Keratoconjunctivitis Sicca In Dogs Research Articles

Subconjunctival liposomal sirolimus vs. cyclosporine or tacrolimus as treatment of keratoconjunctivitis sicca in dogs: A double-blind, randomized study.

To compare the safety and efficacy of a 100 microgram subconjunctival injection of liposome-encapsulated sirolimus (SCJS) to cyclosporine (CsA) or tacrolimus (CsA/T) for the treatment of keratoconjunctivitis sicca (KCS) in dogs. Dogs with signs and symptoms of KCS were block-randomized to one of two treatment groups: Biweekly SCJS or conventional treatment (CsA/T). Schirmer tear test 1 (STT-1) scores, conjunctival hyperemia (CH) scores, corneal opacity (CO) scores, and clinical evaluation of potential side effects were recorded every 2 weeks for 14 weeks for both groups. Differences between groups were analyzed using the mixed results ANOVA and U-Mann Whitney tests (p < .05 was considered significant). A total of 30 eyes were included in the study, of which 20 eyes completed follow-up. There was no statistically significant interaction between the treatment group and time on STT-1 score (p = .165), and median CH and CO scores showed no statistically significant differences between groups (p = .353 and p = .393, respectively). There were no clinically significant side effects present in any subject at any time. In this trial, a 1 mg/mL (100 micrograms) SCJS every 2 weeks showed similar safety and efficacy profiles as daily CsA/T in dogs with KS after 14 weeks of treatment. Larger studies should be performed to further assess SCJS as an alternative treatment for KCS.

Comparison of topical 0.03% tacrolimus and homologous injectable platelet-rich plasma in the treatment of keratoconjunctivitis sicca in dogs.

Keratoconjunctivitis sicca (KCS) is predominantly an immune-mediated chronic inflammatory ocular disease that is commonly diagnosed in dogs. This study aimed to compare the conventional use of topical immunosuppressant tacrolimus 0.03% eye drops and a new therapy injectable homologous platelet-rich plasma (HPRP) into the third eyelid gland and inferior and superior palpebral conjunctiva of dogs with KCS. A total of 66 eyes from 33 dogs were evaluated. The eyes were divided into three equal groups: Negative control group, tacrolimus group (TG), and homologous platelet-rich plasma group (HPRPG). The animals were evaluated using the Schirmer's tear test-1 (STT-1), osmolarity test (OT), strip meniscometry test (SMT), tear film break-up test (TBUT), fluorescein test, lissamine green test (LGT), and cytological and histopathological analyses. In TG, there was a significant increase (p < 0.05) in the STT-1 and SMT values, and goblet cell count in the palpebral conjunctiva by the end of the study. In HPRPG, 36% (four dogs) received three applications, 55% (six dogs) received two applications, and 9% (one dog) received one application before the initial ocular signs improved. There was a significant decrease (p < 0.05) in the lymphocyte and neutrophil counts of the palpebral conjunctiva in HPRPG than in TG. Both groups showed equivalent improvements in TBUT, OT, and LGT values. Tacrolimus 0.03% eye drops were more efficient than HPRP in increasing tear production and the number of goblet cells. However, injectable HPRP was more efficient than tacrolimus in decreasing the number of conjunctival inflammatory cells. Treatment with injectable HPRP requires an average of two to three applications, is safe and feasible, and can be used as a cheaper alternative or as an adjuvant to conventional treatment with topical immunosuppressants.

Comparison of strip meniscometry and Schirmer tear test results and tear film breakup time between healthy dogs and dogs with dry eye disease.

