Publications by authors named "Karen R Armbrust"

14 Publications

  • Page 1 of 1

Thrombocytopenia and Clear Corneal Incision Cataract Surgery.

J Cataract Refract Surg 2021 Apr 22. Epub 2021 Apr 22.

1 Drexel University College of Medicine, Philadelphia, Pennsylvania, USA 2 Department of Ophthalmology, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota, USA 3 Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, USA 4 Department of Ophthalmology and Visual Sciences, University of Wisconsin - Madison, Madison, Wisconsin, USA 5 Ocular Immunology Division, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Purpose-: To investigate complications and outcomes of clear corneal incision cataract surgery in patients with thrombocytopenia.

Setting-: One veterans hospital and two academic medical centers DESIGN-: Multi-center retrospective chart review.

Methods-: All eyes of thrombocytopenic patients that underwent clear corneal incision cataract surgery with a platelet count ≤100 x 10/µl measured ≤30 days prior to surgery were included. Subject demographics, intraoperative complications, use of pupil expansion devices, use of local anesthetic injections, and change in best corrected visual acuity were recorded.

Results-: Three sites recorded 40,113 clear corneal incision cataract surgeries, of which 0.49% (196 eyes) were performed on 150 thrombocytopenic patients. The mean platelet count in the study subjects was 73.0x10/µl ± 20.5x10/µl. Two cases of intraoperative iris hemorrhage which were readily controlled occurred in conjunction with pupillary expansion. There were no bleeding complications associated with retrobulbar, peribulbar, or sub-Tenon anesthetic injections. There was a statistically significant improvement (p <0.0001) in visual acuity postoperatively.

Conclusion-: Clear corneal incision cataract surgery with pupillary expansion devices and local anesthetic injections can be safely performed in patients with thrombocytopenia.
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http://dx.doi.org/10.1097/j.jcrs.0000000000000676DOI Listing
April 2021

Cancer-Associated Retinopathy due to Clear Cell Renal Carcinoma.

Ocul Oncol Pathol 2021 Mar 18;7(1):31-35. Epub 2020 Dec 18.

Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, USA.

An 84-year-old female presented with bilateral scotomas and progressive nyctalopia over 1 year. Best-corrected visual acuity was 20/50 in both eyes with reduced color vision. Goldmann visual field showed bilateral cecocentral scotomas and generalized constriction of the visual fields. This led to an electroretinogram showing an electronegative pattern consistent with autoimmune retinopathies. Infectious workup was negative. Anti-retinal antibodies were positive, leading to a presumed diagnosis of cancer-associated retinopathy (CAR). Imaging showed a previously unknown left renal lower pole mass, and she underwent a radical nephrectomy. Biopsy showed nuclear grade-3 clear cell renal carcinoma staged T1. The patient was treated with oral prednisone with no ocular improvement. We report on a rare case of clear cell renal carcinoma causing CAR. CAR is an important paraneoplastic syndrome to diagnose since the majority of ocular cases precede other manifestations of malignancy. Therefore, a timely diagnosis of CAR can be lifesaving or at least life-extending.
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http://dx.doi.org/10.1159/000511189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989776PMC
March 2021

Rituximab for autoimmune retinopathy: Results of a Phase I/II clinical trial.

Taiwan J Ophthalmol 2021 Jan-Mar;11(1):64-70. Epub 2020 Jul 27.

Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Purpose: This prospective study evaluates whether rituximab is a safe and potentially effective treatment for nonparaneoplastic autoimmune retinopathy (npAIR).

Materials And Methods: Five npAIR patients were enrolled in a Phase I/II, prospective, nonrandomized, open-label, single-center study. All patients received a cycle of 1000 mg intravenous rituximab at weeks 0 and 2, with a second cycle of rituximab 6 to 9 months later. Clinical evaluation was performed at baseline, 6 and 12 weeks after each rituximab cycle, and then every 3 months for a total duration of 18 months. The primary outcome for this study was treatment success based on visual field and full-field electroretinography at 6 months. The secondary outcomes included treatment success at months 12 and 18, drug-related adverse events, changes in visual symptoms, and changes in quality of life.

Results: Two patients met criteria for treatment success: one based solely on electroretinography and the other based solely on visual field area, but treatment success was not sustained. Clinical response over the course of the 18-month study showed disease stabilization in three patients and treatment failure in two patients. There were no severe drug-related adverse events.

Conclusion: This is the first clinical trial prospectively evaluating the effect of rituximab in npAIR and, although rituximab was well tolerated, there was no clear-cut clinical improvement conferred by B cell depletion with rituximab.
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http://dx.doi.org/10.4103/tjo.tjo_32_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971443PMC
July 2020

Accuracy of self-reported risk factors for hydroxychloroquine retinopathy.

