Continually Updated Clinical Reference
 
 
  All Sources     eMedicine     Medscape     Drug Reference     MEDLINE
 
eMedicine - Glaucoma, Pseudoexfoliation : Article by

Quick Find
Authors & Editors
Introduction
Clinical
Differentials
Workup
Treatment
Medication
Follow-up
Miscellaneous
Acknowledgments
Multimedia
References

Related Articles
Glaucoma, Pigmentary

Glaucoma, Primary Open Angle

Uveitis, Fuchs Heterochromic




Patient Education
Glaucoma Center

Glaucoma Overview

Glaucoma Causes

Glaucoma Symptoms

Glaucoma Treatment

Understanding Glaucoma Medications

Glaucoma FAQs




Author: Mauricio E Pons, MD, Associate Physician, Charles A Garcia, MD, PA

Mauricio E Pons is a member of the following medical societies: American Academy of Ophthalmology and Association for Research in Vision and Ophthalmology

Coauthor(s): Babak Eliassi-Rad, MD, Assistant Professor, Department of Ophthalmology, Boston University School of Medicine

Editors: Bradford Shingleton, MD, Assistant Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary; Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles; Martin B Wax, MD, Clinical Professor, Department of Ophthalmology, University of Texas Southwestern Medical School; Vice President, Ophthalmology Research and Development, Head, Ophthalmology Discovery Research, Alcon Labs, Inc; Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri; Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Author and Editor Disclosure

Synonyms and related keywords: exfoliation glaucoma, pseudoexfoliation glaucoma, capsular glaucoma, glaucoma capsulare, exfoliative glaucoma, pseudoexfoliative glaucoma, pseudoexfoliation syndrome, fibrillopathia epitheliocapsularis, FEC, epithelio-capsular fibrillopathy



Background

In 1917, a Finnish ophthalmologist named Lindberg first described pseudoexfoliation syndrome. This entity is characterized by flakes of granular material at the pupillary margin of the iris and throughout the inner surface of the anterior chamber. It is also associated with secondary open-angle glaucoma, known as pseudoexfoliation glaucoma, which is the most common identifiable form of secondary open-angle glaucoma worldwide. Dvorak-Thebold suggested the term pseudoexfoliation to differentiate it from true exfoliation or lamellar delamination of the lens capsule found in glassblowers. True exfoliation syndrome is due to heat or infrared-related changes in the anterior lens capsule.

Pathophysiology

Pseudoexfoliation syndrome is a common ocular manifestation of a systemic disease, known to cause disease primarily in the eye. Exact etiology of this condition remains unknown.

Pseudoexfoliation material is associated with abnormalities of the basement membrane in epithelial cells and has a wide distribution throughout the body. Pseudoexfoliative material has been found in the walls of the vortex veins and the central retinal artery. Extraocular tissues involved include lung, skin, liver, heart, kidney, gallbladder, blood vessels, extraocular muscle, connective tissue in the orbit, and meninges. In the anterior segment of the eye, it is characterized by deposition of pseudoexfoliative amyloidlike material on the anterior lens capsule, ciliary body, zonules, pupillary margin of the iris, corneal endothelium, anterior vitreous, and trabecular meshwork.

Some investigators believe that the iris pigment epithelium, the ciliary epithelium, and the peripheral anterior lens epithelium produce this pseudoexfoliative amyloidlike material, which moves into the aqueous humor and is carried to the trabecular meshwork, following the normal flow. Obstruction of the trabecular meshwork by this fibrillar material and pigment associated with degenerative changes in the Schlemm canal and the juxtacanalicular area causes elevation of the intraocular pressure (IOP) with associated glaucoma.

Zenkel et al have studied genes differentially expressed in anterior segment tissues and have postulated that pseudoexfoliation syndrome is a stress-induced elastic microfibrillopathy.1

Frequency

United States

Roth and Epstein reported that pseudoexfoliation glaucoma was present in 12% of patients with glaucoma.2 Kozart and Yanoff reported that glaucoma was present in 7% of 100 consecutive patients with pseudoexfoliation syndrome in Philadelphia.3 In the Framingham study, prevalence of pseudoexfoliation syndrome was 1.8%. In a prospective study, Cashwell and Shields found that the prevalence of pseudoexfoliation syndrome in the southeastern United States was 1.6% of the total population and in 6% of an open-angle glaucoma subpopulation.4 Prevalence of pseudoexfoliation syndrome in the glaucoma population of south Louisiana was found to be 2.7% in white patients and 0.4% in African American patients. Karger et al determined that the incidence of newly diagnosed pseudoexfoliation syndrome in residents of Olmsted County, Minnesota, was 25.9 cases per 100,000 population.5

Because of the increased mean age of populations, pseudoexfoliation syndrome may become more prevalent in the future.

International

Prevalence of pseudoexfoliation syndrome in Europe was found to be 4.7% in England, 6.3% in Norway, 4% in Germany, 1.1% in Greece, and 5.5% in France.

Bartholomew reported an 8.2% prevalence of pseudoexfoliation syndrome in the Bantu tribes of South Africa.6 In Asia, the prevalence in a Japanese population was 3.4%. Hospital-based studies showed a prevalence of 6.45% in Pakistan and 7.4% in India. A prevalence rate of 0.4% in patients aged 60 years or older was identified in China.

Mortality/Morbidity

In a retrospective study, Shrum et al found no association between ocular pseudoexfoliation and cardiovascular or cerebrovascular mortality.7 However, other authors have found that pseudoexfoliation is linked with Alzheimer disease, senile dementia, cerebral atrophy, chronic cerebral ischemia, stroke, transient ischemic attacks, heart disease, and hearing loss. Vessani et al found that homocysteine levels were higher among patients with pseudoexfoliation syndrome and pseudoexfoliative glaucoma compared with controls.8 Roedl et al reported increased homocysteine concentrations in tear fluid and plasma of patients with pseudoexfoliation glaucoma.9 Elevated plasma homocysteine levels have been described as a risk factor for cardiovascular disease.

