Publications by authors named "Judy E Kim"

111 Publications

Assessing the Influence of OCT-A Device and Scan Size on Retinal Vascular Metrics.

Transl Vis Sci Technol 2020 10 7;9(11). Epub 2020 Oct 7.

Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.

Purpose: The purpose of this study was to investigate the effect of device and scan size on quantitative optical coherence tomography angiography (OCT-A) metrics.

Methods: The 3 × 3 mm scans from Optovue AngioVue and Zeiss AngioPlex systems were included for 18 eyes of 18 subjects without ocular pathology. The foveal avascular zone (FAZ) was segmented manually by two observers, from which estimates of FAZ area (using both the nominal image scale and the axial length corrected image scale) and acircularity were derived. Three scan sizes (3 mm, 6 mm HD, and 8 mm) from the AngioVue system were included for 15 eyes of 15 subjects without ocular pathology. For each subject, larger image sizes were resized to the same resolution as 3 × 3 mm scans, aligned, then cropped to a common area. FAZ area, FAZ acircularity, average and total parafoveal intercapillary area, vessel density, and vessel end points were computed.

Results: Between the devices used here, there were no significant differences in FAZ acircularity ( = 0.88) or FAZ area using scaled ( = 0.11) or unscaled images ( = 0.069). Although there was no significant difference in FAZ area across scan sizes ( = 0.30), vessel morphometry metrics were all significantly influenced by scan size.

Conclusions: The scan devices and sizes used here do not affect FAZ area measures derived from manual segmentations. In contrast, vessel morphometry metrics are affected by scan size. As individual differences in axial length induce differences in absolute scan size, extreme care should be taken when interpreting metrics of vessel morphometry, both between and within OCT-A devices.

Translational Relevance: A better characterization of the confounds surrounding OCT-A retinal vasculature metrics can lead to improved application of these metrics as biomarkers for retinal and systemic diseases.
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http://dx.doi.org/10.1167/tvst.9.11.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545061PMC
October 2020

Digital technology, tele-medicine and artificial intelligence in ophthalmology: A global perspective.

Prog Retin Eye Res 2020 Sep 6:100900. Epub 2020 Sep 6.

Singapore National Eye Center, Duke-NUS Medical School Singapore, Singapore. Electronic address:

The simultaneous maturation of multiple digital and telecommunications technologies in 2020 has created an unprecedented opportunity for ophthalmology to adapt to new models of care using tele-health supported by digital innovations. These digital innovations include artificial intelligence (AI), 5th generation (5G) telecommunication networks and the Internet of Things (IoT), creating an inter-dependent ecosystem offering opportunities to develop new models of eye care addressing the challenges of COVID-19 and beyond. Ophthalmology has thrived in some of these areas partly due to its many image-based investigations. Tele-health and AI provide synchronous solutions to challenges facing ophthalmologists and healthcare providers worldwide. This article reviews how countries across the world have utilised these digital innovations to tackle diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, glaucoma, refractive error correction, cataract and other anterior segment disorders. The review summarises the digital strategies that countries are developing and discusses technologies that may increasingly enter the clinical workflow and processes of ophthalmologists. Furthermore as countries around the world have initiated a series of escalating containment and mitigation measures during the COVID-19 pandemic, the delivery of eye care services globally has been significantly impacted. As ophthalmic services adapt and form a "new normal", the rapid adoption of some of telehealth and digital innovation during the pandemic is also discussed. Finally, challenges for validation and clinical implementation are considered, as well as recommendations on future directions.
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http://dx.doi.org/10.1016/j.preteyeres.2020.100900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474840PMC
September 2020

Polypoidal Choroidal Vasculopathy: Consensus Nomenclature and Non-Indocyanine Green Angiograph Diagnostic Criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup.

Ophthalmology 2021 Mar 11;128(3):443-452. Epub 2020 Aug 11.

Nune Eye Hospital, Seoul, South Korea.

Purpose: To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV) and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiography (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photography findings.

Design: Evaluation of diagnostic test results.

Participants: Panel of retina specialists.

Methods: As part of the Asia-Pacific Ocular Imaging Society, an international group of experts surveyed and discussed the published literature regarding the current nomenclature and lesion components for PCV, and proposed an updated consensus nomenclature that reflects our latest understanding based on imaging and histologic reports. The workgroup evaluated a set of diagnostic features based on OCT images and color fundus photographs for PCV that may distinguish it from typical nAMD and assessed the performance of individual and combinations of these non-ICGA features, aiming to propose a new set of diagnostic criteria that does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts.

Main Outcome Measures: Consensus nomenclature system for PCV lesion components and non-ICGA-based criteria to differentiate PCV from typical nAMD.

Results: The workgroup recommended the terms polypoidal lesion and branching neovascular network for the 2 key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based major criteria (sub-retinal pigment epithelium [RPE] ring-like lesion, en face OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset 80 eyes achieved an accuracy of 82%.

