High Dose Aflibercept in Diabetic Macular Edema in Patients With Previous Vitrectomy

Summary

Patients with diabetic macular edema (DME) sometimes must undergo vitrectomy surgery (PPV) for diabetic and non-diabetic related issues. Patients may have improved DME with anti-VEGF therapy and ranibizumab has been found to reduce central macular thickness (CMT) with anti-VEGF therapy following vitrectomy. Those patients still require intravitreal injections but the pharmacokinetics of a vitrectomized eye are different than those eyes that have not undergone vitrectomy. The clearance of protein molecules is quicker in vitrectomized eyes so these patients may be more refractory to standard of care anti-VEGF therapy. In rabbit models, the half-life of both bevacizumab and ranibizumab were reduced by a factor 1.8 and 1.3, respectively, after pars plana vitrectomy. In a study examining intravitreal triamcinolone acetonide in human eyes, the half-life was found to be 18.6 days in non-vitrectomized eyes and 3.2 days in vitrectomized eyes, but there was considerable intrasubject variation. Patients with various disease states, including neovascular age-related macular degeneration (nAMD) have been managed with monthly anti-VEGF therapy successfully after vitrectomy surgery. Another study performed by the DRCR net showed that patients with DME treated with anti-VEGF are not affected in the long term if they had had a previous vitrectomy. High dose aflibercept may improve anatomic and visual outcomes in this patient population. Also, high dose aflibercept may allow for longer treatment intervals in these vitrectomized eyes.

Timeline

Start

2025-07-07

Primary completion

2026-08-15

Completion

2027-08-15

Publications

• Background Adrean SD, Knight D, Chaili S, Ramkumar HL, Pirouz A, Grant S. Long term results of patients with neovascular age-related macular degeneration switched from other anti-VEGF agents to intravitreal Aflibercept. Int J Retina Vitreous. 2022 Feb 10;8(1):11. doi: 10.1186/s40942-022-00361-9.
• Background Adrean SD, Chaili S, Grant S, Pirouz A. Recurrence Rate of Choroidal Neovascularization in Neovascular Age-Related Macular Degeneration Managed with a Treat-Extend-Stop Protocol. Ophthalmol Retina. 2018 Mar;2(3):225-230. doi: 10.1016/j.oret.2017.07.009. Epub 2017 Sep 28.
• Background Bressler SB, Melia M, Glassman AR, Almukhtar T, Jampol LM, Shami M, Berger BB, Bressler NM; Diabetic Retinopathy Clinical Research Network. RANIBIZUMAB PLUS PROMPT OR DEFERRED LASER FOR DIABETIC MACULAR EDEMA IN EYES WITH VITRECTOMY BEFORE ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY. Retina. 2015 Dec;35(12):2516-28. doi: 10.1097/IAE.0000000000000617.
• Background Mun Y, Park KH, Park SJ, Woo SJ. Efficacy of anti-vascular endothelial growth factor agents for treating neovascular age-related macular degeneration in vitrectomized eyes. PLoS One. 2021 Jun 10;16(6):e0252006. doi: 10.1371/journal.pone.0252006. eCollection 2021.
• Background Beer PM, Bakri SJ, Singh RJ, Liu W, Peters GB 3rd, Miller M. Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection. Ophthalmology. 2003 Apr;110(4):681-6. doi: 10.1016/S0161-6420(02)01969-3.
• Background Christoforidis JB, Williams MM, Wang J, Jiang A, Pratt C, Abdel-Rasoul M, Hinkle GH, Knopp MV. Anatomic and pharmacokinetic properties of intravitreal bevacizumab and ranibizumab after vitrectomy and lensectomy. Retina. 2013 May;33(5):946-52. doi: 10.1097/IAE.0b013e3182753b12.
• Background Laugesen CS, Ostri C, Brynskov T, Lund-Andersen H, Larsen M, Vorum H, Sorensen TL. Intravitreal ranibizumab for diabetic macular oedema in previously vitrectomized eyes. Acta Ophthalmol. 2017 Feb;95(1):28-32. doi: 10.1111/aos.13160. Epub 2016 Jul 30.

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