Race

Although it occurs in virtually every area of the world, a considerable racial variation exists in the incidence of pseudoexfoliation glaucoma.

  • In Scandinavian countries, more than 50% of cases of open-angle glaucoma are caused by pseudoexfoliation syndrome.
  • Pseudoexfoliation syndrome is relatively rare among African Americans and Eskimos. It was not observed at all in the Inuit who live throughout the Canadian Arctic.
  • Prevalence is high in the Sami people who are indigenous of northern Europe.
  • Among the Bantu tribes of South Africa, exfoliation was found in 19% of patients in a glaucoma clinic.
  • In Saudi Arabia, Summanen and Tonjum reported a prevalence of pseudoexfoliation syndrome of 13%.10
  • Prevalence of pseudoexfoliation syndrome in Spanish Americans in New Mexico was estimated to be 3-6%.

Sex

Pseudoexfoliation syndrome is more common in females than in males. In a series by Kozart and Yanoff, pseudoexfoliation syndrome was 3 times more common in women than in men.3

Age

Pseudoexfoliation syndrome is rarely seen before age 50 years, and its incidence increases steadily with age.

  • In Norway, Aasved reported that the prevalence of pseudoexfoliation was 0.4% in individuals aged 50-59 years and 7.9% in individuals aged 80-89 years.11 The reported mean age of pseudoexfoliation syndrome ranges from 69-75 years.
  • Jonasson et al reported a 10% annual increase for both open-angle glaucoma and pseudoexfoliation in persons aged 50 years and older in Iceland.12



History

Patient may be asymptomatic, or they may complain of decreased visual acuity secondary to cataract or glaucomatous visual field changes.

Physical

  • Pseudoexfoliation syndrome is diagnosed clinically by slit lamp examination with an 85% sensitivity rate and a 100% specificity rate.  
    • Pseudoexfoliative material can be seen on the pupillary border of the iris without dilation.
    • The most commonly recognized feature is the 3-ring sign on the anterior lens capsule, formed by a central disk, a peripheral ring, and a clear zone, which separates the two. The clear zone varies in diameter and may exhibit curled edges.
    • The central disc measures 1-2.5 mm in diameter and has well-demarcated borders.
    • The peripheral ring typically is seen after pupillary dilation. Its size is variable, and its inner border has many radial striations.
    • The translucent zone most likely is created by the physiologic rubbing of the posterior surface of the iris against the lens. It scrapes the pseudoexfoliative material from the surface of the lens. This scraping results in a secondary pigmentary dispersion syndrome, with a loss of melanin from the iris pigment epithelium at the pupillary margin and an accumulation of melanin granules in the trabecular meshwork. Peripupillary iris atrophy is a common finding.
    • Gonioscopy shows a discontinuous pigmentation of the trabecular meshwork, usually less dense than seen in pigmentary glaucoma. Also, pigment characteristically is deposited on the Schwalbe line or anterior to the Schwalbe line (the Sampaolesi line). A high incidence of narrow, or occludable, angles in eyes with pseudoexfoliation has been reported.
    • Elevated IOP leads to glaucoma development in about 50% of patients. Puska et al reported that the conversion rate from pseudoexfoliation syndrome to pseudoexfoliation glaucoma was 3.2% per year.13 Jeng et al found that, in patients with pseudoexfoliation, the probability of developing glaucoma was 44% after 15 years, and, in a study by Grodum et al, 55.1% of patients developed glaucoma after a mean of 8.7 years.14, 15
    • When glaucoma develops, it is frequently referred to as capsular glaucoma. Patients with pseudoexfoliation syndrome have higher IOP than patients with primary open-angle glaucoma. Because of these higher IOPs, visual field loss and optic nerve damage are more pronounced.
    • Other signs of pseudoexfoliation syndrome are insufficient mydriasis, posterior synechiae, pigment deposition on the iris surface, deposition of pigment and pseudoexfoliation material on the corneal endothelium, pigment liberation after pupillary dilation, and pseudoexfoliation material covering the ciliary processes and the zonules. Phacodonesis, lens subluxation, and corneal endothelial decompensation can be present. An associated nuclear cataract is a common finding.
    • Pseudoexfoliation syndrome typically presents unilaterally. Why this occurs remains unknown. The fellow eye develops signs of pseudoexfoliation in more than 40% of cases, but pseudoexfoliation material can almost always be demonstrated in fellow eyes on electron microscopy.
    • Pseudoexfoliation syndrome is associated with reduced ocular blood flow, iris hypoperfusion, and anterior chamber hypoxia.

Causes

  • Whether pseudoexfoliation syndrome occurs as part of a genetic process or in association with other diseases is not clear. Familial aggregation supports the notion that it may be inherited as an autosomal dominant trait with incomplete penetrance and late onset.
  • Its frequency increases with age; however, it is not part of normal aging. Possible predisposing factors include ultraviolet light, northern latitudes, and altitude. Climate factors may not play a definitive role in the pathogenesis of the disease.
  • The exact nature of pseudoexfoliation material remains unknown, although its close association with zonular fibers supports the idea of pseudoexfoliation syndrome as a type of elastosis, affecting elastic microfibrils. It seems to arise from abnormal aggregation of elastin microfibrillar components.
  • In a recent study, Thorleifsson et al showed that two nonsynonymous single-nucleotide polymorphisms in exon 1 of the LOXL1 gene on chromosome 15q24.1 confer risk for pseudoexfoliation glaucoma.16 According to the authors, the product of the LOXL1 gene modifies elastin fibers that are a major constituent of the intraocular lesions in pseudoexfoliation glaucoma.16 Approximately 25% of the general population is positive for these variants.
  • Glaucoma is a secondary event. Blockage of the trabecular spaces by pseudoexfoliation material promotes accumulation of pigment and cellular debris, which causes obstruction of the aqueous channels and limits access to the Schlemm canal. Accumulation of pseudoexfoliation material in the juxtacanicular tissue adjacent to the Schlemm canal leads to narrowing of the canal lumen, collapse of its walls, disruption of its endothelium, and partial obliteration. These changes appear to be the causative factors for chronic IOP elevation and pseudoexfoliation glaucoma.
  • Zonular laxity allows forward movement of the lens, causing decreased anterior chamber depth and pupillary or angle closure glaucoma.
  • Pseudoexfoliation syndrome itself does not produce optic nerve damage.



