Download Drug Induced Glaucoma –A Review

Miscellaneous
Miscellaneous
Drug Induced Glaucoma –A
Review
Ravi Chandil
Ravi Chandil DOMS
Consultant Glaucoma, Ratan Jyoti Netralaya, Gwalior, M.P
G
laucoma is an optic neuropathy with characteristic
structural damage to the optic nerve and visual field
loss. It is usually associated with raised Intra ocular pressure
(IOP).
The glaucoma has traditionally been divided on the basis
of primary and secondary forms. Drug-induced glaucoma
is a form of secondary glaucoma induced by topical and
systemic medications. Although most common one is
glucocorticoid1, but it is not the only one. Drug induced
glaucoma is not synonymous to steroid induced glaucoma.
There are many other non-steroidal systemic medicines
(Table 1) as well as ophthalmic medicines which
(Table 2) have the potential to raise IOP, even anti glaucoma
drugs…. YES antiglaucoma drugs.
Mechanisms of IOP elevation in drug-induced
glaucoma
closure mechanism. These are topical anticholinergic
or sympathomimetic pupil dilating drops, tricyclic antidepressants, monoamine oxidase inhibitors, antihistamines,
anti-Parkinson drugs, antipsychotic medications and
antispasmolytic agents. These drugs will incite an attack
in individuals with very narrow anterior chamber angles
that are prone to occlusion, especially when the pupils are
dilated.
Idiosyncratic reaction
Sulfonamide-containing medications may induce an
angle closure glaucoma (ACG) by a different mechanism,
involving the anterior rotation of the cilliary-body5,6,7,8,9,10.
Typically, the angle-closure is bilateral and occurs within
the first few doses. Patients with narrow or wide open
angles are susceptible to this rare idiosyncratic reaction.
IOP elevation can occur via an open-angle or angle-closure
mechanism (Table 1 and 2).
Pathophysiology of Drug-induced Glaucoma
(Figure 1)
Open-angle
Open-angle
Corticosteroid is a group of drugs that may produce IOP
elevation by open-angle mechanism. Not all the patients
taking steroid will develop IOP elevation. The risk factors
include preexisting primary open-angle glaucoma (OAG), a
family history of glaucoma, high myopia, diabetes mellitus
and young age and rheumatoid arthritis2,3,4.
The exact pathophysiology of steroid-induced glaucoma is
unknown. It is known that steroid-induced IOP elevation is
It has been shown that 18-36% of the general population
respond to topical ocular administration of corticosteroids
with an elevation of IOP. IOP rises usually within 2-4
weeks after therapy has been instituted. Topically applied
eye drops and creams to the periorbital area and intravitreal
injections are more likely to cause IOP elevation than
intravenous, parenteral and inhaled forms.
Closed-angle
Some drugs may produce IOP elevation acutely by angle-
Figure 1: Mechanism of Drug Induced Glaucoma
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secondary to increased resistance to aqueous outflow11,12.
But the following observations and theories have been
reported.
1. Some evidence shows that there could be increased
accumulation of glycosaminoglycans producing
biological oedema13,14 or increased production
of trabecular meshwork-inducible glucocorticoid
response (TIGR) protein, which could mechanically
obstruct the aqueous outflow.
2. Other evidence suggests that the corticosteroidinduced cytoskeletal changes could inhibit pinocytosis
of aqueous humour or inhibit the clearing of
glycosaminoglycans, resulting in the accumulation of
this substance and blockage of the aqueous outflow15.
3. Direct physical obstruction of the trabecular meshwork
with crystalline steroid particles16,17.
Pathophysiology of Non Steroidal drugs e.g dicyclomine
causing open-angle glaucoma are much more varied
including the release of pigment during the pupillary dilation
with subsequent obstruction of the trabecular meshwork,
and a possible increase of inflow during pupillary dilation.
Closed-angle
The pathophysiology of angle-closure glaucoma is
usually due to pupillary blockage, i.e. iris-lens contact
at the pupillary border resulting from pupillary dilation.
Medications have a direct or secondary effect, either in
stimulating sympathetic or inhibiting parasympathetic
activation causing pupillary dilation, which can precipitate
acute angle-closures in patients with occludable anterior
chamber angles.
Sulfa-containing medications result in acute angle-closures
in a different mechanism18,19. This involves the anterior
rotation of the ciliary body with or without choroidal
effusions, resulting in a shallow anterior chamber and
blockage of the trabecular meshwork by the iris. The
exact reason causing ciliary body swelling is unknown in
susceptible individuals.
Clinical Assessment for Drug-induced Glaucoma
History
The patient’s detailed history regarding systemic illness
which could require chronic corticosteroid use like uveitis,
collagen vascular disease, asthma, dermatitis should be
asked. History of neurological disease and medications
should be carefully elicited.
Patient’s risk factor to be steroid responders like preexisting
primary open-angle glaucoma, a family history of primary
open-angle glaucoma, diabetes mellitus, high myopia, or
connective tissue diseases should be elicited.
