Primary Open-Angle Glaucoma (POAG)

Updated: Jun 14, 2023
Author: Kristin S Biggerstaff, MD, MS; Chief Editor: Inci Irak Dersu, MD, MPH 


Practice Essentials

Primary open-angle glaucoma (POAG) is described distinctly as a multifactorial optic neuropathy that is chronic, progressive, and irreversible, with a characteristic acquired loss of optic nerve fibers. Such loss develops in the presence of open anterior chamber angles, characteristic visual field abnormalities, and intraocular pressure that is too high for the continued health of the eye. It manifests by cupping of the optic disc (see the image below) in the absence of other known causes of the disease.[1, 2]

Advanced glaucomatous damage with increased cuppin Advanced glaucomatous damage with increased cupping and substantial pallor of the optic nerve head. Courtesy of M. Bruce Shields, MD.

Signs and symptoms

Because of the silent nature of glaucoma, patients usually don’t present with any symptoms or visual complaints until late in the disease course, particularly with primary open-angle glaucoma. However, narrow/closed-angle glaucoma and secondary glaucomas can cause a rapid rise in intraocular pressure, which is usually symptomatic, particularly when intraocular pressure is 35 mm Hg or more.

Significant attention should be given to the following in the patient’s clinical history:

  • Past ocular history
  • Previous ocular surgery, including photocoagulation or refractive procedures
  • Ocular/head trauma
  • Past medical history
  • Current medications
  • Risk factors for glaucomatous optic neuropathy

See Clinical Presentation for more detail.


Screening the general population for primary open-angle glaucoma is most effective if targeted toward those at high risk, such as African Americans and elderly individuals, especially if the screening consists of intraocular pressure measurements combined with assessment of optic nerve status.

Examination of patients with suspected primary open-angle glaucoma includes the following:

  • Slit lamp examination of the anterior segment
  • Funduscopy
  • Tonometry
  • Gonioscopy
  • Pachymetry

Lab Tests

Laboratory tests that may be used to rule other causes for optic neuropathy in patients suspected of having normal-tension glaucoma include the following:

  • CBC count
  • Erythrocyte sedimentation rate
  • Serology for syphilis (micro-hemagglutination- Treponema pallidum [MHA-TP], not Venereal Disease Research Laboratory [VDRL] test)
  • Rarely, serum protein electrophoresis: For individuals with potential autoimmune etiology for some glaucomatous optic neuropathies

Imaging studies

The following imaging studies may be used to evaluate patients with suspected primary open-angle glaucoma:

  • Fundus photography
  • Retinal nerve fiber layer imaging on high-contrast black and white film using red-free techniques
  • Confocal scanning laser ophthalmoscopy
  • Scanning laser polarimetry
  • Optical coherence tomography
  • Neuroimaging, if suggested by the patient’s pattern of visual field loss

Investigational imaging modalities in the evaluation and management of patients with primary open-angle glaucoma include the following:

  • Fluorescein angiography
  • Ocular blood flow analysis via laser Doppler flowmetry
  • Color vision measurements
  • Contrast sensitivity testing
  • Electrophysiologic tests
  • Ultrasound biomicroscopy

See Workup for more detail.


Current medical therapy for primary open-angle glaucoma is limited toward lowering intraocular pressure. A rational approach to choosing antiglaucoma medications should minimize the number of medications and the probability of significant adverse effects.

If one medication is not adequate in reaching the target pressure, a second medication should be chosen that has a different mechanism of action, so that the 2 drug therapies will have an additive effect.


Medications used in the management of primary open-angle glaucoma include the following:

  • Beta-adrenergic blockers (eg, levobunolol, timolol, carteolol, betaxolol, metipranolol, levobetaxolol)
  • Adrenergic agonists (eg, brimonidine, apraclonidine)
  • Less-selective sympathomimetics (eg, dipivefrin, epinephrine)
  • Carbonic anhydrase inhibitors (eg, dorzolamide, brinzolamide, acetazolamide, methazolamide)
  • Prostaglandin analogs (eg, latanoprost, bimatoprost, travoprost, tafluprost, latanoprostene bunod, omidenepag isopropyl)
  • Miotic agents (eg, pilocarpine)
  • Hyperosmotic agents (eg, isosorbide dinitrate, mannitol, glycerin)
  • Beta-blocker/alpha agonist combination (eg, brimonidine/timolol)
  • Beta-blocker/carbonic anhydrase inhibitor combination (eg, dorzolamide/timolol)
  • Alpha agonist/carbonic anhydrase inhibitor (eg, brimonidine/brinzolamide)
  • Rho kinase inhibitor (eg, netarsudil)

Laser therapy

Laser can be used as primary or adjunctive treatment. It is indicated in cases of noncompliance with medications or if the patient is on maximum tolerated medical therapy and needs further intraocular pressure reduction.

The following are laser options that may be used for primary open-angle glaucoma:

  • Argon laser trabeculoplasty (ALT)
  • Selective laser trabeculoplasty (SLT)
  • Micropulse diode laser trabeculoplasty (MDLT)


Surgery is indicated in primary open-angle glaucoma when glaucomatous optic neuropathy worsens (or is expected to worsen) at any given level of intraocular pressure and the patient is on maximum tolerated medical therapy.

The following are surgical options that may be used for primary open-angle glaucoma:

  • Trabeculectomy
  • Drainage implant surgery
  • Cyclophotocoagulation (CPC)

Minimally invasive glaucoma surgery (MIGS) consists of newer techniques that hold potential as surgical options in primary open-angle glaucoma, including the following:

  • Deep sclerectomy/viscocanalostomy
  • 360-degree suture canaloplasty
  • Trabectome ®
  • Endoscopic cyclophotocoagulation (ECP)
  • iStent implant ®
  • Gonioscopy-assisted transluminal trabeculotomy (GAAT)
  • Kahook dual blade ®
  • Xen ® Gel Implant

See Treatment and Medication for more detail.


The definition of glaucoma has changed drastically since its introduction around the time of Hippocrates (approximately 400 BC). The word glaucoma came from the ancient Greek word glaucosis, meaning clouded or blue-green hue, most likely describing a patient having corneal edema or rapid evolution of a cataract precipitated by chronic elevated pressure. Over the years, extensive refinement of the concept of glaucoma has continued to the present date.

Glaucoma is currently defined as a characteristic progressive degeneration of the optic nerve, which may also lead to specific visual field defects over time. This process can be slowed by adequate lowering of intraocular pressure (IOP). Nevertheless, some controversy still exists as to whether IOP should be included in the definition, as some subsets of patients can exhibit the characteristic optic nerve damage and visual field defects while having an IOP within the normal range. The generic term glaucoma should only be used in reference to the entire group of glaucomatous disorders as a whole, because multiple subsets of glaucomatous disease exist. A more precise term should be used to describe the glaucoma, if the specific diagnosis is known.

Primary open-angle glaucoma (POAG) is glaucoma in the presence of open anterior chamber angles. It manifests by cupping of the optic disc (shown in the image below), in the absence of other known causes of glaucomatous disease.[1, 2]

Advanced glaucomatous damage with increased cuppin Advanced glaucomatous damage with increased cupping and substantial pallor of the optic nerve head. Courtesy of M. Bruce Shields, MD.

POAG may develop in the absence of documented elevated IOP. This condition has been termed normal-tension or low-tension glaucoma.

People who maintain elevated pressures in the absence of nerve damage or visual field loss exist. They are considered at risk for glaucoma and have been termed ocular hypertensives (see Ocular Hypertension). POAG is a major worldwide health concern, because of its usually silent, progressive nature, and because it is one of the leading preventable causes of blindness in the world. With appropriate screening and treatment, glaucoma usually can be identified and its progress arrested before significant effects on vision occur.


The exact cause of glaucomatous optic neuropathy is not known, although many risk factors have been identified, to include the following: elevated IOP, family history, race, age older than 40 years, and myopia.

Elevated IOP is the most studied of these risk factors because it is the main clinically treatable risk factor for glaucoma. Multiple theories exist concerning how IOP can be one of the factors that initiates glaucomatous damage in a patient. Two of the major theories include the following: (1) onset of vascular dysfunction causing ischemia to the optic nerve, and (2) mechanical dysfunction via cribriform plate compression of the axons.

In addition to vascular compromise and mechanically impaired axoplasmic flow, contemporary hypotheses of possible pathogenic mechanisms that underlie glaucomatous optic neuropathy include excitotoxic damage from excessive retinal glutamate, deprivation of neuronal growth factors, peroxynitrite toxicity from increased nitric oxide synthase activity, immune-mediated nerve damage, and oxidative stress. The exact role that IOP plays in combination with these other factors and their significance to the initiation and progression of subsequent glaucomatous neuronal damage and cell death over time is still under debate; the precise mechanism is still a hot topic of discussion.

However, IOP is the only clinical risk factor that has been able to be successfully manipulated to date. Categorizing and managing patients based on their IOP and determining when IOP should be treated to prevent optic nerve damage became the forefront issue of glaucoma management for most of the last half of the 20th century.

Several studies over the years have shown that as IOP rises above 21 mm Hg, the percentage of patients developing visual field loss increases rapidly, most notably at pressures higher than 26-30 mm Hg. A patient with an IOP of 28 mm Hg is about 15 times more likely to develop field loss than a patient with a pressure of 22 mm Hg. Therefore, a patient population of those with elevated IOP should not be thought of as homogeneous. Furthermore, before initiating treatment of a patient based on a specific IOP measurement, the following factors should be considered regarding that IOP level obtained:

  • Variability of tonometry measurements per examiner (usually found to be about 10%, or 1-2 mm Hg)

  • Effect corneal thickness has on accuracy of IOP measurements (see Other Tests)

  • Diurnal variation of IOP (often highest in the early morning hours, but maximum IOP can be at any time of day in some patients)

  • In addition, remember that while normal eyes have a diurnal variation of approximately 3-4 mm Hg, glaucomatous eyes have even higher variation (>10 mm Hg). Note: Multiple readings should be taken over time and should be considered with correlative evidence of visual field and optic nerve examination before any diagnosis or therapy is rendered.

A study by Costa et al supports the need to more accurately assess the relationship of 24-hour IOP to 24-hour diastolic perfusion pressure in patients with glaucoma. Future methodology that performs noninvasive, real-time IOP measurements throughout the 24 hours of the day may enable a more complete understanding of the roles that IOP and blood pressure have to the etiology of glaucomatous damage and progression of the disease.[3]

Other points of importance when considering a diagnosis of POAG are described below.

Disc cupping and nerve fiber layer loss of up to 40% have been shown to occur before actual visual field loss has been detected. Therefore, visual field examination cannot be the sole tool used to determine when a patient has begun to sustain undeniable glaucomatous damage, and it should not be used in isolation as the benchmark for treatment.

