Primary and secondary
open-angle glaucoma

Referral priority: Moderate

Patients who have a high intraocular pressure and/or signs of glaucoma should be referred to an ophthalmologist following local guidelines.

Written by
Marko Lukic
Edited by
Svein Tindlund and Jon Gjelle
June 2023


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Physical examination

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Diagnostic procedures

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Management and treatment

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Glaucoma is a big public health problem. It is the leading cause of irreversible blindness worldwide and is associated with a reduced quality of life.(1) An estimated 57.5 million people worldwide are affected by primary open-angle Glaucoma (POAG), with a global prevalence of 2.2%.(2) In Europe, 7.8 million people were affected by POAG, and the prevalence is 2.51%.(3-5)

Glaucoma describes a group of progressive conditions with characteristic cupping of the optic disc with corresponding visual field defects due to retinal ganglion cell loss.(6) Primary open-angle glaucoma (POAG) is a subset, defined by an open, normal-appearing anterior chamber angle and raised intraocular pressure (IOP) with no other underlying disease.(6,7) If there is an identifiable underlying cause for raised IOP, this is termed secondary open-angle glaucoma. If the IOP is within normal limits, this is termed normal-tension glaucoma (NTG).(6,7)

Several risk factors are identified for POAG: IOP, age, race, corneal thickness, and family history. The most important one is intraocular pressure, which is also the only that can be modified, compared to the other risk factors. Patients with ocular hypertension, who have an increased intraocular pressure but no damage to optic discs/visual fields, have a higher risk of developing glaucoma, as per the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study.(8,9) Furthermore, both studies revealed that the incidence of POAG increases with age. (8,9) Several studies have shown POAG to be more prevalent in people of African-Caribbean descent than Caucasians. In addition, ocular hypertension is more likely to progress in POAG in patients of African-Caribbean descent.(10,11) If some has a first-degree relative with POAG, they have a higher risk for developing POAG.(12,13) This has been reported in several studies, with the odds ratio varying from 3 to 13.(7) There is controversy and no consensus on whether myopia, hypertension, and diabetes are risk factors.

There are multiple mechanisms that explain the pathomechanism of glaucoma development. Some are IOP-dependent, and some are non-IOP-dependent. There is consensus that increased IOP is secondary to obstruction of trabecular meshwork flow rather than hyperproduction of the aqueous humour. The elevated pressure either causes mechanical damage to the optic nerve head at the lamina cribrosa or causes vascular damage, which causes ischaemia. The obstructed trabecular meshwork may be a result of several mechanisms:

  • trabecular meshwork obstruction with foreign material
  • trabecular endothelial cell loss
  • loss of trabecular endothelial cell phagocytic activity
  • loss of giant vacuoles of the endothelium of Schlemm’s canal
  • loss of pore density and reduced pore size in the wall of the Schlemm’s canal

The non-IOP-dependent mechanisms are:

  • reduced ocular perfusion pressure
  • excitotoxic damage from excessive glutamate
  • autoimmune damage
  • loss of protective neurotrophic factors
  • failure of cellular repair mechanisms
  • abnormal regulation of choroidal and retinal vasculature


Normal-tension glaucoma (NTG)
Numerous studies revealed and calculated the physiologic mean of the IOP.(14-18) As per consensus, the upper limit of the normal IOP is 21 mmHg. However, the Baltimore Eye Survey identified that 50% of the patients with POAG had an IOP lower than 22 mmHg.(19) Several mechanisms (non-IOP related) have been proposed as important in the pathophysiology of NTG: systemic and local vascular dysregulation, hematologic abnormalities, impaired cerebrospinal fluid (CSF) circulation resulting in stagnation and decreased optic nerve protection, and structural anomalies, including structural weakness of the lamina cribrosa. Nonetheless, the Collaborative Normal Tension Study showed a slowing of the progression of the disease in patients who had achieved a 30% or more reduction of an already normal IOP.(20,21)

Secondary open-angle glaucoma (SOAG)
Secondary open-angle glaucoma is any form of glaucoma with an identifiable cause of increased eye pressure, resulting in optic nerve damage and vision loss. It may be caused by an eye injury, inflammation, certain drugs such as steroids, and advanced cases of cataracts or diabetes.(22) Below is a list of types that represent secondary open-angle glaucomas:

