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In addition to pain management and the prevention or treatment of infection, one of the goals of therapy when managing any type of corneal ulceration is the promotion of healing. Certainly, identifying and addressing any underlying cause for the ulceration is paramount as well as preventing self-trauma that can result if the animal rubs the affected eye. Don’t forget that E. collar!
Derivatives of blood have long been mentioned as one possible consideration in the management of ulcerative keratitis - specifically the topical application of autologous serum or plasma. These blood products are rich in a variety of bioactive substances including immunoglobulins, macroglobulins (inhibitors of proteases), various growth factors, as well as fibronectin. These components have the potential to be of most benefit in veterinary patients with superficial chronic corneal epithelial defects (SCCEDs / indolent or refractory corneal ulcerations) and in cases in which there is keratomalacia (e.g. “melting” corneal ulcer).
Although use of autologous serum or plasma is mentioned as a consideration in many textbooks and peer-reviewed publications, very little has been written regarding protocols for the preparation, handling, or administration (e.g. frequency of drop application and duration of use). What is frequently mentioned is the potential for these products to become contaminated, and it’s been suggested that to minimize this risk and the associated consequences (iatrogenic infection of the cornea) that duration of use should not exceed 7 days in animals with ulcerative keratitis. However, this suggestion is essentially anecdotal and certainly not evidence-based.
Although the theoretical benefits of its use are supported by in vitro studies and our understanding of the pathologies that develop in these diseased corneas, there is a lack of direct evidence from in vivo studies as to its efficacy. As such, veterinary ophthalmologists vary in their opinions and recommendations regarding the use of topical serum or plasma in the treatment of corneal ulcerations. In addition to personal preference, these opinions may vary based on their training (what they learned from mentors), as well as the concern for contamination, and thus, making a bad situation worse … “above all else, do no harm.”
A paper was published regarding a study of the use of plasma eye drops in the management of ulcerative keratitis in dogs[1], and was the subject of a past Specialty Update.
Comment by Brad Holmberg, DVM, MS, PhD, DACVO:
My colleagues and I also recently published a manuscript in JAVMA examining the effects of serum on healing rates of SCCEDS (indolent corneal ulcers) in dogs. We found no improvement in healing rates when serum was used compared to placebo. Therefore, I personally do not recommend the use of topical serum in cases of indolent corneal ulceration.
Please read the reference: Effects of topically applied heterologous serum on reepithelialization rate of superficial chronic corneal epithelial defects in dogs. Eaton, et. al. JAVMA 2017, 250: 1014-1022
Comment by Sheri L. Berger, DVM, DACVO:
Hi Brad! Thanks for sharing this. Here is a link to the abstract for that paper.
Question for you ... do you use serum in treating melting corneal ulcers?
During my internship and residency, none of my mentors were in the camp of using serum in managing eye cases. I followed suit during my practice years and did not include it in my treatment plans - though I was often asked about it from referring DVMs who had read about it or had been groomed to use it during their veterinary school training.
It's always nice to see evidence that supports our approaches to treating patients (or that causes us take pause and rethink why we do the things we do). You all did a nice job with this study looking at the use of serum for treating SCCEDs. I think that a study to look at its efficacy for managing melting corneal ulcers would be much more difficult to design and interpret.
Comment by Brad Holmberg, DVM, MS, PhD, DACVO:
I definitely do use serum for melting corneal ulcers as I believe it has superior anticollagenase factors (alpha 1 antitrypsin and alpha 2 macroglobulin if memory serves me correct). What I have found to be helpful is to have a "bank" of serum at the hospital so that you don't need to take blood from the patient. This prevents inadvertent trauma (or rupture) of the affected eye during the blood collection process. We use a blood donor dog and store aliquots of 2 ml each in the freezer (-20 Celsius). In cases we need serum, we will then thaw an aliquot and provide it to the owner. We always recommend keeping the serum refrigerated and only use for 4 days to prevent potential secondary bacterial invasion.
We also use tetracyclines to reduce corneal melting, including topical terramycin (oxytetracycline) and oral doxycycline (which is secreted into the tear film). Tetracyclines inhibit matrix metalloproteinases 2 and 9 (MMP2, MMP9) which are involved in proteolytic activity involved in corneal remodeling.
I agree, trying to design a study to look at the efficacy of serum in melting ulcers would be difficult in a clinical situation as each case would present with different degrees of corneal malacia and infection. This would unfortunately need to be studied in a controlled trial with experimentally induced melting ulcers.
[1] Evaluation of microbial contamination of canine plasma eyedropper bottles following clinical use in canine patients. Vet Ophthal 2018;00:1-7