Publications by authors named "Austin Igelman"

11 Publications

  • Page 1 of 1

Effect of Pharmacological Pupil Dilation on Dark-Adapted Perimetric Sensitivity in Healthy Subjects Using an Octopus 900 Perimeter.

Transl Vis Sci Technol 2021 12;10(14):18

Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA.

Purpose: To determine whether dilation status has a clinically meaningful effect on sensitivity in normal subjects undergoing two-color dark-adapted perimetry, which can be useful to assess rod function.

Methods: A perimeter measured naturally and pharmacologically dilated scotopic sensitivities using a test grid consisting of 16 points across the horizontal meridian ranging from 60° temporal to 45° nasal using cyan (500 nm wavelength) or red (650 nm wavelength) stimuli. The primary outcome was average overall sensitivity based on dilation status, which was compared using a linear mixed effect model for each color stimuli. A difference of 2 dB or more was considered clinically significant.

Results: Twenty-nine eyes from 15 subjects (nine female) ages 23 to 63 with no known retinal pathology were included. Pharmacologically dilated eyes were 0.54 dB (95% confidence interval [CI], 0.05 dB to 1.03 dB; P = 0.032) more sensitive to a red stimulus than naturally dilated eyes, but this was not statistically significant after correction for multiple comparisons. Pharmacologically dilated eyes were 0.03 dB (95% CI, -0.20 dB to 0.14 dB; P = 0.734) less sensitive to a cyan stimulus compared to naturally dilated eyes.

Conclusions: These findings show no clinically significant differences in sensitivity of scotopic perimetry in eyes without retinal pathology based on dilation status for both cyan and red stimuli.

Translational Relevance: In this study, pharmacological dilation did not have a clinically meaningful effect on sensitivity, suggesting that this is not necessary when using two-color dark-adapted perimetry to assess for rod function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/tvst.10.14.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685405PMC
December 2021

Expanding the clinical phenotype in patients with disease causing variants associated with atypical Usher syndrome.

Ophthalmic Genet 2021 12 5;42(6):664-673. Epub 2021 Jul 5.

Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA.

Atypical Usher syndrome (USH) is poorly defined with a broad clinical spectrum. Here, we characterize the clinical phenotype of disease caused by variants in , and .Chart review evaluating demographic, clinical, imaging, and genetic findings of 19 patients from 18 families with a clinical diagnosis of retinal disease and confirmed disease-causing variants in , or .-related disease included sensorineural hearing loss (SNHL) in 6/7 patients and demonstrated a broad phenotypic spectrum including: vascular attenuation, pallor of the optic disc, intraretinal pigment, retinal pigment epithelium mottling, areas of mid-peripheral hypo-autofluorescence, outer retinal atrophy, mild pigmentary changes in the macula, foveal hypo-autofluorescence, and granularity of the ellipsoid zone. Nonsense and frameshift variants in showed mild retinal disease with progressive, non-congenital SNHL. variants resulted in a characteristic pericentral pattern of hypo-autofluorescence with one patient reporting non-congenital SNHL. -related disease showed rod-cone dystrophy with macular involvement, early and severe decreased best corrected visual acuity, and non-congenital SNHL ranging from unreported to severe.This study serves to expand the clinical phenotypes of atypical USH. Given the variable findings, atypical USH should be considered in patients with peripheral and macular retinal disease even without the typical RP phenotype especially when SNHL is noted. Additionally, genetic screening may be useful in patients who have clinical symptoms and retinal findings even in the absence of known SNHL given the variability of atypical USH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13816810.2021.1946704DOI Listing
December 2021

Characterization of the Spectrum of Ophthalmic Changes in Patients With Alagille Syndrome.

Invest Ophthalmol Vis Sci 2021 06;62(7):27

Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.

Purpose: The purpose of this study was to characterize the phenotypic spectrum of ophthalmic findings in patients with Alagille syndrome.

Methods: We conducted a retrospective, observational, multicenter, study on 46 eyes of 23 subjects with Alagille syndrome. We reviewed systemic and ophthalmologic data extracted from medical records, color fundus photography, fundus autofluorescence, optical coherence tomography, visual fields, electrophysiological assessments, and molecular genetic findings.

