A Transient Developmental Background Finding in the Retina Observed in Neonatal Dogs in Juvenile Toxicology Studies.

In a juvenile toxicology program, an unexpected finding of vacuolation of inner nuclear, ganglion cell, and nerve fiber layers of the retina was observed microscopically in routine Davidson's fixed and hematoxylin and eosin-stained tissue sections of eyes in beagle dogs at approximately 5 weeks of age. There was no necrosis or degeneration of the affected cells and no associated inflammation. Fluorescein angiography revealed no vascular leakage. Optical coherence tomography (OCT) indicated swollen cells in the same layers of the retina as observed at light microscopic examination. Transmission electron microscopy revealed that the retinal vacuolation likely was consistent with intracellular swelling of amacrine, horizontal, and/or bipolar cells of the inner nuclear layer as affected cells had an expanded cytoplasm but contained normal nucleus and organelles. As assessed by animal behavior and full-field electroretinography, the retinal vacuolation appeared to have no impact on visual function. Retinal vacuolation was seen in approximately 40% of dogs at 5 weeks of age using OCT and/or light microscopic examination. Because the change was transient and age related, did not result in degenerative retinal changes, and was not present in dogs older than 5 weeks of age, it was considered a background developmental observation in beagle dogs.

EVALUATION OF THE SURGICAL TRAY OPENING PROCEDURE IN OPERATING SUITES: SYSTEMATIC REVIEW AND RECOMMENDATIONS.

INTRODUCTION: Optimizing the processes involved in managing operating suite activities is an essential element in obtaining gains in efficiency. The early opening of surgical trays could represent an innovative practice for reducing operating times and wait periods between surgeries as well as for increasing the number of daily surgeries. The purpose of this systematic review is to assess the risks and benefits of introducing this practice in the operating room. METHODOLOGY: A systematic literature review was conducted in various indexed databases as well as in the grey literature in order to identify synthesis studies, clinical guidelines and randomized and non-randomized studies on the impact of opening surgical trays early. The following indicators were sought: time lapse between the patient's entrance and the beginning of surgery, the frequency of surgical tray contamination, and the rate of surgical wound infection. RESULTS: An original study and four practice guides were included after a quality assessment. No studies on efficiency gains associated with the early opening of surgical trays were found. The results of the experimental study suggest that the contamination rate for uncovered surgical trays is low for the first 30 minutes (4%) and increases over time with exposure to the ambient air. Most clinical guidelines recommend preparing the surgical instruments as close to the beginning of surgery as possible without specifying the minimum time interval to be respected as well as whether or not the patient is in the operating room. DISCUSSION: The analysis- of all the available data does not make it possible to determine the optimal moment for opening the surgical trays. Given the uncertainty regarding the risks of infection, and the lack of data on the associated benefits, the decision to opt for a change in practice in the opening of surgical trays should be based on a range of factors. An assessment of the data therefore suggests caution and that a feasibility analysis, including a review of all processes and parameters for managing the risks associated with the early opening of surgical trays, be conducted before initiating any changes in the institutions where a change of practice is being sought.

Lymphocytic Microparticles Modulate Angiogenic Properties of Macrophages in Laser-induced Choroidal Neovascularization.

Pathological choroidal neovascularization (CNV) is the common cause of vision loss in patients with age-related macular degeneration (AMD). Macrophages possess potential angiogenic function in CNV. We have demonstrated that human T lymphocyte-derived microparticles (LMPs) exert a potent antiangiogenic effect in several pathological neovascularization models. In this study, we investigated the alteration of proangiogenic properties of macrophages by LMPs treatment in vitro and in vivo models. LMPs regulated the expression of several angiogenesis-related factors in macrophages and consequently stimulated their antiangiogenic effects evidenced by the suppression of the proliferation of human retinal endothelial cells in co-culture experiments. The involvement of CD36 receptor in LMPs uptake by macrophages was demonstrated by in vitro assays and by immunostaining of choroidal flat mounts. In addition, ex vivo experiments showed that CD36 mediates the antiangiogenic effect of LMPs in murine and human choroidal explants. Furthermore, intravitreal injection of LMPs in the mouse model of laser-induced CNV significantly suppressed CNV in CD36 dependent manner. The results of this study suggested an ability of LMPs to alter the gene expression pattern of angiogenesis-related factors in macrophages, which provide important information for a new therapeutic approach for efficiently interfering with both vascular and extravascular components of CNV.

Transduction of photoreceptors with equine infectious anemia virus lentiviral vectors: safety and biodistribution of StarGen for Stargardt disease.

