Grand Rounds

August 2, 2013

Yuna Rapoport, MD

3

Case Presentation

CC: “I can’t see at all”

HPI: 7y/o F with history of seizures and headaches c/o

blurry vision one morning. Reportedly taken to

optometrist, refracted to 20/20, sent home with glasses

Rx. She took a nap and when she awoke she “could

only see bright lights.” On the way to the ER, she

developed red eyes, swollen eyelids, light sensitivity

and tearing.

5

Review of Systems

No pain in her eyes, no burning, no itching, no

pain with EOMs

No mucus discharge

No dizziness

No weight loss

No N/V, no malaise

No focal neurological complaints

No SOB/ cough

No neck stiffness, no fever

History

PMH: 3 seizures characterized by head

bobbling with abnormal eye movements before

age 3, seizure-free since then, with one recent

focal seizure

Social History: lives with mom, dad and cat

No known family ocular history

NKDA

Exam 5/21/2013 in ED

VA: LP at 20’ OU

Pupils: 6mm, minimally reactive, no rAPD OU

EOMI OU

IOP: 40, 41

Fields: constricted 360 degrees OU

External: slightly edematous upper and lower lid

OU

DDx of Elevated IOP and

Seizures in Children

Sturge Weber

Klippel-Trenaunay-Weber

Syndrome

Wyburn-Mason syndrome

Tuberous Sclerosis

Neurofibromatosis

Aicardi Syndrome

The Ring 14 Syndrome

CASK mutation

Exam

Narrow angles OU

DDx of Childhood Narrow

Angles

Congestion

Nanophthalmos

Ciliochoroidal effusion

Inflammation: scleritis, uveitis, JIA

Drug-induced

Post-surgical (Sturge Weber,

Klippel Trenaunay Weber)

Tumor

Retinoblastoma

Medulloepithelioma

Exudative RD (Coats’ Disease)

Persistent fetal vasculature

Retinopathy of prematurity

Posterior ‘Pushing’ mechanism:

Anterior rotation of ciliary body:

Pressure from posterior segment:

Contraction of retrolental tissue:

Corneal anomalies: microcornea, cornea

plana/ sclerocornea, megalocornea

Axenfeld-Rieger syndrome, Peters

anomaly, iridoschisis

Aniridia

Ectopia lentis (trauma, Marfan’s

homocystinuria, Ehler’s Danlos, Weill-

Marchesani)

Congenital iris ectropion syndrome

▪ Aphakia

▪ Microspherophakia

Neovascular (tuberous sclerosis)

Peripheral Anterior Synechiae

Without pupillary block

Anterior ‘Pulling’ Mechanism:

With Pupillary block:

Anterior segment dysgenesis:

Ant Segment Photo: OD 5/22/13

Ant Segment Photo: OS 5/22/13

Exam Continued

SLE:

Lids/ lashes: slightly edematous upper and lower lids OU

Sclera/ conj: 1+ injection, chemosis temporally OU

K: no K edema OU

AC: diffusely shallow throughout OU

Iris: intact, regular insertion, no iris bombe OU

Lens: clear OU

uDFE:

ON: 0.25, pink and crisp OU

Macula: flat OU Vessels: normal c/c OU

Normal Ant Segment OCT

Scleral spur

Reflex saturation

beam

Ant Segment OCT: OD

OS

Iridocorneal

apposition

Anterior lens vault Anterior iris

convexity

More History and Exam… in ER

POH: none

Medications: Topiramate 25mg QHS x 2 weeks,

cyproheptadine 1 tsp by mouth QHS

VA: LP at 20’, CF at 14”, 20/20 at 3” OU

DDx of Childhood Narrow

Angles

Congestion

Nanophthalmos

Ciliochoroidal effusion

Inflammation: scleritis, uveitis, JIA

Post-surgical (Sturge Weber,

Klippel Trenaunay Weber)

Tumor

Retinoblastoma

Medulloepithelioma

Exudative RD (Coats’ Disease)

Persistent fetal vasculature

Retinopathy of prematurity

Posterior ‘Pushing’ mechanism:

Anterior rotation of ciliary body:

Pressure from posterior segment:

Contraction of retrolental tissue:

Corneal anomalies: microcornea, cornea

plana/ sclerocornea, megalocornea

Axenfeld-Rieger syndrome, Peters

anomaly, iridoschisis

Aniridia

Ectopia lentis (trauma, Marfan’s

homocystinuria, Ehler’s Danlos, Weill-

Marchesani)

Congenital iris ectropion syndrome

▪ Aphakia

▪ Microspherophakia

Neovascular (tuberous sclerosis)

Peripheral Anterior Synechiae

Without pupillary block

Anterior ‘Pulling’ Mechanism:

With Pupillary block:

Anterior segment dysgenesis:

Drug-induced

Acute angle closure from

Topiramate

First case reported in July 2001 by Banta et al. (1)

Largest case series 2004 by Fraunfelder, et al. (2): n=115

83 cases of bilateral, 3 cases of unilateral angle closure

Ages: 3-70, mean 34

Doses: <50mg (47%), 50-75mg (33%), 100mg (13%,

>100mg (7%)

Time of onset:

5 cases within hours when dose doubled

1-49 days, mean 7 days; 85% occurred within first 2

weeks

1. Banta, et al. Presumed topiramate-induced bilateral acute angle-closure glaucoma.Am J Ophthalmol, 132 (2001),

pp. 112-114

2. Fraunfedler, et al. Topiramate-assoicated acute, bilateral, secondary angle-closure glaucoma. Ophth. 2004; p. 109-

111.

