Skip to main content
Top
Published in: International Ophthalmology 6/2019

01-06-2019 | Original Paper

Effects of kallidinogenase in patients undergoing vitrectomy for diabetic macular edema

Authors: Yuki Yoshizumi, Zaigen Ohara, Hitoshi Tabuchi, Hitomi Sumino, Yukiko Maeda, Hideki Mochizuki, Ken Yamane, Yoshiaki Kiuchi

Published in: International Ophthalmology | Issue 6/2019

Login to get access

Abstract

Purpose

To evaluate the effectiveness of the combination of vitrectomy with kallidinogenase for diabetic macular edema (DME).

Methods

This study was designed as a prospective, randomized, multicenter study comparing 19 eyes of 19 patients who received 150 units of kallidinogenase administered a day for 52 weeks from the day after vitrectomy (study group) with 20 eyes of 20 patients who received no kallidinogenase (control group). The main outcome measurements included logMAR visual acuity and central foveal thickness (CFT) before surgery and at 3, 6, 9, and 12 months after vitrectomy.

Results

During follow-up, 11 patients dropped out (six in the study group and five in the control group), leaving 28 eyes in 28 patients for analysis (13 in the study group and 15 in the control group). Visual acuity improved significantly at 12 months in both groups compared with before surgery. The degree of improvement did not differ significantly between the groups. At 12 months, the mean CFT decreased significantly in both groups, with no significant difference in the rate of change between the two groups. In the study group, the visual acuity and CFT significantly improved from 3 to 12 months and from 6 to 12 months, whereas these parameters did not continue to improve in the control group after 6 months (for visual acuity) or 3 months (for CFT).

