Establishing a Correlation Between Cornea Neovascularization and Cornea Opacity in a Suture Induce CNV Model in Rabbit

Abstract

Purpose : Corneal transparency is preserved by a balance between angiogenic and antiangiogenic factors. A disruption of the aforementioned balance results in corneal neovascularization (CNV), characterized by the formation of new blood vessels growing on cornea. CNV arises in diseases like pterygium, blepharitis, virus infection, mechanical or chemicals insults to cornea, contact lenses, etc. CNV causes a significant loss in corneal transparency. We have used improved in-vivo quantification methods to establish a correlation between corneal transparency and CNV in a suture induced CNV rabbit model.

Methods : Five (group 1) or four (group 2) silk sutures (1.5-3.8 mm in length) were placed parallel in 3 (group 1) or 2 (group 2) rows, 1.5 mm away from the limbus in the superior cornea. Clinical ophthalmic examinations following modified McDonald-Shadduck Scoring System, slit lamp photography, fluorescein angiography (FA), and optical coherence tomography (OCT) were performed weekly. Electroretinography (ERG) was performed before and on day 21. Image J and HEYEX™ were used to quantify CNV area.

Results : Corneal suture placement was associated with conjunctival congestion/hyperemia, swelling, discharge and corneal opacity. All eyes produced a robust induction of CNV. Corneal opacity progressed and was greater in Group 1 (Baseline: 0; Day 7: 2; Day 21: 4) than Group 2 (Baseline: 0; Day 7: 1.74; Day 21: 2). Slit-lamp image measurements from day 0 to 21 revealed a greater CNV progression in Group 1 (0 to 77.4 mm2) than Group 2 (0 to 49.1 mm2). Similarly, progression of CNV area from day 7 to 21 was observed with FA in Group 1 (27.6 to 61.0 mm2) and Group 2 (18.2 to 34.0 mm2). Severity of CNV by FA grading in Group 1 (3.0 to 4.0) was higher than Group 2 (1.3 to 3.3). A robust percent increase in corneal thickness, central (Group 1: 86%; Group 2: 22%), close to CNV (Group 1: 94%; Group 2: 66%), and on CNV area (Group 1: 132%; Group 2: 90%) was determined. Suture placement and CNV progression had no adverse effects on retinal function as observed by ERG.

Conclusions : Our results show that corneal transparency is impaired by the progression of CNV. These improved in-vivo quantification methods and animal models with varying grade of CNV may contribute to the accurate evaluation of the efficacy of anti-angiogenic and anti-inflammatory drugs for cornea neovascularization.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.