Treatment of equine keratomycosis, part 2: reporting common systemic and ocular complications to enhance decision-making for equine clinicians and owners

Hannah L. Smith Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

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Kim R. Love K.R. Love QCC, Athens, GA

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Ariana Antezana Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

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Erin M. Barr Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

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Brian C. Gilger Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

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 DVM, MS, DACVO, DABT https://orcid.org/0000-0002-7771-9166
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Annie Oh Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

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 DVM, MS, DACVO

Abstract

OBJECTIVE

The primary aims were to provide descriptive data on systemic and ocular complications associated with the treatment of equine keratomycosis. The secondary aims were to determine if complication rates differ between treatment types or are related to surgical and anesthetic factors.

METHODS

The study was a retrospective evaluation of 126 cases between 2004 and 2020 with confirmed fungal infection and recorded incidence of complications during hospitalization and surgical intervention if pursued. Additional information recorded included the size of the donor graft if utilized, time under general anesthesia, and prescribed medications. Fisher exact and χ2 tests were used to evaluate complication frequency differences. Logistic regression models determined the effects of donor graft size, anesthesia time, and duration of hospitalization on complication rates.

RESULTS

Hypercreatininemia followed by colic were the most frequent systemic complications in the medical treatment group. Colic and conjunctival graft dehiscence were the most frequent systemic and ocular complications in all surgery treatment groups, respectively. The frequency of systemic complications did not vary between treatment groups, although colic rates were significantly higher following general anesthesia. All colic cases were resolved with supportive care. Donor graft size, anesthesia time, and duration of hospitalization did not impact complication frequency. The mainstays of medical therapy included topical fluoroquinolones, topical voriconazole, topical atropine, oral NSAIDS, and oral gastroprotectants.

CONCLUSION

Treatment of keratomycosis is associated with a range of complications. Colic remains a significant risk, with increased frequency reported following general anesthesia.

CLINICAL RELEVANCE

Reporting common complications associated with treatment aids in decision-making for equine clinicians and owners.

Abstract

OBJECTIVE

The primary aims were to provide descriptive data on systemic and ocular complications associated with the treatment of equine keratomycosis. The secondary aims were to determine if complication rates differ between treatment types or are related to surgical and anesthetic factors.

METHODS

The study was a retrospective evaluation of 126 cases between 2004 and 2020 with confirmed fungal infection and recorded incidence of complications during hospitalization and surgical intervention if pursued. Additional information recorded included the size of the donor graft if utilized, time under general anesthesia, and prescribed medications. Fisher exact and χ2 tests were used to evaluate complication frequency differences. Logistic regression models determined the effects of donor graft size, anesthesia time, and duration of hospitalization on complication rates.

RESULTS

Hypercreatininemia followed by colic were the most frequent systemic complications in the medical treatment group. Colic and conjunctival graft dehiscence were the most frequent systemic and ocular complications in all surgery treatment groups, respectively. The frequency of systemic complications did not vary between treatment groups, although colic rates were significantly higher following general anesthesia. All colic cases were resolved with supportive care. Donor graft size, anesthesia time, and duration of hospitalization did not impact complication frequency. The mainstays of medical therapy included topical fluoroquinolones, topical voriconazole, topical atropine, oral NSAIDS, and oral gastroprotectants.

CONCLUSION

Treatment of keratomycosis is associated with a range of complications. Colic remains a significant risk, with increased frequency reported following general anesthesia.

CLINICAL RELEVANCE

Reporting common complications associated with treatment aids in decision-making for equine clinicians and owners.

Equine keratomycosis remains a prevalent ocular disease depending on the geographic location and season.13 Treatment can be fraught as the clinician is not only facing challenges in managing the inciting fungal infection and subsequent ocular inflammatory response, but additional factors associated with hospitalization and general anesthesia may impact the systemic and ocular health of the patient. In the few papers4,5 evaluating systemic complications, colic is the main systemic complication described with the reported frequency from 19.5% to 21.4%. The majority of reported cases experienced mild colic signs. Scherrer et al6 compared patients hospitalized for treatment of ocular and orthopedic diseases and did not find a difference in colic rates (8% and 5%, respectively) suggesting that similar hospitalization risk factors existed between these populations.

