A retrospective comparison of surgical removal and subsequent CO2 laser ablation versus topical administration of mitomycin C as therapy for equine corneolimbal squamous cell carcinoma

Objective To compare the complications and nonrecurrence rate following topical mitomycin C (MMC) therapy vs. CO₂ laser ablation for treating equine corneolimbal squamous cell carcinoma (SCC). Study design Retrospective study. Sample population Twenty‐five horses with corneolimbal SCC. Procedures Medical records of horses undergoing surgical tumor resection followed by either topical MMC therapy (0.04%) or CO₂ laser ablation between the years of 2004 and 2010 were reviewed. Recurrence and complications were compared between groups and within MMC subgroups defined by the time at which treatment was initiated relative to surgery. Results Therapy with topical MMC resulted in a nonrecurrence rate comparable to that achieved with CO₂ laser ablation (82.4% vs. 85.7%, respectively). Initiation of MMC following epithelialization of the surgical site a mean of 15 days postoperatively did not result in increased recurrence rates relative to treatment in the immediate postoperative period. Vision‐ or globe‐threatening complications tended to occur with greater frequency in horses receiving topical MMC in the immediate postoperative period (5 of 6 major complications) relative to following epithelialization of the surgical site (1 of 6 major complications). Conclusions Horses receiving adjunctive topical MMC therapy were no more likely to experience tumor recurrence than were horses undergoing CO₂ laser ablation in the horses in this study. Initiation of two to three rounds of MMC following epithelialization of the surgical site results in fewer major complications and achieves comparable disease resolution relative to treatment in the immediate postoperative period.     

The use of mitomycin C as an adjunctive treatment for equine ocular squamous cell carcinoma

OBJECTIVE: To assess the effectiveness of topical mitomycin C application as an alternative adjunctive therapy to CO2 laser ablation in the treatment of equine ocular squamous cell carcinoma. DESIGN: A retrospective clinical study of eight client owned horses in which 10 affected eyes were treated for ocular squamous cell carcinoma over a 17 month period. (March 2003 to August 2004). PROCEDURE: Each horse was given a general anaesthetic to allow CO2 laser ablation of the lesion(s). Mitomycin C at a concentration of 0.4 mg/mL was then applied intraoperatively to the affected areas for 1 or 5 minutes. Postoperatively a triple antibiotic eye ointment was applied to the eye twice daily and each horse was treated with systemic non-steroidal anti-inflammatory drugs for 7 days. RESULTS: Recurrence following treatment was noted in three eyes. Two of these were retreated and no further signs developed. The remaining eye was enucleated at the request of the owner. Overall 90% of treated eyes appeared free of tumour a minimum of 11 months post treatment. CONCLUSION: In this case series mitomycin C appeared to offer a valid alternative to other adjunctive therapies currently employed in the treatment of equine ocular squamous cell carcinoma.     

Superficial keratectomy and topical mitomycin C as therapy for a corneal squamous cell carcinoma in a dog

A 10-year-old female West Highland white terrier was presented with refractory hyperplastic keratitis of the left cornea of one month's duration. At this time, a vascularised and rough lesion 5 mm in diameter was observed on the left cornea. No other abnormality was recognised on the affected eye. The corneal neoplasm was surgically removed and histologically diagnosed as a squamous cell carcinoma. For two months after the surgery, 0.04 percent mitomycin C (MMC) eye drops were applied as adjuvant chemotherapy. Primary corneal squamous cell carcinoma with no history of keratoconjunctivitis sicca is rare in dogs. In the present report, surgical removal of the neoplasm was combined with the topical administration of the anticancer drug mitomycin C and a good prognosis was obtained. The result indicates that the combination treatment used in this case may be an appropriate therapeutic choice for corneal squamous cell carcinoma in dogs.     

