Short-term choroidal vascular changes after aflibercept therapy for neovascular age-related macular degeneration

Marco Pellegrini, Federico Bernabei, Andrea Mercanti, Stefano Sebastiani, Enrico Peiretti, Claudio Iovino, Giamberto Casini, Pasquale Loiudice, Vincenzo Scorcia, Giuseppe Giannaccare, Marco Pellegrini, Federico Bernabei, Andrea Mercanti, Stefano Sebastiani, Enrico Peiretti, Claudio Iovino, Giamberto Casini, Pasquale Loiudice, Vincenzo Scorcia, Giuseppe Giannaccare

Abstract

Introduction: The purpose of this study was to evaluate choroidal vascular changes in patients with neovascular age-related macular degeneration (nAMD) treated with aflibercept injection over a 3-month period.

Methods: Enhanced depth imaging optical coherence tomography scans of 60 eyes with treatment-naïve nAMD and 60 unaffected fellow eyes were retrospectively analyzed. Data was collected at baseline and after 3 monthly intravitreal injections of aflibercept. The ImageJ software was used to binarize OCT scans and measure total choroid area (TCA), luminal area (LA), and stromal area (SA). Choroidal vascularity index (CVI) was defined as the ratio of LA to TCA.

Results: After treatment, subfoveal choroidal thickness (CT) in nAMD eyes significantly decreased from 210. 6 ± 61.6 to 194.6 ± 58.7 μm (P < 0.001), TCA from 1.620 ± 0.502 to 1.500 ± 0.451 mm2 (P < 0.001), LA from 1.075 ± 0.335 to 0.985 ± 0.307 mm2 (P < 0.001), SA from 0.545 ± 0.176 to 0.516 ± 0.153 mm2 (P = 0.005), and CVI from 66.36 ± 2.89 to 65.46 ± 2.87% (P = 0.009). The decrease of CVI after treatment was significantly correlated with baseline CVI (Rs = 0.466, P < 0.001), but not with the change in BCVA and presence of dry macula after treatment (always P > 0.05).

Conclusion: Choroidal thickness and vascularity significantly decreased after treatment with aflibercept in nAMD eyes. Besides the pharmacologic effect on the neovascular lesion, aflibercept may induce vascular changes also on the underlying choroid.

Keywords: Age-related macular degeneration; Anti-VEGF; Choroidal vascularity index; Optical coherence tomography.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Choroidal vascularity index calculation with binarization of spectral-domain OCT images. a Choroidal boundaries are traced to identify the total choroidal area (red lines). b The image is binarized with Niblack’s auto-local threshold. c The color threshold tool is used to select the dark pixels, representing the luminal area (yellow lines). The choroidal vascularity index is computed dividing luminal area by total choroidal area
Fig. 2
Fig. 2
Enhanced depth imaging OCT with calculation of choroidal vascularity index in a representative eye with neovascular age-related macular degeneration at baseline (a) and after 3 monthly intravitreal injections of aflibercept (b)
Fig. 3
Fig. 3
Scatterplots showing the relationship between age and subfoveal choroidal thickness (a), total choroidal area (b), and choroidal vascularity index (c) in eyes with neovascular age-related macular degeneration at baseline. Age was significantly correlated with subfoveal choroidal thickness and total choroidal area but not with choroidal vascularity index
Fig. 4
Fig. 4
Scatterplots showing the relationship between choroidal vascularity index at baseline and intraocular pressure (a) and decrease of choroidal vascularity index after 3 monthly intravitreal injections of aflibercept (b) in eyes with neovascular age-related macular degeneration

