Anti-VEGF Injection IOP Elevations
Anti-VEGF agents have been employed for a variety of uses in the treatment of ocular disease, and several reports have shown both acute and chronic increases in intraocular pressure following injection of these drugs. This article will review these data and their relevance to glaucoma.
In 2004, pegatinib (Macugen) was the first anti-VEGF agent approved for intravitreal injection for the treatment of neovascular age-related macular degeneration. Since then, a host of other agents including ranibizumab (Lucentis), bevacizumab (Avastin), aflibercept (Eylea), and more recently brolucizumab (Beovu) have been approved for the treatment of macular edema secondary to diabetes, branch retinal vein occlusion, and central retinal vein occlusions as well as degenerative myopia. 
Soon after the introduction of these drugs, reports of acute spikes in intraocular pressure (IOP) began to emerge and have been reported in multiple studies.              Nonetheless, the MARINA and ANCHOR clinical trials, which demonstrated the efficacy of Bevacizumab for treatment of neovascular age-related macular degeneration, found that these spikes were transient.  However, in a post-hoc analysis by Bakri et al, patients treated with anti-VEGF agents were found to have a greater likelihood of an increase in pre-injection IOP ≥6 mmHg from baseline and a concurrent IOP of ≥21 mmHg or ≥25 mmHg at ≥2 consecutive visits compared to those who received sham injections over a 24-month follow up period. Since then, a host of studies have been conducted demonstrating a sustained increase IOP following anti-VEGF injection. Given that the same aging population for which these drugs are most often employed is also at risk for developing glaucoma, understanding the potential for short- and long-term IOP spikes and the impact of anti-VEGF injections on glaucomatous progression is of critical importance. In this article, we will discuss data on the post-injection spike, long-term sustained IOP elevation, the impact on glaucomatous progression in susceptible eyes, and possible prophylactic measures that may be taken.
Post-injection spike in IOP
A post-injection spike in IOP is a logical outcome as the eye undergoes volume expansion. Summing the effect of 14 studies on short-term pressure effects of anti-VEGF injections (median 60 injected eyes, 12-853), Hoguet et al found 100% of patients had an increase in IOP (mean ≤18 mmHg pre-injection) to 28.3-55.2 at 1 minute; at 10-15 minutes the IOP decreased to 22.8-25.8 mmHg, and at 30 minutes it further decreased to 17.6-24.5 mmHg2. IOP continued to decrease over time in studies that captured longer time points, suggesting these IOP spikes were transient. Typically, post-injection IOP returned to baseline within 1 hour.
Long-term sustained IOP elevation
The best evidence for sustained IOP elevation following anti-VEGF injections comes from a post-hoc analysis of the MARINA and ANCHOR trials by Bakri et al which found the incidence of a >6 mmHg IOP spike from baseline in at least one visit with a simultaneous IOP ≥21 mmHg was 23.6% in the 0.3mg ranibizumab group, 26.1% in the 0.5 mg ranibizumab group, and 13.6% in the sham injection groups. Several studies have replicated these findings in different populations as shown in the table below.           Several cases have also been documented in which sustained IOP elevation following injection necessitated surgical filtration procedures.   In fact, a recent case-control study in Canada found that eyes with ≥7 annual injections had a significantly greater odds ratio of undergoing glaucoma drainage surgery than controls. This finding is bolstered by several studies showing total number of injections to be a risk factor for sustained IOP elevation as well as greater frequency of injections and pre-existing diagnosis of glaucoma prior to initiation of IVIs.     
