Hypoxic drive caused type 3 neovascularization in a preclinical model of exudative age-related macular degeneration.

Hypoxia associated with the high metabolic demand of rods has been implicated in the pathology of age-related macular degeneration (AMD), the most common cause of adult blindness in the developed world. The majority of AMD-associated severe vision loss cases are due to exudative AMD, characterized by neovascularization. To further investigate the causes and histopathology of exudative AMD, we conditionally induced hypoxia in a novel preclinical AMD model (Pde6gcreERT2/+;Vhl-/-) by targeting Vhl and used multimodal imaging and immunohistochemistry to track the development of hypoxia-induced neovascularization. In addition to developing a preclinical model that phenocopies exudative AMD, our studies revealed that the photoreceptor hypoxic response initiates and drives type 3 neovascularization, mainly in the outer retina. Activation of the VHL-HIF1a-VEGF-EPO pathway in the adult retina led to long-term neovascularization, retinal hemorrhages and compromised retinal layers. Our novel preclinical model would accelerate the testing of therapies that use metabolomic approaches to ameliorate AMD.

Mechanisms of neurodegeneration in a preclinical autosomal dominant retinitis pigmentosa knock-in model with a RhoD190N mutation.

D190N, a missense mutation in rhodopsin, causes photoreceptor degeneration in patients with autosomal dominant retinitis pigmentosa (adRP). Two competing hypotheses have been developed to explain why D190N rod photoreceptors degenerate: (a) defective rhodopsin trafficking prevents proteins from correctly exiting the endoplasmic reticulum, leading to their accumulation, with deleterious effects or (b) elevated mutant rhodopsin expression and unabated signaling causes excitotoxicity. A knock-in D190N mouse model was engineered to delineate the mechanism of pathogenesis. Wild type (wt) and mutant rhodopsin appeared correctly localized in rod outer segments of D190N heterozygotes. Moreover, the rhodopsin glycosylation state in the mutants appeared similar to that in wt mice. Thus, it seems plausible that the injurious effect of the heterozygous mutation is not related to mistrafficking of the protein, but rather from constitutive rhodopsin activity and a greater propensity for chromophore isomerization even in the absence of light.

Comparative Analysis of Functional and Structural Decline in Retinitis Pigmentosas.

Retinitis pigmentosa (RP) is a category of inherited retinal dystrophies that is best prognosticated using electroretinography (ERG). In this retrospective cohort study of 25 patients with RP, we evaluated the correlation between 30 Hz flicker ERG and structural parameters in the retina. Internationally standardized 30 Hz flicker ERG recordings, short-wavelength autofluorescence (SW-AF), and spectral domain-optical coherence tomography (SD-OCT) were acquired at two visits at least one year apart. Vertical and horizontal hyperautofluorescent ring diameter measurements with SW-AF, as well as ellipsoid zone (EZ) line width measurements with SD-OCT, were used as structural parameters of disease progression. The 30 Hz flicker ERG amplitude decreased by 2.2 ± 0.8 µV/year (p = 0.011), while implicit times remained unchanged. For SD-OCT, the EZ line decreased by 204.1 ± 34.7 µm/year (p < 0.001). Horizontal and vertical hyperautofluorescent ring diameters decreased by 161.9 ± 25.6 µm/year and 146.9 ± 34.6 µm/year, respectively (p = 0.001), with SW-AF. A correlation was found between the progression rates of the 30 Hz flicker amplitude recorded with Burian-Allen electrodes and both the horizontal ring diameter (p = 0.020) and EZ line (p = 0.044). SW-AF and SD-OCT, two readily available imaging techniques, may be used to prognosticate disease progression because of the reliability of their measurements and correlation with functional outcome.

Genetic Rescue Reverses Microglial Activation in Preclinical Models of Retinitis Pigmentosa.

