Minimally invasive Dorsal cheilectomy and Hallux metatarsophalangeal joint arthroscopy for the treatment of Hallux Rigidus.

BACKGROUND: Minimally invasive dorsal cheilectomy (MIDC) has become a popular alternative to an open approach for treating Hallux Rigidus (HR). To reduce some of the complications related to the MIDC approach, a first metatarsophalangeal (MTP) joint arthroscopy can be performed in addition to address the intra-articular pathology associated with Hallux Rigidus. This study aims to examine the effectiveness of MIDC with first MTP arthroscopy in patients with HR with a minimum 1-year follow-up. METHODS: This was a multicenter retrospective review for adult patients with Coughlin and Shurnass Grade 0-3 who were treated with MIDC and first MTP arthroscopy between 3/1/2020 and 8/1/2022, with at least one year of follow-up data. Demographic information, first MTP range of motion (ROM), visual analog scale (VAS), Manchester-Oxford Foot Questionnaire (MOXFQ), and EQ-5D-5 L scores were collected. Continuous data was expressed as a mean and standard deviation, categorical data was expressed as a percentage. Wilcoxon Rank Sum test was used to compare continuous variables. All P < 0.05 was considered significant. RESULTS: A total of 31 patients were included in the study. Average follow-up time was 16.5 months (range: 12 to 26.2). There was 1 (3.2%) undersurface EHL tendon tear, 2 (6.5%) conversions to an MTP fusion, and 1 (3.2%) revision cheilectomy and capsular release for MTP joint contracture. There was a significant improvement in patient's ROM in dorsiflexion (50 vs 89.6 degrees, P = 0.002), postoperative VAS pain scores (6.4 vs 2.1, P < 0.001), MOXFQ pain scores (58.1 vs 30.7, P = 0.001), MOXFQ Walking/Standing scores (56.6 vs 20.6, P = 0.001), MOXFQ Social Interaction scores (47.3 vs 19.36, P = 0.002), and MOXFQ Index scores (54.7 vs 22.4, P < 0.001). CONCLUSION: We found that MIDC with first MTP arthroscopy was effective at improving patient-reported outcomes at one year with low complication and revision rates. These results suggest that MIDC with first MTP arthroscopy is an effective treatment for early-stage HR. LEVEL OF EVIDENCE: IV.

Novel Presentation of Hemiplegic Migraine in a Patient With Cockayne Syndrome.

BACKGROUND: Cockayne syndrome is a rare DNA repair disorder marked by premature aging, poor growth, and intellectual disability. Neurological complications such as seizures, movement disorder, and stroke have been reported. Hemiplegic migraine has not been reported in association with Cockayne syndrome. METHODS: We report a male with Cockayne syndrome due to biallelic heterozygous pathogenic variants in ERCC6 who presented repeatedly with transient focal neurological deficits and headache, which were consistent with hemiplegic migraine. Two siblings also had Cockayne syndrome and presented with similar symptoms. RESULTS: Our patient was originally diagnosed based on clinical suspicion and then confirmed by targeted exome analysis of genes associated with Cockayne syndrome. The family's research exome sequencing data were reanalyzed to identify variants in genes known to cause familial hemiplegic migraine. No variants in the genes known to cause familial hemiplegic migraine were identified. CONCLUSION: This is a novel association of familial hemiplegic migraine in three full siblings with Cockayne syndrome. Hemiplegic migraine has not previously been described as part of the Cockayne syndrome presentation. A separate genetic cause of familial hemiplegic migraines was not identified in an exome-based analysis of genes known to cause this condition. This report may represent an expansion of the Cockayne syndrome phenotype.

Novel Achilles tendon repair technique utilizing an allograft and hybrid external fixator in dogs.

