Definition

Glaucoma
Glaucoma describes a group of ocular disorders of multifactorial aetiology united by a clinically characteristic optic neuropathy w/ clinically visible changes at the optic nerve head,
comprising focal or generalised thinning of the neuroretinal rim w/ excavation and enlargement of the optic cup, representing neurodegeneration of retinal ganglion cell axons and
deformation of the corresponding diffuse and localised nerve-fibre-bundle pattern, visual field loss may not be detectable in early stages; while visual acuity is initially spared, progression
can lead to complete loss of vision; the constellation of clinical features is diagnostic.

Prevalence
 Leading cause of worldwide blindness; in 2010, glaucoma represented approx. 25% of the blind population (Quigley & Broman 2016)
 50% of cases are undiagnosed worldwide (Mitchell et al 1996, Wong et al 2004)

Classifications
Pathophysiology
 Understanding of glaucoma is poor; ischaemia, biomechanical stress, neurotoxicity, and genetic susceptibility are all factors thought to interplay, resulting in glaucoma.

 Biomechanical stress – not solely IOP-mediated; other factors that interplay to place stress on the eyes
o IOP – pressure exerted by eyeball
o At atmospheric-corneal interface i.e., trans-corneal pressure gradient
o Trans-corneal pressure is not representative to translaminal pressure gradient i.e., not representative of forces upon ONH

 Cerebrospinal fluid and IOP

o Translaminar pressure = difference between IOP and CSF
  Higher translaminar pressure gradient is thought to drive RGC axon lesson.
 Reduced distance intraocular component (IOP) and retrolaminar cribrosa (CSF)  greater gradient
 In other words, stress placed upon lamina cribrosa  deformation and trauma to axons
 Other biomechanical factors
o Hysteresis (stiffness) and thickness  may lead to underestimation and overestimation of IOP
o Corneal thickness – thickness is not correlated w/ LC
 Ischaemia – poor blood flow to ONH results in chronic ischaemic damage
o Superficial RNFL – arterioles in adjacent retina (peripapillary capillaries)
o Posterior lamina cribrosa and lamina cribrosa – from short posterior carotid artery and arterial circle Z-H
o Lamina cribrosa – capillaries near LC conform to the pattern of the LC septae
o Retro lamina cribrosa – pial arties and short PCA system
 Vascular stress – especially relevant in NTG

Intraocular pressure
 Normal IOP does not exist; the normal range is based on a statistically normative distribution that is not normally distributed.
 The pressure of episcleral veins is 5 to 6mmHg, any pressures less is hypotony and deflation of the eye.

Systemic disease – risk factors

 Diseases are correlated but not necessarily causative
 E.g., DM, HTN/ hypotension, hyperlipidaemia, obstructive sleep apnoea, migraine, peripheral vasospasm or Raynaud’s phenomenon, thyroid disease, smoking

Individual or genetic susceptibility

 Explains why
o Not all individuals w/ elevated IOPs develop glaucoma
o Not all glaucoma is equally progression
o There are ethnic variations in glaucoma
o Family history is an important factor
 Genes
o MYOC, myocilin gene – trabecular meshwork-inducible glucocorticoid response gene; regulates IOP in the CM
o LOXLI – related to Pseudoexfoliation
o CYPIBI – related to primary congenital glaucoma
 +ve Fhx increases the risk of glaucoma by approx. 4x, more so w/ 1st degree relatives  familial glaucoma
 50% patients do not have a confirmed Fhx  sporadic glaucoma

Signs
 Cupping – specific to glaucoma; almost never occurs in other optic neuropathies except AAION b/c NRR is generally preserved
 Disc haemorrhages
o Mechanical – shearing forces at the lamina cribrosa; hb occurs secondary to RNFL loss
o Vascular – ischaemia/ microinfarction at the ONH, perturbation of BRB, or due to a primary vascular problem

 Peripapillary atrophy
 o Mechanical or benign – incomplete opening due to mismatch of retinal layers e.g., in myopia
o Pathological – in glaucoma, it is theorised to represent localised ischaemia around the ONH

Staging Glaucoma
 Mild (pre-perimetric)– definite optic disc or RNFL abnormalities consistent w/ glaucoma and a normal visual field as tested w/ standard automated perimetry
 Moderate – definite optic disc or RNFL abnormalities consistent w/ glaucoma as detailed above, and visual field abnormalities in one hemifield that are not within 5 degrees of fixation
as tested w/ SAP
 Severe – definite optic disc or RNFL abnormalities consistent w/ glaucoma as detailed above, and visual field abnormalities in both hemifield and/ or loss within 5 degrees of fixation in
at least one hemifield as tested w/ SAP
 Indeterminate – definite optic disc or RNFL abnormalities consistent w/ glaucoma as detailed above, inability of pt to perform VF testing, unreliable/ uninterpretable VF test results, or
VF not performed yet
Primary Open Angle Glaucoma
Overview
POAG is the 2nd leading cause of blindness worldwide after cataracts. It involves glaucomatous optic neuropathy in the presence of an open angle and no other ocular abnormality to
account for a secondary mechanism. POAG is a diagnosis of exclusion. There are two subtypes – high tension glaucoma and normal tension glaucoma.

Risk factors
There are severe risk factors associated with POAG including:
 Optic Nerve Head – increased CD ratio, thinning RNFL, & disc haemorrhages (6-fold increased risk of developing POAG in OHTS)
 IOP – increased IOP, high variability in diurnal IOP, & large differences b/w eyes
 Age – prevalence & incidence increases with age
 Race – African Americans
 Family history

Signs
The diagnosis of POAG involves a clinical detection of glaucomatous optic neuropathy, characteristic visual field loss (arcuate, nasal step, and paracentral patterns), and change on structural
and functional testing. Diagnosis also involves the consideration of coexisting factors such as pseudoexfoliation, family history, migraine, and myopia. For POAG suspects, disc examination
typically reveals:
 CD ratio – increased, asymmetry, vertical elongation
 NFL defects – inferior to temporal, wedge defects (red-free filter), diffuse in advanced disease
 Disc haemorrhages
 Notches, thinning
 ISNT
 Disc size
 Peripapillary atrophy – non-specific
 Bayonetting – gap at the rim of the nerve and vessel
 Nasalisation – vessels become more nasal

Management
Management for POAG involves a consideration of:
· POAG stage or disease severity
· IOP levels
· Ocular and systemic risk factors
· Lifetime risk of visual disability
· Costs
· Benefit to patient
· Compliance
· Lifestyle
· Family history

Patients at risk need to be educated on the associated risk and responsibilities e.g., frequent administration of anti-glaucoma drops. These patients also need to be monitored regularly in
the first two years for any rapid progression and adherence to topical treatment. Patients who are unable to instil drops may elected to have SLT or other surgeries performed, or otherwise
need to be closely monitored. A target IOP needs to be established in the management plan; the target IOP must be at least a 20% reduction in IOP or even higher reduction (lower IOP) in
advanced disease or rapid disease progression.

Ocular Hypotension
Ocular hypotension occurs when IOP is elevated above normal, but the eye remains healthy with no pathological optic nerve cupping and visual field defects. In OHT, there is no structural
or functional damage, angles are open, and there is no evidence of ocular or systemic causes of elevated IOP.
The risk of progression from ocular hypertension to primary open angle glaucoma is greater with:
· OHTS – older age, thinner CCT, increased C/D ratio, greater IOP, greater pattern standard deviation
o At least 25% of retinal ganglion cells are lost before a significant change is seen on visual fields.
· Positive family history, lower systolic IOP, and lower ocular perfusion pressures.

Treatment for OHT involves the assessment of:

· Progression risk to POAG
· Patient factors (age, medical status, life expectancy, and patient preferences)
· Other ocular conditions e.g., CRVO
o If pt has CRVO, treatment is strongly indicated b/c IOPs are likely to increase
· Contralateral eye

In the OHTS, 20% reduction in IOP decreased the incidence of glaucoma by more than 50%. Therefore, the aim of treatment is 20 – 25% reduction in IOP. Treatment options for OHT include
topical medications (PGAs, Beta-blockers, CAI, Alpha-2-agonists) or selective laser trabeculoplasty.
 Risk of progression from Ocular Hypertension to Glaucoma
Baseline Predictor 0 1 2 3 4
Age <45 years 45 – 55* years 55 – 65* years 65 – 75* years ≥75 years
Mean IOP <22 mmHg 22 – 23 mmHg 24 – 25 mmHg 26 – 27 mmHg 28+ mmHg
Mean CCT >600 576 – 599 551 – 575 526 – 550 525 or less
Vertical C/D <0.3 0.3 0.4 0.5 0.6 or more
Mean PSD <1.8 1.8 – 2.0* 2.0 – 2.4* 2.4 – 2.8* ≥2.8
Sum of points 0–6 7–8 9 – 10 11 – 12 ≥12
Estimated 5-year risk <4% 10% 15% 20% ≥33%
*not inclusive of…

Normal Tension Glaucoma

Normal tension glaucoma is a condition where IOPs are within normal range but there is cupping of the optic nerve, retinal nerve fibre layer thinning, characteristic visual field loss (typically,
paracentral), and absence of secondary features. Japan has the highest prevalence of NTG and in Australia, NTG makes up 20-30% of glaucoma. The clinical findings for NTG are the same as
POAG except IOP ≤ 21 mmHg. The risk factors for disease progression include
 Optic disc haemorrhages
 Lower perfusion pressure – low BP or reduced ocular blood flow
 Migraines or Raynaud phenomenon – hx
 Ischaemia vascular disorders – hx
 Obstructive sleep apnoea syndrome – causes primary vascular dysregulation and hypoxia, compromising circulation at optic nerve

Careful and complete work-up is required to distinguish NTG from other forms of glaucomatous and non-glaucomatous optic neuropathy.

Primary Angle Closure Glaucoma

Angle closure occurs when the trabecular meshwork becomes occluded due to iridotrabecular contact involving the peripheral iris
which ultimately leads to obstruction of aqueous outflow; increase IOP is caused by impaired outflow facility secondary to appositional
or synechial closure of the anterior chamber drainage angle. Majority of patients are asymptomatic, and visually PACG is more
destructive than POAG. Risk factors for PACG include age, female gender, family history, hyperopia, race – Chinese, thicker lens,
shorter axial length, and more anteriorly positioned lens. There are several stages leading to primary angle closure glaucoma:
1. Primary angle closure suspect – iridotrabecular contact with normal optic disc, VF and IOP.
 2. Primary angle closure – iridotrabecular contact, raised IOP, peripheral anterior synechiae or symptoms, & normal disc and VF.
a. Acute – pressures rise high
b. Intermittent – pressures are high intermittently
c. Chronic – pressures are high chronically; pressures may not be as high as acute form. More prevalent form that may develop after an acute PAC or following gradual
asymptomatic closure of the angle. The latter is more common.
3. Primary angle closure glaucoma – iridotrabecular contact, structural glaucomatous changes in optic nerve or glaucomatous visual field loss.

