Daniel Biros, DVM, DACVO
The corneal ulcer condition represents a wide spectrum of disease from the smallest surface abrasion to the total loss of corneal stroma leading to a complete descemetocele (Figure 1) or corneal rupture. As such, the prognosis and treatment plans vary as much as all the different types of corneal ulcerative disease we see. Small injuries can heal with time and symptomatic treatment while complicated disease requires weeks of treatment and possibly single or multiple surgeries just to preserve the eye and vision. Wound repair of the cornea demands that there be minimal scarring and structural integrity in order to avoid functional vision loss. In veterinary medicine fortunately we are not faced with the same rigors of vision demands by contrast to human vision needs, so there is some “wiggle room” to allow for scarring and partial vision loss. In general, steroid or NSAIDs in topical form are to be avoided during the wound repair period and even afterwards due to their collagenolytic activity even though in humans topical steroids and topical NSAIDs can be used to reduce scarring and preserve visual acuity and cosmesis with judicious use during ulcer healing.
The broad points of care in every ulcerated cornea are addressing the primary cause of the ulcer, infection control, pain and inflammation management, and wound repair. These four priorities must be addressed in every patient. Often the acute treatment plan for severe ulcerative keratitis is intense, and the monitoring necessary is often day to day. Recovery can take weeks to months in some cases, and medical treatment can be augmented by surgical repair and stabilization by referral in the most severe situations. Under certain conditions relapse is a concern, especially in the most vulnerable, including brachycephalics, those with difficult-to-treat dry eye, and those suffering from canine ocular herpes to name three examples.
To walk through the experience of managing complicated corneal ulcers, there are six achievement goals on which we will focus:
I. Create the environment for a safe and productive examination.
II. Establish parameters of the wound area including size and stability.
III. Look for common problems that can create a severe ulcer.
IV. Consider advanced diagnostics to speed the characterization of the condition and direct therapy.
V. Put a definitive plan in place for monitoring and therapy adjustment, but be ready to adjust treatment on the go.
VI. Educate the client to the realities of significant corneal disease including discussions on outlook for vision and comfort. Set realistic expectations.
I. Create the environment for a safe and productive examination
The essential part of a successful corneal examination lies in getting a good and long look at the ocular surface and the anterior chamber, evaluating the adnexa, and checking the vision status of the affected eye. Comfortable and secure manual restraint with the aid of a systemic pain medication as needed (methadone, buprenorphine) will neutralize some of the anxiety of the patient, and topical anesthesia is almost always implemented (e.g. proparicaine) when there is marked blepharospasm. If possible, any cultures of the ocular surface should be taken prior to topical anesthetic since the topical drops may affect the culture results. Any crusting or thick mucus should be wiped away carefully as to not cause significant disturbance to the cornea in case it has or is near rupture. After topical anesthetic has taken effect (up to 5 minutes for full effect lasting 30 min) and the cornea is not fully visible due to mucus, you may consider gently irrigating the surface area with saline to reveal the ocular surface. Care must be taken if blood or fibrin is suspected which could indicate a leaking cornea or recent leak due to a full thickness perforation or puncture.
II. Establish parameters of the wound area including size and stability
Careful documentation of the wound will be important to monitor progress and guide prognosis. Is it deep? What is the diameter or other dimensions of the surface area? Are the wound edges discreet or blurred? Is there any evidence of leaks? Can you visualize the anterior chamber and is there any blood, fibrin, hypopyon, or synechiae abutting the corneal surface? Once the visualization of the cornea is possible, culture swabs should be gently taken and set aside if there are indications for it, such as stromal melting, especially if ulceration is superficial stromal or deeper. We often use cytology brushes (Microbrush brand) to test the stability of the corneal surface, explore briefly the depth or extent of corneal lacerations, dislodge superficial foreign bodies, and differentiate possible mucus from fibrin plugs. Photography is often helpful to document the wound over time, and with experience, estimating dimensions of wounds is a good practice to have some objective data in the medical record. Illustrations are also very helpful for characterizing the lesion and are done with every eye examination we do. If there is aqueous humor leakage suspected or if you suspect the eye will leak with any manipulation, then touching the tissue should be minimized until in a safe surgical setting or until the wound has stabilized sufficiently on its own with time and supportive care.
III. Look for common problems that can create a severe ulcer
Once the patient is comfortable for evaluation and the wound area has been initially checked, a look around the injury is essential at better characterizing the conditions that may have led to the changes seen. With a good history, you may be inclined to look for other associated ocular disease such as lagophthalmos, distichiae, ectopic ciliae, dry eye, or foreign bodies that could be directly involved with the pathology. Some of these conditions can be addressed on the spot while others may need long term care. Remember, a Schirmer tear test will be lower in patients who have received topical proparicaine, so this test may be skipped until the eye is more stable.
