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Symptoms

Usually asymptomatic until the later stages. Symptoms may include visual field defects. Usually bilateral, but can present asymmetrically. Severe field damage and loss of central fixation typically do not occur until late in the disease.

Signs

  • Intraocular pressure (IOP): Although many patients will have an elevated IOP (normal range of 10 to 21 mm Hg), nearly half have an IOP of 21 mm Hg or lower at any one screening.
  • Gonioscopy: Normal-appearing, open anterior chamber angle. No peripheral anterior synechiae (PAS).
  • Optic nerve: See Figure 9.1.1. Characteristic appearance includes loss of rim tissue (includes notching; increased and/or progressive narrowing most commonly inferiorly followed by superiorly, more rarely nasally or temporally), cupping, nerve fiber layer defect, splinter or nerve fiber layer hemorrhage that crosses the disc margin (Drance hemorrhage), acquired pit, cup/disc (C/D) asymmetry >0.2 in the absence of a cause (e.g., anisometropia, different nerve sizes), bayoneting (sharp angulation of the blood vessels as they exit the nerve), enlarged C/D ratio (>0.6; less specific), progressive enlargement of the cup, and greater disc damage likelihood scale (DDLS) score (see Figure 9.1.2).
  • Visual fields: Characteristic visual field loss patterns include nasal step, paracentral scotoma, arcuate scotoma extending from the blind spot nasally (defects usually respect the horizontal midline or are greater in one hemifield than the other), altitudinal defect, or generalized depression (see Figure 9.1.3).

9-1.3 Humphrey visual field showing a superior arcuate defect or scotoma of the left eye.

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9-1.2 Disc damage likelihood scale (DDLS).

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9-1.1 Primary open-angle glaucoma with advanced optic nerve cupping.

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Other

Large fluctuations in IOP, inter-eye IOP asymmetry >5 mm Hg, beta-zone peripapillary atrophy, absence of microcystic corneal edema, and absence of secondary features (e.g., pseudoexfoliation, inflammation).

Differential Diagnosis

If anterior chamber angle open on gonioscopy:

  • Ocular hypertension: Normal optic nerve and visual field. See 9.3, OCULAR HYPERTENSION.
  • Physiologic optic nerve cupping: Static enlarged C/D ratio without rim notching or visual field loss. Usually normal IOP and large optic nerve (>about 2 mm). Often familial.
  • Secondary open-angle glaucoma: Identifiable cause for open-angle glaucoma including inflammatory, exfoliative, pigmentary, steroid-induced, angle recession, traumatic (as a result of direct injury, blood, or debris), and glaucoma related to increased episcleral venous pressure (e.g., Sturge–Weber syndrome, carotid–cavernous fistula), intraocular tumors, degenerated red blood cells (ghost cell glaucoma), lens-induced, degenerated photoreceptor outer segments following chronic rhegmatogenous retinal detachment (Schwartz–Matsuo syndrome), or developmental anterior segment abnormalities.
  • Low-tension glaucoma: Same as primary open-angle glaucoma (POAG) except normal IOP. See 9.2, LOW-TENSION PRIMARY OPEN-ANGLE GLAUCOMA (NORMAL PRESSURE GLAUCOMA).
  • Previous glaucomatous damage (e.g., from steroids, uveitis, glaucomatocyclitic crisis, trauma) in which the inciting agent has been removed. Nerve appearance now static.
  • Optic atrophy: Characterized by disproportionally more optic nerve pallor than cupping. IOP usually normal unless a secondary or unrelated glaucoma is present. Color vision and central vision are often decreased, although not always. Causes include tumors of the optic nerve, chiasm, or tract; syphilis, ischemic optic neuropathy, drugs, retinal vascular or degenerative disease, and others. Visual field defects that respect the vertical midline are typical of intracranial lesions localized at the chiasm or posterior to it.
  • Congenital optic nerve defects (e.g., tilted discs, colobomas, optic nerve pits): Visual field defects may be present but are static.
  • Optic nerve drusen: Optic nerves not usually cupped and drusen often visible. Visual field defects may remain stable or progress unrelated to IOP. The most frequent defects include arcuate defects or an enlarged blind spot. Characteristic calcified lesions can be seen on B-scan ultrasonography (US) (as well as on computed tomography [CT]). Autofluorescence can also highlight nerve drusen.

If anterior chamber angle closed or partially closed on gonioscopy:

  • Chronic angle closure glaucoma (CACG): Shallow anterior chamber. May present with history of episodic blurred vision or headache. PAS present on gonioscopy. See 9.5, CHRONIC ANGLE CLOSURE GLAUCOMA.

