Primary Open Angle Glaucoma
• Primary open angle glaucoma is an irreversible optic neuropathy typically associated with elevated intraocular pressure.
• Primary open angle glaucoma is the most common form of glaucoma and is projected to affect more than 3 million Americans in 2020. It is more common in African-Americans (6%–7%), Asians (2%–3%), and Hispanics (2%) and less common in whites (1%). It is more common in older adults: 1%–2% in 50-year-olds compared to 6%–12% in 80-year-olds.
• Primary open angle glaucoma is diagnosed by a complete ophthalmic examination, including dilated stereoscopic optic nerve examination and formal visual field.
• Untreated primary open angle glaucoma can lead to slow irreversible loss of vision and blindness. Other common causes of slow and progressive vision loss in older adults include cataracts, macular degeneration, and diabetic retinopathy.
Acute Angle Closure Glaucoma
• Pupillary block in susceptible patients leads to block of aqueous drainage and sudden and extreme rise of intraocular pressure. Acute angle closure can damage the optic nerve, resulting in acute angle closure glaucoma.
• About 0.5% to 1.0% of U.S. adults are at risk for acute angle closure. It is more common in Inuits and Asians and rare in African- Americans. The risk of acute angle closure increases with age. It is also more common in hyperopes.
• Patients can present with blurry vision, red eye, pain, headache, nausea, or vomiting. Acute angle closure is sometimes misdiagnosed as migraines or gastrointestinal illnesses. Patients with conjunctivitis, keratitis, uveitis, and corneal abrasion can also present with the same symptoms.
• Peripheral iridotomy prevents acute angle closure in susceptible patients. High intraocular pressure can result in irreversible damage of the optic nerve within hours, making acute angle closure one of the true ophthalmic emergencies.
Primary Open Angle Glaucoma
• Topical eye drops, including β-blockers, selective α2 agonists, carbonic anhydrase inhibitors, and prostaglandin analogues can be used to reduce intraocular pressure.
• Oral carbonic anhydrase inhibitors are typically used in recalcitrant cases until surgery can be performed.
• Laser trabeculoplasty may be used as first-line or adjunct therapy.
• Glaucoma surgery, including trabeculectomy, tube shunt, and cyclodestruction, may be performed if goal intraocular pressure cannot be reached with medical therapy or in nonadherent patients.
Acute Angle Glaucoma
• All glaucoma eye drops are used to reduce intraocular pressure.
• Oral and intravenous medications are added sequentially to reduce intraocular pressure as needed.
• Laser iridotomy can be performed as prophylactic treatment or acutely to break the pupillary block if the patient is unresponsive to medical intervention.
• Emergent glaucoma incisional surgery is performed if the patient is unresponsive to all other treatments.
Glaucoma is an optic neuropathy with characteristic optic nerve head appearance: narrowing of the neuroretinal rim. The optic nerve is a collection of more than 1 million axons from the retinal ganglion cells. The anterior 1-mm portion of the optic nerve within the globe is referred to as the optic disk or simply the disk. When the disk is examined with direct or indirect ophthalmoscopy, a cup, or a physiologic empty space, is observed centrally. The remainder of the disk, which has a yellow-orange appearance, contains the axons and is referred to as the neuroretinal rim. The area of the cup compared to the entire disk is the cup-to-disk ratio, which is normally less than 0.4 (Figure 1A). When patients develop glaucoma, axons are lost from the neuroretinal rim and the size of the cup increases in relation to the disk. Narrowing of the neuroretinal rim and increased cup-to-disk ratio are the hallmarks of glaucomatous optic neuropathy (Figure 1B).
FIGURE 1 Disk appearance. A, Normal disk. Cup-to-disk ratio is less than 0.4. B, Glaucoma. Increased cup-to-disk ratio and narrow neuroretinal rim superiorly and inferiorly (arrows).
