based and cell based treatment
 Drug delivery
• Using drainage devices as drug reservoirs
• Impregnated nasolacrimal plugs

 Aim should be removing the cause of glaucoma.
 IOP lowering agents can be given
 Prostaglandin analogues (if no inflammation is present)
 Beta adrenergic antagonists
 Alpha analogues
 Carbonic anhydrase inhibitors
 Pilocarpine
 Cycloplegics

 Reduction of intraocular pressure
 IV carbonic anhydrase inhibitors
 Topical beta blockers
 Alpha agonists
 Prostaglandin analogues
 In difficult cases IV mannitol / Oral Glycerol can be given
 Miotics
 Unless the pressure is controlled, miotics will not work because of pressure induced
ischaemia of the iris, causing paralysis of ciliary muscle
 To break the pupillary block
 1-3 hours after IOP lowering agent
 1%-2% pilocarpine

OD - CDR FIELD OF VISION TARGET IOP
MILD <0.65 Mild to no visual loss 15-17
MODERATE 0.7-0.85 One hemisphere, not
within 10 degrees of
central fixation
12-15
SEVERE >0.9 Both hemispheres or
within 10 degrees of
central fixation
10-12
1. POAG and PACG after iridotomy
2. Ocular hypertension - 18mmHG
• If IOP>28mmHg
• If risk factors are present
3. Normal tension glaucoma – IOP fall by 30%

Topical drugs Concentration Frequency Side effects
Latanoprost 0.005% OD  Conjunctival hyperaemia
 Pigmentation
 Inflammation
 Hypertrichosis
 Herpes simplex reactivation
Travoprost 0.004% OD
Bimatoprost 0.03% OD
Tafluprost 0.0015% OD
Timolol 0.5% BD  Systemic adrenergic side
effects
 Mucous layer of tear film
 Cicatricial pemphigoid
 Corneal anaesthesia, PEEs
Betaxolol 0.25% BD
Apraclonidine 1%, 0.5% TID  Allergic reaction
 Oral dryness
 CNS depression
Brimonidine 0.2% TID
Dorzolamide 2% TID  Corneal endothelial loss
 Allergic reaction
 Bitter taste
Brinzolamide 1% TID
Pilocarpine 0.5% - 4% QID  Brow ache
 Can cause inflammatory
reaction
 Systemic sympathetic side
effects

Systemic drugs Dose Side effects
Acetazolamide • Traditional dose is 250mg
QID/ 500mg BD
• Children 5-10mg/kg body
weight every 4-6 hours
• IV – 250mg stat, followed by
250 mg tabs
• Paraesthesia
• Potassium
depletion
• Metabolic
acidosis
Glycerol 1-1.5g/kg body weight • Nausea
• Vomiting
• Dehydration
Mannitol 5 x body weight
20% solution
IV over 30 mins
Given up to 3 times
• Acidemia
• Chills, fever
• Volume
overload
Fixed drug combinations
Bimatoprost 0.03% + Timolol 0.5%
Latanoprost 0.005% + Timolol 0.5%
Travoprost 0.004% + Timolol 0.5%
Brimonidine 0.2% + Timolol 0.5%
Dorzolamide 2% + Timolol 0.5%
Brinzolamide 1% + Timolol 0.5%
Brinzolamide 1% + Brimonidine 0.2%

Medical management of glaucoma

Medical management of glaucoma

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