Primary Open-Angle Glaucoma (POAG) Clinical Presentation

Updated: Mar 14, 2019
  • Author: Kristin Schmid Biggerstaff, MD; Chief Editor: Inci Irak Dersu, MD, MPH  more...
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Presentation

History

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]

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Physical

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).

Gonioscopy

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.

Pachymetry

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]

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Causes

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]

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Complications

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

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