In primary angle closure, the three forms can overlap and coexist. Reopening of the angle prior to ultrastructural changes should restore the natural outflow pathway. However, in some
cases the angle is open, but IOP does not drop b/c the pt has had previous chronic iridotrabecular contact and trabecular meshwork may not work as well – may be blocked by pigment.
Therefore, IOP control depends on the amount of trabecular damage and extent of closure.

Angle Closure Disease Spectrum

Overview
 Spectrum of narrowing of the anterior chamber angle with the endpoint being glaucoma.
 May relate to any process where there is an impairment of aqueous outflow from the eye – may be pupil block or angular narrowing, but typically, it is mixed.
 Angle closure disease has a greater propensity to cause bilateral blindness.

Staging
1. Open angles – all PTM or deeper
2. PAC suspect – 3+ quadrants w/ iridotrabecular contact (ITC)
3. PAC – 3+ quadrants w/ ITC + elevated IOP and/ or synechiae
4. PAC glaucoma – 3+ quadrants w/ ITC + elevated IOP and/ or synechiae + glaucomatous changes
Pathophysiology
 Plateau iris configuration – variant of angle closure disease
o Double hump sign on indentation - displacement of CB causes mechanical hump peripherally

Prevalence
 Significant public health problem in China/ Asia and developing countries.
o Quigley & Broman 2006 found prevalence is highest in China then Japan and lowest in European and Indian groups.

Signs
 Synechiae – iridocorneal adhesions occurring due to inflammatory mediations, fibrin and protein deposition
o Anterior – iridotrabecular contact is important; does the adhesion obscure the TM
o Posterior
Primary Angle Closure
Overview
Primary angle closure involves the combination of physical proximity of the iris and trabecular meshwork, and exaggerated physiology characteristics that can cause iridotrabecular contact
and secondary IOP elevation.

There are three main mechanisms involved with PAC:

· Total iridotrabecular contact which procedures “symptomatic” angle closure
· Prolonged appositional iridotrabecular contact which may result in the formation of synechiae scars between iris and trabecular meshwork, and ultimately obstruct aqueous outflow
· Iridotrabecular contact which causes frictional contact between the iris and trabecular over prolonged periods, degrading trabecular meshwork architecture and function

Mechanisms that cause iridotrabecular contact include:

· Pupillary block – failure of aqueous flow through the pupil, leading to a pressure differential between the anterior and posterior chambers, resulting in the anterior bowing of the iris
and finally iridotrabecular contact
· Anterior non-pupil block – plateau iris (anteriorly positioned ciliary processes), thicker iris
· Lens induced
· Retrolenticular – gas, vitreous haemorrhage

And, causes of iridotrabecular contact include:

· Iris and ciliary body cysts
· Iatrogenic – retinal surgery
· Posterior segment mass – haemorrhage or tumour
· Uveitis
· Neovascularisation – CRVO, DM
· Pharmacological dilation
Subtypes
 Acute PAC
o Acute PAC accounts for 15-45% of PAC and is an ocular emergency due to its vision threatening nature. Patients may report haloes around lights, pain and headaches. Signs include
poor VA, very high IOP, conjunctival hyperaemia, shallow angle-closure, corneal epithelial oedema, mid-dilated unreactive pupil, and narrow angles in the fellow eye. Extremely
elevated IOP leads to rapid blindness if not treated properly, and the longer the duration of the attack, the greater the damage.
 Intermittent PAC
o In the intermittent phase, patients may report milder symptoms of blurring with no associated pain.
 Chronic PAC
o In chronic PAC, visual acuity is usually normal, optic nerve depends on severity of damage and IOP elevation may be intermittent.

Signs and Symptoms

 Majority of patients with PAC are symptomatic (intermittent and chronic).
 Precipitants of PAC include – dark room, pharmacological dilation and system medications more specifically, topiramate.
 Glaucomflecken – elevated IOP compresses anterior capsule causing a scar
 Posterior embryotoxon – anteriorly displaced Schwalbe’s line – white arcuate ridge
o In isolation, it is not significant; prevalent in the general population (~6%)
o Accompanying iridocorneal adhesions – there is an increased risk of glaucoma e.g., Axenfeld-Reiger syndrome, iris hypoplasia, corectopia, polycoria
Management
Treatment for acute PAC includes:
 Topical therapy (beta blockers, PGAs, alpha agonist)
 Systemic CAI (acetazolamide)
 Analgesia, antimetric for nausea
 Pilocarpine
 Topical steroid (predforte q.i.d. to reduce inflammation)
 Hyperosmotic agents (mannitol intravenously – contracts vitreous and lowers IOP, contraindicated in patients with heart conditions/failure or renal failure)
 Laser peripheral iridotomy - definitive treatment but is susceptible to recurrent attacks and progression PAS especially if non-pupillary block mechanisms are present. 40-80% chance of
developing an acute attack in the fellow eye within 5-10 years
 Laser peripheral iridoplasty – when iridotomy is contraindicated

Goals of treatment in PAC include instantly reducing IOP; reopening and modifying the AC angle; and controlling residual IOP elevation if irreversible TM dysfunction has occurred. Other
treatment procedures in angle closure include:
 Removing cataract – angle w/ visually significant cataract (cataract extraction can lower IOP since lens is significant in the development of relative pupillary block). Note, cataract
extraction in the setting of an acute angle-closure attack is technically difficult since eye will be inflamed w/ significant corneal oedema, shallow AC, atrophic and iris that is difficult to
dilate, and possible zonular weakness.
 Selective laser trabeculoplasty
 Laser peripheral iridotomy – clear lens, pupil block. Effective in acute, symptomatic angle closure.
 Laser iridoplasty – tightening (contracting) of peripheral iris by applying a series of laser burns that mechanically pulls open the appositionally closed angle. This procedure can be
performed to lower pressure prior to iridotomy.
 Lens extraction – removal of lens results in a significant increase in AC depth and angle width.
 Filtration surgery – indications: medical unresponsiveness, lack of laser availability, or signs of glaucomatous optic neuropathy present.

Once a closed angle has been reopened, residual pressure elevation needs to be treated and can be done so in the same manner as secondary open angle glaucoma.

Secondary Angle Closure Glaucoma

Overview
 Angle closure that occurs secondary to another primary pathology – almost all are mechanical obstructions.
 Causes include:
o Phacomorphic
o Iridociliary cyst
o Uveitis – multiple mechanisms
 Pupil block
 Chronic synechiae angle closure
 Forward displacement of iris-lens diaphragm – rare; CB is affected and/ or posterior segment involvement
o Neovascularisation
o Drug-induced – dose-related effect
 Osmotic disturbance in lens, ciliochoroidal effusion, and CB swelling leads to an anterior shift in lens-iris diaphragm

Secondary Open Angle Glaucoma

In secondary glaucoma, there is a presence of glaucomatous optic neuropathy with signs of pathological processes, including:
 High IOP
 Pseudoexfoliation
 Pigment Dispersion – pigment deposits in the trabecular meshwork
 Angle recession – widening of the ciliary band
 Fuchs’ Heterochronic Iridocyclitis
 Posner-Schlossman Syndrome – glaucomatocyclitic crisis; typified by acute, unilateral, recurrent attacks of elevated intraocular pressure accompanied by mild anterior chamber
inflammation. Pathophysiology is unclear; however, it has been postulated to be autoimmune or infectious.

In secondary open angle glaucoma, the cause of glaucoma or elevated IOP is clinically apparent.

Pseudoexfoliation/ Pseudoexfoliation Glaucoma

Overview
 Pseudoexfoliation syndrome is an age-related systemic syndrome where there is a gradual deposition of fibrillary white flaky material (exfoliation) from the lens on the anterior segment
of the eye; mainly on the anterior lens capsule, ciliary body, zonules, corneal endothelium, iris, pupillary margin/ border, and trabecular meshwork.
 Pseudoexfoliation glaucoma is the most common form of secondary open-angle glaucoma; it may be secondary open or closed angle glaucoma. It occurs when deposition of the white
dandruff-like material in the trabecular meshwork increases aqueous outflow resistance by obstructing the aqueous outflow pathway; this leads to elevated IOP and glaucoma.
 Pseudoexfoliation is thought to have both ocular and systemic manifestations
o Deposits may occur in other organs
o Induces elastic microfibrillopathy which leads to ischaemic heart disease and aortic aneurysm
o Most common systemic association is homocysteinuria

Pathophysiology
 The pathophysiology is unclear however, it thought that abnormalities of the extracellular matrix and basement membrane produces exfoliative material. There is a genetic link to the
gene LOXL1 which belongs to the family of enzymes that are active in cross-linking of collagen and elastin the extracellular matrix.
 It has been proposed that UV light damage causes shedding but there have been no clear associations.
 Iris transillumination defect at the border of the pupil margin is caused by rubbing of the anterior lens; the iridolenticular friction causes a vicious cycle of release
Pseudoexfoliation & zonules
 Weakened lens zonules
o Deposition of exfoliative material leads to proteolytic disintegration of the zonule
o This does not explain significant nuclear sclerosis
 Clinical signs: anterior lens shift i.e., shallow AC and phacodonesis (vibration of lens accompanying eye movement)
 Cataract surgery – indicated w/ significant wrinkling of the anterior capsule

Pseudoexfoliation to glaucoma
 Extra-trabecular (existing outside TM)
o Iridolenticular friction causes dispersion into anterior chamber
o Blockage of Schlemm’s canal results in increased outflow resistance
 Endo-trabecular
o Concomitant disruption and breakdown of normal network of Schlemm’s canal  connective tissue disease
 Changes occurring at the cellular level in the TM  decrease in flexibility of tissues within TM leading to a disruption in the integrity of TM cells and disruption of outflow or
homeostasis
o Disruption of TM homeostasis
o Poor structural integrity
 Not simply intraocular pressure related; there are pressure-independent processes at play
o Elastosis adversely affects tissue elasticity increasing the susceptibility of nerve fibres
 In other words, tissues stiffen and this increases the susceptibility of the lamina cribrosa to injury
o Alterations to vasculature around the optic nerve head interferes with vascular supply
Prevalence
 Higher prevalence in Caucasians especially in Eskimos and Northern Europe (Norway, Sweden, Finland, Icelandic), and Ireland, Greece, and Saudi Arabia.
 Associations w/ climate e.g., Aboriginal Australians vs Caucasian Australians
 Patients with Pseudoexfoliation syndrome are at 5 – 10 times higher risk of developing glaucoma, with 25% of patients developing high IOP.
 Asymmetry: majority of cases convert from unilateral to bilateral over 5 years (~80%).

