Publications by authors named "Sruthi Arepalli"

41 Publications

Identifying RNA Biomarkers and Molecular Pathways Involved in Multiple Subtypes of Uveitis.

Am J Ophthalmol 2021 Jan 24;226:226-234. Epub 2021 Jan 24.

From the Department of Ophthalmology/Casey Eye Institute (J.T.R., A.Z., S.A., P.K, C.M., L.W., S.R.P., T.M.M., D.C.); Department of Medicine (J.T.R., D.C.), and; OHSU-PSU School of Public Health (D.C.), Oregon Health & Science University, Portland, Oregon, USA; and; Graduate School of Dentistry, Kyung Hee University, Seoul, Korea (D.C.).

Purpose: Uveitis is a heterogeneous collection of diseases. We tested the hypothesis that despite the diversity of uveitides, there could be common mechanisms shared by multiple subtypes, and that evidence of these common mechanisms may be detected as gene expression profiles in whole blood.

Design: Cohort study.

Methods: Ninety subjects with uveitis including axial spondyloarthritis (n = 17), sarcoidosis (n = 13), inflammatory bowel disease (n = 12), tubulointerstitial nephritis with uveitis (n = 10), or idiopathic uveitis (n = 38) as well as 18 healthy controls were enrolled, predominantly at Oregon Health & Science University. RNA-Seq data generated from peripheral, whole blood identified 19,859 unique transcripts. We analyzed gene expression pathways via Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO). We validated our list of upregulated genes by comparison to a previously published study on peripheral blood gene expression among 50 subjects with diverse forms of uveitis.

Results: Both the Kyoto Encyclopedia of Genes and Genomes and GO analysis identified multiple shared pathways or GO terms with a P value of <.0001. Almost all pathways related to the immune response and/or response to an infection. A total of 119 individual transcripts were upregulated by at least 1.5-fold and false discovery rate <.05, and 61 were downregulated by similar criteria. Comparing mRNA from our study with a false discovery rate <.05 and the prior report, we identified 10 common gene transcripts: ICAM1, IL15RA, IL15, IRF1, IL10RB, GSK3A, TYK2, MEF2A, MEF2B, and MEF2D.

Conclusions: Many forms of uveitis share overlapping mechanisms. These data support the concept that a single therapeutic approach could benefit diverse forms of this disease.
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http://dx.doi.org/10.1016/j.ajo.2021.01.007DOI Listing
January 2021

Optimizing Visualization of Membranes in Macular Surgery With Heads-Up Display.

Ophthalmic Surg Lasers Imaging Retina 2020 10;51(10):584-587

Background And Objective: To determine which optical parameter profiles (OPPs) can be utilized to improve the visualization of epiretinal membranes (ERMs) and the internal limiting membrane (ILM) using a three-dimensional heads-up microscope during 25-gauge pars plana vitrectomy.

Patients And Methods: Fourteen independent graders were asked to complete a questionnaire comparing each of the OPPs against the unaltered control image for each given surgical case.

Results: Analysis of the graders' responses indicated that higher values of hue are correlated with better visualization of ERM/ILM before and after dye application. There was overall agreement that OPPs could be used to enhance the visualization of the ERM and ILM during surgery.

Conclusions: The use of OPPs to improve the visualization of specific structures is still new and heavily dependent on surgeon preference. The authors' study shows that some OPPs may enhance the visualization of the ERM and ILM during macular surgery. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:584-587.].
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http://dx.doi.org/10.3928/23258160-20201005-06DOI Listing
October 2020

Patient-Reported Complications after Intravitreal Injection and Their Predictive Factors.

Ophthalmol Retina 2020 Oct 12. Epub 2020 Oct 12.

Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.

Purpose: The intravitreal injection (IVI) of pharmacologic agents is the most commonly performed ocular procedure and is associated with a host of complications. Most IVI-related complications data are derived from randomized controlled clinical trials, which report a high adverse event rate. The nature of these protocol-driven trials limit their applicability to the diverse circumstances seen in routine clinical practice. The goal of this study was to determine the prevalence of patient-reported IVI-related complications, their risk factors, and the manner in which patients sought treatment at a tertiary eye care center.

Design: Retrospective, institutional review board-approved study.

Participants: Forty-four thousand seven hundred thirty-four injections in 5318 unique patients at the Cleveland Clinic Cole Eye Institute from 2012 through 2016.

Methods: Intravitreal injection.

Main Outcome Measures: Complication occurrence within 15 days of injection.

Results: From 2012 through 2016, a total of 44734 injections were performed in 5318 unique patients. Overall, complication rates were low, representing 1.9% of all injections, with 1031 unique complications in 685 patients (12.9%). The most common minor complications, or those not requiring intervention, were irritation (n = 312) and subconjunctival hemorrhage (n = 284). The most common serious complications, or those requiring intervention, were corneal abrasion (n = 46) and iritis (n = 31). Most complications (66%) were managed adequately by a telephone or Epic (Epic Systems Corp., Verona, WI) electronic message encounter only. Importantly, no injection protocol parameter, such as type of anesthesia, preparation, or post-injection medication, increased the risk of a complication. However, a patient's gender, age, number of previous injections, and provider strongly influenced the risk of patient-reported complications.

Conclusions: Overall, complication rates seen in routine clinical practice were low compared with clinical trial reporting. Providers should feel confident in the safety and administration of IVI during times when follow-up office visits and resources may be limited. When performing an IVI, factors such as a patient's gender, age, number of previous injections, and provider must be taken into account to ensure the best possible outcomes.
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http://dx.doi.org/10.1016/j.oret.2020.09.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548755PMC
October 2020

Revising the Diagnosis of Idiopathic Uveitis by Peripheral Blood Transcriptomics.