In cases where POAG is associated with increased IOP, the cause for the elevated IOP generally is accepted to be decreased facility of aqueous outflow through the trabecular meshwork. Occurrence of this increase in resistance to flow has been suggested by multiple theories, to include the following:

  • An obstruction of the trabecular meshwork by accumulated material

  • A loss of trabecular endothelial cells

  • A reduction in trabecular pore density and size in the inner wall endothelium of the Schlemm canal

  • A loss of giant vacuoles in the inner wall endothelium of the Schlemm canal

  • A loss of normal phagocytic activity

  • Disturbance of neurologic feedback mechanisms

Other processes thought to play a role in resistance to outflow include altered corticosteroid metabolism, dysfunctional adrenergic control, abnormal immunologic processes, and oxidative damage to the meshwork.

Numerous other undetermined factors are considered to be at work in the pathogenesis of glaucoma. Basic and clinical science research continues to play a role in the search for such factors that contribute to the development and prognosis of the patient with POAG.



United States

Multiple population studies (eg, Framingham, Beaver Dam, Baltimore, Rotterdam, Barbados, Egna-Neumarkt) have been performed to estimate the prevalence of eye disease, including that of POAG and those individuals with ocular hypertension (OHT) who are at risk for POAG.

Estimates of the prevalence of glaucoma in studies involving only the United States suggest the following: glaucoma is a leading cause of irreversible blindness, second only to macular degeneration; only one half of the people who have glaucoma may be aware that they have the disease; and more than 2.25 million Americans aged 40 years and older have POAG.

More than 1.6 million have significant visual impairment, with 84,000-116,000 bilaterally blind in the United States alone. These statistics emphasize the need to identify and closely monitor those at risk of glaucomatous damage.

In a white population at risk for glaucoma, visual field loss can be expected to develop in about 3% of subjects over 10 years of follow up without treatment. Risk increases with age and IOP.[4]

In the United States, 3-6 million people, including 4-10% of the population older than 40 years, are currently without detectable signs of glaucomatous damage using present-day clinical testing, but they are at risk due to IOP of 21 mm Hg or higher. Roughly 0.5-1% per year of those individuals with elevated IOP will develop glaucoma over a period of 5-10 years. The risk may be declining to less than 1% per year, now that ophthalmoscopic and perimetric techniques for detecting glaucomatous damage have improved significantly.

Diagram showing the relative proportion of people Diagram showing the relative proportion of people in the general population who have elevated pressure (horizontally shaded lines) and/or damage from glaucoma (vertically shaded lines). Notice that most have elevated pressure but no sign of damage (ie, ocular hypertensives), but there are also those with normal pressures who still have damage from glaucoma (ie, normal tension glaucoma). Courtesy of M. Bruce Shields, MD.OHT = horizontal lines only NTG = vertical lines only POAG and other glaucomas with both elevated intraocular pressure and damage = overlapping horizontal and vertical lines
Diagram of intraocular pressure distribution, with Diagram of intraocular pressure distribution, with a visible skew to the right (somewhat exaggerated compared to the actual distribution). Note that, while uncommon, field loss among individuals with pressures in the upper teens can occur. Also, note that the average pressure among those with glaucomas is in the low 20s, even though most individuals with pressures in the low 20s do not have glaucoma. Used by permission from Survey of Ophthalmology.


Glaucoma is the second leading cause of blindness in the world (surpassed only by cataracts, a reversible condition). More than 3 million people are bilaterally blind from POAG worldwide, and more than 2 million people will develop POAG each year.


Over a 5-year period, several studies have shown the incidence of new onset of glaucomatous damage in previously unaffected patients to be about 2.6-3% for IOPs 21-25 mm Hg, 12-26% incidence for IOPs 26-30 mm Hg, and approximately 42% for those higher than 30 mm Hg.

The Ocular Hypertension Treatment Study (OHTS) found that the overall risk for patients with IOPs ranging from 24-31 mm Hg but with no clinical signs of glaucoma have an average risk of 10% of developing glaucoma over 5 years, with that risk being cut in half if patients are preemptively started on IOP-lowering therapy. Significant subsets of higher and lower risk exist when pachymetry (central corneal thickness [CCT]) is taken into account (see the image below).

Ocular hypertension study (OHTS). Percentage of pa Ocular hypertension study (OHTS). Percentage of patients who developed glaucoma during this study, stratified by baseline intraocular pressure (IOP) and central corneal thickness (CCT).

Some patients' first sign of morbidity from elevated IOP can be presentation with sudden loss of vision due to a central retinal vein occlusion (CRVO), the second most common risk factor for CRVO behind systemic hypertension.

See References for additional resources.


Prevalence of POAG is 3-4 times higher in blacks than in Caucasians; in addition, blacks are up to 6 times more susceptible to optic disc nerve damage than Caucasians. A higher prevalence of larger cup-to-disc ratios exists in the normal black population as compared with white controls.

Glaucoma is the most common cause of blindness among people of African descent. They are more likely to develop glaucoma early in life, and they tend to have a more aggressive form of the disease.

The Barbados Eye Study over 4 years showed a 5 times higher incidence of developing glaucoma in a group of black ocular hypertensives as compared with a predominantly white population.

Some population studies have found the mean IOP in blacks to be higher than Caucasian controls. Other studies (eg, Baltimore) found no difference. Consequently, further study needs to be conducted to clarify this issue.

Furthermore, the OHTS has suggested that black patients overall may have a thinner average central corneal thickness, thereby leading to underdiagnosis of elevated pressure, and consequently, exposure to higher risk of developing glaucoma. Therefore, pachymetry measurement is particularly important in establishing a baseline for African-American patients who are glaucoma suspects.


Reports on sex predilection also differ. Although some age-controlled studies have reported significantly higher mean IOP values in women than in men, others have failed to find such a difference, while others have even shown males to have a higher prevalence of glaucoma.


Age older than 40 years is a risk factor for the development of POAG, with up to 15% of people affected by the seventh decade of life.

Consequently, glaucoma is found to be more prevalent in the aging population, even after compensating for the fact that mean IOP slowly rises with increasing age.

However, the disease itself is not limited to only middle-aged and elderly individuals.


Prognosis is generally good for patients with POAG. With careful follow-up care and compliance with therapy, the vast majority of patients with POAG retain useful vision throughout their lifetime.

Patient Education

Patient education is essential for successful treatment of glaucoma. The patient who understands the chronic, potentially progressive nature of glaucoma is more likely to comply with therapy. Numerous handouts are available to patients, including the following:

  • "Understanding and Living with Glaucoma: A Reference Guide for People with Glaucoma and Their Families," Glaucoma Research Foundation, 1-800-826-6693.

  • "Glaucoma Patient Resource: Living More Comfortably with Glaucoma," Prevent Blindness America, 1-800-331-2020.

For patient education resources, see the Eye and Vision Center. Also, see the patient education articles Primary Open-Angle Glaucoma, Glaucoma FAQs, Normal-Tension Glaucoma, Glaucoma Medications, and Ocular Hypertension.




The initial patient interview is extremely important in the evaluation for POAG or other ocular diseases secondarily causing elevated IOP.

Because of the silent nature of glaucoma, patients will not usually present with any symptoms or visual complaints until late in the disease course, particularly with POAG. However, narrow/closed angle glaucoma and secondary glaucomas can cause rapid closure of the trabecular meshwork, with an equally rapid rise in IOP, which is usually symptomatic, particularly when IOP is equal to or greater than 35 mm Hg.

Significant attention should be given to the patient's past ocular history and other factors.

Past ocular history includes the following:

  • History of eye pain or redness

  • Multicolored halos

  • Headache

  • Previous ocular disease, including cataracts

  • Uveitis

  • Diabetic retinopathy

  • Vascular occlusions

Other factors include the following:

  • Previous ocular surgery, including photocoagulation or refractive procedures

  • Ocular/head trauma

  • Past medical history - Any surgeries or pertinent vasculopathic systemic illnesses

  • Current medications, including any hypertensive medications (which may indirectly cause fluctuation of IOP) or topical/systemic corticosteroids

  • An association between glaucoma and Alzheimer disease has been reported.[5]

Risk factors for glaucomatous optic neuropathy

Strong implications are as follows:

  • History of elevated IOP; advanced age, particularly after 50 years; African American descent; positive family history of glaucoma (first-degree relative, especially correlative if present in a sibling; relative risk 3.7-fold higher than if no family history of glaucoma); myopia

  • Be specific when asking family history (Which family members? Was there actual visual loss from glaucoma or other causes of visual field loss? Are they under control on one or more medications? Did they require surgery for adequate control?)

Possible implications are as follows:

  • Systemic cardiovascular disease

  • Diabetes mellitus

  • Migraine headache

  • Systemic hypertension

  • Vasospasm

Anecdotal risk factors are as follows:

  • Obesity

  • Smoking

  • Alcohol

  • History of stress

  • Anxiety

  • Sleep apnea

Risk factors for rapid glaucoma progression

Patients with open-angle glaucoma who have a worse mean deviation to their visual field, a greater vertical cup-to-disc ratio at baseline, or who are older are significantly more likely to experience a rapid decay of their visual field, according to a recent study of 767 eyes from 566 participants in the Advanced Glaucoma Intervention Study.[6] Rapid progression was defined as a rate of changes in the visual field of at least 36% per year. Other factors associated with an increased risk for progression that did not reach significance included being male and having worse baseline visual acuity.[6]


Screening the general population for POAG is most effective if targeted toward those at high risk, such as African Americans and elderly individuals, especially if the screening consists of IOP measurements combined with assessment of optic nerve status.

Perform screening at least every 3-5 years in asymptomatic patients aged 40 years or younger and more often if the person is African American or older than 40 years. For those with multiple risk factors, evaluate and monitor on a more frequent basis, as appropriate.

Perform a standard comprehensive eye examination, such as that outlined in the American Academy of Ophthalmology (AAO) Preferred Practice Patterns, on the initial visit. If any visual field or optic nerve changes consistent with early glaucoma are present, then diagnose the patient as having such.

A flowchart for evaluation of suspected glaucoma is shown below.

Flowchart for evaluation of a patient with suspect Flowchart for evaluation of a patient with suspected glaucoma. Used by permission of the American Academy of Ophthalmology.

Emphasize the following points during the examination to distinguish POAG from either secondary causes of glaucoma or from OHT in patients with only elevated IOP and no damage.

Compare visual acuity with previous known acuities. If declining, rule out secondary causes of vision loss, whether it is from cataracts, age-related macular degeneration (ARMD), ocular surface disorders (eg, dry eye), or adverse effects from topical medications (especially if using miotics).

Pupils - Test for relative afferent pupillary defect (Marcus Gunn pupil).

