Letter to the Editor

Intravitreal ranibizumab,

with or without filter?

Javier A. Montero,1,2 Jose M. Ruiz-Mo-reno2,3 and Eugenia Sanchis-Merino4

1Ophthalmology Unit, Pio del Rio

Hortega University Hospital, Valladolid,Spain2VISSUM, Alicante Institute of Oph-thalmology, Alicante, Spain3Ophthalmology Unit, Albacete MedicalSchool, Castilla La Mancha University,Albacete, Spain4Pio del Rio Hortega University Hospi-tal, Allergy Unit, Valladolid, Spain

doi: 10.1111/j.1755-3768.2011.02278.x

Editor

I ntravitreal ranibizumab (Lucen-tis�; Novartis Pharma AG, Basel,

Switzerland) is at present the treat-ment of choice for subfoveal choroidalneovascularization (CNV) secondaryto age-related macular degeneration.The commercial presentation of Lu-centis� is a 3 ml vial with a chlorobu-tyl rubber stopper containing 0.23 mlof ranibizumab; a blunt 18-gauge filterneedle and a 30-gauge injection needleare also included in the package(http://www.novartis.com.au/PI_PDF/luc.pdf).

The manufacturer instructions rec-ommend using a filter needle toremove the drug from the vial andchanging to a 30-gauge needle to per-form the intravitreal injection. How-ever, owing to the high cost ofranibizumab and the presence of drugin the dead space of the filter needle,it is not an uncommon practice toaspirate ranibizumab with an ordinaryneedle to obtain enough drug to treatmore than one patient per vial.

Filter needles are usually recom-mended to remove fluids from vialswith rubber stoppers for intravenoususe to prevent embolic episodes. Eventhough intravitreal injections do notseem to present such risk, the presenceof small particles in intravitreal injec-tions specially when repeated severaltimes as occurs with CNV treatmentmay obstruct the trabecular meshwork

leading to increased intraocular pres-sure and cause foreign body–inducedinflammation (Buller et al. 1990).

To determine the presence of rubberparticles, we have performed a lightmicroscopy study of the fluid aspi-rated from Lucentis� vials using dif-ferent gauged needles.

Lucentis� vials were filled with fil-tered water which was repeatedly aspi-rated into 10 cc syringes through 21-,25- and 32-gauge needles as well as ablunt 18-gauge 5 lm filter needle (18-,21- and 25-gauge from Beckton-Dick-inson, Huesca, Spain; 32-gauge fromMeso-relle, Biotekne srl, Casalecchiodi Reno, Italy). The procedure wasrepeated 100 times and the aspiratedfluid was filtered through a 1.2 lm filter(Alaris Medical Systems, Basingstoke,UK; Impromediform, Ludenscheld,Germany). Afterwards, the filteringmembrane was removed, placed ontoa glass slide and covered with trans-parent tape to be examined by lightmicroscopy. The fluid aspiratedthrough 21-, 25- and 32-gauge needlespresented several rubber particles,which did not appear in the fluid aspi-rated through 18-gauge filter needle orin the control non-used filter (Fig. 1).

In a second phase we evaluated theamount of fluid retained in two differ-ent types of needles following wateraspiration. Ten 30-gauge needles and

10 18-gauge filter needles wereweighed for three consecutive times ina high precision bascule. Followingrinse with distilled water, the needleswere immediately weighed again andthe amount of fluid retained withinthe needles lumen was estimated. Theaverage weight of the 30- and18-gauge dry needles was 0.176 and0.722 g, respectively, and for thewater-rinsed needles 0.226 and0.795 g, respectively. The amount offluid retained in the needle lumen wasestimated as 0.051 and 0.073 g,respectively, (equivalent to 51 and73 ll) representing one and 1.5 intra-vitreal ranibizumab doses.

The injection of rubber particles hasbeen previously reported in patientson insulin therapy. (Asakura et al.2001) The presence of rubber particlesin intravitreal injections may lead tounexpected inflammatory reactions aswell as sustained increased IOPsecondary to trabecular meshworkobstruction. (Montanari et al. 1996)Latex allergy has been occasionallyreported in patients injected from vialswith rubber stoppers. (Vassallo et al.1995) However, this event is unlikelyin patients treated with Lucentis� asthe stopper is made of chlorobutylrubber and is latex free.

Even though using non-filteringneedles to aspirate Lucentis� from the

(C) (D)

(B)(A)

Fig. 1. Light microscopy of the membranes after filtration of the fluid aspirated through 21G

(A), 25G (B) and 32G (C) needles and through the 18G filter needle (D). Notice the presence of

rubber particles in 1A–C (arrows). (40 · ; bar = 250 lm).

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rubber-stopper vials against the manu-facturer’s instructions may result in agreater amount of available drug, thisprocedure may cause the introductionof rubber material into the eye andlead to unexpected local or even sys-temic side effects.

ReferencesAsakura T, Seino H, Nozaki S & Abe R

(2001): Occurrence of coring in insulin vials

and possibility of rubber piece contamina-

tion by self-injection. Yakugaku Zasshi

121: 459–463.

Buller C, Johnson DH & Tschumper RC

(1990): Human trabecular meshwork

phagocytosis. Observations in an organ

culture system. Invest Ophthalmol Vis Sci

31: 2156–2163.

Montanari P, Troiano P, Marangoni P, Pino-

tti D, Ratiglia R & Miglior M (1996):

Glaucoma after vitreo-retinal surgery with

silicone oil injection: epidemiologic aspects.

Int Ophthalmol 20: 29–31.

Vassallo SA, Thurston TA, Kim SH & To-

dres ID (1995): Allergic reaction to latex

from stopper of a medication vial. Anesth

Analg 80: 1057–1058.

Correspondence:

Javier A Montero, MD, PhD

Pio Del Rio Hortega University Hospital

Calle Dulzaina s ⁄ n47012 Valladolid

Spain

Tel: +34 696 628 427

Fax: + 34 983 331 566

Email: javmonmor@hotmail.com

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