Glaucoma is the second leading cause of permanent blindness in the United States and occurs most often in older adults. There are four general categories of adult glaucoma: primary open-angle and angle-closure, and the secondary open and angle-closure glaucoma. The most common type in the United States is primary, open-angle glaucoma (POAG). Glaucoma is defined as an acquired loss of retinal ganglion cells and axons within the optic nerve or optic neuropathy that results in a characteristic optic nerve head appearance and a corresponding progressive loss of vision. This pattern of peripheral loss of vision can also be a distinguishing characteristic from other forms of vision loss.
The patient with POAG is often asymptomatic until the optic nerve damage is severe unless signs of early glaucoma are recognized on a routine eye exam. Acute angle-closure glaucoma, in contrast, can develop suddenly and result in a more rapid decline in vision with associated corneal edema, eye pain, headache, nausea, and emesis. Secondary glaucoma is usually correlated with a prior eye injury or disease state, causing elevated intraocular pressure (IOP) and related optic neuropathy. The last type is normal or low-tension type glaucoma in which patients have the same visual loss pattern as POAG but at normal intraocular pressure readings.
While there are congenital, infantile, development glaucomas, and a juvenile variant of POAG, the four previously mentioned glaucoma types typically occur in people over the age of 40. The cause is generally correlated with increased intraocular pressure, though it has not been proven to have a direct cause-and-effect relationship. There may also be a genetic component to the development of glaucoma. Monozygotic twin pairs have a higher percentage of concordance, but not pairs, which suggests that environmental factors also influence the development of the disease. Currently, glaucoma cannot be prevented or cured, but progression can be controlled to help prevent further vision loss either through medication, glaucoma laser treatment, or incisional glaucoma surgeries.
Currently, the exact etiology of glaucoma is unknown, but there is a clear correlation with elevated eye pressures in the majority of POAG cases. Open-angle glaucoma typically manifests as slow, painless damage to the optic nerve that is thought to be due to the drainage system in the eye becoming ineffective. In glaucoma, the resistance to drainage of aqueous humor most commonly starts at the inner wall of Schlemm’s canal at the juxtacanalicular trabecular meshwork. The decreased outflow facility, or increased resistance to outflow of aqueous results in the gradual elevation of IOP and a characteristic damage pattern to the optic nerve ganglion cell nerve fiber layer. Another theory is that the increased IOP causes decreased blood flow to the optic nerve fibers, which leads to subtle ischemic damage. Either way, POAG patients often have elevated intraocular pressure (IOP) readings that seem to correlate with characteristic optic nerve damage patterns. As the disease progresses, there is a slow loss of peripheral vision in both eyes; eventually leading to loss of central vision if left undetected or untreated. It is because of this pattern of loss that affected persons do not notice a change in their vision until their loss is advanced and affecting the central vision.
There are a couple of subsets of open-angle glaucoma, which are juvenile open-angle glaucoma and low-tension/normal-tension glaucoma. Juvenile open-angle glaucoma affects patients between the ages of 5-35 years old. It is uncommon and tends to be found later in the disease process because of its early but gradual IOP elevation. Patients also typically present with eye pressures greater than 30 mm Hg. Juvenile open-angle is thought to follow the same process of increased IOP leading to optic neuropathy as POAG, just in a younger patient population.
Low-tension or normal-tension glaucoma resembles POAG as there are the characteristic optic disc cupping and peripheral visual-field loss finding, but the IOP readings are consistently less than 21 mm Hg. Theories include having an abnormally pressure-sensitive optic nerve or intermittent ischemic change due to atherosclerosis/vascular insufficiency. There appears to be a higher prevalence of vasospastic disorders such as migraines, Raynaud phenomenon, autoimmune diseases, ischemic vascular diseases, and coagulopathies seen in these patients, which may suggest a vascular autoregulatory defect playing a role in the pathogenesis of the disease. Normal-tension also tends to have a greater frequency of nerve fiber layer hemorrhages and a neuroretinal rim that is thinner inferiorly and inferotemporally than those with open-angle type. Visual field defects are more focal, deeper, and closer to fixation rather than the classic arcuate scotoma pattern in open-angle.
