Frequency of sustained IOP elevation in patients receiving intravitreal injections of anti-vegf agents for exudative age-related macular degeneration

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Frequency of sustained IOP elevation in patients receiving intravitreal injections of anti-vegf agents for exudative age-related Aim Frequency of sustained IOP elevation in patients receiving

1 Frequency of sustained IOP elevation in patients receiving intravitreal injections of anti-vegf agents for exudative age-related Aim Frequency of sustained IOP elevation in patients receiving intravitreal injections of anti-vegf agents for exudative age-related Sukhpal S Sandhu 1,2,3, Ashley Kras 1, Fakir M Amirul Islam 2, Farshad Abedi 2, Sanjeewa Wickramsinghe 1,2,3, Robyn H Guymer 1,2,3, Salmaan Qureshi 1,2,3, Colin A Harper 1,2,3 1 The Royal Victorian Eye and Ear Hospital, Melbourne, Australia; 2 Centre for Eye Research Australia, Melbourne, Australia; 3 University of Melbourne, Australia Intravitreal anti-vegfinjectionsarenowconsideredstandardof care intreatingage-related(amd) andother conditionsasociatedwithchoroidal neovascularization. 1,2 Avolume-relatedtransient intraocular presure(iop) increaseisa wel knowncomplication, but thesepost-injectioniopspikesusualy returntonormal within30to60minutes. 3-6 Rarely, anacutespikecan oposecentral retinal arteryperfusionrequiringurgent paracentesis. However, thedatapertainingtosustainediopelevationisfar les consistent. Theaimof thisstudyistoreport therateof sustainediop elevationinpatientsreceivingongoingintravitreal anti-vegf therapy. Methods This was a retrospective cohort study of patients receiving intravitreal anti-vegf treatment from initiation at a single site. For each patient, baseline data including demographic information, past ocular diagnoses and surgeries, ocular medications and baseline IOP were recorded. Patients were treated with a treat and extend regimen, aiming to extend the interval between injections based on clinical response to treatment. Inclusion criteria: 1. Patients with neovascular AMD 2. Patients treated with one of the following anti-vegf agents: i. bevacizumab, ii. ranibizumab. Baseline IOP was calculated as the mean of the two most recent documented recordings prior to treatment commencement. For new patients, the IOP from the first visit was used as baseline. IOP was routinely recorded by Goldmann applanation tonometry, and by Tonopen when unavailable. Endpoints Results A total of 483 eyes of 402 patients received anti-vegf treatment for neovascular AMD at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia, between April 2006 and September Characteristics of the whole cohort are shown in Table 1. The mean baseline IOP was 16.5 (95%CI: ) mmhg. A total of 14 (2.9%) eyes developed sustained IOP elevation. Four patients were treated topically with good control. No patient required surgical intervention. Pre-existing glaucoma (p=0.88) and the type of anti-vegf (p=0.57) was not a significant risk factor for sustained IOP elevation, Table 2. Sub-group analysis of 321 patients who had only one eye treated was conducted so that treated eyes could be compared with untreated control eyes. The mean baseline IOP in treated eyes was 16.7 (95%CI: ) mmhg, compared to untreated eyes 16.8 (95%CI: ), p=0.44. A total of 8 (2.5%) treated eyes developed sustained IOP elevation (OR 2.03;95%CI: ), with a maximal IOP rise of 24.0 (95%CI: ) mmhg, compared with 4 (1.2%) untreated control eyes developed sustained IOP elevation, with a maximal IOP rise of 25.8 (95%CI: ) mmhg,. The mean number of injections over the period was 8.9 (95%CI: ). Increasing number of injections did not significantly increase the risk of sustained IOP elevation, p>0.33, Table 3. Conclusions Bibliography 1. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related. ANCHOR Study Group. N Engl J Med 2006;355(14): Brown DM, Michels M, Kaiser PK, et al. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related : Two-year results of the ANCHOR study. Ophthalmology 2009;116(1):57-65 e5. 3. Kim JE, Mantravadi AV, Hur EY, et al. Short-term intraocular pressure changes immediately after intravitreal injections of anti-vascular endothelial Sukhpal S Sandhu 1,2,3, Ashley Kras 1, Fakir M Amirul Islam 2 growth factor agents. Am J Ophthalmol 2008;146(6):930-4, Farshad Abedi 2 e1. ophthalmology. Journal Canadien d Ophtalmologie 2007;42(6): SIOP rise NO rise SIOP rise NO rise p value, Sanjeewa Wickramsinghe 1,2,3, Robyn H Guymer 1,2,3, Salmaan Qureshi 1,2,3 model. Acta Ophthalmologica Scandinavica 2007;85(7): , Colin A Harper 1,2,3 Incidence Experimental Ophthalmology 2008;246(7): Ophthalmic Surg Lasers Imaging 2009;40(3): Injec on 1 number Ocular Pharmacology and Therapeutics 2010;26(1): Royal Victorian Eye and Ear Hospital, Ophthalmol 2011;95(8): < growth factor therapy. Retina 2013;33(1): < therapy for neovascular age-related. Journal of Glaucoma 2012;21(4): Center for Eye Research Australia, < AAO Annual Meeting; Chicago, IL, and ranibizumab. Retina 2012;32(7): > University of Melbourne. Primary end point: Sustained IOP elevation defined as IOP 22mmHg, with a 6mmHg increase from baseline for 2 consecutive visits Secondary end point: Initiation of IOP lowering treatment number and type of anti-vegf injections Table 1: Characteristics of patients receiving intravitreal anti- VEGF treatment for neovascular AMD. n=483 eyes, 402 patients Mean Age Male:Female 197:287 Right:Left 260:224 Mean follow up (days) Mean no. injections 8.9 Sub-group analysis Table 2: Risk factors for sustained IOP (SIOP) elevation Risk factor SIOP rise No rise p value Glaucoma (n=40) No Glaucoma (n=443) Ranibizumab only (n=254) Ranibizumab + Bevacizumab (n=144) Bevacizumab only (n=99) Table 3: Sub-group analysis of 321 patients who had only one eye treated was conducted so that treated eyes could be compared with untreated control eyes. n=321 treated control p= p=0.57 Discussion Several studies report that patients are experiencing delayed and persistently elevated IOP lasting for several weeks to months following intravitreal anti-vegf injections for neovascular AMD Despite the original studies not reporting IOP increases, post-hoc analysis has suggested sustained IOP in these patients. 1,2,13 A recent study concluded that the incidence of elevated IOP following intravitreal anti-vegf treatment was low and did not differ between injected and control eyes. 14 The results of this study show that for eyes receiving intravitreal anti- VEGF for AMD, treated eyes are not significantly more likely to develop sustained IOP elevation than eyes not receiving treatment. Pre-existing glaucoma, the number of injections or type of anti-vegf are not an associated risk for sustained IOP elevation. Several theories include a mechanical, physiological or toxic effect on the trabecular meshwork, or an immune-mediated inflammatory response. 7,9,10,12,14-16 For eyes receiving intravitreal anti-vegf for AMD, treated eyes are not significantly more likely to develop sustained IOP elevation than eyes not receiving treatment. Pre-existing glaucoma, the number of injections or type of anti-vegf are not an associated risk for sustained IOP elevation. 4. Wu H, Chen TC. The effects of intravitreal ophthalmic medications on intraocular pressure. Seminars in Ophthalmology 2009;24(2): Hollands H, Wong J, Bruen R, et al. Short-term intraocular pressure changes after intravitreal injection of bevacizumab. Canadian journal of 6. Kotliar K, Maier M, Bauer S, et al. Effect of intravitreal injections and volume changes on intraocular pressure: clinical results and biomechanical 7. Bakri SJ, McCannel CA, Edwards AO, et al. Persisent ocular hypertension following intravitreal ranibizumab. Graefe's Archive for Clinical and 8. Kahook MY, Kimura AE, Wong LJ, et al. Sustained elevation in intraocular pressure associated with intravitreal bevacizumab injections. 9. Adelman RA, Zheng Q, Mayer HR. Persistent ocular hypertension following intravitreal bevacizumab and ranibizumab injections. Journal of 10. Good TJ, Kimura AE, Mandava N, et al. Sustained elevation of intraocular pressure after intravitreal injections of anti-vegf agents. Br J 11. Hoang QV, Tsuang AJ, Gelman R, et al. Clinical predictors of sustained intraocular pressure elevation due to intravitreal anti-vascular endothelial 12. Tseng JJ, Vance SK, Della Torre KE, et al. Sustained increased intraocular pressure related to intravitreal antivascular endothelial growth factor 13. Bakri SJ MD, Rundle A, et al. IOP in eyes treated with monthly ranibizumab: a post hoc analysis of data from the MARINA and ANCHOR trials. 14. Wehrli SJ, Tawse K, Levin MH, et al. A lack of delayed intraocular pressure elevation in patients treated with intravitreal injection of bevacizumab 15. Jalil A, Fenerty C, Charles S. Intravitreal bevacizumab (Avastin) causing acute glaucoma: an unreported complication. Eye 2007;21(12): Bakri SJ, Ekdawi NS. Intravitreal silicone oil droplets after intravitreal drug injections. Retina 2008;28(7):