|Author||Definition of IOP elevation||# Eyes||Mean # Injections||Mean Follow-Up (Weeks)||Preinjection IOP (Mean)||IOP at Study End (Mean)||% With Sustained IOP Elevation|
|Al-Abdullah 2015||IOP ≥6 mmHg above baseline, increase >20%, or IOP >24 mmHg on ≥2 consecutive visits||760||3.4||78.0||17.2||17||5.8%|
|Atchison 2018||IOP ≥6 mmHg above baseline and >21 mmHg on ≥2 consecutive visits||23776||7.9||96.6||15.3||14.4||2.6%|
|Choi 2011||IOP >25 mmHg on 2 separate visits||155||7.0||57.4||14.4||15.3||5.5%|
|Freund 2015||IOP >21 mmHg for ≥2 consecutive visits||595||16.0||96.0||15||NR||8.4%|
|Hoang 2012||IOP >5 mmHg above baseline on ≥2 consecutive visits||207||20.8||148.6||NR||NR||11.6%|
|Kim 2014||IOP >5 mmHg above baseline on ≥2 consecutive visits||629||9.5||151.7||14.1||14.2||3.7%|
|Mathalone 2012||IOP ≥22 mmHg and change from baseline of ≥6 mmHg recorded on ≥2 consecutive visits and lasting ≥30 days||201||4.0 (median)||68.0||14.8||15.5||11.0%|
|Bilgic 2020||IOP ≥6 mmHg above baseline and/or >24mmHg on 2 or more consecutive visits||1021||NR||183.7||NR||NR||8.9%|
|Gabrielle 2020||IOP ≥6 mmHg above baseline and >21mmHg at a single visit||3429||NR||52.0||14.4||13.9||4.9%|
|Cui 2019||having filled a prescription for IOP-lowering medication or having a new diagnosis of glaucoma, glaucoma suspect, or ocular hypertension||17113||NR||135.2||NR||NR||12.0%|
NR = not recorded
A handful of reports have been published in which no increased risk of IOP elevation over a 1-40 month period was found.      Only one of these studies, however, explicitly defines IOP elevation. Wehrli et al found no significant difference in sustained IOP elevation between 270 injected eyes and 195 control eyes with sustained IOP elevation defined as ≥22mmHg on 2 consecutive visits or >26mmHg on a single visit over a 5 year period. Compared to the studies which did find an increased risk of IOP elevation in anti-VEGF-treated eyes, these studies were limited by smaller sample sizes (average 111 vs 4,372 eyes) and shorter follow-up periods (72 vs. 106 weeks). Several risk factors have been shown to be associated with sustained IOP elevation following injection. First, and perhaps least surprisingly, is total number of injections. In a multitude of studies the total number of injections has been shown to be associated with an increased risk of sustained IOP elevation.       Some have suggested that the an accumulation of some component of the injection may effectively clog the trabecular meshwork, which is supported by the decrease in outflow facility seen by Schiøtz tonography. Importantly, a pre-existing glaucoma diagnosis was found to be associated with sustained IOP elevation with sustained IOP defined as ≥22 mm Hg lasting ≥30 days, recorded on at least two separate visits and a change from baseline of >6 mm Hg. Another study similarly found an association with preexisting glaucoma with sustained IOP defined as a rise in IOP above baseline by ≥6 mmHg and/or >24 mmHg on 2 or more consecutive visits. Other risk factors studied have included higher injection volume and specific anti-VEGF agents, with two studies finding ranibizumab to be associated with more IOP elevation than aflibercept.
Development of Glaucoma
Whether or not the use of anti-VEGF agents is associated with the development of glaucoma is of great interest. Filek et al found an increased cup-to-disc ratio and cup volume was observed over a 2 year study period in patients undergoing treatment with ranibizumab for diabetic macular edema, however there was no significant trend in deterioration of visual fields. Similarly, Gómez-Mariscal et al found significant cup widening, deepening, and RNFL thinning seen in eyes treated with anti-VEGF agents. Regarding a diagnosis of glaucoma, Wingard et al found the incidence of glaucoma or ocular hypertension diagnosis was significantly higher in patients undergoing a higher frequency of anti-VEGF injection for AMD for each additional injection over the most injection-intense 6 month period for any given subject. Furthermore, several studies have found an increased incidence of surgical filtration surgeries among patients undergoing repeated anti-VEGF injections.  