Microglia cells (MGCs) play a key role in scavenging pathogens and phagocytosing cellular debris in the central nervous system and retina. Their activation, however, contributes to the progression of multiple degenerative diseases. Given the potential damage created by MGCs, it is important to better understand their mechanism of activation. Here, we explored the role of MGCs in the context of retinitis pigmentosa (RP) by using four independent preclinical mouse models. For therapeutic modeling, tamoxifen-inducible CreER was introduced to explore changes in MGCs when RP progression halted. The phenotypes of the MGCs were observed using live optical coherence tomography, live autofluorescence, and immunohistochemistry. We found that, regardless of genetic background, MGCs were activated in neurodegenerative conditions and migrated beyond the layers where they are typically found to the inner and outer segments, where degeneration was ongoing. Genetic rescue not only halted degeneration but also deactivated MGCs, regardless of whether the intervention occurred at the early, middle, or late stage of the disease. These findings suggest that halting long-term disease progression may be more successful by downregulating MGC activity while co-administering the therapeutic intervention.

Reprogramming the metabolome rescues retinal degeneration.

Metabolomics studies in the context of ophthalmology have largely focused on identifying metabolite concentrations that characterize specific retinal diseases. Studies involving mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy have shown that individuals suffering from retinal diseases exhibit metabolic profiles that markedly differ from those of control individuals, supporting the notion that metabolites may serve as easily identifiable biomarkers for specific conditions. An emerging branch of metabolomics resulting from biomarker studies, however, involves the study of retinal metabolic dysfunction as causes of degeneration. Recent publications have identified a number of metabolic processes-including but not limited to glucose and oxygen metabolism-that, when perturbed, play a role in the degeneration of photoreceptor cells. As a result, such studies have led to further research elucidating methods for prolonging photoreceptor survival in an effort to halt degeneration in its early stages. This review will explore the ways in which metabolomics has deepened our understanding of the causes of retinal degeneration and discuss how metabolomics can be used to prevent retinal degeneration from progressing to its later disease stages.

Clustered Regularly Interspaced Short Palindromic Repeats-Based Genome Surgery for the Treatment of Autosomal Dominant Retinitis Pigmentosa.

PURPOSE: To develop a universal gene therapy to overcome the genetic heterogeneity in retinitis pigmentosa (RP) resulting from mutations in rhodopsin (RHO). DESIGN: Experimental study for a combination gene therapy that uses both gene ablation and gene replacement. PARTICIPANTS: This study included 2 kinds of human RHO mutation knock-in mouse models: RhoP23H and RhoD190N. In total, 23 RhoP23H/P23H, 43 RhoP23H/+, and 31 RhoD190N/+ mice were used for analysis. METHODS: This study involved gene therapy using dual adeno-associated viruses (AAVs) that (1) destroy expression of the endogenous Rho gene in a mutation-independent manner via an improved clustered regularly interspaced short palindromic repeats-based gene deletion and (2) enable expression of wild-type protein via exogenous cDNA. MAIN OUTCOME MEASURES: Electroretinographic and histologic analysis. RESULTS: The thickness of the outer nuclear layer (ONL) after the subretinal injection of combination ablate-and-replace gene therapy was approximately 17% to 36% more than the ONL thickness resulting from gene replacement-only therapy at 3 months after AAV injection. Furthermore, electroretinography results demonstrated that the a and b waves of both RhoP23H and RhoD190N disease models were preserved more significantly using ablate-and-replace gene therapy (P < 0.001), but not by gene replacement monotherapy. CONCLUSIONS: As a proof of concept, our results suggest that the ablate-and-replace strategy can ameliorate disease progression as measured by photoreceptor structure and function for both of the human mutation knock-in models. These results demonstrate the potency of the ablate-and-replace strategy to treat RP caused by different Rho mutations. Furthermore, because ablate-and-replace treatment is mutation independent, this strategy may be used to treat a wide array of dominant diseases in ophthalmology and other fields. Clinical trials using ablate-and-replace gene therapy would allow researchers to determine if this strategy provides any benefits for patients with diseases of interest.

CRISPR/Cas9 genome surgery for retinal diseases.

Retinal diseases that impair vision can impose heavy physical and emotional burdens on patients' lives. Currently, clustered regularly interspaced short palindromic repeats (CRISPR) is a prevalent gene-editing tool that can be harnessed to generate disease model organisms for specific retinal diseases, which are useful for elucidating pathophysiology and revealing important links between genetic mutations and phenotypic defects. These retinal disease models are fundamental for testing various therapies and are indispensible for potential future clinical trials. CRISPR-mediated procedures involving CRISPR-associated protein 9 (Cas9) may also be used to edit genome sequences and correct mutations. Thus, if used for future therapies, CRISPR/Cas9 genome surgery could eliminate the need for patients with retinal diseases to undergo repetitive procedures such as drug injections. In this review, we will provide an overview of CRISPR/Cas9, discuss the different types of Cas9, and compare Cas9 to other endonucleases. Furthermore, we will explore the many ways in which researchers are currently utilizing this versatile tool, as CRISPR/Cas9 may have far-reaching effects in the treatment of retinal diseases.

