Skip to main content
Top
Published in: Journal of Inflammation 1/2011

Open Access 01-12-2011 | Research

Vitreous inflammatory factors and serous retinal detachment in central retinal vein occlusion: a case control series

Authors: Hidetaka Noma, Hideharu Funatsu, Tatsuya Mimura, Shuichiro Eguchi

Published in: Journal of Inflammation | Issue 1/2011

Login to get access

Abstract

Background

This study investigated whether the vitreous fluid levels of soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), pigment epithelium-derived factor (PEDF), and soluble intercellular adhesion molecule 1 (sICAM-1) were associated with the occurrence of serous retinal detachment (SRD) in patients with central retinal vein occlusion (CRVO).

Methods

We recruited 33 patients with CRVO and macular edema, as well as 18 controls with nonischemic ocular diseases. Eighteen of the 33 patients with CRVO showed SRD on optical coherence tomography of the macula (defined as subretinal accumulation of fluid with low reflectivity), while the other 15 patients only had cystoid macular edema (CME, defined as hyporeflective intraretinal cavities). Retinal ischemia was evaluated by measuring the area of capillary non-perfusion using fluorescein angiography and the public domain Scion Image program, while central macular thickness (CMT) was examined by optical coherence tomography. Vitreous fluid samples were obtained during pars plana vitrectomy and levels of the target molecules were measured by enzyme-linked immunosorbent assay.

Results

Ischemia was significantly more common in the SRD group (17/18 patients) than in the CME group (5/15 patients) (P < 0.001). The vitreous fluid level of sICAM-1 increased significantly across the three groups from the control group (4.98 ± 1.73 ng/ml) to the CME group (15.4 ± 10.1 ng/ml) and the SRD group (27.1 ± 17.7 ng/ml) (p trend < 0.001). The vitreous fluid level of sVEGFR-2 also showed a significant increase across the three groups (1083 ± 541 pg/ml, 1181 ± 522 pg/ml, and 1535 ± 617 pg/ml, respectively, p trend = 0.019). On the other hand, the vitreous fluid level of PEDF showed a significant decrease across the three groups (56.4 ± 40.0 ng/ml, 24.3 ± 17.3 ng/ml, and 16.4 ± 12.6 ng/ml, respectively, p trend < 0.001).