Treatment of equine keratomycosis often involves surgical intervention either via standing sedation or under general anesthesia. Reported postanesthetic colic rates for elective nonabdominal surgeries range from 2.5% to 10.5%.711 The frequency of postanesthesia colic in keratomycosis cases may be higher than in other elective nonabdominal procedures due to the prolonged duration of the surgery. Curto et al12 determined that the anesthesia, surgery, and recovery times were significantly greater for ophthalmic versus orthopedic and diagnostic imaging procedures. The overall postanesthesia colic rate was 17% in that study population, which included a high proportion of ophthalmic procedures (19%).

Hospitalization complications may also occur including diarrhea, acute kidney injury, fever, respiratory infections, trauma, lameness, laminitis, and phlebitis related to intravenous catheter use and intravenous injections. Serial bloodwork to monitor patient status may reveal biochemical derangements, most commonly hypercreatininemia, hypoalbuminemia, and electrolyte disturbances before clinical signs of systemic disease are observed.13,14 Hospitalization causes stress by exposing patients to a new environment, stall confinement, erratic sleep schedules due to frequent medical treatments, and potentially different hay and feed sources.15 Medications commonly used to treat equine keratomycosis may also contribute to systemic complications. Systemic NSAID drugs, specifically flunixin meglumine, and topical atropine are widely prescribed in keratomycosis cases to manage associated reflex uveitis and ocular pain. Reported systemic complications in horses associated with NSAID use include acute kidney injury, gastric ulceration, and right dorsal colitis.1618 Systemic absorption of topical atropine may reduce borborygmi and intestinal myoelectric activity in the cecum and colon.19

Potential ocular complications associated with medical treatment of keratomycosis include uncontrolled uveitis, corneal perforation, and lack of response to medical therapy; these may also be indications to proceed with surgical therapy.20 Recurrence of fungal and bacterial infections is possible in cases where treatment is discontinued prematurely or additional environmental exposure occurs on ulcerated corneal surfaces. Subpalpebral lavage catheter (SPL) complications can be common with a 29% overall complication rate reported for dorsally placed SPLs.21 Additional complications associated with conjunctival grafting procedures include conjunctival graft dehiscence, vascular compromise and graft necrosis, and corneal perforation.20 Penetrating keratoplasty is a surgical procedure where both donor (harvested equine cornea or acellular xenograft) and conjunctival grafts are used to allow for a water-tight seal of the surgical site; the donor graft replaces the full-thickness corneal resection and the conjunctival graft is placed over the donor graft.22 Donor corneal tissue used in penetrating keratoplasty can experience graft failure due to poor quality, infection, malacia, dehiscence, and microleakage of aqueous humor from suture tracks.20

There are few publications reporting on treatment complications for this disease as generally the focus is on diagnostic results and clinical outcomes. A thorough evaluation of outcome indicators, including clinical outcome, treatment cost, and hospitalization duration, is provided in our companion paper.23 The primary aims of this study were to describe the systemic and ocular complications associated with the treatment of equine keratomycosis at a university teaching hospital located in the southern US and to determine if there was a difference in the complication frequency between medical and surgical treatment groups. Secondary aims included the determination of whether longer anesthetic times resulted in an increased risk of systemic complication or increased incidence of colic, whether delaying time to surgery or increasing hospitalization duration affected complications, and whether the size of the donor graft during penetrating keratoplasty affected ocular complications. Finally, this study cataloged the medication protocols prescribed by the clinicians at the university teaching hospital.

Methods

Data collection

In this retrospective study, animal owners or owners’ representatives provided written consent for the treatment provided and the use of medical records for research purposes. Cases were selected as previously described in the companion study.23 Briefly, cases with a confirmed diagnosis of equine keratomycosis from the North Carolina State University College of Veterinary Medicine (NCSU CVM) between January 2004 and November 2020 with at least 1-month follow-up were selected. Cases were categorized by general treatment category (medical or surgical) and specific treatment type (medical treatment, superficial keratectomy, keratectomy with conjunctival graft, and penetrating keratoplasty). Additional case information collected for this study included systemic and ocular complications, total time under general anesthesia if performed, time from initial examination to the surgery date, size of donor graft if penetrating keratoplasty was performed, and medications prescribed by NCSU CVM. Medications prescribed were categorized by medication category, drug name, and route of administration.

