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Glaucoma is a group of eye diseases that result in damage to the
optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual information from the retina to the brain. In humans, the optic nerve is derived from ...
(or retina) and cause
vision loss Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment� ...
. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the
drainage angle Drainage is the natural or artificial removal of a surface's water and sub-surface water from an area with excess of water. The internal drainage of most agricultural soils is good enough to prevent severe waterlogging (anaerobic conditio ...
for fluid within the eye remains open, with less common types including closed-angle (narrow angle, acute congestive) glaucoma and
normal-tension glaucoma Normal tension glaucoma (NTG) is an eye disease, a neuropathy of the optic nerve, that shows all the characteristics of primary open angle glaucoma except one: the elevated intraocular pressure (IOP) - the classic hallmark of glaucoma - is missing ...
. Open-angle glaucoma develops slowly over time and there is no pain.
Peripheral vision Peripheral vision, or ''indirect vision'', is vision as it occurs outside the point of fixation, i.e. away from the center of gaze or, when viewed at large angles, in (or out of) the "corner of one's eye". The vast majority of the area in the ...
may begin to decrease, followed by central vision, resulting in blindness if not treated. Closed-angle glaucoma can present gradually or suddenly. The sudden presentation may involve severe eye pain, blurred vision, mid-dilated
pupil The pupil is a black hole located in the center of the iris of the eye that allows light to strike the retina.Cassin, B. and Solomon, S. (1990) ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company. It appears black b ...
, redness of the eye, and nausea. Vision loss from glaucoma, once it has occurred, is permanent. Eyes affected by glaucoma are referred to as being glaucomatous. Risk factors for glaucoma include increasing age, high pressure in the eye, a family history of glaucoma, and use of steroid medication. For eye pressures, a value of above atmospheric pressure (760 mmHg) is often used, with higher pressures leading to a greater risk. However, some may have high eye pressure for years and never develop damage. Conversely,
optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual information from the retina to the brain. In humans, the optic nerve is derived from ...
damage may occur with normal pressure, known as normal-tension glaucoma. The mechanism of open-angle glaucoma is believed to be the slow exit of
aqueous humor The aqueous humour is a transparent water-like fluid similar to plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the posteri ...
through the
trabecular meshwork The trabecular meshwork is an area of tissue in the eye located around the base of the cornea, near the ciliary body, and is responsible for draining the aqueous humor from the eye via the anterior chamber (the chamber on the front of the ...
, while in closed-angle glaucoma the
iris Iris most often refers to: *Iris (anatomy), part of the eye *Iris (mythology), a Greek goddess * ''Iris'' (plant), a genus of flowering plants * Iris (color), an ambiguous color term Iris or IRIS may also refer to: Arts and media Fictional ent ...
blocks the trabecular meshwork. Diagnosis is achieved by performing a dilated
eye examination An eye examination is a series of tests performed to assess vision and ability to focus on and discern objects. It also includes other tests and examinations pertaining to the eyes. Eye examinations are primarily performed by an optometrist, op ...
. Often, the optic nerve shows an abnormal amount of cupping. If treated early, it is possible to slow or stop the progression of disease with medication,
laser A laser is a device that emits light through a process of optical amplification based on the stimulated emission of electromagnetic radiation. The word "laser" is an acronym for "light amplification by stimulated emission of radiation". The firs ...
treatment, or surgery. The goal of these treatments is to decrease eye pressure. A number of different classes of
glaucoma medication Glaucoma medication is divided into groups based on chemical structure and pharmacologic action. The goal of currently available glaucoma therapy is to preserve visual function by lowering intraocular pressure (IOP), below a level that is likely ...
are available. Laser treatments may be effective in both open-angle and closed-angle glaucoma. A number of types of glaucoma surgeries may be used in people who do not respond sufficiently to other measures. Treatment of closed-angle glaucoma is a medical emergency. About 70 million people have glaucoma globally, with about two million patients in the United States. It is the leading cause of blindness in African Americans. It occurs more commonly among older people, and closed-angle glaucoma is more common in women. Glaucoma has been called the "silent thief of sight", because the loss of vision usually occurs slowly over a long period of time. Worldwide, glaucoma is the second-leading cause of blindness after
cataract A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble wi ...
s. Cataracts caused 51% of blindness in 2010, while glaucoma caused 8%. The word "glaucoma" is from the Ancient Greek ''glaukos'', which means "shimmering." In English, the word was used as early as 1587 but did not become commonly used until after 1850, when the development of the
ophthalmoscope Ophthalmoscopy, also called funduscopy, is a test that allows a health professional to see inside the fundus of the eye and other structures using an ophthalmoscope (or funduscope). It is done as part of an eye examination and may be done as part ...
allowed doctors to see the optic nerve damage.


