Open Angle Glaucoma

Article Author:
Lisa Foris
Article Editor:
Koushik Tripathy
1/23/2019 12:03:46 PM
PubMed Link:
Open Angle Glaucoma


Open-angle glaucoma (OAG) is a chronic, progressive, and irreversible multifactorial optic neuropathy that is characterized by open angle of the anterior chamber, typical optic nerve head changes, progressive loss of peripheral vision (typical visual field changes) followed by central visual field loss (blindness) for which intraocular pressure (IOP) is an important risk factor. The disease is usually bilateral, but asymmetry is often seen.

The proposed definition for definite OAG by Rotterdam study[1] is 'a glaucomatous optic neuropathy in eyes with open angles in the absence of history or signs of secondary glaucoma characterized by glaucomatous changes based on the 97.5 percentile for this population together with glaucomatous visual field loss. In the absence of the latter or of a visual field test, it is proposed to speak of probable OAG based on the 99.5th or possible OAG based on the 97.5th percentiles of glaucomatous disc changes for a population under study.


Open-angle glaucoma is characterized by partial blockage of the trabecular meshwork in the eye, though the drainage angle between the cornea and iris remains open. Due to this blockage, the pressure in the eye gradually (very slowly) increases, resulting in damage to the optic nerve (progressive visual loss).  

The rapid deterioration of visual field in OAG is associated with the following baseline features:  worst mean deviation, a greater vertical cup-to-disc ratio at baseline, or older age.[0]


Glaucoma is the second leading cause of blindness globally,[3] and in the USA. Glaucoma is the leading cause of blindness in blacks.[4] Overall, open-angle glaucoma is more common in populations of European or African descent than in populations of Asian descent in whom angle-closure glaucoma is more common. There are at least 2.7 million people aged  ≥40 years with glaucoma in the United States.[5] In 2015, there were 57.5 million people worldwide with primary OAG, and in 2020 65.5 million people are expected to be affected.[6]Bilateral blindness due to OAG has been estimated to affect 4.5 million people in 2010 and 5.9 million people in 2020.[7]


The exact cause of neuropathy encountered in open-angle glaucoma is not well known, though multiple risk factors have been identified. 

These include

  • Old age
  • Race- The prevalence of OAG is three times higher in African-Americans compared to non-Hispanic whites in the USA. The prevalence of OAG has been noted to be high in Afro-Caribbean, West African and people of Latino Hispanic origin.
  • Family history- The Rotterdam Eye study found 9.2 times higher risk of having OAG if first degree relatives had glaucoma.[8]
  • Elevated IOP
  • Myopia
  • Increased cup to disc ratio
  • Disc hemorrhage
  • Thin central corneal thickness
  • Low ocular perfusion pressure
  • Low blood pressure (systolic and diastolic)[9]
  • High blood pressure (systemic arterial hypertension)- Several studies have shown an association of hypertension with OAG, while others have not found an association.[10]
  • Type 2 diabetes mellitus
  • High pattern standard deviation (PSD) on visual fields
  • Migraine or vasospasm
  • Low intracranial (cerebrospinal fluid) pressure
  • Oral contraceptive pill
  • Other risk factors include smoking, obesity, alcohol, anxiety, stress, and sleep apnea

Elevated Intraocular pressure:

Of these risk factors, the most studied risk factor had been elevated IOP, as it is modifiable. It has been shown that once IOP rises above 21 mmHg, there is a significant increase in the risk of developing visual field loss (even with only small increases in IOP), especially once IOP rises above 26 mmHg to 30 mmHg.  High IOP is an important risk factor for the progression of glaucoma. High fluctuation of IOP may also lead to glaucoma progression. Reduction of IOP leads to less progression or stabilization of the glaucomatous optic nerve changes and visual field changes. About 40-50% of all OAG cases have IOP below 22 mm Hg in a single screening.[11][10]

Pathomechanism of glaucoma:

The two main proposed mechanisms by which an elevated IOP is thought to contribute to glaucomatous damage includes vascular dysfunction resulting in ischemia to the optic nerve, and mechanical dysfunction as a result of compression of the axons by the cribriform plate.