Conclusion

After vitrectomy for DME, visual acuity and CFT improved significantly in both groups, but only patients treated with kallidinogenase continued to have significant improvement throughout the study period.
Appendix
Available only for authorised users
Literature
1.
go back to reference Wako R, Yasukawa T, Kato A, Omori T, Ishida S, Ishibashi T, Ogura Y (2014) Causes and prevalence of visual impairment in Japan. Nippon Ganka Gakkai Zasshi 118(6):495–501 (in Japanese) Wako R, Yasukawa T, Kato A, Omori T, Ishida S, Ishibashi T, Ogura Y (2014) Causes and prevalence of visual impairment in Japan. Nippon Ganka Gakkai Zasshi 118(6):495–501 (in Japanese)
2.
go back to reference Klein R, Klein BE, Moss SE, Cruickshanks KJ (1995) The Wisconsin epidemiologic study of diabetic retinopathy. XV. The long-term incidence of macular edema. Ophthalmology 102(1):7–16CrossRefPubMed Klein R, Klein BE, Moss SE, Cruickshanks KJ (1995) The Wisconsin epidemiologic study of diabetic retinopathy. XV. The long-term incidence of macular edema. Ophthalmology 102(1):7–16CrossRefPubMed
3.
go back to reference Cunningham ET Jr, Adamis AP, Altaweel M et al (2005) Macugen Diabetic Retinopathy Study Group: a phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology 112(10):1747–1757CrossRefPubMed Cunningham ET Jr, Adamis AP, Altaweel M et al (2005) Macugen Diabetic Retinopathy Study Group: a phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology 112(10):1747–1757CrossRefPubMed
4.
go back to reference Arevalo JF, Fromow-Guerra J, Quiroz-Mercado H et al (2007) Pan-American collaborative retina study group: primary intravitreal bevacizumab (Avastin) for diabetic macular edema: results from the Pan-American collaborative retina study group at 6-month follow-up. Ophthalmology 114:743–750CrossRefPubMed Arevalo JF, Fromow-Guerra J, Quiroz-Mercado H et al (2007) Pan-American collaborative retina study group: primary intravitreal bevacizumab (Avastin) for diabetic macular edema: results from the Pan-American collaborative retina study group at 6-month follow-up. Ophthalmology 114:743–750CrossRefPubMed
5.
go back to reference Diabetic Retinopathy Clinical Research Network (2008) A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology 115(9):1447–1449CrossRefPubMedCentral Diabetic Retinopathy Clinical Research Network (2008) A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology 115(9):1447–1449CrossRefPubMedCentral
6.
go back to reference Brown DM, Nguyen QD, Marcus DM, Boyer DS, Patel S, Feiner L, Schlottmann PG, Rundle AC, Zhang J, Rubio RG, Adamis AP (2013) Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology 120(10):2013–2022CrossRefPubMed Brown DM, Nguyen QD, Marcus DM, Boyer DS, Patel S, Feiner L, Schlottmann PG, Rundle AC, Zhang J, Rubio RG, Adamis AP (2013) Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology 120(10):2013–2022CrossRefPubMed
7.
go back to reference Schmidt-Erfurth U, Lang GE, Holz FG, Schlingemann RO, Lanzetta P, Massin P, Gerstner O, Bouazza AS, Shen H, Osborne A, Mitchell P (2014) Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study. Ophthalmology 121(5):1045–1053CrossRefPubMed Schmidt-Erfurth U, Lang GE, Holz FG, Schlingemann RO, Lanzetta P, Massin P, Gerstner O, Bouazza AS, Shen H, Osborne A, Mitchell P (2014) Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study. Ophthalmology 121(5):1045–1053CrossRefPubMed
8.
go back to reference Lewis H, Abrams GW, Blumenkranz MS, Campo RV (1992) Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology 99(5):753–759CrossRefPubMed Lewis H, Abrams GW, Blumenkranz MS, Campo RV (1992) Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology 99(5):753–759CrossRefPubMed
9.
go back to reference Harbour JW, Smiddy WE, Flynn HW Jr, Rubsamen PE (1996) Vitrectomy for diabetic macular edema associated with a thickened and taut posterior hyaloid membrane. Am J Ophthalmol 121(4):405–413CrossRefPubMed Harbour JW, Smiddy WE, Flynn HW Jr, Rubsamen PE (1996) Vitrectomy for diabetic macular edema associated with a thickened and taut posterior hyaloid membrane. Am J Ophthalmol 121(4):405–413CrossRefPubMed
10.
