Ganglion Cell Layer Thickness after Anti-Vascular Endothelial Growth Factor Treatment in Retinal Vein Occlusion

Ji Young Lee; Hyung Chan Kim

doi:10.3341/jkos.2016.57.1.63

Journal List > J Korean Ophthalmol Soc > v.57(1) > 1010563

Go to TopGo to Top Go to BottomGo to Bottom


J Korean Ophthalmol Soc. 2016 Jan;57(1):63-70. Korean. Published online Jan 13, 2016. https://doi.org/10.3341/jkos.2016.57.1.63
©2016 The Korean Ophthalmological Society


Ganglion Cell Layer Thickness after Anti-Vascular Endothelial Growth Factor Treatment in Retinal Vein Occlusion
Ji Young Lee, MD and Hyung Chan Kim, MD, PhD
Department of Ophthalmology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
Address reprint requests to Hyung Chan Kim, MD, PhD. Department of Ophthalmology, Konkuk University Medical Center, #120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, Korea. Tel: 82-2-2030-8180, Fax: 82-2-2030-5273, Email: eyekim@kuh.ac.kr

Received May 15, 2015; Revised September 23, 2015; Accepted November 20, 2015.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Purpose To evaluate the effect of repeated intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) on the thickness of the ganglion cell layer (GCL) in patients with retinal vein occlusion. Methods The present retrospective study included 60 patients with branch retinal vein occlusion and central retinal vein occlusion who received more than 3 anti-VEGF injections. GCL thickness was measured using spectral-domain optical coherence tomography. GCL thickness measurements were made at 9 Early Treatment Diabetic Retinopathy Study grid regions. We evaluated correlations between changes in the GCL thickness and other factors such as intraocular pressure, times of injection, and changes in central macular thickness (CMT). Results As a result of multiple intravitreal anti-VEGF treatments, GCL thickness was significantly decreased from 42.99 ± 5.39 to 38.99 ± 5.53 (p < 0.001). Changes in GCL thickness were correlated with CMT and the number of injections (p = 0.02 and p = 0.048, respectively). However, multivariate analysis showed the change in mean GCL thickness in the retinal vein occlusion (RVO) was strongly associated only with CMT (p < 0.001). Conclusions As a result of multiple intravitreal injections of anti-VEGF, GCL thickness decreased significantly in RVO patients and changes in GCL thickness and CMT were correlated.


Keywords: Autosegmentation; Ganglion cell layer; Intravitreal anti-vascular endothelial growth factor injection; Retinal vein occlusion; Spectral domain optical coherence tomography

Figures


	Figure 1 Automatic segmentation of retina by SD-OCT. (A) Segmentation editor view of retina by SD-OCT Spectralis software version 0.6. A segmentation line marks and belongs to either a certain retinal structure (ILM, ELM, PR1, PR2, RPE, BM) or the outer boundary of a retinal or sub-retinal layer (RNFL, GCL, IPL, INL, OPL, ONL, CHO). (B) Thickness map of GCL, RNFL, and IPL. ILM = internal limiting membrane; RNFL = retinal nerve fiber layer; GCL = ganglion cell layer; IPL = inner plexiform layer; INL = inner nuclear layer; OPL = outer plexiform layer; ELM = external limiting membrane; PR1 = first photoreceptor layer; PR2 = second photoreceptor layer; RPE = retinal pigment epithelium; BM = Bruch's membrane; CHO = choroid; ETDRS = Early Treatment Diabetic Retinopathy Study; SD-OCT = spectral domain optical coherence tomography; ONL = outer nuclear layer.
	Click for larger image


