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Acta Diabetologica
Published in: Acta Diabetologica 3/2020

01-03-2020 | Angiography | Original Article

Diabetic macular edema with neuroretinal detachment: OCT and OCT-angiography biomarkers of treatment response to anti-VEGF and steroids

Authors: Stela Vujosevic, Caterina Toma, Edoardo Villani, Andrea Muraca, Emanuele Torti, Giordana Florimbi, Francesco Leporati, Marco Brambilla, Paolo Nucci, Stefano De Cilla’

Published in: Acta Diabetologica | Issue 3/2020

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Abstract

Purpose

To assess and compare early changes in neuroinflammatory and vascular parameters in diabetic macular edema (DME) with subfoveal neuroretinal detachment (SND) after treatment with intravitreal dexamethasone (DEX-I) and ranibizumab (IVR).

Methods

Thirty-three eyes (33 patients) with treatment naïve DME with SND were retrospectively evaluated at baseline and 2 months after DEX-I (15 eyes) and 1 month after 3 monthly IVR injections (18 eyes). Inclusion criteria were: complete eye examination, good quality OCT and OCT-A images. OCT parameters included: central macular thickness (CMT); number of hyper-reflective retinal spots (HRS) in inner, outer (IR, OR) and full retina; choroidal thickness (CT), extent of disorganization of inner retinal layers (DRIL), outer retina integrity (OR). On OCT-A: foveal avascular zone (FAZ) parameters in the superficial capillary plexus (SCP); cysts area and perfusion density (PD) in SCP and deep capillary plexus (DCP) and flow voids (FV) in choriocapillaris. FAZ was analyzed using ImageJ, perfusion parameters and FV using MATLAB.

Results

BCVA increased equally after both treatments (13.0 ± 10.0 ETDRS letters, p < 0.0001). There was a similar decrease (p < 0.05) in: height of SND, cysts area at SCP, central and mean CT, increase in FAZ perimeter and OR integrity, after both treatments. A greater decrease in DEX-I versus IVR group was found in: CMT (− 38.7% vs. − 22.2%, p = 0.012), HRS number in IR (− 29.2% vs. − 14.0%, p = 0.05) and full retina (− 24.7% vs. − 8.0%, p = 0.03), DRIL extension (− 62.0% vs. − 24%, p = 0.008), cysts area at DCP (− 68.7% vs. − 26.1%, p = 0.03), FAZ-CI (− 19.1% vs. − 8.3%, p = 0.02), PD at DCP (− 27.5%  vs. + 4.9%, p = 0.02). FV did not change.