Signs and symptoms

As open-angle glaucoma is usually painless with no symptoms early in the disease process, screening through regular eye exams is important. The only signs are gradually progressive
visual field loss The visual field is the "spatial array of visual sensations available to observation in introspectionist psychological experiments". Or simply, visual field can be defined as the entire area that can be seen when an eye is fixed straight at a point ...
and optic nerve changes (increased
cup-to-disc ratio The optic cup is the white, cup-like area in the center of the optic disc. The ratio of the size of the optic cup to the optic disc (cup-to-disc ratio, or C/D) is one measure used in the diagnosis of glaucoma. Different C/Ds can be measured horizo ...
on fundoscopic examination). About 10% of people with closed angles present with acute angle closure characterized by sudden ocular pain, seeing halos around lights, red eye, very high
intraocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated t ...
(>), nausea and vomiting, suddenly decreased vision, and a fixed, mid-dilated pupil. It is also associated with an oval pupil in some cases. Acute angle closure is an emergency. Opaque specks may occur in the lens in glaucoma, known as glaukomflecken.


Causes

Ocular hypertension Ocular hypertension is the presence of elevated fluid pressure inside the eye (intraocular pressure), usually with no optic nerve damage or visual field loss. For most individuals, the normal range of intraocular pressure is between 10 mmHg and 2 ...
(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. Ocular hypertension—an intraocular pressure above the traditional threshold of or even above —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. 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. Open-angle glaucoma accounts for 90% of glaucoma cases in the United States. 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 Asia East Asia is the eastern region of Asia, which is defined in both geographical and ethno-cultural terms. The modern states of East Asia include China, Japan, Mongolia, North Korea, South Korea, and Taiwan. China, North Korea, South Korea and ...
n countries).


Dietary

No clear evidence indicates that vitamin deficiencies cause glaucoma in humans. As such, oral vitamin supplementation is not a recommended treatment. Caffeine increases
intraocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated t ...
in those with glaucoma, but does not appear to affect normal individuals.


Ethnicity

Many people of
East Asian East Asia is the eastern region of Asia, which is defined in both geographical and ethno-cultural terms. The modern states of East Asia include China, Japan, Mongolia, North Korea, South Korea, and Taiwan. China, North Korea, South Korea and ...
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. Higher rates of glaucoma have also been reported for
Inuit Inuit (; iu, ᐃᓄᐃᑦ 'the people', singular: Inuk, , dual: Inuuk, ) are a group of culturally similar indigenous peoples inhabiting the Arctic and subarctic regions of Greenland, Labrador, Quebec, Nunavut, the Northwest Territories, and ...
populations, compared to
White White is the lightest color and is achromatic (having no hue). It is the color of objects such as snow, chalk, and milk, and is the opposite of black. White objects fully reflect and scatter all the visible wavelengths of light. White on ...
populations, in Canada and Greenland.


Genetics

Positive family history is a risk factor for glaucoma. The relative risk of having primary open-angle glaucoma (POAG) is increased about two- to four-fold for people who have a sibling with glaucoma. Glaucoma, particularly primary open-angle glaucoma, is associated with
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...
s in several
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s, including ''
MYOC Myocilin, trabecular meshwork inducible glucocorticoid response (TIGR), also known as MYOC, is a protein which in humans is encoded by the ''MYOC'' gene. Mutations in ''MYOC'' are a major cause of glaucoma. Gene location The cytogenetic locati ...
, ASB10,
WDR36 WD repeat-containing protein 36 is a protein that in humans is encoded by the ''WDR36'' gene. This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracke ...
, NTF4'', '' TBK1'', and ''
RPGRIP1 X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 is a protein in the ciliary transition zone that in humans is encoded by the ''RPGRIP1'' gene. RPGRIP1 is a multi-domain protein containing a coiled-coil domain at the N-ter ...
'', although most cases of glaucoma do not involve these genetic mutations. Normal-tension glaucoma, which comprises one-third of POAG, is also associated with genetic mutations (including '' OPA1'' and '' OPTN'' genes). Various rare congenital/genetic eye malformations are associated with glaucoma. Occasionally, failure of the normal third-trimester gestational atrophy of the
hyaloid canal Hyaloid canal (Cloquet's canal and Stilling's canal) is a small transparent canal running through the vitreous body from the optic nerve disc to the lens. It is formed by an invagination of the hyaloid membrane, which encloses the vitreous body. ...
and the
tunica vasculosa lentis The tunica vasculosa lentis is an extensive capillary network, spreading over the posterior and lateral surfaces of the lens of the eye. It disappears shortly after birth. See also * Persistent tunica vasculosa lentis Persistent tunica vasc ...
is associated with other anomalies. Angle closure-induced ocular hypertension and glaucomatous optic neuropathy may also occur with these anomalies and has been modelled in mice.