Symptoms
In drug induced open angle glaucoma, the pressure elevation
is gradual. Therefore, there are very few symptoms during
the early stage of disease. Some time patient may complain
of coloured haloes. At a later stage, patients may complain
of loss of the peripheral visual field. At the more advanced
stage, when the central vision is also affected, patients may
complain of blurring of vision.
In drug-induced acute angle-closure glaucoma, the
symptoms are the same as in primary acute angle-closure
glaucoma. These include sudden eye pain, headache
associated with nausea and/ or vomiting, blurring of vision
and halos around bright objects.
Physical Examination
A complete ophthalmic examination should be performed
including:
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Figure 2: Optic disc changes in steroid induced glaucoma case
Visual acuity, pupil reaction, intraocular pressure
measurement, anterior chamber examination for assessment
of anterior chamber depth. Signs of other secondary
glaucoma such as uveitic, pigment dispersion and
pseudoexfoliation glaucoma should looked for. Posterior
subcapsular cataract may present in chronic steroid users.
Gonioscopic examination
Gonioscopy for evaluation of angle anatomy i.e. open or
narrow and to determine whether the angle is occludable
during pupil dilation.
Optic disc evaluation
Stereoscopic examination of the optic disc (Figure 2) is
necessary to document glaucomatous damage. This can be
done by slit lamp biomicroscopy (78D & 90D).
Investigations
Perimetry
Visual Field testing such as Humphrey (Figure 3) is used
to evaluate the severity of optic neuropathy. Even when
optic nerve damage not present, baseline documentation
of visual field is essential.
Optical Coherence Tomography (OCT)
OCT is an optical signal acquisition and processing method.
It is used to evaluate the retinal nerve fibre thickness around
the optic disc (Figure 4) in glaucoma patients. Serial scans
can be used to demonstrate any progression of disease.
Ultrasound Biomicroscopy (UBM)
UBM is an imaging technique that uses high frequency
ultrasound to produce images of the eye at near microscopic
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Figure 3: Humphery visual field changes
in steroid induced glaucoma case
resolution. This technique is used to evaluate the anterior
chamber angle configuration i.e. open or closed and the
position of the cilliary body e.g. anterior rotation (Figure 5)
Anterior Segment OCT (ASOCT)
It applies the same principle as OCT but it provides images
of the anterior chamber including the angle and the lens.
Treatment of Drug-induced Glaucoma
If the patient’s underlying medical condition can tolerate
discontinuation of drugs, then cessation of the medication
will usually result in normalization of IOP.
Medical management for Open-angle drug induced
glaucoma
In the case of topical corticosteroid drops, using a lower
potency steroid medication, such as the phosphate
forms of prednisolone, loteprednol or fluorometholone
should be considered. These drugs have a lesser chance
of IOP rise20,21,22, but they are usually not as effective as
an anti-inflammatory drug. Topical NSAID medications
can be considered, but they may not have enough antiinflammatory activity to treat the patient’s underlying
condition23,24.
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In cases in which the patient’s IOP does not normalize
upon cessation of the steroid or in those patients who
must continue to be on corticosteroid medications, topical
antiglaucoma medications are considered.
Medical management for Closed-angle drug induced
glaucoma
If the aetiology is because of sulfa-containing medications,
the increase in IOP generally will resolve upon stopping the
medication. However, severe cases of sulfonamide-induced
angle-closure may not respond to simply discontinuing
the offending medication. These cases may respond to
intravenous mannitol.
For other aetiologies of drug-induced angle-closure, they
are treated similar to primary acute angle-closure glaucoma
by using antiglaucoma medications including topical beta
blockers, prostaglandin analogues, cholinergic agonists
and often oral acetazolamide.
Figure 4: OCT RNFL changes in steroid
induced glaucoma case
Laser treatment
For open-angle glaucoma, Argon laser trabeculoplasty
or selective laser trabeculoplasty can be applied in the
absence of ocular inflammation if the IOP is suboptimal
with medication25,26.
In closed-angle glaucoma, argon laser peripheral iridoplasty
(ALPI) may be applied to deepen the anterior chamber and
widen the angle. Laser iridotomy (LI) can be performed
to reverse pupillary block or to prevent further pupillary
block.
Laser iridotomy is not effective in cases of acute ACG
caused by sulfa drug like topiramate because secondary
angle closure glaucoma occurs without pupillary block.
Surgical treatment for Open-angle and Closed
angle cases
Indication
1. Medical therapy is ineffective in lowering the IOP to
target pressure or
2. The patient is intolerant of medical therapy or
3. In patients whom both medical and laser therapy have
failed to lower the IOP adequately.
Usually, trabeculectomy, a guarded filtration procedure,
with or without intraoperative antimetabolites, is the
primary procedure.
In case of posterior subtenon steroid and in intravitreal
steroid, vitrectomy is helpful to lower the load of steroid
and IOP.
Conclusion
Uncontrolled increase in IOP can lead to permanent optic
nerve damage and permanent blindness. Drug-induced
Figure 5: Anterior rotation of the ciliary body
with choroidal effusion
IOP rise can be asymptomatic initially especially in openangle type. General practitioners should be aware of
the risk factors for glaucoma before prescribing a drug
that has the potential to cause, precipitate or exacerbate
glaucoma whenever in doubt, an ophthalmologist should
be consulted. When prescribing such medicines for long
term, regular and complete eye checkup should be done.
