@article{zibura_salmon_lopez_lascelles_westermeyer_2021, title={Glaucoma-associated pain results in mechanical sensitivity changes in dogs: A pilot study}, volume={24}, ISSN={["1463-5224"]}, DOI={10.1111/vop.12800}, abstractNote={Abstract Purpose To explore the effects of chronic, uncontrolled glaucoma on pressure sensitivity in dogs before and after enucleation of the painful globe. Methods Client‐owned dogs undergoing enucleation for chronic glaucoma with no other sources of pain were enrolled. Normal dogs of similar breeds and skull morphology were enrolled as controls. Craniofacial ratio (CFR) and relative palpebral fissure width (RPFW) were assessed in all patients. Serial mechanical quantitative sensory testing (QST) was performed the day before surgery, and 14, 30, 60, and 120 days after surgery. QST consisted of electronic Von Frey (eVF), and blunt algometry (BA) performed above and below the nonglaucomatous eye, the metacarpus, and metatarsus. Cochet‐Bonnet esthesiometry (CB) was also performed on the remaining eye. Results Twelve dogs (6 per group) were included. Compared to baseline values, sensitivity tended to decrease over time (increased thresholds) in treatment dogs while it stayed constant or increased slightly in control dogs. The difference in change from baseline sensitivity between control and treatment groups was significant at day 120 using BA at supraorbital ( P = .0153), infraorbital ( P = .0209), and metacarpal sites ( P = .007) and overall ( P = .0470). This divergence was also significant using CB ( P = .0470) on the opposite cornea. As patient CFR and RPFWV increased, both eVF ( P = .005‐.023) and BA ( P = .004‐.041) increased. Conclusions Sensitivity to mechanical stimuli decreased both locally and at remote sites in dogs following enucleation for painful chronic glaucoma. Cranial conformation is associated with differences in sensitivity.}, journal={VETERINARY OPHTHALMOLOGY}, author={Zibura, Ashley E. and Salmon, Jacklyn H. and Lopez, Beatriz Belda and Lascelles, B. Duncan X. and Westermeyer, Hans D.}, year={2021}, month={Mar}, pages={116–124} }
 @article{gilger_crabtree_song_llanga_cullen_blanchard_salmon_patel_zarnitsyn_hirsch_2020, title={A Fixed-Depth Microneedle Enhances Reproducibility and Safety for Corneal Gene Therapy}, volume={39}, ISSN={["1536-4798"]}, DOI={10.1097/ICO.0000000000002182}, abstractNote={Drug delivery directly to the corneal stroma currently relies on microscopic injections that demonstrate low reproducibility and clinician-dependent variability. With use of biological drugs such as adeno-associated viral (AAV) vectors, precise and consistent drug deposition is critical to reduce concerns related to off-target transduction and the host's immune response to the viral capsid and/or transgene-derived product. Therefore, a precise corneal injection (PCI) microneedle was designed to allow accurate depth-specific injections into the corneal stroma in a macroscopic setting.High-frequency ultrasound and confocal microscopy demonstrated the consistent ability to predetermine the precise injection depth using PCI needles of varying sizes. Next, a comparison between a standard 31-G needle and PCI needles was performed in vivo using AAV vector gene delivery.Intrastromal corneal injections using the PCI microneedle resulted in less vector leakage at the site of injection and fewer anterior chamber penetrations compared with a standard 31-G needle. Although reporter gene expression appeared similar when the vector was administered with either needle type, a trend toward increased vector genomes was noted in the PCI-injected corneas at the experimental conclusion. As hypothesized, corneal perforation resulted in increased detection of AAV vector genomes in nontarget tissues, highlighting the importance of consistency for biological drug applications in the cornea.Further development of the PCI microneedle is warranted especially for AAV corneal gene therapy and offers the potential to enhance transduction while significantly reducing safety concerns and intraclinician and interclinician injection variability.}, number={3}, journal={CORNEA}, author={Gilger, Brian C. and Crabtree, Elizabeth and Song, Liujiang and Llanga, Telmo and Cullen, Megan and Blanchard, Allison and Salmon, Jacklyn and Patel, Samirkumar and Zarnitsyn, Vladimir and Hirsch, Matthew}, year={2020}, month={Mar}, pages={362–369} }
 @article{crabtree_song_llanga_bower_cullen_salmon_hirsch_gilger_2019, title={AAV-mediated expression of HLA-G1/5 reduces severity of experimental autoimmune uveitis}, volume={9}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/s41598-019-56462-3}, DOI={10.1038/s41598-019-56462-3}, abstractNote={Abstract Non-infectious uveitis (NIU) is an intractable, recurrent, and painful disease that is a common cause of vision loss. Available treatments of NIU, such as the use of topical corticosteroids, are non-specific and have serious side effects which limits them to short-term use; however, NIU requires long-term treatment to prevent vision loss. Therefore, a single dose therapeutic that mediates long-term immunosuppression with minimal side effects is desirable. In order to develop an effective long-term therapy for NIU, an adeno-associated virus (AAV) gene therapy approach was used to exploit a natural immune tolerance mechanism induced by the human leukocyte antigen G (HLA-G). To mimic the prevention of NIU, naïve Lewis rats received a single intravitreal injection of AAV particles harboring codon-optimized cDNAs encoding HLA-G1 and HLA-G5 isoforms one week prior to the induction of experimental autoimmune uveitis (EAU). AAV-mediated expression of the HLA-G-1 and -5 transgenes in the targeted ocular tissues following a single intravitreal injection of AAV-HLA-G1/5 significantly decreased clinical and histopathological inflammation scores compared to untreated EAU eyes (p < 0.04). Thus, localized ocular gene delivery of AAV-HLA-G1/5 may reduce the off-target risks and establish a long-term immunosuppressive effect that would serve as an effective and novel therapeutic strategy for NIU, with the potential for applications to additional ocular immune-mediated diseases.}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Crabtree, E. and Song, L. and Llanga, T. and Bower, J.J. and Cullen, M. and Salmon, J.H. and Hirsch, M.L. and Gilger, B.C.}, year={2019}, month={Dec}, pages={19864} }
 @article{hirsch_conatser_smith_salmon_wu_buglak_davis_gilger_2017, title={AAV vector-meditated expression of HLA-G reduces injury-induced corneal vascularization, immune cell infiltration, and fibrosis}, volume={7}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/s41598-017-18002-9}, DOI={10.1038/s41598-017-18002-9}, abstractNote={Abstract Over 1.5 million individuals suffer from cornea vascularization due to genetic and/or environmental factors, compromising visual acuity and often resulting in blindness. Current treatments of corneal vascularization are limited in efficacy and elicit undesirable effects including, ironically, vision loss. To develop a safe and effective therapy for corneal vascularization, adeno-associated virus (AAV) gene therapy, exploiting a natural immune tolerance mechanism induced by human leukocyte antigen G (HLA-G), was investigated. Self-complementary AAV cassettes containing codon optimized HLA-G1 (transmembrane) or HLA-G5 (soluble) isoforms were validated in vitro . Then, following a corneal intrastromal injection, AAV vector transduction kinetics, using a chimeric AAV capsid, were determined in rabbits. One week following corneal trauma, a single intrastromal injection of scAAV8G9-optHLA-G1 + G5 prevented corneal vascularization, inhibited trauma-induced T-lymphocyte infiltration (some of which were CD8 + ), and dramatically reduced myofibroblast formation compared to control treated eyes. Biodistribution analyses suggested AAV vectors persisted only in the trauma-induced corneas; however, a neutralizing antibody response to the vector capsid was observed inconsistently. The collective data demonstrate the clinical potential of scAAV8G9-optHLA-G to safely and effectively treat corneal vascularization and inhibit fibrosis while alluding to broader roles in ocular surface immunity and allogenic organ transplantation.}, number={1}, journal={Scientific Reports}, publisher={Springer Nature}, author={Hirsch, Matthew L. and Conatser, Laura M. and Smith, Sara M. and Salmon, Jacklyn H. and Wu, Jerry and Buglak, Nicholas E. and Davis, Rich and Gilger, Brian C.}, year={2017}, month={Dec} }
