primary%20open-angle%20glaucoma
PRIMARY OPEN-ANGLE GLAUCOMA
Primary open-angle glaucoma (POAG) is a chronic, progressive, usually bilateral disease of the eye with an insidious onset.
It is most often characterized by optic nerve damage, defects in the retinal fiber layer and subsequent visual field loss in the absence of underlying ocular disease or congenital abnormalities.
It is generally asymptomatic until it has caused a significant loss of visual field.
Occasionally, patients with very high intraocular pressure may complain of nonspecific headache, discomfort, intermittent blurring of vision or even halos caused by corneal edema.

Principles of Therapy

  • The goal of primary open-angle glaucoma (POAG) treatment is to preserve the quality of life and maintain the visual status of the patient
    • Maintain IOP within the target range
    • Preserve optic nerve/retinal nerve fiber layer status
    • Maintain stable visual fields
  • Can be achieved by the judicious use of IOP lowering modalities
  • When deciding the most appropriate therapy, evaluate each eye individually
  • Aside from IOP lowering effect, choice of therapy must take into account tolerability, compliance and cost

Target intraocular pressure (IOP)

  • Prior to initiation of treatment, an individualized target IOP should be established
  • Target pressure is the highest IOP level where further glaucomatous damage will not occur and will most likely preserve the patient’s vision
  • Ideal IOP varies between eyes and among patients
    • There is no threshold IOP for initiating treatment in POAG
    • 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
  • Lowering the pretreatment IOP by ≥25% has been shown by several studies to prevent POAG progression
    • A lower IOP can be targeted in the presence of a rapidly progressing or severe optic neuropathy or risk factors
  • 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

Therapeutic Options

  • Initial treatment option to lower the IOP is usually by topical medications
    • Medical therapy should start with one 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
    • 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
  • If the IOP reduction is still insufficient to reach the target IOP with 1 medication at maximum dose:
    • Consider switching first to a different class of medication prior to adding another drug
    • Next option would be adjunctive medical therapy (either fixed combination therapies or additional separate medications) 
  • Maximum tolerated medical therapy is attained when no escalation of pharmacotherapy is available, appropriate or likely to provide a clinically significant effect (eg IOP reduction) in preventing glaucoma progression
    • When this is reached, laser or incisional surgical therapy should be considered

Ocular Hypertension (OH)

  • In ocular hypertension, consider other risk factors for glaucomatous damage to determine the appropriate target pressure
  • A treatment target IOP of ≤24 mmHg and IOP reduction of ≥20% from baseline is recommended
  • Ocular hypertension can be usually controlled by pharmacotherapy alone
  • In deciding to treat OH, the clinician must balance between prevention of progression to POAG with the risks and cost of medical therapy
  • If the IOP is uncontrolled by medications or if glaucoma progression is documented, then treat as POAG

Pharmacotherapy

Topical Glaucoma Preparations

  • Either decrease aqueous humor production (adrenergic agonists, beta blockers, carbonic anhydrase inhibitors) or increase aqueous humor outflow (adrenergic agonists, parasympathomimetics, prostaglandins, rho kinase inhibitor)
  • 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
  • In patients with ocular surface disease, consider preservative-free formulations

Prostaglandin Analogues

  • Eg Bimatoprost, Latanoprost, Latanoprostene bunod, Tafluprost, Travoprost and Unoprostone
  • Generally considered and approved as first line of treatment for reducing IOP in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH)
  • Lowers IOP by increasing uveoscleral outflow
  • IOP reduction: 25-35%
  • Appear effective and well tolerated (with few systemic side effects) by POAG and OH patients
  • 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 agent due to their effectiveness, low cost and tolerability
  • Along with prostaglandin analogues, are licensed for first- and second-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
  • Beta1-selective beta-blockers (eg Betaxolol) have less pulmonary side effects but have similar potential cardiac side effects as compared to nonselective beta-blockers
  • 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

Adrenergic Agonists

  • Appear as effective as beta-blockers but with more ocular side effects

Alpha2-selective Adrenergic Agonists

  • Eg Apraclonidine, Brimonidine
  • Act by reducing aqueous humor production and increasing uveoscleral outflow
  • IOP reduction: 20-25%
  • Useful in preventing IOP elevation after ophthalmic laser procedures
  • 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

Nonselective Adrenergic Agonists

  • Eg Dipivefrine
  • Act by increasing aqueous humor outflow
  • IOP reduction: 15-20%
  • May be associated with hypertension, tachycardia and arrhythmia

Carbonic Anhydrase Inhibitors (CAI)

  • Eg Brinzolamide, Dorzolamide
  • Reduce IOP by inhibition of carbonic anhydrase, resulting in decreased aqueous humor production
  • IOP reduction: 15-20%

Parasympathomimetics

  • Eg Pilocarpine, Carbachol, Demecarium, Ecothiophate
  • 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

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
  • IO reduction: 20%

Systemic Glaucoma Preparations

Oral Carbonic Anhydrase Inhibitors

  • Eg Acetazolamide, Dichlorphenamide, Methazolamide
  • Lower IOP by decreasing aqueous production through inhibition of carbonic anhydrase and are used as adjunct in the treatment of POAG
  • IOP reduction: 30-40%
  • May be used in emergency situations when acute lowering of elevated IOP or to reduce IOP before surgical intervention is required
  • For short-term use only due to their systemic side effects

Hyperosmotic Agents

  • Eg Glycerol, Mannitol, Isosorbide
  • 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, thus improving compliance
    • Studies have shown that combining topical glaucoma medications into a single formulation helps increase patient compliance
  • 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
    • Once with contraindications to any one of the agents, combination product should not be used

Laser Treatment

  • While topical medications are the usual first line of treatment, laser trabeculoplasty may be an effective initial treatment option to primary open-angle glaucoma (POAG), especially in cases of a very high intraocular pressure (IOP), severe glaucoma, need for >2 topical medications, known intolerance or allergy to topical agents, and concerns about patient compliance
  • Reduces IOP by improving aqueous outflow and is performed using argon, diode and frequency-doubled neodymium: yttrium-aluminum-garnet (Nd:YAG) lasers
  • Possible complications include IOP spike, transient iritis, temporary blurring of vision, endothelial burns, corneo-refractive changes, suprachoroidal effusion
Argon Laser Trabeculoplasty (ALT)
  • Works by activation of trabeculocytes to improve trabecular meshwork (TM) function
  • Full effect of treatment may be apparent after 6 weeks
    • Evidence showed comparability of the long-term efficacy of primary argon laser trabeculoplasty with primary medical treatment for patients with open-angle glaucoma
  • Re-treatments in the same area may, however, cause scarring of the TM and raised IOP
  • Less successful in eyes without pigmentation of the trabecular meshwork

Selective Laser Trabeculoplasty (SLT)

  • Similar to ALT but makes use of a laser with a very short duration of discharge
  • Same mechanism of action as ALT but raised IOP is less likely to occur due to less photocoagulative damage to adjacent tissue
  • Same IOP lowering effect as ALT but produces less thermal damage to the trabecular meshwork
  • Shown to have comparable efficacy in reducing IOP with prostaglandin analogues
  • Causes less scarring and can be repeated
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