Phenotypic characterization of complete CSNB in the inbred research beagle: how common is CSNB in research and companion dogs?

PURPOSE: Although congenital stationary night blindness (CSNB) has been described in a Japanese beagle dog research colony, certain clinical correlates with human CSNB have not yet been described, nor has an estimate of frequency of the condition been made in inbred and outbred beagle populations. METHODS: A beagle with CSNB obtained from a commercial research dog supplier in the USA and matched control dogs (n = 3) underwent examination, refraction, ocular imaging, assessment of visual navigation ability and detailed electroretinography (ERG). Retrospective review of ERGs in two independent groups of inbred (n = 15 and 537, respectively) and one group of outbred dogs (n = 36) was used to estimate CSNB frequency in these populations. RESULTS: In the affected dog, there were absent dark-adapted b-waves in response to dim-light flashes, severely reduced dark-adapted b-waves in response to bright-light flashes, and normal light-adapted b-waves with a-waves that had broadened troughs. Long-flash ERGs confirmed a markedly reduced b-wave with a preserved d-wave, consistent with cone ON-bipolar cell dysfunction. There was evidence of normal rod photoreceptor a-wave dark adaptation, and rapid light adaptation. In the wider beagle populations, five inbred beagles had a b/a wave ratio of < 1 in dark-adapted bright-flash ERG, whereas no outbred beagles had ERGs consistent with CSNB. CONCLUSIONS: The identified dog had clinical findings consistent with complete type CSNB, similar to that described in the Japanese colony. CSNB appears to be a rare disorder in the wider beagle population, although its detection could confound studies that use retinal function as an outcome measure in research dogs, necessitating careful baseline studies to be performed prior to experimentation.

The effects of topical aqueous sirolimus on tear production in normal dogs and dogs with refractory dry eye.

PURPOSE: To evaluate the effect of twice daily aqueous 0.02% sirolimus drops on tear production in normal dogs and dogs with refractory keratoconjunctivitis sicca (KCS). METHODS: Two groups of dogs were studied. Ten normal dogs with no signs of ocular disease were administered topical 0.02% sirolimus ophthalmic solution in right eye, and a vehicle control in the left eye twice daily for 4 weeks. Complete ophthalmic examinations, including Schirmer tear test were performed weekly. Eighteen dogs with refractory KCS were randomly assigned to receive 0.02% sirolumus ophthalmic solution or 0.02% tacrolimus ophthalmic solution twice daily. Complete ophthalmic examinations were was performed at 2 and 6 weeks following treatment. RESULTS: Tear production in the sirolimus-treated eyes of normal dogs was greater when compared to vehicle controls with a mean difference over all time points of 3.46 mm (95% CI 1.17, 5.75; P = 0.006). After 4 weeks of treatment, the mean difference was 5 mm (95% CI 1.95, 8.05; P = 0.002). In dogs with refractory dry eye, 37.5% of eyes treated with sirolimus exhibited increased tear production >4 mm/min after 6 weeks of treatment, compared to 20% of eyes receiving tacrolimus (P = 0.433). One normal dog experienced topical irritation to both sirolimus and vehicle-treatment. Side effects were not reported in any treated eyes with chronic KCS. CONCLUSION: Topical 0.02% sirolimus might be an alternative treatment for canine patients with keratoconjunctivits sicca. The drug appears safe when applied topically in an aqueous suspension for up to 6 weeks. While initial results are promising, further studies are warranted.

Causes of endogenous uveitis in cats presented to referral clinics in North Carolina.