Conclusions: We propose updated terminology for PCV lesion components that better reflects the nature of these lesions and is based on international consensus. A set of practical diagnostic criteria applied easily to spectral-domain OCT results can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not performed routinely.
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http://dx.doi.org/10.1016/j.ophtha.2020.08.006DOI Listing
March 2021

Fundamentals of artificial intelligence for ophthalmologists.

Curr Opin Ophthalmol 2020 Sep;31(5):303-311

Palo Alto Medical Foundation, Palo Alto, California, USA.

Purpose Of Review: As artificial intelligence continues to develop new applications in ophthalmic image recognition, we provide here an introduction for ophthalmologists and a primer on the mechanisms of deep learning systems.

Recent Findings: Deep learning has lent itself to the automated interpretation of various retinal imaging modalities, including fundus photography and optical coherence tomography. Convolutional neural networks (CNN) represent the primary class of deep neural networks applied to these image analyses. These have been configured to aid in the detection of diabetes retinopathy, AMD, retinal detachment, glaucoma, and ROP, among other ocular disorders. Predictive models for retinal disease prognosis and treatment are also being validated.

Summary: Deep learning systems have begun to demonstrate a reliable level of diagnostic accuracy equal or better to human graders for narrow image recognition tasks. However, challenges regarding the use of deep learning systems in ophthalmology remain. These include trust of unsupervised learning systems and the limited ability to recognize broad ranges of disorders.
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http://dx.doi.org/10.1097/ICU.0000000000000679DOI Listing
September 2020

The structural basis for monoclonal antibody 5D2 binding to the tryptophan-rich loop of lipoprotein lipase.

J Lipid Res 2020 10 20;61(10):1347-1359. Epub 2020 Jul 20.

Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

For three decades, the LPL-specific monoclonal antibody 5D2 has been used to investigate LPL structure/function and intravascular lipolysis. 5D2 has been used to measure LPL levels, block the triglyceride hydrolase activity of LPL, and prevent the propensity of concentrated LPL preparations to form homodimers. Two early studies on the location of the 5D2 epitope reached conflicting conclusions, but the more convincing report suggested that 5D2 binds to a tryptophan (Trp)-rich loop in the carboxyl terminus of LPL. The same loop had been implicated in lipoprotein binding. Using surface plasmon resonance, we showed that 5D2 binds with high affinity to a synthetic LPL peptide containing the Trp-rich loop of human (but not mouse) LPL. We also showed, by both fluorescence and UV resonance Raman spectroscopy, that the Trp-rich loop binds lipids. Finally, we used X-ray crystallography to solve the structure of the Trp-rich peptide bound to a 5D2 Fab fragment. The Trp-rich peptide contains a short α-helix, with two Trps projecting into the antigen recognition site. A proline substitution in the α-helix, found in mouse LPL, is expected to interfere with several hydrogen bonds, explaining why 5D2 cannot bind to mouse LPL.
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http://dx.doi.org/10.1194/jlr.RA120000993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529051PMC
October 2020

Treatment for a Subtype of Exudative Macular Degeneration-Another Mountain Climbed.

JAMA Ophthalmol 2020 09;138(9):942-944

The Eye Institute, Medical College of Wisconsin, Milwaukee.

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http://dx.doi.org/10.1001/jamaophthalmol.2020.2421DOI Listing
September 2020

Standard 6-mm Compared with Widefield 16.5-mm OCT for Staging of Posterior Vitreous Detachment.

Ophthalmol Retina 2020 11 19;4(11):1093-1102. Epub 2020 May 19.

The Froedtert Eye Institute, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address:

Purpose: To assess whether 6-mm OCT scans, which image the macula, can distinguish complete from partial posterior vitreous detachment (PVD) in comparison with 16.5-mm OCT scans, which image the macula, optic nerve, and mid periphery.

Design: Retrospective cross-sectional study.

Participants: We compared 6-mm and 16.5-mm scans in 157 eyes of 157 retina clinic patients (mean age, 50 years; range, 10-64 years) with diabetic retinopathy (36%), no retinal disease (19%), and various retinal conditions (45%). We also analyzed 16.5-mm scans in 35 healthy eyes (asymptomatic fellow eyes of patients with unilateral retinal conditions; mean age, 46 years; range, 9-63 years).

Methods: Each participant underwent Heidelberg Spectralis imaging with the standard lens (6-mm scan) and/or the 55° lens (16.5-mm scan). On 6-mm scans, we classified eyes as stage 3 partial PVD when the posterior vitreous cortex was visualized without visible attachment. On 16.5-mm scans, we classified eyes as stage 3 when the vitreous was attached at the optic nerve and separated from the macula. On both scan types, we classified eyes as stage 4 when neither the premacular bursa nor the posterior vitreous cortex were visualized. We assessed the accuracy of this system for detecting complete PVD on 6-mm scans by calculating test characteristics using 16.5-mm scans as a reference standard.

Main Outcome Measure: Posterior vitreous detachment stage (0-4).