	Figure 2 Changes in GCL thickness after multiple anti-VEGF injections in BRVO. Right eye of a 60-year-old woman with BRVO. (A) Initial fundus photography and SD-OCT image with retinal hemorrhage at ST area and cystoid macular edema. (B) Initial thickness map of GCL in BRVO patient. (C) Fundus photography and SD-OCT image after 7 anti-VEGF injections show reduction of retinal hemorrhage and macular edema. (D) Thickness map of GCL in BRVO patient after 7 anti-VEGF injections. ETDRS = Early Treatment Diabetic Retinopathy Study; GCL = ganglion cell layer; VEGF = vascular endothelial growth factor; BRVO = branch retinal vein occlusion; SD-OCT = spectral domain optical coherence tomography; ST = superotemporal.
	Click for larger image


	Figure 3 Changes in GCL thickness after multiple anti-VEGF injections in CRVO. Right eye of a 54-year-old man with CRVO. (A) Initial fundus photography and SD-OCT image with diffuse retinal hemorrhage at ST area and cystoid macular edema. (B) Initial thickness map of GCL in CRVO patient. (C) Fundus photography and SD-OCT image after 4 anti-VEGF injections show reduction of retinal hemorrhage and macular edema. (D) Thickness map of GCL in CRVO patient after 4 anti-VEGF injections. ETDRS = Early Treatment Diabetic Retinopathy Study; GCL = ganglion cell layer; VEGF = vascular endothelial growth factor; CRVO = central retinal vein occlusion; SD-OCT = spectral domain optical coherence tomography; ST = superotemporal.
	Click for larger image

Tables


	Table 1 Baseline characteristics of patients
	Click for larger image


	Table 2 Changes in GCL and CMT before and after treatment
	Click for larger image


	Table 3 Correlation of changes in GCLT with other variables
	Click for larger image


	Table 4 Multivariate regression analysis^* of variables associated with GCL thickness
	Click for larger image

References


1.	Klaver CC, Wolfs RC, Vingerling JR, et al. Age-specific prevalence and causes of blindness and visual impairment in an older population: the Rotterdam Study. Arch Ophthalmol 1998;116:653–658.

2.	Attebo K, Mitchell P, Smith W. Visual acuity and the causes of visual loss in Australia. The Blue Mountains Eye Study. Ophthalmology 1996;103:357–364.

3.	The Korean Retina Society. Retina. 4th ed. Seoul: Jin Printing and Communication; 2015. pp. 283-305. Vol. 1.

4.	Rehak J, Rehak M. Branch retinal vein occlusion: pathogenesis, visual prognosis, and treatment modalities. Curr Eye Res 2008;33:111–131.

5.	Noma H, Funatsu H, Yamasaki M, et al. Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6. Am J Ophthalmol 2005;140:256–261.

6.	Yoshimura T, Sonoda KH, Sugahara M, et al. Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases. PLoS One 2009;4:e8158.

7.	Fujikawa M, Sawada O, Miyake T, et al. Correlation between vascular endothelial growth factor and nonperfused areas in macular edema secondary to branch retinal vein occlusion. Clin Ophthalmol 2013;7:1497–1501.

8.	Hoeh AE, Ach T, Schaal KB, et al. Long-term follow-up of OCT-guided bevacizumab treatment of macular edema due to retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 2009;247:1635–1641.

9.	Prager F, Michels S, Kriechbaum K, et al. Intravitreal bevacizumab (Avastin) for macular oedema secondary to retinal vein occlusion: 12-month results of a prospective clinical trial. Br J Ophthalmol 2009;93:452–456.

*10.*	Ehlers JP, Decroos FC, Fekrat S. Intravitreal bevacizumab for macular edema secondary to branch retinal vein occlusion. Retina 2011;31:1856–1862.

*11.*	Hikichi T, Higuchi M, Matsushita T, et al. Two-year outcomes of intravitreal bevacizumab therapy for macular oedema secondary to branch retinal vein occlusion. Br J Ophthalmol 2014;98:195–199.

*12.*	Lee YS, Kim MS, Yu SY, Kwak HW. Two-year results of intravitreal bevacizumab injection in retinal vein occlusion. J Korean Ophthalmol Soc 2011;52:1039–1047.

*13.*	Carmeliet P, Ruiz de Almodovar C. VEGF ligands and receptors: implications in neurodevelopment and neurodegeneration. Cell Mol Life Sci 2013;70:1763–1778.

