medical management of glaucoma Flashcards
how do we treat glaucoma
reduce IOP
Every treatment we use decreases the IOPs cause thats the only thing we know that works
what is “neuroprotection”
idea that protects the nerve from damage - nothing proven yet
what is the target IOP for glaucoma management for mild moderate and severe damage
Mild damage 30% reduction from baseline
Moderate damage 35%
Severe damage 35-40%
Target IOP needs to be reviewed regularly to consider effectiveness of treatment - rate of progression informs next stage of patient management
we would not record target IOPs for legal reasons
how are aims made for glaucoma tx
need to be realistic, consider patients age, we want to slow down glaucoma enough so it doesnt have as much as an effect on the patient in their lifetime
Tx options for glaucoma
Topical hypotensives (monotherapy to maximal therapy)
Selective Laser Trabeculoplasty (SLT)
YAG laser peripheral iridotomy if narrow angles
Trabeculectomy
Deep Sclerectomy
oral acetazolamide
Angle Surgery (Phaco, istent, trabectome, canaloplasty)
Cyclodiode Laser Ciliary Ablation
Tube or valve surgery
why are patients not given more than one type of glaucoma drop from the same therapeutic class
Patients are only ever on one drug from a therapeutic class at any given time, as to combine the same therapeutic class would give no increased effect, as drugs in the same class are acting on the same receptors
can be given combined drugs from different therapeutic class
6 classes of topical IOP lowering drugs
-Prostaglandin analogue/prostamide
-Beta blocker
-Carbonic anhydrase inhibitor
-Alpha 2 agonist
-Miotic
-ROCK inhibitor
order of prescribing, 1st, 2nd, 3rd and 4th
1st Line: Prostaglandin analogue (generic latanoprost per NICE CG81)
2nd Line: beta blocker OR carbonic anhydrase inhibitor OR alpha agonist
3rd Line: as for 2nd line, add from a different therapeutic class
4th Line: used rarely but as for 3rd line, or pilocarpine in some cases
what were the NICE guidelines updates to in 2022 for glaucoma tx
recommend selective laser trabeculoplasty (SLT) as first line treatment for newly diagnosed OHT and glaucoma rather than topical treatment
Doesn’t happen right now because we don’t have lasers and not enough people to work the lasers, doesn’t have the compliance problems or side effects of the drops
examples of Prostaglandin Analogues
Latanoprost (Xalatan) od
Travoprost (Travatan) od
Bimatoprost 0.01/0.03% (Lumigan) od
Tafluprost (Saflutan) od
mechanism of action for prostaglandin analogue
(Prostaglandins are pro inflammatory molecules
They are produced when arachidonic acid is metabolized by COX 1 and 2 enzymes
Prostaglandin analogues act at F2-alpha receptors in ciliary muscle)
Increase aqueous outflow via uveoscleral route by inducing ciliary muscle relaxation
25-35% reduction in IOP
dosage for prostaglandin analogues
time till max effect
once a day - at night
3-5 weeks for max effect, inital effect after 2 hours
Prostaglandin Analogues - Contraindications
Uveitis
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
Prostaglandin Analogues - Side Effects
-Mild conjunctival hyperaemia ( up to 40%)
-Mild punctate keratopathy
-Foreign body sensation
-Ocular irritation
-Increased iris pigmentation (20%)
-Lengthening of eyelashes
-Cystoid macular oedema (pseudo or aphakic)
-Reactivation of herpes simplex keratitis
-Very rarely exacerbation of asthma
-Exacerbation of uveitis
-Lower Lid skin hyperpigmentation (rarely orbital fat atrophy)
Carbonic Anhydrase Inhibitors drug examples and % of effect on IOP
Dorzolamide (trusopt) bd/tds
Brinzolamide (azopt) bd
~20% reduction in IOP
Drops are in suspension form, so need to be shaken before use
Carbonic Anhydrase Inhibitor mechanism
Reduces aqueous production by inhibiting the enzyme carbonic anhydrase which is found within the ciliary epithelium
Carbonic Anhydrase Inhibitors Ocular Side Effects
blurred vision (transient)
eye irritation
eye pain
foreign body sensation
ocular hyperaemia
CAIs may affect metabolism of corneal endothelium, so use in caution as may cause corneal thickening and loss of clarity in unhealthy endothelium – eg Fuch’s endothelial dystrophy
Carbonic Anhydrase Inhibitors Systemic Side Effects
Sulphonamide hypersensitivity
Stevens-Johnson syndrome
Toxic epidermal necrosis
Aplastic anaemia
All the above rare with topical medication and if occur are
more likely with systemic acetazolamide
Beta-blockers – mechanism of action