Conclusions

More pronounced changes in specific inflammatory parameters in the inner retina are documented after steroid versus anti-VEGF treatment. These include reduction in HRS number, DRIL extension, CMT, cysts area at DCP. These data may help in further study of noninvasive imaging biomarkers for better evaluation of treatment response.
Literature
1.
Otani T, Kishi S, Maruyama Y (1999) Patterns of diabetic macular edema with optical coherence tomography. Am J Ophthalmol 127(6):688–693CrossRef
2.
Gaucher D, Sebah C, Erginay A et al (2008) Optical coherence tomography features during the evolution of serous retinal detachment in patients with diabetic macular edema. Am J Ophthalmol 145(2):289–296CrossRef
3.
Catier A, Tadayoni R, Paques M et al (2005) Characterization of macular edema from various etiologies by optical coherence tomography. Am J Ophthalmol 140(2):200–206CrossRef
4.
Sonoda S, Sakamoto T, Yamashita T, Shirasawa M, Otsuka H, Sonoda Y (2014) Retinal morphologic changes and concentrations of cytokines in eyes with diabetic macular edema. Retina 34(4):741–748CrossRef
5.
Vujosevic S, Torresin T, Berton M, Bini S, Convento E, Midena E (2017) Diabetic macular edema with and without subfoveal neuroretinal detachment: two different morphologic and functional entities. Am J Ophthalmol 181:149–155CrossRef
6.
Vujosevic S, Simó R (2017) Local and systemic inflammatory biomarkers of diabetic retinopathy: an integrative approach. Invest Ophthalmol Vis Sci 58(6):BIO68–BIO75CrossRef
7.
Vujosevic S, Bini S, Midena G, Berton M, Pilotto E (2013) Hyperreflective intraretinal spots in diabetics without and with non proliferative diabetic retinopathy: an in vivo study using spectral domain OCT. J Diabetes Res 3:491835
8.
Vujosevic S, Bini S, Torresin T et al (2017) Hyperreflective retinal spots in normal and diabetic eyes: b-scan and en face spectral domain optical coherence tomography evaluation. Retina 37(6):1092–1103CrossRef
9.
Vujosevic S, Torresin T, Bini S et al (2017) Imaging retinal inflammatory biomarkers after intravitreal steroid and anti VEGF treatment in diabetic macular oedema. Acta Ophthalmol 95(5):464–471CrossRef
10.
Madeira MH, Boia R, Santos PF, Ambrósio AF, Santiago AR (2017) Contribution of microglia-mediated neuroinflammation to retinal degenerative diseases. Med Inflamm 95(S259):673090
11.
Sohn HJ, Han DH, Kim IT et al (2011) Changes in aqueous concentrations of various cytokines after intravitreal triamcinolone versus bevacizumab for diabetic macular edema. Am J Ophthalmol 152(4):686–694CrossRef
12.
Vujosevic S, Berton M, Bini S, Casciano M, Cavarzeran F, Midena E (2016) Hyperreflective retinal spots and visual function after anti-vascular endothelial growth factor treatment in center-involving diabetic macular edema. Retina 36(7):1298–1308CrossRef
13.
Bhanushali D, Anegondi N, Gadde SG et al (2016) Linking retinal microvasculature features with severity of diabetic retinopathy using optical coherence tomography angiography. Invest Ophthalmol Vis Sci 57(9):OCT519–OCT525CrossRef
14.
15.
Kim K, Kim ES, Yu SY (2018) Optical coherence tomography angiography analysis of foveal microvascular changes and inner retinal layer thinning in patients with diabetes. Br J Ophthalmol 102(9):1226–1231CrossRef
16.
Ting DSW, Tan GSW, Agrawal R et al (2017) Optical coherence tomographic angiography in type 2 diabetes and diabetic retinopathy. JAMA Ophthalmol 135(4):306–312CrossRef
17.
Lee J, Moon BG, Cho AR, Yoon YH (2016) Optical coherence tomography angiography of DME and its association with anti-VEGF treatment response. Ophthalmology 123(11):2368–2375CrossRef
18.
Toto L, D’Aloisio R, Di Nicola M et al (2017) Qualitative and quantitative assessment of vascular changes in diabetic macular edema after dexamethasone implant using optical coherence tomography angiography. Int J Mol Sci 18(6):E1181CrossRef
19.
Mastropasqua R, D’Aloisio R, Di Nicola M et al (2018) Relationship between aqueous humor cytokine changes and retinal vascular changes after intravitreal aflibercept for diabetic macular edema. Sci Rep 8(1):16548CrossRef
20.
21.
22.