Exacerbation of Glaucoma
Exacerbation of glaucoma following the use of anti-VEGF agents has been documented. In 2017, Eadie et al used a big-data approach to investigate the risk of necessitating glaucoma surgery in all patients in British Columbia receiving bevacizumab injections for ARMD over a four-year period. Using 10:1 matched controls for age, glaucoma diagnosis, data, and follow-up time, there was an adjusted risk ratio of 2.48 for undergoing glaucoma surgery in patients receiving bevacizumab. Furthermore, 7 or more injections was associated with an increased risk of surgery. Additionally, in 2019 Du et al found a higher rate of visual field decline, glaucoma surgery, and RNFL thinning in injected glaucomatous eyes over an eight year period compared to those not undergoing injection. This study was limited by a small sample size and a high percentage of retinal vein occlusions in the glaucomatous group (which are associated with RNFL thinning). Nonetheless, significant RNFL thinning and cup widening following repeated injections has been observed in another study by Gómez-Mariscal et al in which age-related macular degeneration was the primary indication for anti-VEGF injection.
Proposed Mechanism for sustained IOP increase following anti-VEGF Injection
Multiple mechanisms have been proposed to explain a sustained increase in IOP following anti-VEGF injections. A decrease in outflow facility has been one proposed mechanism secondary to either obstruction by some component of the injection or an inflammatory response. Supporting this theory is one study which found outflow facility to be significantly decreased in eyes receiving anti-VEGF therapy as measure by Schiøtz tonography when patients had ≥20 intravitreal injections. Microparticle obstruction of the trabecular meshwork is one possibility that has been explored by multiple groups, whether due to high-molecular weight protein aggregates from medication packaging or silicone microdroplets from syringes.   Alternatively, a direct inflammatory effect of anti-VEGF agents on trabecular meshwork cells has been explored. Kahook et al demonstrated 4 mg/ml bevacizumab slows the metabolism and replication of trabecular meshwork cells in vitro, possibly contributing to decreased outflow facility. Additionally, an inflammatory response to monomer antibodies, protein aggregates or high molecular weight molecules may lead to a trabeculitis with impaired aqueous humor outflow.  Disruption of nitric oxide signaling secondary to VEGF blockade has also been proposed to disrupt aqueous outflow and contribute to ocular hypertension59.
Management and Prevention
Several prophylactic measures have been suggested to prevent the acute post-injection IOP spike in patients for whom large IOP fluctuations pose a risk such as those with advanced glaucomatous disease. Pre-injection topical glaucoma medications have proven successful in limiting post-injection IOP elevation in several studies.      Additionally, the presence of vitreous reflux following injection has been associated with a lower IOP spike.  Other factors found to prevent acute IOP spikes include ocular decompression by cotton swabs, a history of glaucoma surgery, pseudophakia, and anterior chamber paracentesis.
Regarding sustained IOP elevation following long-term anti-VEGF therapy, no successful mitigation strategy has been thoroughly investigated. Wingard et al suggested that patients with known risk factors for sustained IOP elevation should consider lower frequency injections at initiation of therapy and extension of the inter-injection interval. Nonetheless, foregoing anti-VEGF therapy or extending the intervals of injection risks progression of the diseases these agents treat. Ultimately, patients should be monitored for development of ocular hypertension, and those who develop a sustained increase in IOP should be evaluated periodically for glaucomatous changes via an optic nerve OCT and visual field testing. Referral to a glaucoma specialist should be considered in patients with concerning features.
- Gragoudas ES, Adamis AP, Cunningham ET, Jr., Feinsod M, Guyer DR. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med. 2004;351(27):2805-16.
- Hoguet A, Chen PP, Junk AK, Mruthyunjaya P, Nouri-Mahdavi K, Radhakrishnan S, et al. The Effect of Anti-Vascular Endothelial Growth Factor Agents on Intraocular Pressure and Glaucoma: A Report by the American Academy of Ophthalmology. Ophthalmology. 2019;126(4):611-22.
- Markham A. Brolucizumab: First Approval. Drugs. 2019;79(18):1997-2000.
- El Chehab H, Agard E, Russo A, Boujnah Y, Dot C. Intraocular Pressure Spikes after Aflibercept Intravitreal Injections. Ophthalmologica. 2016;236(1):43-7.