To compare strip meniscometry and Schirmer tear test 1 results and tear film breakup time between dogs with normal eyes and dogs diagnosed with keratoconjunctivitis sicca. Methods: One-hundred fifty-six eyes of 78 dogs, 88 normal eyes, and 68 eyes diagnosed with keratoconjunctivitis sicca were included in the study. The tests were performed in the following sequence: Schirmer tear test 1 was used to allocate the dogs to the normal or keratoconjunctivitis sicca group, followed by the strip meniscometry test and tear film breakup time measurement. The results (mean ± standard deviation) of the tests in the normal group were as follows: Schirmer tear test 1, 22.75 ± 3.88 mm/min; strip meniscometry test, 10.01 ± 2.35 mm/5 sec; and tear film breakup time, 25.82 ± 5.47 sec. In the keratoconjunctivitis sicca group, the results were as follows: Schirmer tear test 1, 6.10 ± 4.44 mm/min; strip meniscometry test, 3.03 ± 2.62 mm/5 sec; and tear film breakup time, 10.78 ± 4.23 sec. The Spearman correlation coefficient in the keratoconjunctivitis sicca group was very high, with a significant difference between the strip meniscometry test and Schirmer tear test 1 (r=0.848, p<0.001), and moderate and significant between the strip meniscometry test and tear film breakup time (r=0.773, p<0.001). The cutoff for the strip meniscometry test for keratoconjunctivitis sicca was 7.0 mm/5 sec. Keratoconjunctivitis sicca was suspected when the values were <10 mm/5 sec. This study provided strip meniscometry test values from dogs with normal eyes and eyes with keratoconjunctivitis sicca, with high sensitivity and specificity compared with those of the Schirmer tear test 1. In the future, the strip meniscometry test may be another important quantitative test and could complement the gold standard Schirmer tear test for the diagnosis of keratoconjunctivitis sicca in dogs, an excellent animal model for the study of the disease.

Long-lasting otic medications may be a rare cause of neurogenic keratoconjunctivitis sicca in dogs.

To characterize the clinical course and long-term prognosis of a suspected novel cause of neurogenic keratoconjunctivitis sicca (nKCS) secondary to florfenicol, terbinafine hydrochloride, mometasone furoate (Claro and Neptra) or florfenicol, terbinafine, betamethasone acetate (Osurnia). 29 client-owned dogs. Online survey and word-of-mouth recruitment were conducted to identify dogs that developed clinical signs of nKCS after application of otitis externa medication containing terbinafine and florfenicol. A retrospective analysis of medical records of dogs meeting inclusion criteria was then conducted. Included dogs had onset of clinical signs of nKCS within 1 day after application of otitis externa medications containing terbinafine and florfenicol and had documentation of low Schirmer tear test value (< 15 mm/min) of affected eyes. 29 dogs with medical records available for review met the inclusion criteria. Documented return of clinically normal tear production was identified in 24 of 29 dogs, with a median time from application of ear medication to documented return of clinically normal tear production of 86 days (range, 19 to 482 days). A corneal ulcer was diagnosed in 68% (20/29). Multivariable Cox regression analysis showed being referred to an ophthalmologist (P = .03) and having a deep ulcer (P = .02) were associated with a longer time to documentation of Schirmer tear test ≥ 15 mm/min. Dogs that developed nKCS within 1 day after application of otitis externa medications containing terbinafine and florfenicol had a good prognosis for return of normal tear production within 1 year.

Study shows there are lots of dry eyes in the house.

Georgina Mills reports on research that examines the frequency and breed-related risk factors for keratoconjunctivitis sicca in dogs.

Keratoconjunctivitis sicca in dogs under primary veterinary care in the UK: an epidemiological study.

To estimate the frequency and breed-related risk factors for keratoconjunctivitis sicca (KCS) in dogs under UK primary veterinary care. Analysis of cohort electronic patient record data through the VetCompass Programme. Risk factor analysis used multivariable logistic regression. There were 1456 KCS cases overall from 363,898 dogs [prevalence 0.40%, 95% confidence interval (CI) 0.38-0.42] and 430 incident cases during 2013 (1-year incidence risk 0.12%, 95% CI 0.11-0.13). Compared with crossbreds, breeds with the highest odds ratio (aOR) for KCS included American cocker spaniel (aOR 52.33: 95% CI 30.65-89.37), English bulldog (aOR 37.95: 95% CI 26.54-54.28), pug (aOR 22.09: 95% CI 15.15-32.2) and Lhasa apso (aOR 21.58: 95% CI 16.29-28.57). Conversely, Labrador retrievers (aOR 0.23: 95% CI 0.1-0.52) and border collie (aOR 0.30: 95% CI 0.11-0.82) had reduced odds. Brachycephalic dogs had 3.63 (95% CI 3.24-4.07) times odds compared to mesocephalics. Spaniels had 3.03 (95% CI 2.69-3.40) times odds compared to non-spaniels. Dogs weighing at or above the mean bodyweight for breed/sex had 1.25 (95% CI 1.12-1.39) times odds compared to body weights below. Advancing age was strongly associated with increased odds. Quantitative tear tests are recommended within yearly health examinations for breeds with evidence of predisposition to KCS and might also be considered in the future within eye testing for breeding in predisposed breeds. Breed predisposition to KCS suggests that breeding strategies could aim to reduce extremes of facial conformation.

