Our Summary

This research paper discusses a new approach to improving the success rate of corneal transplants. Usually, corneal transplants are quite successful, because the cornea (the clear front part of the eye) doesn’t have its own blood supply and the eye as a whole has some protection from the body’s immune system. However, in high-risk patients, there’s a 20% chance that the body will reject the transplant because the recipient’s cornea has developed its own blood vessels. This process is called neovascularization (NV) and it can lead to the immune system attacking the transplant.

To solve this problem, this study tests a modified donor cornea, known as OXB-202 (or EncorStat®), which has been genetically altered to produce human proteins that suppress the growth of new blood vessels. This is done using a harmless virus derived from horses, which carries the relevant genes into the cells of the cornea.

In previous tests on rabbits, this approach was shown to significantly reduce NV and the likelihood of transplant rejection. The current study presents new data from a second rabbit model, which better represents the situation in high-risk human patients, and also includes safety data from a three-month toxicity study.

The results show that the modified corneas significantly reduce NV and transplant rejection, with no signs of toxicity or significant spread of the modifying virus up to 13 weeks after surgery. This suggests that targeting NV is a valid strategy for preventing cornea transplant rejection in high-risk patients, and that the genetically modified corneas are safe and well-tolerated in an animal model. These findings support the idea of testing OXB-202 in human trials.

FAQs

  1. What is the problem with corneal transplants in high-risk patients?
  2. What is the purpose of the genetically modified donor cornea, OXB-202?
  3. What were the results of the study testing OXB-202 on a second rabbit model?

Doctor’s Tip

A doctor might tell a patient undergoing a corneal transplant to follow post-operative care instructions carefully, including taking any prescribed medications to prevent rejection of the transplant. Additionally, they may advise the patient to avoid rubbing or touching their eyes to reduce the risk of complications. It is also important for the patient to attend all follow-up appointments with their ophthalmologist to monitor the success of the transplant and address any concerns.

Suitable For

Patients who are typically recommended for corneal transplant are those with conditions such as:

  1. Keratoconus: A degenerative disorder of the eye in which the cornea becomes thin and cone-shaped, leading to distorted vision.

  2. Fuchs’ dystrophy: A condition in which cells in the inner layer of the cornea gradually die off, leading to cloudy vision.

  3. Corneal scarring: Caused by injury, infection, or other trauma to the eye, resulting in vision impairment.

  4. Corneal ulcers: Open sores on the cornea that can be caused by infection, injury, or other underlying conditions.

  5. Corneal edema: Swelling of the cornea due to fluid accumulation, often as a result of dysfunction in the endothelial cells that maintain corneal clarity.

  6. Previous corneal transplant failure: Patients who have had a previous corneal transplant that was unsuccessful may be recommended for another transplant.

  7. High-risk patients with neovascularization: Patients with a high risk of transplant rejection due to the development of new blood vessels in the cornea may benefit from a genetically modified cornea that suppresses neovascularization.

Timeline

  • Before corneal transplant:
  1. Patient experiences vision problems such as blurred vision, glare, and light sensitivity due to a damaged or diseased cornea.
  2. Patient undergoes a comprehensive eye examination to determine the need for a corneal transplant.
  3. Patient is placed on a waiting list for a suitable donor cornea.
  4. Once a donor cornea is available, patient undergoes pre-operative assessments and consultations with the surgeon.
  5. Surgery is scheduled and patient receives instructions on pre-operative care.
  • After corneal transplant:
  1. Patient undergoes corneal transplant surgery, which involves removing the damaged cornea and replacing it with the donor cornea.
  2. Patient is monitored closely for any signs of complications or rejection in the immediate post-operative period.
  3. Patient is prescribed medications to prevent infection and rejection of the transplant.
  4. Patient follows a strict post-operative care regimen, including frequent eye drops, eye protection, and follow-up visits with the surgeon.
  5. Over time, patient’s vision gradually improves as the transplant heals and integrates with the surrounding tissue.
  6. Patient may require glasses or contact lenses to achieve optimal vision after the transplant.
  7. Patient continues to be monitored regularly for any signs of rejection or complications in the long-term.

What to Ask Your Doctor

Some questions a patient should ask their doctor about corneal transplant include:

  1. What is the success rate of corneal transplants in general, and what factors might increase the risk of rejection in my case?
  2. Can you explain the process of neovascularization and how it can lead to the rejection of a corneal transplant?
  3. Have you heard about the new approach using genetically modified donor corneas to prevent neovascularization and rejection? What are your thoughts on this technique?
  4. Are there any risks or potential side effects associated with using genetically modified corneas for a transplant?
  5. How would I be monitored and evaluated after the surgery to ensure the success of the transplant and to detect any signs of rejection?
  6. Are there any specific lifestyle changes or medications I should consider to support the healing process and prevent rejection?
  7. What is the timeline for recovery after a corneal transplant, and what can I expect in terms of vision improvement and overall outcome?
  8. Are there any ongoing clinical trials or research studies related to corneal transplants that I might be eligible for or should consider participating in?
  9. Can you provide me with additional resources or information about corneal transplants, neovascularization, and the use of genetically modified corneas for transplantation?
  10. What are the next steps if I decide to proceed with a corneal transplant using a genetically modified donor cornea?

Reference

Authors: Fouladi N, Parker M, Kennedy V, Binley K, McCloskey L, Loader J, Kelleher M, Mitrophanous KA, Stout JT, Ellis S. Journal: Hum Gene Ther. 2018 Jun;29(6):687-698. doi: 10.1089/hum.2017.184. Epub 2018 Mar 19. PMID: 29361840