IV. Consider advanced diagnostics to speed the characterization of the condition and direct therapy
The core ophthalmic tests for most eye exams include a testing for a menace response, pupillary light reflexes, palpebral reflexes, Schirmer tear test, tonometry, fluorescein stain, and visualization of the eyelids, conjunctiva, cornea, anterior chamber, lens, and fundus (retina). In severe corneal disease additional testing can also involve aerobic bacterial corneal culture, fungal culture, cytology, Seidel testing for leakage of the aqueous humor through the cornea, and PCR testing for herpes. In an emergency situation all tests may not be possible or indicated, but in complicated corneal ulcers where there has been chronic antibacterial treatment or rapid progression of the ulcer size and depth despite therapy, culture first (with option for submission later on), and then cytology may be most helpful. Aerobic culture should be sufficient when looking at types of cultures to submit in New England, but in some geographic areas fungal testing would be warranted (e.g. the South). Cytology can be Diff-Quik or gram stain, and done in clinic or send off to a cytologist. Seidel testing is a variation on the fluorescein test where the test strip is actually applied in contact briefly to an area of cornea suspected of leakage—whether an ulcer, a tear, or a surgical incision—leaving a concentrated area of fluorescein on the corneal surface which is bright orange. If there is a leak, the orange will quickly change to green and often the green streaks that result in a leaking cornea will track the course of the aqueous humor along the ocular surface. The eyelids have to be kept open to have good test results as fluid from tears or even eye wash will also cause the same type of dilution. The patient has to be very still for the test to be interpreted properly and any excess mucus or fluid on the ocular surface rinsed away to get the best view of the test.
V. Put a definitive plan in place for monitoring and therapy adjustment, but be ready for adjusting treatment on the go
Treatment plans for severe corneal ulcers are often quite labor intensive and in the case of melting ulcers, recommendations of up to three meds hourly for several days is one standard approach to reverse the rapid melting process and save the eye. By now cultures and cytology are turned in and there is likely CBC and chemistry panel results that will help focus the options for systemic care. In specialty care clinics with 24-hour services, round-the-clock care can be offered to lessen the burden of care and allow the clients to get some sleep. Making sure the patient’s anxiety is as low as possible will also help them take the medication without the added problems of nausea, inappetence, high blood pressure, or aggression. Unless there is high risk from anesthesia, surgical stabilization by referral with conjunctival grafting is often offered when the ulceration is large, deep or actively leaking and the leak is no larger than 5-7 mm (Figure 2). Risks for graft failure go up with larger injury (larger graft), but recent advancements in grafting options including amniotic membrane, synthetic or biological collagen implants over the wound area; collagen cross linking; and even corneal transplants in certain situations are used to save an eye that would otherwise be lost to medical therapy alone or that would greatly accelerate the wound healing process. There is also benefit, if possible, to stabilize the cornea with medication for up to 24-48 hours prior to moving to surgical correction of the corneal ulcer. Grafts fail when the inflammation is profound and the grafts succumb to neutrophilic digestion. However, with a few days of anti-inflammatory and antibiotic care, the surgical field can become more stable and accepting of grafts.
We will often use during hospitalization ofloxacin, cefazolin (compounded to 55 mg/ml in bacteriostatic water-refrigerated-good for at least two weeks), and whole serum diluted up to 25-50% with artificial tears up to every hour for up to 3-4 days to start intensive treatment for a melting ulcer and then taper down to a frequency that the clients can handle at home once the wound is showing signs of repair. Atropine use can be very helpful especially if the uveitis is profound, and can be used up to 4-6 times daily initially to dilate the pupil at the onset of treatment, but then tapered to the lower effective frequency to sustain dilation, often one to 2 times daily. If profound uveitis with hyphema or hypopyon, systemic antibiotics are suitable to reach therapeutic intraocular concentrations. Systemic pain medication like includes carprofen and gabapentin. We also will use methadone, meloxicam, and other options depending on the patient’s weight and history with these drugs. Trazadone can also be helpful if there is high anxiety, and cerenia or similar is often used during hospitalization if there is any perceived risk for nausea. When to send a patient with a healing ulcer for home care will depend on what the pet owner can do and how stable the pet is doing. In general, we like to string together 2-3 successive days of improvement, feel confident the wound is not going to destabilize, and try to get the treatments down to at most every 4-6 hours.
VI. Educate the client to the realities of significant corneal disease including discussions on outlook for vision and comfort. Set realistic expectations.
