The Cryosurgical Treatment of Pigmentary Keratitis in Dogs An Experimental and Clinical Study

Forty normal dogs were exposed to double freezes of a 1 cm diameter area of their central corneas using a liquid nitrogen spray. Postoperative sequelae and final histopathologic results were evaluated. All eyes suffered epithelial damage and developed corneal edema, but dogs followed for 3 weeks returned to a normal or near normal condition. Nine clinical cases of pigmentary keratitis were subsequently treated by cryosurgery. The complications following this technique were similar to those seen in the experimental dogs. Reduction in corneal pigmentation and improvement of vision occurred in all cases.     

Surgical repair of deep melting ulcers with porcine small intestinal submucosa (SIS) graft in dogs and cats

PURPOSE: To evaluate the efficacy of using a porcine small intestinal submucosa (SIS) graft for the surgical repair of deep melting ulcers in dogs and cats. METHODS: Two cats and five dogs presented with deep and large melting ulcers of the cornea. In each case, the necrotic and collagenolytic tissue of the cornea was removed by keratectomy. A SIS graft, 1 mm greater than the corneal defect, was rehydrated in sterile saline and sutured to the edges of the ulcer with a simple interrupted pattern of 9/0 polyglactin 910. A nictitating membrane flap was utilized in two cats and four dogs for 2 weeks. All cases were treated postoperatively with topical and systemic antibiotics, a systemic anti-inflammatory drug and topical atropine. All animals were re-evaluated 15 days, 4 weeks, 35-45 days, 2-3 months and 6 months postsurgery. RESULTS: At 15 days postsurgery, a superficial intense corneal neovascularization surrounded the SIS graft. No ocular discomfort was present and fluorescein staining was negative in all cases. At 4 weeks the SIS graft was thick and opaque in all cases, although in one cat the SIS graft had partially detached. Between 35 and 45 days, SIS graft integration was evident in all eyes, and corneal neovascularization had decreased progressively. All eyes healed without complications and retained corneal transparency. This occurred even in the presence of corneal perforation in two cases: one prior to and one during surgery. CONCLUSION: Results of our study suggest the SIS graft may be an effective alternative surgical treatment to the traditional conjunctival grafts commonly used to repair melting ulcers in dogs and cats. The advantages of using a SIS graft include good corneal transparency, preservation of corneal integrity and maintenance of vision.     

Radiotherapy for canine chronic superficial keratitis using soft X-rays (15 kV)

Objective  To evaluate the effect of soft X-ray therapy in the treatment of refractory chronic superficial keratitis (CSK).
Animals studied  Thirteen dogs with severe CSK, that had been refractory to prior medical and/or surgical therapy were treated with soft X-ray therapy.
Procedures  Both corneas of each dog were irradiated with soft X-rays (15 kV), to a total dose of 30 Gy, administered as two fractions over 48–96 h. Treatment was carried out under deep sedation in all dogs. Three dogs were treated by superficial lamellar keratectomy 48 h prior to radiotherapy. Changes in the extent of corneal pigmentation, pigment density and corneal vascularization were documented using a semi-quantitative grading scheme, schematic drawings and clinical photographs.
Results  Only minor, transient adverse effects of treatment, such as photophobia, epiphora and blepharitis were noted. Overall the effect of soft X-rays on the course of the keratitis was superior when compared to the effect of Sr-90 irradiation that had been determined in a previous study.
Conclusion  Soft X-ray irradiation combined with keratectomy is a safe and effective new treatment option for severe and advanced CSK with significant visual impairment due to corneal pathology.     

The use of xenologous amniotic membrane to repair canine corneal perforation created by penetrating keratectomy

