Customize your JAMA Network experience by selecting one or more topics from the list below.
Rarely, drugs, mostly sulfa-related compounds, have produced uveal effusions,
forward rotation of the iris-lens diaphragm, transient myopia, and secondary
angle closure.1 We have recently encountered
2 cases in which uveal effusions have occurred after administration of topiramate
(Topamax; Ortho-McNeil Pharmaceutical, Raritan, NJ), a new anticonvulsant
Report of Cases
A 34-year-old white woman was seen in our emergency department with
severe headaches and progressively blurry vision in both eyes. Her medical
history was notable for depression. Her ocular history was unremarkable, she
had never worn glasses, and she denied ocular disease within the family. Her
medications included clonazepam, buspirone hydrochloride, citalopram hydrobromide,
orlistat, fluvoxamine maleate (a selective serotonin reuptake inhibitor [SSRI],
which she started 2 days prior to initial examination), and topiramate (which
she started 2 weeks prior to initial examination).
On examination her visual acuity was 20/250 OU. Slitlamp examination
revealed trace conjunctival injection and chemosis, relatively clear corneas,
and shallow anterior chambers (approximately 2 corneal thickness deep centrally).
The pupils were widely dilated, and the lenses were clear. Intraocular pressures
measured 51 mm Hg OD and 45 mm Hg OS. Funduscopic examination findings were
normal with a cup-disc ratio of 0.3 OU. No choroidal effusions were seen by
indirect ophthalmoscopy. On gonioscopy there was a steep iris convexity with
appositional angle closure. With compression, trabecular meshwork was seen
in both eyes without peripheral anterior synechiae.
The diagnosis of bilateral angle-closure glaucoma was made. The patient
was treated with 0.5% timolol maleate, dorzolamide hydrochloride, brimonidine
tartrate, oral acetazolamide (500 mg), and latanoprost. Her pressures eventually
decreased to 28 mm Hg OD and 27 mm Hg OS. 1% Pilocarpine was added to alleviate
the pupillary mydriasis.
She was seen the following day with examination findings relatively
unchanged, except that her pupils were now mid-dilated and tensions were 29
mm Hg OD and 32 mm Hg OS. The anterior chambers were still shallow in both
eyes. A manifest refraction revealed the formerly emmetropic patient now had
measurements of −8.75 sphere OD and −7.25 sphere OS. A B scan
was performed and demonstrated a separation between the choroidal layer and
the sclera 360° with the crystalline lens shifted anteriorly (Figure 1, D). Ultrasound biomicroscopy was
also performed and demonstrated a closed angle with a forward shift of the
ciliary body (Figure 1, A and B).
Case 1. A, Ultrasound biomicroscopy (UBM) demonstrating uveal effusion
(asterisk) at the time of initial presentation. B, UBM obtained at initial
examination showing a shallow anterior chamber. C, UBM after treatment for
the uveal effusion demonstrating deep anterior chamber and resolution of the
uveal effusion. D, B scan at the time of initial examination with arrow pointing
to the uveal effusion. E, Repeated B scan after treatment without the uveal
effusion. S indicates sclera; CB, ciliary body; and AC, anterior chamber.
A diagnosis of bilateral uveal effusion was made. Pilocarpine hydrochloride
was discontinued and scopolamine hydrochloride was administered. An oral steroid
taper was also started to decrease the inflammatory response within the suprachoroidal
space. After consultation with her psychiatrists, she stopped receiving fluvoxamine
maleate and the topiramate was tapered over 2 weeks. She was seen every 2
to 3 days. She reported alleviation of her symptoms by the sixth day after
initial examination. By then, her myopic shift had resolved and her chambers
were deep. On gonioscopy, she was open to ciliary body band without synechiae
in both eyes. Her intraocular pressures were 11 to 14 mm Hg OU. She finished
her prednisone taper and stopped receiving the antiglaucoma medications within
1 week. Subsequently, the scopolamine was stopped, and her pupils returned
to normal size. Her vision returned to 20/25 OU without correction. Repeated
B scans and ultrasound biomicroscopy were performed 3 weeks after initial
examination, which revealed a resolution of the effusion (Figure 1, C and E). Her axial lengths were 23.54 mm OD and 23.74
A 53-year-old white woman with blurry vision in both eyes on awakening
was seen at another clinic. Her medical history was notable for depression
and high cholesterol levels. Her medications included premarin, venlafaxine
hydrochloride (an SSRI), atorvastatin calcium, and topiramate (which she started
10 days prior to the onset of her symptoms).