- Falkenstein IA, Cheng L, Freeman WR. Changes of intraocular pressure after intravitreal injection of bevacizumab (avastin). Retina. 2007;27(8):1044-7.
- Farhood QK, Twfeeq SM. Short-term intraocular pressure changes after intravitreal injection of bevacizumab in diabetic retinopathy patients. Clin Ophthalmol. 2014;8:599-604.
- Frenkel RE, Mani L, Toler AR, Frenkel MP. Intraocular pressure effects of pegaptanib (Macugen) injections in patients with and without glaucoma. Am J Ophthalmol. 2007;143(6):1034-5.
- Gismondi M, Salati C, Salvetat ML, Zeppieri M, Brusini P. Short-term effect of intravitreal injection of Ranibizumab (Lucentis) on intraocular pressure. J Glaucoma. 2009;18(9):658-61.
- Hollands H, Wong J, Bruen R, Campbell RJ, Sharma S, Gale J. Short-term intraocular pressure changes after intravitreal injection of bevacizumab. Can J Ophthalmol. 2007;42(6):807-11.
- Kiddee W, Montriwet M. Intraocular Pressure Changes in Non-Glaucomatous Patients Receiving Intravitreal Anti-Vascular Endothelial Growth Factor Agents. PLoS One. 2015;10(9):e0137833.
- Kim JE, Mantravadi AV, Hur EY, Covert DJ. Short-term intraocular pressure changes immediately after intravitreal injections of anti-vascular endothelial growth factor agents. Am J Ophthalmol. 2008;146(6):930-4.e1.
- 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(7):777-81.
- Lim HB, Kim MS, Jo YJ, Kim JY. Short-Term Visual Acuity and Intraocular Pressure Changes and Their Correlation after Anti-Vascular Endothelial Growth Factor Injection. Ophthalmologica. 2016;236(1):36-42.
- Mojica G, Hariprasad SM, Jager RD, Mieler WF. Short-term intraocular pressure trends following intravitreal injections of ranibizumab (Lucentis) for the treatment of wet age-related macular degeneration. Br J Ophthalmol. 2008;92(4):584.
- Omay E, Elgin U, Sen E, Yilmazbas P. The early effects of intravitreal anti vascular endothelial growth factor agents on intraocular pressure and central corneal thickness. Int Ophthalmol. 2016;36(5):665-70.
- Wu L, Evans T. [Immediate changes in intraocular pressure after an intravitreal injection of 2.5 mg of bevacizumab]. Arch Soc Esp Oftalmol. 2010;85(11):364-9.
- Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1419-31.
- Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1432-44.
- Bakri SJ, Moshfeghi DM, Francom S, Rundle AC, Reshef DS, Lee PP, et al. Intraocular pressure in eyes receiving monthly ranibizumab in 2 pivotal age-related macular degeneration clinical trials. Ophthalmology. 2014;121(5):1102-8.
- Al-Abdullah AA, Nowilaty SR, Asghar N, Al-Kharashi AS, Ghazi NG. Intraocular pressure trends after intravitreal injections of anti-vascular endothelial growth factor agents for diabetic macular edema. Retina. 2015;35(3):440-8.
- Atchison EA, Wood KM, Mattox CG, Barry CN, Lum F, MacCumber MW. The Real-World Effect of Intravitreous Anti-Vascular Endothelial Growth Factor Drugs on Intraocular Pressure: An Analysis Using the IRIS Registry. Ophthalmology. 2018;125(5):676-82.
- Choi DY, Ortube MC, McCannel CA, Sarraf D, Hubschman JP, McCannel TA, et al. Sustained elevated intraocular pressures after intravitreal injection of bevacizumab, ranibizumab, and pegaptanib. Retina. 2011;31(6):1028-35.
- Freund KB, Hoang QV, Saroj N, Thompson D. Intraocular Pressure in Patients with Neovascular Age-Related Macular Degeneration Receiving Intravitreal Aflibercept or Ranibizumab. Ophthalmology. 2015;122(9):1802-10.