Deferoxamine-induced electronegative ERG responses.

PURPOSE: To report a case of deferoxamine-induced retinopathy characterized by electroretinography (ERG), optical coherence tomography angiography (OCT-A), and other multimodal imaging. METHODS: This is an observational case report of one patient. Full-field ERG was performed. OCT-A, spectral-domain optical coherence tomography (SD-OCT), color fundus photography, and fundus autofluorescence were used to characterize the retinopathy induced by deferoxamine use. RESULTS: A 64-year-old man with a history of ß-thalassemia intermedia presented with worsening visual acuity, nyctalopia, and electronegative ERG. OCT-A revealed atrophy of the choriocapillaris in areas of hypoautofluorescence, corresponding to regions of retinal atrophy. SD-OCT showed disruption of the ellipsoid zone, granular hyperreflective deposits within the retinal pigment epithelium, thinning of the retinal layers, and extensive choroidal sclerosis and atrophy of the retinal pigment epithelium. CONCLUSION: Deferoxamine-induced retinopathy can manifest with electronegative maximal ERG responses, and OCT-A can be used to detect deferoxamine toxicity.

Lung lobe torsion in dogs: 52 cases (2005-2017).

OBJECTIVE: To report outcomes and risk factors for mortality in dogs that underwent surgical management of lung lobe torsion. STUDY DESIGN: Retrospective case series from 5 veterinary teaching hospitals (2005-2017). ANIMALS: Fifty dogs with 52 instances of lung lobe torsion. METHODS: Data collected from medical records included signalment, clinical findings, results of clinicopathologic testing and diagnostic imaging, surgical treatment, lung lobe affected, intraoperative and postoperative complications, histopathologic and microbiologic findings, and outcome. Follow-up was obtained from medical records and telephone contact with primary care veterinarians. RESULTS: Fifty-two instances of lung lobe torsion were identified in 50 dogs, with a median follow-up of 453 days (range, 0-3075). Forty-six (92%) dogs survived to discharge. Dogs with concurrent torsion of the right cranial and middle lung lobes were less likely to survive (2/4) than those with torsion of the left cranial lung lobe (22/22). No other risk factors for mortality prior to hospital discharge were identified. Overall median survival time after hospital discharge was 1369 days. Four dogs had >1 episode of lung lobe torsion. CONCLUSION: The percentage of dogs surviving to discharge after surgical treatment of lung lobe torsion was higher than previously reported. The short- and long-term prognosis was excellent with surgical treatment of lung lobe torsion. CLINICAL SIGNIFICANCE: Surgery should be recommended when lung lobe torsion is suspected because of the high survival to discharge rate and excellent long-term prognosis.

A comprehensive examination of breast cancer risk loci in African American women.

Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions (1q32, 3p24, 10q25), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive disease. We also observed suggestive associations with variants (at P < 5 × 10(-6)) in three separate regions (6q25, 14q13, 22q12) that may represent novel risk variants. Directional consistency of association observed for ∼65-70% of currently known genetic variants for breast cancer in women of African ancestry implies a shared functional common variant at most loci. To validate and enhance the spectrum of alleles that define associations at the known breast cancer risk loci, as well as genome-wide, will require even larger collaborative efforts in women of African ancestry.

Gene discovery for Mendelian conditions via social networking: de novo variants in KDM1A cause developmental delay and distinctive facial features.

