Corneal cross-linking in veterinary medicine

Corneal cross-linking is a therapeutic technique that has been in use for approximately 20 years in human ophthalmology. It is the treatment of choice for keratoconus – a condition where progressive thinning of the cornea results in intercellular weakness and vision disruptions.

Although they differ in aetiology, as well as clinically and histopathologically, the technique has been adapted to veterinary ophthalmology as treatment for bullous keratopathy – and, more commonly, keratomalacia.

Keratomalacia can occur in dogs and cats, and is characterised by a corneal insult that rapidly deteriorates due to an increase in endogenous and exogenous proteinases, whereby the cornea cannot maintain its stability with the physiological level of anti-proteinases. The patient will present with a typical “melting” appearance of the cornea, accompanied by ocular discharge and corneal oedema.

The keratomalacia patient is high maintenance when treating medically, with topical drops requiring application every one to two hours. Drug protocols can include broad-spectrum antibiotics, collagenase inhibitors, atropine, topical lubrication and systemic NSAIDs. This can be a challenging situation with significant variability of patient cooperation.

Corneal cross-linking aims to increase the number of molecular bonds within the cornea’s collagen fibres and glycosaminoglycans – and, therefore, improve its strength and durability, and reduce corneal oedema. This method also has an innate antimicrobial effect, and has been used to treat cases of infectious keratitis.

Procedure

The technique involves the patient undergoing either a sedation or a general anaesthetic for the duration of the procedure, which can vary from 30 to 60 minutes depending on the protocol.

In the first step, the cornea is saturated with riboflavin. Vitamin B₂ enhances the absorption of UV light used in the second step, and additionally acts as an energy absorber, protecting the cornea to a degree (termed “riboflavin shielding”) from excessive damage from the UV-A rays.

The aim is to penetrate to a depth of 300 microns of cornea – the full depth being an average of 560 microns thick in the dog; however, damage to deeper structures can occur, such as the corneal endothelium or even the lens epithelium.

Studies

A handful of veterinary studies have reported on the success of corneal cross-linking in the treatment of keratomalacia, and even fewer on its use in the treatment of bullous keratopathy.

For example, the University of Zurich analysed 49 canine and feline eyes with melting keratitis, and concluded a similar success rate between the control group and the corneal cross-linking group, despite a poorer initial presentation in the corneal cross-linking group.

Furthermore, 9 control eyes required “rescue stabilisation” – 7 of which then responded to corneal cross-linking. Cats had a lower failure rate (1/11) compared to dogs (13/38) – possibly pointing to a difference in aetiology.

Presence of concurrent disease (diabetes mellitus, ketoacidosis and hyperadrenocorticism) was also a compromising factor. The limitations of this study were that the group size was statistically insignificant, and distribution between the control and corneal cross-linking groups was not randomised or uniform (Pot et al, 2014).

More recent veterinary studies in dogs and cats are looking to further advance corneal cross-linking techniques to reduce the delivery time and improve method efficiency.

A 2013 study in a French referral centre reported results of an accelerated corneal cross-linking technique, whereby the affected corneas were irradiated for 3 minutes (instead of 30 minutes) with 30mW/cm² (instead of 3mW/cm²). A 30-day follow-up saw success in all 8 dogs, with reduced pain only 3 days after the one-off treatment (Famose, 2014).

All in all, although more studies should be performed to support its relevance, corneal cross-linking has so far proven to be a promising therapeutic.