Conclusions

Higher levels of inflammatory factors (sICAM-1 and sVEGFR-2) and lower levels of anti-inflammatory PEDF were observed in macular edema patients with SRD, suggesting that inflammation plays a key role in determining the severity of CRVO.
Appendix
Available only for authorised users
Literature
1.
go back to reference Green WR, Chan CC, Hutchins GM, Terry JM: Central retinal vein occlusion: a prospective histopathologic study of 29 eyes in 28 cases. Trans Am Ophthalmol Soc. 1981, 79: 371-422.PubMedPubMedCentral Green WR, Chan CC, Hutchins GM, Terry JM: Central retinal vein occlusion: a prospective histopathologic study of 29 eyes in 28 cases. Trans Am Ophthalmol Soc. 1981, 79: 371-422.PubMedPubMedCentral
2.
3.
go back to reference Ozdemir H, Karacorlu M, Karacorlu S: Serous macular detachment in central retinal vein occlusion. Retina. 2005, 25: 561-563. 10.1097/00006982-200507000-00003.PubMedCrossRef Ozdemir H, Karacorlu M, Karacorlu S: Serous macular detachment in central retinal vein occlusion. Retina. 2005, 25: 561-563. 10.1097/00006982-200507000-00003.PubMedCrossRef
4.
go back to reference Tsujikawa A, Sakamoto A, Ota M, Kotera Y, Oh H, Miyamoto K, Kita M, Yoshimura N: Serous retinal detachment associated with retinal vein occlusion. Am J Ophthalmol. 2010, 149: 291-301. 10.1016/j.ajo.2009.09.007. e5PubMedCrossRef Tsujikawa A, Sakamoto A, Ota M, Kotera Y, Oh H, Miyamoto K, Kita M, Yoshimura N: Serous retinal detachment associated with retinal vein occlusion. Am J Ophthalmol. 2010, 149: 291-301. 10.1016/j.ajo.2009.09.007. e5PubMedCrossRef
5.
go back to reference Dvorak HF, Brown LF, Detmar M, Dvorak AM: Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995, 146: 1029-1039.PubMedPubMedCentral Dvorak HF, Brown LF, Detmar M, Dvorak AM: Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995, 146: 1029-1039.PubMedPubMedCentral
6.
go back to reference Noma H, Funatsu H, Mimura T: Vascular Endothelial Growth Factor and Interleukin-6 are Correlated With Serous Retinal Detachment in Central Retinal Vein Occlusion. Curr Eye Res. 2012, 37: 62-67.PubMedCrossRef Noma H, Funatsu H, Mimura T: Vascular Endothelial Growth Factor and Interleukin-6 are Correlated With Serous Retinal Detachment in Central Retinal Vein Occlusion. Curr Eye Res. 2012, 37: 62-67.PubMedCrossRef
7.
go back to reference Park SP, Ahn JK, Mun GH: Aqueous vascular endothelial growth factor levels are associated with serous macular detachment secondary to branch retinal vein occlusion. Retina. 2010, 30: 281-286. 10.1097/IAE.0b013e3181b9f153.PubMedCrossRef Park SP, Ahn JK, Mun GH: Aqueous vascular endothelial growth factor levels are associated with serous macular detachment secondary to branch retinal vein occlusion. Retina. 2010, 30: 281-286. 10.1097/IAE.0b013e3181b9f153.PubMedCrossRef
8.
go back to reference Dawson DW, Volpert OV, Gillis P, Crawford SE, Xu H, Benedict W, Bouck NP: Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science. 1999, 285: 245-248. 10.1126/science.285.5425.245.PubMedCrossRef Dawson DW, Volpert OV, Gillis P, Crawford SE, Xu H, Benedict W, Bouck NP: Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science. 1999, 285: 245-248. 10.1126/science.285.5425.245.PubMedCrossRef
9.
go back to reference Lu M, Perez VL, Ma N, Miyamoto K, Peng HB, Liao JK, Adamis AP: VEGF increases retinal vascular ICAM-1 expression in vivo. Invest Ophthalmol Vis Sci. 1999, 40: 1808-1812.PubMed Lu M, Perez VL, Ma N, Miyamoto K, Peng HB, Liao JK, Adamis AP: VEGF increases retinal vascular ICAM-1 expression in vivo. Invest Ophthalmol Vis Sci. 1999, 40: 1808-1812.PubMed
10.
go back to reference Zhang SX, Wang JJ, Gao G, Shao C, Mott R, Ma JX: Pigment epithelium-derived factor (PEDF) is an endogenous antiinflammatory factor. Faseb J. 2006, 20: 323-325.PubMed Zhang SX, Wang JJ, Gao G, Shao C, Mott R, Ma JX: Pigment epithelium-derived factor (PEDF) is an endogenous antiinflammatory factor. Faseb J. 2006, 20: 323-325.PubMed
11.
