Combination phacoemulsification and pars plana vitrectomy for retinal reattachment surgery in the Siberian Husky breed.

Objective: To report the success rate and complications of combined phacoemulsification and pars plana vitrectomy (PPV) for treatment of cataracts and retinal detachment in the Siberian Husky breed.

Animals Studied: Client-owned Siberian Husky dogs that underwent combined phacoemulsification and PPV at two veterinary referral centers.

Procedure: Retrospective study of 16 Siberian Husky dogs that underwent combined phacoemulsification and PPV with a minimum 3-month postoperative follow-up.

Lamellar Keratoplasty Using Acellular Bioengineering Cornea (BioCorneaVet) for the Treatment of Feline Corneal Sequestrum: A Retrospective Study of 62 Eyes (2018-2021).

To retrospectively evaluate the effectiveness and outcome of lamellar keratoplasty using acellular bioengineering cornea (BioCorneaVet) for the treatment of feline corneal sequestrum (FCS). The medical records of cats diagnosed with FCS that underwent lamellar keratoplasty with BioCorneaVet between 2018 and 2021 with a minimum of 3 months of follow-up were reviewed. Follow-up examinations were performed weekly for 3 months, and then optical coherence tomography (OCT) examination was performed on select patients at 0, 3, 6, and 12 months post-operatively.

Discovery of the Selective Protein Kinase C-θ Kinase Inhibitor, CC-90005.

The PKC-θ isoform of protein kinase C is selectively expressed in T lymphocytes and plays an important role in the T cell antigen receptor (TCR)-triggered activation of mature T cells, T cell proliferation, and the subsequent release of cytokines such as interleukin-2 (IL-2). Herein, we report the synthesis and structure-activity relationship (SAR) of a novel series of PKC-θ inhibitors. Through a combination of structure-guided design and exploratory SAR, suitable replacements for the basic C4 amine of the original lead () were identified.

Long-term results (>1 year) in 19 dogs treated with MicroPulse transscleral diode cyclophotocoagulation for refractory glaucoma.

Objective: To report the long-term (>1 year) outcome of MicroPulse transscleral diode cyclophotocoagulation (MP-TSCP) in dogs.

Animals Studied: Client owned dogs that underwent MP-TSCP at a veterinary referral center.

Procedure: Retrospective study of 19 dogs treated with MP-TSCP.

Presumed neuroprotective therapies prescribed by veterinary ophthalmologists for canine degenerative retinal and optic nerve diseases.

Objective: To investigate veterinary ophthalmologists' use of presumed neuroprotective therapies for degenerative retinal and optic nerve diseases in dogs.

Procedures: An online survey was sent to 663 board-certified veterinary ophthalmologists who were Diplomates of the American College of Veterinary Ophthalmologists (ACVO), Asian College of Veterinary Ophthalmologists (AiCVO), Latin American College of Veterinary Ophthalmologists (Colegio Latinoamericano de Oftalmólogos Veterinarios, CLOVE), or European College of Veterinary Ophthalmologists (ECVO). The survey was created using Qualtrics® software and focused on the prescription of presumed neuroprotective treatments for canine glaucoma, sudden acquired retinal degeneration syndrome (SARDS), progressive retinal atrophy (PRA), and retinal detachment (RD).

CC-90009: A Cereblon E3 Ligase Modulating Drug That Promotes Selective Degradation of GSPT1 for the Treatment of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is marked by significant unmet clinical need due to both poor survival and high relapse rates where long-term disease control for most patients with relapsed or refractory AML remain dismal. Inspired to bring novel therapeutic options to these patients, we envisioned protein degradation as a potential therapeutic approach for the treatment of AML. Following this course, we discovered and pioneered a novel mechanism of action which culminated in the discovery of CC-90009.

Prophylactic anti-glaucoma therapy in dogs with primary glaucoma: A practitioner survey of current medical protocols.

Aim: To examine the use of prophylactic anti-glaucoma medications in the normotensive fellow eye in dogs with unilateral overt primary glaucoma by veterinary ophthalmology clinicians.

Methods: A survey of veterinary ophthalmology clinicians was distributed over two international list serves servicing veterinary ophthalmologists, trainees, and individuals whose practice consisted primarily of ophthalmic patients. The survey was developed following analysis of historical and currently available medical options for control of intraocular pressure and for neuroprotection.

