Authors
Fursova A.Zh.1, 2, Gamza Y.A.2, Derbeneva A.S.1, 2, Vasil’eva M.А.1
1 Novosibirsk State Region Hospital, Novosibirsk
2 Novosibirsk State Medical University, Novosibirsk
Abstract
Backgraund: In recent years, the algorithms and standards for the treatment of patients with diabetic macular edema (DME) have changed dramatically due to the widespread use of antiangiogenic therapy and its high clinical efficacy. The safety of intravitreal administration of angiogenesis inhibitors and the risk of possible damaging effects of increased intraocular pressure (IOP) is a subject of discussion and is of great interest. The introduction of the OCT-angiography method provided a unique opportunity not only to study the hemodynamics of the optic nerve disc and the retina, but also to monitor the course of the disease.
Aims: To study the changes in the optic disc and retina hemodynamics in the macular region in patients with DMO and glaucoma after anti-VEGF injection.
Materials and methods: A prospective observational study was conducted at the ophthalmological department of the Novosibirsk State Regional Hospital. The study included 86 patients (172 eyes). Patient groups were formed according to the presence of clinically significant DME and primary open-angle glaucoma (POAG), both in combination and separately. 1st group — 40 patients (40 eyes) with I stage POAG and DME; Group 2 — 46 patients (46 eyes) with DME. All patients received intravitreal injections of aflibercept 0.05 ml (2 mg) in the operating room. The control group included paired eyes of patients into which no drugs were injected. Tonometry and OCT angiography were performed 5 and 30 minutes after the injection.
Results: 5 minutes after the injection of aflibercept, an increase in IOP was noted in group 1 by 8.29 mm Hg (45.9%), in group 2 by 8.42 mm Hg (49.9%), accompanied by a decrease in optic nerve disc perfusion by 3.3% in both groups and the macular region by 6.97% and 2.71%, respectively. After 30, the pressure level decreased by 7.23 mm Hg (27.4%) and 7.88 (31%), but was higher than the initial values by 1.06 mm Hg (5.86%) and 0.54 mm Hg (3.2%), perfusion indices returned to their initial values. The vessel density of the optic disc and macular region before and after injection did not undergo statistically significant changes.
Conclusions: Аnti-VEGF injection are accompanied by a short-term pronounced increase in IOP and a significant decrease in the perfusion of the optic nerve disc and, to a greater extent, the macular region. Monitoring the effect of anti-VEGF injection on the progression of glaucoma and the development of structural and functional changes should be decisive in the development of the regimen and duration of therapy for patients with DMЕ.
Keywords: OCT-angio, optic nerve perfusion, anti-VEGF, glaucoma, diabetic macular edema.
References
1. Kim JE, Mantravadi AV, Hur EY, et al. Short-term intraocular pressure changes immediately after intravitreal injections of anti-vascular endothelial growth factor agents. Am. J. Ophthalmol. 2008; 146(6): 930–934. doi: 10.1016/j.ajo.2008.07.007.
2. Arikan G, Osman Saatci A, Hakan Oner F. Immediate intraocular pressure rise after intravitreal injection of ranibizumab and two doses of triamcinolone acetonide. Int. J. Ophthalmol. 2011; 4(4): 402–405. doi: 10.3980/j. issn.2222-3959.2011.04.16.
3. Sobacı G, Güngör R, Ozge G. Effects of multiple intravitreal anti-VEGF injections on retinal nerve fiber layer and intraocular pressure: a comparative clinical study. Int. J. Ophthalmol. 2013; 6(2): 211–215. doi: 10.3980/j. issn.2222-3959.2013.02.20.
4. Seth RK, Salim S, Shields MB, et al. Assessment of optic nerve cup-to-disk ratio changes in patients receiving multiple intravitreal injections of antivascular endothelial growth factor agents. Retina. 2009; 29(7): 956–959. doi: 10.1097/IAE.0b013e3181a91dfd.
5. Adelman RA, Zheng Q, Mayer HR. Persistent ocular hypertension following intravitreal bevacizumab and ranibizumab injections. J. Ocul. Pharmacol. Ther. 2010; 26(1): 105–110. doi:10.1089/jop.2009.0076.