Topical 5-fluorouracil as an adjunct treatment in equine corneolimbal squamous cell carcinoma

An 11-year-old crossbreed mare was presented with a nodular, pink mass at the temporal corneolimbal junction of the right eye. Histopathology confirmed the diagnosis of invasive squamous cell carcinoma. The mare underwent lamellar keratectomy and conjunctivectomy under general anaesthesia, followed by adjunctive topical chemotherapy with 1% 5-fluorouracil solution for 10 days post-operatively. Adverse effects included moderate conjunctival inflammation and exuberant granulation tissue formation at the surgical site, responding to surgical debulking and topical corticosteroid application. No mass regrowth was present at 12 months following discharge. This report describes the successful use of topical 1% 5-FU as an adjunctive treatment for equine ocular squamous cell carcinoma.     

Aqueous humor and plasma concentrations of a compounded 0.2% solution of terbinafine following topical ocular administration to normal equine eyes

Objective To determine the transcorneal penetration and systemic absorption of a compounded 0.2% terbinafine solution following repeated topical administration to normal equine eyes. Sample population Six healthy adult horses with normal ocular examinations. Procedures One eye of each horse received 0.2 mL of a compounded 0.2% terbinafine solution every 4 h for seven doses. During the 1 h following administration of the final dose, multiple peripheral blood samples were obtained, and a single aqueous humor (AH) sample was collected at the end of the hour. AH and plasma concentrations of terbinafine were determined using high pressure liquid chromatography (HPLC). Stability of the formulation was assessed with HPLC analysis over a 14‐day time period. Results Terbinafine was not detected in the AH or plasma of any horse at any time point. No signs of ocular irritation or systemic toxicity were noted in any horse at any time point. The solution was stable over 14 days. Conclusion Topical ocular administration of compounded 0.2% terbinafine solution does not result in detectable AH or plasma levels following administration to normal equine eyes, suggesting its use for deep corneal or intraocular fungal infections in equine ophthalmology may be limited.     

Phase I Clinical Trial and Pharmacokinetics of Intravesical Mitomycin C in Dogs with Localized Transitional Cell Carcinoma of the Urinary Bladder

Background: Transitional cell carcinoma (TCC) is the most common cancer of the urinary tract in dogs. The most frequent cause of death is urinary obstruction from the primary tumor. Standard medical therapy for TCC is only partially effective. Hypothesis/Objectives: Intravesical administration of mitomycin C (MMC) in dogs with invasive TCC will result in antitumor activity against the primary tumor and minimal systemic drug absorption. Animals: Thirteen privately owned dogs with naturally occurring, histopathologically diagnosed TCC of the urinary bladder. Methods: A prospective phase I trial was performed. MMC was given intravesically (600 μg/mL initial concentration) for 1 h/d for 2 consecutive days each month. The MMC concentration was escalated to a maximum of 800 μg/mL in groups of 3 dogs until the maximum tolerated dose (MTD) was determined. Serum assays for MMC were performed to determine the extent of systemic absorption of the MMC. Results: The MTD of MMC based on local toxicoses was 700 μg/mL (1‐h dwell time, 2 consecutive days). In addition, 2 dogs had severe myelosuppression and appeared to have systemic absorption of MMC. Five dogs had partial remission, and 7 dogs had stable disease. Conclusions: Intravesical MMC has antitumor activity in dogs with invasive TCC. Further study is needed to determine the cause of the myelosuppression associated with MMC administration, and to develop strategies to minimize this risk.     