When open-angle glaucoma in a patient is attributed to elevated IOP, the cause of this increase in IOP is commonly thought occur due to dysfunction in aqueous outflow through the trabecular meshwork of the eye. This may occur as a result of partial obstruction due to foreign material (e.g., accumulated mucopolysaccharides, in the trabecular meshwork), a reduction in the number of trabecular endothelial cells, a decreased density of trabecular pores, number of vacuoles, or size of the inner wall endothelium of the canal of Schlemm, loss of phagocytic activity, or dysfunction in the neurological feedback loop involved in drainage of aqueous humor. It is important to note that unlike angle-closure glaucoma, the drainage angle between the iris and cornea remain open in open-angle glaucoma.

Other proposed mechanisms for obstruction of aqueous humor outflow include oxidative damage to the meshwork, abnormal corticosteroid metabolism, adrenergic dysfunction, or an immunological process.

Finally, it has been proposed that certain individuals may have a genetic predisposition to cell death of individual axons in the eye, resulting in the release of potentially cytotoxic substances such as glutamate, calcium, nitric oxide, and free radicals, as well as apoptosis of neighboring cells.

History and Physical

Early changes in vision due to open-angle glaucoma involves a loss of peripheral vision at first, while visual acuity (e.g., central vision) is maintained until late in the course of the disease. For this reason, open-angle glaucoma progresses relatively asymptomatically, and patients often do not present with symptoms or visual complaints until late in the course of the disease. Thus, it is a silent, but potentially blinding disease. History should include:

  • A previous ocular history such as the history of eye pain or redness, headaches, uveitis, diabetic retinopathy, cataracts, vascular occlusions, or multicolored halos
  • Race or ethnicity
  • Refractive error
  • Chronic use of topical or systemic corticosteroids
  • Ocular surgery like photocoagulation or refractive procedures, cataract surgery, glaucoma surgery, and systemic surgery/ medications
  • Head or ocular trauma
  • Take certain medications such as hypertensive medications that may influence IOP or systemic/topical steroids
  • Medical history of diabetes mellitus, migraine headaches, hypertension, vasospasm, cardiovascular disease, breathlessness, cardiac arrhythmia 
  • Family history (e.g., first-degree relative with glaucoma, especially significant if this is a sibling) that would place them at a greater risk of developing open-angle glaucoma.
  • Old medical documentation of IOP, optic disc, visual field, and others.


OAG is characterized by a typical triad[12] of

  1. Glaucomatous optic disc changes
  2. Typical visual field changes, and
  3. Elevated IOP.

However, for a diagnosis of OAG high IOP is not mandatory.[10][13] The American Academy of Ophthalmology defines primary OAG[10] as 'chronic, progressive optic neuropathy in adults in which there is a characteristic acquired atrophy of the optic nerve and loss of retinal ganglion cells and their axons. This condition is associated with an open anterior chamber angle by gonioscopy.'

If the patient has a history of progressively declining visual acuity, it is important to rule out other potential causes such as cataracts, ocular surface disorders (e.g., dry eyes or blepharitis), age-related macular degeneration, or medication-related side effects (e.g., cholinergic/miotics).  Additionally, before forming a diagnosis of open-angle glaucoma, one must also consider other secondary causes of glaucoma such as pigment dispersion syndrome, steroid-induced glaucoma, intraocular tumors, exfoliation syndrome, ocular inflammatory disorders, elevated episcleral venous pressure, lens-induced glaucoma and other syndromes (e.g., Axenfeld-Rieger syndrome).

