Evaluation of transconjunctival thermal electrocautery for treatment of canine distichiasis: 88 eyelids (2013-2016).

OBJECTIVE: To describe a successful, simple treatment for canine distichiasis. ANIMALS STUDIED: Client-owned dogs presenting to Veterinary Specialty and Emergency Center, Levittown, Pennsylvania. PROCEDURE: Retrospective analysis of medical records for canine patients that underwent transconjunctival thermal electrocautery treatment (TCEC) for distichiasis alone or with concurrent eyelid surgery between 2013 and 2016. Fifty eyes of 26 dogs (n = 88 eyelids) were included in the study. Sixty-five eyelids (74%) were treated for distichia only, while 23 eyelids (26%) underwent concurrent eyelid surgery. Successful treatment was defined as resolution of clinical signs attributable to distichiasis. Forty-eight of 50 eyes (96%) were successfully treated with a single TCEC treatment (mean follow-up 187 ± 222 days). Sixty-one of 88 eyelids (69%) had no distichia at any follow-up time. Twenty-two eyelids (25%) had recurrence at or near a previously treated site (mean 150 ± 152 days). Of the eyes with recurrent distichia, all but 2 (91%) remained asymptomatic, requiring no further treatment. One dog with extensive TCEC treatment had significant recurrence on all eyelids requiring retreatment that resulted in focal entropion of 1 eyelid. Transient eyelid margin pigment loss and mild-to-moderate eyelid swelling were noted in all treated eyelids postoperatively. Suspected treatment site infection occurred 2 days postoperatively in 2/50 eyes (4%) of 1 patient. Two of 10 eyes (20%) with extensive eyelid treatment developed qualitative tear film deficiency OU (554 days postoperatively) and responded to topical tear stimulant therapy. CONCLUSION: TCEC is a successful, simple treatment for canine distichiasis.

Canine CNGA3 Gene Mutations Provide Novel Insights into Human Achromatopsia-Associated Channelopathies and Treatment.

Cyclic nucleotide-gated (CNG) ion channels are key mediators underlying signal transduction in retinal and olfactory receptors. Genetic defects in CNGA3 and CNGB3, encoding two structurally related subunits of cone CNG channels, lead to achromatopsia (ACHM). ACHM is a congenital, autosomal recessive retinal disorder that manifests by cone photoreceptor dysfunction, severely reduced visual acuity, impaired or complete color blindness and photophobia. Here, we report the first canine models for CNGA3-associated channelopathy caused by R424W or V644del mutations in the canine CNGA3 ortholog that accurately mimic the clinical and molecular features of human CNGA3-associated ACHM. These two spontaneous mutations exposed CNGA3 residues essential for the preservation of channel function and biogenesis. The CNGA3-R424W results in complete loss of cone function in vivo and channel activity confirmed by in vitro electrophysiology. Structural modeling and molecular dynamics (MD) simulations revealed R424-E306 salt bridge formation and its disruption with the R424W mutant. Reversal of charges in a CNGA3-R424E-E306R double mutant channel rescued cGMP-activated currents uncovering new insights into channel gating. The CNGA3-V644del affects the C-terminal leucine zipper (CLZ) domain destabilizing intersubunit interactions of the coiled-coil complex in the MD simulations; the in vitro experiments showed incompetent trimeric CNGA3 subunit assembly consistent with abnormal biogenesis of in vivo channels. These newly characterized large animal models not only provide a valuable system for studying cone-specific CNG channel function in health and disease, but also represent prime candidates for proof-of-concept studies of CNGA3 gene replacement therapy for ACHM patients.

Transient photoreceptor deconstruction by CNTF enhances rAAV-mediated cone functional rescue in late stage CNGB3-achromatopsia.