Glaucoma, Pigmentary
Glaucoma, Primary Open Angle
Uveitis, Fuchs Heterochromic

Other Problems to be Considered

True exfoliation syndrome
Primary familial amyloidosis



Imaging Studies

  • Various imaging technologies are being used to document and monitor changes due to glaucomatous damage in the optic disc and the retinal nerve fiber layer.
  • Optical coherence tomography (OCT) is a valuable tool in the evaluation of glaucoma. OCT provides a cross-sectional view of the scanned retinal area that allows differentiation between the retinal layers. The thickness of the retinal nerve fiber layer can be measured using this technique.
  • The confocal scanning laser ophthalmoscope (Heidelberg retina tomograph [HRT]) provides topographical measures of the optic disc as well as indirect measurements of the retinal nerve fiber layer thickness.
  • OCT and HRT have been used to help in the diagnosis and follow-up of patients with glaucoma. Both OCT and HRT have shown a high correlation between the retinal nerve fiber layer thickness and the visual field mean defect during achromatic perimetry.
  • The GDx Nerve Fiber Analyzer has been reported to be a valuable tool in helping the clinician to discriminate between healthy eyes and glaucomatous eyes.

Other Tests

  • Gonioscopy and visual field testing

Histologic Findings

Gottanka et al found marked differences in the optic nerve between primary open-angle glaucoma and pseudoexfoliation glaucoma.17 Eyes with primary open-angle glaucoma were found to have axon loss associated with more connective tissue in the septa and surrounding the central retinal vessels and a decrease in the density of capillaries as compared with eyes with pseudoexfoliation glaucoma where the capillary density did not change with axon loss.



Medical Care

  • Patients with pseudoexfoliation syndrome should have annual eye examinations for early detection of glaucoma. Glaucoma in pseudoexfoliation is more resistant to medical therapy and has a poorer prognosis than primary open-angle glaucoma.
  • The treatment of pseudoexfoliation glaucoma is the same as that of primary open-angle glaucoma; however, topical medications tend to be less effective. Miotics lower IOP, but they aggravate the blood-aqueous barrier dysfunction and decrease iris mobility, thereby increasing the risk of posterior synechiae and cataract formation.
  • Argon laser trabeculoplasty is frequently used with excellent initial success. Its hypotensive effect may be facilitated by enhanced heat absorption because of increased trabecular pigmentation.
  • According to a published study, selective laser trabeculoplasty (SLT) has been shown to be equivalent to argon laser trabeculoplasty in terms of lowering IOP at 1 year. The theoretical advantage of SLT is that SLT is a repeatable procedure because it does not seem to produce thermal damage to the trabecular meshwork.

Surgical Care

  • If medical therapy and laser therapy are unsuccessful to control the glaucoma, trabeculectomy can be performed with similar success rates to that of primary open-angle glaucoma. Because patients with pseudoexfoliation glaucoma have higher IOP, they tend to undergo glaucoma filtering surgery more frequently than patients with primary open-angle glaucoma.
  • Cataracts occur more commonly in patients with pseudoexfoliation syndrome. Weakness of the zonular fibers, spontaneous lens subluxation, and phacodonesis also can be present. Therefore, in these patients, cataract surgery alone or combined cataract surgery and glaucoma filtering surgery in the presence of pseudoexfoliation is associated with a higher incidence of intraoperative complications, most notably zonular dialysis, vitreous loss, and lens dislocation.
  • The increased intraoperative posterior capsule complication rate appears to correlate with the level of cataract maturity. Modern surgical techniques involving the use of capsulorrhexis, small-incision surgery, and better viscoelastics have improved the surgical outcome. Capsular tension rings have been used to decrease surgical stress on the zonules.
  • Postoperative cataract surgery complications can occur after uneventful operations due to continued destabilization of the zonules and capsular contraction.
  • Jacobi et al described a nonfiltering surgical technique consisting of trabecular aspiration with or without cataract removal with encouraging results.18 The operation attempts to increase the outflow facility along the trabecular meshwork by removing pretrabecular and trabecular debris using an externally applied suction device.

Diet

The use of supplements with vitamin B-12 and folic acid to decrease hyperhomocysteinemia in patients at risk has been suggested. A randomized clinical trial is needed to prove its benefit.



Medical therapy is aimed at lowering IOP.

Drug Category: Beta-adrenergic receptor blocking agents

Topical beta-blockers that reduce elevated and normal IOP, with or without glaucoma.