Results: Posterior vitreous detachment stage was identical in 6-mm and 16.5-mm scans in 88% of eyes. Compared with 16.5-mm scans, 6-mm scans detected complete PVD (vs. earlier stages 0-3) with 91% sensitivity and 99% specificity. Seven eyes were classified as no PVD on 6-mm scans and were classified as partial PVD on 16.5-mm scans because vitreoretinal separation was localized to the mid periphery. All 16.5-mm scans showed some degree of PVD, including scans from 9 participants between 9 and 20 years of age.

Conclusions: Six-millimeter scans distinguished complete from partial PVD with good sensitivity and specificity but missed the earliest stages of PVD, which occur in the mid periphery. Posterior vitreous detachment may begin as early as the second decade of life.
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http://dx.doi.org/10.1016/j.oret.2020.05.006DOI Listing
November 2020

Accuracy of Spectral-Domain OCT of the Macula for Detection of Complete Posterior Vitreous Detachment.

Ophthalmol Retina 2020 02 2;4(2):148-153. Epub 2019 Nov 2.

Froedtert Eye Institute, Medical College of Wisconsin, Milwaukee, Wisconsin.

Purpose: To assess the accuracy of macular spectral-domain OCT in detecting complete posterior vitreous detachment (PVD).

Design: Evaluation of diagnostic test or technology using a retrospective comparative study.

Participants: One hundred seventy-five eyes in 175 patients (111 women and 64 men; mean age, 65 years) with preoperative OCT within 90 days of vitrectomy.

Methods: Posterior vitreous detachment status on preoperative macular OCT was compared with PVD determination during vitrectomy. Attached vitreous was identified on OCT by visualizing the posterior vitreous cortex or premacular bursa. Complete PVD was identified by the absence of these findings and considered a positive outcome for the purpose of analysis.

Main Outcome Measures: Sensitivity, specificity, positive predictive value, and negative predictive value of macular OCT for detection of complete PVD compared with findings at surgery.

Results: Of the 38 eyes graded as showing complete PVD on OCT, 20 eyes were found to have pre-existing PVD at the time of surgery (true-positive results), and 18 eyes were found to have attached vitreous at the time of surgery (false-positive results). Of the 137 eyes graded as showing attached vitreous on OCT, 129 eyes had attached vitreous at the time of surgery (true-negative results), and 8 eyes had pre-existing PVD at the time of surgery (false-negative results). The sensitivity of OCT for detecting complete PVD was 71% and the specificity was 88%. In the study population, the positive predictive value of an OCT scan showing complete PVD was 53%, whereas the negative predictive value of an OCT scan showing attached vitreous was 94%.

Conclusions: If the premacular bursa or posterior vitreous cortex are visualized on macular OCT, an accurate determination of attached vitreous can be made. The diagnosis of complete PVD by macular OCT is less accurate and requires ultrasound.
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http://dx.doi.org/10.1016/j.oret.2019.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008078PMC
February 2020

Folding of the β-Barrel Membrane Protein OmpA into Nanodiscs.

Biophys J 2020 01 28;118(2):403-414. Epub 2019 Nov 28.

Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California. Electronic address:

Nanodiscs (NDs) are an excellent alternative to small unilamellar vesicles (SUVs) for studies of membrane protein structure, but it has not yet been shown that membrane proteins are able to spontaneously fold and insert into a solution of freely diffusing NDs. In this article, we present SDS-PAGE differential mobility studies combined with fluorescence, circular dichroism, and ultraviolet resonance Raman spectroscopy to confirm the spontaneous folding of outer membrane protein A (OmpA) into preformed NDs. Folded OmpA in NDs was incubated with Arg-C protease, resulting in the digestion of OmpA to membrane-protected fragments with an apparent molecular mass of ∼26 kDa (major component) and ∼24 kDa (minor component). The OmpA folding yields were greater than 88% in both NDs and SUVs. An OmpA adsorbed intermediate on NDs could be isolated at low temperature and induced to fold via an increase in temperature, analogous to the temperature-jump experiments on SUVs. The circular dichroism spectra of OmpA in NDs and SUVs were similar and indicated β-barrel secondary structure. Further evidence of OmpA folding into NDs was provided by ultraviolet resonance Raman spectroscopy, which revealed the intense 785 cm structural marker for folded OmpA in NDs. The primary difference between folding in NDs and SUVs was the kinetics; the rate of folding was two- to threefold slower in NDs compared to in SUVs, and this decreased rate can tentatively be attributed to the properties of NDs. These data indicate that NDs may be an excellent alternative to SUVs for folding experiments and offer benefits of optical clarity, sample homogeneity, control of ND:protein ratios, and greater stability.
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http://dx.doi.org/10.1016/j.bpj.2019.11.3381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976806PMC
January 2020

Raman and Quantum Yield Studies of Trp48- in Azurin: Closed-Shell and Neutral Radical Species.

J Phys Chem B 2019 08 17;123(30):6430-6443. Epub 2019 Jul 17.

Department of Chemistry and Biochemistry , University of California at San Diego , La Jolla , California 92093-0021 , United States.

