Glaucoma

Glaucoma is a group of eye diseases that lead to damage of the optic nerve, which is important for transmitting visual information from the eye to the brain. This damage is often caused by increased pressure within the eye, known as intraocular pressure (IOP) and may cause vision loss if left untreated.[1] The word glaucoma originated from the Greek word ΓλαύV̇ξ (glaukos), which means "to glow".[5] Glaucoma has been called the "silent thief of sight" because the loss of vision usually occurs slowly over a long period of time.[6] It is associated with old age, a family history of glaucoma, and certain medical conditions or medications.[7]

Glaucoma
Acute angle closure glaucoma of a person's right eye (shown at left). Note the mid-sized pupil, which is non-reactive to light, and redness of the white part of the eye.
SpecialtyOphthalmology, optometry
Symptoms
[1][2]
Usual onsetGradual, or sudden[2]
Risk factorsIncreased pressure in the eye, family history, high blood pressure[1]
Diagnostic methodDilated eye examination[1]
Differential diagnosisUveitis, trauma, keratitis, conjunctivitis[3]
TreatmentMedication, laser, surgery[1]
Frequency6–67 million[2][4]

There are different types of glaucoma, but the most common are called open-angle glaucoma and closed-angle glaucoma.[8] Inside the eye, a liquid called aqueous humor helps to maintain shape and provides nutrients. The aqueous humor normally drains through the trabecular meshwork. In open-angle glaucoma, the draining is impeded, causing the liquid to accumulate and pressure inside the eye to increase. This elevated pressure can damage the optic nerve. In closed-angle glaucoma, the drainage of the eye becomes suddenly blocked, leading to a rapid increase in intraocular pressure. This may lead to intense eye pain, blurred vision, and nausea. Closed-angle glaucoma is an emergency requiring immediate attention.[1]

If treated early, it is possible to slow or stop the progression of glaucoma. Regular eye examinations, especially if the person is over 40 or has a family history of glaucoma, are essential for early detection.[9] Treatment typically includes prescription of eye drops, medication, laser treatment or surgery.[1][10] The goal of these treatments is to decrease eye pressure.[2]

About 80 million people worldwide have glaucoma, with 50% unaware that they are affected.[11] It is the leading cause of blindness in African Americans, Hispanic Americans,[12][13] and Asians.[14] It occurs more commonly among older people,[1] and closed-angle glaucoma is more common in women.[2] Worldwide, glaucoma is the second-leading cause of blindness after cataracts, and is the leading cause of irreversible blindness worldwide.[2][15][16]

Signs and symptoms
Photo showing conjunctival vessels dilated at the corneal edge (ciliary flush, circumcorneal flush) and hazy cornea characteristic of acute angle closure glaucoma

Open angle glaucoma usually presents with no symptoms early in the course of the disease.[15] However, it may gradually progress to involve difficulties with vision.[15] It usually involves deficits in the peripheral vision followed by central vision loss as the disease progresses, but less commonly it may present as central vision loss or patchy areas of vision loss.[15] On an eye examination, optic nerve changes are seen indicating damage to the optic nerve head (increased cup-to-disc ratio on fundoscopic examination).[15]

Acute angle closure glaucoma, a medical emergency due to the risk of impending permanent vision loss, is characterized by sudden ocular pain, seeing halos around lights, red eye, very high intraocular pressure, nausea and vomiting, and suddenly decreased vision.[15] Acute angle closure glaucoma may further present with corneal edema, engorged conjunctival vessels and a fixed and dilated pupil on examination.[17]

Opaque specks may occur in the lens in glaucoma, known as glaukomflecken.[18] The word is German, meaning "glaucoma-specks".

Causes
A normal range of vision
The same view with advanced vision loss from glaucoma

The main cause of glaucoma is damage to the optic nerve. Eventually, this damage leads to vision loss, which can deteriorate with time. Everyone is predisposed to develop glaucoma; there are some people, however, with a higher susceptibility to develop glaucoma due to some risk factors which include:[19]

Ocular hypertension

Ocular hypertension is often wrongly considered a cause, but actually it is a risk factor. Ocular hypertension (increased pressure within the eye) is the most important risk factor for glaucoma, but only about 50% of people with primary open-angle glaucoma actually have elevated ocular pressure.[20] Ocular hypertension—an intraocular pressure above the traditional threshold of 21 mmHg (2.8 kPa) or even above 24 mmHg (3.2 kPa)—is not necessarily a pathological condition, but it increases the risk of developing glaucoma. One study found a conversion rate of 18% within five years, meaning fewer than one in five people with elevated intraocular pressure will develop glaucomatous visual field loss over that period of time.[21] It is a matter of debate whether every person with an elevated intraocular pressure should receive glaucoma therapy; currently, most ophthalmologists favor treatment of those with additional risk factors.[22]

Risk factors for glaucoma include increasing age, high intraocular pressure, a family history of glaucoma, and use of steroid medication.[1] For eye pressures, a value of 21 mmHg or 2.8 kPa above atmospheric pressure (760 mmHg) is often used, with higher pressures leading to a greater risk.[2][23] However, some may have high eye pressure for years and never develop damage.[2] Conversely, optic nerve damage may occur with normal pressure, known as normal-tension glaucoma.[24] The mechanism of open-angle glaucoma is believed to be the slow exit of aqueous humor through the trabecular meshwork, while in closed-angle glaucoma the iris blocks the trabecular meshwork.[2] Diagnosis is achieved by performing a dilated eye examination.[1] Often, the optic nerve shows an abnormal amount of cupping.[2]

Dietary

No clear evidence indicates that vitamin deficiencies cause glaucoma in humans. As such, oral vitamin supplementation is not a recommended treatment.[25] Caffeine increases intraocular pressure in those with glaucoma, but does not appear to affect normal individuals.[26]

Ethnicity

Many people of East Asian descent are prone to developing angle closure glaucoma because of shallower anterior chamber depths, with the majority of cases of glaucoma in this population consisting of some form of angle closure.[27] Higher rates of glaucoma have also been reported for Inuit populations, compared to White populations, in Canada and Greenland.

In the United States, glaucoma is more common in African Americans, Latinos and Asian-Americans.[15]

Genetics

Positive family history is a risk factor for glaucoma. The relative risk of having primary open-angle glaucoma is increased about two- to four-fold for people who have a sibling with glaucoma.[28] Glaucoma, particularly primary open-angle glaucoma, is associated with mutations in several genes, including MYOC, ASB10, WDR36, NTF4, TBK1,[29] and RPGRIP1.[30] Many of these genes are involved in critical cellular processes that are implicated in the development and progression of glaucoma, including regulation of intraocular pressure, retinal ganglion cell health, and optic nerve function.[31] Normal-tension glaucoma, which comprises one-third of primary open-angle glaucoma, is also associated with genetic mutations (including OPA1 and OPTN genes).[32]

Additionally, there are some rare genetic conditions that increase the risk of glaucoma, such as Axenfeld-Rieger syndrome and primary congenital glaucoma, which is associated with mutations in CYP1B1 or LTBP2.[33] They are inherited in an autosomal recessive fashion.[33] Axenfeld-Rieger syndrome is inherited in an autosomal dominant fashion and is associated with PITX2 or FOXC1.[34]

Other
Laser Doppler imaging reveals arterial blood flow reversal in neovascular glaucoma. The color change of the Doppler image in the central retinal artery during the cardiac cycle indicates arterial flow reversal.[35]

Other factors can cause glaucoma, known as "secondary glaucoma", including prolonged use of steroids (steroid-induced glaucoma); conditions that severely restrict blood flow to the eye, such as severe diabetic retinopathy and central retinal vein occlusion (neovascular glaucoma); ocular trauma (angle-recession glaucoma); plateau iris; and inflammation of the middle layer of the pigmented vascular eye structure (uveitis), known as uveitic glaucoma.

Pathophysiology
Human eye cross-sectional view

The underlying cause of open-angle glaucoma remains unclear. Several theories exist on its exact etiology. However, the major risk factor for most glaucomas and the focus of treatment is increased intraocular pressure. Intraocular pressure is a function of production of liquid aqueous humor by the ciliary processes of the eye, and its drainage through the trabecular meshwork. Aqueous humor flows from the ciliary processes into the posterior chamber, bounded posteriorly by the lens and the zonules of Zinn, and anteriorly by the iris. It then flows through the pupil of the iris into the anterior chamber, bounded posteriorly by the iris and anteriorly by the cornea.

