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CORRESPONDENCE

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Avastin Doesn’t Blind People, PeopleBlind People

EDITOR:

WE READ WITH GREAT INTEREST THE PERSPECTIVE BY GON-

zalez and associates regarding how to compound bevaci-zumab safely to minimize the risks of contamination.1 Thearticle, however, overlooks a fact that seems to be lost inthe bevacizumab versus ranibizumab debate: using a med-ication that is approved by the Food and Drug Adminis-tration (FDA) for intraocular injection avoids the need toexpose patients to the added risk of a compounded,off-label agent like bevacizumab.

Although Gonzalez and associates provide a usefulblueprint for compounding bevacizumab, it is unclear ifthis will result in fewer outbreaks down the road. It istrue that bevacizumab does not blind people, but com-pounding the bevacizumab does add several differentsteps before the drug is administered and involvesmultiple people in different pharmacies and deliveryareas—people who are not and will never be infallible.No amount of training, inspection, and regulation isgoing to eliminate completely the risk of human error.The article makes the point that administrating bevaci-zumab may be safer than administrating ranibizumabbecause use of the former agent avoids the need towithdraw the drug from a vial. However, if suppliedaccording to the described method, bevacizumab stillrequires exchanging a cap with a needle. Moreover, toour knowledge, there have never been any outbreaks ofendophthalmitis after using ranibizumab, and endoph-thalmitis outbreaks after compounded bevacizumab aredisasters.2

Although the Comparison of AMD Treatments Trials(CATT) demonstrated that bevacizumab and ranibizumabmay result in similar visual outcomes,3 it is unclear if therisks of these agents are similar because of the need forcompounding with bevacizumab, the unanswered ques-tions regarding bevacizumab’s systemic safety notwith-standing.4 Unfortunately, many patients will not have thehoice—for economic reasons—of using an FDA-ap-roved agent like ranibizumab even if they may feel lesshan comfortable about the risks of compounding. In ourpinion, this is the most troubling take home message fromonzalez and associates’ article.

PAUL B. GREENBERG

MAGDALENA G. KRZYSTOLIK

VICTORIA L. TSENG

Providence, Rhode Island

© 2012 BY ALL RIG610

CONFLICT OF INTEREST DISCLOSURES: ALL AUTHORShave completed and submitted the ICMJE Form for Disclosure ofPotential Conflicts of Interest and none were reported. The viewsexpressed in this article are those of the authors and do not necessarilyreflect the position or policy of the United States (US) Department ofVeterans Affairs or the US government.

REFERENCES

1. Gonzales S, Rosenfeld PJ, Stewart MW, et al. Avastin doesn’tblind people, people blind people. Am J Ophthalmol 2012;153(2):196–203.

. Goldberg RA, Flynn HW, Isom RF, et al. An outbreak ofstreptococcus endophthalmitis after intravitreal injection ofbevacizumab. Am J Ophthalmol 2012;153(2):204–208.

. CATT Research Group, Martin DF, Maguire MG, et al.Ranibizumab and bevacizumab for neovascular age-relatedmacular degeneration. N Engl J Med 2011;364(20):1897–1908.

. Miciele JA, Micieli A, Smith AF. Identifying systemic safetysignals following intravitreal bevacizumab: systematic reviewof the literature and the Canadian Adverse Drug ReactionDatabase. Can J Ophthalmol 2010;45(3):231–238.

REPLY

WE APPRECIATE THE INTEREST FROM GREENBERG AND AS-

sociates in our article “Avastin Doesn’t Blind People,People Blind People,” published in the February 2012 issueof the American Journal of Ophthalmology.1 We agree thatthere will always be the risk of contamination whencompounding a medication and that generally there is alower risk of contamination from a drug manufactured bya pharmaceutical company than one compounded in apharmacy. However, in this situation, the risk of contam-ination comes from transferring a drug manufactured by apharmaceutical company into a syringe. Compared with aranibizumab transfer performed in the nonsterile environ-ment of a clinic, the transfer of bevacizumab should havea much lower risk of contamination because it is performedusing a laminar flow hood and an aseptic technique. Ourstatement in the Perspective, which was referenced intheir letter, that the administration of bevacizumab is saferthan ranibizumab deals with the advantage of the airquality and technique used in the preparation of bevaci-zumab compared with the standard preparation of ranibi-zumab. However, if the compounder fails to follow therecommended guidelines for preparing bevacizumab, thenthe risk of contamination of multiple patients is higherwith bevacizumab. Endophthalmitis will never be elimi-

nated totally from clinical practice, but endophthalmitis

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resulting from a compounding mistake should never betolerated.