Background: Achilles mechanism rupture is a surgical condition involving primary tenorrhaphy with various described means of surgical augmentation and bolstering. Aim: To report complications and outcomes with a novel Achilles repair technique in dogs using a superficial digital flexor tendon (SDFT) or deep digital flexor tendon (DDFT) allograft. Methods: Medical records were reviewed for dogs with chronic rupture or deterioration of the Achilles mechanism. Fibrous tissue was excised and either primary tenorrhaphy or reattachment of the tendon(s) to the calcaneus was performed. The surgical repair was supplemented by an SDFT or DDFT allograft, and postoperative immobilization was provided using a transarticular hybrid external skeletal fixator. Complications were classified as minor, major, or catastrophic, and function was classified as full, acceptable, or unacceptable, based on established guidelines. Results: Complications occurred with 6 out of 12 repairs, including 1 minor, 6 major, and 2 catastrophic complications. The two catastrophic complications were the recurrence of tarsal hyperflexion and lameness at 20 weeks and 18 months following surgery. Of the 12 surgeries performed, 2 resulted in full function, 8 with acceptable function, and 2 with unacceptable function at last follow-up 17-98 weeks postsurgery (mean = 45 weeks) for a success rate of 10/12 cases. Conclusion: The use of SDFT or DDFT allografts, coupled with an external fixator, can provide a moderate rate of full or acceptable functional outcomes and appears a viable treatment. However, complications were frequent and without a comparison group no conclusions can be drawn about the inferiority or superiority of this technique to other techniques for Achilles mechanism repair in dogs.

De novo missense mutation in GRIA2 in a patient with global developmental delay, autism spectrum disorder, and epileptic encephalopathy.

De novo variants are increasingly recognized as a common cause of early infantile epileptic encephalopathies. We present a 4-year-old male with epileptic encephalopathy characterized by seizures, autism spectrum disorder, and global developmental delay. Whole genome sequencing of the proband and his unaffected parents revealed a novel de novo missense variant in GRIA2 (c.1589A>T; p.Lys530Met; ENST00000264426.14). Variants in the GRIA2 gene were recently reported to cause an autosomal dominant neurodevelopmental disorder with language impairments and behavioral abnormalities (OMIM; MIM #618917), a condition characterized by intellectual disability and developmental delay in which seizures are a common feature. The de novo variant identified in our patient maps to the edge of a key ligand binding domain of the AMPA receptor and has not been previously reported in gnomAD or other public databases, making it novel. Our findings provided a long-sought diagnosis for this patient and support the link between GRIA2 and a dominant neurodevelopmental disorder.

Case report and review of the literature: immune dysregulation in a large familial cohort due to a novel pathogenic RELA variant.

OBJECTIVE: To explore and define the molecular cause(s) of a multi-generational kindred affected by Bechet's-like mucocutaneous ulcerations and immune dysregulation. METHODS: Whole genome sequencing and confirmatory Sanger sequencing were performed. Components of the NFκB pathway were quantified by immunoblotting, and function was assessed by cytokine production (IL-6, TNF-α, IL-1ß) after lipopolysaccharide (LPS) stimulation. Detailed immunophenotyping of T-cell and B-cell subsets was performed in four patients from this cohort. RESULTS: A novel variant in the RELA gene, p. Tyr349LeufsTer13, was identified. This variant results in premature truncation of the protein before the serine (S) 536 residue, a key phosphorylation site, resulting in enhanced degradation of the p65 protein. Immunoblotting revealed significantly decreased phosphorylated [p]p65 and pIκBα. The decrease in [p]p65 may suggest reduced heterodimer formation between p50/p65 (NFκB1/RelA). Immunophenotyping revealed decreased naïve T cells, increased memory T cells, and expanded senescent T-cell populations in one patient (P1). P1 also had substantially higher IL-6 and TNF-α levels post-stimulation compared with the other three patients. CONCLUSION: Family members with this novel RELA variant have a clinical phenotype similar to other reported RELA cases with predominant chronic mucocutaneous ulceration; however, the clinical phenotype broadens to include Behçet's syndrome and IBD. Here we describe the clinical, immunological and genetic evaluation of a large kindred to further expand identification of patients with autosomal dominant RELA deficiency, facilitating earlier diagnosis and intervention. The functional impairment of the canonical NFκB pathway suggests that this variant is causal for the clinical phenotype in these patients.