 @article{schaefer_smith_salmon_abbaraju_amin_weiss_grau_velagaleti_gilger_2017, title={Evaluation of Intracameral Pentablock Copolymer Thermosensitive Gel for Sustained Drug Delivery to the Anterior Chamber of the Eye}, volume={33}, ISSN={["1557-7732"]}, DOI={10.1089/jop.2016.0181}, abstractNote={To investigate PTSgels (Pentablock copolymers) as an injectable formulation technology for sustained ocular drug delivery. Drug release profile, tolerability, and polymer degradation for one of the thermosensitive, biodegradable, and biocompatible compositions were investigated through intracameral (IC) injection in rabbits.New Zealand White rabbit eyes were injected IC (50 μL) with 100 μg near-infrared-immunoglobulin G (NIR-IgG) in balanced salt solution (BSS) or 20% PTSgel; or with PTSgel or BSS alone. Ocular irritation scoring, intraocular pressure (IOP), and corneal thickness (CT) measurement, as well as color and infrared photography, were performed for up to 28 days postinjection. Upon euthanasia at 7, 14, or 28 days, eyes underwent ex vivo imaging (Xenogen IVIS) followed by tissue fixation and histopathology.IC injection of PTSgel (liquid at room temperature) was performed without difficulty using a 31G needle. The polymer quickly gelled in the IC space resulting in an inferior anterior chamber deposit. The tested PTSgel was well tolerated, with no significant changes in IOP or CT. Eyes injected with NIR-IgG in PTSgel had visible NIR-IgG through 9 days postinjection, and ex vivo imaging detected a strong NIR-IgG signal in the anterior chamber through day 28. The gel deposit steadily decreased in size over time and was nearly eliminated by 28 days.The PTSgel released IgG for 28 days and was well tolerated. The polymer degraded in parallel with drug release. These results demonstrate the potential of intracameral PTSgel formulations for sustained delivery of biologic therapies to the ocular anterior segment.}, number={5}, journal={JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS}, author={Schaefer, Elizabeth and Smith, Sara M. and Salmon, Jacklyn and Abbaraju, Santhi and Amin, Rasidul and Weiss, Sidney and Grau, Ulrich and Velagaleti, Poonam and Gilger, Brian}, year={2017}, month={Jun}, pages={353–360} }
 @article{smith_abbaraju_salmon_amin_weiss_grau_velagaleti_gilger_2017, title={Evaluation of pentablock co-polymer (PTS sol ) for sustained topical ocular drug delivery}, volume={39}, ISSN={1773-2247}, url={http://dx.doi.org/10.1016/j.jddst.2017.05.005}, DOI={10.1016/j.jddst.2017.05.005}, abstractNote={The purpose of this study is to evaluate ocular retention, tolerability, and sustained pharmacodynamics of a clear topical formulation of brinzolamide (BRZ) in PTSsol pentablock co-polymer. To test for ocular retention, PTSsol or saline containing near infrared dye-labeled (NIR) IgG was applied to the corneal surface of mice and monitored by in vivo imaging. To evaluate pharmacodynamics, dogs were dosed for 3 consecutive days with PTSsol once daily (qd) at doses of 1% and 2.5% and compared to PTSsol qd, or commercial BRZ 1% (Azopt®) three times daily (tid). Intraocular pressure (IOP) and ocular exams were performed each treatment day and two additional days post-treatment. The NIR-IgG saline remained on the ocular surface for <3 h, while NIR-IgG in PTSsol remained for >21 h. All formulations were well tolerated in dogs and by day 3 of dosing, IOP was significantly lower in 2.5% BRZ PTSsol qd dosed eyes compared to vehicle or baseline (p < 0.014). On day 5, 48 h after dosing, IOP remained significantly lower in eyes treated with 2.5% BRZ PTSsol qd compared to those dosed with Azopt (p = 0.036). This suggests that drugs in PTSsol may allow for once a day or less frequent dosing.}, journal={Journal of Drug Delivery Science and Technology}, publisher={Elsevier BV}, author={Smith, Sara M. and Abbaraju, Santhi and Salmon, Jacklyn H. and Amin, Rasidul and Weiss, Sidney L. and Grau, Ulrich and Velagaleti, Poonam and Gilger, Brian C.}, year={2017}, month={Jun}, pages={475–483} }
 @article{curto_messenger_salmon_gilger_2016, title={Cytokine and chemokine profiles of aqueous humor and serum in horses with uveitis measured using multiplex bead immunoassay analysis}, volume={182}, ISSN={["1873-2534"]}, url={https://doi.org/10.1016/j.vetimm.2016.09.008}, DOI={10.1016/j.vetimm.2016.09.008}, abstractNote={To determine whether horses with clinically diagnosed Equine Recurrent Uveitis (ERU) and those with Leptospirosis infection have a specific cytokine profile in their aqueous humor (AH) and serum that differs from horses with uveitis secondary to other ocular inflammatory processes and from horses with normal eyes.Twenty-five client-owned horses with uveitis that were presented to the North Carolina State University Ophthalmology Service, and four University-owned horses without history or clinical signs of ocular disease.Samples of AH and serum were obtained from horses with ERU (n=13), acute or non-recurrent uveitis (UV; n=7), uveitis secondary to infectious keratitis (IK; n=5), and normal eyes (N; n=4). Cytokine levels in AH and serum were quantified using a multiplex bead immunoassay. Leptospiral antibody titers in serum and AH and PCR for Leptospiral DNA in AH were performed.In the AH of horses with ERU, increased levels of IL-1a, IL-4, IL-6, IL-8, IL-12p70, FGF-2, G-CSF, and RANTES were measured compared to UV, IK and N eyes, but the differences were not significant. However, IL-10 was significantly higher in ERU eyes compared to IK and N (P=0.029; 0.013), and IP-10 in ERU eyes was significantly higher than in UV and N (P=0.004). Furthermore, MCP-1 was significantly higher in ERU than N (P=0.04). In the serum, increased levels of IL-1a, IL-4, IL-6, IL-8, IL-12p70, fractalkine, and G-CSF were measured in horses with ERU, but the levels were not significantly higher than those observed in UV, IK, or N horses. However, serum IP-10 levels in horses with ERU were significantly higher than in UV and N horses (P=0.005) and MCP-1 levels were significantly higher in ERU than N (P=0.03). Horses with marked ocular inflammation had significantly higher serum levels of G-CSF, IL-1a, fractalkine, IL-13, IL-4, IL-17a, IL-12p70, IFN-γ, and MCP-1. Elevated IL-10 in AH was significantly associated with disease chronicity, both overall and in ERU eyes (P=0.049), and in horses with positive ocular leptospiral titers or leptospiral PCR, significant elevations of IL-10 (P=0.0018; 0.0032) and IP-10 (P=0.0342; 0.043) were detected in the AH compared to leptospiral negative eyes.The anti-inflammatory cytokine IL-10 and the pro-inflammatory cytokine IP-10 appear to play an important role in ERU. Further studies are needed to further clarify and characterize cytokine profiles of specific ocular inflammatory diseases, but multiplex bead immunoassay technology shows promise as a diagnostically valuable tool.}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, publisher={Elsevier BV}, author={Curto, Elizabeth and Messenger, Kristen M. and Salmon, Jacklyn H. and Gilger, Brian C.}, year={2016}, month={Dec}, pages={43–51} }
