Glaucoma

Some people with ocular hypertension never develop glaucoma, and there are people who develop glaucoma without elevated IOP, known as normal-tension glaucoma.

Ophthalmoscopic examination reveals a deepening of the optic cup and associated increase in cup-to-disk ratio.

Excessive collateral vessel formation may also be seen.

Drance hemorrhages are not specific to glaucoma, although their presence can be an indication of glaucomatous progression.

Drance hemorrhage differential diagnoses include vitreous detachments, diabetic or hypertensive retinopathies.

Progression of optic nerve damage due to glaucoma is thought to have probably occurred, in the absence of other processes and subsequent visual field defects will likely be present in the future.

Severe glaucoma can cause progressive visual field defects.

Treatment of POAG begins with prostaglandin analogues.

Topical β-blockers, α2 agonists, and carbonic anhydrase inhibitors are also all treatment mainstays.

Lasers also may be employed as first-line therapy.

In cases that are refractory to medication or lasers, surgical treatment may be employed.

Glaucomatous optic nerve damage in patients with an IOP of less than 21 mm Hg is referred to as normal-tension glaucoma or low-tension glaucoma.

Average range of pressures is 21-21 mm Hg

Normal tension glaucoma is associated with abnormal vasoregulation and conditions such as migraines Raynaud disease, systemic hypotension and nocturnal dips in blood pressure.

With systemic hypotension, the ocular perfusion pressure is low, making it more difficult to nourish the optic nerve.

Low CSF pressures relative to IOP are also implicated in the pathogenesis of normotensive glaucoma, since the relatively high IOP pressure can cause significant mechanical stress against the optic nerve head.

Normal tension glaucoma treatment follows the same principles as treatment of POAG.

Decrease of the relatively normal IOP in these patients has been shown to prevent progression of the disease.

Primary angle-closure glaucoma (PACG) is defined by a characteristic obstruction of the anterior chamber angle.

The peripheral iris becomes closely apposed to the cornea, preventing aqueous humor from exiting through the trabecular meshwork.

Accounts for one-third of glaucoma patients worldwide, it is responsible for half of all glaucoma-related blindness.

Primary angle closure glaucoma is the predominant form of glaucoma in those of East Asian and Inuit descent.

Open angle glaucoma, a chronic and painless condition, also can be caused when the posterior portion of the iris, surrounding the pupil, adheres to the anterior surface of the lens and prevents intraocular fluid from passing through the pupil into the anterior chamber.

In primary open angle glaucoma the iridocorneal angle appears anatomically open and is morphologically normal on clinical examination.

The 2 primary mechanisms for the closure of the angle are pupillary block and nonpupillary block.

Pupillary block occurs when increased pressures in the posterior chamber displace the lens forward into the iris, blocking the flow of aqueous humor through the pupil into the anterior chamber.

This causes further pressure in the posterior chamber, causing the iris to bow forward, further closing off the anterior chamber angle.

Nonpupillary block PACG is due to anatomic variations having greater thickness in the periphery of the iris.

Nonpupillary block PACG majority experience a slow, progressive disease process similar to POAG, 25% will experience an attack of acute angle-closure glaucoma (AACG) which constitutes an ocular emergency.

Acute angle-closure glaucoma patients present with ocular pain, headache, nausea, vomiting, and blurred vision.

IOP in these attacks can be extremely high, typically ranging from 40 to 90 mm Hg.

Treatment for acute angle closure glaucoma includes topical cholinergic agents such as pilocarpine, causing pupillary constriction and draw the iris away from the angle.

Topical IOP-lowering agents such as β-blockers and systemic carbonic anhydrase inhibitors or hyperosmotic agents act rapidly to lower IOP.

Laser peripheral iridotomy is performed to manage chronic primary angle closed glaucoma and to prevent future acute angle closed glaucoma events.

During the Iridotomy procedure, the iris is perforated with a laser, allowing an alternative route of aqueous flow.

Topical pilocarpine is prescribed in an acute angle closure attack to decrease IOP and prepare the eye for laser iridotomy.

33% of acute attacks are triggered by other medications.

Topical prostaglandin analogues are widely considered first-line primary open angle treatment,as they lower IOP by enhancing uveoscleral outflow of the aqueous humor and providing an alternative path from the obstructed trabecular meshwork.

Prostaglandin analogues include latanoprost, travoprost, bimatoprost, and tafluprost.