Sun JK, Radwan SH, Soliman AZ et al (2015) Neural retinal disorganization as a robust marker of visual acuity in current and resolved diabetic macular edema. Diabetes 64(7):2560–2570CrossRef
23.
Semmlow JL, Griffel B (2014) Biosignal and biomedical image processing: MATLAB-based applications. CRC Press, New Jersey
24.
Gonzalez RC, Woods RE, Eddins SL (2010) Digital image processing using MATLAB, 2nd edn. Mcgraw Hill, New York
25.
Borrelli E, Balasubramanian S, Triolo G, Barboni P, Sadda SR, Sadun AA (2018) Topographic macular microvascular changes and correlation with visual loss in chronic leber hereditary optic neuropathy. Am J Ophthalmol 192:217–228CrossRef
26.
Antonetti DA, Klein R, Gardner TW (2012) Diabetic retinopathy. N Engl J Med 366(13):1227–1239CrossRef
27.
Das A, McGuire PG, Rangasamy S (2015) Diabetic macular edema: pathophysiology and novel therapeutic targets. Ophthalmology 122(7):1375–1394CrossRef
28.
Vujosevic S, Micera A, Bini S, Berton M, Esposito G, Midena E (2015) Proteome analysis of retinal glia cells related inflammatory cytokines in the aqueous humour of diabetic patients. Acta Ophalmol 94(1):56–64CrossRef
29.
Yuuki T, Kanda T, Kimura Y et al (2001) Inflammatory cytokines in vitreous fluid and serum of patients with diabetic vitreoretinopathy. J Diabetes Complicat 15(5):257–259CrossRef
30.
Lee H, Jang H, Choi YA, Kim HC, Chung H (2018) Association between soluble CD14 in the aqueous humor and hyperreflective foci on optical coherence tomography in patients with diabetic macular edema. IOVS 59(2):715–721
31.
Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10(11):1387–1394CrossRef
32.
33.
Chatziralli IP, Sergentanis TN, Sivaprasad S (2016) Hyperreflective foci as an independent visual outcome predictor in macular edema due to retinal vascular disease treated with intravitreal Dexamethasone or Ranibizumab. Retina 36(12):2319–2328CrossRef
34.
Hwang HS, Chae JB, Kim JY, Kim DY (2017) Association between hyperreflective dots on spectral-domain optical coherence tomography in macular edema and response to treatment. IOVS 58(13):5958–5967
35.
Zur D, Iglicki M, Busch C et al (2018) OCT biomarkers as functional outcome predictors in diabetic macular edema treated with Dexamethasone implant. Ophthalmology 125(2):267–275CrossRef
36.
Page C, Hoffman B, Curtis M, Walker M (1997) Integrated pharmacology. Mosby, London
37.
Reichenbach A, Wurm A, Pannicke T, Iandiev I, Wiedemann P, Bringmann A (2007) Müller cells as players in retinal degeneration and edema. Graefes Arch Clin Exp Ophthalmol 245(5):627–636CrossRef
38.
Campochiaro PA, Hafiz G, Mir TA et al (2016) Pro-permeability factors in diabetic macular edema; the diabetic macular edema treated with ozurdex trial. Am J Ophthalmol 168:13–23CrossRef
39.
Bringmann A, Pannicke T, Grosche J et al (2006) Müller cells in the healthy and diseased retina. Progress Retinal Eye Res 25(4):397–424CrossRef
40.
Uckermann O, Kutzera F, Wolf A et al (2005) The glucocorticoid triamcinolone acetonide inhibits osmotic swelling of retinal glial cells via stimulation of endogenous adenosine signaling. Pharmacol Exp Ther 315(3):1036–1045CrossRef
41.
Sun JK, Lin MM, Lammer J et al (2014) Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol 132(11):1309–1316CrossRef
42.
Gallina D, Zelinka CP, Cebulla CM, Fischer AJ (2015) Activation of glucocorticoid receptors in Müller glia is protective to retinal neurons and suppresses microglial reactivity. Exp Neurol 273:114–125CrossRef
43.
44.
Spaide RF (2016) Retinal vascular cystoid macular edema: review and new theory. Retina 36(10):1823–1842CrossRef
45.
Spaide RF, Fujimoto JG, Waheed NK, Sadda SR, Staurenghi G (2018) Optical coherence tomography angiography. Prog Ret Eye Res 64:1–55CrossRef
Metadata
Title
Diabetic macular edema with neuroretinal detachment: OCT and OCT-angiography biomarkers of treatment response to anti-VEGF and steroids
Authors
Stela Vujosevic
Caterina Toma
Edoardo Villani
Andrea Muraca
Emanuele Torti
Giordana Florimbi
Francesco Leporati
Marco Brambilla
Paolo Nucci
Stefano De Cilla’
Publication date
01-03-2020
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 3/2020
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-019-01424-4

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