Effect of topical 1% atropine sulfate on intraocular pressure in normal horses

OBJECTIVE: To determine the effect of topical 1% ophthalmic atropine sulfate on intraocular pressure (IOP) in ocular normotensive horses. Animals Studied Eleven clinically healthy horses. Procedures IOP was measured bilaterally twice daily, at 8 AM and 4 PM, for 5 days. No medication was applied for the first 2 days of the study. Thereafter, one eye of each horse was treated with 0.1 mL of topical 1% atropine sulfate ointment twice daily (7 AM and 7 PM) for 3 days. The contralateral eye served as a control. In eight of the horses, an additional IOP reading was taken 3 days following cessation of the atropine treatment. RESULTS: There was no significant difference in the IOP of control vs. treatment eyes in the pretreatment period, days 1 and 2 (P = 0.97 and 0.55, respectively). During the treatment period, treated eyes of 10 of the horses had significantly lower IOP than control eyes (P = 0.03). The mean IOP reduction in treated eyes, relative to untreated eyes, was 11.2%. One horse had a significant rise in IOP in the treated eye compared to the remaining study animals. The IOP of control eyes did not vary significantly over the observation period (P = 0.27). There was no significant variation in IOP between the 8 AM and 4 PM measurement (P = 0.9). CONCLUSIONS: Topical 1% atropine sulfate causes a small, but significant decline in IOP in most ocular normotensive horses. Because topical atropine may elevate IOP in some horses, it should be used with caution in the treatment of glaucoma in this species.     

Effects of 0.005% latanoprost solution on intraocular pressure in healthy dogs and cats

OBJECTIVE: To evaluate effects of daily topical ocular administration of latanoprost solution on intraocular pressure (IOP) in healthy cats and dogs. ANIMALS: 9 domestic shorthair cats and 14 dogs. PROCEDURE: Latanoprost solution (0.005%) was administered topically to 1 eye (treated) and vehicle to the other eye (control) of all animals once daily in the morning for 8 days. Intraocular pressure was measured twice daily for the 5 days preceding treatment, and IOP, pupillary diameter, conjunctival hyperemia, and blepharospasm were measured 0, 1, 6, and 12 hours after the first 4 treatments and 0 and 12 hours after the final 4 treatments. Measurements continued twice a day for 5 days after treatment was discontinued. Aqueous flare was measured once daily during and for 5 days after the treatment period. RESULTS: Intraocular pressure and pupillary diameter were significantly decreased in the treated eye of dogs, compared with the control eye. Mild conjunctival hyperemia was also detected, but severity did not differ significantly between eyes. Blepharospasm and aqueous flare were not detected in either eye. Intraocular pressure in cats was not significantly affected by treatment with latanoprost. However, pupillary diameter was significantly decreased in the treated eye, compared with the control eye. Conjunctival hyperemia, aqueous flare, and blepharospasm were not detected in either eye. CONCLUSIONS AND CLINICAL RELEVANCE: Once-daily topical ocular administration of latanoprost solution (0.005%) reduced IOP in healthy dogs without inducing adverse effects but did not affect IOP in healthy cats. Latanoprost may be useful for treating glaucoma in dogs.     

Normal structure and age-related changes of the equine retina

Investigations of the pathophysiology of ocular diseases require a detailed knowledge of the microanatomy of the eye. The available information is still inadequate for the equine retina despite the importance of eye diseases in equine medicine. Here we provide a comprehensive analysis of the histologic features of the horse eye as a reference for future studies. Thirty normal eyes of 15 healthy horses were examined immediately after slaughter. The retina of the horse differs considerably in the degree and quantity of neurons and glial elements as well as in vascular patterns compared to the retina of other domestic animals. Morphometric analysis revealed that the thickness of the retina varies between 80 microm at the ora serrata and 250 microm medial to the optic disc. Approximately 90% of the equine retina is comparatively thin (< 130 microm). This is a physiologic response to the distance that oxygen can diffuse in avascular retina. Ganglion cells form a single layer in all parts of the retina. The majority of ganglion cells are very large Nissl-positive cells. Small Nissl-negative ganglion cells are less abundant. A high ganglion cell density is found only in the central area. Vascularization is virtually absent from the retina with the exception of a narrow strip around the disc of the optic nerve, as revealed by lectin histochemistry. Light microscopy of the eyes of older horses repeatedly revealed cystoid degenerations in the retina adjacent to the pars plana of the ciliary body, as well as a destruction of the regular layering of the peripheral region of the retina.     