go back to reference Yoshimura T, Sonoda KH, Sugahara M, Mochizuki Y, Enaida H, Oshima Y, Ueno A, Hata Y, Yoshida H, Ishibashi T: Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases. PLoS One. 2009, 4: e8158-10.1371/journal.pone.0008158.PubMedPubMedCentralCrossRef Yoshimura T, Sonoda KH, Sugahara M, Mochizuki Y, Enaida H, Oshima Y, Ueno A, Hata Y, Yoshida H, Ishibashi T: Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases. PLoS One. 2009, 4: e8158-10.1371/journal.pone.0008158.PubMedPubMedCentralCrossRef
12.
go back to reference Wen Y, Edelman JL, Kang T, Zeng N, Sachs G: Two functional forms of vascular endothelial growth factor receptor-2/Flk-1 mRNA are expressed in normal rat retina. J Biol Chem. 1998, 273: 2090-2097. 10.1074/jbc.273.4.2090.PubMedCrossRef Wen Y, Edelman JL, Kang T, Zeng N, Sachs G: Two functional forms of vascular endothelial growth factor receptor-2/Flk-1 mRNA are expressed in normal rat retina. J Biol Chem. 1998, 273: 2090-2097. 10.1074/jbc.273.4.2090.PubMedCrossRef
13.
go back to reference Elner SG, Elner VM, Pavilack MA, Todd RF, Mayo-Bond L, Franklin WA, Strieter RM, Kunkel SL, Huber AR: Modulation and function of intercellular adhesion molecule-1 (CD54) on human retinal pigment epithelial cells. Lab Invest. 1992, 66: 200-211.PubMed Elner SG, Elner VM, Pavilack MA, Todd RF, Mayo-Bond L, Franklin WA, Strieter RM, Kunkel SL, Huber AR: Modulation and function of intercellular adhesion molecule-1 (CD54) on human retinal pigment epithelial cells. Lab Invest. 1992, 66: 200-211.PubMed
14.
go back to reference Gearing AJ, Newman W: Circulating adhesion molecules in disease. Immunol Today. 1993, 14: 506-512. 10.1016/0167-5699(93)90267-O.PubMedCrossRef Gearing AJ, Newman W: Circulating adhesion molecules in disease. Immunol Today. 1993, 14: 506-512. 10.1016/0167-5699(93)90267-O.PubMedCrossRef
15.
16.
go back to reference Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen HV, Aiello LM, Ferrara N, George L, King GL: Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994, 331: 1480-1487. 10.1056/NEJM199412013312203.PubMedCrossRef Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen HV, Aiello LM, Ferrara N, George L, King GL: Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994, 331: 1480-1487. 10.1056/NEJM199412013312203.PubMedCrossRef
17.
go back to reference 1999 World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension: Guidelines Subcommittee. J Hypertens. 1999, 17: 151-183. 1999 World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension: Guidelines Subcommittee. J Hypertens. 1999, 17: 151-183.
18.
go back to reference The Central Vein Occlusion Study: Baseline and early natural history report. Arch Ophthalmol. 1993, 111: 1087-1095.CrossRef The Central Vein Occlusion Study: Baseline and early natural history report. Arch Ophthalmol. 1993, 111: 1087-1095.CrossRef
19.
go back to reference The Central Vein Occlusion Study Group M report: Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. Ophthalmology. 1995, 102: 1425-1433.CrossRef The Central Vein Occlusion Study Group M report: Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. Ophthalmology. 1995, 102: 1425-1433.CrossRef
20.
go back to reference The Central Vein Occlusion Study Group: Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmol. 1997, 115: 486-491.CrossRef The Central Vein Occlusion Study Group: Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmol. 1997, 115: 486-491.CrossRef
21.
go back to reference Otani T, Kishi S: Tomographic assessment of vitreous surgery for diabetic macular edema. Am J Ophthalmol. 2000, 129: 487-494. 10.1016/S0002-9394(99)00409-2.PubMedCrossRef Otani T, Kishi S: Tomographic assessment of vitreous surgery for diabetic macular edema. Am J Ophthalmol. 2000, 129: 487-494. 10.1016/S0002-9394(99)00409-2.PubMedCrossRef
22.
