Increased angiogenic factors in the aqueous and vitreous

All four extraocular rectus muscles in rabbits were disinserted for induction of anterior segment ischemia (ASI) and changes in concentrations of prostaglandin E2 (PGE2), hypoxia-inducible factor 1 (HIF-1α ) and vascular endothelial growth factor (VEGF) in aqueous and vitreous humor were assessed.

Disinsertion of four rabbit rectus muscles was performed in the rabbit's right eye (ASI group). The concentrations of PGE2, HIF-1α and VEGF in aqueous and vitreous humor were measured at 1, 3, 6, 12 and 24 h by ELISA. The concentrations were compared with those of the other eyes (contralateral group) and normal healthy eyes (control group).

A subconjunctival injection of triamcinolone acetonide (TA) was administered and three concentrations of cytokines in aqueous humor and vitreous humor were measured 12 h after the injection of TA. A total of 48 eyes from 28 rabbits were included. PGE2, HIF-1α, and VEGF concentrations in the aqueous humor of the ASI and contralateral groups were significantly higher than those of the control group (p < 0.05, all).

Aqueous and vitreous humor VEGF concentrations in eyes with concurrent TA injection were significantly lower than in the ASI group (p=0.02, all). The concentration of PGE2, HIF-1α and VEGF in the aqueous humor was increased after induction of ASI, and TA injection appears to be effective in inhibiting the elevation of VEGF in ASI.

Anterior segment ischemia (ISA) is a potentially serious but rare complication of eye surgery. Although the exact prevalence of ASI is unknown, ASI after strabismus surgery occurs in approximately 1/13,000 to 1/30,000, according to the first report1. ASI is diagnosed based on clinical findings. The clinical features of ASI are variable, ranging from mild inflammation of the iris to bulbous phthisis with severe visual loss due to decreased blood flow to the anterior segment.

Most cases of ASI after strabismus surgery occur in the early postoperative period. However, there are no reports on the timing of the postoperative appearance of ASI. In humans, most cases of ASI have been reported after surgery on three or four rectus muscles. The risk of ASI in the four-muscle group was 9.5 times greater than that in the two-muscle group3. A dramatic decrease in blood supply after anterior segment strabismus surgery may lead to an increased risk of ASI. Risk factors for ASI also include advanced age, multi-muscle procedures, vertical muscle procedures, hyperviscosity, and systemic vascular disease4.

Angiogenic and inflammatory factors in the eye may contribute to angiogenesis during the acute phase of ASI. Hypoxic damage promotes vessel regeneration by upregulating several angiogenic factors, including prostaglandin E2 (PGE2), hypoxia-inducible factor (HIF), and vascular endothelial growth factor (VEGF) in the 'aqueous humor. A previous study reported that aqueous VEGF can be used as an indicator of the severity of ASI5. Another study reported that a rupture of the blood-aqueous barrier was observed after tenotomy of the extraocular muscle (EOM) in an animal model6. To prevent ischemia, triamcinolone acetonide (TA) has been used to treat various ocular inflammations, edemas and ischemic diseases7.

To our knowledge, there is no objective ocular marker for the occurrence of ASI after strabismus surgery. Moreover, possible changes in intraocular angiogenic factors during the early stages of ASI have not been identified. The aim of this study was to investigate the changes in aqueous and vitreous levels of PGE2, VEGF and HIF-1α in an animal model with ASI and to evaluate the effect of TA on ASI.