Aspergillus spp. panophthalmitis with intralenticular invasion in dogs: report of two cases

This case series describes the ocular, clinical and histologic manifestations of disseminated Aspergillosis in two dogs. Two dogs presented for severe unilateral panophthalmitis and secondary glaucoma with positive Aspergillus spp. titers. Case 1 showed no clinicopathologic systemic symptoms of fungal dissemination, however, case 2 was affected with acute renal failure. The affected eye of case 1 did not respond to medical therapy and was enucleated for comfort. The affected eye of case 2 responded to aggressive topical and systemic medical therapies, however, the patient was euthanized for acute renal failure. Globes were collected for histologic evaluation at the time of death. Histology of both revealed panophthalmitis with presence of significant intraocular hemorrhage, multifocal fungal granulomas, retinal and optic nerve changes consistent with secondary glaucoma, rupture of the anterior lens capsule, and fungal invasion and colonization of the intralenticular space. These cases represent a unique and devastating ocular manifestation of disseminated Aspergillosis. Cases presenting with uveitis and secondary glaucoma of unknown origin, especially with confirmed or suspected lens capsular rupture, should have serologic testing for this infectious agent.     

Efficacy of topically applied liposome-bound tetracycline in the treatment of dry eye model

Objective To evaluate the effects of liposome‐bound tetracycline eye drops in a rabbit dry eye model evaluating their advantage of being less allergic, preservative free and prolonged action compared with other tear substitutes. Procedures New Zealand albino rabbits were equally divided into control group and dry eye induced groups. Dryness was induced in 24 eyes of 12 healthy adult male albino rabbits by instilling atropine sulfate eye drops 1% three times daily for 1 week, then animals were subdivided into four groups; group 1 (rabbits with dry eye model), groups 2, 3, and 4: rabbits with dry eye model treated for 7 days starting on 7th day of dryness induction with either tetracycline, empty liposome, or combined tetracycline with liposome as topical eye drops respectively. Schirmer (STT) test and tear break up time (TBUT) were assessed on days 0, 2, 4, 7, 9, 11, and 14. Animals were sacrificed on day 14 and histopathological examination of the cornea and conjunctiva was performed. Results Tear break up time and STT test values were significantly improved in groups 2, 3, 4 as compared with group 1. The histopathological examination showed normal cytoarchitecture of corneas and conjunctivae in groups 2, 3, 4 against the dryness effect that continued to affect the cornea and conjunctival epithelium in group 1. There was a significant improvement in the group treated with liposome‐bound tetracycline eye drops (group 4) as compared with tetracycline alone (group 2) and empty liposome (group 3). Conclusion The use of liposome encapsulated tetracycline significantly improved STT and TBUT values as well as reverse surface ocular pathology.     

Effects of topical administration of 1% brinzolamide on intraocular pressure in clinically normal horses

Reasons for performing study: Only few drugs with limited efficacy are available for topical treatment of equine glaucoma. Objective: To evaluate the effect of topical administration of 1% brinzolamide on intraocular pressure (IOP) in clinically normal horses. Methods: Healthy mature horses (n = 20) with normal ocular findings, were studied. The IOP was measured 5 times daily (07.00, 11.00, 15.00, 19.00 and 23.00 h) over 10 days. On Days 1 and 2, baseline values were established. On Days 3–5 one eye of each horse was treated with one drop of 1% brinzolamide every 24 h immediately following the 07.00 h measurement. On Days 6–8 the same eye was treated with 1% brinzolamide every 12 h (07.00 and 19.00 h). Measurements on Days 9 and 10 documented the return of IOP to baseline values. Statistical analysis of the data was performed. Results: In the treated eye a significant decrease in IOP compared to baseline values was noted during both the 24 and 12 h dosing periods (P<0.001). During the once‐daily treatment protocol an IOP reduction of 3.1 ±1.3 mmHg (14%) from baseline was recorded. During the twice‐daily protocol a total IOP reduction of 5.0 ± 1.5 mmHg (21%) was achieved. Conclusion: Intraocular pressure was significantly decreased by 1% brinzolamide in a once‐daily and a twice‐daily treatment protocol in normotensive eyes. These findings suggest that brinzolamide might also be effective in horses with an elevated IOP. Potential relevance: This drug may be useful for treatment of equine glaucoma.     