Statistical analysis

Data analysis was performed using IBM SPSS Statistics, version 29 (IBM Corp), and R, version 4.2.3 (The R Foundation). A P value less than .05 was considered statistically significant for all analyses. The relative occurrence for each complication by treatment type was presented as a percentage of total eyes for ocular complications and of total horses for systemic complications. Surgical complications were categorized as pre- or postsurgical, and only the first instance of an individual complication was recorded. The χ2 test was used to evaluate for differences in the frequency distribution of the following complications by treatment groups: all systemic complications by individual treatment type (medical, standing keratectomy, keratectomy with conjunctival graft, and penetrating keratoplasty), all systemic complications by general treatment category (medical and surgical), postoperative systemic complications for surgical treatment categorized by time to surgery (≤ 2 days or > 2 days), and postoperative ocular complications for surgical treatment categorized by time to surgery (≤ 2 days or > 2 days). Individual systemic and ocular complications of higher prevalence were evaluated for differences in frequency by treatment type with Fisher exact tests. Logistic regression models were used to investigate for relationships between (1) the size of the donor graft in penetrating keratoplasty and postoperative ocular complications, (2) anesthesia time and postoperative systemic complications, and (3) duration of hospitalization and any systemic complications as well as colic as an individual complication.

Additional analysis of colic rate by procedure type (medical only, sedated, and general anesthesia) and timing (pre- and postprocedure) was performed. A mixed effects model found no measurable correlations between pre- and postprocedure colic occurrences within individual horses, indicating that pre- and postprocedure instances of colic were essentially independent. This allowed for a comparison of the colic rates between medical/preprocedure, postsedated procedure, and postgeneral anesthesia procedure by Fisher exact tests. Ocular and systemic medications as prescribed by the NCSU CVM were presented as a percentage of the total number of eyes for ocular medications and the total number of horses for systemic medications. One horse with bilateral involvement with each eye in a different treatment group was excluded from analyses of systemic complications when categorized by treatment group.

Results

Relative frequency of treatment complications

Patient demographic data were provided in the companion publication.23 Complication data were available for 125 patients (126 eyes). In the medical treatment group (n = 40 horses; 40 eyes), the most common systemic complications were hypercreatininemia (12.5%), colic (10%), and hypoalbuminemia (7.5%). Corneal perforation, recurrent fungal infection, and SPL-related complication occurred in 1 case each (2.5%; Table 1). In the superficial keratectomy group (n = 24 horses; 25 eyes), colic was the main systemic complication with preoperative colic occurring in 12.5% and postoperative colic occurring in 8.3% of cases. The most frequent ocular complications for the superficial keratectomy group were conjunctival graft dehiscence (50%), recurrent fungal infection (24%), and recurrent bacterial infection (16%; Table 2). Four horses in the superficial keratectomy group received conjunctival grafts under standing sedation and had a higher rate of dehiscence compared to conjunctival graft procedures performed under general anesthesia. In the keratectomy with conjunctival graft group (n = 39 horses; 40 eyes), the most common systemic complications were postoperative colic (17.9%), fever (7.7%), and diarrhea (5.1%). The most common ocular complications were conjunctival graft dehiscence (22.5%), contralateral eye complication (12.5%), corneal perforation (5%), and recurrent fungal infection (5%; Table 3). In the penetrating keratoplasty group (n = 21 horses; 21 eyes), the most common systemic complications were postoperative colic (28.6%), postoperative hypoalbuminemia (14.3%), and facial nerve paralysis (9.5%). The most common ocular complications were conjunctival graft dehiscence (38.1%), donor graft reaction (14.3%), and recurrent fungal infection (9.5%; Table 4). In all surgical cases with reported conjunctival graft dehiscence, 78.9% had a good clinical outcome.

Table 1

Relative frequency of complications for medical treatment in order of prevalence.

Complication Frequency Percent (%)
Hypercreatininemia 5 12.5
Colic 4 10.0
Hypoalbuminemia 3 7.5
Diarrhea 2 5.0
Corneal perforation 1 2.5
Fever 1 2.5
Lameness or laminitis 1 2.5
Recurrent fungal infection 1 2.5
Subpalpebral lavage–related complication 1 2.5

There were 40 horses in this treatment group.

Table 2

Relative frequency of complications for superficial keratectomy surgery under standing sedation in order of prevalence.

