Corneal Cross-Linking to Treat Ulcerative Keratitis in Horses 

Corneal cross-linking (CXL) is an effective treatment for ulcerative keratitis in horses that can shorten mean time to reepithelialization.
In a 2013 study, researchers used a handheld UVA-light source to perform the corneal cross-linking procedure for 30 minutes to irradiate a corneal ulcer. The edge of the light beam was sharply circumscribed when the lamp was held at a distance of 5 cm from the corneal surface, which enhanced maintaining the correct distance between the lamp and the patient’s eye. | 2013 Hellander-Edman et al.; licensee BioMed Central Ltd.

Ulcerative keratitis can be challenging to treat as it requires frequent medication to control infection and halt proteolytic activity that can melt the cornea. Complications can affect the horse’s vision, especially with melting corneal ulcers. An adjunctive procedure called corneal cross-linking (CXL) strengthens the cornea by increasing the bond between collagen fibers. With stronger collagen fibers, the cornea is better able to resist bacterial and fungal attack and potential melting. Besides collagen fiber strengthening, the objective is to kill bacterial organisms and stop enzymatic degradation of the stroma.

Study on CXL to Treat Ulcerative Keratitis

Researchers in Sweden evaluated horses with ulcerative keratitis treated with CXL compared to traditional ophthalmic therapy. In the study, 24 horses with unilateral ulcerative keratitis presented to two equine hospitals. Researchers treated one group of 12 with CXL. The other 12 horses were controls treated with standard ophthalmic practices. Researchers sedated CXL horses for the procedure and blocked the auriculopalpebral nerve in addition to providing topical corneal anesthesia. They applied the CXL procedure for 30 minutes and followed it with topical atropine and antibiotics if bacteria were seen on cytology and/or if wound healing was not progressing. 

The researchers treated the control horses with topical antibiotics and topical anti-protease treatment with 1.8 mg EDTA/ml autologous serum. They administered ophthalmic drugs via a subpalpebral lavage system. They also administered systemic flunixin meglumine and topical atropine as needed in both CXL and control horses. 

The researchers took photographs with a millimeter scale positioned beneath the eye; they obtained measurements from both clinical examination and photographs.  

Study Results

In the CXL group, they found that: 

  • All 12 eyes with stromal ulcers healed and were fluorescein-negative within two to 29 days. 
  • Six eyes were not infected with bacteria or fungi. Three of these healed within two to seven days with only CXL treatment and no additional topical treatment. The other three received precautionary topical antibiotics in addition to the CXL treatment. 
  • Four of six other eyes with bacterial infection were not healing by Days 4 to 14, so researchers added topical antibiotics to CXL treatment. 
  • With just the CXL treatment, the stromal surfaces of the four eyes with stromal melting improved even without anti-protease therapy. Three of them were treated with topical autologous serum with EDTA and topical antibiotics. 

In the control group, all 12 ulcers healed within six to 42 days despite eight of them being infected with bacteria and one with fungus. 

Mean time to reepithelialization of the ulcer was about five days shorter for CXL treatment. However, the control group ulcers were larger at the start. Healing progressed similarly in both CXL and control groups, indicating that CXL does not have adverse effects on wound healing rates. Melting of the cornea ceased the day after treatment started in both groups. Inflammation and pain also reduced in both groups, in part due to NSAID administration but also because the CXL procedure inhibits an immune response mediated by leukocytes, which the ultraviolet-riboflavin procedure inactivates. 

The end result of the study is encouraging: “The mean wound area was larger in the control group but the mean time to fluorescein negativity was shorter, and the estimated total volume of the ulcers was on average larger in the CXL group.” All eyes retained vision.  

How To Perform the Procedure 

At the 2020 AAEP Virtual Conference, Carol Clark, DVM, Dipl. ACVIM, and Leslie Easterwood, DVM, described an easy standing procedure using CXL. Required equipment includes a 365 nm ultraviolet light (available on Amazon for $15) and 0.1% riboflavin ophthalmic solution available from compounding pharmacies. Sedation, regional nerve blocks, and local anesthetic on the globe keep the eye still during the procedure. Following appropriate ulcer debridement, riboflavin is “painted” on the corneal ulcer, and then the light is shined directly on the lesion from about 1.5-2.5 inches away. Riboflavin absorbs the ultraviolet light and produces energy that influences surrounding collagen to form crosslinks to adjacent collagen fibers. The riboflavin drops are added every three minutes initially. The procedure takes between 5-20 minutes depending on the practitioner. The CXL procedure is done on Day 1 and Day 5, with most horses only needing one or two treatments. If a corneal ulcer won’t heal and continues to worsen, the veterinarian should redo the cross-linking procedure. 

Reference

Edman AH, Strom L, Ekesten B. Corneal cross-linking (CXL) – A clinical study to evaluate CXL as a treatment in comparison with medical treatment for ulcerative keratitis in horses. Veterinary Ophthalmology 2019; DOI: 10.1111/vop.12662

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