From here, the trabecular meshwork drains aqueous humor via the scleral venous sinus (Schlemm's canal) into scleral plexuses and general blood circulation.[36]

In open/wide-angle glaucoma, flow is reduced through the trabecular meshwork, due to the degeneration and obstruction of the trabecular meshwork, whose original function is to absorb the aqueous humor. Loss of aqueous humor absorption leads to increased resistance and thus a chronic, painless buildup of pressure in the eye.[37]

In primary angle closure glaucoma, the iridocorneal angle is narrowed or completely closed obstructing the flow of aqueous humor to the trabecular meshwork for drainage. This is usually due to the forward displacement of the iris against the cornea, resulting in angle closure. This accumulation of aqueous humor causes an acute increase in pressure and damage to the optic nerve.[15]

The pathophysiology of glaucoma is not well understood. There are several theories regarding the mechanism of the damage to the optic nerve in glaucoma. The biomechanical theory hypothesizes that the retinal ganglion cell axons (which form the optic nerve head and the retinal nerve fiber layer) are particularly susceptible to mechanical damage from increases in the intraocular pressure as they pass through pores at the lamina cribrosa. Thus increases in intraocular pressure would cause nerve damage as seen in glaucoma.[15] The vascular theory hypothesizes that a decreased blood supply to the retinal ganglions cells leads to nerve damage. This decrease in blood supply may be due to increasing intraocular pressures, and may also be due to systemic hypotension, vasospasm or atherosclerosis.[15] This is supported by evidence that those with low blood pressure, particularly low diastolic blood pressure, are at an increased risk of glaucoma.[15] And the primary neurodegeneration theory hypothesizes that a primary neurodegenerative process may be responsible for degeneration at the optic nerve head in glaucoma.[15] This would be consistent with a possible mechanism of normal tension glaucoma (those with open angle glaucoma with normal eye pressures) and is supported by evidence showing a correlation of glaucoma with Alzheimer's dementia and other causes of cognitive decline.[38][39]

Degeneration of axons of the retinal ganglion cells (the optic nerve) is a hallmark of glaucoma.[40] The inconsistent relationship of glaucomatous optic neuropathy with increased intraocular pressure has provoked hypotheses and studies on anatomic structure, eye development, nerve compression trauma, optic nerve blood flow, excitatory neurotransmitter, trophic factor, retinal ganglion cell or axon degeneration, glial support cell, immune system, aging mechanisms of neuron loss, and severing of the nerve fibers at the scleral edge.[41][42][43][44][45][46]

Diagnosis
Optic nerve in advanced glaucoma disease
Glaucoma (right eye) with significant optic disc involvement. 80-year-old man. Optic disc topography.

Screening for glaucoma is an integral part of a standard eye examination performed by optometrists and ophthalmologists.[47] The workup for glaucoma involves taking a thorough case history, with the emphasis on assessment of risk factors.

The baseline glaucoma evaluation tests include intraocular pressure measurement by using tonometry, anterior chamber angle assessment by optical coherence tomography, inspecting the drainage angle (gonioscopy), and retinal nerve fiber layer assessment with a dilated fundus examination, measuring corneal thickness (pachymetry), and visual field testing.[47]

Types

Glaucoma has been classified into specific types:[48]

Primary glaucoma and its variants

Primary glaucoma (H40.1-H40.2)

  • Primary open-angle glaucoma, also known as chronic open-angle glaucoma, chronic simple glaucoma, glaucoma simplex
  • High-tension glaucoma
  • Low-tension glaucoma
  • Primary angle closure glaucoma, also known as primary closed-angle glaucoma, narrow-angle glaucoma, pupil-block glaucoma, acute congestive glaucoma
  • Acute angle closure glaucoma (aka AACG)[49]
  • Chronic angle closure glaucoma
  • Intermittent angle closure glaucoma
  • Superimposed on chronic open-angle closure glaucoma ("combined mechanism" – uncommon)

Variants of primary glaucoma

Primary angle closure glaucoma is caused by contact between the iris and trabecular meshwork, which in turn obstructs outflow of the aqueous humor from the eye. This contact between iris and trabecular meshwork (TM) may gradually damage the function of the meshwork until it fails to keep pace with aqueous production, and the pressure rises. In over half of all cases, prolonged contact between iris and TM causes the formation of synechiae (effectively "scars").

These cause permanent obstruction of aqueous outflow. In some cases, pressure may rapidly build up in the eye, causing pain and redness (symptomatic, or so-called "acute" angle closure). In this situation, the vision may become blurred, and halos may be seen around bright lights. Accompanying symptoms may include a headache and vomiting.

Diagnosis is made from physical signs and symptoms: pupils mid-dilated and unresponsive to light, cornea edematous (cloudy), reduced vision, redness, and pain. However, the majority of cases are asymptomatic. Prior to the very severe loss of vision, these cases can only be identified by examination, generally by an eye care professional.

Primary open-angle glaucoma is when optic nerve damage results in a progressive loss of the visual field.[50] This is associated with increased pressure in the eye. Not all people with primary open-angle glaucoma have eye pressure that is elevated beyond normal, but decreasing the eye pressure further has been shown to stop progression even in these cases.

The increased pressure is caused by trabecular meshwork blockage. Because the microscopic passageways are blocked, the pressure builds up in the eye and causes imperceptible very gradual vision loss. Peripheral vision is affected first, but eventually the entire vision will be lost if not treated.

Diagnosis is made by looking for cupping of the optic nerve.

Developmental glaucoma

Developmental glaucoma (Q15.0)

  • Primary congenital glaucoma
  • Infantile glaucoma
  • Glaucoma associated with hereditary or familial diseases

Secondary glaucoma

Secondary glaucoma (H40.3-H40.6)

  • Inflammatory glaucoma
  • Uveitis of all types
  • Fuchs heterochromic iridocyclitis
  • Phacogenic glaucoma
  • Angle-closure glaucoma with mature cataract
  • Phacoanaphylactic glaucoma secondary to rupture of lens capsule
  • Phacolytic glaucoma due to phacotoxic meshwork blockage
  • Subluxation of lens
  • Glaucoma secondary to intraocular hemorrhage
  • Hyphema
  • Hemolytic glaucoma, also known as erythroclastic glaucoma
  • Traumatic glaucoma
  • Angle recession glaucoma: Traumatic recession on anterior chamber angle
  • Postsurgical glaucoma
  • Aphakic pupillary block
  • Ciliary block glaucoma
  • Neovascular glaucoma (see below for more details)
  • Drug-induced glaucoma
  • Corticosteroid induced glaucoma
  • Alpha-chymotrypsin glaucoma. Postoperative ocular hypertension from use of alpha chymotrypsin.
  • Glaucoma of miscellaneous origin
  • Associated with intraocular tumors
  • Associated with retinal detachments
  • Secondary to severe chemical burns of the eye
  • Associated with essential iris atrophy
  • Toxic glaucoma

Neovascular glaucoma, an uncommon type of glaucoma, is difficult or nearly impossible to treat, and is often caused by proliferative diabetic retinopathy (PDR) or central retinal vein occlusion (CRVO). It may also be triggered by other conditions that result in ischemia of the retina or ciliary body. Individuals with poor blood flow to the eye are highly at risk for this condition.

Neovascular glaucoma results when new, abnormal vessels begin developing in the angle of the eye that begin blocking the drainage. People with such condition begin to rapidly lose their eyesight. Sometimes, the disease appears very rapidly, especially after cataract surgery procedures.

Toxic glaucoma is open-angle glaucoma with an unexplained significant rise of intraocular pressure following unknown pathogenesis. Intraocular pressure can sometimes reach 80 mmHg (11 kPa). It characteristically manifests as ciliary body inflammation and massive trabecular edema that sometimes extends to Schlemm's canal. This condition is differentiated from malignant glaucoma by the presence of a deep and clear anterior chamber and a lack of aqueous misdirection. Also, the corneal appearance is not as hazy. A reduction in visual acuity can occur followed neuroretinal breakdown.

Associated factors include inflammation, drugs, trauma and intraocular surgery, including cataract surgery and vitrectomy procedures. Gede Pardianto (2005) reported on four patients who had toxic glaucoma. One of them underwent phacoemulsification with small particle nucleus drops. Some cases can be resolved with some medication, vitrectomy procedures or trabeculectomy. Valving procedures can give some relief, but further research is required.[51]

Absolute glaucoma

Absolute glaucoma (H44.5) is the end stage of all types of glaucoma. The eye has no vision, absence of pupillary light reflex and pupillary response, and has a stony appearance. Severe pain is present in the eye. The treatment of absolute glaucoma is a destructive procedure like cyclocryoapplication, cyclophotocoagulation, or injection of 99% alcohol.

Glaucoma is an umbrella term for eye conditions that damage the optic nerve and that can lead to a loss of vision.[52] The main cause of damage to the optic nerve is intraocular pressure (IOP), excessive fluid pressure within the eye, which can be caused by factors such as blockage of drainage ducts and narrowing or closure of the angle between the iris and cornea.

Glaucoma is primarily categorized as either open-angle or closed-angle (or angle-closure). In open-angle glaucoma, the iris meets the cornea normally, allowing the fluid from inside the eye to drain, thus relieving the internal pressure. When this angle is narrowed or closed, pressure increases over time, causing damage to the optic nerve and leading to blindness.

Primary open-angle glaucoma (also called primary or chronic glaucoma) involves the slow clogging of drainage canals resulting in increased eye pressure, which causes progressive optic nerve damage. This manifests as a gradual loss of the visual field, starting with a loss of peripheral vision, but eventually all vision will be lost if the condition is not treated.[50] This is the most common type of glaucoma, accounting for 90% of cases in the United States, but is less prevalent in Asian countries. Onset is slow and painless, and loss of vision is gradual and irreversible.

With narrow-angle glaucoma (also called closed-angle glaucoma), the iris bows forward, narrowing the angle that drains the eye, increasing pressure within the eye. If untreated, it can lead to the medical emergency of angle-closure glaucoma.