PURPOSE: StarGen is an equine infectious anemia virus (EIAV)-based lentiviral vector that expresses the photoreceptor-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) protein that is mutated in Stargardt disease (STGD1), a juvenile macular dystrophy. EIAV vectors are able to efficiently transduce rod and cone photoreceptors in addition to retinal pigment epithelium in the adult macaque and rabbit retina following subretinal delivery. The safety and biodistribution of StarGen following subretinal delivery in macaques and rabbits was assessed. METHODS: Regular ophthalmic examinations, IOP measurements, ERG responses, and histopathology were carried out in both species to compare control and vector-treated eyes. Tissue and fluid samples were obtained to evaluate the persistence, biodistribution, and shedding of the vector following subretinal delivery. RESULTS: Ophthalmic examinations revealed a slightly higher level of inflammation in StarGen compared with control treated eyes in both species. However, inflammation was transient and no overt toxicity was observed in StarGen treated eyes and there were no abnormal clinical findings. There was no StarGen-associated rise in IOP or abnormal ERG response in either rabbits or macaques. Histopathologic examination of the eyes did not reveal any detrimental changes resulting from subretinal administration of StarGen. Although antibodies to StarGen vector components were detected in rabbit but not macaque serum, this immunologic response did not result in any long-term toxicity. Biodistribution analysis demonstrated that the StarGen vector was restricted to the ocular compartment. CONCLUSIONS: In summary, these studies demonstrate StarGen to be well tolerated and localized following subretinal administration.

Subchronic (26- and 52-week) toxicity and irritation studies of a novel microbicidal gel formulation containing sodium lauryl sulfate in animal models.

The safety of an ethylene oxide/propylene oxide gel formulation containing sodium lauryl sulfate (2%, w/w), that could be a potent candidate as a topical microbicide, has been evaluated. More specifically, the subchronic (26- and 52-week) toxicity of the formulation when applied intravaginally as well as its irritating potential for the rectal, penile, eye, skin and buccal mucosa have been examined in animal models. The results showed that the vaginal administration of the gel formulation containing sodium lauryl sulfate once and twice daily (with doses 12 +/- 2 h apart) for 26 weeks to rats and for 52 weeks to rabbits induced slight to moderate histopathological alterations. When the formulation was applied intrarectally to male and female rabbits once and twice daily (with doses 12 +/- 2 h apart) for 14 days, no macroscopic or microscopic changes were reported. For both vaginal and rectal dosing, no effect was seen on the haematology, coagulation and serum chemistry parameters as well as on the body weight of animals and the relative organ weights. Other sporadic macroscopic and histopathological findings were incidental in origin and of no toxicological significance. The gel formulation containing sodium lauryl sulfate was considered as mildly irritating for the penile mucosa of rabbits, non-irritating for the eye of rabbits, mildly irritating for the skin in a rabbit model and non-irritating for the hamster cheek pouch. It is suggested that the gel formulation containing sodium lauryl sulfate is safe for most tissues that could be exposed to the product under normal use.

The use of carbon dioxide laser for the ablation of meibomian gland adenomas in dogs.

Twelve eyelid meibomian gland adenomas in dogs were surgically ablated using the carbon dioxide (CO(2)) laser. The laser site was not sutured. All procedures resulted in complete removal of the adenoma with no recurrences at 6 months. In addition, no dogs developed corneal disease secondary to the procedure, and the cosmetic appearance of the eyelid margins was good at the end of the 6-month study. Based on results of this study, CO(2) laser ablation of canine meibomian gland adenomas is an effective alternative to standard surgical removal.

The use of porcine small intestinal submucosa for the repair of full-thickness corneal defects in dogs, cats and horses.

OBJECTIVE: To evaluate the efficacy of using a porcine small intestinal submucosa (SIS) graft covered by a conjunctival flap for the surgical repair of full-thickness corneal wounds in dogs, cats and horses. PROCEDURE: All records dating from August 1999 to February 2003 from Purdue University Veterinary Teaching Hospital of patients that had undergone ophthalmic surgical procedures and received a SIS corneal graft for a full-thickness lesion were reviewed. Fifteen cases were identified including six dogs, two cats and seven horses. Requirements for inclusion in this study were that SIS was used as a corneal graft in a full-thickness corneal defect and that the graft was completely covered with a conjunctival flap. RESULTS: Of the 15 cases, one canine patient had received SIS following removal of an epibulbar melanocytoma. The remaining five canine patients had undergone this surgical procedure for the repair of corneal perforation. The two feline patients had been presented for corneal perforation following chronic ulceration. One equine patient had been presented for a deep melting ulcer, three for stromal corneal abscesses, and three for corneal perforations. Complications encountered postoperatively included aqueous leakage, conjunctival flap dehiscence, synechia, cataract and fibrin in the anterior chamber. Fourteen out of 15 patients were visual at the final re-evaluation. CONCLUSION: SIS is an inexpensive, easy-to-handle biomaterial that appears to be suitable for the repair of full-thickness corneal wounds in dogs, cats and horses. Results of our study support the conclusion that this relatively new product is an effective alternative to traditional implantation materials utilized in veterinary ophthalmology.