Infrared ocular thermography in dogs with and without keratoconjunctivitis sicca

Infrared thermography was used to measure temperature differences of the corneal surface between nasal and temporal limbus regions and central cornea of normal dogs and dogs with keratoconjunctivitis sicca (KCS), in order to establish temperature values in normal canine eyes and in patients with decreased Schirmer tear tests (STT) values. Dogs investigated were all either patients seen at the Veterinary Teaching Hospital of Federal University of Paraná or normal dogs that belonged to the same institution. STT were performed in all eyes. A total of 40 control eyes (STT ≥15 mm/min) and 20 eyes with low STT values (STT ≤14 mm/min) were examined. The mean STT value for eyes with normal STT values was 22.9 ± 3.9 mm/min (mean ± standard deviation), and the mean STT value for eyes with low STT value was 7.2 ± 4.8 mm/min. The mean corneal temperature was significantly lower in eyes with low STT values than in control eyes (P < 0.0001). The following significant correlations were found: (i) Schirmer and breakup time (BUT) (P = 0.0001, r = 0.5); (ii) STT values and corneal surface temperature (P = 0.001, r = 0.256); (iii) STT values and age (P = 0.0001, r = ?0.448); (iv) age and corneal surface temperature (P = 0.0001, r = ?0.281); and (v) BUT and corneal surface temperature (P = 0.0001, r = 0.36). Thermography is a method that can differentiate between eyes with normal and abnormal STT values. In the future, thermography might be incorporated as part of the ophthalmic examination and perhaps become a popular ancillary test for the diagnoses of ocular surface disorders.     

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.     

Scanning electron microscopy of experimental keratoconjunctivitis sicca in dogs: cornea and bulbar conjunctiva

Keratoconjunctivitis sicca was produced experimentally in 16 beagles by bilateral surgical removal of the lacrimal and nictitans glands; four dogs were not treated, and 12 received tear-replacement therapy on post-operative days 7 through 28. Keratoconjunctivitis sicca was verified by reduction in Schirmer tear test values by post-operative day 6, and there was no response on day 28 to tear-replacement therapy. Corneas of both normal and tear-deficient dogs had polygonal squamous epithelial cells of light and dark electron density by scanning electron microscopy. Light cells had more microvilli and microplicae than dark cells. Conjunctivae were similar to corneas, except for numerous goblet cells on the surface. Corneal dark-cell density and goblet cell density were not different between groups. Goblet cells most often occurred singly in normal dogs, while they were in clusters in tear-deficient dogs. A hypothesis that petrolatum/mineral oil ointment should provide more effective artificial tear replacement than hydroxymethylcellulose drops for tear-deficient dogs could not be confirmed by objective analysis of corneal dark-cell density or conjunctival goblet cell density.     

Effect of topical 0.02% tacrolimus aqueous suspension on tear production in dogs with keratoconjunctivitis sicca

Objective To investigate the effect of 0.02% tacrolimus in aqueous suspension on tear production in dogs with keratoconjunctivitis sicca (KCS). Animals studied One hundred five dogs diagnosed with KCS [Schirmer tear test (STT) ≤ 10 mm/min and clinical signs of dry eye]. Eyes with marginally decreased STT (11 ≤ 15 mm/min) and clinical signs of dry eye were also evaluated. Procedure The investigation was conducted in two parts: an initial efficacy study and a subsequent double blinded controlled study. In the efficacy study, the effect of topical tacrolimus (formerly FK‐506) on tear production in dogs with primary KCS was evaluated. Dogs were divided into four categories: 1) 59 eyes (38 dogs) naïve to tear stimulation therapy with initial STT ≤ 10 mm/min; 2) 28 eyes (21 dogs) naïve to tear stimulation therapy with initial STT 11 ≤ 15 mm/min; 3) 30 eyes (15 dogs) maintained successfully on CsA therapy; 4) 47 eyes (24 dogs) unresponsive to CsA therapy. STT and clinical signs were evaluated prior to and after 6 to 8 weeks of twice daily tacrolimus administration. Tacrolimus was substituted for CsA therapy in categories 3 and 4. The controlled study compared the effect of topical tacrolimus in aqueous suspension to administration of the aqueous carrier alone on tear production in 20 dogs with primary KCS. Results In the efficacy study, STT increased by 5 mm/min in 84.7%, 25.0%, 26.7% and 51.1% of eyes in categories 1, 2, 3 and 4 respectively after tacrolimus administration. Eighty‐three percent of eyes with extremely low initial STT (≤ 2 mm/min), increased 5 mm/min after tacrolimus. In the controlled study, STT increased by 5 mm/min in 7/10 dogs (14/20 eyes) that received tacrolimus and in none of the 10 dogs that received aqueous carrier alone. Dogs receiving just the aqueous carrier were subsequently treated with tacrolimus, and STT increased 5 mm/min in 9 dogs (18/20 eyes) after administration. Conclusions Twice daily administration of 0.02% tacrolimus in aqueous suspension effectively increased tear production in dogs with KCS. Topical tacrolimus is a promising alternative to topical CsA for treatment of KCS and may be beneficial in patients with less than optimal response to topical CsA.     