PURPOSE: The pace of Mendelian gene discovery is slowed by the "n-of-1 problem"-the difficulty of establishing the causality of a putatively pathogenic variant in a single person or family. Identification of an unrelated person with an overlapping phenotype and suspected pathogenic variant in the same gene can overcome this barrier, but it is often impeded by lack of a convenient or widely available way to share data on candidate variants/genes among families, clinicians, and researchers. METHODS: Social networking among families, clinicians, and researchers was used to identify three children with variants of unknown significance in KDM1A and similar phenotypes. RESULTS: De novo variants in KDM1A underlie a new syndrome characterized by developmental delay and distinctive facial features. CONCLUSION: Social networking is a potentially powerful strategy to discover genes for rare Mendelian conditions, particularly those with nonspecific phenotypic features. To facilitate the efforts of families to share phenotypic and genomic information with each other, clinicians, and researchers, we developed the Repository for Mendelian Genomics Family Portal (RMD-FP; http://uwcmg.org/#/family). Design and development of MyGene2 (http://www.mygene2.org), a Web-based tool that enables families, clinicians, and researchers to search for gene matches based on analysis of phenotype and exome data deposited into the RMD-FP, is under way.Genet Med 18 8, 788-795.

Genome-wide testing of putative functional exonic variants in relationship with breast and prostate cancer risk in a multiethnic population.

Rare variation in protein coding sequence is poorly captured by GWAS arrays and has been hypothesized to contribute to disease heritability. Using the Illumina HumanExome SNP array, we successfully genotyped 191,032 common and rare non-synonymous, splice site, or nonsense variants in a multiethnic sample of 2,984 breast cancer cases, 4,376 prostate cancer cases, and 7,545 controls. In breast cancer, the strongest associations included either SNPs in or gene burden scores for genes LDLRAD1, SLC19A1, FGFBP3, CASP5, MMAB, SLC16A6, and INS-IGF2. In prostate cancer, one of the most associated SNPs was in the gene GPRC6A (rs2274911, Pro91Ser, OR = 0.88, P = 1.3 × 10(-5)) near to a known risk locus for prostate cancer; other suggestive associations were noted in genes such as F13A1, ANXA4, MANSC1, and GP6. For both breast and prostate cancer, several of the most significant associations involving SNPs or gene burden scores (sum of minor alleles) were noted in genes previously reported to be associated with a cancer-related phenotype. However, only one of the associations (rs145889899 in LDLRAD1, p = 2.5 × 10(-7) only seen in African Americans) for overall breast or prostate cancer risk was statistically significant after correcting for multiple comparisons. In addition to breast and prostate cancer, other cancer-related traits were examined (body mass index, PSA level, and alcohol drinking) with a number of known and potentially novel associations described. In general, these findings do not support there being many protein coding variants of moderate to high risk for breast and prostate cancer with odds ratios over a range that is probably required for protein coding variation to play a truly outstanding role in risk heritability. Very large sample sizes will be required to better define the role of rare and less penetrant coding variation in prostate and breast cancer disease genetics.

The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.

The endoplasmic reticulum (ER) is the largest intracellular organelle carrying out a broad range of important cellular functions including protein biosynthesis, folding, and trafficking, lipid and sterol biosynthesis, carbohydrate metabolism, and calcium storage and gated release. In addition, the ER makes close contact with multiple intracellular organelles such as mitochondria and the plasma membrane to actively regulate the biogenesis, remodeling, and function of these organelles. Therefore, maintaining a homeostatic and functional ER is critical for the survival and function of cells. This vital process is implemented through well-orchestrated signaling pathways of the unfolded protein response (UPR). The UPR is activated when misfolded or unfolded proteins accumulate in the ER, a condition known as ER stress, and functions to restore ER homeostasis thus promoting cell survival. However, prolonged activation or dysregulation of the UPR can lead to cell death and other detrimental events such as inflammation and oxidative stress; these processes are implicated in the pathogenesis of many human diseases including retinal disorders. In this review manuscript, we discuss the unique features of the ER and ER stress signaling in the retina and retinal neurons and describe recent advances in the research to uncover the role of ER stress signaling in neurodegenerative retinal diseases including age-related macular degeneration, inherited retinal degeneration, achromatopsia and cone diseases, and diabetic retinopathy. In some chapters, we highlight the complex interactions between the ER and other intracellular organelles focusing on mitochondria and illustrate how ER stress signaling regulates common cellular stress pathways such as autophagy. We also touch upon the integrated stress response in retinal degeneration and diabetic retinopathy. Finally, we provide an update on the current development of pharmacological agents targeting the UPR response and discuss some unresolved questions and knowledge gaps to be addressed by future research.

