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Results of a Prospective Trial. Report No. 2

Jiao, Chunhua, MD*; Eliott, Dean, MD; Spee, Christine, BA; He, Shikun, PhD; Wang, Kai, PhD*; Mullins, Robert F., PhD*; Hinton, David R., MD; Sohn, Elliott H., MD*

doi: 10.1097/IAE.0000000000001952
Original Study

Purpose: We sought to characterize the angiofibrotic and apoptotic effects of vascular endothelial growth factor (VEGF)-inhibition on fibrovascular epiretinal membranes in eyes with traction retinal detachment because of proliferative diabetic retinopathy.

Methods: Membranes were excised from 20 eyes of 19 patients (10 randomized to intravitreal bevacizumab, 10 controls) at vitrectomy. Membranes were stained with antibodies targeting connective tissue growth factor (CTGF) or VEGF and colabeled with antibodies directed against endothelial cells (CD31), myofibroblasts, or retinal pigment epithelium markers. Quantitative and colocalization analyses of antibody labeling were obtained through immunofluorescence confocal microscopy. Masson trichrome staining, cell counting of hematoxylin and eosin sections, and terminal dUTP nick-end labeling staining were performed.

Results: High levels of fibrosis were observed in both groups. Cell apoptosis was higher (P = 0.05) in bevacizumab-treated membranes compared with controls. The bevacizumab group had a nonsignificant reduction in colocalization in CD31–CTGF and cytokeratin–VEGF studies compared with controls. Vascular endothelial growth factor in extracted membranes was positively correlated with vitreous levels of VEGF; CTGF in extracted membranes was negatively correlated with vitreous levels of CTGF.

Conclusion: Bevacizumab suppresses vitreous VEGF levels, but does not significantly alter VEGF or CTGF in diabetic membranes that may be explained by high baseline levels of fibrosis. Bevacizumab may cause apoptosis within fibrovascular membranes.

Although bevacizumab suppresses vitreous vascular endothelial growth factor levels in eyes with diabetic traction retinal detachment, vascular endothelial growth factor and connective tissue growth factor content is unchanged in fibrovascular membranes extracted from the same eyes. Bevacizumab may cause apoptosis within fibrovascular membranes.

*Department of Ophthalmology and Visual Sciences, Stephen A Wynn Institute for Vision Research, University of Iowa Hospitals and Clinics, Iowa City, Iowa;

Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; and

Department of Ophthalmology and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California.

Reprint requests: Elliott H. Sohn, MD, Department of Ophthalmology, 200 Hawkins Drive, Iowa City, IA 52242; e-mail:

Supported by NEI grant R01-EY026547 (EHS).

D. Eliott (Ad hoc consulting: Alcon; Allergan; Avalanche; Dutch Ophthalmic; Ophthotech; and Santen. Clinical trial funding: Neurotech); E. H. Sohn (Research support: GSK; Clinical trial funding: Regeneron and Oxford BioMedica). The remaining authors have no conflicting interests to disclose.

© 2019 by Ophthalmic Communications Society, Inc.