Eyeworld

74 | EYEWORLD | SEPTEMBER 2022 G UCOMA References 1. Liu L, et al. Silicone oil micro- droplets and protein aggregates in repackaged bevacizumab and ranibizumab: effects of long-term storage and product mishandling. Invest Ophthalmol Vis Sci. 2011;52:1023–1034. 2. Kahook MY, et al. High-mo- lecular-weight aggregates in repackaged bevacizumab. Retina. 2010;30:887–892. 3. Atchison EA, et al. The real-world effect of intravitreous anti-vascular endothelial growth factor drugs on intraocular pressure: an analysis using the IRIS Registry. Ophthalmology. 2018;125:676–682. 4. Good TJ, et al. Sustained elevation of intraocular pressure after intravitreal injections of anti-VEGF agents. Br J Ophthal- mol. 2011;95:1111–1114. elevations post-injection of this class of medica- tion has been conflated by observers," he said. He added that there were many reports years ago, including from his group at the Uni- versity of Colorado, that were focused on case clusters of IOP elevation related to compound- ing pharmacy practices. "We found silicone oil bubbles in repackaged bevacizumab syring- es that were related to practices by specific pharmacies and related to shipping-induced mechanical stress on the syringes," he said. 1,2 "I think these events are very different from what is seen in regular practice and with use of FDA-approved versions of anti-VEGF agents. Furthermore, I think compounding pharmacy practices have evolved and are much better now compared to a few years ago." This has resulted in a lower incidence of IOP elevation post-anti- VEGF agents, in Dr. Kahook's experience. Naresh Mandava, MD, has looked at this issue with Dr. Kahook in several studies. Dr. Mandava first became interested in this topic after hearing a talk from a fellow physician who presented a 20% rate of intractable elevation in IOP when injecting bevacizumab. With further exploration into this, Dr. Mandava said he hasn't seen levels that high, but he shared similar com- ments as Dr. Kahook about how certain com- pounding pharmacies seem to have issues, likely due to silicone oil microdroplets in the syringes. This led to further research, as well as con- versations with many large pharmacies. As such, changes have been made to ensure the drug is transferred appropriately. Dr. Mandava added that the way that these syringes were transport- ed on dry ice was also a concern because the drug could freeze and thaw during travel time. "Our multidisciplinary group of clinicians and scientists in ophthalmology and the pharmaceu- tical sciences was the first to elucidate the cause of intractable elevation of intraocular pressure in patients receiving these therapies," he said. "This research led to changes in compounding pharmacy practices, which has decreased the incidence of these complications." Risk factors Dr. Weng said that if the patient has ocular hy- pertension, a diagnosis of glaucoma at baseline, or other risk factors for developing glaucoma, the risk for post-injection IOP elevation is high- er. "Ocular characteristics such as lens status and axial length have been explored without definitive correlation established," she said. "As we age, the sclera becomes increasingly rigid, which could also theoretically contribute to IOP elevation." Dr. Weng added that another factor that seems to increase risk is the frequency or cumu- lative number of injections that a patient has re- ceived. With regard to the medication itself, this is unclear. In one IRIS Registry study of 23,776 patients, on average, 2.6% sustained a clinically significant IOP rise with anti-VEGF drugs overall compared to 1.5% in the fellow untreated eye, Dr. Weng said. However, this difference was not observed with the aflibercept subgroup compared to the bevacizumab and ranibizumab subgroups. 3 Dr. Kahook said his studies have shown that the incidence of IOP spikes was much higher in patients with pre-existing glaucoma. In one study, they found patients with pre-existing glaucoma experienced higher rates of elevated IOP when compared to patients without pre-ex- isting glaucoma (33% vs. 3.1%, respectively; p<0.001). 4 Clinicians should treat patients with extra caution when they require anti-VEGF injections in the setting of co-existing glaucoma and retinal pathology. "Added vigilance to check IOP post-injection and routine check of pressure with Goldmann applanation is key," he said. "When patients are seen in injection clinics, it is imperative that they receive pressure checks as part of the routine workup, something that is not done across the board." Minimizing risk If there is a patient in whom avoidance of an IOP spike is critical, Dr. Weng said the retina specialist could consider performing a pre-in- jection anterior chamber paracentesis and prescribing prophylactic IOP-lowering drops. "Additionally, pre- and post-injection IOP mea- surements as well as close tracking temporally may provide insights into whether a change in treatment frequency or a switch in anti-VEGF agent should be considered." Dr. Mandava said he will always check the pressure before doing an injection. If the continued from page 73

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