A topical aqueous calcineurin inhibitor for the treatment of naturally occurring keratoconjunctivitis sicca in dogs

Purpose The purpose of this study was to evaluate the efficacy of an aqueous calcineurin inhibitor, SCY‐641, in the treatment of naturally occurring canine immune‐mediated keratoconjunctivitis sicca (KCS). Methods A randomized, double‐masked, placebo‐controlled clinical study of 56‐day duration was performed in dogs with naturally occurring immune‐mediated KCS assigned to treatment with either topical twice‐daily aqueous calcineurin inhibitor solution (SCY‐641) or artificial tears (placebo) by the study administrator. Clinical examination and Schirmer tear tests (STT) were performed prior to therapy and at days 7, 14, 28, and 56 after initiation of treatment. Results Twenty dogs were enrolled in the study with ten receiving placebo and 10 receiving SCY‐641 in one or both eyes. No adverse effects were noted with any treatment. There were no significant differences in mean STT values in dogs in group either at day 0 (prior to therapy) or after 7 days of treatment. At 14, 28, and 56 days after initiation of treatment, mean STT and increase in STT over baseline in dogs treated with SCY‐641 were significantly higher than in dogs treated with placebo (P < 0.04). Conclusions SCY‐641 was well tolerated by dogs with naturally occurring KCS, and by 14 days after initiating therapy, dogs treated with SCY‐641 had significantly higher STT than placebo‐treated dogs. These preliminary results indicate that topical SCY‐641, in a stable clear aqueous solution, is efficacious in a spontaneous model of KCS and warrants further evaluation as a treatment of immune‐mediated KCS.     

Clinical evaluation of 1% cyclosporine for topical treatment of keratoconjunctivitis sicca in dogs.

Keratoconjunctivitis sicca (KCS) is a prevalent and often vision-threatening condition in dogs. In several reports, 2% cyclosporine (cyclosporin A, CsA) was described as effective in modulating the clinical signs of KCS. This study was designed to compare the efficacy of 1% CsA vs a placebo, using a randomized double-blind clinical trial. Topical administration of 1% CsA significantly improved Schirmer wetting values and subjective markers of corneal health as compared with the placebo. In the dogs treated with topical administration of 1% CsA, the clinical signs of KCS were improved in 81.8% of cases.     

Keratoconjunctivitis sicca: histopathologic study of nictitating membrane and lacrimal glands from 28 dogs

Forty nictitating membrane glands and 9 main lacrimal glands were obtained for histologic evaluation from 28 dogs with keratoconjunctivitis sicca as the result of azosulfapyridine toxicity, canine distemper, multisystemic autoimmune disease (Sj?gren's syndrome-like syndrome), congenital origin, and unilateral and bilateral idiopathic keratoconjunctivitis sicca. Similar glands from 6 control dogs were studied. The most prevalent (87%) histopathologic finding was variable degrees of multifocal chronic adenitis, characterized by acinar atrophy and replacement with increased numbers of plasma cells and lymphocytes within increased amounts of interacinar fibrous connective tissue stroma. Occasional tubular structures were dilated and filled with neutrophils and cellular debris.     

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.     

Diagnosis and treatment of keratoconjunctivitis sicca in the dog

Keratoconjunctivitis sicca (KCS) is a relatively common eye disease in the dog. The diagnosis is discussed, particularly of the early or mild case. The various types of medical treatment are described, including replacement therapy with artificial tears and ocular inserts, as well as other preparations; lacrimogenics; and other forms of medical treatment, including antibiotics, corticosteroids, mucolytics and hormones. Contraindicated drugs and agents are listed. Surgical treatments, including punctal occlusion, tarsorrhaphy, conjunctival flaps, contact lenses, superficial keratectomy, as well as parotid duct transposition, are discussed and the procedure indicated which is best suited to the case. The choice of treatment according to the severity of the KCS is also given.     

Immunopathogenesis of keratoconjunctivitis sicca in the dog.

Keratoconjunctivitis sicca (KCS), more commonly known as dry eye, is an inflammatory condition of the ocular surface caused by a pathologic reduction in the aqueous component of the tear film. It is seen commonly in the dog and defined as a Schirmer tear test with a reading of less than 10 mm in one minute. While KCS may be caused by neurological disease or drug toxicity, most cases are immune-mediated. Whereas the immunological basis of autoimmune KCS has been extensively investigated in humans and experimental rodent models, little research has been undertaken in the dog. It is hoped that this review spurs further research into the etiopathogenic factors in canine KCS.     

Corneal stromal sequestration and keratoconjunctivitis sicca in a horse

A 19-year-old Shetland pony presented with unilateral ocular discomfort and abnormal ocular appearance. Keratoconjunctivitis sicca, ulcerative keratitis and brown discoloration of the corneal stroma were identified on ophthalmic examination. The etiology of keratoconjunctivitis sicca was not determined in this case. For practical and financial reasons, the owners requested enucleation of the affected eye. Histopathologic examination revealed extensive loss of corneal epithelium overlying a zone of hypereosinophilic, degenerate, and necrotic corneal stroma. This well-circumscribed region of corneal stromal sequestration was surrounded by stromal vascularization, and an intense inflammatory, predominantly polymorphonuclear, cellular infiltrate. The clinical and histopathologic features of this case were considered remarkably similar to those observed in feline corneal stromal sequestration.