Other

Other factors can cause glaucoma, known as "secondary glaucoma", including prolonged use of
steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
s (steroid-induced glaucoma); conditions that severely restrict blood flow to the eye, such as severe
diabetic retinopathy Diabetic retinopathy (also known as diabetic eye disease), is a medical condition in which damage occurs to the retina due to diabetes mellitus. It is a leading cause of blindness in developed countries. Diabetic retinopathy affects up to 80 pe ...
and central retinal vein occlusion (neovascular glaucoma); ocular trauma (angle-recession glaucoma); and inflammation of the middle layer of the pigmented vascular eye structure (
uveitis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and in ...
), known as
uveitic glaucoma Uveitic glaucoma (or uveitis glaucoma, or anterior uveitic glaucoma, or anterior noninfectious uveitic glaucoma, or uveitis associated with glaucoma, or iritic glaucoma) is most commonly a progression stage of noninfectious anterior uveitis or ...
.


Pathophysiology

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 Ocular hypertension is the presence of elevated fluid pressure inside the eye (intraocular pressure), usually with no optic nerve damage or visual field loss. For most individuals, the normal range of intraocular pressure is between 10 mmHg and ...
. Intraocular pressure is a function of production of liquid
aqueous humor The aqueous humour is a transparent water-like fluid similar to plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the posteri ...
by the ciliary processes of the eye, and its drainage through the
trabecular meshwork The trabecular meshwork is an area of tissue in the eye located around the base of the cornea, near the ciliary body, and is responsible for draining the aqueous humor from the eye via the anterior chamber (the chamber on the front of the ...
. Aqueous humor flows from the ciliary processes into the posterior chamber, bounded posteriorly by the
lens A lens is a transmissive optical device which focuses or disperses a light beam by means of refraction. A simple lens consists of a single piece of transparent material, while a compound lens consists of several simple lenses (''elements''), ...
and the
zonules of Zinn The zonule of Zinn () (Zinn's membrane, ciliary zonule) (after Johann Gottfried Zinn) is a ring of fibrous strands forming a zonule (little band) that connects the ciliary body with the crystalline lens of the eye. These fibers are sometimes colle ...
, and anteriorly by the
iris Iris most often refers to: *Iris (anatomy), part of the eye *Iris (mythology), a Greek goddess * ''Iris'' (plant), a genus of flowering plants * Iris (color), an ambiguous color term Iris or IRIS may also refer to: Arts and media Fictional ent ...
. It then flows through the
pupil The pupil is a black hole located in the center of the iris of the eye that allows light to strike the retina.Cassin, B. and Solomon, S. (1990) ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company. It appears black b ...
of the iris into the
anterior chamber The anterior chamber ( AC) is the aqueous humor-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. Hyphema, anterior uveitis and glaucoma are three main pathologies in this area. In hyphema, blood fil ...
, bounded posteriorly by the iris and anteriorly by the
cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical powe ...
. From here, the trabecular meshwork drains aqueous humor via the scleral venous sinus (
Schlemm's canal Schlemm's canal is a circular lymphatic-like vessel in the eye. It collects aqueous humor from the anterior chamber and delivers it into the episcleral blood vessels. Canaloplasty may be used to widen it. Structure Schlemm's canal is an endot ...
) into scleral plexuses and general blood circulation. 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. In close/narrow-angle, the iridocorneal angle is completely closed because of forward displacement of the final roll and root of the iris against the cornea, resulting in the inability of the aqueous fluid to flow from the posterior to the anterior chamber and then out of the trabecular network. This accumulation of aqueous humor causes an acute increase in pressure and pain. Degeneration of
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...
s of the
retinal ganglion cell A retinal ganglion cell (RGC) is a type of neuron located near the inner surface (the ganglion cell layer) of the retina of the eye. It receives visual information from photoreceptors via two intermediate neuron types: bipolar cells and retina ...
s (the
optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual information from the retina to the brain. In humans, the optic nerve is derived from ...
) is a hallmark of glaucoma. The inconsistent relationship of glaucomatous
optic neuropathy Optic neuropathy is damage to the optic nerve from any cause. The optic nerve is a bundle of millions of fibers in the retina that sends visual signals to the brain. Damage and death of these nerve cells, or neurons, leads to characteristic featu ...
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/axon degeneration, glial support cell, immune system, aging mechanisms of neuron loss, and severing of the nerve fibers at the scleral edge.