2 Retrospective cohort study of patients receiving intravitreal anti-vegf treatment for neovascular AMD on a treat and extend regimen Primary end point: Sustained IOP elevation defined as IOP 22mmHg, with a 6mmHg increase from baseline for 2 consecutive visits Secondary end point: Initiation of IOP lowering treatment number and type of anti-vegf injections

3 n=483 eyes, 402 patients Risk factor SIOP rise No rise p value Mean Age Male:Female 197:287 Right:Left 260:224 Mean follow up (days) Mean no. injections 8.9 Glaucoma (n=40) No Glaucoma (n=443) Ranibizumab only (n=254) Ranibizumab + Bevacizumab (n=144) p= Bevacizumab only (n=99) 2 97 p=0.57

4 Control analysis n=321 treated control SIOP rise NO rise SIOP rise NO rise P value Incidence Injection number < < < >

5 intravitreal injections of anti-vegf agents for exudative age-related Conclusions For eyes receiving intravitreal anti-vegf for AMD, treated eyes are not significantly more likely to develop sustained IOP elevation than eyes not receiving treatment. Pre-existing glaucoma, the number of injections or type of anti-vegf are not an associated risk for sustained IOP elevation.

Intraocular Pressure rise after Anti-VEGF Treatment: Prevalence, Possible Mechanisms and Correlations

10.5005/jp-journals-10008-1132 Intraocular Pressure rise after Anti-VEGF Treatment: Prevalence, Possible Mechanisms and Correlations REVIEW ARTICLE Intraocular Pressure rise after Anti-VEGF Treatment: