Ji Young Lee; Hyung Chan Kim

doi:10.3341/jkos.2016.57.1.63

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Lee and Kim: Ganglion Cell Layer Thickness after Anti‐ Vascular Endothelial Growth Factor Treatment in Retinal Vein Occlusion

Original Article

J Korean Ophthalmol Soc 2015;57(1):63-70.

Published online: 29 August 2015

DOI: https://doi.org/10.3341/jkos.2016.57.1.63

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

Ji Young Lee, M.D, Hyung Chan Kim, M.D, 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 E-mail: eyekim@kuh.ac.kr

Received 15 May 201523 September 2015 Accepted 20 November 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 occlu-sion 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 eval-uated 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

References

1. Klaver CC, Wolfs RC, Vingerling JR. . Age-specific preva-lence and causes of blindness and visual impairment in an older population: the Rotterdam Study. Arch Ophthalmol. 1998; 116:653–8.

2. Attebo K, Mitchell P, Smith W. Visual acuity and the causes of visu-al loss in Australia. The Blue Mountains Eye Study. Ophthalmology. 1996; 103:357–64.

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

4. Rehak J, Rehak M. Branch retinal vein occlusion: pathogenesis, visual prognosis, and treatment modalities. Curr Eye Res. 2008; 33:111–31.

5. Noma H, Funatsu H, Yamasaki M. . Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6. Am J Ophthalmol. 2005; 140:256–61.

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

7. Fujikawa M, Sawada O, Miyake T. . Correlation between vas-cular endothelial growth factor and nonperfused areas in macular edema secondary to branch retinal vein occlusion. Clin Ophthalmol. 2013; 7:1497–501.

8. Hoeh AE, Ach T, Schaal KB. . Long-term follow-up of OCT-guided bevacizumab treatment of macular edema due to retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol. 2009; 247:1635–41.

9. Prager F, Michels S, Kriechbaum K. . Intravitreal bevacizumab (Avastin) for macular oedema secondary to retinal vein occlusion: 12-month results of a prospective clinical trial. Br J Ophthalmol. 2009; 93:452–6.

10. Ehlers JP, Decroos FC, Fekrat S. Intravitreal bevacizumab for mac-ular edema secondary to branch retinal vein occlusion. Retina. 2011; 31:1856–62.

11. Hikichi T, Higuchi M, Matsushita T. . Two-year outcomes of intravitreal bevacizumab therapy for macular oedema secondary to branch retinal vein occlusion. Br J Ophthalmol. 2014; 98:195–9.

12. Lee YS, Kim MS, Yu SY, Kwak HW. Two-year results of intra-vitreal bevacizumab injection in retinal vein occlusion. J Korean Ophthalmol Soc. 2011; 52:1039–47.

13. Carmeliet P, Ruiz de Almodovar C. VEGF ligands and receptors: implications in neurodevelopment and neurodegeneration. Cell Mol Life Sci. 2013; 70:1763–78.

14. Brar VS, Sharma RK, Murthy RK, Chalam KV. Evaluation of dif-ferential toxicity of varying doses of bevacizumab on retinal gan-glion cells, retinal pigment epithelial cells, and vascular endothe-lial growth factor–enriched choroidal endothelial cells. J Ocul Pharmacol Ther. 2009; 25:507–11.

15. Foxton RH, Finkelstein A, Vijay S. . VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma. Am J Pathol. 2013; 182:1379–90.

16. Tan O, Chopra V, Lu AT. . Detection of macular ganglion cell loss in glaucoma by Fourier-domain optical coherence tomography. Ophthalmology. 2009; 116:2305–14. e1-2.

17. Kim NR, Kim JH, Lee J. . Determinants of perimacular inner retinal layer thickness in normal eyes measured by Fourier-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2011; 52:3413–8.

18. Wollstein G, Schuman JS, Price LL. . Optical coherence to-mography (OCT) macular and peripapillary retinal nerve fiber lay-er measurements and automated visual fields. Am J Ophthalmol. 2004; 138:218–25.

19. Nakatani Y, Higashide T, Ohkubo S. . Evaluation of macular thickness and peripapillary retinal nerve fiber layer thickness for detection of early glaucoma using spectral domain optical coher-ence tomography. J Glaucoma. 2011; 20:252–9.

20. Cho JW, Sung KR, Lee S. . Relationship between visual field sensitivity and macular ganglion cell complex thickness as meas-ured by spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2010; 51:6401–7.

21. Tan O, Chopra V, Lu AT. . Detection of macular ganglion cell loss in glaucoma by Fourier-domain optical coherence tomography. Ophthalmology. 2009; 116:2305–14. e1-2.

22. Takagishi M, Hirooka K, Baba T. . Comparison of retinal nerve fiber layer thickness measurements using time domain and spectral domain optical coherence tomography, and visual field sensitivity. J Glaucoma. 2011; 20:383–7.