Thoracoscopic resection of lung masses is associated with excellent survival to discharge and good long-term outcomes.

OBJECTIVE: To report and evaluate risk factors for conversion and perioperative and long-term outcomes in dogs undergoing thoracoscopic lung lobectomy for resection of lung masses. ANIMALS: 61 client-owned dogs. METHODS: This retrospective cohort study (June 11, 2008, to February 14, 2020) of data collected from medical records included signalment, results of diagnostic imaging, surgical technique, surgical and anesthesia time, mass location and size, hospitalization time, histopathologic findings, and long-term outcome. Follow-up was obtained from medical records and telephone contact with owners or referring veterinarians. RESULTS: Histopathology results were available for 60 of 61 tumors. Fifty-seven (95%) were considered primary lung tumors, of which 46 (81%) were carcinomas. Clean surgical margins were achieved in 46 of 52 (88%) dogs. Conversion from thoracoscopy to thoracoscopic-assisted or open surgery occurred in 16 of 61 (26%) dogs. Larger tumor diameter (≥ 5 cm) and lymphadenopathy detected by preoperative CT scan were significantly associated with increased risk of conversion. There was no association between conversion and patient weight, body condition score, and tumor location. All 61 dogs survived to discharge, and 56 of 57 were alive 1 month postoperatively. Median overall survival time was 311 days (95% CI, 224 to 570 days). Tracheobronchial lymphadenopathy on preoperative CT scans was associated with shorter postoperative survival (P < .001). Patient age, tumor diameter, adjuvant chemotherapy following surgery, and incomplete margins were not associated with survival time. CLINICAL RELEVANCE: Dogs had high survival to discharge and good long-term prognosis following thoracoscopic lung lobectomy. However, larger tumor size and tracheobronchial lymphadenopathy may increase the likelihood of conversion.

Emerging roles of circular RNAs in retinal diseases.

Retinal disorders are a group of ocular diseases whose onset is associated with a number of aberrant molecular and cellular processes or physical damages that affect retinal structure and function resulting in neural and vascular degeneration in the retina. Current research has primarily focused on delaying retinal disease with minimal success in preventing or reversing neuronal degeneration. In this review, we explore a relatively new field of research involving circular RNAs, whose potential roles as biomarkers and mediators of retinal disease pathogenesis have only just emerged. While knowledge of circular RNAs function is limited given its novelty, current evidence has highlighted their roles as modulators of microRNAs, regulators of gene transcription, and biomarkers of disease development and progression. Here, we summarize how circular RNAs may be implicated in the pathogenesis of common retinal diseases including diabetic retinopathy, glaucoma, proliferative vitreoretinopathy, and age-related macular degeneration. Further, we explore the potential of circular RNAs as novel biomarkers and therapeutic targets for the diagnosis and treatment of retinal diseases.

Proteomic Analysis of Retinal Mitochondria-Associated ER Membranes Identified Novel Proteins of Retinal Degeneration in Long-Term Diabetes.

The mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) is the physical contact site between the ER and the mitochondria and plays a vital role in the regulation of calcium signaling, bioenergetics, and inflammation. Disturbances in these processes and dysregulation of the ER and mitochondrial homeostasis contribute to the pathogenesis of diabetic retinopathy (DR). However, few studies have examined the impact of diabetes on the retinal MAM and its implication in DR pathogenesis. In the present study, we investigated the proteomic changes in retinal MAM from Long Evans rats with streptozotocin-induced long-term Type 1 diabetes. Furthermore, we performed in-depth bioinformatic analysis to identify key MAM proteins and pathways that are potentially implicated in retinal inflammation, angiogenesis, and neurodegeneration. A total of 2664 unique proteins were quantified using IonStar proteomics-pipeline in rat retinal MAM, among which 179 proteins showed significant changes in diabetes. Functional annotation revealed that the 179 proteins are involved in important biological processes such as cell survival, inflammatory response, and cellular maintenance, as well as multiple disease-relevant signaling pathways, e.g., integrin signaling, leukocyte extravasation, PPAR, PTEN, and RhoGDI signaling. Our study provides comprehensive information on MAM protein changes in diabetic retinas, which is helpful for understanding the mechanisms of metabolic dysfunction and retinal cell injury in DR.