Prostaglandin analogue local adverse effects include: thickening and lengthening of the eyelashes and conjunctival hyperemia, permanent darkening of the iris and periorbital fat loss.

Systemic symptoms from prostaglandin analogues are rare, have been known to trigger migraines and even precipitate mild upper respiratory tract symptoms.

Topical β-blockers timolol, betaxolol, and levobunolol, lower IOP by decreasing the production of aqueous humor by the ciliary body.

β-blockers can have systemic effects including: bradycardia, heart block, and hypotension, and bronchospasm, sleep disorders, reduced exercise tolerance, decreased libido, erectile dysfunction, confusion, depression, and dyslipidemia.

Systemically administered β-blockers also lower IOP, and may also mask the potential for an individual to develop glaucoma.

Changing dosage or discontinuing β-blocker may cause significant increases in IOP.

Topical α2 agonists act on the ciliary body to reduce aqueous humor production as well as promote uveoscleral aqueous outflow.

Brimonidine and apraclonidine are examples of topical α2 agonists in this class.

Topical α2 agonists may worsening of vascular insufficiency is a possible adverse effect of these medications.

Moreover, α2 agonists are capable of crossing the blood-brain barrier and causing central nervous system depression and hypotension.

These ophthalmic eye drops are contraindicated in patients younger than 2 years.

Topical carbonic anhydrase inhibitors decrease the production of aqueous humor.

The formation of bicarbonate is key to the ciliary body in establishing an osmotic gradient to pull fluid into the eye.

Dorzolamide and brinzolamide are among the agents in this class.

Systemic carbonic anhydrase inhibitors are employed to decrease IOP spikes in an acute setting and include Acetazolamide and methazolamide.

Carbonic anhydrases are relative contraindicated in patients with a sulfa allergy.

Osmotic agents are used only in emergency departments and operating rooms, and include mannitol and isosorbide, which can be employed in a similar fashion to systemic carbonic anhydrase inhibitors and work by drawing fluid out of the eye and lowering acutely elevated IOPs.

Miotics are used to treat both POAG and AACG and act by causing pupillary constriction, thinning the peripheral iris, and opening the anterior chamber angle.

Systemic adverse effects of miotics. are rare but may include confusion, bradycardia, bronchospasm, and urinary frequency.

Pilocarpine is the most commonly used miotic.

Miotic adverse effects include decreased night vision and increased risk of cataract formation. In addition,

Miotics must be used at least 3 times a day for therapeutic effect.

Anticholinergic medications, including ipratropium used in COPD and tolterodine used in overactive bladder. systemically are contraindicated in patients with some forms of glaucoma, primarily untreated narrow-angle glaucoma.

Anticholinergics cause pupillary dilation.

Pupillary dilation can close off the anterior chamber angle in patients with structurally narrow angles.

Dilating pupils does not have any significant negative impact on POAG.

Anticholinergic medications are contraindicated in patients with acute angle closure glaucoma.

Anticholinergic medication use is safe to use in patients who have been treated with laser iridotomy.

Drugs that possess potent anticholinergic effects include: Tricyclic antidepressants, selective serotonin-reuptake inhibitors, MAOIs, antipsychotics, and antihistamines, and their use in the case of AACG should also be carefully weighed.

Sympathomimetics, also cause pupillary dilation and can exacerbate acute angle closure glaucoma.

Epinephrine and ephedrine, also have adrenergic effects in the eye.

Up to 70% of children of patients with POAG are steroid responders, and the use of corticosteroids is associated with increased IOP in such patients.

Increasing IOP can occur with systemic exposure of steroids, but is more significant in those exposed to steroids administered as eye drops or nasal sprays.

Topical steroid creams can cause an increase in IOP in susceptible patients.

Steroid use in patients susceptible to POAG. should be closely monitored.

Characteristic appearance of the optic nerve cupping is due to the loss of retinal nerve fiber layer tissue.

Associated with an increased cup-to-disc ratio.

Optic disc cupping determined by ophthalmologic exam, disc photographs or through interpretation of special diagnostic tests measuring retinal nerve fiber layer thickness.

Risk factors are: high myopia, family history, black race, and advanced age.

There is a higher incidence of glaucoma-related visual impairment in individuals of African discent compared with those of European discent.

Some patients have normal intraocular pressure, normal tension glaucoma.

Can have elevated intraocular pressure and not develop glaucoma.

