Polarized light biomicroscopic observations on the pre-corneal tear film. 2. Keratoconjunctivitis sicca in the dog

Polarized light biomicroscopy was used to examine the pre-corneal tear film in 16 dogs which were suspected of, or confirmed to be, suffering from keratoconjunctivitis sicca. One animal displayed a normal tear film, while the other 15 showed variable degrees of abnormality. The abnormal features included: contamination of the ocular surface with particulate debris and plaques of mucus, discontinuity and excessive granularity of the surface lipid film, pronounced thinning of the aqueous phase, and breakup of the tear film. After parotid duct transposition, the tear film of some animals was almost indistinguishable from normal. However, in others the surface lipid layer was thinned, discontinuous, or virtual absent. Discontinuity of surface lipid was most obvious in animals with marked salivary epiphora, and was associated with a variable amount of crystalline concretion over the ocular surface. The clinical usefulness of polarized light biomicroscopy for the diagnosis, and subsequent monitoring, of keratoconjunctivitis sicca is 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.     

Analysis of tear uptake by the Schirmer tear test strip in the canine eye

OBJECTIVE: To analyze the uptake of tears in a Schirmer tear test (STT) in vitro and in vitro. MATERIALS AND METHODS: Uptake of fluid by Schirmer tear test strips was studied in vitro by examining fluid uptake over time from an unlimited fluid supply as well as with specific fluid volumes applied to the test strip. Uptake of fluid by Schirmer tear test strips was evaluated in a population of 100 ophthalmologically normal dogs together with a group of 40 dogs with tear film abnormalities such as keratoconjunctivitis sicca (KCS) or epiphora. Each animal was given a full ophthalmic examination followed by a standard Schirmer tear test extended over between 3 and 5 min with the STT reading recorded every 5 s and plotted over time. To determine the effect of ocular irritation by the test strip, uptake of tears by test strips was determined before and after topical anesthesia in 20 dogs. RESULTS: In vitro examination of fluid uptake by the STT strips showed an initial rapid uptake followed by a gradual reduction in rate of uptake. Temporal evaluation of STT in vivo showed a similar rapid initial uptake of tear fluid, followed in the majority of cases by a sudden change to a steady state uptake of fluid. The initial gradient was 29.3 +/- 16.9 mm/min followed by a steady state uptake of 5.2 +/- 2.3 mm/min in normal dogs and 1.9 +/- 1.3 mm/min in dogs with KCS. This corresponds to a steady state tear turnover of 7.8 +/- 3.4 microL/min in normal dogs and 2.8 +/- 1.9 microL/min in animals with KCS. Dogs with nasolacrimal blockage and resultant epiphora showed a high initial gradient but final gradients were not statistically different from those of normal dogs. Discussion and conclusions Temporal evaluation of tear uptake by the STT shows substantial differences in rate of tear uptake at different time-points during the period of the test. RESULTS: of this study suggest that the initial rapid rise in STT value represents uptake from the tear lake followed by a slower tear uptake of tears from steady state tear production. Temporal examination of the Schirmer tear test allows a more precise evaluation of tear production than the standard STT measuring tear uptake in 1 min, together with estimation of the contribution to the test strip tear uptake of tears from the residual tear lake volume and those from continual tear production.     

Biomicroscopy of the tear film: the tear film of the pekingese dog

Polarised light biomicroscopy was used to examine the normal pre-corneal tear film in 21 eyes of 12 pekingese dogs. The purpose of the study was to examine the influence of excessive exophthalmos on the pre-corneal tear film in the dog. The majority of the animals were found to have high levels of ocular surface contamination by particulate material and plaques of viscous mucus. Other abnormalities included surface lipid with an abnormal granular (three dogs) or 'curdled' (two dogs) appearance; excessive thinning of the lipid layer of the tear film; and the presence of dark globular structures in two dogs, which were presumed to be abnormal meibomian lipid. Break up of the tear film was observed in one dog. Grossly, a thread of viscous mucus was frequently observed along the margin of the lower eyelid. It is postulated that this thread forms because of the excessively exophthalmic conformation of the breed, which prevents the normal access of effete mucus and entrapped debris to the lower conjunctival fornix. The combination of the above factors in the pekingese is suggested as the mechanism whereby the tear film has a reduced stability, thus enhancing the risk from factors more usually considered to initiate corneal ulceration in the breed. The possible adverse effects of lid splitting for the mass removal of distichiae in exophthalmic dogs is discussed.     