References

    1. Wong WL, Su X, Li X et al (2014) Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2. 10.1016/S2214-109X(13)70145-1
    1. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419–1431. doi: 10.1056/NEJMoa054481.
    1. Lowe J, Araujo J, Yang J, et al. Ranibizumab inhibits multiple forms of biologically active vascular endothelial growth factor in vitro and in vivo. Exp Eye Res. 2007;85:425–430. doi: 10.1016/j.exer.2007.05.008.
    1. Martin DF, Maguire MG, Ying GS, et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364:1897–1908. doi: 10.1056/NEJMoa1102673.
    1. Nguyen CL, Oh LJ, Wong E, et al. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration: a meta-analysis of randomized controlled trials. BMC Ophthalmol. 2018;18:130. doi: 10.1186/s12886-018-0785-3.
    1. Stewart MW. Aflibercept (VEGF trap-eye): The newest anti-VEGF drug. Br J Ophthalmol. 2012;96:1157–1158. doi: 10.1136/bjophthalmol-2011-300654.
    1. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119:2537–2548. doi: 10.1016/j.ophtha.2012.09.006.
    1. Yamazaki T, Koizumi H, Yamagishi T, Kinoshita S. Subfoveal choroidal thickness after ranibizumab therapy for neovascular age-related macular degeneration: 12-month results. Ophthalmology. 2012;119:1621–1627. doi: 10.1016/j.ophtha.2012.02.022.
    1. Yun C, Oh J, Ahn J, et al. Comparison of intravitreal aflibercept and ranibizumab injections on subfoveal and peripapillary choroidal thickness in eyes with neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2016;254:1693–1702. doi: 10.1007/s00417-015-3260-3.
    1. Gharbiya M, Cruciani F, Mariotti C, et al. Choroidal thickness changes after intravitreal antivascular endothelial growth factor therapy for age-related macular degeneration: ranibizumab versus aflibercept. J Ocul Pharmacol Ther. 2015;31:357–362. doi: 10.1089/jop.2014.0160.
    1. Koizumi H, Kano M, Yamamoto A, et al. Short-term changes in choroidal thickness after aflibercept therapy for neovascular age-related macular degeneration. Am J Ophthalmol. 2015;159:627–633.e1. doi: 10.1016/j.ajo.2014.12.025.
    1. Koizumi H, Kano M, Yamamoto A, et al. Subfoveal choroidal thickness during aflibercept therapy for neovascular age-related macular degeneration twelve-month results. Ophthalmology. 2016;123:617–624. doi: 10.1016/j.ophtha.2015.10.039.
    1. Kim H, Lee K, Lee CS, et al. Subfoveal choroidal thickness in idiopathic choroidal neovascularization and treatment outcomes after intravitreal bevacizumab therapy. Retina. 2015;35:481–486. doi: 10.1097/IAE.0000000000000354.
    1. Ellabban AA, Tsujikawa A, Ogino K, et al. Choroidal thickness after intravitreal ranibizumab injections for choroidal neovascularization. Clin Ophthalmol. 2012;6:837–844. doi: 10.2147/OPTH.S30907.
    1. Minnella AM, Federici M, Falsini B, et al. Choroidal thickness changes after intravitreal ranibizumab for exudative age-related macular degeneration. BioDrugs. 2016;30:353–359. doi: 10.1007/s40259-016-0179-0.
    1. Gupta P, Jing T, Marziliano P, et al. Distribution and determinants of choroidal thickness and volume using automated segmentation software in a population-based study. Am J Ophthalmol. 2015;159:293–301.e3. doi: 10.1016/j.ajo.2014.10.034.
    1. Sansom LT, Suter CA, McKibbin M. The association between systolic blood pressure, ocular perfusion pressure and subfoveal choroidal thickness in normal individuals. Acta Ophthalmol. 2016;94:e157–e158. doi: 10.1111/aos.12794.
    1. Sonoda S, Sakamoto T, Yamashita T, et al. Luminal and stromal areas of choroid determined by binarization method of optical coherence tomographic images. Am J Ophthalmol. 2015;159:1123–1131.e1. doi: 10.1016/j.ajo.2015.03.005.
    1. Agrawal R, Gupta P, Tan KA et al (2016) Choroidal vascularity index as a measure of vascular status of the choroid: measurements in healthy eyes from a population-based study. Sci Rep 6. 10.1038/srep21090
    1. Pellegrini M, Giannaccare G, Bernabei F, et al. Choroidal vascular changes in arteritic and nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol. 2019;205:43–49. doi: 10.1016/j.ajo.2019.03.028.