Glaucoma can result in significant and irreversible loss of vision and is one of the leading causes of blindness in the United States. Early in the disease state, glaucoma is asymptomatic; it is sometimes called “the sneak thief of sight.” As the disease progresses, the patient develops decreased peripheral vision and eventually loss of the central vision.
Glaucoma is typically associated with increased intraocular pressure (IOP), but it is possible to have normal-tension or low- tension glaucoma. Glaucoma treatment is focused on the reduction of IOP to prevent or slow optic nerve damage and preserve visual function.
Glaucoma is classified in many ways, and it is most useful to approach it clinically based on the status of the angle, the area between the cornea and iris where aqueous exits the globe through the trabecular network. We further discuss primary open angle glaucoma, the most common form of glaucoma in the United States, and the management of acute angle closure, one of the true ophthalmic emergencies.
Primary Open Angle Glaucoma
Glaucoma is one of the leading causes of blindness in older adults, especially in patients of African-American descent. Vision loss from glaucoma is irreversible, and the treatment goal is to reduce IOP, slow disease progression, and preserve visual function during the patient’s lifetime. Glaucoma is a slowly progressive disease, and progression to blindness often takes more than 10 years, even in untreated patients.
Given its slow progression and the fact that central vision loss occurs in late disease, most patients do well with early diagnosis and treatment. Treatment is more difficult in late disease because the rate of disease progression and visual deterioration is accelerated, sometimes despite good control of IOP.
Due to the early asymptomatic nature of the disease, the patient’s adherence to and persistence with treatment is often less than optimal. Studies have shown patients who obtain glaucoma information from physicians other than their ophthalmologists have a higher rate of medication adherence. Ophthalmologists have the options to use treatment modalities such as laser and surgery to obtain pressure control and decrease or eliminate the need for medication use.
The American Academy of Ophthalmology recommends asymptomatic patients older than 40 years be referred for ophthalmic evaluation once every several years for early detection of glaucoma and other chronic eye diseases. However, the U.S. Preventive Services Task Force found insufficient evidence to recommend for or against screening for glaucoma in adults. Risks, benefits, and cost effectiveness of screening are beyond the scope of this chapter, but symptomatic patients or patients at high risk for glaucoma (African American ethnicity and family history) might benefit from ophthalmology consultation. It is possible to diagnose glaucoma by direct ophthalmoscopy, but this is not a substitute for binocular assessment of the disk through dilated pupils and formal visual field testing. If glaucoma is suspected or diagnosed, primary care visits should include inquiries regarding glaucoma medication use, medication side effects, and the time of last eye examination. Primary care physicians can improve glaucoma outcome by promoting adherence to medication and follow-up. Glaucoma patients need to follow up with their ophthalmologists at least annually, and in severe cases every 3 months, for intraocular pressure checks.
Topical Glaucoma Medications
Topical glaucoma medications are administered once or twice daily. Patients should look up, pull down their lower eye lid, drop the medication on the inferior conjunctival cul-de-sac, and keep their eyes closed for 5 minutes. Applying gentle pressure next to the bridge of the nose to occlude the puncta can improve absorption of the medication. Medication bottle caps are color-coded by their class, and patients can usually identify their eye drops by color. Glaucoma medications are not subject to first-pass effect through the liver and can sometimes have significant systemic side effects, especially the β- blockers. Topical glaucoma medications are described later and summarized in Table 1.
Topical Glaucoma Medications: Carbonic Anhydrase Inhibitors
Abbreviation: COPD = chronic obstructive pulmonary disease.
Latanoprost (Xalatan), travoprost (Travatan), and bimatoprost (Lumigan) are prostaglandin analogues and are color-coded by teal caps. They are administered once at bedtime but may be administered once at any time during the day to promote adherence. They decrease IOP by increasing aqueous outflow. Side effects are primarily local and include increased conjunctival hyperemia, increased lash growth, and possible irreversible increase in periocular and iris pigmentation.