Preliminary report of postoperative complications of phacoemulsification in Pugs: A multicenter retrospective study of 32 cases.

Objective: To compare complication rates and visual outcomes following phacoemulsification in Pugs versus dogs of other breeds.

Animals Studied: Thirty-two pure-bred Pugs (55 eyes) and 32 dogs of other breeds (56 eyes) undergoing phacoemulsification.

Procedures: Multi-institutional retrospective medical record review of perioperative factors, postoperative complications, and visual outcomes.

Corneal hypoesthesia, aqueous tear deficiency, and neurotrophic keratopathy following micropulse transscleral cyclophotocoagulation in dogs.

Objective: To describe ocular surface complications following micropulse transscleral cyclophotocoagulation (MP-TSCPC) in dogs.

Animals Studied: Eighteen dogs treated with MP-TSCPC at two institutions for glaucoma management.

Procedures: MP-TSCPC was applied to each eye (avoiding 3 and 9 o'clock positions) with 31.

The future of canine glaucoma therapy.

Canine glaucoma is a group of disorders that are generally associated with increased intraocular pressure (IOP) resulting in a characteristic optic neuropathy. Glaucoma is a leading cause of irreversible vision loss in dogs and may be either primary or secondary. Despite the growing spectrum of medical and surgical therapies, there is no cure, and many affected dogs go blind.

Bilateral phacoemulsification and intraocular lens implantation in a young African lion .

An 18-month-old intact female lioness was referred to the Clinica Veterinaria Roma Sud for evaluation of bilateral cataracts. Phacoemulsification and implantation of +30 diopter intraocular lens (IOL) were performed bilaterally. Seven years after surgery, the IOL remained centrally positioned and the patient had normal activity.

Preliminary findings in 30 dogs treated with micropulse transscleral cyclophotocoagulation for refractory glaucoma.

Objective: The purpose of this study was to report the preliminary results of a novel micropulse transscleral diode laser cyclophotocoagulation (MP-TSCP) as primary therapy for glaucomatous dogs.

Animal Studied: Client owned dogs undergoing MP-TSCP therapy at a veterinary referral center.

Procedure: Retrospective study of dogs with glaucoma that were treated with MP-TSCP with a minimum of 1 month (range: 1-18 months) of follow-up.

The combined use of surgical debulking and diode laser photocoagulation for limbal melanoma treatment: a retrospective study of 21 dogs.

Objective: To evaluate effectiveness and safety of debulking and diode laser photocoagulation (DPC) for the treatment of limbal melanoma (LM).

Procedure: Retrospective multi-institutional case series. Medical records of animals diagnosed with LM at the Centro Veterinario Specialistico (CVS) and at the Long Island Veterinary Specialists from 1994 to 2014 were retrieved.

Sudden acquired retinal degeneration in dogs: breed distribution of 495 canines.

Purpose: The purpose of this study was to describe breed, age, gender, and weight distribution of dogs affected with sudden acquired retinal degeneration (SARD) and to investigate whether SARD is more common in small breed dogs.

Methods: Medical records of dogs diagnosed with SARD confirmed by an electroretinogram were reviewed. Breed, age, gender, and weight were recorded when available.

RETROSPECTIVE INVESTIGATION OF CATARACT MANAGEMENT IN AVIAN SPECIES IN A ZOOLOGIC COLLECTION.

A review of avian cataracts at the Wildlife Conservation Society's Bronx Zoo between 1992 and 2011 was conducted. Ninety cataracts in 54 birds from 42 species were identified. Cataracts were found primarily during examination for ocular abnormalities (29/54, 53.

Optimization of a Series of Triazole Containing Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors and the Discovery of CC-115.

We report here the synthesis and structure-activity relationship (SAR) of a novel series of triazole containing mammalian target of rapamycin (mTOR) kinase inhibitors. SAR studies examining the potency, selectivity, and PK parameters for a series of triazole containing 4,6- or 1,7-disubstituted-3,4-dihydropyrazino[2,3-b]pyrazine-2(1H)-ones resulted in the identification of triazole containing mTOR kinase inhibitors with improved PK properties. Potent compounds from this series were found to block both mTORC1(pS6) and mTORC2(pAktS473) signaling in PC-3 cancer cells, in vitro and in vivo.