Angle-closure is the type of glaucoma that can present as a medical emergency in the acute setting. This occurs when the drainage system of the eye becomes blocked abruptly due to the closure of the angle formed between the cornea and the iris. Typically, this occurs due to an age-related thickening of the lens, causing the gradual increase in a relative pupillary block, which then pushes the iris anteriorly. This anteriorly displaced iris along with a natural anatomical variation of a smaller angle, as seen in far-sightedness or certain ethnic groups, allows for the easier blockage of the outflow tract. A pupillary block is considered to be the underlying cause of more than 90% of cases. When sudden pupil dilation occurs due to stimulus or drugs, the iris becomes thick enough in its contracted state, or anteriorly displaced by pupillary block, to block the drainage of fluid via the trabecular meshwork. The pressure then rapidly increases within the eye. It is this rapid change in intraocular pressure that can cause vision loss to occur within a day of onset without intervention, due to retinal vascular occlusion, ischemic optic neuropathy, or glaucomatous optic nerve damage. However, only about 10% of glaucoma cases are this acute angle-closure type.
Angle-closure glaucoma can occur secondary to another cause. One such cause is lens subluxation in Marfan’s syndrome. The lens can displace into the pupil or anterior chamber, causing an acute pupillary block. Plateau iris can also cause an acute pupillary block, and chronic angle closure, due to elongated or anteriorly positioned ciliary processes that push the edges of the iris forward. In Iridocorneal endothelial syndrome, the corneal endothelium is irregular and can migrate onto the trabecular meshwork and peripheral iris. This creates a contraction causing high peripheral anterior synechiae, which can close the angle, preventing outflow. Neovascularization can cause closure of the angle by creating a fibrovascular membrane that flattens the iris and displaces it anteriorly and causing total synechial closure of the angle. Angle-closure can occur after ophthalmic surgery due to ciliary body edema, scleral buckle placement, fibrin deposition, gas, or silicone oil like that used in retinal surgery. Sulfa drugs such as topiramate can induce angle closure due to ciliochoroidal effusion that compresses the lens-iris diaphragm, displacing it anteriorly, thus closing off the angle.
Secondary open-angle type is due to injury, eye disease, and rarely eye surgery causing increased intraocular pressure and, therefore, optic nerve damage like the open-angle form of glaucoma. One mechanism is from laser surgery, which can cause pigment release, inflammatory cells, debris, and mechanical deformation resulting in blockage of the trabecular meshwork leading to increased intraocular pressure. The most common mechanism for the secondary type is from diseases causing neovascularization. Neovascularization can either physically block the outflow tracts. Pseudoexfoliative type is when flaky material peels off the outer lens capsule and collects in the angle, clogging the trabecular meshwork, leading to increased eye pressure. Pigmentary type is similar to exfoliative except the debris are pigment granules from the back of the iris that break off and clog the trabecular meshwork due to contact with the peripheral lens capsule and zonules in typically myopic, or near-sighted eyes. Steroids can induce secondary glaucoma due to increased outflow resistance by the upregulation of glucocorticoid receptors on cells within the trabecular meshwork and accumulation of glycosaminoglycans in the meshwork pores. Steroids also suppress the phagocytic activity, which decreases debris deposition removal from the meshwork as well as stimulates the expression of extracellular matrix proteins. A carotid-cavernous fistula causes an abnormal communication between the cavernous sinus and carotid artery. This causes an arterial flow and venous engorgement leading to elevated episcleral venous pressure. It also causes a dilation of retinal veins and optic disc swelling that can concurrently damage optic nerve fibers. Glaucomatocyclitic Crisis manifests as recurrent acute attacks of increased intraocular pressure that resolve without treatment but with repeated attacks, has been reported to cause glaucomatous damage to the optic nerve over time.
Worldwide, an estimated 60 million people have optic neuropathy due to glaucoma. The African population has the highest prevalence of open-angle type. The likelihood of blindness from open-angle glaucoma is up to 15-times greater in those with African-decent compared to other population groups. The highest prevalence for angle-closure is in the Inuit population and has also been shown to affect a higher rate in women than men, and in those of Asian-decent, with these groups generally having a shallower anterior chamber. Normal-tension type is most prevalent in Japanese populations. Across all types, age is a major risk factor in the continual loss of retinal ganglion cells. Other risk factors for developing glaucoma include those with a family history of glaucoma in a primary relative (mother, father, brother, sister, or children), medical conditions such as diabetes, high blood pressure, heart disease, eye trauma, anatomical differences such as thinner corneas, history of retinal detachment, eye tumors or inflammation, and corticosteroid use for prolonged periods of time.