Biallelic SEPSECS variants in two siblings with pontocerebellar hypoplasia type 2D underscore the relevance of splice-disrupting synonymous variants in disease.

Noncoding and synonymous coding variants that exert their effects via alternative splicing are increasingly recognized as an important category of disease-causing variants. In this report, we describe two siblings who presented with hypotonia, profound developmental delays, and seizures. Brain magnetic resonance imaging (MRI) in the proband at 5 yr showed diffuse cerebral and cerebellar white matter volume loss. Both siblings later developed ventilator-dependent respiratory insufficiency and scoliosis and are currently nonverbal and nonambulatory. Extensive molecular testing including oligo array and clinical exome sequencing was nondiagnostic. Research genome sequencing under an institutional review board (IRB)-approved study protocol revealed that both affected children were compound-heterozygous for variants in the SEPSECS gene. One variant was an initiator codon change (c.1A > T) that disrupted protein translation, consistent with the observation that most disease-causing variants are loss-of-function changes. The other variant was a coding change (c.846G > A) that was predicted to be synonymous but had been demonstrated to disrupt mRNA splicing in a minigene assay. The SEPSECS gene encodes O-phosphoseryl-tRNA(Sec) selenium transferase, an enzyme that participates in the biosynthesis and transport of selenoproteins in the body. Variations in SEPSECS cause autosomal recessive pontocerebellar hypoplasia type 2D (PCHT 2D; OMIM #613811), a neurodegenerative condition characterized by progressive cerebrocerebellar atrophy, microcephaly, and epileptic encephalopathy. The identification of biallelic pathogenic variants in this family-one of which was a synonymous change not identified by prior clinical testing-not only ended the diagnostic odyssey for this family but also highlights the contribution of occult pathogenic variants that may not be recognized by standard genetic testing methodologies.

Long-read whole genome sequencing reveals HOXD13 alterations in synpolydactyly.

Synpolydactyly 1, also called syndactyly type II (SDTY2), is a genetic limb malformation characterized by polydactyly with syndactyly involving the webbing of the third and fourth fingers, and the fourth and fifth toes. It is caused by heterozygous alterations in HOXD13 with incomplete penetrance and phenotypic variability. In our study, a five-generation family with an SPD phenotype was enrolled in our Rare Disease Genomics Protocol. A comprehensive examination of three generations using Illumina short-read whole-genome sequencing (WGS) did not identify any causative variants. Subsequent WGS using Pacific Biosciences (PacBio) long-read HiFi Circular Consensus Sequencing (CCS) revealed a heterozygous 27-bp duplication in the polyalanine tract of HOXD13. Sanger sequencing of all available family members confirmed that the variant segregates with affected individuals. Reanalysis of an unrelated family with a similar SPD phenotype uncovered a 21-bp (7-alanine) duplication in the same region of HOXD13. Although ExpansionHunter identified these events in most individuals in a retrospective analysis, low sequence coverage due to high GC content in the HOXD13 polyalanine tract makes detection of these events challenging. Our findings highlight the value of long-read WGS in elucidating the molecular etiology of congenital limb malformation disorders.

Comparison of osteotomy level with three different canine total hip replacement systems.