Reference(s)

Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: A randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open angle glaucoma. Arch Ophthalmol. 2002;120(6):701-713.

Work Up

Workup
  1. History: Presence of risk factors (family history of blindness or visual loss from glaucoma, older age, African descent, diabetes, myopia, hypertension, or hypotension)? Previous history of increased IOP, chronic steroid use, or ocular trauma? Refractive surgery including laser in situ keratomileusis (LASIK) in past (i.e., change in pachymetry)? Review of past medical history to determine appropriate therapy including asthma, chronic obstructive pulmonary disease (COPD), congestive heart failure, heart block or bradyarrhythmia, renal stones, allergies?
  2. Baseline glaucoma evaluation: All patients with suspected glaucoma of any type should have the following:
    • Complete ocular examination including visual acuity, pupillary assessment for a relative afferent pupillary defect, confrontational visual fields, slit lamp examination, applanation tonometry, gonioscopy, and dilated fundus examination (if the angle is open) with special attention to the optic nerve. Color vision testing is indicated if any suspicion of a neurologic disorder or optic neuropathy.
    • Baseline documentation of the optic nerves. May include meticulous drawings, stereoscopic disc photos, red-free photographs, and/or computerized image analysis (e.g., optical coherence tomography [OCT] with analysis of the nerve fiber layer and ganglion cell layer or Heidelberg retina tomography [HRT]) (see Figure 9.1.4). Documentation should include presence or absence of pallor and/or disc hemorrhages.
    • Formal visual field testing (e.g., Humphrey or Octopus automated visual field). Goldmann visual field tests may be helpful in patients unable to take the automated tests adequately. Standard visual field testing includes evaluation of peripheral and central field (e.g., Humphrey 24-2 strategy). In cases of paracentral defect or advanced disease, specialized central field testing (e.g., Humphrey 10-2 strategy) is recommended.
    • Measure central corneal thickness (CCT). Corneal thickness variations affect apparent IOP as measured with applanation tonometry. Average corneal thickness is 535 to 545 microns. Thinner corneas tend to underestimate IOP, whereas thicker corneas tend to overestimate IOP. Of note, the relationship between corneal thickness and measured IOP is not exactly linear. A thin CCT is an independent risk factor for the development of POAG.
    • Evaluation for other causes of optic nerve damage should be considered when any of the following atypical features are present:
      • Optic nerve pallor out of proportion to the degree of cupping.
      • Visual field defects greater than expected based on amount of cupping.
      • Visual field patterns not typical of glaucoma (e.g., defects respecting the vertical midline, hemianopic defects, enlarged blind spot, central scotoma).
      • Unilateral progression despite equal IOP in both eyes.
      • Decreased visual acuity out of proportion to the amount of cupping or field loss.
      • Color vision loss, especially in the red–green axis.

        If any of these are present, further evaluation may include:

      • History: Acute episodes of eye pain or redness? Steroid use? Acute visual loss? Ocular trauma? Surgery, systemic trauma, heart attack, dialysis, or other event that may lead to hypotension?
      • Diurnal IOP curve consisting of multiple IOP checks during the course of the day.
      • Consider other laboratory workup for nonglaucomatous optic neuropathy: Heavy metals, vitamin B12/folate, angiotensin-converting enzyme, antinuclear antibody, Lyme antibody, rapid plasma reagin or Venereal Disease Research Laboratory, and fluorescent treponemal antibody absorption or treponemal-specific assay (e.g., MHA-TP). If giant cell arteritis (GCA) is a consideration, check erythrocyte sedimentation rate, C-reactive protein, and platelets (see 10.17, ARTERITIC ISCHEMIC OPTIC NEUROPATHY [GIANT CELL ARTERITIS]).
      • In cases where a neurologic disorder is suspected, obtain magnetic resonance imaging (MRI) of the brain and orbits with gadolinium and fat suppression if no contraindications present.
      • Check blood pressure, fasting blood sugar, hemoglobin A1c, lipid panel, and CBC (screening for anemia). Refer to an internist for a complete cardiovascular evaluation.

    9-1.4 Optical coherence tomography of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL) thickness.

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Treatment

General Considerations

  1. Who to treat?

    The decision to treat must be individualized. Some general guidelines are suggested.

    • Is the glaucomatous process present?

