DIS - Glaucoma Treatment and Progression Tutorial - Week 7 Flashcards
Is the majority of glaucoma chronic or acute?
Chronic
What is the first step of glaucoma treatment?
Grading the severity
Describe the MEC glaucoma clinic 5 category classification for glaucoma (GSS). Describe where on the glaucoma continuum each of these fits.
High risk ocular hypertension - acceleration of apoptosis
Pre-perimetric glaucoma - ganglion cell death to RNFL change (detectable)
Early perimetric glaucoma - SWAP and SAP VF changes
Moderate perimetric glaucoma - VF change (moderate)
Severe perimetric glaucoma - VF change (severe) and blindness
Define ocular hypertension.
IOP >21mmHg without structural/functional defects
Does ocular hypertension always mean an increased risk of glaucoma? Explain.
No, some pose no greater risk than normal, while others have a much likelihood of developing into glaucoma
Should all ocular hypertension be treated?
No, only high risk ocular hypertension
List 5 factors that will indicate high risk ocular hypertension.
Central corneal thickness <555um
IOP >26mmHg
Age over 60 years
C/D greater than 0.7
Risk of 15% or more by OHTS risk calculator
Consider the risk given by the OHTS risk calculator, what is a disadvantage and what categories of risk should be treated vs monitored?
It doesnt consider every risk factor
Monitor low/moderate risk
-treat if multiple additional risk factors present
Treat all high risk
Describe what is meant by pre-perimetric glaucoma. Include ocular (3) and imaging signs (2).
No visual field defect, but 3 or more ocular and/or imaging signs of glaucoma
Ocular signs
-rim thinning
-disc haemorrhage
-NFL wedge defect
Imaging signs
-GCC defect
-RNFL defect
What stage of glaucoma is the most likely of all to get wrong and why? Why does this error tend to occur?
Pre-perimetric glaucoma due to red disease (false positives)
-up to 25% of all scans
-tends to occur if OCT is used in routine exams
Describe what is meant by pre-perimetric glaucoma (2). Include three VF defects typical at this stage and give two indications of severity (MD and VFI).
3 or more ocular/imaging signs
Repeatable VF defect
Typical defects are nasal step, arcuate, and paracentral defects
Severity
-MD 0 to -6dB
-VFI 100 to 80%
Describe what is meant by pre-perimetric glaucoma (2). Include a VF defect typical at this stage and give two indications of severity (MD and VFI).
3 or more ocular/imaging signs
Repeatable VF defect
Typically a large defect in one hemifield
Severity
-MD -6 to -12dB
-VFI 80 to 60%
Describe what is meant by pre-perimetric glaucoma (2). Include two VF defects typical at this stage and give three indications of severity (MD and VFI).
3 or more ocular/imaging signs
Repeatable VF defect
Typical defects are a large defect in one hemifield and a moderate defect in the other hemifield
Severity
-MD worse than -12dB
-VFI less than 60%
Any VF defect within 5 degrees of fixation
Up to what percentage of ganglion cells may be lost before early glaucomatous defects become evident?
40-50%
In addition to risk factors, list 5 other factors that influence the decision to treat ocular hypertension to prevent glaucoma.
Patient age
Life expectancy
Medical co-morbidities
Burden of treatment
Patient preference
What percentage of untreated ocular hypertension will progress to glaucoma? What does it reduce to if IOP is lowered by 22%?
10%
Lowering the IOP by 22% reduced glaucoma rate to 5%
When detecting the conversion from ocular hypertension to glaucoma, was this detected predominantly by structural changes or visual field losses?
Predominantly structural change
What percentage of untreated early perimetric glaucoma will remain stable?
38%
Keeping in mind the risk of progressing to glaucoma from ocular hypertension (and early perimetric glaucoma getting worse), describe a major factor that influences whether or not treatment should be initiated. Explain why it matters (2).
You may elect to closely monitor or begin treatment
-can wait for structural/functional losses before deciding to treat
Age at the time of diagnosis is very important
-younger patients usually require treatment as they will have the disease for many years
-often dont need to treat the elderly (>80) as they may not live ling enough to lose vision
Do moderate and severe perimetric glaucoma always require treatment at any age?
Almost always
What must be done if treatment is initiated?
Target IOP must be set
What is considered the baseline IOP when setting a target IOP?
Highest recorded IOP prior to treatment
List 6 factors that can influence target IOP?
