Receiving more anti-VEGF injections increases risk of glaucoma
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unilateral intravitreal Lucentis (ranibizumab) and/or Avastin
(bevacizumab) injections are more likely to suffer intraocular
pressure (IOP) elevation of at least 5 mmHg of 2 or more visits if
they recieve a greater number of injections, according to a new study.
Intravitreal anti-vascular endothelial growth factor (VEGF) agents are
rarely associated with ocular adverse events, including intraocular
inflammation, retinal tears, vitreous hemorrhage, endophthalmitis, and
lens changes. With the addition of fluid into the vitreous cavity, it
is not surprising that intraocular pressure (IOP) increases occur
transiently after intravitreal injections. Elevations of IOP as a
complication of anti-VEGF injections were not noted in the ANCHOR and
MARINA trials, or the VISION trial, but recent reports suggest
sustained ocular hypertension (OHT) can occur after intravitreal
Lucentis or Avastin. A post hoc analysis of data from the ANCHOR and
MARINA trials showed a greater liklihood for preinjection IOP of ≥6
mmHg from baseline and a preinjection IOP of ≥25 mmHg at ≥2
consecutive visits in eyes treated with intravitreal Lucentis versus
eye receiving sham injections over the 24-month follow-up period of
these studies. In addition, in a large-scale study of sustained OHT
after intravitreal anti-VEGF treatment, it was noted that patients
with pre-existing glaucoma had higher rates of IOP elevation (33%)
versus those without pre-existing glaucoma(3.1%).
Methods & Results
In this retrospective cohort study the charts of 207 patients with
neovascular AMD who presented to a single physician at a retinal
referral practice over a 6-month period were retrospectively reviewed.
Data recorded included demographic information, clinical findings,
total number of bevacizumab and ranibizumab injections received and
IOP at each visit. Increases above baseline IOP of >5, >10, or >15
mmHg on ≥2 consecutive visits while under treatment were noted.
The frequency of IOP elevation was compared between treated and
untreated eyes. In addition, among treated eyes, frequency and odds
ratio of experiencing IOP elevation >5 mmHg above baseline on ≥2
consecutive visits was stratified by number of injections. For the
main regression analysis, the outcome variable was IOP elevation >5
mmHg on ≥2 consecutive visits and the main independent variable was
total number of injections.
On ≥2 consecutive visits, 11.6% of treated versus 5.3% of
untreated/control eyes experienced IOP elevation of >5 mmHg. The mean
number of injections was higher in those with (24.4; 95% confidence
interval [CI], 20.9-28.0; range, 9-39) than without IOP elevation of
>5 mmHg (20.4; 95% CI, 18.9-21.8; range, 3-48) on ≥2 consecutive
visits. There was an increased odds ratio (5.75; 95% CI, 1.19-27.8; P
= 0.03) of experiencing IOP elevation >5 mmHg on =2 consecutive visits
in patients receiving ≥29 injections compared with ≤12
injections. Of the factors considered, only the total number of
injections showed a statistically significant association with IOP
elevation >5 mmHg above baseline on ≥2 consecutive visits in
treated eyes (P = 0.05).
Discussion & Conclusions
Elevations of IOP were not noted to be a complication of Lucentis
injections in the ANCHOR and MARINA trials as determined by mean
monthly preinjection measurements during the 2-year follow-up. Mean
values for IOP returned to preinjection levels by 1 week after
injections. In contrast, post-hoc analysis of data from the ANCHOR and
MARINA trials showed a greater likelihood for preinjection IOP ≥6
mmHg from baseline and a preinjection IOP ≥25 mmHg at ≥2
consecutive visits in eyes treated with Lucentis (5%) versus eyes
receiving sham injections (1.3%) over the 24-month follow-up period of
these studies.
Transient increases in IOP are not uncommon with the addition of fluid
into the vitreous cavity. There have been several published reports
demonstrating short-term, transient increases in IOP after
intravitreal anti-VEGF agents, which were shown to return to 5 mmHg
above baseline IOP on ≥2 consecutive visits. The data suggested an
increased odds ratio (5.75) of experiencing IOP elevation >5 mmHg of
≥2 consecutive visits among patients receiving ≥29 intravitreal
Lucentis and/or Avastin injections compared with those who received
≤12 injections. The frequency of IOP elevation >5 mmHg on ≥2
consecutive visits in patients receiving ≤12 injections is 4.2%,
which is similar to that found in the untreated control eyes of these
unilaterally injected patients (5.3%). The frequency of IOP elevation
>5 mmHg on ≥2 consecutive visits in patients receiving ≥29
injections was much higher (20%; 10 of 50 eyes).
Of the factors considered, only the total number of injections showed
a statistically significant association with having IOP elevation
related to intravitreal anti-VEGF treatment for neovascular AMD. There
was not an association of a personal history of glaucoma with
experiencing IOP elevation >5 mmHg on ≥2 consecutive visits,
contrary to a previous report. Of note, this study was not adequately
powered to compare the likelihood of experiencing IOP elevation >5
mmHg on ≥2 consecutive visits in patients who were injected with
Avastin versus Lucentis.
In summary, this study suggests that a greater number of injections
may increase the risk for IOP elevation >5 mmHg on ≥2 consecutive
visits in eyes with neovascular AMD receiving intravitreal anti-VEGF
therapy.
Ophthalmology. 2011 Nov 4. [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/22054994
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