Over 1 million nerve fibers travel via the optic nerve, which transmits the visual signals from the photoreceptors within the outer retina to the visual processing areas of the occipital lobe. The various types of glaucoma all cause damage to the retinal nerve fiber layer. This fluid within the anterior chamber of the eye is called aqueous humor. Aqueous is produced by the non-pigmented epithelial cells of the ciliary body processes, with an individual circadian pattern of production. This fluid has a continuous drainage system first through the pupil and via the trabecular meshwork anterior to the scleral spur and iris insertion, and then into Schlemm’s canal and subsequently to the episcleral venous system and larger orbital venous system into the systemic venous circulation. The trabecular meshwork is made up of multiple layers of connective tissue and the endothelium of Schlemm’s canal. The outflow of fluid via this conventional outflow pathway is the pressure dependent, and functions as a one-way valve for the drainage of aqueous. The uveoscleral outflow pathway, in contrast, allows pressure-independent egress passage of aqueous through the face of the ciliary muscle and iris root, into the supraciliary and suprachoroidal space. This tract is thought to manifest a decrease in outflow with age. With time there manifests a decreased aqueous outflow via the trabecular meshwork as well, while the ciliary body production of aqueous decreases modestly, an imbalance of outflow and aqueous production results in increased average IOP and larger diurnal fluctuations in IOP. Elevated IOP and increased fluctuations in IOP are commonly seen in patients with glaucoma. With a prolonged elevation of IOP, nerve fibers begin to die and atrophy, creating a “cupped” or curved shape to the normal disc shape of the optic nerve seen on fundoscopy. Normal intraocular pressure is considered approximately 16+/- 3 mm Hg but has many factors that cause it to fluctuate throughout the day, such as heart rate, respiration, exercise, fluid status, systemic medications, time of day, alcohol consumption, patient position, and topical medications.
Currently, screening pressure readings greater than 21 mm Hg are considered above normal physiologic eye pressure are concerning for future glaucomatous nerve damage. However, it is hard to know if patients are transiently spiking pressures throughout the day, causing damage and are just going undetected on screening, which is part of why elevated screening pressure can only be a risk factor for developing glaucoma, and is not required for the diagnosis of glaucoma. Diurnal pressure monitoring of IOP may help to catch this patient population.
Patients with normal-tension glaucoma also tend to have systemic vascular conditions such as Raynaud phenomenon, migraines, sleep apnea, carotid artery disease, and larger than normal changes in blood pressure overnight.
In acute angle-closure glaucoma, this trabecular meshwork drainage pathway is closed off either from the iris being pushed forward from pressure, i.e., anteriorly displaced lens or the iris is pulled forward by fibrous tissue. Most commonly, it is due to a pupillary block in which the iris dilates to mid-position and bows anteriorly due contact with the lens and closes off the trabecular meshwork blocking the aqueous outflow.
As previously mentioned above, secondary glaucoma can be caused by a variety of mechanisms, i.e., surgery or neovascularization, precipitating a blockage of the outflow tracts resulting in increased intraocular pressure, and if prolonged, related glaucomatous optic nerve injury.
History and Physical
Many patients with glaucoma, especially early in the disease, are not aware they have this condition until it is discovered on a routine eye exam. People generally slowly lose peripheral vision but retain central vision until the disease process is severe. This can present in a classic arcuate pattern on Humphrey visual field testing. On comprehensive eye examination, optic nerves may have a focally notched neural retinal rim or diffuse cup enlargement, a decrease in peripheral vision detected on visual field testing, and (although not required for diagnosis) an increased intraocular pressure reading on tonometry. Typically changes will be seen bilaterally but may not progress at the same rate, resulting in an asymmetric optic nerve cup. A cup to disc ratio of > 0.5 is considered suggestive for glaucoma and typically starts with a loss on the inferotemporal and superotemporal poles of the optic disc.
Normal-tension glaucoma patients will typically be asymptomatic and have an intraocular pressure of less than 21mm Hg. On slit-lamp examination, changes in the optic disc such as increased cup to disc ratio will be seen, disc hemorrhage in the nerve fiber layer may also be present. Patients also may have a history of vasospasm, coagulopathies, nocturnal hypotension, autoimmune diseases, vascular diseases, thyroid dysfunction, or sleep apnea.