This study was performed to evaluate the use of glycerol-preserved equine amniotic membrane as replacement for full-thickness corneal defects in dogs. Eighteen mixed-breed dogs were used. A perilimbal, full-thickness, 5 mm square corneal defect was created surgically, and a donor implant of equine amniotic membrane of the same size and shape sutured in place with 10–0 nylon simple interrupted sutures. Corneal edema was observed near the implant 24 h after surgery, but was absent after 1 week. Granulation tissue and corneal vascularization superficial to the implant were noticed on postoperative day 7, but were absent on day 30. Corneal vascularization persisted until the end of the experiment. There was no fluorescein retention by postoperative day 30. There was slight clearing of the corneal implant by postoperative 30, and slight pigmentation of the donor implant observed at postoperative day 180. An acute inflammatory process as well as fibroblasts were present at early postoperative stages. At postoperative day 60 there was no inflammatory cellular infiltrate, but fibroblasts and fibrosis were present. Corneal architecture was restored at the end of the experiment, with a layering of the epithelium–stroma–debris of amniotic membrane–stroma–endothelium present, and pigmentation and vascularization present in the deep layers of the cornea. Although vascularization indicated some degree of graft rejection, the clinical and histological evidence indicates that the xenologous amniotic membrane can be useful as a tectonic graft in the repair of full-thickness lesions of the cornea of dogs.     

Microsporidial keratopathy in two dogs

A microsporidial keratopathy is described in two dogs. Both dogs presented with a unilateral stromal keratopathy characterized by multifocal coalescing opacities, and the diagnosis was made on histopathologic examination of keratectomy specimens. Transmission electron microscopy (TEM) on formalin‐fixed, paraffin‐embedded corneal tissue was performed in one dog, and the morphologic features were consistent with Nosema species infection. Both dogs were initially diagnosed and treated by superficial keratectomy. One dog received additional antifungal medication and underwent a penetrating keratoplasty following local recurrence two years later. No other systemic lesions attributable to the microsporidial infection were identified clinically. The clinical and diagnostic pathology findings, treatment, and follow‐up are discussed.     

Treatment of corneal squamous cell carcinoma using topical 1% 5‐fluorouracil as monotherapy

The purpose of this report is to discuss the use of topical 1% 5‐fluorouracil as a sole therapy for canine corneal squamous cell carcinoma (SCC). A 12‐year‐old castrated male pug was evaluated for a well‐demarcated, central, 3 mm in diameter, pale pink, raised, right corneal mass. An incisional biopsy was obtained using a #64 beaver blade after topical anesthesia and without sedation. A definitive diagnosis of corneal SCC was obtained after histopathologic evaluation of the biopsy. Topical 1% 5‐fluorouracil ointment was applied to the right eye four times daily for 2 weeks followed by no treatment for 2 weeks, then treatment again twice daily for 2 weeks. The cornea remained free of recurrence 10 months after cessation of treatment. In dogs affected with corneal SCC, topical 1% 5‐fluorouracil monotherapy may be a viable and cost‐effective treatment option with minimal side effects. This chemotherapy agent may also have an effect on corneal pigmentation. Chronic cyclosporine therapy did not contribute to the pathogenesis of corneal SCC in the case described.     

Cyanoacrylate tissue adhesive for treatment of refractory corneal ulceration

Isobutyl cyanoacrylate tissue adhesive (BCTA) was used in the treatment of refractory superficial corneal ulcers in 17 dogs, one cat, and one rabbit, present 2 weeks to 7 months (mean 6.8 weeks +/- 6.1) prior to referral. Little to no sedation was required in the majority of cases, with only topical anesthetic applied prior to debridement and BCTA application. The presence of the tissue adhesive caused mild discomfort for several days after application, as reported by the owners. The ulcers healed, and the tissue adhesive sloughed in approximately 3 weeks (+/- 1 week). Mild neovascularization of the cornea resolved with topical corticosteroids. The use of BCTA offers a simple, safe and noninvasive treatment for refractory corneal ulcers.     

Use of porcine small intestinal submucosa for corneal reconstruction in dogs and cats: 106 cases

Objectives : To describe the efficacy of porcine small intestinal submucosa in corneal reconstructive surgery in dogs and cats through a large retrospective study. Methods : A retrospective evaluation of 106 cases of surgical reconstruction of the cornea with small intestinal submucosa seen between May 2005 and January 2010 was carried out. The corneal defect was filled by microsurgical grafting of porcine small intestinal submucosa. The biomaterial implant was deposited in one or several layers depending on the depth of the defect. The animals were examined 3, 6 and 12 weeks after surgery. Results : Vision was preserved in all eyes at three months post‐surgery. In 74 cases (69.8%) the corneal scar was either transparent or discrete, whilst in 32 cases (30.2%) a mild or marked scar was observed. Minor complications occurred in 9 cases (8.5%) with partial integration of the small intestinal submucosa and in 24 cases (22.6%) with faint or mild corneal pigmentation, without impairing vision. In cases followed over a period longer than three months, major complications occurred in five dogs resulting in vision impairment because of pronounced pigmentation. Clinical Significance : Corneal grafting of porcine small intestinal submucosa is an effective method for corneal reconstruction resulting in corneal transparency in most cases. It is an excellent alternative to conventional conjunctival grafts.     

