Skip to main content
Top
Published in: Japanese Journal of Ophthalmology 2/2016

01-03-2016 | Clinical Investigation

Effect of leaking capillaries and microaneurysms in the perifoveal capillary network on resolution of macular edema by anti-vascular endothelial growth factor treatment

Authors: Yasuhiro Iesato, Akira Imai, Takao Hirano, Yuichi Toriyama, Toshinori Murata

Published in: Japanese Journal of Ophthalmology | Issue 2/2016

Login to get access

Abstract

Purpose

To investigate the effect of leaking capillaries and microaneurysms (MAs) in the perifoveal capillary network (PCN) on the treatment of fovea-involving macular edema (ME) secondary to branch retinal vein occlusion (BRVO) by intravitreal ranibizumab (IVR) injections combined with focal, grid, and scatter laser photocoagulation.

Methods

Retrospective comparative case series. The MA (+) group consisted of 12 patients with leaking MAs in the PCN and the MA (−) group contained 11 patients without. At 6 months following the initial IVR injection, best corrected visual acuity (BCVA) was evaluated as the primary outcome. Secondary outcomes included central macular thickness (CMT) and the number of IVR injections performed in a pro re nata (PRN) regimen when CMT was ≥300 µm and vision deteriorated by 0.1 logMAR or greater.

Results

Mean BCVA improved by 0.30 ± 0.25 logMAR in the MA (−) group and 0.28 ± 0.20 logMAR in the MA (+) group (both P < 0.0001). Mean CMT was reduced by 237.6 ± 221.4 µm (P < 0.0001) in the MA (−) and 158.2 ± 152.1 µm (P < 0.01) in the MA (+) group. The degrees of improvement in BCVA (P = 0.74) and CMT (P = 0.33) did not vary significantly between the groups. The mean number of additional IVR injections was significantly less in the MA (–) group than in the MA (+) group (2.2 ± 1.0 vs 3.0 ± 0.8; P = 0.04).