Am J Ophthalmol 2021 02 15;222:15-23. Epub 2020 Sep 15.

Department of Ophthalmology/Casey Eye Institute, Oregon Health and Science University, Portland, Oregon, USA; Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA; Oregon Health and Science University-Portland State University School of Public Health, Oregon Health and Science University, Portland, Oregon, USA; Graduate School of Dentistry, Kyung Hee University, Seoul, Korea.

Purpose: To test the hypothesis that idiopathic uveitis can be categorized into subtypes based on gene expression from blood.

Design: Case control study.

Methods: We applied RNA-Seq to peripheral blood from patients with uveitis associated with 1 of 4 systemic diseases, including axial spondyloarthritis (n = 17), sarcoidosis (n = 13), inflammatory bowel disease (n = 12), tubulo-interstitial nephritis with uveitis (n = 10), or idiopathic uveitis (n = 38) as well as 18 healthy control subjects evaluated predominantly at Oregon Health and Science University. A high-dimensional negative binomial regression model implemented in the edgeR R package compared each disease group with the control subjects. The 20 most distinctive genes for each diagnosis were extracted. Of 80 genes, there were 75 unique genes. A classification algorithm was developed by fitting a gradient boosting tree with 5-fold cross-validation. Messenger RNA from subjects with idiopathic uveitis were analyzed to see if any fit clinically and by gene expression pattern with one of the diagnosable entities.

Results: For uveitis associated with a diagnosable systemic disease, gene expression profiling achieved an overall accuracy of 85% (balanced average of sensitivity plus specificity, P < .001). Although most patients with idiopathic uveitis presumably have none of these 4 associated systemic diseases, gene expression profiles helped to reclassify 11 of 38 subjects.

Conclusions: Peripheral blood gene expression profiling is a potential adjunct in accurate differential diagnosis of the cause of uveitis. Validation of these results and characterization of the gene expression profile from additional discrete diagnoses could enhance the value of these observations.
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http://dx.doi.org/10.1016/j.ajo.2020.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935743PMC
February 2021

Aqueous Cytokine Expression and Higher Order OCT Biomarkers: Assessment of the Anatomic-Biologic Bridge in the IMAGINE DME Study.

Am J Ophthalmol 2021 02 5;222:328-339. Epub 2020 Sep 5.

Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA; Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address:

Purpose: To identify biomarkers for predicting response to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular edema (DME) and evaluate any links between cytokine expression and optical coherence tomography (OCT) phenotype.

Design: The IMAGINE is a post hoc image analysis and cytokine expression assessment of the Efficacy & Safety Trial of Intravitreal Injections Combined With PRP for CSME Secondary to Diabetes Mellitus (DAVE) randomized clinical trial.

Methods: Subjects were categorized as anatomical responders or nonresponders, and within the responder group as rebounders and non-rebounders based on quantitative, longitudinal OCT criteria. Retinal layer and fluid features were extracted using an OCT machine-learning augmented segmentation platform. Responders were further sub-classified by rapidity of response. Aqueous concentrations of 54 cytokines were measured at multiple timepoints. Expression was compared between responder groups and correlated with OCT imaging biomarkers.

Results: Of the 24 eyes studied, 79% were anatomical responders with 38% super responders, 17% early responders, and 25% slow responders. Twenty-one percent were nonresponders. Super responders had increased baseline vascular endothelial growth factor (VEGF) (880.0 pg/mL vs 245.4 pg/mL; P = .012) and decreased monocyte chemotactic protein-1 (MCP-1) (513.3 pg/mL vs 809.5 pg/mL; P = .0.042) concentrations compared with nonresponders. Interleukin-6 (-24.9 pg/mL vs 442.8 pg/mL; P = .032) concentrations increased among nonresponders during therapy. VEGF concentrations correlated with central subfield thickness (r = 0.49; P = .01). Panmacular retinal volume correlated with increased interleuckin-6 (r = 0.47; P = .02) and decreased MCP-1 (r = -0.45; P = .03). Matrix metallopeptidase-1 correlated with subretinal fluid volume (r = 0.50; P = .01).

Conclusions: OCT imaging biomarkers correlated with both intraocular cytokines and responsiveness to anti-VEGF therapy, which indicated a possible link to underlying pathways and their relevance to DME prognosis. Baseline concentrations of VEGF and MCP-1 are associated with anatomic response to anti-VEGF therapy.
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http://dx.doi.org/10.1016/j.ajo.2020.08.047DOI Listing
February 2021

Brolucizumab-early real-world experience: BREW study.

Eye (Lond) 2021 Apr 24;35(4):1045-1047. Epub 2020 Jul 24.

Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA.

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http://dx.doi.org/10.1038/s41433-020-1111-xDOI Listing
April 2021

Inferior Corneal Haze and Inflammatory Endotheliopathy Related to Pars Planitis.

Ocul Immunol Inflamm 2020 Jul 1;28(5):798-801. Epub 2019 Oct 1.

Department of Ophthalmology, Oregon Health & Science University, Portland, VA, USA.

Purpose: To describe the finding of inferior corneal haze secondary to presumed inflammatory endothelio-10 pathy in a series of patients with pars planitis.

Methods: Single-center retrospective observational consecutive case-series.

Results: Seven patients with an established diagnosis of pars planitis are described in this case series including four females and three males. The ages ranged from 5 to 31 years at presentation. Pars planitis was bilateral in six patients and unilateral in one patient. Fundus examinations revealed vitreous opacities and pars plana exudates in all seven patients, cystoid macular edema in four patients, and peripheral retinal vasculitis in two patients. Corneal examination revealed opacification of the posterior cornea in an inferior location in 10 of the 13 eyes with pars planitis. Only one of these eyes had keratic precipitates. For a given patient, corneal involvement was more commonly seen in the more inflamed eye. In one patient with active inflammation, microcystic corneal edema was noted to predate the formation of inferior corneal endothelial opacification, suggesting that physical proximity to the site of inflammation at the inferior pars plana is the cause of this notable physical finding.