Isotopologues are valuable vibrational probes that shift features in a vibrational spectrum while preserving the electronic structure of the molecule. We report the vibrational and electronic spectra of perdeuterated tryptophan in solution (l-Trp-), as Trp48- in azurin, and as the photogenerated neutral tryptophan radical, Trp48-, in azurin. The UV resonance Raman bands of the perdeuterated closed-shell tryptophan in solution and in azurin are lower in frequency relative to the protiated counterpart. The observed decrease in frequencies of l-Trp- bands relative to l-Trp- enables the analysis of vibrational markers of other amino acids, e.g., phenylalanine, that overlap with some modes of l-Trp-. The Raman intensities vary between l-Trp- and l-Trp-; these differences likely reflect modifications in normal mode composition upon perdeuteration. Analysis of the W3, W6, and W17 modes suggests that the W3 mode retains its utility as a conformational marker; however, the H-bond markers W6 and W17 appear to be less sensitive upon perdeuteration. The neutral tryptophan radical, Trp48-, was generated in azurin with a slightly lower radical quantum yield than for Trp48-. The visible resonance Raman spectrum of Trp48- is different from that of Trp48-, especially in terms of relative intensities, and all assignable peaks decreased in frequency upon perdeuteration. The absorption and emission spectra of the perdeuterated closed-shell and radical species exhibited hypsochromic shifts of less than 1 nm relative to the protiated species. The data presented here indicate that l-Trp- is a valuable probe of vibrational structure, with minimal modification of photoreactivity and photophysics compared to l-Trp-.
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http://dx.doi.org/10.1021/acs.jpcb.9b04655DOI Listing
August 2019

UV Resonance Raman Spectroscopy as a Tool to Probe Membrane Protein Structure and Dynamics.

Methods Mol Biol 2019 ;2003:327-349

Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.

Ultraviolet resonance Raman (UVRR) spectroscopy is a vibrational technique that reveals structures and dynamics of biological macromolecules without the use of extrinsic labels. By tuning the Raman excitation wavelength to the deep UV region (e.g., 228 nm), Raman signal from tryptophan and tyrosine residues are selectively enhanced, allowing for the study of these functionally relevant amino acids in lipid and aqueous environments. In this chapter, we present methods on the UVRR data acquisition and analysis of the tryptophan vibrational modes of a model β-barrel membrane protein, OmpA, in folded and unfolded conformations.
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http://dx.doi.org/10.1007/978-1-4939-9512-7_14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874512PMC
March 2020

Fundus Hypopigmentation and Loss of Choroidal Nevi Pigmentation Associated With Nivolumab.

JAMA Ophthalmol 2019 Jul;137(7):851-853

Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, Milwaukee.

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http://dx.doi.org/10.1001/jamaophthalmol.2019.0970DOI Listing
July 2019

Imaging Characteristics of Choroidal Neovascular Lesions in the AREDS2-HOME Study: Report Number 4.

Ophthalmol Retina 2019 04 11;3(4):326-335. Epub 2019 Jan 11.

National Eye Institute, Bethesda, Maryland.

Purpose: To characterize choroidal neovascular (CNV) lesions and the corresponding change in visual acuity (VA) in eyes that converted to neovascular age-related macular degeneration (AMD) in the Age-Related Eye Disease Study 2-HOme Monitoring of the Eye Study. (AREDS2-HOME Study).

Design: Cohort study.

Participants: A total of 1520 participants at risk of developing CNV were enrolled, each of whom contributed 1 or both study eye(s) that had a best-corrected VA letter score of ≥54 letters (Snellen equivalent 20/60) and ≥1 large (≥125 μm) macular druse in the absence of neovascular AMD or central geographic atrophy.

Methods: A multicenter clinical trial comparing standard care (SC) versus SC plus ForeseeHome (FH; Notal Vision, Manassas, VA) monitoring strategy in the detection of neovascular AMD. Fluorescein angiograms (FA) and OCT were evaluated by an independent reading center (RC) from the visit in which the ophthalmologist identified progression to CNV (n = 82 eyes).

Main Outcome Measures: Development of CNV on OCT, FA, or both.

Results: The RC confirmed CNV in 67 of 82 eyes (82%); lesions were confirmed in 42 of 70 eyes (60%) with FA, 59 of 72 eyes (82%) with OCT, and on both images in 34 of 67 eyes (51%). Among the FA-confirmed cases, the median lesion size was 0.82 disc area (DA); lesions were subfoveal in 40.5%, occult CNV composition was present in 54.8%, and associated hemorrhage in 50%. Median (interquartile range [IQR]) lesion size on FA was 0.23 (0.0-0.91) DA versus 0.70 (0.0-1.50) DA, P = 0.051) in the FH and SC eyes, respectively. Among the OCT-confirmed cases median (IQR) center point thickness was 209 (175-274) μm, retinal pigment epithelial lesion complex was present in 86.4%, and subretinal fluid (SRF) was present in 76.3%. The median change in VA from baseline was -4.0 letters and -10.0 letters in the FH and SC eyes (P = 0.008) confirmed as CNV at the RC.

Conclusions: Incident CNV lesions were more prevalent on OCT images than on FA; however, the use of both OCT and FA enhanced detection of incident lesions. Lesions were smaller and associated with less vision loss among eyes in the FH group.
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http://dx.doi.org/10.1016/j.oret.2019.01.004DOI Listing
April 2019

Diagnosing Polypoidal Choroidal Vasculopathy Without Indocyanine Green Angiography.