When examining the anterior segment of the eye via slit-lamp examination, the practitioner should also examine the following for any damage, defects or irregularities that may or may not be related to glaucomatous disease:

  • Cornea for keratic precipitates, pigmented endothelium, congenital abnormalities, guttae
  • Anterior chamber for depth, uveitis, hyphema
  • Iris for transillumination defects, atrophy, differences in coloration, ectropion uveae, iris bombe, peripheral iridectomy
  • Lens for presence or progression of cataracts
  • Fundus for disc drusen, optic pits, retinal disease (age-related macular degeneration, diabetic maculopathy, retinal vascular occlusion)
  • Optic nerve/nerve fiber layers for cup-to-disc ratio, disc appearance, nerve fiber appearance.
  • Gonioscopy for the examination of the angle of the anterior chamber

Intraocular pressure:

When determining the IOP of a patient using tonometry, certain variables must be taken into consideration. Tonometry measurements can, for example, vary between examiners differing by approximately 10% per individual, which can translate to a difference in IOP measurement of 1 mmHg to 2 mmHg. An individual’s corneal thickness or diurnal variations of IOP (e.g., higher IOP in early morning hours or other time of the day, or variability in the time of day of maximal IOP between patients) can also have a tremendous effect on the accuracy of IOP measurements.  For this reason, multiple measurements should be taken in any patient suspected of having an elevated IOP, while also correlating measurements with both optic nerve and visual field examinations.  If there are previous tonometry measurements available, they should be reviewed and compared to those that are most recent. Also, the IOP may be different on the same time of the day on different days. Different instruments may capture different values of IOP. 

 If a difference of 3 mmHg or more is noted between the two eyes, there should be an increased suspicion for the presence of glaucoma. Physicians should expect approximately 10% variation between individual measurements, and thus should repeat measurements over at least two to three occasions before deciding on the plan for treatment. Goldmann applanation tonometry (GAT) is thought as the gold standard for measuring IOP but is affected by corneal thickness. Higher corneal thickness gives falsely high values of IOP whereas low corneal thickness leads to a falsely low measurement of IOP.

Evaluation of optic nerve:

The optic nerve should ideally be evaluated using a slit lamp and 90D or 78D lens so that the 3-dimensional features of the optic nerve is better appreciated. Normally, the inferior neuroretinal rim (NRR) is the thickest, followed by superior, nasal, and temporal NRR. This is called ISNT rule. In OAG, this rule is not followed, as superior and inferior NRR gets thinned in the disease. The optic cup should be determined by its contour and not its color.

Typical optic nerve head changes in OAG include:

  • Diffuse or focal narrowing (notching/shelving) of the neuroretinal rim (NRR) specifically at the superior or inferior part of the optic disc
  • Increased vertical cup to disc ratio (CDR) and thinning of NRR
  • Asymmetry of CDR of 0.2 or more
  • Hemorrhage at or around the optic disc
  • Peripapillary atrophy
  • Baring of circumlinear vessels- There is a gap between the superficial vessels and disc margin
  • Bayonetting of vessels- The vessel first goes back and then climbs along the wall of the deep cup and then angles again on the disc margin
  • Very deep (excavated) cup with bean-pot cupping and laminar dot sign
  • Nasalization of optic disc vessels, and 
  • Diffuse or focal (arcuate) thinning/defect of the retinal nerve fiber layer (RNFL) contiguous with an area of NRR-notch
  • The NRR is typically pink and not pale in OAG. Pallor of the NRR usually denotes a neurological cause (eg, pituitary tumor), but may also be seen in primary angle closure glaucoma.

Visual field:

To make a diagnosis of acquired glaucomatous visual field defect Hoddap–Parrish–Anderson criteria is used:[14]

  1. 'Glaucoma hemifield test outside normal limits on at least 2 fields OR
  2.  a cluster of three or more non-edge points in a location typical for glaucoma, all of which are depressed on the pattern deviation plot at a P <5% and one of which is depressed at a P <1% on 2 consecutive fields; or
  3. a corrected pattern standard deviation that occurs in less than 5% of normal fields on 2 consecutive fields.'