Conclusions: Inferior posterior corneal haze related to inflammatory endotheliopathy may occur in eyes with pars planitis. As patients with pars planitis may be otherwise asymptomatic, this corneal finding shouldprompt a detailed funduscopic examination to rule out this form of uveitis.
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http://dx.doi.org/10.1080/09273948.2019.1629603DOI Listing
July 2020

Local therapy for cancer therapy-associated uveitis: a case series and review of the literature.

Br J Ophthalmol 2020 05 13;104(5):703-711. Epub 2019 Aug 13.

Retina and Uveitis, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Background/aims: Immunotherapy and targeted therapy for metastatic cancer may cause immune-related adverse events (irAEs) such as uveitis. If irAEs are severe or require systemic steroids, cancer therapy is often held or discontinued. Local steroid therapy for cancer therapy-associated uveitis allows the continuation of cancer therapy. This series demonstrates successful management of cancer therapy-associated uveitis with local therapy based on uveitis subtype.

Methods: This is an Institutional Review Board-approved retrospective case series of patients with uveitis secondary to immunotherapy or targeted therapy managed with local treatment, and focused literature review.

Results: Five patients (median age: 54, range 31 to 75) were included. Time to uveitis onset following cancer therapy initiation was 3 to 12 months. All patients received checkpoint inhibitor therapy; one patient additionally received targeted therapy. Two patients presented with anterior uveitis, two with panuveitis and one with posterior uveitis. Four of five patients demonstrated evidence of posterior segment inflammation on multimodal imaging. Anterior uveitis was successfully treated with topical prednisolone acetate 1% (PA 1%) alone, and posterior segment involvement recalcitrant to topical PA 1% was treated successfully with topical difluprednate, intravitreal triamcinolone acetonide or a combination. Patients with isolated anterior uveitis did not require maintenance topical therapy; those with posterior and panuveitis required chronic low-dose topical therapy.

Conclusion: Based on our series as well as the existing literature demonstrating the use of local therapy for irAEs, we propose an approach to local therapy for cancer therapy-associated uveitis starting with topical steroids and initiating injectable steroids in cases of recalcitrant panuveitis or posterior uveitis. Subclinical inflammation on posterior segment imaging responds robustly to difluprednate or intravitreal steroid therapy, and patients with posterior segment involvement may require more aggressive management and long-term maintenance.
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http://dx.doi.org/10.1136/bjophthalmol-2019-314403DOI Listing
May 2020

The use of biologics for uveitis associated with spondyloarthritis.

Curr Opin Rheumatol 2019 07;31(4):349-354

Casey Eye Institute.

Purpose Of Review: The term spondyloarthritis (SpA) encompasses a group of chronic inflammatory disorders of the joints, including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease, juvenile SpA and undifferentiated SpA. These diseases can also present with uveitis, or intraocular inflammation, which can be controlled with biologics.

Recent Findings: Profound success has occurred with the tumor necrosis factor-α inhibitors infliximab and adalimumab, moderate success with certolizumab pegol and golimumab and less encouraging results with etanercept. Promising results have also been demonstrated with interleukin-17 (IL-17) antagonists, such as secukinumab ixekizumab or combined IL-12 and 23 medications, such as ustekinumab.

Summary: In cases of uveitis that require long-term control, biologics are an emerging and valuable class of medications for these patients, and may provide avenues to control both their underlying SpA and uveitis manifestations.
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http://dx.doi.org/10.1097/BOR.0000000000000619DOI Listing
July 2019

Sporadic Burkitt Lymphoma with Orbital Extramedullary Infiltration.

Ocul Oncol Pathol 2019 Jan 23;5(1):46-49. Epub 2018 May 23.

Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Background/aims: Sporadic Burkitt lymphoma is rarely associated with orbital involvement.

Methods: We present a case of sporadic Burkitt lymphoma with extramedullary subperiosteal leukemic infiltrates of the orbit and facial bones.

Results: Follow-up examination after chemotherapy and disease remission reveals resolution of the subperiosteal infiltrates.

Conclusion: Despite an aggressive presentation, cure is common with appropriate, intensive treatment. To our knowledge, this report is the first to photographically depict the resolution of extramedullary orbital subperiosteal leukemic infiltrates after appropriate chemotherapy.
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http://dx.doi.org/10.1159/000488710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341329PMC
January 2019

Optic Nerve Compression From MIRAgel Implant Migration in a Monocular Patient.

Ophthalmic Surg Lasers Imaging Retina 2018 10;49(10):815-818

The MIRAgel implantation was popularized in the 1980s as an alternative to silicone for scleral buckle retinal detachment repair. However, long-term follow-up has revealed that the implants can expand, creating globe compression and potentially visually devastating intraocular invasion. The authors document a 33-year-old monocular male patient presenting 20 years after MIRAgel implantation with extensive expansion, posterior migration, globe compression, and possible optic nerve compression. Debulking of the MIRAgel stabilized the vision and restored affected extraocular movements. The authors highlight that posterior MIRAgel migration can cause optic nerve compression, and implant debulking may require a multi-disciplinary approach. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:815-818.].
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http://dx.doi.org/10.3928/23258160-20181002-12DOI Listing
October 2018

Assessment of inner and outer retinal layer metrics on the Cirrus HD-OCT Platform in normal eyes.

PLoS One 2018 4;13(10):e0203324. Epub 2018 Oct 4.