go back to reference Noma H, Funatsu H, Harino S, Mimura T, Eguchi S, Hori S: Vitreous inflammatory factors in macular edema with central retinal vein occlusion. Jpn J Ophthalmol. 2011, 55: 248-255. 10.1007/s10384-011-0016-4.PubMedCrossRef Noma H, Funatsu H, Harino S, Mimura T, Eguchi S, Hori S: Vitreous inflammatory factors in macular edema with central retinal vein occlusion. Jpn J Ophthalmol. 2011, 55: 248-255. 10.1007/s10384-011-0016-4.PubMedCrossRef
23.
go back to reference Noma H, Funatsu H, Mimura T, Eguchi S, Shimada K, Hori S: Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in macular edema with central retinal vein occlusion. Curr Eye Res. 2011, 36: 256-263. 10.3109/02713683.2010.513090.PubMedCrossRef Noma H, Funatsu H, Mimura T, Eguchi S, Shimada K, Hori S: Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in macular edema with central retinal vein occlusion. Curr Eye Res. 2011, 36: 256-263. 10.3109/02713683.2010.513090.PubMedCrossRef
24.
go back to reference Noma H, Funatsu H, Mimura T, Eguchi S, Shimada K: Role of soluble vascular endothelial growth factor receptor-2 in macular oedema with central retinal vein occlusion. Br J Ophthalmol. 2011, 95: 788-792. 10.1136/bjo.2010.192468.PubMedCrossRef Noma H, Funatsu H, Mimura T, Eguchi S, Shimada K: Role of soluble vascular endothelial growth factor receptor-2 in macular oedema with central retinal vein occlusion. Br J Ophthalmol. 2011, 95: 788-792. 10.1136/bjo.2010.192468.PubMedCrossRef
25.
go back to reference Spoerri PE, Afzal A, Li Calzi S, Shaw LC, Cai J, Pan H, Boulton M, Grant MB: Effects of VEGFR-1, VEGFR-2, and IGF-IR hammerhead ribozymes on glucose-mediated tight junction expression in cultured human retinal endothelial cells. Mol Vis. 2006, 12: 32-42.PubMed Spoerri PE, Afzal A, Li Calzi S, Shaw LC, Cai J, Pan H, Boulton M, Grant MB: Effects of VEGFR-1, VEGFR-2, and IGF-IR hammerhead ribozymes on glucose-mediated tight junction expression in cultured human retinal endothelial cells. Mol Vis. 2006, 12: 32-42.PubMed
26.
go back to reference Ojima T, Takagi H, Suzuma K, Oh H, Suzuma I, Ohashi H, Watanabe D, Suganami E, Murakami T, Kurimoto M, Honda Y, Yoshimura N: EphrinA1 inhibits vascular endothelial growth factor-induced intracellular signaling and suppresses retinal neovascularization and blood-retinal barrier breakdown. Am J Pathol. 2006, 168: 331-339. 10.2353/ajpath.2006.050435.PubMedPubMedCentralCrossRef Ojima T, Takagi H, Suzuma K, Oh H, Suzuma I, Ohashi H, Watanabe D, Suganami E, Murakami T, Kurimoto M, Honda Y, Yoshimura N: EphrinA1 inhibits vascular endothelial growth factor-induced intracellular signaling and suppresses retinal neovascularization and blood-retinal barrier breakdown. Am J Pathol. 2006, 168: 331-339. 10.2353/ajpath.2006.050435.PubMedPubMedCentralCrossRef
27.
go back to reference Kim JH, Lee YM, Ahn EM, Kim KW, Yu YS: Decursin inhibits VEGF-mediated inner blood-retinal barrier breakdown by suppression of VEGFR-2 activation. J Cereb Blood Flow Metab. 2009, 29: 1559-1567. 10.1038/jcbfm.2009.78.PubMedCrossRef Kim JH, Lee YM, Ahn EM, Kim KW, Yu YS: Decursin inhibits VEGF-mediated inner blood-retinal barrier breakdown by suppression of VEGFR-2 activation. J Cereb Blood Flow Metab. 2009, 29: 1559-1567. 10.1038/jcbfm.2009.78.PubMedCrossRef
28.
go back to reference Scheppke L, Aguilar E, Gariano RF, Jacobson R, Hood J, Doukas J, Cao J, Noronha G, Yee S, Weis S, Martin MB, Soll R, Cheresh DA, Friedlander M: Retinal vascular permeability suppression by topical application of a novel VEGFR2/Src kinase inhibitor in mice and rabbits. J Clin Invest. 2008, 118: 2337-2346.PubMedPubMedCentral Scheppke L, Aguilar E, Gariano RF, Jacobson R, Hood J, Doukas J, Cao J, Noronha G, Yee S, Weis S, Martin MB, Soll R, Cheresh DA, Friedlander M: Retinal vascular permeability suppression by topical application of a novel VEGFR2/Src kinase inhibitor in mice and rabbits. J Clin Invest. 2008, 118: 2337-2346.PubMedPubMedCentral
29.
go back to reference Liu H, Ren JG, Cooper WL, Hawkins CE, Cowan MR, Tong PY: Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site. Proc Natl Acad Sci USA. 2004, 101: 6605-6610. 10.1073/pnas.0308342101.PubMedPubMedCentralCrossRef Liu H, Ren JG, Cooper WL, Hawkins CE, Cowan MR, Tong PY: Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site. Proc Natl Acad Sci USA. 2004, 101: 6605-6610. 10.1073/pnas.0308342101.PubMedPubMedCentralCrossRef