    1. Iovino C, Pellegrini M, Bernabei F, et al. Choroidal vascularity index: an in-depth analysis of this novel optical coherence tomography parameter. J Clin Med. 2020;9:595. doi: 10.3390/jcm9020595.
    1. Gemmy Cheung CM, Laude A, Wong W, et al. Improved specificity of polypoidal choroidal vasculopathy diagnosis using a modified EVEREST criteria. Retina. 2015;35:1375–1380. doi: 10.1097/IAE.0000000000000482.
    1. Pellegrini M, Veronese C, Bernabei F et al (2019) Choroidal vascular changes in multiple evanescent white dot syndrome. Ocul Immunol Inflamm. 10.1080/09273948.2019.1678650
    1. Koh LHL, Agrawal R, Khandelwal N, et al. Choroidal vascular changes in age-related macular degeneration. Acta Ophthalmol. 2017;95:e597–e601. doi: 10.1111/aos.13399.
    1. Padrón-Pérez N, Arias L, Rubio M, et al. Changes in choroidal thickness after intravitreal injection of anti-vascular endothelial growth factor in pachychoroid neovasculopathy. Investig Ophthalmol Vis Sci. 2018;59:1119–1124. doi: 10.1167/iovs.17-22144.
    1. Invernizzi A, Benatti E, Cozzi M, et al. Choroidal structural changes correlate with neovascular activity in neovascular age related macular degeneration. Investig Ophthalmol Vis Sci. 2018;59:3836–3841. doi: 10.1167/iovs.18-23960.
    1. Kim YK, Park SJ, Woo SJ, Park KH (2016) Choroidal thickness change after intravitreal anti-vascular endothelial growth factor treatment in retinal angiomatous proliferation and its recurrence. Retina 36:1516–1526. 10.1097/IAE.0000000000000952
    1. Mottet B, Aptel F, Geiser MH, et al. Choroidal blood flow after the first intravitreal ranibizumab injection in neovascular age-related macular degeneration patients. Acta Ophthalmol. 2018;96:e783–e788. doi: 10.1111/aos.13763.
    1. Ting DSW, Ng WY, Ng SR, et al. Choroidal thickness changes in age-related macular degeneration and polypoidal choroidal vasculopathy: a 12-month prospective study. Am J Ophthalmol. 2016;164:128–136.e1. doi: 10.1016/j.ajo.2015.12.024.
    1. Sonoda S, Sakamoto T, Otsuka H et al (2013) Responsiveness of eyes with polypoidal choroidal vasculopathy with choroidal hyperpermeability to intravitreal ranibizumab. BMC Ophthalmol 13. 10.1186/1471-2415-13-43
    1. Tilton RG, Chang KC, Lejeune WS, et al. Role for nitric oxide in the hyperpermeability and hemodynamic changes induced by intravenous VEGF. Investig Ophthalmol Vis Sci. 1999;40:689–696.
    1. Peters S, Heiduschka P, Julien S et al (2007) Ultrastructural findings in the primate eye after intravitreal injection of bevacizumab. Am J Ophthalmol 143. 10.1016/j.ajo.2007.03.007
    1. Agrawal R, Wei X, Goud A, Vupparaboina KK, Jana S, Chhablani J. Influence of scanning area on choroidal vascularity index measurement using optical coherence tomography. Acta Ophthalmol. 2017;95:e770–e775. doi: 10.1111/aos.13442.
    1. Margolis R, Spaide RF. A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes. Am J Ophthalmol. 2009;147:811–815. doi: 10.1016/j.ajo.2008.12.008.
    1. Saint-Geniez M, Kurihara T, Sekiyama E et al (2009) An essential role for RPE-derived soluble VEGF in the maintenance of the choriocapillaris. Proc Natl Acad Sci U S A 106:18751–18756. 10.1073/pnas.0905010106
    1. Hikichi T, Agarie M. Reduced vessel density of the choriocapillaris during anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration. Investig Ophthalmol Vis Sci. 2019;60:1088–1095. doi: 10.1167/iovs.18-24522.
    1. Munk MR, Ceklic L, Ebneter A, et al. Macular atrophy in patients with long-term anti-VEGF treatment for neovascular age-related macular degeneration. Acta Ophthalmol. 2016;94:e757–e764. doi: 10.1111/aos.13157.
    1. Giannaccare G, Pellegrini M, Sebastiani S, et al. Choroidal vascularity index quantification in geographic atrophy using binarization of enhanced-depth imaging optical coherence tomographic scans. Retina. 2020;40:960–965. doi: 10.1097/IAE.0000000000002459.

Source: PubMed

3
Subscribe