Glaucoma severity grading
Ocular risk factors
Systemic risk factors
Family history
Age
Life expectancy
Describe the target IOP for low, medium, and high risk given by the NHMRC guidelines.
Low - 20% decrease or 24mmHg
Moderate - 30% decrease or 17mmHg
High - 14mmHg
Describe the target IOP for each stage of the five stages of glaucoma.
High risk OTH - 20%
Pre-perimetric - 25%
Early perimetric - 30%
Moderate perimetric - 40%
Severe perimetric - under 14mmHg
This varies from practitioner to practitioner
If the difference between baseline and target IOP is greater, what is more likely required?
Surgical intervention
List 6 treatment options for glaucoma.
Topical eyedrops
Oral medications
Laser
-SLT
Cataract surgery and MIGS
Incisional surgery
-trabeculectomy
-tube shunts
Ciliary body ablation
What percentage of patients can reach target IOP with a single drug? What about with maximal medical therapy?
Single drug - 50%
MMT - over 90%
-MMT in glaucoma is 4 different classes of drugs
List 5 current classes of topical glaucoma drugs, and two emerging drugs.
Current
-prostaglandin analogues
-beta blockers
-carbonic anhydrase inhibitors
-alpha agonists
-cholinergics
New classes
-nitric oxide
-rho kinase inhibitors
Describe the mechanism of action for pilocarpine in reducing IOP. Include dosing and 4 common side effects.
Pupil miosis, mechanically pulling iris away from trabecular meshwork, increasing outflow
QID dosing
Symptoms include brow-ache, dimmed vision, myopic shift, retinal detachment
Describe the mechanism of action for beta blockers in reducing IOP. Include dosing and 5 potential systemic side effects.
Adrenergic, decreases aqueous production in ciliary bodies
BID dosing
Symptoms include athsma/COPD, impotence, masks hypoglycaemia, bradycardia, postural hypotension/fainting
What three drug classes revolutionised glaucoma treatment?
PGAs, alpha agonists, and carbonic anhydrase inhibitors
Describe the mechanism of action for PGAs in reducing IOP. Does it alter the trabecular meshwork? What of its systemic side effects? What about ocular side effects (4)?
Increased outflow through uveo-scleral pathway
-no alteration to TM
No systmeic side effects
Ocular side effects include conjunctival erythaema, adnexal darkening, lash lengthening, orbital fat atrophy
Describe the mechanism of action for alpha agonists in reducing IOP (2). Include dosing and 3 potential side effects.
Decreased aqueous production
Possible neuroprotection via increased ONH perfusion
BID/TID dosing
Type 4 adnexal allergy
Dry mouth
Nightmares
What can carbonic anhydrase inhibitors be described as, and how does it work? List the dosing and its side effects compared to diamox. Include 2.
Liquid diamox
Decreased aqueous production
BID/TID dosing
Much fewer systemic side effects vs diamox
Possible sulphonamide allergy/SJS, stinging
Why does IOP rise with age (2)?
Reduced outflow due to icnreased rigidity of trabecular meshwork beams and increased GAG extracellular matrix
What is vyzulta a combination of? Explain the mechanism on how it reduces IOP. What is the dosing?
Latanoprost + nitric acid
-once daily
Nitric oxide is a potent vasodilator and smooth muscle relaxant
What is the rationale behind using nitric oxide for IOP reduction? Explain how it affects ocular structures to reduce IOP (3).
NO aqueous levels are lower in glaucoma patients compared to normals
NO relaxes trabecular beams, schlemms canal, and episcleral veins
Explain the problem with delivering nitric oxide to the eye and how it is done in the case of glaucoma treatment.
Gases cant easily reach the eye
-nitric oxide would require a donating moiety
-attached to latanoprost, separates within the eye
Compared to latanoprost alone, by how much does combination with nitric oxide decrease IOP?
~1.5mmHg
What is the estimated reduction in glaucoma progression for every 1mmHg IOP reduction?
10%
Describe how rho kinase inhibitors work to reduce IOP (2), include the dosing, and describe efficacy compared to latanoprost.
Decreases outflow resistance in deep regions of the TM near schlemms canal and in episceral veins
Also decreases aqueous production
Slightly less effective vs latanoprost
Can rho kinase inhibitors be combined with PGAs? Explain.
Yesd
Synergistic uveoscleral and trabecular outflow
What drug class is used in almost all cases as initial therapy?