Diagnostic
Pupil dilation is an important consideration; mydriasis is poor in Pseudoexfoliation. Pupils are generally miotic b/c the pseudo-exfoliative material around the dilator muscles inhibit
contraction.
Signs
 White deposits on anterior lens surface
 Three distinct zones, seen on dilation, created by pseudoexfoliative material:
o Central disc
o Intermediate clear zone – rubbing off by the iris
o Granular peripheral zone
 Pupil border – white flecks
 Lens subluxation
 Angle closure
 Cataract surgery complications – pt do not dilate well b/c of PXF material
 Increased trabecular pigmentation
 Pigment loss from pupillary ruff and iris sphincter region (transillumination)
 Material on zonules; zonules frayed & broken – material on zonules are thought to cause ischaemia and atrophy
 Phacodenesis – subluxation or dislocation of lens can occur
 Poor dilation and contraction (Tekin et all 2018)
 Sampolesi’s line is visible
 High IOP – deposition of material within the trabecular meshwork, however; Pseudoexfoliation and glaucoma may occur in the absence of high IOP suggesting that there is an
independent mechanism linking Pseudoexfoliation and glaucoma

Management
In PXF glaucoma IOP is often elevated and difficult to control, and surgery is typically required. The incidence of PXF increases with age, and systemic associations include TIA, stroke,
myocardial infarction, Alzheimer’s, and hearing loss. Medical therapy is more likely to fail in PXF glaucoma than in POAG, and prognosis is worse than POAG. Patients are more likely to have
optic nerve damage at diagnosis, worse VF, poorer response to medications, and are more likely to need surgery.

Pigment Dispersion Syndrome and Pigmentary Dispersion Glaucoma

General/ Overview
Pigment dispersion syndrome (PDS) and pigment dispersion glaucoma (PDG) represent a spectrum of the same disease that is characterised by excessive pigment liberation. This pigment
liberation from the posterior iris is caused by mechanical rubbing of the iris pigment epithelium against the lens zonules. In PDS, no glaucoma is evident however, conversion to PDG can
occur and is more common in males and Caucasians. Pigment dispersion glaucoma is a subset of secondary open-angle glaucoma that occurs bilaterally. The disease is prevalent in younger
pts between the 3rd and 4th decades and risk factors include male gender, mild to moderate myopia (deeper AC), concave iris and posterior iris insertion, flat corneas, and positive family
history.
Pathophysiology
 Configuration is similar to a reverse pupillary block – iris is bowed backwards hence it rubs on the lens & lens zonules leading to iris transillumination defects. The material that is
liberated (pigment) floats in the anterior chamber.
 Convection currents carry the pigment into the anterior segment and for the same reason the pigment has a specific linear configuration  Kruckenberg’s spindle

 Pigment deposits in the trabecular meshwork

o Uniform, homogenous deposition
o Sampaolesis’s line – may appear in both PDS and PeX
 Pigment dispersion – dark band, homogenous, and thick
 Pseudoexfoliation – mottled appearance; not very dark.

Natural history
There are four phases involved in pigment dispersion:
1. Inactive pigment dispersion – stable IOP
2. Active pigment dispersion phase – as early as mid-teens, IOP normal.
3. Conversion to glaucoma – 10% of PDS convert to PDG in 5 years, increased IOP
4. Possible regression phase – pigment starts clearing away from TM, IOP recovers within normal range, pigment in upper quadrant > lower quadrant.
  Older pts
 After pigment clears away, disease may resemble NTG
 This burnout stage is not well understood however it has been thought to be due to a change in the relationship of the iris and lens zonules. As the iris thickens with age, the iris
is pushed up and there is less contact b/w the iris and lens zonules.

Ocular signs and symptoms include:

· Midperipheral radial iris transillumination defects
· Heavy pigmentation of angle (trabecular meshwork)
· Krukenberg spindle – pigment on corneal endothelium; vertical orientation
· Pigmentation on lens zonules
· Deep angle
· 6-7% retinal detachment
· Elevated IOP, both acute and intense (intermittent)
 Subsequently, haloes surrounding light, blurred vision due to corneal oedema (specific to PDG)
· Pigment storm – during exercise there is increased contact b/w posterior iris pigment epithelium and lens zonules. This is marked by pain, haloes around light, and photophobia. The
symptoms occur as IOP increases and the endothelial pump stops working which leads to corneal oedema. Significant corneal oedema (haloes around lights) leads to disorganisation of
the corneal lamellae and light is scattered. Once, the IOP increases to 40 to 50mmHg or more, iris ischaemia occurs and the pupils cannot constrict.

Management
Management of pigment dispersion glaucoma include topical therapy, low power SLT, and YAG laser peripheral iridotomy (controversial). Lower energy settings are used in SLT to avoid
release of pigment and IOP spikes.
Angle Recession Glaucoma/ Traumatic Glaucoma
Overview
 Widening of the angle usually due to non-penetrating, blunt trauma which results in a split in the longitudinal and circular ciliary muscle fibres
o Blunt trauma forces aqueous humour laterally and posteriorly against iris and angle. This exerts traction on iris root which leads to tear b/w longitudinal and circular muscles of CB.
With enough force, ciliary arteries are broken leading to hyphema. Initial insult may damage TM and SC which leads to early spike in IOP. Long term, scarring and fibrosis of TM and
TC may lead to elevated IOP.
o Longitudinal fibres – most external; contraction opens TM and Schlemm’s canal
o Circular fibres – parallel to limbus; contraction relaxes crystalline lens
o Radial or oblique fibres – intermediate position; contraction opens up uveoscleral space
 Blunt trauma
o Blunt trauma is common, occurring in 52.7 per 1000 individuals per year and often, due to sports, recreational activities, assault
o Blunt trauma – 3.38% develop ARG at 6 months following blunt ocular trauma
o Strong link w/ traumatic hyphema (fine BV within iris or angle are ruptured)
 6% angle recession develop glaucoma
 “Traumatic glaucoma”
o Two peak incidences for glaucoma
 Within weeks to 3 years
 10+ years following trauma
 May develop even 50 years after trauma

Risk factors/ prognostic markers

o Increased pigmentation,
o High IOP
o Hyphema,
o Lens displacement,
 Lens displacement – lens rocks back and forth, pushing the angle closed
 Force of trauma may cause cellular damage in TM
o Angle recession > 180 degrees  makes glaucoma more likely.
 o Sympathetic innervation – trauma in one eye raises the risk of trauma in the contralateral eye; 50% of ARG patients develop OAG in contralateral eye. Hypothesis that AR does not
directly cause elevated IOP but accelerate process in eye at risk.

Clinical Signs
 Widened ciliary body band
 Gonioscopy – recession of ACA
 Iris sphincter tears
 Corneal scars
 Vossius ring
 Iridodialysis
 Phacodenesis
 Hyphema
 Iridodenesis

Management
Same as POAG w/ a few exceptions.
 PCA  should be avoided in ACUTE stage of trauma due to pro-inflammatory effects. However, PGA have theoretical benefit of bypassing TM by increasing uveoscleral outflow and
therefore may be used after acute age.
 BB, alpha agonists, CAIs – may be used
 Pilocarpine  CONTRAINDICATEED – may exacerbate angle recession
 Surgery – laser trabeculoplasty, trabeculectomy
Uveitic Glaucoma
Overview
Uveitic glaucoma is a common complication of uveitis that is often seen in younger patients. Very high IOPs may potentially lead to glaucomatous optic neuropathy and visual field loss.
Uveitic glaucoma is more rapid progressing than POAG.

Causes of high IOP and inflammation relating to secondary glaucoma, not isolated to uveitic glaucoma, include
 Posner – Schlossman Syndrome – few cells, sudden onset, recurrent episodes of elevated IOP 40-60 mmHg with anterior chamber inflammation
 Herpetic Keratouveitis cyclitis – stellate KP, heterochromia, stromal iris atrophy
 Fuch’s uveitis syndrome
 Topical corticosteroids
 Peripheral anterior synechiae
 Angle closure

Steroid response & IOP

Uveitis and treatment of the disease (corticosteroids) may lead to elevated IOP. Risk factors for a steroid response include:
 POAG or first-degree relative w/ POAG
 Old age or < 6 yr old
 High myopia
 DM T1
 Angle recession
 Individual susceptibility – myocilin gene (MYOC)

Topical steroid response typically occurs in weeks whereas systemic may take years. This is b/c topical steroids have a more direct and immediate effect on the eye than other steroid
administrations.

Pathophysiology
 TM – mechanical blockage and loss of cellular integrity
 Steroidogenic functions – genes including MYOC and CYPIBI are highly abundant in CB
o MYOC – highly responsive to prolonged steroid tx
o CYPIBI – capable of metabolising steroids

Management
Management involves treatment of both the uveitis and glaucoma. Referral to a uveitis specialist is important because immunosuppressive drugs can be prescribed to avoid high doses of
steroids.

Neovascular Glaucoma
Overview
 Neovascular glaucoma is a severe form of secondary glaucoma that is characterised by the proliferation of new blood vessels on the surface of the iris and in the anterior chamber
angle. These new vessels, when in the anterior chamber angle, may compromise aqueous flow through the obstruction of the trabecular meshwork. Contraction of these fibrous
membranes can also result in the formation of peripheral anterior synechiae and progressive angle-closure glaucoma.
o Fibrovascular membranes consisting of proliferating myofibroblasts are responsible for anatomical changes: effacement of iris surface, ectropion uveae, peripheral anterior
synechiae (invades angle), and finally, angle closure.
 If left untreated, NVG can cause advanced glaucomatous optic neuropathy and irreversible vision loss.
 NV glaucoma is most commonly associated with retinal ischaemia, with CRVO and diabetic retinopathy accounting for almost 2/3 of NVG cases.
 The progression of rubeosis to advanced NVG can be broken down into three main stages:
o Rubeosis iridis – pupil margin, angle
o Open angle glaucoma
o Angle closure stage
 100-day glaucoma – 50% of eyes develop glaucoma??
 IOP is normal initially but becomes elevated later

Open angle NV glaucoma

 Blood vessels around superficial iris attaches to the cornea. The BV obscures TM flow but the angle is still open.

