Characterization of lacrimal gland lesions and possible pathogenic mechanisms of keratoconjunctivitis sicca in dogs with leishmaniosis

In a previous study, it was found that 2.8% of dogs with leishmaniosis had keratoconjunctivitis sicca (KCS). The aim of this study was to characterize the lesions present in the lacrimal glands of dogs with leishmaniosis and to determine the presence of the parasite by means of immunohistochemistry. The inflammatory infiltrate was described as granulomatous or pyogranulomatous and was located around the ductal component of the glands. Immunoperoxidase staining localized the parasites following the same pattern. Samples from eyes that had clinical signs compatible with KCS presented inflammatory infiltrate and parasite more commonly than those from eyes without clinical signs. One of the mechanisms of KCS in dogs with leishmaniosis may be the inflammatory infiltrate located around the ducts of lacrimal glands, producing retrograde accumulation and retention of secretion. Meibomian gland was the most commonly affected by the infiltrate, highlighting the possibility of a qualitative KCS in these dogs.     

Keratoconjunctivitis sicca associated with sulfonamide therapy in dogs

During a 4-year period, keratoconjunctivitis sicca developed in 14 dogs treated with sulfonamides (13, sulfasalazine; 1, sulfadiazine and trimethoprim). Diagnosis was made in 3 dogs by clinical signs and in 11 by evaluation of the Schirmer tear test. Management of the problem included discontinuance of the sulfonamide, then use of ophthalmic preparations topically and antibiotics systemically. Pilocarpine was administered orally and topically to 11 dogs, with variable success. Lacrimation remained inadequate in 10 dogs and returned to normal in 3. One dog was lost to follow-up. Parotid salivary duct transpositions were performed in 3 dogs (in 2 successfully) with severe, unresponsive keratoconjunctivitis sicca.     

Biomicroscopy of the tear film: aqueous and lipid tear substitutes in the normal and abnormal eye

Polarised light biomicroscopy was used to assess the behaviour and interactions of two polymer-containing preparations of artificial tears, and two lipid-containing ointments, with the normal and abnormal pre-corneal tear film. The preparations were used topically in six normal dogs, and three dogs with keratoconjunctivitis sicca. A transient morphological alteration of the surface lipid layer of the tear film was commonly observed after the use of polymer solutions. The ointments spread as a continuous or semi-continuous layer over the normal, or polymer-supplemented, aqueous tears. Further applications of artificial tears produced only a temporary disruption of this layer. In dogs with keratoconjunctivitis sicca, thickening of the lipid layer of the tear film was observed for over 20 hours after the administration of ointment. These observations are discussed in relation to the prospects for the improved medical treatment of keratoconjunctivitis sicca by the use of polymer-containing solutions and ointments in combination.     

Keratoconjunctivitis sicca in the dog associated with the administration of salicylazosulphapyridine (sulphasalazine)

Thirteen cases of iatrogenic and bilateral keratoconjunctivitis sicca following the administration of the sulphonamide salicylazosulphapyridine (sulphasalazine) for the treatment of colitis were studied. No breed, age or sex incidence was noted in this series, unlike in keratoconjunctivitis sicca cases due to other causes. The lacrimotoxic effect of sulphasalazine was permanent except in one case and it is suggested that dogs on this drug should be monitored for tear secretion at regular intervals. Reports of a similar association between keratoconjunctivitis sicca and this drug and between the disease and other sulphonamides and compounds are discussed.     

Reduced tear production in three canine endocrinopathies

OBJECTIVES: Previous reports have suggested that hypothyroid and diabetic patients can be predisposed to keratoconjunctivitis sicca. This study aimed to measure tear production in dogs with diabetes, hypothyroidism and hyperadrenocorticism using the Schirmer tear test and to compare these results with Schirmer tear test values for a group of normal dogs. METHODS: Schirmer tear tests were performed on 16 dogs with hyperadrenocorticism, 18 with diabetes and 12 with hypothyroidism together with 100 control dogs. Corneal sensitivity was also measured in 12 of the 18 diabetic dogs with a Cochet Bonnet aesthesiometer and compared with age- and breed-matched normal dogs. RESULTS: Schirmer tear test values in dogs with hypothyroidism, hyperadrenocorticism and diabetes were 12.3+/-3.2, 14.0+/-4.0 and 12.3+/-5.3 mm/minutes, respectively. Schirmer tear test values were significantly lower than that for the control group (19.6+/-4.2 mm/minutes) in all dogs with an endocrinopathy. Only in two hypothyroid dogs and three diabetics, this was manifested as profound keratoconjunctivitis sicca with Schirmer tear test value lower than 5 mm/minutes. Diabetic dogs had significantly reduced corneal sensitivity compared with a matched set of control dogs. CLINICAL SIGNIFICANCE: This study shows a significant reduction in tear production in animals with diabetes mellitus, hypothyroidism and hyperadrenocorticism. Further research is needed to elucidate the mechanisms by which this reduction in tear production occurs. Assessment of tear production should be undertaken in animals diagnosed with these endocrinopathies, as these animals may progress to clinical keratoconjunctivitis sicca.     