- Hoang QV, Mendonca LS, Della Torre KE, Jung JJ, Tsuang AJ, Freund KB. Effect on intraocular pressure in patients receiving unilateral intravitreal anti-vascular endothelial growth factor injections. Ophthalmology. 2012;119(2):321-6.
- Kim YJ, Sung KR, Lee KS, Joe SG, Lee JY, Kim JG, et al. Long-term effects of multiple intravitreal antivascular endothelial growth factor injections on intraocular pressure. Am J Ophthalmol. 2014;157(6):1266-71.e1.
- Mathalone N, Arodi-Golan A, Sar S, Wolfson Y, Shalem M, Lavi I, et al. Sustained elevation of intraocular pressure after intravitreal injections of bevacizumab in eyes with neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2012;250(10):1435-40.
- Silva R, Axer-Siegel R, Eldem B, Guymer R, Kirchhof B, Papp A, et al. The SECURE study: long-term safety of ranibizumab 0.5 mg in neovascular age-related macular degeneration. Ophthalmology. 2013;120(1):130-9.
- Bilgic A, Kodjikian L, Chhablani J, Sudhalkar A, Trivedi M, Vasavada V, et al. Sustained Intraocular Pressure Rise after the Treat and Extend Regimen at 3 Years: Aflibercept versus Ranibizumab. J Ophthalmol. 2020;2020:7462098.
- Gabrielle PH, Nguyen V, Wolff B, Essex R, Young S, Hunt A, et al. Intraocular Pressure Changes and VEGF Inhibitor Use in Various Retinal Diseases: Long-Term Outcomes in Routine Clinical Practice: Data from the Fight Retinal Blindness! Registry. Ophthalmol Retina. 2020.
- Cui QN, Gray IN, Yu Y, VanderBeek BL. Repeated intravitreal injections of antivascular endothelial growth factors and risk of intraocular pressure medication use. Graefes Arch Clin Exp Ophthalmol. 2019;257(9):1931-9.
- Eadie BD, Etminan M, Carleton BC, Maberley DA, Mikelberg FS. Association of Repeated Intravitreous Bevacizumab Injections With Risk for Glaucoma Surgery. JAMA Ophthalmol. 2017;135(4):363-8.
- Skalicky SE, Ho I, Agar A, Bank A. Glaucoma filtration surgery following sustained elevation of intraocular pressure secondary to intravitreal anti-VEGF injections. Ophthalmic Surg Lasers Imaging. 2012;43(4):328-34.
- Du J, Patrie JT, Prum BE, Netland PA, Shildkrot YE. Effects of Intravitreal Anti-VEGF Therapy on Glaucoma-like Progression in Susceptible Eyes. J Glaucoma. 2019;28(12):1035-40.
- Pershing S, Bakri SJ, Moshfeghi DM. Ocular hypertension and intraocular pressure asymmetry after intravitreal injection of anti-vascular endothelial growth factor agents. Ophthalmic Surg Lasers Imaging Retina. 2013;44(5):460-4.
- Segal O, Ferencz JR, Cohen P, Nemet AY, Nesher R. Persistent elevation of intraocular pressure following intravitreal injection of bevacizumab. Isr Med Assoc J. 2013;15(7):352-5.
- Beato J, Pedrosa AC, Pinheiro-Costa J, Freitas-da-Costa P, Falcão MS, Melo A, et al. Long-Term Effect of Anti-VEGF Agents on Intraocular Pressure in Age-Related Macular Degeneration. Ophthalmic Res. 2016;56(1):30-4.
- Good TJ, Kimura AE, Mandava N, Kahook MY. Sustained elevation of intraocular pressure after intravitreal injections of anti-VEGF agents. Br J Ophthalmol. 2011;95(8):1111-4.
- Hoang QV, Tsuang AJ, Gelman R, Mendonca LS, Della Torre KE, Jung JJ, et al. Clinical predictors of sustained intraocular pressure elevation due to intravitreal anti-vascular endothelial growth factor therapy. Retina. 2013;33(1):179-87.