With angle-closure glaucoma (also called closed-angle, primary angle-closure or acute glaucoma), the iris bows forward and causes physical contact between the iris and trabecular meshwork, which blocks the outflow of aqueous humor from within the eye. This contact may gradually damage the draining function of the meshwork until it fails to keep pace with aqueous production, and the intraocular pressure rises. The onset of symptoms is sudden and causes pain and other noticeable symptoms, and the condition is treated as a medical emergency. Unlike open-angle glaucoma, angle-closure glaucoma is a result of the closing of the angle between the iris and cornea. This tends to occur in the farsighted, who have smaller anterior chambers, making physical contact between the iris and trabecular meshwork more likely. A variety of tests may be performed to detect those at risk of angle-closure glaucoma.[53] Closed-angle glaucoma accounts for fewer than 10% of glaucoma cases in the United States, but as many as half of glaucoma cases in other nations (particularly East Asian countries).[54]

Normal-tension glaucoma (NTG, also called low-tension or normal-pressure glaucoma) is a condition in which the optic nerve is damaged although intraocular pressure (IOP) is in the normal range (12 to 22 mmHg (1.6 to 2.9 kPa)). Individuals with a family history of NTG, those of Japanese ancestry, those with a history of systemic heart disease and those with Flammer syndrome are at an elevated risk of developing NTG. The cause of NTG is unknown.

Secondary glaucoma refers to any case in which another disease, trauma, drug or procedure causes increased eye pressure, resulting in optic nerve damage and vision loss, which may be mild or severe. This may be the result of an eye injury, inflammation, a tumor or advanced cases of cataracts or diabetes. It can also be caused by certain drugs such as steroids. Treatment depends on whether the condition is identified as open-angle or angle-closure glaucoma.

With pseudoexfoliation glaucoma (also known as PEX or exfoliation glaucoma) the pressure results from the accumulation of microscopic granular protein fibers, which can block normal drainage of the aqueous humor. PEX is prevalent in Scandinavia, primarily in those over 70, and more commonly in women.

Pigmentary glaucoma (also known as pigmentary dispersion syndrome) is caused by pigment cells sloughing off from the back of the iris and floating around in the aqueous humor. Over time, these pigment cells can accumulate in the anterior chamber and begin to clog the trabecular meshwork. It is a rare condition that occurs mostly among white males in their mid-20s to 40s, most of whom are nearsighted.

Primary juvenile glaucoma is a neonate or juvenile abnormality in which ocular hypertension is evident at birth or shortly thereafter and is caused by abnormalities in the anterior chamber angle development that blocks the outflow of the aqueous humor.

Uveitic glaucoma is caused by uveitis, the swelling and inflammation of the uvea, the middle layer of the eye. The uvea provides most of the blood supply to the retina. Increased eye pressure can result from the inflammation itself or from the steroids used to treat it.[55]

Visual field defects in glaucoma
See also: Visual field
Bjerrums area and types of scotomas on the visual field

In glaucoma visual field defects result from damage to the retinal nerve fiber layer. Field defects are seen mainly in primary open angle glaucoma. Because of the unique anatomy of the RNFL, many noticeable patterns are seen in the visual field. Most of the early glaucomatous changes are seen within the central visual field, mainly in Bjerrum's area, 10-20° from fixation.[56]

Following are the common glaucomatous field defects:

  • Generalized depression: Generalized depression is seen in early stages of glaucoma and many other conditions. Mild constriction of central and peripheral visual field due to isopter contraction comes under generalized depression. If all the isopters show similar depression to the same point, it is then called a contraction of visual field. Relative paracentral scotomas are the areas where smaller and dimmer targets are not visualized by the patient.[56] Larger and brighter targets can be seen. Small paracentral depressions, mainly superonasal are seen in normal tension glaucoma (NTG).[57] The generalized depression of the entire field may be seen in cataract also.[58]
  • Baring of blind spot: "Baring of blind spot" means exclusion of blind spot from the central field due to inward curve of the outer boundary of 30° central field.[59] It is only an early non-specific visual field change, without much diagnostic value in glaucoma.[59]
  • Small wing-shaped Paracentral scotoma: Small wing-shaped Paracentral scotoma within Bjerrum's area is the earliest clinically significant field defect seen in glaucoma. It may also be associated with nasal steps. Scotoma may be seen above or below the blind spot.[59]
  • Siedel's sickle-shaped scotoma: Paracentral scotoma joins with the blind spot to form the Seidel sign.
  • Arcuate or Bjerrum's scotoma:
    Arcuate scotoma
    It is formed at later stages of glaucoma by extension of Seidel's scotoma in an area either above or below the fixation point to reach the horizontal line. Peripheral breakthrough may occur due to damage of nerve fibers.[59]
  • Ring or Double arcuate scotoma: Two arcuate scotomas join to form a Ring or Double arcuate scotoma. This defect is seen in advanced stages of glaucoma.
  • Roenne's central nasal step: It is created when two arcuate scotomas run in different arcs to form a right angled defect. This is also seen in advanced stages of glaucoma.
  • Peripheral field defects: Peripheral field defects may occur in early or late stages of glaucoma. Roenne's peripheral nasal steps occur due to contraction of peripheral isopter.[59]
  • Tubular vision:
    Tubular vision
    Since macular fibers are the most resistant to glaucomatous damage, the central vision remains unaffected until end stages of glaucoma. Tubular vision or Tunnel vision is the loss of peripheral vision with retention of central vision, resulting in a constricted circular tunnel-like field of vision. It is seen in the end stages of glaucoma. Retinitis pigmentosa is another disease that causes tubular vision.[60]
  • Temporal island of vision: It is also seen in end stages of glaucoma. The temporal islands lie outside of the central 24 to 30° visual field,[61] so it may not be visible with standard central field measurements done in glaucoma.

Screening

The United States Preventive Services Task Force stated, as of 2013, that there was insufficient evidence to recommend for or against screening for glaucoma.[62] Therefore, there is no national screening program in the US. Screening, however, is recommended starting at age 40 by the American Academy of Ophthalmology.[2]

There is a glaucoma screening program in the UK. Those at risk are advised to have a dilated eye examination at least once a year.[63]

Treatment

The modern goal of glaucoma management is to decrease the intraocular pressure (IOP), thus slowing the progression of glaucoma and preserving the quality of life for patients, with minimal side-effects.[64][65][66] This requires appropriate diagnostic techniques and follow-up examinations, and judicious selection of treatments for the individual patient. Although IOP is only one of the major risk factors for glaucoma, lowering it via various pharmaceuticals and/or surgical techniques is currently the mainstay of glaucoma treatment.

The IOP should be reduced to a target level at which the disease progression is controlled protecting the visual field and improving life quality.[67][68] The target level is set individually depending on multiple factors including the pretreatment IOP, the severity and rate of the disease progression, and the side effects of the medications. In general, the target IOP is equal or lower than 18mmHg in mild, 15mmHg in moderate and 12mmHg in severe stage glaucoma.[69] After setting the target IOP, regular follow-up should be done assessing the IOP and the disease progression.

Vascular flow and neurodegenerative theories of glaucomatous optic neuropathy have prompted studies on various neuroprotective therapeutic strategies, including nutritional compounds, some of which may be regarded by clinicians as safe for use now, while others are on trial. Mental stress is also considered as consequence and cause of vision loss which means that stress management training, autogenic training and other techniques to cope with stress can be helpful.[70]

Medication
Main article: Glaucoma medication

There are several pressure-lowering medication groups that could be used in lowering the IOP, usually eyedrops. The choice of medication usually depends on the dose, duration and the side effects of each medication. However, in general, prostaglandin analogues are the first-line treatment for glaucoma.[71][68]

Prostaglandin analogues, such as latanoprost, bimatoprost and travoprost, reduce the IOP by increasing the aqueous fluid outflow through the draining angle. It is usually prescribed once daily at night. The systemic side effects of this class are minimal. However, they can cause local side effects including redness of the conjunctiva, change in the iris color and eyelash elongation.[71][68]

There are several other classes of medications that could be used as a second-line in case of treatment failure or presence of contraindications to prostaglandin analogues.[72][68] These include:

Each of these medicines may have local and systemic side effects. Wiping the eye with an absorbent pad after the administration of eye drops may result in fewer adverse effects.[73] Initially, glaucoma drops may reasonably be started in either one or in both eyes.[74]

The possible neuroprotective effects of various topical and systemic medications are also being investigated.[25][75][76][77]

Adherence

Poor compliance with medications and follow-up visits is a major reason for treatment failure and disease progression in glaucoma patients. Poor adherence could lead to increased complication rates, thus increasing the need of non-pharmacological interventions including surgery. Patient education and communication must be ongoing to sustain successful treatment plans for this lifelong disease with no early symptoms.[78]

Laser

Argon laser trabeculoplasty (ALT) may be used to treat open-angle glaucoma, but this is a temporary solution, not a cure. A 50-μm argon laser spot is aimed at the trabecular meshwork to stimulate the opening of the mesh to allow more outflow of aqueous fluid. Usually, half of the angle is treated at a time. Traditional laser trabeculoplasty uses a thermal argon laser in an argon laser trabeculoplasty procedure.