Normally, fluid enters the eye by seeping out of the blood vessels in the ciliary body.

This fluid eventually makes its way past the crystalline lens, through the pupil, and into the irido-corneal angle, the anatomical angle formed where the iris and the cornea come together.

Then the fluid passes through the trabecular meshwork in the angle and leaves the eye, via the canal of Schlemm.

If the rate of aqueous fluid is entering the eye is too great, or if the trabecular meshwork drainage is impaired the pressure builds up in what is known as open angle glaucoma.

Open angle glaucoma increases with age.

Can remain asymptomatic until the process is severe, so that there is a high likelihood that the number of affected individuals is much higher than the number known to have the disease.

Only 10-50% of patients have are aware of the diagnosis.

As many as 50% of patients with undiagnosed glaucoma have severe disease on presentation.

Primary open angle glaucoma is the predominant form.

In the US. 80% of cases are open angle glaucoma, but angle closure disease is responsible for a disproportionate number of individuals with severe vision loss.

Primary open angle glaucoma affects approximately 2.2 million individuals in the US.

Primary open angle glaucoma represents the largest pool of preventable blindness in North America.

Both open and closed angle can be primary.

Secondary glaucoma can result from corticosteroids, trauma, inflammation, tumors, pigment dispersion disorders or pseudo-exfoliation

It is estimated that 50% of patients with glaucoma have undiagnosed disease.

The risk of primary angle glaucoma is highest when examination reveals an increase cup-disk ratio, cup-disk ratio asymmetry, disc hemorrhage, or elevated intraocular pressure.

Primary open a new glaucoma is more likely when there is a family history, black race, or advanced age.

Increased risk of developing glaucoma occurs in patients being treated with topical or systemic corticosteroids.

Primary glaucoma without elevated intraocular pressure is known as normal tension glaucoma and is characterized by a glaucomatous optic disc and visual field changes but the intraocular pressure is never greater than 21 mmHg.

The level of intraocular pressure in primary open angle glaucoma is related to the retinal ganglion cell death.

The balance that occurs between the secretion of aqueous humor by the ciliary body and it’s drainage through the trabecular meshwork and uveoscleral output pathway determines the intraocular pressure.

With open angle glaucoma there is increased resistance to aqueous outflow through the trabecula meshwork while the axis to drainage pathways is obstructed, typically by the iris , in patients with angle closure glaucoma.

Intraocular pressure causes mechanical stress and strain on the posterior structures of the eye, particularly the lamina cribosa and adjacent tissues.

The lamina is the weakest point of the wall in the pressured eye and is where the optic nerve fibers exit the eye, and the sclera perforates at that site.

Intraocular pressure induced stress and strain may result in compression and deformity, and remodeling of the lamina cribosa with axonal damage and disruption of axonal transport interrupting delivery of trophic factors to retinal ganglion cells.

Lowering intraocular pressure, even in patients with normal tension glaucoma, slows the disease process.

If the angle between and iris and the cornea is too narrow, or is even closed, then the fluid backs up because it cannot flow out of the eye properly and causes an increased intraocular pressure in what is known as closed angle glaucoma.

In closed angle glaucoma, typically, there is a sudden painful onset.

Closed angle glaucoma can be accompanied by rainbow-colored rings around white lights.

Increased internal pressure can deform the lamina cribrosa, the small cartilaginous section of the sclera at the back of the eye through which the optic nerve passes.

A deformed lamina cribrosa can constrict the nerve fibers passing though it, eventually causing axon death.

Untreated glaucoma eventually leads to optic atrophy and blindness.

Eye pressure is measured by using a tonometer.

The normal range of intraocular pressure (IOP) is 10 mm Hg to 21 mm Hg, with an average of about 16 mm Hg.

Eyes with intraocular tonometry pressure measurements of 21 mm Hg or higher are suspect for glaucoma.

The amount of pressure which will cause glaucoma varies from eye to eye and person to person.

Patients with glaucoma may have normal range normal pressure glaucoma), possibly indicating that their lamina cribrosas are too weak to withstand even normal amounts of pressure.

Many people with high intraocular pressure have no evidence of glaucomatous damage.

Glaucomatous changes in the optic nerve head usually can be detected over time.

Glaucomatous optic nerve changes on direct ophthalmoscopy includes large cup-to disc ratio or hemorrhage at the optic disc.

The risk of inducing an angle closure glaucoma with pharmacological manipulation is 1 in 3800 to 1 in 20,000.