      Glaucomatous damage is likely if any of the following are present: presence of thin or notched optic nerve rim, characteristic visual field loss, retinal nerve fiber layer damage, or if DDLS score is >5 (see Figure 9.1.2). Treatment should be considered in the absence of manifest damage if IOP is higher than 30 mm Hg, and/or IOP asymmetry is more than 10 mm Hg.

    • Is the glaucomatous process active?

      Determine the rate of damage progression by careful follow up. Certain causes of optic nerve rim loss may be static (e.g., prior steroid response). Disc hemorrhages suggest active disease.

    • Is the glaucomatous process likely to cause disability?
    • Consider the patient’s age, overall physical and social health, as well as an estimation of his or her life expectancy.
  2. What is the treatment goal?

    The goal of treatment is to enhance or maintain the patient’s health by halting optic nerve damage while avoiding undue side effects of treatment. The only proven method of stopping or slowing optic nerve damage is reducing IOP. Reduction of IOP by at least 30% appears to have the best chance of preventing further optic nerve damage. An optimal goal may be to reduce the IOP at least 30% below the threshold of progression. If damage is severe, greater reduction in IOP may be necessary.

  3. How to treat?

    The main treatment options for glaucoma include medications, laser trabeculoplasty (LT) (selective [SLT] more commonly than argon [ALT]), and glaucoma surgery. Medications or LT are appropriate initial therapies. LT may be especially suitable in patients at risk for poor compliance, with medication side effects, and who have significant trabecular meshwork (TM) pigmentation. Surgery may be appropriate initial treatment if damage is advanced in the setting of a rapid rate of progression or difficult follow up. Options include glaucoma filtering surgery (e.g., trabeculectomy, tube shunt), minimally invasive glaucoma surgery (MIGS), laser cyclophotocoagulation of the ciliary body (e.g., with diode laser or endolaser), and cyclocryotherapy. Surgery should always be considered for any patient with advanced/progressive disease or IOP uncontrolled by other methods.

NOTE:

MIGS encompasses newer surgical options that offer the advantages of shorter healing times and potentially fewer complications. MIGS is generally considered for patients with mild-to-moderate glaucoma. Some MIGS procedures include trabecular micro-bypass devices, canaloplasty, subconjunctival microstents, deep sclerectomy, endocyclophotocoagulation (ECP), and trabectome trabecular ablation.

Medications

Unless there are extreme circumstances (e.g., IOP >35 mm Hg or impending loss of central fixation), treatment is often started by using one type of drop in one eye (monocular therapeutic trial) with reexamination in 1 to 6 weeks (depending on IOP and individualized risk factors) to check for efficacy.