Background: Numerous cementless total hip replacement (THR) systems are available for application in dogs and one of the potential differences among these systems is the technique for performing a femoral osteotomy and the amount of bone preserved in the calcar region. However, no quantitative comparison of osteotomy level has been performed for canine THRs to date. Aims: To develop and validate a method for quantifying the level of the osteotomy at its most distomedial aspect in conjunction with canine THR and to compare osteotomy level between multiple different THRs. Methods: Immediate post-operative cranial-caudal or caudal-cranial radiographs of 33 dogs treated with 17 Helica and 17 BFX THR were assessed and osteotomy level was quantified using a novel radiographic assessment by 3 independent observers. Correlation among observers was quantified using a Spearman rank order correlation. Osteotomy location was subsequently quantified for an additional 10 Zurich THRs. The osteotomy level for each THR was subsequently compared between Helica, BFX, and Zurich THRs using one-way non-parametric Mann-Whitney rank sum tests and significance set at p < 0.05. Results: R-values assessing correlation between observers were 0.87, 0.72, and 0.60. Osteotomy location was significantly more proximal in conjunction with the Helica (0.75 ± 0.22) versus the BFX (0.97 ± 0.13; p < 0.001) and Zurich (1.1 ± 0.15; p < 0.001) femoral prostheses. Osteotomy location was also significantly more proximal with the BFX prosthesis in comparison to the Zurich THR (p < 0.05). Conclusion: The strong correlations among three different observers indicate that the technique for measuring the location of the distomedial aspect of the osteotomy was acceptably precise. The osteotomies made in conjunction with the short-stemmed Helica implants were significantly more proximal than those made with both of the long-stemmed (BFX and Zurich) femoral prostheses. The distomedial aspect of the osteotomy with the BFX system was significantly more proximal than that with the Zurich THR, indicating that between these two long-stemmed systems the osteotomy level is unique.

Discovery of clinically relevant fusions in pediatric cancer.

BACKGROUND: Pediatric cancers typically have a distinct genomic landscape when compared to adult cancers and frequently carry somatic gene fusion events that alter gene expression and drive tumorigenesis. Sensitive and specific detection of gene fusions through the analysis of next-generation-based RNA sequencing (RNA-Seq) data is computationally challenging and may be confounded by low tumor cellularity or underlying genomic complexity. Furthermore, numerous computational tools are available to identify fusions from supporting RNA-Seq reads, yet each algorithm demonstrates unique variability in sensitivity and precision, and no clearly superior approach currently exists. To overcome these challenges, we have developed an ensemble fusion calling approach to increase the accuracy of identifying fusions. RESULTS: Our Ensemble Fusion (EnFusion) approach utilizes seven fusion calling algorithms: Arriba, CICERO, FusionMap, FusionCatcher, JAFFA, MapSplice, and STAR-Fusion, which are packaged as a fully automated pipeline using Docker and Amazon Web Services (AWS) serverless technology. This method uses paired end RNA-Seq sequence reads as input, and the output from each algorithm is examined to identify fusions detected by a consensus of at least three algorithms. These consensus fusion results are filtered by comparison to an internal database to remove likely artifactual fusions occurring at high frequencies in our internal cohort, while a "known fusion list" prevents failure to report known pathogenic events. We have employed the EnFusion pipeline on RNA-Seq data from 229 patients with pediatric cancer or blood disorders studied under an IRB-approved protocol. The samples consist of 138 central nervous system tumors, 73 solid tumors, and 18 hematologic malignancies or disorders. The combination of an ensemble fusion-calling pipeline and a knowledge-based filtering strategy identified 67 clinically relevant fusions among our cohort (diagnostic yield of 29.3%), including RBPMS-MET, BCAN-NTRK1, and TRIM22-BRAF fusions. Following clinical confirmation and reporting in the patient's medical record, both known and novel fusions provided medically meaningful information. CONCLUSIONS: The EnFusion pipeline offers a streamlined approach to discover fusions in cancer, at higher levels of sensitivity and accuracy than single algorithm methods. Furthermore, this method accurately identifies driver fusions in pediatric cancer, providing clinical impact by contributing evidence to diagnosis and, when appropriate, indicating targeted therapies.

Maternal mosaicism for a missense variant in the SMS gene that causes Snyder-Robinson syndrome.