Timolol (Betimol, Istalol, Timoptic), levobunolol (Betagan), and betaxolol (Betoptic) are color-coded by yellow caps. They are administered once or twice daily and decrease IOP by decreasing aqueous production. Side effects include bradycardia, exacerbation of chronic obstructive pulmonary disease (COPD) and asthma, impotence, and decreased serum high-density lipoprotein (HDL) cholesterol. Physicians need to be aware that a topical β-blocker is a potential cause of acute changes in cardiovascular or pulmonary status. There are several reported incidents of death following the use of topical β-blockers mostly due to exacerbation of asthma.
Selective α2 Agonists
Brimonidine (Alphagan) and apraclonidine (Iopidine) belong to the class of selective α2 receptor agonists, and brimonidine is more commonly prescribed; it is color-coded by purple caps. It is administered twice daily and decreases IOP by decreasing aqueous production. Allergic conjunctivitis has been reported in up to 25% of patients. Rarely, it causes dry mouth and chronic fatigue and drowsiness in the elderly.
Carbonic Anhydrase Inhibitors
Dorzolamide (Trusopt) and brinzolamide (Azopt) are color-coded by orange caps and are sulfa-based medications. They are administered twice daily and decrease IOP by decreasing aqueous production. This class of medication has minimal systemic side effects. However, some patients complain about transient stinging and a bitter taste in the mouth after administration. These side effects, if tolerable, are not indications for discontinuing therapy.
Combined Topical Medications
Timolol and dorzolamide (Cosopt) and timolol and brimonidine (Combigan) are color-coded by blue caps. Brimonidine and brinzolamide (Simbrinza) is color-coded by a light green cap.
Combined medications decrease exposure to preservatives and can decrease irritation and problems with dry eyes. Adherence might also be improved.
Oral Carbonic Anhydrase Inhibitors
Oral carbonic anhydrase inhibitors include acetazolamide (Diamox), 250 mg or 500 mg given twice daily, and methazolamide (Neptazane), 25 mg or 50 mg given twice daily. They are sulfa-based medications and decrease IOP by decreasing aqueous production. Oral carbonic anhydrase inhibitors are not commonly used today because effective topical medications are available. They are typically used on a short- term basis to achieve IOP control in acute or refractory cases. Side effects can include aplastic anemia, kidney stones, bitter taste, indigestion, paresthesia of the extremities, tinnitus, and polyuria.
Clinicians need to consider the possibility of hypokalemia when patients take other diuretics to control blood pressure (Table 2). Acetazolamide may also be given intravenously.
Oral and Intravenous Glaucoma Medications
Abbreviations: CAI = carbonic anhydrase inhibitor; CHF = congestive heart failure.
Argon or selective laser trabeculoplasty can be used to increase aqueous outflow. Laser trabeculoplasty is noninvasive and safe, and it can be performed in the office in less than 10 minutes. Compared to surgery, IOP reduction is limited, up to 25% as primary treatment, but less as an adjunct modality. It is ineffective or less effective in some patients with light trabecular meshwork pigmentation. The effect of laser decreases over time but may be repeated in the case of selective laser trabeculoplasty.
The most commonly performed glaucoma surgeries are trabeculectomy, tube shunt, and cyclodestruction. Trabeculectomy and tube shunt are procedures that create an opening in the sclera to increase aqueous outflow. Cyclodestruction destroys the ciliary body and decreases aqueous production. The procedure can be transscleral or endoscopic; the endoscopic method is typically done at the time of cataract surgery. Alternative surgical methods, such as deep sclerectomy, Trabectome, canaloplasty, and iStent, are being developed and performed to minimize the invasiveness and potential complications associated with traditional glaucoma surgery.
