Sustained elevation of intraocular pressure after intravitreal injections of anti-VEGF agents
We read with great interest the article by Good et al. titled "Sustained elevation of intraocular pressure after intravitreal injections of anti-VEGF agents." Authors of other case series have reported sustained intraocular pressure (IOP) elevation following bevacizumab and ranibizumab injections. Good et al. conducted a retrospective chart review of 215 eyes receiving anti-VEGF injections to answer the following questions: 1) What is the frequency of sustained IOP elevation after anti-VEGF injections? 2) What is the frequency of sustained IOP elevation in patients receiving ranibizumab versus bevacizumab? 3) Is glaucoma a risk factor for sustained IOP elevation in these eyes?
With respect to the first question, the authors report that 13 of 215 (6%) eyes developed sustained IOP elevation after treatment with anti-VEGF injections. Nine of the eyes with sustained IOP elevation were treated with bevacizumab originating from a single compounding pharmacy. The authors hypothesize that the bevacizumab molecule itself may not be the cause of the IOP elevation, but rather the packaging, transportation, or storage of the medication. If these 9 cases are excluded, only 4 of 206 (1.9%) developed sustained IOP elevation. The significance of this number, too, must be interpreted with caution. In the absence of a control group, it is impossible to determine if this number is different from similarly matched untreated eyes followed over time. Indeed, randomized controlled clinical trials have not reported increased rates of sustained ocular hypertension after ranibizumab injections. ,
With respect to the second question, the authors report that three of 96 (3.1%) eyes treated with ranibizumab developed sustained IOP elevation compared to 10 of 101 (9.9%) eyes of patients treated with bevacizumab (p=0.049). When the eyes that received bevacizumab from the particular pharmacy were excluded, only 2.4% of bevacizumab treated eyes developed sustained IOP, which is similar to the 3.1% rate in ranibizumab treated eyes. However, accurate comparison between the two groups requires consideration of follow-up times, which the authors do not report. Unless every patient had equivalent lengths of follow-up, these data would be more appropriately summarized as cumulative incidence (events per eye per year), or in a Kaplan-Meier curve, either of which would control for varying follow-up time.
With respect to the third question, the authors report that seven of 21 (33%) eyes with glaucoma treated with anti-VEGF injections developed sustained IOP elevation, which was higher than the overall rate of sustained IOP elevation using a Fisher exact test (p<0.001). Again, variable follow-up times must be considered when comparing these groups. The Kaplan-Meier curve presented in figure 1 compares all patients to glaucoma patients as a function of interval between injections, not as a function of follow-up times. More importantly, in the absence of a control group of untreated eyes with glaucoma, it is impossible to determine if the IOP elevation is due to the anti-VEGF injections, injection of fluid itself into the eye, or simply the natural course of the disease.
In summary, not accounting for variable follow-up and the absence of control eyes severely limits the conclusions that can be drawn from this paper. Based on the results presented, one cannot conclude that anti-VEGF injections result in increased risk of sustained IOP elevation. In addition, one cannot conclude that glaucoma patients receiving anti-VEGF injections are at increased risk of sustained IOP elevation compared to glaucoma patients not receiving these injections.
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