Slit lamp examination of the anterior segment

Findings may include the following:

  • Cornea - Signs of microcystic edema (found only with acute elevation of IOP); keratic precipitates, pigment on endothelium (Krukenberg spindle); congenital anomalies

  • Anterior chamber - Cell or flare, uveitis, hyphema, angle closure

  • Iris - Transillumination defects, iris atrophy, synechiae, rubeosis, ectropion uveae, iris bombe, difference in iris coloration bilaterally (eg, Fuchs heterochromic iridocyclitis), pseudoexfoliation (PXF) material

  • Lens - Cataract progression (ie, signs of phacomorphic glaucoma, pseudoexfoliation, phacolytic glaucoma with a Morgagnian cataract)

  • Optic nerve/nerve fiber layer - Stereoscopically examine for evidence of glaucomatous damage, including the following: cup-to-disc ratio in horizontal and vertical meridians (describe by color and slope, and diagram, if needed); appearance of disc; progressive enlargement of the cup; evidence of nerve fiber layer damage with red-free filter; notching or thinning of disc rim (see the image below), particularly at superior and inferior poles (because nerve fibers at the superior and inferior poles of the disc can often be affected first); pallor; presence of hemorrhage (most common inferotemporally); asymmetry between discs; parapapillary atrophy (possible association with development of glaucoma); or congenital nerve abnormalities.

    Illustration of progressive optic nerve damage. No Illustration of progressive optic nerve damage. Notice the deepening (saucerization) along the neural rim, along with notching and increased excavation/sloping of the optic nerve and circumlinear vessel inferiorly. Courtesy of M. Bruce Shields, MD.
    Optic nerve asymmetry in a patient with glaucomato Optic nerve asymmetry in a patient with glaucomatous damage, left eye, showing optic nerve excavation inferiorly (similar to Image 5). Courtesy of M. Bruce Shields, MD.
    Glaucomatous optic nerve damage, with sloping and Glaucomatous optic nerve damage, with sloping and nerve fiber layer rim hemorrhage at the 7-o'clock position. Hemorrhage is indicative of progressive damage, usually due to inadequate pressure control. Further notching and pallor corresponding to the area of hemorrhage usually is seen several weeks after resorption of the blood. Courtesy of M. Bruce Shields, MD.
  • Fundus - Other abnormalities that could account for any nonglaucomatous visual field defects or vision loss present (eg, disc drusen, optic pits, retinal disease), vitreous hemorrhage, or proliferative retinopathy.

Baseline stereo fundus photographs for future reference/comparison; if unavailable, record representative drawings.

Tonometry (see also Other tonometric methods in Other Tests)

IOP varies from hour-to-hour in any individual. The circadian rhythm of IOP usually causes it to rise most in the early hours of the morning; IOP also rises with a supine posture.

When checking IOP in both eyes, the method used (Goldmann applanation is the criterion standard) and the time of the measurement should all be recorded.

Previous tonometry readings, if available, should be reviewed (eg, Is the reading reproducible? What method was used to obtain the reading? What time of the day was it? Where does it fall on the diurnal pressure curve? Do both eyes have similar measurements?).

In obese patients, the possibility of a Valsalva movement causing an increased IOP should be considered when measured in the slit lamp by Goldman applanation. Measurement should be tried via Tono-Pen, Perkins, or pneumotonometer with the patient resting back in the examination chair.

A difference between the 2 eyes of 3 mm Hg or more indicates greater suspicion of glaucoma. An average of 10% difference between individual measurements should be expected. The measurements should be repeated on at least 2-3 occasions before deciding on a treatment plan. The measurement should be completed in the morning and at night to check the diurnal variation, if possible. (A diurnal variation of more than 5-6 mm Hg may be suggestive of increased risk for POAG.) Early POAG is suspected strongly when a steadily increasing IOP is present.

Pachymetry affects applanation tonometry values and, therefore, should be checked on the initial examination (see also Pachymetry and Other tonometric methods in Other Tests).


Perform gonioscopy to rule out angle-closure or secondary causes of IOP elevation, such as angle recession, pigmentary glaucoma, and PXF.

Check the peripheral contour of the iris for plateau iris, and examine the trabecular meshwork for peripheral anterior synechiae, as well as neovascular or inflammatory membranes.

The Schlemm canal may be seen with blood refluxing through the canal into the posterior trabecular meshwork. This possibly could indicate elevated episcleral venous pressure, with such conditions as carotid-cavernous fistula, Graves orbitopathy, or Sturge-Weber syndrome needing to be ruled out.


A pachymeter is used to measure CCT. According to the OHTS, pachymetry is now the criterion standard for every baseline examination in patients who are at risk for or suspected of having glaucoma (see the image below).

Ocular hypertension study (OHTS). Percentage of pa Ocular hypertension study (OHTS). Percentage of patients who developed glaucoma during this study, stratified by baseline intraocular pressure (IOP) and central corneal thickness (CCT).

Visual field testing

Perform automated threshold testing (eg, Humphrey 24-2) to rule out any glaucomatous visual field defects. A Humphrey visual field is shown below.

Humphrey visual field, right eye, showing patient Humphrey visual field, right eye, showing patient with advanced glaucomatous field loss. Notice both the arcuate extension from the blind spot (Bjerrum scotoma) and the loss nasally (nasal step), which often occurs early in the disease process. Courtesy of M. Bruce Shields, MD.

If the patient is unable to perform automated testing, Goldmann testing may be substituted.

Caveats about visual field analysis are outlined below (see also Other Tests).

New-onset glaucomatous defects are found most commonly as an early nasal step, temporal wedge, or paracentral scotoma (more frequent superiorly); generalized depression related to IOP level also can be found.

Swedish interactive thresholding algorithm (SITA)-based software algorithms may decrease testing time and boost reliability, especially in older patients.

Short wavelength automated perimetry or blue-yellow perimetry (SWAP) may provide a more sensitive method of detecting visual field deficits, especially in those previously labeled as ocular hypertensive. If the Humphrey visual field testing results are normal, SWAP should be considered to help detect visual field loss earlier. Recent studies suggest SWAP may detect visual loss/progression up to 3-5 years earlier than conventional perimetry, as well as in 12-42% of patients previously diagnosed with only OHT. Because the testing time may be lengthened, it may be tiring for some patients. However, new SITA-SWAP algorithm software may speed up the testing time and thus improve reliability.

Frequency doubling perimetry (also called frequency doubling technology or FDT, which is enhanced with MATRIX software) is a newer technology that projects an alternating pattern of gridlines onto a screen and stimulates specific neurons that may be damaged early in OHT or POAG. As in SWAP, this may also be able to help detect nerve fiber layer loss at an earlier stage in the glaucomatous disease process, thereby screening out more people who are currently misdiagnosed as having OHT instead of early POAG. Current sensitivities and specificities are continually improving, but continued baseline data is needed to determine in what setting this newer technology will prove to be most useful.

Examination results must take into account that visual field defects may not be apparent until over 40% loss of the nerve fiber layer has occurred. Therefore, the therapy should be based on the overall clinical picture and not on visual field testing alone (see Treatment).

The pupil size should be documented at each testing session, as constriction can reduce retinal sensitivity and mimic progressive field loss.

Risk factors, specifically for the development of glaucomatous field loss in OHT, have recently been studied, and it was found that several presumed risk factors (ie, presence of hypertension, diabetes, refractive error, race, family history of glaucoma, gender, smoking or ethanol use, disc area) were not significant for prediction of eventual field loss.

Significant positive predictive factors for progressive field loss included higher IOP, older age, presence of peripapillary atrophy, larger cup-to-disc ratio, smaller rim-disc area ratio, and cup asymmetry. A study by De Moraes et al found some of the same risk factors for visual field progression in treated glaucoma/POAG: female sex, African or Latin, exfoliation syndrome, older age, cornea thinner and decreased CCT, peak IOP 1.13 mm Hg higher, disc hemorrhage, and beta zone peripapillary atrophy.[7] Consequently, the relationship of risk factors for OHT and POAG compared with that of actual field loss development is much more complex than has been previously presumed.

The initial visual field baseline may need to be repeated at least twice on successive visits, especially if initial testing shows low reliability indices. Newer glaucoma progression analysis (GPA) software can help identify reliable perimetric baselines, and probability-based analyses of subsequent fields can assist in determining if there is true progression over time versus artifact. In follow-up, if a low risk of onset of glaucomatous damage is present, then repeat testing may be performed once a year. If a high risk of impending glaucomatous damage is present, then testing may be adjusted (as frequent as every 2 mo).

The rate of progression of visual field loss, as measured by mean deviation, is related to the amount of visual field loss present at initial presentation; the rate is greater the more loss is initially present.[8] A study by Nouri-Mahdavi et al suggests that accelerating the frequency of visual field testing from annually to biannually increases the ability to detect progression of glaucoma.[9]

In some patients with glaucoma, the addition of a 10-2 visual field (VF) test to the standard 24-2 VF test or modification of the 24-2 VF equipment to assess more test points may help to detect early central macular damage.[10, 11] In a prospective observational study of 100 eyes from 74 patients with glaucomatous optic neuropathy and a 24-2 VF test with mean deviation better than −6 dB, Traynis et al found that the 24-2 VF test failed to detect early glaucomatous damage in the central macula in 13 of 83 hemifields (15.7%) subsequently shown to be abnormal on 10-2 VF testing. Thus, the 10-2 VF test revealed abnormalities in 22.7% of the 22 eyes that appeared normal with 24-2 VF testing.[11] Among the abnormal hemifields on 10-2 VF testing, 68% were classified as arcuatelike, 8% as widespread, and 25% as other.[10, 11]


The exact cause of elevated IOP in POAG is not certain, although the role of accumulating mucopolysaccharides in the trabecular meshwork beams continues to be a focus of research.

In general, the physiologic chain of events that leads to glaucomatous optic nerve damage from pressure or other secondary mechanisms is unknown, although various theories, as described below, have been proposed.

The disease affects the individual axons of the optic nerve, which may die by apoptosis, also known as programmed cell death, as follows:

  • There has been some laboratory data that shows glutamate may play a role in glaucoma-related apoptosis, via neurotransmitter excitatory toxicity. However, so far, a human subject trial of the glutamate inhibitor (also referred to as an N-methyl D-aspartate [NMDA] inhibitor), memantine, has been unsuccessful in meeting its endpoints. To date, it has not been specifically approved by the US Food and Drug Administration (FDA) for the treatment of glaucomatous optic neuropathy. It is available in the United States and is approved for the treatment of other neurodegenerative diseases, such as certain types of dementia.

  • As a whole, the subjects in the memantine trial did not show a significant difference in their rates of progression whether on memantine or placebo. However, on further analysis of the different study population subgroups, those subjects with severe glaucomatous vision loss did possibly show a benefit on memantine. Future studies are needed to confirm, characterize, and quantify this potential benefit.

Other various theories (see Pathophysiology) have been advanced to explain the possible etiologic role of elevated IOP in glaucomatous optic neuropathy, as follows:

  • The mechanical compression theory suggests that elevated IOP causes a backward bowing of the lamina cribrosa, kinking the axons as they exit through the lamina pores. This may lead to focal ischemia, deprive the axons of neurotrophins, or interfere with axoplasmic flow, triggering cell death.

  • The vascular theories propose that cell death is triggered by ischemia, whether induced by elevated IOP or as a primary insult.

