Case Report

First case of post-conceptionVerteporfin exposure: pregnancyand neonatal outcome

Marco De Santis, Brigida Carducci, Lidia De Santis,

Angela Lucchese and Gianluca Straface

Telefono Rosso, Teratology Information Service, Department of Obstetrics and

Gynaecology, Catholic University of the Sacred Heart, Rome, Italy

ABSTRACT.

Purpose: To assess pregnancy and neonatal outcomes in a woman accidentally

exposed to Verteporfin photodynamic therapy in the third week of pregnancy.

Methods: Post-conception counselling and prospective follow-up by telephone

interview at Telefono Rosso (Teratology Information Service) were carried out.

The baby was examined at birth and at 26months.

Results: The outcome of the pregnancy was normal and a healthy female child with

a normal birthweight was born. The baby’s follow-up was normal at 26months.

Conclusions: This is the first reported case of a childbearing woman being

accidentally exposed to Verteporfin during pregnancy. No fetal or neonatal

adverse effects were documented.

Key words: Verteporfin – phototherapy – pregnancy – neonatal outcome

Acta Ophthalmol. Scand. 2004: 82: 623–624Copyright # Acta Ophthalmol Scand 2004.

doi: 10.1111/j.1600-0420.2004.00247.x

Introduction

Verteporfin (Visudyne), a benzopor-phyrin derivative monoacid A, is asecond generation, light-activated agent.It is approved for the treatment of age-related macular degeneration (AMD)and pathological myopia (PM) inpatients with subfoveal choroidal neo-vascularization (CNV) (Food & DrugAdministration 2000; Harding 2001).

Verteporfin photodynamic therapy isa two-step process that requires intra-venous infusion of the medicine for10min. The therapy is then activated5min after the end of the injection by83 seconds of exposure to a 689� 3 nmwavelength light from a non-thermallaser diode (Food & Drug Administra-tion 2000). Light activation of Verte-

porfin in the plasma results in localdestruction in the neovascular endothe-lium and subsequent vessel occlusion,without damage to normal surroundingtissue (Schmidt-Erfurth & Hasan 2000).

Verteporfin is a suitable alternative tolaserphotocoagulation,whichcandamagethe retina and cause anopsia. However,no longterm clinical trials of Verteporfintherapy are currently available.

According to the Food and DrugAdministration, Verteporfin is classi-fied as a Category C drug and shouldbe given only if the potential benefitjustifies the potential risk to the fetus(Food & Drug Administration 1980).

Preclinical studies using rat fetuseshave reported an increasing incidence

of anophthalmia and microphthalmiaafter Verteporfin intravenous infusionat 10mg/kg/day, which is a dosage 40times higher than the human dose(Food & Drug Administration 2000).In rabbit fetuses the same dosage causeda decrease in weight gain and food con-sumption, but no teratogenic effects(Food & Drug Administration 2000).Fetuses of dams treated with 25mg/kg/day showed wavy ribs, anophthalmiaand microphthalmia (Food & DrugAdministration 2000).

No effects on male or female fertilityhave been observed in rats followingintravenous administration of Verte-porfin up to 10mg/kg/day (Food &Drug Administration 2000).

At present there are no epidemi-ological studies or case reports relatingto Verteporfin exposure in humanpregnancy. We report the only caseof Verteporfin photodynamic therapyin pregnancy referred to our TeratologyInformation Service in the last 3 years.

Case Report

A 35-year-old woman, a primigravida,consulted our Teratology InformationService (TIS) 10weeks into her pregnancybecause she had been exposed to Verte-porfin in the first week after conceiving.

The woman, who was affected bymyopic subfoveal CNV, had been treat-ed with Verteporfin photodynamictherapy. We informed her that only pre-clinical investigations and no human

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data were available, and that ocularlesions have been documented in thefetuses of dams exposed to higherdosages than are used in humans.

We also considered that the mostsensitive period for gestational eyedevelopment is at 6weeks of gestationalage. The woman had been exposed earl-ier. The ultrasound estimate ofembryonic age was in agreement withher last menstrual period.

The subject continued her pregnancyand had a normal outcome, delivering ahealthy female infant at 38weeks ofgestational age (2750 g, Apgar score 9/10). The delivery was carried out byCaesarean section because of obstetric-al indications. Before being dis-charged, the baby was examined bya paediatrician, who excluded any con-genital anomalies. The child’s follow-upexamination at 26months was normal.

Discussion

Verteporfin photodynamic therapy hasbeen shown to be effective in treatingAMD following classic subfoveal CNV(Woodburn et al. 2002). Recently, byextending the therapy’s indications toneovascularization membranes second-ary to myopia (Landy & Brown 2003),it has become more common to treatyounger people with this modality, withthe result that it is no longer a rareoccurrence for a woman of childbearing

age to receive the treatment. As a conse-quence the likelihood of Verteporfinexposure in pregnancy is increasing, butVerteporfin may be administered only ifthe potential benefit justifies the poten-tial risk to the fetus. No data on gesta-tional exposure in human beings are yetavailable.

Preclinical studies have documentedeye anomalies secondary to Verteporfinexposure during the development ofvisual organs. However, the dosageused was at least 40 times higher thanhuman therapeutic doses (Food & DrugAdministration 2000).

Our patient had no side-effects andher fetus showed no malformations. Itis essential to remark that the womanwas exposed at 3weeks of gestationalage, when fetal eye development hadnot yet begun. The present case reportdocuments the sole incidence of Verte-porfin phototherapy in pregnancy so farreported. As a consequence, we considerit advisable to remain cautious aboutVerteporfin treatment inpregnantwomen.

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Harding S (2001): Photodynamic therapy in

the treatment of subfoveal choroidal neovas-

cularization. Eye 15 (3): 407–412.

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photodynamic therapy. Curr Opin Ophthal-

mol 14 (3): 163–168.

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Verteporfin for the treatment of age-related

macular degeneration. Surv Ophthalmol 45

(3): 195–214.

WoodburnKW,EngelmanCJ&BlumenkranzMS

(2002): Photodynamic therapy for choroidal

neovascularization: a review. Retina 22 (4):

391–405.

Received on May 1st, 2003.

Accepted on January 14th, 2004.

Correspondence:

Marco De Santis MD

Telefono Rosso – Teratology Information

Service

Department of Obstetrics and Gynaecology

Catholic University of the Sacred Heart

Largo A Gemelli, 8

00168 Rome

Italy

Tel:þ 39 06 301 56 525

Fax:þ 39 06 355 100 31

Email: marcodesantis@rm.unicatt.it

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