Cole Eye Institute, Cleveland Clinic, Cleveland, OH, United States of America.

Purpose: Ellipsoid zone (EZ) and outer retinal integrity are strongly linked to visual prognosis, but quantitative normative data is lacking. This study evaluates the EZ, outer retina, and inner retina in eyes without macular disease across a wide age spectrum.

Methods: An IRB-approved study was performed for eyes without macular pathology undergoing Spectral Domain Optical Coherence Tomography (SD-OCT) scans on the Cirrus HD-OCT system (Carl Zeiss Meditec, Oberkochen, Germany). Scans were analyzed using a previously described automated EZ mapping tool with line-by-line manual verification. Segmentation included internal limiting membrane (ILM), outer nuclear layer/Henle fiber layer complex (ONL/HFL), EZ, and the retinal pigment epithelium (RPE). The output included metrics for the inner retina (ILM-OPL/HFL), outer retina (ONL/HFL-RPE), EZ-RPE area and volume, and en face EZ mapping. EZ-RPE attenuation on en face mapping was defined as EZ-RPE thickness < 20 um, and total attenuation was 0 um. Imaging parameters were assessed for the group and compared to age, sex, visual acuity and spherical equivalent.

Results: 167 eyes from 167 subjects were included. Mean age was 49.7 years (range 10-84 years). The mean foveal retinal thickness was 200.58 ± 19.22 um. Mean inner retinal thickness was 21.47 ± 13.60 um. Mean outer retinal thickness was 179.11 ± 18.52 um. Mean EZ-RPE thickness was 50.58 ± 6.01um. The mean EZ-RPE volume was 1.20 ± 0.10 mm3. Mean EZ attenuation percentage per macular map area was 0.87% ± 1.13% and mean percentage total attenuation was 0.12% ± 0.14%. Total and inner retinal thickness metrics decreased with age. Mean outer retinal thickness increased with age. EZ-RPE parameters were unchanged with age. However, EZ attenuation was negatively correlated with age.

Conclusion: This study provides important information for inner and outer retinal parameters. Future research on quantitative EZ integrity can utilize this data for comparison.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203324PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171834PMC
March 2019

Treatment Duration and Side Effect Profile of Long-Term Use of Intravitreal Preservative-Free Triamcinolone Acetonide in Uveitis.

Am J Ophthalmol 2018 10 24;194:63-71. Epub 2018 Jul 24.

Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. Electronic address:

Purpose: Noninfectious uveitis has been treated historically with corticosteroid therapy in varying doses and routes. Triesence, a preservative-free sterile formulation of triamcinolone acetonide, has been used in a wide spectrum of ocular pathologies, but there have been few large studies validating its dosing or detailing long-term side effects in uveitic disease. The primary aim of this study was to describe the relative duration of action and side effects of 2 doses of preservative-free intravitreal triamcinolone acetonide (PF-IVTA) in uveitis.

Design: Retrospective, comparative consecutive case series.

Methods: Charts of all patients receiving PF-IVTA (2 mg or 4 mg) in a defined time period (2012-2014) at the Cole Eye Institute were examined for patient demographics, time to treatment failure (TTF), use of systemic immunosuppression, use of intraocular pressure-lowering therapies, date of cataract surgery and glaucoma filtration surgery, and adverse events.

Results: The final data set examined 514 injections in 214 eyes. Mean duration of follow-up was 1.5 years. There was similar demographic distribution between eyes that received 2 mg PF-IVTA only and eyes that received a combination of 4 + 2 mg PF-IVTA. No statistically significant difference in TTF between injection dosages was observed. There was a higher incidence of glaucoma filtering surgery and cataract surgery in eyes that received 4 + 2 mg PF-IVTA as well as a shorter time to glaucoma surgery, when compared to eyes that received 2 mg PF-IVTA alone.

Conclusions: This retrospective study supports that 2 mg PF-IVTA displayed noninferior treatment duration to 4 mg PF-IVTA, and may carry a significantly lower side-effect profile of cataract development and glaucoma filtering surgery.
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http://dx.doi.org/10.1016/j.ajo.2018.07.003DOI Listing
October 2018

Mild Bilateral Hemorrhagic Occlusive Retinal Vasculitis Following Intracameral Vancomycin Administration in Cataract Surgery.

Ophthalmic Surg Lasers Imaging Retina 2018 05;49(5):369-373

A patient underwent cataract surgery with prophylactic intracameral vancomycin (Vancocin; Pfizer, New York City, NY) in each eye, 2 weeks apart. Four weeks after, the patient presented with a mild bilateral hemorrhagic occlusive retinal vasculitis (HORV). A systemic work-up was negative for syphilis, toxoplasmosis, Bartonella, tuberculosis, and sarcoidosis. The patient was treated with oral steroids and one intravitreal steroid injection in the left eye. Ten months after presentation, the patient's vasculitis was quiescent. Although the literature describes primarily severe forms of HORV, the authors' case describes bilateral, mild HORV and highlights the potential underreporting of these cases in the literature. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:369-373.].
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http://dx.doi.org/10.3928/23258160-20180501-12DOI Listing
May 2018

Paracanthal "One-Snip" Decompression in a Cadaver Model of Retrobulbar Hemorrhage.

Ophthalmic Plast Reconstr Surg 2018 Sep/Oct;34(5):428-431

Cole Eye Institute, Cleveland Clinic, Cleveland.

Purpose: The authors assess the effectiveness of a modified paracanthal or "one-snip" procedure compared with the traditional lateral canthotomy and inferior cantholysis in the reduction of intraocular pressure (IOP) and proptosis in a human cadaveric model of retrobulbar hemorrhage.