PGAs
List the topical treatment paradigm for glaucoma (6).
Start with PGAs
Change to a different PGA
Add a beta blocker (usually a combo)
Add CAI
Add alpha agonist (alphagan or simbrinza)
Add cholinergic (pilocarpine)
Describe the rule of tenths for glaucoma (2).
Of 100% of those with glaucoma, 10% fail to reach target IOP with maximal medical therapy (4 drug classes)
10% of those may progress to bilateral blindness even with best treatment
List three uses of oral diamox in the context of glaucoma. What is chronic use limited due to?
Acute angle closure glaucoma
Post-operative cataract surgery IOP spikes
Short term use while waiting for glaucoma filtration surgery
Chronic use limited due to systemic side effects
Describe a use for oral beta blockers in the context of glaucoma.
Lower conversion from OHT to glaucoma in those taking oral beta blockers
Useful if unable to manage eyedrops (ie arthritis)
Name an actual supplement that can actually decrease IOP. List its ingredients (2) and dosage. What else can it do aside from decreased IOP? What is its onset of action and efficacy vs topical glaucoma therapy? What is a disadvantage? In what three cases is this a good choice?
Mirtogenol
-bilberry extract (30%)
-french maritime pine bark extract (70%)
-one or two capsules daily
Reduces IOP, increases ocular blood flow to the ONH
Slower onset of action vs topical therapy
Less effective alone than in combination with latanoprost
Expensive (no PBS)
Excellent option for patients with ocular surface disease, optic nerve head drusen, other optic neuropathies
What do studies suggest of the efficacy of vitamins A and C for glaucoma (2).
Dietary intake showed a beneficial association with open angle glaucoma
Blood levels of vitamins do not show a clear relation
What do studies suggest of the efficacy of low and high dose vitamin B3 for glaucoma (2)?
Lower dose had no effect on IOP but was neuroprotective
Higher dose lowered IOP and was also neuroprotective
-done in a mouse model
What is the efficacy of SLT surgery comparable to (topical medication)?
Similar to PGA (25 to 30%)
List three advantages and 5 disadvantages of SLT surgery.
Advantages
No patient compliance issues
Lower drug costs over time
Repeatable
Disadvantages
IOP lowering effect not sustained
Patients potentially lost to follow-up
Doesnt always work
Doesnt work well with NTG
May make PGAs less effective
From an ophthalmology perspective, what is the suitability of SLT for initial therapy of glaucoma vs topical drops?
SLT more cost effective than drops
Describe why cataract surgery decreases IOP and whether or not the effect is sustained.
Less lens volume in posterior chamber
Effect sustained for several years
List three areas a stent can be placed for glaucoma surgery.
Trabecular
Suprachoroidal space
Subconjunctival space
-recalled due to endophthalmitis
Describe incisional therapy.
Creates an opening in the eye to allow aqeuous to leave the globe, into the subconjunctival space
What is ciliary body ablation surgery reserved for?
Painful blind eyes with elevated IOP
When should a patient be reviewed after treatment is initiated?
4 weeks
What should be done if target IOP is reached? Include review schedule (3).
Reinforce the need for ongoing treatment
-cessation will cause IOP to rise
-review again in a month
-again in three months
-again every 6 months
What are two possible reasons why IOP tagret hasnt been reached?
Drops havent been used
-patients are in denial
-havent gotten into regular habits yet
Drops may actually be ineffective
-use the treatment paradigm
How long does it usually take patients to form habits with eyedrops?
66 days
Is poor compliance easy or hard to detect?
Very hard, patients will lie on purpose
What is the average adherence to oral drug, glaucoma drug, and behavioural compliance (diet/exercise) like?
Oral - 75%
Glaucoma - 50%
Diet/exercise - 10%
What must be done once target IOP is reached?
Monitor for deterioration
-if stable, continue therapy as is
-if deteriorating, IOP must be reduced further
When looking for structural changes in glaucoma, should the latest scans be compared to the previous scans, or baseline scans?
Always compare to baseline scans
What does event analysis detect?
Detects change has occurred in a part of the visual field
What does trend analysis detect?
Detects rate of change of the whole visual system over time
Does glaucoma progression tend to occur via structural or functional losses, or both together?
Infrequently together, mostly tends to occur with just either one
If progression is confirmed, by how much should IOP be lowered?
A further 10%
Can all glaucoma cases be made to stabilise?
Not
