Post-Surgical Corneal Endothelial Cells (CEC) Loss
- Loss of corneal endothelial cells (CECs), which maintain the transparency of the cornea, is a common complication of cataract surgery and results in part from oxidative stress. These cells cannot regenerate efficiently, and loss of CECs may ultimately lead to impairment or loss of vision.
- Omaveloxolone is a potent inducer of antioxidant protein expression in CECs in preclinical studies and may also improve metabolism in these energy-intensive cells.
- Omaveloxolone was evaluated in a Phase 2 study of omaveloxolone in cataract surgery patients (GUARD).
Cataract surgery, the procedure most often used to break up and remove the natural lens, produces oxidative stress. Corneal endothelial cells, or CECs, have high mitochondrial density, high requirements for energy production, and are sensitive to oxidative stress. Because of this, CECs are particularly susceptible to surgically-induced damage1.
During cataract surgery, patients may lose 10% to 15% of their CECs, but in some instances the magnitude of CEC loss can be up to 50%2. CECs do not regenerate and are required for vision. Therefore, CEC loss represents a vision-threatening complication of cataract surgery3.
Mechanism of Action
We believe that omaveloxolone may have utility in preventing the loss of corneal endothelial cells, or CECs, during cataract surgery. Although improvements in surgical procedures can help minimize CEC loss, we are not aware of any existing pharmacotherapies that can protect this critical cell layer from surgical insult.
In a series of preclinical studies, a topically applied suspension of omaveloxolone was highly effective in inducing expression of antioxidant gene expression in the corneal epithelium and endothelium and also substantially reduced markers of post-operative inflammation4.
- Joyce NC. Proliferative capacity of corneal endothelial cells. Exp Eye Res. 2012 Feb;95(1):16-23.
- Soliman Mahdy et al. Relationship between endothelial cell loss and microcoaxial phacoemulsification parameters in noncomplicated cataract surgery.
- Joyce. Proliferative capacity of the corneal endothelium. Prog Retin Eye Res. 2003 May;22(3):359-89.
- Reata Pharmaceuticals, Inc., internal data.