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Overview of Glaucoma

By

Douglas J. Rhee

, MD, University Hospitals/Case Western Reserve University

Reviewed/Revised Apr 2023
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Glaucomas are a group of eye disorders characterized by progressive optic nerve damage in which an important part is a relative increase in intraocular pressure (IOP) that can lead to irreversible loss of vision.

Glaucoma is the 2nd most common cause of blindness worldwide and the 2nd most common cause of blindness in the United States, where it is the leading cause of blindness for Black and Hispanic people. About 3 million Americans and 64 million people worldwide have glaucoma, but only half are aware of it. Glaucoma can occur at any age but is 6 times more common among people > age 60.

Glaucomas are categorized as

Table
Table
Table

The “angle” refers to the angle formed by the junction of the iris and cornea at the periphery of the anterior chamber (see figure ). The angle is where > 98% of the aqueous humor exits the eye via either the trabecular meshwork and the Schlemm canal (the major pathway, particularly in older people) or the ciliary body face and choroidal vasculature (also called the uveoscleral pathway and can make up to 50% of outflow in people younger than 30). These outflow pathways are not simply a mechanical filter and drain but instead involve active physiologic processes.

Glaucomas are further subdivided into primary (cause of outflow resistance or angle closure is unknown) and secondary (outflow resistance results from a known disorder), accounting for > 20 adult types.

Aqueous humor production and flow

Most of the aqueous humor, produced by the ciliary body, exits the eye at the angle formed by the junction of the iris and cornea. It exits primarily via the trabecular meshwork and the Schlemm canal (pink arrows). A smaller amount drains through the ciliary body face entering the uveoscleral pathway (black arrows). In early adulthood, the ratio of drainage is approximately equal in both pathways. With aging, drainage occurs predominantly through the trabecular meshwork and Schlemm canal.

Aqueous humor production and flow

Pathophysiology of Glaucoma

Axons of retinal ganglion cells travel through the optic nerve carrying visual information from the eye to the brain. Damage to these axons causes ganglion cell death with resultant optic nerve atrophy and patchy vision loss. Elevated intraocular pressure (IOP) plays a role in axonal damage, either by direct nerve compression or diminution of blood flow. However, the relationship between externally measured pressure and nerve damage is complicated. Normal IOP ranges (ie, within 2 standard deviations of the mean) from 11 to 21 mm Hg. Of people with IOP > 21 mm Hg (ie, ocular hypertension), only about 1 to 2% a year (about 10% over 5 years) develop glaucoma. Additionally, about one third of patients with glaucoma do not have IOP > 21 mm Hg (known as low-tension glaucoma or normal-tension glaucoma).

One factor may be that externally measured IOP does not always reflect true IOP; the cornea may be thinner than average, which leads to a higher IOP measurement, or thicker than average, which leads to a lower IOP measurement, inside the eye than externally measured IOP. Another factor may be that a vascular disorder compromises blood flow to the optic nerve. Also, it is likely that there are factors within the optic nerve that affect susceptibility to damage.

IOP is determined by the balance of aqueous secretion and drainage. Elevated IOP is caused by inhibited or obstructed outflow, not oversecretion; a combination of factors in the trabecular meshwork (eg, dysregulation of extracellular matrix, cytoskeletal abnormalities) appear to be involved. In open-angle glaucoma Primary Open-Angle Glaucoma Primary open-angle glaucoma is a syndrome of optic nerve damage associated with an open anterior chamber angle and an elevated or sometimes average intraocular pressure (IOP). Symptoms are a... read more Primary Open-Angle Glaucoma , IOP is elevated because outflow is inadequate despite an angle that appears macroscopically unobstructed. In angle-closure glaucoma Angle-Closure Glaucoma Angle-closure glaucoma is glaucoma associated with a physically obstructed anterior chamber angle, which may be chronic or, rarely, acute. Symptoms of acute angle closure are severe ocular pain... read more , IOP is elevated when a physical distortion of the peripheral iris mechanically blocks outflow.