There is increasing recognition for the contribution of genetic mosaicism to human disease, particularly as high-throughput sequencing has enabled detection of sequence variants at very low allele frequencies. Here, we describe an infant male who presented at 9 mo of age with hypotonia, dysmorphic features, congenital heart disease, hyperinsulinemic hypoglycemia, hypothyroidism, and bilateral sensorineural hearing loss. Whole-genome sequencing of the proband and the parents uncovered an apparent de novo mutation in the X-linked SMS gene. SMS encodes spermine synthase, which catalyzes the production of spermine from spermidine. Inactivation of the SMS gene disrupts the spermidine/spermine ratio, resulting in Snyder-Robinson syndrome. The variant in our patient is absent from the gnomAD and ExAC databases and causes a missense change (p.Arg130Cys) predicted to be damaging by most in silico tools. Although Sanger sequencing confirmed the de novo status in our proband, polymerase chain reaction (PCR) and deep targeted resequencing to ∼84,000×-175,000× depth revealed that the variant is present in blood from the unaffected mother at ∼3% variant allele frequency. Our findings thus provided a long-sought diagnosis for the family while highlighting the role of parental mosaicism in severe genetic disorders.

Hypomorphic alleles pose challenges in rare disease genomic variant interpretation.

Exon skipping associated with an ATP7B intronic variant in a patient with Wilson's disease. (A) Sashimi plot visualization of aligned RNA sequencing data from proband liver tissue at ATP7B exons 14-13-12. The red track shows traditional RNA-seq data; the blue track shows RNA-seq enriched with exon capture (cDNA-cap) which achieves higher depth of protein-coding transcripts. The histogram indicates overall sequencing depth while arcs tabulate the number of junction-spanning reads supporting exon pairs. (B) The domain structure (top) and exon structure (bottom) of ATP7B. Loss of exon 13 (dashed box) would remove a transmembrane domain and disrupt the first phosphorylation domain.

Randomized Controlled Trial Comparing Autologous Protein Solution to Hyaluronic Acid Plus Triamcinolone for Treating Hip Osteoarthritis in Dogs.

Twenty-three dogs with bilateral hip osteoarthritis were used to compare the efficacy of intra-articular injections of autologous protein solution (APS) to hyaluronic acid plus triamcinolone (HAT). Prior to treatment, owner assessments of pain and mobility were obtained using the canine brief pain inventory (CBPI) and Liverpool Osteoarthritis for Dogs (LOAD) questionnaires. Owners were also asked to list all medications used to control signs of pain associated with hip osteoarthritis (OA). In addition, objective kinetic data using a pressure sensitive walkway was used to quantify the relative weight bearing of each of the limbs (total pressure index; TPI). One hip was then selected using a random number generator for injection with HAT and the contralateral hip was injected with APS under the same sedation event. At 1-, 3-, and 6 months following injection, medication usage was recorded and dogs were re-assessed using the CBPI and LOAD questionnaires and using objective gait analysis to determine the TPI. Twenty dogs completed all aspects of the study and statistically significant (p < 0.05) improvements were noted by dog owners at every post-treatment time point in every category of pain and mobility as assessed by the CBPI and LOAD questionnaires. Only 5 dogs, compared to 14 pre-treatment, received any oral NSAID or other analgesic for the duration of the 6-month study period. The TPI, and change in TPI from baseline, were not statistically significantly different between the two treatments at any time point. These data suggest clinical efficacy of both APS and HAT, but fail to show superiority of one treatment vs. the other. The inability to detect a statistically significant difference between the two treatments could be attributable to a true lack of a difference, or a type II statistical error.

Complications with the Zurich Canine Total Hip Replacement System in an Initial Series of Cases Performed by a Single Surgeon.