Conclusions

Although leaking MAs and capillaries in the PCN did not adversely affect improvements in BCVA and CMT, these manifestations led to an increased number of IVR injections needed to sustain resolution of ME involving the fovea.
Literature
1.
go back to reference Klein R, Moss SE, Meuer SM, Klein BE. The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study. Arch Ophthalmol. 2008;126:513–8.CrossRefPubMed Klein R, Moss SE, Meuer SM, Klein BE. The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study. Arch Ophthalmol. 2008;126:513–8.CrossRefPubMed
2.
go back to reference Hirashima T, Chihara T, Bun T, Utsumi T, Hirose M, Oh H. Intravitreal bevacizumab alone or combined with macular laser photocoagulation for recurrent or persistent macular edema secondary to branch retinal vein occlusion. J Ophthalmol. 2014;2014:173084.PubMedCentralCrossRefPubMed Hirashima T, Chihara T, Bun T, Utsumi T, Hirose M, Oh H. Intravitreal bevacizumab alone or combined with macular laser photocoagulation for recurrent or persistent macular edema secondary to branch retinal vein occlusion. J Ophthalmol. 2014;2014:173084.PubMedCentralCrossRefPubMed
3.
go back to reference The Branch Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch vein occlusion. Am J Ophthalmol. 1984;98:271–82.CrossRef The Branch Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch vein occlusion. Am J Ophthalmol. 1984;98:271–82.CrossRef
4.
go back to reference Campochiaro PA, Heier JS, Feiner L, Gray S, Saroj N, Rundle AC, et al. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010;117(1102–12):e1. Campochiaro PA, Heier JS, Feiner L, Gray S, Saroj N, Rundle AC, et al. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010;117(1102–12):e1.
5.
go back to reference Sophie R, Hafiz G, Scott AW, Zimmer-Galler I, Nguyen QD, Ying H, et al. Long-term outcomes in ranibizumab-treated patients with retinal vein occlusion; the role of progression of retinal nonperfusion. Am J Ophthalmol. 2013;156:693–705.PubMedCentralCrossRefPubMed Sophie R, Hafiz G, Scott AW, Zimmer-Galler I, Nguyen QD, Ying H, et al. Long-term outcomes in ranibizumab-treated patients with retinal vein occlusion; the role of progression of retinal nonperfusion. Am J Ophthalmol. 2013;156:693–705.PubMedCentralCrossRefPubMed
6.
go back to reference Campochiaro PA, Sophie R, Pearlman J, Brown DM, Boyer DS, Heier JS, et al. Long-term outcomes in patients with retinal vein occlusion treated with ranibizumab: the RETAIN study. Ophthalmology. 2014;121:209–19.CrossRefPubMed Campochiaro PA, Sophie R, Pearlman J, Brown DM, Boyer DS, Heier JS, et al. Long-term outcomes in patients with retinal vein occlusion treated with ranibizumab: the RETAIN study. Ophthalmology. 2014;121:209–19.CrossRefPubMed
7.
go back to reference Shah AM, Bressler NM, Jampol LM. Does laser still have a role in the management of retinal vascular and neovascular diseases? Am J Ophthalmol. 2011;152(332–9):e1.PubMed Shah AM, Bressler NM, Jampol LM. Does laser still have a role in the management of retinal vascular and neovascular diseases? Am J Ophthalmol. 2011;152(332–9):e1.PubMed
8.
go back to reference Hayashi A, Yunoki T, Miyakoshi A, Mitarai K, Fujino T, Yanagisawa S. Intravitreal injection of bevacizumab combined with macular grid laser photocoagulation for macular edema in branch retinal vein occlusion. Jpn J Ophthalmol. 2011;55:625–31.CrossRefPubMed Hayashi A, Yunoki T, Miyakoshi A, Mitarai K, Fujino T, Yanagisawa S. Intravitreal injection of bevacizumab combined with macular grid laser photocoagulation for macular edema in branch retinal vein occlusion. Jpn J Ophthalmol. 2011;55:625–31.CrossRefPubMed
9.
go back to reference Donati S, Barosi P, Bianchi M, Al Oum M, Azzolini C. Combined intravitreal bevacizumab and grid laser photocoagulation for macular edema secondary to branch retinal vein occlusion. Eur J Ophthalmol. 2012;22:607–14.CrossRefPubMed Donati S, Barosi P, Bianchi M, Al Oum M, Azzolini C. Combined intravitreal bevacizumab and grid laser photocoagulation for macular edema secondary to branch retinal vein occlusion. Eur J Ophthalmol. 2012;22:607–14.CrossRefPubMed
10.
go back to reference Farese E, Cennamo G, Velotti N, Traversi C, Rinaldi M, De Crecchio G. Intravitreal bevacizumab combined with grid photocoagulation in recurrent macular edema secondary to retinal vein occlusion. Eur J Ophthalmol. 2014;24:761–70.CrossRefPubMed Farese E, Cennamo G, Velotti N, Traversi C, Rinaldi M, De Crecchio G. Intravitreal bevacizumab combined with grid photocoagulation in recurrent macular edema secondary to retinal vein occlusion. Eur J Ophthalmol. 2014;24:761–70.CrossRefPubMed
11.