Methods: This study comprised a comparative interventional study in a cadaveric model of retrobulbar hemorrhage. Six orbits of 3 fresh cadavers were included in the study. Baseline measurements of IOP and proptosis were recorded for all 6 orbits before and after simulation of retrobulbar hemorrhage as previously described. Right orbits (n = 3) underwent traditional lateral canthotomy and inferior cantholysis. Left orbits (n = 3) underwent modified paracanthal or "one-snip" procedure. The primary outcome measures were reduction in IOP and proptosis between the 2 techniques.

Results: Following lateral canthotomy and inferior cantholysis of each right orbit, the average IOP dropped to 14 mm Hg (range of 11-18 mm Hg), corresponding to a mean decrease of 32 mm Hg. Following the "one-snip" procedure of each left orbit, the average IOP dropped to 19 mm Hg with a range of 16 to 23 mm Hg, corresponding to a mean decrease of 22 mm Hg. There was no statistically significant difference in IOP reduction (p = 0.36) or proptosis reduction (p = 0.23) between the 2 treatment groups.

Conclusions: Compared with traditional lateral canthotomy xand inferior cantholysis, the modified paracanthal or "one-snip" procedure is effective for IOP reduction and led to mild improvement of proptosis in a cadaveric model of retrobulbar hemorrhage. The authors hope this study helps improve orbital compartment syndrome outcomes by providing an option that more providers will feel comfortable performing and therefore decreasing time to surgical decompression.
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http://dx.doi.org/10.1097/IOP.0000000000001032DOI Listing
September 2018

The Prevalence of Adverse Ocular Hemorrhagic Events in Patients Utilizing Oral Anticoagulant and Antiplatelet Therapy in Routine Clinical Practice.

Ophthalmic Surg Lasers Imaging Retina 2018 01;49(1):27-34

Background And Objective: Previous literature assessing ocular hemorrhagic complications of anticoagulant/antiplatelet medications in routine clinical practice is limited. This study evaluates the prevalence of spontaneous ocular hemorrhagic events associated with anticoagulation/antiplatelet therapy.

Patients And Methods: A retrospective study was performed to identify patients taking anticoagulants (rivaroxaban [Xarelto; Janssen Pharmaceuticals, Beerse, Belgium], bivalirudin [Angiomax; The Medicines Company, Parsippany, NJ], lepirudin [Refludan; Bayer HealthCare Pharmaceuticals, Berlin, Germany], dabigatran [Pradaxa; Boehringer Ingelheim, Ingelheim am Rhein, Germany], and argatroban) and antiplatelet agents (clopidogrel [Plavix; Bristol-Myers Squibb, New York City, NY], prasugrel [Effient; Lilly Medical, Indianapolis, IN], and ticagrelor [Brilinta; AstraZeneca, Cambridge, UK]) who presented for an eye examination. Location of hemorrhage, relevant systemic and ocular comorbidities, baseline demographics, and concomitant aspirin use were noted.

Results: A total of 44 patients with spontaneous ocular hemorrhage were identified. Thirty patients had a single episode, whereas 14 patients had multiple episodes (two or more hemorrhagic events). Prevalence of spontaneous ocular hemorrhage on prasugrel (7.2%) and rivaroxaban (3.1%) was higher compared to dabigatran (1.9%), clopidogrel (2.0%), and ticagrelor (2.7%).

Conclusion: Prevalence of spontaneous ocular hemorrhage with use of anticoagulant/antiplatelet agents is higher in routine clinical practice as compared to previously reported literature. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:27-34.].
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http://dx.doi.org/10.3928/23258160-20171215-04DOI Listing
January 2018

ELLIPSOID ZONE MAPPING AND OUTER RETINAL ASSESSMENT IN STARGARDT DISEASE.

Retina 2018 07;38(7):1427-1431

Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.

Purpose: To quantify and correlate ellipsoid zone and photoreceptor outer segment changes with visual acuity in Stargardt disease.

Methods: An institutional review board-approved study of 32 eyes with Stargardt disease was performed. After spectral domain optical coherence tomography, the macular cube was exported into a novel analysis tool and volumetric assessment from the ellipsoid zone to the retinal pigment epithelium was performed. Using this information, mapping was completed with en face representation of the height between the ellipsoid zone and retinal pigment epithelium. This analysis provided quantification of ellipsoid zone and photoreceptor outer segments, including atrophy (ellipsoid zone to retinal pigment epithelium thickness = 0 μm) and attenuation (ellipsoid zone to retinal pigment epithelium thickness <20 μm). These parameters were compared with visual acuity and controls (n = 12 eyes).

Results: Visual acuity ranged from 20/30 to 20/250. The central foveal B-scan area of ellipsoid and photoreceptor outer segments was significantly less than controls (0.13 ± 0.05 mm vs. 0.17 ± 0.03 mm, respectively, P = 0.0074). The central foveal B-scan mean thickness measured 22.52 ± 9.0 μm in Stargardt versus 30.0 ± 5.08 μm (P = 0.0096). Atrophy and attenuation were significantly higher in Stargardt patients (22% vs. 1%, P = 0.005 and 43% vs. 1%, P = 0.0002). Visual acuity directly correlated with ellipsoid zone/outer segment volume (R = 0.57, P < 0.005) and inversely correlated with attenuation and atrophy (R = -0.53 and -0.57; P < 0.005 for all).

Conclusion: Eyes with Stargardt disease frequently have significant disruption of the ellipsoid zone and outer segments. This degenerative change was successfully quantified with a novel assessment platform and identified correlates with visual function. This software provides the opportunity for quantitative assessment and possible longitudinal surveillance.
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http://dx.doi.org/10.1097/IAE.0000000000001716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718981PMC
July 2018

The application of optical coherence tomography angiography in uveitis and inflammatory eye diseases.