OBJECTIVE: The aim of this study was to quantify the complications using the Zurich total hip replacement system in an initial series of cases performed by a single surgeon who had experience with other total hip replacement systems. MATERIALS AND METHODS: This was a retrospective study in which complications were classified as major if any treatment was needed or if the outcome was less than near-normal function. Complications that did not warrant treatment and that did not result in function that was inferior to near-normal were considered minor. Outcomes were assessed by radiographic review, physical examination, subjective gait evaluation or, in one case, by objective gait analysis. Bilateral total hip replacements were considered separate procedures. RESULTS: The first 21 procedures in 19 dogs performed by a single surgeon were included. The mean time to follow-up was 48 weeks (range: 8-120 weeks; standard deviation: 36 weeks). Two cases (of 21) experienced major complications including one dog with excess internal femoral rotation during weight bearing and one dog having luxation. One case (of 21) had a minor complication; femoral fracture in the presence of an intact bone plate that maintained alignment and healed without treatment. CLINICAL SIGNIFICANCE: A high rate of successful outcomes with few major complications can be obtained in the initial cases treated using the Zurich total hip replacement system for surgeons with prior experience with other total hip replacement systems.

Outcomes Associated With Osteochondral Allograft Transplantation in Dogs.

The purpose of this study was to retrospectively characterize outcomes and complications associated with osteochondral allograft transplantation for treating chondral and osteochondral lesions in a group of client-owned dogs with naturally-occurring disease. Records were reviewed for information on signalment, treated joint, underlying pathology (e.g., osteochondritis dissecans; OCD), and type, size, and number of grafts used. Complications were classified as "trivial" if no treatment was provided, "non-surgical" if non-surgical treatment were needed, "minor surgical" if a minor surgical procedure such as pin removal were needed but the graft survived and function was acceptable, or "major" if the graft failed and revision surgery were needed. Outcomes were classified as unacceptable, acceptable, or full function. Thirty-five joints in 33 dogs were treated including nine stifles with lateral femoral condyle (LFC) OCD and 10 stifles with medial femoral condyle (MFC) OCD treated with osteochondral cylinders or "plugs." There were 16 "complex" procedures of the shoulder, elbow, hip, stifle, and tarsus using custom-cut grafts. In total there were eight trivial complications, one non-surgical complication, two minor surgical complications, and five major complications for a total of 16/35 cases with complications. Accordingly, there were five cases with unacceptable outcomes, all of whom had major complications while the other 30 cases had successful outcomes. Of the 30 cases with successful outcomes, 15 had full function and 15 had acceptable function. Based on these subjective outcome assessments, it appears osteochondral allograft transplantation is a viable treatment option in dogs with focal or complex cartilage defects. However, no conclusions can be made regarding the inferiority or superiority of allograft transplantation in comparison to other treatment options based upon these data.

Corrigendum: Outcomes Associated With Osteochondral Allograft Transplantation in Dogs.

[This corrects the article DOI: 10.3389/fvets.2021.759610.].

T1ρ, T2 mapping, and EPIC-µCT Imaging in a Canine Model of Knee Osteochondral Injury.

The dog is the most commonly used large animal model for the study of osteoarthritis. Optimizing methods for assessing cartilage health would prove useful in reducing the number of dogs needed for a valid study of osteoarthritis and cartilage repair. Twelve beagles had critical-sized osteochondral defects created in the medial femoral condyle of both knees. Eight dogs had T1ρ and T2 magnetic resonance imaging (MRI) performed approximately 6 months after defect creation. Following MRI evaluations, all 12 dogs were humanely euthanatized and cartilage samples were obtained from the medial and lateral femoral condyles, medial and lateral tibial plateaus, trochlear groove, and patella for proteoglycan and collagen quantification. Equilibrium partitioning of an ionic contrast (EPIC)-µCT was then performed followed by the histologic assessment of the knees. Correlations between T1ρ, T2, EPIC-µCT and proteoglycan, collagen, and histology scores were assessed using a multivariate analysis accounting for correlations from samples within the same knee and in the same dog. Pearson's correlation coefficients were calculated to assess the strength of significant relationships. Correlations between µCT values and biochemical or histologic assessment were weak to moderately strong (0.09-0.41; p < 0.0001-0.66). There was a weak correlation between the T2 values and cartilage proteoglycan (-0.32; p = 0.04). The correlation between T1ρ values and cartilage proteoglycan were moderately strong (-0.38; p < 0.05) while the strongest correlation was between the T1ρ values and histological assessment of cartilage with a correlation coefficient of 0.58 (p < 0.0001). These data suggest that T1ρ shows promise for possible utility in the translational study of cartilage health and warrants further development in this species. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:368-377, 2020.