go back to reference Salinas-Alaman A, Zarranz-Ventura J, Caire Gonzalez-Jauregui JM, Sadaba-Echarri LM, Barrio-Barrio J, Garcia-Layana A. Intravitreal bevacizumab associated with grid laser photocoagulation in macular edema secondary to branch retinal vein occlusion. Eur J Ophthalmol. 2011;21:434–9.CrossRefPubMed Salinas-Alaman A, Zarranz-Ventura J, Caire Gonzalez-Jauregui JM, Sadaba-Echarri LM, Barrio-Barrio J, Garcia-Layana A. Intravitreal bevacizumab associated with grid laser photocoagulation in macular edema secondary to branch retinal vein occlusion. Eur J Ophthalmol. 2011;21:434–9.CrossRefPubMed
12.
go back to reference Pielen A, Mirshahi A, Feltgen N, Lorenz K, Korb C, Junker B, et al. Ranibizumab for Branch Retinal Vein Occlusion Associated Macular Edema Study (RABAMES): six-month results of a prospective randomized clinical trial. Acta Ophthalmol. 2015;93:e29–e37. doi:10.1111/aos.12488.CrossRefPubMed Pielen A, Mirshahi A, Feltgen N, Lorenz K, Korb C, Junker B, et al. Ranibizumab for Branch Retinal Vein Occlusion Associated Macular Edema Study (RABAMES): six-month results of a prospective randomized clinical trial. Acta Ophthalmol. 2015;93:e29–e37. doi:10.​1111/​aos.​12488.CrossRefPubMed
13.
go back to reference Campochiaro PA, Hafiz G, Mir TA, Scott AW, Solomon S, Zimmer-Galler I, et al. Scatter photocoagulation does not reduce macular edema or treatment burden in patients with retinal vein occlusion: the RELATE trial. Ophthalmology. 2015;122:1426–37. doi:10.1016/j.ophtha.2015.04.006.CrossRefPubMed Campochiaro PA, Hafiz G, Mir TA, Scott AW, Solomon S, Zimmer-Galler I, et al. Scatter photocoagulation does not reduce macular edema or treatment burden in patients with retinal vein occlusion: the RELATE trial. Ophthalmology. 2015;122:1426–37. doi:10.​1016/​j.​ophtha.​2015.​04.​006.CrossRefPubMed
14.
go back to reference Early Treatment Diabetic Retinopathy Study Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 2. Ophthalmology. 1987;94:761–74.CrossRef Early Treatment Diabetic Retinopathy Study Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 2. Ophthalmology. 1987;94:761–74.CrossRef
15.
go back to reference Budzynski E, Smith JH, Bryar P, Birol G, Linsenmeier RA. Effects of photocoagulation on intraretinal PO2 in cat. Invest Ophthalmol Vis Sci. 2008;49:380–9.CrossRefPubMed Budzynski E, Smith JH, Bryar P, Birol G, Linsenmeier RA. Effects of photocoagulation on intraretinal PO2 in cat. Invest Ophthalmol Vis Sci. 2008;49:380–9.CrossRefPubMed
16.
go back to reference Rosser DA, Cousens SN, Murdoch IE, Fitzke FW, Laidlaw DA. How sensitive to clinical change are ETDRS logMAR visual acuity measurements? Invest Ophthalmol Vis Sci. 2003;44:3278–81.CrossRefPubMed Rosser DA, Cousens SN, Murdoch IE, Fitzke FW, Laidlaw DA. How sensitive to clinical change are ETDRS logMAR visual acuity measurements? Invest Ophthalmol Vis Sci. 2003;44:3278–81.CrossRefPubMed
17.
go back to reference Wessel MM, Nair N, Aaker GD, Ehrlich JR, D’Amico DJ, Kiss S. Peripheral retinal ischaemia, as evaluated by ultra-widefield fluorescein angiography, is associated with diabetic macular oedema. Br J Ophthalmol. 2012;96:694–8.PubMedCentralCrossRefPubMed Wessel MM, Nair N, Aaker GD, Ehrlich JR, D’Amico DJ, Kiss S. Peripheral retinal ischaemia, as evaluated by ultra-widefield fluorescein angiography, is associated with diabetic macular oedema. Br J Ophthalmol. 2012;96:694–8.PubMedCentralCrossRefPubMed
18.
go back to reference Patel RD, Messner LV, Teitelbaum B, Michel KA, Hariprasad SM. Characterization of ischemic index using ultra-widefield fluorescein angiography in patients with focal and diffuse recalcitrant diabetic macular edema. Am J Ophthalmol. 2013;155(1038–44):e2.PubMed Patel RD, Messner LV, Teitelbaum B, Michel KA, Hariprasad SM. Characterization of ischemic index using ultra-widefield fluorescein angiography in patients with focal and diffuse recalcitrant diabetic macular edema. Am J Ophthalmol. 2013;155(1038–44):e2.PubMed
19.
go back to reference Takamura Y, Tomomatsu T, Matsumura T, Arimura S, Gozawa M, Takihara Y, et al. The effect of photocoagulation in ischemic areas to prevent recurrence of diabetic macular edema after intravitreal bevacizumab injection. Invest Ophthalmol Vis Sci. 2014;55:4741–6.CrossRefPubMed Takamura Y, Tomomatsu T, Matsumura T, Arimura S, Gozawa M, Takihara Y, et al. The effect of photocoagulation in ischemic areas to prevent recurrence of diabetic macular edema after intravitreal bevacizumab injection. Invest Ophthalmol Vis Sci. 2014;55:4741–6.CrossRefPubMed
20.
go back to reference Murakami T, Tsujikawa A, Miyamoto K, Sakamoto A, Ota M, Ogino K, et al. Relationship between perifoveal capillaries and pathomorphology in macular oedema associated with branch retinal vein occlusion. Eye (Lond). 2012;26:771–80.PubMedCentralCrossRefPubMed Murakami T, Tsujikawa A, Miyamoto K, Sakamoto A, Ota M, Ogino K, et al. Relationship between perifoveal capillaries and pathomorphology in macular oedema associated with branch retinal vein occlusion. Eye (Lond). 2012;26:771–80.PubMedCentralCrossRefPubMed
