Primary%20angle-closure%20glaucoma Treatment

Goals of Treatment

• Prevent or reverse angle closure process
• Control IOP
• Prevent optic nerve damage
• Preserve visual function
• Maintain quality of life

Setting Target IOP

• Lowering IOP is the only clinically established method of treating glaucoma
• Target IOP refers to the upper limit of a stable range of measured IOPs seen likely to prevent further optic damage
  
  • Needs constant reevaluation and documentation at each visit

• Target IOP depends on different factors such as patient’s age and life expectancy, pretreatment IOP level, stage and rate of progression of glaucoma, presence of other risk factors, risks and side effects of therapy, and patient preference
  
  • A lower IOP can be targeted in the presence of disease progression

• Therapeutic medical trial on one eye may be done to determine IOP lowering effectiveness of medication except in the presence of severe glaucomatous damage or when IOP is extremely high

Medical Therapy

• Initial treatment of acute angle-closure is directed towards lowering the IOP to relieve acute symptoms and potential harm of high IOP
• Remains the most common method of lowering IOP
• Most patients are treated immediately with medications, followed by iridotomy as soon as feasible
• In patients with ocular surface disease, consider preservative-free formulations

Preoperative Medical Therapy

• Serves to lower IOP to relieve the symptoms and signs so that laser iridotomy or iridectomy is possible
• Once any angle closure component has been appropriately treated, management is similar to POAG
• IOP lowering mechanisms work by either:
  
  • Reducing aqueous production by the non-pigmented epithelium of the ciliary body [eg alpha₂-adrenergic agonists, beta-blockers, carbonic anhydrase inhibitors(CAI)]
  • Increasing outflow pathways or by uveoscleral pathways (eg alpha₂-adrenergic agonists, miotics, prostaglandin derivatives)

• Primary angle-closure glaucoma (PACG) with pupillary block mechanism
  
  • Reduction of aqueous production
    
    • Systemic CAI (eg Acetazolamide)
    • Please see full discussion under Systemic Glaucoma Preparations
    • Topical alpha₂-selective adrenergic agonists (eg Apraclonidine, Brimonidine)
      Please see full discussion under Topical Glaucoma Preparations
    • Topical beta-blockers (eg Timolol)
      Please see full discussion under Topical Glaucoma Preparations
  • Dehydration of vitreous body
    
    • Hyperosmotics are the most effective agents (eg oral Glycerol, Mannitol)
      
      • Glycerol: 1-1.5 g/kg PO; Mannitol: 1-1.5 g/kg IV
    • Patients must be evaluated for kidney or heart disease prior to administration of hyperosmotics; glycerol may alter blood glucose levels and should not be given to diabetes mellitus (DM) patients
      Please see full discussion under Systemic Glaucoma Preparations
  • Pupillary constriction
    
    • Topical parasympathomimetics (eg Pilocarpine 1% or 2%, Aceclidine 2% 2-3 times within 1 hour)
      Please see full discussion under Topical Glaucoma Preparations
  • Reduction of inflammation: Topical steroids every 5 minutes for 3 times, then 4-6 times daily

• PACG with plateau iris mechanism
  
  • Pupillary constriction
    
    • Modest pupillary constriction may prevent further angle-closure
    • Topical parasympathomimetics (eg Pilocarpine 1%, Aceclidine 2%, Carbachol 0.75%)
      Please see full discussion under Topical Glaucoma Preparations

Postoperative Medical Therapy (IOP control)

• Initial treatment option to lower the IOP is usually by topical medications
  
  • Medical therapy should start with one drug
    
    • If 1st choice of treatment has no effect or tachyphylaxis occurs, change the initial therapy rather than adding a further drug
  • Consider balancing between effectiveness of the medications and side effects to achieve desired IOP
    
    • Pre-treatment baseline IOP values should be considered in the evaluation of efficacy of therapy
  • In order to maximize patient compliance and adherence, aim to utilize the minimum number of medications with minimum dosing frequency to achieve the target IOP
  • Surgery may, however, be initially considered in cases where there is severe glaucomatous damage, very high IOP or concern regarding patient compliance
• Systemic medications are only used as a temporary measure

Topical Glaucoma Preparations

• Any one or a combination of the following may be used depending on the severity of glaucoma, response to the medication, and ocular and health status of the patient
• Always start with the least amount of medication to achieve therapeutic response
• Systemic absorption may take place via the nasal mucosa which may lead to systemic effects
  
  • To minimize this, patients should be taught to apply finger pressure on the medial canthus for 1-2 minutes after instilling the eye drop

