Glaucoma, Open Angle

Article Author:
Lisa Foris
Article Editor:
William Gossman
Updated:
10/27/2018 12:31:36 PM
PubMed Link:
Glaucoma, Open Angle

Introduction

Open-angle glaucoma (OAG) is a chronic, progressive, and irreversible multifactorial optic neuropathy that is characterized by progressive loss of peripheral vision followed by central visual field loss (blindness).

Etiology

Open-angle glaucoma is characterized by partial blockage of the trabecular meshwork in the eye, through the drainage angle between the cornea and iris remains opened. Due to this blockage, the pressure in the eye gradually (very slowly) increases, resulting in damage to the optic nerve (progressive visual loss).  It is not well known why the elevated intraocular pressure (IOP) seen in open-angle glaucoma results in optic nerve damage. However, it has been observed that individuals at highest risk of developing open-angle glaucoma are those with a previous history of elevated IOP, advanced age (older than 50 years), African American descent, family history of glaucoma, and history of myopia. Additional risk factors that have been proposed include smoking, obesity, alcohol, anxiety, stress, and sleep apnea.

Open-angle glaucoma has also been shown to result in a more rapid decline in visual acuity in patients with a worse mean deviation of their visual field (e.g., changes in the visual field of at least 36% in one year), a greater vertical cup-to-disc ratio at baseline, or older age (e.g., older than 50 years old).

Epidemiology

Glaucoma is a leading cause of irreversible blindness, second only to macular degeneration, which is also irreversible, in the United States, and cataracts, which are reversible, worldwide. Among African Americans, open-angle glaucoma is the leading cause of blindness. 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 an estimated 2.8 million people in the United States and 57.5 million people worldwide with glaucoma. More than three million individuals with glaucoma are suffering from bilateral blindness as a result of open-angle glaucoma, worldwide, and it is estimated that greater than two million individuals will develop open-angle glaucoma, per year.

Risk factors for developing open-angle glaucoma include age, family history, black race, and elevated intraocular pressure (IOP).  The incidence of open-angle glaucoma and the rate of associated blindness both increase with age, particularly those older than 40 years old, with up to 15% of individuals affected by their 60s. Though mean IOP also slowly increases with age, the incidence of open-angle glaucoma is still higher in the aging population, even when this is estimated. 

The relative risk of open-angle glaucoma has been shown to increase by 3.7-fold in an individual with an affected sibling and 2.2-fold in an individual with an affected parent. The inheritance pattern of open-angle glaucoma is thought to be complex, and likely involving the interaction of multiple genes with additional environmental factors.

The race is an important risk factor to consider, as open-angle glaucoma occurs at a rate three times greater in blacks than in whites – 6.6 times greater in blacks when the number is adjusted for age. Blindness also occurs, on average, ten years earlier in blacks than it does in whites with open-angle glaucoma.

Finally, an IOP of 21 mmHg or higher increases the risk of open-angle glaucoma by approximately 0.% to 1% per year over a period of 5 to 10 years.

Pathophysiology

The exact cause of neuropathy encountered in open-angle glaucoma is not well known, though multiple risk factors have been identified.  These include age, race, family history, elevated IOP, and myopia. Of these, the most studied risk factor had been elevated IOP, as it is a treatable variable.

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. 

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.

Additional risk factors that are thought to contribute to the development of open-angle glaucoma include cardiovascular disease, diabetes, systemic hypertension and resultant arteriosclerosis, systemic hypotension and resultantly reduced perfusion, and migraine headaches associated with vasospasm.

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 later 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. Clinical suspicion should, therefore, be high in the following patients who have or have had:

  • A previous ocular history such as history of eye pain or redness, headaches, uveitis, diabetic retinopathy, cataracts, vascular occlusions, or multicolored halos
  • Ocular surgery like photocoagulation or refractive procedures such as laser eye surgery)
  • 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
  • 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.

Evaluation

Screening for open-angle glaucoma should be performed at least every three to five years in patients younger the age of 40, without any symptoms. In older (older than 40 years) patients, African American patients, or individuals with multiple risk factors for open-angle glaucoma, screening should be performed more frequently. Screening should include a standard comprehensive eye examination involving gonioscopy (e.g., to rule out angle-closure or other potential causes of elevated IOP: angle recession, pigmentary glaucoma, or pseudoexfoliative glaucoma), binocular views of the optic discs, and quantitative visual field testing (as outlined by the American Academy of Ophthalmology). It is also important to take into consideration the individuals personal and family medical history.

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 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, 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
  • Anterior chamber for uveitis, hyphema, or angle closure
  • Iris for transillumination defects, atrophy, differences in coloration, ectropion uveae, iris bombe
  • Lens for presence or progression of cataracts
  • Fundus for vitreous hemorrhage, proliferative retinopathy, disc drusen, optic pits, retinal disease
  • Optic nerve/nerve fiber layers for cup-to-disc ratio, disc appearance, nerve fiber appearance.

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 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.

Another important factor to consider is that up to 40% of nerve fiber loss can occur before a patient may experience any symptoms of visual field loss. For this reason, visual field examinations alone should not be used to determine whether or not a patient has an elevated IOP or has sustained glaucomatous damage.

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.

Treatment / Management

The goal of treatment of open-angle glaucoma is to reduce IOP before or to prevent the progression of, vision loss. Most commonly used drug classes for treating open-angle glaucoma include alpha-agonists, beta-blockers, carbonic anhydrase inhibitors, miotics, and prostaglandin analogs. 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. Many physicians may also delay treatment with medications due to the high cost, toxic side effects or reactions, patient noncompliance, or inconvenience of use.

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. It may be helpful to begin treatment with medications only in one eye, to assess effectiveness and side effects of chosen medications before treating both eyes.

A goal IOP should be set individually for each patient, depending on risk factors. Most sources suggest a 20% to 25% reduction of IOP should be the initial goal of treatment. Additional sources suggest a reduction of IOP by 20% to 30%, if only minimal risk factors are present, reduction by 30% to 40% if a moderate number of risk factors are present, and a reduction of 40% to 60% if a patient has significantly elevated IOP and many risk factors. Regardless of the regimen, the target IOP should occasionally be re-evaluated to determine whether sufficient improvements have been achieved. 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).

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.

If IOP worsens while the patient is on the maximum tolerated medical therapy (varies between individuals and may be a combination of more than one drug from one or multiple classes), surgery (e.g., trabeculoplasty, drainage implant surgery, ciliary body ablation or deep sclerectomy/viscocanalostomy) may be warranted.