Closed angle NV glaucoma

 Iridoangle contact – iris is dragged to contact the angle; it is not significant until it becomes iridotrabecular contact.
Treatment for NV glaucoma include:
· Reducing ischaemia drive (neovascularisation stimulus) – anti-VEGF and panretinal photocoagulation
· Managing inflammation and pain – topical steroids and cycloplegic agents
· Reducing IOP – topical tx, surgery, cyclodestructive procedures

Other Secondary Glaucoma

 Lens induced open angle glaucoma
o Phacolytic – leakage of proteins through an intact capsule
o Phacoanaphylactic – immune complex formation causes a granulomatous uveitis
o Lens particle – retained lens material and inflammatory cells
 Iridocorneal Endothelial Syndrome (ICE)
o Progressive iris atrophy
o Synechial angle closure
o Corneal oedema (abnormal endothelium)
 Post trauma
Non-Glaucomatous Disease
 Compressive e.g., lesion on ON
 Infiltrative
 Ischaemic – Non-Arteritic Anterior Ischaemic Optic Neuropathy (NAAION) can mimic glaucoma, but ONH typically not cupped; AAION causes cupping.
 Disc Drusen
 Moderate to high myopic eyes w/ tilted disc may have non-progressive glaucomatous VF defects

Red Flags (indicating disease is not glaucomatous)

 Pallor
 Bitemporal or homonymous VF defect
 VF defect out of proportion to the severity of disc cupping
 Vertically aligned VF defect
o Glaucoma respects horizontal meridian, any condition that respects the vertical meridian is likely neurological
 Loss of visual acuity
o May occur in advanced glaucoma
 Colour vision abnormality
o May occur in advanced glaucoma
 RAPD – can occur in asymmetric disease

Glaucoma Work-Up
1. Clinical History
· Thorough medical and ocular hx
o Previous high IOP and treatment
o Rule out secondary causes e.g. trauma and uveitis
o Medications – topical and systemic e.g., steroids, anti-VEGF, beta-blockers
o Hypertension, hypotension, cardiac disease, obstructive sleep apnoea syndrome (OSAS)
o FHx (of glaucoma)
2. Clinical Examination
· Refraction & VA
· Pupils
· Slit-lamp – pigment dispersion, PXF, iritis, trauma, lens
· CCT
· Gonioscopy
· Visual fields
· Optic nerve and RNFL assessment e.g., bayonetting of vessels, drance haemorrhages
 Optic Nerve Assessment
· Focal or generalised thinning
· Asymmetry
· Disc haemorrhage
· CD ratio
· Retinal/fundus photography
· OCT
 · Visual field
 Gonioscopy
· Indicated for patients with glaucoma.
· Gonioscopy is important as it allows for correct diagnosis, especially since, therapy for each glaucoma type is specific and it is important to determine the mechanism.
· Limitation: may overlook angle closure and other forms of secondary glaucoma: peripheral anterior synechiae; pigmentation; abnormal blood vessels; and angle recession.

Treatment
Selective Laser Trabeculoplasty
SLT is an effective and safe treatment that can be repeated several times. SLT is either used as primary therapy or performed in adjunct to medical therapy. Indications for SLT include POAG,
OHT, PXF, PDS, and NTG. Generally, this procedure is performed in patients with high pressures, if the procedure is performed on pt’s with low pressures, it may cause a spike in their
pressures; SLT does not work well in patients with lower pressures. SLT is useful for non-compliant patients and patients who are intolerant to certain medications.
 If patient’s pressures are very high, lower energy is recommended to prevent a pressure spike. Alpha agonist will also help prevent a pressure spike.

The procedure involves a 532nm frequency doubled Q switched Nd: YAG laser with a spot size of 400micro. The laser fires 100 shots over 360 degrees, targeting the trabecular meshwork.
Less energy is used for pigmented angles. The patient is set up behind a slit-lamp and given apraclonidine or brimonidine prior the procedure. Ophthalmologists will typically wait 6 weeks
before assessing the pt’s response to tx. 70-80% of patients will experience a 20% reduction in IOP.
There are several complications of SLT including:
· Mild inflammation – may administer steroids to counter inflammation
· IOP spike
· Corneal oedema

Peripheral Iridotomy
Peripheral iridotomy eliminates pupil block to allow aqueous to pass directly from the posterior chamber into the anterior chamber bypassing the pupil. The procedure widens the angle,
reduces IOP, and reduces the risk of future AAC due to pupil block, but 20-25% of patients will still experience appositional angle closure. Peripheral iridotomy is indicated in acute primary
angle closure, fellow eye APAC, chronic angle closure with ocular hypertension, and narrow or occludable angle. Patients are given pilocarpine and apraclonidine or brimonidine prior to the
procedure. The laser is aimed superiorly underneath the eyelid, near the limbus. Post-op, patients are given topical steroids – pred forte for 1 week.
Peripheral iridotomy reduces the risk of future AAC due to pupil block, reduces IOP and changes the configuration of the angle to reduce the risk of progression to chronic ACG.
Complications of peripheral iridotomy include: endothelial damage and decompensation, cataract formation and progression, IOP spike, uveitis, hyphaema, monocular diplopia, and glare.
Peripheral Iridoplasty
Peripheral iridoplasty is useful when peripheral iridotomy cannot be performed due to corneal oedema, shallow AC, severe inflammation or mydriasis. Peripheral iridoplasty is indicated
plateau iris syndrome (anteriorly displacement of the peripheral iris by the ciliary body narrows the angle in the presence of normal central AC depth) and lens related angle closure as a
temporary measure before cataract surgery. Peripheral iridoplasty opens an appositionally closed angle.
The procedure involves applying a low power, long duration, argon laser to the peripheral iris in 20-24 spots over 360 degrees. This action contracts the iris stroma, creating a space between
the anterior iris surface and trabecular meshwork, pulling open the angle. Patients are given pilocarpine and apraconidine or brimonidine prior to the procedure, and topical steroids post-
op. Complications of peripheral iridoplasty include uveitis, IOP spike, endothelial burns, corectopia (displacement of pupil) and mydriasis.
Trabeculectomy
Trabeculectomy is the most effective in lowering IOP. In trabeculectomy, aqueous humour is diverted into the subconjunctival space from the anterior chamber via a filtering bleb which is
created underneath the upper lid. Excessive flow of aqueous may result in low IOP (hypotony) and scarring may lead to filtration failure. Trabeculectomy is a high-risk surgical procedure that
requires intensive post-op management. Patients may experience a slight reduction in vision due to refractive change, astigmatism, reduced axial length, cataract and hypotony.
Indications for trabeculectomy include:
 Inadequate IOP control despite medical therapy
 Progressive visual field loss despite medical therapy
 Intolerance to glaucoma medications – allergy or side effects
 Poor compliance with progressive glaucomatous damage
 Progressive damage that is likely to lead to functional impairment during the patient’s lifetime.

Complications of trabeculectomy include shallow anterior chamber leading to pupillary block, over filtration and malignant glaucoma; failure of filtration; bleb leakage; blebitis; and
endophthalmitis.
Minimally invasive glaucoma surgeries (MIGS)
 Suprachoroidal and canal-enhancing procedures
 Indicated for mild to moderate disease
 Reduces or eliminates the need for glaucoma drops or invasive
 Most commonly performed at the time of cataract surgery

iStent Inject
 Less than 1mm in length
 Titanium
 2 are inserted at the time of cataract surgery m
 Creates a bypass between the AC and Schlemm’s canal

Hydrus
 Curved flexible stent
 Nickel and titanium
 Scaffold to widen and dilate Schlemm’s canal
 Reduces outflow resistance

Cypass – now recalled b/c it created epithelial cell loss (device sitting too far out)
 6mm
 Suprachoroidal space

Xen
 Soft flexible gelatin implant
 6mm long
 Creates a bleb under the eyelid to allow aqueous humour to flow from AC to subconjunctival space
 Less invasive and faster recovery than trabeculectomy however, it may create scarring and does not lower pressures as much as trabeculectomy

Glaucoma drainage implant – performed in pt where trabeculectomy has failed

 Tube attached to a posterior episcleral explant
 Reduction of IOP is due to passive, pressure dependent flow of aqueous across the capsular wall
 Baerveldt implant – silicone tube connected to a large area silicone plate
 Aqueous is diverted from anterior chamber to an external reservoir
 Covered with a scleral patch
 Indications:
o Uncontrolled glaucoma despite previous trabeculectomy
o Secondary glaucoma
o Eyes with severe conjunctival scarring
 Complications
o Excessive drainage
o Malposition – endothelial or lenticular touch
o Tube erosion through the conjunctiva
o Tube blockage
o Late drainage failure

Cyclodioide
 Destruction of ciliary processes, reduces aqueous production and lowers IOP
 Uncontrolled end-stage disease with poor vision, to control pain
 Performed in the operating theatre under anaesthetic block
 Transscleral burns posterior to the limbus around 360 degrees
 Complications: pain, inflammation, hypotony (low IOP), phthisis, retinal detachment, corneal decompensation

Target IOP
Target IOP refers to the mean IOP obtained with treatment that is expected to prevent or delay further damage. Target IOP is flexible and can be modified as the patient’s ocular and
physical condition changes. In some patients, disease progression may occur despite achieving the target IOP, in these cases continue to lower IOP and consider surgical treatment or SLT.

Glaucoma Drugs – OBA Approved

Trade Name Generic Name Concentration Bottle Size Formulation Schedule Pregnancy PBS
Iopidine Apraclonidine 0.5% [10mL] S4 B3 MP only
Betaquin Betaxolol 0.5% [5mL] Solution S4 C MP, OP
Betoptic
Lumigan Bimatoprost 0.03% [3mL] Solution S4 B3 MP, OP
Lumigan PF (30 x 0.4mL) Unit dose
Alphagan Brimonidine 0.2% [5mL] Solution S4 B3 MP, OP
Alphagan P 0.15% [5mL]
Azopt Brinzolamide 1% [5mL] Suspension S4 B3 MP, OP
BrinzoQuin
Trusopt Dorzolamide 2% [5mL] Solution S4 B3 MP, OP
Xalatan Latanoprost 0.005% [2.5mL] Solution S4 B3 MP, OP
Isopto Carpine Pilocarpine 1%, 2%, 4% [15mL] Solution S4 B3 MP, OP
Saflutan Tafluprost 0.0015% [30 x 0.3mL] Solution S4 C MP, OP
Timoptol Timolol 0.25% [2.5mL] Solution S4 C MP, OP
0.5% [5mL]
Travatan Travoprost 0.004% [2.5mL] Solution S4 B3 MP, OP
Topical Glaucoma Drugs (5 major classes)
Class Mechanism of Action
Prostaglandin Analogs ↑Aqueous outlflow (uveoscleral)
Beta Blockers ↓ Aqueous production Bronchospasm, bradycardia, congestive heart failure
Carbonic Anhydrase Inhibitors ↓ Aqueous production Paraesthesia (pins & needles), depression, anorexia
Alpha Agonists ↓ Aqueous production Conjunctival hyperaemia, headache
↓ Outflow resistance
Miotics/ Cholinergic agonists ↑ Aqueous outflow Eye/brow pain, myopia, visual effects

Glaucoma Treatment Paradigm

Goals of treatment:
 Preserve visual function
 Quality of life
 Sustainable cost for patient and society

Stages of disease
 Undetectable disease
o Normal
o Acceleration of apoptosis
o Ganglion cell death/ axon loss
 Asymptomatic disease
o Retinal nerve fibre layer change (undetectable)
 Functional impairment
o Short wavelength automated perimetry VF change
o VF change (moderate)
o VF change (severe)
o Blindness

Treatment considerations
 Life expectancy (how old is the pt & how long do they have to live?)
 Treatment side effects
 Financial impact
 Impact on quality of life (will tx improve their quality of life?)

