Glaucoma - Medical Management Flashcards
How to treat IOP?
- Reduce IOP
o Reduce aqueous inflow rate
o Increase aqueous outflow rate - Neuroprotection?
o Tx that protects nerve from damage somehow – could be gamechanger if found to work
How low does pressure need to be?
- Historically, less than 22mmHg but more complicated that that
- Pressure needed completely depends on px & their eyes as well as:
o Presenting pressure
o Severity of disease – e.g. already lost half their field
o Rate of progression – need about 3 or 4 visits – through fundus pics, fields and OCTs – hard as don’t see them often so could take 2 or 3yrs to build this up
o Risk of visual loss within px lifetime – e.g. two pxs with same severity of disease one aged 40 and one aged 90 – 40yo would be treated first - Over-tx of glaucoma is a real issue – all these eyedrops have side-effects and stressful for pxs especially elderly
o Depends on px and their memory, dexterity, carers etc
What is the target IOP?
- Mild damage 30% reduction from baseline
- Moderate damage 35%
- Severe damage 25-40%
- Target IOP needs to be reviewed regularly to consider effectiveness of tx – rate of progression informs next stage of px management
o Have some idea of what want IOP to be but never note it down as can easily change – just note about the IOP that day
o Glaucoma is a lifelong condition – can manage it but not cure it
Setting the target IOP: - Not always about getting IOP as low as possible – slow down progression of glaucoma enough that it doesn’t cause px anymore visual issue within lifetime – tricky to do
What are the aims of treatment in glaucoma?
- European Glaucoma Society: “preservation of visual function adequate to individuals needs with minimal or no side effects, for the expected lifetime of the px without any disruption of his/her normal activities at a sustainable cost”
What are the treatment options for treating glaucoma?
- Topical hypotensives (monotherapy to maximal therapy)
o Monotherapy = one drop, maximal therapy = up to 4/5 drops (multiple times a day – not ideal to have pxs on 3 or more tx) - Selective Laser Trabeculoplasty (SLT) – now recommended as 1st line tx for glaucoma instead of drops
- YAG laser peripheral iridotomy if narrow angles – happens less now, more happy to do cataract surgery now
- Trabeculectomy
- Deep Sclerectomy
- Oral acetazolamide – oral meds are not great long term but good to get IOP down quickly
- Angle Surgery (Phaco, istent, trabectome, canaloplasty) – later stage option
- Cyclodiode Laser Ciliary Ablation
- Tube or valve surgery
Most pxs don’t go past the first two management options (drops or SLT) – could be both if needed
What are the topical treatment options for glaucoma?
- 6 classes of topical IOP lowering drugs currently available in UK
o 1. Prostaglandin analogue/prostamide
o 2. Beta blocker
o 3. Carbonic anhydrase inhibitor
o 4. Alpha 2 agonist
o 5. Miotic
o 6. ROCK inhibitor - 1-4 are the main txs
- Miotic (pilocarpine) not used as much
- ROCK inhibitor – new drug – grey area in Scotland, licensed and technically available but not approved through NHS systems for cost effectiveness can technically get privately – medical consortium in Scotland have not approved it yet, may need to try other things first and then use that – may be approved next year)
What is the order of prescribing for glaucoma tx?
o 1st line: prostaglandin analogue (generic latanoprost per NICE CG81)
o 2nd Line: beta blocker OR carbonic anhydrase inhibitor OR alpha agonist
o 3rd Line: as for 2nd line, add from a different therapeutic class
o 4th Line: used rarely but as for 3rd line, or pilocarpine in some cases
o In 2022 NICE treatment guidelines for glaucoma were updated to recommend Selective Laser Trabeculoplasty (SLT) as first line treatment for newly diagnosed OHT and glaucoma, rather than topical treatment
If SLT doesn’t work or px doesn’t want it then try drugs
NICE guidelines say it but does not happen yet as first line – not enough lasers, not enough people able to use them eventually will be the case, not as many side-effects or compliance problems with drops so good recommendation but not yet
How is normal tension glaucoma treated?
Normal tension glaucoma – is also treated by lowering IOP as that’s only tx we have – more likely caused by vascular issue – could get control over that (through GP) – may be better with beta blocker for this
Describe prostaglandin analogues: the options of drugs, mechanism of action, contraindications and side-effects?