Efficacy of adjunctive therapy using Vizoovet in improving clinical signs of keratoconjunctivitis sicca in dogs: A pilot study.

To assess the clinical safety and efficacy of adjunctive therapy using Vizoovet to ameliorate clinical signs of keratoconjunctivitis sicca (KCS) in dogs. Twenty client-owned dogs. Canine patients diagnosed with KCS were enrolled in this prospective study. Patients were randomly selected to receive either Vizoovet or GenTeal drops twice daily in addition to twice daily tacrolimus 0.03% solution. Data were collected from only one eye of each patient and included STT-1, IOP, TFBUT, and results of objective clinical scoring performed by pet owners. Statistical significance was set at P≤.05. In all, 20 dogs (20 eyes) were enrolled in this prospective randomized study. Females (n=12; 60%) outnumbered males (n=8; 40%) and all dogs were spayed/neutered. Mean age of all dogs was 10.6±3.79years. In both treatment groups, the improvement in STT-1 values over the course of the study was significant (P=.002). When comparing the STT-1 improvements between groups, no significance was found (P=.78). In both groups, the improvement in TFBUT was significant (P=.0018). When comparing the TFBUT improvements between groups, no significance was found (P=.14). Squinting, rubbing, ocular discharge, and medication administration scores all significantly improved throughout the course of the study; however, they did not differ significantly between groups. Throughout the study, no adverse side effects were noted clinically or by the pet owner in either group. Adjunctive treatment with Vizoovet was as safe and effective as GenTeal drops at improving clinical signs of dry eye in dogs.

Clinical-dosimetric relationship between lacrimal gland dose and keratoconjunctivitis sicca in dogs with sinonasal tumors treated with radiation therapy.

BackgroundDogs with sinonasal tumor can develop keratoconjunctivitis sicca (KCS) after radiation therapy (RT). In humans, the incidence of xerophtalmia is associated with the mean radiation dose received by the ipsilateral lacrimal gland (LG).Hypothesis/ObjectivesThe eyes receiving a higher mean LG dose are more likely to develop KCS. The aim of the study was to determine a starting threshold dose to use as dose constraint for intensity‐modulated radiation therapy (IMRT).AnimalsDogs with nasal tumors treated with RT between August 2013 and December 2016.MethodsCase control retrospective study of dogs with sinonasal tumor treated with 42 Gray (Gy) in 10 fractions using IMRT. Dogs were included if development of KCS after RT was documented (cases) or adequate follow‐up information with Schirmer tear test (STT) result for ≥6 months after RT was available (controls). Lacrimal glands were contoured and dose distribution was calculated using the original treatment plan to determine prescribed doses to LGs.ResultsTwenty‐five dogs were treated with RT and 5 dogs (20%) developed KCS. Fifteen dogs met the inclusion criteria including 5 unilateral KCS and 10 control dogs, resulting in 5 KCS eyes and 25 control eyes. KCS developed at a median of 111 days (84‐122) after 1st RT. The mean LG dose reached using a 4.2 Gy per fraction was 33.08 Gy (range: 23.75‐42.33) for KCS eyes and 10.33 Gy (1.8‐24.77) for control eyes (P < .001). The minimum LG mean dose for developing KCS was 23.75 Gy. No eyes that received a mean LG dose <20 Gy developed KCS versus 5/7 (71%) developed with >20 Gy.Conclusion and Clinical ImportanceContouring and applying a dose constraint on LGs should be performed when using IMRT in dogs with sinonasal tumors to reduce the risk of KCS.

Effect of Autologous Plasma Treatment on the Cornea Regeneration with Keratoconjunctivitis Sicca in Dogs

Effect of Autologous Plasma Treatment on the Cornea Regeneration with Keratoconjunctivitis Sicca in Dogs

Reduction in the inflammatory markers CD4, IL-1, IL-6 and TNFα in dogs with keratoconjunctivitis sicca treated topically with mesenchymal stem cells