OBJECTIVE: To investigate the causes of endogenous uveitis in cats presenting to referral ophthalmology clinics in North Carolina. PROCEDURE: Medical records of cats diagnosed with endogenous uveitis at North Carolina State University's College of Veterinary Medicine (NCSU-CVM) or Animal Eye Care Associates of Cary, NC between 2003 and 2015 were reviewed. Inclusion criteria were cats that had complete diagnostic workups, including clinical, clinicopathological, serological, and histopathological data, as well as imaging modalities. Serology was consistently completed for feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), feline coronavirus (FCoV), Toxoplasma gondii, and Bartonella spp. RESULTS: One hundred and twenty cats met the inclusion criteria. Seroprevalence of FeLV (2.7%), FIV (7.3%), FCoV (34.7%), T. gondii (23.7%), and Bartonella spp. (43.2%) was observed, with a combined seroprevalence of 59.2%. Nineteen cats (15.8%) were diagnosed with feline infectious peritonitis (FIP) based on clinical, hematological, serological, histopathological, and necropsy findings. The average age of all cases was 7.62 years, while the average age of cats diagnosed with FIP was 1.82 years. Neoplasia was diagnosed in six cats (5.0%). No underlying etiology was found in 49 cats (40.8%). CONCLUSIONS: Both idiopathic and neoplastic causes of uveitis were less prevalent than previously reported in studies, while seropositivity was higher than previously reported for the study area. This may be due to improved diagnostic capabilities or that cats with infectious disease were more likely to be referred. Because of the high prevalence of FIP, young cats with uveitis should be evaluated for hyperglobulinemia and FCoV serology should be performed as minimal diagnostics.

Efficacy of COX-2 inhibitors in controlling inflammation and capsular opacification after phacoemulsification cataract removal.

OBJECTIVE: To evaluate the efficacy of 0.9% bromfenac (Xibrom™) or a celecoxib-impregnated intraocular lens (celecoxib-IOL) compared with 1% prednisolone acetate (PA) in controlling postoperative inflammation and posterior capsule opacification (PCO). ANIMAL STUDIED: Fifty-nine dogs undergoing cataract extraction by phacoemulsification. PROCEDURE: Bilateral patients received bromfenac or celecoxib-IOL plus PA in one eye, and PA in the contralateral eye. Unilateral patients received bromfenac or PA. Complete ophthalmic examination including tonometry, slit-lamp grading of flare and PCO, and digital image acquisition for masked PCO evaluation was performed within 24 h and 1, 4, 12, 24, and 56 weeks following surgery. RESULTS: Celecoxib-IOL/PA-treated eyes had significantly less flare than PA-treated eyes, which had significantly less flare than bromfenac-treated eyes 24 h postoperatively. There was no significant difference in intraocular pressure (IOP) postoperatively, or at 1, 24, or 56 weeks. Celecoxib-IOL/PA-treated eyes had significantly lower IOP measurements than bromfenac and PA-treated eyes at 4 and 12 weeks. There was no significant difference in PCO level between groups using slit-lamp biomicroscopy at any time point. Masked evaluation of digital images revealed significantly less PCO in celecoxib-IOL/PA- vs. bromfenac-treated eyes at 4 weeks, and in bromfenac- vs. PA-treated eyes at 56 weeks. CONCLUSIONS: Eyes receiving celecoxib-IOL/PA had better initial control of inflammation. Bromfenac was equally effective compared with PA in controlling inflammation. There was no association between COX-2 inhibitor administration and ocular hypertension. Celecoxib-IOL/PA-treated eyes showed better initial control of PCO (up to 12 weeks), while eyes receiving bromfenac had better long-term control of PCO (56 weeks).

Comparison of capsular opacification and refractive status after placement of three different intraocular lens implants following phacoemulsification and aspiration of cataracts in dogs.

OBJECTIVE: To evaluate the effect of lens design and biomaterial on formation of posterior capsular opacification (PCO) and refractive correction. Animals studied Sixty dogs undergoing bilateral phacoemulsification for mature or diabetic cataracts. PROCEDURES: One randomly selected eye received a rounded edge 41D polymethyl-methacrylate (PMMA) intraocular replacement lens (IOL) and the contralateral eye received either a squared edge 41D hydrophilic acrylic IOL (n = 35) or a squared edge 40D hydrophobic acrylic IOL (n = 25). At the (mean = 79 day) reexamination period, PCO was graded using direct slit-lamp observation and by masked observer evaluation of digital images of the IOLs. Streak retinoscopy and B-mode ultrasound were performed at this period. RESULTS: The PCO score via direct slit-lamp was significantly lower for the hydrophilic acrylic IOL when compared to the PMMA IOL. Masked observer evaluation of digital images revealed that the acrylic IOLs had lower but generally not statistically significant PCO scores than the PMMA IOLs. Streak retinoscopy showed that the PMMA IOL was significantly closer to emmetropia (+0.44 D) when compared to either the hydrophilic acrylic (+0.96 D) or the hydrophobic acrylic (+1.2 D) IOLs. B-mode ultrasonography revealed the center of the hydrophilic acrylic IOL is 0.31 mm closer to the retina and the center of the hydrophobic acrylic IOL is 0.63 mm further from the retina when compared to the center of the PMMA to retina distance. CONCLUSIONS: Square edged foldable acrylic IOLs show a predisposition towards generating slightly less PCO than round edged PMMA IOLs in the early postoperative period, however, both acrylic IOLs had greater persistent hyperopia than the PMMA IOLs.

Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa.

BACKGROUND: The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina. METHODS: Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months. RESULTS: Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Müller cells were found in five of six eyes. Neuronal connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly. CONCLUSIONS: Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated graft counteracts this effect and rescues rods from degeneration.

Experimental Ehrlichia canis infection in the dog does not cause immunosuppression.

A carrier state develops in some Ehrlichia canis-infected dogs due to ineffective host defenses. The subsequent development of immune-mediated diseases or opportunistic infections in chronic ehrlichiosis suggests dysregulation of immunity; however, the immunobiology of this infection has not been well characterized. In this study, eight dogs were infected with E. canis, and changes in seroreactivity, serum immunoglobulin (Ig) concentrations, peripheral blood T cell subsets, lymphocyte blastogenesis (LBT), and lymphokine-activated killer (LAK) activity were evaluated over 4 months. Infection, which was documented by seroconversion, polymerase chain reaction, and blood culture, caused self-limiting fever and thrombocytopenia. Infected dogs developed an anti-E. canis antibody response but were not immune to re-infection. Serum IgM, IgG, and IgA concentrations were unaffected by E. canis. The percentage of circulating CD4(+) T cells was similar in uninfected and infected dogs at all points. Infected dogs developed a CD8(+) lymphocytosis 6 weeks after inoculation that subsequently subsided, despite organism persistence. Functional defects of cell-mediated immunity, measured as suppression of LAK activity or mitogen-driven LBT, were not observed. These results suggest that immune responses are not grossly impaired in young dogs during the first several months following experimental E. canis infection.

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) < or = 10 mm/min and clinical signs of dry eye]. Eyes with marginally decreased STT (11 < or = 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 < or = 10 mm/min; 2) 28 eyes (21 dogs) naïve to tear stimulation therapy with initial STT 11 < or = 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 (< or = 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.

Comparison of histologic lesions of endophthalmitis induced by Blastomyces dermatitidis in untreated and treated dogs: 36 cases (1986-2001).

OBJECTIVE: To compare prevalence of organisms and histologic changes in eyes from dogs with blastomycosis that were either untreated or undergoing treatment with itraconazole. DESIGN: Retrospective study. ANIMALS: 36 dogs with endophthalmitis associated with blastomycosis. PROCEDURE: Signalment, results of ophthalmic examination, and duration of treatment with itraconazole were extracted from medical records. Histologic sections from eyes were examined for prevalence and viability (ie, budding) of fungal organisms. A scoring system was devised to assess the degree of inflammation. RESULTS: Clinically, all eyes were blind and had signs of severe endophthalmitis. Histologically, the type and degree of inflammation and prevalence of Blastomyces dermatitidis were not significantly different between dogs treated with itraconazole and untreated dogs or among groups of dogs treated for different time periods (4 to 14, 15 to 28, or 29 to 72 days). Replication of the organisms in vascular tissues as well as avascular spaces in the eyes was similar in treated and untreated dogs. Lens rupture was seen in 12 of 29 (41%) eyes. CONCLUSIONS AND CLINICAL RELEVANCE: Persistence of inflammation in eyes of dogs with naturally occurring blastomycosis is likely attributable to the continued presence of B. dermatitidis, regardless of the duration of treatment with itraconazole. Lens capsule rupture, a common and previously unreported histologic finding, may contribute to cataract formation and continued inflammation.