Nd:YAG laser peripheral iridotomy (LPI) may be used in patients susceptible to or affected by angle closure glaucoma or pigment dispersion syndrome. During laser iridotomy, laser energy is used to make a small, full-thickness opening in the iris to equalize the pressure between the front and back of the iris, thus correcting any abnormal bulging of the iris. In people with narrow angles, this can uncover the trabecular meshwork. In some cases of intermittent or short-term angle closure, this may lower the eye pressure. Laser iridotomy reduces the risk of developing an attack of acute angle closure. In most cases, it also reduces the risk of developing chronic angle closure or of adhesions of the iris to the trabecular meshwork. CFD simulations have shown that an optimal iridotomy size to relieve the pressure differential between the anterior and posterior side of the iris is around 0.1 mm to 0.2 mm.[79] This coincides with clinical practice of LPI where an iridotomy size of 150 to 200 microns is commonly used. However, larger iriditomy sizes are sometimes necessary.

Diode laser cycloablation lowers IOP by reducing aqueous secretion by destroying secretory ciliary epithelium.[80]

Surgery
Conventional surgery to treat glaucoma makes a new opening in the trabecular meshwork, which helps fluid to leave the eye and lowers intraocular pressure.
Main article: Glaucoma surgery

Both laser and conventional surgeries are performed to treat glaucoma. Surgery is the primary therapy for those with congenital glaucoma.[81] Generally, these operations are a temporary solution, as there is not yet a cure for glaucoma.

Canaloplasty

Canaloplasty is a nonpenetrating procedure using microcatheter technology. To perform a canaloplasty, an incision is made into the eye to gain access to the Schlemm's canal in a similar fashion to a viscocanalostomy. A microcatheter will circumnavigate the canal around the iris, enlarging the main drainage channel and its smaller collector channels through the injection of a sterile, gel-like material called viscoelastic. The catheter is then removed and a suture is placed within the canal and tightened.

By opening the canal, the pressure inside the eye may be relieved, although the reason is unclear, since the canal (of Schlemm) does not have any significant fluid resistance in glaucoma or healthy eyes. Long-term results are not available.[82][83]

Trabeculectomy

The most common conventional surgery performed for glaucoma is the trabeculectomy. Here, a partial thickness flap is made in the scleral wall of the eye, and a window opening is made under the flap to remove a portion of the trabecular meshwork. The scleral flap is then sutured loosely back in place to allow fluid to flow out of the eye through this opening, resulting in lowered intraocular pressure and the formation of a bleb or fluid bubble on the surface of the eye.

Scarring can occur around or over the flap opening, causing it to become less effective or lose effectiveness altogether. Traditionally, chemotherapeutic adjuvants, such as mitomycin C (MMC) or 5-fluorouracil (5-FU), are applied with soaked sponges on the wound bed to prevent filtering blebs from scarring by inhibiting fibroblast proliferation. Contemporary alternatives to prevent the scarring of the meshwork opening include the sole or combinative implementation of nonchemotherapeutic adjuvants such as the Ologen collagen matrix, which has been clinically shown to increase the success rates of surgical treatment.[84][85][86][87]

Collagen matrix prevents scarring by randomizing and modulating fibroblast proliferation in addition to mechanically preventing wound contraction and adhesion.

Glaucoma drainage implants
Main article: Glaucoma valve

The first glaucoma drainage implant was developed in 1966.[88] Since then, several types of implants have followed on from the original: the Baerveldt tube shunt, or the valved implants, such as the Ahmed glaucoma valve implant or the ExPress Mini Shunt and the later generation pressure ridge Molteno implants. These are indicated for glaucoma patients not responding to maximal medical therapy, with previous failed guarded filtering surgery (trabeculectomy). The flow tube is inserted into the anterior chamber of the eye, and the plate is implanted underneath the conjunctiva to allow a flow of aqueous fluid out of the eye into a chamber called a bleb.

  • The first-generation Molteno and other nonvalved implants sometimes require the ligation of the tube until the bleb formed is mildly fibrosed and water-tight.[89] This is done to reduce postoperative hypotony—sudden drops in postoperative intraocular pressure.
  • Valved implants, such as the Ahmed glaucoma valve, attempt to control postoperative hypotony by using a mechanical valve.
  • Ab interno implants, such as the Xen Gel Stent, are transscleral implants by an ab interno procedure to channel aqueous humor into the non-dissected Tenon's space, creating a subconjunctival drainage area similar to a bleb.[90][91] The implants are transscleral and different from other ab interno implants that do not create a transscleral drainage, such as iStent, CyPass, or Hydrus.[92][93]

The ongoing scarring over the conjunctival dissipation segment of the shunt may become too thick for the aqueous humor to filter through. This may require preventive measures using antifibrotic medications, such as 5-fluorouracil or mitomycin-C (during the procedure), or other nonantifibrotic medication methods, such as collagen matrix implant,[94][95] or biodegradable spacer, or later on create a necessity for revision surgery with the sole or combinative use of donor patch grafts or collagen matrix implant.[95] And for glaucomatous painful blind eye and some cases of glaucoma, cyclocryotherapy for ciliary body ablation could be considered to be performed.[80]

Laser-assisted nonpenetrating deep sclerectomy

The most common surgical approach currently used for the treatment of glaucoma is trabeculectomy, in which the sclera is punctured to alleviate intraocular pressure.

Nonpenetrating deep sclerectomy (NPDS) surgery is a similar, but modified, procedure, in which instead of puncturing the scleral bed and trabecular meshwork under a scleral flap, a second deep scleral flap is created, excised, with further procedures of deroofing the Schlemm's canal, upon which, percolation of liquid from the inner eye is achieved and thus alleviating intraocular pressure, without penetrating the eye. NPDS is demonstrated to have significantly fewer side effects than trabeculectomy.[96] However, NPDS is performed manually and requires higher level of skills that may be assisted with instruments. In order to prevent wound adhesion after deep scleral excision and to maintain good filtering results, NPDS as with other non-penetrating procedures is sometimes performed with a variety of biocompatible spacers or devices, such as the Aquaflow collagen wick,[97] ologen Collagen Matrix,[86][98][99] or Xenoplast glaucoma implant.[100]

Laser-assisted NPDS is performed with the use of a CO2 laser system. The laser-based system is self-terminating once the required scleral thickness and adequate drainage of the intraocular fluid have been achieved. This self-regulation effect is achieved as the CO2 laser essentially stops ablating as soon as it comes in contact with the intraocular percolated liquid, which occurs as soon as the laser reaches the optimal residual intact layer thickness.

Clear lens extraction
Main article: Clear lens extraction

For people with chronic closed-angle glaucoma, lens extraction can relieve the block created by the pupil and help regulate the intraocular pressure.[101] A study found that CLE is even more effective than laser peripheral iridotomy in patients with angle closure glaucoma.[102]

Treatment approaches for primary glaucoma

Primary angle closure glaucoma: Once any symptoms have been controlled, the first line (and often definitive) treatment is laser iridotomy. This may be performed using either Nd:YAG or argon lasers, or in some cases by conventional incisional surgery. The goal of treatment is to reverse and prevent contact between the iris and trabecular meshwork. In early to moderately advanced cases, iridotomy is successful in opening the angle in around 75% of cases. In the other 25%, laser iridoplasty, medication (pilocarpine) or incisional surgery may be required.

Primary open-angle glaucoma: Prostaglandin agonists work by opening uveoscleral passageways. Beta-blockers, such as timolol, work by decreasing aqueous formation. Carbonic anhydrase inhibitors decrease bicarbonate formation from ciliary processes in the eye, thus decreasing the formation of aqueous humor. Parasympathetic analogs are drugs that work on the trabecular outflow by opening up the passageway and constricting the pupil. Alpha 2 agonists (brimonidine, apraclonidine) both decrease fluid production (via inhibition of AC) and increase drainage. A review of people with primary open-angle glaucoma and ocular hypertension concluded that medical IOP-lowering treatment slowed down the progression of visual field loss.[10]

Neovascular glaucoma

Anti-VEGF agents as injectable medications, along with other standard of care treatment for decreasing intraocular pressure, may improve pressure in people with neovascular glaucoma for short periods of time.[103] Evidence suggests that this improvement may last 4–6 weeks.[103] There is no strong evidence to suggest that anti-VEGF medications are effective for longer-term treatment.[103] The short, medium, and long-term safety of anti-VEGF treatment has not been well investigated.[103]

Other

Cannabis is not suggested for treatment of glaucoma by the American Glaucoma Society for adults or for children.[104][105]

Prognosis

In open-angle glaucoma, the typical progression from normal vision to complete blindness takes about 25 years to 70 years without treatment, depending on the method of estimation used.[106] The intraocular pressure can also have an effect, with higher pressures reducing the time until blindness.[107]

Epidemiology
Disability-adjusted life year for glaucoma per 100,000 inhabitants in 2004[108]
  no data
  fewer than 20
  20–43
  43–66
  66–89
  89–112
  112–135
  135–158
  158–181
  181–204
  204–227
  227–250
  more than 250

As of 2010, there were 44.7 million people in the world with open angle glaucoma.[109] The same year, there were 2.8 million people in the United States with open angle glaucoma.[109] By 2020, the prevalence is projected to increase to 58.6 million worldwide and 3.4 million in the United States.[109]

Both internationally and in the United States, glaucoma is the second-leading cause of blindness.[2] Globally, cataracts are a more common cause. Glaucoma is also the leading cause of blindness in African Americans, who have higher rates of primary open-angle glaucoma.[110][111] Bilateral vision loss can negatively affect mobility and interfere with driving.[112]

