Pro-Permeability Factors after Dexamethasone Implant in Retinal Vein Occlusion; The Ozurdex for Retinal Vein Occlusion (ORVO) Study

Peter A Campochiaro, Gulnar Hafiz, Tahreem A. Mir, Adrienne Scott, Raafay Sophie, Syed M. Shah, Howard S. Ying, Lili Lu, Connie Chen, J. Peter Campbell, Saleema Kherani, Ingrid E Zimmer Galler, Adam Wenick, Ian Han, Yannis Paulus, Akrit Sodhi, Guohua Wang, Jiang Qian

Research output: Contribution to journalArticle

Abstract

Purpose To correlate aqueous vasoactive protein changes with macular edema after dexamethasone implant in retinal vein occlusion (RVO). Design Prospective, interventional case series. Methods Twenty-three central RVO (CRVO) and 17 branch RVO (BRVO) subjects with edema despite prior anti-vascular endothelial growth factor (VEGF) treatment had aqueous taps at baseline and 4 and 16 weeks after dexamethasone implant. Best-corrected visual acuity (BCVA) and center subfield thickness were measured every 4 weeks. Aqueous vasoactive protein levels were measured by protein array or enzyme-linked immunosorbent assay. Results Thirty-two vasoactive proteins were detected in aqueous in untreated eyes with macular edema due to RVO. Reduction in excess foveal thickness after dexamethasone implant correlated with reduction in persephin and pentraxin 3 (Pearson correlation coefficients = 0.682 and 0.638, P =.014 and P =.003). Other protein changes differed among RVO patients as edema decreased, but ≥50% of patients showed reductions in hepatocyte growth factor, endocrine gland VEGF, insulin-like growth factor binding proteins, or endostatin by ≥30%. Enzyme-linked immunosorbent assay in 18 eyes (12 CRVO, 6 BRVO) showed baseline levels of hepatocyte growth factor and VEGF of 168.2 ± 20.1 pg/mL and 78.7 ± 10.0 pg/mL, and each was reduced in 12 eyes after dexamethasone implant. Conclusions Dexamethasone implants reduce several pro-permeability proteins providing a multitargeted approach in RVO. No single protein in addition to VEGF can be implicated as a contributor in all patients. Candidates for contribution to chronic edema in subgroups of patients that deserve further study include persephin, hepatocyte growth factor, and endocrine gland VEGF.

Original languageEnglish (US)
Pages (from-to)313-321.e19
JournalAmerican Journal of Ophthalmology
Volume160
Issue number2
DOIs
StatePublished - Aug 1 2015

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Retinal Vein Occlusion
Dexamethasone
Permeability
Vascular Endothelial Growth Factor A
Hepatocyte Growth Factor
Endocrine Glands
Edema
Proteins
Macular Edema
Enzyme-Linked Immunosorbent Assay
Endostatins
Retinal Vein
Insulin-Like Growth Factor Binding Proteins
Protein Array Analysis
Visual Acuity

ASJC Scopus subject areas

  • Ophthalmology
  • Medicine(all)

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Pro-Permeability Factors after Dexamethasone Implant in Retinal Vein Occlusion; The Ozurdex for Retinal Vein Occlusion (ORVO) Study. / Campochiaro, Peter A; Hafiz, Gulnar; Mir, Tahreem A.; Scott, Adrienne; Sophie, Raafay; Shah, Syed M.; Ying, Howard S.; Lu, Lili; Chen, Connie; Campbell, J. Peter; Kherani, Saleema; Zimmer Galler, Ingrid E; Wenick, Adam; Han, Ian; Paulus, Yannis; Sodhi, Akrit; Wang, Guohua; Qian, Jiang.

In: American Journal of Ophthalmology, Vol. 160, No. 2, 01.08.2015, p. 313-321.e19.

Research output: Contribution to journalArticle

Campochiaro, Peter A ; Hafiz, Gulnar ; Mir, Tahreem A. ; Scott, Adrienne ; Sophie, Raafay ; Shah, Syed M. ; Ying, Howard S. ; Lu, Lili ; Chen, Connie ; Campbell, J. Peter ; Kherani, Saleema ; Zimmer Galler, Ingrid E ; Wenick, Adam ; Han, Ian ; Paulus, Yannis ; Sodhi, Akrit ; Wang, Guohua ; Qian, Jiang. / Pro-Permeability Factors after Dexamethasone Implant in Retinal Vein Occlusion; The Ozurdex for Retinal Vein Occlusion (ORVO) Study. In: American Journal of Ophthalmology. 2015 ; Vol. 160, No. 2. pp. 313-321.e19.
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abstract = "Purpose To correlate aqueous vasoactive protein changes with macular edema after dexamethasone implant in retinal vein occlusion (RVO). Design Prospective, interventional case series. Methods Twenty-three central RVO (CRVO) and 17 branch RVO (BRVO) subjects with edema despite prior anti-vascular endothelial growth factor (VEGF) treatment had aqueous taps at baseline and 4 and 16 weeks after dexamethasone implant. Best-corrected visual acuity (BCVA) and center subfield thickness were measured every 4 weeks. Aqueous vasoactive protein levels were measured by protein array or enzyme-linked immunosorbent assay. Results Thirty-two vasoactive proteins were detected in aqueous in untreated eyes with macular edema due to RVO. Reduction in excess foveal thickness after dexamethasone implant correlated with reduction in persephin and pentraxin 3 (Pearson correlation coefficients = 0.682 and 0.638, P =.014 and P =.003). Other protein changes differed among RVO patients as edema decreased, but ≥50{\%} of patients showed reductions in hepatocyte growth factor, endocrine gland VEGF, insulin-like growth factor binding proteins, or endostatin by ≥30{\%}. Enzyme-linked immunosorbent assay in 18 eyes (12 CRVO, 6 BRVO) showed baseline levels of hepatocyte growth factor and VEGF of 168.2 ± 20.1 pg/mL and 78.7 ± 10.0 pg/mL, and each was reduced in 12 eyes after dexamethasone implant. Conclusions Dexamethasone implants reduce several pro-permeability proteins providing a multitargeted approach in RVO. No single protein in addition to VEGF can be implicated as a contributor in all patients. Candidates for contribution to chronic edema in subgroups of patients that deserve further study include persephin, hepatocyte growth factor, and endocrine gland VEGF.",
author = "Campochiaro, {Peter A} and Gulnar Hafiz and Mir, {Tahreem A.} and Adrienne Scott and Raafay Sophie and Shah, {Syed M.} and Ying, {Howard S.} and Lili Lu and Connie Chen and Campbell, {J. Peter} and Saleema Kherani and {Zimmer Galler}, {Ingrid E} and Adam Wenick and Ian Han and Yannis Paulus and Akrit Sodhi and Guohua Wang and Jiang Qian",
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T1 - Pro-Permeability Factors after Dexamethasone Implant in Retinal Vein Occlusion; The Ozurdex for Retinal Vein Occlusion (ORVO) Study

