Glaucoma

Glaucoma
Specialty	Ophthalmology

Human eye cross-sectional view. Courtesy NIH National Eye Institute

File:Glaucoma,optic nerve.jpg

The pink rim of disc contains nerve fibers. The white cup is a pit with no nerve fibers. As glaucoma advances, the cup enlarges until it occupies most of the disc area. Courtesy AgingEye Times

Glaucoma is a group of diseases of the optic nerve involving loss of retinal ganglion cells in a characteristic pattern of optic neuropathy. Although raised intraocular pressure is a significant risk factor for developing glaucoma, there is no set threshold for intraocular pressure that causes glaucoma. One person may develop nerve damage at a relatively low pressure, while another person may have high eye pressures for years and yet never develop damage. Untreated glaucoma leads to permanent damage of the optic nerve and resultant visual field loss, which can progress to blindness.

Glaucoma has been nicknamed "the sneak thief of sight". Worldwide, it is the second leading cause of blindness. Glaucoma affects 1 in 200 people aged 50 and younger and 1 in 10 over the age of 80.

Risk factors and diagnosis

A normal range of vision. Courtesy NIH National Eye Institute

The same view with advanced vision loss from glaucoma.

People with a family history of glaucoma have about a six percent chance of developing glaucoma. Diabetics and African people are three times more likely to develop primary open angle glaucoma. Asians are prone to develop angle-closure glaucoma, and Inuit have a 20 to 40 times higher risk than white people to develop primary angle closure glaucoma. Women are three times more likely than men to develop acute angle-closure glaucoma due to their shallower anterior chambers. Use of steroids can also cause glaucoma.

There is increasing evidence of ocular blood flow to be involved in the pathogenesis of glaucoma. Current data indicate that fluctuations in blood flow are more harmful to GON than steady reductions. Unstable blood pressure and dips are linked to optic nerve head damage and correlate with visual field deterioration.

A number of studies also suggest that there is a correlative, not necessarily causal, relationship between glaucoma and systemic hypertension (i.e. high blood pressure). In normal tension glaucoma, nocturnal hypotension may play a significant role.

Screening for glaucoma is usually performed as part of a standard eye examination performed by ophthalmologists and optometrists. Testing for glaucoma should include measurements of the intraocular pressure via tonometry, changes in size or shape of the eye, and an examination of the optic nerve to look for any damage to it. If there is any suspicion of damage to the optic nerve, a formal visual field test should be performed. Scanning laser ophthalmoscopy may also be performed.

Those at risk for glaucoma are advised to have dilated eye examination at least every two years.

Treatment

Although intraocular pressure is only one of the risk factors (albeit a major one) of glaucoma, lowering it via pharmaceuticals or surgery is currently the mainstay of glaucoma treatment. In Europe, Japan, and Canada laser treatment is often the first line of therapy. In the U.S., adoption of early laser has lagged, even though prospective, multi-centered, peer-reviewed studies, since the early '90's, have shown laser to be at least as effective as topical medications in controlling intraocular pressure and preserving visual field.

Drugs

Intraocular pressure can be lowered with medication, usually eye drops. There are several different classes of medications to treat glaucoma with several different medications in each class. Prostaglandin analogs like latanoprost (Xalatan), bimatoprost (Lumigan) and travoprost (Travatan) increase uveoscleral outflow of aqueous. Topical beta-adrenergic receptor antagonists such as timolol, levobunolol (Betagan) , and betaxolol decrease aqueous humor production by the ciliary body. Alpha2-adrenergic agonists such as brimonidine (Alphagan) work by a dual mechanism, decreasing aqueous production and increasing uveo-scleral outflow. Less-selective sympathomimetics like epinephrine and dipivefrin (Propine) increase outflow of aqueous humor through trabecular meshwork and possibly through uveoscleral outflow pathway, probably by a beta2-agonist action. Miotic agents (parasympathomimetics) like pilocarpine work by contraction of the ciliary muscle, tightening the trabecular meshwork and allowing increased outflow of aqueous through traditional pathways. Carbonic anhydrase inhibitors like dorzolamide (Trusopt), brinzolamide (Azopt), acetazolamide (Diamox) lower secretion of aqueous humor by inhibiting carbonic anhydrase in the ciliary body. Each of these medicines may have local and systemic side effects. Adherence will medication protocol can be confusing and expensive; if side effects occur, the patient must be willing either to tolerate these, or to communicate with the treating physician to improve the drug regimen.

Poor compliance with medications and follow-up visits is a major reason for vision loss in glaucoma patients. Patient education and communication must be ongoing to sustain successful treatment plans for this lifelong disease with no early symptoms.