  • Other risk factors may play a role in the development of POAG, including a history of migraine headaches (a condition associated with vasospasm), cardiovascular disease, diabetes, systemic hypertension (leading to arteriosclerosis), and systemic hypotension (leading to decreased perfusion).

  • Genetic theories propose that cell death is triggered by genetic predisposition. Following the death of individual axons, substances may be released into the environment that causes a secondary triggering of apoptosis in neighboring cells, including glutamate (a neurotransmitter that may cause excitotoxicity), calcium, nitric oxide, and free radicals.

Glaucoma is not just a disease of IOP but rather a multifactorial optic neuropathy. However, patients with OHT who have IOP outside of the statistically normal range should continue to have periodic follow-up examinations, because they are always at risk for development of glaucoma. Consider the following:

  • Other causes for optic neuropathy should be considered in all patients with apparent normal-tension glaucoma, and appropriate lab or radiologic testing should be initiated if history and/or physical findings are suggestive.

  • Patients who do not have elevated IOP but glaucomatous optic discs or visual fields may have normal-tension glaucoma. It is a diagnosis of exclusion (after other causes for optic neuropathy, such as temporal arteritis, have been investigated and ruled out).

Several secondary causes of glaucoma must be considered before diagnosing POAG. These causes include the following (see also Differentials):

  • Exfoliation syndrome

  • Pigment dispersion syndrome (pigmentary glaucoma)

  • Lens-induced glaucoma

  • Ocular inflammatory diseases

  • Intraocular tumors

  • Raised episcleral venous pressure

  • Topical or systemic corticosteroid use

  • Syndromes (eg, Axenfeld-Rieger syndrome)

Patients with glaucoma should be asked about cognitive status, since an association between Alzheimer disease and glaucoma has been found.[5]


With poor control of IOP, continuing changes to the optic nerve and visual field occur.





Laboratory Studies

Patients suspected of having normal-tension glaucoma may need workup to rule out other causes for optic neuropathy, including, but not limited to, CBC, erythrocyte sedimentation rate (ESR), serology for syphilis (micro-hemagglutination-Treponema pallidum [MHA-TP], not Venereal Disease Research Laboratory [VDRL] test), and if suggested by the pattern of visual field loss, neuroimaging.

Progressive visual field loss in a patient with glaucoma is shown in the image below.

Example of progressive visual field loss over time Example of progressive visual field loss over time (from top to bottom) in a patient with glaucoma. Notice the early appearance of an inferior nasal step and arcuate loss, with progressive enlargement and increasing density of the scotomata over time. Courtesy of M. Bruce Shields, MD.

Some researchers have suggested an autoimmune etiology for some glaucomatous optic neuropathies and have identified monoclonal gammopathies. Serum protein electrophoresis can identify these rare individuals.

Imaging Studies

Fundus photography provides a permanent record of the appearance of the optic disc. Photographs taken over a period of time may be compared to track the progression of glaucoma.

The retinal nerve fiber layer sometimes can be imaged on high-contrast black and white film using red-free techniques. This can allow identification of nerve fiber layer defects that are characteristic of glaucomatous damage.

New techniques that use optical analysis of different physical properties of light can document the status of the optic nerve and the thickness of the nerve fiber layer, and they can be used to detect changes over time. The value of these technologies for diagnosing and following glaucoma over time continues to be an active topic of discussion and investigation. Modalities of the various technologies continue to be upgraded and enhanced, hopefully increasing the accuracy and likelihood of detecting glaucomatous damage.

Confocal scanning laser ophthalmoscopy (eg, HRT III) can examine the optic disc and peripapillary retina in 3 dimensions and provides quantitative information about the cup, neuroretinal rim, and contour of the nerve fiber layer. Increased resolution and software enhancements continue to improve this technology.

Scanning laser polarimetry (eg, GDX) measures the change in the polarization state of an incident laser light passing through the naturally birefringent nerve fiber layer to provide indirect estimates of peripapillary nerve fiber layer thickness. Improvements in neutralizing corneal light polarization (as opposed to that of the nerve fiber layer) have helped to decrease artifact in data obtained by this methodology.

Optical coherence tomography (eg, Stratus OCT) uses reflected light in a manner analogous to the use of sound waves in ultrasonography to create computerized cross-sectional images of the retina and optic disc, and it also gives quantitative information about the peripapillary retinal nerve fiber layer thickness. Newer increased resolution and three-dimensional spectral analysis hardware and software are also helping to propel this technology. Retinal nerve fiber layer (RNFL) thickness maps generated by spectral-domain OCT can help detect the progression of RNFL in glaucoma patients.[12]

For these technologies, continuing studies show good reproducibility over time for the same instrument. However, significant variability and fluctuating correlation between instruments is still noted, especially when compared with visual field testing results and other clinical examination findings. Therefore, testing results for each modality should be clinically confirmed by examination findings and other testing and not just singly used for clinical decision-making.[13]

The combination of structural and functional measurements with standard automated perimetry and optical coherence tomography performs better in estimating the rate of retinal ganglion cell loss in glaucoma patients than either measure alone.[14]

Fluorescein angiography, ocular blood flow analysis via laser Doppler flowmetry, color vision measurements, contrast sensitivity testing, and electrophysiological tests (eg, pattern electroretinograms) are used currently as research tools in the evaluation and management of patients with POAG. Routine clinical use is not advocated at this time.

Ultrasound biomicroscopy (UBM) may prove to be helpful in the future for obtaining a better view of the angle, iris, and ciliary body structures to rule out anatomical pathology and secondary causes of elevated IOP.

Other Tests

Other tonometric methods

Goldmann applanation tonometry is considered the criterion standard. However, Goldmann applanation is dependent on corneal rigidity, curvature, thickness (measured by pachymetry), and other biomechanical properties, so there is much room for error in patients with atypical corneas or other eye conditions. Particularly, with the advent of refractive corneal procedures, and the subsequent exponential increase of postsurgical eyes, the issue of tonometric accuracy is becoming more and more paramount.

Studies now strongly suggest that applanation pressures vary significantly depending on corneal thickness, as follows:

  • Some patients diagnosed with OHT actually may be normotensive when corrected for increased corneal thickness.

  • Some supposed glaucoma suspects or patients with apparent low-tension glaucoma (with normal range IOPs on applanation) can have abnormally thin corneas on pachymetry (central corneal thickness measurements); therefore, their IOP measurements are underestimated by applanation.

  • Corneal thickness plays a role in the development of glaucoma in those with OHT (see Mortality/Morbidity and image below).

Ocular hypertension study (OHTS). Percentage of pa Ocular hypertension study (OHTS). Percentage of patients who developed glaucoma during this study, stratified by baseline intraocular pressure (IOP) and central corneal thickness (CCT).

Previously used correction algorithms for adjusting IOP based on corneal thickness are not recommended, since viscoelastic properties of the cornea also play a role and there is no linear relationship between corneal thickness and IOP.

Other technology

Other technologies for measuring intraocular pressure continue to be studied to determine if they are more accurate than Goldmann tonometry. To date, none have been able to surpass it in accuracy for all patients; however, in the future, they may be useful for those who have abnormal pachymetry or other corneal properties. Their role is yet to be finalized.[15, 16, 17, 18] Two examples of new technology are described below.

The Ocular Response Analyzer (ORA)® from Reichert[19] uses a rapid air impulse and an electro-optical system to record two applanation pressure measurements; one measurement is while the cornea is moving inward, and the other measurement is as the cornea returns. Because of its biomechanical properties, the cornea resists the dynamic air puff, thereby causing delays in the inward and outward applanation events and resulting in two different pressure values. See the image below.

Intraocular pressure measurements. Adapted from Re Intraocular pressure measurements. Adapted from Reichert Ophthalmic Instruments, Ocular Response Analyzer, How does it work Web page.

The average of these two pressure values provides a repeatable, Goldmann-correlated IOP measurement. The difference between these two values is referred to as corneal hysteresis, which is a measurement of the corneal tissue properties that is a result of viscous damping in the corneal tissue. Low corneal hysteresis demonstrates that the cornea is less capable of absorbing (damping) the energy of the air pulse. There is good evidence that glaucoma progresses at a faster rate in patients who have low corneal hysteresis.

Some experts hypothesize that this is not primarily a function of corneal thinning, but rather a result of weakening of the tissue structure related to creation of the flap. Decreased corneal hysteresis may also play a role in indicating the presence or onset of other corneal tissue disorders.

The PASCAL Dynamic Contour Tonometer is a digital contact tonometer that directly measures IOP continuously based on a numeric output of IOP and ocular pulse amplitude (OPA). Unlike applanation tonometry, which is influenced by corneal thickness and other characteristics of the cornea, the PASCAL Dynamic Contour Tonometer provides a direct measurement of IOP, independent of interindividual variations in corneal properties and biomechanics, and also measures pulsatile pressure fluctuations caused by the change in ocular blood flow during systole versus diastole.[1, 19]

In cases of increased corneal or scleral rigidity (ie, S/P keratoplasty, scleral buckle), the newer methods, as described above, as well as other alternatives, such as pneumotonometry or Tono-Pen, may also be more accurate than applanation methods.

Other tests

Other tests of historical and research interest include the following:

  • Tonography, which has been used to help determine trabecular outflow facility, is primarily a research tool used in testing pharmacologic agents.

  • Provocative testing (eg, water-drinking test) was used in the past to try to differentiate who would develop early open-angle glaucoma. This test was of no aid in distinguishing those patients who would develop visual field defects from those who would not develop them.

Patients whose visual field defects seem to progress in a manner uncharacteristic of glaucoma should have a workup for other causes of visual loss.


See Surgical Care.



Medical Care

Major drug classes for medical treatment of POAG include the following: alpha-agonists, beta-blockers, carbonic anhydrase inhibitors, miotic agents, prostaglandin analogs, and rho kinase inhibitors.

Various classes of glaucoma medications, including adenosine analogs and nitric oxide–donating drops that aim at increasing trabecular outflow, are getting closer to FDA approval.

Medical marijuana is not indicated for glaucoma treatment, as marijuana lowers IOP minimally and its duration of action is very short. In the future, topical derivatives that affect cannabinoid M receptors governing aqueous dynamics may be effective, but this still is under early investigation.

The other drug classes mentioned above have much more documented duration of action and efficacy without the systemic cannabinoid adverse effects. Furthermore, other options to treat ocular pain from end-stage glaucoma have arisen (eg, trans-scleral or endoscopic cyclophotocoagulation, absolute alcohol [ethanol] or chlorpromazine retrobulbar injections), which directly and more effectively alleviate the problem than in the past when marijuana was used for eye pain from end-stage glaucoma.

Legal justification of glaucoma as an indication for systemic medical marijuana use is scientifically and medically improper, as well as unethical; education of the public and legislators is needed on this subject.

Some physicians incorrectly treat all elevated IOPs over 21 mm Hg with the above topical medications. Other physicians do not treat unless evidence of optic nerve damage exists, although nerve fiber layer loss of up to 40% may occur before visual field defects occur, so do not treat based on visual field testing alone. Most physicians select and treat those patients thought to be at greatest risk for POAG damage and/or progression (most common approach). See History for a list of risk factors for glaucomatous field loss.