Diagnosis

Screening for glaucoma is usually performed as part of a standard
eye examination An eye examination is a series of tests performed to assess vision and ability to focus on and discern objects. It also includes other tests and examinations pertaining to the eyes. Eye examinations are primarily performed by an optometrist, op ...
performed by
optometrist Optometry is a specialized health care profession that involves examining the eyes and related structures for defects or abnormalities. Optometrists are health care professionals who typically provide comprehensive primary eye care. In the Uni ...
s and
ophthalmologist Ophthalmology ( ) is a surgical subspecialty within medicine that deals with the diagnosis and treatment of eye disorders. An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Following a medic ...
s. Testing for glaucoma includes measurements of the intraocular pressure using tonometry, anterior chamber angle examination or
gonioscopy Gonioscopy a routine ophthalmological procedure that measures the angle between the iris and the cornea (the iridocorneal angle), using a goniolens (also known as a gonioscope) together with a slit lamp or operating microscope. Its use is import ...
as well as examination of the optic nerve to discern visible damage, changes in the
cup-to-disc ratio The optic cup is the white, cup-like area in the center of the optic disc. The ratio of the size of the optic cup to the optic disc (cup-to-disc ratio, or C/D) is one measure used in the diagnosis of glaucoma. Different C/Ds can be measured horizo ...
, rim appearance and vascular change. A formal
visual field test A visual field test is an eye examination that can detect dysfunction in central and peripheral vision which may be caused by various medical conditions such as glaucoma, stroke, pituitary disease, brain tumours or other neurological deficits ...
is performed. The retinal nerve fiber layer can be assessed with imaging techniques such as
optical coherence tomography Optical coherence tomography (OCT) is an imaging technique that uses low-coherence light to capture micrometer-resolution, two- and three-dimensional images from within optical scattering media (e.g., biological tissue). It is used for medic ...
,
scanning laser polarimetry Scanning laser polarimetry is the use of polarised light to measure the thickness of the retinal nerve fiber layer as part of a glaucoma workup. The GDx-VCC is one example. However a Dutch study found that while there is a correlation between st ...
or
scanning laser ophthalmoscopy Scanning laser ophthalmoscopy (SLO) is a method of examination of the eye. It uses the technique of confocal laser scanning microscopy for diagnostic imaging of the retina or cornea of the human eye. As a method used to image the retina with a ...
(Heidelberg retinal tomogram). Visual field loss is the most specific sign of the condition, though it occurs later in the course of the disease. As all methods of tonometry are sensitive to corneal thickness, methods such as Goldmann tonometry may be augmented with
pachymetry Corneal pachymetry is the process of measuring the thickness of the cornea. A pachymeter is a medical device used to measure the thickness of the eye's cornea. It is used to perform corneal pachymetry prior to refractive surgery, for Keratocon ...
to measure the central corneal thickness (CCT). A thicker cornea can result in a pressure reading higher than the true pressure but a thinner cornea can produce a pressure reading lower than the true pressure. Because pressure-measurement error can be caused by more than just CCT (such as by corneal hydration or elastic properties), it is impossible to adjust pressure measurements based only on CCT measurements. The frequency-doubling illusion can also be used to detect glaucoma with the use of a frequency-doubling technology perimeter. Examination for glaucoma is assessed with attention given to gender, race, history of drug use, refraction, inheritance and family history. Glaucoma has been classified into specific types:


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) :*Chronic angle closure glaucoma :*Intermittent angle closure glaucoma :*Superimposed on chronic open-angle closure glaucoma ("combined mechanism" – uncommon) Variants of primary glaucoma *
Pigmentary glaucoma Pigment dispersion syndrome (PDS) is an eye disorder that can lead to a form of glaucoma known as pigmentary glaucoma. It takes place when pigment cells slough off from the back of the iris and float around in the aqueous humor. Over time, thes ...
*
Exfoliation glaucoma Pseudoexfoliation syndrome, often abbreviated as PEX and sometimes as PES or PXS, is an aging-related systemic disease manifesting itself primarily in the eyes which is characterized by the accumulation of microscopic granular amyloid-like protein ...
, also known as pseudoexfoliative glaucoma or glaucoma capsulare *
Primary juvenile glaucoma Primary juvenile glaucoma is glaucoma that develops due to ocular hypertension and is evident either at birth or within the first few years of life. It is caused due to abnormalities in the anterior chamber angle development that obstruct aqueous o ...
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. Once any symptoms have been controlled, the first line (and often definitive) treatment is laser
iridotomy An iridectomy, also known as a surgical iridectomy or corectomy, is the surgical removal of part of the iris.Cline D; Hofstetter HW; Griffin JR. ''Dictionary of Visual Science''. 4th ed. Butterworth-Heinemann, Boston 1997. 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. Prostaglandin agonists work by opening uveoscleral passageways. Beta-blockers, such as timolol, work by decreasing aqueous formation.
Carbonic anhydrase inhibitor Carbonic anhydrase inhibitors are a class of pharmaceuticals that suppress the activity of carbonic anhydrase. Their clinical use has been established as anti-glaucoma agents, diuretics, antiepileptics, in the management of mountain sickness, g ...
s 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 Apraclonidine ( INN), also known under the brand name Iopidine, is a sympathomimetic used in glaucoma therapy. It is an α2 adrenergic receptor agonist and a weak α1 adrenergic receptor agonist. Topical apraclonidine is administered at a conc ...
) both decrease fluid production (via inhibition of AC) and increase drainage.