 @article{schaefer_abbaraju_walsh_newman_salmon_amin_weiss_grau_velagaleti_gilger_et al._2016, title={Sustained Release of Protein Therapeutics from Subcutaneous Thermosensitive Biocompatible and Biodegradable Pentablock Copolymers (PTSgels)}, volume={2016}, ISSN={["2090-3022"]}, url={https://doi.org/10.1155/2016/2407459}, DOI={10.1155/2016/2407459}, abstractNote={Objective . To evaluate thermosensitive, biodegradable pentablock copolymers (PTS gel ) for sustained release and integrity of a therapeutic protein when injected subcutaneously. Materials and Methods . Five PTS gels with PEG-PCL-PLA-PCL-PEG block arrangements were synthesized. In vitro release of IgG from PTS gels and concentrations was evaluated at 37°C. Released IgG integrity was characterized by SDS-PAGE. In vitro disintegration for 10GH PTS gel in PBS was monitored at 37°C over 72 days using gravimetric loss and GPC analysis. Near-infrared IgG in PTS gel was injected subcutaneously and examined by in vivo imaging and histopathology for up to 42 days. Results . IgG release was modulated from approximately 7 days to more than 63 days in both in vitro and in vivo testing by varying polymer composition, concentration of PTS gel aqueous solution, and concentration of IgG. Released IgG in vitro maintained structural integrity by SDS-PAGE. Subcutaneous PTS gels were highly biocompatible and in vitro IgG release occurred in parallel with the disappearance of subcutaneous gel in vivo . Conclusions . Modulation of release of biologics to fit the therapeutic need can be achieved by varying the biocompatible and biodegradable PTS gel composition. Release of IgG parallels disappearance of the polymeric gel; hence, little or no PTS gel remains after drug release is complete.}, journal={JOURNAL OF DRUG DELIVERY}, publisher={Hindawi Limited}, author={Schaefer, Elizabeth and Abbaraju, Santhi and Walsh, Mary and Newman, Donna and Salmon, Jacklyn and Amin, Rasidul and Weiss, Sidney and Grau, Ulrich and Velagaleti, Poonam and Gilger, Brian and et al.}, year={2016} }
 @article{abarca_salmon_gilger_2013, title={Effect of Choroidal Perfusion on Ocular Tissue Distribution After Intravitreal or Suprachoroidal Injection in an Arterially Perfused Ex Vivo Pig Eye Model}, volume={29}, ISSN={1080-7683 1557-7732}, url={http://dx.doi.org/10.1089/jop.2013.0063}, DOI={10.1089/jop.2013.0063}, abstractNote={To compare tissue distribution of dye-drug surrogates after intravitreal (IVT) and suprachoroidal (SCS) delivery to determine the influence of drug lipophilicity and choroidal circulation.Thirty-two pig eyes were collected immediately after euthanasia. Sixteen eyes were perfused for 30 min through one long posterior ciliary artery with nondye containing nutrient media. An IVT or SCS injection was performed with either a 100 μL balanced salt solution (BSS, n=8), 1% sodium fluorescein (NaF, n=12) or 0.12% lipophilic carbocyanine dye (DiI, n=12). Globes were maintained at 37°C for 15 min, and then snap-frozen and dissected. Aqueous extraction and measurement of NaF or DiI concentration was performed using spectrophotometry and spectrofluorometry, respectively.After SCS delivery of NaF scleral, iris-ciliary body, choroidal and vitreous dye levels were higher in nonperfused eyes compared to perfused eyes. After DiI SCS or IVT delivery, no significant differences were found in dye tissue concentrations in perfused eyes compared to nonperfused eyes. Following perfusion, a better and even drug distribution was found in the retinal pigmented epithelium (RPE)-choroid following IVT and SCS delivery of the hydrophilic drug and after IVT injection of the lipophilic drug compared to nonperfused eyes.Choroidal circulation reduces the tissue drug concentration of the hydrophilic drug suggesting an early clearance mechanism after SCS delivery. SCS injections of lipid and hydrophilic drugs allowed direct drug delivery to the retina and RPE-choroid with limited exposition to the anterior segment.}, number={8}, journal={Journal of Ocular Pharmacology and Therapeutics}, publisher={Mary Ann Liebert Inc}, author={Abarca, Eva M. and Salmon, Jacklyn H. and Gilger, Brian C.}, year={2013}, month={Oct}, pages={715–722} }
 @article{gilger_abarca_salmon_patel_2013, title={Treatment of Acute Posterior Uveitis in a Porcine Model by Injection of Triamcinolone Acetonide Into the Suprachoroidal Space Using Microneedles}, volume={54}, ISSN={1552-5783}, url={http://dx.doi.org/10.1167/iovs.13-11747}, DOI={10.1167/iovs.13-11747}, abstractNote={To evaluate the effect of triamcinolone acetonide (TA) administered into the suprachoroidal space (SCS) using a microneedle and compare it with intravitreal (IVT) TA injections in a porcine model of acute posterior segment inflammation.An IVT injection of balanced salt solution (BSS) or lipopolysaccharide (LPS) was followed 24 hours later with an injection of 0.2 mg or 2.0 mg of TA into the SCS or IVT. The SCS was accessed using microneedles in a minimally invasive procedure. Ocular inflammatory scores and IOP measurements were collected daily, whereas electroretinography, optical coherence tomography, and wide-field ocular fundus photography was performed on -1, 0, and 3 days after treatment. Aqueous and vitreous humor cell counts and protein levels and histopathology were also compared.Delivery of TA to the SCS using microneedles was simple, effective, and not associated with adverse effects or toxicity. SCS injection of low (0.2 mg) and high doses (2.0 mg) of TA was as effective in reducing acute inflammation in the ocular posterior segment as high-dose IVT injection. Low-dose SCS TA was also effective in reducing inflammation; however, low-dose IVT TA was not.Results from this study suggest that 0.2 mg and 2.0 mg of SCS TA was as effective in reducing inflammation as 2.0 mg IVT TA injection in a model of acute posterior segment inflammation. There were no adverse effects, increased IOP, or evidence of procedural or drug toxicity following injection of TA into the SCS in porcine eyes.}, number={4}, journal={Investigative Opthalmology & Visual Science}, publisher={Association for Research in Vision and Ophthalmology (ARVO)}, author={Gilger, Brian C. and Abarca, Eva M. and Salmon, Jacklyn H. and Patel, Samirkumar}, year={2013}, month={Apr}, pages={2483} }
 @article{gilger_stoppini_wilkie_clode_pinto_hempstead_gerding_salmon_2013, title={Treatment of immune-mediated keratitis in horses with episcleral silicone matrix cyclosporine delivery devices}, volume={17}, ISSN={1463-5216}, url={http://dx.doi.org/10.1111/vop.12087}, DOI={10.1111/vop.12087}, abstractNote={Abstract Purpose To describe the use of episcleral silicone matrix cyclosporine ( ESMC ) drug delivery devices in horses with immune‐mediated keratitis ( IMMK ) with evaluation of tolerability and efficacy in long‐term control of inflammation. Methods Retrospective study. ESMC implants (1.2 cm length, 30% wt/wt cyclosporine (CsA) in silicone; with approximately 2 μg/day steady‐state release for at least 400 days) were used. Results Nineteen horses (20 eyes) received two or more ESMC implants for superficial stromal ( n = 9), midstromal ( n = 3), or endothelial ( n = 5) IMMK . Three additional horses received two or more ESMC implants for pigmentary keratouveitis ( PK ). Nine eyes of eight horses with superficial and five eyes of five horses with endothelial IMMK were well controlled after placement of ESMC implants (mean follow‐up 176.8 and 207.2 days, respectively). Horses with midstromal IMMK and PK were not controlled with ESMC implants alone, but instead required frequent use of other medications or surgery to control the disease. The mean duration of disease prior to ESMC implantation of horses with midstromal IMMK was 495 ± 203.9 days, compared with 121.6 ± 92.7 days with superficial IMMK . ESMC implants were well tolerated by all horses without documented loss of the device. Conclusions Results from this preliminary retrospective study suggest that the ESMC implants were well tolerated and associated with treatment success with superficial and endothelial IMMK , especially if placed early in the disease process. Further study is needed to determine the duration of efficacy, number of implants required, and better therapies for chronic midstromal IMMK and pigmentary keratouveitis.}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Gilger, Brian C. and Stoppini, Riccardo and Wilkie, David A. and Clode, Alison B. and Pinto, Nelson H. and Hempstead, Julie and Gerding, Joseph and Salmon, Jacklyn H.}, year={2013}, month={Aug}, pages={23–30} }