Static automated threshold perimetry is used with white stimulus on white background. Most studies used the Humphrey Field Analyzer, but other perimeters like Octopus have also been used successfully. SWAP (short-wavelength automated perimetry using blue stimulus on yellow background) and frequency doubling perimetry may pick up early visual field defects. The visual field must be reliable and field defects should be repeatable on at least 2 fields. The same machine, the same degree of field and protocol (eg, 24-2, 30-3, or 10-2) should be used to compare the fields to note for progression or stability. It has been estimated that at least 40%-50% ganglion cell loss is needed to reliably show visual field defects in threshold perimetry.[15][16] Thus, structural changes of the optic nerve occur earlier than functional change (visual field loss) in OAG. This gives rise to the concept of Preperimetric glaucoma which has been defined as 'the presence of characteristic glaucomatous changes in the optic disc and increased vulnerability to damage in the retinal nerve fiber layer (RNFL), without the presence of visual field defects detectable with standard automated perimetry'.[17]

Typical visual field changes in OAG include.

  • Increased variability of responses in an area which later developed field defects
  • Asymmetry of the visual field between the eyes
  • Paracentral scotoma- commonly superonasal
  • Roenne's nasal step- an area of depression above or below the horizontal meridian in the nasal side 
  • Temporal wedge
  • Sickle-shaped (Seidel's) scotoma
  • Bjerrum's scotoma or arcuate scotoma
  • Annular/ring scotoma when arcuate scotoma is present on both above and below the horizontal meridian
  • General constriction of peripheral field
  • A temporal island of the visual field


Gonioscopy should be performed to document the status of angle and to document that the angle is open, which is an important pre-requisite for diagnosing OAG.

Photographic documentation of the optic nerve head is done by color and red-free disc photo preferably stereo photos. Red-free images highlight area of RNFL defects.

 Automated analysis and detection of deviation from normal of the optic nerve head and retinal nerve fiber layer may be performed using various technologies including

  • Optical coherence tomography (Optovue, Cirrus, Spectralis, and others)
  • Scanning laser polarimetry (GDx-VCC) 
  • Confocal scanning laser ophthalmoscopy (Heidelberg retinal tomogram or HRT II)

Treatment / Management

The goal of treatment of open-angle glaucoma is:

  • Prevention of progression of optic nerve head changes
  • Prevention of deterioration of visual field

To achieve this goal, the concept of Target IOP was introduced.  It is the upper limit of IOP, below which it is estimated that the visual field and the optic nerve head/RNFL parameters will not deteriorate, and the quality of life of the patient will not get compromised. 

Glaucoma medications:

Debate exists over the optimal time to initiate treatment of Open-angle glaucoma with some physicians initiating treatment of IOP once it reaches above only 21 mmHg, and others reserving treatment either until there is evidence of optic nerve damage or if the patient is at high risk of damage or progression of open-angle glaucoma. 

Treatment should be initiated if signs of damage as a result of open-angle glaucoma are evident (e.g., disc hemorrhage, nerve fiber layer defects, asymmetric cupping, vertical ovalization or notching of the cup) or if symptoms of elevated IOP are present (e.g., halos, blurred vision, pain, IOP consistently above 28 mmHg to 30mmHg) due to the high risk of optic nerve damage in the setting of elevated IOP. Some physicians begin a monocular trial with medications only in one eye, to assess the effectiveness and side effects of chosen medications before treating both eyes. However, different eyes might have a different response to the same drug, asymmetric IOP fluctuation may occur, and the drug may have a contralateral effect.

A target IOP should be set individually depending on the severity of structural and functional damage, baseline IOP, age, race, family history, corneal thickness, corneal hysteresis, and other risk factors.[18]

Follow-up should also be scheduled based on the level of success in IOP reduction between visits (e.g., more frequent follow-up with slower progression in treatment response) and the severity of optic nerve damage/visual field loss.