Can J Ophthalmol 2021 Feb 16. Epub 2021 Feb 16.

Department of Ophthalmology, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minn.; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minn.. Electronic address:

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http://dx.doi.org/10.1016/j.jcjo.2021.01.021DOI Listing
February 2021

Corticosteroid-Resistant Sarcoid Choroidal Granuloma Presenting With Optic Disc Edema.

J Neuroophthalmol 2021 Jan 15. Epub 2021 Jan 15.

Department of Ophthalmology and Visual Neurosciences (KRA, MSL), University of Minnesota, Minneapolis, Minnesota; and Department of Ophthalmology (KRA), Veterans Affairs Health Care System, Minneapolis, Minnesota.

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http://dx.doi.org/10.1097/WNO.0000000000001168DOI Listing
January 2021

Title: BILATERAL UVEITIS AND HYPOTONY FOLLOWING TREATMENT WITH TOPICAL CIDOFOVIR.

Retin Cases Brief Rep 2020 Nov 20. Epub 2020 Nov 20.

Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota.

Purpose: To report a case of bilateral uveitis and hypotony associated with topical cidofovir treatment.

Methods: Case report.

Results: A 59-year-old diabetic male with HIV/AIDS presented with photophobia, ocular pain, and decreased vision. He was found to have bilateral hypotony, anterior uveitis, and serous choroidal detachments. Infectious disease workup, patient-reported history, and review of the patient's electronic medication list did not identify the etiology. Treatment with intensive topical corticosteroids led to resolution of uveitis and choroidal effusions within 3 months and resolution of hypotony within 9 months. Two years after his initial presentation, the patient developed acute recurrence of bilateral hypotony, anterior uveitis, and serous choroidal detachments shortly after intravenous cidofovir treatment. Careful re-evaluation of the patient's outside medical records revealed that he had initiated treatment for rectal herpes simplex virus with compounded topical cidofovir one month prior to his initial presentation.

Conclusion: To our knowledge, this is the first reported case of topical cidofovir causing ocular toxicity. Compounded and topical medications, like cidofovir in this case, may not appear on a patient's electronic medication list, so a focused review of outside medical records may be beneficial when a particular medication toxicity is suspected.
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http://dx.doi.org/10.1097/ICB.0000000000001101DOI Listing
November 2020

Post-intravitreal injection endophthalmitis secondary to Turicella otitidis: a case report.

BMC Ophthalmol 2020 Apr 10;20(1):142. Epub 2020 Apr 10.

Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 420 Delaware Street Southeast, MMC 493, Minneapolis, MN, 55455, USA.

Background: Endophthalmitis is a rare but potentially devastating complication of intravitreal injection. The causative organism plays an important role in prognosis following endophthalmitis. Here we present the first reported case of Turicella otitidis endophthalmitis, which is notable for a delayed presentation.

Case Presentation: A 71 year old male who was receiving intravitreal aflibercept injections for neovascular age-related macular degeneration presented 4 weeks after his most recent intravitreal injection and was found to have endophthalmitis. Polymerase chain reaction (PCR) testing of aqueous fluid was positive for Turicella otitidis. The endophthalmitis responded well to treatment with intravitreal antibiotics.

Conclusions: Coryneform bacteria are a rare cause of endophthalmitis, and this is the first reported case of endophthalmitis caused by the corynebacterium species Turicella otitidis. As in this case, post-intravitreal injection endophthalmitis may have a bacterial etiology even with delayed presentation. The relatively indolent disease course and excellent response to intravitreal antibiotics is consistent with previous ophthalmic reports regarding other corynebacteria, as well as with otolaryngology and hematology oncology reports addressing Turicella otitidis specifically. This case supports the growing body of evidence for pathogenicity of Turicella otitidis and demonstrates the utility of PCR for diagnosis in small volume aqueous specimens.
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http://dx.doi.org/10.1186/s12886-020-01412-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146956PMC
April 2020

Logistic Regression Classification of Primary Vitreoretinal Lymphoma versus Uveitis by Interleukin 6 and Interleukin 10 Levels.

Ophthalmology 2020 07 5;127(7):956-962. Epub 2020 Feb 5.

Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland. Electronic address:

Purpose: To assess the diagnostic performance and generalizability of logistic regression in classifying primary vitreoretinal lymphoma (PVRL) versus uveitis from intraocular cytokine levels in a single-center retrospective cohort, comparing a logistic regression model and previously published Interleukin Score for Intraocular Lymphoma Diagnosis (ISOLD) scores against the interleukin 10 (IL-10)-to-interleukin 6 (IL-6) ratio.

Design: Retrospective cohort study.

Participants: Patient histories, pathology reports, and intraocular cytokine levels from 2339 patient entries in the National Eye Institute Histopathology Core database.