 @article{gilger_wilkie_salmon_peel_2012, title={A topical aqueous calcineurin inhibitor for the treatment of naturally occurring keratoconjunctivitis sicca in dogs}, volume={16}, ISSN={1463-5216}, url={http://dx.doi.org/10.1111/j.1463-5224.2012.01056.x}, DOI={10.1111/j.1463-5224.2012.01056.x}, abstractNote={Abstract 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.}, number={3}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Gilger, Brian C. and Wilkie, David A. and Salmon, Jacklyn H. and Peel, Michael R.}, year={2012}, month={Jul}, pages={192–197} }
 @article{pate_clode_olivry_cullen_salmon_gilger_2012, title={Immunohistochemical and immunopathologic characterization of superficial stromal immune-mediated keratitis in horses}, volume={73}, ISSN={["0002-9645"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84863476431&partnerID=MN8TOARS}, DOI={10.2460/ajvr.73.7.1067}, abstractNote={To describe the immunopathologic characteristics of superficial stromal immune-mediated keratitis (IMMK) immunopathologically by characterizing cellular infiltrate in affected corneas of horses.10 client-owned horses with IMMK.Immunohistochemical staining was performed on keratectomy samples with equine antibodies against the T-cell marker CD3 and B-cell marker CD79a (10 eyes) and the T-helper cytotoxic marker CD4 and T-cell cytotoxic marker CD8 (6 eyes). Percentage of positively stained cells was scored on a scale from 0 (no cells stained) to 4 (> 75% of cells stained). Equine IgG, IgM, and IgA antibodies were used to detect corneal immunoglobulin via direct immunofluorescence (10 eyes). Serum and aqueous humor (AH) samples from 3 horses with IMMK were used to detect circulating and intraocular IgG against corneal antigens via indirect immunofluorescence on unaffected equine cornea.Percentage scores (scale, 0 to 4) of cells expressing CD3 (median, 2.35 [range, 0.2 to 3.7]; mean ± SD, 2.36 ± 1.08) were significantly greater than scores of cells expressing CD79a (median, 0.55 [range, 0 to 1.5]; mean, 0.69 ± 0.72). All samples stained positively for CD4- and CD8-expressing cells, with no significant difference in scoring. All samples stained positively for IgG, IgM, and IgA. No serum or AH samples collected from horses with IMMK reacted with unaffected equine cornea.Pathogenesis of superficial stromal IMMK included cell-mediated inflammation governed by both cytotoxic and helper T cells. Local immunoglobulins were present in affected corneas; however, corneal-binding immunoglobulins were not detected in the serum or AH from horses with IMMK.}, number={7}, journal={American Journal of Veterinary Research}, author={Pate, D.O. and Clode, A.B. and Olivry, T.M. and Cullen, J.M. and Salmon, J.H. and Gilger, B.C.}, year={2012}, pages={1067–1073} }
 @article{davis_yi_salmon_charlton_colitz_gilger_2012, title={Sustained-Release Celecoxib from Incubated Acrylic Intraocular Lenses Suppresses Lens Epithelial Cell Growth in an Ex Vivo Model of Posterior Capsule Opacity}, volume={28}, ISSN={["1080-7683"]}, DOI={10.1089/jop.2011.0196}, abstractNote={Purpose: To determine whether celecoxib (CXB) can be released from incubated intraocular lenses (IOLs) sufficiently to inhibit lens epithelial cell (LEC) growth in an ex vivo model of posterior capsule opacification (PCO). Materials: LEC growth was evaluated for 14 days in canine lens capsules (LCs) that had been exposed to media containing 20 μM CXB for 1–5 days. After the incubation of hydrophilic and hydrophobic IOLs in CXB solution, the determination of the in vitro release of CXB from the IOLs was performed for up to 28 days. The incubated and nonincubated IOLs were evaluated in the ex vivo model of PCO, and the rate of LEC growth was evaluated over 28 days. Results: The treatment of LCs with 20 μM CXB for 4 and 5 days completely inhibited LEC growth. LEC repopulation did not occur after the removal of CXB. IOLs incubated in CXB for 24 h resulted in a sustained release of CXB in vitro at levels theoretically sufficient to inhibit PCO. LCs in the ex vivo model of PCO treated with acrylic IOLs incubated in CXB had significantly suppressed LEC ingrowth compared with untreated and IOL-only LCs. Conclusions: A 4-day treatment of LCs with a concentration of 20 μM CXB may effectively prevent PCO. IOLs incubated in CXB for 24 h resulted in a sustained release of CXB in vitro at levels sufficient to inhibit LEC growth in the ex vivo model of PCO. Further studies are needed to determine whether CXB-incubated IOLs can effectively prevent the development of PCO in vivo.}, number={4}, journal={JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS}, author={Davis, Jennifer L. and Yi, Na Young and Salmon, Jacklyn H. and Charlton, Anna N. and Colitz, Carmen M. H. and Gilger, Brian C.}, year={2012}, month={Aug}, pages={359–368} }
 @article{clode_davis_davidson_salmon_lafevers_gilger_2011, title={Aqueous humor and plasma concentrations of a compounded 0.2% solution of terbinafine following topical ocular administration to normal equine eyes}, volume={14}, ISSN={1463-5216}, url={http://dx.doi.org/10.1111/j.1463-5224.2010.00841.x}, DOI={10.1111/j.1463-5224.2010.00841.x}, abstractNote={To determine the transcorneal penetration and systemic absorption of a compounded 0.2% terbinafine solution following repeated topical administration to normal equine eyes. Sample population Six healthy adult horses with normal ocular examinations.One eye of each horse received 0.2 mL of a compounded 0.2% terbinafine solution every 4 h for seven doses. During the 1 h following administration of the final dose, multiple peripheral blood samples were obtained, and a single aqueous humor (AH) sample was collected at the end of the hour. AH and plasma concentrations of terbinafine were determined using high pressure liquid chromatography (HPLC). Stability of the formulation was assessed with HPLC analysis over a 14-day time period.Terbinafine was not detected in the AH or plasma of any horse at any time point. No signs of ocular irritation or systemic toxicity were noted in any horse at any time point. The solution was stable over 14 days.Topical ocular administration of compounded 0.2% terbinafine solution does not result in detectable AH or plasma levels following administration to normal equine eyes, suggesting its use for deep corneal or intraocular fungal infections in equine ophthalmology may be limited.}, number={1}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Clode, Alison and Davis, Jennifer and Davidson, Gigi and Salmon, Jacklyn and Lafevers, Heath and Gilger, Brian}, year={2011}, month={Jan}, pages={41–47} }
 @article{seiler_salmon_mantuo_feingold_dayton_gilger_2011, title={Effect and Distribution of Contrast Medium after Injection into the Anterior Suprachoroidal Space in Ex Vivo Eyes}, volume={52}, ISSN={1552-5783}, url={http://dx.doi.org/10.1167/iovs.11-7525}, DOI={10.1167/iovs.11-7525}, abstractNote={To determine the effects and posterior distribution of injections made into the anterior suprachoroidal space (SCS).The anterior SCS of adult porcine and canine ex vivo eyes was cannulated. Latex injections and high frequency ultrasound (50 MHz) was used to image the effect and distension of the SCS. Flow characteristics and percentage maximal distribution of microbubble contrast injection into the SCS were assessed by 2D and 3D ultrasound.Mean (SD) distension of the SCS with PBS increased from 1.57 (0.48) mm after injection of 250 μL to 3.28 (0.57) mm with 1000 μL PBS. Eyes injected at physiologic IOP had no significant difference in SCS distension. In real-time 2D ultrasound, the contrast agent flowed from the injection site to the opposite ventral anterior SCS and the posterior SCS. Contrast arrived at the opposite and posterior SCS 7.8 (4.6) and 7.7 (4.6) seconds after injection, respectively. In sagittal images, contrast was visible in 24.0%to 27.2% of the SCS; in 10 of 12 eyes, contrast reached the posterior pole of the eye. In 3D images, contrast medium occupied 39.0% to 52.1% of the entire SCS.These results suggest that the SCS can expand, in a dose-dependent manner, to accommodate various volumes of fluid and that it is possible to image the SCS with ultrasound contrast. The authors' hypothesis that a single anterior SCS injection can reach the ocular posterior segment was supported. Further development of SCS injections for treatment of the ocular posterior segment is warranted.}, number={8}, journal={Investigative Opthalmology & Visual Science}, publisher={Association for Research in Vision and Ophthalmology (ARVO)}, author={Seiler, Gabriela S. and Salmon, Jacklyn H. and Mantuo, Rebecca and Feingold, Steven and Dayton, Paul A. and Gilger, Brian C.}, year={2011}, month={Jul}, pages={5730} }