Overall, treatment should be individualized, taking into consideration the risk factors, systemic complications of medication use, the patient’s life expectancy, medical history, concomitant conditions, and the patient’s desire to receive treatment. The target IOP should be revised based on the behavior of optic nerve head damage and visual function (visual field).

If IOP/visual field/optic nerve head worsens while the patient is on medical therapy the compliance to therapy must be checked. Also, systemic factors including diabetes, smoking, and nocturnal hypotension should be controlled. The physician should himself/herself confirm from the patient the drops and how many times the patient is using these. A check should also be done to note if the administration of topical drops is correct or not. Closure of eyelids after administration of drops with nasolacrimal duct occlusion may prevent systemic absorption of the topical medication.

Topical medications:

Prostaglandin analog- Reduces IOP by 25% -33%. The usual dose in once daily. Side effects include lengthening of eyelashes, pigmentation of lids/ iris, exacerbation of uveitis/herpetic infection, and cystoid macular edema. It is preferred as initial therapy. 

  • Latanoprost 
  • Travoprost
  • Bimatoprost 
  • Tafluprost
  • Latanoprostene Bunod- This molecule donates has nitric oxide-donating property.

Adrenergic agents: Reduces IOP by 20%-25%. Brimonidine may cause allergic blepharoconjunctivitis and apnea/lethargy/bradycardia in children.

  • Brimonidine
  • Apraclonidine

Beta-blockers: Reduces IOP by 20%-25%. Non-selective beta-blockers should be avoided in chronic obstructive pulmonary disease and asthma. Other contraindications include heart block, hypotension, and bradycardia.

  • Non-selective-
    • Timolol
  • Selective
    • Betaxolol

Carbonic anhydrase inhibitor: Reduces IOP by 15%-20%.[10]

  • Dorzolamide
  • Brinzolamide

Cholinergic/parasympathomimetic agents: Reduces IOP by 20%-25%.

  • Pilocarpine

Systemic agents:

These are used in the acute rise of IOP or when topical medications are not tolerated.

Carbonic anhydrase inhibitor: 

  • Acetazolamide 

Osmotic agents

  • Mannitol
  • Glycerol

Laser therapy for OAG: 

Laser trabeculoplasty

The indications of laser trabeculoplasty include

  • As a primary therapy for OAG
  • To reduce the number of glaucoma drops
  • Non-compliance/intolerance to medical therapy
  • Failure of medical therapy as a less invasive alternative therapy compared to surgery

The available methods of laser trabeculoplasty are:

  • ALT (Argon laser trabeculoplasty)- More than 75% of unoperated eyes have a good reduction of IOP initially. Within 5 years, 30% to >50% eyes need additional surgical management. Repeat ALT usually (90%) fails to control IOP by 2 years.
  • SLT (Selective laser trabeculoplasty)- It uses Q-switched frequency doubled Nd-YAG. The efficacy of SLT is similar to ALT.
  • Micropulse laser trabeculoplasty-

Diode laser cyclophotocoagulation (DLCP)

DLCP is a method for ablation of the ciliary processes which secrete aqueous. Indications for DLCP include:

  • Uncontrolled IOP in eyes with ambulatory vision if chances of surgical success are poor
  • Uncontrolled IOP in painful blind eyes or eyes with minimal visual potential
  • Uncontrolled IOP with maximal medication after failed glaucoma surgery/ies

Surgical Management of OAG:

Indications for surgical management of glaucoma are

  • IOP above target pressure or progression of visual fields and optic disc changes despite good compliance and maximally tolerable glaucoma medication
  • To avoid excessive glaucoma drops
  • Significant barriers to effective and regular medication use including cost, compliance, physical disability, inconvenience, side effects, psychosocial
  • Primary therapy for advanced glaucoma requiring very low target IOP
  • Patient preference over other options

