Abstract
Purpose :
Pterygium is an ocular surface disease with benign fibrovascular growth onto the cornea that can impair vision. The current standard of care is surgery and there is no approved drug to treat pterygium. Using two animal models, we investigated whether CBT-001 ophthalmic solution can potentially be used to treat pterygium.
Methods :
CBT-001 at 0.2% BID, 0.2% TID, 0.05% BID, and 0.05% TID were studied in a rabbit suture-induced corneal neovascularization model to determine its inhibitory effects on cornea neovascularization, a key component of pterygium. Vehicle and 0.05% sunitinib TID served as negative and positive controls. Dosing started 8 days after suture surgery and continued through day 16. Cornea neovascularization area on day 7, 10, 12, and 14 was determined with ImageJ software based on color photographs. The effects of CBT-001 on pterygium lesion growth was studied in a mouse model that was developed by injecting 1X104 human pterygium epithelial cells (hPECs) into the nasal subconjunctival space in athymic nude mice. Treatment began after 7 days when pterygium lesion grew onto cornea. CBT-001 and saline were administered to the right and left eyes, respectively, from day 7 through day 17. Pterygium lesion area on cornea was measured with ImageJ using photos taken on day 7, 10, 14, and 17.
Results :
CBT-001 substantially inhibited suture-induced corneal neovascularization in the rabbit suture model. After 2 days dosing, all CBT-001 treated corneas had significantly less neovascularization than that of the vehicle group. Similar effects were observed 4 and 6 days after dosing. TID dosing was more effective than BID and 0.2% was more effective than 0.05%. The mouse model study showed that CBT-001 caused regression of human pterygium lesion growing on the cornea of nude mice. In CBT-001 treated group, pterygium lesion started to regress from day 10 and continued to shrink through day 17, while the lesion in the saline treated eyes continued to grow.
Conclusions :
CBT-001 inhibited corneal neovascularization in a dose-dependent manner in the rabbit suture model. CBT-001 regressed human pterygium lesion growing on the cornea of immune-deficient mice, demonstrating efficacy of a small molecule drug in this model for the first time. The results indicate that CBT-001 has potential for treating pterygium.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.