 @article{clode_davis_salmon_lafevers_gilger_2010, title={Aqueous humor and plasma concentrations of ciprofloxacin and moxifloxacin following topical ocular administration in ophthalmologically normal horses}, volume={71}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.71.5.564}, DOI={10.2460/ajvr.71.5.564}, abstractNote={Abstract Objective —To determine the degree of ocular penetration and systemic absorption of commercially available topical ophthalmic solutions of 0.3% ciprofloxacin and 0.5% moxifloxacin following repeated topical ocular administration in ophthalmologically normal horses. Animals —7 healthy adult horses with clinically normal eyes as evaluated prior to each treatment. Procedures —6 horses were used for assessment of each antimicrobial, and 1 eye of each horse was treated with topically administered 0.3% ciprofloxacin or 0.5% moxifloxacin (n = 6 eyes/drug) every 4 hours for 7 doses. Anterior chamber paracentesis was performed 1 hour after the final dose was administered, and blood samples were collected at 24 (immediately after the final dose), 24.25, 24.5, and 25 hours (time of aqueous humor [AH] collection). Plasma and AH concentrations of ciprofloxacin or moxifloxacin were determined by use of high-performance liquid chromatography. Results —Mean ± SD AH concentrations of ciprofloxacin and moxifloxacin were 0.009 ± 0.008 μg/mL and 0.071 ± 0.029 μg/mL, respectively. The AH moxifloxacin concentrations were significantly greater than those of ciprofloxacin. Mean ± SD plasma concentrations of ciprofloxacin were less than the lower limit of quantification. Moxifloxacin was detected in the plasma of all horses at all sample collection times, with a peak value of 0.015 μg/mL at 24 and 24.25 hours, decreasing to < 0.004 μg/mL at 25 hours. Conclusions and Clinical Relevance —Moxifloxacin was better able to penetrate healthy equine corneas and reach measurable AH concentrations than was ciprofloxacin, suggesting moxifloxacin might be of greater value in the treatment of deep corneal or intraocular bacterial infections caused by susceptible organisms. Topical administration of moxifloxacin also resulted in detectable plasma concentrations.}, number={5}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Clode, Alison B. and Davis, Jennifer L. and Salmon, Jacklyn and LaFevers, Heath and Gilger, Brian C.}, year={2010}, month={May}, pages={564–569} }
 @article{mcmullen_davidson_campbell_salmon_gilger_2010, title={Evaluation of 30- and 25-diopter intraocular lens implants in equine eyes after surgical extraction of the lens}, volume={71}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.71.7.809}, DOI={10.2460/ajvr.71.7.809}, abstractNote={Abstract Objective —To determine appropriate intraocular lens (IOL) implant strength to approximate emmetropia in horses. Sample Population —16 enucleated globes and 4 adult horses. Procedures —Lens diameter of 10 enucleated globes was measured. Results were used to determine the appropriate-sized IOL implant for insertion in 6 enucleated globes and 4 eyes of adult horses. Streak retinoscopy and ocular ultrasonography were performed before and after insertion of 30-diopter (D) IOL implants (enucleated globes) and insertion of 25-D IOL implants (adult horses). Results —In enucleated globes, mean ± SD lens diameter was 20.14 ± 0.75 mm. Preoperative and postoperative refractive state of enucleated globes with 30-D IOL implants was −0.46 ± 1.03 D and −2.47 ± 1.03 D, respectively; preoperative and postoperative difference in refraction was 2.96 ± 0.84 D. Preoperative anterior chamber (AC) depth, crystalline lens thickness (CLT), and axial globe length (AxL) were 712 ± 0.82 mm, 11.32 ± 0.81 mm, and 40.52 ± 1.26 mm, respectively; postoperative AC depth was 10.76 ± 1.16 mm. Mean ratio of preoperative to postoperative AC depth was 0.68. In eyes receiving 25-D IOL implants, preoperative and postoperative mean refractive error was 0.08 ± 0.68 D and −3.94 ± 1.88 D, respectively. Preoperative AC depth, CLT, and AxL were 6.36 ± 0.22 mm, 10.92 ± 1.92 mm, and 38.64 ± 2.59 mm, respectively. Postoperative AC depth was 8.99 ± 1.68 mm. Mean ratio of preoperative to postoperative AC depth was 0.73. Conclusions and Clinical Relevance —Insertion of 30-D (enucleated globes) and 25-D IOL implants (adult horses) resulted in overcorrection of refractive error.}, number={7}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={McMullen, Richard J. and Davidson, Michael G. and Campbell, Nigel B. and Salmon, Jacklyn H. and Gilger, Brian C.}, year={2010}, month={Jul}, pages={809–816} }
 @article{gilger_wilkie_clode_mcmullen_utter_komaromy_brooks_salmon_2010, title={Long-term outcome after implantation of a suprachoroidal cyclosporine drug delivery device in horses with recurrent uveitis}, volume={13}, ISSN={1463-5216}, url={http://dx.doi.org/10.1111/j.1463-5224.2010.00807.x}, DOI={10.1111/j.1463-5224.2010.00807.x}, abstractNote={To determine the long-term efficacy, complications, and duration of effect of a cyclosporine (CsA) suprachoroidal implant (CSI) in horses with equine recurrent uveitis (ERU).Horses with ERU were treated with a 6-mm diameter, 25 mg, reservoir matrix CsA implant in the deep sclera adjacent to the suprachoroidal space. Horses with follow-up >1 year were examined for frequency of uveitis episodes, complications, and vision at last recheck.Data from 151 eyes of 133 horses from the USA and Europe that had CsA devices implanted for ERU were reviewed. Follow-up time ranged from 13 to 85 months after surgery, with a mean and median follow-up time of 28.9 and 26.3 months, respectively. Overall, at last follow-up 78.8% of eyes were considered visual and the overall mean frequency of uveitis episodes after CSI was 0.09 ± SD 0.08 episodes per month. The most common complications leading to vision loss at last follow-up were persistent uveitis episodes (54%), glaucoma (22%), mature cataracts (16%), and retinal detachment (6%). Persistent uveitis episodes tended to be the highest cause of vision loss in horses with <24 months and >48 months of follow-up.This study demonstrated the long-term maintenance of vision of horses with ERU implanted with a CSI. The increased vision loss related to uveitis episode of inflammation in eyes after the likely depletion of CsA from the CSI suggests that a repeat CSI may be required at or before 48 months after surgery.}, number={5}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Gilger, Brian C. and Wilkie, David A. and Clode, Allison B. and McMullen, Richard J., Jr. and Utter, Mary E. and Komaromy, Andras M. and Brooks, Dennis E. and Salmon, Jacklin H.}, year={2010}, month={Sep}, pages={294–300} }