- Latanoprost (Xalatan) od
- Travoprost (Travatan) od
- Bimatoprost 0.02/0.03% (Lumigan) od
- Tafluprost (Saflutan) od
o Variations of the same thing
o Not really any evidence on difference of effectiveness
o Never have px on more than one of these as won’t help
o Won’t ever really change a px from one PGA to the other
Unless red eye – e.g. change for preservative free or different preservative
o On paper biggest IOP reduction
o od = once a day since last up to 24 hrs - Action:
o Increased uveoscleral outflow by ciliary muscle relaxation - 25-35% reduction in IOP
- Mechanism of Action:
o Prostaglandins are pro inflammatory molecules
o They are produced when arachidonic acid is metabolized by COX 1 and 2 enzymes
o Prostaglandin analogues act at F2-alpha receptors in ciliary muscle
o Increase aqueous outflow via uveoscleral route by inducing ciliary muscle relaxation
o ?remodeling of extracellular matrix in uveoscleral pathway
o ?Some increase in outflow by conventional trabecular route
o Initial effect after 2 hours
o Peak effect 8-12 hours
o Duration of effect up to 24 hours
o Several weeks from starting treatment to maximum effect – need to see them back wks later to see full effect - Contraindications:
o Prostaglandins found throughout the body – act in different ways at different receptors usually due to drug acting on receptors elsewhere in body.
o Contra-indicated (?) in:
Uveitis – evidence low on making it worse – but since PGAs are pro-inflammatory and could technically keep eye inflamed
Cystoid Macular Oedema (CMO) - Relative contraindication in pseudophakic and aphakic patients (due to risk of CMO)
Recurrent herpes simplex keratitis (reactivation)
Not used in pregnancy due to potential effect of prostaglandin on the uterus - Prostaglandins are used to induce labour – so MUST not be used in pregnant pxs or pxs trying to become pregnant
- Relatively rare to have to think of this in glaucoma clinic due to ages of pxs
- Side-effects: ones in bold are those normally mentioned to pxs
o Mild conjunctival hyperaemia (up to 40%)
o Mild punctate keratopathy
o Foreign body sensation
o Ocular irritation
o Increased iris pigmentation (20%) – more so in pxs already with mixed colour irises
o Lengthening of eyelashes
o Cystoid macular oedema (pseudo or aphakic)
o Reactivation of herpes simplex keratitis
o Very rarely exacerbation of asthma – v small chance it could exacerbate that but mention to px (same for COPD)
o Exacerbation of uveitis
Can get hair growth under the eye so be careful where drop is inserted & try not to have some run down cheek
Describe carbonic anhydrase inhibitors: the options of drugs, mechanism of action, contraindications and side-effects?
- Dorzolamide (Trusopt) bs/tds
- Brinzolamide (Azopt) bd
o Brinzolamie > dorzolamide dorzolamide is stingy on insertion - ~20% reduction in IOP
- Drops are in suspension form, so NEED to be shaken before use
- Suspension – powder in the liquid so px MUST shake the bottle
o Px may have white power along lashes – they need to shake it - Mechanism:
o Reduces aqueous production by inhibiting enzyme carbonic anhydrase which is found within ciliary epithelium
o ?Possible improved optic nerve perfusion due to local vasodilation but unproven - Ocular Side-Effects:
o Blurred vision (transient)
o Eye irritation
o Eye pain
o Foreign body sensation
o Ocular hyperaemia
o CAIs may affect metabolism of corneal endothelium, so use in caution as may cause corneal thickening and loss of clarity in unhealthy endothelium – e.g. Fuch’s endothelial dystrophy
CONTRAINDICATED in Fuch’s and even pre-Fuch’s - Systemic Side-Effects: rare with topical drops but be aware
o Sulphonamide hypersensitivity
o Stevens-Johnson syndrome
o Toxic epidermal necrosis
o Aplastic anaemia
o All the above rare with topical medication and if occur are more likely with systemic acetazolamide
Describe the autonomic nervous system - aadrenergic receptors and adrenergic agents?
- ANS (sympathetic & parasympathetic) controls all vital organs
- Sympathetic – norepinephrine & epinephrine neurotransmitters
- Parasympathetic – acetylcholine neurotransmitter
- Post Synaptic Receptors:
o Alpha 1 and 2 (sympathetic) and Beta 1, 2 and 3 (sympathetic)
o Nicotinic and Muscarinic (parasympathetic) - Beta blockers and alpha 2 agonists both work on ANS
- Adrenergic Receptors:
o Present in many organs & tissues
o Heart, arteries & veins, airways, intestine, bladder, glands, smooth muscle in vessels/airways
o Effect of neurotransmitters or drugs that affect the receptors depends on the type of receptor (alpha 1,2, Beta1,2,3) & also on which organ or tissue
o Heart: beta 1 stimulation results in faster rate while beta1 blocking results in slow pulse rate
If block beta receptors in heart slows heart rate
o Lungs: beta2 stimulation opens airways and beta2 blockade causes constriction or closing of airway
Cannot give beta-blockers to pxs with asthma (can block airways) - Adrenergic Agents:
o Propine (dipivefrin) & epinephrine – not used now, more in 70s
o Alpha-2-agonists (brimonidine [Alphagan], apraclonidine [Iopidine])
Brimonidine – more used
Apraclonidine – more expensive & suffers from tachyphylaxis stops working after a time so not used long-term
o Beta-blockers:
Timolol, levobunolol, carteolol, metipranolol are all non-selective
Betaxolol is cardioselective (Beta1)
Describe beta blockers: the options of drugs, mechanism of action, contraindications, systemic side-effects and ocular side-effects?