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.     

Polarized light biomicroscopic observations on the pre-corneal tear film. 1. The normal tear film of the dog

Polarized light biomicroscopy was used to examine the normal pre-corneal tear film in 25 dogs. Blink rates were also determined. The normal range of surface morphology of the canine tear film was established. Three categories of surface patterning of the lipid layer of the tear film were identified. These were: (a) a wave-like pattern, (b) a pattern of irregular islets, and (c) a pattern resembling the polished surface of granite. All three patterns may occur in the same eye. The inter-blink thickness of the lipid layer of the pre-corneal tear film varied between 0·013 μm (the minimum thickness discernable by this method) and over 0·581 μm (the maximum thickness at which coloured interference fringes are clearly defined) in localized areas. The mean total blink rate was 14·2/min. Overall, incomplete blinks constituted approximately 66 per cent of the total blink rate, but the ratio of complete to incomplete blinks varied considerably between animals. By dividing the dogs into thick and thin lipid layer groupings, it was possible to demonstrate a statistically greater rate of complete blinks (P < 0·05, Mann-Whitney U test) in animals with a thinner lipid layer. The applicability of polarized light biomicroscopy to veterinary clinical ophthalmology is discussed.     

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.     

Topical effect of various agents on gelatinase activity in the tear film of normal dogs

OBJECTIVE: To evaluate the topical effect of various agents, currently used in the treatment of melting ulcers, on gelatinase activity present in the tear film of normal dogs. ANIMAL STUDIED: Eight normal adult beagles. PROCEDURES: Each animal received the following agents: cyclosporine A 1%, N-acetylcysteine 10%, ciprofloxacin 0.3%, ethylenediaminetetraacetic acid (EDTA) 1%, doxycycline 0.001%, polysulfated glycosaminoglycans (PSGAG) 5%, autoserum, and artificial tears during a 48-h period following a Latin square design. Tear samples were collected with micro-capillary pipettes following a corneal surface irrigation of each eye with sterile saline on four different occasions. Basal and total gelatinase activities were evaluated by optical density after processing in a commercial gelatinase activity assay. From the optical density ratio, a semi-quantitative measure of gelatinase activity was obtained. Basal and total activities were measured in all samples. RESULTS: The lowest total gelatinase activity, representing a percent decline in the enzyme activity although not significant, was observed 1 h after the last treatment in seven out of the eight ophthalmic agents; EDTA (68%), ciprofloxacin (76%), cyclosporine A (68%), doxycycline (47%), artificial tears (26%), PSGAG (25%), and N-acetylcysteine (20%). However, only the reduction observed with EDTA 6 h after the last treatment was significantly lower compared to the reduction observed with the artificial tears. CONCLUSION: This study indicated that only EDTA was able to significantly reduce the gelatinase activity in a persistent manner in the tear film of normal canine eyes. Further studies will be required to evaluate the effect of EDTA under ulcerative conditions and to more accurately ascertain the potential in vivo effect of the other agents.     

Polarized light biomicroscopic observations on the pre-corneal tear film. 3. The normal tear film of the cat

Polarized light biomicroscopy was used to examine the pre-corneal tear film in 14 normal cats. Blink rates were also determined. The normal range of surface morphology of the feline tear film was established. Two principal categories of surface patterning of the lipid layer of the tear film were identified. These occurred in all eyes examined and were: (a) a wave-like pattern, and (b) a pattern of variable character resembling the polished surface of granite. Over most of the area of the tear film, the thickness of its lipid layer between blinks was under 0·089 μm in all cats examined. However, narrow streaks of thicker lipid (up to 0·511 μm) were occasionally observed. The mean total blink rate was 2·4/min. Overall, incomplete blinks constituted approximately 50 per cent of the total blink rate. The tear film of the cat is compared with that of man and the dog.     

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).     

