Drug-Induced secondary glaucoma

By Eric Peters,2014-02-14 00:19
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Drug-Induced secondary glaucoma Sumalee Boonyaleephan MD Ophthalmology Department, Faculty of medicine, Srinakharinwirot University Background: The term glaucoma refers to a group of disease that have in common a characteristic optic neuropathy with associated visual field loss for which elevated intraocular pressure (IOP) is one of the primary risk..

    Drug-Induced secondary glaucoma

    Sumalee Boonyaleephan MD

    Ophthalmology Department, Faculty of medicine, Srinakharinwirot University


     The term glaucoma refers to a group of disease that have in common a characteristic optic neuropathy with associated visual field loss for which elevated intraocular pressure (IOP) is one of the primary risk factors. Drug-induced glaucoma should be considered as a form of the secondary glaucoma because it is brought about by specific systemic or topical medications.

     Although there is a high prevalence of glaucoma worldwide, the incidence of drug-induced glaucoma is uncertain. Several classes of drugs have the potential to cause the elevation of IOP which able to occur via an opened-angle mechanism or a closed-angle mechanism.

Opened angle:

     Drug-induced elevation of IOP is more common by an opened-angle mechanism. The most recognized medications associated with this mechanism are the corticosteroids. One study have been presented that about 5 to 6% of normal individuals will develop marked elevation of IOP 4 to 6 weeks after continuous administration of topical 1,2dexamethasone or betamethasone eye drops. Additionally, the number

    of people responding with an elevated IOP is directly related to the route of administration, frequency of administration and duration of usage of this medication. In most cases, glaucoma is found to be associated with a topically applied medication in the form of an eye drop or an ointment. However,it can also be found with alternative route of administration, such as intravitreal injection, periocular injection, systemic administration and inhaled routes of administration.

     Not at all patients taking corticosteroids will develop elevated IOP. Risk factors include preexisting primary opened-angle glaucoma, a 34family history of glaucoma, high myopia, diabetes mellitus, and history

    of connective tissue disease, particularly rheumatoid arthritis.

     The exact pathophysiology of steroid-induced glaucoma is unknown. It is known that the elevated IOP is a result of an increased 5-7resistance to aqueous outflow in the trabecular meshwork.

     The most effective line of treatment is prevention of corticosteroid- induced glaucoma through the judicious use of corticosteroids and frequent monitoring of IOP in patients who require prolonged corticosteroid theraphy. Once the diagnosis has been made, the corticosteroids should be discontinuated immediately if the patient’s underlying medical condition able to tolerate cessation of corticosteroids.

     In the case of topical corticosteroid drops, consider using a low potency steroid drugs such as fluoromethalone or medrysone. Less potent steroids are less likely to produce IOP elevation. Topical nonsteroidal anti-inflammatory medications are an alternative agents that have no potential to elevated IOP, but they may not have enough anti-inflammatory activity.

     If IOP remains elevated after discontinuation of steroid therapy or if steroids must be continued, treatment follows the same line as for primary opened-angle glaucoma ( antiglaucoma medications, laser and surgery ).

Closed angle:

     Several classes of medications have been published to induce or precipitate acute angle closure glaucoma, especially in individuals predisposed with occludable angles. The causes of closed angle glaucoma associated with these agents are also varied. The more common cause of closed angle glaucoma in these patients appears to be pupillary block mechanism. The classes of medications include antipsychotic drugs, antidepressants, monoamine oxidase inhibitors, antihistamines, antiparkinonian agents, antispasmolytic drugs, mydriatic agents, the 8sympathetic agents and botulinum toxin. Sulfamate derivative

    medications may induce angle closure glaucoma by a different angle closure mechanism, involving anterior rotation of the ciliary body.

     The pathophysiology of drug-induced angle-closure glaucoma is usually pupillary block from pupillary dilation. Medications have a direct or secondary effect, either to stimulate sympathetic or inhibit parasympathetic activiation causing pupillary dilation which able to precipitate acute angle-closure glaucoma in patients with occludable 9angles.

     The different angle-closure mechanism of sulfamate derivative medications involves anterior rotation of ciliary body and /or choroidal effusions, resulting in narrowing of angle. Pupillary dilation and occludable angles are not necessary. The exact mechanism that causes the 9ciliary body swelling is unclear.

     The following sections review the most prominent classes of

medications which induced angle-closure glaucoma.

    Antipsychotic drugs:

     The antipsychotic drugs such as perphenazine (Trilafon) and fluphenazine (Prolixin) have been reported to induce angle-closure glaucoma. The mechanism of these agents are the anticholinergis effect 9on the eyes.

Antidepressant drugs:

     The tricyclic agents such as amitryptilline and imioramine and the nontricyclic agents such as fluoxetine and mianserin hydrochloride have 9been documented to precipitated attack of angle closure glaucoma.

     Citalopram and paroxetine are an antidepressant of the selective serotonin reuotake inhibitor (SSRI) class which induced acute angle-10-11closure glaucoma. The pathophysiological mechanism of SSRI

    remains unclear, even though anti-cholinergic effects or increased level of 8serotonin, which cause partial pupillary dilation have been implicated.

    Antiparkinsonian drugs:

     Trihexyphenidyl HCl (Artane) has been reported to exacerbate 12angle-closure glaucoma. This finding is felt reflect the anticholinergic action of this agents.


     Although the anticholinergic effect is mild, orphenadrine citrate (Norgesic), an H1 antihistamine, has been documented to precipitate an 9attack of angle-closure glaucoma.

Inhalation agents:

     The anticholinergic action of ipratropium and the effect of salbutamol on aqueous humor production have been reported to induced 13 angle-closure glaucoma.