Diagnosing Glaucoma
 Presenting history
 Risk factors
 Ocular examination
 Monitoring

Treatment
When to treat Glaucoma?
When to treat Glaucoma suspects?
 Consider all known risk factors for pt and estimate their probability of developing glaucoma
 Determine who will progress and who will remain stable
o Difficult. Extent of damage present and disease progression will help determine progression rate.
 Risk assessment: OHTS-EGPS risk calculator
o OHTS and EGPS data
o Estimates the 5-year risk of converting to glaucoma based on:
 Age
 IOP (baseline)
 Central corneal thickness
 Vertical cup/disc ration
 HFA PSD (Humphrey field analyser, pattern standard deviation)
o Assessment
 <5%: risk level low  monitor
 5 – 15% risk level moderate  consider therapy; discuss w/ pt
 >15% risk level high  treat
o Limitations
 Reliability applicable only to pts who resemble recruited subjects
 Validated in European population
 Does not consider other important risk factors e.g., family h/x
 Does not consider other factors e.g., life expectancy, cost of
treatment, effect on quality of life, patient preferences
 Level of risk to commence treatment is arbitrarily selected
 RAND-UCLA Appropriateness Method (RAM)
o Point system used to predict the appropriateness of initiating treatment
for a glaucoma suspect
o Assessment
 Treat ≥ 7 pts
 Inappropriate to treat ≤ 3 pts
o Strength – validated method
o Limitation – does not consider every risk factor for glaucoma

OBA Requirements
 Options for managing pts with glaucoma:
o Refer to ophthal
 o Collaborative care with ophthal
o Initiate tx, monitor response and refer to ophthal within 4 months (OBA Guidelines)
 To comply with OBA guidelines for managing glaucoma, endorsed optometrists must
o Have all equipment specified

Level Hierarchy of glaucoma examination

Very good level IOP, gonioscopy, threshold VF, optic disc images and RNFL images

Good IOP, gonioscopy, threshold VF, optic disc images or RNFL images

Satisfactory IOP, gonioscopy, threshold VF, clinical optic disc examination

Insufficient IOP

 Assessment of IOP, CCT, threshold VF, anterior chamber angle, optic nerve head, and retinal nerve fibre layer
 Ideally, applanation tonometry is recommended for IOP
 Standard automated perimetry is recommended for VF
o Refer to NHMRC guidelines when setting target IOP and deciding review frequency
o Communicate with pt’s other health practitioners (GP, ophthal or other practitioners)
o Remain cognisant of the mandatory referral triggers
 Anti-glaucoma drops do not stabilise pt’s condition
 Pt needs assessment for surgical or laser tx
 Pt is experiencing side effects of initial tx
 In any event, referral to ophthal within 4 months of starting tx
 Referral - providing pt letter and sending copy to ophthal

OBA Guidelines for emergency management of acute primary angle closure

 Standard management is emergency referral to ophthal or hospital.
 First Aid for acute angle-closure
1. Oral dose of acetazolamide 500mg (Diamox)
 Optom are advised to liaise with medical practitioner to arrange supply of Diamox for pt
 Pharmacist can supply Diamox when requested to do so via telephone order from medical practitioner
 If Diamox cannot be tolerated orally, pt is likely to need IM or IV administration of Diamox  referral and transfer to ophthal or hospital
emergency department
2. Instil the following topical medications (allowing 2 minutes b/w each drop):
 One drop beta-blocking agent e.g., timolol 0.5%
 One drop alpha agonist e.g., brimonidine 0.2% or apraclonidine 0.5%
 One drop carbonic anhydrase inhibitor e.g., brinzolamide 1.0%
3. If eye is red and inflamed
  One drop high-penetrance topical steroid
 Instil a further three drops at regular intervals in the first hour, then hourly thereafter
 Either pt or optom
4. Pilocarpine 2%
 Withhold instillation until IOP has been reduced except in the rare instance of an angle-closure event caused through routine pupil dilation
 Instil 1 drop 2% pilocarpine just before pt is transferred
 After discussion with ophthal confirming that pilocarpine is indicated
 Instil a further drop after 15 minutes
 Contraindicated for retro lenticular causes of angle closure as well as those involving aphakic or pseudophakic closure events
 Indicated for phakic pupillary block or angle crowding

Management principles
 Select target pressure
 Select therapy
o Topical glaucoma medication – PGA, beta-blocker, CAI, adrenergic agonists
o Laser trabeculoplasty – ALT, SLT
o Filtration surgery

Treatment Paradigm (hierarchy)

 1st line therapy
o Topical prostaglandin analogues (PGA) or
o Selective laser trabeculoplasty (SLT)
 2nd line therapy
o PGA or SLT or
o Topical CAI or Brimonidine (alpha agonist) or beta-blocker or
o Fixed combination
 3rd line therapy
o Either add Brimonidine or Dorzolamide or SLT
o Filtration surgery  advanced cases
 4th line therapy
o Filtration surgery

Setting Target IOP

 Target IOP when there is no progression with VF, ONH, and imaging
o NHMRC – 25% from baseline, with a further 20% if progression occurs
o Record IOP

Stage Target IOP Evidence

Suspect 20% OHTS, EGPS
 Early 25% EMGTS, CIGTS
Moderate 30% CNTGS, AGIS
Advanced Lower than 14 mmHg AGIS, Odberg

Selection of medication: NHMRC Recommendations

 Achieve IOP
 Most adorable
 Lowest effective concentration
 Best safety profile
 Simplest regimen
 Preferably once daily administration

Selection of medication: Considerations

 Target IOP
 Ocular history
 Contralateral eye
o E.g., if the other eye is blind, choose a medication that has greater control over IOP
 Medical history
 Drug efficacy

Preparations by class Mechanism of action Efficacy Daily Wash-out period Order of tx choices
Dosage
Prostaglandin analogues Increase aqueous outflow 25-30% 1x 4-6 weeks First
· Latanoprost 0.005%
· Travoprost 0.004%
· Bimatoprost 0.03%

Beta – blockers Decrease aqueous 20-25% 1x to 2x 2-5 weeks First

Non-selective agents production
· Timolol 0.25%, 0.5%, 0.1%
· Levobunolol 0.25%

Selective agents
· Betaxolol 0.25%, 0.5%

Proprietary-fixed combinations As for individual 25-30% · 2x As for individual components Second

· Combigan (brimonidine 0.2% + timolol components · 2x
0.5%) · 1x
· Cosopt (dorzolamide 2% + timolol 0.5%) · 1x
· DuoTrav (travoprost 0.004% + timolol
 0.5%)
· Xalacom (latanoprost 0.005% + timolol
0.5%)

Alpha 2 agonists Increase aqueous outflow 20-25% 2x to 3x 1-3 weeks Second

· Brimonidine 0.2% and decrease aqueous
· Apraclonidine 0.5% production

Carbonic anhydrase inhibitors Decrease aqueous 15-20% 2x to 3x 1 week Second

Topical production
· Dorzolamide 2%
25-30% 2x to 4x 3 days Third
· Brinzolamide 1%

Systemic
· Acetazolamide 250 mg

Cholinergic (Miotics) Increase aqueous outflow 20-25% 3x to 4x 3 days Third

· Pilocarpine 1%, 2%
· Carbachol 1.5%, 3%

Class Diurnal Efficacy (Day Nocturnal Efficacy

time)
Prostaglandins 18 – 31% 8.5 – 17%
Beta-blockers 20 – 27% Little or none
Alpha agonists 12.5 – 29% Little or none
Carbonic Anhydrase 13.2 – 22% Modest efficacy
Inhibitors Brinzolamide has an additive
nocturnal effect with Latanoprost

Miotics (Pilocarpine) - -

Initiating Medication
 Initiated ONE medication at a time
o Don’t start with multiple medication b/c it is hard to determine the effect of each
 Assess efficacy on pt’s return
o PGA: 2 – 4 weeks
o Timolol: 4 weeks
o Alpha agonists and topical CAI: 2 weeks
 Consider trialling one eye
 o Controversial? Questions have been raised on the validity of monocular trials
o Recent study (King 2016) demonstrated monocular trial significantly improves precision of estimation of tx effect

Modifying medication
 IOP is too high
 IOP is variable
 Optic nerve progression
 Visual field progression

Steps for initiating tx

1. Start tx (glaucoma medication) in one eye (monocular)
2. Assessment the eye
 IOP, OCT, VF, ONH
3. If the trial is successful, implement tx in the contralateral eye
4. If the trial is unsuccessful, substitute the medication with a difference class before adding another class as an adjunct or combination therapy
Adjunctive Therapy
 Indications
o Monotherapy fails to achieve target IOP
o Disease progression, regardless of IOP
 Adjunctive therapy should be limited to one drug from each class
o Using more than one drug from the same class provides no additional benefits
 In adjunctive therapy, no more than 2 bottles should be used, and application should be no more than twice a day
o Up to 4 medications can be used, if fixed combination drugs are used
o 31% success with 3rd agent (3 bottles  reduced adherence)
o 14% success with 4th agent (bottle)
 Issues
o Increased non-compliance with increased number of bottles
o Wash-out effect
 Occurs when second drop of medication is instilled before the first drop is absorbed
o Increased exposure to benzalkonium chloride (ocular surface damage)
 Alpha agonist, beta-blockers, and CAI, when used in combination with PGA, all have similar effect in lowering mean diurnal IOP
 CAI in combination with latanoprost (PGA) has a nocturnal IOP-lowering efficacy
 CAI may be the best additive class

Additive Effects (Adjunctive Tx)

Class of Alpha 2 – agonists Beta-blockers Topical CAI Cholinergic PGAs Sympathomimetics
Medication
Alpha 2 – agonists +* + + + -
Beta-blockers +* +* + +* +
Topical CAI + +* + + +
Cholinergic + + + +/- +
PGAs + +* + +/-
+ good additive IOP-lowering effect
- Poor additional IOP-lowering effect
* Available in combined preparation