Results: Cardiovascular abnormalities were found in 83% of all cases (of those, 74% had cardiac murmur), whereas 61% had a positive history of hepatobiliary issues, and musculoskeletal anomalies were present in 61% of all patients. Dysmorphic facies were present in 16 patients, with a broad forehead being the most frequent feature. Ocular symptoms were found in 91%, with peripheral vision loss being the most frequent complaint. Median (range) Snellen visual acuity of all eyes was 20/25 (20/20 to hand motion [HM]). Anterior segment abnormalities were present in 74% of the patients; of those, posterior embryotoxon was the most frequent finding. Abnormalities of the optic disc were found in 52%, and peripheral retinal abnormalities were the most frequent ocular finding in this series, found in 96% of all patients. Fifteen JAG1 mutations were identified in 16 individuals; of those, 6 were novel.

Conclusions: This study reports a cohort of patients with Alagille syndrome in which peripheral chorioretinal changes were more frequent than posterior embryotoxon, the most frequent ocular finding according to a number of previous studies. We propose that these peripheral chorioretinal changes are a new hallmark to help diagnose this syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.62.7.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254011PMC
June 2021

Noncoding mutation in contributes to inherited retinal degenerations.

Mol Vis 2021 18;27:95-106. Epub 2021 Mar 18.

Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.

Purpose: Despite the extensive use of next-generation sequencing (NGS) technology to identify disease-causing genomic variations, a major gap in our understanding of Mendelian diseases is the unidentified molecular lesion in a significant portion of patients. For inherited retinal degenerations (IRDs), although currently close to 300 disease-associated genes have been identified, the mutations in approximately one-third of patients remain unknown. With mounting evidence that noncoding mutations might contribute significantly to disease burden, we aimed to systematically investigate the contributions of noncoding regions in the genome to IRDs.

Methods: In this study, we focused on , which has been linked to various IRD phenotypes, including Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), and macular dystrophy (MD). As several noncoding mutant alleles have been reported in and we observed that the mutation carrier frequency of is higher in patient cohorts with unsolved IRDs, we hypothesized that mutations in the noncoding regions of might be a significant contributor to pathogenicity. To test this hypothesis, we performed whole-genome sequencing (WGS) for 25 patients with unassigned IRD who carry a single mutation in .

Results: Three noncoding variants in , including a 2,890 bp deletion and two deep-intronic variants (c.2710+233G>A and c.1468-263G>C), were identified as putative second hits of in three patients with LCA. The mutant alleles were validated with direct sequencing or in vitro assays.

Conclusions: The results highlight the significance of the contribution of noncoding pathogenic variants to unsolved IRD cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056464PMC
November 2021

The Content Quality of YouTube Videos for Professional Medical Education: A Systematic Review.

Acad Med 2021 10;96(10):1484-1493

G.E. Woodworth is professor of anesthesiology and perioperative medicine, Oregon Health and Sciences University School of Medicine, Portland, Oregon; ORCID: http://orcid.org/0000-0002-1924-801X.

Purpose: To evaluate the content quality of YouTube videos intended for professional medical education based on quality rating tool (QRT) scores and determine if video characteristics, engagement metrics, or author type are associated with quality.

Method: The authors searched 7 databases for English-language studies about the quality of YouTube videos intended for professional medical education from each database's inception through April 2019. To be included, studies had to be published in 2005 (when YouTube was created) or later. Studies were classified according to the type of QRT used: externally validated, internally validated, or limited global. Study information and video characteristics and engagement metrics were extracted. Videos were classified by video author type.

Results: Thirty-one studies were included in this review. Three studies used externally validated QRTs, 20 used internally validated QRTs, and 13 used limited global QRTs. Studies using externally validated QRTs had average scores/total possible scores of 1.3/4, 26/80, and 1.7/5. Among the 18 studies using internally validated QRTs, from which an average percentage of total possible QRT score could be computed or extracted, the average score was 44% (range: 9%-71%). Videos with academic-physician authors had higher internally validated QRT mean scores (46%) than those with nonacademic-physician or other authors (26%; P < .05).

Conclusions: The authors found a wide variation in QRT scores of videos, with many low QRT scores. While videos authored by academic-physicians were of higher quality on average, their quality still varied significantly. Video characteristics and engagement metrics were found to be unreliable surrogate measures of video quality. A lack of unifying grading criteria for video content quality, poor search algorithm optimization, and insufficient peer review or controls on submitted videos likely contributed to the overall poor quality of YouTube videos that could be used for professional medical education.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ACM.0000000000004121DOI Listing
October 2021

Identification of Deep-Intronic Splice Mutations in a Large Cohort of Patients With Inherited Retinal Diseases.