Evaluation of computer-aided design software methods for assessment of the three-dimensional geometry of the canine radius.

OBJECTIVE: To describe methods to measure the 3-D orientation of the proximal, diaphyseal, and distal segments of the canine radius by use of computer-aided design software (CADS) and to compare the repeatability and reliability of measurements derived by those methods. SAMPLE: 31 canine radii with biapical deformities and 24 clinically normal (control) canine radii. PROCEDURES: Select CT scans of radii were imported into a CADS program. Cartesian coordinate systems for the humerus and proximal, diaphyseal, and distal radial segments were developed. The orientation of each radial segment in the frontal, sagittal, and transverse planes was measured in triplicate by 3 methods. The repeatability and reliability of those measurements were calculated and compared among the 3 measurement methods. RESULTS: The mean ± SD within-subject repeatability of radial angular measurements for all 3 methods was 1.40 ± 0.67° in the frontal plane, 3.17 ± 2.21° in the sagittal plane, and 3.01 ± 1.11° in the transverse plane for control radii and 2.56 ± 1.95° in the frontal plane, 3.59 ± 2.39° in the sagittal plane, and 3.47 ± 1.19° in the transverse plane for abnormal radii. Mean ± SD bias between radial measurement methods was 1.88 ± 2.07° in the frontal plane, 6.44 ± 6.80° in the sagittal plane, and 2.27 ± 2.81° in the transverse plane. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that use of CADS to assess the 3-D orientation of the proximal, diaphyseal, and distal segments of normal and abnormal canine radii yielded highly repeatable and reliable measurements.

Adult stem cells and niche cells segregate gradually from common precursors that build the adult Drosophila ovary during pupal development.

Production of proliferative follicle cells (FCs) and quiescent escort cells (ECs) by follicle stem cells (FSCs) in adult Drosophila ovaries is regulated by niche signals from anterior (cap cells, ECs) and posterior (polar FCs) sources. Here we show that ECs, FSCs, and FCs develop from common pupal precursors, with different fates acquired by progressive separation of cells along the AP axis and a graded decline in anterior cell proliferation. ECs, FSCs, and most FCs derive from intermingled cell (IC) precursors interspersed with germline cells. Precursors also accumulate posterior to ICs before engulfing a naked germline cyst projected out of the germarium to form the first egg chamber and posterior polar FC signaling center. Thus, stem and niche cells develop in appropriate numbers and spatial organization through regulated proliferative expansion together with progressive establishment of spatial signaling cues that guide adult cell behavior, rather than through rigid early specification events.

Analysis of risk factors associated with complications following mandibulectomy and maxillectomy in dogs.

OBJECTIVE: To provide information about complication rates and the risk factors for complications with mandibulectomy and maxillectomy procedures in dogs. ANIMALS: 459 client-owned dogs that underwent a mandibulectomy or maxillectomy between January 1, 2007, and January 1, 2018. PROCEDURES: Inclusion criteria included a complete medical record that contained an anesthesia record, surgical report, available histopathology results, and results of CBC and serum biochemical analysis before surgery. A minimum follow-up of 90 days after surgery was required. RESULTS: 271 complications occurred in 171 of 459 (37.3%) dogs. Eighteen complications were not given a severity description. Of the remaining 253 complications, most were considered minor (157/253 [62.1%]). Multivariable logistic regression analysis revealed that only increased surgical time had a significant (OR, 1.36; 95% CI, 1.12 to 1.54) association with the occurrence of ≥ 1 complication. For each additional hour of surgery, the odds of complications increased by 36%. Preoperative radiation therapy or chemotherapy increased the odds of incisional dehiscence or oral fistula formation (OR, 3.0; 95% CI, 1.3 to 7.2). Additionally, undergoing maxillectomy, compared with mandibulectomy, increased the odds of incisional dehiscence or oral fistula formation (OR, 1.8; 95% CI, 1.1 to 3.1). Two hundred forty-four of 271 (90.0%) complications occurred in the perioperative period (0 to 3 months after surgery). CONCLUSIONS AND CLINICAL RELEVANCE: Compared with mandibulectomy, performing maxillectomy increased the risk for incisional dehiscence or oral fistula formation. Mandibulectomy and maxillectomy had a moderate risk for a complication.