Use of capecitabine to prevent acute renal allograft rejection in dog erythrocyte antigen-mismatched mongrel dogs

OBJECTIVE: To assess efficacy and toxicity of a capecitabine (CAP)-based regimen for preventing rejection of renal allografts in dog erythrocyte antigen (DEA)-mismatched mongrel dogs. STUDY DESIGN: Prospective, pilot study. ANIMALS: Eight healthy, unrelated, DEA mismatched, adult mongrel dogs. METHODS: All dogs received CAP, starting at 50 mg/m2 PO b.i.d. 4 days preoperatively, increasing to 200 mg/m2 PO b.i.d. by the day of surgery. All dogs received cyclosporine-A (CsA) and prednisolone starting 2 days preoperatively. Standard heterotopic renal transplantation with native nephrectomy was performed. After 90 days, surviving dogs were euthanatized and histopathologic examination was performed. RESULTS: Two of 8 dogs developed acute neurotoxicity leading to death or euthanasia within 5 days of surgery. For the 6 remaining dogs, there were no statistically significant changes in complete blood count or serum biochemical values. No opportunistic infections developed during the study period. Five of 6 dogs had no to minimal evidence of graft rejection. Two of 6 dogs developed superficial and pigmentary keratitis. Significant histopathologic findings in all dogs included mild lymphoplasmacytic gastroenteritis, steroid hepatopathy, and corneal epithelial thinning. One dog had moderate interstitial nephritis and pyelitis. CONCLUSIONS: In this experimental model, a CAP-CsA-prednisolone immunosuppressive regimen was effective in preventing rejection of allografts in DEA-mismatched dogs. Severe, unpredictable neurotoxicity and variable ocular toxicity significantly limit clinical applications at this time. CLINICAL RELEVANCE: A CAP-CsA-prednisolone protocol is an effective, oral immunosuppressive regimen for prevention of allograft rejection in DEA-mismatched mongrel dogs. For clinical application, identification of patients susceptible to toxic side effects would be necessary.     

The effect of UV-blocking contact lenses as a therapy for canine chronic superficial keratitis

Objective To evaluate the effect of UV‐blocking soft contact lenses in treatment for chronic superficial keratitus (CSK). Methods Twenty six dogs with CSK were treated continuously with UV‐blocking contact lenses for 6 months. A contact lens was placed on one eye of each dog; the other eye remained without a lens as a control eye. After this primary study, five of the dogs were further treated and they wore then contact lenses in both eyes. Continuously, all patients were concurrently treated topically with cyclosporine. The contact lenses were changed every 4 weeks and an ophthalmic examination performed. Evaluation criteria included corneal alterations as pigmentation, edema, pannus and vascularization. To determine the transmittance characteristics of the contact lenses before and after use, 32 contact lenses were measured with a UV‐vis‐NIR spectrophotometer. Results Pigmentation increased in eyes wearing lenses and in control eyes over the evaluation period of 6 months. Corneal edema increased in the eyes wearing lenses, but remained unaffected in the control eyes. A significant difference in the incidence of pannus and the extent of corneal vascularisation could not be evaluated. Adverse effects were noted in six cases (corneal edema and vascularisation, conjunctivitis, blepharospasm). All new lenses studied reduced UV‐radiation to a safe level, whereas used lenses did not maintain their transmittance characteristics. Conclusions No positive effect of UV‐blocking contact lenses could be proven with the study design used.     