Her vision was recorded as counting fingers OD and 20/160 OS. Slitlamp
examination revealed chemosis, diffuse corneal edema, and diffusely shallow
anterior chambers. Her intraocular pressures were recorded as 72 mm Hg OD
and 74 mm Hg OS. Funduscopic examination findings were reported as normal
with normal-appearing optic nerves. A diagnosis of bilateral angle closure
Peripheral iridotomies were performed that same day in both eyes, and
medications were administered without reduction of her intraocular pressures.
One hour postlaser, paracenteses were made to both eyes to relieve the pressure
and then repeated several hours later with reduction of her intraocular pressure
to 45 mm Hg OD and 48 mm Hg OS. The patient continued to receive topical and
oral antiglaucoma medications. She discontinued only the topiramate since
this was the only recent change to her medications. She was seen the next
day. Her anterior chambers were deeper centrally but still shallow peripherally.
Her intraocular pressure was 25 mm Hg OU. Gonioscopy revealed no angle structures,
and funduscopic examination did not show clinically evident choroidal effusions.
Tropicamide was administered. By the next day, her intraocular pressure was
12 mm Hg OU, and her anterior chambers were deep. Repeated gonioscopy revealed
angles open to scleral spur.
She was seen at our service 1 month after her initial presentation.
Her vision was 20/25 OU uncorrected. Slitlamp examination revealed clear corneas
with deep, quiet anterior chambers in both eyes. Intraocular pressure was
14 mm Hg OU, and gonioscopy revealed grade III open angles without synechiae
in both eyes. Funduscopic examination revealed a cup-disc ratio of 0.6 with
Spontaneous uveal effusions are most common in individuals with microphthalmic
eyes or with abnormal sclera.2 Drug-induced
uveal effusions have been cited, although they also occur rarely. Both of
our patients received topiramate as adjunctive therapy for depression approximately
2 weeks prior to presentation. We feel that topiramate has some relation to
the cause of the patients' bilateral uveal effusions, though it is unclear
whether it is topiramate alone or in conjunction with an SSRI.
Topiramate is a sulfamate-substituted monosaccharide, used primarily
as an antiepileptic medication. Topiramate is thought to possess a state-dependent
sodium channel–blocking action. It also potentiates the activity of
GABA (γ-aminobutyric acid) and antagonizes the ability of kainate to
activate the kainate/AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic
acid) subtype of excitatory amino acid receptor. Topiramate also has a weak
carbonic anhydrase inhibition.3 These mechanisms
of action help explain the antiepileptic nature of the drug, though the mechanism
of choroidal effusions remains unclear. Topiramate does cross the blood-brain
barrier and has also been detected in the vitreous.4
To our knowledge, these are the first reported cases of choroidal effusions
associated with topiramate. It is therefore our suggestion that if a patient
is seen with bilateral angle-closure glaucoma, a history of topiramate usage
should be sought.
We thank Herbert Knauf, MD, for his clinical information and Danny Gauthier,
MD, and Lois Hart, RD, MS, for their technical assistance.
Corresponding author: Cynthia L. Grosskreutz, MD, PhD, Department
of Ophthalmology, Glaucoma Consultation Service, Massachusetts Eye and Ear
Infirmary, 243 Charles St, Boston, MA 02114-3096.
Sankar PS, Pasquale LR, Grosskreutz CL. Uveal Effusion and Secondary Angle-Closure Glaucoma Associated With Topiramate Use. Arch Ophthalmol. 2001;119(8):1210–1211. doi:
Monkeypox Resource Center