Achromatopsia is a genetic disorder of cones, and one of the most common forms is a channelopathy caused by mutations in the ß-subunit, CNGB3, of the cone cyclic nucleotide-gated (CNG) channel. Recombinant adeno-associated virus of serotype 5 (rAAV5)-mediated gene transfer of human CNGB3 cDNA to mutant dog cones results in functional and structural rescue in dogs <0.5 years of age, but treatment is minimally effective in dogs >1 year. We now test a new therapeutic concept by combining gene therapy with the administration of ciliary neurotrophic factor (CNTF). Intravitreal CNTF causes transient dedifferentiation of photoreceptors, a process called deconstruction, whereby visual cells become immature with short outer segments, and decreased retinal function and gene expression that subsequently return to normal. Cone function was successfully rescued in all mutant dogs treated between 14 and 42 months of age with this strategy. CNTF-mediated deconstruction and regeneration of the photoreceptor outer segments prepares the mutant cones optimally for gene augmentation therapy.

Successful treatment of distichiasis in a cat using transconjunctival electrocautery.

A 2-year-old male castrated Domestic Short-haired cat presented to the Ophthalmology Service at the Matthew J. Ryan Veterinary Hospital at the University of Pennsylvania for evaluation of chronic bilateral ocular discharge and blepharospasm. Initial ophthalmic examination revealed severe conjunctivitis and keratitis and the presence of upper eyelid distichiae bilaterally. Initial therapy for suspected feline herpesviral infection provided moderate, but not complete, resolution of the clinical signs. Over the subsequent year, the cat suffered from recurrent, severe, ulcerative keratitis in both eyes despite appropriate medical therapy. Approximately 13 months after the initial presentation, the distichiae were surgically removed using transconjunctival electrocautery, which resulted in complete resolution of the clinical signs. This report documents bilateral distichiasis in a cat, a condition that is considered rare in this species.

Surgical extraction of an intraocular infection of Parelaphostrongylus tenuis in a horse.

CASE DESCRIPTION: A 4-year-old Hanoverian gelding was evaluated because of a mobile worm-like structure in the right eye. CLINICAL FINDINGS: Ophthalmologic examination of the right eye revealed a white, thin, coiled, mobile parasite, which was presumed to be a nematode, located in the ventral portion of the anterior chamber of the eye; there also were vitreal strands located temporally and inferiorly near the margin of the pupil. Results of ophthalmologic examination of the left eye were unremarkable. TREATMENT AND OUTCOME: The horse was treated with a neomycin-polymyxin B-dexamethasone ophthalmic solution applied topically (1 drop, q 8 h) to the right eye and penicillin V potassium (22,000 U/kg [10,000 U/lb], IV, q 6 h). The horse was anesthetized. A stab incision was made in the cornea, and a viscoelastic agent was infused around the parasite. The parasite was extracted via the incision by use of an iris hook and tying forceps. The horse had an uncomplicated recovery from the procedure and retained vision in the right eye. Gross and microscopic examination was used to identify the parasite as an adult metastrongyloid nematode consistent with a fully developed male Parelaphostrongylus tenuis. CLINICAL RELEVANCE: To the authors' knowledge, this is the first report of intraocular parelaphostrongylosis in a horse. This report provided evidence that vision could be retained after treatment for intraocular P tenuis infection in a horse.

Antimicrobial susceptibility of foodborne pathogens in organic or natural production systems: an overview.

Organic and natural food production systems are increasing in popularity, at least partially because consumers perceive that these niche markets provide healthier and safer food products. One major difference between these niche markets and conventional production systems is the use of antimicrobials. Because antimicrobial agents exert selective pressures for antimicrobial resistance, relating antimicrobial susceptibility of foodborne bacteria to niche market production systems is of interest. Other differences between production systems might also influence the susceptibility of foodborne pathogens. The objective of this review is to compare the impact of food animal production systems on the antimicrobial susceptibility of common foodborne bacterial pathogens. Studies comparing the susceptibility of such pathogens were diverse in terms of geographic location, procedures, species of bacteria, and antimicrobials evaluated; thus, it was difficult to draw conclusions. The literature is highly variable in terms of production type and practices and susceptibility associations, although few studies have compared truly organic and conventional practices. When statistical associations were found between production type and minimum inhibitory concentrations or percentage of isolates resistant for a particular pathogen, the isolates from conventionally reared animals/products were more commonly resistant than the comparison group (organic, antibiotic free, etc.). Therefore, further studies are needed to better assess public health consequences of antimicrobial resistance and food animal production systems, specifically organic or natural versus conventional.