Complication Frequency Percent (%)
Conjunctival graft dehiscence (postoperation) 2 50.0
Recurrent fungal infection (postoperation) 6 24.0
Recurrent bacterial infection (postoperation) 4 16.0
Colic (preoperation) 3 12.5
Colic (postoperation) 2 8.3
Hypercreatininemia (postoperation) 1 4.2
Hypoalbuminemia (postoperation) 1 4.2
Contralateral eye complication (postoperation) 1 4.0
Corneal perforation (postoperation) 1 4.0
Subpalpebral lavage–related complication 1 4.0
Topical medication reaction (postoperation) 1 4.0

There were 25 eyes in this treatment group. Systemic complications were excluded from 1 horse with bilateral involvement in 2 separate treatment groups; the frequency of systemic complications was calculated out of 24 horses. Four horses received conjunctival grafts and were grouped separately for complications involving the conjunctival graft.

Table 3

Relative frequency of complications for keratectomy with conjunctival graft surgery under general anesthesia in order of prevalence.

Complication Frequency Percent (%)
Conjunctival graft dehiscence (postoperation) 9 22.5
Colic (postoperation) 7 17.9
Contralateral eye complication (postoperation) 5 12.5
Fever (postoperation) 3 7.7
Corneal perforation (postoperation) 2 5.0
Diarrhea (postoperation) 2 5.1
Recurrent fungal infection (postoperation) 2 5.0
Facial nerve paralysis (postoperation) 1 2.6
Hypercreatininemia (preoperation) 1 2.6
Hypercreatininemia (postoperation) 1 2.6
Hypoalbuminemia (preoperation) 1 2.6
Hypoalbuminemia (postoperation) 1 2.6
Lameness or laminitis (postoperation) 1 2.6
Phlebitis (postoperation) 1 2.6
Pneumonia (postoperation) 1 2.6
Rhabdomyolysis (postoperation) 1 2.6
Trauma related to sedation (preoperation) 1 2.6
Trauma related to surgery (postoperation) 1 2.6
Upper respiratory tract infection (postoperation) 1 2.6
Secondary bacterial infection (postoperation) 1 2.5
Subpalpebral lavage–related complication (postoperation) 1 2.5

There were 40 eyes in this treatment group. Systemic complications were excluded from 1 horse with bilateral involvement in 2 separate treatment groups; the frequency of systemic complications was calculated out of 39 horses.

Table 4

Relative frequency of complications for penetrating keratoplasty surgery under general anesthesia in order of prevalence.

Complication Frequency Percent (%)
Conjunctival graft dehiscence (postoperation) 8 38.1
Colic (postoperation) 6 28.6
Cornea/graft reaction (postoperation) 3 14.3
Hypoalbuminemia (postoperation) 3 14.3
Facial nerve paralysis (postoperation) 2 9.5
Recurrent fungal infection (postoperation) 2 9.5
Contralateral eye complication (postoperation) 1 4.8
Facial edema (postoperation) 1 4.8
Fever (postoperation) 1 4.8
Gastric ulcers (postoperation) 1 4.8
Hypercreatininemia (postoperation) 1 4.8
Nystagmus (postoperation) 1 4.8
Rhabdomyolysis (postoperation) 1 4.8
Thrombocytopenia (postoperation) 1 4.8

There were 21 horses in this treatment group.

There was no statistically significant difference in the frequency of systemic complications between medically and surgically treated eyes (P = .431) or between the 4 treatment groups (P = .106). Evaluation of the most common individual systemic complications did not identify differences in complication frequency by treatment group including colic (P = .330), diarrhea (P = .628), fever (P = .485), hypercreatininemia (P = .670), and hypoalbuminemia (P = .324). Likewise, there was no significant difference in common individual ocular complications between treatment groups, including conjunctival graft dehiscence (P = .252) and recurrent bacterial infection (P = .061). The incidence of recurrent fungal infections was higher in the superficial keratectomy group, but this was not statistically significant when compared between individual treatment groups.

Time under general anesthesia

Total anesthetic time was recorded in 40/41 horses, and the median was 147.5 minutes (range, 77 to 290 minutes). Increasing time under general anesthesia was not associated with an increased risk of postoperative systemic complications (P = .264) or postoperative colic (P = .070).