- Demirel S, Yanik O, Batioglu F, Ozmert E. Intraocular pressure changes related to intravitreal injections of ranibizumab: analysis of pseudophakia and glaucoma subgroup. Int Ophthalmol. 2015;35(4):541-7.
- Boyer DS, Goldbaum M, Leys AM, Starita C. Effect of pegaptanib sodium 0.3 mg intravitreal injections (Macugen) in intraocular pressure: posthoc analysis from V.I.S.I.O.N. study. Br J Ophthalmol. 2014;98(11):1543-6.
- Gado AS, Macky TA. Dexamethasone intravitreous implant versus bevacizumab for central retinal vein occlusion-related macular oedema: a prospective randomized comparison. Clin Exp Ophthalmol. 2014;42(7):650-5.
- Güler M, Capkın M, Simşek A, Bilak S, Bilgin B, Hakim Reyhan A, et al. Short-term effects of intravitreal bevacizumab on cornea and anterior chamber. Curr Eye Res. 2014;39(10):989-93.
- Rusu IM, Deobhakta A, Yoon D, Lee M, Slakter JS, Klancnik JM, et al. Intraocular pressure in patients with neovascular age-related macular degeneration switched to aflibercept injection after previous anti-vascular endothelial growth factor treatments. Retina. 2014;34(11):2161-6.
- Wehrli SJ, Tawse K, Levin MH, Zaidi A, Pistilli M, Brucker AJ. A lack of delayed intraocular pressure elevation in patients treated with intravitreal injection of bevacizumab and ranibizumab. Retina. 2012;32(7):1295-301.
- Yoganathan P, Deramo VA, Lai JC, Tibrewala RK, Fastenberg DM. Visual improvement following intravitreal bevacizumab (Avastin) in exudative age-related macular degeneration. Retina. 2006;26(9):994-8.
- Wen JC, Reina-Torres E, Sherwood JM, Challa P, Liu KC, Li G, et al. Intravitreal Anti-VEGF Injections Reduce Aqueous Outflow Facility in Patients With Neovascular Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2017;58(3):1893-8.
- Filek R, Hooper P, Sheidow TG, Gonder J, Chakrabarti S, Hutnik CM. Two-year analysis of changes in the optic nerve and retina following anti-VEGF treatments in diabetic macular edema patients. Clin Ophthalmol. 2019;13:1087-96.
- Gómez-Mariscal M, Puerto B, Muñoz-Negrete FJ, de Juan V, Rebolleda G. Acute and chronic optic nerve head biomechanics and intraocular pressure changes in patients receiving multiple intravitreal injections of anti-VEGF. Graefes Arch Clin Exp Ophthalmol. 2019;257(10):2221-31.
- Wingard JB, Delzell DA, Houlihan NV, Lin J, Gieser JP. Incidence of Glaucoma or Ocular Hypertension After Repeated Anti-Vascular Endothelial Growth Factor Injections for Macular Degeneration. Clin Ophthalmol. 2019;13:2563-72.
- Gómez-Mariscal M, Muñoz-Negrete FJ, Rebolleda Fernández G. Effects of Intravitreal Anti-VEGF Therapy on Glaucoma-like Progression in Susceptible Eyes. J Glaucoma. 2020;29(6):e54-e5.
- Bracha P, Moore NA, Ciulla TA, WuDunn D, Cantor LB. The acute and chronic effects of intravitreal anti-vascular endothelial growth factor injections on intraocular pressure: A review. Surv Ophthalmol. 2018;63(3):281-95.
- Kahook MY, Liu L, Ruzycki P, Mandava N, Carpenter JF, Petrash JM, et al. High-molecular-weight aggregates in repackaged bevacizumab. Retina. 2010;30(6):887-92.
- Liu L, Ammar DA, Ross LA, Mandava N, Kahook MY, Carpenter JF. Silicone oil microdroplets and protein aggregates in repackaged bevacizumab and ranibizumab: effects of long-term storage and product mishandling. Invest Ophthalmol Vis Sci. 2011;52(2):1023-34.