The goal of our article was to provide a basic overviewof United States Pharmacopeia 797 as it relates to theappropriate compounding or repackaging of Avastin(Genentech/Roche, South San Francisco, California, USA)for intravitreal injection and to provide specific recom-mendations to prevent microbial contamination by thepreparer. We had no intention of entering into the debateover which anti–vascular endothelial growth factor drug aphysician should prescribe, which is a decision best madebetween the physician and the patient. We also had nointention of comparing the safety of one drug versus theother, which is being addressed by ongoing comparativestudies and was addressed by another recent Perspective inthe Journal.2 As Greenberg and associates acknowledge inheir letter, economics will continue to play a role in therug selection process between repackaged Avastin andgents approved by the Food and Drug Administration,uch as Lucentis (Genentech/Roche) or Eylea (Regeneron,arrytown, New York, USA). Keep in mind that not allatients who are financially disadvantaged qualify for freerug or copay assistance and that there is widespread use ofepackaged Avastin outside of the United States. Thehetorical question we always hear asked is, “Which drugould you use if price wasn’t the issue?” This question haso answer because price is always an issue, whether it’s an

ssue for the patient or the payer. In the end, we all end upaying. The more appropriate question is, “Which drugould you use if you had to pay out of pocket for the drug?”he answer to this second question is fairly obvious. Mostf us would use Avastin, but we would want it preparedafely.

It is also important to note that repackaged Avastin issed not only for wet age-related macular degeneration oracular edema occurring after retinal vein occlusions,hich are the Food and Drug Administration-approved

ndications for Lucentis. Repackaged Avastin also is usedor other off-label ophthalmic indications, such as diabeticacular edema, proliferative diabetic retinopathy, neovas-

ular glaucoma, and retinopathy of prematurity. The off-abel use of drugs in ophthalmology and general medicines extremely common, legal, necessary, and expected. Themportance of compounding and repackaging has nevereen greater than in the present pharmaceutical environ-ent, where there are current shortages for so many

ifferent manufactured drugs. Adhering to optimal com-ounding procedures as discussed in our Perspective willnsure that pharmacists and physicians provide the bestossible care for patients.

SERAFIN GONZALEZ

PHILIP J. ROSENFELD

Miami, FloridaMICHAEL W. STEWART

Jacksonville, Florida

CORRESPONVOL. 154, NO. 3

CONFLICT OF INTEREST DISCLOSURES: SEE THE ORIGINALarticle1 for any disclosures of the authors.

REFERENCES

1. Gonzalez S, Rosenfeld PJ, Stewart MW, Brown J, Murphy SP.Avastin doesn’t blind people, people blind people. Am JOphthalmol 2012;153(2):196–203.

2. Davis J, Olsen TW, Stewart M, Sternberg P Jr. How thecomparison of age-related macular degeneration treatmentstrial results will impact clinical care. Am J Ophthalmol2011;152(4):509–514.

The Effect of Alpha Antagonists onPupil Dynamics: Implications for theDiagnosis of Intraoperative FloppyIris Syndrome

EDITOR:

THEODOSSIADIS AND ASSOCIATES INVESTIGATED THE USE

of a recent technology to perform quantitative assessmentof the pupil dynamics in patients receiving systemictreatment with �1-adrenergic receptor antagonists.1 Theyuggested that preoperative identification of the eyes likelyo demonstrate intraoperative floppy iris syndrome (IFIS)hould be performed, because it allows “the surgeon to plannd prepare for a more complicated procedure and findotential solution in a timely manner to prevent anyostoperative visual disturbances.” In fact, they added thatIFIS might increase the risk of vision-threateningomplications.”

We respectfully highlight that patients receiving �1-lockers are a tiny percentage, representing 2% of theataract population.2 If it is true that with aging of the

male population the incidence of benign prostatic hyper-plasia increases, the awareness regarding the possibility ofIFIS during cataract surgery has been raised over the pastfew years among physicians, who are encouraged to use thesystemic drugs that are less likely induce IFIS, such asalfuzosin.3 Current good medical practice recommendsthat cataract surgery in all the patients with history of�1-blockers treatment should be assigned to expert sur-geons who master all the complimentary strategies shownto be effective in minimizing the risk of intraoperativecomplications related to IFIS. These include appropriatewound construction, use of intracameral adrenergic drugs,mechanical pupillary dilation, appropriate ophthalmic vis-cosurgical device, and low-motion phacoemulsification. Infact, in a multicenter prospective study involving seniorcataract surgeons using some of the above-named strate-gies, Chang and associates observed that 95% of thetreated eyes achieved a final corrected distance visual

acuity of 20/40 or better, with a posterior capsule rupture

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