In any case, the goal of treatment is reduction of the pressure before it causes progressive loss of vision. Considering the high average monthly cost of glaucoma medication, along with the possible risks of adverse effects or toxic reactions from drugs, inconvenience of use, and incidence of noncompliance, a strong reason not to treat indiscriminately exists.

Several questions should be asked when considering treatment, to include the following: Is the elevated pressure significant? Will this patient develop visual loss if left untreated? Is the treatment worth the risk for adverse effects of the medications?

One should consider treatment more strongly if the patient reliability or the consequences of missing field loss is an issue (eg, poor reliability on visual field examination, 1-eyed patient, poor availability for follow-up care, younger patient, patient whose optic nerve is difficult to visualize, history of vascular occlusion).

Treatment is highly recommended if signs of damage consistent with glaucomatous optic neuropathy (eg, disc hemorrhage; visible nerve fiber layer defects; notching or vertical ovalization of the cup; asymmetric cupping, especially if >0.7) are observed.

Progressive cupping, even in the absence of visual field loss, can be glaucoma and should be treated as such, although systemic and neurologic workup/correlation for other disorders, including possible neuroimaging studies, should be considered, particularly if there are other nonophthalmologic symptoms. Otherwise, it depends on the assessment of risk factors and benefit of therapy to the patient, as to whether therapy should be initiated.

Discussion with the patient about the pros and cons of treatment versus observation should be completed. Individualization of therapy is the key; an ideal pressure in one patient may cause glaucomatous damage in another patient. Risk factors, systemic conditions, life expectancy of the patient, quality of life issues, and the patient's desire for therapy should be weighed when considering treatment.

Due to the high risk for optic nerve damage, most ophthalmologists treat if pressures are consistently above 28-30 mm Hg. If treatment is based on a high IOP only, then it should be ensured that the risks of treatment do not exceed the risk of the disease. Other reasons to treat include such symptoms as halos, blurred vision, pain, or recent elevation of IOP, with continuing elevation on successive visits.

Initiation of a monocular trial (see Medication) may be useful in helping to decide whether or not to treat (ie, if the medication is effective in achieving good pressure reduction without adverse effects, which may argue in favor of treatment, instead of just observation).

Considering all the above, no consensus exists on what is the appropriate medical treatment for preventing or delaying the damage due to POAG when a patient has only elevated IOP and no other signs of POAG. No one has been able to define conclusively which subgroups will develop damage if left untreated, as opposed to those who will not sustain damage even if not treated.

The question of medical therapy versus observation in patients with solely elevated IOP is being addressed in the OHTS, an ongoing multicenter randomized clinical trial. The OHTS is a multicenter, prospective, randomized, controlled, clinical trial studying over 1600 participants to evaluate the safety and efficacy of medical treatment in preventing or delaying onset of visual field loss and/or optic nerve damage in patients with OHT who are at moderate risk of developing POAG. Their medical therapy goal for the treated group is stepped therapy to reduce IOP by at least 20% from the average baseline IOP with its treated absolute value of 24 mm Hg or less. So far, their results show a 10% risk over 5 years of developing glaucoma in those patients with baseline IOP of 24-31 mm Hg. This risk was reduced to 5% with medical therapy. The OHTS has also revealed the importance of pachymetry as a diagnostic tool as well as in the workup.

Several sources agree on this initial goal of 20-25% reduction, whereas some specialists feel that more absolute numbers of less than 15 should be the goal of treatment. Keep in mind that the IOP goal must be set independently for each patient, depending on the risk factors, as an IOP level for one person with minimal risk factors may be far too high for a patient with multiple risk factors for sustaining glaucomatous damage.

Other regimens have been suggested, as follows: for minimal risk factors, consider lowering IOP by 20-30%; if moderate number of risk factors are present, lower by 30-40%; and in cases of numerous risk factors with markedly elevated pressures, reduction in the 40-60% range may need to be achieved to prevent neuronal loss.

If the patient is older than 65 years, consider treatment to keep IOP 25 mm Hg or less, secondary to 3% risk for vascular occlusion in patients with OHT.

In any case, the target IOP should be reevaluated periodically, and regular review of IOP trends should be performed to determine whether the patient is consistently maintaining that goal.

According to Preferred Practice Patterns published by the American Academy of Ophthalmology, the interval between follow-up visits should be determined based on whether the target IOP has been achieved and whether glaucoma is progressing. If there is progression, treatment should be adjusted and the patient should be monitored every 1-2 months. If there is no progression but IOP is not at target, follow-up visits every 3-6 months are appropriate. If there is no progression and the IOP is at target, follow-up visit intervals can be extended to 6-12 months.

Other caveats concerning follow-up care are as follows:

  • If a new visual field defect becomes apparent on testing, confirmation with repeat (possibly multiple) examinations during future office visits should be performed, before using it as a basis for the treatment of presumed progression of POAG.

  • Gonioscopy should be performed at least once every 1-2 years if a significant increase in IOP occurs, or if miotic therapy is instituted.

  • Optic disc photos should be repeated after the initial examination if a change in disc appearance is noted (or every 1-2 years if available). Considerations are as follows:

    • Technologic and financial barriers, as well as increasing lack of trained ophthalmic staff, are making optic disc photos more difficult to obtain in many practices.

    • Whether nerve fiber layer imaging technologies (instead of recurring, serial optic disc photos) are sufficient for mainstream nontertiary ophthalmology practices remains under debate.

Retinal tomography, ocular coherence tomography, and/or laser polarimetry should be measured at baseline and then every 6-12 months. Results should be correlated with visual field results, IOP measurements, and examination findings.

Surgical Care

Surgery is indicated when glaucomatous optic neuropathy worsens (or is expected to worsen) at any given level of IOP and the patient is on maximum tolerated medical therapy (MTMT).

MTMT varies considerably between individuals, and it may consist of medicines from 1 or several classes (including a beta-adrenergic antagonist, a prostaglandin agent, an alpha-agonist, and a topical carbonic anhydrase inhibitor). Some patients are observed to progress simply because adherence to the medical regimen becomes too difficult because of the following: high drug costs, inability to remember the schedule of multiple medications, inability to instill them in the eyes properly secondary to arthritis or other incapacitation (especially common among elderly patients or those with other chronic systemic conditions), or intolerable ocular and systemic adverse effects.

A brief mention of surgical options is listed below. Detailed information on surgical procedures, indications, and postoperative care is beyond the scope of this chapter.

Argon laser trabeculoplasty

Argon laser trabeculoplasty (ALT) uses a laser beam focused through a goniolens to treat at the border between anterior and posterior trabecular meshwork. A full treatment consists of 100 spots placed over the entire 360 degrees of the trabecular meshwork. This may be divided between 2 sessions consisting of 50 spots over 180 degrees.

Aqueous outflow improves after the procedure.

The specific mechanism of this improved outflow is unknown, but one hypothesis is up-regulation of trabecular endothelial cells.

IOP reduction obtained is usually in the 7-10 mm Hg range, and it may last up to 3-5 years following ALT.

A study by Heijl et al studied patients with low IOP levels before ALT. The study found that IOP before ALT significantly influenced the IOP reduction produced by ALT, in that a much larger decrease was observed in eyes with higher IOP before ALT.[20]

Unfortunately, the decrease in IOP usually is not permanent. Approximately 10% of treated patients will return to pretreatment IOP for each year following treatment.

Complications include a brief, but potentially significant, increase in IOP after the procedure (therefore, alpha-agonists often are used either preoperatively or postoperatively for prophylaxis of this occurrence); transient iritis or corneal opacities; peripheral anterior synechiae; and hyphema.

ALT usually is pursued after MTMT has been reached, but it may be performed sooner in the treatment algorithm if pseudoexfoliation or pigmentary glaucoma is present, or if the patient is of Black ethnicity, because laser therapy may be most effective in these individuals.

Selective laser trabeculoplasty

Selective laser trabeculoplasty (SLT) uses a Q-switched 532 Nd:YAG laser to selectively target pigmented cells of the trabecular meshwork in a nonthermal manner, increasing fluid outflow and thereby lowering IOP.

The 3-nanosecond high-energy specific wavelength of light used induces the same cell replacement mechanism as traditional ALT but without the destructive burning and obliteration of structural support tissue in the meshwork. The short pulse of the laser does not allow time for heat to spread to other cells. SLT delivers just enough energy to the trabecular meshwork to target specific melanin-rich cells, without incurring collateral thermal damage and scarring to adjacent nonpigmented trabecular meshwork cells and underlying trabecular beams. When treated with SLT, a primarily biologic response is induced in the trabecular meshwork that involves the release of cytokines that trigger macrophage recruitment as well as other changes leading to IOP reduction.

The laser beam bypasses surrounding tissue leaving it undamaged by light. Unlike ALT, SLT can be repeated several times. Whereas patients treated with ALT can receive only 2 treatments in their lifetime, patients treated with SLT can receive more than 2 lifetime treatments.

SLT requires a specially designed laser, as follows:

  • A short pulse to allow for thermal relaxation

  • Precise wavelength for optimal melanin absorption

  • Sufficient energy to heat melanin to the point that it releases cytokines

  • Sufficient spot size to ensure full coverage at the trabecular meshwork


Trabeculectomy surgery usually is performed after MTMT and ALT have failed to control IOP adequately. If IOP is so high that ALT and SLT are likely to be ineffective in reaching target IOP, then proceeding from MTMT to penetrating surgery may be indicated.

A superficial flap of sclera is dissected anteriorly to the trabecular meshwork, and a section of trabecular meshwork is removed underneath the flap.

This alternate outflow pathway is created to increase passage of aqueous from the anterior chamber to the subconjunctival space, creating a filtering bleb and, thereby, lowering IOP.

Either releasable sutures or laser suture-lysis may be used to control aqueous drainage and corresponding IOP postoperative. Alternatively, to maximize surgical success, antimetabolites (eg, 5-fluorouracil, mitomycin C) may be applied during or after surgery to decrease fibroblast proliferation and scar formation.

Risks and complications of filtering surgery include the following: hypotony, blebitis/endophthalmitis, hyphema, suprachoroidal hemorrhage or effusions, encapsulation of the bleb with resultant transient IOP elevation, loss of 1 or more lines of visual acuity, and increased risk of cataract formation.

With the risk of severe complications from trabeculectomy and the need for frequent postoperative follow-up care (ie, usually weekly for 1 month, initially), some patients with transportation, financial, or long-distance issues concerning postoperative follow-up care may be better served by tube shunt surgery instead. See the Tube versus Trabeculectomy Study below.

Vision loss may be a serious complication after trabeculectomy, with severe and ongoing unexplained loss ("snuff-out") experienced by as many as 2% of patients. Attendant risk factors such as split fixation on visual fields prior to surgery, preoperative number of quadrants with split fixation, and postoperative choroidal effusions with eventual resolution are possible.[21]

Drainage implant (ie, seton/tube/shunt) surgery

Generally, this procedure is performed after multiple attempts at successful trabeculectomy have failed.