Prostaglandin Analogues

• Eg Bimatoprost, Latanoprost, Latanoprostene bunod, Tafluprost, Travoprost and Unoprostone
• Generally considered and approved as 1st-line of treatment for reducing IOP
  
  • First choice in cases of complete synechial closure 
• Lowers IOP by increasing uveoscleral outflow
• IOP reduction: 25-35%
• Appear effective and well tolerated (with few systemic side effects)
• Alternative for patients with contraindication to initial therapy with beta-blockers

Beta-blockers

• Eg Betaxolol, Carteolol, Levobunolol, Metipranolol, Timolol
• Have been a traditional choice of therapy as initial IOP lowering agents due to their effectiveness, low cost and tolerability
• Along with prostaglandin analogues, are licensed for 1st- and 2nd-line use
• Act by decreasing aqueous humor production
• IOP reduction: 20-25%
• Associated with few ocular side effects and have a long duration of action which allows once- or twice-daily dosing
• Studies have shown that if patient is on systemic beta-blocker, the decrease in IOP with topical beta-blockers is likely to be reduced; in this case, other drug classes should be considered first

Alpha₂-selective Adrenergic Agonists

• Eg Apraclonidine, Brimonidine
• Act by reducing aqueous humor production and increasing uveoscleral outflow
• IOP reduction: 20-25%
• May be given 1 hour prior to surgery or immediately afterwards to reduce the magnitude and frequency of acute post-operative IOP spikes and decrease bleeding due to the vasoconstrictor effect
• Brimonidine exhibits highly selective alpha₂-agonism (1000:1 over alpha₁ agonism)
  
  • Selectivity results in absence of both mydriasis and vasoconstriction 
• Long-term use of Apraclonidine is limited due to tachyphylaxis and increased risk of allergy with time

Carbonic Anhydrase Inhibitors (CAI)

• Eg Brinzolamide, Dorzolamide
• Reduce IOP by inhibition of carbonic anhydrase resulting in decreased aqueous humor production
• IOP reduction: 20%

Parasympathomimetics

• Eg Carbachol, Demecarium, Ecothiophate, Pilocarpine
• Lower IOP by decreasing resistance to aqueous humor outflow from the anterior chamber and increasing trabecular outflow
  
  • They may, however, reduce uveoscleral outflow which may cause a paradoxical rise in IOP in patients with severely compromised trabecular outflow
• IOP reduction: 20-25%
• Have fewer systemic side effects than beta-blockers but with more significant ocular side effects
• Long-term post-op use of Pilocarpine may be given to patients with plateau iris syndrome, ie angle remains narrow despite a patent laser iridotomy

Hyperosmotic Agents

• Eg topical Glycerol
• May be given in cases of acute angle-closure attacks in the presence of an edematous cornea
• IOP reduction: 15-30%
• Glycerol can cause irritation when given topically; a local anesthetic may be given before application of glycerol to cornea to reduce likelihood of a painful response

Rho Kinase Inhibitor

• Eg Netarsudil
• Lowers IOP by increasing outflow of aqueous humor through the expansion of the juxtacanalicular connective tissue and dilating the episcleral veins
• IOP reduction: 20-25%

Systemic Glaucoma Preparations

Oral Carbonic Anhydrase Inhibitors (CAI)

• Eg Acetazolamide, Methazolamide
• Lower IOP by decreasing aqueous production through inhibition of carbonic anhydrase
• IOP reduction: 30-40%
• May be given pre-operatively in acute angle-closure or severe glaucoma patients to prevent IOP spikes
• For short-term use only due to their systemic side effects

Hyperosmotic Agents

• Eg Glycerol, Isosorbide, Mannitol
• Dehydrates and reduces vitreous volume
• Most effective agents to control acutely elevated IOP
• IOP reduction: 15-30%
• For short-term use in cases where a large rapid reduction in the IOP is required
• Prior to use, patients must be evaluated for heart and kidney disease due to their potential to increase blood volume

Adjunctive Medical Therapy

• Medications may be combined with each other or serve as additional therapy to surgical treatment
• Drugs belonging from the same class should not be combined
• Additional drugs should be used only to achieve target IOP

Fixed Combination Topical Therapy

• As an adjunctive therapy given to patients who fail to achieve their target IOP with monotherapy
• Offers a convenient and simple dosing regimen, and preferred over the use of 2 separate agents
  
  • When available, fixed combination drugs may be preferable than 2 separate agents which may improve compliance due to reduced dosing schedule

• Generally, superior IOP lowering efficacy is seen in combination therapy with agents from different classes than using the individual components alone
• In employing fixed combination treatment, use agents which have both shown individual efficacy (but as individual agent, was insufficient in reaching the target IOP)
  
  • Do not combine 2 drugs with the same mechanism of action