Fixed combination
 For fixed combination drugs to be approved, it needs to have better efficacy than each of the component used
 Fixed combinations are viewed as a single tx
 Advantages:
o Enhanced convenience
o Improved adherence
o Reduced exposure to preservatives
o Possible cost savings
 Fixed Combination Drugs
Fixed Combination Brand Name Dosage
Timolol + PGA Ganfort, Ganfort PF 1 drop/ day
 Timolol 0.5% + Bimatoprost 0.03%
Xalacom, Xalamol
 Timolol 0.5% + Latanoprost 0.005%
DuoTrav
 Timolol 0.5% + Travoprost 0.004%
Timolol + CAI Azarga 1 drop, 2x/ day
 Timolol 0.5% + Brinzolamide 1%
Cosdor, Cosopt
 Timolol 0.5% + Dorzolamide 2%
Timolol + alpha agonist Combigan 1 drop, 2x/ day
 Timolol 0.5% + Brinzolamide 0.2%
Alpha agonist + CAI Simbrinza 1 drop, 2x/ day
 Brimonidine 0.2% + Brinzolamide 1%

Canadian Journal of Optometry Guidelines

European Glaucoma Society Guidelines: Therapeutical Algorithm
Communication
 Educate pt on their diagnosis, prognosis, and treatment options for shared decision making
 For tx with medication, advise pt on
o Cost
o side effects
o dosage
o instillation
 Referral to ophthal within 4 months of initiating therapy
 Communication w/ pt’s health care practitioners e.g., GP

Recall Period – NHMRC Guidelines

NHMRC Recall Guidelines
Treatment Status Success Frequency
On High Risk Achieving Target Review Tonometry Gonioscopy Optic Nerve and NFL Stereoscopic, digitally Automated
medication assisted imaging on NFL threshold perimetry
No No N/A 6-12/24 months Multiple/every visit Sufficient to set 6-24 months or every Sufficient to set baseline Sufficient to set
baseline – then other visit – then every two years baseline – then
Yes N/A 3-12 months annually 6-18 monthly annually
 Yes Yes Yes 3-12 months 6-18 monthly
No <4 months 3-12 monthly

Follow-up guidelines
 Questions to ask pt/ comprehensive hx:
o How are your eyes and vision?
 Determine if there any changes esp. to functional vision
o Are you managing to take your medication as discussed? If not, what are the problems or difficulties that you face?
 Compliance and barriers to compliance
o Is there anything about your condition or your tx plan that you would like explained?
 Pt education and compliance
o Do you have any other medical conditions? If yes, have they been exacerbated recently?
o Are you taking any prescriptions or over-the-counter drugs, if so what?
 Drug interactions
o Do you have plans to conceive or are you already pregnant? If yes, do you plan to breastfeed?
o When did you last attend eye examination or have your condition monitored?
 Examination recommended
o VA
o IOP (applanation)
 Review target IOP and adjust if indicated
o Anterior segment examination
o Gonioscopy if indicated
o ONH/RNFL assessment  volk, photography, OCT
o Standard automated perimetry visual field assessment

Prostaglandins
General Mechanism of Action Types
· Lipid compounds derived from · ↑ uveoscleral outflow of aqueous humour · Bimatoprost
arachidonic acid · Latanoprost
· Excellent 24-hour control of IOP Mechanism · Tafluprost
· Once daily dosage · PGAs bind to prostaglandin receptors, EP and FP, found in TM, Schlemm’s Canal, and CB. · Travoprost
· Few systemic effects o Action results in relaxation of ciliary muscle and enlargement of uveoscleral pathway which ↑
aqueous outflow.
o EP and FP disrupt ECM turnover
· PGA ↑ metalloproteinases (MMP) expression.
o MMP upregulation, ↓ collagen and other extracellular matrix constituents (MMPs degrade ECM),
creating optically empty spaces b/w muscle bundles in CB. In the long term, this creates well-
established outflow channels through the CB and enhance aqueous outflow.
 o MMP reduce hydraulic resistance around muscle fibre.
o Remodelling of ECM tissues occurs b/c of MMP upregulation.

Adverse Reactions
Conjunctival Hyperaemia Hypertrichosis Periorbital Darkening Common (>1%)
· Vasodilation caused by the release of · Longer, darker, thicker, and increased number · Uncommon: 1.5% latanoprost; 2.9% · Iris hyperpigmentation, eyelash
nitric oxide and europeptides of hairs on the lower lid – temporal bimatoprost; 2.9% travoprost. changes, periorbital changes,
· Minimal to mild · Opening of K+ channels in peri-follicular vessels · Reversible conjunctival hyperaemia, eye irritation,
· Frequency: 5 – 50% causes vasodilation and stimulates follicular hair · Manifests in months to 3 years. allergic conjunctivitis, blurred vision,
o More common in Bimatoprost & growth punctate keratitis, blepharitis, HA
Travoprost > Latanoprost · Frequency: Prostaglandin Periorbitopathy
o Latanoprost: 0 – 25% · Deepening of lid sulcus; upper lid ptosis; Infrequent (0.1–1%)
Inflammatory Complications o Travoprost: 0.7 – 52% involution of dermatochalasis (excess skin esp. · Reversible macular oedema (including
· Reactivate anterior uveitis; reactive o Bimatoprost: 3 – 36% in lower lid); periorbital fat atrophy; mild CMO), eyelid and conjunctival oedema,
and/or cause cystoid macular oedema; · Reversible enophthalmos; inferior scleral show; increased iritis or uveitis
reactivate Herpes Simplex. prominence of lid vessels; tight eyelids.
o Precaution in pt w/ prior hx of Trichiasis - occasional · More frequent with Bimatoprost. Rare (<0.1%)
anterior uveitis, herpetic keratitis, Iris Pigmentation (Hyper) · Reversible · Reactivation of herpetic keratitis
or macula disease associated with · Onset – within first months to years of tx
CMO · Frequency
· Rare o Latanoprost: 5.1 – 10.1%
· Resolves on discontinuation o Bimatoprost: 1.1 – 1.5%
o Travoprost: 1.0 – 3.1%
· Irreversible – counsel pt

Contraindications Precautions Indication Practice Points

· Active herpetic keratitis · Intraocular inflammation (iritis, uveitis) – PGAs · Glaucoma · Double DOT technique (Digital
can worsen inflammation · OHT occlusion of tear duct and don’t open
· Herpetic keratitis – h/x of infection technique)
· Pseudophakia w/ torn posterior lens capsule, · Evening dosing is preferred for optimal
aphakia, risk factors for macula oedema effect
· Pregnancy · Increase in IOP may occur with 2 PGAs
o Limited human data, avoid use if possible. are used together
· Breastfeeding – safe to use

Bimatoprost
General Concentrations Dosage Indication
· Active Ingredient: Bimatoprost · 0.03% [3mL] · Adult, child – 1 drop, once daily at night · Ocular Hypertension (OHT)
· Preservative: Benzalkonium Chloride · Fixed-dose combination with timolol 0.5% · Open-angle Glaucoma (OAG)
(BKC) or Preservative-free (PF) Products o 1st line therapy; monotherapy or
· PBS, unrestricted · 0.03%, 3 mL, Bimprozt, Bimtop, Lumigan, PBS combination
· B3 · 0.03%, 0.4 mL x 30, unit dose, Lumigan PF, PBS

Contraindications Precautions Adverse Reactions Interactions

· Active intraocular inflammation e.g., · Intraocular inflammation (uveitis) Common · Other prostaglandins
 uveitis · Hx of herpetic keratitis · Iris hyperpigmentation; eyelash changes;
· Aphakia, pseudophakia, torn lens/capsule periorbital changes; conjunctival hyperaemia; · NSAIDs eyedrops
· Known risk factors for macular oedema eye irritation; allergic conjunctivitis; blurred
vision; superficial punctate keratitis (SPK);
blepharitis; headaches

Infrequent
· Reversible macula oedema; eyelid &
conjunctival oedema; uveitis

Rare
· Reactivation of herpetic keratitis

Latanoprost
General Concentrations Dosage Indication
· Active Ingredient: Latanoprost · 0.005% [2.5mL] · Adult, child – 1 drop, once daily at night · OHT
· Preservative: BKC · OAG
· PBS, unrestricted Products o 1st line therapy; monotherapy or
· B3 · 0.005%, 2.5 mL, Xalaprost, Xalatan, PBS combination

Contraindications Precautions Adverse Reactions Interactions

· Same as Bimatoprost (see above) · Same as Bimatoprost · Same as Bimatoprost · Same as Bimatoprost
· Common
o Periorbital rash

Tafluprost
General Concentrations Dosage Indication
· Active ingredient: Tafluprost · 0.0015% [0.3mL], single use (PF) · Adult – 1 drop, once daily at night · Same as Bimatoprost
· PBS, unrestricted
· B3 Products
· 0.0015%, 0.3 mL x 30, unit dose, Saflutan, PBS

Contraindications Precautions Adverse Reactions Interactions

· Same as Bimatoprost · Same as Bimatoprost · Same as Bimatoprost · Same as Bimatoprost

Travoprost
General Concentrations Dosage Indication
· Active Ingredient: Travoprost · 0.004% [2.5mL] · Adult, child – 1 drop, once daily at night · Same as Bimatoprost
· Preservative: Polyquaternium
· PBS, unrestricted Products
· B3 · 0.004%, 2.5 mL, Travatan, PBS

Contraindications Precautions Adverse Reactions Interactions

· Same as Bimatoprost · Same as Bimatoprost · Same as Bimatoprost · Same as Bimatoprost

Beta-Blockers (topical)
General Mechanism of Action Types
· β 1 – heart · ↓ Aqueous production Non-selective (affects all beta receptors)
· β 2 – pulmonary system (lungs) · Proposed mechanism: blockade of beta receptors, predominantly β 2 , located on the ciliary epithelium. · Timolol
 Exact mechanism is not known.
Selective
· Betaxolol (Cardio-selective, beta-1)

Adverse Effects Practice Points

General Cardiovascular Central Nervous System · Double DOT technique
· Lethargy · Bradycardia · Anxiety, depression
· Weakness · Worsening of congestive heart failure (CHF) · Decreased libido · Treatment alongside a systemic beta
· Inability to ↑ heart rate during exercise · Emotional lability – exaggerated changes in blocker - ↑risk of systemic adverse
Pulmonary · Hypotension mood effect
· Bronchospasm · Hallucination, confusion Treatment alongside drugs that cause
· Heart block ·
· Reduced pulmonary function · Psychosis bradycardia – may further decrease HR.
· Syncope (fainting)
 Avoid combination with
verapamil unless under the
supervision of specialist.

Indications Precautions Contraindications

· Glaucoma · Cardiovascular – potential cardiovascular effects · Bradyarrhythmia or 2nd or 3rd degree
· OHT · Respiratory – may precipitate bronchospasm. atrioventricular block.
 Betaxolol may be used with caution in COPD and asthma. · Asthma
· Surgery - ↑risk of bradycardia and hypotension
· Elderly – ↑risk of systemic adverse effects
· Pregnancy – may be used but monitor foetus for possible adverse effects e.g., bradycardia.
· Breastfeeding – safe to use; adverse effects are unlikely but monitor the infant.