 @article{yi_davis_salmon_gilger_2008, title={Ocular distribution and toxicity of intravitreal injection of triamcinolone acetonide in normal equine eyes}, volume={11}, ISSN={1463-5216 1463-5224}, url={http://dx.doi.org/10.1111/j.1463-5224.2008.00636.x}, DOI={10.1111/j.1463-5224.2008.00636.x}, abstractNote={Abstract Objective To determine ocular distribution and toxicity of a single injection of intravitreal triamcinolone acetonide (TA) in normal horses. Animals studied Six adult horses, donated to North Carolina State University. Procedures Six horses were injected intravitreally with either 10, 20, or 40 mg ( n = 2 each) of TA. The opposite eye of each horse was injected with balanced salt solution (BSS). Ocular toxicity was assessed by biomicroscopy, tonometry, indirect ophthalmoscopy, and electroretinogram. Aqueous humor (AH), vitreous humor (VH), and plasma samples were collected. Horses were euthanized 7 or 21 days after injection and eyes enucleated for histopathology. TA concentrations in AH, VH, and plasma were measured by HPLC. Results Three control eyes and one TA eye developed inflammation after injection or collection of AH. Positive bacterial cultures ( Corynebacterium spp., Staphylococcus spp., and Streptococcus spp.) were obtained from three of these eyes. Other than transient corneal edema in TA injected eyes, which resolved by 7 days after injection, no other changes were observed. TA crystals were visible within the vitreous body. No evidence of TA toxic effect was noted on histopathology. TA was detected in all AH and VH samples from treated eyes following injection. Drug was not detected in the plasma. Conclusions There was no evidence of overt toxicity from intravitreal TA in normal horses and a single intravitreal injection resulted in TA ocular levels for 21 days. However, the risk for bacterial infections with intravitreal injection or anterior chamber aspirations in horses is high. Use of topical and systemic antibiotics after injection is recommended.}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Yi, N. Y. and Davis, J. L. and Salmon, J. H. and Gilger, B. C.}, year={2008}, month={Sep}, pages={15–19} }
 @article{douglas_yi_davis_salmon_gilger_2008, title={Ocular toxicity and distribution of subconjunctival and intravitreal rapamycin in horses}, volume={31}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1111/j.1365-2885.2008.00986.x}, DOI={10.1111/j.1365-2885.2008.00986.x}, abstractNote={In vitro photosensitivity of rapamycin (RAPA) and ocular toxicity and distribution of intravitreal and subconjunctival RAPA was evaluated in normal horses. RAPA (2.5 mg, 5 mg, and 10 mg) was placed in 10 mL of PBS and maintained in a water bath at 37 °C, kept in the dark or subjected to room light, and sampled for up to 3 months for RAPA levels. Six normal adult horses received either 5 mg ( n = 2) or 10 mg ( n = 2) of RAPA intravitreally or 10 mg ( n = 2) subconjunctivally. Ophthalmic exams and electroretinography (ERG) were performed prior to injection and on days 1, 7, 14, and 21 post‐injection. Eyes were enucleated and samples were collected for RAPA concentrations and histopathology. No difference in light vs. dark RAPA concentrations was observed, suggesting a lack of RAPA phototoxicity. No evidence of ocular toxicity was noted on ophthalmic examination or histopathology. RAPA was not detected intraocularly 7 days post‐injection in eyes receiving subconjunctival RAPA, but was detected in the vitreous at 21 days post‐injection. Drug could be detected in both the aqueous and vitreous humor after intravitreal injection. Further study is needed to determine the efficacy of intravitreal RAPA.}, number={6}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Douglas, L. C. and Yi, N. Y. and Davis, J. L. and Salmon, J. H. and Gilger, B. C.}, year={2008}, month={Dec}, pages={511–516} }
 @article{gilger_salmon_yi_barden_chandler_wendt_colitz_2008, title={Role of bacteria in the pathogenesis of recurrent uveitis in horses from the southeastern United States}, volume={69}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.69.10.1329}, DOI={10.2460/ajvr.69.10.1329}, abstractNote={Abstract Objective —To determine the role of intraocular bacteria in the pathogenesis of equine recurrent uveitis (ERU) in horses from the southeastern United States by evaluating affected eyes of horses with ERU for bacterial DNA and intraocular production of antibodies against Leptospira spp. Sample Population —Aqueous humor, vitreous humor, and serum samples of 24 clinically normal horses, 52 horses with ERU, and 17 horses with ocular inflammation not associated with ERU (ie, non-ERU inflammation). Procedures —Ribosomal RNA quantitative PCR (real-time PCR) assay was used to detect bacterial DNA in aqueous humor and vitreous humor from clinically normal horses (n = 12) and horses with chronic (> 3-month) ERU (28). Aqueous humor and serum were also evaluated for anti- Leptospira antibody titers from clinically normal horses (n = 12), horses with non-ERU inflammation (17), and horses with confirmed chronic ERU (24). Results —Bacterial DNA was not detected in aqueous humor or vitreous humor of horses with ERU or clinically normal horses. No significant difference was found in titers of anti- Leptospira antibodies in serum or aqueous humor among these 3 groups. Only 2 horses, 1 horse with ERU and 1 horse with non-ERU inflammation, had definitive intraocular production of antibodies against Leptospira organisms. Conclusions and Clinical Relevance —In horses from the southeastern United States, Leptospira organisms may have helped initiate ERU in some, but the continued presence of the organisms did not play a direct role in the pathogenesis of this recurrent disease.}, number={10}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Gilger, Brian C. and Salmon, Jacklyn H. and Yi, Na Y. and Barden, Curtis A. and Chandler, Heather L. and Wendt, Jennifer A. and Colitz, Carmen M. H.}, year={2008}, month={Oct}, pages={1329–1335} }
 @article{gilger_salmon_wilkie_cruysberg_kim_hayat_kim_kim_yuan_lee_et al._2006, title={A Novel Bioerodible Deep Scleral Lamellar Cyclosporine Implant for Uveitis}, volume={47}, ISSN={1552-5783}, url={http://dx.doi.org/10.1167/iovs.05-1540}, DOI={10.1167/iovs.05-1540}, abstractNote={To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis.A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep scleral lamellar CsA implants and were monitored for up to 3 years.Dexamethasone-fluorescein and CsA penetrated the in vitro equine sclera poorly; however, low but detectable levels of CsA were detected intraocularly in vivo. The implant placed episclerally failed to control inflammatory episodes in ERU. CsA implants placed in the deep sclera adjacent to the suprachoroidal space resulted in high levels of CsA in most ocular tissues. In clinical equine patients with ERU, frequency of uveitic flare-ups was significantly decreased after implantation of a deep scleral lamellar CsA implant.Diffusion of CsA across the sclera from the episcleral space was not a feasible method of drug delivery to the equine eye. However, placing a deep scleral lamellar CsA implant adjacent to the suprachoroidal space was effective in achieving therapeutic ocular drug concentrations and controlling uveitis in horses with ERU.}, number={6}, journal={Investigative Opthalmology & Visual Science}, publisher={Association for Research in Vision and Ophthalmology (ARVO)}, author={Gilger, Brian C. and Salmon, Jacklyn H. and Wilkie, David A. and Cruysberg, Lars P. J. and Kim, Jonghyeon and Hayat, Matt and Kim, Hyuncheol and Kim, Stephanie and Yuan, Peng and Lee, Susan S. and et al.}, year={2006}, month={Jun}, pages={2596} }