Front Genet 2021 2;12:647400. Epub 2021 Mar 2.

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, United States.

High throughput sequencing technologies have revolutionized the identification of mutations responsible for a diverse set of Mendelian disorders, including inherited retinal disorders (IRDs). However, the causal mutations remain elusive for a significant proportion of patients. This may be partially due to pathogenic mutations located in non-coding regions, which are largely missed by capture sequencing targeting the coding regions. The advent of whole-genome sequencing (WGS) allows us to systematically detect non-coding variations. However, the interpretation of these variations remains a significant bottleneck. In this study, we investigated the contribution of deep-intronic splice variants to IRDs. WGS was performed for a cohort of 571 IRD patients who lack a confident molecular diagnosis, and potential deep intronic variants that affect proper splicing were identified using SpliceAI. A total of six deleterious deep intronic variants were identified in eight patients. An minigene system was applied to further validate the effect of these variants on the splicing pattern of the associated genes. The prediction scores assigned to splice-site disruption positively correlated with the impact of mutations on splicing, as those with lower prediction scores demonstrated partial splicing. Through this study, we estimated the contribution of deep-intronic splice mutations to unassigned IRD patients and leveraged and methods to establish a framework for prioritizing deep intronic variant candidates for mechanistic and functional analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.647400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960924PMC
March 2021

Electronic Health Records in Ophthalmology: Source and Method of Documentation.

Am J Ophthalmol 2020 03 5;211:191-199. Epub 2019 Dec 5.

Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon, USA; Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon, USA. Electronic address:

Purpose: This study analyzed and quantified the sources of electronic health record (EHR) text documentation in ophthalmology progress notes.

Design: EHR documentation review and analysis.

Methods: Setting: a single academic ophthalmology department.

Study Population: a cohort study conducted between November 1, 2016, and December 31, 2018, using secondary EHR data and a follow-up manual review of a random samples. The cohort study included 123,274 progress notes documented by 42 attending providers. These notes were for patients with the 5 most common primary International Statistical Classification of Diseases and Related Health Problems, version 10, parent codes for each provider. For the manual review, 120 notes from 8 providers were randomly sampled. Main outcome measurements were characters or number of words in each note categorized by attribution source, author type, and time of creation.

Results: Imported text entries made up the majority of text in new and return patients, 2,978 characters (77%) and 3,612 characters (91%). Support staff members authored substantial portions of notes; 3,024 characters (68%) of new patient notes, 3,953 characters (83%) of return patient notes. Finally, providers completed large amounts of documentation after clinical visits: 135 words (35%) of new patient notes, 102 words (27%) of return patient notes.

Conclusions: EHR documentation consists largely of imported text, is often authored by support staff, and is often written after the end of a visit. These findings raise questions about documentation accuracy and utility and may have implications for quality of care and patient-provider relationships.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajo.2019.11.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073273PMC
March 2020

Phenotypic Spectrum of Pentosan Polysulfate Sodium-Associated Maculopathy: A Multicenter Study.

JAMA Ophthalmol 2019 Nov;137(11):1275-1282

Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia.

Importance: A unique pigmentary maculopathy was recently described in 6 patients with long-term exposure to pentosan polysulfate sodium (PPS), a long-standing oral therapy for interstitial cystitis.

Objective: To characterize the exposure characteristics and clinical manifestations of PPS-associated maculopathy.

Design, Setting, And Participants: In this multi-institutional case series, medical records of patients who exhibited the characteristic maculopathy in the setting of prior PPS exposure were retrospectively reviewed. Data were collected from August 1, 2012, to October 1, 2018, and data were analyzed from October 2018 to January 2019.

Main Outcomes And Measures: Drug exposure, visual acuity, and retinal imaging characteristics.