Developmental glaucoma

Developmental glaucoma (Q15.0) *Primary congenital glaucoma *Infantile glaucoma *Glaucoma associated with hereditary or familial diseases


Secondary glaucoma

Secondary glaucoma Secondary glaucoma is a collection of progressive optic nerve disorders associated with a rise in intraocular pressure (IOP) which results in the loss of vision. In clinical settings, it is defined as the occurrence of IOP above 21 mmHg requiring th ...
(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 Hyphema is a condition that occurs when blood enters the front (anterior) chamber of the eye between the iris and the cornea. People usually first notice a loss of vision or decrease in vision. The eye may also appear to have a reddish tinge, or ...
:*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 Diabetic retinopathy (also known as diabetic eye disease), is a medical condition in which damage occurs to the retina due to diabetes mellitus. It is a leading cause of blindness in developed countries. Diabetic retinopathy affects up to 80 pe ...
(PDR) or central retinal vein occlusion (CRVO). It may also be triggered by other conditions that result in
ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems w ...
of the
retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then p ...
or
ciliary body The ciliary body is a part of the eye that includes the ciliary muscle, which controls the shape of the lens, and the ciliary epithelium, which produces the aqueous humor. The aqueous humor is produced in the non-pigmented portion of the ciliary ...
. 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. A new treatment for this disease, as first reported by Kahook and colleagues, involves the use of a novel group of medications known as anti-VEGF agents. These injectable medications can lead to a dramatic decrease in new vessel formation and, if injected early enough in the disease process, may lead to normalization of intraocular pressure. Currently, there are no high-quality controlled trials demonstrating a beneficial effect of anti-VEGF treatments in lowering IOP in people with neovascular glaucoma. Toxic glaucoma is open-angle glaucoma with an unexplained significant rise of intraocular pressure following unknown pathogenesis. Intraocular pressure can sometimes reach . It characteristically manifests as ciliary body inflammation and massive trabecular o
edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...
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.


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 The pupillary light reflex (PLR) or photopupillary reflex is a reflex that controls the diameter of the pupil, in response to the intensity (luminance) of light that falls on the retinal ganglion cells of the retina in the back of the eye, thereby ...
and
pupillary response Pupillary response is a physiological response that varies the size of the pupil, via the optic and oculomotor cranial nerve. A constriction response (miosis), is the narrowing of the pupil, which may be caused by scleral buckles or drugs such ...
, 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.


Types

Glaucoma is an umbrella term for eye conditions that damage the
optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual information from the retina to the brain. In humans, the optic nerve is derived from ...
and that can lead to a loss of vision. 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 Peripheral vision, or ''indirect vision'', is vision as it occurs outside the point of fixation, i.e. away from the center of gaze or, when viewed at large angles, in (or out of) the "corner of one's eye". The vast majority of the area in the ...
, but eventually all vision will be lost if the condition is not treated. 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 The trabecular meshwork is an area of tissue in the eye located around the base of the cornea, near the ciliary body, and is responsible for draining the aqueous humor from the eye via the anterior chamber (the chamber on the front of the ...
, which blocks the outflow of
aqueous humor The aqueous humour is a transparent water-like fluid similar to plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the posteri ...
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 Far-sightedness, also known as long-sightedness, hypermetropia, or hyperopia, is a condition of the eye where distant objects are seen clearly but near objects appear blurred. This blurred effect is due to incoming light being focused behind, in ...
, 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. 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 (). Individuals with a family history of NTG, those of Japanese ancestry, those with a history of systemic heart disease and those with
Flammer syndrome Flammer syndrome is a described clinical entity comprising a complex of clinical features caused mainly by dysregulation of the blood supply. It was previously known as vascular dysregulation. It can manifest in many symptoms, such as cold hands ...
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
cataract A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble wi ...
s or
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
. It can also be caused by certain drugs such as
steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
s. Treatment depends on whether the condition is identified as open-angle or angle-closure glaucoma. With
pseudoexfoliation glaucoma Pseudoexfoliation syndrome, often abbreviated as PEX and sometimes as PES or PXS, is an aging-related systemic disease manifesting itself primarily in the eyes which is characterized by the accumulation of microscopic granular amyloid-like protein ...
(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 Scandinavia; Sámi languages: /. ( ) is a subregion in Northern Europe, with strong historical, cultural, and linguistic ties between its constituent peoples. In English usage, ''Scandinavia'' most commonly refers to Denmark, Norway, and Swed ...
, primarily in those over 70, and more commonly in women.
Pigmentary glaucoma Pigment dispersion syndrome (PDS) is an eye disorder that can lead to a form of glaucoma known as pigmentary glaucoma. It takes place when pigment cells slough off from the back of the iris and float around in the aqueous humor. Over time, thes ...
(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 Primary juvenile glaucoma is glaucoma that develops due to ocular hypertension and is evident either at birth or within the first few years of life. It is caused due to abnormalities in the anterior chamber angle development that obstruct aqueous o ...
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 Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and in ...
, the swelling and inflammation of the
uvea The uvea (; Lat. ''uva'', "grape"), also called the ''uveal layer'', ''uveal coat'', ''uveal tract'', ''vascular tunic'' or ''vascular layer'' is the pigmented middle of the three concentric layers that make up an eye. History and etymolog ...
, 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.