Drug NameTimolol (Timoptic, Betimol, Istalol)
DescriptionFirst-line treatment. Precise mechanism by which timolol decreases IOP is not well established, although believed to be through reduction of aqueous formation.
Adult Dose1 gtt of 0.25% or 0.5% in affected eye qd or bid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; bronchial asthma or history of bronchial asthma; chronic obstructive pulmonary disease; sinus bradycardia; second- or third-degree atrioventricular block; overt cardiac failure; cardiogenic shock
InteractionsOccasionally, mydriasis results from concomitant therapy with epinephrine; potential additive effects on patients receiving oral beta-adrenergic blocking agents; possible atrioventricular conduction disturbances, left ventricular failure, and hypotension with concomitant use of calcium antagonists; avoid coadministration in patients with impaired cardiac function; possible additive effects, hypotension and marked bradycardia, vertigo, syncope, or postural hypotension with concomitant use of catecholamine-depleting drugs
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in patients with cerebrovascular insufficiency; in myasthenic syndromes, may potentiate muscle weakness; patients with an anaphylactic reaction may be unresponsive to usual dose of epinephrine

Drug NameBetaxolol (Betoptic)
DescriptionCardioselective beta1-adrenergic receptor blocking agent with minimal effect on pulmonary and cardiovascular parameters. Precise mechanism by which betaxolol decreases IOP is believed to be through reduction of aqueous formation.
Adult Dose1 gtt of 0.25% in affected eye(s) bid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; sinus bradycardia greater than first degree; atrioventricular block; cardiogenic shock; overt cardiac failure
InteractionsPotential additive effects on patients receiving oral beta-adrenergic blocking agents; possible additive effects, hypotension, and marked bradycardia with concomitant use of catecholamine-depleting drugs; caution in patients using adrenergic-psychotropic drugs concomitantly
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsMay be absorbed systemically; death due to bronchospasm in patients with asthma and death in association with cardiac failure have been reported; may mask signs and symptoms of acute hypoglycemia and certain clinical signs of hyperthyroidism; abrupt withdrawal might precipitate a thyroid storm in patients suspected of developing thyrotoxicosis; in myasthenic syndromes, may potentiate muscle weakness; may need to be withdrawn gradually prior to general anesthesia because of reduced ability of the heart to respond to sympathetic reflex stimuli; patients with an anaphylactic reaction may be unresponsive to usual dose of epinephrine

Drug NameCarteolol hydrochloride (Cartrol, Ocupress)
DescriptionNonselective beta-adrenergic receptor blocking with intrinsic sympathomimetic activity. Precise mechanism by which carteolol decreases IOP is believed to be through reduction of aqueous formation.
Adult Dose1 gtt of 1% in affected eye(s) bid
Pediatric DoseNot established
ContraindicationsDocumented sensitivity; bronchial asthma or history of bronchial asthma; chronic obstructive pulmonary disease; sinus bradycardia; overt cardiac failure; cardiogenic shock; second- or third-degree atrioventricular block
InteractionsPossible additive effects, hypotension and marked bradycardia, vertigo, syncope, or postural hypotension with concomitant use of catecholamine-depleting drugs; use of 2 or more beta-adrenergic receptor blocking agents not recommended
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsPatients with anaphylactic reaction may be unresponsive to usual dose of epinephrine; caution in diabetes mellitus, thyrotoxicosis, and cerebrovascular or pulmonary insufficiency

Drug NameLevobunolol hydrochloride (Betagan, AKBeta)
DescriptionNoncardioselective beta-adrenergic receptor blocking agent. Precise mechanism by which levobunolol decreases IOP is believed to be through reduction of aqueous formation.
Adult Dose1 gtt of 0.25% or 0.5% in affected eye(s) qd/bid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; bronchial asthma or history of bronchial asthma; chronic obstructive pulmonary disease; sinus bradycardia; overt cardiac failure; cardiogenic shock; second- or third-degree atrioventricular block
InteractionsOccasionally, mydriasis results from concomitant therapy with epinephrine; possible additive effects of hypotension, bradycardia, vertigo, syncope, or postural hypotension with concomitant use of catecholamine-depleting drugs or systemic beta-adrenergic blocking agents; possible atrioventricular conduction disturbances, left ventricular failure, and hypotension with concomitant use of calcium antagonists; avoid coadministration in patients with impaired cardiac function; use of 2 or more beta-adrenergic receptor blocking agents not recommended
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in cerebrovascular or pulmonary insufficiency

Drug NameMetipranolol (OptiPranolol)
DescriptionNonselective beta-adrenergic receptor blocking agent. Precise mechanism by which metipranolol decreases IOP is believed to be through reduction of aqueous formation.
Adult Dose1 gtt in affected eye(s) bid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; bronchial asthma or history of bronchial asthma; chronic obstructive pulmonary disease; sinus bradycardia; second- or third-degree atrioventricular block; overt cardiac failure; cardiogenic shock
InteractionsPossible additive effects, hypotension and marked bradycardia, vertigo, syncope, or postural hypotension with concomitant use of catecholamine-depleting drugs; possible atrioventricular conduction disturbances, left ventricular failure, and hypotension with concomitant use of calcium antagonists; avoid coadministration in patients with impaired cardiac function and concomitant administration with adrenergic psychotropic drugs; potential additive effects on patients receiving oral beta-adrenergic blocking agents; use of 2 or more beta-adrenergic receptor blocking agents not recommended
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in cerebrovascular, cardiac, or pulmonary insufficiency

Drug Category: Cholinergic parasympathomimetic agents

Pilocarpine is a miotic agent. Reduce IOP.

Drug NamePilocarpine hydrochloride (Isopto)
DescriptionProduces miosis through direct stimulation of muscarinic neuroreceptors. Also produces contraction of iris sphincter, causing opening of trabecular meshwork spaces to facilitate outflow of aqueous humor.
Adult DoseGel: Apply 0.5-inch ribbon in lower conjunctival sac of affected eye(s) hs
Solution (1%, 2%, 4%): 1 gtt in affected eye(s) q6h
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; cases where miosis is not desirable
InteractionsMay not be effective when used in patients treated with topical nonsteroidal anti-inflammatory medications
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsMiosis usually causes difficulty in dark adaptation; may cause decreased vision in patients with cataracts; caution in night driving or hazardous occupations; miotics may cause retinal detachment in susceptible eyes

Drug Category: Prostaglandins

May decrease IOP by increasing outflow of aqueous humor.