Prog Retin Eye Res 2017 07 29;59:178-201. Epub 2017 Apr 29.

Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA.

Since its introduction in the early 1990s, optical coherence tomography (OCT) has evolved in resolution and technological advances, and in recent years its initial application of assessing the morphology of a tissue has been implemented by the study of its functional blood flow, through optical coherence tomography angiography (OCTA). This novel technique details capillary networks by comparing the amount of light returned from static and moving targets without the need for intravenous dye administration. While this imaging modality has been used for various ocular conditions, the application OCTA to uveitis conditions remains sparse. This review aims to establish the basis of OCTA and its current application to ocular inflammatory disorders, with an emphasis on monitoring progression and response to treatment, as well as predicting visual complications. In particular, this review explores the use of OCTA in iris vessel dilation seen in various forms of iritis, as a predictive factor for further episodes of inflammation. OCTA can also depict ischemia in the deep plexus layers of the retina and identify true choroicapillaris ischemia in cases of placoid diseases or masking of the indocyanine green dye, as in multiple evanescent white dot syndrome. In addition, OCTA can depict neovascularization in granulomatous disease of the retina or choroid not previously depicted with previous imaging methods. While OCTA provides several advancements in the imaging, management and prognosis of uveitis diseases, we emphasize that further studies are required to fully understand its application to these conditions.
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http://dx.doi.org/10.1016/j.preteyeres.2017.04.005DOI Listing
July 2017

Choroidal metastases: origin, features, and therapy.

Indian J Ophthalmol 2015 Feb;63(2):122-7

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

The choroid is the most common ocular site for metastatic disease, owing to abundant vascular supply. The primary cancers that most commonly lead to choroidal metastases include breast cancer (40-47%) and lung cancer (21-29%). Bilateral, multifocal metastases are most often secondary to breast cancer, whereas unilateral, unifocal metastasis are more commonly found with lung cancer. The treatment of choroidal metastasis depends on the systemic status of the patient and number, location, and laterality of the choroidal tumors. Treatment options include observation in patients with poor systemic status or those with resolved or asymptomatic disease; systemic chemotherapy, immunotherapy, hormone therapy, or whole eye radiotherapy if the metastases are active, multifocal and bilateral; plaque radiotherapy, transpupillary radiotherapy, or photodynamic therapy for active, solitary metastasis; and enucleation for those with blind painful eye. A database search was performed on PubMed, using the terms "choroidal metastasis," or "choroidal metastases," in combination with terms such as "treatment," "features," or "diagnosis." Relevant articles were extracted and reviewed.
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http://dx.doi.org/10.4103/0301-4738.154380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399120PMC
February 2015

Posterior tunica vasculosa lentis and "brittle star" of persistent fetal vasculature.

J Pediatr Ophthalmol Strabismus 2014 Nov 19;51 Online:e69-71. Epub 2014 Nov 19.

A 17-month-old girl referred for a suspected ciliary body medulloepithelioma was found to have persistent fetal vasculature. Fluorescein angiography showed perfused hyaloid artery posterior tunica vasculosa lentis with brittle star appearance and nonperfused anterior pupillary membrane. Ultrasound biomicroscopy confirmed absence of iris or ciliary body solid tumor.
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http://dx.doi.org/10.3928/01913913-20141111-01DOI Listing
November 2014

Choroidal osteoma shows bone lamella and vascular channels on enhanced depth imaging optical coherence tomography in 15 eyes.

Retina 2015 Apr;35(4):750-7

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: To describe enhanced depth imaging optical coherence tomography findings of choroidal osteoma.

Methods: Retrospective, observational case series of 15 eyes with choroidal osteoma imaged with EDI-OCT.

Results: The mean age at presentation was 27 years. There were 10 women and 3 men. The visual acuity ranged from 20/20 to hand motion, with reduced visual acuity secondary to photoreceptor loss in the foveola (n = 5) or subfoveal fluid (n = 1), and additional choroidal neovascular membrane (n = 3). The mean basal tumor diameter was 8.0 mm, and ultrasonographic thickness was 1.5 mm. Using enhanced depth imaging optical coherence tomography, the mean tumor thickness was 589 μm when compared with a matched choroidal region in the unaffected eye of 247 μm (138% increased thickness) (P = 0.009). The tumor surface topography was classified (ultrasonography vs. enhanced depth imaging optical coherence tomography) as flat (87 vs. 13%), dome (13 vs. 40%), or undulating (0 vs. 47%). On enhanced depth imaging optical coherence tomography, unique features included horizontal lamellar lines (presumed bone lamella) (n = 15, 100%) and hyperreflective horizontal lines (presumed cement lines) (n = 8, 53%). Other features included horizontal tubular lamella with optically empty center (presumed Haversian canals or vascular channels) (n = 9, 60%), vertical tubular lamella (presumed Volkmann canals or vascular channels) (n = 2, 13%), and speckled regions (presumed compact or small trabecular bone) (n = 6, 40%). Of the nine eyes with subfoveolar osteoma, the tumor was completely ossified (n = 4), partially deossified (n = 2), or completely deossified (n = 3). Photoreceptor thinning/atrophy was found in all five eyes with deossified osteoma, whereas intact photoreceptor appearance was noted in the four eyes with ossified subfoveal osteoma.

Conclusion: Enhanced depth imaging optical coherence tomography reveals characteristic surface topography of choroidal osteoma as dome or undulating (87%) with unique intrinsic features of horizontal lamellar lines (100%), horizontal (60%) or vertical (13%) tubules, and speckled regions (40%). Photoreceptor loss was evident in every case of tumor deossification.
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http://dx.doi.org/10.1097/IAE.0000000000000376DOI Listing
April 2015

Combined hamartoma of the retina and retinal pigment epithelium: findings on enhanced depth imaging optical coherence tomography in eight eyes.