21.
go back to reference Tolentino MJ, Miller JW, Gragoudas ES, Jakobiec FA, Flynn E, Chatzistefanou K, et al. Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate. Ophthalmology. 1996;103:1820–8.CrossRefPubMed Tolentino MJ, Miller JW, Gragoudas ES, Jakobiec FA, Flynn E, Chatzistefanou K, et al. Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate. Ophthalmology. 1996;103:1820–8.CrossRefPubMed
22.
go back to reference Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, 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;140:256–61.CrossRefPubMed Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, 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;140:256–61.CrossRefPubMed
23.
go back to reference Noma H, Minamoto A, Funatsu H, Tsukamoto H, Nakano K, Yamashita H, et al. Intravitreal levels of vascular endothelial growth factor and interleukin-6 are correlated with macular edema in branch retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol. 2006;244:309–15.CrossRefPubMed Noma H, Minamoto A, Funatsu H, Tsukamoto H, Nakano K, Yamashita H, et al. Intravitreal levels of vascular endothelial growth factor and interleukin-6 are correlated with macular edema in branch retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol. 2006;244:309–15.CrossRefPubMed
24.
go back to reference Finkelstein D. Ischemic macular edema. Recognition and favorable natural history in branch vein occlusion. Arch Ophthalmol. 1992;110:1427–34.CrossRefPubMed Finkelstein D. Ischemic macular edema. Recognition and favorable natural history in branch vein occlusion. Arch Ophthalmol. 1992;110:1427–34.CrossRefPubMed
25.
go back to reference Campochiaro PA, Bhisitkul RB, Shapiro H, Rubio RG. Vascular endothelial growth factor promotes progressive retinal nonperfusion in patients with retinal vein occlusion. Ophthalmology. 2013;120:795–802.CrossRefPubMed Campochiaro PA, Bhisitkul RB, Shapiro H, Rubio RG. Vascular endothelial growth factor promotes progressive retinal nonperfusion in patients with retinal vein occlusion. Ophthalmology. 2013;120:795–802.CrossRefPubMed
26.
go back to reference Campochiaro PA, Hafiz G, Shah SM, Nguyen QD, Ying H, Do DV, et al. Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator. Mol Ther. 2008;16:791–9.CrossRefPubMed Campochiaro PA, Hafiz G, Shah SM, Nguyen QD, Ying H, Do DV, et al. Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator. Mol Ther. 2008;16:791–9.CrossRefPubMed
27.
go back to reference Heier JS, Campochiaro PA, Yau L, Li Z, Saroj N, Rubio RG, et al. Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial. Ophthalmology. 2012;119:802–9.CrossRefPubMed Heier JS, Campochiaro PA, Yau L, Li Z, Saroj N, Rubio RG, et al. Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial. Ophthalmology. 2012;119:802–9.CrossRefPubMed
28.
go back to reference Senger DR, Connolly DT, Van de Water L, Feder J, Dvorak HF. Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor. Cancer Res. 1990;50:1774–8.PubMed Senger DR, Connolly DT, Van de Water L, Feder J, Dvorak HF. Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor. Cancer Res. 1990;50:1774–8.PubMed
29.
30.
go back to reference Tan MH, McAllister IL, Gillies ME, Verma N, Banerjee G, Smithies LA, et al. Randomized controlled trial of intravitreal ranibizumab versus standard grid laser for macular edema following branch retinal vein occlusion. Am J Ophthalmol. 2014;157:237–47.e1.CrossRefPubMed Tan MH, McAllister IL, Gillies ME, Verma N, Banerjee G, Smithies LA, et al. Randomized controlled trial of intravitreal ranibizumab versus standard grid laser for macular edema following branch retinal vein occlusion. Am J Ophthalmol. 2014;157:237–47.e1.CrossRefPubMed
31.
go back to reference Liegl R, Langer J, Seidensticker F, Reznicek L, Haritoglou C, Ulbig MW, et al. Comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema. PLoS One. 2014;9:e113981.PubMedCentralCrossRefPubMed Liegl R, Langer J, Seidensticker F, Reznicek L, Haritoglou C, Ulbig MW, et al. Comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema. PLoS One. 2014;9:e113981.PubMedCentralCrossRefPubMed
Metadata
Title
Effect of leaking capillaries and microaneurysms in the perifoveal capillary network on resolution of macular edema by anti-vascular endothelial growth factor treatment
Authors
Yasuhiro Iesato
Akira Imai
Takao Hirano
Yuichi Toriyama
Toshinori Murata
Publication date
01-03-2016
Publisher
Springer Japan
Published in
Japanese Journal of Ophthalmology / Issue 2/2016
Print ISSN: 0021-5155
Electronic ISSN: 1613-2246
DOI
https://doi.org/10.1007/s10384-016-0425-5

Other articles of this Issue 2/2016

Japanese Journal of Ophthalmology 2/2016 Go to the issue