- Mechanism of Actions:
o Timolol & others
o Decreases aqueous production by reducing ultrafiltration
o Ultrafiltration is one of the 3 processes by which aqueous is produced in ciliary epithelium (other two are diffusion & active secretion)
o 20-30% reduction in IOP
o Suffer from tachyphylaxis
o No difference with 0.25 or 0.5 or even 0.1%
Timolol 0.5 – lots of people are on it but if use high concs doesn’t always lower the pressure more. No reason to now give this to px but also no point changing if it works for the px. 0.25% and 0.1% are more used, 0.1 is gel form - Ocular Side-Effects:
o Corneal hypaesthesia
o Punctate keratopathy
o Dry eye syndromes
o Burning/stinging
o Pseudopemphigoid - Systemic Side-Effects:
o Anxiety
o Hallucinations
o Disorientation
o Dysarthria
o Decrease HDL cholesterol
o Loss of libido
o Masking of hypoglycaemic episodes in diabetics
o Skin disorders
o Depression
o Gastrointestinal disturbance
o Raynauds
o Bradycardia
o Arrhythmia
o Systemic hypotension
o Heart failure
o Syncope
o Dyspnoea
o Exacerbation of asthma - Contraindications:
o Do not prescribe to patients with arrhythmias, cardiac failure, COPD/Asthma
o Caution in patients taking calcium channel blockers due to additive effect
o Use in caution with patients already on systemic beta blockers
o Use in caution in the elderly
Elderly pxs may have lower heart rate and so may not want to risk if they are already at risk
Need to ask if have asthma/COPD
If px on beta blockers – ask them about falls, any fainting, any issues with breathing
If already on systemic beta blockers may get more side-effects so use with caution – causing more reduction etc
Describe adrenergic agonists: the options of drugs, mechanism of action, ocular side-effects, systemic side-effects and contraindications?
Can work well with other drugs
* Apraclonidine and Brimonidine
o Brimonidine not used as much due to high rate of allergy
* Reduction in aqueous production and increased uveoscleral outflow
* Acts on alpha-2 receptors which then inhibit enzymes involved in pathway causing production of aqueous
* 20-25% reduction in IOP
* Additive with other hypotensive agents, less effective as monotherapy
* Experimental neuroprotective properties?
* Tachyphylaxis (apraclonidine) – used when exhausted all other options
* Ocular Side-Effects:
o High rate of allergy (15-25% for Brimonidine)
o Conjunctival hyperaemia
o Follicular conjunctivitis (10%)
* Systemic Side-Effects:
o Dry mouth
o systemic blood pressure reduction (not used in children)
o Fatigue and drowsiness
* Contraindications:
o Patients taking mono amine oxidase inhibitors or tricyclic antidepressants due to effect on drug metabolism and consequent risk of increased systemic side effects such as hypotension
o Severe cardiac disease
Describe cholinergic agents (parasympathomimetics & miotics) : action and side effects?
- Increase trab outflow via ciliary muscle contraction plus some minor decrease in aqueous inflow
o Pilocarpine 1-4% qds
~20% reduction in IOP from baseline - Pilocarpine – side-effects:
o Ciliary muscle spasm
o Brow ache
o Accommodative myopia
o Miosis with constriction of visual fields
o Increased risk of retinal detachment
o Keratopathy
o Hypersensitivity
o Exacerbation of uveitis / cataract formation
o Retinal detachment
o Acute or chronic angle closure - Systemic side-effects: Bradycardia, nausea, sweating, diarrhoea, bronchospasm
Describe ROCK inhibitors - mechanism, side-effects and availability?
- Rho Kinase Inhibitors
- Available in USA since 2019, Europe 2021, UK 2023
- Rho kinase is a protein kinase involved in regulation of cell shape and size by acting on the cytoskeleton
- Increase aqueous outflow by reducing outflow resistance via trabecular (conventional) outflow route
- Thought to achieve this by reducing cell stiffness in Schlemm’s canal, and possibly in the trabecular meshwork
- ROCK inhibitors are the only currently available glaucoma medication to act on the trabecular (conventional) outflow pathway
- Side-effects:
o Conjunctival hyperaemia – up to 50% of patients
o Conjunctival haemorrhages (often peri limbal) ?10-15% of patients – very small haemorrhages on conjunctiva
o Corneal verticillata 10% of patients Not usually visually significant
Seen in amiodarone use, vertical striate pattern in cornea, no visual issues – most pxs won’t know but see on SL - Availability:
o In UK Roclanda = latanoprost 50mg/ml and netarsudil 200mg/ml in fixed combination
o No standalone ROCK inhibitor currently available in UK
o Available as Rhopressa (USA) and Rhokiinsa (EU) as netarsudil 200mg/ml