AU - Campochiaro, Peter A

AU - Hafiz, Gulnar

AU - Mir, Tahreem A.

AU - Scott, Adrienne

AU - Sophie, Raafay

AU - Shah, Syed M.

AU - Ying, Howard S.

AU - Lu, Lili

AU - Chen, Connie

AU - Campbell, J. Peter

AU - Kherani, Saleema

AU - Zimmer Galler, Ingrid E

AU - Wenick, Adam

AU - Han, Ian

AU - Paulus, Yannis

AU - Sodhi, Akrit

AU - Wang, Guohua

AU - Qian, Jiang

PY - 2015/8/1

Y1 - 2015/8/1

N2 - Purpose To correlate aqueous vasoactive protein changes with macular edema after dexamethasone implant in retinal vein occlusion (RVO). Design Prospective, interventional case series. Methods Twenty-three central RVO (CRVO) and 17 branch RVO (BRVO) subjects with edema despite prior anti-vascular endothelial growth factor (VEGF) treatment had aqueous taps at baseline and 4 and 16 weeks after dexamethasone implant. Best-corrected visual acuity (BCVA) and center subfield thickness were measured every 4 weeks. Aqueous vasoactive protein levels were measured by protein array or enzyme-linked immunosorbent assay. Results Thirty-two vasoactive proteins were detected in aqueous in untreated eyes with macular edema due to RVO. Reduction in excess foveal thickness after dexamethasone implant correlated with reduction in persephin and pentraxin 3 (Pearson correlation coefficients = 0.682 and 0.638, P =.014 and P =.003). Other protein changes differed among RVO patients as edema decreased, but ≥50% of patients showed reductions in hepatocyte growth factor, endocrine gland VEGF, insulin-like growth factor binding proteins, or endostatin by ≥30%. Enzyme-linked immunosorbent assay in 18 eyes (12 CRVO, 6 BRVO) showed baseline levels of hepatocyte growth factor and VEGF of 168.2 ± 20.1 pg/mL and 78.7 ± 10.0 pg/mL, and each was reduced in 12 eyes after dexamethasone implant. Conclusions Dexamethasone implants reduce several pro-permeability proteins providing a multitargeted approach in RVO. No single protein in addition to VEGF can be implicated as a contributor in all patients. Candidates for contribution to chronic edema in subgroups of patients that deserve further study include persephin, hepatocyte growth factor, and endocrine gland VEGF.

AB - Purpose To correlate aqueous vasoactive protein changes with macular edema after dexamethasone implant in retinal vein occlusion (RVO). Design Prospective, interventional case series. Methods Twenty-three central RVO (CRVO) and 17 branch RVO (BRVO) subjects with edema despite prior anti-vascular endothelial growth factor (VEGF) treatment had aqueous taps at baseline and 4 and 16 weeks after dexamethasone implant. Best-corrected visual acuity (BCVA) and center subfield thickness were measured every 4 weeks. Aqueous vasoactive protein levels were measured by protein array or enzyme-linked immunosorbent assay. Results Thirty-two vasoactive proteins were detected in aqueous in untreated eyes with macular edema due to RVO. Reduction in excess foveal thickness after dexamethasone implant correlated with reduction in persephin and pentraxin 3 (Pearson correlation coefficients = 0.682 and 0.638, P =.014 and P =.003). Other protein changes differed among RVO patients as edema decreased, but ≥50% of patients showed reductions in hepatocyte growth factor, endocrine gland VEGF, insulin-like growth factor binding proteins, or endostatin by ≥30%. Enzyme-linked immunosorbent assay in 18 eyes (12 CRVO, 6 BRVO) showed baseline levels of hepatocyte growth factor and VEGF of 168.2 ± 20.1 pg/mL and 78.7 ± 10.0 pg/mL, and each was reduced in 12 eyes after dexamethasone implant. Conclusions Dexamethasone implants reduce several pro-permeability proteins providing a multitargeted approach in RVO. No single protein in addition to VEGF can be implicated as a contributor in all patients. Candidates for contribution to chronic edema in subgroups of patients that deserve further study include persephin, hepatocyte growth factor, and endocrine gland VEGF.

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