Mechanism

Underlying mechanism- ciliochoroidal effusion--> ciliary body

edema-->relaxation of zonular fibers -->lens thickening --> anterior

displacement of lens -iris complex--> secondary ACG and high

myopia

Cilio-choroidal effusion caused by sulfonamides is an idiosyncratic

response in uveal tissue

Dose independent

Hapten hypothesis: reactive drug metabolites bind to proteins,

forming altered proteins which are recognized as foreign

substances and incite immune reactions

Myopia 87% related to lens thickening and 13% related to anterior

lens displacement, from A-scan measurements

Hook et al. Transient myopia induced by sulfonamides. Am J Ophthalmol. 1986; 101; 495-496.

Senthil S, et al. bilateral simultaneous acute angle closure caused by sulphonamide derivatives: a case series. Indian J Ophthalmol. 2010; 58(3):248-52.

Fraunfedler, et al. Topiramate-assoicated acute, bilateral, secondary angle-closure glaucoma. Ophth. 2004; p. 109-111.

Other Sulfonamides

Other sulfonamides have been reported to cause

similar clinical syndrome:

acetazolamide

indapamide (thiazide diuretic) (1) (2)

sulfasalazine (3)

hydrochlorothiazide (3)

Risk of adverse reaction to sulfonamides is 3% (4)

1. Senthil S, et al. bilateral simultaneous acute angle closure caused by sulphonamide derivatives: a case series. Indian J Ophthalmol. 2010;

58(3):248-52.

2. Blain P, Pβques M, Massin P, Erginay A, Santiago P, Gaudric A. Acute Transient Myopia Induced by Indapamide. Am J Ophthalmol

2000;129:538-4

3. Lee GC, et al. Bilateral angle closure glaucoma induced by sulphonamide-derived medications. Clin Experiment Ophthalmol. 2007;

35(1):55-8.

4. Panday VA, et al. Review of sulfonamide induced acute myopia and acute bilateral angle-closure glaucoma. Compr

Ophthalmol Update. 2007; 8(5): 271-6

Clinical Findings from

Topiramate

Macular folds (from choroidal effusion)

1. Kumar, M, et al. Macular folds: an unusual association in topiramate toxicity. Clin Exp Optom. 2012 95(4):449-52.

Clinical Findings from

Topiramate

Choroidal detachment

1. Kumar, M, et al. Macular folds: an unusual association in topiramate toxicity. Clin Exp Optom. 2012 95(4):449-52.

Clinical Findings from

Topiramate

Ciliochoroidal detachment

1. Kumar, M, et al. Macular folds: an unusual association in topiramate toxicity. Clin Exp Optom. 2012 95(4):449-52.

Treatment

Immediate d/c of topiramate

Aqueous suppressants: PO/ IV Acetazolamide, +/- Mannitol

Topical ocular hypotensives

Topical cycloplegics - retracts ciliary processes and deepen AC

Angle closure usually resolves within 24-48 hrs with medical treatment

Myopia resolves 1-2 weeks of discontinuing the topiramate

Peripheral iridectomy and miotics are not indicated (pupillary block not an

underlying mechanism of this syndrome)

If refractory, PO/ IV steroids(1), Argon laser peripheral iridoplasty (2),

surgical intervention (choroidal drainage (3), vitrectomy, CE/ IOL, glaucoma

surgeries)

1. Rhee DJ, et al. Rapid resolution of topiramate-induced angle-closure glaucoma with methylprednisolone and mannitol

2. Zalta AH, et al. Peripheral iridoplasty efficacy in refractory topiramate-associated bilateral acute angle-closure glaucoma. Ophthalmol. 2008; 126(11):1603-5

3. Parikh, R, et al. J Glaucoma. 2007. 16(8):691-3.

Few case reports in Children

Topiramate is approved over age >2

Included in series but no information provided:

Fraunfedler et al. : age 3 (1)

Thambi, et al.: age 5(2)

2 Case reports:

8 y/o M - c/o “blind” both eyes, Mrx: -6.00 OU, IOP 19 OU. Tx: d/c Topiramate, vision

normalized within 48 hrs (3)

5y/o F - HA, N, fatigue; 10 days, IOPs 50, 46, conj hyperemia, microcystic K edema,

shallow ACs without iris bombe or IK touch; used pilocarpine, timolol, Trusopt, switched

to cyclopentolate and pred forte after Bscan showed 360 degrees of ciliochroidal

effusion; Mrx: -5.50, -6.00 correlated to 9.6, 7.5 diopter shift (4)

1. Fraunfedler, et al. Topiramate-assoicated acute, bilateral, secondary angle-closure glaucoma. Ophth. 2004; p. 109-111.

2. Thabmi, L, et al. Topiramate- Associated Secondary Angle-Closure Glaucoma: A Case Series. Arch Ophthalmol. 2002; 120():1108.

3. Hussein MAW,et al. Acute transient myopia in a child. Medscape Ophthalmology (online) 2002; 3(2)

4. Lin J, et al. Bilateral angle closure glaucoma in a child receiving oral topiramate. J of AAPOS 2003;7:66-8.

Treatment Course in clinic

Date OD OS IOP OD OS

5/22 20/200 20/150 23 21

20/60 20/40+3

Cont PO Diamox, Cosopt, add Cyclogel TID

5/24 20/25- 20/40+3 16 8

D/C Diamox, cont Cosopt, Cyclogel

5/29 20/25+3, 20/25 12 11

20/20 20/20

D/C Cosopt, Cyclogel

7/24 20/20 20/20 13 12

Imaging 7/24/13

26

Take away message

Primary narrow angle glaucoma is rare under 40 years of

age

Consider secondary angle closure glaucoma in pediatric

patients

Bilateral blurred vision is frequently the presenting

symptom of angle closure from Topiramate toxicity

85% of cases of IOP elevation occurs within two weeks of

use

27

Thank you

Dr. Joos

Dr. Benegas

Dr. Kuchtey