JAMA Ophthalmol 2019 06;137(6):667-668

Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, Milwaukee.

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http://dx.doi.org/10.1001/jamaophthalmol.2019.0583DOI Listing
June 2019

An innovative visual acuity chart for urgent and primary care settings: validation of the Runge near vision card.

Eye (Lond) 2019 07 21;33(7):1104-1110. Epub 2019 Feb 21.

Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, Milwaukee, WI, USA.

Objective: We evaluated the Runge card, a near-vision eye chart designed for ease of use, by testing agreement in visual acuity results between it and the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. As a clinical reference point, we compared the Runge card and an electronic Snellen chart with respect to agreement with ETDRS results.

Methods: Participants consisted of adult eye clinic patient volunteers who underwent a protocol refraction, followed by testing with a Runge card, ETDRS chart, and Snellen chart. Mean logMAR visual acuities were calculated for each method. Agreement levels among the tests were assessed for the group overall and for subjects with good (ETDRS logMAR < 0.6; better than 20/80 Snellen equivalent) and poor (logMAR ≥ 0.6) acuity.

Results: One hundred and thirty-eight participants completed testing. The mean ( ± standard deviation) logMAR visual acuities (Snellen equivalent) with Runge, ETDRS, and Snellen, respectively, were 0.66 ± 0.50 (20/91, n = 138), 0.59 ± 0.51 (20/78, n = 138), and 0.67 ± 0.62 (20/94, n = 137). Runge testing agreed similarly with ETDRS and Snellen testing, with CCC 0.92 between Runge and ETDRS, and 0.87 between Runge and Snellen (p = 0.14). Runge agreed better with ETDRS than Snellen agreed with ETDRS in participants with poor acuity (CCC = 0.79 vs. 0.63, respectively, p = 0.001) but not in those with good acuity (CCC = 0.70 vs. 0.87, respectively, p = 0.005).

Conclusion: Visual acuity measurements with the Runge near card agreed with measurements from the ETDRS to approximately the same degree as did the Snellen chart, suggesting potential utility of the Runge near card, particularly given its user-friendly characteristics and ease of use.
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http://dx.doi.org/10.1038/s41433-019-0372-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707193PMC
July 2019

Variability of Foveal Avascular Zone Metrics Derived From Optical Coherence Tomography Angiography Images.

Transl Vis Sci Technol 2018 Sep 1;7(5):20. Epub 2018 Oct 1.

Cell Biology, Neurobiology, & Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.

Purpose: To characterize sources of inter- and intrasubject variability in quantitative foveal avascular zone (FAZ) metrics.

Methods: Two 3×3-mm optical coherence tomography angiography scans (centered on the fovea) were acquired in both eyes of 175 subjects. An image of the superficial plexus was extracted from each scan and segmented twice by a single observer. Four quantitative FAZ morphology metrics (area, axis ratio, acircularity, major horizontal axis angle) were calculated, and a variance components analysis was performed.

Results: Mean (±SD) age was 27.9 ± 11.9 years, and 55% were female. Area had the largest amount of variance resulting from intersubject differences (93.1%). In contrast, there was large interocular variance for axis ratio, acircularity, and major horizontal axis angle (55.0%, 53.7%, 70.7%, respectively), though only axis ratio showed significant asymmetry between fellow eyes ( < 0.05). Neither repeated images from the same eye nor repeated segmentation on the same image were significant sources of variance.

Conclusions: Metrics of FAZ morphology show excellent repeatability and reliability. Excluding FAZ area, there was a high amount of variance attributed to interocular differences for the other FAZ metrics; therefore, the fellow eye should not be considered a control for FAZ studies when using these metrics.

Translational Relevance: Vision scientists must be prudent when choosing FAZ metrics, as they display varying degrees of within-subject differences relative to between-subject differences. It seems likely that different metrics will be best suited for different tasks, such as monitoring small changes over time within a single subject or assessing whether a given FAZ is abnormal.
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http://dx.doi.org/10.1167/tvst.7.5.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166903PMC
September 2018

Pneumatic Displacement of Submacular Hemorrhage with Subretinal Air and Tissue Plasminogen Activator: Initial United States Experience.

Ophthalmol Retina 2018 03 28;2(3):180-186. Epub 2017 Sep 28.

Department of Ophthalmology, Oakland University, William Beaumont School Of Medicine, Associated Retinal Consultants, Royal Oak, Michigan. Electronic address:

Purpose: To present the initial multicenter experience of using subretinal air injection in combination with tissue plasminogen activator (tPA) at the time of pars plana vitrectomy (PPV) to displace submacular hemorrhage (SMH).

Design: Retrospective, noncomparative, interventional case series.

Participants: Patients with SMH resulting from age-related macular degeneration or polypoidal choroidal vasculopathy.