A meta-analysis published in 2009 found that people with primary open angle glaucoma do not have increased mortality rates, or increased risk of cardiovascular death.[113]

History

The association of elevated intraocular pressure (IOP) and glaucoma was first described by Englishman Richard Banister in 1622: "...that the Eye be grown more solid and hard, then naturally it should be...".[114] Angle-closure glaucoma was treated with cataract extraction by John Collins Warren in Boston as early as 1806.[115] The invention of the ophthalmoscope by Hermann Helmholtz in 1851 enabled ophthalmologists for the first time to identify the pathological hallmark of glaucoma, the excavation of the optic nerve head due to retinal ganglion cell loss. The first reliable instrument to measure intraocular pressure was invented by Norwegian ophthalmologist Hjalmar August Schiøtz in 1905. About half a century later, Hans Goldmann in Berne, Switzerland, developed his applanation tonometer which still today - despite numerous new innovations in diagnostics - is considered the gold standard of determining this crucial pathogenic factor. In the late 20th century, further pathomechanisms beyond elevated IOP were discovered and became the subject of research like insufficient blood supply – often associated with low or irregular blood pressure – to the retina and optic nerve head.[116] The first drug to reduce IOP, pilocarpine, was introduced in the 1870s; other major innovations in pharmacological glaucoma therapy were the introduction of beta blocker eye drops in the 1970s and of prostaglandin analogues and topical (locally administered) carbonic anhydrase inhibitors in the mid-1990s.. Early surgical techniques like iridectomy and fistulating methods have recently been supplemented by less invasive procedures like small implants, a range of options now widely called MIGS (micro-invasive glaucoma surgery).

Etymology

The word "glaucoma" comes from the Ancient Greek γλαύκωμα,[117] a derivative of γλαυκóς,[118] which commonly described the color of eyes which were not dark (i.e. blue, green, light gray). Eyes described as γλαυκóς due to disease might have had a gray cataract in the Hippocratic era, or, in the early Common Era, the greenish pupillary hue sometimes seen in angle-closure glaucoma.[119][120] This colour is reflected in the Chinese word for glaucoma, 青光眼 (qīngguāngyǎn), literally “cyan-light eye”.

Research

Eye drops vs. other treatments

The TAGS randomised controlled trial investigated if eye drops or trabeculectomy is more effective in treating advanced primary open-angle glaucoma. After two years researchers found that vision and quality of life are similar in both treatments. At the same time eye pressure was lower in people who underwent surgery and in the long-run surgery is more cost-effective.[121][122]

The LiGHT trial compared the effectiveness of eye drops and selective laser trabeculoplasty for open angle glaucoma. Both contributed to a similar quality of life but most people undergoing laser treatment were able to stop using eye drops. Laser trabeculoplasty was also shown to be more cost-effective.[123]

Neuroprotective agents

A 2013 Cochrane systematic review compared the effect of brimonidine and timolol in slowing the progression of open angle glaucoma in adult participants.[124] The results showed that participants assigned to brimonidine showed less visual field progression than those assigned to timolol, though the results were not significant, given the heavy loss-to-followup and limited evidence.[124] The mean intraocular pressures for both groups were similar. Participants in the brimonidine group had a higher occurrence of side effects caused by medication than participants in the timolol group.[124]

Health disparities in glaucoma

In diagnosis

A study conducted in UK showed that people living in an area of high deprivation were likely to be diagnosed in the later stage of the disease.[125] It also showed that there were lack of professional ophthalmic services in the area of high deprivation.

In treatment

A study in 2017 shows that there is a huge difference in the volume of glaucoma testing depending on the type of insurance in the US.[126] Researchers reviewed 21,766 persons age ≥ 40 years old with newly diagnosed open-angle glaucoma (OAG) and found that Medicaid recipients had substantially lower volume of glaucoma testing performed compared to patients with commercial health insurance.

In research and clinical trials

Results from a meta-analysis of 33,428 primary open-angle glaucoma (POAG) participants published in 2021 suggest that there are substantial ethnic and racial disparities in clinical trials in the US.[127] Although ethnic and racial minorities have a higher disease burden, the 70.7% of the study participants was White as opposed to 16.8% Black and 3.4% Hispanic/Latino.