Methods: Patient diagnoses of PVRL versus uveitis and associated aqueous or vitreous IL-6 and IL-10 levels were collected retrospectively. From these data, cytokine levels were compared between diagnoses with the Mann-Whitney U test. A logistic regression model was trained to classify PVRL versus uveitis from aqueous and vitreous IL-6 and IL-10 samples and compared with ISOLD scores and IL-10-to-IL-6 ratios.

Main Outcome Measures: Area under the receiver operating characteristic curve (AUC) for each classifier and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at the optimal cutoff (maximal Youden index) for each classifier.

Results: Seventy-seven lymphoma patients (10 aqueous samples, 67 vitreous samples) and 84 uveitis patients (19 aqueous samples, 65 vitreous samples) treated between October 5, 1999, and September 16, 2015, were included. Interleukin 6 levels were higher and IL-10 levels were lower in uveitis patients compared with lymphoma patients (P < 0.01). For vitreous samples, the logistic regression model, ISOLD score, and IL-10-to-IL-6 ratio achieved AUCs of 98.3%, 97.7%, and 96.3%, respectively. Sensitivity, specificity, PPV, and NPV at the optimal cutoffs for each classifier were 94.2%, 96.9%, 97%, and 94% for the logistic regression model; 92.7%, 100%, 100%, and 92.9% for the ISOLD score; and 94.2%, 95.3%, 95.6%, and 93.9% for the IL-10-to-IL-6 ratio. All models achieved complete separation between uveitis and lymphoma in the aqueous data set.

Conclusions: The accuracy of the logistic regression model and generalizability of the ISOLD score to an independent patient cohort suggest that intraocular cytokine analysis by logistic regression may be a promising adjunct to cytopathologic analysis, the gold standard, for the early diagnosis of primary vitreoretinal lymphoma. Further validation studies are merited.
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http://dx.doi.org/10.1016/j.ophtha.2020.01.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311235PMC
July 2020

Gradient Boosted Decision Tree Classification of Endophthalmitis Versus Uveitis and Lymphoma from Aqueous and Vitreous IL-6 and IL-10 Levels.

J Ocul Pharmacol Ther 2017 05 3;33(4):319-324. Epub 2017 Feb 3.

1 Laboratory of Immunology, National Eye Institute, National Institutes of Health , Bethesda, Maryland.

Purpose: To investigate the effectiveness of gradient boosting to classify endophthalmitis versus uveitis and lymphoma by intraocular cytokine levels.

Method: Patient diagnoses and aqueous and vitreous levels of interleukin (IL)-6 and IL-10 were retrospectively extracted from a National Eye Institute Histopathology Core database and compared by Kruskal-Wallis and post hoc Dunn tests. A gradient-boosted decision tree classifier was trained to differentiate endophthalmitis versus uveitis and lymphoma from vitreous IL-6 and IL-10, vitreous IL-6 only, and aqueous IL-6 only data sets; and was tested with 80-20 train-test split and 3-fold cross-validation of the training set.

Results: Seven endophthalmitis, 29 lymphoma, and 49 uveitis patients were included. IL-6 was higher in endophthalmitis than uveitis (P = 0.0713 aqueous, 0.0014 vitreous) and lymphoma (P = 0.0032 aqueous, 0.0001 vitreous). IL-10 was significantly higher in lymphoma than uveitis (P = 0.0017 aqueous, 0.0014 vitreous). Three-fold cross validation demonstrated 95% ± 5%, 95% ± 4%, and 97% ± 5% predictive accuracy for vitreous IL-6 and IL-10, vitreous IL-6 only, and aqueous IL-6 only data sets. Upon validation with the testing set, vitreous IL-6 and IL-10 and aqueous IL-6 only data sets achieved 100% predictive accuracy and vitreous IL-6 only data achieved 93% predictive accuracy with 100% sensitivity, 92% specificity, and an area under the receiver operating characteristic curve (ROC/AUC) of 96%.

Conclusions: With limited sample size, gradient boosting can differentiate endophthalmitis from uveitis and lymphoma by IL-6 and IL-10 with high sensitivity and specificity; however, a larger cohort is needed for further validation.
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http://dx.doi.org/10.1089/jop.2016.0132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421627PMC
May 2017

Pharmacologic Treatment of Noninfectious Uveitis.

Handb Exp Pharmacol 2017;242:231-268

Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bldg 10 Room 10N109, 10 Center Drive, Bethesda, MD, 20892, USA.