Botulinum toxin:

     Periocular botulinum toxin injection has been documented to produce an attack of angle-closure glaucoma. The mechanism is due to the effet of this drug on the ciliary ganglion, producing papillary 14 mydriasis.

Sulfamate-derivative druge:

     15,16 The sulfamate-derivative drugs such as acetazolamide, 1517,18sulfamethoxazole/trimethoprim and topiramate have been reported

    to induced acute angle-closure glaucoma. Although the mechanism is unknown, it may be associated with ciliochoroidal effusion with forward displacement of lens-iris diaphragm and anterior chamber shallowing, 19 resulting in acute angle-closure glaucoma.

Treatment of Nonsteroidal drug-induced glaucoma:

     The initial management is discontinuation of precipitating drugs. If the etiology is because of pupillary block, the patient is treated similarly to the primary acute angle-closure glaucoma. If the etiology is because of sulfamate-derivative medications, treatment of this condition is primarily supportive along with discontinuation of the medication. As the mechanism of angle closure dose not involve pupillaly block, peripheral 20iridectomy and topical miotics are not useful in the treatment.

     If intraocular pressure remains uncontrolled, additional therapies 1721such as topical IOP-lowering medications, cycloplegic drugs, 2223 high dose steroids and choroidal drainge may need to be considered.


     In opened angle, it is recommended that all patients who use chronic corticosteroid medications should have a full ophthalmic examination and regularly follow-up evaluation by ophthalmologist to minitor their ocular condition and IOP.

     In closed angle, it is recommended that patients older than the 40 years should have routine eye evaluations to screen for narrow anterior chamber angles. If drugs must be used, IOP should be monitored closely.

     Clinicians should be mindful of the possibility of drug-induced glaucoma, whether or not it is listed as a contraindication and, if in doubt, consult an ophthalmologist.


    1. Armaly MF. Statistical attributes of the steroid hypertensive response in

     the clinically normal eye.I. the demonstration of three levels of

     response. Invest Ophthalmol 1965;4:187.

    2. Armaly MF. Effect of corticosteroids on intraocular pressure and fluid

     dynamics.I. The effects of dexamethasone in the normal eye.

     Arch ophthalmol 1963;70:88.

    3. Podos SM, Becker B, Morton WR. High myopia and primary open-

     angle glaucoma. Am J Ophthamol 1966;62:1039.

    4. Becker B. Diabetes mellitus and primary open-angle glaucoma ( The

     twenty-seventh Edward Jackson Memorial Lecture ) Am J Ophthalmol


    5. Armaly MF. Effect of corticosteroids on intraocular pressure and fluid

     dynamics.II. The effects of dexamethasone in the glaucomatous eye.

     Arch ophthalmol 1963;70:492.

    6. Miller D, Peczon JD, Whitworth CG. Corticosteroids and functions in

    the anterior segment of the eye. Am J Ophthalmol 1965;59:31.

    7. Kupfer C, Ross K. Studies of aqueous humor dynamics in man.I.

     Measurements in young normal subjects. Invest Ophthalmol


     8. Tripathi RC, Tripathi BJ,Haggerty C. Drug-induced glaucoma’s

     Mechanism and management. Drugs safety 2003;26(11):749-767.

     9. Adel abdel Razik Farag . Drug-induced glaucoma.

    10. Croos R,Thirumalai S, Hassan S, Davis Jda R. Citalopram associated

     with acute angle-closure glaucoma:case report. BMC Ophthalmol

     2005 4;5:23.

    11. Eke T, Bates A K, Carr S. Acute angle closure glaucoma associated

     With paroxetine. BMJ 1997;314:1387.

    12. Friedman Z, Neuman E. Benzhexalol induced blindness in

     Parkinson’s disease. Br Med J 1972;1:605.

    13. Malawi JT, Rhobinson GM, Seneviratne H. Ipratropium bromide

     induced Angle closure glaucoma(letter). NZ Med J 1982;95:759.

    14. Krpfer C. Selective block of synaptic transmission in ciliary ganglion

     by A botulinum toxin in Rabbit. Proc Soc Exp Biol Med 1958;99:474.

    15. Bovino JA, Marcus DF. The mechanism of transient myopia induced

     by sulfonamide therapy. Am J Ophthalmol 1982;94:99-102.

    16. Krieg PH, Schipper I. Drug-induced ciliary body oedema: a new

     theory. Eye 1996;10:121-6.

    17. Chen T C, Chao C W, Sorkin J A. Topiramate induced myopic shift

     and angle closure glaucoma. Br J Ophthamol 2003;87(5):648-649.

    18. Fraunfelder FW, Fraunfelder FT, Keates EU. Topiramate-associated

     acute,bilateral,secondary angle-closure glaucoma. Ophthalmology


    19. Craig JE, Ong TJ, Louis DL, Wells JM. Mechanism of topiramate-

     induced acute-onset myopia and angle closure glaucoma. Am J


    20. Stangler F, Prietsch RF, Fortes Filho JB. Bilateral acute angle closure

     glaucoma in a young patient receiving oral topiramate:case report.

     Arq Bras Oftamol . 2007;70(1):133-6.

    21.Cynthia L. Grosskreutz. Uveal effusion and secondary angle-closure

     glaucoma associated with topiramate use. Arch Ophthalmol.


    22.Rhee DJ, Ramos-Esteban JC, Nipper KS. Rapid resolution of

     topiramate-induced angle-closure glaucoma with methylprednisolone

     and manitol. Am J Ophthalmol. 2006;141(6):1133-4.

    23.Parikh R, Parikh S, Das S, Thomas R. Choroidal drainage in the

     management of acute angle closure after topiramate toxicity.

     J Glaucoma. 2007;16(8):691-3.

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