Visual Impairment and Blindness
Patients who are visually impaired (Snellen vision of less than 20/40) or legally blind (Snellen vision of less than 20/200 or visual field of less than 20 degrees) may have significantly decreased mobility and ability to function. Continued glaucoma treatment is still important in these patients because even maintenance of count-finger vision can allow the patients some degree of independence. Low-vision devices and services, including high-contrast video magnifiers, audiobooks, eccentric viewers, and mobility training, can allow patients maximal use of their residual vision and improve their confidence and quality of life.
Acute Angle Closure Glaucoma
Pupillary block in susceptible patients blocks aqueous drainage and leads to sudden and extreme rise of intraocular pressure. Acute angle closure can damage the optic nerve, resulting in acute angle closure glaucoma.
About 0.5% to 1.0% of U.S. adults is at risk for acute angle closure. It is more common in Inuits and Asians and rare in African Americans. The risk of acute angle closure increases with age. It is also more common in hyperopes (farsightedness).
Mechanism of Acute Angle Closure: Pupillary Block
After aqueous is produced in the ciliary body in the posterior chamber, it travels through the pupil and exits the anterior chamber through the trabecular meshwork located between the iris and the cornea. Pupillary block occurs when the iris comes in contact with the lens and obstructs the flow of aqueous through the pupil. Increased posterior chamber pressure displaces the iris anteriorly against the trabecular meshwork and stops aqueous outflow.
Patients at risk for acute angle closure have narrow occludable angles. These patients have smaller eyes, allowing the lens to contact the iris to initiate papillary block. The distance between the iris and the lens is the shortest when the pupil is mid-dilated. Therefore, patients who present with acute angle closure might have a history of dim light exposure (movies) or use of medications with anticholinergic properties (antihistamines, decongestants, antispasmodics). High IOP causes iris and corneal endothelial cell dysfunction, resulting in nonreactive pupil and hazy cornea, respectively. High IOP also results in inflammation and red eye as well as severe pain, nausea, and vomiting (Figure 2). Elevated IOP can damage the optic nerve within hours, and acute angle closure needs to be treated emergently to prevent permanent loss of vision.
FIGURE 2 Acute angle closure patient with red eye and mid-dilated and nonreactive pupil.
Patients with acute angle closure can present with blurry vision, red eye, pain, headache, nausea, or vomiting. History can include hyperopia, onset after exposure to a dim environment, or taking anticholinergic medications. Examination findings include decreased vision, conjunctival hyperemia, mid-dilated, nonreactive pupil with or without an afferent papillary defect, and increased IOP (by palpation or tonometry). Acute angle closure is sometimes misdiagnosed as migraines or gastrointestinal illness. Patients with conjunctivitis, keratitis, uveitis, and corneal abrasion can also present with the same symptoms.
If acute angle closure is suspected, an emergent referral to ophthalmology is indicated. If an ophthalmologist is not immediately available, the goal will be to medically control the IOP as soon as possible. One drop of topical aqueous suppressant—β-blocker, selective α2 agonist, or carbonic anhydrase inhibitor—should be administered (timolol, brimonidine, dorzolamide) (see Table 1). The maximum dose of oral or intravenous carbonic anhydrase inhibitor is given: acetazolamide 500 mg or methazolamide 50 mg (see Table 2).
The patient is placed in the supine position to allow the lens and iris to fall posteriorly. The patient is reassessed in 30 minutes, and if the condition is not improved, topical drops are repeated. If there is no improvement after another 30 minutes, a hyperosmotic, oral glycerin (Osmoglyn) 1 g/kg or intravenous mannitol (Osmitrol) 1 g/kg over 30 minutes, is administered. Hyperosmotics may be contraindicated in patients with congestive heart failure, and glycerin can cause severe hyperglycemia in diabetic patients.
An ophthalmologist can break the pupillary block by medically lowering the IOP or by performing anterior chamber paracentesis, compression gonioscopy, laser peripheral iridotomy, and, in recalcitrant cases, emergent trabeculectomy. Once the pressure is controlled, it is important to perform an iridotomy in both eyes to prevent future episodes. Patients with patent iridotomies may safely take anticholinergic medications.
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