go back to reference Pendergast SD, Hassan TS, Williams GA, Cox MS, Margherio RR, Ferrone PJ, Garretson BR, Trese MT (2000) Vitrectomy for diffuse diabetic macular edema associated with a taut premacular posterior hyaloid. Am J Ophthalmol 130(2):178–186CrossRefPubMed Pendergast SD, Hassan TS, Williams GA, Cox MS, Margherio RR, Ferrone PJ, Garretson BR, Trese MT (2000) Vitrectomy for diffuse diabetic macular edema associated with a taut premacular posterior hyaloid. Am J Ophthalmol 130(2):178–186CrossRefPubMed
11.
go back to reference Yamamoto T, Akabane N, Takeuchi S (2001) Vitrectomy for diabetic macular edema: the role of posterior vitreous detachment and epimacular membrane. Am J Ophthalmol 132(3):369–377CrossRefPubMed Yamamoto T, Akabane N, Takeuchi S (2001) Vitrectomy for diabetic macular edema: the role of posterior vitreous detachment and epimacular membrane. Am J Ophthalmol 132(3):369–377CrossRefPubMed
12.
go back to reference La Heij EC, Hendrikse F, Kessels AG, Derhaag PJ (2001) Vitrectomy results in diabetic macular oedema without evident vitreomacular traction. Graefes Arch Clin Exp Ophthalmol 239(4):264–270CrossRefPubMed La Heij EC, Hendrikse F, Kessels AG, Derhaag PJ (2001) Vitrectomy results in diabetic macular oedema without evident vitreomacular traction. Graefes Arch Clin Exp Ophthalmol 239(4):264–270CrossRefPubMed
13.
go back to reference Rosenblatt BJ, Shah GK, Sharma S, Bakal J (2005) Pars plana vitrectomy with internal limiting membranectomy for refractory diabetic macular edema without a taut posterior hyaloid. Graefes Arch Clin Exp Ophthalmol 243(1):20–25CrossRefPubMed Rosenblatt BJ, Shah GK, Sharma S, Bakal J (2005) Pars plana vitrectomy with internal limiting membranectomy for refractory diabetic macular edema without a taut posterior hyaloid. Graefes Arch Clin Exp Ophthalmol 243(1):20–25CrossRefPubMed
14.
go back to reference Hoerauf H, Brüggemann A, Muecke M, Lüke J, Müller M, Stefánsson E, Hammes HP, Weiß C (2011) Pars plana vitrectomy for diabetic macular edema. Internal limiting membrane delamination vs posterior hyaloid removal. A prospective randomized trial. Graefes Arch Clin Exp Ophthalmol 249(7):997–1008CrossRefPubMedPubMedCentral Hoerauf H, Brüggemann A, Muecke M, Lüke J, Müller M, Stefánsson E, Hammes HP, Weiß C (2011) Pars plana vitrectomy for diabetic macular edema. Internal limiting membrane delamination vs posterior hyaloid removal. A prospective randomized trial. Graefes Arch Clin Exp Ophthalmol 249(7):997–1008CrossRefPubMedPubMedCentral
15.
go back to reference Yamamoto T, Hitani K, Tsukahara I, Yamamoto S, Kawasaki R, Yamashita H, Takeuchi S (2003) Early postoperative retinal thickness changes and complications after vitrectomy for diabetic macular edema. Am J Ophthalmol 135(1):14–19CrossRefPubMed Yamamoto T, Hitani K, Tsukahara I, Yamamoto S, Kawasaki R, Yamashita H, Takeuchi S (2003) Early postoperative retinal thickness changes and complications after vitrectomy for diabetic macular edema. Am J Ophthalmol 135(1):14–19CrossRefPubMed
16.
go back to reference Suzuki H, Ishizaki E, Kakurai K et al (2011) Comparative study of kallidinogenase efficacy in treating diabetic macular edema. Atarashii Ganka 28:1457–1459 (in Japanese) Suzuki H, Ishizaki E, Kakurai K et al (2011) Comparative study of kallidinogenase efficacy in treating diabetic macular edema. Atarashii Ganka 28:1457–1459 (in Japanese)
17.
go back to reference Kato N, Hou Y, Lu Z, Lu C, Nagano H, Suzuma K, Takagi H, Matsumoto Y (2009) Kallidinogenase normalizes retinal vasopermeability in streptozotocin-induced diabetic rats: potential roles of vascular endothelial growth factor and nitric oxide. Eur J Pharmacol 606(1):187–190CrossRefPubMed Kato N, Hou Y, Lu Z, Lu C, Nagano H, Suzuma K, Takagi H, Matsumoto Y (2009) Kallidinogenase normalizes retinal vasopermeability in streptozotocin-induced diabetic rats: potential roles of vascular endothelial growth factor and nitric oxide. Eur J Pharmacol 606(1):187–190CrossRefPubMed
18.
go back to reference Nakamura S, Morimoto N, Tsuruma K, Izuta H, Yasuda Y, Kato N, Ikeda T, Shimazawa M, Hara H (2011) Tissue kallikrein inhibits retinal neovascularization via the cleavage of vascular endothelial growth factor-165. Arterioscler Thromb Vasc Biol 31(5):1041–1048CrossRefPubMed Nakamura S, Morimoto N, Tsuruma K, Izuta H, Yasuda Y, Kato N, Ikeda T, Shimazawa M, Hara H (2011) Tissue kallikrein inhibits retinal neovascularization via the cleavage of vascular endothelial growth factor-165. Arterioscler Thromb Vasc Biol 31(5):1041–1048CrossRefPubMed