A tube is placed in the anterior chamber to shunt aqueous to an equatorial reservoir, and then posteriorly to be absorbed in the subconjunctival space.

Types of implants include Molteno, Baerveldt, Ahmed, and Krupin, as follows:

  • Most shunts function by allowing passive drainage of aqueous from the anterior chamber.

  • The Molteno implant consists of a silicone drainage tube, which is connected to 1 or 2 acrylic plates that are sutured to the sclera.

  • The Baerveldt implant is available with larger plates with increased reservoir size. The seton (tube) connected to the reservoir usually is tied off with an absorbable suture, allowing flow to initiate 4-6 weeks postoperative once some conjunctival wound remodeling has taken place, thereby reducing the risk for immediate postoperative hypotony.

  • The Ahmed and Krupin implants have 1-way valves, which are designed to maintain pressure above 8 mm Hg. These implants may reduce the risk for hypotony, a complication of nonvalved shunts in the early postoperative period.

Because of less numerous postoperative visits, tube shunts may be indicated as primary surgery when patients are unable to come as frequently for follow-up care (because of transportation, financial, or long-distance issues). This can be a particular concern in rural areas that cover large distances.

A valved shunt may also be indicated as primary surgery if a patient has a strenuous job or other activities that require strenuous exertion. Severe exertion may cause a significant Valsalva maneuver, significantly increasing venous pressure postoperatively, which could result in a delayed suprachoroidal hemorrhage and possible severe loss of vision.

The Tube versus Trabeculectomy Study has been undertaken to see if glaucoma tube shunt surgery may actually be a viable first-line alternative to (or even surpass) trabeculectomy surgery.

One-year data have shown nonvalved tube shunt surgery was more likely to maintain IOP control and to avoid persistent hypotony or reoperation for glaucoma than trabeculectomy at 1 year, although both procedures produced similar IOP reduction. Failure rates during 5 years of follow-up were 29.8% in the tube group and 46.9% in the trabeculectomy group.

Less supplemental medical therapy has been needed in the trabeculectomy group at 1 year; however, at 5 years, there was no difference.

The incidence of postoperative complications at 1 year was higher in the trabeculectomy group. Serious complications resulting in reoperation and/or vision loss occurred with similar frequency in both groups at 1 year. The reoperation rate for IOP reduction was higher in the trabeculectomy group than in the tube group at 5 years.

Ciliary body ablation

Postoperative pain and inflammation are common complaints. Loss of 1 or more lines of visual acuity has been reported. Phthisis is a concern after this procedure, although it has not been reported as of yet after the diode laser method of cycloablation.

This procedure is indicated as a last resort for patients who have failed medical management and other surgeries or for those patients who have limited visual potential (often 20/200 or less).

By destroying a portion of the nonpigmented ciliary epithelium, aqueous humor production is limited.

The ciliary body epithelium can be destroyed by cyclocryotherapy, diathermy, ultrasound, transscleral Nd:YAG or diode laser (known as cyclophotocoagulation), or a newer endoscopic laser (EndoOptiks, Inc).[22]

Several of the newer surgical procedures are promising, but many ideas have been tried before and few have stood the test of time. Generally, the less complications, the less effective in lowering IOP. There is the possibility that visual loss can be better prevented, with fewer complications, and treatment can be tailored to the individual patient. If simple, safe procedures become available, surgery could be performed earlier in the disease process and adherence to medications could become less problematic.

The ideal glaucoma procedure would use the healthy portions of the outflow system and bypass the diseased portions; control IOP without infection and other risks of a thin-walled bleb; reduce the risk of hypotony during the perioperative period, with less postoperative care management and complications, as compared with trabeculectomy and setons; and provide adequate IOP control for the life of the patient.

Many innovative glaucoma surgical techniques and devices are on the horizon. Interest in this new frontier is because of the lack of an existing, ideal glaucoma procedure despite decades of research. Many devices are not yet approved by the FDA for use in the United States.

Newer techniques

Deep sclerectomy/viscocanalostomy/with or without collagen implant – This is probably not as effective as trabeculectomy and is technically more difficult, but it is associated with less complications.

360-degree suture canaloplasty (iScience) – This is a useful alternative in infants (with congenital glaucoma or juvenile glaucoma) to trabeculotomy. In adults, suture under tension left in the Schlemm canal to further open the trabecular meshwork (similar mechanism to miotics).

New devices

New devices are as follows:

ExPress shunt® (Alcon) 

Considerations include the following:

  • Erosion problems if used without scleral flap
  • Now mainly used underneath trabeculectomy flap to better regulate flow through sclerostomy
  • Advantage of avoiding surgical iridectomy in patients at high risk of bleeding
  • Easy to learn, appears effective, and complication rate that is similar to that of trabeculectomy

iStent® (Glaukos) 

Considerations include the following:

  • Shunt device from the anterior chamber into the Schlemm canal
  • Internal placement approach in association with cataract surgery
  • May need multiple devices placed
  • Still undergoing continuing research for long-term results

Cypass Microstent® (Alcon)

Considerations include the following:

  • Shunt device from the anterior chamber into the suprachoroidal space
  • Internal placement approach
  • Recently approved by the FDA

Solx® gold suprachoroidal space microshunt (Solx) 

Considerations include the following:

  • Shunts fluid from the anterior chamber into the suprachoroidal space via gold microchannels
  • External placement approach
  • Possibly titratable effect with titanium-sapphire laser to modify microchannel size
  • US clinical trials are ongoing

Trabectome® (NeoMedix) 

Considerations include the following:

  • FDA approved
  • Ablates all of the trabecular meshwork for 90 degrees to 180 degrees via electrocautery and aspiration of the internal wall of the Schlemm canal
  • Similar idea to goniotomy but prevents rescarring of the Schlemm canal edges, as all tissue is removed
  • May have a place between trabeculoplasty and anterior filtering operations
  • Safer than trabeculectomy or tube shunt but may be less effective
  • Needs more long-term data on complication rate and persistence of effect


Neuro-ophthalmology consultation may have a role in those patients who are experiencing progressive visual loss that does not appear to follow a typical glaucomatous pattern or if there are systemic symptoms or complaints.

A neurologist should be consulted for patients with glaucoma who exhibit signs of cognitive dysfunction, since an association between Alzheimer disease and glaucoma has been found.[5]


Some studies show that a moderate amount of exercise can decrease IOP in both POAG patients and normal individuals. Whether it results in actual long-term IOP control and prevention of visual loss has yet to be determined.

Long-Term Monitoring

Depending on the amount of optic nerve damage and level of IOP control, patients with POAG may need to be seen from every 2 months to yearly, even sooner if a marked lack of IOP control is present. Follow-up studies/examinations should be performed as detailed under Treatment.

Glaucoma still should be a concern in people with elevated IOP in the presence of normal discs and visual fields or in people who have normal IOP with suspicious-looking discs and fields. These patients should be observed closely, because they are at an increased risk for development of glaucomatous damage. SWAP visual field testing may also play a role, because it may help detect visual field defects earlier in these otherwise healthy patients.



Medication Summary

Medical therapy is limited toward lowering IOP. A rational approach to choosing antiglaucoma medications should minimize the number of medications and the probability of significant adverse effects. The ideal drug for treatment of POAG should have the following characteristics: (1) effectively lower IOP, (2) no adverse effects or systemic exacerbation of disease, and (3) inexpensive with once-a-day dosing. However, because no medicine possesses all the above, these qualities must be prioritized based on the patient's individual needs and risks; then, therapy should be chosen accordingly.

Once a medicine has been initiated, close follow-up care should be performed to assess its effect. Initial follow-up care should be performed 3-4 weeks after the beginning of therapy. IOP should be rechecked at the drug's peak and trough times to see if the target IOP has been reached and is maintained throughout the day. Look for signs of allergy (eg, hyperemia, skin rash, follicular reaction). Inform the patient of systemic adverse effects and symptoms that may occur. Treatment should be continued if a therapeutic trial has shown effective lowering of IOP without adverse effects. Reevaluation should be performed 2-4 months later depending on the clinical picture. 

A monocular therapeutic trial should be considered when first initiating the medical therapy, as the other eye's IOP can be used as a baseline control to gauge effect of a medication (particularly useful in patients with a widely fluctuating diurnal curve). A difference of more than 4 mm Hg between the 2 eyes posttreatment is strongly suggestive of a clinical effect. However, some agents (especially beta-blockers) may have crossover effects on the other eye even with monocular treatment, so clinical correlation must be kept in mind. If monocular therapy is found to be effective, then initiation of binocular therapy may be considered.

Some medications (eg, latanoprost, brimonidine) may have an effect that plateaus at 6-8 weeks in certain patients; keep this effect in mind when scheduling further follow-up examinations. Other patients will be nonresponders to some therapies. If this occurs, the medication should be discontinued and a new drug initiated. While discontinuing or changing therapies, keep in mind that many drugs have a wash-out period of up to 2-4 weeks (especially beta-blockers), during which they may still have some IOP-lowering effect or residual systemic response.

If one medication is not adequate in reaching the target pressure, a second medication should be chosen that has a different mechanism of action, so that the 2 drug therapies will have an additive effect. (Usually, no additive effect is seen if 2 medications from the same drug class are used.)

The fixed-dose combination of a Rho-kinase inhibitor and a prostaglandin F2-alpha analogue (netarsudil/latanoprost) was approved by the FDA in 2019. Approval of netarsudil/latanoprost ophthalmic was based on 2 phase 3 trials, MERCURY 1 (n=718) and MERCURY 2 (n=750). The studies compared the mean IOP after 3 months of once-daily ophthalmic administration of netarsudil/latanoprost, netarsudil, or latanoprost. Patients who received the netarsudil/latanoprost combination achieved an average of 1-3 mm Hg lower mean IOP compared with netarsudil or latanoprost monotherapy. Nearly twice as many patients taking the combination achieved a diurnal IOP of 16 mm Hg or less, and nearly 3 times as many reached 14 mm Hg or lower compared with latanoprost.[23]

A specific plan of pharmacotherapy should be administered only after the possible effects of the systemic medications that a patient is taking (eg, beta-blockers, calcium channel blockers, ACE inhibitors) have been taken into consideration.

Before mention of particular medications currently used in most practices, note that as the mechanisms of axonal death by apoptosis are becoming better understood, therapies are being developed to protect nerve fibers from undergoing injury and death by several possible theoretical mechanisms. This halting of processes that is believed to contribute to ganglion cell death in glaucoma has been termed neuroprotection, and several new pharmaceuticals are being developed that hopefully will work in this manner. Agents under investigation as neuroprotective include glutamate receptor blockers, calcium channel blockers, inhibitors of nitric oxide synthase, free radical scavengers, and drugs to increase blood flow to the optic nerve.

See Ocular Hypertension and AAO monograph #13 for further in-depth descriptions of particular drugs.