  • Pseudo-exfoliative glaucoma is present in patients with the pseudo-exfoliative syndrome. It is a systemic condition characterised by the deposition of white dandruff-like material, called exfoliation material, within the anterior segment of the eye and other organs such as the heart, lungs, and kidneys. 50% of patients with exfoliation syndrome are ultimately diagnosed with glaucoma. It is often unilateral and slowly progressive; therefore, patients present at a late stage of the disease.(23)
  • Neovascular glaucoma (open-angle stage) occurs in patients with severe retinal ischaemia (secondary to proliferative diabetic retinopathy, ischaemic central retinal vein occlusion, and ischaemic ocular syndrome). Read more in this chapter.
  • Steroid-induced glaucoma – The use of topical and systemic corticosteroids for a longer time can result in a rise in intraocular pressure, which is usually reversible once the patient stops using the medication.(24)
  • Pigmentary glaucoma – In certain eyes, pigment particles may circulate abnormally in the aqueous fluid, which may cause blockage at the drainage angle.(24)
  • Traumatic glaucoma is caused by trauma. One of the mechanisms is the blockage of trabecular meshwork by blood.
  • Lens-induced phacolyitic glaucoma – Lens material may cause blockage of the outflow of the aqueous at the drainage angle, which may occur after injury (including cataract surgery) or when lens material leaks through the lens capsule of a mature/hypermature lens.(24)
  • Uveitic glaucoma – In uveitis, cells and proteins in the anterior chamber disturb the normal outflow of aqueous fluid through the trabecular meshwork, causing a raised intraocular pressure.(24)
  • Congenital glaucoma is developmental glaucoma that occurs before the age of three due to an obstruction that prevents adequate drainage of aqueous humour, caused by abnormal development of the trabecular meshwork and the anterior chamber angle.(25)


Most patients with POAG and NTG are asymptomatic. Patients with the more advanced stage of the diseases may complain of blurry vision and defects in visual fields. Sometimes, they may notice visual-field defects if they perform monocular tasks.

Other potential causes of optic disc damage should be excluded for patients with optic disc changes secondary to NTG. It is important to review accompanied neurologic symptoms such as headache, weakness, dizziness, diplopia, or loss of consciousness. Then, it is also important to take a thorough medical history and ask specifically about the following conditions:

  • sleep apnoea
  • syncope
  • Raynaud’s phenomenon
  • anaemia
  • hypotension
  • prior events of a significant vascular compromise requiring blood transfusions (they may cause issues with ocular perfusion pressure which is one of the proposed causes of NTG)

Patients with secondary open-angle glaucoma may be asymptomatic or symptomatic, depending on the cause and degree of the elevated pressure. Patients usually experience eye pain when the IOP is above 35 mmHg. Those patients may also have eye redness, and may complain of seeing halos of light and blurry vision.

Please note that pain thresholds may vary among patients. Do not rely on eye pain when you suspect glaucoma. Any IOP above 21 mmHg should be monitored and further investigated for potential glaucoma.


Physical examination

The physical examination assesses the IOP, anterior chamber angle, optic disc, and visual field.

Intraocular pressure measurement
The golden standard for IOP measurement is Goldmann Applanation Tonometry (GAT). Fluorescein dye is placed on the patient’s eye to highlight the tear film. A split-image prism divides the image of the tear meniscus into a superior and an inferior arc. The intraocular pressure is taken when these arcs are aligned such that their inner margins touch.(25)

Errors that may cause false IOP are:

  • central foveal thickness
  • excessive or insufficient fluorescein in the tear film affecting the thickness of the overlapping arcs
  • high astigmatism
  • irregular or scarred cornea
  • pressure from a finger on the eyelid while taking the measurement
  • breath holding or Valsalva manoeuvre by the patient during measurement

The option is rebound tonometry (iCare device uses this technique). It has a good agreement with Goldman and Tono-pen readings. A 1.8mm diameter plastic ball on a stainless steel wire is held in place by an electromagnetic field in a battery-powered handheld device. A spring drives the wire and ball forward rapidly when you push a button. When the ball hits the cornea, the ball and wire decelerate; the deceleration is more rapid if the IOP is high and slower if the IOP is low. The speed of deceleration is measured and converted by the device into IOP. No anaesthetic is necessary. Central corneal thickness also affects the accuracy of IOP measurement.(26)

Air Puff Tonometer, ORA, Tono Pen, and Schiotz are other options to measure IOP.