Surgical options include

  • Trabeculectomy- Success rate may vary from 31-88%. The success rate increases with the use of mitomycin C or 5-fluorouracil. These agents, however, increase the risk of late-onset bleb leak, hypotony, and bleb-related infection.
  • Glaucoma drainage device- Molteno, Baerveldt, Ahmed. 
  • Non-penetrating glaucoma surgery:
    • Deep sclerectomy
    • Viscocanalostomy
    • Canaloplasty
  • Minimally invasive or micro-invasive glaucoma surgery (MIGS)[19]- MIGS provides is a conjunctiva-sparing surgery with an ab-interno approach to reduce IOP in mild to moderate glaucoma. The different approaches include:[19]
    • 'increasing trabecular outflow (Trabectome, iStent, Hydrus stent, gonioscopy-assisted transluminal trabeculotomy, excimer laser trabeculotomy);
    • suprachoroidal shunts (Cypass micro-stent);
    • reducing aqueous production (endocyclophotocoagulation); and
    • subconjunctival filtration (XEN gel stent)'


This is another method of cycloablation using cryotherapy usually reserved for painfully blind eyes.

Painful blind eyes from glaucoma may need

  • Enucleation
  • Retrobulbar injection of absolute alcohol

Differential Diagnosis

  • Optic nerve head diseases including
    • Physiological cup- A deep cup with a healthy neuroretinal rim, normal retinal nerve fiber layer thickness, and no visual field defect. The disc size may be large
    • Optic disc drusen
    • Optic disc coloboma
    • Anomalous optic disc
    • Tilted disc
    • Ischemic optic neuropathy
  • Retinal diseases causing similar visual field defects
    • Branch retinal vein occlusion
    • Branch retinal artery occlusion
    • Retinitis pigmentosa
    • Panretinal photocoagulation
  • Central nervous system diseases
    • Pituitary tumor- The NRR is typically pale, pallor is more than cupping, and there is bitemporal hemianopia which respects vertical line passing through the fixation (contrary to glaucoma, it which visual field respects horizontal meridian)
    • Cerebrovascular accident
    • Multiple sclerosis


The Americal Academy of Ophthalmology (AAO) preferred practice pattern (PPP)[10] classifies the severity of glaucomatous damage to different categories:

'Mild: definite optic disc or RNFL abnormalities consistent with glaucoma as detailed above and a normal visual field as tested with standard automated perimetry (SAP)

Moderate: definite optic disc or RNFL abnormalities consistent with glaucoma as detailed above, and visual field abnormalities in one hemifield that are not within 5 degrees of fixation as tested with SAP

Severe: definite optic disc or RNFL abnormalities consistent with glaucoma as detailed above, and visual field abnormalities in both hemifields and/or loss within 5 degrees of fixation in at least one hemifield as tested with SAP

Indeterminate: definite optic disc or RNFL abnormalities consistent with glaucoma as detailed above, inability of patient to perform visual field testing, unreliable/uninterpretable visual field test results, or visual fields not performed yet'


Advanced POAG may cause optic atrophy and no perception of light, though most OAG patients will not lose vision in their lifetime. Risk factors for progression of OAG include[10]:

  • Old age
  • Elevated IOP
  • Increased cup to disc ratio or small optic rim area
  • Beta peripapillary atrophy
  • Disc hemorrhage
  • Thin central corneal thickness
  • Reduced corneal hysteresis
  • Low ocular perfusion pressure
  • Poor compliance to therapy
  • Pseudoexfoliation

In 10 years, the cumulative probability of end-stage glaucoma in at least one eye in untreated cases was 35% in a study.[20]


Complications of glaucoma include:

  • Blindness- usually painless
  • Painful blind eye/Absolute glaucoma- OAG predisposes to central retinal venous occlusion, which can give rise to neovascular glaucoma and painful blind eye.


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