Visual field defects in glaucoma

In glaucoma visual field defects result from damage to the
retinal nerve fiber layer The retinal nerve fiber layer (RNFL) or nerve fiber layer, stratum opticum, is formed by the expansion of the fibers of the optic nerve; it is thickest near the optic disc, gradually diminishing toward the ora serrata. As the nerve fibers pass t ...
. 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. 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. Larger and brighter targets can be seen. Small paracentral depressions, mainly superonasal are seen in normal tension glaucoma (NTG). The generalized depression of the entire field may be seen in cataract also. * 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. It is only an early non-specific visual field change, without much diagnostic value in glaucoma. * 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. * Siedel's sickle-shaped scotoma: Paracentral scotoma joins with the blind spot to form the
Seidel sign Seidel's sign (also called Seidel's scotoma) is a sickle-shaped scotoma that is a superior or inferior extension of the blind spot. It occurs in some patients with glaucoma Glaucoma is a group of eye diseases that result in damage to the op ...
. * Arcuate or Bjerrum's 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. * 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. * 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 Tunnel vision is the loss of peripheral vision with retention of central vision, resulting in a constricted circular tunnel-like field of vision. Causes Tunnel vision can be caused by: Eyeglass users Eyeglass users experience 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 Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visual field). As peripheral vision worsens, people may ...
is another disease that causes tubular vision. * 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, so it may not be visible with standard central field measurements done in glaucoma.


Screening

The
United States Preventive Services Task Force The United States Preventive Services Task Force (USPSTF) is "an independent panel of experts in primary care and prevention that systematically reviews the evidence of effectiveness and develops recommendations for clinical preventive services". ...
stated, as of 2013, that there was insufficient evidence to recommend for or against screening for glaucoma. Therefore, there is no national screening program in the US. Screening, however, is recommended starting at age 40 by the American Academy of Ophthalmology. 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.


Treatment

The modern goals of glaucoma management are to avoid glaucomatous damage and nerve damage, and preserve visual field and total quality of life for patients, with minimal side-effects. This requires appropriate diagnostic techniques and follow-up examinations, and judicious selection of treatments for the individual patient. Although intraocular pressure (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. 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. 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.


Medication

Intraocular pressure can be lowered with medication, usually eye drops. Several classes of medications are used to treat glaucoma, with several medications in each class. By reducing pressure, eye drops also help to lower the risk of sight loss. Latanoprost, for example, seems to halve this risk. 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, like the growth of eyelashes and hyperpigmentation in the eyelid. Initially, glaucoma drops may reasonably be started in either one or in both eyes. The possible neuroprotective effects of various topical and systemic medications are also being investigated. *
Prostaglandin analogs Prostaglandin analogues are a class of drugs that bind to a prostaglandin receptor. Wider use of prostaglandin analogues is limited by unwanted side effects and their abortive potential. Uses Prostaglandin analogues such as misoprostol are used ...
, such as
latanoprost Latanoprost, sold under the brand name Xalatan among others, is a medication used to treat increased pressure inside the eye. This includes ocular hypertension and open angle glaucoma. It is applied as eye drops to the eyes. Onset of effects ...
,
bimatoprost Bimatoprost, sold under the brand name Lumigan among others, is a medication used to treat high pressure inside the eye including glaucoma. Specifically it is used for open angle glaucoma when other agents are not sufficient. It may also be us ...
and
travoprost Travoprost, sold under the brand name Travatan among others, is a medication used to treat high pressure inside the eye including glaucoma. Specifically it is used for open angle glaucoma when other agents are not sufficient. It is used as an e ...
, increase uveoscleral outflow of aqueous humor. Bimatoprost also increases trabecular outflow. * Topical beta-adrenergic receptor antagonists, such as
timolol Timolol is a beta blocker medication used either by mouth or as eye drops. As eye drops it is used to treat increased pressure inside the eye such as in ocular hypertension and glaucoma. By mouth it is used for high blood pressure, chest pa ...
,
levobunolol Levobunolol (trade names AKBeta, Betagan, Vistagan, among others) is a non-selective beta blocker. It is used topically in the form of eye drops to manage ocular hypertension (high pressure in the eye) and open-angle glaucoma. Contraindications ...
, and betaxolol, decrease aqueous humor production by the epithelium of the
ciliary body The ciliary body is a part of the eye that includes the ciliary muscle, which controls the shape of the lens, and the ciliary epithelium, which produces the aqueous humor. The aqueous humor is produced in the non-pigmented portion of the ciliary ...
. * Alpha2-adrenergic agonists, such as brimonidine and
apraclonidine Apraclonidine ( INN), also known under the brand name Iopidine, is a sympathomimetic used in glaucoma therapy. It is an α2 adrenergic receptor agonist and a weak α1 adrenergic receptor agonist. Topical apraclonidine is administered at a conc ...
, work by a dual mechanism, decreasing aqueous humor production and increasing uveoscleral outflow. * Less-selective alpha agonists, such as
epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
, decrease aqueous humor production through vasoconstriction of ciliary body blood vessels, useful only in open-angle glaucoma. Epinephrine's mydriatic effect, however, renders it unsuitable for closed-angle glaucoma due to further narrowing of the uveoscleral outflow (i.e. further closure of trabecular meshwork, which is responsible for absorption of aqueous humor). * Miotic agents (
parasympathomimetic A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs because ac ...
s), such as
pilocarpine Pilocarpine is a medication used to reduce pressure inside the eye and treat dry mouth. As eye drops it is used to manage angle closure glaucoma until surgery can be performed, ocular hypertension, primary open angle glaucoma, and to bring ab ...
, work by contraction of the
ciliary muscle The ciliary muscle is an intrinsic muscle of the eye formed as a ring of smooth muscleSchachar, Ronald A. (2012). "Anatomy and Physiology." (Chapter 4) . in the eye's middle layer, uvea ( vascular layer). It controls accommodation for viewing ...
, opening the
trabecular meshwork The trabecular meshwork is an area of tissue in the eye located around the base of the cornea, near the ciliary body, and is responsible for draining the aqueous humor from the eye via the anterior chamber (the chamber on the front of the ...
and allowing increased outflow of the aqueous humour. Echothiophate, an acetylcholinesterase inhibitor, is used in chronic glaucoma. *
Carbonic anhydrase inhibitors Carbonic anhydrase inhibitors are a class of pharmaceuticals that suppress the activity of carbonic anhydrase. Their clinical use has been established as anti-glaucoma agents, diuretics, antiepileptics, in the management of mountain sickness, g ...
, such as dorzolamide,
brinzolamide Brinzolamide (trade names Azopt, Alcon Laboratories, Befardin, Fardi Medicals, ) is a carbonic anhydrase inhibitor used to lower intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Brinzolamide was approved as a g ...
, and
acetazolamide Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, altitude sickness, periodic paralysis, idiopathic intracranial hypertension (raised brain pressure of unclear cause), urine alkal ...
, lower secretion of aqueous humor by inhibiting carbonic anhydrase in the ciliary body.


