Sustained elevated intraocular pressures after intravitreal injection of anti-VEGF agents
MyVisionTest
anti-vascular endothelial growth factor (VEGF) agents for age-related
macular degeneration (AMD) is not uncommon, but this study failed to
identify any significant risk factors for its occurrence.
Studies investigating transient increases in intraocular pressure
(IOP) measurements after intravitreal injection (IVI) of anti-VEGF
agents have consistently shown that despite the rapid increase in IOP
measurements at the time of the injection, normalization of IOP
measurements takes place within the first 30 minutes to 60 minutes.
The MARINA and ANCHOR trials revealed no sustained increases in IOP
measurements with Lucentis (ranibizumab) treatment. The VISION and
PA_CORES trials also failed to show any increases in IOP measurements
with Macugen (pegaptanib) and Avastin (bevacizumab) treatments,
respectively. However, recently, there have been several case reports
(28 patients) of sustained elevated IOP measurements in eye receiving
either Lucentis (9 cases) or Avastin (19 cases).
Methods & Results
A retrospective review of medical records identified a total of 127
patients (155 eyes) received an intravitreal injection of
anti-vascular endothelial growth factor agents (bevacizumab,
ranibizumab, or pegaptanib) ranging from 1 to 39 injections for more
than a period of 30 to 1759 days. Among this population, 12 patients
(14 eyes; 9.4%) developed elevated IOP >25 mmHg. Of these, 7 patients
(5.5%) developed sustained elevated IOP (IOP >25 mmHg on 2 separate
visits requiring glaucoma medication or surgery), of which 8 eyes
required topical medications and 1 eye underwent glaucoma surgery.
Mean IOP of injected eyes receiving intravitreal injection was 15.2
± 2.4 mmHg, and the mean IOP was 14.9 ± 2.6 mmHg for
noninjected eyes. Among eyes that had elevated IOPs, there was no
association with injection frequency, number of injections, or
anti-vascular endothelial growth factor agent used.
Discussion & Conclusions
Transient increases in IOP measurements after the injection of
anti-VEGF agents have been well described. However, recent studies
have shown that pressure elevations can occur over a prolonged period.
Interestingly, this phenomenon was not described in the initial
large-scale studies of each individual anti-VEGF agent and although
mechanisms such as low-grade inflammatory reactions, outflow tract
occlusion, and other mechanisms have been proposed, the exact cause of
the sustained elevated IOP measurements continues to be poorly
understood.
The researchers analyzed the collective set of IOP measurements over a
set period of 300 days to determine whether there was any pattern of
change in IOP measurements correlating with the number of injections
received during this time. They hypothesized that the increase in
pressure should correlate with the number of injections. Based on the
reletively flat slope of FIGURE 2, they did not observe any
association between the frequency of injections an eye received and a
change in IOP measurements. Additionally, as in FIGURE 3, there was no
observed association between the number of injections and increase in
IOP measurements among those who did not show a sustained elevation in
IOP measurements. The researchers found no evidence that one can
predict a tendency toward increasing measured IOP as one continues to
administer IVIs. Thus, this study suggests that sustained elevated IOP
measurements are independent of the frequency of injections and can
occur after a single IVI and after as many as 39 injections. These
findings argue against the recent theory that sustained elevated IOP
measurements are being caused by outflow tract obstruction by
high-molecular-weight protein aggregates found in injection packaging.
Some previous case reports have speculated that an increase in IOP may
be more specific to either Lucentis or Avastin, while other studies
have suggested that this can occur with either drug. This study
supports this latter assertion but also brings to attention that
sustained elevated IOP measurements can occur after intravitreal
Macugen (pegaptanib) injection. To our knowledge, there has been no
previously reported cases of sustained increased IOP measurements
immediately after Macugen injections, although there have been a total
of two reported cases of sustained pressure elevations in patients who
initially had Macugen injections before switching to intravitreal
Avastin and/or Lucentis injections. At this point, we have
insufficient data to determine if the risk is different between these
three anti-VEGF agents.
The current study of sustained elevated IOP measurements certainly
confirms the reports of others that sustained elevated IOP
measurements can occur after IVIs. However, the study does not support
but cannot rule out any of the currently proposed explanations, which
include low-grade inflammatory reactions not detectable by standard
slit-lamp examination, direct drug toxicity to the physiologic
functioning of the trabecular meshwork, and mechanical obstruction by
injected materials in the trabecular meshwork. The etiology of this
problem remains unknown, and we have to consider more idiosyncratic
factors for its pathogenesis, including the unique genetic makeup of
each patient.
In summary, elevated IOP, sustained or unsustained, after intravitreal
injection is not uncommon. No association with patient demographics or
injection history was identified in the authors' study population.
Retina. 2011 Jun;31(6):1028-35
http://www.ncbi.nlm.nih.gov/pubmed/21836409
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