References
  1. "Facts About Glaucoma". National Eye Institute. Archived from the original on 28 March 2016. Retrieved 29 March 2016.
  2. Mantravadi AV, Vadhar N (September 2015). "Glaucoma". Primary Care. 42 (3): 437–449. doi:10.1016/j.pop.2015.05.008. PMID 26319348.
  3. Ferri FF (2010). Ferri's differential diagnosis : a practical guide to the differential diagnosis of symptoms, signs, and clinical disorders (2nd ed.). Philadelphia, PA: Elsevier/Mosby. p. Chapter G. ISBN 978-0323076999.
  4. Vos, Theo; Allen, Christine; Arora, Megha; et al. (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282.
  5. Tsatsos, Michael; Broadway, David (November 2007). "Controversies in the history of glaucoma: is it all a load of old Greek?". The British Journal of Ophthalmology. 91 (11): 1561–1562. doi:10.1136/bjo.2007.114298. ISSN 0007-1161. PMC 2095442. PMID 17947272.
  6. "Glaucoma: The 'silent thief' begins to tell its secrets" (Press release). National Eye Institute. 21 January 2014. Archived from the original on 23 July 2015.
  7. "Glaucoma: The 'silent thief' begins to tell its secrets | National Eye Institute". www.nei.nih.gov. Retrieved 11 September 2023.
  8. "Glaucoma: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 11 September 2023.
  9. "Glaucoma - Symptoms and causes". Mayo Clinic. Retrieved 11 September 2023.
  10. Vass C, Hirn C, Sycha T, Findl O, Bauer P, Schmetterer L (October 2007). "Medical interventions for primary open angle glaucoma and ocular hypertension". The Cochrane Database of Systematic Reviews. 2007 (4): CD003167. doi:10.1002/14651858.CD003167.pub3. PMC 6768994. PMID 17943780.
  11. willem3bergen (8 March 2018). "Statistics". Glaucoma Information. Retrieved 11 September 2023.
  12. Ou Y. "Glaucoma in the African American and Hispanic Communities". Bright Focus Foundation. Retrieved 26 June 2022.
  13. "Glaucoma in the African-American and Latino Communities: Studies Release More Data". American Academy of Ophthalmology. 1 June 2010. Retrieved 11 September 2023.
  14. Belamkar, Aditya; Harris, Alon; Oddone, Francesco; Verticchio Vercellin, Alice; Fabczak-Kubicka, Anna; Siesky, Brent (28 April 2022). "Asian Race and Primary Open-Angle Glaucoma: Where Do We Stand?". Journal of Clinical Medicine. 11 (9): 2486. doi:10.3390/jcm11092486. ISSN 2077-0383. PMC 9099679. PMID 35566612.
  15. Stein, Joshua D.; Khawaja, Anthony P.; Weizer, Jennifer S. (12 January 2021). "Glaucoma in Adults—Screening, Diagnosis, and Management: A Review". JAMA. 325 (2): 164–174. doi:10.1001/jama.2020.21899. PMID 33433580. S2CID 231585520.
  16. Resnikoff S, Pascolini D, Etya'ale D, Kocur I, Pararajasegaram R, Pokharel GP, Mariotti SP (November 2004). "Global data on visual impairment in the year 2002". Bulletin of the World Health Organization. 82 (11): 844–851. hdl:10665/269277. PMC 2623053. PMID 15640920.
  17. "Angle-Closure Glaucoma - American Academy of Ophthalmology". www.aao.org.
  18. Friedman NJ, Kaiser PK, Pineda II R (2014). The Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology E-Book. Elsevier Health Sciences. p. 234. ISBN 9780323225274.
  19. Kaleem, Mona. "Glaucoma".
  20. Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch JD, Javitt J, Singh K (August 1991). "Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey". Archives of Ophthalmology. 109 (8): 1090–1095. doi:10.1001/archopht.1991.01080080050026. PMID 1867550.
  21. Kelly SR, Khawaja AP, Bryan SR, Azuara-Blanco A, Sparrow JM, Crabb DP (October 2020). "Progression from ocular hypertension to visual field loss in the English hospital eye service". The British Journal of Ophthalmology. 104 (10): 1406–1411. doi:10.1136/bjophthalmol-2019-315052. PMID 32217541.
  22. Gordon MO, Kass MA (May 2018). "What We Have Learned From the Ocular Hypertension Treatment Study". American Journal of Ophthalmology. 189: xxiv–xxvii. doi:10.1016/j.ajo.2018.02.016. PMC 5915899. PMID 29501371.
  23. Rhee DJ (2012). Glaucoma (2nd ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 180. ISBN 9781609133375. OCLC 744299538.
  24. Mi XS, Yuan TF, So KF (16 September 2014). "The current research status of normal tension glaucoma". Clinical Interventions in Aging. 9: 1563–1571. doi:10.2147/CIA.S67263. PMC 4172068. PMID 25258525.
  25. Rhee DJ, Katz LJ, Spaeth GL, Myers JS (2001). "Complementary and alternative medicine for glaucoma". Survey of Ophthalmology. 46 (1): 43–55. doi:10.1016/S0039-6257(01)00233-8. PMID 11525790.
  26. Li M, Wang M, Guo W, Wang J, Sun X (March 2011). "The effect of caffeine on intraocular pressure: a systematic review and meta-analysis". Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht von Graefes Archiv für Klinische und Experimentelle Ophthalmologie. 249 (3): 435–442. doi:10.1007/s00417-010-1455-1. PMID 20706731. S2CID 668498.
  27. Wang N, Wu H, Fan Z (November 2002). "Primary angle closure glaucoma in Chinese and Western populations". Chinese Medical Journal. 115 (11): 1706–1715. PMID 12609093.
  28. Yanoff M, Duker JS (2009). Ophthalmology (3rd ed.). Mosby Elsevier. p. 1096. ISBN 9780323043328.
  29. Online Mendelian Inheritance in Man (OMIM): Glaucoma, Primary Open Angle; POAG - 137760
  30. Fernández-Martínez L, Letteboer S, Mardin CY, Weisschuh N, Gramer E, Weber BH, et al. (April 2011). "Evidence for RPGRIP1 gene as risk factor for primary open angle glaucoma". European Journal of Human Genetics. 19 (4): 445–451. doi:10.1038/ejhg.2010.217. PMC 3060327. PMID 21224891.
  31. Wiggs, Janey L.; Pasquale, Louis R. "Genetics of glaucoma". Human Molecular Genetics. 26 (1): 21–27.
  32. Online Mendelian Inheritance in Man (OMIM): Glaucoma, Normal Tension, Susceptibility to - 606657
  33. Badawi, Abdulrahman H.; Al-Muhaylib, Ahmed A.; Al Owaifeer, Adi Mohammed; Al-Essa, Rakan S.; Al-Shahwan, Sami A. (1 October 2019). "Primary congenital glaucoma: An updated review". Saudi Journal of Ophthalmology. 33 (4): 382–388. doi:10.1016/j.sjopt.2019.10.002. ISSN 1319-4534. PMC 6950954. PMID 31920449.
  34. Zamora, Edgar A.; Salini, Baby (2023), "Axenfeld-Rieger Syndrome", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30860739, retrieved 22 September 2023
  35. Puyo L, Paques M, Atlan M (2020). "Retinal blood flow reversal in out-of-plane vessels imaged with laser Doppler holography". arXiv:2008.09813 [physics.med-ph].
  36. Alguire P (1990). "The Eye Chapter 118 Tonometry>Basic Science". In Walker HK, Hall WD, Hurst JW (eds.). Clinical methods: the history, physical, and laboratory examinations (3rd ed.). London: Butterworths. ISBN 978-0-409-90077-4. PMID 21250045.
  37. Mozaffarieh M, Grieshaber MC, Flammer J (January 2008). "Oxygen and blood flow: players in the pathogenesis of glaucoma". Molecular Vision. 14: 224–233. PMC 2267728. PMID 18334938.
  38. Helmer, Catherine; Malet, Florence; Rougier, Marie-Bénédicte; Schweitzer, Cédric; Colin, Joseph; Delyfer, Marie-Noëlle; Korobelnik, Jean-François; Barberger-Gateau, Pascale; Dartigues, Jean-François; Delcourt, Cécile (September 2013). "Is there a link between open-angle glaucoma and dementia?: The Three-City-Alienor Cohort". Annals of Neurology. 74 (2): 171–179. doi:10.1002/ana.23926. PMID 23686609. S2CID 28166631.
  39. Ko, Fang; Muthy, Zaynah A.; Gallacher, John; Sudlow, Cathie; Rees, Geraint; Yang, Qi; Keane, Pearse A.; Petzold, Axel; Khaw, Peng T.; Reisman, Charles; Strouthidis, Nicholas G.; Foster, Paul J.; Patel, Praveen J. (1 October 2018). "Association of Retinal Nerve Fiber Layer Thinning With Current and Future Cognitive Decline: A Study Using Optical Coherence Tomography". JAMA Neurology. 75 (10): 1198–1205. doi:10.1001/jamaneurol.2018.1578. PMC 6233846. PMID 29946685.
  40. Jadeja RN, Thounaojam MC, Bartoli M, Martin PM (2020). "Implications of NAD+ Metabolism in the Aging Retina and Retinal Degeneration". Oxidative Medicine and Cellular Longevity. 2020: 2692794. doi:10.1155/2020/2692794. PMC 7238357. PMID 32454935.
  41. Osborne NN, Wood JP, Chidlow G, Bae JH, Melena J, Nash MS (August 1999). "Ganglion cell death in glaucoma: what do we really know?". The British Journal of Ophthalmology. 83 (8): 980–986. doi:10.1136/bjo.83.8.980. PMC 1723166. PMID 10413706.
  42. Levin LA, Peeples P (February 2008). "History of neuroprotection and rationale as a therapy for glaucoma". The American Journal of Managed Care. 14 (1 Suppl): S11–S14. PMID 18284310.
  43. Varma R, Peeples P, Walt JG, Bramley TJ (February 2008). "Disease progression and the need for neuroprotection in glaucoma management". The American Journal of Managed Care. 14 (1 Suppl): S15–S19. PMID 18284311.
  44. Hernández M, Urcola JH, Vecino E (May 2008). "Retinal ganglion cell neuroprotection in a rat model of glaucoma following brimonidine, latanoprost or combined treatments". Experimental Eye Research. 86 (5): 798–806. doi:10.1016/j.exer.2008.02.008. PMID 18394603.
  45. Knox DL, Eagle RC, Green WR (March 2007). "Optic nerve hydropic axonal degeneration and blocked retrograde axoplasmic transport: histopathologic features in human high-pressure secondary glaucoma". Archives of Ophthalmology. 125 (3): 347–353. doi:10.1001/archopht.125.3.347. PMID 17353405.