Time to surgery

The median time to surgery following patient presentation was 2 days (range 0 to 45 days). Delaying the time to surgery by 2 or more days did not affect postoperative systemic complication rates (P = .257) or postoperative ocular complication rates (P = .000).

Colic rates

When assessing colic rates between medical/presurgical cases, postoperative sedated procedures, and postoperative general anesthesia procedures, there was a significantly higher rate of colic in the postoperative general anesthesia group compared to the medical/presurgery group (P = .004).

Duration of hospitalization

The median duration of hospitalization for the study population was 9 days (range, 0 to 78 days). Longer hospitalization time was not associated with an increased risk of systemic complications overall (P = .269). Hospitalization duration did not affect systemic complications when assessed by general treatment groups (medical vs surgical) (P = .231) or procedure type (medical vs sedated procedure vs general anesthesia) (P = .144). Longer duration of hospitalization was also not associated with an increased risk of colic (P = .252).

Donor graft size

The donor graft size was reported for 19/21 patients undergoing penetrating keratoplasty. The median donor graft size was 8 mm (range, 5 to 18 mm). Equine donor cornea was used for 17 grafts, and single-layer acellular porcine bladder matrix (ACell Vet) was used for 2 grafts. There was no apparent relationship between the size of the donor graft and the frequency of postoperative ocular complications (P = .796).

Prescribed medications

A summary of prescribed medications for the study population is provided (Supplementary Table S1). The medication regime commonly included topical antibiotics (98.4%), topical antifungals (96%), systemic antifungals (66.4%), topical atropine (97.6%), oral NSAIDs (96%), and oral gastroprotectants (80%). Based on cytology and culture results, NCSU CVM mainly prescribed fluoroquinolones, with moxifloxacin (41.3%), ofloxacin (26.2%), and ciprofloxacin (19.8%) being the most common. The most frequent topical antifungal prescribed was voriconazole (85.7%) followed by natamycin (23%) and miconazole (13.5%).

Discussion

This study provides a retrospective review of systemic and ocular complications related to treating equine keratomycosis at a university teaching hospital. Systemic complication rates did not vary between the medical and surgical groups in our study population, and the frequency of the most common individual systemic complications also did not vary by treatment type. Patients undergoing a general anesthetic procedure experienced a significantly higher rate of colic postoperatively compared to medically treated and preoperative cases combined.

Colic was one of the most common systemic complications in all treatment groups. Hospitalization may increase risks for gastrointestinal complications due to housing-related stress and chronic NSAID use.14,18 The colic rate in horses hospitalized for ocular disease has been reported at 8%, 19.5%, and 21.4%.46 Our study reports a similar colic frequency in keratomycosis patients (17.6%). Patipa et al5 found that hospitalization duration greater or equal to 8 days and young or advanced age were risk factors for colic in horses hospitalized for ocular disease. Our study did not appreciate significantly higher colic rates with increasing hospitalization duration. This may be an effect of our smaller study population or related to differences in patient treatments as Patipa et al5 included patients treated for any ocular disease. Scherrer et al6 identified general anesthesia in equine ocular patients as a risk factor for colic. Penetrating keratoplasty has also been associated with longer anesthesia times and the occurrence of colic.12 The present study did not find a statistically significant difference in the occurrence of colic between individual treatment types; however, there was a significantly higher risk of colic in postoperative general anesthesia cases compared to medically treated and preoperative cases combined. General anesthesia has long been recognized as a risk factor for colic; therefore, this finding is not unexpected and reflects an inherent anesthetic risk not specific to keratomycosis cases.711 However, in this study, systemic signs in all colic cases were relatively mild. None of the patients experiencing colic required surgical intervention, and all were resolved with enteric and/or intravenous fluids and supportive care.

