Is IOP Measurement Immediately After Intravitreal Injection of Anti-VEGF Therapy Necessary?
With a better understanding behind the pathophysiology of ocular diseases and the development of new pharmacologic agents to treat them, drug delivery systems for ophthalmic diseases are evolving rapidly. Drug delivery via intravitreal injections have been used since 1910. However, use of intravitreal injections in the management of ocular diseases has exploded since the 1990s with the advent of anti-vascular endothelial growth factor (VEGF) agents. The era of anti-VEGF therapy has revolutionized treatment of disorders such as age-related macular degeneration, macular edema secondary to vascular disorders and neovascularization of the iris and angle. As intravitreal injections become utilized more frequently, questions arise regarding the risks and complications that accompany this delivery system. With each injection, consideration is given to such risks as endophthalmitis, retinal detachment, uveitis, ocular hypertension, intraocular hemorrhage, and cataract.1 In addition to optimizing safety for our patients, practices must remain efficient as the climate of health care changes and patients' demands increase. Common to both the safety and efficiency of intravitreal injections is the injection technique.
One particular aspect of the injection process that highlights these important overlapping concepts of patient safety and clinic efficiency is the monitoring of intraocular pressure (IOP) after injection. Injecting a fixed volume into a closed system undoubtedly raises pressure and this aspect opens the door to important questions. How high does the pressure go immediately following an injection? How long does the pressure remain elevated? How long does it take for IOP to normalize and with what interventions? Is anterior chamber paracentesis necessary? How long is the patient required to wait after injection before being able to leave the office safely? There have been a number of studies over the past few years that address these questions.
Variables that may play a role in IOP changes following intravitreal injections include initial volume of the eye, drug injected, volume injected, size of needle used, and whether there was any reflux after the injection. Injecting the same given volume into a smaller eye may elevate IOP to a greater degree than injecting the same volume into a larger eye. Injecting drugs in a larger volume into the eye will also elevate IOP to a greater extent. Using a large bore needle for the injection may result in a lower IOP and this may be due to more reflux through the larger opening after injection.2,3 This reflux would be more common when the needle is withdrawn without tamponading.
There is also a question of differing IOP elevation based on the agent injected. In reviewing studies that have examined post-injection IOP in patients treated with anti-VEGF agents for age-related macular degeneration, we can begin to appreciate the safety profile for each agent which may guide us in post-injection monitoring of IOP. In studies that examined injection of .09mL of pegaptanib, the majority of patients had normalization of their IOP to less than 30 mmHg after 30 minutes. There were no patients who required intervention with a paracentesis or pressure-lowering medication.3,4,5
In studies that examined injection of .05mL of either bevacizumab or ranibizumab, nearly every patient had an IOP of less than 30 mmHg after 30 minutes. No patients required a paracentesis and only one patient in one study was treated with short-term IOP-lowering agents.3,5,6,7 One should remember, however, that the needle bore used for 0.09 ml of pegaptanib is larger than the needles that are used for injection of ranibizumab and bevacizumab. For short-term IOP change, we believe the injection volume, needle bore size, and the amount of reflux may be more important than the agent used for intravitreal injection.
When measured immediately or shortly after injection, most patients are found to have an acute rise in IOP, although the degree of elevation is variable.3,6,7 However, nearly all patients showed normalization of IOP by 30 minutes post-injection in these studies. Further, it appeared that there was no short-term side effect of intravitreal injections due to changes in IOP. However, most of the patients on anti-VEGF therapy require multiple injections; we do not know the long-term adverse event profile of these injections related to IOP. In addition, in patients with advanced glaucoma or severe vein occlusion, where the ocular perfusion may already be compromised significantly, one should take additional precautions against severe acute IOP elevation from intravitreal injections.
Post-injection monitoring varies among physicians and may include visual acuity measurement, IOP measurement, and evaluation of optic nerve perfusion. While measuring visual acuity and observing the optic nerve perfusion can be performed quickly, monitoring IOP for normalization can take much longer. Not only can this decrease efficiency in the office, but requires the patient to spend more time waiting in the office. Given the data provided in the studies to date, it is reasonable to consider eliminating post-injection IOP measurements in uncomplicated injections. We recommend checking vision with hand movement or counting fingers and/or examining the optic nerve for perfusion but do not feel that it is necessary to keep the patients in the office until the IOP normalizes.3
In conclusion, while intravitreal injections have revolutionized management of disorders such as exudative age-related macular degeneration, they are accompanied by risks and pose a challenge for efficiency in office flow. For routine, uncomplicated anti-VEGF injections at the current volume of 0.05 ml/injection, we can be comfortable knowing that IOP normalizes by 30 minutes, thus potentially eliminating the need to measure IOP post-injection. For injections with larger volumes, patients with a pre-existing history of advanced glaucoma or severe central retinal vein occlusion, or injection into smaller eyes, one may consider additional IOP monitoring post-injection. This is just one method that may improve efficiency and satisfy patient demand without compromising safety.
1. Jager RD, Aiello LP, Patel SC, Cunningham ET Jr. Risks of intravitreous injection: a comprehensive review. Retina 2004;24:676-698
2. Kotliar K, Maier M, Bauer S, Feucht N, Lohmann C, Lanzl I. Effect of intravitreal injections and volume changes on intraocular pressure: clinical results and biomechanical model. Acta Ophthalmol Scand 2007;85:777-781
3. Kim JE, Mantravadi AV, Hur EY, Covert DJ. Immediate Intraocular Pressure Changes Following Intravitreal Injections with Anti-VEGF Agents. Am J Ophthalmol 2008;146:930-934.
4. Hariprasad SM, Shah GK, Blinder KJ. Short-term intraocular pressure trends following intravitreal pegaptanib (Macugen) injection. Am J Ophthalmol 2006;141:200-201
5. Bakri SJ, Pulido JS, McCannel CA, Hodge DO, Diehl N, Hillemeier J. Immediate intraocular pressure changes following intravitreal injections of triamcininolone, pegaptanib, and bevacizumab. Eye 2009;23:181-185
6. Hollands H, Wong J, Bruemn R, Campbell RJ, Sharma S, Gale J. Short-term intraocular pressure changes after intravitreal injection of bevacizumab. Can J Ophthalmol 2007;42:807-811
7. Falkenstein IA, Cheng L, Freeman WR. Changes of intraocular pressure after intravitreal injection of Bevacizumab (Avastin). Retina 2007;27:1044-1047
From the Medical College of Wisconsin, Milwaukee, WI
Inquiries to Judy E. Kim, MD, The Eye Institute, Medical College of Wisconsin, 925 N. 87th street, Milwaukee, WI 53226, 414-955-7875, firstname.lastname@example.org
Funded in part by the Research to Prevent Blindness, Inc.
Brian Larsen, MD: None to disclose
Judy E. Kim, MD: Advisory Board for Alimera Sciences, Allergan, Genentech
About our author(s):
Brian P. Larsen, MD
The Chicago Eye Consultants
Judy E. Kim, MD
The Eye Institute
Medical College of Wisconsin