  46. "Issue on neuroprotection". Can. J. Ophthalmol. 42 (3). June 2007. ISSN 1715-3360. Archived from the original on 12 May 2007.
  47. "Glaucoma diagnosis". Mayo Clinic. 30 September 2022. Retrieved 22 September 2023.
  48. Paton D, Craig JA (1976). "Glaucomas. Diagnosis and management". Clinical Symposia. 28 (2): 1–47. PMID 1053095.
  49. Logan CM, Rice MK (1987). Logan's Medical and Scientific Abbreviations. Philadelphia: J. B. Lippincott Company. p. 3. ISBN 978-0-397-54589-6.
  50. "Primary Open-Angle Glaucoma: Glaucoma: Merck Manual Professional". Merck.com. Archived from the original on 28 November 2010. Retrieved 24 January 2011.
  51. Pardianto G (2006). "Difficulties on glaucoma". Mimbar Ilmiah Oftalmologi Indonesia. 3: 48–9.
  52. Sit AJ (23 April 2006). "Many types of glaucoma, one kind of damage to optic nerve". Chicago Tribune. Archived from the original on 6 October 2012. Retrieved 18 August 2015. Glaucoma is a broad term for a number of different conditions that damage the optic nerve, the 'cable' that carries visual information from the eye to the brain, thereby causing changes in vision.
  53. Jindal A, Ctori I, Virgili G, Lucenteforte E, Lawrenson JG (May 2020). "Non-contact tests for identifying people at risk of primary angle closure glaucoma". The Cochrane Database of Systematic Reviews. 5 (7): CD012947. doi:10.1002/14651858.cd012947.pub2. PMC 7390269. PMID 32468576.
  54. Allison, Karen; Patel, Deepkumar; Besharim, Caren (2021). "The Value of Annual Glaucoma Screening for High-Risk Adults Ages 60 to 80". Cureus. 13 (10): e18710. doi:10.7759/cureus.18710. ISSN 2168-8184. PMC 8582616. PMID 34790465.
  55. "Types of Glaucoma | National Eye Institute". www.nei.nih.gov. Retrieved 25 October 2020.
  56. "Glaucoma". Parsons' diseases of the eye (22nd ed.). Elsevier. 15 July 2015. pp. 288–295. ISBN 978-81-312-3818-9.
  57. Salmon JF. "Glaucoma". Kanski's Clinical ophthalmology (9th ed.). Elsevier. pp. 362–365.
  58. Carroll JN, Johnson CA (22 August 2013). "Visual Field Testing: From One Medical Student to Another".
  59. Khurana AK, Khurana B (31 August 2015). "Glaucoma". Comprehensive ophthalmology (6th ed.). Jaypee, The Health Sciences Publisher. pp. 223–224. ISBN 978-93-5152-657-5.
  60. "Retinitis pigmentosa". Genetics Home Reference.
  61. Themes UF (11 July 2016). "Visual Fields in Glaucoma". Ento Key.
  62. "Summaries for patients. Screening for glaucoma: U.S. Preventive Services Task Force recommendation statement". Annals of Internal Medicine. 159 (7): I-28. October 2013. doi:10.7326/0003-4819-159-6-201309170-00685. PMID 23836133.
  63. "Glaucoma – National Institutes of Health". Nihseniorhealth.gov. Archived from the original on 25 December 2010. Retrieved 24 January 2011.
  64. Noecker RJ (June 2006). "The management of glaucoma and intraocular hypertension: current approaches and recent advances". Therapeutics and Clinical Risk Management. 2 (2): 193–206. doi:10.2147/tcrm.2006.2.2.193. PMC 1661659. PMID 18360593.
  65. Parikh RS, Parikh SR, Navin S, Arun E, Thomas R (1 May 2008). "Practical approach to medical management of glaucoma". Indian Journal of Ophthalmology. 56 (3): 223–230. doi:10.4103/0301-4738.40362. PMC 2636120. PMID 18417824.
  66. Weinreb, Robert N.; Aung, Tin; Medeiros, Felipe A. (14 May 2014). "The Pathophysiology and Treatment of Glaucoma: A Review". JAMA. 311 (18): 1901–1911. doi:10.1001/jama.2014.3192. ISSN 0098-7484. PMC 4523637. PMID 24825645.
  67. Weinreb, Robert N.; Aung, Tin; Medeiros, Felipe A. (14 May 2014). "The Pathophysiology and Treatment of Glaucoma: A Review". JAMA. 311 (18): 1901–1911. doi:10.1001/jama.2014.3192. ISSN 0098-7484. PMC 4523637. PMID 24825645.
  68. Schuster, Alexander K.; Erb, Carl; Hoffmann, Esther M.; Dietlein, Thomas; Pfeiffer, Norbert (27 March 2020). "The Diagnosis and Treatment of Glaucoma". Deutsches Ärzteblatt International. 117 (13): 225–234. doi:10.3238/arztebl.2020.0225. ISSN 1866-0452. PMC 7196841. PMID 32343668.
  69. Sihota, Ramanjit; Angmo, Dewang; Ramaswamy, Deepa; Dada, Tanuj (2018). "Simplifying "target" intraocular pressure for different stages of primary open-angle glaucoma and primary angle-closure glaucoma". Indian Journal of Ophthalmology. 66 (4): 495–505. doi:10.4103/ijo.IJO_1130_17. ISSN 0301-4738. PMC 5892050. PMID 29582808.
  70. Sabel BA, Wang J, Cárdenas-Morales L, Faiq M, Heim C (June 2018). "Mental stress as consequence and cause of vision loss: the dawn of psychosomatic ophthalmology for preventive and personalized medicine". The EPMA Journal. 9 (2): 133–160. doi:10.1007/s13167-018-0136-8. PMC 5972137. PMID 29896314.
  71. Weinreb, Robert N.; Aung, Tin; Medeiros, Felipe A. (14 May 2014). "The Pathophysiology and Treatment of Glaucoma: A Review". JAMA. 311 (18): 1901–1911. doi:10.1001/jama.2014.3192. ISSN 0098-7484. PMC 4523637. PMID 24825645.
  72. Wagner, Isabella V.; Stewart, Michael W.; Dorairaj, Syril K. (December 2022). "Updates on the Diagnosis and Management of Glaucoma". Mayo Clinic Proceedings: Innovations, Quality & Outcomes. 6 (6): 618–635. doi:10.1016/j.mayocpiqo.2022.09.007. PMC 9673042. PMID 36405987.
  73. Xu L, Wang X, Wu M (February 2017). "Topical medication instillation techniques for glaucoma". The Cochrane Database of Systematic Reviews. 2017 (2): CD010520. doi:10.1002/14651858.CD010520.pub2. PMC 5419432. PMID 28218404.
  74. Leffler CT, Amini L (October 2007). "Interpretation of uniocular and binocular trials of glaucoma medications: an observational case series". BMC Ophthalmology. 7: 17. doi:10.1186/1471-2415-7-17. PMC 2093925. PMID 17916260.
  75. Ritch R (June 2007). "Natural compounds: evidence for a protective role in eye disease". Canadian Journal of Ophthalmology. 42 (3): 425–438. doi:10.3129/can.j.ophthalmol.i07-044. PMID 17508040.
  76. Tsai JC, Song BJ, Wu L, Forbes M (September 2007). "Erythropoietin: a candidate neuroprotective agent in the treatment of glaucoma". Journal of Glaucoma. 16 (6): 567–571. doi:10.1097/IJG.0b013e318156a556. PMID 17873720. S2CID 27407031.
  77. Mozaffarieh M, Flammer J (November 2007). "Is there more to glaucoma treatment than lowering IOP?". Survey of Ophthalmology. 52 (Suppl 2): S174–S179. doi:10.1016/j.survophthal.2007.08.013. PMID 17998043.
  78. Quaranta, Luciano; Novella, Alessio; Tettamanti, Mauro; Pasina, Luca; Weinreb, Robert N.; Nobili, Alessandro (October 2023). "Adherence and Persistence to Medical Therapy in Glaucoma: An Overview". Ophthalmology and Therapy. 12 (5): 2227–2240. doi:10.1007/s40123-023-00730-z. ISSN 2193-8245. PMC 10441906. PMID 37311908.
  79. Cai, Jian-Cheng; Chen, Yan-Ling; Cao, Yue-Hong; Babenko, Andrii; Chen, Xi (1 February 2022). "Numerical study of aqueous humor flow and iris deformation with pupillary block and the efficacy of laser peripheral iridotomy". Clinical Biomechanics. 92: 105579. doi:10.1016/j.clinbiomech.2022.105579. ISSN 0268-0033. PMID 35085976. S2CID 246361118.
  80. Pardianto G, et al. (2006). "Some difficulties on Glaucoma". Mimbar Ilmiah Oftalmologi Indonesia. 3: 49–50.
  81. Online Mendelian Inheritance in Man (OMIM): Glaucoma, Congenital: GLC3 Buphthalmos - 231300
  82. Shingleton B, Tetz M, Korber N (March 2008). "Circumferential viscodilation and tensioning of Schlemm canal (canaloplasty) with temporal clear corneal phacoemulsification cataract surgery for open-angle glaucoma and visually significant cataract: one-year results". Journal of Cataract and Refractive Surgery. 34 (3): 433–440. doi:10.1016/j.jcrs.2007.11.029. PMID 18299068. S2CID 23904366.
  83. Lewis RA, von Wolff K, Tetz M, Korber N, Kearney JR, Shingleton B, Samuelson TW (July 2007). "Canaloplasty: circumferential viscodilation and tensioning of Schlemm's canal using a flexible microcatheter for the treatment of open-angle glaucoma in adults: interim clinical study analysis". Journal of Cataract and Refractive Surgery. 33 (7): 1217–1226. doi:10.1016/j.jcrs.2007.03.051. PMID 17586378. S2CID 36397585.
  84. Dada T, Sharma R, Sinha G, Angmo D, Temkar S (2016). "Cyclodialysis-enhanced trabeculectomy with triple Ologen implantation". European Journal of Ophthalmology. 26 (1): 95–97. doi:10.5301/ejo.5000633. PMID 26044372. S2CID 83593.
  85. Yuan F, Li L, Chen X, Yan X, Wang L (2015). "Biodegradable 3D-Porous Collagen Matrix (Ologen) Compared with Mitomycin C for Treatment of Primary Open-Angle Glaucoma: Results at 5 Years". Journal of Ophthalmology. 2015 (637537): 637537. doi:10.1155/2015/637537. PMC 4452460. PMID 26078875.
  86. Tanuj D, Amit S, Saptorshi M, Meenakshi G (July 2013). "Combined subconjunctival and subscleral ologen implant insertion in trabeculectomy". Eye. 27 (7): 889. doi:10.1038/eye.2013.76. PMC 3709396. PMID 23640614.
  87. Cillino S, Casuccio A, Di Pace F, Cagini C, Ferraro LL, Cillino G (March 2016). "Biodegradable collagen matrix implant versus mitomycin-C in trabeculectomy: five-year follow-up". BMC Ophthalmology. 16 (24): 24. doi:10.1186/s12886-016-0198-0. PMC 4779569. PMID 26946419.
  88. "Eyelights Newsletter: About Glaucoma New Zealand" (PDF). Glaucoma.org. Archived (PDF) from the original on 13 January 2015. Retrieved 20 February 2014.