Beta-adrenergic blockers

Class Summary

Topical beta-adrenergic receptor antagonists decrease aqueous humor production by the ciliary body. Adverse effects are due to systemic absorption of the drug, decreased cardiac output, and bronchoconstriction. In susceptible patients, this may cause bronchospasm, bradycardia, heart block, or hypotension. The patient's pulse rate and blood pressure also should be monitored if symptoms emerge after initiation of treatment. Patients may be instructed to perform punctal occlusion after administering the drops to reduce systemic absorption. Depression or anxiety may be experienced in some patients, and sexual dysfunction may be initiated or exacerbated. Ocular adverse effects may include blurred vision, eye ache, and corneal anesthesia.

Levobunolol (Betagan)

Nonselective beta-adrenergic blocking agents that lower IOP by reducing aqueous humor production.

Timolol (Timoptic XE, Istalol, Betimol)

Nonselective agents that may reduce elevated and normal IOP, with or without glaucoma, by reducing production of aqueous humor.

The brands Timoptic XE and Istalol are both administered once daily. However, Timoptic XE is a gel-forming solution, while Istalol is an aqueous solution.

Carteolol ophthalmic

Blocks beta1- and beta2-receptors and has mild intrinsic sympathomimetic activity (ISA), with possibly fewer cardiac and lipid profile adverse effects.

Betaxolol ophthalmic (Betoptic S)

Beta1-selective adrenergic antagonist, with possibly less pulmonary effects than nonselective agents. IOP-lowering effect is slightly less than nonselective beta-blockers.

Metipranolol hydrochloride

Beta-adrenergic blocker that has little or no intrinsic sympathomimetic effects and membrane stabilizing activity. Has little local anesthetic activity. Reduces intraocular pressure by reducing production of aqueous humor.

Alpha2 Agonists, Ophthalmic

Class Summary

Alpha2-adrenergic agonists work by decreasing aqueous production. Systemic adverse effects include dry mouth, fatigue, and drowsiness. Ocular adverse effects include allergic (follicular) conjunctivitis and contact dermatitis.

Of this class, the alpha2-selective agonist, brimonidine, is used most commonly to treat POAG. Apraclonidine also is alpha2-selective but is believed to have more of an allergic potential; therefore, it is used less commonly as a long-term medication.

Brimonidine (Alphagan-P)

Lowering of IOP of up to 27% reported. Bid dosing used initially, especially if in combination with other classes of agents. Three times per day dosing used most often in single-agent therapy that does not adequately control IOP with twice daily dosing. A moderate risk of allergic response to this drug exists. Caution should be used in individuals who have developed an allergy to Iopidine.

The brand Alphagan-P contains the preservative Purite and has been shown to be much better tolerated than its counterpart Alphagan or generic brimonidine.

Apraclonidine (Iopidine)

Reduces IOP whether or not accompanied by glaucoma. Selective alpha-adrenergic agonist without significant local anesthetic activity. Has minimal cardiovascular effect.

Carbonic anhydrase inhibitors

Class Summary

Reduce secretion of aqueous humor by inhibiting carbonic anhydrase (CA) in the ciliary body. In acute angle-closure glaucoma, administer systemically; apply topically in patients with open-angle glaucoma. These drugs are less effective, and their duration of action is shorter than many other classes of drugs. Adverse effects are relatively rare but include superficial punctate keratitis, acidosis, paresthesias, anorexia, nausea, depression, dysgeusia, and lassitude.

Oral agents, such as acetazolamide and methazolamide, primarily are used only for the treatment of refractory POAG and secondary glaucomas because they have increased systemic adverse effects. However, oral CAIs can have a slightly greater effect than topical CAI medications and are appropriate to use in certain clinical situations. The mechanism of IOP reduction is similar to other CAIs, being accomplished by reduction of bicarbonate accumulation in the posterior chamber, with a resultant decrease in sodium and associated fluid movement linked to the bicarbonate ion. An additional IOP-lowering effect exists by the creation of a relative metabolic acidosis.

Dorzolamide (Trusopt)

More commonly used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one ophthalmic drug is being used, administer drugs at least 10 min apart. Either drug reversibly inhibits CA, reducing hydrogen ion secretion at renal tubule, and increases renal excretion of sodium, potassium bicarbonate, and water to decrease production of aqueous humor.

Brinzolamide (Azopt)

Catalyzes reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. May use concomitantly with other topical ophthalmic drug products to lower IOP.

May cause less ocular discomfort on instillation, secondary to a buffered pH, but can still cause foreign body sensation.

If more than one topical ophthalmic drug being used, administer drugs at least 10 min apart.

Acetazolamide (Diamox)

Reduces rate of aqueous humor formation by direct inhibition of enzyme carbonic anhydrase (CA) on secretory ciliary epithelium, causing in turn a reduction in intraocular pressure (IOP). More than 90% of CA must be inhibited before IOP reduction can occur. May reduce IOP by 40-60%. Effects are seen in about an hour, they peak in 4 h, and trough in about 12 h. The usual maximum dose is 250 mg QID for tablets or 500 mg BID for long-lasting sequel capsules. It is derived chemically from sulfa drugs; however, cross-reaction allergy between sulfa-derived antibiotic and diuretic is not very common.

Used for adjunctive treatment of chronic simple (open-angle) glaucoma and secondary glaucoma and preoperatively in acute angle-closure glaucoma when delay of surgery desired to lower IOP


Reduces aqueous humor formation by inhibiting enzyme carbonic anhydrase, which results in decreased IOP.

Antiglaucoma, Combos

Class Summary

Combination solution may further decrease aqueous humor secretion compared to each solution used as monotherapy, while improving compliance.

Timolol and brimonidine (Combigan)

Brimonidine is a selective alpha2 adrenergic receptor agonist and timolol is a nonselective beta-adrenergic receptor inhibitor. Each of these agents decrease elevated IOP, whether or not associated with glaucoma.

Timolol and dorzolamide (Cosopt, Cosopt PF)

Dorzolamide is a carbonic anhydrase inhibitor that decreases aqueous humor secretion, causing a decrease in IOP. This agent presumably slows bicarbonate ion formation with subsequent reduction in sodium and fluid transport. Timolol is a nonselective beta-adrenergic receptor blocker that decreases IOP by decreasing aqueous humor secretion.

Both agents administered together bid may result in additional IOP reduction compared with either component administered alone, but reduction is not as much as when dorzolamide tid and timolol bid are administered concomitantly.

Brinzolamide and brimonidine (Simbrinza)

This combination product contains the carbonic anhydrase inhibitor brinzolamide and the alpha2 adrenergic receptor agonist brimonidine. It is indicated for reduction of elevated intraocular pressure in patients with primary open-angle glaucoma.

Latanoprost/netarsudil ophthalmic (Rocklatan)

Fixed-dose combination of a Rho-kinase inhibitor and a prostaglandin F2-alpha analogue. Each drug increases outflow of aqueous humor and thereby lowers IOP. The ophthalmic combination is indicated for reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

Miotic agents (parasympathomimetics)

Class Summary

Miotics work by contraction of the ciliary muscle, tightening the trabecular meshwork and allowing increased outflow of aqueous through traditional pathways. Miosis results from action of these drugs on the pupillary sphincter. Adverse effects include brow ache, induced myopia, and decreased vision in low light. These agents are used less commonly today since the advent of newer drugs with fewer adverse effects.

Pilocarpine is one of the more commonly used agents in this class. Less frequently used miotics include phospholine iodide (0.03%, 0.06%, 0.125%, 0.25% qd/bid) and carbachol (0.75%, 1.5%, 3% tid/qid).

Pilocarpine ophthalmic (Isopto Carpine)

A naturally occurring alkaloid, pilocarpine mimics the muscarinic effects of acetylcholine at postganglionic parasympathetic nerves. Directly stimulates cholinergic receptors in the eye, decreasing resistance to aqueous humor outflow.

Instillation frequency and concentration are determined by patient's response. Individuals with heavily pigmented irides may require higher strengths.

If other glaucoma medication also is being used, at bedtime, use gtt at least 5 min before gel.

Patients may be maintained on pilocarpine as long as IOP is controlled and no deterioration in visual fields occurs.

May use alone or in combination with other miotics, beta-adrenergic blocking agents, epinephrine, CAIs, or hyperosmotic agents to decrease IOP. Use with prostaglandin analogs can have a small additive effect.

Prostaglandin analogs

Class Summary

Increase uveoscleral outflow of aqueous. One mechanism of action may be through induction of metalloproteinases in the ciliary body, which breakdown the extracellular matrix, thereby reducing resistance to outflow through the uveoscleral pathway. Can be used in conjunction with beta-blockers, alpha-agonists, or topical CAIs. Many patients respond well to these agents; other patients do not respond at all. Adverse effects include conjunctival hyperemia, iris pigmentation, CME, and uveitis.

Latanoprost (Xalatan, Xelpros)

Decreases IOP by increasing outflow of aqueous humor through uveoscleral pathways.

Bimatoprost (Lumigan)

Prostaglandin agonist that selectively mimics effects of naturally occurring substances, prostamides. Exact mechanism of action unknown but believed to reduce IOP by increasing outflow of aqueous humor through trabecular meshwork and uveoscleral routes. Used to reduce IOP in open-angle glaucoma or ocular hypertension.

Bimatoprost ophthalmic implant (Durysta)

Intracameral implant indicated to reduce IOP in patients with open-angle glaucoma or ocular hypertension. Provides sustained IOP lowering.

Travoprost (Travatan-Z)

Prostaglandin F2-alpha analog and selective FP prostanoid receptor agonist. Exact mechanism of action unknown but believed to reduce IOP by increasing uveoscleral outflow.

Tafluprost (Zioptan)

Tafluprost is a preservative-free, topical, ophthalmic prostaglandin analog indicated for elevated IOP associated with open-angle glaucoma or ocular hypertension. The exact mechanism by which it reduces IOP is unknown, but it is thought to increase uveoscleral outflow.

Latanoprostene bunod ophthalmic (Vyzulta)

The first prostaglandin analog with nitric oxide (NO) as one of its metabolites is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Latanoprostene bunod is believed to lower intraocular pressure by increasing outflow of aqueous humor through the trabecular meshwork and uveoscleral routes. Intraocular pressure is a major risk factor for glaucoma progression. Reduction of intraocular pressure reduces risk of glaucomatous visual field loss.

Omidenepag isopropyl ophthalmic (Omlonti)

Indicated to reduce elevated intraocular pressure (IOP) in adults with open-angle glaucoma. Selective prostaglandin (EP2) receptor agonist that decreases IOP, possibly by increasing uveoscleral outflow. Additionally, prostaglandin-associated periorbitopathy in patients with glaucoma is not associated with EP2 receptor agonists, but has been a cosmetic problem with prostaglandin F receptor (FP) agonists. Alleviation of periorbitopathy symptoms after switching from an FP agonist to omidenepag isopropyl has been observed. 

