Short Reports

Bilateral response following unilateral intravitrealbevacizumab injection in a child with uveitic cystoidmacular edemaHassan Al-Dhibi, MD,a,b and Arif O. Khan, MDc

Untreated cystoid macular edema (CME) is a major cause for visualloss in intermediate and posterior forms of uveitis. Conventionaltreatments for inflammatory CME include steroids, nonsteroidalantiinflammatory agents, and carbonic anhydrase inhibitors; how-ever, not all patients respond, even after quieting of the uveitis. In-travitreal injection of bevacizumab, a monoclonal antibody tovascular endothelial growth factor, has recently been suggestedas a short-term treatment for inflammatory CME in adults. Becauseunilaterally injected bevacizumab can reach the contralateral eyevia the systemic circulation there may be a contralateral clinical ef-fect; however, the few reports that evaluate this in adults are con-flicting. The purpose of this report is to document bilateralreduction of uveitic CME following unilateral intravitreal bevacizu-mab injection in an 8-year-old girl.

Case Report

An 8-year-old girl with a 6-year history of insulin-dependent diabetes and a 2-year history of idio-pathic bilateral intermediate uveitis complained

of gradual bilateral visual deterioration over the precedingseveral months with no other constitutional symptoms. Foralmost 2 years she was being treated with oral methotrexate7.5 mg weekly and supplemental folate 1 mg daily except forthe day of oral methotrexate. An extensive medical evalua-tion to determine a cause for the uveitis was unremarkable.The evaluation included general pediatric physical exami-nation, routine blood chemistries, angiotensin-convertingenzyme level, rapid plasma reagin, C-reactive protein, anti-nuclear antibody levels, anti-DNA antibody levels, rheu-matoid factor, chest x-ray, and magnetic resonanceimaging of the brain and orbits. Best-corrected visual acuitywas 20/100 in the right eye and 20/200 in the left eye. Intra-ocular pressure by Goldmann tonometry was 27 mm Hg in

See editorial on page 329.

Author affiliations: aDivisions of Uveitis, bVitreoretinal Disease, and cPediatricOphthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia

Funding: None.Conflict of Interest: None.Submitted February 6, 2009.Revision accepted March 22, 2009.Published online May 30, 2009.Reprint requests: Arif O. Khan, MD, Division of Pediatric Ophthalmology, King Khaled

Eye Specialist Hospital, PO Box 7191, Riyadh 11462, Saudi Arabia (email: arif.khan@mssm.edu).J AAPOS 2009;13:400-402.

Copyright � 2009 by the American Association for Pediatric Ophthalmology andStrabismus.

1091-8531/2009/$36.00 1 0doi:10.1016/j.jaapos.2009.03.006

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either eye. Slit-lamp examination was significant for keraticprecipitates, mild cell and flare, optic nerve head edema,and cystoid macular edema (CME). There was no diabeticretinopathy. Fluorescein angiography and optical coher-ence tomography (RTVue-100; Optovue, Fremont, CA)confirmed bilateral CME. Topical steroids (prednisolone1% every hour while awake) and antiglaucoma medications(timolol 0.5% twice daily, dorzolamide 2% twice daily)controlled the anterior segment inflammation and intraoc-ular pressure, respectively, but the CME persisted. For thepersistent CME, 1.25 mg/0.50 mL bevacizumab (Avastin;Genentech, San Francisco, CA) was injected into the righteye inferotemporally and 3.5 mm from the limbus to themid-vitreous via a 30-gauge needle while the child was un-der general anesthesia. This procedure was performed afterthorough discussion and informed consent with the family,including the fact that the effect and safety of such treat-ment in children is not well documented. One week later,the patient had bilateral visual improvement (20/80 in theright eye, 20/160 in the left eye) as well as bilateral reductionin CME on optical coherence tomography despite that onlythe right eye was injected (Figure 1). Two weeks after theinjection in the right eye, the left eye was injected in thesame manner. Two months following the second injection,bilateral CME began to recur (Figure 1). There were nolocal or systemic adverse effects detected following eitherinjection.

Discussion

There are few reports of intravitreal bevacizumab use inchildren1-3 and none to our knowledge that document a bi-lateral effect from unilateral injection. We document itsuse in an 8-year-old child without local or systemic adverseeffects. Bilateral reduction of uveitic CME and improve-ment in visual acuity was observed following unilateral in-travitreal injection. Further bilateral reduction in CMEwas documented following injection of the contralateraleye. The effect of the intravitreal injection abated at8 weeks, although there was still some apparent effect16 weeks following injection.