Methods: Chart review of patients who underwent displacement of SMH with PPV, subretinal injection of air and tPA (125 mg/mL), partial fluid-air exchange with gas tamponade, and preoperative, intraoperative, or postoperative intravitreal injection of anti-vascular endothelial growth factor agent at 5 sites in the United States. None of the surgeons had prior experience with using subretinal air.

Main Outcome Measures: Frequency and extent of SMH displacement, preoperative and postoperative visual acuities and retinal thickness, and postoperative complications.

Results: Twenty-four eyes of 24 patients were included (11 men; mean age, 79.1 years) with a mean follow-up of 12.5 months (range, 3-28 months). At 3 months after surgery, complete displacement of SMH from the foveal center was achieved in 24 eyes (100%), displaced beyond the arcades in 75% and beyond the equator in 20%. Residual subretinal pigment epithelial hemorrhage was seen in 5 eyes (20.8%). Mean preoperative and postoperative visual acuity was 1.95 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/1783) and 0.85 logMAR (Snellen equivalent, 20/141; P < 0.0001), respectively. Visual acuity improved in 23 eyes (95.8%) and was unchanged in 1 eye. Mean central retinal thickness improved from 463.7 μm before surgery to 311.3 μm at the final visit (P = 0.026).

Conclusions: This initial experience of injecting subretinal air at the time of tPA injection during PPV showed the technique to be effective, with high consistency to displace SMH away from the fovea and even out to the periphery, and resulted in improved VA and retinal thickness. Some cases of subretinal pigment epithelial hemorrhage also benefit from this technique.
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http://dx.doi.org/10.1016/j.oret.2017.07.012DOI Listing
March 2018

INTRAOPERATIVE IMAGING OF RETAINED PERFLUOROCARBON LIQUID USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

Retin Cases Brief Rep 2019 ;13(4):381-384

Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin.

Purpose: To report images of retained perfluorocarbon liquid (PFCL) on the surface of the retina obtained during an intraoperative use of hand-held spectral domain optical coherence tomography.

Methods: A 54-year-old man underwent pars plana vitrectomy with injection of PFCL to repair retinal detachment. Postoperatively, visually significant PFCL droplets were found to be retained in the eye. During the surgical removal of PFCL, a hand-held spectral domain optical coherence tomography was used to image the retina with the patient supine.

Results: Spectral domain optical coherence tomography images of the retained PFCL illustrated magnification of the areas of the outer retina underlying PFCL bubbles. The images obtained had some similarities to the patient's own observation of "floaters."

Conclusion: Droplets of PFCL over the retina result in imaging artifact, most likely due to a lensing effect caused by differences in refractive index between the PFCL and vitreous humor. Although the utility of hand-held spectral domain optical coherence tomography for infants has previously been established, this case presents further application of spectral domain optical coherence tomography in adults when imaging in the supine position is required.
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http://dx.doi.org/10.1097/ICB.0000000000000607DOI Listing
March 2020

High-Resolution Imaging of Intraretinal Structures in Active and Resolved Central Serous Chorioretinopathy.

Invest Ophthalmol Vis Sci 2017 01;58(1):42-49

Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.

Purpose: We improved our understanding of central serous chorioretinopathy (CSC), we performed an analysis of noninvasive, high-resolution retinal imaging in patients with active and resolved CSC.

Methods: Adaptive optics scanning light ophthalmoscopy (AOSLO) and spectral-domain optical coherence tomography (SD-OCT) were performed on five subjects with CSC. A custom AOSLO system was used to simultaneously collect confocal and split-detector images. Spectral domain-OCT volume scans were used to create en face views of various retinal layers, which then were compared to montaged AOSLO images after coregistration.

Results: Three distinct types of intraretinal hyperreflective clusters were seen with AOSLO. These clusters had a well-demarcated, round, and granular appearance. Clusters in active CSC over areas of serous retinal detachment were termed type-1. They were found primarily in the outer nuclear layer (ONL) and were associated with large defects in the photoreceptor mosaic and ellipsoid zone. Clusters in areas where the retina had reattached were termed type-2. They also were located primarily in the ONL but showed stability in location over a period of at least 8 months. Smaller clusters in the inner retina along retinal capillaries were termed type-3.

Conclusions: Retinal imaging in CSC using en face OCT and AOSLO allows precise localization of intraretinal structures and detection of features that cannot be seen with SD-OCT alone. These findings may provide greater insight into the pathophysiology of the active and resolved phases of the disease, and support the hypothesis that intraretinal hyperreflective foci on OCT in CSC are cellular in nature.
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http://dx.doi.org/10.1167/iovs.16-20351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225998PMC
January 2017

CLINICAL EVALUATION OF THE RAPID ACCESS VITREAL INJECTION GUIDE: A Handheld Instrument for Assisting Intravitreal Injections.

Retina 2017 Apr;37(4):778-781

*Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin; †Departments of Ophthalmology and Visual Sciences, and Epidemiology, University of Michigan, Ann Arbor, Michigan; and ‡Retina Associates, PA, Shawnee Mission, Kansas.