A Pilot Clinical Study Assessing Treatment of Canine Hip Dysplasia Using Autologous Protein Solution.

Five dogs with bilateral hip dysplasia and without osteoarthritis of other joints were enrolled in this pilot study. Objective kinetic data using a pressure sensitive mat and owner assessments using the canine brief pain inventory (CBPI) and Liverpool Osteoarthritis for Dogs (LOAD) questionnaires were obtained prior to treatment. Enrolled dogs were treated in one hip with autologous protein solution (APS) and the contralateral hip was injected with an equal volume of saline. The hip to be treated was selected using a random number generator. At exactly 28 days following treatment dogs were re-assessed using the pressure sensitive mat and the CBPI and LOAD questionnaires. No dogs were treated with any other medications or supplements throughout the study period. Assessment of the total pressure index (TPI) collected using the pressure sensitive mat showed that the hips treated with APS improved significantly more than hips treated with saline (p = 0.0005) and that the hips treated with APS bore significantly more weight than the hips treated with saline at day 28 (p < 0.05). Statistically significant improvement was noted by owners in "pain" and "function" as assessed by the CBPI as well "mobility at exercise" using the LOAD questionnaire. This pilot study provided proof of principle that APS is beneficial in treating pain and lameness in dogs affected by coxofemoral osteoarthritis.

Effect of propofol and ketamine-diazepam on intraocular pressure in healthy premedicated dogs.

OBJECTIVE: To compare the effect of propofol and ketamine/diazepam for induction following premedication on intraocular pressure (IOP) in healthy dogs. STUDY DESIGN: Prospective, quasi-experimental, unmasked, longitudinal. ANIMALS: A total of 61 client-owned dogs. METHODS: Dogs were anesthetized twice with a 4 week washout period. Premedication with dexmedetomidine (5 µg kg-1) and hydromorphone (0.1 mg kg-1) intramuscularly was followed by either propofol (4 mg kg-1) or ketamine (5 mg kg-1) and diazepam (0.25 mg kg-1) intravenously for induction and inhaled isoflurane for maintenance. IOP was measured by applanation tonometry using TonoPen-XL before premedication and after 5, 10, 20 and 30 minutes. IOP was measured again immediately after induction and after 3, 5, 10, 15, 20, 30 and 40 minutes. Data were analyzed using one- or two-way repeated measures ANOVA. RESULTS: No difference was found between right and left IOP (p = 0.45), and data from both the eyes of each dog were averaged and considered as one set of data. Following premedication, IOP was significantly lower at all time points than at baseline when animals were grouped together, mean difference -1.6 ± 0.2 mmHg (p < 0.05). IOP increased immediately (12.2 ± 2.4 mmHg before versus 17.1 ± 3.8 mmHg after) and at 3, 5 (p < 0.001), 10 and 40 minutes (p = 0.009 and 0.045, respectively) after propofol administration. For ketamine/diazepam, IOP was increased immediately post-induction (13.0 ± 2.7 mmHg before versus 14.7 ± 2.8 mmHg after) and at 3, 5 (p < 0.001), 30 and 40 minutes (p = 0.010 and 0.037, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Sedation with hydromorphone and dexmedetomidine significantly decreased IOP in normal dogs and may be an appropriate choice for dogs that cannot tolerate acute increases in IOP. However, IOP increased significantly after both induction protocols, abolishing the effect of premedication.