Symptoms and Signs of Glaucoma

Diagnosis of Glaucoma

  • Characteristic optic nerve changes

  • Characteristic visual field defects

  • Exclusion of other causes

  • Intraocular pressure (IOP) usually > 21 mm Hg (but not required for the diagnosis)

Glaucoma should be suspected in a patient with any of the following:

  • Abnormal optic nerve on ophthalmoscopy

  • Elevated IOP

  • Typical visual field defects

  • Family history of glaucoma

Such patients (and those with any risk factors) should be referred to an ophthalmologist for a comprehensive examination that includes a thorough history, family history, examination of the optic disks (preferably using a binocular examination technique), formal visual field examination, tonometry Tonometry The eye can be examined with routine equipment, including a standard ophthalmoscope; thorough examination requires special equipment and evaluation by an ophthalmologist. History includes location... read more (measurement of IOP), measurement of central corneal thickness, optic nerve and/or retinal nerve fiber layer imaging (using optical coherence tomography Optical coherence tomography The eye can be examined with routine equipment, including a standard ophthalmoscope; thorough examination requires special equipment and evaluation by an ophthalmologist. History includes location... read more ), and gonioscopy (visualization of the anterior chamber angle with a special mirrored contact lens prism).

Glaucoma is diagnosed when characteristic findings of optic nerve damage are present and other causes (eg, multiple sclerosis) have been excluded. Elevated IOP makes the diagnosis more likely, but elevated IOP can occur in the absence of glaucoma and is not essential for making the diagnosis. Low-tension (low-pressure) or normal-pressure glaucoma (glaucoma occurring with IOP < 21 mmHg) comprises about one third of all open-angle glaucomas in the United States and is even more common in Asia.

Screening

Screening for glaucoma can be done by primary physicians (more commonly an optometrist or ophthalmologist) by checking visual fields with frequency-doubling technology (FDT) perimetry and ophthalmoscopic evaluation of the optic nerve. FDT perimetry involves use of a desktop device that can screen for visual field abnormalities suggestive of glaucoma in 2 to 3 minutes per eye. Although IOP should be measured, screening based only on IOP has low sensitivity, low specificity, and low positive predictive value. Patients > 40 years and those who have risk factors for open-angle Etiology Etiology or angle-closure glaucoma Pathophysiology Angle-closure glaucoma is glaucoma associated with a physically obstructed anterior chamber angle, which may be chronic or, rarely, acute. Symptoms of acute angle closure are severe ocular pain... read more should receive a comprehensive eye examination every 1 to 2 years.

Treatment of Glaucoma

  • Decreasing intraocular pressure (IOP) by using medications or laser or incisional surgery

Patients with characteristic optic nerve and corresponding visual field changes are treated regardless of IOP measurement. Lowering the IOP is the only clinically proven treatment. For chronic adult and juvenile glaucomas, the initial target IOP measurement is at least 20 to 40% below pretreatment readings.

Three methods are available: medications, laser surgery, and incisional surgery. The type of glaucoma determines the appropriate method or methods.

Medications and most laser surgeries (trabeculoplasty) modify the existing aqueous secretion and drainage system.

Traditional incisional surgeries (eg, guarded filtration procedures [trabeculectomy], glaucoma drainage implant devices [tube shunts]) create a new drainage pathway between the anterior chamber and subconjunctival space. Newer incisional surgeries enhance trabecular or uveoscleral outflow without creating a full-thickness fistula.

Prophylactic IOP lowering in patients with ocular hypertension delays the onset of glaucoma. However, because the rate of conversion from ocular hypertension to glaucoma in untreated people is low, the decision to treat prophylactically should be individualized based on the presence of risk factors, magnitude of IOP elevation, and patient factors (ie, preference for medications vs surgery, medication adverse effects). Generally, treatment is recommended for patients with IOP > 30 mm Hg even if the visual field is full and the optic nerve disk appears healthy because the likelihood of damage is significant at that IOP level.

Key Points

  • Glaucoma is common, often asymptomatic, and contributes heavily to blindness worldwide.

  • Suspect glaucoma if patients have elevated IOP, optic nerve abnormalities on ophthalmoscopy, or a family history of glaucoma.

  • Do not rule out glaucoma because IOP is not high.

  • Screen patients > 40 years and patients with risk factors every 1 to 2 years, based mainly on results of ophthalmoscopy and frequency-doubling technology (to assess visual fields).

  • Treat by decreasing IOP.

  • Prophylactically decrease IOP if > 30 mm Hg, even if glaucoma is absent.

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