6. Zhao D, Cho J, Kim MH, et al. Diabetes, fasting glucose, and the risk of glaucoma: a meta-analysis. Ophthalmology. 2015; 122: 72–78. doi: 10.1016/j.ophtha.2014.07.051.
7. Rossino MG, Dal Monte M, Casini G. Relationships between neurodegeneration and vascular damage in diabetic retinopathy. Front Neurosci. 2019; 8(13): 1172. doi: 10.3389/fnins.2019.01172.
8. Hoguet A, Chen PP, Junk AK, et al. The Effect of Anti-Vascular Endothelial Growth Factor Agents on Intraocular Pressure and Glaucoma. Ophthalmology. 2018; 126(4): 611–622. doi: 10.1016/j.ophtha.2018.11.019.
9. Aref AA. Management of immediate and sustained intraocular pressure rise associated with intravitreal antivascular endothelial growth factor injection therapy. Curr. Opin. Ophthalmol. 2012; 23(2): 105–110. doi: 10.1097/ICU.0b013e32834ff41d.
10. Abedi G, Adelman RA, Salim S. Incidence and management of elevated intraocular pressure with antivascular endothelial growth factor agents. Sem. Ophthalmol. 2013; 28(3): 126–130. doi: 10.3109/08820538.2013.771195.
11. Frenkel MP, Haji SA, Frenkel RE. Effect of prophylactic intraocular pressure-lowering medication on intraocular pressure spikes after intravitreal injections. Arch. Ophthalmol. 2010; 128(12): 1523–1527. doi: 10.1001/ archophthalmol.2010.297.
12. Sacu S, Pemp B, Weigert G, et al. Response of retinal vessels and retrobulbar hemodynamics to intravitreal anti-VEGF treatment in eyes with branch retinal vein occlusion. Invest. Ophthalmol. Vis. Sci. 2011; 52(6): 3046–3050. doi: 10.1167/iovs.10-5842.
13. Fontaine O, Olivier S, Descovich D, et al. The effect of intravitreal injection of bevacizumab on retinal circulation in patients with neovascular macular degeneration. Invest. Ophthalmol. Vis. Sci. 2011; 52(10): 7400–7405. doi: 10.1167/iovs.10-6646.
14. Hashimoto R, Sugiyama T, Ubuka M, et al. Autoregulation of optic nerve head blood flow induced by elevated intraocular pressure during vitreous surgery. Curr Eye Res. 2017; 42: 625–628. doi: 10.1080/02713683. 2016.1220592.
15. Kim JA, Kim TW, Lee EJ, et al. Microvascular changes in peripapillary and optic nerve head tissues after trabeculectomy in primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2018; 59: 4614–4621. doi: 10.1167/iovs.18-25038.
16. Mamikonyan VR, Galoyan NS, Budzinskaya MV, et al. Intraocular pressure and ocular blood flow features intravitreal infection of anti-vascular endothelial growth factor agents. Vestnik oftal’mologii. 2014; 130(5): 16–21 (In Russ).
17. Wen JC, Chen CL, Rezaei KA, et al. Optic Nerve Head Perfusion Before and After Intravitreal Antivascular Growth Factor Injections Using Optical Coherence Tomography-based Microangiography. J Glaucoma. 2019 Mar; 28(3): 188–193. doi: 10.1097/IJG.0000000000001142.
18. Fursova AZh., Gamza YA, Tarasov MS, et al. Comparative study of structural and microcirculatory parameters in patients with primary open-angle glaucoma and diabetes mellitus. Rossiiskii oftal’mologicheskii zhurnal. 2020; 13(3): 42–50. (In Russ). doi: 10.21516/2072-0076-2020-13-3-42-50.
19. Fursova AZh, Gamza YA, Derbeneva AS, et al. Anti-VEGF therapy of diabetic macular edema in patients with primary open-angle glaucoma. Vestnik oftal’mologii. 2020; 136(6): 185–194 (In Russ). doi: 10.17116/oftalma2020136062185.