Drug NameLatanoprost (Xalatan)
DescriptionProstaglandin F2-alpha agonist. Decreases IOP by increasing uveoscleral outflow.
Adult Dose1 gtt in affected eye(s) hs
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsCoadministration with eye drops containing the preservative thimerosal may reduce effects (administer at intervals of 5 min between applications)
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsDo not administer while wearing contact lenses; may gradually change eye color, increasing the amount of brown pigment in the iris by increasing the number of melanosomes in melanocytes; increased inflammation and granulomatous uveitis have been reported; may cause thickening and darkening of the eyelashes

Drug NameTravoprost ophthalmic solution (Travatan, Travatan Z)
DescriptionProstaglandin F2-alpha analog and selective FP prostanoid receptor agonist. Exact mechanism of action unknown but believed to reduce IOP by increasing uveoscleral outflow.
Adult Dose1 gtt in affected eye(s) hs; not to exceed 1 dose/d
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; pregnancy; signs of inflammation
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCommonly causes ocular hyperemia; may cause permanent increase in pigment to iris (ie, increases brown pigment) and eyelid; eyelash growth may increase; bacterial keratitis may occur; caution in uveitis or macular edema; do not instill if wearing contact lenses

Drug NameBimatoprost (Lumigan)
DescriptionProstaglandin agonist that selectively mimics effects of naturally occurring substances, prostamides. Exact mechanism of action unknown but believed to reduce IOP by increasing outflow of aqueous humor through trabecular meshwork and uveoscleral routes. Used to reduce IOP in open-angle glaucoma or ocular hypertension.
Adult Dose1 gtt in affected eye(s) hs; not to exceed 1 dose/d
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; signs of inflammation
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsMay cause permanent increase in pigment to iris (ie, increases brown pigment) and eyelid; eyelash growth may increase; bacterial keratitis may occur; caution in uveitis or macular edema; do not instill if wearing contact lenses

Drug NameUnoprostone isopropyl (Rescula)
DescriptionProstaglandin F2-alpha analog and selective FP prostanoid receptor agonist. Exact mechanism of action unknown but believed to reduce IOP by increasing uveoscleral outflow.
Adult Dose1 gtt in affected eye(s) bid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; signs of inflammation
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCommonly causes ocular hyperemia; may cause permanent increase in pigment to iris (ie, increases brown pigment) and eyelid; eyelash growth may increase; bacterial keratitis may occur; caution in uveitis or macular edema; do not instill if wearing contact lenses

Drug Category: Sympathomimetics

Decrease aqueous production and increase outflow facility.

Drug NameDipivefrin hydrochloride (AKPro, Propine)
DescriptionConverted to epinephrine in eye by enzymatic hydrolysis. Appears to act by decreasing aqueous production and enhancing outflow facility. Has same therapeutic effect as epinephrine with fewer local and systemic adverse effects. May be used as an initial therapy or as an adjunct with other antiglaucoma agents for the control of IOP.
Adult Dose1 gtt in affected eye(s) bid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; narrow angles; dilation of pupil may predispose patient to attack of angle-closure glaucoma
InteractionsIncreased or synergistic effects are seen when used concurrently with agents that lower IOP
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsMay produce tachycardia, arrhythmias, hypertension, follicular conjunctivitis, mydriasis, and adrenochrome deposits in the conjunctiva and cornea; macular edema reported in aphakic patients; discontinuation of treatment generally results in reversal of maculopathy

Drug NameEpinephrine (Glaucon)
DescriptionLower IOP by increasing outflow and reducing production of aqueous humor. Used as adjunct to miotic or beta-blocker therapy. Combination of miotic and sympathomimetic has additive effects in lowering IOP.
Adult Dose1 gtt of 0.5%, 1%, or 2% in affected eye(s) qd/bid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; narrow- or shallow-angle glaucoma; aphakia
InteractionsIncreases toxicity of beta- and alpha-blocking agents and that of halogenated inhalational anesthetics
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in elderly patients, prostatic hypertrophy, hypertension, cardiovascular disease, diabetes mellitus, hyperthyroidism, and cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias

Drug Category: Alpha2-adrenergic receptor antagonists

Reduce IOP.

Drug NameApraclonidine HCl (Iopidine)
DescriptionDecreases IOP by reducing aqueous humor production. Generally used in short-term therapy.
Adult Dose1 gtt in affected eye(s) tid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; patients on MAOIs or have taken them in the past 14 d
InteractionsMonitor pulse and BP frequently when giving cardiovascular drugs; not for use concurrently with MAOIs
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in coronary insufficiency, chronic renal failure, recent myocardial infarction, cerebrovascular disease, Raynaud disease, thromboangiitis obliterans, and in patients who are depressed

Drug Category: Alpha-adrenergic receptor agonists

Brimonidine tartrate is an alpha-adrenergic receptor agonist that reduces IOP.

Drug NameBrimonidine (Alphagan P)
DescriptionReduces aqueous humor production and may have a small effect on increasing uveoscleral outflow.
Adult Dose1 gtt in affected eye(s) bid or tid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; patients receiving MAOIs
InteractionsCoadministration with topical beta-blockers may further decrease IOP; tricyclic antidepressants may decrease effects of brimonidine; CNS depressants, such as barbiturates, opiates, and sedatives, may potentiate effects of brimonidine
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in cardiovascular disease, depression, cerebral or coronary insufficiency, orthostatic hypotension, and Raynaud syndrome; in neonates, may produce symptoms of bradycardia, hypotonia, hypotension, and apnea

Drug Category: Carbonic anhydrase inhibitors

Brinzolamide is a sulfonamide that reduces IOP.