MHC class II risk haplotype associated with canine chronic superficial keratitis in German Shepherd dogs

Canine chronic superficial keratitis (CSK) is an inflammatory ocular disease of an autoimmune origin leading to blindness if untreated. The main symptoms of CSK are progressive, bilateral vascularisation, fibrous tissue formation and pigmentation of the anterior corneal stroma. Although CSK is found in many breeds it is most prevalent in German Shepherd dogs (GSDs). Since Major Histocompatibility Complex (MHC) class II is associated with several autoimmune diseases in dogs we investigated the possible role of DLA-DRB1, -DQA1 and -DQB1 in GSDs affected with CSK. Our study population included 25 healthy controls and 30 CSK dogs. Most of the affected dogs were females suggesting a female predisposition. We identified 11 unevenly distributed haplotypes of which DLA-DRB1*01501/DQA1*00601/DQB1*00301 was significantly associated with the CSK dogs (OR=2.67, CI=1.17-6.44, p=0.02). We also found that overall homozygosity of MHC class II increases risk for CSK (OR=4.37, CI=1.27-18.46, p=0.02) and homozygosity of the risk haplotype by over eight-fold (OR=8.5, 95% CI=1.4-224, p=0.017). This study identifies a MHC class II risk haplotype for CSK in GSD and further supports the autoimmune origin of the disease.     

Chronic superficial keratitis in dogs: detection of cellular hypersensitivity.

Dogs affected with chronic superficial keratitis (CSK) and clinically normal dogs were tested for cellular hypersensitivity, using the leukocyte migration-inhibition (LMI) technique to 3 ocular antigens (Staphylococcus aureus and corneal and iridal proteins). Affected dogs had statistically significant increases in hypersensitivity cellular responses against corneal and iridal antigens. Affected dogs did not differ from clinically normal dogs in their cell response to S aureus.     

The effect of topical pimecrolimus on keratoconjunctivitis sicca and chronic superficial keratitis in dogs: results from an exploratory study

OBJECTIVE: Pimecrolimus is an ascomycin derivative that interferes selectively with the activation of T cells and mast cells and inhibits the production of inflammatory cytokines. This study evaluated the efficacy of an experimental ophthalmic formulation of pimecrolimus in treating keratoconjunctivitis sicca (KCS) and chronic superficial keratitis (CSK) in dogs. ANIMALS AND PROCEDURES: Eight dogs with KCS and six with CSK were included. The dogs were of various breeds, suffered from chronic conditions, and had been pretreated unsuccessfully. The affected eyes were treated with 1 drop of an experimental, corn oil-based pimecrolimus 1% formulation three times a day. Parameters evaluated included Schirmer tear test (STT), ocular discharge, conjunctival inflammation, corneal inflammatory cell infiltrate and scarring, and comfort level. RESULTS: The effect of pimecrolimus 1% was pronounced (increase in STT values to higher than 4 mm/min, no signs of inflammation) or moderate (increase in STT values of 3-4 mm/min, mild signs of corneal/conjunctival inflammation) in a total of 6/8 animals with KCS. In 4/6 animals with CSK, the effect was either pronounced (total regression of fibrovascular infiltration into the cornea, no corneal scarring) or moderate (distinct regression of pannus, mild corneal scarring). The response to treatment was unsatisfactory in four of 14 animals. CONCLUSION: Results of this exploratory study suggest that topical 1% pimecrolimus may be a new effective treatment for keratoconjunctivitis sicca and chronic superficial keratitis in dogs.     

A retrospective study of 30 cases of frozen lamellar corneal graft in dogs and cats

Frozen lamellar corneal grafts and nictitating membrane flaps were used in 18 dogs and 12 cats to repair deep corneal defects. In all dogs either melting corneal ulcers or descemetoceles were present. In the 12 cats, nine had either a melting corneal ulcer or descemetocele, two animals had acute bullous keratopathy, and one cat had corneal sequestrum. Initial vascularization with gradual clearing of the graft occurred during the first 45 days postoperatively. At 60 days postoperatively, all eyes were visual. Frequent postoperative complications included: focal dehiscence of the wound ( n  = 9); melting of part of the graft ( n  = 7); and pigmentation of the graft ( n  = 4). The frozen lamellar corneal graft was a very safe technique, and restored the tectonic and the optical function of the cornea. It provided the best results in corneas with nonperforating corneal defects. This technique provides poorer results when the cornea was perforated prior to surgery or during the surgical procedure.     

Corneal anatomical differences in the aetiology of chronic superficial keratitis

The apparently normal corneas of 14 diseased eyes of German shepherd dogs (GSDs) were shown to possess very thin epithelial layers on microscopy. Normal corneas of 38 GSDs and 113 dogs of various breeds and crossbred animals were compared for epithelial thickness, structure of corneal stroma and corneal strength. Due to lower values for these criteria found in the GSDs they are considered to play an important role in the aetiology of chronic superficial keratitis.     