Keratoconjunctivitis sicca (KCS) is of predominantly immune-mediated origin. Dogs are an excellent model for understanding this disease, as the origin of KCS in dogs is like that in humans. The objective of this study was to localize and quantify immunological markers, such as CD4 lymphocytes, interleukin (IL)-1, IL-6 and tumor necrosis factor alpha (TNFα), before and after topical treatment with mesenchymal stem cells (MSCs). Twenty-two dogs positive for KCS were topically treated with 50 μL (1 × 106 MSCs) in the conjunctival sac and were evaluated for 6 months. The levels of the markers CD4, IL-6, IL-1 and TNFα were analyzed in conjunctival biopsy and cytology of the third eyelid gland by immunohistochemistry and immunocytochemistry. The results showed that before treatment, there was marked expression of all the markers (CD4, IL-6, IL-1 and TNFα), and after 6 months, there were significant (p < .05) reductions in the expression levels of all the markers. These results demonstrated that topical MSC treatment promotes a significant decrease in the expression levels of these inflammatory markers and could be used as adjuvant therapy in the treatment of KCS in dogs and humans. In addition, these markers can be excellent tools for diagnosing and analyzing the progression of KCS.

The Effect of Periocular Fatty Acids and 0.15% Hyaluronate Eye Drops Application on Keratoconjunctivitis Sicca in Dogs: An Exploratory Study

The aim of this exploratory study was to evaluate the efficacy of a periophthalmic cream of a pool of fatty acids (FAG®) in association with 0.15% hyaluronate eye drops in alleviating the clinical symptoms of keratoconjunctivitis sicca (KCS) in a case series of dogs.The study was conducted on 10 dogs diagnosed with idiopathic KCS. All dogs had been previously treated with topical tobramycin alone, which had been ineffective in improving clinical signs. The affected eyes were treated with 2 applications daily of a periophthalmic cream of FAG® and 1 drop 3 times a day of 0.15% of hyaluronate eye drops for 8 weeks. Schirmer tear test I (STT I) values were recorded and ocular signs (conjunctival hyperemia, ocular discharge, corneal opacity, vascularization and pigmentation, and discomfort level) were collected, scored on a 3-point scale (grade 0, grade 1, and grade 2). Differences between scores and STT data recorded at baseline and at 8 weeks of therapy were statistically analysed. The effect of treatment was pronounced (increase in STT values by more than 4 mm/min, no signs of inflammation) in 8/18 eyes; moderate (increase in STT values of 3-4 mm/min or mild improvement in signs of corneal/conjunctival inflammation) in 3/18 eyes; and unsatisfactory in 7 of 18 eyes. Median of STT values significantly improved compared with baseline levels, while statistically significant decreases in clinical-sign scores of conjunctival hyperemia, ocular discharge, and discomfort were recorded. However, in moderate and advanced stages, reduction of neovascularization or corneal pigmentation was not observed throughout the treatment period. No noticeable adverse reactions were recorded. Preliminary results indicate that the application of periocular FAG and topical 0.15% hyaluronate eye drops may be a suitable treatment for KCS in dogs in selected cases. A larger comparative study is necessary to further confirm these findings.

EFFECTS OF AUTOLOGOUS SERUM EYE DROPS FOR TREATMENT OF KERATOCONJUNCTIVITIS SICCA IN DOGS

In humans, autologous serum (AS) eye drops has been applied for the treatment of refractory keratoconjunctivitis sicca (KCS) for several decades. However, there are few researches to investigate the AS eye drops in dogs with KCS. The objective of this study was to evaluate the effects of AS eye drops on treatment of KCS in dogs. Eighteen eyes of ten client-owned dogs with refractory KCS were used in this study. Schirmer tear test (STT), tear film breakup time (TBUT), fluorescein (FL) staining score, and Rose Bengal (RB) staining score were used to measure the status of cornea prospectively at baseline and 1–3 months after treatment. Additionally, the results were further stratified by their STT value, sex, and age. The results indicated that the mean TBUT, FL staining score, and RB staining score were significantly improved after treatment except STT. In 18 eyes, 77.8% eyes had decreased mucopurulent ocular discharge and 38.9% eyes got wet. Besides, both TBUT and RB staining score were significantly improved in a subgroup of dogs with age less than 9 years old. As far as we know, this study is the first trial to determine the efficacy and safety of 20% AS eye drops for cKCS. In conclusion, AS eye drops seemed to be effective and safe for dogs with KCS, and it could improve tear film stability, ocular surface health, and subjective clinical symptoms, especially in dogs younger than 9 years old.