Drug NameBrinzolamide (Azopt)
DescriptionInhibits the enzyme CA in the ciliary process, decreasing aqueous humor secretion.
Adult Dose1 gtt in affected eye(s) tid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsMay have additive systemic effects if patient is already on oral CA inhibitors; acid-base and electrolyte disturbances reported with concomitant high-dose salicylate therapy
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsNot recommended in severe renal impairment; caution in hepatic impairment; discontinue use in case of ocular reactions

Drug NameDorzolamide hydrochloride (Trusopt)
DescriptionSulfonamide that reduces IOP. Inhibits enzyme CA in the ciliary process, decreasing aqueous humor secretion.
Adult Dose1 gtt in affected eye(s) tid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsCoadministration with high-dose salicylate therapy may increase toxicity; may have additive systemic effects if patient is already on oral CA inhibitors; acid-base and electrolyte disturbances reported with concomitant high-dose salicylate therapy
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsNot recommended in patients with severe renal impairment; caution in hepatic impairment; discontinue in case of ocular reactions



Prognosis

  • Most investigators agree that the prognosis for pseudoexfoliation glaucoma is worse than that for primary open-angle glaucoma because of higher IOP levels, rapid progression, and more severe optic nerve damage and visual field defects.
  • Brinchmann-Hansen et al reported that the response to pilocarpine treatment was less effective in controlling the IOP in patients with pseudoexfoliation glaucoma than in patients with open-angle glaucoma.19
  • Pseudoexfoliation glaucoma patients are more likely to require laser trabeculoplasty or filtering procedures.

Patient Education



Medical/Legal Pitfalls

  • Cataract surgery may be more difficult. Patients need to be aware of this possible risk preoperatively.



The authors and editors of eMedicine gratefully acknowledge the contributions of previous coauthor, Dong H Shin, MD, PhD, to the development and writing of this article.



Media file 1:  Pseudoexfoliative material can be seen in this eye with pseudoexfoliation glaucoma. Courtesy of S. Fabian Lerner, MD.
Click to see larger pictureClick to see detailView Full Size Image
Media type:  Photo