 @article{beale_salmon_michau_gilger_2006, title={Effect of ophthalmic Nd:YAG laser energy on intraocular lenses after posterior capsulotomy in normal dog eyes}, volume={9}, ISSN={1463-5216 1463-5224}, url={http://dx.doi.org/10.1111/j.1463-5224.2006.00473.x}, DOI={10.1111/j.1463-5224.2006.00473.x}, abstractNote={Abstract Objective To determine Nd:YAG laser energy requirements for posterior capsulotomy and intraocular lens (IOL) damage threshold for foldable acrylic IOLs as compared to traditional polymethylmethacrylate (PMMA). Materials and procedures Four groups of five–six fresh canine cadaver eyes were used in this study. The groups included (1) unaltered eyes (2) aphakic eyes (3) eyes implanted with PMMA IOLs, and (4) eyes implanted with acrylic IOLs. Laser energy was delivered to the posterior capsule in grid fashion for 10 sites each of five levels of laser energy ranging from 0.5 mJ to 9 mJ. Number of successful capsulotomy sites was recorded based on slit‐lamp observation. Sites of IOL damage were evaluated using scanning electron microscopy (SEM). Statistical analysis of number of capsulotomies and IOL defects per laser energy level was conducted among and between groups using anova with Tukey's HSD test. Results When comparing groups (a) including all energy levels ( n = 25) and (b) by specific energy levels ( n = 5), there was no significant difference ( P < 0.05) in number of successful capsulotomy sites between IOL types. The 50% incidence threshold for successful capsulotomy was 2.74 mJ for acrylic IOLs and 2.64 mJ for PMMA IOLs. Energy‐dependent damage to both types of IOL was detected for medium, high‐medium, and high laser energy. Calculated 50% damage threshold was 4.9 mJ for acrylic IOL and 5.7 mJ for PMMA IOL. Damage to the IOL varied subjectively between IOL type, but there was no significant difference in number of defects caused, with the exception of high‐medium energy. Conclusions Both posterior lens capsules and IOLs were disrupted in an energy‐dependent manner with minimal difference in number of capsulotomy sites or damage to the IOL between acrylic and PMMA IOLs. A therapeutic margin between capsulotomy threshold (2.6–2.7 mJ) and IOL damage threshold (4.9–5.7 mJ) was determined to reliably achieve capsulotomies with minimal IOL damage for both acrylic and PMMA IOLs in normal canine cadaver eyes.}, number={5}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Beale, A. Brady and Salmon, Jacklyn and Michau, Tammy M. and Gilger, Brian C.}, year={2006}, month={Sep}, pages={335–340} }
 @article{clode_davis_salmon_michau_gilger_2006, title={Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses}, volume={67}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.67.2.296}, DOI={10.2460/ajvr.67.2.296}, abstractNote={Abstract Objective —To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses. Animals —11 healthy adult horses. Procedure —Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via high-performance liquid chromatography. Five horses received a single orally administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was performed, and voriconazole concentrations in AH were measured. Results —Mean ± SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%, and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 ± 0.37 μg/mL, 2.35 ± 0.78 μg/mL, and 2.40 ± 0.29 μg/mL, respectively. The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations than the 0.5% solution, and only the 3.0% solution induced signs of ocular toxicosis. Voriconazole was detected in the plasma for 1 hour after the final topically administered dose of all solutions. Mean ± SD voriconazole concentration in AH after a single orally administered dose was 0.86 ± 0.22 μg/mL. Conclusions and Clinical Relevance —Results indicated that voriconazole effectively penetrated the cornea in clinically normal eyes and reached detectable concentrations in the AH after topical administration. The drug also penetrated noninflamed equine eyes after oral administration. Low plasma concentrations of voriconazole were detected after topical administration.}, number={2}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Clode, Alison B. and Davis, Jennifer L. and Salmon, Jacklyn and Michau, Tammy Miller and Gilger, Brian C.}, year={2006}, month={Feb}, pages={296–301} }
 @article{davis_salmon_papich_2006, title={Pharmacokinetics and tissue distribution of doxycycline after oral administration of single and multiple doses in horses}, volume={67}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.67.2.310}, abstractNote={Abstract Objective —To determine pharmacokinetics, safety, and penetration into interstitial fluid (ISF), polymorphonuclear leukocytes (PMNLs), and aqueous humor of doxycycline after oral administration of single and multiple doses in horses. Animals —6 adult horses. Procedure —The effect of feeding on drug absorption was determined. Plasma samples were obtained after administration of single or multiple doses of doxycycline (20 mg/kg) via nasogastric tube. Additionally, ISF, PMNLs, and aqueous humor samples were obtained after the final administration. Horses were monitored for adverse reactions. Results —Feeding decreased drug absorption. After multiple doses, mean ± SD time to maximum concentration was 1.63 ± 1.36 hours, maximum concentration was 1.74 ± 0.3 μg/mL, and elimination half-life was 12.07 ± 3.17 hours. Plasma protein binding was 81.76 ± 2.43%. The ISF concentrations correlated with the calculated percentage of non-protein-bound drug. Maximum concentration was 17.27 ± 8.98 times as great in PMNLs, compared with plasma. Drug was detected in aqueous humor at 7.5% to 10% of plasma concentrations. One horse developed signs of acute colitis and required euthanasia. Conclusions and Clinical Relevance —Results suggest that doxycycline administered at a dosage of 20 mg/kg, PO, every 24 hours will result in drug concentrations adequate for killing intracellular bacteria and bacteria with minimum inhibitory concentration ≤ 0.25 μg/mL. For bacteria with minimum inhibitory concentration of 0.5 to 1.0 μg/mL, a dosage of 20 mg/kg, PO, every 12 hours may be required; extreme caution should be exercised with the higher dosage until more safety data are available.}, number={2}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Davis, JL and Salmon, JH and Papich, MG}, year={2006}, month={Feb}, pages={310–316} }
 @article{davis_salmon_papich_2006, title={Pharmacokinetics of voriconazole after oral and intravenous administration to horses}, volume={67}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.67.6.1070}, abstractNote={Abstract Objective —To characterize pharmacokinetics of voriconazole in horses after oral and IV administration and determine the in vitro physicochemical characteristics of the drug that may affect oral absorption and tissue distribution. Animals —6 adult horses. Procedures —Horses were administered voriconazole (1 mg/kg, IV, or 4 mg/kg, PO), and plasma concentrations were measured by use of high-performance liquid chromatography. In vitro plasma protein binding and the octanol:water partition coefficient were also assessed. Results —Voriconazole was adequately absorbed after oral administration in horses, with a systemic bioavailability of 135.75 ± 18.41%. The elimination half-life after a single orally administered dose was 13.11 ± 2.85 hours, and the maximum plasma concentration was 2.43 ± 0.4 μg/mL. Plasma protein binding was 31.68%, and the octanol:water partition coefficient was 64.69. No adverse reactions were detected during the study. Conclusions and Clinical Relevance —Voriconazole has excellent absorption after oral administration and a long half-life in horses. On the basis of the results of this study, it was concluded that administration of voriconazole at a dosage of 4 mg/kg, PO, every 24 hours will attain plasma concentrations adequate for treatment of horses with fungal infections for which the fungi have a minimum inhibitory concentration ≤ 1 μg/mL. Because of the possible nonlinearity of this drug as well as the potential for accumulation, chronic dosing studies and clinical trials are needed to determine the appropriate dosing regimen for voriconazole in horses.}, number={6}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Davis, JL and Salmon, JH and Papich, MG}, year={2006}, month={Jun}, pages={1070–1075} }
