Findings from immunohistochemical analysis of vascular endothelial growth factor (VEGF) receptor expression on pathology specimens of orbital vascular tumors suggest a potential therapeutic role for anti-VEGF agents.
Take-home message: Findings from immunohistochemical analysis of vascular endothelial growth factor (VEGF) receptor expression on pathology specimens of orbital vascular tumors suggest a potential therapeutic role for anti-VEGF agents.
Reviewed by Elizabeth A. Atchison, MD
Rochester, MN-Most benign vascular lesions of the orbit express vascular endothelial growth factor receptors (VEGFRs). This finding suggests that anti-VEGF therapy may offer effective non-surgical intervention, according to investigators from Mayo Clinic, Rochester, MN.
“Orbital vascular lesions are not malignant, but they can cause significant morbidity secondary to mass effect on critical functional anatomy,” said Elizabeth A. Atchison, MD.
Currently, removal by excisional surgery is the most common treatment for orbital vascular lesions that are causing problems. However, surgery can be difficult because these lesions may lie near critical orbital structures, she noted, and surgery can have its own morbidity, causing bleeding and damage to local structures.
“Our study showing that these vascular lesions express VEGF receptors lays a foundation for investigating anti-VEGF therapy as a medical treatment alternative to surgical removal of orbital vascular lesions,” she added.
Dr. Atchison participated in the study as an ophthalmology resident at the Mayo Clinic. She is currently a surgical retina fellow, Rush University and Illinois Retina Associates, Chicago.
Expression of VEGFRs in orbital vascular lesions and determination of the receptor type and pattern of expression was investigated through immunohistochemical staining of 55 stored pathology specimens from 52 patients operated on by James A. Garrity, MD, between 2000 and 2010. The specimens included 38 venous malformations, 4 capillary hemangiomas, 7 lymphatic malformations, and 6 lymphaticovenous malformations.
After confirming the pathologic diagnosis through surgical specimen review, sections were stained for VEGF and for the three major receptors for VEGF (VEGFR types 1, 2, and 3).
The analyses showed all samples were positive for VEGFR and nearly all stained positive for VEGFR type 2 (98%) and VEGFR type 3 (96%). VEGFR1 staining was positive on 55% of the lesions.
Staining for VEGFR2 was diffuse for 52 of the 54 specimens staining positive for this VEGFR subtype. The high expression rate and diffuse distribution of VEGFR type 2 is of particular interest considering the type 2 receptor is bound by VEGF-A and mediates endothelial cell proliferation and differentiation.
Results from various previous studies provide further support for the idea that blocking VEGF binding to VEGFR2 may be effective treatment for orbital vascular lesions. The evidence includes findings that VEGFR2 expression is upregulated during the proliferative phase of infantile hemangiomas and that the viability of the hemangioma cells is decreased by knockout of VEGFR2.
VEGFR2 has also been shown to be overexpressed by pterygia, and there are reports that pterygia recurrence may be reduced after intralesional anti-VEGF injections.
“Intralesional anti-VEGF injection has also been associated with favorable results in a small series of patients with periocular epithelioid hemangioma,” Dr. Atchison said. “Several reports describing intralesional injection of a sclerosing agent into orbital vascular lesions indicate the feasibility of this route of administration.”
Elizabeth A. Atchison, MD
This article was adapted from Dr. Atchison’s presentation at the 2015 meeting of the American Academy of Ophthalmology. A paper describing the study was subsequently published [Atchison EA et al. Ophthalmology. 2016;1:209-213]. Dr. Atchison did not indicate any proprietary interest in the subject matter.