Purpose: The Rapid Access Vitreal Injection (RAVI) guide combines the function of an eyelid speculum and measuring caliper into a single instrument for assisting intravitreal injections. This study clinically evaluated the RAVI guide with respect to patient acceptance, complication rates, and operative goals.

Methods: A prospective study was performed on 54 patients undergoing intravitreal injections using the RAVI guide (n = 32) or the speculum/caliper (n = 22). Device-related pain was assessed using the Wong-Baker scoring system, scaled from 0 (no pain) to 10 (agonizing pain).

Results: Mean device-related pain score did not differ significantly between the 2 groups, with scores of 0.6 and 0.7 for the RAVI guide and speculum groups, respectively. The rate of significant pain (score of ≥2) was twice as high in the speculum group (7 of 22, 32%) compared with the RAVI guide group (5 of 32, 16%), but this difference was not statistically significant (P = 0.19, Fisher's exact test). Operative goals of avoiding needle touch to lashes/lids and guiding needle insertion to the intended site were achieved in all patients.

Conclusion: The RAVI guide appeared equivalent to the eyelid speculum in achieving operative goals, with similarly low pain scores. It has the potential for facilitating efficient, accurate, and safe intravitreal injections.
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http://dx.doi.org/10.1097/IAE.0000000000001229DOI Listing
April 2017

Update on Screening Recommendations for Hydroxychloroquine Retinopathy.

JAMA Ophthalmol 2016 07;134(7):849

Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California.

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http://dx.doi.org/10.1001/jamaophthalmol.2016.1252DOI Listing
July 2016

EFFECTIVENESS OF DIFFERENT MONITORING MODALITIES IN THE DETECTION OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The Home Study, Report Number 3.

Retina 2016 Aug;36(8):1542-7

*Clinical Trials Branch, National Eye Institute/National Institutes of Health, Bethesda, Maryland; †The EMMES Corporation, Rockville, Maryland; ‡The Retina Division at the Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland; §Elman Retina Group, Baltimore, Maryland; ¶Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin; **Retina Group of Washington, Washington, D.C.; ††Ophthalmic Consultants of Boston, Boston, Massachusetts; ‡‡Scheie Eye Institute, Philadelphia, Pennsylvania; §§Retina-Vitreous Associates Medical Group, Los Angeles, California.

Purpose: To determine the effectiveness of different monitoring modalities to detect incident neovascularization associated with age-related macular degeneration (AMD).

Methods: Secondary analyses compared the rates of detecting incident neovascular AMD in prescheduled office visits versus office visits triggered by monitoring device or by symptom realization in a randomized trial evaluating home telemonitoring device plus standard care (device arm) versus standard care alone.

Results: At prescheduled office visits, neovascular AMD was detected in 14/1927 visits (0.7%, 95% confidence interval [CI]: 0.4%-1.1%) and 14/1949 visits (0.7%, 95% CI: 0.3%-1.1%) in the device and standard care alone arms, respectively. Thirty-seven participants with neovascular AMD were detected in 318 office visits (11.6%, 95% CI: 8.1%-15.2%) triggered by device or symptom realization and 17 neovascular AMD in 65 office visits (26%, 95% CI: 15.5%-36.8%) triggered by symptom realization in the device and standard care alone arms, respectively. The home device strategy had a higher neovascular-AMD detection rate than prescheduled office visits (relative risk = 16.0 [95% CI: 8.8-29.3]). Neovascular AMD detected at triggered visits were associated with less vision loss from baseline in the device arm versus standard care alone arm (-3 letters vs. -11.5 letters, respectively, P = 0.03).

Conclusion: Telemonitoring may alter the management of patients with AMD and improve vision outcomes.
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http://dx.doi.org/10.1097/IAE.0000000000000940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961546PMC
August 2016

Which Test Is the Best for Hydroxychloroquine Toxicity Screening?

Authors:
Judy E Kim

JAMA Ophthalmol 2016 May;134(5):520-521

Department of Ophthalmology, Medical College of Wisconsin, Milwaukee.

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http://dx.doi.org/10.1001/jamaophthalmol.2016.0323DOI Listing
May 2016

Comparison of Aflibercept, Bevacizumab, and Ranibizumab for Treatment of Diabetic Macular Edema: Extrapolation of Data to Clinical Practice.

JAMA Ophthalmol 2016 Jan;134(1):95-9

Palmetto Retina Center, West Columbia, South Carolina.

Importance: The Diabetic Retinopathy Clinical Research Network (DRCR Network), sponsored by the National Eye Institute, reported the results of a comparative effectiveness randomized clinical trial (RCT) evaluating the 3 anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept (2.0 mg), bevacizumab (1.25 mg), and ranibizumab (0.3 mg) for treatment of diabetic macular edema (DME) involving the center of the retina and associated with visual acuity loss. The many important findings of the RCT prompted the American Society of Retina Specialists to convene a group of experts to provide their perspective regarding clinically relevant findings of the study.

Objectives: To describe specific outcomes of the RCT judged worthy of highlighting, to discuss how these and other clinically relevant results should be considered by specialists treating DME, and to identify unanswered questions that merit consideration before treatment.