Evaluation of the Schirmer tear test in clinically normal rabbits

Mean (+/- SD) value for results of the Schirmer tear test without use of topical anesthesia on 142 rabbit eyes was 5.30 (+/- 2.96) mm/min; range was 15 mm/min, with low value of 0 and high value of 15 mm/min. Two SD from the mean provided a normal clinical range of 0 to 11.2 mm/min for inclusion of 95% of the population. Significant differences were not evident between eye (right vs left) or gender or among breeds; interaction among eye, gender, and breed also was not observed. Although mean values for 2 breeds were significantly different from values in the other 10 breeds and from each other, they were still within the proposed normal range of 2 SD. The Schirmer tear test without topical anesthesia may be useful in rabbits for evaluation of increased values correlated with ocular irritation, rather than for determination of decreased values associated with keratoconjunctivitis sicca.     

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.     

Characterization of ocular gland morphology and tear composition of pinnipeds

Objective The importance of tear film integrity to ocular health in terrestrial mammals is well established, however, in marine mammals, the role of the tear film in protection of the ocular surface is not known. In an effort to better understand the function of tears in maintaining health of the marine mammal eye surface, we examined ocular glands of the California sea lion and began to characterize the biochemical nature of the tear film of pinnipeds. Procedures Glands dissected from California sea lion eyelids and adnexa were examined for gross morphology, sectioned for microscopic analysis, and stained with hematoxylin and eosin. The tear film was examined using interferometry. Tears were collected from humans and pinnipeds for the analysis of protein and carbohydrate content. Results The sea lion has sebaceous glands in the lid, but these glands are different in size and orientation compared with typical meibomian glands of terrestrial mammals. Two other accessory ocular glands located dorsotemporally and medially appeared to be identical in morphology, with tubulo‐acinar morphology. An outer lipid layer on the ocular surface of the sea lion was not detected using interferometry, consistent with the absence of typical meibomian glands. Similar to human tears, the tears of pinnipeds contain several proteins but the ratio of carbohydrate to protein was greater than that in human tears. Conclusions Our findings indicate that the ocular gland architecture and biochemical nature of the tear film of pinnipeds have evolved to adapt to the challenges of an aquatic environment.     

Use of punctal occlusion in the treatment of canine keratoconjunctivitis sicca

Twenty eyes of 10 dogs with keratoconjunctivitis sicca (KCS) were treated by occlusion of the ventral nasolacrimal punctum with a silicone punctal plug in order to increase the volume of the remaining tear lake. Punctal size was measured using a commercially available punctal gauge and the appropriate sized plug was inserted under local anaesthesia. Seven dogs showed an increase in Schirmer tear test I (STT) value. STT values immediately prior to plug placement were 2.3 +/- 1.7 mm/minute. STT values with punctal occlusion were 6.1 +/- 4.1 mm/minute, giving a mean increase of 3.8 +/- 2.7 mm/minute (P<0.001). In 14 eyes of eight dogs, the increase in STT values was accompanied by a clinical improvement in the appearance of the ocular surface. In the three dogs with no increase in STT values, the use of punctal plugs reduced the frequency of artificial tear replacement therapy required to maintain a healthy ocular surface. These results show that use of punctal plugs in dogs with KCS may be appropriate where other lacrimomimetic medications have been unsuccessful.     

Qualitative tear film disease

Abnormalities of the lipid and mucin components of the preocular tear film may result from diseases of the eyelid margins and conjunctiva. Chronic keratoconjunctivitis with epithelial edema and superficial corneal neovascularization, with or without ulceration, characterizes qualitative tear diseases. Tear components other than lipid and mucin that carry probable clinical significance include tear proteins, all-trans retinal, cholesterol, glucose, and electrolytes. Although less common than quantitative or aqueous deficiencies, qualitative abnormalities are recognized as primary or secondary causes of ocular surface disease in companion animals.     

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.     

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.     

Reconstruction of the eyelids of a dog using grafts of oral mucosa.

A five-month-old English cocker spaniel with distichiasis had been treated four times surgically by a tarsomeibomian resection technique. As a result, three-quarters of the margins of its upper eyelids had been eliminated and the lower eyelids had become considerably thinner. The dog had developed upper entropion and upper eyelid trichiasis, and keratoconjunctivitis sicca. It was treated medically and grafts of oral mucosa were used to reconstruct its upper eyelids. A year after surgery, the new palpebral margin was completely functional and cosmetically acceptable. The dog's eyes appear normal and only require treatment with artificial tears.     

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 )     

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.