Rho Kinase/Norepinephrine Transporter Inhibitor

Class Summary

These agents increase aqueous humor outflow through the trabecular meshwork route. In December 2017, the FDA approved netarsudil, a first-in-class inhibitor of rho kinase and norepinephrine transporter, for the treatment of elevated intraocular pressure (IOP) caused by open-angle glaucoma or ocular hypertension. Approval was based on 2 phase III clinical trials (Rocket 1 and Rocket 2), which enrolled 1,167 patients. Patients were randomized to receive netarsudil once daily (Rocket 1 or Rocket 2) or BID (Rocket 2 only). Timolol was dosed BID in both studies. Treatment with netarsudil once daily produced clinically and statistically significant reductions of IOP from baseline (P< 0.001) and was noninferior to timolol in the per-protocol population with maximum baseline IOP < 25 mm Hg in both studies.[24]

Netarsudil ophthalmic (Rhopressa)

Indicated for the reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension.

Hyperosmotic agents

Class Summary

These agents are used infrequently, most commonly to reduce extremely elevated IOP in acute situations of angle-closure or certain secondary glaucomas, or selectively as a preoperative measure before intraocular surgery.

Osmotics lower IOP by increasing the osmotic gradient between the blood and ocular fluids, resulting in loss of water from the eye (especially the vitreous) into the hyperosmotic blood plasma, with concomitant lowering of IOP, but an increase in intravascular volume. Therefore, care should be used in any patient with cardiac, renal, or hepatic abnormalities.

Systemic adverse effects include nausea, vomiting, headache, increased thirst, chills, fever, confusion or disorientation, electrolyte imbalances, and urinary retention.

Isosorbide dinitrate (Dilatrate-SR, Isordil Titradose)

In the eyes, may create an osmotic gradient between plasma and ocular fluids and induce diuresis by elevating osmolarity of glomerular filtrate. Effects may, in turn, inhibit tubular reabsorption of water. Treatment is preferred when less risk of nausea and vomiting than that posed by other oral hyperosmotic agents desired. Palatability best if poured over ice before ingestion. May use in patients with diabetes.

Mannitol (Osmitrol, Resectisol)

Reduces elevated IOP when the pressure cannot be lowered by other means.

Initially assess for adequate renal function in adults by administering a test dose of 200 mg/kg, given IV over 3-5 min. Should produce a urine flow of at least 30-50 mL/h of urine over 2-3 h.

In children, assess for adequate renal function by administering a test dose of 200 mg/kg, given IV over 3-5 min. Should produce a urine flow of at least 1 mL/h over 1-3 h.

The 20% w/v solution most commonly is used IV. Alternatively, concentrations of 10%, 15%, or 25% may be used.

NMDA Antagonists

Class Summary

Neuroprotection in glaucoma has been aimed at protecting those neurons that are damaged or likely to be damaged in glaucomatous optic neuropathy, which consists of neurons along the entire visual pathway, chiefly the retinal ganglion cells (RGC) axons. Using an NMDA antagonist may prevent RGC loss where excitotoxicity, resulting from NMDA receptor overactivation, is implicated.

Memantine (Namenda, Namenda XR)

Memantine is a noncompetitive, low-affinity, open channel blocker that exhibits selective blockade of the excessively open channels with a fast-off rate, thus inhibiting excessive N-methyl-D-aspartate (NMDA) receptor activity while maintaining normal neuronal cell function as it does not accumulate significantly within the channel.

Indicated for moderate-to-severe Alzheimer disease; memantine failed initial phase III trial endpoints for glaucoma indication, although subgroup analysis shows possible efficacy for patients with severe visual loss from glaucoma; possible neuroprotective systemic treatment of glaucoma, although as of now, this is a non-FDA approved off-label use of the drug.


Questions & Answers


What is primary open-angle glaucoma (POAG)?

What are the signs and symptoms of primary open-angle glaucoma (POAG)?

What is the focus of clinical history in the evaluation of primary open-angle glaucoma (POAG)?

Which patient groups should be screened for primary open-angle glaucoma (POAG)?

What is included in the physical exam for primary open-angle glaucoma (POAG)?

What is the role of lab testing in the diagnosis of primary open-angle glaucoma (POAG)?

Which imaging studies are performed in the workup of primary open-angle glaucoma (POAG)?

How is primary open-angle glaucoma (POAG) treated?

Which medications are used in the treatment of primary open-angle glaucoma (POAG)?

What is the role of laser therapy in the treatment of primary open-angle glaucoma (POAG)?

What is the role of surgery in the treatment of primary open-angle glaucoma (POAG)?

Which surgical treatments are used for primary open-angle glaucoma (POAG)?

Which minimally invasive glaucoma surgery (MIGS) techniques are used for the treatment of primary open-angle glaucoma (POAG)?

What is primary open-angle glaucoma (POAG)?

What is the pathophysiology of primary open-angle glaucoma (POAG)?

How is intraocular pressure (IOP) used in the categorization and treatment of primary open-angle glaucoma (POAG)?

What are the limitations of a visual field exam in the diagnosis of primary open-angle glaucoma (POAG)?

What causes increased intraocular pressure (IOP) in primary open-angle glaucoma (POAG)?

What is the prevalence of primary open-angle glaucoma (POAG) in the US?

What is the global prevalence of primary open-angle glaucoma (POAG)?

What is the morbidity associated with primary open-angle glaucoma (POAG)?

What is the racial predilection of primary open-angle glaucoma (POAG)?

What is the sexual predilection of primary open-angle glaucoma (POAG)?

Which age groups are at highest risk for primary open-angle glaucoma (POAG)?

What is the prognosis of primary open-angle glaucoma (POAG)?

What should be included in patient education about primary open-angle glaucoma (POAG)?


What are the signs and symptoms of primary open-angle glaucoma (POAG)?

Which clinical history findings are characteristic of primary open-angle glaucoma (POAG)?

What are the risk factors for glaucomatous optic neuropathy in primary open-angle glaucoma (POAG)?

What are the risk factors for rapid glaucoma progression in primary open-angle glaucoma (POAG)?

Who should receive primary open-angle glaucoma (POAG) screening?

Which tests are performed in primary open-angle glaucoma (POAG) screening?

What is the algorithm for evaluation of open-angle glaucoma (POAG)?

Which slit lamp exam findings are characteristic of primary open-angle glaucoma (POAG)?

What is the role of tonometry in the evaluation of primary open-angle glaucoma (POAG)?

What is the role of gonioscopy in the evaluation of primary open-angle glaucoma (POAG)?

What is the role of pachymetry in the evaluation of primary open-angle glaucoma (POAG)?

What is the role of visual field testing in the evaluation of primary open-angle glaucoma (POAG)?

What causes primary open-angle glaucoma (POAG)?

What is the role of apoptosis in the etiology of primary open-angle glaucoma (POAG)?

What causes elevated intraocular pressure (IOP) in primary open-angle glaucoma (POAG)?

Which disorders should be included in the differential diagnoses of primary open-angle glaucoma (POAG)?

What are the possible complications of primary open-angle glaucoma (POAG)?


What are the differential diagnoses for Primary Open-Angle Glaucoma (POAG)?


What is the role of lab testing in the workup of primary open-angle glaucoma (POAG)?

What is the role of imaging studies in the workup of primary open-angle glaucoma (POAG)?

What is the role of Goldmann applanation tonometry in the workup of primary open-angle glaucoma (POAG)?

What is the role of the Ocular Response Analyzer (ORA) in the workup of primary open-angle glaucoma (POAG)?

What is the role of the PASCAL Dynamic Contour Tonometer in the workup of primary open-angle glaucoma (POAG)?

What is the role of tonography in the workup of primary open-angle glaucoma (POAG)?

What is the role of provocative testing in the workup of primary open-angle glaucoma (POAG)?

When should other causes of visual loss be considered in the evaluation of primary open-angle glaucoma (POAG)?


Which medications are used in the treatment of primary open-angle glaucoma (POAG)?

How is primary open-angle glaucoma (POAG) treated?

What should be discussed with the patient prior to treatment selection for primary open-angle glaucoma (POAG)?

What should be considered when initiating treatment for primary open-angle glaucoma (POAG)?

How is the damage from primary open-angle glaucoma (POAG) prevented or delayed?

What are concerns during follow-up care for primary open-angle glaucoma (POAG)?

What is the role of iStent (Glaukos) in the surgical treatment of primary open-angle glaucoma (POAG)?

What is the role of using Solx gold suprachoroidal space microshunt (Solx) in the surgical treatment of primary open-angle glaucoma (POAG)?

When is the role of surgery in the treatment of primary open-angle glaucoma (POAG)?

What is the role of argon laser trabeculoplasty in the treatment of primary open-angle glaucoma (POAG)?

What is the role of selective laser trabeculoplasty (SLT) in the treatment of primary open-angle glaucoma (POAG)?

What is the role of trabeculectomy in the management of primary open-angle glaucoma (POAG)?

What is the role of drainage implant surgery in the treatment of primary open-angle glaucoma (POAG)?

What is the efficacy of drainage implant surgery in the treatment of primary open-angle glaucoma (POAG)?

What is the role of ciliary body ablation in the treatment of primary open-angle glaucoma (POAG)?

What are newer techniques for the surgical treatment of primary open-angle glaucoma (POAG)?

What are is the role of ExPress shunt (Alcon) in the surgical treatment of primary open-angle glaucoma (POAG)?

What is the role of using Cypass Microstent in the surgical treatment of primary open-angle glaucoma (POAG)?

What is the role of Trabectome (NeoMedix) in the surgical treatment of primary open-angle glaucoma (POAG)?

Which specialist consultations are beneficial to patients with primary open-angle glaucoma (POAG)?

Which activity modifications are used in the treatment of primary open-angle glaucoma (POAG)?

What is included in long-term monitoring of primary open-angle glaucoma (POAG)?


What is the role of medications in the treatment of primary open-angle glaucoma (POAG)?

Which medications in the drug class NMDA Antagonists are used in the treatment of Primary Open-Angle Glaucoma (POAG)?

Which medications in the drug class Hyperosmotic agents are used in the treatment of Primary Open-Angle Glaucoma (POAG)?

Which medications in the drug class Rho Kinase/Norepinephrine Transporter Inhibitor are used in the treatment of Primary Open-Angle Glaucoma (POAG)?

Which medications in the drug class Prostaglandin analogs are used in the treatment of Primary Open-Angle Glaucoma (POAG)?

Which medications in the drug class Miotic agents (parasympathomimetics) are used in the treatment of Primary Open-Angle Glaucoma (POAG)?

Which medications in the drug class Antiglaucoma, Combos are used in the treatment of Primary Open-Angle Glaucoma (POAG)?

Which medications in the drug class Carbonic anhydrase inhibitors are used in the treatment of Primary Open-Angle Glaucoma (POAG)?

Which medications in the drug class Alpha2 Agonists, Ophthalmic are used in the treatment of Primary Open-Angle Glaucoma (POAG)?

Which medications in the drug class Beta-adrenergic blockers are used in the treatment of Primary Open-Angle Glaucoma (POAG)?