Decreases aqueous production by reducing ultrafiltration
Ultrafiltration is one of the 3 processes by which aqueous is produced in the ciliary epithelium (the other two are diffusion and active secretion)
20-30% reduction in IOP
Suffer from tachyphylaxis
No difference with 0.25 or 0.5% or even 0.1%
what types of drugs are beta blockers
Timolol and others
Beta-blockers - Ocular Side Effects
Corneal hypaesthesia
Punctate keratopathy
Dry eye syndromes
Burning/stinging
Pseudopemphigoid
Beta-blockers – Systemic Side Effects
Bradycardia
Arrhythmia
Systemic hypotension
Heart failure
Syncope
Dyspnoea
Exacerbation of asthma
Anxiety
Hallucinations
Disorientation
Dysarthria
Decrease HDL cholesterol
Loss of libido
Masking of hypoglycaemic episodes in diabetics
Skin disorders
Depression
Gastrointestinal disturbance
Raynauds
Beta-blockers - Contraindications
Do not prescribe to patients with arrhythmias, cardiac failure, COPD/Asthma
Caution in patients taking calcium channel blockers due to additive effect
Use in caution with patients already on systemic beta blockers
Use in caution in the elderly
Alpha-2 Agonists drug types
Apraclonidine and Brimonidine
mechanism for Alpha-2 Agonists
-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)
Alpha-2-Agonist - Ocular Side Effects
High rate of allergy (15-25% for Brimonidine)
Conjunctival hyperaemia
Follicular conjunctivitis (10%)
Alpha-2-Agonist - Systemic Side Effects and Contraindications
Systemic Side Effects
Dry mouth
systemic blood pressure reduction (not used in children)
Fatigue and drowsiness
Contraindications
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
Severe cardiac disease
mechanism of action for Cholinergic Agents (parasympathomimetics & miotics) and drug type
Increase trabecular outflow via ciliary muscle contraction plus some minor decrease in aqueous inflow
Pilocarpine 1-4% qds
~ 20% reduction in IOP from baseline
pilocarpine side effects
Ciliary muscle spasm
Brow ache
Accommodative myopia
Miosis with constriction of visual fields
Increased risk of retinal detachment
Keratopathy
Hypersensitivity
Exacerbation of uveitis / cataract formation
Retinal detachment
Acute or chronic angle closure
Systemic: Bradycardia, nausea, sweating, diarrhoea, bronchospasm
what does ROCK inhibitors stand for
Rho Kinase Inhibitors
Available in USA since 2019, Europe 2021, UK 2023
ROCK Inhibitors - mechanism
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
ROCK inhibitors side effects
-Conjunctival hyperaemia up to 50% of patients
-Conjunctival haemorrhages (often peri limbal) ?10-15% of patients
-Corneal verticillata 10% of patients. Not usually visually significant
ROCK Inhibitors – availability
No standalone ROCK inhibitor currently available in UK
(In UK Roclanda = latanoprost 50mg/ml and netarsudil 200mg/ml in fixed combination.
Available as Rhopressa (USA) and Rhokiinsa (EU) as netarsudil 200mg/ml)
examples of combined preperations
Cosopt (Timolol and Dorzolamide)
Azarga (Timolol and Brinzolamide)
Eylamdo (Timolol and Dorzolamide)
Xalacom (Timolol and Xalatan)
Duotrav (Timolol and Travatan)
Ganfort (Timolol and Lumigan)
Taptiqom (Timolol and Tafluprost)
Fixapost ( Timolol and Latanoprost)
Combigan (Timolol and Brimonidine)
Simbrinza (Brimonidine and Brinzolamide)
Roclanda (Latanoprost and Netarsudil)
Advice given while using glaucoma drops
Often preservative related
Remember nasolacrimal duct occlusion
Vaseline to lids
Drops at least 5 mins apart
Close eyes for 1 to 3 mins after drop
preservatives glaucoma drops
-evidence that preservatives in drops like Benzalkonium Chloride are harmful in the long term to the ocular surface
-Intolerance/ irritation
-Allergy
-Exacerbates dryness especially in susceptible patients and those on multiple drops
-Trend towards prescribing preservative free glaucoma medications (long term) in -Europe places heavy demand on existing supplies
-Cost issues
Preservative-Free Preparations examples
Timolol and -Tiopex 0.1%
Apraclonidine (Iopidine)
Pilocarpine
Dorzolamide (trusopt or Eyedelto)
Timolol/dorzolamide (Cosopt or Eylamdo)
Tafluprost (Saflutan)/ Taptiqom (saflutan and timolol)
Travatan (BAK free – Polyquad)
Bimatoprost (Lumigan UD or Eyreida)
Ganfort UD (Timolol + Bimatoprost)
Monopost (Latanoprost pres free)/ Fixapost (latano + timolol)
further therapies
Latanoprostene Bunod (Vyzulta -nitrous oxide releasing)
Drug eluting implants
Contact lenses
punctal plugs
Silicone rings
Sub-conjunctival implants
Intra-ocular drug implants