Ocular effects of topical 0.03% bimatoprost solution in normotensive feline eyes

OBJECTIVE: The current study was undertaken to evaluate the effects of topically applied bimatoprost, an ocular hypotensive lipid, on intraocular pressure (IOP) and pupil size (PS) in healthy cats. ANIMAL STUDIED: Nine European Shorthair cats free from clinically relevant ocular abnormalities were used in the study. PROCEDURES: Pretreatment baseline measurements of IOP and PS were obtained bilaterally at 8 am, 2 pm, and 8 pm for five consecutive days (days 1 to 5). Then the cats received one drop twice daily (10 am and 6 pm) of bimatoprost ophthalmic solution 0.03% (Lumigantrade mark, Allergan Inc., Irvine, CA USA), in one randomly selected eye and one drop of artificial tears in the fellow eye (control eye) for 5 days (days 6 to 10). Values for IOP and PS were obtained under the same conditions as in the pretreatment phase. The potential for ocular irritation following bimatoprost application was also evaluated. RESULTS: During the pretreatment period, the mean IOP and mean PS were not significantly different between the eyes subsequently treated with bimatoprost and those subsequently determined as controls. During the treatment period, the mean IOP in bimatoprost-treated eyes was not significantly lower than in control eyes (14.2+/-2.3 vs. 14.5+/-2.8 mmHg). Mean IOP in control eyes was not significantly changed at any time during the study period. A marked reduction of PS was seen in all bimatoprost-treated eyes, but no other clinically relevant side effects were observed. CONCLUSION: Twice daily topical applications of bimatoprost produced miosis but had no significant effect on IOP in healthy cats.     

Successful use of topical mitomycin C for the treatment of a putative neoplastic vascular mass on the nictitating membrane of a dog

A nine-year-old female desexed Great Dane presented with a painful, proliferative, soft red putative neoplastic vascular mass on the nictitating membrane. Three 7-day cycles of the topical cytotoxic drug mitomycin C 0.04%, applied four times daily to the lesion using a low-dose alternate-week pulse therapy, brought about rapid remission of the lesion. The lesion was still in remission at time of euthanasia some 13 months later.     

Computed tomographic dimensions of the normal adult equine eye

There are limited data on whether the dimensions of the equine eye and its internal structures change with bodyweight in horses. The aim of this study was to identify whether the size of the equine eye and its individual structures varied in a predictable manner with bodyweight, and to examine the reliability of computed tomography (CT) scans in the measurement of the equine eye. Ninety horses which had undergone CT examination of the head for non‐ocular disease were included. All measurements of the eye were performed twice on all eyes by the same operator to quantify intra‐operator agreement, and in 10 cases were also performed by a second operator to quantify inter‐operator agreement. Agreement was excellent for all but the rostrocaudal measurement of the anterior chamber, which was fair. The following variables correlated significantly with bodyweight: anterior‐posterior size of the globe (correlation coefficient: 0.586) and posterior segment (correlation coefficient: 0.554); the latero‐medial size of the globe (correlation coefficient: 0.452), anterior chamber (correlation coefficient: 0.504) and posterior segment (correlation coefficient: 0.455); and the orbital fossa diameter (correlation coefficient: 0.219). The lens size and anterior‐posterior distance of the anterior chamber did not correlate significantly with bodyweight. These results suggest that overall eye size and the size of the orbital fossa change with the bodyweight of the horse, but lens size remains consistent, and that CT measurements of the internal structures of the eye are repeatable and reproducible. This information aids in interventional procedures for ocular pathology and assessment of normal anatomy.     