- Bakri SJ, Ekdawi NS. Intravitreal silicone oil droplets after intravitreal drug injections. Retina. 2008;28(7):996-1001.
- Kahook MY, Ammar DA. In vitro effects of antivascular endothelial growth factors on cultured human trabecular meshwork cells. J Glaucoma. 2010;19(7):437-41.
- Georgopoulos M, Polak K, Prager F, Prünte C, Schmidt-Erfurth U. Characteristics of severe intraocular inflammation following intravitreal injection of bevacizumab (Avastin). Br J Ophthalmol. 2009;93(4):457-62.
- Sniegowski M, Mandava N, Kahook MY. Sustained intraocular pressure elevation after intravitreal injection of bevacizumab and ranibizumab associated with trabeculitis. Open Ophthalmol J. 2010;4:28-9.
- Morshedi RG, Ricca AM, Wirostko BM. Ocular Hypertension Following Intravitreal Antivascular Endothelial Growth Factor Therapy: Review of the Literature and Possible Role of Nitric Oxide. J Glaucoma. 2016;25(3):291-300.
- El Chehab H, Le Corre A, Agard E, Ract-Madoux G, Coste O, Dot C. Effect of topical pressure-lowering medication on prevention of intraocular pressure spikes after intravitreal injection. Eur J Ophthalmol. 2013;23(3):277-83.
- Kozobolis V, Panos GD, Konstantinidis A, Labiris G. Comparison of dorzolamide/timolol vs brinzolamide/brimonidine fixed combination therapy in the management of primary open-angle glaucoma. Eur J Ophthalmol. 2017;27(2):160-3.
- Ozcaliskan S, Ozturk F, Yilmazbas P, Beyazyildiz O. Effect of dorzolamide-timolol fixed combination prophylaxis on intraocular pressure spikes after intravitreal bevacizumab injection. Int J Ophthalmol. 2015;8(3):496-500.
- Pece A, Allegrini D, Montesano G, Dimastrogiovanni AF. Effect of prophylactic timolol 0.1% gel on intraocular pressure after an intravitreal injection of ranibizumab: a randomized study. Clin Ophthalmol. 2016;10:1131-8.
- Theoulakis PE, Lepidas J, Petropoulos IK, Livieratou A, Brinkmann CK, Katsimpris JM. Effect of brimonidine/timolol fixed combination on preventing the short-term intraocular pressure increase after intravitreal injection of ranibizumab. Klin Monbl Augenheilkd. 2010;227(4):280-4.
- Carnota-Méndez P, Méndez-Vázquez C, Otero-Villar J, Saavedra-Pazos JA. Effect of prophylactic medication and influence of vitreous reflux in pressure rise after intravitreal injections of anti-VEGF drugs. Eur J Ophthalmol. 2014;24(5):771-7.
- Knecht PB, Michels S, Sturm V, Bosch MM, Menke MN. Tunnelled versus straight intravitreal injection: intraocular pressure changes, vitreous reflux, and patient discomfort. Retina. 2009;29(8):1175-81.
- Pang CE, Mrejen S, Hoang QV, Sorenson JA, Freund KB. ASSOCIATION BETWEEN NEEDLE SIZE, POSTINJECTION REFLUX, AND INTRAOCULAR PRESSURE SPIKES AFTER INTRAVITREAL INJECTIONS. Retina. 2015;35(7):1401-6.
- Gregori NZ, Weiss MJ, Goldhardt R, Schiffman JC, Vega E, Mattis CA, et al. Ocular decompression with cotton swabs lowers intraocular pressure elevation after intravitreal injection. J Glaucoma. 2014;23(8):508-12.
- Lam J, Luttrell I, Ding L, Rezaei K, Chao JR, Chee Y, et al. Effect of prior glaucoma surgery on intraocular pressure immediately after anti-vascular endothelial growth factor injection. Graefes Arch Clin Exp Ophthalmol. 2019;257(11):2489-94.
- Knip MM, Välimäki J. Effects of pegaptanib injections on intraocular pressure with and without anterior chamber paracentesis: a prospective study. Acta Ophthalmol. 2012;90(3):254-8.