Despite the best intentions of intensive medical therapy, some patients are poor responders, and if we don’t see improvement in 3-4 days at the latest, we will discuss options in replacement of or in addition to the medical therapy already implemented. Obvious cases that would have us consider surgical referral immediately would be those where the cornea is already perforated or perforation is imminent. Descemetoceles and deep ulcers also are considered for the fast track to surgical referral (Figure 1) if the patient is stable and the goal of care will enable the preservation of some vision—or just keeping the eye knowing it will be blind if the client is averse to enucleation. If the cornea is beyond repair having considered both surgery and medication options, then we can offer enucleation as the humane course of therapy for the severest cases to alleviate pain and speed the recovery quickly. For some the financial costs are too strenuous for intensive medical care, and the clients are not equipped to treat at home to meet the needs of the patient. But if they are willing to do the best that they can do at home there is nothing lost if the client wants to treat intensively at home to the best of their ability with reasonable rechecks every day or so. Initial testing and evaluation for a melting ulcer on emergency including evaluation, tests, cultures, and medication can be upwards of $800. If the patient stays for intensive eye care in hospital, the cost can be up to $500 per day. Urgent surgery to repair a severely damaged cornea can cost in the range of $2,500 to $3,500 for the surgery and post-op care alone.
Basic training in managing corneal ulceration does not always prepare one for dealing with advanced cases of corneal melting or large, deep ulcerative conditions. By considering additional steps in the path of diagnosing and treating ulcerative keratitis, some advanced cases may continue to have vision with ramped-up medical and or surgical treatment by referral. The vision survival rate for serious corneal ulcers in dogs is going to be lower by contrast to patients with less serious ulcers, but with some adjustments to conventional therapy, many of these cases can stand a better chance to heal with functional vision.
- Dan G. O’Neill, Monica M. Lee, Dave C. Brodbelt, David B. Church, and Rick F. Sanchez Corneal ulcerative disease in dogs under primary veterinary care in England: epidemiology and clinical management. Canine Genet Epidemiol. 2017; 4: 5.
- Pot SA1, Gallhöfer NS, Matheis FL, Voelter-Ratson K, Hafezi F, Spiess BM. Corneal collagen cross-linking as treatment for infectious and noninfectious corneal melting in cats and dogs: results of a prospective, nonrandomized, controlled trial. Vet Ophthalmol. 2014 Jul;17(4):250-60.
- Ledbetter EC1, Franklin-Guild RJ2, Edelmann ML Capnocytophaga keratitis in dogs: clinical, histopathologic, and microbiologic features of seven cases. Vet Ophthalmol. 2018 Nov;21(6):638-645.
- Ledbetter EC1, Riis RC, Kern TJ, Haley NJ, Schatzberg SJ. Corneal ulceration associated with naturally occurring canine herpesvirus-1 infection in two adult dogs. J Am Vet Med Assoc. 2006 Aug 1;229(3):376-84.
- Wilkie, David A. et al. Surgery of the Cornea. In Veterinary Clinics: Small Animal Practice, Volume 27, Issue 5, 1067 – 1107.
- Ledbetter EC, Gilger BC. Diseases and surgery of the canine cornea and sclera. In: Gelatt KN, Gilger BC, Kern TJ, editors. Veterinary Ophthalmology, vol. 2. 5th ed. Oxford: Wiley-Blackwell; 2013. p. 976–1049.
- Vanore M, Chahory S, Payen G, Clerc B. Surgical repair of deep melting ulcers with porcine small intestinal submucosa (SIS) graft in dogs and cats. Vet Ophthalmol. 2007;10(2):93–9.
- Lacerda RP, Peña Gimenez MT, Laguna F, Costa D, Ríos J, Leiva M. Corneal grafting for the treatment of full-thickness corneal defects in dogs: a review of 50 cases. Vet Ophthalmol. 2016;1–10.
Figure 1. Five to eight mm diameter Descemetocele with a darkened non-fluorescein stain uptake in the ulcer bed, but fluorescein retention at the wound edges where there is still stroma exposed. Despite robust vascularization superior to the ulcer, this wound has developed due to low tear production (note the dried mucus at the eyelids), corneal exposure from a poor blink response, and a poor location that is lengthy distance from the corneal blood vessel supply (endogenous wound repair). Conjunctival grafting should be considered in this situation as well as addressing the causes for the poor blinking and dryness in order to preserve vision and accelerate healing.
Figure 2. The appearance of a conjunctival graft weeks post surgery for wound stabilization and repair of a deep ulcer (Courtesy Willows Vet).