Previous reports6,18 have associated systemic NSAID administration with an increased risk of colic in patients with ocular and orthopedic disease. Systemic NSAID administration was also common practice in this study population, with 120/125 (96%) of cases receiving an oral NSAID during hospitalization at NCSU CVM. A previous study6 reported a 98% increase in odds of developing colic with every 1-mg/kg increase in daily NSAID dose. At this institution, the baseline dosage of flunixin meglumine was 0.25 mg/kg every 12 hours, whereas at NCSU CVM the baseline dosage is commonly 1.1 mg/kg every 12 to 24 hours. The standard NCSU CVM dose is at or double the label dosage for flunixin meglumine.24 Given that nearly all patients were treated with oral NSAIDs, it was not possible to determine whether a higher rate of colic was related to NSAID use. Serum biochemical derangements due to oral NSAID use, ie, hypercreatininemia and hypoalbuminemia, were found in all treatment groups although, for the most part, these changes were subclinical. The frequency of diarrhea was overall low in this study with 2 patients in the medical group and 2 patients in the keratectomy with conjunctival graft group developing clinical diarrhea. A definitive diagnosis of acute kidney injury was not reported. Despite a high-dosing frequency of oral NSAIDs at our institution, severe complications were uncommon as patients had baseline and serial bloodwork performed every 2 to 3 days while in the hospital to monitor for biochemical abnormalities as markers for potential clinical disease.

Topical atropine use has been anecdotally implicated as a cause of colic in patients treated for ocular disease. Topical atropine is essential to treating keratomycosis as it relieves ocular pain, reduces synechiae formation, and stabilizes the blood-ocular barrier.25,26 Scherrer et al did not report an association between topical atropine use and colic in a clinical setting.6 Topical atropine administration was nearly ubiquitous in our study population (123/126 eyes [97.6%]). While atropine dosing intervals were variable throughout an individual patient’s hospitalization period and therefore not recorded, it is standard practice for the NCSU CVM to prescribe topical atropine every 12 to 24 hours, with a maximum dosing interval of every 8 hours. The systemic effect of atropine appears frequency dependent; previous publications19,2729 have found that dosing topical atropine at every 1- to 3-h dosing frequency is related to reduced intestinal motility and colic while every 6-h dosing is well tolerated. Therefore, it is unlikely that topical atropine administration significantly impacted colic outcomes in our patient population.

Longer durations of anesthesia have been previously reported to be associated with higher complication rates in equine ophthalmic patients. Longer anesthetic time has also been associated with fever and facial neuropathy.12 There were 4 instances of patients with postoperative fevers in our study population. One was likely associated with phlebitis and another horse also experienced colic postoperatively. Three patients experienced postanesthesia facial nerve paralysis, although 2 of them had anesthesia durations close to the median and only 1 was prolonged with 290 minutes under general anesthesia. Our study found that longer anesthesia time was not related to statistically higher postoperative systemic complication rates or increased risk of postsurgical colic. However, our case numbers may have been too low to identify significant associations between anesthesia time and complication rates. Administration of oral fluconazole has been associated with prolonged recovery rates in equine patients.12,30 Following the Krein et al30 publication in 2014, the rate of fluconazole administration before a general anesthetic event at our institution was reduced from 26/38 patients (68.4%; 2004 to 2013) to 3/11 patients (27.3%; 2014 to 2020). Recovery times and association with fluconazole administration were not evaluated in this study.

The median time to surgery following the initial examination was 2 days. This was not surprising as it is our clinical impression that after starting aggressive medical therapy, most patients will respond and show improvement in clinical signs. However, around the 48-hour mark, cases that require surgery start to decline. It has also been our clinical impression that cases treated medically for a prolonged period in the hospital before surgery resulted in higher systemic complications. On the contrary, delaying the time from presentation to surgery by more than 2 days to first institute medical therapy did not result in a statistically significant difference in postoperative complication outcomes overall. The lack of significance may be a consequence of a small sample size or low frequency of complications reported overall. Moreover, choosing 2 days as a criterion variable may not have captured the clinical situation and 8 days should have been chosen as previously described.5