Uveitis encompasses a spectrum of diseases whose common feature is intraocular inflammation, which may be infectious or noninfectious in etiology (Nussenblatt and Whitcup 2010). Infectious causes of uveitis are typically treated with appropriate antimicrobial therapy and will not be discussed in this chapter. Noninfectious uveitides are thought have an autoimmune component to their etiology and are thus treated with anti-inflammatory agents.
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http://dx.doi.org/10.1007/164_2016_21DOI Listing
April 2019

Mutant β-III spectrin causes mGluR1α mislocalization and functional deficits in a mouse model of spinocerebellar ataxia type 5.

J Neurosci 2014 Jul;34(30):9891-904

Departments of Genetics, Cell Biology and Development, Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, Department of Neurology, and Genetics Institute, College of Medicine, University of Florida, Gainesville, Florida 32610

Spinocerebellar ataxia type 5 (SCA5), a dominant neurodegenerative disease characterized by profound Purkinje cell loss, is caused by mutations in SPTBN2, a gene that encodes β-III spectrin. SCA5 is the first neurodegenerative disorder reported to be caused by mutations in a cytoskeletal spectrin gene. We have developed a mouse model to understand the mechanistic basis for this disease and show that expression of mutant but not wild-type β-III spectrin causes progressive motor deficits and cerebellar degeneration. We show that endogenous β-III spectrin interacts with the metabotropic glutamate receptor 1α (mGluR1α) and that mice expressing mutant β-III spectrin have cerebellar dysfunction with altered mGluR1α localization at Purkinje cell dendritic spines, decreased mGluR1-mediated responses, and deficient mGluR1-mediated long-term potentiation. These results indicate that mutant β-III spectrin causes mislocalization and dysfunction of mGluR1α at dendritic spines and connects SCA5 with other disorders involving glutamatergic dysfunction and synaptic plasticity abnormalities.
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http://dx.doi.org/10.1523/JNEUROSCI.0876-14.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107406PMC
July 2014

A pain in the eye.

Surv Ophthalmol 2014 Jul-Aug;59(4):474-7. Epub 2013 Oct 21.

Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas.

A 38-year-old woman presented with chronic left retro-orbital pain and photophobia. Palpation of the left occipital prominence revealed tenderness in the area of the greater occipital nerve and reproduced the eye pain. The diagnosis of cervicogenic headache was confirmed by symptom resolution following left greater occipital nerve blockade. The functional association between the greater occipital nerve and the trigeminal nerve provides a potential mechanism for this case of cervicogenic eye pain.
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http://dx.doi.org/10.1016/j.survophthal.2013.10.006DOI Listing
December 2014

Spectrin mutations that cause spinocerebellar ataxia type 5 impair axonal transport and induce neurodegeneration in Drosophila.

J Cell Biol 2010 Apr;189(1):143-58

Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.

Spinocerebellar ataxia type 5 (SCA5) is an autosomal dominant neurodegenerative disorder caused by mutations in the SPBTN2 gene encoding beta-III-spectrin. To investigate the molecular basis of SCA5, we established a series of transgenic Drosophila models that express human beta-III-spectrin or fly beta-spectrin proteins containing SCA5 mutations. Expression of the SCA5 mutant spectrin in the eye causes a progressive neurodegenerative phenotype, and expression in larval neurons results in posterior paralysis, reduced synaptic terminal growth, and axonal transport deficits. These phenotypes are genetically enhanced by both dynein and dynactin loss-of-function mutations. In summary, we demonstrate that SCA5 mutant spectrin causes adult-onset neurodegeneration in the fly eye and disrupts fundamental intracellular transport processes that are likely to contribute to this progressive neurodegenerative disease.
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http://dx.doi.org/10.1083/jcb.200905158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854382PMC
April 2010

Spectrin mutations cause spinocerebellar ataxia type 5.

Nat Genet 2006 Feb 22;38(2):184-90. Epub 2006 Jan 22.

Department of Genetics, Cell Biology, and Development, University of Minnesota, 321 Church St. SE, Minneapolis, Minnesota 55455 USA.

We have discovered that beta-III spectrin (SPTBN2) mutations cause spinocerebellar ataxia type 5 (SCA5) in an 11-generation American kindred descended from President Lincoln's grandparents and two additional families. Two families have separate in-frame deletions of 39 and 15 bp, and a third family has a mutation in the actin/ARP1 binding region. Beta-III spectrin is highly expressed in Purkinje cells and has been shown to stabilize the glutamate transporter EAAT4 at the surface of the plasma membrane. We found marked differences in EAAT4 and GluRdelta2 by protein blot and cell fractionation in SCA5 autopsy tissue. Cell culture studies demonstrate that wild-type but not mutant beta-III spectrin stabilizes EAAT4 at the plasma membrane. Spectrin mutations are a previously unknown cause of ataxia and neurodegenerative disease that affect membrane proteins involved in glutamate signaling.
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http://dx.doi.org/10.1038/ng1728DOI Listing
February 2006