  1. Zenkel M, Pöschl E, von der Mark K, Hofmann-Rummelt C, Naumann GO, Kruse FE, et al. Differential gene expression in pseudoexfoliation syndrome. Invest Ophthalmol Vis Sci. Oct 2005;46(10):3742-52. [Medline].
  2. Roth M, Epstein DL. Exfoliation syndrome. Am J Ophthalmol. Apr 1980;89(4):477-81. [Medline].
  3. Kozart DM, Yanoff M. Intraocular pressure status in 100 consecutive patients with exfoliation syndrome. Ophthalmology. Mar 1982;89(3):214-8. [Medline].
  4. Cashwell LF Jr, Shields MB. Exfoliation syndrome in the southeastern United States. I. Prevalence in open-angle glaucoma and non-glaucoma populations. Acta Ophthalmol Suppl. 1988;184:99-102. [Medline].
  5. Karger RA, Jeng SM, Johnson DH, Hodge DO, Good MS. Estimated incidence of pseudoexfoliation syndrome and pseudoexfoliation glaucoma in Olmsted County, Minnesota. J Glaucoma. Jun 2003;12(3):193-7. [Medline].
  6. Bartholomew RS. Pseudocapsular exfoliation in the Bantu of South Africa. II. Occurrence and prevalence. Br J Ophthalmol. Jan 1973;57(1):41-5. [Medline].
  7. Shrum KR, Hattenhauer MG, Hodge D. Cardiovascular and cerebrovascular mortality associated with ocular pseudoexfoliation. Am J Ophthalmol. Jan 2000;129(1):83-6. [Medline].
  8. Vessani RM, Ritch R, Liebmann JM, Jofe M. Plasma homocysteine is elevated in patients with exfoliation syndrome. Am J Ophthalmol. Jul 2003;136(1):41-6. [Medline].
  9. Roedl JB, Bleich S, Reulbach U, Rejdak R, Kornhuber J, Kruse FE, et al. Homocysteine in tear fluid of patients with pseudoexfoliation glaucoma. J Glaucoma. Mar 2007;16(2):234-9. [Medline].
  10. Summanen P, Tönjum AM. Exfoliation syndrome among Saudis. Acta Ophthalmol Suppl. 1988;184:107-11. [Medline].
  11. Aasved H. Mass screening for fibrillopathia epitheliocapsularis, so-called senile exfoliation or pseudoexfoliation of the anterior lens capsule. Acta Ophthalmol (Copenh). 1971;49(2):334-43. [Medline].
  12. Jonasson F, Damji KF, Arnarsson A, Sverrisson T, Wang L, Sasaki H, et al. Prevalence of open-angle glaucoma in Iceland: Reykjavik Eye Study. Eye. Aug 2003;17(6):747-53. [Medline].
  13. Puska PM. Unilateral exfoliation syndrome: conversion to bilateral exfoliation and to glaucoma: a prospective 10-year follow-up study. J Glaucoma. Dec 2002;11(6):517-24. [Medline].
  14. Jeng SM, Karger RA, Hodge DO, Burke JP, Johnson DH, Good MS. The risk of glaucoma in pseudoexfoliation syndrome. J Glaucoma. Jan 2007;16(1):117-21. [Medline].
  15. Grødum K, Heijl A, Bengtsson B. Risk of glaucoma in ocular hypertension with and without pseudoexfoliation. Ophthalmology. Mar 2005;112(3):386-90. [Medline].
  16. Thorleifsson G, Magnusson KP, Sulem P, Walters GB, Gudbjartsson DF, Stefansson H, et al. Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science. Sep 7 2007;317(5843):1397-400. [Medline].
  17. Gottanka J, Kuhlmann A, Scholz M, Johnson DH, Lütjen-Drecoll E. Pathophysiologic changes in the optic nerves of eyes with primary open angle and pseudoexfoliation glaucoma. Invest Ophthalmol Vis Sci. Nov 2005;46(11):4170-81. [Medline].
  18. Jacobi PC, Dietlein TS, Krieglstein GK. Bimanual trabecular aspiration in pseudoexfoliation glaucoma: an alternative in nonfiltering glaucoma surgery. Ophthalmology. May 1998;105(5):886-94. [Medline].
  19. Brinchmann-Hansen O, Albrektsen T, Anmarkrud N. Pilocarpine drops do not reduce intraocular pressure sufficiently in pseudoexfoliation glaucoma. Eye. 1993;7 (Pt 4):511-6. [Medline].
  20. Aasved H. Intraocular pressure in eyes with and without fibrillopathia epitheliocapsularis (so-called senile exfoliation or pseudoexfoliation). Acta Ophthalmol (Copenh). 1971;49(4):601-10. [Medline].
  21. Aasved H. The geographical distribution of fibrillopathia epitheliocapsularis, so-called senile exfoliation or pseudoexfoliation of the anterior lens capsule. Acta Ophthalmol (Copenh). 1969;47(3):792-810. [Medline].
  22. Ball SF. Exfoliation syndrome prevalence in the glaucoma population of South Louisiana. Acta Ophthalmol Suppl. 1988;184:93-8. [Medline].
  23. Bayramlar H, Hepsen IF, Yilmaz H. Mature cataracts increase risk of capsular complications in manual small-incision cataract surgery of pseudoexfoliative eyes. Can J Ophthalmol. Feb 2007;42(1):46-50. [Medline].
  24. Cahill M, Early A, Stack S, Blayney AW, Eustace P. Pseudoexfoliation and sensorineural hearing loss. Eye. May 2002;16(3):261-6. [Medline].
  25. Colin J, Le Gall G, Le Jeune B, Cambrai MD. The prevalence of exfoliation syndrome in different areas of France. Acta Ophthalmol Suppl. 1988;184:86-9. [Medline].
  26. Damji KF, Bovell AM, Hodge WG, Rock W, Shah K, Buhrmann R, et al. Selective laser trabeculoplasty versus argon laser trabeculoplasty: results from a 1-year randomised clinical trial. Br J Ophthalmol. Dec 2006;90(12):1490-4. [Medline].
  27. Elsching A. Detachment of the zonular lamellae in glassblowers. Klin Monatsbl Augenheilkd. 1922;69:732-4.
  28. Forsius H. Prevalence of pseudoexfoliation of the lens in Finns, Lapps, Icelanders, Eskimos, and Russians. Trans Ophthalmol Soc U K. Jul 1979;99(2):296-8. [Medline].
  29. Forsius H, Forsman E, Fellman J, Eriksson AW. Exfoliation syndrome: frequency, gender distribution and association with climatically induced alterations of the cornea and conjunctiva. Acta Ophthalmol Scand. Oct 2002;80(5):478-84. [Medline].
  30. Gradle HS, Sugar HS. Glaucoma capsulare. Am J Ophthalmol. 1947;30:12.
  31. Hann CR, Bahler CK, Johnson DH. Cationic ferritin and segmental flow through the trabecular meshwork. Invest Ophthalmol Vis Sci. Jan 2005;46(1):1-7. [Medline].
  32. Hansen E, Sellevold OJ. Pseudoexfoliation of the lens capsule. I. Clinical evaluation with special regard to the presence of glaucoma. Acta Ophthalmol (Copenh). 1968;46(6):1095-104. [Medline].
  33. Hiller R, Sperduto RD, Krueger DE. Pseudoexfoliation, intraocular pressure, and senile lens changes in a population-based survey. Arch Ophthalmol. Jul 1982;100(7):1080-2. [Medline].