References
1.
2.
3.
4.
5.
Tripathi RC, Parapuram SK, Tripathi BJ, et al. Corticosteroids and
glaucoma risk. Drugs Aging 1999;15:439-450.
Podos SM, Becker B, Morton WR. High myopia and primary openangle glaucoma. Am J Ophthalmol. 1966; 62(6):1038-1043.
Becker B. Diabetes mellitus and primary open-angle glaucoma. Am
J. Ophthalmol. 1971; 1-16.
Gaston H, Absolon MJ, Thurtle OA, et al. Steroid responsiveness in
connective tissue diseases. Br J Ophthalmol. 1983; 67(7):487-490.
Kakaria V, Chalam, Tillis T, Farhana S, Brar SA. Acute bilateral
simultaneous angle closure glaucoma Topiramate administration: a
case report. J Med Case Reports 2008;2:1.
www. dosonline.org l 57
Miscellaneous
6. GuMHP, Thiagalingam S, Ong P, Goldberg I. Bilateral acute angle
closure caused by supraciliary effusion associated with Velafaxine
intake. MJA 2005; 182:121- 123.
7. Nemet A, Nesher R, Almog Y, Assia E. Bilateral acute angle closure
glaucoma following Topiramate treatment. Harefuah 2002; 141:5979.
8. Singh SK, Thapa SS, Badhu BP. Topiramate induced bilateral angleclosure glaucoma. Kathmandu University Medical Journal 2007;
5:234.
9. Chan KCY, Sachdev N, Wells AP. Bilateral acute angle closure
secondary to uveal effusions associated with Flucloxacillin and
Carbamazepine. Br J. Ophthalmol. 2008; 92:428-430.
10. Levy J, Yagev R, Petrova A, Lifshitz T. Topiramate – induced bilateral
angle-closure glaucoma. Can J Ophthalmol. 2006; 41:221-5.
11. Jones R III, Rhee DJ. Corticosteroid-induced ocular hypertension and
glaucoma: a brief review and update of the literature. Curr Opin
Ophthalmol. 2006; 17(2):163-167.
12. Kersey JP, Broadway DC. Corticosteroid-induced glaucoma: a
review of the literature. Eye 2006; 20(4):407-416.
13. François J. The importance of the mucopolysaccharides in intraocular
pressure regulation. Invest Ophthalmol. 1975; 14(3):173-176.
14.François J, Victoria-Troncoso V. Mucopolysaccharides and
pathogenesis of cortisone glaucoma [in German]. Klin Monatsbl
Augenheilkd. 1974; 165(1):5-10.
15. Bill A. The drainage of aqueous humor [editorial]. Invest Ophthalmol.
1975;14(1):1-3
16. Singh I P, Ahmad SI, Yeh D, et al. Early rapid rise in intraocular
pressure after intravitreal triamcinolone acetonide injection. Am J
Ophthalmol. 2004;138(2):286-287.
17. Im L, Allingham RR, Singh I, et al. A prospective study of early
58 l DOS Times - Vol. 19, No. 3 September, 2013
intraocular pressure changes after a single intravitreal triamcinolone
injection. J Glaucoma 2008;17(2):128-132.
18. Tripathi RC, Triathi BJ, Haggerty C. Drug-induced glaucomas:
mechanism and management. Drug 2003; 26:749–767.
19. Geanon JD, Perkins TW. Bilateral acute angle-closure glaucoma
associated with drug sensitivity to hydrochlorothiazide. Arch
Ophthalmol. 1995; 113:1231–1232.
20. Leibowitz HM, Ryan WJ Jr, Kupferman A. Comparative antiinflammatory efficacy of topical corticosteroids with low glaucomainducing potential. Arch Ophthalmol. 1992;110(1):118-120.
21. Mindel JS, Tavitian HO, Smith H Jr, et al. Comparative ocular pressure
elevation by medrysone, fluorometholone, and dexamethasone
phosphate. Arch Ophthalmol. 1980;98(9):1577-1578.
22. Morrison E, Archer DB. Effect of fluorometholone (FML) on the
intraocular pressure of corticosteroid responders. Br J Ophthalmol.
1984;68(8):581-584.
23. Gieser DK, Hodapp E, Goldberg I, et al. Flurbiprofen and intraocular
pressure. Ann Ophthalmol. 1981;13(7):831-833.
24. Strelow SA, Sherwood MB, Broncato LJ, et al. The effect of diclofenac
sodium ophthalmic solution on intraocular pressure following
cataract extraction. Ophthalmic Surg 1992;23(3):170-175.
25. Ricci F, Missiroli F, Parravano M. Argon laser trabeculoplasty in
triamcinolone acetonide induced ocular hypertension refractory
to maximal medical treatment. Eur J Ophthalmol. 2006;16(5):756757.
26. Rubin B, Taglienti A, Rothman RF, et al. The effect of selective laser
trabeculoplasty on intraocular pressure in patients with intravitreal
steroid induced elevated intraocular pressure. J Glaucoma
2008;17(4):287-292.