Retina 2014 Nov;34(11):2202-7

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: To assess combined hamartoma of the retina and retinal pigment epithelium with enhanced depth imaging optical coherence tomography.

Methods: Retrospective, observational cases series in eight eyes of eight patients, with comparison between affected and unaffected eyes regarding enhanced depth imaging optical coherence tomography features of tumor, fovea, and choroid.

Results: The mean age at presentation was 7 years. The tumor was macular (n = 5) or extramacular (n = 3). Enhanced depth imaging optical coherence tomography revealed irregularities in inner retina (n = 8) and/or all retinal layers (n = 3), with epiretinal membrane (n = 8), causing an inner retinal sawtooth (mini-peak) pattern (n = 2), full thickness retinal folds (maxi-peak) (n = 3), or both (n = 3). In the 5 macular tumors, foveal retinal thickness measured mean 608 μm compared with 244 μm in the unaffected eye (P = 0.0004). Mean tumor epicenter retinal thickness in 8 tumors measured 650 μm compared with 327 μm in a corresponding area in the unaffected eye (P = 0.01). In all cases, choroidal thickness beneath the tumor epicenter was decreased at mean 210 μm compared with 328 μm in the corresponding area of unaffected eye (P = 0.009).

Conclusion: Enhanced depth imaging optical coherence tomography of combined hamartoma revealed epiretinal membrane with vitreoretinal traction in a sawtooth (mini-peak) or folded (maxi-peak) pattern. Combined hamartoma seems to be a thickened retinal mass secondary to focal vitreoretinal traction.
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http://dx.doi.org/10.1097/IAE.0000000000000220DOI Listing
November 2014

Ciliary body medulloepithelioma association with pleuropulmonary blastoma in a familial tumor predisposition syndrome.

J Pediatr Ophthalmol Strabismus 2014 Jul 16;51 Online:e48-50. Epub 2014 Jul 16.

Ciliary body medulloepithelioma can rarely present in association with pleuropulmonary blastoma as part of a familial tumor predisposition syndrome. This is thought to occur secondary to a germline mutation in the DICER1 gene. The authors describe a case of ciliary body medulloepithelioma in a 9-year-old girl with a known medical history of pleuropulmonary blastoma.
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http://dx.doi.org/10.3928/01913913-20140709-03DOI Listing
July 2014

Morning glory disc anomaly with Chiari type I malformation.

J Pediatr Ophthalmol Strabismus 2014 Apr 30;51 Online:e22-4. Epub 2014 Apr 30.

Morning glory disc anomaly is a rare optic nerve dysplasia associated with various neovascular abnormalities. Due to these associations, children with morning glory disc anomaly have brain imaging and angiography to detect other congenital defects. The authors report the case of an infant with morning glory disc anomaly and coexisting Chiari type I malformation.
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http://dx.doi.org/10.3928/01913913-20140423-03DOI Listing
April 2014

Iris stromal cyst management with absolute alcohol-induced sclerosis in 16 patients.

JAMA Ophthalmol 2014 Jun;132(6):703-8

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Importance: The management of symptomatic iris stromal cyst is challenging using methods of aspiration with or without adjunctive cryotherapy, intracameral cautery, or photocoagulation. Failed cases often require surgical resection, with risks for epithelial downgrowth, glaucoma, blindness, and loss of the eye.

Objective: To study the safety and efficacy of the management of iris stromal cysts with aspiration and alcohol irrigation to induce cyst sclerosis.

Design, Setting, And Participants: Interventional case series at a tertiary referral center among 16 patients.

Exposures: Microscopically monitored transcorneal aspiration of cysts was performed with a 30-gauge needle on a 3-way T-extension into a 3-mL syringe, followed by immediate infusion of absolute alcohol from a separate 1-mL syringe through the other arm of the T-extension. Subsequent alcohol aspiration and repetition of the cycle was performed until the collapsed cyst wall appeared gray.

Main Outcomes And Measures: Cyst involution, visual acuity, and treatment complications.

Results: The iris stromal cysts were primary congenital (n = 6), primary acquired (n = 4), or secondary (n = 6). The cysts had a median basal diameter of 12 mm and a thickness of 4 mm, occupying 50% or more of the anterior or posterior chamber in each case. Treatment was administered following failure of simple aspiration (n = 16) and additional methods (n = 8). During a median follow-up period of 5 years, treatment was successful in 14 of 15 patients (1 patient was lost to follow-up). Cyst sclerosis with stabilization (n = 1) or involution (n = 13) was achieved following 1 (n = 10), 2 (n = 2), or 3 (n = 2) procedures. The single failure occurred in a 3-year-old child with cyst recurrence and severe photophobia requiring resection. Visual acuity remained stable or had improved in 14 patients and was reduced in 1 patient because of cataract. Complications included transient corneal edema (n = 4) and transient anterior chamber inflammation (n = 1), which resolved following topical corticosteroid therapy. No evidence was seen of treatment-related glaucoma, epithelial downgrowth, tissue necrosis, cataract, posterior segment toxic effects, or need for enucleation.

Conclusions And Relevance: Microscopically monitored aspiration and absolute alcohol-induced sclerosis of iris stromal cysts is safe and effective, with cyst involution obtained in 93% (14 of 15) of patients.
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http://dx.doi.org/10.1001/jamaophthalmol.2014.160DOI Listing
June 2014

Combined hamartoma of the retina and retinal pigment epithelium in branchio-otic syndrome.