Evidence Review: The DRCR Network-authored publication on primary outcomes of the comparative effectiveness RCT at 89 sites in the United States. The study period of the RCT was August 22, 2012, to August 28, 2013.

Findings: On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and with visual acuity impairment, including mean (SD) improvements by +13.3 (11.1) letters with aflibercept vs +9.7 (10.1) letters with bevacizumab (P < .001) and +11.2 (9.4) letters with ranibizumab (P = .03). Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept (+18.9 [11.5]) over bevacizumab (+11.8 [12.0]) or ranibizumab (14.2 [10.6]) 1 year later (P < .001 for interaction with visual acuity as a continuous variable, and P = .002 for interaction with visual acuity as a categorical variable). It is unknown whether different visual acuity outcomes associated with the use of the 3 anti-VEGF agents would be noted with other treatment regimens or with adequately repackaged bevacizumab, as well as in patients with criteria that excluded them from the RCT, such as persistent DME despite recent anti-VEGF treatment.

Conclusions And Relevance: On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and visual acuity impairment. Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept over bevacizumab or ranibizumab 1 year later. Care needs to be taken when attempting to extrapolate outcomes of this RCT to differing treatment regimens. With access to adequately repackaged bevacizumab, many specialists might initiate therapy with bevacizumab when visual acuity is good (ie, 20/32 to 20/40 as measured in the DRCR Network), recognizing that the cost-effectiveness of bevacizumab outweighs that of aflibercept or ranibizumab.
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http://dx.doi.org/10.1001/jamaophthalmol.2015.4110DOI Listing
January 2016

Resonance Raman Analysis of the Tryptophan Cation Radical.

J Phys Chem Lett 2014 Sep 21;5(17):3009-14. Epub 2014 Aug 21.

Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.

Electron transfer (ET) reactions within proteins are accomplished by a broad set of redox-active molecules, including natural amino acids. Tryptophan participates in ET chemistry as both a cation and a neutral radical. Identification and characterization of the biologically relevant species is essential to understand efficient ET mechanisms in proteins. We present resonance Raman spectra and excitation profiles of the tryptophan cation radical generated by combining a strong oxidant, Ce(IV), with tryptophan model compounds in a fast-flow mixing device. Isotopically modified derivatives, coupled with calculations, allowed the assignment of the normal modes of this radical. Raman bands that are sensitive to protonation state and hydrogen bonding environment of the cation radical were identified. The present findings, along with resonance Raman spectra of the closed-shell and neutral radical counterparts, form a foundation for probing tryptophan-mediated ET reactions in proteins.
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http://dx.doi.org/10.1021/jz5012324DOI Listing
September 2014

Insights into Protein Structure and Dynamics by Ultraviolet and Visible Resonance Raman Spectroscopy.

Biochemistry 2015 Aug 29;54(31):4770-83. Epub 2015 Jul 29.

Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.

Raman spectroscopy is a form of vibrational spectroscopy based on inelastic scattering of light. In resonance Raman spectroscopy, the wavelength of the incident light falls within an absorption band of a chromophore, and this overlap of excitation and absorption energy greatly enhances the Raman scattering efficiency of the absorbing species. The ability to probe vibrational spectra of select chromophores within a complex mixture of molecules makes resonance Raman spectroscopy an excellent tool for studies of biomolecules. In this Current Topic, we discuss the type of molecular insights obtained from steady-state and time-resolved resonance Raman studies of a prototypical photoactive protein, rhodopsin. We also review recent efforts in ultraviolet resonance Raman investigations of soluble and membrane-associated biomolecules, including integral membrane proteins and antimicrobial peptides. These examples illustrate that resonance Raman is a sensitive, selective, and practical method for studying the structures of biological molecules, and the molecular bonding, geometry, and environments of protein cofactors, the backbone, and side chains.
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http://dx.doi.org/10.1021/acs.biochem.5b00514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5092233PMC
August 2015

Unilateral Perivascular Infiltrates in Lupus Retinopathy.

JAMA Ophthalmol 2015 Jun 11;133(6):e145367. Epub 2015 Jun 11.

Department of Ophthalmology, Medical College of Wisconsin, Milwaukee.

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http://dx.doi.org/10.1001/jamaophthalmol.2014.5367DOI Listing
June 2015

Attempted auto-enucleation in two incarcerated young men with psychosis.

Saudi J Ophthalmol 2015 Apr-Jun;29(2):172-4. Epub 2014 Sep 27.

Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, WI, USA.

Auto-enucleation is a sign of untreated psychosis. We describe two patients who presented with attempted auto-enucleation while being incarcerated. This is an observation two-case series of two young men who suffered untreated psychosis while being incarcerated. These young men showed severe self-inflicted ocular trauma during episodes of untreated psychosis. Injuries included orbital bone fracture and dehiscence of the lateral rectus in one patient and severe retinal hemorrhage and partial optic nerve avulsion in the second patient. Auto-enucleation is a severe symptom of untreated psychosis. This urgent finding can occur in a jail setting in which psychiatric care may be minimal.
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http://dx.doi.org/10.1016/j.sjopt.2014.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398797PMC
April 2015