Adherence

Poor compliance with medications and follow-up visits is a major reason for vision loss in glaucoma patients. A 2003 study of patients in an
HMO In the United States, a health maintenance organization (HMO) is a medical insurance group that provides health services for a fixed annual fee. It is an organization that provides or arranges managed care for health insurance, self-funded heal ...
found half failed to fill their prescriptions the first time, and one-quarter failed to refill their prescriptions a second time. Patient education and communication must be ongoing to sustain successful treatment plans for this lifelong disease with no early symptoms. Adherence to medication protocol can be confusing and expensive; if side effects occur, the patient must be willing either to tolerate them or to communicate with the treating physician to improve the drug regimen. Initially, glaucoma drops may reasonably be started in either one or in both eyes.


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 Argon is a chemical element with the symbol Ar and atomic number 18. It is in group 18 of the periodic table and is a noble gas. Argon is the third-most abundant gas in Earth's atmosphere, at 0.934% (9340 ppmv). It is more than twice as abu ...
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 Pigment dispersion syndrome (PDS) is an eye disorder that can lead to a form of glaucoma known as pigmentary glaucoma. It takes place when pigment cells slough off from the back of the iris and float around in the aqueous humor. Over time, these ...
. 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. Diode laser cycloablation lowers IOP by reducing aqueous secretion by destroying secretory ciliary epithelium.


Surgery

Both
laser A laser is a device that emits light through a process of optical amplification based on the stimulated emission of electromagnetic radiation. The word "laser" is an acronym for "light amplification by stimulated emission of radiation". The firs ...
and conventional surgeries are performed to treat glaucoma. Surgery is the primary therapy for those with
congenital A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
glaucoma. Generally, these operations are a temporary solution, as there is not yet a cure for glaucoma.


Canaloplasty

Canaloplasty is a nonpenetrating procedure using micro catheter 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.


Trabeculectomy

The most common conventional surgery performed for glaucoma is the
trabeculectomy Trabeculectomy is a surgical procedure used in the treatment of glaucoma to relieve intraocular pressure by removing part of the eye's trabecular meshwork and adjacent structures. It is the most common glaucoma surgery performed and allows draina ...
. 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 Mitomycin C is a mitomycin that is used as a chemotherapeutic agent by virtue of its antitumour activity. Medical uses It is given intravenously to treat upper gastro-intestinal cancers (e.g. esophageal carcinoma), anal cancers, and breast c ...
(MMC) or
5-fluorouracil Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancrea ...
(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. Collagen matrix prevents scarring by randomizing and modulating fibroblast proliferation in addition to mechanically preventing wound contraction and adhesion.