Marijuana has been shown to lower the intraocular pressure in a few studies but this is generally not used clinically. Studies in the 1970s showed that marijuana, when smoked, lowers intraocular pressure.. In an effort to determine whether marijuana, or drugs derived from marijuana, might be effective as a glaucoma treatment, the US National Eye Institute supported research studies from 1978 to 1984. These studies demonstrated that some derivatives of marijuana lowered intraocular pressure when administered orally, intravenously, or by smoking, but not when topically applied to the eye. However, none of these studies demonstrated that marijuana -- or any of its components -- could safely and effectively lower intraocular pressure any more than a variety of drugs then on the market. In 2003, the American Academy of Ophthalmology released a position statement asserting that "no scientific evidence has been found that demonstrates increased benefits and/or diminished risks of marijuana use to treat glaucoma compared with the wide variety of pharmaceutical agents now available."

The first patient in the United States federal government's Compassionate Investigational New Drug program, Robert Randall, was afflicted with glaucoma and had successfully fought charges of marijuana cultivation because it was deemed a medical necessity (U.S. v. Randall) in 1976.

The possible neuroprotective effects of various topical and systemic medications are also being investigated.

Surgery

Main article: Glaucoma surgery

Both laser and conventional surgeries are performed to treat glaucoma. Laser trabeculoplasty may be used to treat open angle glaucoma. A 50 um argon laser spot is aimed at the trabecular meshwork to stimulate opening of the mesh to allow more outflow of aqueous fluid. Usually, half of the angle is treated at a time. Laser peripheral iridectomy may be used in patients susceptible to angle closure glaucoma. In it, the laser is aimed at the iris to make an opening in it. This allows a new channel for fluid to flow when the usual channel through the dilated pupil is blocked.

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 made under the flap to remove a portion of the trabecular meshwork. The scleral flap is then sutured loosely back in place. This allows fluid to flow out of the eye through this opening, resulting in lowered intraocular pressure. Scarring can occur around or over the flap opening, causing it to become less effective or lose effectiveness altogether. One person can have multiple surgical procedures of the same or different type.

There are also several different glaucoma drainage implants, which may be the old design non-valved tubes, like Molteno implant or the Baerveldt tube shunt, or or the newer valved implant, like the Ahmed glaucoma valve implant. 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 flow of aqueous fluid out of the eye. Molteno and other non-valved implants require ligating the tube till the surgical wound is mildly fibrosed and water-tight. This induced potentially dangerous spikes in the intraocular pressure (IOP). Ahmed glaucoma valve on the other hand does not have such a limitation and avoids spikes in IOP. 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 anti-fibrotic medication like 5-fluorouracil (5-FU) or mitomycin-C (during the procedure), or creating a necessity for additional surgery.

Surgery is the primary therapy for those with congenital glaucoma.

Generally, these surgeries are a temporary solution, as there is not yet a cure for glaucoma.

Major studies

• Advanced Glaucoma Intervention Study (AGIS) - large American National Eye Institute (NEI) sponsored study designed "to assess the long-range outcomes of sequences of interventions involving trabeculectomy and argon laser trabeculoplasty in eyes that have failed initial medical treatment for glaucoma." It recommends different treatments based on race.
• Early Manifest Glaucoma Trial (EMGT) -Another NEI study found that immediately treating people who have early stage glaucoma can delay progression of the disease.
• Ocular Hypertension Treatment Study (OHTS) -NEI study findings: "...Topical ocular hypotensive medication was effective in delaying or preventing onset of Primary Open Angle Glaucoma (POAG) in individuals with elevated Intraocular Pressure (IOP). Although this does not imply that all patients with borderline or elevated IOP should receive medication, clinicians should consider initiating treatment for individuals with ocular hypertension who are at moderate or high risk for developing POAG."
• Blue Mountains Eye Study "The Blue Mountains Eye Study was the first large population-based assessment of visual impairment and common eye diseases of a representative older Australian community sample." Risk factors for glaucoma and other eye disease were determined.

Classification of glaucoma

Glaucoma has been classfied into specific types:

• Primary glaucoma

• Primary open-angle glaucoma, also known as chronic open-angle glaucoma, chronic simple glaucoma, glaucoma simplex
• Low-tension glaucoma
• Primary closed-angle glaucoma, also known as primary angle-closure glaucoma, narrow-angle glaucoma, iris-block glaucoma, acute congestive glaucoma

• Acute angle-closure glaucoma
• Chronic angle-closure glaucoma
• Intermittent angle-closure glaucoma
• Superimposed on chronic open-angle closure glaucoma (combined mechanism)

• Variants of primary glaucoma

• Pigmentary glaucoma
• Exfoliation glaucoma, also known as pseudoexfoliative glaucoma or glaucoma capsulare

• Developmental glaucoma

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

• Secondary glaucoma

• 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
• 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 deatchments
• Secondary to severe chemical burns of the eye
• Associated with essential iris atrophy

• Absolute glaucoma

See also

• List of eye diseases and disorders
• Ocular hypertension
• Glaucoma valves
• Mansour F. Armaly
• Laszlo Z. Bito
• Charles D. Phelps
• American Glaucoma Society

External links

• Global Association of International Glaucoma Societies - featuring a hymn about the successful treatment of glaucoma
• Overview from the US National Eye Institute
• Glaucoma Research Foundation
• Nonprofit Foundation for Glaucoma
• National Glaucoma Research
• DJO | Digital Journal of Ophthalmology