*14.*	Brar VS, Sharma RK, Murthy RK, Chalam KV. Evaluation of differential toxicity of varying doses of bevacizumab on retinal ganglion cells, retinal pigment epithelial cells, and vascular endothelial growth factor–enriched choroidal endothelial cells. J Ocul Pharmacol Ther 2009;25:507–511.

*15.*	Foxton RH, Finkelstein A, Vijay S, et al. VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma. Am J Pathol 2013;182:1379–1390.

*16.*	Tan O, Chopra V, Lu AT, et al. Detection of macular ganglion cell loss in glaucoma by Fourier-domain optical coherence tomography. Ophthalmology 2009;116:2305–2314. e1–e2.

*17.*	Kim NR, Kim JH, Lee J, et al. Determinants of perimacular inner retinal layer thickness in normal eyes measured by Fourier-domain optical coherence tomography. Invest Ophthalmol Vis Sci 2011;52:3413–3418.

*18.*	Wollstein G, Schuman JS, Price LL, et al. Optical coherence tomography (OCT) macular and peripapillary retinal nerve fiber layer measurements and automated visual fields. Am J Ophthalmol 2004;138:218–225.

*19.*	Nakatani Y, Higashide T, Ohkubo S, et al. Evaluation of macular thickness and peripapillary retinal nerve fiber layer thickness for detection of early glaucoma using spectral domain optical coherence tomography. J Glaucoma 2011;20:252–259.

*20.*	Cho JW, Sung KR, Lee S, et al. Relationship between visual field sensitivity and macular ganglion cell complex thickness as measured by spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci 2010;51:6401–6407.

*21.*	Tan O, Chopra V, Lu AT, et al. Detection of macular ganglion cell loss in glaucoma by Fourier-domain optical coherence tomography. Ophthalmology 2009;116:2305–2314. e1–e2.

*22.*	Takagishi M, Hirooka K, Baba T, et al. Comparison of retinal nerve fiber layer thickness measurements using time domain and spectral domain optical coherence tomography, and visual field sensitivity. J Glaucoma 2011;20:383–387.

*23.*	Park CH, Lee KI, Park HY, et al. Changes in the retinal nerve fiber layer after intravitreal injections of bevacizumab in glaucoma patients. J Korean Ophthalmol Soc 2014;55:693–701.

*24.*	Martinez-de-la-Casa JM, Ruiz-Calvo A, Saenz-Frances F, et al. Retinal nerve fiber layer thickness changes in patients with age-related macular degeneration treated with intravitreal ranibizumab. Invest Ophthalmol Vis Sci 2012;53:6214–6218.

*25.*	Kim MJ, Woo SJ, Park KH, Kim TW. Retinal nerve fiber layer thickness is decreased in the fellow eyes of patients with unilateral retinal vein occlusion. Ophthalmology 2011;118:706–710.

*26.*	Brar VS, Sharma RK, Murthy RK, Chalam KV. Bevacizumab neutralizes the protective effect of vascular endothelial growth factor on retinal ganglion cells. Mol Vis 2010;16:1848–1853.

*27.*	Iriyama A, Chen YN, Tamaki Y, Yanagi Y. Effect of anti-VEGF antibody on retinal ganglion cells in rats. Br J Ophthalmol 2007;91:1230–1233.

*28.*	Shin HJ, Shin KC, Chung H, Kim HC. Change of retinal nerve fiber layer thickness in various retinal diseases treated with multiple intravitreal antivascular endothelial growth factor. Invest Ophthalmol Vis Sci 2014;55:2403–2411.

*29.*	Williamson TH. Central retinal vein occlusion: what's the story? Br J Ophthalmol 1997;81:698–704.

*30.*	Munk MR, Sacu S, Huf W, et al. Differential diagnosis of macular edema of different pathophysiologic origins by spectral domain optical coherence tomography. Retina 2014;34:2218–2232.