Timolol
General Concentrations Dosage Indication
· Potent, non-selective, beta-adrenergic · 0.25% [2.5mL], 0.5% [5mL] · Adult, child > 12months – 1 drop, b.i.d. · OHT
blocking agent  Binds with ocular melanin; darker irises · Chronic OAG
· Gold standard – good IOP-lowering need higher concentrations. · Fixed-dose combination with Bimatoprost, · Aphakia with glaucoma
efficacy Latanoprost, Travoprost, brimonidine,
 FDA requires the efficacy of new Products (ophthalmic) brinzolamide, or dorzolamide
glaucoma medications to be · 0.5%, 2.5 mL, Timoptol-XE, PBS  0.5% Timolol
measured against Timolol · 0.5%, 5 mL, Timoptol, PBS

· Active Ingredient: Timolol maleate

· Preservative: BKC
· PBS, unrestricted
· Pregnancy: C

Contraindications Precautions Adverse Reactions Practice Points

· Bronchial asthma · Diabetes Common (>1%) Interactions
· Bronchospasm · Hyperthyroidism · Stinging on instillation; bradycardia; blurred · Other beta blockers
· Reactive airways disease · Cardiac failure vision · Adrenaline (epinephrine)
· Severe chronic obstructive pulmonary · Depression · Catecholamine depletors
disease (COPD) · Elderly and children Infrequent (0.1 – 1%) · Clonidine
· Sinus bradycardia  Adverse systemic effects are more · Decrease corneal sensation; hypotension; · Ca2+ channel blockers
· Overt cardiac failure common in vulnerable populations fainting; fatigue; confusion; hallucinations;  Verapamil – use under specialist
· CHF bronchospasm supervision
· Cardiogenic shock
· Ocular hypotensive action of Timolol
persists 2 weeks after withdrawal in pts
with chronic 2x/ day use.
 IOP needs to be monitored/
measured after discontinuation.

Betaxolol
General Concentrations Dosage Indication
· Cardio-selective; less affinity for beta-2 · 0.25% or 0.5% solution · Adult, child – 1 drop, b.i.d. · OHT
pulmonary receptors – ↓ systemic effects.  0.25% suspension is as effective as 0.5% · Chronic OAG
· ↓ efficacy compared to Timolol solution; suspension reduces local stinging · Monotherapy or combination
· Potential neuroprotective and blood flow thereby, ↑compliance
properties
Products
· 0.5% (solution), 5 mL, Betoptic, Betoquin, PBS
· Active Ingredient: Betaxolol hydrochloride
· Preservative: BKC
· PBS, unrestricted
· Pregnancy: C

Contraindications Precautions Adverse Reactions Interactions

· Sinus bradycardia >1st degree block · Cardiac failure Common · Other beta blockers
· Cardiogenic shock · Heart block hx · Stinging on instillation; bradycardia; blurred · Ca2+ channel blockers
· Overt cardiac failure hx · Severe cardiac disease vision  Verapamil – use under specialist
· Cerebrovascular insufficiency supervision
· Cardiovascular disease Infrequent · Adrenaline
· Decreased corneal sensitivity; hypotension; · Catecholamine depletors
fainting; fatigue; confusion; hallucinations; · Antiarrhythmics
bronchospasm · Digitalis

Non-selective Adrenergic Agonist

General Mechanism of Action Side effects Types
· Alpha & beta receptors · Various mechanisms: aqueous humour flow, · High frequency of adverse events · Epinephrine
· Weak efficacy trabecular outflow, uveoscleral outflow · Propine
· Rarely used anymore

Alpha Agonist
General Mechanism of Action Types Indications
· Alpha 1 receptor – smooth muscle, heart, · Suppress the production of aqueous humour Alpha-2 selective · Glaucoma
& liver and ↑ uveoscleral outflow of aqueous humour · Apraclonidine hydrochloride (slight selectivity)
· Alpha 2 receptor – iris, ciliary body, retina, · Brimonidine (high selectivity)
RPE, platelets, vascular smooth muscle,
nerve termini, and pancreatic islets.

Adverse Effects Precautions Practice Points

General Ocular allergy · Severe cardiovascular disease · May be used by ophthalmologists in

· Lethargy · Allergic blepharoconjunctivitis (less with · Do not use in children acute angle-closure crisis or to prevent
o Lethargy is more common in children, Brimonidine) ocular hypertension following laser
frail individuals, elderly, small · Usually presents as follicular conjunctivitis with surgery
individuals sx such as hyperaemia, tearing, and fb · Double DOT technique
· Fatigue sensation.
· Drowsiness · Potential periocular dermatitis
· Dry mouth & nose
Common (>1%)
Cardiovascular · Ocular allergy, hyperaemia, ocular irritation, dry
· Mild ↓in blood pressure mouth and nose, taste disturbance, conjunctival
blanching, lid retraction, headache.

Apraclonidine Hydrochloride

General Concentration Dosage Indications

· Active Ingredient: Apraclonidine · 0.5% [5mL or 10mL] solution · Adult – 1 drop, b.i.d. or t.i.d. · Glaucoma
hydrochloride · Short-term control of IOP (≤ 3months)
· Selective alpha-2-receptor Products in pts on maximum-tolerated glaucoma
sympathomimetics · Eye drop, 0.5%, 5 mL, Iopidine therapy
· PBS, restricted MP only · Eye drop, 0.5%, 10 mL, Iopidine, PBS-R o Effect declines over time
· Pregnancy: B3 o Restricted for short term reduction of IOP · During ocular surgery to prevent acute
in pts on maximally tolerated anti- rise in IOP
glaucoma therapy o Limited use in clinical care of
glaucoma due to high frequency
of allergic reactions

Contraindications Precautions Adverse Reactions Interactions

· Systemic clonidine hypersensitivity · Severe cardiovascular disease · Common: ocular irritation, dry mouth & nose, · Beta-blockers: additive effect
· Concurrent monoamine oxidase inhibitors · Pregnancy: avoid use & seek specialist advice and taste disturbances · Cardiac glycosides
(MAOIs) · Breastfeeding: unlikely to be a concern o High frequency of allergic reactions (48%) · CNS depressants (alcohol, opiates,
· Tricyclic antidepressants (TCAs) due to adrenergic function of drug – sedatives, anaesthetics, TCAs)
· Systemic sympathomimetics follicular conj
· Infrequent: mydriasis, conjunctival blanching,
lid retraction
· Rare: fainting, chest tightness, reduction in BP,
headaches

Brimonidine
General Concentrations Dosage Indication
· Active Ingredient: Brimonidine tartrate · 0.15% [5mL] or 0.2% [5mL] solution · Adult, child > 12 years – 1 drop, b.i.d. · Chronic OAG or OHT as
· Preservative: BKC o 0.15% (Purite preservative) appears to · Peak & trough effects: reduced half-life. monotherapy/combination
· PBS, unrestricted lower IOP to a similar extent as 0.2% o Pt may require t.i.d. if Brimonidine is o Fixed-dose combination with
· Pregnancy: B3 (BKC) and may cause fewer adverse used as the sole agent. beta-blocker/ timolol
· Highly selective alpha-2 agonist effects o Reduced nocturnal efficacy and more o Fixed-dose combination with
· IOP reduction ~ 22% effective during waking (diurnal) hours brinzolamide
· Neuroprotection – reduces retinal Products · 2nd or 3rd line agent
ganglion cell death and lowers rate of VF · Eye drop, 0.15%, 5 mL, Alphagan P 1.5, PBS · Effective when used long term
defect progression · Eye drop, 0.2%, 5 mL, Alphagan, Enidin, PBS

Contraindications Precautions Adverse Reactions Interactions

· Concomitant monoamine oxidase · Avoid use in children < 12 years Common (>1%) · Beta-blocker
inhibitor · Severe cardiovascular disease · Fatigue, drowsiness, dizziness · Antihypertensives
· Children < 2 years · Pregnancy · Same as above, alpha-agonist. · Cardiac glycosides
o Higher risk of serious adverse o Limited data, but safe to use. · CNS depressants
effects e.g., CNS events especially in o Avoid use close to delivery due to Infrequent (0.1% – 1%)
children <6 years or <20kg theoretical risk of CNS depression and · Bradycardia, hypotension (systemic)
apnoea in neonate. · Systemic allergic reactions, depression,
· Breastfeeding palpitations
o Avoid use due to theoretical risk of CNS
Rare (<0.1%)
depression and apnoea in infant
· Uveitis
· Driving or operating machinery
o May cause drowsiness or dizziness
 Favourable ocular & systemic safety profile.
 Lower incidence of ocular allergy compared to
apraclonidine

Carbonic Anhydrase Inhibitors (CAI)

General Mechanism of Action Type
Topical · Inhibits carbonic anhydrase II which ↓aqueous humour formation. Oral
· Nocturnal IOP lowering efficacy o Carbonic anhydrase generates Na+ and HCO3- ions, allowing water to enter ciliary epithelial cells, · Acetazolamide – Diamox
o Additive effect: brinzolamide + leading to aqueous humour formation. · Methazolamide
latanoprost
· Additive effect of prostaglandin derivates and carbonic anhydrase inhibitors: Topical
o PGAs improve uveoscleral outflow, but also increase carbonic anhydrase activity in the ciliary · Brinzolamide
epithelium which causes a secondary increase in aqueous humour secretion. This decreases the · Dorzolamide
efficacy of PGAs. The addition of a topical CAI leads to the inhibition of carbonic anhydrase and
improves PGA efficacy.