Clinical evaluation of topical tacrolimus ointment usage in different stages of keratoconjunctivitis sicca in dogs

This study was conducted to investigate the effect of topical tacrolimus (0.1%) ointment in stimulating tear production in dogs with keratoconjunctivitis sicca (KCS). Thirty-six dogs (58 eyes) diagnosed with KCS were included in this study. KCS was grouped as early (E, n = 21 eyes), late (L, n = 21 eyes), and reflex tear due to corneal ulceration (R, n = 16 eyes) based on Schirmer tear test (STT) readings. The dogs in each group were randomly allotted treatment with either tacrolimus 0.1% ointment applied once daily (ET, n = 11 eyes; LT, n = 10 eyes; RT, n = 6 eyes) or cyclosporine (CsA) 0.05% eye drops instilled five times daily (EC, n = 10 eyes; LC, n = 11 eyes; RC, n = 10 eyes) for 2 months. The efficacy of the treatments was evaluated and comparison was made based on complete ophthalmic examination and a scoring system for various parameters like menace reflex, palpebral reflex, pupillary light reflex, conjunctival hyperemia, ocular discharge, corneal clarity, corneal ulceration, corneal vessel length, corneal vessel density, corneal pigmentation area, corneal pigmentation density, STT readings, fluorescein dye test, and Rose Bengal dye test. The effect of treatment was evaluated on day 15, 30, and 60 after treatments. Good quality digital photographs from a fixed distance were taken at each interval to aid subjective evaluation. Data were analyzed using one-way and repeated-measures ANOVA followed by Tukey?s HSD test, Wilcoxon signed rank test, and Kruskal?Wallis test followed by Dunn?s test to identify significant interactions. The level of significance was set to P < 0.05. Improvement in menace reflex and pupillary light reflex was observed in both treatment groups. Conjunctival hyperemia and ocular discharge decreased significantly after treatment with both of the drugs. There was no significant difference in improvement in tear production between treatment groups but tacrolimus 0.1% ointment significantly arrested the progression of pigments. The study concluded that both tacrolimus 0.1% ointment and CsA 0.05% eye drops improve tear production in KCS-affected dogs. Topical tacrolimus 0.1% ointment effectively arrests the progression of pigmentation compared to CsA 0.05% eye drops in KCS-affected dogs.

Allogeneic Mesenchymal Stem Cell Transplantation in Dogs With Keratoconjunctivitis Sicca.

Keratoconjunctivitis sicca (KCS) is a dysfunction in tear production associated with clinical signs, which include conjunctival hyperemia, ocular discharge, discomfort, pain, and, eventually, corneal vascularization and pigmentation. Immunosuppressive drugs are routinely administrated for long periods to treat KCS but with side effects and limited results. Evaluation of the clinical benefits of intralacrimal transplantation of allogeneic mesenchymal stem cells (MSCs) in dogs with mild-moderate and severe KCS was done. A total of 24 eyes with KCS from 15 dogs of different breeds were enrolled in the present study. A single transplantation of MSCs (1 × 106) directly into lacrimal glands (dorsal and third eyelid) was performed. The Schirmer tear tests (STTs) and ocular surface improvements were used to assess short- and long-term effects of these cells. The STTs were carried out on day 0 (before MSCs transplantation) and on days 7, 14, 21, and 28, as well as 6 and 12 months after MSC transplantation. Our data demonstrate that allogeneic MSC transplantation in KCS dogs is safe since no adverse effects were observed immediately after transplantation and in short- and long-term follow-ups. A statistically significant increase in the STT and ocular surface improvements was found in all eyes studied. In all the eyes with mild-moderate KCS, STT values reverted to those of healthy eyes, while in eyes with severe KCS, although complete reversion was not found, there was improvement in tear production and in other clinical signs. Our study shows that a single dose of a low number of MSCs can be used to treat KCS in dogs. In contrast to immunosuppressive drug use, MSC transplantation has an effect over a long period (up to 12 months), even after a single administration, and does not require daily drug administration.

Ocular lubricants: what is the best choice?

ABSTRACT: Ocular lubricants are used to supplement one or more layers of the lacrimal film. They are often prescribed to treat keratoconjunctivitis sicca (KCS) and other diseases of ocular surface in humans. These lubricants may also protect the ocular surface and promote epithelial regeneration. The active component of ocular lubricants is the lubricating agent. The key properties of different lubricating agents are the electrolyte composition, osmolarity, and addition of preservatives. Although lacrimomimetics are not typically used to treat KCS in dogs, they can be used as an adjunctive therapy. Knowledge of the properties of lacrimomimetics will help in making the appropriate therapeutic choice.