Intravenously administered bevacizumab can treat bothunilateral and bilateral ocular disease in adults4; however,it has been less clear whether or not intravitreal bevacizu-mab injection can treat disease in the contralateral eye byspreading through the systemic circulation.5-7 In rabbits,approximately 1.6% of the injected dose enters the

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FIG 1. Macular thickness before and after injection. A, Appearance at presentation. B, 1 week following injection of the right eye only, the bilateralcentral macular thickness clearly decreased. C, 1 week after injection of the left eye, further decrease was documented. D and E, 8 and 16 weeksthereafter the effect seemed to abate. OD, right eye; OS, left eye; BCVA, best-corrected visual acuity; CMT, central macular thickness in micrometers.

systemic circulation and can be detected 4 weeks later inthe contralateral eye.5 In adult diabetics, unilateral injec-tion can decrease bilateral proliferative diabetic retinopa-thy.6 However, a pilot study in bilateral diabetic macularedema suggested no significant effect in the contralateraleye.7 In the current case, there was a clear contralateral ef-fect following unilateral injection. The smaller body massof a child and an increased ocular permeability in the set-ting of intermediate uveitis are factors that may have al-lowed bevacizumab to enter the contralateral eye insufficient quantity to have a clinical effect.

The fact that bevacizumab reduced uveitic CME in thischild and in previous reports of adults supports the role ofvascular endothelial growth factor in the pathogenesis of

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uveitic CME.8-10 Increased concentrations of vascular en-dothelial growth factor have been correlated with CMEin uveitis (in contrast to uveitis without CME) as well aswith other forms of CME.8 Although most reports docu-ment that intravitreal bevacizumab has only a short-termeffect on uveitic CME, there is a role for its use because un-treated persistent CME leads to photoreceptor damageand/or retinal ischemia.8

Literature Search

An English-language PubMed search, without date restric-tions, was performed on January 10, 2009, for the terms

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pediatric and bevacizumab. Relevant references of the identi-fied articles were also reviewed.

References

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2. Cakir M, Cekic O, Yilmaz OF. Intravitreal bevacizumab and triam-cinolone treatment for choroidal neovascularization in Best disease.J AAPOS 2009;13:94-6.

3. Travassos A, Teixeira S, Ferreira P, Regadas I, Travassos AS,Esperancinha FE, et al. Intravitreal bevacizumab in aggressive poste-rior retinopathy of prematurity. Ophthalmic Surg Lasers Imaging2007;38:233-7.

4. Moshfeghi AA, Rosenfeld PJ, Puliafito CA, Michels S, Marcus EN,Lenchus JD, Venkatraman AS. Systemic bevacizumab (Avastin)therapy for neovascular age-related macular degeneration: Twenty-four-week results of an uncontrolled open-label clinical study.Ophthalmology 2006;113:2002.e1-12.

5. Bakri SJ, Snyder MR, Reid JM, Pulido JS, Ezzat MK, Singh RJ. Phar-macokinetics of intravitreal bevacizumab (Avastin). Ophthalmology2007;114:855-9.

6. Avery RL, Pearlman J, Pieramici DJ, Rabena MD, Castellarin AA,Nasir MA, et al. Intravitreal bevacizumab (Avastin) in the treatmentof proliferative diabetic retinopathy. Ophthalmology 2006;113:1695-705.

7. Velez-Montoya R, Fromow-Guerra J, Burgos O, Landers MB 3rd,Morales-Caton V, Quiroz-Mercado H. The effect of unilateral intra-vitreal bevacizumab (Avastin), in the treatment of diffuse bilateraldiabetic macular edema: A pilot study. Retina 2009;29:20-26.

8. Rothova A. Inflammatory cystoid macular edema. Curr Opin Oph-thalmol 2007;18:487-92.

9. Cordero Coma M, Sobrin L, Onal S, Christen W, Foster CS.Intravitreal bevacizumab for treatment of uveitic macular edema.Ophthalmology 2007;114:1574-9.

10. Mackensen F, Heinz C, Becker MD, Heiligenhaus A. Intravitrealbevacizumab (Avastin) as a treatment for refractory macularedema in patients with uveitis: A pilot study. Retina 2008;28:41-5.

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