Severe inflammation caused by Avastin obtained from a single batch
MyVisionTest
endophthalmitis occurred after intravitreal injection of Avastin
(bevacizumab) obtained from a single batch that occured in Japan circa
2009.
Intravitreous Avastin (IVB) can cause complications, including
traumatic cataract, retinal detachment, and endophthalmitis, with the
reported incidence of endophthalmitis ranging from 0.014% to 0.082%.
Although several cases of sterile endophthalmitis have been reported,
most of these cases have been sporadic, and in most instances, the
inflammation subsided with no treatment or with topical treatment.
In late December 2008, Genentech issued a letter informing
ophthalmologists of about 36 cases of intraocular adverse reactions
after the off-label use of IVB. Most cases that have been reported
occurred in patients who received IVB from a single batch. However,
the precise ocular symptoms, reaction to the treatment, and the visual
prognosis have not been reported.
Methods & Results
One vial of Avastin (100 mg/4 mL) was divided into 20 sterile
injections and kept at 4 degrees C before use. Avastin (1.25 mg/0.05
mL) was injected intravitreally into 19 eyes of 15 patients to treat
macular edema or choroidal neovascularization. All treatments were
performed within 1 week of the Avastin, which was from a single batch,
being aliquotted into the 20 doses.
Of the 19 eyes, 14 showed moderate to severe ocular inflammation
immediately after injection. Cultures of aqueous humor and vitreous
from 5 eyes were negative for bacteria and fungi. Eyes with moderate
inflammation received topical or systemic antibiotics and steroid
treatment. Five eyes with severe inflammation underwent pars plana
vitrectomy because of dense vitreous opacity. Visual acuity returned
to preendophthalmitis levels in 12 eyes but had decreased in 2 eyes at
1 month after the injection.
Case Report
This representative patient was an 82-year-old woman with choroidal
neovascularization (CNV) secondary to high myopia; axial length was
32.0 mm in each eye. Her left eye had been treated 3 times with IVB
previously. Because new CNV had developed in each eye, she had
received intravitreal injections of 1.25 mg Avastin in each eye, with
an interval of 3 months. On the day after the second injection, she
noted moderate ocular pain and conjunctival hyperemia in both eyes.
Slit-lamp examination showed moderate cellular infiltrate in the
anterior chamber and vitreous cavity, but no hypopyon. The aqueous
humor was collected for culture, and intravenous antiobiotic
(imipenem) and topical antibiotic (gatifloxacin and cefmenoxime)
treatment was begun. On the third day after IVB, however, the vitreous
opacity became so dense that the optic disc could barely be seen, and
visual acuity declined to count fingers. Urgent vitrectomy was
performed with instillation of intravitreal antibiotics (vancomycin
and ceftazidime); a sample of the aqueous humor and vitreous was
collected for culture. Both of these cultures and the previously
performed test on aqueous humor were negative for gram negative
bacteria, gram positive bacteria, and fungi. The inflammation subsided
within 1 week, the visual acuity returned to 1.0 logMAR in both eyes
by 1 month after the operation.
Discussion & Conclusions
This study consisted of 14 consecutive cases of endophthalmitis after
intravitreal injection of Avastin that had ben derived from a single
batch. Becuase cultures of the aqueous humor and vitreous from 5 eyes
with severe endophthalmitis were negative for bacteria and fungi,
these eyes were believed to have sterile endophthalmitis. Except for 2
eyes with severe endophthalmitis, the visual acuity returned to that
measured initially. Although it is possible that inflammatory signs
were not seen in those patients who did not return to the hospital for
several days after examination on the day immediately after that of
IVB injection, for analysis, the 19 cases were classified into 3
groups: no inflammation, moderate inflammation and severe
inflammation.
Because Avastin is a full-length humanized IgG antibody, repeated
injection might increase the risk of sterile endophthalmitis. However,
in this study, prior IVB did not affect the severity of ocular
inflammation. Wickremasinghe et al have reported 19 cases of acute
severe intraocular inflammation after IVB treatment at 6 different
clinical practices. They suggested the possibility that trace
endotoxin contamination of the Avastin, contamination whose level was
not sufficient to cause any sign when administered systemically, might
have resulted in the intraocular inflammation. The current reported
cluster caused by a single batch of Avastin seem to support this
hypothesis. The 14 cases in this study might represent a sterile
endotoxin-induced uveitis, considering that 5 eyes were negative for
culture, and the inflammatory reaction in the remaining 9 eyes
subsided with steroid treatment.
In summary, this paper reports 14 consecutive cases of sterile
endophthalmitis after intravitreal injection of Avastin that was
derived from a single batch. Most of these cases developed
inflammatory signs a few days after IVB injection. All eyes, except
two, had a return of visual acuity after treatment, including pars
plana vitrectomy, to that measured initially.
Retina. 2010 Mar;30(3):485-90
http://www.ncbi.nlm.nih.gov/pubmed/19952993
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