Glaucoma drainage implants

The first glaucoma drainage implant was developed in 1966. 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. 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. The implants are transscleral and different from other ab interno implants that do not create a transscleral drainage, such as iStent, CyPass, or Hydrus. 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, 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. And for glaucomatous painful blind eye and some cases of glaucoma, cyclocryotherapy for ciliary body ablation could be considered to be performed.


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. 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, ologen Collagen Matrix, or Xenoplast glaucoma implant. 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.


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.


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. The intraocular pressure can also have an effect, with higher pressures reducing the time until blindness.


Epidemiology

As of 2010, there were 44.7 million people in the world with open angle glaucoma. The same year, there were 2.8 million people in the United States with open angle glaucoma. By 2020, the prevalence is projected to increase to 58.6 million worldwide and 3.4 million in the United States. Both internationally and in the United States, glaucoma is the second-leading cause of
blindness Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment� ...
. Globally,
cataract A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble wi ...
s 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. Bilateral vision loss can negatively affect mobility and interfere with driving. A
meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
published in 2009 found that people with primary open angle glaucoma do ''not'' have increased
mortality rate Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of de ...
s, or increased risk of cardiovascular death.


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...". Angle-closure glaucoma was treated with cataract extraction by John Collins Warren in Boston as early as 1806. The invention of the ophthalmoscope by
Hermann Helmholtz Hermann Ludwig Ferdinand von Helmholtz (31 August 1821 – 8 September 1894) was a German physicist and physician who made significant contributions in several scientific fields, particularly hydrodynamic stability. The Helmholtz Association, ...
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 Hans Goldmann (20 November 1899 in Komotau, Kingdom of Bohemia, Austro-Hungarian Empire – 19 November 1991 in Bern) was an Austrian-Swiss ophthalmologist and inventor. Biography Goldmann completed his Gymnasium education in Komotau (now known as ...
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. The first drug to reduce IOP,
pilocarpine Pilocarpine is a medication used to reduce pressure inside the eye and treat dry mouth. As eye drops it is used to manage angle closure glaucoma until surgery can be performed, ocular hypertension, primary open angle glaucoma, and to bring ab ...
, was introduced in the 1870s; other major innovations in pharmacological glaucoma therapy were the introduction of
beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack (secondary prevention). They are al ...
eye drops in the 1970s and of
prostaglandin analogue Prostaglandin analogues are a class of drugs that bind to a prostaglandin receptor. Wider use of prostaglandin analogues is limited by unwanted side effects and their abortive potential. Uses Prostaglandin analogues such as misoprostol are use ...
s and topical (locally administered)
carbonic anhydrase inhibitor Carbonic anhydrase inhibitors are a class of pharmaceuticals that suppress the activity of carbonic anhydrase. Their clinical use has been established as anti-glaucoma agents, diuretics, antiepileptics, in the management of mountain sickness, g ...
s 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, a derivative of γλαυκóς, 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. 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. 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.;


Rho kinase inhibitors

Rho kinase Rho-associated protein kinase (ROCK) is a kinase belonging to the AGC (PKA/ PKG/PKC) family of serine-threonine specific protein kinases. It is involved mainly in regulating the shape and movement of cells by acting on the cytoskeleton. ROCKs ( ...
inhibitors, such as
ripasudil Ripasudil (trade name Glanatec), a derivative of fasudil, is a rho kinase inhibitor drug (previously known as K-115) used for the treatment of glaucoma and ocular hypertension. Pharmacology Pharmacodynamics Ripasudil's mechanism of action a ...
, work by inhibition of the actin cytoskeleton, resulting in the morphological changes in the trabecular meshwork and increased aqueous outflow. More compounds in this class are being investigated in phase 2 and phase 3 trials.


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. 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. 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.


Cannabis

Studies in the 1970s reported that the use of
cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: ''Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternativel ...
may lower intraocular pressure. In an effort to determine whether marijuana, or drugs derived from it, might be effective as a glaucoma treatment, the US
National Eye Institute The National Eye Institute (NEI) was established in 1968. It is located in Bethesda, Maryland, United States. The NEI is one of 27 institutes and centers of the US National Institutes of Health (NIH), an agency of the US Department of Health and ...
supported research studies from 1978 to 1984. These studies demonstrated some derivatives of marijuana lowered intraocular pressure when administered orally, intravenously, or by smoking, but not when topically applied to the eye. In 2003, the American Academy of Ophthalmology released a position statement stating that cannabis was not more effective than prescription medications. Furthermore, no scientific evidence has been found that demonstrates increased benefits and/or diminished risks of cannabis use to treat glaucoma compared with the wide variety of pharmaceutical agents now available. In 2010 the American Glaucoma Society published a position paper discrediting the use of cannabis as a legitimate treatment for elevated intraocular pressure, for reasons including short duration of action and side effects that limit many activities of daily living.


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. 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. 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. 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


External links

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GeneReview/NCBI/NIH/UW entry on Primary Congenital Glaucoma
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