Results: Of the 35 included patients (70 eyes), 34 (97%) were female, and the median (range) age was 60 (37-79) years. The median (range) duration of PPS intake was 15 (3-22) years, and the median (range) cumulative exposure was 1.61 (0.44-4.31) kg. The leading visual symptoms were metamorphopsia, blurred vision, and prolonged dark adaptation. Median (range) logMAR visual acuity of all eyes was 0.10 (-0.12 to 1.18). Fundus examination often revealed hyperpigmented macular spots (34 of 64 eyes [53%]) with interspersed pale-yellow deposits, although less commonly in eyes that exhibited retinal pigment epithelial atrophy (6 of 26 eyes [23%]; P < .001). Optical coherence tomography showed foci of retinal pigment epithelium elevation or thickening associated with hyperreflectance on near-infrared reflectance imaging. Fundus autofluorescence imaging typically revealed a symmetric, confluent pattern of hyperautofluorescent and hypoautofluorescent spots that involved the fovea in all eyes and extended to the retinal periphery in 24 eyes (36%). Longitudinal evaluation demonstrated dynamic changes in pigmentary abnormalities.

Conclusions And Relevance: These findings suggest that PPS-associated maculopathy is a vision-threatening condition that can manifest in the setting of long-term exposure to the drug. Multimodal imaging posits a distinctive clinical phenotype, characterized in this cohort by dynamic alterations within the retinal pigment epithelium and at the retinal pigment epithelium-photoreceptor interface. Ongoing work might explore causality and direct screening guidelines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaophthalmol.2019.3392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735406PMC
November 2019

Redundancy of Progress Notes for Serial Office Visits.

Ophthalmology 2020 01 21;127(1):134-135. Epub 2019 Jun 21.

Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon; Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ophtha.2019.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925342PMC
January 2020

Culture-Proven Endophthalmitis After Intravitreal Injection: A 10-Year Analysis.

Ophthalmic Surg Lasers Imaging Retina 2019 01;50(1):33-38

Background And Objective: To report on the microbiology, management, and visual outcomes of intravitreal injection (IVI)-associated, culture-proven endophthalmitis.

Patients And Methods: All patients seen at a tertiary referral center with culture-proven endophthalmitis associated with an IVI between June 2007 and July 2017 were included in this retrospective analysis.

Results: Thirty-five patients with culture-positive endophthalmitis following IVI were identified. All gram-positive organisms (34 of 35) were susceptible to vancomycin. Cases due to pathogens associated with oral or respiratory flora were common (31.4%, n = 11), presented earlier (2.0 days vs. 4.6 days, P < .001), were more likely to undergo pars plana vitrectomy (81.8% vs. 25.0%, P = .002) and had worse visual acuity outcomes.

Conclusion: IVI-associated endophthalmitis pathogens and anti-microbial susceptibilities in the Pacific Northwest are similar to those reported from other geographic locations. Bacteria associated with the oral and respiratory flora are common isolates that result in a more aggressive course and worse visual outcomes. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:33-38.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3928/23258160-20181212-05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875494PMC
January 2019

Preclinical development of anti-BCMA immunotoxins targeting multiple myeloma.

Antib Ther 2018 Jun 20;1(1):19-25. Epub 2018 Aug 20.

Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892,USA.

Background: Multiple myeloma (MM) is a B-cell malignancy that is incurable for the majority of patients. New treatments are urgently needed. Recombinant immunotoxins (RITs) are chimeric proteins that are composed of the Fv or Fab portion of an antibody fused to a bacterial toxin. B-cell maturation antigen (BCMA) is a lineage-restricted differentiation protein and an ideal target for antibody-based treatments for MM.

Methods: RITs were produced by expressing plasmids encoding the components of the anti-BCMA RITs in followed by inclusion body preparation, solubilization, renaturation, and purification by column chromatography. The cytotoxic activity of RITs was tested by WST-8 assays. We also measured their binding to human and mouse serum albumins and to BCMA and measured their serum half-life in mice.

Results: Using Fvs from different anti-BCMA antibodies, we produced RITs that specifically kill BCMA-expressing MM cells . To increase the serum half-life , we generated RITs that are fused with albumin-binding domains (ABDs). All RITs with ABDs have some decreased activity compared to the parent RIT, which is not due to decreased binding to BCMA.

Conclusions: Various new anti-BCMA immunotoxins were produced and evaluated. None of these were better than LMB-75 (anti-BCMA BM306-disulfide-stabilized Fv-LRggs) supporting the further preclinical development of LMB-75.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/abt/tby004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157621PMC
June 2018
-->