CASE REPORT: Unilateral eyelid lesion and ophthalmologic findings in an aardvark (Orycteropus afer): case report and literature review

Objective To summarize the medical knowledge surrounding aardvarks to date, to describe the ophthalmic examination of a specimen with a chronic history of an upper eyelid lesion, of an assumed blind left eye, and to detail the anesthesia procedure performed. Procedure A 23‐year‐old aardvark was examined under general anesthesia and multiple ocular abnormalities were detected in the left eye (globe deviation, corneal opacities, iridodonesis, and aphakia). A thickening of the palpebral conjunctiva affecting the medial upper eyelid with erosion of the normal eyelid margin anatomy was identified. The adnexal lesion was resected by a wedge resection and histopathology was performed. Suture breakdown 3 days postoperatively required a second surgery, where buried sutures were used. The surgical techniques and postoperative care are discussed. Results The histopathology revealed mucosal hyperplasia and moderate neutrophilic and lymphoplasmacytic blepharitis. No causal organisms were identified. Following initial wound dehiscence and a modified surgical technique, the upper eyelid healed without complication and retained complete function. Conclusions The eyelid lesion involved a benign inflammatory and hyperplastic pathology of unknown etiology. Adjusting routine ophthalmic surgical techniques to wildlife and zoo animals can be challenging and complicated. It is important to understand the nature of the animals being managed, their circadian cycle, and habitat, to adjust and individualize the surgical approach, instrumentation, suture material, and perioperative treatment.     

Concentration profiles and safety of topically applied betulinic acid and NVX‐207 in eight healthy horses—A randomized,blinded, placebo‐controlled,crossover pilot study

The naturally occurring betulinic acid (BA) and its derivative NVX‐207 show anticancer effects against equine malignant melanoma (EMM) cells and a potent permeation in isolated equine skin in vitro. The aim of the study was to determine the in vivo concentration profiles of BA and NVX‐207 in equine skin and assess the compounds’ local and systemic tolerability with the intent of developing a topical therapy against EMM. Eight horses were treated percutaneously in a crossover design with 1% BA, 1% NVX‐207 or a placebo in a respective vehicle twice a day for seven consecutive days with a seven‐day washout period between each formulation. Horses were treated at the neck and underneath the tail. Concentration profiles of the compounds were assessed by high‐performance liquid chromatography in the cervical skin. Clinical and histopathological examinations and blood analyses were performed. Higher concentrations of NVX‐207 were found in the skin compared to BA. Good systemic tolerability and only mild local adverse effects were observed in all three groups. This study substantiates the topical application of BA and NVX‐207 in further clinical trials with horses suffering from EMM; however, penetration and permeation of the compounds may be altered in skin affected by tumors.     

Tissue distribution of dexamethasone in canine ocular compartments following topical application of dexamethasone-21-isonicotinate and oxytetracycline HCl

Objective  To study the dexamethasone (DXM) concentration at different time points in various compartments of the canine eye following topical application of DXM-21-isonicotinate and oxytetracycline hydrochloride
Animals studied  Thirty dogs to be euthanized for reasons not related to this study were selected and their ocular health status evaluated. Selected animals were treated with DXM-oxytetracycline ointment and euthanized after 6, 11 or 16 h.
Procedure  The concentration of DXM was determined in the following compartments of the eye: third eyelid, cornea, aqueous humor, iris, lens, vitreous body and choroid/retina. The DXM concentration in the eye was measured by radioimmunoassay. The applied amount of DXM was 0.04 mg in 0.2 mL ointment. Dogs were treated once with Corti Biciron^® eye ointment (DXM-21-isonicotinate and oxytetracycline hydrochloride, S & K Pharma, Perl, Germany) and were euthanized 6, 11 and 16 h after treatment.
Results  At 6 h following topical application the mean DXM concentration was highest in the anterior structures of the eye (third eyelid: 18 ng/g, cornea: 36 ng/g). The concentration in the posterior structures was below detection level. A decreased DXM concentration in the anterior structures was measured 11 and 16 h after treatment.
Conclusion  It could be demonstrated that therapeutically relevant concentrations of DXM after a single topical administration are only achieved in anterior structures of the eye. A dosing interval of 6–11 h is recommended to achieve therapeutic drug concentration in those structures. The posterior structures of the eye are not reached by topical administration.