  34. Jacobi PC, Dietlein TS, Krieglstein GK. Comparative study of trabecular aspiration vs trabeculectomy in glaucoma triple procedure to treat pseudoexfoliation glaucoma. Arch Ophthalmol. Oct 1999;117(10):1311-8. [Medline].
  35. Jones W, White RE, Magnus DE. Increased occurrence of exfoliation in the male, Spanish American population of New Mexico. J Am Optom Assoc. Sep 1992;63(9):643-8. [Medline].
  36. Karp CL, Fazio JR, Culbertson WW, Green WR. True exfoliation of the lens capsule. Arch Ophthalmol. Aug 1999;117(8):1078-80. [Medline].
  37. Konstas AG, Jay JL, Marshall GE, Lee WR. Prevalence, diagnostic features, and response to trabeculectomy in exfoliation glaucoma. Ophthalmology. May 1993;100(5):619-27. [Medline].
  38. Küchle M, Naumann GO. Occurrence of pseudoexfoliation following penetrating keratoplasty for keratoconus. Br J Ophthalmol. Feb 1992;76(2):98-100. [Medline].
  39. Layden WE, Ritch R, Shields, MB. Exfoliation syndrome. In: The Secondary Glaucomas. St. Louis, Mo: CV Mosby; 1982:115.
  40. Lemmela S, Forsman E, Sistonen P, Eriksson A, Forsius H, Jarvela I. Genome-wide scan of exfoliation syndrome. Invest Ophthalmol Vis Sci. Sep 2007;48(9):4136-42. [Medline].
  41. Lindberg J. Clinical Studies of Depigmentation of the Pupillary Margin and Transillumination of the Iris in Cases of Senile Cataract and also in Normal Eyes of the Aged [thesis]. Diss Helsingfors, Finland: 1917.
  42. Mistlberger A, Liebmann JM, Greenfield DS, Pons ME, Hoh ST, Ishikawa H, et al. Heidelberg retina tomography and optical coherence tomography in normal, ocular-hypertensive, and glaucomatous eyes. Ophthalmology. Oct 1999;106(10):2027-32. [Medline].
  43. Mitchell P, Wang JJ, Smith W. Association of pseudoexfoliation syndrome with increased vascular risk. Am J Ophthalmol. Nov 1997;124(5):685-7. [Medline].
  44. Miyazaki M, Kubota T, Kubo M, Kiyohara Y, Iida M, Nose Y, et al. The prevalence of pseudoexfoliation syndrome in a Japanese population: the Hisayama study. J Glaucoma. Dec 2005;14(6):482-4. [Medline].
  45. Naumann GO, Schlotzer-Schrehardt U, Kuchle M. Pseudoexfoliation syndrome for the comprehensive ophthalmologist. Intraocular and systemic manifestations. Ophthalmology. Jun 1998;105(6):951-68. [Medline].
  46. Ohrt V, Nehen JH. The incidence of glaucoma capsulare based on a Danish hospital material. Acta Ophthalmol. 1981;59:888-93.
  47. Puustjarvi T, Blomster H, Kontkanen M, Punnonen K, Terasvirta M. Plasma and aqueous humour levels of homocysteine in exfoliation syndrome. Graefes Arch Clin Exp Ophthalmol. Sep 2004;242(9):749-54. [Medline].
  48. Rao RQ, Arain TM, Ahad MA. The prevalence of pseudoexfoliation syndrome in Pakistan. Hospital based study. BMC Ophthalmol. 2006;6:27. [Medline].
  49. Repo LP, Suhonen MT, Terasvirta ME, Koivisto KJ. Color Doppler imaging of the ophthalmic artery blood flow spectra of patients who have had a transient ischemic attack. Correlations with generalized iris transluminance and pseudoexfoliation syndrome. Ophthalmology. Aug 1995;102(8):1199-205. [Medline].
  50. Reus NJ, Lemij HG. Diagnostic accuracy of the GDx VCC for glaucoma. Ophthalmology. Oct 2004;111(10):1860-5. [Medline].
  51. Ritch R. Exfoliation syndrome: the most common identifiable cause of open angle glaucoma. J Glaucoma. 1994;3:176-8.
  52. Ritch R, Shields M, Krupin T. Exfoliation syndrome. In: The Glaucomas. 2nd ed. St. Louis, Mo: Mosby-Year Book Inc; 1996:993-1022.
  53. Ritland JS, Egge K, Lydersen S, Juul R, Semb SO. Exfoliative glaucoma and primary open-angle glaucoma: associations with death causes and comorbidity. Acta Ophthalmol Scand. Aug 2004;82(4):401-4. [Medline].
  54. Sampaolesi R, Zarate J, Croxato O. The chamber angle in exfoliation syndrome. Clinical and pathological findings. Acta Ophthalmol Suppl. 1988;184:48-53. [Medline].
  55. Schlötzer-Schrehardt U, Naumann GO. Ocular and systemic pseudoexfoliation syndrome. Am J Ophthalmol. May 2006;141(5):921-937. [Medline].
  56. Schlötzer-Schrehardt U, Naumann GO. Trabecular meshwork in pseudoexfoliation syndrome with and without open-angle glaucoma. A morphometric, ultrastructural study. Invest Ophthalmol Vis Sci. Aug 1995;36(9):1750-64. [Medline].
  57. Schlötzer-Schrehardt U, Wirtz PM, Müller HG, Lang GK, Naumann GO. [Morphometric analysis of age-dependent changes of the human ciliary body]. Fortschr Ophthalmol. 1990;87(1):59-68. [Medline].
  58. Shaban RI, Asfour WM. Ocular pseudoexfoliation associated with hearing loss. Saudi Med J. Sep 2004;25(9):1254-7. [Medline].
  59. Streeten BW, Bookman L, Ritch R, Prince AM, Dark AJ. Pseudoexfoliative fibrillopathy in the conjunctiva. A relation to elastic fibers and elastosis. Ophthalmology. Nov 1987;94(11):1439-49. [Medline].
  60. Sveinsson K. The frequency of senile exfoliation in Iceland. Fibrillopathy or pseudoexfoliation. Acta Ophthalmol (Copenh). 1974;52(5):596-602. [Medline].
  61. Taylor HR, Hollows FC, Moran D. Pseudoexfoliation of the lens in Australian Aborigines. Br J Ophthalmol. Jul 1977;61(7):473-5. [Medline].
  62. Topouzis F, Wilson MR, Harris A, Anastasopoulos E, Yu F, Mavroudis L, et al. Prevalence of open-angle glaucoma in Greece: the Thessaloniki Eye Study. Am J Ophthalmol. Oct 2007;144(4):511-9. [Medline].
  63. Turacli ME, Ozdemir FA, Tekeli O, Gokcan K, Gerceker M, Duruk K. Sensorineural hearing loss in pseudoexfoliation. Can J Ophthalmol. Feb 2007;42(1):56-9. [Medline].
  64. Wollensak J, Becker HU, Seiler T. Pseudoexfoliation syndrome and glaucoma. Does glaucoma capsulare exist?. Ger J Ophthalmol. 1992;1(1):32-4. [Medline].
  65. Young AL, Tang WW, Lam DS. The prevalence of pseudoexfoliation syndrome in Chinese people. Br J Ophthalmol. Feb 2004;88(2):193-5. [Medline].
  66. Zangwill LM, Chan K, Bowd C, Hao J, Lee TW, Weinreb RN, et al. Heidelberg retina tomograph measurements of the optic disc and parapapillary retina for detecting glaucoma analyzed by machine learning classifiers. Invest Ophthalmol Vis Sci. Sep 2004;45(9):3144-51. [Medline].

Glaucoma, Pseudoexfoliation excerpt

Article Last Updated: Feb 25, 2008