Keratoconjunctivitis sicca: immunological evaluation of 62 canine cases

The etiology of keratoconjunctivitis sicca (KCS) in 62 dogs was evaluated, using immunologic techniques. Using direct fluorescent antibody testing, autoantibodies within the lacrimal, salivary, or pancreatic glands were detected in 5 of 8 dogs tested. Circulating antibodies to the nictitating membrane gland, main lacrimal gland, parotid salivary gland, or mandibular salivary gland were detected using indirect fluorescent antibodies in 9 of 31, 3 of 31, 5 of 31, and 5 of 31 sera, respectively. Using radial immunodiffusion, hyper-gamma-globulinemia was detected in 21 of 30 dogs with KCS. Antinuclear antibodies, primarily in a nucleolar pattern, were demonstrated in 20 of 50 dogs with KCS. Lymphocytic infiltrates were evident in 5 of 9 labial salivary biopsies, 2 of 4 parotid gland specimens, 2 of 4 mandibular gland specimens, and 2 of 3 thyroid gland specimens taken from dogs with KCS. Autoimmune diseases had been previously documented in 4 of 62 dogs. Twenty-five of the 62 dogs (40%) had concurrent problems indicative of an underlying immunologic disorder.     

Canine meibometry: establishing baseline values for meibomian gland secretions in dogs

Meibomian lipid secretions are essential in preventing tear evaporation. Disorders of the meibomian glands may therefore play an important role in the pathogenesis of some forms of keratoconjunctivitis sicca (KCS). Until now, meibomian lipid secretions have never been quantitatively evaluated in dogs. With the aim of establishing baseline values of canine meibomian lipid secretions, meibometry was conducted in 42 healthy dogs, 16 of which were Miniature Schnauzers. The mean meibomium level in 84 eyes of the 42 dogs was 179+/-60 Meibometer units. Age, gender and side did not affect the results. However, meibomium levels were significantly lower in the Miniature Schnauzers, a breed that is susceptible to KCS, compared to other breeds. This report demonstrates that meibometry is a simple and minimally invasive technique that may be readily used in conscious dogs to quantify meibomian gland secretions and explicate tear film dynamics in normal and dry canine eyes.     

Evaluation of the presence of Leishmania spp. by real-time PCR in the lacrimal glands of dogs with leishmaniosis

Leishmania infantum infection is highly prevalent in endemic areas. Dogs with leishmaniosis may develop keratoconjunctivitis sicca (KCS). The goals of this study were (1) to quantify Leishmania amastigotes in the Meibomian glands (MG), main lacrimal gland (MLG) and nictitating membrane gland (NMG) from dogs with leishmaniosis; (2) to compare these results to immunohistochemistry (IHC), and (3) to explore the association between the Leishmania parasite load and the presence of ocular clinical signs. Twenty-five dogs diagnosed with leishmaniosis were included. MG, MLG and NMG from both eyes were collected. Histopathology, IHC and real-time PCR were performed. All specimens yielded positive real-time PCR results. For all three glands, samples from dogs with ocular clinical signs had mean ΔCt (cycle threshold) values significantly lower (higher parasite loads) than those from dogs without signs. Cut-off values of ΔCt<0, ΔCt<4 and ΔCt<4.9 for MG, MLG and NMG, resulted in a likelihood ratio of positives of 5.9, 6.38 and 6.38, respectively. Samples with ΔCt values below the reported cut-off were significantly more likely to display clinical signs related to KCS than those with results above the cut-off, for all three glands. Similarly, ΔCt values below the cut-off were significantly associated with positive IHC. In this study real-time PCR has been standardised for use in MG, MLG and NMG. A cut-off value established for each of these tissues may aid the clinician in the discrimination between ocular signs related to Leishmania from those associated with other causes of KCS.     

Effect of removal of lacrimal and third eyelid glands on Schirmer tear test results in cats

Schirmer tear tests I and II values for 10 healthy cats were 16.2 +/- 3.8 mm/min and 13.2 +/- 3.4 mm/min, respectively. Surgical removal of the lacrimal gland or the third eyelid gland from the left eye resulted in decreased Schirmer tear test-I values. Clinical signs of keratoconjunctivitis sicca were not seen until the lacrimal and third eyelid glands were removed, at which time the Schirmer tear test-I value was close to 0 mm/min. Conjunctival glands (accessory lacrimal glands of Krause and Wolfring) appeared to contribute little to tear production in these cats.     