The most common ocular complications were assessed individually in each treatment group and varied depending on whether a conjunctival graft and/or donor graft was placed. Conjunctival graft dehiscence was the most common ocular complication in patients who underwent conjunctival grafting procedures. Royce et al31 reported conjunctival graft dehiscence in 6/25 (24%) of equine patients surgically treated for infective corneal diseases. In our study, the frequency of conjunctival graft dehiscence was higher for the few superficial keratectomy cases that received conjunctival grafts while under standing sedation (2/4 eyes [50%]) compared to keratectomy surgeries performed under general anesthesia (17/61 eyes [27.9%]), although low sample numbers precluded meaningful statistical comparison. This may reflect surgical challenges in using magnifying loupes with lower magnification in the sedated patient compared to higher magnification achieved using the operating microscope for patients under general anesthesia. Movement of the patient’s head and/or eye can also complicate conjunctival grafting procedures in sedated patients. Out of the 19 cases with recorded conjunctival graft dehiscence, 15 cases (78.7%) had a good clinical outcome with 10 cases not requiring additional action, 4 cases requiring repair of the conjunctival graft under standing sedation, and 1 case receiving a third eyelid flap under standing sedation. One case had a second conjunctival graft placed under general anesthesia and then was subsequently enucleated due to dehiscence, and 3 additional cases resulted in enucleation. The exact causes of conjunctival graft dehiscence in these cases are unknown, but reported causes include insufficient water-tight seal resulting in aqueous humor leakage or corneal reperforation, loss of graft vascularization and tissue viability, and bacterial and fungal infection resulting in corneal malacia.20

The reported frequency of donor graft reaction was low in the penetrating keratoplasty group (3/21 [14.5%]), with all cases responding to medical management and having positive outcomes. In human medicine, an immune response to the corneal donor graft resulting in neovascularization is considered a graft reaction and is undesirable as the aim is clear and functional vision through the donor cornea.32 However, the goal of penetrating keratoplasty in equids is to create a water-tight seal and provide tectonic support to the cornea. Thus, neovascularization of the donor cornea, whether it be harvested equine cornea or acellular xenograft, is an expected and acceptable outcome. Neovascularization of the donor graft results in swelling of the donor graft around 5 to 10 days after penetrating keratoplasty and, in most instances, does not cause any significant ocular discomfort or progressed ocular changes.33 However, a substantial immune response to the donor graft resulting in an acute onset of severe ocular pain, worsening postoperative uveitis, swelling underneath the conjunctival graft, and/or significantly progressed corneal edema around the conjunctival graft occurred in 3 cases in the present study. The cause of donor graft reaction was not elucidated in this study. Interestingly, the 2 cases that received acellular xenografts in this study experienced donor graft reactions. It is possible that the graft reactions associated with acellular xenografts were a result of microleakage of the graft and associated worsening uveitis and edema, or immune-mediated reaction to the graft. Compared to an acellular xenograft, donor equine cornea would be expected to have a higher risk of immune-mediated graft reaction but provide better tectonic support through a water-tight seal for full-thickness grafting. Our sample size of 21 penetrating keratoplasty cases was too small to detect statistical differences in complication rates between ACell Vet and donor equine cornea grafts.

The recurrence of fungal infection appeared higher in the superficial keratectomy group (24%) compared to keratectomy with conjunctival graft (5%) and penetrating keratoplasty (9.5%) surgery groups, although this finding was not statistically significant. All infected tissue may not have been removed in cases that underwent a superficial keratectomy as only the superficial stroma is excised. More widespread use of preoperative high-frequency ultrasound biomicroscopy may improve surgical outcomes by allowing a more accurate estimate of lesion depth compared to slit-lamp biomicroscopy.34 The vascular conjunctival graft may, additionally, provide immune cells to remove the residual fungus.33 In 2 cases, recurrent fungal infection was not confirmed on histopathology following globe enucleation; however, the clinicians’ description was consistent with fungal infection and resulted in the recommendation for enucleation. Secondary bacterial infection was also reported at a higher frequency in the superficial keratectomy group (16%) than in the keratectomy with conjunctival graft group (2.5%). Exposed corneal stromal postoperatively in the superficial keratectomy group may result in an increased risk of bacterial invasion.

There was a low rate (n = 3; 2.4%) of SPL-related complications reported in this study. All 3 cases experienced superior eyelid cellulitis and had their SPL replaced in the inferior eyelid. A large retrospective study21 evaluating complications associated with dorsally placed SPLs reported superior eyelid cellulitis or abscessation in 5.5% of cases. This study also noted a much higher frequency of ocular (21.2%) and nonocular (7.9%) complications than the present study, with the most common complications being corneal ulcers and accidental SPL removal by the horse. Minor complications such as skin suture replacement and tangled SPL tubing were included.21 A separate case series35 of 8 horses with stromal abscesses treated with penetrating keratoplasty reported SPL-related complications in 2 horses. The low SPL complication rate in the current study is likely due to the underreporting of minor complications. In our clinical experience, skin suture replacement is required in most patients during their 6- to 8-week treatment course. Other minor complications that do not have significant associated ocular complications, such as breakage of the SPL line, are not uncommon.