Successful treatment of an unusually large corneal epithelial inclusion cyst using equine amniotic membrane in a dog

A 10‐year‐old intact male Yorkshire Terrier was referred for investigation of a large raised and nonpainful corneal lesion oculus dexter. Clinical examination revealed a pale, translucent corneal mass, which occupied half of the corneal surface and measured 11 mm × 11 mm × 13 mm. The mass was removed by superficial keratectomy and equine amniotic membrane (AM) was transplanted into the large corneal defect to cover the wound and provide tectonic support for the remaining cornea. The mass was histologically confirmed as a corneal epithelial inclusion cyst. There was no evidence of recurrence or complication at the surgical site 100 days postoperatively. Corneal epithelial inclusion cysts are uncommon in dogs. Although superficial keratectomy is the recommended treatment for corneal inclusion cyst, the combination of superficial keratectomy and AM transplantation had to be considered as an alternative for repair of large corneal defects. This is the first case report of the combined application of AM and superficial keratectomy to successfully treat a corneal inclusion cyst in a dog.     

Corneal epithelial inclusion cyst in the dog

Unilateral corneal epithelial inclusion cysts are recorded in a series of 16 dogs. The cysts were not congenital, there was no breed incidence, and in 11 patients there was history of corneal trauma or ulceration before cyst formation. There was some variability in clinical presentation, and sight was affected in six dogs. Fifteen patients were treated successfully by superficial keratectomy without cyst recurrence.     

Corneal squamous cell carcinoma in two dogs

Purpose To report two cases of corneal squamous cell carcinoma (SCC) in dogs. Methods Corneal tumors were resected by superficial keratectomy in two cases. Immunohistochemistry of the corneal tissues was performed using anti‐p53 antibody. Results The prominent features of the cases were a clinical history of pigmentary keratitis and chronic keratitis. In each case, a corneal mass was surgically removed with a superficial keratectomy and histologically diagnosed as corneal SCC. Both masses were negative for p53. To reduce chronic corneal irritation, 0.1% hyaluronate sodium ophthalmic solution was applied. After more than 15 months of postsurgical follow‐up there has been no recurrence of either neoplasm. Conclusion and discussion Chronic corneal irritation was suspected as the primary etiology for the corneal SCC. Appropriate surgical removal of the mass and subsequent conservative treatment for keratitis provided effective therapy in these two cases.     

Bilateral parotid duct transposition for keratoconjunctivitis sicca in a Connemara stallion

A 7‐year‐old Connemara stallion was presented with a 4 month history of blepharospasm, recurrent corneal ulcerations, mucopurulent ocular discharge, and keratoconjunctivitis sicca (KCS) in both eyes unresponsive to medical therapy. Ophthalmic examination revealed lackluster corneas, axial corneal scarring and pigmentation with associated neovascularization, and absolute KCS in both eyes. Computed tomography scan and endoscopic evaluation of the upper airway and guttural pouches revealed no structural abnormalities to indicate neurogenic KCS. The stallion was diagnosed with immune‐mediated dacryoadenitis as all other causes of KCS were excluded. Parotid duct transposition (PDT) was performed in the right eye followed by PDT in the left eye 4 weeks later. The right PDT was functional 2 years post‐operatively with significant improvement in ocular comfort and reduced corneal fibrosis and neovascularization. The left PDT developed a salivary‐cutaneous fistula over the left masseter muscle post‐operatively due to avascular necrosis of the distal parotid duct (PD). Surgical reconstruction of the PDT using an expanded‐polytetrafluoroethylene (e‐PTFE) tube graft, an e‐PTFE tube graft to autogenous caudal auricular vein graft, and an autogenous saphenous vein graft were all unsuccessful. Tear production in the left eye improved at 1 year post‐surgery as a result of long term lacrostimulant therapy, and a permanent PD‐cutaneous fistula was performed on the left PD at the level of the ventral mandible. Bilateral PDT in the horse is effective in resolving clinical signs associated with KCS; however, morbidity associated with avascular necrosis of the transposed PD may be significant and can result in surgical failure.