  89. Molteno AC, Polkinghorne PJ, Bowbyes JA (November 1986). "The vicryl tie technique for inserting a draining implant in the treatment of secondary glaucoma". Australian and New Zealand Journal of Ophthalmology. 14 (4): 343–354. doi:10.1111/j.1442-9071.1986.tb00470.x. PMID 3814422.
  90. Lewis RA (August 2014). "Ab interno approach to the subconjunctival space using a collagen glaucoma stent". Journal of Cataract and Refractive Surgery. 40 (8): 1301–1306. doi:10.1016/j.jcrs.2014.01.032. PMID 24943904.
  91. "Xen Gel Stent". AqueSys. Archived from the original on 29 June 2015. Retrieved 27 June 2015.
  92. "Advances in Glaucoma Filtration Surgery". Glaucoma Today. Archived from the original on 29 June 2015. Retrieved 27 June 2015.
  93. Otarola F, Virgili G, Shah A, Hu K, Bunce C, Gazzard G (March 2020). "Ab interno trabecular bypass surgery with Schlemm´s canal microstent (Hydrus) for open angle glaucoma". The Cochrane Database of Systematic Reviews. 2020 (3): CD012740. doi:10.1002/14651858.cd012740.pub2. PMC 7061024. PMID 32147807.
  94. Rosentreter A, Schild AM, Dinslage S, Dietlein TS (February 2012). "Biodegradable implant for tissue repair after glaucoma drainage device surgery". Journal of Glaucoma. 21 (2): 76–78. doi:10.1097/IJG.0b013e3182027ab0. PMID 21278584. S2CID 40206358.
  95. Rosentreter A, Mellein AC, Konen WW, Dietlein TS (September 2010). "Capsule excision and Ologen implantation for revision after glaucoma drainage device surgery". Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht von Graefes Archiv für Klinische und Experimentelle Ophthalmologie. 248 (9): 1319–1324. doi:10.1007/s00417-010-1385-y. PMID 20405139. S2CID 10384646.
  96. Chiselita D (April 2001). "Non-penetrating deep sclerectomy versus trabeculectomy in primary open-angle glaucoma surgery". Eye. 15 (Pt 2): 197–201. doi:10.1038/eye.2001.60. PMID 11339590.
  97. Ahmed IK (1 September 2005). "Making the Case for Nonpenetrating Surgery". Review of Ophthalmology. 12 (9).
  98. Aptel F, Dumas S, Denis P (2009). "Ultrasound biomicroscopy and optical coherence tomography imaging of filtering blebs after deep sclerectomy with new collagen implant". European Journal of Ophthalmology. 19 (2): 223–230. doi:10.1177/112067210901900208. PMID 19253238. S2CID 22594085.
  99. Matthew SJ, Sarkisian S, Nathan B, James MR (May 2012). Initial experience using a collagen matrix implant (ologen) as a wound modulator with canaloplasty: 12 month results. ARVO. Ft. Lauderdale.
  100. Anisimova SY, Anisimova SI, Larionov EV (2012). "Biological drainage – Xenoplast in glaucoma surgery (experimental and 10-year of clinical follow-up)" (PDF). Copenhagen: EGS Congress. Archived (PDF) from the original on 17 October 2013.
  101. Ong AY, Ng SM, Vedula SS, Friedman DS (March 2021). "Lens extraction for chronic angle-closure glaucoma". The Cochrane Database of Systematic Reviews. 2021 (3): CD005555. doi:10.1002/14651858.CD005555.pub3. PMC 8094223. PMID 33759192.
  102. Tanner, Luke; Gazzard, Gus; Nolan, Winifred P.; Foster, Paul J. (January 2020). "Has the EAGLE landed for the use of clear lens extraction in angle-closure glaucoma? And how should primary angle-closure suspects be treated?". Eye. 34 (1): 40–50. doi:10.1038/s41433-019-0634-5. ISSN 1476-5454. PMC 7002615. PMID 31649349.
  103. Rittiphairoj, Thanitsara; Roberti, Gloria; Michelessi, Manuele (3 April 2023). "Anti-vascular endothelial growth factor for neovascular glaucoma". The Cochrane Database of Systematic Reviews. 4 (4): CD007920. doi:10.1002/14651858.CD007920.pub4. ISSN 1469-493X. PMC 10069372. PMID 37010901.
  104. Grossman, Adriana L.; Javitt, Matthew J.; Moster, Steven J.; Grajewski, Alana L.; Beck, Allen D.; Blieden, Lauren S.; Bitrian, Elena; Chang, Ta C.; Freedman, Sharon F.; Hodapp, Elizabeth; Joos, Keren M.; Reiser, Bibiana J.; Tanna, Angelo P. (1 November 2019). "American Glaucoma Society Position Statement on Cannabinoid Use in Pediatric Glaucoma Patients". Ophthalmology Glaucoma. 2 (6): 365–366. doi:10.1016/j.ogla.2019.07.007. ISSN 2589-4196. PMID 32672568. S2CID 214292703.
  105. Jampel H (February 2010). "American glaucoma society position statement: marijuana and the treatment of glaucoma". Journal of Glaucoma. 19 (2): 75–76. doi:10.1097/ijg.0b013e3181d12e39. PMID 20160576.
  106. Heijl A, Bengtsson B, Hyman L, Leske MC (December 2009). "Natural history of open-angle glaucoma". Ophthalmology (Submitted manuscript). 116 (12): 2271–2276. doi:10.1016/j.ophtha.2009.06.042. PMID 19854514.
  107. "Glaucoma". Coopereyecare.com. 25 July 2013. Archived from the original on 13 December 2013. Retrieved 20 February 2014.
  108. "Death and DALY estimates for 2004 by cause for WHO Member States" (xls). World Health Organization. 2004. Archived from the original on 27 January 2012.
  109. Quigley HA, Broman AT (March 2006). "The number of people with glaucoma worldwide in 2010 and 2020". The British Journal of Ophthalmology. 90 (3): 262–267. doi:10.1136/bjo.2005.081224. PMC 1856963. PMID 16488940.
  110. Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch JD, Javitt JC, et al. (November 1991). "Racial differences in the cause-specific prevalence of blindness in east Baltimore". The New England Journal of Medicine. 325 (20): 1412–1417. doi:10.1056/NEJM199111143252004. PMID 1922252.
  111. "Glaucoma and Marijuana use". National Eye Institute. 21 June 2005. Archived from the original on 27 December 2009.
  112. Ramulu P (March 2009). "Glaucoma and disability: which tasks are affected, and at what stage of disease?". Current Opinion in Ophthalmology. 20 (2): 92–98. doi:10.1097/ICU.0b013e32832401a9. PMC 2692230. PMID 19240541.
  113. Akbari M, Akbari S, Pasquale LR (February 2009). "The association of primary open-angle glaucoma with mortality: a meta-analysis of observational studies". Archives of Ophthalmology. 127 (2): 204–210. doi:10.1001/archophthalmol.2008.571. PMID 19204241.
  114. Bannister R (1622). Treatise of One Hundred and Thirteen Diseases of the Eyes and Eyelids. London.
  115. Leffler CT, Schwartz SG, Wainsztein RD, Pflugrath A, Peterson E (2017). "Ophthalmology in North America: Early Stories (1491-1801)". Ophthalmology and Eye Diseases. 9: 1179172117721902. doi:10.1177/1179172117721902. PMC 5533269. PMID 28804247.
  116. Albert D, Edwards D (1996). The History of Ophthalmologist. Cambridge, Mass.{{cite book}}: CS1 maint: location missing publisher (link)
  117. Harper, Douglas. "glaucoma". Online Etymology Dictionary.
  118. γλαυκός. Liddell, Henry George; Scott, Robert; A Greek–English Lexicon at the Perseus Project.
  119. Leffler CT, Schwartz SG, Giliberti FM, Young MT, Bermudez D (2015). "What was Glaucoma Called Before the 20th Century?". Ophthalmology and Eye Diseases. 7: 21–33. doi:10.4137/OED.S32004. PMC 4601337. PMID 26483611. Archived from the original on 23 April 2016.
  120. Leffler CT, Schwartz SG, Hadi TM, Salman A, Vasuki V (2015). "The early history of glaucoma: the glaucous eye (800 BC to 1050 AD)". Clinical Ophthalmology. 9: 207–215. doi:10.2147/OPTH.S77471. PMC 4321651. PMID 25673972.
  121. "Advanced glaucoma: surgery lowers pressure in the eye more effectively than eye drops". NIHR Evidence (Plain English summary). National Institute for Health and Care Research. 31 March 2022. doi:10.3310/alert_49606. S2CID 247918434.
  122. King AJ, Fernie G, Hudson J, Kernohan A, Azuara-Blanco A, Burr J, et al. (November 2021). "Primary trabeculectomy versus primary glaucoma eye drops for newly diagnosed advanced glaucoma: TAGS RCT". Health Technology Assessment. 25 (72): 1–158. doi:10.3310/hta25720. hdl:2164/18078. PMID 34854808.
  123. Gazzard G, Konstantakopoulou E, Garway-Heath D, Garg A, Vickerstaff V, Hunter R, et al. (April 2019). "Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial". Lancet. 393 (10180): 1505–1516. doi:10.1016/S0140-6736(18)32213-X. PMC 6495367. PMID 30862377.; Lay summary in: "A laser eye procedure can be effective and safe if used early as treatment for glaucoma". NIHR Evidence. National Institute for Health and Care Research. 4 June 2019. doi:10.3310/signal-000774. Plain English summary
  124. Sena DF, Lindsley K (January 2017). "Neuroprotection for treatment of glaucoma in adults". The Cochrane Database of Systematic Reviews. 1 (1): CD006539. doi:10.1002/14651858.CD006539.pub4. PMC 5370094. PMID 28122126.
  125. Day F, Buchan JC, Cassells-Brown A, Fear J, Dixon R, Wood F (September 2010). "A glaucoma equity profile: correlating disease distribution with service provision and uptake in a population in Northern England, UK". Eye. 24 (9): 1478–1485. doi:10.1038/eye.2010.73. PMID 20508654. S2CID 23130257.
  126. Elam AR, Andrews C, Musch DC, Lee PP, Stein JD (October 2017). "Large Disparities in Receipt of Glaucoma Care between Enrollees in Medicaid and Those with Commercial Health Insurance". Ophthalmology. 124 (10): 1442–1448. doi:10.1016/j.ophtha.2017.05.003. PMC 6145133. PMID 28583710.
  127. Allison K, Patel DG, Greene L (May 2021). "Racial and Ethnic Disparities in Primary Open-Angle Glaucoma Clinical Trials: A Systematic Review and Meta-analysis". JAMA Network Open. 4 (5): e218348. doi:10.1001/jamanetworkopen.2021.8348. PMC 8132140. PMID 34003274.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.