23. Park CH, Lee KI, Park HY. . 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. . Retinal nerve fiber layer thickness changes in patients with age-re-lated macular degeneration treated with intravitreal ranibizumab. Invest Ophthalmol Vis Sci. 2012; 53:6214–8.

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; 118:706–10.

26. Brar VS, Sharma RK, Murthy RK, Chalam KV. Bevacizumab neu-tralizes the protective effect of vascular endothelial growth factor on retinal ganglion cells. Mol Vis. 2010; 16:1848–53.

27. Iriyama A, Chen YN, Tamaki Y, Yanagi Y. Effect of anti-VEGF an-tibody on retinal ganglion cells in rats. Br J Ophthalmol. 2007; 91:1230–3.

28. Shin HJ, Shin KC, Chung H, Kim HC. Change of retinal nerve fi-ber layer thickness in various retinal diseases treated with multiple intravitreal antivascular endothelial growth factor. Invest Ophthalmol Vis Sci. 2014; 55:2403–11.

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. . Differential diagnosis of macular edema of different pathophysiologic origins by spectral domain optical coherence tomography. Retina. 2014; 34:2218–32.

Figure 1.

Automatic segmentation of retina by SD-OCT. (A) Segmentation editor view of retina by SD-OCT Spectralis software ver-sion 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.

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 thick-ness 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.

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.

Table 1.

Baseline characteristics of patients

	BRVO	CRVO	Total	p-value
No. of patients (eyes)	35	25	60	-
Male/female	14/21	13/12	27/33	0.434^*
Age (years)	62.54 ± 8.52	64.28 ± 10.67	63.27 ± 9.43	0.509^†
Follow up period (months)	19.54 ± 17.41	22.44 ± 17.16	20.75 ± 17.22	0.467^†
No. of injections	5.26 ± 2.59	6.48 ± 10.67	5.77 ± 3.27	0.329^†
Initial IOP (mm Hg)	14.02 ± 2.37	16.28 ± 2.59	14.97 ± 2.69	0.001^†
Initial CMT (μ m)	385.83 ± 135.94	463.56 ± 158.92	418.22 ± 149.72	0.062^†
Initial average GCLT (μ m)	42.30 ± 4.78	43.94 ± 6.12	42.99 ± 5.39	0.161^†

Values are presented as mean ± SD unless otherwise indicated.

BRVO = branch retinal vein occlusion; CRVO = central retinal vein occlusion; IOP = intraocular pressure; CMT = central macular thick-ness; GCLT = ganglion cell layer thickness.

^* Chi-square test

^† Mann-Whitney test.

Table 2.

Changes in GCL and CMT before and after treatment

	Total (BRVO + CRVO)
	Pre-treatment	Post-treatment	p-value^*
GCLT
Fovea (μ m)	22.20 ± 10.02	18.25 ± 8.25	0.038
SC (μ m)	54.47 ± 7.93	50.02 ± 9.97	<0.001
SP (μ m)	37.37 ± 5.95	34.42 ± 7.57	0.003
NC (μ m)	54.97 ± 7.46	50.97 ± 8.18	<0.001
NP (μ m)	41.55 ± 5.48	40.43 ± 5.80	0.099
IC (μ m)	54.15 ± 11.34	47.98 ± 13.24	<0.001
IP (μ m)	35.60 ± 6.46	33.20 ± 6.72	0.003
TC (μ m)	49.85 ± 8.38	41.87 ± 8.59	<0.001
TP (μ m)	38.05 ± 6.72	33.78 ± 7.08	<0.001
Average	42.99 ± 5.39	38.99 ± 5.53	<0.001
CMT (μ m)	418.22 ± 149.72	306.93 ± 89.02	<0.001

Values are presented as mean ± SD unless otherwise indicated.

GCL = ganglion cell layer; CMT = central macular thickness; BRVO = branch retinal vein occlusion; CRVO = central retinal vein occlu-sion; GCLT = ganglion cell layer thickness; SC = superior-central; SP = superior-peripheral; NC = nasal-central; NP = nasal-peripheral; IC = inferior-central; IP = inferior-peripheral; TC = temporal-central; TP = temporal-peripheral.

^* Paired t-test.

Table 3.

Correlation of changes in GCLT with other variables

Variables	r	p-value^*
Age (years)	0.129	0.326
Changes in IOP	0.082	0.535
Changes in CMT	0.392	0.002
No. of injections	0.256	0.048

GCLT = ganglion cell layer thickness; IOP = intra ocular pres-sure; CMT = central macular thickness.

^* Spearman correlation test.

Table 4.

Multivariate regression analysis^* of variables associated with GCL thickness

Variables	95% CI^*	R-square^*	p-value^*
Changes in CMT	0.0264-0.0577	0.048	<0.001

GCL = ganglion cell layer; CI = confidence interval; CMT = central macular thickness.

^* Multivariate regression analysis after univariate regression 10% selection, backward elimination.

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