 @article{gilger_michau_salmon_2005, title={Immune-mediated keratitis in horses: 19 cases (1998-2004)}, volume={8}, ISSN={1463-5216 1463-5224}, url={http://dx.doi.org/10.1111/j.1463-5224.2005.00393.x}, DOI={10.1111/j.1463-5224.2005.00393.x}, abstractNote={The purpose of this study is to describe clinical and histologic findings, treatment, and outcome of horses with suspected immune-mediated keratitis (IMMK).Retrospective study.Nineteen horses that presented to NCSU-VTH from 1998 to 2004 with IMMK. Procedures Information retrieved from the medical records included signalment, duration of clinical signs, therapy prior to initial examination, ophthalmic abnormalities, diagnostics performed, therapy instituted, and long-term vision.Nineteen horses (22 eyes) were diagnosed with IMMK. Three distinct clinical groups were identified based on the depth of the lesion in the cornea: superficial stromal (n = 11 eyes), midstromal (n = 6 eyes), or endothelial (n = 5 eyes). Horses ranged from 5 to 19 years of age, with a mean age +/- SD of 11.9 +/- 3.6 years. Eleven horses had 12 months or greater duration of clinical signs of corneal disease prior to referral. Overall there was a mean duration of 11.8 +/- SD 8.3 months. Superficial stromal keratitis appeared as a superficial stromal cellular infiltrate with diffuse vascularization. Midstromal keratitis appeared as midstromal cellular infiltrate with mild, surrounding corneal edema and vascularization. Endothelial disease appeared as endothelial cellular infiltrate with diffuse corneal edema. In all types of IMMK, signs of uveitis or severe discomfort were not observed.Horses with superficial IMMK responded to topical medical therapy, but responded best to surgical removal of the lesion. Horses with midstromal keratitis responded to topical cyclosporine therapy. Endothelial disease was the least amenable to therapy.}, number={4}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Gilger, Brian C. and Michau, Tammy Miller and Salmon, Jacklyn H.}, year={2005}, month={Jul}, pages={233–239} }
 @article{davis_salmon_papich_2005, title={Pharmacokinetics and tissue distribution of itraconazole after oral and intravenous administration to horses}, volume={66}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.2005.66.1694}, abstractNote={Abstract Objective —To determine the pharmacokinetics of itraconazole after IV or oral administration of a solution or capsules to horses and to examine disposition of itraconazole in the interstitial fluid (ISF), aqueous humor, and polymorphonuclear leukocytes after oral administration of the solution. Animals —6 healthy horses. Procedure —Horses were administered itraconazole solution (5 mg/kg) by nasogastric tube, and samples of plasma, ISF, aqueous humor, and leukocytes were obtained. Horses were then administered itraconazole capsules (5 mg/kg), and plasma was obtained. Three horses were administered itraconazole (1.5 mg/kg, IV), and plasma samples were obtained. All samples were analyzed by use of high-performance liquid chromatography. Plasma protein binding was determined. Data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Results —Itraconazole reached higher mean ± SD plasma concentrations after administration of the solution (0.41 ± 0.13 µg/mL) versus the capsules (0.15 ± 0.12 µg/mL). Bioavailability after administration of capsules relative to solution was 33.83 ± 33.08%. Similar to other species, itraconazole has a high volume of distribution (6.3 ± 0.94 L/kg) and a long half-life (11.3 ± 2.84 hours). Itraconazole was not detected in the ISF, aqueous humor, or leukocytes. Plasma protein binding was 98.81 ± 0.17%. Conclusions and Clinical Relevance —Itraconazole administered orally as a solution had higher, more consistent absorption than orally administered capsules and attained plasma concentrations that are inhibitory against fungi that infect horses. Administration of itraconazole solution (5 mg/kg, PO, q 24 h) is suggested for use in clinical trials to test the efficacy of itraconazole in horses. ( Am J Vet Res 2005;66:1694–1701)}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Davis, JL and Salmon, JH and Papich, MG}, year={2005}, month={Oct}, pages={1694–1701} }
 @article{davis_salmon_papich_2005, title={Pharmacokinetics and tissue fluid distribution of cephalexin in the horse after oral and i.v. administration}, volume={28}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2005.00683.x}, abstractNote={The purpose of this study was to determine the pharmacokinetics and tissue fluid distribution of cephalexin in the adult horse following oral and i.v. administration. Cephalexin hydrate (10 mg/kg) was administered to horses i.v. and plasma samples were collected. Following a washout period, cephalexin (30 mg/kg) was administered intragastrically. Plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected. All samples were analyzed by high-pressure liquid chromatography (HPLC). Following i.v. administration, cephalexin had a plasma half-life (t(1/2)) of 2.02 h and volume of distribution [V(d(ss))] of 0.25 L/kg. Following oral administration, the average maximum plasma concentration (C(max)) was 3.47 mug/mL and an apparent half-life (t(1/2)) of 1.64 h. Bioavailability was approximately 5.0%. The AUC(ISF):AUC(plasma) ratio was 80.55% which corresponded to the percentage protein-unbound drug in the plasma (77.07%). The t(1/2) in the ISF was 2.49 h. Cephalexin was not detected in the aqueous humor. The octanol:water partition coefficient was 0.076 +/- 0.025. Cephalexin was concentrated in the urine with an average concentration of 47.59 microg/mL. No adverse events were noted during this study. This study showed that cephalexin at a dose of 30 mg/kg administered orally at 8 h dosage intervals in horses can produce plasma and interstitial fluid drug concentrations that are in a range recommended to treat susceptible gram-positive bacteria (MIC < or = 0.5 microg/mL). Because of the low oral bioavailability of cephalexin in the horse, the effect of chronic dosing on the normal intestinal bacterial flora requires further investigation.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Davis, JL and Salmon, JH and Papich, MG}, year={2005}, month={Oct}, pages={425–431} }
 @article{gilger_yang_salmon_jaffe_allen_2002, title={Expression of a chemokine by ciliary body epithelium in horses with naturally occurring recurrent uveitis and in cultured ciliary body epithelial cells}, volume={63}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.2002.63.942}, abstractNote={Abstract Objective —To determine whether a chemokine (RANTES)-like protein expressed by ciliary epithelium plays a role in uveitis. Sample Population —3 clinically normal horses intradermal, 5 eyes from 5 horses with recurrent uveitis, and 10 normal eyes from 5 age- and sex-matched horses. Procedure —Cross-reactivity and sensitivity of recombinant human (rh)-regulated upon activation, normal T-cell expressed and secreted (RANTES) protein were evaluated in horses by use of intradermal hypersensitivity reactions and a chemotaxis assay. Aqueous humor and ciliary body of eyes from clinically normal horses and horses with uveitis were examined for RANTES expression by use of an ELISA and reverse transcription-polymerase chain reaction (RT-PCR). Expression of RANTES mRNA and protein content of primary cultures of equine ciliary pigmented epithelial cells (RT-PCR) and culture supernatant (ELISA) were measured 6 or 24 hours, respectively, after cultures were stimulated with interleukin-1β and tumor necrosis factor-α. Results —Strong reactions to intradermal hypersensitivity testing and significant chemotaxis of equine leukocytes to rh-RANTES wereas observed. Aqueous humor of eyes from horses with uveitis contained increased concentrations of rh-RANTES-like protein (mean ± SD, 45.9 ± 31.7 pg/ml), compared with aqueous humor from clinically normal horses (0 pg/ml). Ciliary body from horses with uveitis expressed RANTES mRNA, whereas ciliary body from clinically normal horses had low mRNA expression. Stimulated ciliary pigmented epithelial cells expressed increased amounts of rh-RANTES-like protein (506.1 ± 298.3 pg/ml) and mRNA, compared with unstimulated samples. Conclusions and Clinical Relevance —Ciliary epithelium may play a role in recruitment and activation of leukocytes through expression of RANTES. ( Am J Vet Res 2002;63:942–947)}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Gilger, BC and Yang, P and Salmon, JH and Jaffe, GJ and Allen, JB}, year={2002}, month={Jul}, pages={942–947} }
 @article{gilger_stoppini_wilkie_clode_pinto_hempstead_gerding_salmon, title={Treatment of immune-mediated keratitis in horses with episcleral cyclosporine-silicone matrix- implant}, volume={30}, number={6}, journal={Pferdeheilkunde}, author={Gilger, B. C. and Stoppini, R. and Wilkie, D. A. and Clode, A. B. and Pinto, N. H. and Hempstead, J. and Gerding, J. and Salmon, J. H.}, pages={711–712} }