19.
go back to reference Fukuhara J, Noda K, Murata M, Namba S, Kinoshita S, Dong Z, Ando R, Lennikov A, Kanda A, Ishida S (2013) Tissue kallikrein attenuates choroidal neovascularization via cleavage of vascular endothelial growth factor. Invest Ophthalmol Vis Sci 54(1):274–279CrossRefPubMed Fukuhara J, Noda K, Murata M, Namba S, Kinoshita S, Dong Z, Ando R, Lennikov A, Kanda A, Ishida S (2013) Tissue kallikrein attenuates choroidal neovascularization via cleavage of vascular endothelial growth factor. Invest Ophthalmol Vis Sci 54(1):274–279CrossRefPubMed
20.
go back to reference Ise S, Furuta M, Sekiryu T (2016) Adjuvant kallidinogenase in patients with vitrectomy for diabetic macular edema. Atarashii Ganka 33:145–150 (in Japanese) Ise S, Furuta M, Sekiryu T (2016) Adjuvant kallidinogenase in patients with vitrectomy for diabetic macular edema. Atarashii Ganka 33:145–150 (in Japanese)
21.
go back to reference Flaxel CJ, Edwards AR, Aiello LP, Arrigg PG, Beck RW, Bressler NM, Bressler SB, Ferris FL 3rd, Gupta SK, Haller JA, Lazarus HS (2010) Factors associated with visual acuity outcomes after vitrectomy for diabetic macular edema: diabetic retinopathy clinical research network. Retina 30(9):1488–1495CrossRefPubMed Flaxel CJ, Edwards AR, Aiello LP, Arrigg PG, Beck RW, Bressler NM, Bressler SB, Ferris FL 3rd, Gupta SK, Haller JA, Lazarus HS (2010) Factors associated with visual acuity outcomes after vitrectomy for diabetic macular edema: diabetic retinopathy clinical research network. Retina 30(9):1488–1495CrossRefPubMed
22.
go back to reference Diabetic Retinopathy Clinical Research Network Writing Committee, Haller JA, Qin H, Apte RS, Beck RR, Bressler NM, Browning DJ, Danis RP, Glassman AR, Googe JM, Kollman C, Lauer AK, Peters MA, Stockman ME (2010) Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmol 117(6):1087–1093CrossRef Diabetic Retinopathy Clinical Research Network Writing Committee, Haller JA, Qin H, Apte RS, Beck RR, Bressler NM, Browning DJ, Danis RP, Glassman AR, Googe JM, Kollman C, Lauer AK, Peters MA, Stockman ME (2010) Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmol 117(6):1087–1093CrossRef
24.
go back to reference Shah SP, Patel M, Thomas D, Aldington S, Laidlaw DA (2006) Factors predicting outcome of vitrectomy for diabetic macular oedema: results of a prospective study. Br J Ophthalmol 90(1):33–36CrossRefPubMedPubMedCentral Shah SP, Patel M, Thomas D, Aldington S, Laidlaw DA (2006) Factors predicting outcome of vitrectomy for diabetic macular oedema: results of a prospective study. Br J Ophthalmol 90(1):33–36CrossRefPubMedPubMedCentral
25.
go back to reference Kumagai K, Furukawa M, Ogino N, Larson E, Iwaki M, Tachi N (2009) Long-term follow-up of vitrectomy for diffuse nontractional diabetic macular edema. Retina 29(4):464–472CrossRefPubMed Kumagai K, Furukawa M, Ogino N, Larson E, Iwaki M, Tachi N (2009) Long-term follow-up of vitrectomy for diffuse nontractional diabetic macular edema. Retina 29(4):464–472CrossRefPubMed
26.
go back to reference Kakinoki M, Sawada O, Sawada T, Saishin Y, Kawamura H, Ohji M (2012) Effect of vitrectomy on aqueous VEGF concentration and pharmacokinetics of bevacizumab in macaque monkeys. Invest Ophthalmol Vis Sci 53:5877–5880CrossRef Kakinoki M, Sawada O, Sawada T, Saishin Y, Kawamura H, Ohji M (2012) Effect of vitrectomy on aqueous VEGF concentration and pharmacokinetics of bevacizumab in macaque monkeys. Invest Ophthalmol Vis Sci 53:5877–5880CrossRef
27.
go back to reference Smiddy WE (2012) Clinical applications of cost analysis of diabetic macular edema treatments. Ophthalmology 119(12):2558–2562CrossRefPubMed Smiddy WE (2012) Clinical applications of cost analysis of diabetic macular edema treatments. Ophthalmology 119(12):2558–2562CrossRefPubMed
Metadata
Title
Effects of kallidinogenase in patients undergoing vitrectomy for diabetic macular edema
Authors
Yuki Yoshizumi
Zaigen Ohara
Hitoshi Tabuchi
Hitomi Sumino
Yukiko Maeda
Hideki Mochizuki
Ken Yamane
Yoshiaki Kiuchi
Publication date
01-06-2019
Publisher
Springer Netherlands
Published in
International Ophthalmology / Issue 6/2019
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI
https://doi.org/10.1007/s10792-018-0945-8

Other articles of this Issue 6/2019

International Ophthalmology 6/2019 Go to the issue