30.
go back to reference Wang K, Wang Y, Gao L, Li X, Li M, Guo J: Dexamethasone inhibits leukocyte accumulation and vascular permeability in retina of streptozotocin-induced diabetic rats via reducing vascular endothelial growth factor and intercellular adhesion molecule-1 expression. Biol Pharm Bull. 2008, 31: 1541-1546. 10.1248/bpb.31.1541.PubMedCrossRef Wang K, Wang Y, Gao L, Li X, Li M, Guo J: Dexamethasone inhibits leukocyte accumulation and vascular permeability in retina of streptozotocin-induced diabetic rats via reducing vascular endothelial growth factor and intercellular adhesion molecule-1 expression. Biol Pharm Bull. 2008, 31: 1541-1546. 10.1248/bpb.31.1541.PubMedCrossRef
31.
go back to reference Zhang X, Bao S, Lai D, Rapkins RW, Gillies MC: Intravitreal triamcinolone acetonide inhibits breakdown of the blood-retinal barrier through differential regulation of VEGF-A and its receptors in early diabetic rat retinas. Diabetes. 2008, 57: 1026-1033. 10.2337/db07-0982.PubMedPubMedCentralCrossRef Zhang X, Bao S, Lai D, Rapkins RW, Gillies MC: Intravitreal triamcinolone acetonide inhibits breakdown of the blood-retinal barrier through differential regulation of VEGF-A and its receptors in early diabetic rat retinas. Diabetes. 2008, 57: 1026-1033. 10.2337/db07-0982.PubMedPubMedCentralCrossRef
32.
go back to reference Tombran-Tink J, Lara N, Apricio SE, Potluri P, Gee S, Ma JX, Chader G, Barnstable CJ: Retinoic acid and dexamethasone regulate the expression of PEDF in retinal and endothelial cells. Exp Eye Res. 2004, 78: 945-955. 10.1016/j.exer.2003.12.013.PubMedCrossRef Tombran-Tink J, Lara N, Apricio SE, Potluri P, Gee S, Ma JX, Chader G, Barnstable CJ: Retinoic acid and dexamethasone regulate the expression of PEDF in retinal and endothelial cells. Exp Eye Res. 2004, 78: 945-955. 10.1016/j.exer.2003.12.013.PubMedCrossRef
33.
go back to reference Tachi N, Hashimoto Y, Ogino N: Vitrectomy for macular edema combined with retinal vein occlusion. Doc Ophthalmol. 1999, 97: 465-469. 10.1023/A:1002432032354.PubMedCrossRef Tachi N, Hashimoto Y, Ogino N: Vitrectomy for macular edema combined with retinal vein occlusion. Doc Ophthalmol. 1999, 97: 465-469. 10.1023/A:1002432032354.PubMedCrossRef
34.
go back to reference Leizaola-Fernandez C, Suarez-Tata L, Quiroz-Mercado H, Colina-Luquez J, Fromow-Guerra J, Jimenez-Sierra JM, Guerrero-Naranjo JL, Morales-Canton V: Vitrectomy with complete posterior hyaloid removal for ischemic central retinal vein occlusion: series of cases. BMC Ophthalmol. 2005, 5: 10-10.1186/1471-2415-5-10.PubMedPubMedCentralCrossRef Leizaola-Fernandez C, Suarez-Tata L, Quiroz-Mercado H, Colina-Luquez J, Fromow-Guerra J, Jimenez-Sierra JM, Guerrero-Naranjo JL, Morales-Canton V: Vitrectomy with complete posterior hyaloid removal for ischemic central retinal vein occlusion: series of cases. BMC Ophthalmol. 2005, 5: 10-10.1186/1471-2415-5-10.PubMedPubMedCentralCrossRef
35.
go back to reference Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, Rundle AC, Rubio RG, Murahashi WY: Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010, 117: 1124-1133. 10.1016/j.ophtha.2010.02.022. e1PubMedCrossRef Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, Rundle AC, Rubio RG, Murahashi WY: Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010, 117: 1124-1133. 10.1016/j.ophtha.2010.02.022. e1PubMedCrossRef
Metadata
Title
Vitreous inflammatory factors and serous retinal detachment in central retinal vein occlusion: a case control series
Authors
Hidetaka Noma
Hideharu Funatsu
Tatsuya Mimura
Shuichiro Eguchi
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2011
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/1476-9255-8-38

Other articles of this Issue 1/2011

Journal of Inflammation 1/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.