Using a slitlamp ophthalmoscopy or stereoscopic photographs one can better evaluate three dimensional architecture and more accurately assesses the cup-to-disk ratio.

If the optic cup increases in size over a period of months or years, or if notching is observed around the nerve head rim, and/or if an asymmetry is observed between the optic cups of the two eyes, then glaucoma may be expected.

Optic nerve damage visual field loss is measured by perimetry and compared over time.

Field loss due to glaucoma usually not measurable until 25% to 40% of the optic nerve’s axons have been destroyed.

The first optic nerve fibers damaged are the larger fibers, which primarily carry form and motion information and are this type of impairment is detected by pattern discrimination perimetry.

Smaller optic fibers, which primarily detect light, are damaged later and is best detected by conventional perimetry.

Therefore discrimination peripheral perimetry seems to be more sensitive than a standard perimeter in detecting early glaucomatous visual field losses.

As many as 40% of axons can be lost before standard visual tests indicate the presence of an abnormal result.

Testing for optic nerve cupping is determined by ophthalmologic examination, reviewing stereo photographs, or the interpretation of specialized tests that measures the retinal nerve fiber layer thickness.

Early glaucoma usually affects peripheral vision and is asymptomatic, ,as central vision is relatively spared until later stages of the process.

Usually, the elevated pressure in open angle glaucoma can be controlled using glaucoma medications, which either decrease the production of aqueous fluid or else increase its outflow from the eye.

Closed angle glaucoma often requires surgical intervention to be controlled.

Early stages is mostly asymptomatic and requires specialized testing to diagnosis.

Visual field loss affecting the peripheral vision in early stages and progresses to involve the central field much later in the disease process.

Physical signs of the disease include cupping of the optic nerve.

Currently no cure and lowering the intraocular pressure is the primary treatment.

Progression of primary open angle glaucoma can be slowed with treatment.

Vision loss is asymptomatic and irreversible.

Characterized by progressive damage of optic that usually begins with a subtle loss of peripheral vision that can progress, if untreated, to loss of central vision and blindness.

Elevated intraocular pressure leads to optic nerve damage, in some cases.

Normal pressure glaucoma is related to poor regulation of blood flow to the optic nerve.

Leading cause of irreversible blindness worldwide.

6 million people in the US have bilateral blindness from this process.

As many as half the individuals with the disease do not know they are afflicted, due to the asymptomatic nature of the process and subtle loss of peripheral vision.

Pressure in the eye maintains its shape and tone and intraocular pressure ranges from 8-22 mm Hg.

With elevated intraocular pressure the delicate fibers in the optic nerve are damaged.

Open-angle type-impaired aqueous outflow results from dysfunction of the drainage system.

Open-angle type-progressive optic neuropathy with acquired loss of retinal ganglion cells and atrophy of the optic nerve.

Degeneration of axons of the retinal ganglion cells of the optic nerve is a hallmark of glaucoma.

Open-angle type-accounts for more than 90% of cases of glaucoma in the U.S.

Angle closure type-impaired aqueous outflow results from occlusion of the anterior chamber angle itself, impairing access of the aqueous to the drainage system.

Adequate intraocular pressure control can markedly reduce glaucomatous progression in normal tension glaucoma and virtually halt it in primary-open-angle glaucoma.

Despite treatment approximately 10% of patients will exhibit progressive visual field loss.

Patients with advanced damage to the neural rim and parapapillary tissue are more likely to progress.

Patients with more advanced damage need to be maintained at lower intraocular pressure levels to decrease or halt progression of disease.

Optic nerve damage generally precedes visual field loss.

Therapy is based on reduction of intraocular pressure with topical medications, laser surgical procedure and intraocular surgery.

Cataract surgery has been demonstrated to lower intraocular pressure (IOP) in eyes with glaucoma.

In angle-closure patients that cataract surgery improves IOP and dramatically reduces the future risk for IOP spikes and acute attacks.

Randomized controlled trials (RCTs) have shown that cataract surgery may be preferable to laser iridotomy or phacotrabeculectomy.

Clear lens extraction may be appropriate following acute attacks and in cases of uncontrolled IOP in angle closure glaucoma.

The case favoring cataract surgery in open-angle glaucoma (OAG) is more controversial.

Latanoprost a prostaglandin analog is commonly prescribed treatment and can reduce risk of vision loss in people with open angle glaucoma.