Adverse Effects
Oral Oral Oral Topical
Pulmonary Hematologic Renal Common (>1%)
· Respiratory decompensation in chronic · Agranulocytosis – severe leukopenia · Nephrolithiasis – process of forming a kidney · Ocular irritation (more w/
obstructive pulmonary disease o Leukopenia lowered white blood cell stone dorzolamide), transient blurred vision
count especially, neutrophils · Renal failure (more w/ brinzolamide), FB sensation,
Gastrointestinal bitter taste
· Cramps (neutropenia) Other Infrequent (0.1 – 1%)
· Diarrhoea · Aplastic anaemia – deficiency of all blood cell · Hypokalaemia (low K+ levels in blood serum) · GI disturbance, HA, paraesthesia,
· Epigastric burning types (RBC, WBC, and platelets) · Metabolic acidosis (build-up of acid in the body) dizziness, dermatitis
· Metallic taste · Acute leukopenia · Steven-Johnson syndrome – a rare, serious
· Nausea · Neutropenia – lowered neutrophils disorder of the skin and mucous membranes. Rare (<0.1%)
o Nausea and vomiting may be · Allergic reactions e.g., urticaria,
associated with drug-induced angioedema
metabolic acidosis

Adverse Effects Indications Precautions Practice Points

Topical Topical Topical Topical
· Safe medication with fewer systemic side · Glaucoma or OHT · Compromised corneal endothelium · Double DOT
effects · 2nd or 3rd line drug; can be used as o May increase risk of corneal oedema · Avoid driving or operating machinery
· Side effects: monotherapy. · Allergy to sulfonamides o Blurred vision and discomfort
o Ocular – hyperaemia · Excellent efficacy when used in combination. o May increase risk of allergy to carbonic after drops
o Systemic – metallic taste anhydrase inhibitors
· Brinzolamide is better tolerated than · Pregnancy: limited data, avoid use
dorzolamide. Breastfeeding: limited data, safe to use

Acetazolamide – Oral
General Concentrations Dosage Indication
· Active ingredient: Acetazolamide · 250 mg · Adult, 250 – 1000mg/ 24 hrs in divided doses · Acute reduction of IOP e.g.,
· B3 perioperatively, acute angle-closure
Product crisis (acute ACG)
· Tablet, 250 mg (scored), 100, Diamox, PBS · Chronic OAG where other tx have failed

Contraindications Precautions Adverse Reactions Interactions

· Adrenal or respiratory failure or metabolic · Gout – may worsen (defective metabolism of · Up to 50% of pt do not tolerate · High-dose aspirin
acidosis uric acid causing arthritis) · Lithium
o ↑ risk of profound acidosis · Elderly - ↑risk of adverse events e.g., metabolic Common (>1%) · Cyclosporine
· Hyponatraemia or hypokalaemia (sodium acidosis · Paraesthesia (face, hand, feet), fatigue, · Diuretics
or potassium depletion) drowsiness, depression, decreased libido; · Digoxin
o May worsen electrolyte bitter/metallic taste, nausea, vomiting,
abdominal cramps, diarrhoea, black faeces,
disturbances
polyuria, renal stones, metabolic acidosis;
o
electrolyte disturbances (hypokalaemia,
o May ↑ risk of allergy to
hyponatraemia)
sulfonamides; contraindicated by
manufacturer Infrequent (0.1 – 1%)
· Renal disease · Transient myopia, bullous skin eruptions (SJS)
o CrCl <10 mL/ minute –↑ risk of
profound acidosis Rare (<0.1%)
· Hepatic impairment or cirrhosis (liver · Aplastic anaemia, thrombocytopenia,
damage where healthy cells are replaced agranulocytosis, neutropenia, anaphylaxis
by scar tissue)
o ↑ risk of hepatic encephalopathy
 Brinzolamide – Topical
General Concentrations Dosage Indication
· Active ingredient: brinzolamide · 1% [5mL] suspension · Adult, child – 1 drop b.i.d. · OHT
· Preservative: BKC · OAG
· PBS, unrestricted Products o Fixed-dose combination with
· Pregnancy: B3 · Eye drop, 1% (suspension), 5 mL, Azopt, 0.5% timolol
· Brinzolamide + Latanoprost – significantly BrinzoQuin, PBS o Fixed-dose combination with
reduce IOP during sleep/ nocturnal period brimonidine
Fixed-dose combinations
· Eye drop, brinzolamide 1%, brimonidine 0.2%
(suspension), 5 mL, Simbrinza, PBS-R
o Restricted for OAG, OHT

Contraindications Precautions Adverse Reactions Interactions

· Pregnancy (avoid use AMH 2020) · Compromised corneal endothelium Common · Miotics
o Corneal grafts · Ocular irritation, foreign body sensation, bitter · Oral CAI
o Endothelial dystrophy – ↑ corneal taste, transient blurred vision · Adrenergic agonists
oedema (may precipitate corneal
Infrequent
decompensation)
· Conjunctivitis, blepharitis, keratitis
· Sulfonamides-allergy
· Vision changes, corneal staining, GI
· Breastfeeding: limited data, safe to use
disturbances, headaches, paraesthesia,
dizziness, dermatitis
· Avoid driving or operating heavy machinery
Rare
· Allergic reactions – urticaria, angioedema,
bronchospasm

Dorzolamide – Topical
General Concentrations Dosage Indication
· Active ingredient: dorzolamide · 2% [5mL] solution · Adult, child – 1 drop t.i.d. (monotherapy) or · Same as Brinzolamide
· Preservative: BKC · 1 drop b.i.d. (adjunct to beta-blocker)
· PBS, unrestricted Products
· B3 · Eye drop, 2%, 5 ML, Trusamide, Truopst, PBS

Contraindications Precautions Adverse Reactions Interactions

· Pregnancy · Same as Brinzolamide · Same as Brinzolamide · Oral CAI
· Adrenergic agonists
Common
· Allergic conjunctivitis and blepharitis, SPK

Miotics
General Mechanism of Action Types
· Cholinergic agonist · Cholinergic effect contracts: · Pilocarpine
o Iris sphincter  miosis (no effect on reducing IOP)
o Ciliary muscle  produces posterior traction on scleral spur thereby, ↑outflow through trabecular
 meshwork (mechanical opening of TM), lowering IOP
·

Pilocarpine
General Concentrations Dosage Indication
· Active ingredient: Pilocarpine · 1%, 2%, 4% [15mL] · Adult, child > 2 years – 1 drop 1% pilocarpine · Chronic OAG
hydrochloride o Usual concentration for glaucoma is 1-4% t.i.d. – q.i.d. · Acute ACG
· Preservative: BKC o Dark irises may benefit from 6%. · Child 1 month to 2 years – 1 drop 1%
· PBS, unrestricted o Higher concentration = ↑side effects pilocarpine t.i.d.
· Pregnancy: B3 o 4% can be used b.i.d. with beta-blocker

Products
· Eye drop, 1%, 15 mL, Isopto Carpine, PBS
· Eye drop, 2%, 15 mL, Isopto Carpine, PBS
· Eye drop, 2%, 0.5 mL (single use), 20, Minims
Pilocarpine
· Eye drop, 4%, 15 mL, Isopto Carpine, PBS

Contraindications Precautions Adverse Reactions Interactions/ Practice Points

· Anterior uveitis · Previous retinal detachment, pre-existing retinal · Drug is rarely used now due to topical side · Instil pilocarpine last if more than one
o Acute inflammatory disease of damage, young pts with myopia effects eye drop is used
anterior segment and conditions o ↑ risk of RD · Long-term use may cause permanent miosis, · Avoid driving or operating heavy
where pupillary constriction is not · Pregnancy: limited data, safe to use lens opacities have also been reported. machinery
recommended, eg, uveitis, iritis and · Breastfeeding: limited data, safe to use · Double DOT technique
some forms of secondary glaucoma. Common
· Headaches (frontal HA/ brow ache due to ciliary
spasm, esp. in young pt); blurred vision;
myopia; reduced vision in low light; constriction
of VF; ocular irritation

Infrequent
· Lacrimation

Rare
· Retinal detachment; systemic effects (increased
sweating; diarrhoea; bronchospasm;
bradycardia)

Fixed Combination Drugs

Timolol + Prostaglandins Timolol + Carbonic Anhydrase Inhibitors
General Concentrations General Concentrations
· PBS MP, OP · Ganfort 3 mL, Ganfort PF 0.4 mL x 30 · PBS MP, OP · Azarga, 5 mL, suspension
· Pregnancy: C+ o Timolol 0.5% + bimatoprost 0.03% · Pregnancy: C+ o Timolol 0.5% + brinzolamide 1%
· Restricted benefits: clinical criteria · Xalacom, Xalamol 2.5 mL · Restricted benefits: clinical criteria (same as · Cosdor, Cosopt 5 mL, Cosopt PF 0.2 mL
o Elevated IOP o Timolol 0.5% + latanoprost 0.005% above) x 60
o Inadequately controlled with · DuoTrav 2.5 mL · Dosage: 1 drop, b.i.d. o Timolol 0.5% + dorzolamide 2%
 monotherapy o Timolol 0.5% + travoprost 0.004%
o OAG/OHT
· Dosage: 1 drop, q.d.

Timolol + Alpha agonist Alpha agonist + Carbonic Anhydrase Inhibitor

General Concentrations General Concentrations
· PBS: MP, OP · Combigan 5 mL · PBS: MP, OP · Simbrinza 5 mL, suspension
· Pregnancy: C+ o Timolol 0.5% + brimonidine 0.2% · Pregnancy: B3 o Brimonidine 0.2% + brinzolamide
· Restricted benefits (same as above) · Restricted benefits (same as above) 1%
· Dosage: 1 drop b.i.d.

Preservative- free Therapy Nitric Oxide (new drug)

General Adverse Reactions (Preservatives) General Adverse effects/ Precautions
· Prostaglandin Analogues · Ocular surface disease (OSD) – commonly in · Mechanism of action: dual action · Similar to PGA
o Bimatoprost 0.03% - Lumigan PF elderly o PGA
o Tafluprost 0.015% - Saflutan o Preservatives may exacerbate pre-existing o NO induces trabecular meshwork cell
· Beta-blockers OSD relaxation which widens intercellular
o Timolol 0.25% or 0.5% - Timoptic in · BKC – may be neurotoxic to corneal tissue spaces, ↑ outflow
Ocudose · Indications: 1st or 2nd–line therapy for OAG &
· Miotics OHT
o Pilocarpine 2% - Pilocarpine minims · Product/ dosage: Vyzulta, Latanoprostene
· Fixed Combinations bunod 0.024%, once daily
o Bimatoprost 0.03% + Timolol 0.5% - o FDA approved, 2017
Ganfort PF · LUNAR & APOLLO trials: non-inferior to Timolol
o Dorzolamide 2% + Timolol 0.5% - · VOYAGER trial: 1.2 mmHg additional IOP
Cosopt PF lowering effect compared to latanoprost

Rho-Kinase Inhibitor (new drug)

General Concentrations Indication Adverse Reactions
· Mechanism of action: ↑aqueous outflow · Netarsudil, 0.02%, Rhopressa, q.d. · 2nd line tx · Conjunctival hyperaemia (~50%);
through trabecular meshwork and ↓ o FDA approved, 2017 · Role in secondary glaucoma – steroid-induced subconjunctival haemorrhage (~20%);
episcleral venous pressure · Netarsudil + latanoprost, Rocklatan, q.d. glaucoma and corneal verticillata (~20%)
· ROCKET trial – non-inferior Timolol b.i.d. o FDA approved, 2019 o Corneal verticillata is reversible
o ≥ 30% mean IOP reduction on discontinuation
& ↓IOP by ~4 mmHg.