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 intraocular pressure (IOP) treatment is to preserve the quality of life & maintain the visual status of the patient
    • Maintain IOP w/in the target range
    • Preserve optic nerve/retinal 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 & 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 & will most likely preserve the patient’s vision
  • Ideal IOP varies between eyes & among patients
    • There is no threshold IOP for initiating treatment in primary open-angle glaucoma (POAG)
    • Target IOP depends on different factors such as patient’s age & life expectancy, pretreatment IOP level, stage & rate of progression of glaucoma, presence of other risk factors, risks & side effects of therapy, & 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 w/ one drug
    • Consider balancing between effectiveness of the medications & 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 w/ 1 medication at max 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)  
  • Max 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
  • Ocular hypertension can be usually controlled by pharmacotherapy alone
  • In deciding to treat OH, the clinician must balance between prevention of progression to POAG w/ the risks & 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)
  • Any one or a combination of the following may be used depending on the severity of glaucoma, response to the medication & ocular & health status of the patient
  • Always start w/ 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
    • Studies have shown that applying finger pressure also helps increase availability of ophthalmic drugs by approx 35%
  • In patients w/ ocular surface disease, consider preservative-free formulations

Prostaglandin Analogues

  • Eg Bimatoprost, Latanoprost, Tafluprost, Travoprost & Unoprostone
  • Generally considered & approved as first line of treatment for reducing IOP in patients w/ primary open-angle glaucoma (POAG) or ocular hypertension (OH)
  • Lowers IOP by increasing uveoscleral outflow
  • IOP reduction: 25-33%
  • Appear effective & well tolerated (w/ few systemic side effects) by POAG & OH patients
  • Alternative for patients w/ contraindication to initial therapy w/ 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 & tolerability
  • Along w/ prostaglandin analogues, are licensed for first- & second-line use
  • Act by decreasing aqueous humor production
  • IOP reduction: 20-25%
  • Associated w/ few ocular side effects & 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 w/ 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 w/ more ocular side effects

Alpha2-Selective Adrenergic Agonists

  • Eg Apraclonidine, Brimonidine
  • Act by reducing aqueous humor production & 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 & vasoconstriction
  • Long-term use of Apraclonidine is limited due to tachyphylaxis & increased risk of allergy w/ time

Nonselective Adrenergic Agonists

  • Eg Dipivefrine
  • Act by increasing aqueous humor outflow
  • IOP reduction: 15-20%
  • May be associated w/ hypertension, tachycardia & 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
  • Lower IOP by decreasing resistance to aqueous humor outflow from the anterior chamber & increasing trabecular outflow
    • They may, however, reduce uveoscleral outflow which may cause a paradoxical rise in IOP in patients w/ severely compromised trabecular outflow
  • IOP reduction: 20-25%
  • Have fewer systemic side effects than beta-blockers but w/ more significant ocular side effects

Systemic Glaucoma Preparations

Oral Carbonic Anhydrase Inhibitors

  • Eg Acetazolamide, Dichlorphenamide, Methazolamide
  • Lower IOP by decreasing aqueous production through inhibition of carbonic anhydrase & are used as adjunct in the treatment of POAG
  • For short-term use only due to their systemic side effects

Hyperosmotic Agents

  • Eg Glycerol, Mannitol, Isosorbide
  • Dehydrates & reduces vitreous volume
  • Most effective agents to control acutely elevated IOP
  • 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 & kidney disease due to their potential to increase blood volume

Adjunctive Medical Therapy

  • Medications may be combined w/ 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 w/ monotherapy
  • Offers a convenient & simple dosing regimen, & 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 w/ 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 w/ the same mechanism of action
    • Once w/ 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, & concerns about patient compliance
  • Reduces IOP by improving aqueous outflow & is performed using argon, diode & frequency-doubled YAG lasers
  • 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 w/ primary medical treatment for patients w/ open-angle glaucoma
    • Re-treatments in the same area may, however, cause scarring of the TM & raised IOP
  • Selective Laser Trabeculoplasty
    • Similar to ALT but makes use of a laser w/ 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
  • Option for patients who have failed to respond to medications or laser therapy
  • Involves the creation of a filtration bleb that would permit the flow of aqueous humor from the eyes
  • Complications & risks may arise, including cataract & permanent loss of vision
Editor's Recommendations
Most Read Articles
Roshini Claire Anthony, 05 Oct 2017

Olfactory impairment in older adults may point to an elevated risk of developing Parkinson’s disease (PD), particularly in Caucasian men, a small US study found.

Elvira Manzano, Yesterday
Bisphosphonates have proven antifracture efficacy and remain to be the cornerstone of osteoporosis treatment. However, a drug holiday is of particular importance with bisphosphonates due to some signals with long-term use of the drug, including rare incidence of atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ), says a leading endocrinologist at AFOS 2017.
07 Oct 2017
Women who follow a low-fat dietary pattern appear to have reduced breast cancer mortality, according to data from the Earlier Women’s Health Initiative Dietary Modification trial.
Pearl Toh, 5 days ago
Women with higher plasma tryptophan concentrations were less likely to have poor sleep quality during pregnancy, especially among those with anxiety symptoms, according to the GUSTO* study.