Ocular complications of anti–VEGF therapy for AMD
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neovascular age-related macular degeneration (AMD) is associated with
increased risk of endophthalmitis, uveitis, and vitreous hemorrhage,
according to a recent study.
Since 2005, the advent and widespread use of anti–vascular
endothelial growth factor (VEGF) drugs for the treatment of
neovascular AMD has changed dramatically the management of this
disease. Although the visual prognosis for these patients has
improved, each intravitreal injection poses a risk of infection,
postinjection inflammation, retinal tear or detachment, and vitreous
hemorrhage.
A review of safety data from 4 randomized trials of Lucentis (MARINA,
ANCHOR, SAILOR, PIER), in which 3252 patients received more than
28,500 injections, found a 0.05% rate of endophthalmitis per
injection. Retrospective reviews looking at bevacizumab, pegaptanib,
and ranibizumab have found rates of endophthalmitis per injection of
0%, 0.02%, 0.077%, and 0.16%.
Rates of serious intraocular inflammation have ranged widely from
0.03% per injection in the 4 randomized trials of Lucentis, to 0.09%
in a 12-month study of Avastin, to 1.5% in a retrospective review of
Lucentis and Avastin injections. Rates of mild or moderate intraocular
inflammation have been much higher, occurring in up to 17.1% of
patients in the ANCHOR study. Retinal tear and retinal detachment have
been rare in published studies to date; the rate of retinal detachment
was 0% in the MARINA trial, 0.03% in the ANCHOR study, and 0.16% in a
retrospective review of Avastin injections.
To date, the ocular complications of intravitreal injections have not
been studied in the Medicare population. This study examines the
ocular complications of anti-VEGF injections given for neovascular AMD
in a nationally representative longitudinal cohort of elderly persons.
This represents the largest reported sample studying ocular
complications of patients undergoing anti-VEGF treatment and offers
the advantage of reducing surgeon- and center-specific factors.
Methods & Results
Using the Medicare 5% claims database, diagnoses of neovascular AMD
and anti-VEGF injections of Lucentis (ranibizumab), Avastin
(bevacizumab), or Macugen (pegaptanib) were identified from
International Classification of Diseases and Current Procedural
Terminology procedure codes. Six thousand one hundred fifty-four
individuals undergoing anti-VEGF treatment for neovascular AMD (total
of 40,903 injections) were compared with 6154 matched controls with
neovascular AMD who did not undergo anti-VEGF treatment. Propensity
score matching was used to match individuals receiving anti-VEGF
injections with controls. Rates of postinjection adverse outcomes
(endophthalmitis, rhegmatogenous retinal detachment, retinal tear,
uveitis, and vitreous hemorrhage) were analyzed by cumulative
incidence and Cox proportional hazards model to control for
demographic factors and ocular comorbidities.
At the 2-year follow-up, the rates of endophthalmitis per injection
(0.09%; P < .01), uveitis (0.11%; P < .01), and vitreous hemorrhage
per injection (0.23%; P < .01) were significantly higher in the
anti-VEGF treatment group. With Cox proportional hazards modeling, the
anti-VEGF treatment group had a 102% higher risk of severe ocular
complications overall and a 4% increased risk per injection, both of
which were statistically significant (P < .01).
Discussion & Conclusions
Anti-VEGF injections have altered treatment of neovascular AMD
dramatically. Visual prognoses have improved, but treatment requires
as frequent as monthly intravitreal injections with all of the
accompanying risks of endophthalmitis, rhegmatogenous retinal
detachment, retinal tear, uveitis, and vitreous hemorrhage.
The rate of endophthalmitis per injection was 0.09% in this study,
which is higher than that reported for randomized controlled trials
(0.05%), but is comparable with rates reported in retrospective
observational studies. The higher rate of endophthalmitis in this
cohort compared with the randomized clinical trial data may be more
representative of variations in patient populations and actual
practices before and after injection than data from clinical trials
with rigorous prophylaxis protocols.
The study was not powered to detect differences between rates of
endophthalmitis between different types of anti-VEGF treatments. The
rates of endophthalmitis, uveitis, and vitreous hemorrhage were
significantly higher in the anti-VEGF treatment group when compared
with the matched control group, but the differences in rates of
rhegmatogenous retinal detachment and retinal tear were not
statistically significant. The anti-VEGF treatment group probably was
more likely to have active choroidal neovascularization, which may be
responsible for the higher rates of vitreous hemorrhage in this group.
Even after controlling for demographic factors and other ocular
comorbidities, anti-VEGF treatment was associated with a higher
overall risk of ocular complications, with double the risk of serious
ocular complication for those in the anti-VEGF treatment group and a
4.1% higher risk for each anti-VEGF treatment. However, ocular
complications with anti-VEGF treatment still are quite rare and
actually are lower than reported risks with other types of
intravitreal injections. A review of 1739 intravitreal triamcinolone
injections reported rates of endophthalmitis of 0.6% per injection.
This study used a large, nationally representative longitudinal sample
of Medicare 5% inpatient, outpatient, Part B, and durable medical
equipment claims files. This cohort of 20,671 patients with
neovascular AMD, of whom 6154 received 40,903 anti-VEGF injections,
represents the largest study of ocular complications of anti-VEGF
treatment to date, and no other studies have used Medicare claims data
to examine patterns in this particular patient population.
A deficiency of insurance claims is that the data collected are for
billing purposes and do not contain detailed clinical information,
such as the exact level of intraocular inflammation.
In summary, using a nationally representative longitudinal sample of
individuals undergoing anti-VEGF treatment for neovascular AMD, we
found a higher risk of endophthalmitis per injection in this study
(0.09%, or approximately 1 case per 1111 injections) compared with the
rate reported in randomized, clinical trials (0.05%, or 1 case per
2000 injections). The risk of ocular complications also was
significantly higher for persons undergoing anti-VEGF injection when
compared with persons with neovascular AMD who did not receive
anti-VEGF treatment. The results of this study reflect actual practice
patterns at clinical sites across the country, rather than controlled
study environments.
Am J Ophthalmol. 2011 Aug;152(2):266-72
http://www.ncbi.nlm.nih.gov/pubmed/21664593
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