July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Elevated Expression of Angiopoietin-like 4 in the Aqueous of Retinal Vein Occlusion Patients Who Develop Neovascular Glaucoma
Author Affiliations & Notes
  • Kathleen Jee
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Syed Hassan
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Davinder Grover
    Glaucoma Associates of Texas, Dallas, Texas, United States
  • Gregg Semenza
    Vascular Program, Institute for Cell Engineering; Departments of Pediatrics, Medicine, Oncology, Radiation Oncology, Biological Chemistry, and Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Silvia Montaner
    Department of Oncology and Diagnostic Sciences, School of Dentistry; Department of Pathology, School of Medicine; Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland, United States
  • Akrit Sodhi
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Kathleen Jee, None; Syed Hassan, None; Davinder Grover, None; Gregg Semenza, None; Silvia Montaner, None; Akrit Sodhi, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2570. doi:
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      Kathleen Jee, Syed Hassan, Davinder Grover, Gregg Semenza, Silvia Montaner, Akrit Sodhi; Elevated Expression of Angiopoietin-like 4 in the Aqueous of Retinal Vein Occlusion Patients Who Develop Neovascular Glaucoma. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2570.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Treatment options for neovascular glaucoma (NVG), the most severe consequence of retinal vein occlusions (RVOs), are limited and include scatter laser photocoagulation and glaucoma surgery. Therapies targeting vascular endothelial growth factor (VEGF) have been reported to temporarily delay the progression of NVG in some – but not all – RVO patients, implicating additional factor(s) in NVG development. We recently identified angiopoietin-like 4 (ANGPTL4) as a novel hypoxia-regulated angiogenic factor that promotes retinal neovascularization in ischemic retinal disease. Here we examine whether ANGPTL4 contributes to anterior segment neovascularization in RVO patients.

Methods : Aqueous samples were obtained from patients with branch, hemi-, and central RVO (BRVO, HRVO, and CRVO, respectively) and control patients without a history of ischemic retinal disease. CRVO patients included patients with and without NVG. Aqueous levels of ANGPTL4 and VEGF were determined by enzyme-linked immunosorbent assay. Statistical differences between groups were determined by Student’s t test, one-way ANOVA with Holm-Sidak’s multiple comparisons test, chi-square test, and Pearson’s correlation.

Results : Aqueous VEGF levels were not statistically significantly different between control (n=19) and RVO (n=18) patients or among patients with BRVO (n=8), HRVO (n=5), and CRVOs (n=5). Conversely, aqueous ANGPTL4 levels were elevated in RVO patients (p=0.005, 15.0 ±19.14 ng/mL) compared to controls (n=19, 1.9 ± 0.5 ng/mL) and correlated with the area of retinal involvement: highest in CRVO (n=5, 28.9 ± 29.0 ng/mL; 15.2-fold increase) compared to HRVO (n=5, 20.9 ± 10.8 ng/mL; 11-fold increase) and BRVO (n=8, 2.7 ± 2.4 ng/mL; 1.4-fold increase). Aqueous levels of both VEGF and ANGPTL4 were increased in patients with CRVO with NVG [n=6, 0.7 ± 1.0 ng/mL (3.5-fold increase) and 120.0 ± 58.0 ng/mL (7.6-fold increase), respectively] compared to without NVG (n=16, 0.2 ± 0.1 ng/mL and 15.8 ± 21.2 ng/mL, respectively). Aqueous ANGPTL4 levels were unaffected by recent treatment with anti-VEGF therapy and correlated better with intraocular pressure (r=0.7, p<0.0001) compared to VEGF (r=0.4, p=0.02).

Conclusions : Collectively, our results suggest that ANGPTL4 may be an effective diagnostic marker and therapeutic target for patients with RVOs with and without NVG.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.


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