The NCSU CVM preferentially prescribed topical fluoroquinolones and voriconazole to treat keratomycosis. Topical antifungal and antibiotic selection differ based on the presence or absence of a corneal ulcer, lesion depth, cytology and culture results, geography, clinician preferences, placement of an SPL, and cost and availability of medications. Solution or suspension is preferably used to allow for administration via SPL, which ensures patient compliance and allows for frequent administration required for a successful outcome. Additional antifungal treatments were pursued in a limited number of cases including intrastromal injection of voriconazole and subconjunctival injection of amphotericin B (Supplementary Table S1). Oral fluconazole was administered in a high proportion of cases. While previous studies3639 have shown that Aspergillus and Fusarium species have limited to no susceptibility to fluconazole in vitro, oral therapy may be helpful in cases with susceptible fungal species and where additional penetration into the aqueous humor is warranted. Due to prolonged general anesthesia recovery rates, oral fluconazole is mainly administered postoperatively.12,30

Topical atropine and oral NSAIDs were frequently prescribed by NCSU CVM. These medications were also widely prescribed in previous reports. In a study40 from the University of Florida, topical atropine was prescribed 94.1% of patients and oral NSAIDs to 100% of patients. University of California-Davis reported39 topical atropine prescription in 68% of cases and oral NSAID in 100% of cases. These data highlight the importance of pain control and anti-inflammatory therapy in the treatment of keratomycosis cases. Gastroprotectant medications were also frequently prescribed in the University of Florida study40 (omeprazole, 88.2%; ranitidine, 2%) and the current study (omeprazole, 59.2%; ranitidine, 24.8%). Given the frequency of gastrointestinal complications observed in the current study, prophylactic gastroprotectant medications are advised especially in patients treated with oral NSAIDs.

The main limitations of this study are related to its retrospective design. Complete records were not available in all cases and the study relied on clinician descriptions of systemic and ocular complications. Clinical records were not consistently detailed enough to report on more specific posttreatment ocular complications. It was not possible to correlate specific medical therapies to systemic and ocular complications as medications and treatment frequencies were not standardized between patients or within treatment groups. Posttreatment bacterial and fungal cultures were infrequently performed to confirm treatment efficacy. Recurrent fungal and bacterial infections were based on confirmation by culture, cytology, and histopathology except in 2 previously mentioned cases. Further investigation into factors relating to the types of colic associated with hospitalization for ocular disease is warranted; however, it was not possible in this study due to the lack of in-depth descriptions of the colic episodes.

Hospitalization and surgical treatment of keratomycosis in equine patients is associated with similar rates of systemic and ocular complications. Similar environmental stressors exist for patients hospitalized for keratomycosis treatment, and medical therapies tend to be similar across treatment types. The most common individual systemic and ocular complications did not vary in frequency between treatment groups. Increased anesthesia time was not associated with a higher postoperative systemic complication frequency nor was increased duration of hospitalization associated with increased systemic complications including colic. Delaying the time from initial presentation to surgery by more than 2 days did not affect systemic or ocular complication outcomes. While colic was more common following general anesthesia procedures compared to presurgery and medically treated cases combined, the overall colic frequency was comparable to previous studies. These results highlight that appropriate therapy based on exam finding should be recommended to owners with the goal of achieving a positive clinical outcome rather than avoiding surgical treatments based on perceived risk, as long as patient comorbidities are also taken into account when considering procedures performed under heavy sedation or general anesthesia. Monitoring hospitalized patients for both systemic and ocular complications associated with treatment is critical for success. The authors would recommend serial bloodwork for equine patients being managed on high doses of NSAIDs to reduce the likelihood of systemic complications.

Supplementary Materials

Supplementary materials are posted online at the journal website: avmajournals.avma.org.

Acknowledgments

The authors thank Valerie Ball Basham for her assistance with medical record acquisition and organization.

Disclosures

Dr. Gilger served as Guest Editor for this JAVMA Supplemental Issue. He declares that he had no role in the editorial direction of this manuscript. The other authors have declared no conflicting interests.

No AI-assisted technologies were used in the generation of this manuscript.

Funding

The authors have no funding sources to disclose.

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