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TOXIC ANTERIOR SEGMENT SYNDROME, AVASTIN ASSOCIATED - CANADA
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A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>
Date: Wed 3 Dec 2008
From: David Patrick <david.patrick@bccdc.ca>
The trademarked drug Avastin (bevacizumab) contains a monoclonal
antibody directed against vascular endothelial growth factor. It is
manufactured for the treatment of metastatic colon cancer. Off-label
intravitreal injection has been used extensively and safely to date
for the treatment of age-related macular degeneration (ARMD).
The reported baseline incidence of sterile endophthalmitis also
described as acute intra-ocular inflammation (1) in this setting
ranges from 0.01-2 percent (1,2). Clinical features include a toxic
anterior segment inflammation (TASS) and variable vitritis. A sudden
increase in sterile endophthalmitis was observed involving patients
in British Columbia from 3-27 Oct 2008. 22 of a cohort of 195
patients treated with Avastin experienced the complication. There had
been no important change in practice among the reporting
ophthalmologists.
A cohort study in this population indicated a relative risk of 9.77
(95 percent CI [confidence interval]: 2.79 to 34.31) associated with
the use of a specific lot of Avastin (Box lot No. B3002B028, Vial No.
30028). No other significant explanatory factors came to light.
Reports of similar experiences have been communicated from at least 6
other Canadian centres (separated by thousands of kilometers) between
3 Oct 2008 and 27 Oct 2008 and are under investigation. Surveillance
and investigation is ongoing, but no cases were reported after
cessation of use of the implicated lot.
Health Canada and Roche have been very helpful in discussions to
date. The box lot number is coded in 2 parts -- B3002 is the
production batch number and B028 is the shipping lot number. Shipping
lot no. B028 of Avastin (tm) (bevacizumab) was only distributed in
Canada with production lot no. B3002 distributed worldwide, except
the USA.
Explanation of the increase in sterile endophthalmitis remains
critical for ophthalmologists. Alternative preparations for treating
the most common cause of age related blindness are unaffordable for
many.
The BC Centre for Disease Control recommends that practitioners using
Avastin for treatment of ARMD record a lot number, patient
indications/outcomes, and would request that you notify us if our
reported association has been replicated in other countries
(<epidserv@bccdc.ca>).
References
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1. Montan P, Lundstrom M, Stenevi U, Thorburn W: Endophthalmitis
following cataract surgery in Sweden: The 1998 National Prospective
Survey. Acta Ophtalmol Scand 2002; 80(3): 258-261 [available at
<http://www3.interscience.wiley.com/cgi-bin/fulltext/118927389/PDFSTART>].
2. Wickremasinghe SS, Michalova K, Gilhotra J, et al: Acute
intraocular inflammation after intravitreous injections of
bevacizumab for treatment of neovascular age-related macular
degeneration. Ophthalmology 2008; 115(11): 1911-5 [abstract available
at
<http://www.ajo.com/article/S0161-6420(08)00445-4/abstract>].
3. Holland SP, Morck DW, Lee TL: Update on toxic anterior segment
syndrome. Curr Opin Ophthalmol 2007; 18(1): 4-8 [abstract available at
<http://www.ncbi.nlm.nih.gov/pubmed/17159439>].
4. Mamalis N, Edelhauser HF, Dawson DG, et al: Toxic anterior segment
syndrome. Review/update. J Cataract Refract Surg 2006; 32: 324-333.
--
David Patrick, MD, FRCPC, MHSc
Director, Epidemiology Services
BC Centre for Disease Control
Vancouver, BC Canada
<david.patrick@bccdc.ca>
Dr.S.Holland, MB, FRCSC, Eye Care Center, BC
Dr.N.Skuridina, MD, MHSC, University of British Columbia
Dr. Lorne Bellan, MD, FRCSC, University of British Columbia
Richard Mathias, MD, FRCPC, University of British Columbia
[ProMED-mail thanks Dr Patrick and his colleagues for this posting.
The HealthMap/ProMED-mail interactive map of Canada is available at
<http://healthmap.org/promed/en?v=55.4,-101.9,4>.
The following discussion is taken from the previous ProMED-mail
posting on this entity, which was associated with endotoxin
contamination of an ophthalmic saline solution:
Toxin anterior segment syndrome (TASS) is not an entity commonly
discussed on ProMED-mail. The following is a discussion on TASS and
its differentiation from infectious endophthalmitis
(<http://ophthalpedia.com/tiki-index.php?page=TASS>):
It is important to differentiate TASS from true infectious
endophthalmitis, because the treatments are completely different, and
the treatment for one isn't appropriate for the other. Symptoms for
the 2 conditions may overlap, making diagnosis difficult. In fact,
surgeons often initially treat TASS as infectious endophthalmitis.
Here are some pointers for separating the 2:
- Early onset: TASS usually is seen soon after surgery, later the
same day or the next. Infectious endophthalmitis, in contrast, most
commonly shows up 3 to 4 days postoperatively.
- Corneal edema: with TASS, patients complain of pain and blurred
vision, and the biggest hallmark is profound limbus-to-limbus corneal
edema. The limbus is the edge between the cornea and the sclera (the
white part of the eye). Some edema will occur with endophthalmitis,
but typically not diffuse limbus-to-limbus corneal edema. Edema after
surgery is specific to areas of trauma, so it tends to be near the
wound or opposite the wound, but some areas are not affected; not so
with TASS.
- Inflammation: on ophthalmological examination, TASS patients have a
marked increase in inflammation in the anterior segment. An increase
in the number of white blood cells and sometimes even a hypopyon (pus
on the anterior chamber of the eye between the cornea and the iris)
can be seen.
- Fixed pupil: TASS impairs the iris sphincter function, and the
pupil tends to be fairly dilated and does not react well to light.
- High intraorbital pressure (IOP): TASS also affects the trabecular
meshwork, a network of fibers involved in the drainage of the aqueous
humor of the eye and located at the iridocorneal angle between the
anterior chamber of the eye and the venous sinus of the sclera. In
endophthalmitis, IOP usually is not elevated. A pressure of 40-70
mmHg is much more likely with TASS.
In a toxic reaction such as TASS, the inflammation will stabilize or
even get slightly better a few hours later. If it is infectious,
signs will get a little worse. If any hint that an infectious process
is occurring early, vitreous fluid aspiration and culture should be
immediately done and antibiotics begun. If it is TASS, the patient
should be treated with a topical corticosteroid every hour and a
non-steroidal 4 times a day.
At one to 3 weeks, TASS may still appear inflamed, but the eye still
may recover nicely if treated properly. If it still looks
significantly inflamed at 6 weeks, however, further improvement is
not likely to occur.
Severe TASS can cause substantial damage such as permanent damage to
the corneal endothelium; profound cystoid nonresolving macular edema;
a permanently dilated fixed pupil; and permanent damage to the
trabecular meshwork, leading to resistant glaucoma that requires
multiple surgical procedures. Milder cases of TASS get better in a
couple of weeks without treatment, so it is likely that cases are
missed. - Mod.LL]
[see also:
2006
----
Endotoxins, ophthalmic solution - USA: recall 20060218.0535]
...................................ll/mj/lm
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