In the acute angle-closure type, patients typically present with severe sudden ocular pain, redness, blurry vision/decreased visual acuity, headache, nausea or vomiting, and may complain of seeing halos of light. Patients will have an unresponsive mid-dilated pupil on examination and a firm feeling eyeball on palpation. Typically, attacks are precipitated by pupillary dilation due to weak mydriatic, or dilating, drops. Intraocular pressure will typically be high and often in the 30-50 mm Hg range. The angle between the iris and the cornea will be around 20° or less on examination with gonioscopy and/or an anterior chamber depth of less than 2.5mm can be predisposing risk factors. Patients with these findings should be warned to avoid dilating medications to reduce their risk of developing an acute attack. On slit-lamp examination, a large optic cup with narrowing of the neuroretinal rim and splinter hemorrhages may also be present.
Patients with Secondary glaucoma will typically have a history of a recent ophthalmic procedure, trauma, or health condition causing neovascularization like diabetes. However, some patients will not have a clear precipitating factor in their history but will have sometime subtle clinical exam findings pointing to the cause of the IOP elevation. On exam, findings can include exfoliative material on the anterior lens capsule, pigment deposition on the corneal endothelium, cell and flare in the anterior chamber typical of uveitis, abnormal blood vessels on the iris or evidence of trauma; depending on the underlying etiology.
Evaluation is based on a fundoscopic examination, visual field testing, tonometry, optical coherence tomography, and gonioscopy. Other helpful tests include visual acuity to see if vision is being affected, pachymetry to evaluate corneal thickness, and retinal scans to help monitor for progressive changes in the retinal nerve fiber layer.
Glaucoma is diagnosed based on characteristic clinical findings of progressive optic neuropathy or visual field defects based on the testing modalities listed above. There is no single ‘gold standard’ test for the diagnosis of glaucoma. Providers must recognize the characteristic optic nerve appearance, risk factors, and collate the results of ancillary testing to establish a correct diagnosis and staging of glaucoma. Currently, the American Academy of Ophthalmology recommends routine comprehensive eye examinations for patients with risk factors for glaucoma with a frequency determined on an individual basis, considering age, risk factors, race, and family history.
In making the diagnosis of primary open-angle glaucoma, other disease processes that can cause optic neuropathy must be ruled out. Other possible diagnoses to keep in mind are previous ischemic optic neuropathy, optic atrophy, and compressive non-glaucomatous optic neuropathy can cause similar patterns of visual field loss and in some case “pseudo-cupping” of the optic nerve. In the case that elevated IOP or characteristic glaucomatous optic nerve changes are noted, it’s important to evaluate with gonioscopy to determine if the anterior chamber is open, narrow, or closed. Additionally, it is important to evaluate for the often time subtle signs of the many types of secondary glaucoma, review the medication list for possible idiosyncratic drug reactions, steroid response, and to take a thorough history of prior ocular trauma and surgery.
With an acute presentation like that of acute angle-closure, other possible diagnoses to keep in mind are iritis, traumatic hyphema, conjunctivitis, episcleritis, migraine, cluster headache, conjunctivitis, subconjunctival hemorrhage, corneal abrasion, endophthalmitis, orbital compartment syndrome, corneal ulcer, periorbital infections, and infectious keratitis. With a careful history and slit-lamp examination, the clinician can narrow the differential and arrange for appropriate examination and referral.
Enhancing Healthcare Team Outcomes
Glaucoma is a chronic and serious disease that can result in permanent vision loss if not taken care of properly. To reduce the morbidity of the disorder, the condition is best managed by an interprofessional team that is dedicated to the management of patients with vision problems. The key to treatment is patient education. The pharmacist should emphasize the importance of medication compliance and the need to follow up with the eye surgeon. The ophthalmic nurse should assess the intraocular pressure and convey the result to the ophthalmologist.
Regular eye appointments and compliance with medication are vital to helping slow down disease progression. Since glaucoma has a hereditary component, it is important to educate family members that they may be at an increased risk of developing glaucoma and may need to have screening done regularly by an eye doctor for early detection.
No member of the team should change the dose or frequency without first consulting with the ophthalmologist. Only through open communication between the members can the morbidity of glaucoma be decreased.(Level V)
Glaucoma is not a benign disorder, and if left untreated can lead to permanent vision loss. The higher the pressure, the greater the risk of damaging the optic nerve. However, with treatment, the prognosis is good for most patients.