Safety concerns with anti-VEGF agents for wet AMD


Caroline Baumal, MD: Tom, you talked a little bit about safety. What sort of conversation do you have with your patients about safety, especially if it is a treatment-naïve patient and it is the first injection, and have you had any issues with safety in your own practice over the last decade? Have you seen changes in the anti-VEGF safety?

Thomas Albini, MD: The most important conversation to have, one that is routine for me but not for the patient, concerns the risk of endophthalmitis. Those numbers have been steady, with about 1 in 3000 or so patients being at risk with intravitreal injections. That is important to talk about. The other issues that I used to worry about back in 2005, such as retinal detachments or vitreous hemorrhages, are now uncommon. I may mention that, but retinal detachments never quite materialized, so endophthalmitis is the biggest concern I have.

The one concern that is becoming increasingly discussed is intraocular inflammation. That is a low-risk condition, so I do not always talk to patients about that. Even when we would see occasional outbreaks of intraocular inflammation with aflibercept, those cases were self-limited. You could treat them with topicals; the inflammation would go away, and the patients would visually do well. Now that we have seen some more severe cases with occlusive vasculitis with brolucizumab, I have had that discussion with the patients I have on brolucizumab, so that they are aware of what risk exists in reference to vision loss with that agent. There is such a differential between the other agents. Endophthalmitis risk is the same regardless of what agent you use as far as we can tell, but the inflammation and the severity of vision loss associated with that inflammation differs. That is going to be a key feature of agents going forward.

We have been lucky with how well these agents work. We have been really lucky, considering how safe they were, especially now that, in retrospect, we can see what pharmaceutical companies are having difficulties with, with the new agents coming up. Also, we have had an amazing revolution in imaging. We have been very lucky with OCT [optical coherence tomography]. It helps us guide all of these therapies. We do not have to approach this with standard injection protocols for every patient, since treatment is really guided by the anatomy that you see on the scan on a monthly basis.

Caroline Baumal, MD: Since we are talking about safety, Aleksandra, how do you feel about bilateral injections? Do you make any modifications? Do you try to get different lot numbers? Do you use a different setup per eye?

Aleksandra Rachitskaya, MD: I do bilateral injections, and usually it is patient-driven, as are many of the topics we have talked about today. Many patients just want to get it done and do not want to come back. I try to do separate lot numbers. I am not sure if there is any evidence to support that, and sometimes I believe that is for my own peace of mind more than anything else. But there is not a hard and fast rule for that. I have the patient numbed in both eyes at the same time, but I do finish one eye and let them wash the eye before I do the other injection. There is definitely a role for that for a patient who wants to proceed with that, who has a ride and does not want to come back.

Caroline Baumal, MD: Anyone else do anything different? I do bilateral injections for the occasional patient, but it took me some time to get comfortable with it.

Michael Singer, MD: I also try to go for different lot numbers because, although inflammation is very rare in the standard drugs, I was part of the aflibercept group. I had a case of inflammation, and obviously I feel better. In response to Tom’s point and Aleksandra’s, however, I’m probably treating myself more than I am treating the patient. They are so well packaged that it probably does not make a difference, but it makes me feel better.

Thomas Albini, MD: One other important safety concern is about bevacizumab. We must be careful about our source of bevacizumab, because there have been clustered outbreaks. We had a case in Florida where we had 20 strep endophthalmitis cases, with the majority of them going on to NLP [no light perception] vision. There was a subsourcing from one pharmacy to another, and the medicine was processed at a place that did not have experience with aliquoting the medicine, and that is what caused the outbreak. You have to be careful; there can be things happening behind the scenes of which you are unaware. Those of us who work in hospital settings are lucky because we know that it is controlled. There is less control in the external world.

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