J AAPOS 2014 Apr;18(2):201-3

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address:

A 15-month-old boy with established branchio-otic syndrome was evaluated for decreased red reflex in the left eye. Fundus examination of left eye revealed a gray epiretinal membrane with retinal traction and ill-defined macular thickening, found on ultrasonography as a dense flat region 1.7 mm in thickness. Enhanced depth imaging optical coherence tomography revealed an epiretinal membrane with macular thickening, retinal folding, and full-thickness retinal disorganization, consistent with combined hamartoma of the retina and retinal pigment epithelium. Over 5 years of follow-up, the branchio-otic syndrome was unchanged and the combined hamartoma remained stable.
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http://dx.doi.org/10.1016/j.jaapos.2013.11.022DOI Listing
April 2014

Intra-arterial chemotherapy for retinoblastoma in 70 eyes: outcomes based on the international classification of retinoblastoma.

Ophthalmology 2014 Jul 21;121(7):1453-60. Epub 2014 Mar 21.

Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Objective: To analyze our 5-year experience of intra-arterial chemotherapy (IAC) for retinoblastoma as primary or secondary therapy.

Design: Retrospective interventional case series.

Participants: A total of 70 eyes of 67 patients.

Intervention: Ophthalmic artery chemotherapy infusion under fluoroscopic guidance was performed using melphalan (3, 5, or 7.5 mg) in every case, with additional topotecan (1 mg) and/or carboplatin (30 or 50 mg) as necessary.

Main Outcome Measures: Tumor control and treatment complications.

Results: The mean patient age at IAC was 30 months. The treatment was primary in 36 eyes and secondary in 34 eyes. Those primary therapy eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group A (n = 0), B (n = 1), C (n = 4), D (n = 17), or E (n = 14). The secondary therapy eyes had failed previous intravenous chemotherapy (n = 34) in every case. Each eye received a mean of 3 IAC sessions per eye (median, 3; range, 1-7 sessions). After IAC with a mean follow-up of 19 months, globe salvage was achieved in 72% of primary-treated cases and in 62% of secondary-treated cases. Specifically, primary therapy achieved globe salvage for group B (100%), group C (100%), group D (94%), and group E (36%). Of all 70 eyes, complete regression was achieved for solid tumor in 48 of 51 eyes (94%), subretinal seeds in 40 of 42 eyes (95%), and vitreous seeds in 34 of 39 eyes (87%). After each catheterization (n = 198), the main complications included transient eyelid edema (5%), blepharoptosis (5%), and forehead hyperemia (2%). More lasting complications included vitreous hemorrhage (2%), branch retinal artery obstruction (1%), ophthalmic artery spasm with reperfusion (2%), ophthalmic artery obstruction (2%), partial choroidal ischemia (2%), and optic neuropathy (<1%). Over the past 3 years, the combined incidence of ophthalmic, retinal, and choroidal vascular ischemia was reduced to 1%. There was no patient with stroke, seizure, neurologic impairment, limb ischemia, secondary leukemia, metastasis, or death.

Conclusions: Five-year experience with IAC indicates that this technique is remarkably effective for the management of retinoblastoma as both a primary and a secondary treatment.
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http://dx.doi.org/10.1016/j.ophtha.2014.01.026DOI Listing
July 2014

Choroidal lymphoma shows calm, rippled, or undulating topography on enhanced depth imaging optical coherence tomography in 14 eyes.

Retina 2014 Jul;34(7):1347-53

*Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania; and †Eye Clinic, Department of Biomedical and Clinical Science "Luigi Sacco", Luigi Sacco Hospital, University of Milan, Milan, Italy.

Purpose: To describe the features of choroidal lymphoma on enhanced depth imaging optical coherence tomography.

Methods: This retrospective observational case series included 14 eyes of 13 patients, with choroidal lymphoma, studied by enhanced depth imaging optical coherence tomography.

Results: The mean age at presentation was 63 years (median, 65 years; range, 32-87 years). Systemic lymphoproliferative disease was present in 2 cases as non-Hodgkin lymphoma (n = 1) or Waldenstrom macroglobulinemia (n = 1). On clinical examination, the choroidal infiltrate was classified as unifocal (n = 3), multifocal (n = 4), or diffuse (n = 7). Enhanced depth imaging optical coherence tomography scans through the tumor epicenter revealed infiltration of the choroid with apparent inward compression of choroidal vascular structures, creating an anterior tumor surface topography that appeared smooth (calm) (n = 7), mini-wavy (rippled) (n = 2), or maxi-wavy (undulating) (n = 5). Greater tumor thickness correlated with increasing tumor surface fluctuation as calm was mean 1.7mm, rippled was 2.8 mm, and undulating surface was 4.1 mm in ultrasonographic thickness. On enhanced depth imaging optical coherence tomography, the mean subfoveolar choroidal thickness, measurable in 9 eyes, was 484 μm (median, 423 μm; range, 156-1,002 μm) (81% greater) versus 267 μm (median, 276 μm; range, 142-501 μm) in the unaffected eye. The mean maximal tumor thickness, measurable in 8 eyes, was 117% greater at 602 μm (median, 538 μm; range, 241-966 μm) compared with the corresponding unaffected choroid in the contralateral eye at 278 μm (median, 245 μm; range, 189-511 μm) (P = 0.046). Inability to measure choroidal thickness was due to dense tumor-induced optical shadowing with inability to visualize the sclerochoroidal junction (P = 0.009). There was no visible infiltration into the overlying retina in any case.

Conclusion: Enhanced depth imaging optical coherence tomography of choroidal lymphoma revealed 1 of 3 surface topographical patterns resembling an ocean as calm (n = 7), rippled (n = 2), or undulating (n = 5), correlating with increasing tumor thickness.
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http://dx.doi.org/10.1097/IAE.0000000000000145DOI Listing
July 2014