Keratoconjunctivitis sicca and diabetes mellitus in a dog.

Diabetes mellitus and keratoconjunctivitis sicca were diagnosed in a female Poodle. The dog was treated for diabetes and keratoconjunctivitis sicca until blood glucose concentrations were within normal limits. Treatment for keratoconjunctivitis sicca was suspended then, and signs of this disorder did not appear again. Most of the factors known to predispose to keratoconjunctivitis sicca were not applicable to this dog. On the basis of observations made in this dog, we suggest that diabetes mellitus and keratoconjunctivitis sicca may be linked. Clinical signs of the disorders developed simultaneously and resolved when diabetes mellitus was controlled with insulin.     

Topical administration of cyclosporine for treatment of keratoconjunctivitis sicca in dogs.

Sixty dogs with chronic keratoconjunctivitis sicca were treated by topical administration of 2% cyclosporine twice daily. Causes and duration of keratoconjunctivitis varied. Tear production improved in 75 of 100 eyes, and corneal pigmentation decreased in 45 of 67 eyes. Six factors were evaluated to determine their influence on treatment outcome. The only significant variable was the initial Schirmer tear test value. Side effects were few. Evidence of burning in response to application of cyclosporine resolved with change in the formulation of the topical solution.     

Breed predisposition to congenital alacrima in dogs

Objective  To evaluate the clinical characteristics and breed predisposition of congenital alacrima in dogs.
Animals studied  Dogs with congenital keratoconjunctivitis sicca.
Procedures  A search of the medical records of the University of Tennessee Veterinary Teaching Hospital from 1974–2005 and the University of California–Davis Veterinary Teaching Hospital from 1986–2006 for dogs under 1 year of age with a diagnosis of keratoconjunctivitis sicca (KCS) was performed. These cases were further reviewed for dogs with a Schirmer's tear test I of ≤ 5 mm/min before 6 months of age, with no known causes for KCS, which did not respond to appropriate KCS therapy; these cases were considered to have congenital alacrima. These breeds were compared to all other breeds using the Fisher's exact test with correction for multiple comparisons.
Results  Congenital alacrima was identified in 19 dogs representing 11 breeds and mixed breeds. Yorkshire Terriers and Bedlington Terriers were statistically overrepresented compared to reference populations ( P  < 0.01 and P  = 0.04, respectively).
Conclusions  Yorkshire terriers are significantly at risk for congenital alacrima compared to other breeds. The significance of the increase in congenital alacrima in Bedlington Terriers in this study may not be clinically relevant and may be due to the small total number of dogs of this breed that presented to the both hospitals. Based on the poor response to therapy in humans with congenital alacrima, it may be prudent to offer guarded prognoses for KCS in juvenile Yorkshire terriers.     

Facial neuropathy in dogs and cats: 95 cases (1975-1985)

The medical records of 79 dogs and 16 cats admitted to the New York State College of Veterinary Medicine between January 1975 and October 1985 with facial nerve dysfunction were reviewed. In 31 dogs and 8 cats, facial neuropathy was the only abnormal finding. In 48 dogs and 8 cats, the clinical findings most often noted in the records in addition to facial neuropathy were vestibular signs. Facial neuropathy appeared unassociated with gender or right vs left sides in both dogs and cats, or with hypothyroidism in dogs. Facial neuropathy was associated with increased age, with certain breeds in both dogs and cats, and with otitis media/interna and keratoconjunctivitis sicca in dogs. Causes of facial nerve dysfunction in dogs and cats included surgical and nonsurgical trauma, neoplasia, and otitis media/interna. Facial neuropathy was judged to be idiopathic in 74.7% of dogs and 25% of cats.     

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.     

Atypical Reaction to Acetaminophen Intoxication in a Dog

Objective: To report an unusual manifestation of acetaminophen intoxication in a dog.
Case Summary: A Miniature Pinscher was presented for evaluation of lethargy and facial swelling after ingestion of 500–750 mg/kg of acetaminophen. Laboratory testing revealed eccentrocytes, Heinz bodies, hemoglobinemia, and a declining packed red cell volume consistent with oxidative damage to the erythrocytes. Hepatocellular damage, as monitored by serum alanine aminotransferase, was not documented. The dog responded well to therapeutic intervention, and was discharged from the hospital. The dog returned to the hospital 2 days later with clinical signs and diagnostic tests consistent with acute keratoconjunctivitis sicca, which was assumed to be due to a toxic etiology. The dog responded well to therapy, regaining normal levels of tear production within six weeks.
New or Unique Information Provided: Acetaminophen intoxication may be associated with severe erythrocytic oxidative damage in the absence of detectable hepatic injury in dogs. Acetaminophen intoxication may have the potential to cause acute keratoconjunctivitis sicca in dogs. ( J Vet Emerg Crit Care 2001; 11(2): 123–126 )     

Squamous cell carcinoma of the corneoscleral limbus in a dog.