Central corneal thickness measurement
Central corneal thickness (CCT) is one of the biomechanical attributes of the cornea. Thick corneas may give false positive high IOPs, while thin corneas may give false normal IOPs. Normal corneal thickness is considered between 540 and 560 microns. CCT may be useful in baseline risk profiling, but despite existing IOP correction algorithms, the European Glaucoma Society suggests avoiding them.(28)

Anterior chamber angle examination
There are a few methods to examine the anterior angle: gonioscopy on a slit lamp, ultrasound biomicroscopy, or anterior OCT.

Gonioscopy is essential to diagnose POAG and should be performed on the initial visit. Various classification systems have been described to assess the extent of an open angle. Gonioscopy helps to differentiate POAG from SOAGs.

There are different classification systems to classify whether the anterior angle is closed or opened. The Shaffer classification system describes the degree to which the angle is open rather than the degree to which it is closed (compared to the Scheie’s system). It approximates the angle at which the iris inserts relative to the trabecular meshwork.

Grade number Angle width Description Risk of closure
4 45° – 35° Wide open Impossible
3 35°-20° Wide open Impossible
2 20°-10° Narrow Possible
1  10° Extremely narrow Probable
Slit Slit Narrowed to slit Probable
0 0° Closed Closed

Table 1: Schaffer classification system(16)


Diagnostic procedures

Slit lamp examination/colour fundus photography is helpful in examining people with suspected glaucoma. The following features should be considered in patients with suspected glaucoma(29):

  • High cup: disc ratio
  • Cup: disc ratio asymmetry between eyes (usually considered significant if greater than 0.2)
  • Vertical elongation of cup
  • Focal neuro-retinal rim thinning or notching
  • Vessel bayoneting
  • Beta-zone peripapillary atrophy (occurs as a result of atrophy of the RPE and choriocapillaris)
  • Disc haemorrhage

Optical coherence tomography is part of routine imaging in glaucoma patients. It analyses the retinal nerve fiber layer (RNFL) and the optic nerve head.

Image 2. OCT report indicated RNFL thinning and optic disc cupping.

Visual-fields test – automated threshold perimetry is used to diagnose early signs of visual-field defects and to monitor progression. The defects involved in POAG are:

  • Localised defects respecting the horizontal meridian
  • Nasal step
  • Arcuate scotoma
  • Generalised depression
  • Abnormal Glaucoma Hemifield Test
Image 3. Case of advanced POAG – Humphrey visual-fields image.
Image 4. Mid-peripheral defect in superonasal fields in a patient with pigmentary glaucoma.

Management and treatment

The only proven treatment for POAG is lowering the IOP. The Advanced Glaucoma Intervention Study (AMIG) and the Early Manifest Glaucoma Trial (EMGT) have proven that lowering IOP reduces the progression of POAG. The Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study (EPGS) showed that lowering IOP slows the progression of ocular hypertension to POAG.(8,9,30,31)

The IOP may be lowered by medical therapy (topical and systemic), laser therapy, and surgical procedures.

Topical medical therapy

  • Alpha-agonists (apraclonidine, brimonidine)
  • Beta-blockers (timolol, betaxolol, carteolol, levobunolol)
  • Carbonic anhydrase inhibitors (brinzolamide, dorzolamide)
  • Prostaglandins (latanoprost, bimatoprost, travoprost)

Typical first-line therapies are prostaglandin analogues and beta-blockers. Prostaglandin analogues are more effective and have fewer systemic side effects. There is also a combination of two drugs on the market, which should cause better compliance in those who need to take more than one type of local anti-glaucoma drug. Always ask your patients about compliance.

Side effects related to prostaglandins are hyperemia, lengthening of lashes, darkening of iris colour, and peri-ocular skin pigmentation.

Side effects of beta blockers are more systemic and include breathlessness, reduced exercise tolerance, and falls.

Non-selective beta blockers are contraindicated in patients with respiratory diseases and some cardiac conditions.

Systemic medical therapy
This includes acetazolamide (carbonic anhydrase inhibitor given orally or intravenously) and hyperosmotic agents (glycerin, mannitol).

Oral beta blockers are not prescribed to control intraocular pressure. Be aware that if the patient takes oral beta-blockers, they may have worse side effects than by using local beta blockers.

Surgical procedures

  • Laser-selective trabeculoplasty
  • Trabeculectomy
  • Non-penetrating drainage surgery
  • Shunt procedures
  • Cyclodestructive procedures (cyclodiode, cyclocryotherapy)


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