Immune-mediated keratoconjunctivitis sicca in dogs: current perspectives on management.

Keratoconjunctivitis sicca (KCS) is a frequent canine ophthalmic disease, resulting from the deficiency of one or more elements in the precorneal tear film. There are different known causes of KCS in dogs, including congenital, metabolic, infectious, drug induced, neurogenic, radiation, iatrogenic, idiopathic, and immune mediated, though the last one is the most prevalent form in dogs. Initially, clinical signs of KCS include blepharospasm caused by ocular pain, mucoid to mucopurulent ocular discharge, and conjunctival hyperemia; secondary bacterial infection may also occur, with chronicity, corneal epithelial hyperplasia, pigmentation, neovascularization, and corneal ulceration. The diagnosis of KCS is based on the presence of consistent clinical signs and measurement of decreased aqueous tear production using the Schirmer tear test. Therapy is based on administering the following topical drugs: ocular lubricant, mucolytics, antibiotics, corticosteroids, pilocarpine, and immunomodulators. These last drugs (eg, cyclosporine, pimecrolimus, and tacrolimus) have immunosuppressive activity and stimulate tear production. Furthermore, the nerve growth factor is a new subject matter of the research. Although these therapies are advantageous, stimulation of natural tear production seems to provide the highest recovery in clinical signs and prevention of vision loss. The goal of the following article is to describe the recent developments about KCS in dogs emphasizing the use of new therapies.

Cyclosporine A (CsA) treatment of chronic autoimune-mediated keratoconjunctivitis sicca in dogs

The paper is a five year retrospective study of the efficacy of 0.2% Cyclosporine A eye cream in the treatment of chronic autoimmunemediated KCS in dogs. 114 dogs of 32 breeds, both sexes, and different ages with chronic autoimmune-mediated KCS were treated with 0.2% Cyclosporine A in the form of eye cream (Optimmune®, Schering - Plough Animal Health) applied to the lower lid conjunctiva at a dose of 6 mm length of the cream strip every 12 hours, during 90 days. Dogs treated with CsA had an improved STT score, specially dogs which had STT values >5 mm/min at the start. Improvement of the clinical picture and healing of superficial corneal lesions were also recorded.

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

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). 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. 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). 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.

The Pharmacologic Assessment of A Novel Lymphocyte Function-Associated Antigen-1 Antagonist (SAR 1118) for the Treatment of Keratoconjunctivitis Sicca in Dogs

Keratoconjunctivitis sicca (KCS) is characterized by inflammation and decreased production of tears containing increased levels of cytokines. The release occurs in the setting of conjunctival and lacrimal gland inflammation, potentially mediated by the interaction between lymphocyte function-associated antigen (LFA)-1, a cell surface protein found on lymphocytes, and its cognate ligand intercellular adhesion molecule (ICAM)-1. SAR 1118 is a novel LFA-1 antagonist and may be an effective therapeutic agent for the treatment of KCS. The following studies were performed to assess the in vitro activity of SAR 1118 and to evaluate the clinical efficacy of topical SAR 1118 for the treatment of idiopathic canine KCS. Pharmacodynamics were assessed by measuring the ability of SAR 1118 to inhibit Jurkat T-cell binding with recombinant human ICAM-1 and to inhibit cytokine release from human peripheral blood mononuclear cells (PBMCs) stimulated by staphylococcal enterotoxin B. For the assessment of clinical efficacy, 10 dogs diagnosed with idiopathic KCS were treated with SAR 1118 1% topical ophthalmic solution three times daily for 12 weeks. Schirmer's tear test (STT) was used to measure tear production. SAR 1118 demonstrated concentration-dependent inhibition of Jurkat T-cell attachment, inhibition of lymphocyte activation, and release of inflammatory cytokines, particularly the Th1, Th2, and Th17 T-cell cytokines IFN-γ, IL-2, and IL-17F, respectively. Mean STT values increased from 3.4 mm during week 1 to 5.8 mm at week 12 (P < 0.025). No SAR 1118-related adverse events were observed. SAR 1118 appears to be an effective anti-inflammatory treatment for KCS. Additional studies are warranted to establish the efficacy of SAR 1118 for the treatment of KCS in humans.

犬の乾性角結膜炎に対する自家製シクロスポリン点眼液の臨床評価

犬の乾性角結膜炎に対する自家製シクロスポリン点眼液の臨床評価