Squamous cell carcinoma is an uncommon tumor of the cornea in dogs. A 12-year-old Shih Tzu with a history of chronic keratoconjunctivitis sicca was diagnosed as having squamous cell carcinoma of the corneoscleral limbus. The lesion was treated by surgical resection and cryotherapy. One year after surgery, multiple tumors, apparently unrelated to the first tumor, appeared on the same cornea. Keratoconjunctivitis sicca may have predisposed the dog to corneal squamous cell carcinoma development.     

The use of hydrophilic contact lenses in corneal diseases of the dog and cat: A preliminary report

ABSTRACT
Two types of hydrophilic contact lenses were tested in dogs and cats as part of the therapeutic régime of recurrent corneal erosions, superficial corneal ulcers and keratoconjunctivitis sicca. It was found that the lenses are well tolerated by these species when properly fitted to the cornea. If the lenses were not properly fitted, they were lost before their therapeutic effectiveness could be evaluated. The use of hydrophilic contact lenses appeared to be beneficial in the treatment of superificial corneal ulcers and recurrent corneal erosions in the dog and cat, but ineffective in the treatment of keratoconjunctivitis sicca.     

Pseudallescheria boydii keratomycosis in a dog.

A dog that had a chronic history of keratoconjunctivitis sicca and was being treated topically with antibiotics and corticosteroids was examined for evaluation of a melting corneal ulcer. Cytologic examination and cultures revealed the pathogen to be Pseudallescheria boydii, a saprophytic fungus. The eye was surgically removed and evaluated histologically. Fungal keratitis is rarely reported in dogs, but needs to be considered in refractory infections or in dogs treated with antibiotics or corticosteroids.     

Effect of age, gender, weight, and time of day on tear production in normal dogs

OBJECTIVE: To investigate the effects of age, weight, gender, and of time of day on tear production in normal dogs. ANIMALS: studied One hundred ophthalmoscopically and systemically unremarkable dogs. PROCEDURE: Schirmer tear tests (STT) were performed every 2 h during the day on one randomly chosen eye of each of 100 dogs. RESULTS: There was a statistically significant effect of time of day and age on the STT measurement. The mean STT decreased by 0.4 mm for every 1 year that age increased (P=0.007). Mean STT values taken at 10:00 am were 0.7 mm lower than values taken at 4:00 pm (P=0.04). CONCLUSIONS: Tear production decreases with age in the normal dog. In this population of dogs the largest difference was between the 10:00 am and the 4:00 pm STT measurements, but this still only amounted to 0.7 mm. This value is unlikely to be of clinical significance in the diagnosis of keratoconjunctivitis sicca (KCS).     

Keratoprosthesis with retrocorneal fixation: preliminary results in dogs with corneal blindness

Objective To evaluate the use and complications of a penetrating keratoprosthesis implantation in the management of corneal opacification in dogs. Methods A retrospective clinical study describes the indications for the surgical technique utilized and the outcomes of this procedure in 20 eyes of 19 dogs with blindness of corneal origin. A successful surgical outcome was defined as a clear keratoprosthesis optic and improvement or restoration of functional vision over a follow‐up period ranging from at least 8 months to a maximum of 7 years. Results Eyes with total corneal opacification resulting from chronic superficial keratitis (n = 11), keratoconjunctivitis sicca (n = 5), endothelial dystrophy (n = 3) and chemical burn (n = 1) were treated by unilateral (n = 18) or bilateral (n = 1) full‐thickness implantation of a keratoprosthesis. Keratoprostheses were retained in 15 eyes (75%) which regained vision to the date of reporting. Among these eyes, six had uncomplicated postoperative course, five developed retroprosthetic membranes and four developed granulation tissue over the optic of the keratoprostheses. These complications were successfully removed surgically in the nine eyes. The five remaining eyes (25%) developed serious early postoperative complications, for which enucleation had to be performed. Conclusion In keratopathies in which the corneal opacification could not be treated by standard medical or surgical procedures, this keratoprosthesis appears to be promising to restore vision in chronic superficial keratitis and deep corneal dystrophy. It appears to have a poor prognosis in keratoconjunctivitis sicca in brachycephalic dogs. The post operative complications retro‐prosthetic membranes and granulomatous overgrowth could be treated well.