Discovery of mammalian target of rapamycin (mTOR) kinase inhibitor CC-223.

We report here the synthesis and structure-activity relationship (SAR) of a novel series of mammalian target of rapamycin (mTOR) kinase inhibitors. A series of 4,6- or 1,7-disubstituted-3,4-dihydropyrazino[2,3-b]pyrazine-2(1H)-ones were optimized for in vivo efficacy. These efforts resulted in the identification of compounds with excellent mTOR kinase inhibitory potency, with exquisite kinase selectivity over the related lipid kinase PI3K.

Suture anchor placement technique around the insertion of the ventral rectus muscle for the replacement of the prolapsed gland of the third eyelid in dogs: 100 dogs.

Objective: To evaluate a rapid and efficacious procedure to anchor the prolapsed gland of the third eyelid in dogs.

Methods: This is a retrospective study of 100 affected dogs (122 eyes) with third eyelid gland prolapse that were surgically anchored with a nonabsorbable suture around the insertion of the ventral rectus muscle.

Results: Hundred dogs (122 eyes) were included in this study.

Screening ADAMTS10 in dog populations supports Gly661Arg as the glaucoma-causing variant in beagles.

Purpose: Previously, we mapped the disease locus in the beagle model of autosomal recessive primary open angle glaucoma (POAG) to a 4-Mb interval on chromosome 20, and identified a Gly661Arg variant in ADAMTS10 as the candidate disease-causing variant. The purpose of this study was to test the hypothesis that the Gly661Arg variant of ADAMTS10 causes glaucoma by genotyping dogs of various breeds affected and unaffected by primary glaucoma.

Methods: Dogs of various breeds, affected or unaffected with primary glaucoma, were genotyped for the Gly661Arg variant of ADAMTS10, as well as 7 other nonsynonymous single nucleotide polymorphisms (SNPs) in other genes in the beagle POAG locus that segregate with disease.

Use of core modification in the discovery of CC214-2, an orally available, selective inhibitor of mTOR kinase.

We report here the discovery of a novel series of selective mTOR kinase inhibitors and the identification of CC214-2, a compound with demonstrated anti-tumor activity upon oral dosing in a PC3 prostate cancer xenograft model. A series of 4,6-disubstituted-3,4-dihydropyrazino[2,3-b]pyrazine-2(1H)-ones were discovered through a core modification of our original compound series. Analogs from this series have excellent mTOR potency and maintain selectivity over the related PI3Kα lipid kinase.

Refractive state following retinal reattachment and silicone oil tamponade in dogs.

Objective: To evaluate the refractive error induced by intraocular administration of silicone oil (SiO) in dogs.

Animals: 47 client-owned dogs evaluated for blindness secondary to retinal detachment.

Procedures: -3-port pars plana vitrectomy with perfluoro-octane and SiO exchange (1,000- or 5,000-centistoke SiO) was performed in 1 or both eyes for all dogs (n = 63 eyes), depending on which eye or eyes were affected.

Partial ligation of the transposed parotid duct at the level of the parotid gland for excessive salivary secretions.

Objective: To determine the outcome and effect of a partial ligation of the transposed parotid duct at the level of the parotid gland in four dogs with excessive salivation and ocular irritation.

Methods: Four dogs were previously diagnosed with absolute keratoconjunctivitis sicca. After a parotid duct transposition (PDT) surgery, these dogs experienced excessive saliva production and abundant salivary precipitates, which resulted in epiphora, moist dermatitis, blepharospasm, and keratitis.

Discovery of CC-930, an orally active anti-fibrotic JNK inhibitor.

In this Letter we describe the discovery of potent, selective, and orally active aminopurine JNK inhibitors. Improving the physico-chemical properties as well as increasing the potency and selectivity of a subseries with rat plasma exposure, led to the identification of four structurally diverse inhibitors. Differentiation based on PK profiles in multiple species as well as activity in a chronic efficacy model led to the identification of 1 (CC-930) as a development candidate, which is currently in Phase II clinical trial for IPF.