  • Prostaglandin agonists (e.g., latanoprost 0.005% q.h.s., bimatoprost 0.01% or 0.03% q.h.s., travoprost 0.004% q.h.s., tafluprost 0.0015% q.h.s. [preservative free]) are to be used with caution in patients with active uveitis or cystoid macular edema (CME) and are contraindicated in pregnant women or in women wishing to become pregnant. Inform patients of potential pigment changes in iris and periorbital skin, as well as hypertrichosis of eyelashes. Irreversible iris pigment changes rarely occur in blue or dark brown eyes; those at highest risk for iris hyperpigmentation have hazel, gray irides.
  • Beta-blockers (e.g., levobunolol or timolol 0.25% to 0.5% daily or b.i.d.) should be avoided in patients with asthma, COPD, heart block, bradyarrhythmia, unstable congestive heart failure, depression, or myasthenia gravis. In addition to bronchospasm and bradycardia, other side effects include hypotension, decreased libido, central nervous system (CNS) depression, and reduced exercise tolerance.
  • Selective α2-receptor agonists (brimonidine 0.1%, 0.15%, or 0.2% b.i.d. to t.i.d.) are contraindicated in patients taking monoamine oxidase inhibitors (risk of hypertensive crisis) and relatively contraindicated in children under the age of 5 (risk for cardiorespiratory and CNS depression). See 8.11, CONGENITAL/INFANTILE GLAUCOMA. Apraclonidine 0.5% or 1% is rarely used due to tachyphylaxis and high allergy rate but may be used for short-term therapy (3 months).
  • Topical carbonic anhydrase inhibitors (CAIs) (e.g., dorzolamide 2% or brinzolamide 1% b.i.d. to t.i.d.) should be avoided, but are not contraindicated, in patients with sulfa allergy. These medications theoretically could cause the same side effects as systemic CAIs, such as metabolic acidosis, hypokalemia, gastrointestinal symptoms, weight loss, paresthesias, and aplastic anemia. However, systemic symptoms from topical CAIs are extremely rare. There have been no reported cases of aplastic anemia from topical use. Corneal endothelial dysfunction may be exacerbated with topical CAIs; these medications should be used cautiously in patients with Fuchs corneal dystrophy and post keratoplasty.
  • Miotics (e.g., pilocarpine q.i.d.) are usually used in low strengths initially (e.g., 1% to 2%) and then built up to higher strengths (e.g., 4%). Commonly not tolerated in patients <40 years because of accommodative spasm. Miotics are usually contraindicated in patients with retinal holes and should be used cautiously in patients at risk for retinal detachment (e.g., high myopes and aphakes).
  • Sympathomimetics (dipivefrin 0.1% b.i.d. or epinephrine 0.5% to 2.0% b.i.d.) rarely reduce IOP to the degree of the other drugs but have few systemic side effects (rarely, cardiac arrhythmias). They often cause red eyes and may cause CME in aphakic patients.
  • Systemic CAIs (e.g., methazolamide 25 to 50 mg p.o. b.i.d. to t.i.d., acetazolamide 125 to 250 mg p.o. b.i.d. to q.i.d., or acetazolamide 500 mg sequel p.o. b.i.d.) are relatively contraindicated in patients with renal failure. Potassium levels must be monitored if the patient is taking other diuretic agents or digitalis. Side effects such as fatigue, nausea, confusion, and paresthesias are common. Rare, but severe, hematologic side effects (e.g., aplastic anemia) and Stevens–Johnson syndrome have occurred. Allergy to sulfa drugs is not an absolute contraindication to the use of systemic CAIs, but extra caution should be exercised in monitoring for an allergic reaction. Intravenous forms of systemic CAIs (e.g., acetazolamide 250 to 500 mg i.v.) may be utilized if IOP decrease is urgent or if IOP is refractory to topical therapy. Consider checking baseline creatinine in patients with suspected or confirmed renal disease.
NOTE:

Pilocarpine is not routinely used at Wills Eye due to its adverse side effect profile including associated increased risk for uveitis and retinal detachment, possibility for miosis-induced angle closure, and symptoms such as headache.

NOTE:

Patients should be instructed to press a fingertip into the inner canthus to occlude the punctum for 10 seconds after instilling a drop. Doing so will decrease systemic absorption. If unable to perform punctal occlusion, keeping the eyelids closed without blinking for 1 to 2 minutes after drop administration also reduces systemic absorption.

Argon Laser Trabeculoplasty

In some patients, as previously defined, ALT may be used as first-line therapy. It has an initial success rate of 70% to 80%, dropping to 50% in 2 to 5 years.

Selective Laser Trabeculoplasty

The IOP-lowering effect of SLT is equivalent to ALT. SLT utilizes lower energy and causes less tissue damage, which makes this procedure repeatable.

Guarded Filtration Surgery

Trabeculectomy and tube-shunt surgery may obviate the need for medications. Adjunctive use of antimetabolites (e.g., mitomycin C, 5-fluorouracil) in trabeculectomy surgery may aid in the effectiveness of the surgery but increases the risk of complications (e.g., bleb leaks and hypotony).

Follow Up

  1. Patients are reexamined 4 to 6 weeks after starting a new β-blocker or prostaglandin or after ALT/SLT to evaluate efficacy. Topical CAIs, α-agonists, and miotics quickly reach a steady state, and a repeat examination may be performed at any time after 3 days.
  2. Closer monitoring (e.g., 1 to 3 days) may be necessary when damage is severe and the IOP is high.
  3. Once the IOP has been reduced adequately, patients are reexamined in 3- to 6-months intervals for evaluation of the optic nerve, retinal nerve fiber layer, and IOP.
  4. Typically, gonioscopy is performed annually or more often as needed to assess angle anatomy.
  5. Formal visual fields and optic nerve imaging (e.g., photographs, OCT, or HRT) are rechecked as needed, often about every 4 to 12 months. If IOP control is not thought to be adequate, visual fields may need to be repeated more often. Once stabilized, formal visual field testing can be repeated annually.
  6. Dilated retinal examinations should be performed yearly.
  7. If glaucomatous damage progresses, check patient compliance with medications before initiating additional therapy. Consider LT or surgical therapy in setting of progressive damage and poor compliance.
  8. Patients must be questioned about side effects associated with their specific agent(s). They often do not associate eye drops with impotence, weight loss, lightheadedness, or other significant systemic symptoms.